CA2480570C - Method for collecting a desired blood component and performing a photopheresis treatment - Google Patents

Abstract

An improved method for separating whole blood into components and collecting a desired blood component. The method allows a desired blood component to be subjected to centrifugal forces within a separator for prolonged periods of time, yielding a cleaner cut and higher yield of the desired blood component. Whole blood is drawn from a source and pumped into a separator, the undesired blood components are removed from the separator at rates so as to build up the desired blood component in the separator. The desired blood component is only removed after a predetermined amount of the desired blood component has built up in the separator. It is preferred that the desired blood component be buffy coat and that the method be used to perform photopheresis treatments. In another aspect, the invention is a method of performing a full photopheresis treatment to treat diseases in a reduced time, preferably less than about 70 minutes, and more preferably less than about 45 minutes.

Description

METHOD FOR COLLECTING A DESIRED BLOOD COMPONENT AND
PERFORMING A PHOTOPHERESIS TREATMENT
Technical Field of the Invention

[0002] The present invention relates generally to methods for separating whole blood into blood components and collecting a desired blood component, and specifically to methods of treating diseases with a photopheresis treatment.
Background of the Invention

[0003] Several treatments for disease require the removal of blood from a patient, processing the one or more components of the blood, and return of the processed components for a therapeutic effect. Those extracorporeal treatments require systems for safely removing blood from the patient, separating it into components, and returning the blood or blood components to the patient.. With the advance of medical sciences, it has become possible to treat a patient's blood in closed-loop processes, returning the patient's own treated blood back to him in one medical treatment. An example of such processes include external treatment methods for diseases in which there is a pathological increase of lymphocytes, such as cutaneous T-cell lymphoma or other diseases affecting white blood cells. In such methods, the patient's blood is irradiated with ultraviolet light in the presence of a chemical or an antibody. Ultraviolet light affects the bonding between the lymphocytes and the chemical or antibody that inhibits the metabolic processes of the lymphocytes.
[00041 Photopheresis systems and methods have been proposed and used which involve separation of huffy coat from the blood, addition of a photoactivatable drug, and UV
irradiation of the buffy coat before re-infusion to the patient.
Extracorporeal photopheresis may be utilized to treat numerous diseases including Graft-versus-Host disease, Rheumatoid Arthritis, Progressive Systematic Sclerosis, Juvenile Onset Diabetes, Inflammatory Bowel Disease and other diseases that are thought to be T-cell or white blood cell mediated, including cancer. Apheresis systems and methods have also been proposed and used which involve separation of blood into various components.
[00051 During one of these medical treatments, a centrifuge bowl, such as, for example, a Latham bowl, as shown in U.S. Patent No. 4,303,193, is operated to separate whole blood into red blood cells ("RBCs"), plasma, and buffy coat. The Latham bowl is a blood component separator that has been used for some time in the medical apheresis market as well as in innovative medical therapies such as extracorporeal photopheresis (ECP). PCT Applications WO 97/36581 and WO
97/36634, and U.S. Patent Nos. 4,321,919; 4,398,906; 4,428,744; and 4,464,166 provide descriptions of extracorporeal photopheresis, [00061 Latham bowl efficiency is often measured by the white blood cell ("WBC") "yield,"
which is typically about 50%. Yield is defined as the percentage of cells collected versus the number processed. When compared to other types of whole blood separators, this high yield enables the Latham bowl separator to collect much larger volumes of WBCs while processing much less whole blood from the donor patient. However, a major drawback to the Latham bowl separator is that the separation process must be repeatedly stopped to remove the packed RBCs and plasma once they fill the inside of the bowl, creating a "batch-type"
treatment process. Although the Latham bowl separator has a high volume yield, the constant filling and emptying of this bowl wastes time; thus, the process is considered less efficient with respect to time.
[0007] Prior photopheresis and apheresis systems and methods usually require batch processes and therefore take several hours to treat a patient or to obtain a sufficient supply of separated blood fragments. Furthermore, the systems are very complex to manufacture. It is a constant objective to reduce the time it takes to perform a complete photopheresis treatment session. Another objective is to reduce the amount of blood that must be drawn form a patient and processed in closed-loop processes per photopheresis treatment session. Yet another objective to increase the amount of white blood cell yield or obtain a cleaner cut of buffy coat per volume of whole blood processed.
Disclosure of the Invention [0008] An object of the present invention is to provide an improved method for separating a fluid, such as blood or other biological fluid, into its components. An additional object is to increase the efficiency of current fluid separation processes by decreasing the time necessary to separate out a desired amount of a fluid component from the fluid. Yet other objects of the present invention are to treat a patient more efficiently, to improve a photopheresis process, or to improve a platelet removal process. An additional object of the present invention is to separate and remove targeted cells by their specific gravity. Another object of the present invention is to eliminate the need to perform fluid separation processes in "batch" form. A
still further object of the present invention is to increase the percent yield of a desired fluid component from a fluid being separated.
[0009] The present invention solves the inadequacies of the prior art by being able to continuously separate fluid components without interrupting the process to empty a centrifuge bowl and remove a separated component. Thus, the present invention eliminates batch processing and other Latham bowl batch-type techniques. These objects and others are met by the present invention which is directed at improving the methods for separating whole blood into its components and collecting a desired blood component. Depending on the intended treatment, the desired blood component may be buffy coat, red blood cells, plasma, or any component thereof. The present invention is also directed at improving existing methods of treating diseases using photopheresis therapies. Specifically, the present invention provides a continuous process for whole blood separation of sufficient fragment for photopheresis treatment so as to greatly reduce the photopheresis treatment time for a patient.
[00101 When it is desired to collect buffy coat from whole blood, the invention in one aspect is a method comprising: providing a separator having an inlet, a first outlet, and a second outlet; drawing whole blood from a source; adding an anticoagulant fluid to the whole blood in a predetermined ratio to form a mixture of whole blood and anticoagulant fluid; pumping the mixture of whole blood and anticoagulant fluid into the separator via the inlet at a selected inlet rate; separating the mixture into blood components of different densities;
withdrawing plasma and red blood cells from the separator while continuing to pump the mixture of whole blood and anticoagulant fluid into the separator, the plasma and red blood cells being withdrawn at rates so as to build up huffy coat in the separator, the plasma being withdrawn via the first outlet and the red blood cells being withdrawn via the second outlet;
and upon a predetermined amount of buffy coat building up in the separator, collecting the buffy coat from the separator.
10011] By withdrawing the red blood cells and the plasma at rates so that the huffy coat is allowed to build up within the separator, which is preferably a centrifuge bowl, the buffy coat is subjected to the centrifugal force of the separator for a prolonged period of time.
Increasing the time which the buffy coat is subjected to centrifugal force yields a cleaner fraction of buffy coat and an increased white blood cell yield. Additionally, this prolonged exposure can be used to further separate the buffy coat into its constituent parts, including platelets and various kinds of leukocytes.
[0012] When pumping the mixture of whole blood and anticoagulant fluid into the separator, it is preferred that the mixture pass through, and be routed by, a cassette for controlling fluid flow. It is further preferable that the buffy coat be collected from the separator by discontinuing the withdrawal of red blood cells from the second outlet, thereby causing the red blood cells to push the buffy coat out of the separator via the first outlet as whole blood continues to enter the separator. The withdrawn buffy coat can be collected in a treatment bag that is fluidly connected to the separator via an outlet line. In this embodiment, the collection of buffy coat is preferably discontinued when red blood cells are detected in the outlet line. This will minimize red blood cells from being mixed with the desired buffy coat.
[0013] In performing this method, it is also preferable that only the plasma be withdrawn from the separator until a predetermined amount of red blood cells are detected in the separator. Then, upon the predetermined amount of red blood cells being detected in the separator, the red blood cells will be drawn from the separator at a rate so as to maintain the amount of red blood cells present in the separator at approximately the predetermined amount. The predetermined amount of red blood cells can be detected using a hematocrit sensor that can detect a red cell line within the centrifuge bowl itself.
[0014] When the method is being used in a closed loop process where the source of the whole blood is a patient, it is important to return fluids back to the patient during processing.
In order to achieve this, it is preferable that the withdrawn plasma be collected in a plasma storage bag, mixed with a priming fluid, and returned to the patient when a selected amount of plasma is collected in the plasma storage bag. It is further preferable to mix the withdrawn red blood cells with the plasma and priming fluid mixture from the plasma collection bag and returning the red blood cell-plasma-priming fluid mixture to the patient at a rate approximately equal to the inlet rate.
[0015] This method can be used in connection with photopheresis treatment. In a photopheresis treatment, the method will further comprise injecting a photoactivation chemical into the collected buffy coat, and irradiating the collected buffy coat within an irradiation chamber until a predetermined amount of energy has been transferred to the

4 collected buffy coat. In order to ensure that a proper amount of energy is transferred to the buffy coat, for example to induce apoptosis, it is preferable to recirculate the collected buffy coat between a treatment bag and the irradiation chamber. Before the irradiated buffy coat is returned to the patient undergoing the photopheresis therapy, the irradiated buffy coat should pass through a filter. Using this method, enough buffy coat can be collected and irradiated to perform a full photopheresis treatment in less than about 70 minutes. More preferably, the overall treatment time is less than about 45 minutes.
[0016] It may also be desired to collect the red blood cells from the separator for other types of treatments. Because the red blood cells can be subjected to prolonged centrifugal force, the current method provides a very packed amount of red cells. These red blood cells can be withdrawn and collected for further use, such as in apheresis therapy.
[0017] In yet another aspect, the invention is a method of performing a photopheresis treatment for ameliorating diseases. This method comprises: drawing whole blood from a source; adding an anticoagulant fluid to the whole blood in a predetermined ratio to form a mixture of the whole blood and the anticoagulant fluid; separating the mixture of whole blood and anticoagulant into a plurality of blood components according to density;
mixing a photoactivation chemical with at least one the blood components to form a mixture of the photoactivation chemical and the at least one blood component; irradiating the combination of the at least one blood component and photoactivation chemical; and returning the irradiated combination to a patient; wherein the entire photopheresis treatment is completed in less about than 70 minutes. More preferably, the entire photopheresis treatment is completed in less about than 45 minutes. This is a vast improvement over previous photopheresis treatments which usually required a treatment time of two hours or more.
[0018] In this aspect of the invention, the at least one blood component can be buffy coat, a leukocyte, or platelets. Buffy coat is preferred. In performing the photopheresis treatment, the mixture of whole blood and anticoagulant fluid is preferably pumped into a separator having an inlet, a first outlet, and a second outlet. Because buffy coat is the desired blood component in a photopheresis therapy session, plasma and red blood cells are withdrawn from the separator while continuing to pump the mixture of whole blood and anticoagulant fluid into the separator. The plasma and red blood cells are preferably withdrawn at rates so as to build up buffy coat in the separator, allowing the buffy coat to be exposed to prolonged centrifugal forces. The plasma is withdrawn via the first outlet and the red blood cells being withdrawn via the second outlet. Buff,' coat is preferably collected from the separator for irradiation only after a predetermined amount of buffy coat builds up therein.
[0019] The separated buffy coat is preferably collected from the separator through an outlet line that is fluidly connected to a treatment bag. The buffy coat can be collected from the separator by discontinuing the withdrawal of red blood cells from the second outlet while continuing to pump in whole blood. This causes the red blood cells to push the buffy coat out of the separator via the first outlet. Buffy coat collection is preferably stopped when red blood cells are detected in the outlet line by a hematocrit sensor. The collected buffy coat is preferably irradiated within an irradiation chamber until a predetei __ mined amount of energy has been transferred to the collected buffy coat. The predetermined amount of energy is preferably sufficient to induce apoptosis.
[0020] This photopheresis treatment is preferably performed in a closed-loop system where the patient is also the source. Finally, instead of separating only buffy coat, the buffy cells can be further separated if desired into their components such as platelets and leukocytes.
[0021] Finally, an effective method of collecting red blood cells is achieved by another aspect of the invention which is a method of collecting a desired blood component, comprising: providing a separator having an inlet, a first outlet, and a second outlet; drawing whole blood from a source; adding an anticoagulant fluid to the whole blood in a predetermined ratio to form a mixture of whole blood and anticoagulant fluid;
pumping the mixture of whole blood and anticoagulant fluid into the separator via the inlet at a selected inlet rate; separating the mixture into blood components of different densities; withdrawing plasma and buffy coat from the separator while continuing to pump the mixture of whole blood and anticoagulant fluid into the separator, the plasma and buffy coat being withdrawn at rates so as to build up red blood cells in the separator, the plasma and buffy coat being withdrawn via the first outlet; and upon a predetennined amount of red blood cells building up in the separator, collecting the red blood cells from the separator via the second outlet.
This method allows the red blood cells to build up in the separator and be subjected to a maximum amount of prolonged centrifugal force In one embodiment, there is provided a method of collecting a desired blood component comprising: providing a separator having an inlet, a first outlet, and a second outlet; adding an anticoagulant fluid to whole blood drawn from a source in a predetermined ratio to form a mixture of whole blood and anticoagulant fluid; pumping the mixture of whole blood and anticoagulant fluid into the separator via the inlet at a selected inlet rate;
separating the mixture into blood components of different densities; withdrawing plasma and red blood cells from the separator while continuing to pump the mixture of whole blood and anticoagulant fluid into the separator, the plasma and red blood cells being withdrawn at rates so as to build up buffy coat in the separator, the plasma being withdrawn via the first outlet and the red blood cells being withdrawn via the second outlet; and upon a predetermined amount of buffy coat building up in the separator, collecting the buffy coat from the separator, the method further comprising injecting a photoactivation chemical into the collected buffy coat; and irradiating the collected buffy coat within an irradiation chamber until a predetermined amount of energy has been transferred to the collected buffy coat; and wherein overall treatment time is less than about 70 minutes.
In another embodiment, there is provided a system for collecting a desired blood component, the system comprising: means for combining anticoagulant with whole blood withdrawn from a patient at a selected ratio of anticoagulant to whole blood; a fluid flow controller; a pump; a separator; means for controlling the pump to: pump the combination of whole blood and anticoagulant through the fluid flow controller to the separator, wherein the separator is configured to operate until air is displaced; and continue to pump the combined whole blood and anticoagulant into the separator until a selected amount of plasma is collected; means for mixing plasma with a priming fluid and for returning the mixture of plasma and priming fluid to the patient at the same rate as incoming whole blood until red blood cells are detected; means for withdrawing red blood cells; means for controlling the speed of the pump so as to maintain a red blood cell line selected level in the separator while buffy coat is collected in the separator; means for, at a selected time, when a desired amount of buffy coat cells are collected in the separator, causing the pump to continue to pump whole blood into the separator while discontinuing pumping red blood cells, thereby causing the red blood cells to push buffy coat out of the separator until a desired amount is collected in a buffy coat collector; and means for discontinuing collection of buffy coat when red blood cells have been detected, wherein the DOCSTOR. 2581708\1 6a separator is configured to separate the mixture of whole blood and anticoagulant into a plurality of blood components according to density, wherein the system further comprises: means for mixing a photoactivation chemical with at least one of the blood components to form a mixture of the photoactivation chemical and the at least one blood component; and means for irradiating the combination of the at least one blood component and photoactivation chemical to produce an irradiated combination for return to the patient.
In another embodiment, there is provided a method of treating blood for photopheresis treatment comprising: adding an anticoagulant fluid to whole blood withdrawn from a source in a predetermined ratio to form a mixture of whole blood and anticoagulant fluid;
separating the mixture of whole blood and anticoagulant into a plurality of blood components according to density; mixing a photoactivation chemical with at least one of the blood components to form a mixture of the photoactivation chemical and the at least one blood component;
irradiating the combination of the at least one blood component and photoactivation chemical for return to a patient; wherein the entire photopheresis treatment is completed in less than about 70 minutes;
and wherein the step of separating the mixture of whole blood and anticoagulant fluid comprises:
providing a separator having an inlet, a first outlet, and a second outlet;
pumping the mixture of whole blood and anticoagulant fluid into the separator via the inlet at a selected inlet rate; and withdrawing plasma and red blood cells from the separator while continuing to pump the mixture of whole blood and anticoagulant fluid into the separator, the plasma and red blood cells being withdrawn at rates so as to build up buffy coat in the separator, the plasma being withdrawn via the first outlet and the red blood cells being withdrawn via the second outlet; and upon a predetermined amount of buffy coat building up in the separator, collecting the buffy coat from the separator.
Brief Description of the Drawings [0022] The invention is described in detail with respect to the accompanying drawings, which illustrate an embodiment of the inventive apparatus, assemblies, systems, and methods.
6b FIG. 1 is a schematic representation of an embodiment of a disposable kit for use in photopheresis therapy embodying features of the present invention.
FIG. 2 is an elevated perspective view of an embodiment of a cassette for controlling fluid flow in the disposable photopheresis kit of FIG. 1.
FIG. 3 is an exploded view of the cassette of FIG. 2.
FIG. 4 is a top view of the cassette of FIG. 2 with the cover removed and showing internal tubular circuitry.
FIG. 5 is a bottom view of a cover of cassette of FIG. 2.
FIG. 6 is an elevated perspective view of an embodiment of a filter assembly..
FIG. 7 is bottom perspective view of the filter assembly of FIG. 6.
FIG. 8 is an exploded view of the filter assembly of FIG. 6.
FIG. 9 is a rear perspective view of the filter assembly of FIG. 6.
FIG. 10 is schematic representation of the filter assembly of FIG. 6 coupled to pressure sensors and a data processor.
FIG. 11 is a front view of an irradiation chamber.
FIG. 12 is a side longitudinal view of the irradiation chamber of FIG. 11.
FIG. 13 is a side transverse view of the irradiation chamber of FIG. 11 FIG. 14 is a cut-away view of a section of the first plate and the second plate prior to being joined together to form the irradiation chamber of FIG. 11.
FIG. 15 is a cut-away dimensional end view of the irradiation chamber of FIG.
11.
FIG. 16 is a perspective view of the irradiation chamber of FIG. 11 positioned within a UVA light assembly.
FIG. 17 is an elevated perspective view of an embodiment of a permanent tower system for use in conjunction with a disposable kit for facilitating a photopheresis therapy session.
FIG. 18 is a cross-sectional view of an embodiment of the photoactivation chamber, without a UVA light assembly, used in the tower system of FIG. 17.
FIG. 19 is a cross-sectional view of an embodiment of the centrifuge chamber used in the tower system of FIG. 17.
FIG. 20 is an electrical schematic of the leak detection circuit provided in the photoactivation chamber of FIG. 18.
FIG. 21 is an electrical schematic of the leak detection circuit provided in the centrifuge chamber of FIG. 19.

J
FIG. 22 is an elevated perspective view of an embodiment of the fluid flow control deck of the tower system of FIG. 17.
FIG. 23 is a perspective bottom view of the control deck of FIG. 22.
FIG. 24 is an exploded view of the control deck of FIG. 22.
FIG. 25 is a top perspective view of the control deck of FIG. 22 with the cassette of FIG.
2 loaded thereon.
FIG. 26 is a flowchart of an embodiment of a photopheresis treatment process.
FIG. 27 is a schematic of an embodiment of the fluid flow circuit used in performing the treatment process of FIG. 26.
FIG. 28 is top perspective view an embodiment of a peristaltic pump.
FIG. 29 is a cross sectional side view of the peristaltic pump of FIG. 28.
FIG. 30 is a top perspective view the rotor of the peristaltic pump of FIG.
29.
FIG. 31 is a bottom perspective view of the rotor of FIG. 30.
FIG. 32 is a top view of the peristaltic pump of FIG. 28.
FIG. 33 is a top view of the peristaltic pump of FIG. 28 in a loading position and near the cassette of FIG. 2.
FIG. 34 is an electrical schematic of the infrared communication port circuit.
FIG. 35 illustrates an embodiment of a centrifuge bowl and a rotating frame.
FIG. 36 is a dimensional view of the bowl of FIG. 35.
FIG. 37 is an exploded view of the bowl of FIG. 36.
FIG. 38 shows a cross sectional view of the bowl of FIG. 36 along the line XIX-XIX.
FIG. 39A shows a cross sectional view of a connection sleeve in place with a lumen connector of the bowl of FIG 38 along the line XX.
FIG. 39B shows another cross sectional view of a connection sleeve in place with a lumen connector of the bowl of FIG 38.
FIG. 40 shows a cross sectional view of the top core of the bowl of FIG. 37.
FIG. 41 shows a dimensional view of the top core and upper plate of FIG. 37.
FIG. 42 shows a bottom view of the top core of FIG. 41.
FIG. 43A shows a dimensional exploded view of the bottom core and a lower plate of the bowl of FIG. 37.
FIG. 43B shows an dimensional cross section view of the bottom core and a lower plate of the bowl of FIG. 43A attached together.
FIG. 44 shows an exploded side view of the bottom core and a lower plate of FIG. 43A.

FIG. 45 shows a dimensional view of another embodiment of a conduit assembly.
FIG. 46 shows a dimensional view of the connection sleeve of FIG. 45.
=
FIG. 47 shows a dimensional view of one end of conduit assembly of FIG. 45.
FIG. 48 shows a dimensional view of an anchor end of the present invention.
FIG. 49 shows a lateral cross-sectional view of an anchor end.
FIG. 50 shows a horizontal cross-sectional view of an anchor end taken along line XXI.
FIG. 51 illustrates a dimensional view of the rotating frame of FIG. 35.
FIG. 52 is an enlarged view of a holder for an external conduit.
FIG. 53 shows an alternative embodiment of the bowl with the cross-section taken similarly to that shown in FIG. 38.
FIG. 54 shows an alternative embodiment of the top core.
FIG. 55 shows an alternative embodiment of the connection sleeve.
Modes for Carrying Out The Invention 100231 Features of the present invention are embodied in the permanent blood driving equipment, the disposable photopheresis kit, the various devices which make up the disposable kit, and the corresponding treatment process. The following written description is outlined as follows:
I. Disposable Photopheresis Kit A. Cassette for Controlling Fluid Flow 1. Filter Assembly B. Irradiation Chamber C. Centrifuge Bowl 1. Drive Tube II. Permanent Tower System A Photoactivation Chamber B. Centrifuge Chamber C. Fluid Flow Control Deck 1. Cassette Clamping Mechanism 2. Self-Loading Peristaltic Pumps D. Infra-Red Communication Photopheresis Treatment Process 10024] The above-outline is included to facilitate understanding of the features of the present invention. The outline is not limiting of the present invention and is not intended to categorize or limit any aspect of the invention. The inventions are described and illustrated in sufficient detail that those skilled in this art can readily make and use them. However, various alternatives, modifications, and improvements should become readily apparent.

=
Specifically, while the invention is described in the context of a disposable kit and permanent blood drive system for use in photopheresis therapy, certain aspects of the invention are not so limitedand are applicable to kits and systems used for rendering other therapies, such as apheresis or any other extracorporeal blood treatment therapy.
I. Disposable Photopheresis Kit [0025] FIG. 1 illustrates disposable photopheresis kit 1000 embodying features of the present invention. It is necessary that a new disposable sterile kit be used for each therapy session. In order to facilitate the circulation of fluids through photopheresis kit 1000, and to treat blood fluids circulating therethrough, photopheresis kit 1000 is installed in permanent tower system 2000 (FIG. 17). The installation of photopheresis kit 1000 into tower system 2000 is described in detail below.
[0026] Photopheresis kit 1000 comprises cassette 1100, centrifuge bowl 10, irradiation chamber700, hematocrit sensor 1125, removable data card 1195, treatment bag 50, and plasma collection bag 51. Photopheresis kit 1000 further comprises saline connector spike 1190 and anticoagulant connector spike 1191 for respectively connecting saline and anticoagulant fluid bags (not shown). Photopheresis kit 1000 has all the necessary tubing and connectors to fluidly connect all devices and to route the circulation of fluids during a photopheresis treatment session. All tubing is sterile medical grade flexible tubing. Tripoli connectors 1192 are provided at various positions for the introduction of fluids into the tubing if necessary.
[0027] Needle adapters 1193 and 1194 are provided for respectively connecting photopheresis kit 1000 to needles for drawing whole blood from a patient and returning blood fluids to the patient. Alternatively, photopheresis kit 1000 can be adapted to use a single needle to both draw whole blood from the patient and return blood fluids to the patient.
However, a two needle kit is preferred because of the ability to simultaneously draw whole blood and return blood fluids to the patient. When a patient is hooked up to photopheresis kit 1000, a closed loop system is formed.
[0028] Cassette 1100 acts both as a tube organizer and a fluid flow router.
Irradiation chamber 700 is used to expose blood fluids to UV light. Centrifuge bowl 10 separates whole blood into its different components according to density. Treatment bag 50 is a 1000mL
three port bag. Straight bond port 52 is used to inject a photoactivatable or photosensitive ___________________________________ CA 02480570 2004-09-03 ___________________________________ compound into treatment bag 50. Plasma collection bag 51 is 1000mL two port bag. Both treatment bag 50 and plasma collection bag 51 have a hinged cap spike tube 53 which can be used for drainage if necessary. Photopheresis kit 1000 further comprises hydrophobic filters 1555 and 1556 which are adapted to connect to pressure transducers 1550 and 1551 to filter 1500 via vent tubes 1552 and 1553 for monitoring and controlling the pressures within tubes connecting the patient (FIG. 10). Monitoring the pressure helps ensure that the kit is operating within safe pressure limits. The individual devices of photopheresis kit 1000, and their functioning, are discussed below in detail.
A. Cassette for Controlling Fluid Flow 100291 FIG. 2 shows a top perspective view of a disposable cassette 1100 for valving, pumping, and controlling the movement of blood fluids during a photopheresis treatment session. Cassette 1100 has housing 1101 that forms an internal space that acts as a casing for its various internal components and tubular circuitry. Housing 1101 is preferably made of hard plastic, but can be made of any suitably rigid material. Housing 1101 has side wall 1104 and top surface 1105. Side wall 1104 of housing 1101 has tabs 1102 and 1103 extending therefrom. During a photopheresis treatment, cassette 1100 needs to be secured to deck 1200 of tower system 2000, as is best illustrated in FIG. 25. Tabs 1102 and 1103 help position and secure cassette 1100 to deck 1200.
[0030] Cassette 1100 has fluid inlet tubes 1106, 1107, 1108, 1109, 1110, 1111, and 1112 for receiving fluids into cassette 1100, fluid outlet tubes 1114, 1115, 1116, 1117, 1118, and 1119 for expelling fluids from cassette 1100, and fluid inlet/outlet tube 1113 that can be used for both introducing and expelling fluids into and out of cassette 1100. These fluid input and output tubes fluidly couple cassette 1100 to a patient being treated, as well as the various devices of photopheresis kit 1000, such as centrifuge bowl 10, irradiation chamber700, treatment bag 50, plasma collection bag 51, and bags containing saline, anticoagulation fluid to form a closed-loop extracorporeal fluid circuit (FIG. 27).
100311 Pump tube loops 1120, 1121, 1122, 1123, and 1124 protrude from side wall 1104 of housing 1101. Pump tube loops 1120, 1121, 1122, 1123, and 1124 are provided for facilitating the circulation of fluids throughout photopheresis kit 1000 during therapy. More specifically, when cassette 1100 is secured to deck 1200 for operation, each one of said pump tube loops 1120, 1121, 1122, 1123, and 1124 are loaded into a corresponding peristaltic pump 1301, 1302, 1303, 1304, and 1305 (FIG. 4). Peristaltic pumps 1301, 1302, 1303, 1304, and 1305 drive fluid through the respective pump tube loops 1120, 1121, 1122, 1123, and 1124 in a predetermined direction, thereby driving fluid through photopheresis kit 1000 (FIG.
1) as necessary. The operation and automatic loading and unloading of peristaltic pumps 1301, 1302, 1303, 1304, and 1305 is discussed in detail below with respect to FIGS. 28-33.
[0032] Turning now to FIG. 3, cassette 1100 is shown with housing 1101 in an exploded state. For ease of illustration and description, the internal tubular circuitry within housing 1101 is not illustrated in FIG. 3. The internal tubular circuitry is illustrated in FIG. 4 and will be discussed in relation thereto. Cassette 1100 has filter assembly 1500 positioned therein and in fluid connection with inlet tube 1106, outlet tube'1114, and one end of each of pump tube loops 1120 and 1121. Filter assembly 1500 comprises vent chambers 1540 and 1542.
Filter assembly 1500, and its functioning, is discussed in detail below with respect to FIGS.
6-10.
[0033] Housing 1101 comprises cover 1130 and base 1131. Cover 1130 has top surface 1105, a bottom surface 1160 (FIG. 5), and side wall 1104. Cover 1130 has openings 1132 and 1133 for allowing vent chambers 1540 and 1542 of filter assembly 1500 to extend therethrough. Side wall 1104 has a plurality of tube slots 1134 to allow the inlet tubes, outlet tubes, and pump loop tubes to pass into the internal space of housing 1101 for connection with the internal tubular circuitry located therein. Only a few tube slots 1134 are labeled in FIG. 3 to avoid numerical crowding. Tabs 1102 and 1103 are positioned on side wall 1104 so as not to interfere with tube slots 1134. Cover 1130 has occlusion bars 1162 and 1162A
extending from bottom surface 1160 (FIG. 5). Occlusion bars 1162 and 1162A are preferably molded into bottom surface 1160 of cover 1130 during its formation.
[0034] Base 1131 has a plurality of U-shaped tube-holders 1135 extending upward from top surface 1136. U-shaped tube holders 1135 hold the inlet tubes, outlet tubes, pump loop tubes, filter assembly, and internal tubular circuitry in place. Only a few U-shaped holders 1135 are labeled in FIG. 3 to avoid numerical crowding. Preferably, a U-shaped holder 1135 is provided on base 1131 at each location where an inlet tube, an outlet tube, or a pump loop tube passes through a tube slot 1134 on side wall 1104. Male extrusions 1136 protrude from top surface 1136 of base 1131 for mating with corresponding female holes 1161 located on bottom surface 1160 of cover 1130 (FIG. 5). Preferably, a male protrusion 1136 is located at or near each of the four corners of base 1130 and near filter 1500. Male protrusions 1136 mate with the female holes 1161 to form a snap-fit and secure base 1131 to cover 1130.

[00.35] Base 1131 further comprises a hub 1140. Hub 1140 is a five-way tube connector used to connect five tubes of the internal tubular circuitry. Preferably, three apertures 1137 are located near and surround three of the tubes leading into hub 1140. Hub 1140 acts as a centralized junction which can be used, in conjunction with compression actuators 1240-1247 (FIG. 22), to direct fluids through photopheresis kit 1000 and to and from the patient. In addition to hub 1140, appropriate tube connectors, such as T-connectors 1141 and Y-connector 1142, are used to obtain the desired flexible tubing pathways.
[0036] Five apertures 1137 are located on the floor of base 1130. Each aperture 1137 is surrounded by an aperture wall 1138 having slots 1139 for passing portions of the internal tubular circuitry therethrough. An elongated aperture 1157 is also provided on the floor of base 1131. Apertures 1137 are located on base 1131 to align with corresponding compression actuators 1243-1247 of deck 1200 (FIG. 22). Aperture 1157 is located on base 1131 to align with compression actuators 1240-1242 of deck 1200 (FIG. 22).
Each aperture 1137 is sized so that a single compression actuator 1243-1247 can extend therethrough.
Aperture 1157 is sized so that three compression actuators 1240-1242 can extend therethrough. Compression actuators 1240-1247 are used to close/occlude and open certain fluid passageways of the internal tubular circuitry in order to facilitate or prohibit fluid flow along a desired path. When it is desired to have a certain passageway open so that fluid can flow therethrough, the compression actuator 1240-1247 for that passageway is in a lowered position However, when it is desired to have a certain fluid passageway closed so that fluid can not flow therethrough, the appropriate compression actuator 1240-1247 is raised, extending the compression actuator 1240-1247 through aperture 1137 or 1157 and compressing a portion of the flexible tubular circuitry against bottom surface 1160 (FIG. 5) of cover 1130, thereby closing that passageway. Preferably, occlusion bars 1163 and 1173 (FIG. 5) are positioned on bottom surface 1160 to align with the compression actuators 1240-1247 so that the portion of flexible tubing being occluded is compressed against occlusion bar 1163 or 1173. Alternatively, the occlusion bar can be omitted or located on the compression actuators themselves.
[0037] It is preferable for cassette 1100 to have a unique identifier that can communicate with and relay information to permanent tower system 2000. The unique identifier is provided to ensure that the disposable photopheresis kit is compatible with the blood drive equipment into which it is being loaded, and that the photopheresis kit is capable of running the desired treatment process. The unique identifier can also be used as a means to ensure that the disposable photopheresis kit is of a certain brand name or make. In the illustrated example, the unique identifier is embodied as data card 1195 (FIG. 2) that is inserted into data card receiving port 2001 of permanent tower system 2000 (FIG. 17). Data card 1195 has both read and write capabilities and can store data relating to the treatment therapy performed for future analysis. The unique identifier can also take on a variety of forms, including, for example, a microchip that interacts with the blood drive equipment when the kit is loaded, a bar code, or a serial number.
[00381 Cover 1130 has data card holder 1134 for holding data card 1195 (FIG.
1). Data card holder 1134 comprises four elevated ridges in a segmented rectangular shape for receiving and holding data card 1195 to cassette 1100. Data card holder 1134 holds data card 1195 in place via a snap-fit (FIG. 2).
[00391 Referring now to FIGS. 1 and 4, the internal tubular circuitry of cassette 1100 will now be discussed. At least a portion of the internal tubular circuitry is preferably made of flexible plastic tubing that can be pinched shut by the exertion of pressure without compromising the hermetic integrity of the tube. Base 1131 of cassette 1100 is illustrated in FIG. 4 so that the internal tubular circuitry can be viewed. Inlet tubes 1107 and 1108 and outlet tube 1115 are provided for coupling cassette 1100 to centrifuge bowl 10 (FIG. 1).
More specifically, outlet tube 1115 is provide for delivering whole blood from cassette 1100 to centrifuge bowl 10, and inlet tubes 1107 and 1108 are respectively provide for returning a lower density blood components and higher density blood components to cassette 1100 for further routing through photopheresis kit 1000. The lower density blood components can include, for example, plasma, leukocytes, platelets, buffy coat, or any combination thereof.
The higher density components can include, for example, red blood cells.
Outlet tube 1117 and inlet tube 1112 fluidly couple cassette 1100 to irradiation chamber 700.
More specifically, outlet tube 1117 is provided for delivering an untreated lower density blood component, for example buffy coat, to irradiation chamber700 for exposure to photo energy, while inlet tube 1112 is provided for returning the treated lower density blood component to cassette 1100 for further routing.
10040] Inlet tube 1111 and outlet tube 1116 couple treatment bag 50 to cassette 1100. Outlet tube 1116 is provided to deliver an untreated low density blood component, for example buffy coat, to treatment bag 50. Outlet tube 1116 has hematocrit ("HCT") sensor 1125 operably connected thereto to monitor for the introduction of a high density blood component, such as red blood cells. HCT sensor 1125 is a photo sensor assembly and is operably coupled to a controller. HCT sensor 1125 sends a detection signal to the controller when red blood cells are detected in outlet tube 1116 and the controller will take the appropriate action. Inlet tube 1111 is provided to return the untreated low density blood component from treatment bag 50 to cassette 1100 for further routing. Inlet tubes 1109 and 1110 are respectively connected to a saline and anticoagulant storage bags (not shown) via spikes 1190 and 1191 and are provided for delivering saline and an anticoagulant fluid to cassette 1100 for further routing to the patient.
[0041] Inlet/Outlet tube 1113 and outlet tube 1118 couple plasma collection bag 50 to cassette 1100. More specifically, outlet tube 1118 delivers a blood component, such as plasma, to plasma collection bag 51. Inlet/Outlet tube 1113 can be used to either deliver red blood cells to plasma collection bag 51 from cassette 1100 or return the blood component(s) that build up in plasma collection bag 51 to cassette 1100 for further routing. Inlet tube 1106 and outlet tubes 1119 and 1114 are coupled to a patient. Specifically, outlet tube 1114 is provided to return treated blood, saline, untreated blood components, treated blood components, and other fluids back to the patient. Inlet tube 1106 is provided for delivering untreated whole blood (and a predetermined amount of an anticoagulant fluid) from the patient to cassette 1100 for routing and treatment within photopheresis kit 1000. Outlet tube 1119 is specifically provided for delivering an anticoagulant fluid to inlet tube 1106. It is preferable that all tubing is disposable medical grade sterile tubing.
Flexible plastic tubing is the most preferred.
[0042] Cassette 1100 has five pump tube loops 1120, 1121, 1122, 1123, and 1124 for driving blood fluids throughout cassette 1100 and photopheresis kit 1000. More specifically, pump tube loop 1121 loads into whole blood pump 1301 and respectively drives whole blood in and out of cassette 1100 via inlet tube 1106 and outlet tube 1115, passing through filter 1500 along the way. Pump loop tube 1120 loads into return pump 1302 and drives blood fluids through filter 1500 and back to the patient via outlet tube 1114. Pump loop tube 1122 loads into red blood cell pump 1305 and draws red blood cells from centrifuge bowl 10 and drives them into cassette 1100 via inlet line 1108. Pump loop tube 1123 loads into anticoagulant pump 1304 and drives an anticoagulant fluid into cassette 1100 via inlet tube 1124 and out of cassette 1100 to via outlet tube 1119, which connects with inlet tube 1106.
Pump loop tube 1124 loads into recirculation pump 1303 and drives blood fluids, such as plasma, through treatment bag 50 and irradiation chamber700 from cassette 1100.

[0043] Each of peristaltic pumps 1301-1305 are activated when necessary to perform the photopheresis treatment therapy according to an embodiment of the method of the present invention which is described below in relation to FIGS. 26-27. Peristaltic pumps 1301-1305 can be operated one at a time or in any combination. The pumps 1301-1305 work in conjunction with compression actuators 1240-1247 to direct fluids through desired pathways of photopheresis kit 1000. Apertures 1137 and 1157 are strategically located on base 1131 along the internal tubular circuitry to facilitate proper routing. Through the use of compression actuators 1240-1247, the fluids can be directed along any pathway or combination thereof.
1. The Filter Assembly [0044] Filter 1500, which is located within cassette 1100 as described above, is illustrated in detail in FIGS. 6-10. Referring first to FIGS. 6 and 7, filter 1500 is illustrated fully assembled. Filter 1500 comprises a filter housing 1501. Filter housing 1501 is preferably constructed of a transparent or translucent medical grade plastic. However, the invention is not so limited and filter housing 1501 can be constructed of any material that will not contaminate blood or other fluids that are flowing therethrough.
[0045] Filter housing 1501 has four fluid connection ports extruding therefrom, namely whole blood inlet port 1502, whole blood outlet port 1503, treated fluid inlet port 1504, and treated fluid outlet port 1505. Ports 1502-1505 are standard medical tubing connection ports that allow medical tubing to be fluidly connected thereto. Ports 1502-1505 respectively contain openings 1506, 1507, 1508 and 1509. Openings 1506, 1507, 1508 and 1509 extend through ports 1502, 1503, 1504 and 1505, forming fluid passageways into filter housing 1501 at the desired locations.
100461 Ports 1502, 1503, 1504 and 1505 are also used to secure filter 1500 within cassette 1100. In doing so, ports 1502, 1503, 1504 and 1505 can engage U-shaped fasteners 1135 of cassette 1100 (FIG. 3). Filter housing 1501 also has a protrusion 1510 extending the bottom surface of housing floor 1518. Protrusion 1510 fits into a guide hole of base 1131 of cassette 1100 (FIG. 3).
[0047] Referring now to FIG. 8, filter 1500 is illustrated in an exploded state. Filter housing 1501 is a two-piece assembly comprising roof 1511 and base 1512. Roof 1511 is connected to base 1512 by any means known in the art, such as ultrasonic welding, heat welding, applying an adhesive, or by designing roof 1511 and base 1512 so that a tight fit results between the two. While filter housing 1501 is illustrated as a two-piece assembly, filter housing 1501 can be either a single piece structure or a multi-piece assembly.
[0048] Base 1512 has chamber separation wall 1513 extending upward from a top surface of housing floor 1518 (FIG. 7). When base 1512 and roof 1511 are assembled, top surface 1515 of chamber separation wall 1513 contacts the bottom surface of roof 1511, forming two chambers within the filter housing, whole blood chamber 1516 and filter chamber 1517.
Fluid can not directly pass between whole blood chamber 1516 and filter chamber 1517.
[0049] Whole blood chamber 1516 is a substantially L-shaped chamber having floor 1514.
Whole blood chamber 1516 has a whole blood inlet hole 1519 and a whole blood outlet hole (not illustrated) in floor 1514. Whole blood inlet hole 1519 and the whole blood outlet hole are located at or near the ends of the substantially L-shaped whole blood chamber 1516.
Whole blood inlet hole 1519 forms a passageway with opening 1506 of inlet port 1502 so that a fluid can flow into whole blood chamber 1516. Similarly, the whole blood outlet hole (not illustrated) forms a passageway with opening 1507 of outlet port 1503 so that fluid can flow out of whole blood chamber 1516.
[0050] Filter chamber 1517 has floor 1520. Floor 1520 has elevated ridge 1521 extending upward therefrom. Elevated ridge 1521 is rectangular and forms a perimeter.
While elevated ridge 1521 is rectangular in the illustrated embodiment, elevated ridge 1521 can be any shape so long as it forms an enclosed perimeter. The height of elevated ridge 1521 is less than the height of chamber separation wall 1513. As such, when roof 1511 and base 1512 are assembled, space exists between the top of elevated ridge 1521 and the bottom surface of roof 1511. Elevated ridge 1521 and chamber separation wall 1513 form a trench 1524 there between.
[0051] In order to facilitate fluid flow through filter chamber 1517, floor 1520 of filter chamber 1517 has treated fluid inlet hole 1522 and treated fluid outlet hole 1523. Treated fluid inlet hole 1522 is located exterior of the perimeter formed by elevated ridge 1521 and forms a passageway with opening 1508 of inlet port 1504 so that a fluid can flow into filter chamber 1517 from outside filter housing 1501. Treated fluid outlet hole 1523 is located interior of the perimeter foimed by elevated ridge 1521 and forms a passageway with opening 1509 of outlet port 1505 so that a fluid can flow out of filter chamber 1517.
[0052] Filter 1500 further comprises filter element 1530. Filter element 1530 comprises frame 1531 having filter media 1532 positioned therein. Frame 1531 has a neck 1534 that forms a filter inlet hole 1533. Filter element 1530 is positioned in filter chamber 1517 so that frame 1531 fits into trench 1524 and neck 1534 surrounds treated blood inlet hole 1522.
Filter inlet hole 1533 is aligned with treated fluid inlet hole 1522 so that incoming fluid can freely flow through holes 1522 and 1533 into filter chamber 1517. Frame 1531 of filter element 1530 forms a hermetic fit with elevated ridge 1521. All fluid that enters filter chamber 1517 through holes 1522 and 1533 must pass through filter media 1532 in order to exit filter chamber 1517 via treated fluid outlet hole 1523. Filter media 1532 preferably has a pore size of approximately 200 microns. Filter media 1532 can be formed of woven mesh, such as woven polyester.
[00531 Filter chamber 1517 further comprises filter vent chamber 1540 within roof 1511.
Filter vent chamber 1540 has gas vent 1541 in the form of a hole (FIG. 9).
Because gas vent 1541 opens into filter vent chamber 1540 which in turn opens into filter chamber 1517, gases that build-up within filter chamber 1517 can escape through gas vent 1541.
Similarly, whole blood chamber 1516 comprises blood vent chamber 1542 within roof 1511. Blood vent chamber 1541 has gas vent 1543 in the form of a hole. Because gas vent 1543 opens into blood vent chamber 1542 which in turn opens into whole blood chamber 1517, gases that build-up in whole blood chamber 1516 can escape via gas vent 1543.
[00541 FIG. 10 is a top view of filter 1500 having pressure sensors 1550 and 1551 connected to gas vents 1541 and 1543. Pressure sensors 1550 and 1551 are preferably pressure transducers. Pressure sensor 1550 is connected to gas vent 1541 via vent tubing 1552. Vent tubing 1552 fits into gas vent 1541 so as to form a tight fit and seal.
Because gas vent 1541 opens into filter vent chamber 1540 which in turn opens into filter chamber 1517, the pressure in vent tubing 1552 is the same as in filter chamber 1517. By measuring the pressure in vent tubing 1552, pressure sensor 1550 also measures the pressure within filter chamber 1517. Similarly, pressure sensor 1551 is connected to gas vent 1543 via vent tubing 1553. Vent tubing 1553 fits into gas vent 1543 so as to form a tight fit and seal and pressure sensor 1551 measures the pressure within whole blood chamber 1516. Filter vent chamber 1540 and blood vent chamber 1542 extend through openings 1132 and 1133 of cassette 1100 when filter 1500 is positioned therein (FIG. 2). This allows the pressure within chambers 1516 and 1517 to be monitored while still protecting filter chamber 1500 and the fluid connections thereto.
[0055] Pressure sensors 1550 and 1551 are coupled to controller 1554, which is a properly programmed processor. Controller 1554 can be a main processor used to drive the entire system or can be a separate processor coupled to a main processor. Pressure sensors 1550 and 1551 produce electrical output signals representative of the pressure readings within chambers 1517 and 1516 respectively. Controller 1554 receives on a frequent Or continuous basis data representing the pressure within chambers 1516 and 1517. Controller 1554 is programmed with values representing desired pressures within chambers 1516 and 1517.
Controller 1554 continuously analyzes the pressure data it receives from pressure sensors 1550 and 1551 to determine whether the pressure readings are within a predetermined range from the desired pressure for chambers 1517 and 1516. Controller 1554 is also coupled to whole blood pump 1301 and return pump 1302. In response to the pressure data received from pressure sensors 1551 and 1550, controller 1554 is programmed to control the speed of whole blood pump 1301 and return pump 1302, thereby adjusting the flow rates through the pumps 1301 and 1301. Adjusting these flow rates in turn adjust the pressure within whole blood chambers 1516 and filter chamber 1517 respectively. It is in this way that the pressure within the lines drawing and returning blood to and from the patient is maintained at acceptable levels.
[0056] The functioning of filter 1500 during a photopheresis therapy session will now be discussed in relation to FIGS. 1, 6, and 10. While the functioning of filter 1500 will be described in detail with respect to drawing whole blood from a patient and returning a component of said whole blood back into the patient after it is treated, the invention is not so limited. Filter 1500 can be used in connection with almost any fluid, including red blood cells, white blood cells, buffy coat, plasma, or a combination thereof [00571 Whole blood pump 1601 draws whole blood from a patient who is connected to photopheresis kit 1000 via a needle connected to port 1193. The rotational speed of whole blood pump is set so that the pressure of the line drawing the whole blood from the patient is at an acceptable level. Upon being drawn from the patient, the whole blood passes into cassette 1100 via inlet tube 1106. Inlet tube 1106 is fluidly connected to inlet port 1502 of filter 1500. The whole blood passes through opening 1506 of inlet port 1502 and into ',-shaped whole blood chamber 1516. The whole blood enters chamber 1516 through inlet hole 1519 which is located on floor 1514. As more whole blood enters chamber 1516, the whole blood spills along floor 1514 until it reaches the whole blood outlet hole (not illustrated) at the other end of L-shaped whole blood chamber 1516. As discussed above, the whole blood outlet whole forms a passageway with opening 1507 of outlet port 1503. The whole blood that is within chamber 1516 flows across floor 1514, through the whole blood outlet hole, into outlet port 1503, and out of filter 1500 through opening 1507.

[0058] As the whole blood passes through whole blood chamber 1516, gases that are trapped in the whole blood escape. These gases collect in blood vent chamber 1542 and then escape via gas vent 1543. Pressure sensor 1551 continuously monitors the pressure within blood chamber 1516 through vent tube 1553 and transmits corresponding pressure data to controller 1554. Controller 1554 analyzes the received pressure data and if necessary adjusts the speed of whole blood pump 1301, thereby adjusting the flow rate and pressure within chamber 1516 and inlet tube 1106. Controller 1554 adjust the pump speed to ensure that the pressure is within the desired pressure range.
[0059] The whole blood then exits filter 1500 through outlet port 1503 and passes out of cassette 1100 via outlet tube 1115. The whole blood is then separated into components and/or treated as described in detail below. Before being returned to the patient, this treated fluid (i.e. treated blood or blood components) must be filtered. Untreated fluids such as red blood cells also must be filtered and will subjected to the below filtering process. The treated fluid is fed into filter chamber 1517 through opening 1508 of inlet port 1504.
Inlet port 1504 is fluidly connected to pump loop tube 1120. The treated fluid enters filter chamber 1517 through inlet hole 1522 and passes through filter inlet hole 1533 of filter element 1530. The treated fluid fills filter chamber 1517 until it spills over frame 1531 of filter element 1530, which is secured to elevated ridge 1521. The treated fluid passes through filter media 1532.
Filter media 1532 removes contaminants and other undesired materials from the treated fluid while at the same facilitating the release of trapped gases from the treated fluid. The treated fluid that passes through filter media 1532 gathers on floor 1520 of filter chamber 1517 within the perimeter formed by elevated ridge 1521. This treated fluid then passes into treated fluid outlet hole 1523 and out of filter 1500 through opening 1506 of outlet port 1502.
The treated fluid is then returned to the patient via outlet tube 1114, which is fluidly connected to outlet port 1502. The treated fluid is driven through filter chamber 1517 and outlet tube 1114 by return pump 1302.
[0060] Gases that are trapped in the treated fluid escape and collect in filter vent chamber 1540 as the treated fluid flows through filter chamber 1517. These gases then escape filter 1500 via gas vent 1541. Pressure sensor 1550 continuously monitors the pressure within filter chamber 1517 through vent tube 1552 and transmits corresponding pressure data to controller 1554. Controller 1554 analyzes the received pressure data and compares it to the desired pressure value and range. If necessary, controller 1554 adjusts the speed of return pump 1302, thereby adjusting the flow rate and pressure within chamber 1517 and outlet tube 1114.
B. Irradiation Chamber 10061) FIGS. 11-16 illustrate irradiation chamber700 of photopheresis kit 1000 in detail.
Referring first to Fig. 11, irradiation chamber700 is formed by joining two plates, a front and a back plate having a thickness of preferably about 0.06 in. to about 0.2 in., which are preferably comprised of a material ideally transparent to the wavelength of electromagnetic radiation. In the case of ultraviolet A radiation, polycarbonate has been found most preferred although other materials such as acrylic may be employed. Similarly, many known methods of bonding may be employed and need not be expanded on here.
[0062] The first plate 702 has a first surface 712 and a second surface 714.
In a preferred embodiment the first plate 702 has a first port 705 on a first surface 712, in fluid communications with the second surface 714. The second surface 714 of the first plate 702 has a raised boundary 726A defining an enclosure. The boundary 726A preferably extends substantially perpendicular from the second surface 714 (i.e. about 80-100 degrees).
Extending from the second surface 714 (preferably substantially perpendicularly) are raised partitions 720A. The boundary 726A surrounds the partitions 720A. One end of each partition 720A extends and contacts the boundary 726A.
[0063] The second plate 701 has a first surface 711 and a second surface 713.
In a preferred embodiment the second plate 701 preferably has a second port 730 on a first surface 711, in fluid communications with the second surface 713. The second surface 713 of the back plate 701 has a raised boundary 72613 defining an enclosure. The boundary 726B
preferably extends substantially perpendicular from the second surface 713 (i.e. about 80-100 degrees).
Extending from the second surface 713 (preferably substantially perpendicular) are raised partitions (720B). The boundary 726B surrounds the partitions 720B. One end of each partition 720A extends and contacts one side of boundary (726B).
[0064] The joining of the second surfaces of the first and second plates results in a fluid tight junction between boundaries 726A and 726B thereby forming boundary 726.
Partitions 720A
and 720B are also joined forming a fluid tight junction thereby forming partition 720. The boundary 726 forms an irradiation chamber700 and together with the partitions 720 provides a pathway 710 having channels 715 for conducting fluid. The pathway maybe serpentine, zig-zag, or dove-tailed. Currently preferred is a serpentine pathway.

[0065] With reference to FIG. 11 and 12, irradiation chamber700 comprises a serpentine pathway 710 for conducting patient fluid, such as buffy coat or white blood cells, from inlet port 705 to outlet port 730, i.e., the serpentine pathway 710 is in fluid communication with inlet port 705 of front plate 702 and outlet port 730 of back plate 701.
Patient fluid is supplied from cassette 1100 to inlet port 705 via outlet tube 1117. After photoactivation and passing through serpentine pathway 710, the treated patient fluid is returned to cassette 1100 via inlet tube 1112 (FIGS. 1 and 4). The patient fluid is driven by recirculation pump 1303.
Self-shielding effects of the cells is reduced while the cells are photoactivated by irradiation impinging upon both sides of irradiation chamber700. ' [0066] Figure 11 shows pin 740 and recess 735 which align the two plates of irradiation chamber prior to being joined together in a sealing arrangement by RF welding, heat impulse welding, solvent welding or adhesive bonding. Joining of the plates by adhesive bonding and RF welding is more preferred. Joining of the front and back plates by RF
welding is most preferred as the design of the raised partitions 720 and perimeter 725 minimizes flashing and allows for even application of RF energy. Locations of pin 740 and recess 735 may be inside serpentine pathway 710 or outside of serpentine pathway 710. Figure 2 also shows a view of an irradiation chamber with axis L. Rotation of chamber 700 180 degree about axis L gives the original configuration of the irradiation chamber. The irradiation chamber of the present invention has C2 symmetry about axis L.
[0067] Referring to FIGS. 11, 13, and 16, the leukocyte enriched blood, plasma, and priming solution are delivered through inlet port 705 of front plate 702 of irradiation chamber700 into channel 715. The channel 715 in the irradiation chamber700 is relatively "thin" (e.g. on the order of approximately 0.04" as distance between two plates) in order to present large surface area of leukocyte rich blood to irradiation and reduce the self-shielding effects encountered with lower surface area/volume ratios. The cross section shape of channel 715 is substantially rectangular (e.g. rectangular, rhomboidal or trapezoidal) which has as its long side the distance between partition 720 and the distance between the plates as its short side.
The shape of the cross section is designed for optimal irradiation of cells passing through channel 715. While a serpentine pathway 710 is preferred in order to avoid or minimize stagnant areas of flow, other arrangements are contemplated.
[0068] The irradiation chamber 700 allows efficient activation of photoactivatable agents by irradiation from a light array assembly, such as the PHOTOSETTEe's two banks of UVA
lamps (758) for activation (Figure 16). The irradiation plate and UVA light assembly (759) I
are designed to be used in a setting where edge 706 is oriented downward and edge 707 points upward. In this orientation, fluids entering input port 705 can exit from outlet port 730 with the aid of gravity. In the most preferred embodiment, irradiation of both sides of the irradiation chamber takes place concurrently while still permitting facile removal of the chamber. UVA light assembly 759 is located within UV chamber 750 of permanent tower system 2000 (FIGS. 17 and18).
[0069] The irradiation chamber's fluid pathway loops to form two or more channels in which the leukocyte-enriched blood is circulated during photoactivation by UVA
light. Preferably, irradiation chamber 700 has between 4 to 12 channels. More preferably, the irradiation chamber has 6 to 8 channels. Most preferably, the irradiation chamber has 8 channels.
[0070] Figure 14 shows cut-away views of the irradiation chamber. The channels 715 of serpentine pathway 710 are formed by the joining of raised partition 720 and perimeter 726 of the plates.
[0071] The irradiation chamber of the present invention can be made from a biocompatible material and can be sterilized by known methods such as heating, radiation exposure or treatment with ethylene oxide (ETO).
[00721 The method of irradiating cells using irradiation chamber 700 during extracorporeal treatment of cells with electromagnetic radiation (UVA) to be used in the treatment of a patient (such as to induce apoptosis in the cells and administer the cells into the patient) will now be discussed. Preferably the cells treated will be white cells.
[0073] In one embodiment of this method, a photoactivatable or photosensitive compound is first administered to at least a portion of the blood of a recipient prior to the extracorporeal treatment of the cells. The photoactivatable or photosensitive compound may be administered in vivo (e.g., orally or intravenously). The photosensitive compound, when administered in vivo may be administered orally, but also may be administered intravenously and/or by other conventional administration routes. The oral dosage of the photosensitive compound may be in the range of about 0.3 to about 0.7 mg/kg., more specifically, about 0.6 mg/kg.
[0074] When administered orally, the photosensitive compound may be administered at least about one hour prior to the photopheresis treatment and no more than about three hours prior to the photopheresis treatment. If administered intravenously, the times would be shorter.
Alternatively, the photosensitive compound may be administered prior to or contemporaneously with exposure to ultraviolet light. The photosensitive compound may be administered to whole blood or a fraction thereof provided that the target blood cells or blood components receive the photosensitive compound. A portion of the blood could first be processed using known methods to substantially remove the erythrocytes and the photoactive compound may then be administered to the resulting enriched leukocyte fraction. In one embodiment, the blood cells comprise white blood cells, specifically, T-cells.
[0075] The photoactivatable or photosensitive compound may, in the case of some psoralens, be capable of binding to nucleic acids upon activation by exposure to electromagnetic radiation of a prescribed spectrum, e.g., ultraviolet light.
[0076] Photoactive compounds may include, but are not limited to, compounds known as psoralens (or furocoumarins) as well as psoralen derivatives such as those described in, for example, U.S. Pat. No. 4,321,919 and U.S. Pat. No. 5,399,719. The photoactivatable or photosensitive compounds that may be used in accordance with, the present invention include, but are not limited to, psoralen and psoralen derivatives; 8-methoxypsoralen;
4,5'8-trimethylpsoralen; 5-methoxypsoralen; 4-methylpsoralen; 4,4-dimethylpsoralen;
4-5'-dimethylpsoralen; 4'-aminomethy1-4,5',8-trimethylpsoralen; 4'-hydroxymethy1-4,5',8-trimethylpsoralen; 4',8-methoxypsoralen; and a 4'-(omega-amino-2-oxa) alky1-4,5',8-trimethylpsoralen, including but not limited to 4'-(4-amino-2-oxa)buty1-4,5',8-trimethylpsoralen. In one embodiment, the photosensitive compound that may be used comprises the psoralen derivative, amotosalen (S-59) (Cerus, Corp., Concord, CA). See, e.g., U.S. Patent Nos. 6,552,286; 6,469,052; and 6,420,570. In another embodiment, the photosensitive compound that may be used in accordance with the invention comprises 8-methoxypsoralen.
[0077] Methoxsalen is a naturally occurring photoactive substance found in the seed of the Ammi majus (umbelliferae plant). It belongs to a class of compounds known as psoralens or furocoumarins. The chemical name is 9-methoxy-7H-furo[3,2-011-benzopyran-7-one. The formulation of the drug is a sterile liquid at a concentration of 20 mcg/mL in a 10 mL vial.
See http://www.therakos.com/TherakosUS/pdf/uvadexpi.pdf. Toxicology studies of extracorporeal photopheresis and different dosages of UVADEX and ultraviolet light in beagle dogs is located in the investigator's brochure.
[0078] Next, the portion of the subject's blood, recipient's blood, or the donor's blood to which the photoactive compound has been administered is treated by subjecting the portion of the blood to photopheresis using ultraviolet light. The photopheresis treatment may be carried out using long wavelength ultraviolet light (UVA) at a wavelength within the range of . , CA 02480570 2004-09-03 ::='. It. si4Y.:..?: II, ; : ' = . .i : ' . . . .. . .
. = . - . 0..1. =
.4 . =
:
'... *:ii.. 'f :.', ::....,:. -.11 . . = . P, .; = - i . . : , . = .
. =
= = = .
- = . .
..5. , :::t. ..}., ' .r = . ; ; ... . .
.
. . . .. = .=
. . , . . ..
: . ..
. . = . . . ,.'.... - ... -= i- ......, '.:',f...1.- .;:'' .4 .:: = ' =
= . .
, . = = = .. ....... : =
. .
. = . =
== IT. i .. ''..;= ":: = .= * tio 40013m. 3uch it rang'. . e is lint Ihniting, however, but is merelY prOvidett, as attexample. = = ' ' = - 1.. = . ' =:.=-:s . = , '.. =:1.: i'. ==== .-; = i.
The exposure to ultraviolet light during the photoPheresis treatment.maY
htv.e.a duration of ': = =;===, ' = ' ' :' ;: -1,:: ......t... ..0 = eaffieient length to deliver, for example, about 1-2 Ifcra2to the blood..
-, ....i.... i - .:, .:.. , = = === ..; = .
..
= . === = = = . .. =
... ..1' '; = .:',.= .1,- ==. 4007Sit. The photopheresis, step is carried out in vitro by installing irradiation t=bernbe.r 700 .
- v= ' :: =,.F . . = . ,.. = :
.:=...7.. i : = .. ':' :;::':=... into pliitnactivation chamber 730 of permanent tower system 2000 (keg... Ii= and 18),== In - " µ == = ,==
. , = .1. ',.*: . - = ==
one anhodimentõ when the photopheresis step is carried out in ..vitre, at leinfi fraction of the . . = ::: = == . ='...:3 =
==,,, ,"'''= -! ' ','= - treated blood is retained to the subject, recipient, or donor: The treated blood Or the treated ===== ===
:=:.'='= '= : ''' ..'' == -3.4.: -._.:: .,=: , .
=:= =!i,..: ',= . ==== :;
:nriched. leukocyte fraction (as the case may be) may then be adminiitered bick to the. = . = , = = . .===;,:µ: '= .:: .= =.' -'....-1:9 ==== i'.1-. === - 2 ===:! :', ==== = , = = , =
.......1.3'. t.!;: ..y. - 43-010crt4 recipient, or &Mot. ! = .
. ===,. = = ; = = =
40080 ' iillie= P. hotoPheriais process consists of three pluses including 1) the tiollection of a == . = . .. ' '1 .:
.......1:;.,....' x '.,,- ==: -, ֬ = -.., . .= =
blAffy-coat,fraciion (leukocyte-enriched), 2) irradiation of the collected jiiifficoat.itaction, = .... .. .. . ..=;:== ... . = :
=
4,4,== = ===.::=:: .. ==and $yteintbsion of the treated white blood cells. This Process will be discaµsed below in . .". = ': .... =
==
.. ...i: i = ,;...1 .:...iiceat.er!,,detill. Generally; whole blood is centrifisged and separated in C, .ittarlifiiiieboW1.10.; A ': == . = = .!:
==== - = .:..
õ . ....=
=,.., i..i., .......:1,i ..= '4otaiiotar.oproximately.240 rill. of buffi coat arid 300 mi of plasmeare Separi4ed and saved for..! = . = . . = =*. =,= ..= .
= :::
...-.: ..11=':i...':.=?'?= :1-- f..t,iitA fit' afilation, = ' = " . =
. ..
= = , = =
= . = .. = = = = = . .. =. .
= ===4'= i.::;µ,=;=e. '.= : = = = .> .
.. = .. , , . .. .
--....-1,= ,..i.:. '.7.= = ' =
100811 The :collected Plasma and buffy coat are Mixed with hepatinized. normal saline and = '. . . = ='' " i === ''':' !..:==,====4., !,....,;y.:1.1. = ==,..::- . . . , ..,...
. = ==! = = 4. = = =
: ='..4. '.4,1:i====='4 ==-=========='.-0/4.015Xtit. (water saluble8-inetholOpsoralin), This mixture flows in a 14 turn thick layer = . = . . ;
.: ==
= ==:,.....;.-1,......::,.. ; :,.=...;:. - ... .... =
.
'==='..:4:t ..1.- '=== ==== : =
through the irradiation Chamber of the present invention. The irradiation chamber 700, is ::. = ' .. = ' -..... 'P.c. :=== = =!; . ''. : ininited= in photoactivation chamber 150 of tower system 2000 between twethanks oftiVA :. ' .... ....:=:== *: ' : i ;
===t =.J.E=== ! = =.:=: = f.= = .: = == ... : '= =
..., 1::i:===1== = ==t= = = . lamislottlie=pliarosirrn (Ple. ..15). -PHOTOSETTE. I.NA lamps inndiate both Sides.... - . = .....',',=.' . .,' =====
:=., ;;=======:. . '.....z I.: : .. .. . .i . , :
= , . . .. = .
. . 7.= "c ; ==== ....;
of this irradiation chamber 700, periMIting exposure, to ultraviolet=Nlight, = . .. = = .. ;=== = .= = ., ;=:.;=, .'= . =.= ..i. ....yoidnig an average exposure per lymphocyte of 1-2 J/cm2. FolloWin4lhelibotoaetividort .. . = - == ,: ... = . .. ==
==='= :`,.' =='= :4; = iperiodi.thecolls are removed from the irradiation chamber 709. - :. : 1. . = = = . *., . = .1 = ''.....1.
,.., ... :
:=:; i',.....1.....:`& =;=.f.= = - "....., : .1. =,:.. %.
= .. = = , '===:' ==',:i ' :: ''=: == '10084 In preferred embodiment of the present invention the nion e ce are removed by the action = = ' . : == , ..; = ==
...'...44=!:'.n.i =,., ==='==== . =
. . . = . . . .
.' ij.:. :. =.# = === of irtivity and any cellirreinaining in chamber are displaced .front the cl:,.;mber With = . . , =
= = = . ..-'.. A.:. f.. : ',,' ..:',:t ===== : .=====additibnal'=fluid seleeted from the group consisting tisane, plasma, Old combinations .
.,_. .. = ..
:;" ''.(:),'.-.::::':' . .= =-=thereo.f . PerPah"enti Who, are Mull Such as children (e.g. under 30kg). Or patients whose = ' ....... - ' '. =*, µ' =!..t.='!.= ====.',..- :t.. ====== - ; õ.. = -_ , ..= .. el = _ :' 1 = !.' ==,!;:. .. = = ==== ;1.148001er System is easily overloaded with fluids the amount of additiOnal. 'filid used to was . = = = . =.:'. . , ::
' = . -;=;',.: . :1. ::: . .... =,= the irradiation chamber will preferably be not more than 25( the volume film chamber, = = = . = .= ' = . ., . =:, , .. .,E. r.. = ,.=..1.. .4, . ===. .: , = ; .
: = t" ''' ='= = = .= = oreferablynot=morethen 1X the volume of the chamber, more preferably dot more. thin 0.$1t = - = :: . : = . -....k.+:-..i,,..:i!. .g. -.... =,:,;'.-......,. = ... : = -"' .
die volume the chamber 0.25X the volume of the chamlier., the treated bells Volume is '. '.. . , .: ,. . ..... =
--.4,14=I'='[i ':-...';'.= == == ==;===
=====.' = = = = = ... =: .. ;
-',. f..i=== ','...'..r.:', '= : -.= i. - = = '. = .
, .. . . . , . = .
',...= .-õ, '......k.. "t =.' :.... = ! :. = ;
;
! 4.:$ =?.:=... ..,,: . .= = = ,.. õ. .., " . ;
7..- Ifi.'4:' =:?;' I ..'s- . === v . .= . = . = = = , . :. , ,, %. = t = = .. ' : = = . .
' ' ; 1: ::i: :i.' ' . .= = . .
. . :.. . , :
.. . .i = .. .." , :. : . ' .'''...7.; . :
''...T..,..i.. - : '''::
. . !
-' . E.i... i= .:5.- S; , ..: ' . = ' : * . .
= . :, . .... . .....*
. ....; ' " . ' ',. - '... .. '..: = . !.;:. '"- .::,.:
..':-. .
. .
. .
=

[0083] For a description of similar photopheresis systems and methods, see U.S. Patent Application No. 09/480,893. Also useful herein are the methods and systems described in U.S. Patent Nos. 5,951,509; 5,985,914; 5,984,887, 4,464,166; 4,428,744;
4,398,906;
4,321,919; PCT Publication Nos. WO 97/36634; and WO 97/36581.
[0084] The effective amount of light energy that is delivered to the biological fluids may be determined using the methods and systems described in U.S. Patent No.
6,219,584.
Indeed, the application of ECP to the various diseases described herein may require an adjustment of the amount of light energy to optimize the treatment process.
[0085] Furthermore, the photosensitizing agent used in the ECP process may be removed prior to returning the treated biological fluid to the patient. For example, Methoxsalen (UVADEXC) is utilized in the ECP process. Methoxsalen belong to a group of compounds known as psoralens The exposure to methoxsalen or other psoralens may cause undesirable effects on the subject, recipient, or donor such as phototoxicity or other toxic effects associated with psoralen and their decomposition products.
Therefore, the psoralen, psoralen derivatives, or psoralen decomposition products that may remain in the biological fluid may be removed after UV exposure. A process for the removal of psoralen biological fluids is described in U.S. Patent No 6,228,995.
C. Centrifuge Bowl [0086] In a specific embodiment, the present invention relates to methods and apparatus that separate fluid components, such as, for example, the components of a biological fluid by density or weight. Biological fluids encompass fluids that comprise, exist in, or are used in, or delivered to living organisms. Indeed, biological fluids may comprise bodily fluids and their components, such as blood cells, plasma, and other fluids that comprise biological components, including living organisms such us bacteria, cells, or other cellular components. Biological fluids may also comprise whole blood or specific whole blood components, including red blood cells, platelets, white blood cells, and precursor cells. In particular, it may be desirable to remove blood from a patient for treatment, such as for example, extracorporeal treatment. It is to be understood, however, that the present invention is DOCS'I OR 2046299 \ 1 . CA 02480570 2004-09-03 . ..... *.ii .?.. .
,:;..' . = .- = .
. . .. . : .. ...
= = ' 1 . = = = ¨ : ' , .1: = ===.- . :. ::.
....:1,...: = ..4. i== - ,^, = - ':' :' ' ' =
= . ' . - = 1. ' . .. . :" 7i=-'' ===.::"' z ;' ;.!;;i:i....= .. -=:".. . = ,== = : .
: =:;,...:== ,==== ==== = " .= , . .
. " . = . . .
.: = =
=
= = ' :.'? = =.='. , g = .7...
'=== f ; i ; :.t. : . . ..
. ,. .
'.===.= ,.......r..: A.; . . .
.
. ...= ,, =.= = .
=". i =,.4.'.. :=.':. = . ..
=
.. . .
. . . . = .. .
'===:f :1.'..!...s:i: = . adaptable to Use with various centrifugal processing apparatus, and the ipecittc exaMpla. = ' ===== ' .='= ==== . ======= s: ' ''' . ''....
./:..1,11-.' '.....= .'''.; = ...given herein is merely for illustrative Puiposes. Other uses for the SeparatioriAichniques= and . == = . == = .::: =
=== === , ====' = i --:.:: .1....,,.: = =i:....0 ....= =,. . 'giver*: may include. other Medical Processes Such as dialysis, chearta.therapy, Platelet = = * '. , . .
..!......* =:=.= .'...:
,.. = = = "
..:. i .....,.; ,..;:.... ===, .
separation and removal, and separation and removal of other specific cells .Additionally, the = . . ' ' .= 5..*:.... '. = ======
= .ii. i.'s?.. '''. presentOvention maybe used to separate oilier types of fluids that include a*ide Variety Of . : =.: . = = = :......- * ===
== ,.../..= ===.=: = r. , : . . . . _= = -:=Aoti-medical uses, such as, for example, oil and fluid coMponent.separatiou-,'All components,. == ...= '.... .. ''=== ....
=====:=:',...;='. '.= .;i . , . :. .. . .
: ¨ : , ==== - -"..=
used hills present invention should net adveisely affect biological fluids or rendei them. . : :,.... . . ..
.unsuitable for their intended such as those described herein and *
brimadeof any : . '. = = - .!., ==== . '...
- . ,. , ,.. . = . . , . !, . , ....= ,1*.... ' ..: = =:' = == suitable Material compatible with uses described, herein including, but not knitted to. plastics, ==
. = -= ..-- . ' :::
==....= I ==....: = ... == ., .
=== ...; = : ..: . .F. . .
= .= i?.. ==:. = ;-.:. .".=
:Suchl'ai polyc.arbonate,= methyl methacrylate, styrene.acrylordtrile;
acrylic, *rem,' = - = .=-= :".-. .'= = ... , == ,..1===; = ;?:. :."- ==.=.; = 1 =
. i = = _, L:
= .., - , = : =:=== . =acryloritrili or any other plastic. Where parts of the present invention are initlicated to be . : -- - ". = -. '...= === ' * =
::
= ' i '.1. = ...,. .=:.a =-=== . = = =
attached together and form a fluid tight seal any appropriate conventional Means eijoining : . = . = l= .... : == ..
' -'=-.'-1.....,-.... A. ..:... i -..
= =:. e. . = = = = = - = : =: .. . ' .
'...= : I ...i=-= .f.`,........:t! = ....the parts may be used including but MA limited to, adhesives,. ultrasonic welding or RE' = . , t'. .., = ==
....;
i=- :=F'.. 7.7.:;='.,...i.:=':= 1 - .: = .',11. = ' ", =: = =-= =
, .... = , . !
i.' :=': 'I.;4:':... ''..I.i.::.======ff:* :-. '::iiire41.11.41' . = .
. ' i. = = . = = , = ' ' :-...'..,'".;,: ''...; ====, #10.10.71.The present invention has several advantages (lifer centrifuges what use Conventional .'=.
. *. . ,.....F: . == :.= = ..
.., == .ii..... ,. , s . . , ' '' 4 = ...= ===
Latbant.bowl The Latliain bowl in the UV.Alt. XTe4 system has one inlet.part that illows = . ..: . . ::=== ' ..... = ..''.' ::.:: 11..?'= '== .2::, ;;..' = = ...who'. leiiilOod-M come into the bowl and one. outlet port thatallows plasma and. buffY ceat to= = . .
. ... .. .
. . . . .
= = =i =
= -......! ====== .':==== :: ..=Corne OUt.. Having ()saki two ports hints the volume of buffy coat that can be collected per " = . ...- = =
.. =
:.:-.:-."..i: f. =): :.'.. =:=,., ...-:',=.: :oyole...t4ch cycle:involves filling the bowl with whole blood; 2) 'hitting !Ilia bovirl tO . . = .. ..
. ,.... . .. ..
..:= ".;.:=.*: .:.1..i.. ;r... s...) ::...7:.:...seperiiie Whole=blood.into plasma, biFy coat, and red blood cells; 3) i011eet.ing huffY.=coat for = .
. ..:=,.. = : . '.:
=
= = = . . = = ..... . = =
*7 *.::.'1=:' '.***. ''''4* = : t teemtent, 4) bringing the bowl to rest, and 5) returning collected plasma *MI redblond.scells. , = .... - . .... .. =-= = .,.. ;t:
''''-:.::::::: 1:1..:....111 ='; - . =.:=:. = . ....... ........ ; . -. .....
.=:....;ii.1:"..,= ...:::::??, ..; .::===ThiS.b.uffy coat collection method may be clunacterized as being ".b.s*Iii#21a0 the volume = ' .. = ' =..
'''..... - . ., = :
' .': i : i ... = ...., ; = Of buffy Coat required for irradiation 'treatment can only be .collected after several cycles of ..'. . . .
. *... i; 15.: ===!1: .:;', .....
===.= .... .- .= ' = .,. . .
": '': =;:i ===,.., =...-. .',' ...: *.buffy!coat:collection: The limited volume of collected bUtry Coat per cyck$Iresalts:=.frOmilis . .= '. , . ..
===:... . - : ....
..'. 1, i =,:....'.' 4, =accumulated red blood cells remained inside the bowl, Thus thOticctiiroaferi red blood cells '' = .. '.',.:,2 . ..,::: ' . ...1 =
. , . .
=", :!. -,1.õ;==.: ==:. '.',.. = '... that Can only be einptiedat the end Of a huffy coat collection cycle is an intSrom limitation of ..= .- - .. = '... - =
s ..:
,,..4.ce: =-i...-, .....:!..,.tii!Lithern:Bowl- = . = :
. . . = . .
, . . .
. .
. = ... ..., .= . = .=
'.= .: 4:-....,:.,.,..... = = = = " : . =
D.! .'... .1. ;', .. .4. ...=:, . ... :7 . t00.80.- The bowl of the instant invention has three separate fluid Conduits that can be used. as . = .. = .
... =. '. . .i...
::.: : = ):''''''.i. *i .... = ..-..41 - W.'. . : = it and two=.Outlet ports.
The additional fluid conduits. allolya.foi.=i) reduce:Patient . = = '..= .
.. .. ...
= = .:' 41" = '= . ='.1 ; ' = = et P '=
,.: .. !fi,....! ' ....'= .;E.' ............. treatment time by having continuo* spinning during the entire but coat =ollection process = . ..r...
. ....
'.', -,...= .1.;:i......f.. ,i = .: withOut having to stop spinning the bowl for removal of accumulated: zed !iic,i4. cells, . .; 2) treat . . . : .... ==
:;.. = ...., : = ...'-'.
, 1"; ! = :..1.... ?.
= ' . - ., ., = = i.
:',.....:=,.:f i==== ..!;:. :i..., ......: , : small blood volume patients; by having collected red blood cells returned =o Patients = , . ., = , .
.... . . ..=
.=========== ii===;=;.'.....',:l i ... ...........co+uously, these patients may be more amenable to medical treatments requiring the use Of '== . '', .
i :. .......:
.r.i.:3-::. ::;= F. =
= , : . ' = . .
, =
27 ' . .
. , = - . ' :
. . . .
I..f ..f..1,..= = ...': 4 .
.. .= . . = . . .
. I. =
.., .1 = .. ..:. .. = .. :4... = :..., : -.':===
.
.. : = ',:s: i = == ' 1=:. . = ..
= .
. ' = = = = = 4 =
' : '. = ' = 4.
= ='= = . * - ' ' = '1***.' . '''.1r .-.=!....4'.1**,...:7.
=
' === == = ' === '.. .. = -- .."
*

. .
.1. ." = __ s if,.':==== =
= = = = ...;
:
= = . , .
.i .
= = = - = = === . = ..=
. .=
. . =
..".*:-:il, ''',.....?.: .:.i = . = .
. . = = = == : = = = ....7' = .....( '.! 4.1 '..7'.!;=4. .= .
, = 5. = :. :::! '..1 = , .
...
. =
..... I:. ; .,(.. .4:.... ... = õ . = . . .
. 40,,:.. 1. = .', . ;the buffY coat or freedom thereof such as extracorporeal photopheresisg= 3) belt* 'separation = . . . : .. =.;:. '... ".. . = ==:.;
=== ===== = =7! =====: t. =-= . === == õ : = . ===
, ..: .,:. ., =
;of different components of fractions of cells within the huffy =coat due to. the iiicreesed .. : = . =
:.1.:,. :::: ..:õ, = =-=
: . " = . . : . . = = ., . ..
, =,....... __ = -.6.
: === . = , : 4.= Spinning or rotation time and 4) the ability to separate high densitifted hlOcuieCells ,fiuctions = 3.: = = ====-= .r. = - , = , ==
........ ..1,...; ....,;.= .==.= = . frOm.whOle.blood. This centriftge bowl also provides the opportunity for reduced .. = = = . , = . ..,.
,. ...; . .. ,... ..,i ....lime for arty *medical procedure requiring huffy coat fractcmS to be =Colliicied'itoin patio* __ == __ . ., __ : . ' = = ".
=== -:=::-.= ;= =,== ;.- . = that are substantially flee of red blood 'cells, such as extra corporeal=phetopheitesis. .. . ==' . ...' '='. = . =
- '=
µ...e.'..?: ....'= =.' 1==
. '='. == = = ' . ' . . = 4.. ; ..
= ' : ..i . = ..... = .= 100891 . To achieve the objects in accordance with the purpose of the present inventiOn, as . .... == . =
.7' 4.. .::=,.. ':, . , ': .. , .. : .
µ.....1 '= ,:. . r '... anbodied and broadly describetherein, FIGS. 35 and .36 depict specific embodiments Of the . .= = . = . :!===== . ...
= .... !;..: .,.,....... =;....= ". = ..., = == = :
- = =
*.i...it = =='== __ . __ :.
present invention. 'The 'embodiment depicted in iIO. 3$ comprises a centritie bowl' 10A,' . = . ' l.: ' :' .:=
. ....
'......i! .. ' ''':. =s='''= = = conduit assembly 860A,=fra. me 910A and stationary restraint 918A. The ceritiifugebowl .10A __ = : __ :: = __ ' :.
= 1 'i:'... = ..===;. .,; '= is nil* communications With external conduit 20A of conduit assembly 840A. Lower __ ' , . = __ ='. = == = =
:.: '==!== ,- - __= . Sleeve end 832A (PO. 46) of cormecifen sleeve 500A. it secured to bowl 104. Upper sleeve .. . = . = = ==.= = ==
..=== -4=.'= ,':=== =.:.: =====:.= .= _:=== - = = . = --: =:',... ...,... .!. ", 'end 831A of connection =sleeve SOOA is secured to external conduit 20A,' connecting the . . . . == == . = '' . = = = :.
4:
: ..!,,.... ; ..-,...; :::: = . =IiitteMil, conduit 20A to bowl WA and providing fluid comaiunicatiOni.from!external Conduit .: = = "`..' = ' -. = . . = : . = . = -:.
õ...1...pi........,.,. .1.......
WA to irWi. 10A. The fluid communications enables fluid $00 to be supplied &tonsil' = .. . = .. = = =-. . e . , = =, = J
'...'..1.:.'?... ..:?: .:4 ... 'external conduit 20A. to the bowl 10A:, SimilarlY this fluid comnumiCiitioni also enables: . . : ' = = . '... - = : "' ., .µ ' ,!) :4'=';'..i'= ====='==. I === ..;=== ===== ==: ., =
= == ' . = ; = =
:i ====L:- .*:- = ;= :,'= - .. ====,Separat(id &lid components 810 and 820 =to be removed frorn bowl iim.lbroo external = = = . . .= . = = ' : '.
1", . .
= :::
;:. ==,=,....:.f,==õ1*. -,, CondOit 20A. = Bow110A and frame 910A are adapted to be rotated around csimer ails 11.A.= ' __ . __ .. .
.. . . . .. . .
, ..i.:=,ii...,; ..:=.=;,...! '...1009Ø1. iReferring to FM 36, bowl 104 comprises outer housing 10A,=ConnOction sleeve . == .. __ === __ ., ==== = __ '=
=
.: .:!=:..... '-. = :.!: '======.: ..': .= 500A, top core 200A, bottom core 201A, and housing floor 1.80A.. Outer honsing 100A May = . . =
::: = =:..
'..C.% ==='.:===':= = =====, .' === .. :== = =
...,..,:. : ..; . ,. be constructed of any suitable biocorroadble material as previously described for thepirPose : . = . , , = .,:i = . = =
=
.:1. ' - = = f ' Of the illustration in FIG 36 the outer housing 100A
is constructed Of Clear .iiastic so that . = ' " ..... = = . '...
:.; .-.=4=.i ...I. .1i: .: === _. . . = :..... , . =
.. =:==:i:..."';.:........-:=, '4 = ...l.cores 2604 ..and 2014 ere Visible there through. Outer housing 100A iS...atutOied to. aho:aging .. ". ' = f;
... .
.... .
: = = "! :". ;' = ===
floor 1804, which in turn comprises protrusions 150A for locking bOvd leAthtto a rotational .''' ". : `:.= ' '= '' :: ''======1 f =:=:::::.... = = device...'stio.h. as rotational device 900.k..
Bowl 10A is preferably siniplifled.04,Cons*uction and '; . . =:, . = . :
=== .. -.J., 1. '.. :, = ,= " = == . i.
===..-.4::,:==:. -= ==.= . ==.... = =
= ".., =*:== ==== . == ==". , :. iseaSY,te Mannikin:0 by Molding or Other known minufieturing.preeesiesilsUch that it may == = .. . '..f = = =
, .
, . === .1. si = = ::' . - be disposable or Used for a limited number it treatments, and. is Most preferably capable of : = .'= = ====== .=.- == =
;. = t...{..= ! ,, :". .;.= , . . .
..... . . ,, = .1 , . ; . .4. - .
: ===4,..!=== ,' =-= = : ' containing about 125 nil .ofilitid such fluid possibly being Presiurized.. In *lternative. = = ...
=
= .. = , . .
'r''.. =:',V.F.....i....,'=',:i ....,...embediments, the volume capacity of the bowl may vary depending upon the.. ''.,:= health of the.. , ...= .. == -= = . =
a' .
=
. . . .. ; __ I
igr.' il...:1; ..':i;: ...:::.'''' iiailept*land.bis or her¨allowahle extraco:
xporeal volume. The volume capaci*orthe=liowl = = . = ..: ."5-. .7 = -''..: ' ;.. -...'1 =.1 - .-...'. ..,:= .., ,=::
..... ...... ...!., = - == = == , , . ... = ...
: ...:t':0 .:'= '-ri ...' ...: may also Vary depodmg upon the use. of t,he bowl or the particular treatuvMt. 'i for whieh. the.
"=:. '''. ' ! = = :- '...ii :" :bowl is irtiliked... Additionally, to avoid contamination of biological fluids, . 4r exposure of .. . L.
' '.= ..,,i," .'..====?= ..:. :, . .=: iscsmia involved in, the; processing operation to the fluids, the transfer opeoritiMis are ..====:i- ff.';....!:; .1 .:=. ,'71 .: ...'.... = = 21 = =
. = .., , .- . .
. . =
. .., ',!:-.1:.::!'74.=;-. = ''. '. - ' I ; ' ' === . - .. .
=
-= = = ..
= . . . =., = ,;=,... .,.. .. ..==,:i.
....=;. ...ik == .::......."..: .. ' =: . = .: :: : . = ' = . .' = : . ' = .i ' . , =::-= I' i':...:..'=.......:=== =
...-..i. z.....,=:.....! .. I.. ..,..:...
. . = .. :. . = : ,..,,,, . ,.. =
.. .=, ....
. 1.: = ' = ' . .... .: .. :!'= : .= ..-; 'i.. ....' ..'.
:

..
::::.4:.;,...t."....'ii:: . .. .
i= . .
. = .4. . '=
!.:71.:1.:, '..,;i:====.!1:'= *:= .::: = = = ='= = : . :
= .
: .
. == = =
= . , . = 1 .. .
7 P.V. ',.:. 1. - '. ' =' .; , . .
=
, - = . = . V : - , ' ==:' A '.4.µ = ...i: -v . . . =
= =
:;,:=::=?.... :..:.....i 74 : .., . , .
=
.. .? -. . 1 .
. , ... =..=:=== . i...;. :' ....,: ''';'..
:preferably Carried out within a sealed flow system, possibly pressurized, Preferably formed of . = . i '.=== ' . .. .l.
.'i... ... =='...' .... = *I= = flexible plastic or similar Material Which can be disposed of after eacliuse .1: .. - . ' ' . : .' "...:. :: ==
=======
. 4.....,......... ....; . , .100911 AS is illustrated in FIGS. 36 and 37, the outer housing100A it substantially conical . . : , . = ','.. ...:......=
., ===I'''''i: 1 ===':.i. ' .====Ihavil.ng an upper housing end 110A; an outer housing Wall 120A and Slow4housimi end ... . .' . . .....õ, ' , = , ..., :: .f.?i=-=:=,.. ?e. , '. . = ' ., ' . : ' ::.19.0k . Outer housing 100A may be made of plastic .(such as those plastics listed previously), ' . ...'. = = . = =::
::: ..i.j =:L i.... ,..,:...:...., . ..., . .:i= ..., :E.., '...
. or any other suitable tutorial.. Upper housing end 110A has in outer surface 1101j, inner ''. .,....: ' =."
=41:1.21100 110C and housing outlet 700A providing a passage between said suifaces 'Preferably.
..= = ,':..=.. j.:. :,.. .=:::. . ;
the ***..housing will 'also. have a neck i ISA .formed about the housing.
trio, 700A. The = = . =
='. 4.f,s:',:.:-.... = ''':;': . =... - - .' -' = ' = ..,;,;'=' = .= = 1 .
,. .,i= .,: : : . ,,.. . .: housing Outlet 700A and neck 115A are sized to allow hadY ae .uhAer-= the connection sleeve . . ..-. . ., i =
f . -,* . .: '51i0A to pass through while retaining sleeve flange 790A, which extends from the body 830A
. .' '.... - . = ..
: !i ..'.: =:- !i: .
....: ,.. _ . .. . ..
.,. `.:.1.1-....!. .....,.:,...Z,. .. .: Of connection sleeve 500A. In one einbodiment of the present invention an O,-iirig 791A may . ... .
=, 1?ti.ii.1)04.344/1.
' .1i, i sleeve ,flatigt 790A and inner surface 110t sof.tlieg end 110A' ' ' . ..*':' ' ' ' '= ..:'.
...'..4o.eitairre: a fluid tight teal Is provided. In an alternative embodiment Oftheirreastit invention: ' ..= . 'ff. ... ......
:== ::.1:=:=. ..,.';======:',z -'. = . = : *, = :. : , = .
.=''... -'!"'===''' .:' "."' = ' illuttrited in FIG 53, a second sleeve flange 790B extends from the 830A of Connection . ' = '" . ' ... ..i: ,...:. -?. " i . = ....: . .: . . .
::"..1....', . ''.=:'. ,i;', =. ...õ.sleeve $0011:diatal to. the sleeve' flange 790A. Both sleeve flange.7popiii4 74.30n bong . ........... .
..'.S;r-i =:: = = : ': = . .:==:=, ..' . = = ' .-...'.";==.!...= =
'....., ...:: adapted. to sit within neck 115A and retain o-ring 791A th.elebetWeen, A fit,6 tight seal is.. . - , = . ':.... = . .. ....
, =:.-.. iV,.: t...'::5: .i ,... :, = .
= . =:' = = = . = .
provided ..4 === .; :== ="=;==== ? .= ,==== pded in this embodiment the 0-ring contacting body 830A and Inner 1.10C Of = .... ' = ' '';' = = ' ' ' =
....,...,..====4=....i.i... ...: - .....
. = . . ,. . = . = . 1.. = = =
' .: .1.=;.,; .. '.... = .
.... the 'housing end 110A adjacent to the neck 115A.
However, connection sleeve 500A- can be = == : ' ====== ' = .= ' 1'.=!'..1:.;.,i.'...i..t...--1.; ', =., seeurred.to bowl 10A :by any suitable Means, including for exaMple, alip, grleove, or tilt fit . , .. '..
.i.k.......,......;!.. ===_;;= = :=:. . = . = = : ,, ===" -A: ,== ' = ... ::Y.; == '. and adhesive with a component of kiwi 10A.
The outer housing wall joinslthe upper housing . ' . ' = ..= .:
-== i ''',.- ''.:, 1:i.g.: ===:., : = ==
=., = - = ' = .. = ! = . . ... -. =
: . . = = ... - = ...=;.:
.."..::. q.'==i...=.".'....'. .)..!. ...; ..::,. end .1.10A. and lower housing end 190A.. Lower housing end 190A is attached to a housing = . = .= . .i;.
. . ....,:..
floor 80A of greater dianietei. than Upper end 110A, Housing floor *Alii adapted to mate . ' .....:. .: ' ....:
. . :i. ,i': : .:====,=.: ''..?..
', j.:.with the lower housing end 190A and provide a fluid tight seal therewith. . Any conventional = ., ..= .=1 ' . ''.
.' 1.......; :: ;== .-..;. ' ; ... meatia.nierY be. used tr.) Securethe loWer housing end 190A to the hooting ie., Or 180A., = . . . ==== ,=. s, '. = =
..=..", ' ' .1......i : = . .'.' ".:
including but not limited to, adhesives, Ultrasonic welding or RP Welding, ,,.t..o, using .floor . = ' ' ... : .' ..' .,i.::...H., i .. e:,:. :=,.).':'' ',.. ' =
. , , ..: = = , = -=,.. 4.-: , = :=::, ...i.i : ...::: 180A may have, an. indentation 185A that is used to collect denser .fluid 01p, The di.imeter of : .. , 1., , ==
...., . " '" ..= ...= ''.;=. . = .:. outer housing 1.00A increases from tipper housing end 110i to lower housing end 196*, . .. = = c:. ====!
..:'...i ''.? ===:*: = , 00911 Outer housing 100A is adapted to rotatably connect to a rotational device 900 (FIG. .= = . = s.... :. .1,.....
= , , .
.. ===':'..: . :.. .',. . 35); Suchas for example a rotor driVe systeni or a rotating hnicket 910.= The rotatable : = =,i. ,... ":.... ':, . '.',,.... = , = ! . = .. . = , .. .,=.
, = ..: =
= =
... = = = connection may, for example, be a bearing that allews free rotation OfbovVi 104.. *Otter = = - .,. - ,..:
.,..;:..,::L'. : ; :4.= ......z. - .:==., . . = . .. =
:..-: -; ...,...... = i,, %. = ..housing 100A preferably has a locking mechanism. The loakinirneehani¨ ii.M' may be One or '. = . - = ' = =,, ...".
== = i.
:. ..=.;j'.,=:.:.....!!_'.. :.(.: ' = = -. : ' . = , =
= .' = = =.... ,t, . : moreprotrusions 150A, designed to Interact With corresponding it,idetitritioie in a Centrifuge, == . ...':1; = = * ======
..'=
= :-....1:',.',...=,.µ. =µ:, : . :. = .. ....= = : . =
,. :
. = =.= i....i.i, ,..';'.4, = =:: '1. ==== i.
, ::. ir.: ; i i '.µ - , ' =
'-' = = = = ...== . . .
. .. .
4...... .....=,. :%.... -= . . . .
.1 - . . . =
..

. .
: ====.=.:.',....:, ..,. , .1.. :.2., ...
; . . . . . . .
.,..'...,...i.rl.. ;.='.. 'A. .. = :: = .. = .
, : . . = = = ; .. . ' . : = :.,..i..
. . . õ . ,.. : ...-.
.
.õ .. .... .. .... , .
. . . . . . ..
' = '. =ii...: =..: !....== t. :: =:
' . *: . ... = . - ; . . .. . .
... .
.. ..... ..
=
" ' = = - =
...
. .:... . ,..,.
: '.:.fi,...:, .... ii= .1,.. ' ..- = . . .. .
. = . = . . .. = . . . ...
. . .
:. .. ..1 . . == .. . .: . .=......=
; .... , ... ..., , . .. . . . .
. ........y... ..,... .=:.?:: . ..... .. : .:
. : . 1 . .. .. ....

. .. CA 02480570 2004-09-03 ..f).=31.1.(,..=.. . . .. . .
,.-, :/..,5,.=-=... ....4... ,. = : . .. = .. . .. . .. . .. .
.. . 4 .. =
.:..4.,!...-......4 . =. -= . = = :
=
= = ..,:=.,.:== =1 ......
.. ,... 4,L ' i '. ====,;,.. -:,7 = = . ' =
='.1....,,P.J.7 =: '=7::-.==='i.". = =
= . = = =
:= ...., .''' ==== = -.. ' ' . ' s= ; ' '='? :: = 7=="..:
..=== V*.; ' .77.` -::. ' . . = = ' = = = . : = 1 = =-=1:: = = = . = = - =7 .
1 7....-, ',..=:=17== ==-;==
I. . '-! :== :':: .. ,1=.= , == . 06040ii* or any other suitable interconnect or locking mechanism or equivalent knoWn in the ' ' ,'.. . ' = ..*:: *.= ' =
''. '' ,= i',.:.=:':'=.=-=::'; : ====-= -= : = = = = ... === = .. ====":' =:': ===
=!.=
===== I '. = = : = . z:
it.r;, : The locking mechanism may also :comprise a key slot 160. (FIG 50: -= i = " = = ' : = . ' = .: .'" .= -= = = =,. .-.= :
...= =?;== '1. ::== '4 .. I0093)' Referring to FICi. 37; outer housing 1004 and the base Ii04.define .an interior =
====:'''== = :========= .'tr = ' : = = ' ' ' ' , . :
= I
. . i 1 ' . 7' = 'volume 710A in which Cores 2004 and 201A will fit when bow1104 is assgairibled. When = = ' .. y =
= ; 4=======;:" :==== t = .." := , ' 7 = = 7' = =
;.:i= ;:f....=:, ====== = .:r: .=:, fully assembled, corgi 1004 and 2014 are fully within interior volume110* of miter = ,.. : ,.... . : = ., ..,=.-.1*),i : ', housing 100*, occupying a coaxial volume of interior volume 7104 about ails 114. , = ' , = ' -- ..= . .:
:s.' iii.,=':.===== = ., := : =-= = : = .
= = .,1 ===*. . ,:: .i. ..*=.100941.4eferring t,o. FIGS 38, 40 and. 44, the top core 2004 arid 'bottorn core2014 , are .
= .
' 4 , s , .::. *.;i. .. . , = = = = = = = = t- . .. ....:
. - :.!:='... * = ,: Is. s . .iibitentially conical and respectively haveupper core ands 1054,,206*; onto r. core walla = .= ='. .=µ=:.. = = = !
..= .. .. = = = . , . .. = ..
=
.::'s -.: ..::. ..;. ' 21044 1114.; and lower core ends 2954, 1964. The cores 2004,1014 occupy coaxial = .... = - . . =
.- .1.= !.:.:=: - 7 = " =
..-: Ill '',,'= ===?: '=
volumes of interior volume 710.4 of bOw1104 and firming separation.'yOlunire1204between = "7'. :== " .= =='===
''= I' ' - =-!.....:-.1 = ;pipit ft:m.1206A and Wier wall 2104 Of ton core 2004 and outer...Wall 211.4 =and. low* core. = = . . .. .
========1". :f= = ==== i'= . = l=end 1964 of bottom core 201* and outer housing 1004. Separation volume 220*. is that =
= - ' -1. ..* ''' - =':
". i .1. ====:. '':',:.i ::* = .=
' ' =.= .= = . . = = . = . . .. -= :7 . ' .
== i .;'.7"' f.'= :1: = i apace of interior volume 7104 that is between cores1004 and 201* and 'Oilier hene018 Um& .
:.=!...:1"::.''.= ====i: .1.......1.,, (009J As in Figures 40 and 41 top Core 2004 Comprises upper 004 end 2054 sand a . = . . .= = "=
:...44,1== .:Y A ..1,-.= ..,,.. -... = = =
. . ; i..
........1:,i....,;, :.',10Wei,r 0Ora end 1954 that are joined by outer core wall 1104. The miter to. i* wall 2104 1...*:,======'======.N. : == = " * == =:' =
..: = - , = :i. =
=''= ..7.....:; .= ' -t: ..
having an outer suttee 21011 and inner wall surface 210C and a lniferedge;10D.
The . . = === ,.= =': '. '.."..
i:-=!=-'z' 1 *= ==.: ''..= ' ==== = = -' = ====' ' - = = .., = i -; ........i. =i. ... ====,, diameter = of top core 200* preferably increases from upper core end 205* td lower Core and *.= ....; ... . . :,...:.. . == =.-..
- = d... 1.'' ': ' '''' 7 29544-. Upper core end 2054 also comprises an outer surface 2050 and in inner surface =
- =.
.!= 11;=.i..".::==::. ,=:, =:. 40,1=5......, Centrally located about center;
axis and extending perpenditailarly=fiiiim the upper , = .: =. = i .'.
,. = . :
= , õ
.....1 : =
=,:-::.t ;:..==..;:.c:. =:?.... i -kniface,205Bit lumen connector 4514. Lumen connector 4814 his= it!top sti:rfacoe 4524 and . ... . = . . ... .. .:
- - =-...41.. = = E . = =
n wall:._ .. =:=7 ..;.; .7 i=====.'=. = ==., .' =47t,1 .... 'aUrce 402*li Tap surface 4824 has two passages 303B and 315D that provide fluid ' = == .
:..'= '= , = = ..:
:i=:..2=.i);t:==,===?.=.::.i4. :, .=:. = .....: = i .. .., . :
.
:;:"..; ..:..("aminimications tbrough the upper core end 2054 with second bowl chatine-1:4104 and first == . === = .. -= =======...: :=.q, t.. ::'.. 4. :',! '= ,. = ' .= = .=,= ' = = . = ., .
= =,1=:.:1,,,:....6........, . = ..:howj Channel 4204 resPectively. Second bowl channel 4104 is a conguitti:tat,has 'a conduit' .= ,. = .= . . 5-....., =
.......= .,....
:=-_,*.i.-= =='E.: t==,,.!=-= =-= = - =-= = ' -.=.- =
=====:: ii =,=:' =-= If = ...wilt 3154 that extends' perpendicsular1y from the inner surface 481C of lini4n connector' = = = 7 = . .-: .. .. ..
..*:...5...), ...="...7==:====Fr ",==== '= '= = = "" = ===
= = = = . . = . = ",., = . = , . .
481it= = ===== : =
. ;
= . =
:.==.ii.=..i.., =;=:=......f00961. As Shown on FIGS. 39B, 394 and 40; second bowl chimne1410.1iollusid.: =
. .
. . .
= =-: ;*. 'LI:, =,.::... = .:
communication with conduit channel 7604 through conduit 3114having e first end 311B = = _ = -.:. õ, . ..=
: .1 ..1.:=== .. = -, : = . .
,,.;:====4=1-;': ..;; ==='=:".= = : ':. and atiecond end 311C that is adapted to fit into passage 325D oflumen crnlatector 6514. In= . = = ,, =..:. ,.: == .
' === l'''"==!... :4=-= :=''' '' == ' .:== ' = ''' . .
= ' = . = = = == = ncl ' 20A=hris Ijuid=
./Xinunic'' *don wi= di. briwt = = ... = : .:=== = :". ======
= = -1 *,..1= . -i =.:== ,-.:,..,0eration cendua chimpel 760,4 of extetnal co tut .
= =====.= '.;o=
=====: ==si... . - = .1 :=.::...,41.==.9.......==:. .y ...:== : =.chainiel, 4104, First. bowl. channel 4204 is a second. conduit that nas a channel Willi 40!.k. . . ' ..::. . , ......
''''''''. VI ::'...i- . s::: '' ''. ===== that extends substantially perpendicularly from inner surface 451C of.theliimen connector == - '.....''' = '... . .. = ==
= ==='4.1==....==,..:'.1!.. ":=' ,==='. =;. =,, == . , = . . . = -. . ..
= =
==== .1: = i== ==' ...:i = = ,.= 4314. =As shown in FIGS.' 394,.39131and 40, first bowl channel 420* has fluid. .= , ' =
= :".-= =:, = :=.:==..,r-= :=;4 = ,-= ." = = = =
.'.- .,==== = 2 ....... = -...= ''. =====...conununication with conduit channel 780* Of external conduit 104,..-t*CuOholloW cylinder , = , = =-7:
..-.; ., . .: =
;......,...r?..n.,== ..F.,, µ;; .. : = . , == =. =
=:::=õ:1..====,., ....iõ ....1 : . .:z - ..: . , , 30 , . ..
.: = 7 . fr: '' = -.= ;4 = -=.' = :-. =
.: -. 7 ' = .. . . . =' , . . : ==
- ===== I ' ' = 1 - S.
. = .i. .",'"
- :;:,' =; . .1.' = i::, : n= = '7.7; '.
"' .. = - ' = - I ' ' .
. .
... . . = . = . = = .
=
.
. .
. = = . = = =
= .
=
. = = 4; =-= : i . '.. = = . . . = - =
= .===,..'..=====. .r.... = ,.-.:::::.',-,.....
. .
==== + r-= ....:,; = ;... :: = ' = ' .. .= = `.. , S. = - , =i . . ' = . ; .... -.1. %.:: =
.. = ,.. ... , ' : . ..: 'i=-: , =====:!:=.-:

d.
s "
1 . . .
i = ..
.... 'If i!-= :.'"i= .::, . " ... , `; ' ; =
= . . . -. - 4,.. , .. .t"1.4.. 4 .
= = = = - ' = ' '',:..t.:;,..1.-:.;.fl'= 41. .
, . . .i: .. . =:' !
.. ''1. ,:q ....:' ''';', = ' - . = ' " = . ' .. =,;= ....' . : . ': .. 322A haying a first end 32211 and a second end 322C
adapted to fit 'openingf303114op sitifice,' ' ' - == :....= . : . ==..'..
= 4. = '.... =:, . .- = = - . === ' =
.
......,.... ..f. .i: .' = 4814; ' Ai is illustrated in one embodiment of the present Invention, seeiM4bira.tehannil ' .= = == *".. ... - =-r=
. - = .. -. , -.n 410A is disposed within first bowl channel 420A. In an alternative etitbodintent of the = = ' . ... . . =
, ..... . . =
== ..i.:!. = .1:= .:; , .. ..= ;
= - . , .. .,. . . . .. .. . . ., .2,preStatt invention illustrated in FIG. $3, conduit wall 325A may be c4r#io' Siiii¨of upper : part : . ...' ' 'I:. = = '...' .....=
...,..f.12:51rOl1ower part 328G and be fuSed with channel walls 401Aand 402,A;
. '.' . ' . . ' *.; . = *: == ' = := ====
. = .f.i= ? .1. .:,.. . porn. Top surface 482A also has indentation 483A which provides fluid ciiinnuinicatiena = = , . = . ... ' . -.........1.,' ',,-== . ,=. =.?..:. = == = . .. ' = .
- ' -=
-..t.., . =;= = = ..With chamber 740A. ' When assembled,. chamber 740A is defined bylUMen,ineurging. :recess . ''. = . . ='..i. . : ' =`.
.... ..!.. .; 1.-. ,.= - = . = = =
.....v::::. ... '..,= . .... 881A less the volumes occupied by hollow cylinders 321A, and .322A in the connection = ' = ' ; :. == = = ='=
.: lq....;=: 'sr.' = ====_ = === =
':. ===4 *. ' .==.=- = 'i ' junction of connection sleeve 590A and lumen connector 481A. ' Chaitiberi,40A
has 'fluid ' = ..... = .= .=
7 X. ; .7.. .i: .= = . , ": = ===
-'. i *, : =
1 :::.1 :::::..=, ::::.. ''.i. . o.3iiir4unidittion With conduit channel. 770A
and With separation volume 220* , . 1 ... ,... ..; , ....:
=,118A..tiffeugh indentation 483A. Thus indentation 483A forms a passageway for the rensivat, '.' . = ' = ::.: = ..... :. .....
', 1 : ;.....1z,= ..'...... ' :: ,.. : .
- .i. : ., === : ... ; of second separated fluid component1120 through bowl chamber 740A.. Optionally Present , .= ".'. ==
...,.'..f,i= , õI:4.. ..il - .
on the miter. surface' 20$11 are a plurality of space's, 207A which extend:frOii, the onter surface . . .. .-.....' .. = = : ; :.' =
...i. ... .....= ., . ; , and :contact the unix surface =110C or the upper housing end 110A to ensure fluid = .
. . . ..
; =
.
.... ...;===::!,.. ..-õ, , ..... =
communications between the separation volume 220A. and the passageway rafted by the s , = . = , . .=
=
..t; . =
. =;,..i. : =====i= .:===,:. = - == :: . .
==..-.'i.4.'=-?.?..,1; ,':=-= : intientationa483*.:.
: .
, ?....4.f.==;;:=;,''.;' =;,,,= . ======,:. = =. = .,. = , : = .
; ': =''', ;= -:'===== =i= . --: 100911Inan alternative. embodiment.
illisnated in FIGS, 53,54 and 55,,Ceridizita321i. and = = ====.= , = = . =
t ,-= === ='.
= P "ra :. :.";;!:::..4 = = '7'2. :.; .',.. = , ===
:: 31....,.. ..';;.. ,I........::: 322k. may be affixed to openings 3281) and 3030 in the top. surface 482A cif the hinten = .= .. ..,... .... ..
=;..., ..,.. ....= = .-:' ..= .... connector 481A. Additionally' 'indentations 483A may form a plurality channels an the 'Witten . =
' .... 1. '=,.. .......P :.;.' .. ; .., = ' .==== = = = =
. = == . = ' = = =
=:;===1 ' .== ' 'õI',..;":::: . :.::,:=connector-481A and*, adapted to form chamber 74011 when connectedta:'connection Sleet,* = .. ;,.. . =-. = .:
. ..i...- " = = ',:- :== .= socik or =5000, Chamber 7400 is adapted to have one or more surfaces 742A. that can mate ' = ' = . ; :õ.. = = = ...
:: ..).'....., . ,. s':i...., = ;====.; ,., ,. . , .:. . r , = ; .:5,- ' .. = , with.ilie male end 8004 of the connection sleeve soo.A. (male end sis.,A. sail' ... 'uncli end 801 Of =
=== ii...i. : = ='',., .. .. ..., ...
..: . .. . .. .. .. . ,.
; x = :; - .'). = , 'external conduit 20A). To facilitate the correct orientation of the cotinecti4ii sleoic800A.to ' = = = = 5'. = = = = = '' ' - ';':.;=:,i = .S. .3 ....= '.. . =.' - ' . = ,..
= , theliMeti -connector 4814 the shape of the male end 883A and :chamber 7400 may be = '. = . . :=:.. === . ::
:: : = .:,.1-.. y= = :.::. '1' . '.... :. ... = .... =!.= =
= = =
= , "t=f. :=:.. -;),. = '..,. nonmeminetriral or as is illustrated iti FIGS
53, 54 and 55 a guide 855Ain4 hiprovi. tied' =====1"!...??======'.;- .:'. .= 1 = = = = = . ==.. .
.1,0i)elt extends from the top surface of thelumen'connector 481A and is adapted to fr.k.within= ..
.. ;.:: i:. t : ..r.i.: ..r.: = :* - == .. ' ...._ = . .= = = ' . 1.
, = ...., === .......
1.1:: ;0%.', I, :.>.;;:=I= . .: ....!;.: opining 857A brthe.aleeve flange 790A. ' . = = ...
.
. .. .=
, . .,. . ..
[own Referring back to figures. 40, the lower core end 295A.cOmpriliain upper plate 2.99AL
lizivi*g a top SurfaceipsA, a bottom staface. 297A, and an edge 2991 thatititadvii and makes is . . ''; = ' ...: ' .: . =1== ....! ...[...:''' . : .:
direct contact with Irriver edge 210D of the outer core wall 210A; The .failde 2990 of the '' == = = ::: .'.. = : ..,..:.
- 4:-.1. = :: -, - ='. = =
' =.' = = ,! - ' = = =
=='' :"1..z. ' ''... ''.' ' = ' upper plate1299A is adapted to be jciitied with lower edge 2/01) of outer ; re wall 218A and , ':=-=.=it ; ,.;.=.=. :, 1. . .......: ...=
= ,., ; = : . . . .
====:- ,.3:.'7,1 ....`;::, . I.' : .:; fornietuid tight Seat. therewith.
ittending perp' endicularlY fiont the tep', . = ;=== ; : 29M of ' . . ':=:- : = '.: =,.
='.. ===..: '=-: '.::; :...! ' .:=. =
'':. :; ' ....__z=traw ...1 '..: '.i i . =,..` =si=
i: = upPer plate 299A is =a channel wall 402A, having an upper end isanitalewer end 402C : ...:, s . =.;,..= -,=
.:...it., ==;.:.!1 .'...'== -..=i ... = : =
-;.
-.: it. ===..! :f..= ..!== == . = ...= = .
. . = sr .' =,. .. == = =
.. = == . ... = =
=-. . - .= = p -...t. .f... .: :: . . .
- =:1.......= .:.. ),.., :. : = = = ' = = . ..
= = = - = .:
A =
. . .
.. = . . := :1 =
= :

. , ..
...=.4:'.1... ..,.; ===.J ,. i. =
. i . = : = = = . . == = = i . = , . . .
''.=-=I'.-=,Y.',..!;.= ' ''...- = ===. . . .= .
. .. . = i . . .. . ....... .. = ,. , ..
=,; .t., . . ==; = ':: = t == - = .
==
w ...., : t= ....-.....;
: .... . . z = .-..........*
.t.,.... ==;- ===.-.. ==.;;:,; . . .
= . = . .1- = , . . . . .
===== . .i...:1:.ii'... '..F. , : . : . . , . .
. . ; .
= , .
= = r ==== -:== .. = .-1=.'==. : ='= = :\ i . == === = . , and surrounds opening 3034 which is substantially in the center of upper Oats 2994 A ,= . ' = . = ===:.. . = ..' "
: 41.1- 1.: ,=,:' ==' =nuMber of:fins 403A, attached to the outside surface of channel wall 402A and top Suffice -= == - 't == ' '. =
= .:. 0..2.,==== .:.:: .; = :,= ===. :. ... .
......,.4.; i.....!õ..;:j. ..: .,,, 29$4,= supports lumen Wall 402A, The channel *all 402A is adapted to mate with channel. = === . , , = = .. ,=..:
: = ... = : ;.
:= ,..?...::!..= ':;-=;.... ===E; = . = ; I :. 'well 401A fbrming a hind light seal" and providing lumen 400A. 'First boy:l= channel 420A is .. ====== =,:,; ''.. = :.:
=
..,''... t...f.: ,':. - ': : = hi fiiiii. co4minum.' .
'cations with conduit channel 780A of external conduit 24=throigh=conduit: ...
.''. ' ' = t''', ' ' === ;:s.' ,...",:i= 1.: ''.. ..:; : .. '. . = , ... . =
= , =,..= ,.õ :. .: ==:.
: 3224 Opening 303A provides fluid communications from lumen 4004=fo separation :=. ; = = = = " . =
======.i.;'..-= ==.!. =,. : - . - -___ ..: = - -...... .1 '.=:==". ',:. = ''.I .õ :
volume 220A as Will: be further discnssed. First bowl channel 420i.alSO=4tionnds 'second = . = = . .:.1... . . ::.
,== it :. : = :::i., .,:i =.: =..., =
..,.. : :, = . . õ
- ,!=,=...V7.:. = ',.: 1 = ..=.:=======boiskehanne1 410A. . : i : =
.
,"....'....:::=:J= ..4....::.' =.:: = = =,, =.; .. = .
1001001 _ . .. . . . ,= .
...= .':' :: ...= '' =;=1 = ; :
" = Referring to Figures 43A, 438 and 44, bottom cOns 201A comprises an upper.= : ' .== '!..... , = : = = ':
=:;; .t.i= ai :';!:-..= i,:== ' =i =, : = = =" =
1' "=== . = = f= = = "==
core end 206A, a Outer core wall 211A and a lower core end 296*. The outer tete *all . .:: : = = . ,..:J.; .= == :
..'.,=,,..k.l. : 't`= ==='. ,, , - 2114 having an outer surface 211D, an inner wall 211C and lower edge 2i1D. The diameter , . ..." -= :'=.='= . -===::
. i, =======. ::=-=::, -..=:: , = =!..= == ==
= .: ji= = ) ==.'= ... ' . =.=
of bottom coin 201A preferably increases from upper core end 206A tp lower core and 296A . ' = = ?,' = :'===
: r f..i...:... J.:,.....,=. ; s = ."
. ....! , = :
.BOttom,Onie=201A also has atop surface 309A and. a bottom surface 30,911; ..
Top surface ... . :" . . ..i.*. . .., .=,.
: .: i= = : ...= .:,. .-s. 3094 has an indentation 186A (preferably generally circular) substantial in-the center of the. . ' s'.. = = = :
:. ''''''.1'4, = ',..".:: ".. = :'= surface 309A of the upper core end 206A, The indentation 186A has in upper surface 186R. : . : . : =:,=:==.=. : = = ..
':
'.:'..4.=:..:=7:=:::,. " = = .= .=
: ''....'= =:=, = "
and in inner surface 1.86C, The upper surface 186D. of the indentitiOn .14A
has therein an. : , ' = ==*.! . =;7.=
*:. :.= ti.,... ::: ....:. , ......... .
opening 32413 which extends through to the inner surfaCe.186C.= in an :alternative . = = ;; . = ,õ " -.
..i.,...;=== : = ,:i. = == . = = : = = =
: .õ ,:.i ::: :o. r. = = , =,.
. = = = = . f .= ..
...4.= .'.; i ; ., '.
embodiment of the Present invention illustrated in FIG 53, the upper"
=surthce:18613, may also . = . . = :... : ., . !
::.,. 4.4: ." ..z.:-.- " .. = - = == '= ' =
= ========== = . '" ==== : ' ... have a recess al8613:
adapted to receive an oqing and form a fluid tyPestil !retied the lower = =
==== !: = = = . : ======
'....: i -:.:=====.= =='.':. .17 , ' ..., = . t. .: = ' =
, s::: .1..'il. = ==== :-... - = ''= =
and of 325D of conduit wilt 325A. 'Extending perpcndionlarlyfroMinnerface'186C
. = ' ' ' ' . = = ..i.: ' == =.:
', : = = ' ; = ..1... : i' 7. = : ..;:. = I r.; = .
: . : ' : = . '= = = ' . . ..
':-..: :1'..i1J:.*::;::õ.f:. =.' ==== i *build said opening 324D is conduit wall 324A havinga distal end 324 DdiOn the top 'surface .= === = .; :.. .....=
* =:....
-.,3...i . :i- .4 . =.=.... .. = = =
= - . . -4-- ' ::t === : .; 's :' . 309A extending fibriiihe indentation 186A to the outer surface 211D of the outer core wall ..= = - .",: .= = : : '. = '-.
......::::1.2. , =;:. ====!.. .. ====
= = . = . = , = ===== . " = ..
..,'... i: '...14,.3 .. ...,..= 211A are ene or more channels 305A. The top sure 309A maybe liC4ntel= or slope ' = . = ' : = = . '?... ==== = : =====i=
========= ====.t - ====n::'= : ==='= :==== .: Upward. or downward front indentation 186A.. If top surface 309A slopes upward or = .. = = .. = :
?' == = ====..
: .;:ti's.e;:. ..,='= 1.i; == ...= = ==. . .: = , .
: ..: ='' ' ' ...-= *====== . ''= ;
downward from indentation 186A to gore end 206A, one Skilled in theart,isloald be able to :'='-'===.== ..1.===:=== = =;.:::f:' == ...= .'====
== == = . . = .. , . =.! ' =
- ...I === ' r. :?' ''' === = adjust the shapes oftipper plate 299A and upper core end 295A accOrdingly. Channels -305A == :. -.; :i .. :
..... = = ... . . . . .
may have an even depth through out the length of the channel 308Ail: However, channel = . . ... .
-= ,...;:,...:=.!.,=.:;. -,...k = = :-.... =. == : ...
.= ,===4,...:, .. ..,:, .....:.: . ,õ *A may.slope downward or upward radially from the center; 00 :skilled in the art would = . .: . = '.
.:'= =='.-;:=::i.....4 t: . i' ':', ..: = = '' = . .
.. =: .1"-:: ...i ::: , : : . see that if top surf:400'309A slopes upward or downward and Channel 305A his a constant .; ,...=.:1:: ..,..,,:==
=:',..:, .,.....= = = .: ...., = = - . =
=, - = ='. : 1 '='.=-i =: '''. = = '= '.. :: = .. = = dip*, then channel. 303,A =
slopes upward or downward accordhtgly, : . = J. : = = . . = . :: .
.. .
: ; l', 'VI:: :!µ..:t...*. ':. = . .= ..
, : t , . .
'.
:,.. ......C.- = ''== '...= '...".= . 106104 = .
Referring to Figures; 38, the bottom surface 297A297Aof .''lipperiplate 299A is in. = . ... ;?...= . = . ::::.:',...R. l'.',=
='! ',,,.'.... = . ;= .., = :. , ... .; .. . , . :
. = ::..= .. , :, .
.: - " '' ' '''' =: ' = direct contact with the top surface area 309A of bottom core201AWhen Completely ...=
..
=..: " -:===,...1.: '==== .s.' = = . . -, = = = . =
= - .' = i : ===== = : =
assembled. This contact forms 'a thud tight seal between the two surface igen forming an ;::
µ. 1 ..= . .= '. =:-.=
. = = === :.; . = . ;
. = ; . = . ... . =
- . . =
A = .:".. .. .. , ;
':, ''''''..1., 1 ..1,;,1=':: .43: ' ,.. . = *: ' .32 . I
!.:1, .7., ..=': = k, '1. = : .. = : . =
= . .
=,.. 1..1. :.:. J: = 'y = ' , ' " = ' = . . = . . .
'1'. :". :!:: :... "..`= ,: = . ... . = .
..' = ' I. '= ' t . .. c.i . : .. . ,.
::... . , : ..,7, = .
. = . = ..
. .
''' ' ''. '..i. ....; . :'':. , ..' , : ', ' .: .
' . . . . : = ..:, , =
---7,---...I.j.0:= '*-: 4 = -'=i= . == =
'. .... : !4=;=.= = .'= = .Y.
; . . ) ' . I = = = I., .... ; === = '.1,=,, ilt' :. '= = I .
: . a :=.'.-.4.=:... ',===== '..,$/ = = .!..= , .µ i* , . . .
. , , =
. . . = = .1 .; ' ..õ',.. A= =.===== . * . . ' .!== = :. .
. , = ..
..:....1.;i1:7: ==;... ' ** .. s ' - ' = . = , .:
= = = " . ' :..'= _'..11== ====:t1: .
. , . .5- = ='., = f -4.:!: = '.1,'. . . = =
= . ' = .
-. '=.' .'!' :';'' '..i, .: Opening 3058.1kom the indentation 184A to channel 305A.. A second CPenit4305C from === = '' . ..... . ',......: = .',.... ==,-;.::
.,,...4:.:::. = ='... :f.:. : 'Ominii430SA is formed in the outer surface 211B
of outer core wall 211A. the opening = = .. === = , = '.'..'. = '= , :
... ' 4.;:i= ,:::==1'.. . 30511iprovides fluid cemmunications from indentation 186A through Chami4305A.and -. = = . = .= -'.'=:=-= . = , ====:
:- .1. :; = ...- ; = = - :,=': = :
'; 1, = =-= '= ...= = , openmg 30:W to separation volume 220A (FIGS, 38 and 40). = This fluid sod ilotvs' through ; : .:===== . = ',. =
tondUit channel 7804 and subsequently passes through first bowl Channel 420A.
'Proin first . .= = = ; = ' = ' =.= . .= 1.
= = 2:
......0owitititannel .420A, fluid 300 then goes to through channel 365A to the seParieion.volume , :. . = õ =-=. ', :. :-.......
====1 ? f. ...?:=,, :ill = . .. : ....- = 7'..
'....;.; õ..i: =;;.:1.= '.: 120.*: '.= === . . . - ... = ' õ
. . . .... . =.
...-1. - == === -µ: = .,1001024., .. Iteferri4 to Figures' 43A and 44; die lovver core end 29.6A $ a lower plate .:
== = : = j. '.- "... ":
.1 --4.,.... ';'= ....:': 1, = ;., '''.' .. = " =====:' -'1': '== 160A. which has a tai,ataface 3008, a bottom surface. 300c and outer edge $00D:Extestdiri .' ''. ' = "..i...f: :=-= ===.".
'. :.
J... ; ,-. ..p. .. .frgmthe bottom surface 300C of the lower plate 300 are one or More promations 301A. The = = = .. , .. .
:=.-!.':i -1.! :2?...4 : =
= '' .. = = = , == = .
','= ==if,. ;: ,.'...' , it ===
outer edge 300D is adapted to be attached to the lower edge 2111) of the .outer. core Wall . = ' -'= = . : = . .= .:
: -..: '!.:',...-.1 .- I,.:.- =======',:. . 211A '.i.ii4 provide a ihild tight seal therewith. Positioned above housing floor 1.804 lower . = ==
=.µ,.'. = = = ..=.'.=
, _= , : ....4 .-!' ....: . :Y.. , ...'=.:
plate 300A is circular and curves upward radially from its center (illuitratetelin FM 44); = = : , .';= .: . . = ..., . "s. = : -- - = . ' : .
Alternatively, lower plate 300A' can be flat As shown in ilia 38 when PoSitioned above. : .= = : ',.= -2'===., ' , ,=' ...';',.:.
' 4. :- -',. =., = ='.= : ..
.6 .
..... ..,. F . ...'.:... *.... = :;
housing 180* is:Velume 220C exists between lower plate 300kand .
... : .õ using floor .= = ..; = ; = =z .:== .. 2 144.. This volume, 220c is in fluid Communication with separation, volume 236A.. = Lower "
=
.1 .
2.:.....3.: '..;=:',. ...7 . . r.
plate 300* may be made of plastic or any other suitable inateried.
'Additionally, extending. . = . = .:: .: .. = ..=:.
7 ' :1' '...F .. .?= =;.. : ': 1 "-.EnbitainiallY:perpeadiCularly from the lower surface 300C of lower plate 300* is teonduit = ' : : '.., ". = ==
= ===:. :r.....: ...=';= ''.. ==
= = - == = == = : ,., '. :. 4' i,,, ....i.= i: , - ..= :=320k: Conduit 320A has first end 320B that extends into the space 220cbotween lower . . ., .'.. . . ..
......i:::.',. = ,.. ....:'; : :
plate 300* and housing Iloor 180A and a second end 320C that eitentlialioVe the top surface - = '.: = i; ; .. ' :.
.., . .
=.... 1 ., :: - ====!.., . .. ' 300$ of lower plate 300A; The diameter of conduit 320* is adapted taint4 a tight fit with :. = '. ; . ". .-i -* ,..
.. = =
; ._ '.coridOi Wall end 32,4B. The volume inside conduit walls 324A and 325*
a Iiimen= . == .= .' : , .: .. .:..
....i :T- F ..r., '...i ... . :...' . " '='= = ' .....:1'; i.' . ===:!". ..ii: '= ':, ...' = =400*. The Volumedefined.by lower plate 300A, inner surface 211C,:andiOeiling253A of . -= . . . . -.. ===:
.,, .......?
:.:1,i- '-': '1 = = ; = = =,= : :: = ' = = =
. :== -'1. '= ' : . ..: ==== == '-bottom core 201A,' excluding Second bowl channel 410A, may comprise oar or solid. : ! = ' ' :!:',- = .= = ='"
., . . .
.= - t. õ ..-... ,=:, ,. .= = = :=. =
. -.4,1 ' - ,i=-= =ri =., material (See FIGS.' 4313 and 44). ..=
= ... = . ... =
= = .;
= t" ='! ==='. i -(00103), = In an alternative embodiment of the present invention as illtianatedinF.141. 53, . , = = . , 'i... = 1.," . .. :
. = =c==.= .:...,..-,=;.;-; .= :. - = . , . =
'..=.,..1 ill ',;=...y..: ,!=;=.,,;.:i"; , support :Walla 405i and 401A May be optionally present, Support Wail 405* extends = : ... . . . = . .,...; .
: = ....:
=== 1 '.' = ='== ''''= : . . == perpendicularly irOin..bottom surface 3098.
Support wall 461A=eininidsp4pendicularly'ficm -.= = . ' ...' = ... ===
:..':-: 3 ...i. -.. 'f:'1.=;........., = then* surface 3008 of lower plate 300A and connects with support wall 4054 when the ''. = = . . , '.. ,. .. ;
='';=,=P=:'==== l; . === 7 ==== .
" : = = : = . ' - = .. . : = . = ! . = ..
.
.. ....: = ... ...
=======4'..i'. ' .1. ' ,=:. : ....." -boWin core 201A is. assembled. Conduit wall 324A maybe. connected to-onduit 320A to .. = . : . = ..: ..r:f .. = :
.....
-1 '.i. .......; -w = = ...=' = = = =
.:. '.= = .=.:. ......
-form=ithiia tight seal and conduits $24A, 320A may be fized respeCiiv*
With supports' = : ::: ' . ' ...::
i .1 0 . =...i, ...g..: =: . .. ".: . .
. ... " = = . ,-. .
....'. '.f..., -=,=== f.;.,== ..s. . . . , .. Walls 40SA and 401A, Additionally present extending from the bottom Sdithce-300C of =
" , . ..
i,:=sy..;=.i. :i. ...... .... ., ..... .
''.3;=.;.!;:,=!=.====;:i=-..= =I= ',, ;:". '.. . ' ; -..' . .: . =
, . : ' .õ
... . .i=
. .
":== ':..r, .1". ='= .7= '. - 2 .. ... = ' .. = . .
: . .
. .. = . ... = =
=,, ''= .;j:=:1= ='!=..;r2 I .... ;.-,.= : , : .
1, =
1. =,`.1: ': '',.. .:;=' .. .: ; '.. . , ' ' 33.
:. ;X:. ; = i.!",, :ti, - -". . .. '= = = = ' = =
... . '= . . . .. = .== . = .
' i: :=..4* =
=
. .
=! = = . ''' '.
.... ''.. ..*:..::.; ...... 4 === :. = 'f : ' ;= = =-=
:\:======= `:;"µj:''.. f:::::.:=.."..i:=============:..)': 44' ,7....r;"=,..'..?;:=..f. .: " ...'. . .. = ' .... r ' .
...- . . .. . .

, CA 02480570 2004-09-03 , .,::, f;.:q..sf::1. , .- ' = ..,. ..... ......
.......,1" .õ 1.:..= =I! ...., ':'.7' - . . . . .
..; .4..... .1.: 41 " = : ; =,;. :.= . :
. . , - :. = :A ' ' : : = ... '= = : s! :i', = '::
'....4 .'=:.....ti..:::i .7te=i .' .. . . .
. , .
. . . . .
, ::::::',,t.:::1',;:;.::, .. = '===: .1. : . : .
r . , . = ' =
. . .
= .r . ..
. , = ¨
= : . . = , . = = = , . = . ==
. . . :
¨.. -I..: ...1.,.1',. -.. lower Plate 300A are one or more orientation spacers 409A that mite WithhtlindentAtiOn . ' '.. = = . ' = l'.. =:' = ;
,= = ii ';', ..".i.,... ...k= ... :
.= . i= .i....1 ,"..:7 !.... ......,I$5A, ';'= . = .
' . . ..
= :. ',....= st:F, i,== ..,,Z.- ,f:: , ..= ': =
.. = == . = = , . = i . .. . . . .".... , . =
:, ..',. 4.,-: ''.,-,:',.,.1:;. . i';.:, - , = ..; 001041., : AS will be readily apparent toone of ordiwy Wit in the tuthe liow1,10A .= . : = = . '':'=:' :.1.= = = ''..'==== '..:.
.. . . . ,.
".' R , 4.:.' ::' =
". ; = . : == '=
= ':5' "-!..' :".:.:
. -f :.= 1. Willneed to: be balanced .about Center was 11A, Accordingly' Weiglitajniays$0; added ria part =:":" ...... : = = ...."!..====:= ......===
..:
:-....4..):- .4.=-= 1. ,....:
= .- .:= = = = . .,.... .......,.
=
....4.;;=:=::::::...;. = . -pf the .iievice as is appropriate to facilitate the balancing of the bowl 10A sugh= as .weight . -.. .; :... ....:. .. :. y:
ii.,...13....i = ;:.!.; ..t....j.,,,.. .: . .. . = .: . .
. -= , µ..;.1.zi.. .;!.?: =,,,..i = ..c.740sA, illustrated in PIG 53, . = ', =
= . .
.:
. . .. :
: ...; il===...';,..'i,.; . .1091Ø4ti = . Refetring to PIG 38, bowl 10A is adapted so that OtorbOUSIng 100* cores' ,2 .= = = ' 1::, . ..!;='.'=
t . .. .200A. and 201A, lower plate 300A and upper plate 299A, housing floor lapis. . external . .; == = .. . ,..:. : .. . :
:. .. ...i.....! .. :='!... 4' : . ..!, conduits 204 and connection sleeve 504)A, and lumens 400A and 4008 iirelit 'connection and =:. : ". ! = , = ';:-=
': ..'.:.::=;i2:1== ::.'.........!;:., .
rotate together Housing floor 180A Of outer housing 100A comprisesreceises iiik on its .. ' .... : = .. ...."=::,...; ::: . = ....=
... 't = = = === :k ' ....top innfiCi and these recesses are shaped to fit protrusion 301A 'ciflOWer pl.ttte 300A.: As .. . ' .:. = 7.' :. :=== . -. .
= , j__, _.=
.
..: = .1 .., ; ,f': . .'.. ..- .
shown, lower plate 300A has 'round Protrusion 301A on itabottont surface 4.00e to restrict = ; '.=. ' ' ' ..:.
= == .1-1, z- ':(. l 4 . :
= ." ====,=:: '= . =,. A '=
movement of lower plate 300A with respect to housing floor 180A. When gambled, each .=
= . "=:.= = = =
; :: :,:y = :-. !i:... 7. : -= ; .
i..,,'.....,..li;:..,..jr. i....i:.:õ....../ ..... ........... single i.:protrus;., . ion 301A. on the. bottom surface of lower plate 308A fa* a tight fit with .. . ..,. .; - . ......
reCOSs illiA. on housing floor 110A. :. Thus, when 'outer housing 100A
iarogned, . atonal = = , '. . .. . %-::',''' . . ' .'7.':
..:-:.:1.!.! -. 7,',:' ''', === : ',.. : µi:. , ..,, ... ... , . . :. .. .
; = i ' . - = . . , .
=
' '12::"I= ='.. '. = '= = ocitidiiit 20A and. connection sleeve 500A, 'top core 200A,, upper. plate 299A1, bottom Core . .
, : k=== ,1...14.:?!........$. ., ; . , ...
, , , . . .. . :. . . , . . . . .
. .
i .s.....7,=:=,..;.... AI;
:' 1 . = = . .
.'=
.Z.1::' ....=:Y.::;?.: ., ......====202'4 lower plate 300A, housing Boer 180A, and lumens 400A and.4001+ill rotate.
. ...,fir:..µ..i...11':;-.:;'-', ' =-= - = ' " ' .: ==== ' =
==, =-=:-.'.4..?,I.1' =11 ..,' -:',.: thereWith. = = = ' . = ' ' ! . ' . . . . . ,. : . ....1 ', =
. : = . = . .==':=====.,::. . ....
.. = ...t,::.. '.... .s.::. ; .: ..
: .., ..: . .
' l'=i :;=== ':1:: = ::: - J001061 = As. illustrated in FIG 08 lumen 400A allows whole blood 00 to come 42.(i'. : . :.::: ,..4) -:. : ..= ....1.
=====!... =,?-:.!,,- 'i ,, :4 :, :' ': .. . . ..
!::::...;:ii...,..,-....i ......,i; hOWliOA :via a first. how. 1 channel 440A.
First.bowl. charmel 420Aliio4idiiii: is. pasSagevvay Air . .= ....
....,:,..... = ''.= =======
.
. ... .. . .
: .: . = .i.. =...f.:' .,1*. c . i , inflow of 800 through Inman 400A to indention 186A and dwelt) theropirationi. volume .
." ' : ',..= ..: .: =.:='.
. , . ..
2204 through channel 3.05A. Lumen 400A is located inside top core 200f:A. .
Lumen 400A ..: = . = .. , .. . ..t . .:... ..,. =:.
has t, height from upper lumen end 480A and lower lumen end 402qõ .Lunikett 400A is ...: = . : . :: :======= ..: === = ' 4. ,` 1.', ; = , . ':.' '''' ... : '... . =
õ i ; .
fanned by the connection of . Channel. wall 402.A extending from thoinne.r7urface 481C of ===== : . ,. . .!..= ' =.=.=:.
i';;.;. :1:.=,:' .'...:: =;:.7. ..., ': , == lumen Connector 481A and channel Will 402A extending from the top suilice 29$A of upper .: .. . = . =-=== =
..::
'..== ',..! -4::=;.: = ..:,.' :1; - .... plate 299A. Channel Wal1401A is Bupported hy a pluralitY of fins 251A :,ihidt. ere antic. beg., ' -..."';'' - ==. =. -=.`1,.. ...',:===== :', :''.......... -f.....: =.'=.r; .1- .........: k --. -. to the inner wall surface 210C of the outer core Wall 2104 and intrw skirt:40205C Of the = . = . .' = .'= = .
= '.' :. ===-=.i.,..4..:3,:='z ':.='=:', µi,:. =.= ::. upper, care end 205A,' and Channel *all. 402A is supported by a plurality of'fini. 46.3A. (FIG .. ..; ' .
....,.. : = ,:.
= = .:
. . = = . .. s...:
; ,: 4.- i'. r=-..= =..`,' ; ..... 4(t; .-It cart readily be seen that height of lumen 400A, can be adjusted by; changing the sizes . . . =
.=''... . = -:
....====....i.ii====:::.':,:-." .. µ;-. == . -::. '''= : ==
'wt. shapes of core .00A, channel Wall 401A, channel wall 402A, cdriduItVidi 325A, Budgie ' ' ... = ..=. '': .= . =.: .-.,1..
;-=======.1:: ''.;. i.:i = '....'==...===:,: i....1... == = = . =
= = :, = - .
.=;:=.;-i .'= 4 V.n, 4. " ,''' i' height Of conduit will 3244.
'...::=:=;.'=1 "..z:,..,..:-.....7.:,..= [Onien= . = . As.:illuslrated in FIG.
38,Iumen 400A, from upper lumen end 400A to lower ,, .: ... .. ?.i.:. - ...=
.:.. =
.: .!.. ii. i = ...:2. :! - . juin'en eact 402c 'encloses an inner lumen 4061.
Lower Wawa. ..end 4024 has an opening : = = .. ' .. ' ''.. = = . '..õ.*:
4::: 4.= .;$ - ....=:. > = ..... = == - - ;
= 1.
. ' .34 . . - .: .
: .; .
= . .
. . .
i -.= -1-,,,=.=:i .1 = . .= . = !
: .
4,..-= . =4.t ..z :-: =.-= = ..,..... = , . . . =
= = :
. ... . .
. .
1 . ..
I.
. : ... . .. ... .= .
= .

r.= :r= ni.F. O. =....
. , , . = , i ..j'..3: .
: = ''.
..-.:'...::'.', c.: = = . . .
= " .. = ' .. , . . = .,. , = . = ,.=
= . = .. = . =..... .....=
'=,?.....iz.i. if.4 ......... ,. r. ' . =
= . . .
,,,...-.....!=..,i....' ...=
= ... ......,i.
,...,........f......;= ...i:. ,,,- . . .
. .. .:, . . .
= == t:I= .: 'I: .. 4'. . 41- . . . .. . . =
..
. .
' '..- = 1 = ... . ".. .r. . = . : $0314: Witith is in fluid coinrounic00. n with separation voigthe 220- 'A; thronlgli. a inianher Of .. : ' : . ==-: : - ; '=
.. .= -'.. .. ';===== :7; = ,==
channel 305A. . in the illustrated embodiment lumen 400A comprises first bowl'ehannell .. ' .:- , = ==
4 . = il: ' s==;i. =1": ..= :'' : = =
:. : = P.i": ..t i . : *,,' .4204: Second bowl channel 410A.4 located inside fast bowl channel 426A of the top eige . .1 ' õ=:::: = 1. ';.
=
" == 'r ' - ..'. ¨ ....= 209A and is enclosed therein from Inman end 480A and to lumen 402C Furthermore,. , .. = = '''=:. = :
: ;=.:! = ....; =k.'., = = = .., . : . =
: = = :-=:%=.;õ;..,;: ..11. - =- , =
. .fi= J : ...!.. =... = ,'= second bowl charnel 410A forms a tlassageway through lumen 4001 frenilbelii* lower plate = = ' - "7.. . ' .. '====It=I'..7.....f, = ,.., :== 300A. for the removal of a first separated fluid component 810. that sithertin indentation = , = . ....-.. = =
.=
== . -.; '. :,=,.. -:
.= .1.8$A ofhoining floor 180,A. Second bowl channel 410A extends fkOm hoining floor 1S0A.. = = ,-= .. : ;== ... .....*.
'.1... ',''...'.1',:... *.i: ...:',E..:... =,....., of outer housing 100A *through lumen 4001 and to conduit channel -450,s't:==14f external conduit ' = - . = ';...' = :. '..; :
= =====: .::C`i:.=;:=======,.....;.
. *.. . = : . = . . . , : =
' . cs t'i.:..=== :'..t.',.. == ' :
204.....;. .. . .. . -.
. = =,...
... õ..... ..., ..; ' ....,....100,10S).. =
Referti without ng Figure 38 (shown thout conduit 321C), inner l*nert 4001 alloWt.., , .= .*:,;... = , .. '..
,-.s....!;....,:r. = '.1-.: :;',;:. =:',... reablooa cells 810 to ,exit howl 10A, via a second bowl channel 410A that iroVides'ilisid : . . = ' = ..:,..
, '.. = '.::=
:1=====:;:!i=-:. -A,-:'= Z.,=.. - * .: :*=,= =====, = , = .= :
' - . ' ;
...:.'=''.1:=;:. ===:* .=;'= .='=:' ';" 004141Unif:t4iOn from the housing floor above indentation 185A to opening 24E line!. : *. .=-==== ' , ,.
:
i '... 1....;.-.... I.-. "===1 hinita:40011 has an upper conduit end 325C and slower conduit end 32411 =comprises = . . :. . , ;;"c;===....r.......i..;=.-e.. I =; = ; ===.= = '..- ''=
: . .= . = - .. : = = = . 3 . .. .= = =
=.:== = =
i= *: :i ; ! ...-' = .::- " tsirs) Conduit walls 324A and 325A winch are connected in a fluid tight manner and fp,. rin . ' .. . . ' :==.. ., ...*, .:....,===-e!:":-=;=,...t ; ';', = = .: .:',.-........-. = ===
= = =
; ; . ;= == - = === - :
second bowl channel 410A that has a smaller diameter than and is seParatetand distinct from .. = = == ' ' ' .!.. z i; I or s * == :, = . = = , .... = . ' µ: 1 '=;=.:=== = '===' .:. ..% .. first bowl channel 4204. Conduit Wall 328A
Is by it fin 252.A. that extends '...., :-. A 7 ' = 1=== = s =
charnel wall 40IA. and attaches to conduit wall '325A. Unlike luinert4004.
Which has .one ¨ = =
==0 =.: =:=...'g .;=:.::: === . ; - = -.: = =
" . . = . , , . , . . . ===
'',....=.., i .! ..,:i. .... . ':. gad near indentation 186A, lumen 4001 extends beyond. indentation 1S6Annd through =
== =====';'...=....:' '..' ...:!*.... ...em pl.. . ' .........
. = =
===== === ,41.4- 1...1 . ;
noteate 300A Oa first conduit wall 325A. has an uppet esul 325C =whir.11 has an . . . = = . . ..,= === .. . ,..
.: = === i=-='. '...= = == '''..;:.
opening 325D on the top ; surface 4112A of lumen connector 481A= and a lOWer end 3251 = .. = .. . .."..' .* ..= .
:::';'......r':'.'.1,, = -=====.......,.1. =Ff.. ..... == - = =:-'. ==== = 1. ,. . = , = ' = = = l=
=== =*i. :, = ' = ... . = - =
::. = = = ,.. ' = =======' '': . '===== ,..:nailizig to Opening 325E adapted to .fit lightly with upper end 324C of conduit wall. 324A. =
:.....,',1=== ..;;; ..,r, = !., .. ... .:....= , ,h.
. .. .
. . .
'' ...1::'''' '''''...5.. *. =
Upper end 324t of conduit wall 3241A is higher than indentatian.286*.and has an opening; , = . ; === . ' == ' ''.
........14.:1,1,,,:=,: i'= ' ....,..*.... . . = ; '. = = =
..i ===== r.3 ''." :i.'-' - : , 3241)Conduit wall'324A also has end lower aid 32411 and is suPpOltet ifraiiluralitY of . ::: ' ' = , ===== " . = =
.......
f::= ; .4== === i -,:r ' = . = . === =
' == :===== . ' ' . = .. . == . . = , . . . === . = . ..
k. '''. l' ! == .===== ,':',. ; *fins 252A. Lower d 3241 having operiing.
end is adapted in connect conduit 320A .=
='..i4'........i:=:'''. ..== = = :. = =,.
.= . . . , :..:,'=:.'.' =:. '.:, ,i, .. ..,'..'hc*ipg opening 302A. located near the center of lower plate 300A. The connection . : . ...... =
1:-...F.=;:lt.'.....;;,.....f.... ,: .' = = ' = -. ;.', . =
. ..-1,..3 . :=.,', g ' '....:.... openings 325E and. (i2A provide *lid communication between lumen 40011 and the. space .. = .
:;=:: ...,= 3: = :s. ====== . . == = . õ .. .
'=== = ' = 'I.: ' :,.. . ';-; . '= ; %toe between lower. plate 300A and housing floor 1110A. The space ;20(7 between Iowa-, =,:......:.; ..- Jr. :;, = : . .:== = - = = : = " . =
"3 ' ' = . ' .' , " :' : .. . '''' .
.. ' : ' 4 ..... ...:' 2. = : -ohne 300A and housing floor 1110A in turn has fluid communication With aepatsdion Volume = . .= . ..:õ: , = ..
.4,. --,. 4.',......!===:..1; :='t ...., f:=.::.- ,.......
= = . ; == . ., .. = =
=:i=A til= :i.':== li = µ :.;,.,...210k . . . , . ... ,.. . . ...... . ,.
,......=====10,f, ;L.; .'7,,. ......'= =;..... ...: =,..... ' , =
. = = ; ,= = . . . ...... :, = , .1.. ..
= = ; . . . *.== ... .... = . :i = .. ...f .;.:
=::===,...-.1;, ";..= -;:c.. i:?!.: .. ' '=': .1001091_ = = '. Conduit 320A.
provides a tight fit with lower end 5241,..p4ridi:ng support for:. ', :-. .
====.. ' ' ..* r 1/4===='==,..'1.:=,;: ..µi,1:-,-...,.. . -...
L, .. _.= = .,. . ... = = .... .. = . . .=
' '= . -.: ' " ".' = =
second bowl channel 410A = Each bowl channel 420A and 410A may be made fatly type of ''. I' == = .==== '';'.** " =
flexible or rigid tubing (such as medical tubing) or other such device.provOing a sealed , = = ... = ..= . = :-

5.: = - -;1; *,='.- - ==?==== ..1.: .= = = == = ' , . = ==
= .
:====== ''..'',..if,i.:' '41;=;.1.1=,, '.; ...; = ; :f.= ' = = == = = = = ; . . . i. =.
. =
= - =
',:;.i....!.7.-1...:;:;:i e.; i .../.' = ='', ''. :. ' ....1===ii.!='; 01' '-.: ='= : = = = . = ¨ = = . .
35' . = ..... =.: . . = =
!.........'..:'%,:it=--==;31:' *.. = '....,.= . = =-= i. =
* ; = .. = = . . - .: .' : = f...1: .
'.. = .. = ='. :. :µ . . s; = = ...r.:.*:: ...*::,.:::i '..= .: = = = :IL% :=;i = s.".' It;= .= =:. . = : . . i .
=
, . : =: .= , ..= = . = ==
': = ' /lb ' = ' ? :*:
' = = === : =:=?1 .i: . ' = = 1 . . .
= = -= ' ., .

=
:
. .
= , .= . . ==.... . = ..= = ==.:= = = = =
, .

, =
=== ..= ....., .
'....... :t4.:: .;;.t: 1' ..' = .; ; ... .: , ' . . : = =
=
' = . i' "., = . ,'='...= 1.=::.=.' ==7..
..' ;?'::.. ''...-1!¨=== = : 4 ..; . 1 . .
. .= .
= .:...if.... A. 1 = . , .
. ' 1 ' " ' = ::'¨''' ' ''. ''''''.
.1.; ?...µ.! ' 'tie:. ..1:. ' = . .. . . . . . , ., ' . ' i'... = : = = =';'.
. ."4 ' ...= !;== 1 . =
: . =
''s! UV... .,:i .1 : . .= .
,. . , ',' C
: ;....i, . ,' ::: .1:: ' ..' ' ' . ''.. : : . : , . =
.
... ..' A' : ' = ' ...
. ''. :;i" :: = . I ''.` . . passageway, possibly for pressurized Or unpressurized fluid flow, and WhiCkprefaubly can = ... = ' = ' . 4,, = ..: .
:" --= :=
-rs ..:!=== ==:. ==== = ''.: =
be disposable and steril.izeble, i.e., of Simple and efficient manufacture.* ' ': = = ' = . : : . ' ...,::..- ' , ' =.= ,====
= ,.. =
...., . .= - ...- .-= ....=.:t: == ::'= -....'!,'= -:: = === = ' " ='- =
Drivel**
1 .:
== = .. = = ... .
. . = ' - .:
'. 3'. ====:.'.' ...). ' .= ' - ' == =
-. .t..: '..... .i: ;..40010.1 As illustrated in tIGS. '39A and 39B, conduit assembly:86'(Mi is attached to . = . ; ''.'.." == ====:'-'=
.= =:i = ==== ' = ':' = ...bowl 10A via connection sleeve 500A which is attached onto *Elitist and 861A of '.=external .. ...1-, ... .. = .1,=
=.= i - =...= == ,i' ),== : ==
conduit 20* having a first conduit Channel 780A, a second conduit cherine1160kand'a third = . = . = ".==== . ' - :====
. .. , .A
.
., . l'....=,: .....1... ::
conduit channel 770* Each conduit Channel has fluid communication = with.*
firsi. braid . . = ,=-= = . -...',..... . '... .:."-',4-'s ' ,:;., . .5, = ',..:charira$ .426A, a second bowl channel 410A, and .a bowl chamber 1401. ' The three conduit .= ..." ' '!.=... =.: = == .-= :
- = - ;
= = :::-. . : , ... .1. ::.= ====='; = i', :
channels are equally spaced 120 apart and equal in diameter in external :conduit 20A(Sei . = = = . ===..= ': ': : -=
== : . =
. =
.= = ' ': = = :.=
FIG ; $0, .'*iiito fluidly connect to eXternal conduit 20A and boWileA,=coliduit channel . = ' - . '" - '=== =.' = ' ========
,:=====.r.'.';.- == s= = . _. = = = - ' = =
'-: .'...r.:=,:.. =.... ,' ',...t =
180*. is fluidly connected with first bowl channel 420A for inflOWitigifluid00.1konrextethal; = = .. = = = : '5' = = = .='=
.-...i.:,.con.di.tit:211.A. into bowl 10* for separation.- Similarly, second conditit-Chantiel 710A fluidly = = = , ' ' . . '' .i.õ , = ...,:
=
::. = === = t'=:==.= ==== = = ....connects to . second bowl channel 410A
for relieving first separated. fluid cEinieictient 810 .
.. F'..1.==::==== ,==='=== == = , = ,1 : = ' = = '='= - === --; .= = ==.=
from bowl into external conduit 20*. Finally, third conduit eliitinel7t0A connects. to "
,= : = . .
: ,,i - , ....-.;:, . .4 = .: .. . =
...: .-.1 .:, ...,.... ..t..i. ..: ..., bowl Chamber 740A for removing second separated fluid component 820 from bowl 10A. ' = ...: '' = -=
= =
- =;- .- === ,.' = .= =100111).
As is illustrated in FIG. 45, external conduit 20A has a Cnoneclion: sleeve . . . . .
. . .
== ======;-= ' .-"' .=:=== = = ,..:. - - .= .= -:: .i===:= ,..= .=:::' : . .,: 581A on the first end 861* and an anchor sleeve 870A on the seconcfendli6i4 of *external : = ,.! = = : :.
:.... ...?!.`. .=:... -5 ....cop4iit 20A. Optionally present between the connection sleeve SOOA and anchor sleek.. = ':, : =:.....s. = == ... "
. = = J = . .. : =:: = ...: = === . = . .= :
-.'..f.:.i .:::== -:'.; ' .== :. 870.kon external conduit 20A are a first shoulder 882. and a second should er 884 which:- s . = = - =;. = ''' ..-',7 . . . . . . .
..: ..1. , .:. .. , = extend perpendicularly front external' conduit 20A
and are of a larger *luster. Between .
.... = - = = . , .1::
:: :..1,: ' :-=-= .:i. . .:: , tha..4nnciCtiOn sleeve 500.A. And anchor sleeve 870A (Or if present the= firsii*d second.: = = = ==== ' = . . ... = =
= = = . ..) . ...
- := ===== = ===:, .:',. = : == === shoulder 882, 884) ,are a first and second hearing rings 871A ariti=e71A. Bicteintil= conduit = = = .. ' === * '.....:
' = = ' =
!=====:1:=.'; . :.: 41 = ===== =
',= =,.. = == - : - - = ' : = i . =
.. s ii" .., ======= - ....= 20k anchor sleeve 870*, and connection sleeve may be prepared from the- same or different .
= = = 1 =
. ..====.:k . ,- : -; -.' == = == - biocompatible materials=of suitable Strength and flexibilitY for use 'inihiatype Oftubitig in a = ' ' ==.õ-, ' = = -= =
...;= =
= '7-= s:i.: - -:i.:. .-1., = = =:.:.. centrifuge (one such preferred material is HYTRE1.6). The connection sleeve 500A end the . = ,. 1, = -: = ;.= =='.. '... =
. = = = ., :=.1 = . . . .;
====== .: ii: ::..=== .===., ' .=.4. = !,= .=
anchor sleeve 870A= may be attached through any suitable means such as eFlhesiv,esr. Welding = ' ''.. == . . ' ===== ==1,1 ..=:::. -=-'.4 ,...:::: : = =
..= : . . .. , =
:., . :rip. =====:.,...,...,,: .. = =,.= ,..= etc., however, for ease of raanufactdre it is preferred that the connection sleeve 500A= and the : .:
. ....= . = . = , :
-== -='= 'I..; == ===== = == 's anchor sleeve 870* be overmoldedito the external conduit 20A. ' - = = = =. ' . .. . .
. . .
. .
= t .
, . =. .
1061121 . ; =
Referring to FIGS. 45, 4* and 49 anchor sleeve 870A comprises a body 1774.,:
.. - : = =:'!. . ...... '':
.4.
--;===1:=:',1:,:i.=:! =-=i' ' '--.= having a first anchor 'end 873A and second 'anchor end 874A. Anchor 'sleeve 870A.:fi!- . ' = = =.= ..- = = 7:-...= = =
::
-.=='',,:-....;====,:========ii.i = . :"=,:
... =:, . = : = , .,: , . . . .. õ .. .
., ==.::,,:i=-`.';i. ===,:.:i.'. c-,.;=,=:, 4. ; i .ate4bed to second Conduit and 862* of external conduit 20A (preferably ;.by ovennOlding). '= = == ,- :.
.--1!: :=: = . . ''..i.
.'= 1.;:i '..,=.*: ..; ...`"..
and increases in diameter from first collar 873A to the caller 874*. f.SPai4X1 distally from ,- = = = ... = - = == = -:::
,.,.,;=i====.;:. =,..11:::: i..=.: :. ::. = ,. :.
. =i .
. , ..-.
-". :iffq- ===== =-.1 = ===., ' ; ' .. =
=
= = ..
',...t,-. ... ',... = , .. . =:. , . i = , . ' = . : ==
'1 = ' .. = ..' .= .. '. :- - .c. ' .. =:.',..;.
,: q ' ': = i. ' 'I . = . : . ='. t" " . =:
.. I. . : = = = = = I
' .
.........

. , ':-...=:.4;===';
-.: .4 ;,1='' i:== === = '.
.. = = ' . , ...,.
. , , ....=..: ,.. ... ....... : . = .
i..;..':. ..-1,..;.:. : = = = -... i: ...= .= = . = .
= .
=
. . = . . . , . , ==
".= ti.-/..= ===:== = = ' . . . . " . =.: = = =:. = -,..:..==:==........:.;==,... ....;
1 = =
'''..:::=14.1......t `.::' .. .
= .. . .
. .
=.;.=.:Ii;i".':.=:.==: .......= . == ...=== ....=
= . i, .. .., ,, . , . :2. .,1;., .... ,..,... ....= . .
second end $74A is a collar 0116A, which extends perpendicularly from bed,87711:and of a = .... i ' µ ',== ....-, .. =*-....- ;:. =:=:.
= : k. =,' 'T.. ' larger diameter than the body 8773 of the anchor sleeve SSA.. A Plurality #fribs=877A, ..... 4.,.L. ....i.': :;.. = =:===:, .haiingit first n'ti end 877B betvveen the collar 1156A and second anchor Osicl'73A mid a .: = , . -. -,....
..',= ==:.
: : ,..? i : = .- =I'.. :,.. : ,secancl ri"ti end 877C eitending beyond the first anchor end. 873A are attached to the body = = = ' == ...;".. .'" = = -....
: ' . i'. -f...= = f'. j.?= ' "...
= = == ==== :.= = = ' =. . , =
- , :k '= = ?:: . y; = = , , 5771).= The=second rib ends 8/1C enjoined together by. a ring 880A; :Whithlis alsOittached =.:: = : . = =
======= .. .....' ======.=
===== ::.t.''':. -!;= =?..: =- - : .
, . . = . . . .:;
=== A" '= = =-: ,...! '.. .:'===to edema conduit vpit,.. The ribs 877* run parallel to the external conduit 20A and are . ' .... = = '..; = : '.......:
'' = .';' 7 ...rj.; = ;,* I '. : : ' . -¨ . L = , = , . , :
.. ::,4::;,...'=;;;*. ,:',;. . :
preferably placed over the region where conduit channels 760A, 7704, int-700A, are closest :
= ...! == -= : -.. .., . .õ . , .
== : 1 , ,.''... ===!. = ==='.;:
= *to thotsurface of the external conduit t 20AfFIG. 50). =
The regions Where th4 Conduit cherinele...:: = : * '.. ''' '';':.
-,.14:::-.....: ='.== :.!, - : s: = . : =.:".. - " .. =
= = ' =
,..: .."":.; =-;'.... ',..
760*, 710* and 780A are Closest to the outside diameter of external eni4aiitt 20.4 unless ..;
i'=== = =-=== '' - === - === = ' = == : = = :. == = = .....' . = =
...I:. :if j . = ..:..''=". ::-, r ...reinforced tend 10..44. outing high speed rotation. Having ribs parallel with* conduit - = = : = : . : :
''.- .====4-: ==== . .... . k = ===, . channels beyond the anchor sleeve end 873A provides reinforcement to thi.1, region and . = . : :. : .. ===== = .
.
...I.. .1.1....i;-,....i.....: -. '..,.....=prevents:Condtrit -*litre at high speed rotation. In one aspeet,.the riba.preritit lb.*: busPiclhig !::. = .
= . ...-',-. . : = .'s ,== =,. =_. :I . ''',' :4 ... '.='=
the external conduit 2.4* in this region end act as structural elements iti ir:iiiefer= the torsional : = =.. .: = .. ; = '', . =
'==== t. IT ;=== = .??!'".'.i.. = ====7'....5.4"40.ki.E.Ote.: anchor ateeveir70A. = i , :, , .. .....i...====:.i.:=?..*: . = .....= = == === : == = =
: = :. = = :
: :, 1...;,..4,,.. :=:: =.:7 = ...=1014131 = = , Connection, sleeve sp.OA
coninrises body 030A havipgan4Per=sleeire end - === = ::'.... . '= = :
f...',-i : '. =r= - '= = . :' === = ? S31* and. lower sleeve end 832k(Flizit. 46 and 47). . Lower sleeve end 83A has sleeve : .= : = ' =:=;='.= .::'. .:::
...1 ?..:1.:-,:1, .1 ...f. .., . = .. .. .
= = :. ..: ===J:
'......:r. 7. :.......t,2s.:
flange 790* and a plurality of protrOsions: 843A, which are sized to engage:"
indentations ; i: = : .= = '.-. = = , = ' :'.
.."==v= =....' =.'.. ..= = : ==
., . ' .. = ., :1.
. ..... A.-: i . ::: -.!: .. : === . ,, 4844 on the wall surface 432Aof lUmen Connector 4814 *hen the bowl is assembled, . . .:.;..: = . .. ..
;= !.:.'.;:::.-..µi! :1, -; = .... ..., : = = : . .... ,.
...
.,' 1 . === = .. .; 7 ..a &id tight may. be provided by placing o-ring 791A around" body 83(A and . . .
, : . , : .,.:," . ; = ...
1 ,.. . , . . . .
1 = '' :''..::: :.
compressing.'. the o4iiik 7914. between flange 190A, and 10.0* . thipir- sleeve end * = '..: . = ' - c..., ...., . . ..
. = , , =. =.======, d = -,:__ : 4 = .
031A .is adapted :to. be secured to external conduit 20A. Itr;ferring to :1r10. '46;39A and 39Bõ ..- . , = = ...: : , ... ,..:, = ''= ==-) '' = .": ' :: = connection :sleeve 500A is secured to bowl 10A by means of sleeve fl.an8e1790:4-.and is . = ' `4!. : ''. ' :
adapted to fluidly Connect conduit channels100A.,160A, 770A= of ektrana$
Oond'uit 20A to =
: '' = . ;I ' . ''' - = =======; . ===:. ='. - - : - :
= . : . , .
=:*. fs= .;.. --; .3! : : - bowl channels 420A. and 410A, and.chamber 7404 of bowl 10A. When iiiembled,: = ' ' . ' : . : !,.: =.µ ===
=====:'...c, :::====!!:
.: ' ; ' = = = = , == =
cOnnection.aleeve.S1X4 is mounted to lumen connector 401A (Pig& 394, and 9B):.
. ' ''''. = =
.
. ...
.- ".4,:=:=.'." =.:, . =-; ::: = : . =
. : = = : i.
:1: '.:. ":;:: ===,. ..''.= - ',..=:.,= .., ; ====== (0004]...
= Connection sleeve 500A preferably increases in diameter ftorn upper sleeve =.: , ,- = : = =:" '.'.
======= 4....:;,..... :F=.i.; .'.......:;.. end.531A to lower sleeve end 832*
and is overnolded to first conduit en41161A of external = == , . , =
... ..=
.: -7".q..1.: ,fi...--k .:-. ' = : conduit . ' ' = . ' . . .
======,'=:. =1"=-i. 's "..ii :. ===.:;..
20A. Connection 506.A. oOnnects:boWl:10A to external ton'duit 20A
without= . = ''-; .. . ". l=
:: -.4,1 .,.., ':-; . ¨ ==k . .
: .:: ni ....:":. ..7.." .4 .',..=:;,.
use of arotatable seat, which would otherwlie normally be located between bowl WA and =.= = = '. . ==
;', == =L'a=-=: =4' ". === = ' .=
= :' = = 4.
:;..',;==:).!; = ,.:!===== =,..? -. ...;.,...cOn#Octirin sleeve, soil& The seal-less connection between bowl = WA and connection sleeve = . = = ;: =,, , s ' = === 1:',1==:::,i,..-1: ' '=,:
500* may occur as explained eboie., or alternatively throUgh tis,e.o.tfli;r etuirPleõ,=air 0-ring, a . =.'',........ " =
. = ;::. .-.1..: -F.. . ;... -'.; = = . -= -= = = == - - .
.
. ... ...i...1!...i,.. -I, ....;===
groove, or lip, groinmemype connection; welding,' or a tight fit with or sithorit adhesive in ".= :, = : :: ...: =..,:, . ..1,::,.; .1g, = i;.: .....= = .,.
: =.,==.;Ii=i = l'.....: =.; === --.=::::... = eithir bowl 10A Of connection sleeve 500A. . . .
= . ::=
. ::. if.... .e = l'= . :"; i ': = =
'= = . = . .. '= t = = . 1 .' :ir ..... = :". .i.: . :..: ' .... . ; = = ' . 37 ' . =: = .

' . .. = .. .
==== == "= = "
I.
:=.t ,t. .-== =ij ==A ::' = ' = ' ' =
. . - ,- . = . . = ., A ..=== = .. ..
. .. :
= ' == i; s ......:::
=
.= : = = : ' . . = . . ... .. ,.
. . .
= ',... ¨
:
. .
. i . , .

, CA 02480570 2004-09-03 -f: ..ii.Z : :.. :=:4., õ. . .
':.:. 1 =-.!.`.;. :......:='.:; .,' :' ' - = , = = . , .. : 1 . . . = "
: .. ..., - ::: -47.i ' s.:!:.: . tµ . ... : .: ' . ' ' .=
' . .
. ; . .. . . .
it 1.-:. '!.; 'I. , ='... k . ,. = , ., '..;;i=
.,s..):.:',....: 't... .....: . : =
: ...
,'.',' ;v." ....i.
;...J.: !"..r:=== :':''... ...-: :=:: ' . .
.. ...4.. . ,. -. , - .., =., , ..
1001151' ' ' As illustrated in Figure 46 and 3013, sleeve flange 790A
has itAtottbm surface . : = . . . ,=%=-... . -, i.
= .. . .. .... . . .=
'.,,,-; j.., ===, = =::.,. .. ' . 1.1owever, lumen connector 4814 has a plurality of indentation 483A that.pOvidesfer=finid: . = .. .= = .. .i.. = =
,õ , .:= = 7.
= µ ===5=.i :=4= ==== . = = :
. ..õ . , .
=
.:: : .... ..'"=.: ' ': ; ''' :!,= 3:-',.i-== .-,,'..-4. = ....- -, ,.= . . . : . , , = , . , .
.......4.....:=.*:. '...:. !::, . : . :=== Space Occupied by hollow cylinders 321A and 322A. dit., plurality Of protrusions 8434ot:the ' .*µ = ..=
=:.: = ' =====
.: = f ii: : = : =!: = r ,.
bottom singles 847A of sleeve flange i790A engages. and slides IMO
indentations =484A on the ' = = ====== ' = 2:
. , = 1.;.:; - '..:1.
=,.: = = . , . == F ; ... = =
=
. . = =.= . . -. =,,,i =.= ==== 1, ....I. .:='= ' = === =
== = = = . .
, . .. =.= = = == . =, ==. = .=
== = -1?======.- = ", " :3 = .: :=thitafliddly connecting :external condnit 20A to howl 104. This :fluid connection 'enables = i .. ; ..= =
... ...._ =
....
, .
:7....4...:=. ;...:.;.= 4.. ,:=.. :==== fluid sOoto.besuppiied through external conduit 20A to bowl 10A, *. Shnilmity, this fluid . . . =
; .
= .`.... :====:'= :==== :=ii:=:== T === : =c,mmecta" .
"On also enables separated fluid Components IN 820 to be removed il;lil bowl = 10A = = = : ' :="....,. .. ': ...:.
'i,.i'...i...1'= *.'-=:.i..1 ====== ....). = :?*..., ..
===== ,.: V.I.s, :. ',:!..3-1 = .: : , through external conduit 204. ' '. : .
' = . ==
' = ' =::... ... . .-:
, = i . . , . .= .., : .. . . .
.. :::' '..i.:=;.': .;=====*: 4 .. = ...4001171 . External conduit 20A has an approximately constant diaMetOr which helps to = , = ':' = = = , :='.
=': = :=,- =.= ' " ''= i'' = = ======redtioa lhe'SgiditY. :An excessively rigid external conduit 20A Will heat 'up and fail more .. : . : = .
.. ::==zt... ...." ,::: .. .,== = ..
: . = = . ,.= = .
=== ,... :,=== i = ...,='.. .' .....quiekty, , Additionally, a constant diameter conduit is cheap/easy to utertuta#tura, allows easy. . = = ;
, . r,.. -.== .= -, ..
== . . . , = = =
=== .... 4....; ,;:...::, ....r..
experimentation with connection sleeve SOOA and anchor sleeve 870A sizes, and allows .
. .
: = . ,.....:=:;., ..====: ., = ... = .. .
: ,: .. :1=,..,...:=.,:.. ..i. ..... = :
$7.1ik and $72A will be constrained by first and second shoulders 8$24....anti.884.4. External = = ' . . ,. = ....... ...:
f..: = = 4.: ...-:;: ..4.= . -:.:
conduit 20A may be Made of any type of flexible:tubing (such Medical tubing) or ether . : ' . : ==ii... . = = = : :
.. , = == =
= ::'= = ' " == '==:== == = = such device providing a sealed passageway fbr tlie floW of fluids, whir* n4y be pretismized,':' . = ': = .. === ' .. == ' , .. :4.'= t == -1"..) = ..." = = = - = = . -:.:.: = i ...;'":.-')-.: -.into or out of a reservoir of any sort, and vvhich preferably can be disposable and Sterilizable.== = : = ===.== , ., ! = ?...i......, .0, :...õ. , =
,... . .... .. = . .. . . .
!=== ,== 4:µ,=======,..!µ ;if . === ,... s . == = :. . . . .., , . .
. , == 11 4,14=- =;==!:,...= =:.!! = ....= U.===!=Perritenent TOWer-:system . . . . . = ..
=
. : . : ' = = = == ) . i: = ::: ' = '= ','= :=',..=. = :: .-.:
....= :. ' :::!?= l':' ..,-. ..1"- ' : ===:.. = ' :: ..
;=;,...:1,. i '.':-.. .:1,,. .': ".. 1000, such as, cassette=1100, irradiation chamber %0, and centrifuge bow 10 (1210. 1). , . . : µ .. ...;:,' , ,..
= = ..:=
: =
= = === = . = . . . . - .
':.=-=c==== ==,i'...*; ' ==e:. ,..,,,'g " -:' '100W through disposable photophererls kit 1096. Tower System 2000. PalOtivi all ak.f the " . ' . =
:1 =1===::: : ,... '.=====.
.: .. ? :'.= '.:r - 44 ''' .
= . = = .i 1::!: fil.',!22. .Lr. ..=?..:. ' .. '= , :=
necessary control fimotion=automarWallY through the use of a Properly programmed , . = ..
= ,. ,. , =
::::.= :=., '''..1..., h., ...:'; .: :, = = . controller,for, example a processor Or IC circuit, coupled to all of the necehs. . .4., my components. = . = , ' ' - . . = .1:
i '. == ==i ;'==== ...," ,..ii ===== : 'While anew disposable kit must he discarded after each pbotopheieSia tlitirepV session, tower , =') i :
==....
j,,,.....:71 f?..: ,I== p = . 7.. ., . .. .
..,...,...':-.: 4 :=;1....'4. .:,i..i =
...:... = '; .,.= .. ..2 .
::. I.: '1.:.==== ===:..4 '.:, -'. ' ' = -: = : 38 .
.
. . .4.
..
. ¨ .. = , = = .' =t= t. = :.;= = ===
= "::' : . = ' = . . . ..... . . .
' : = ? " ,= ...f = . = ' = = ' .
. = . ' = . i = ' !., . = .,:!;,: :.'; =
.'= ,=i=..
.===
= .. .
. .
. .
. .
. ' =

:.i :..e.,...,'=....1;: :1=:== . =.;='" ',. ' .. :
. .< = , =
= = '' ' . , = , , .,..,....:.=":7 õ: i, ..q=
:;PF.=!====='='=': ''!!. === t= .' ., ; ,1: . , . . l=
. = = = ?
. = '' ' - = =1: ...?e: = ' ,...1., :: .11%i';'====== "7.;...2'. . ' '. , . .; ., . -. 1. = .. . :.
. . . . ..,. = i ' = = . . 4 .õ.. ........ : .....!:.: f= r. '14 .':' re ..0 =.::.. : r'... . . . = = =
== ..i ,..=:. .* = i.. ''..g ' ...i. ..1=!:."'...: . ..=:==== . ' . =
'.. A ...i.µ .....:. = :k. .
... 'µ .
= ='V. ( : ......4. .:
' ' ' ' = .. = !..I'....; ====:,..\:;..4:
' it. ' i... j,==== ,::: ; ' . == õ' 'i ' . : .
' = = .
. !. ....
,,.. . .... = 1.. ' .. .. = = .. : : : .' ... .
......?: =".. '.' " ...;==
...: 7-7.1i . ii`õ .3; ". . = .., system 2000 is used aVer and over again, Tower 'system 2000 can be swamp*
tO=pertornia ... ." . , ..:!:::.. .== =,'.. :.";.::
...... 4.'j... :::: 't = ..:.: .= = ' = ; = .
':',.--:: ,. ==='.;. == .:number of extracorporeal blood circuit treatments, for example' apherMis,liY.T.pnoPerly'= = ... : : ...= ' '.;,.... ...=
....=:::.*:
=
= = ,. , . .
=. .1,'. ',.. ....-. .,..,.. = programming the controller or by changing some of its components: .." *.= : ', = - . ...
. .... = ;
=-= ., t ' ..:=.= .::', =:
..-.. :J..... '. = .:=.',. ;! = == t0011.9 = , Tower system 20:10 has a housing having an upper portion 2150 and a base = .*:,n= i ...::= - ..., ' . ' .= =
" . ,. = = ,. ...., .
. .. ...
. ==.:1 ., i: = '..,: 7.?.. '===,=
portion 2200 Base pardon 2200 has a top 2201 and a bottom2202. `4.Vheati 2203 era . .. = .= ===== === =: .':. == = =
.:. =====:- . .. . =-... ..i...
==, provided at or near ihe battoni 2202 apase portion 2200 so that towei system'. .2000 is ntob5e ' * = - . '.1: == . = ..t=
õ.
,..f. ;=;'=::. -;=== == -.' and tan.easily be moved from room to room in a hospital setting: . Preferabli, the fiont =,. . = = - = , l'i :. :. ...%
.... i: ;,...... ..i...: . :, wheoli 2203 .are.piyotable about a vertical axis to allow ease in steering anclimanetivering . ; . .. .. ... = = , .1,' . ... ,. . ...... ., ., . =
,:: ..t!...; j.:....i,= ' toWeiSystern=2000. Top 2201 of base portion 2200 has a top surface 2204.1iiving control . ..õ . ..
.-. ' i=-...-; ====..j.. ..i., = ': deck /200, hest illustrated in. FIG..22;
built therehi (see FIG.22). Itt FIG. 1eassette 1100 is.
= ": " - :., .., =c ..
loaded onto control deck 1200. Base portion 2200 also has hooks (wit il1uitate), or Other . :.= = = : =-:i.. ...-" ' ::
. ..." ii.=. ,:=.=== = =:=.: . õconnectors, to hang plasma collection bag 51 and treatment bag so therefrom. . Such hooka . '.I, = = ' = ...' = '= == =
:. . = ..$ : =,. ,..:;., :=.E.! ,' . . i , .
. i ;I; -.'====:õ. .;t = : untie:located anywhere on tower system 2000 so long as their positioning iota not interfere .. = ' : == = = . ...... ' .;
.: = ..1=====1........ : -'-. = = =-...witit tie=imictioning of the system during therapy. Base portion* 2200 has Piiat*Stiviticon* . .* . = = 1 .
.=':'';'.... ". " "..
=-====1=:.4-44 ===2-: i,'= :-: . . . = . . = =
;= = , = . .
=
µJ'. if'.., !... ...=i.: ...if .. ., =bchamber ISO (FIG, 15) located.belinti door 751 Additional hooks (riot illiiittrated) are = , = = = ===== = ' =
:
=.=!..". l:;,'., . = =i=-: :.;===== =.;.-.
provided on tower system 2000 for hanging saline and anticoagulant bags.....breferahlY, these ,=
- ..,=... .= = = ,. ....', hooks are.
located On upper poi-don 2100 = . . . ..4 ' ..
. , . . , . .. .. .. .
.:;..:[001201=
PhotoaCtivation chamber 760 (FIG. 18) is provided in base portion 2200 of = = = = = = ,....." = = .,.
".. ,...11 ..!.- 7-,.. = = .. .: ==== =
' zit;17.....=====;:.;...:., tower system 2000 bitivien top 220/ and bottom 2202 behind door 751... lia.ar 151 is .. . = =
. . . , .
,....;,:.=.,.....ht.i.ifrOly connected to hose portion 2200 and is provided for !tac0.$8 to ph.otiiacti*ion ' . = . = ' = . . I, = .: - ..:
.4 . = t.,=.; "Al.:: ......
diaint=er 150 and to allow the operator to close photoactivition chat**. 150 So that UV light ' - = *... . : = :-...1....i. - : . . .:.=.= = '; = .= .: .
==µ=.=== : = = = .. :.1 ' -," . . .
. .. .i......-.. ... ====. ... .. does not escape into the surrounding dun,' Ig.treatmen. Access 752 is provided to allow tuba .'.. 4;. ', .'..., =.:......?.= . .
.1112, 1117 (me 1).0 pass Intophotoactivation chamber 150 when irradiation chamber 700.= . , = = := . ' .. ' '. '.:-=== == ==,..3 '. == '-===== :6 '= ===`= is leaded and when door 751 is closed.
The photoaclivation chaMberii=Ocueseil in detail* . ' .= == = " 4: .:. = ==
',' 1=:'= ';',::-.'..f:'= , = ==:.'... = 4 .=;='. = : = .. = . = =:, .' respect t._=
1==== 4====::: 1.: ::&; below : ' =C''... with afIGS.
16 and IL , = . .. = . . .
===== -:.( -.." ==?- I-- = .
= " = . ' " == . . ...
.=....:!: .....===.- ..=.::.; . ':.... 1001411 Upper pardon 2100 is located atop base portion 2200.; Centtifuga chamber . = . 2. . ..
' . =1 . ...
" .... .
=
==== ::': "- = ." 4' .= .:= ".211)L(FIO. =19) is located in upper pardon 2100 behind centrifuge chamber door 2102. = = . . ... == = = , --,:=1- ..,.... = . - .: = =
= =:, =:: == ==: ''' = = . , Centrifuge 'chamber door 2102 has i window 2103 so an operator Can see in cerinifuge = - ." ' . ' = = . =;-- " == . ' = = :t..:.,:. ,..,,i.........1. : .: . .. ., .
=
= . ..= .= = . =
" --I: .r,:-.= .';-.. - :,.., . chittow 2101 and Monitor for any toroblems.
.Window 2103 is..cai.laittotet With glass thick .. - ;:.='.. =., = ===== =
.
' ,. ...-F= 1.= == =:=:'... ',: = : ......- : :. 1 = =
=
...:...i.::t-.....ic' Ø , ..===
enough to withstand any forces that may be exerted on it from an aocidamIduting. = = ' = = = = =
=
- = = = = =
:'1. : = .1-: =.q.= = =
: . - = , . ., . = - : - = ' = .":
r=
.ce*ItUgatipn which can rotate the Centrifuge bowl at speeds greeterthait.4500 R1olvls: = . = ' .. = '... == . .=
...,= ;.1.... i -.....i... if, . ==== ...:.. Preferably, window 2103 is constructed of shatter-proof glass. Door 2102 is hingesily : . : µ. . .
. ...r.... =.= .
' i, " = .. connected to. upper Portion 2100 and has an automatic locking MecliardiM that is activated . ' = = = ===== = ' = '' ' :
....= ,.i: ...4...: =..=== :=.-; .= = = = ...= . :.
= = . - = = 39 . = = ' == = = ==
==.? ,' =====': '.=i=
. .
'..11':-t ;:: .:=, .; ''= : ' = .:. : = . ' . . .
.. = . =
= . = - I: =
= = - = = .= = ..= = .c. :,==
: = . .. " , , .7 - = . .
. . = µ.: :=.= = ' = l'= ' - = : i''''' =': .-.....t====':.,';' ".......:
'=?:/l'i.....; .! V.'''. '''' . .
. . , .. ..
:
= , = . =
=
= . .
' = =

. , i...4 .., :- .4. = :: . . ;= . .
. .
0 1.'.`.:!: = i'l. if . I =
; ' : .. . . - .. . = .. ..E = .. . - :.- =:.:1-':1;1 .::4..... :-'===:.'= ' = = .= ''' = . , . =
=
. = = 1. =! " II =
= . .. ". " = " =
e ..,..'f:.; i::::',,'. ''= '== = . . . = :'= 1 ;:. V....4...TH).. .
: . . ..
, = .. = . ..:======= = ' =:, c=
...:','..tii: .:;.:.:1, ,,, '::: , . i...., .µ= .. = = = = ; .
: .= :... = '= 1 = ---:- --,--41106- .µ '.
....4....., .. . -,, i = =i,.. '; '.. ......-tbe aky*tnnit controller dating system operation.
Centrifuge chamber 1101. is OiscussedbeloW . ' = = ('=:== , . I.=
.......:.=
..:...c t ....:": :.i. = : ' . , - . ... . .. . - = . ! ,:r.: =.-.....: : , =
: :
.!...:11:11 .1......, =!::,i ,. :c=j1.1ntere: detail with respect to 1710.
19.=
g -17.: ....=" ...41 C; .' = ' .
,., - . = . . = .,. . =
' ....= 4....,..,..,.. 1 . :,..001221 .. . Preferably, dock 1200 is located CM
top surface 2204,=ofbaSe,Portion.2200.ater = ==== . ===:.;.µ - = :: ...= =
..:.:
=
, .!.. , i.. ==,.... il .. =near the front of sYstemtoWer 2000 Widie upper portion 2100 is extending 'timid from base = = = = == = =
=-=
.=:::: .3..;': . '==:' ='.1. . ' portion 1200 near the rear Of tower system 2000. This allows the (limiter eitity access to= ' . ; . ' :.'...,.= , - : ... -1.
=;,,-is....V:.'". V.:.:.:7 = = -': = = ' , == i=i==..! = .=..
'.,co' *1..deek 1200 While simultaneously (abiding' the operator access to cenirifuge chamber : . '= ...:.' = = = ..= ."
...1,1== , ==== ...i. =
. 2 ? .=:=,=...i.....1:. ' .' 2101, By designing tower System 2000 to have the centrifuge chamber 2101 in the ti.riper ' ==== ' = ... =
. µ.="1"=;=.:=.; :::.= .',...= . .;.portion 2100. and having the photoactivation chamber '750 and deck 1260 h% base Portion = ., = ,. .
.., ====.f.=,. :. ..Y= .... =
1. . .: =
.= - - i ..:.- .% , . 2300 an uixigitt configuration is 'achieved. M s.irch, system tower 2000 ha a radioed = === : '..: . = .. ' -.: : -:' ..' =;:=t'.1,!:====:, '''='. .... =': fOotixhit size and takes'. up it reduced amount of valuable hospital floor space. The height Of = = . . ...i =.=
......
=.:r. ==1.tj - -=.==. '.',== -'=::::===== :. :: ==:======µ= .: = = = === = = == i..= =
= = = = ' = .. =.. = 2 . ==..=
= , .s.,:;.;... =r= .:=,,, . ,.: :system tower 1000 remains below sixty inches so that one view Is not obstrtl.ctet When , . = µ`. . = = , = .,... : .
= =, '..i,....:t.: ...'.. '. '=:.-= ':::, = :-transporting the machine around the hospital form the rear.
Additionally,:hving deck 1200 == = .. : = . ........ ......
..1. 4:,.. =.:::. ',1.f.: :. = :
.....,.....i ...!,...,i, ::. =, J.n, horizontaltifej4y.ri,.0sition will provide the operator with e place to set.dtivices=Of , . .. ., . : . i : :, . , ,= : , . ... .;
t.- 4`, ....,= .=== , =,.= ... itheioPhettglis kit. i000:41/400 the loading of other devices, facilitating ettek:Oading, Tower = ===== . = ,--.-. ..=== ' . =.= ====
;=1=4:...... "c: . ....] . = õ , = - ..., , = = ...
....1., 1( ! ..,. :;,:: ..e.i.... :-: f,eyetta* 2000 is robust 'enough to withstand forces and vibrations brought = on;by the = , . = .. = .. =
:=.::: . =
...J....Pi :=====,t).7. ',.======!= ,== l*. ,...= . = == = .
' ' :. c.....r4. ::=,-,,:.==:=: =.,== -.=.:.ceatrifitgation intent': = =
= = : .. . .= = = ==i= = = = = = : . = = = : = .= :
1.: = ===. , ;
. = , ..... ....4.- fooam. . .
A Monitor 2104 is provided on centrifuge chamber door 2102 above window- ., - = i . '. ..: = = - = f.
71 !. i= : ..'f. ',;;...= ' '. '..2105: ',Monitor 2104 has edisplay area 2105 for, visually displaying *nate:Mr operator, such " : = ': . = .
. ..;41.,':=== .,, ..i .. : ..=., as; for example, user interfaces for data entry, loading instructions, gittp*C11, warnings, aleris,..=== -= ..... . =
= .,.
=:= 4 = =
= 1,1 ... ::: .c. , , :therapy data, or therapy, piogress. Monitor 2104 is coupled to and controlled by the system ".: ' . = ==' = = -, = = :
-. =.µt ' ...,.===.: :='=.=== , '.. = Controller.: A . data card receiving port 2001 is provided on it side Moen or 21041:- pate cad ...'. .. . = i.
= = "=,=
..-.- =ir. = .-.....-- - =.: == = = = ' =
. .,. = if:. = ...;' ..;; .. . ....marling port 2001 is provided to sl'idably receive data card 1195 Which hqupplied with = - = ., . . .';-: . = = :...
., .: =:1::. - =,;=====; =:='7. = = = ! === -= -:,. , = . . - ' .= .'. . . . . .
=
= . , t:=-=== ===='= i-:- == =,== , = eaChdispoitible photoplieresis kit lopo (Ea 1). As mentioned above, data raid 1195 eatibe ' = .= , == , =: , . .= s;
. ., . .. . = . === .. : =.
Pro;pititgranuned to store serve a variety of data to supply to the iyateni*trollei of tower : = . . :=:. = ,s. .
. . = .1 .
,.. , ..=.., .,.....,.. 4.: . . : = 'system...2,009, For example, data card 1195 can be, programmed to relay'i,7, utiation. so That '.. . . .= .,....: '.... = =i . ...= .it:' ; ...-:-...' 5 '.. ... .. : , = . = =
.
; : .= ===== '.= '. '': - :. : = thesystent controller Can ensure: (1) that the disposable. photopho* tat. as compatible with.= = .. . : !..... : . ..
= ::, i ==1 = -:'; :-..,:' =;====== =
''' ' .v4....;' = .:" . ' : . , thetd000 drive equipment into which it is being loaded; (2) that thaphOtettl:teresia= kit is . = = - ..
.... . . .
. 1.=:.= .= '.::. ....; ===== 1: =
capable of rapping the desired treannent process; (3) that the disposable pliotopheresis kris . = 3.. .. . "
...:. 1,i ..'''..f.;.: .., '.. '... .;=`=.: . .= = .
,......4:.i......1.4.' ....... of:a0ertain:brand name or make. Data card receiving port 2001 has the necessary hardware .: .. = = = . ,. : .= ==
: =:;11-i=======r,.j. :. '== ...= :-= = =. - ... .. , =
= *. = : == . '4 and circuitry to both iced data from, and write data to, data card. 1190, :Preferably, data card " , = .-; . = . - .
,.:=,,i1:',1 i===;: '.e.. ',, ..= .,: :. . = .. -, ::=11&:;.......:::::..... :.:.= receiVing port 2201 Will record treatment therapy data to data card 1195.... '$lirch information. .= . . = ..:: - i ..
',, ., ' ri.','= '.... ;".= ¨ = can include for example, collection times, collection volumes, treatment dines, volumetric = = õ : == '..;=:.: . 5.=
.....!
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on tower system .3000 so long as it Is Coupled to the system controller Or other appropriate : . = ". ' ' "*::::. .. ...' ;==, c.....''...?ti.11.:!...;?; :',.. , =i. ttsettitie1.'itemiS. ' = .. .
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' = ' - .. :====,, , :..' .=..;:. = = , . . A. PhotOactivation Chamber for Receiving Irradiation Chanter . = ..1, =
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Referring now to FICill, 16 and 18, photoactivation chamber.7,50 is illustrated = .. = = = . ====:. ' . ...
. = === ifl'= =.'= =:il. .*; =
in Cross Section. PhotOacti. yatien chanter 7504 fatted by housint786.. *Using 75.6 fits = . = .-r. : = = = ':' = .
thin base portion 2200. of tower system 2000 behind door 7sitila'.....6..
ihOtoaCtil:tation. = = . .. = . .µ:.=. .... = =.. = .:
, .= ..i..= .=.......... .:;', = si.ChaMber 750 his a plurality of electrital connection ports 763 prOvid' et1 on bisclt vit11.754, .. . . , . ...::.
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= ..' :!......?? .;=::: ,:....'...... _ ,. -=.: . .' . 1 , -.71Alecincid connection Ports 153 are electrically coupled to a Source of eiectri$1. energi. = = = = : ==..': '= . = == , r ';.,== .='.1:::=:'== .1 :.:1: .:'i.=µ .: '. Pit 'on).* *eon' Vatiort chanter 760 is designed to receive UVA light asSetrai;13;'= 754 (FIe. "16). = ' = .. = = 4',. = 'Is.' = '' * ' == = = = .''... - = =
When litlly=loadedint0 photoactivation chamber 750, electrical contacts nrtt.
illustrated) . = = = ." === ==== = =".
. ' === .5 ". - q== .: ; ..õlocated on contact wa11155 of UVA light assembly 755 form an electrical connection With . = . - = . :,.:. = == *:
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=1:;'= '-i...* = === :: =i== : ' L.elecisictd= connection ports 753 :This electrical connection allows electrical .Oriergy to be = . ... ..= =
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= == It=.===!==,=?=:;.= . ===== .. ,.=- . . =
= '1..= = = =====' : ' H.: .= suPplied=to=UVA lamps 755 so that they can be activated; Preferably, three ilectrical .
' :-.: = :if :;='=. t":;."i= = .....- = ..= i.
=== =.= .= == = == = = ,.= = = .
connection ports are provided for each set of UVA lamps 758. Mt.**.
Oefeta:bly, UVA light '...1'1==== '::::' .f:: ::: '===:::
.759 has. ttiVC! 5* Of UVA lamps 758 forming a space whiCititred/ition olialflite'r= = ..== = - .. .. = = ... ' = = : : :.:.:4.1.::.':1';:' assembly,?..-...*....,,'......=",..- ' '' = L= = : = = = = = =
= = ..1. = - : : .f.-. .
4: . I.'? = ':'. -...; :=t:;.100Ciiilbeinsetted. The supply of electrical energy. to UVA lamps 75$ is =Contr011ed by the = = . === '= : . = . =
:.%,=:=*... = -. . = =='.
'.. :7.. t..i. 7.:: ,:::. ',', E-!:- . : ; : = . .; - . . =
.1: :,.....1 .::', ...z. .::. = ::.properly programmed system controller using a svvitek. UVA lamps 758.a,.r:lia.th.iv;ate.0 a:01.- . = .: .* = .r.======
: '.= .:'= ===
....i.::1.: :1;;;;,....,',..==.4.; ,, ..., =,,deactivated WI 'necessary by the comr011er during the photopheresis therept:Sessien. , - .: = == .:;:',..
. : . ' ......
.===.:::i=00051 , ' = . Vent. he. 18757 is proVided in the top Of housing iSi teitrbeeic wall.'756. of . = :.* . : ...,...=== = == . = ': == =
,. = . : ===4,..
: .= s.- . .. :. . . .. :. .
::';:=::.1.:7,...:. .....;':::: lif'j . ...:.',...phoMitcti ....'vati . on :chambers.7.50. Vent bole 757 connects to vent duct'60 .7:wiii*leads out Of . : .
. = = = . = , .. ' ........
'iheback of lower system 2000 When heat generated by UVA lamps 758 Wilds up*
: - -= == ;.:. .. . . ;
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=
-'11. s:: ..- .:=' "phOtOitctivation chamber 750 during a treatment therapy, this heat escapes Ohototte.tivation . . ........ =
...=
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.= =
-: , '.'x':'=.;=:==:== *='=.:= ....i. ==. = =-.. Chainbir 750 via vent hale 757 and vent duct 760. The heat exits tower system.2000 through, . .., , .
:=',..'=== : . = :....
. . . . .
....i',..if: ii: 1.3:'; ..,=4 '. :. :: tolfor:houqing hole. 161 located in the rear of tower system 2000, away froth the patient and .... ., .; . =, .4,..- -.==== .=.=-.
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= : ., = ...
r===;=='...4"::::: ...''':' .-1: ...=- ' . irradiatiOn' ' . chamber 700 and holding irradiation in an uptight positiiMbetWiten IN k lamps.. : = . .. ...; , :::
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'; ...: '.".;: . - .....,; =':!: , I .758,. itiii;it 762 is at or near the bottom of photoactivation=chanter 700. Pivit*.ibly,.a=loak '3' .:.:.. l'...;;;I:. =2:.:,...:).t., = : .... =:...doleotor. circuit 763 is provided beloiv.tract 762 to detect any fitticl: leaks== .inlidiaticti chanter : = =...: . .. '= : = .........
'f =-= =4;:-1 .:=..,'. .1..= '=:'. ==== 700 chtring, before, or after operation. Leak detector circuit 763 has two =ipfeireites.patterne4 == = '' =
'...;;. õ= : .1 ,:=
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for application of a short circuit to test for discontinuities. One end of each electrode goes to an integrated circuit while the other end of each electrode is tied to a solid-state switch. The solid-state switch can be used to check for continuity of the electrodes. By closing the switch the electrodes are shorted to one another. The integrated circuit then detects the short.
Closing the switch causes a situation equivalent to the electrodes getting wet (i.e., a leak). IN
If the electrodes are damaged in any way, the continuity check will fail. This is a positive indication that the electrodes are not damaged. This test can be performed each time at system start-up or periodically during normal operation to ensure that leak detection circuit 762 is working properly. Leak detection circuit 762 helps ensure that leaks do not go unnoticed during an entire therapy session because the leak detection circuit is damaged. An electrical schematic of leak detector circuit 762 is provided in FIG. 20.
B. Centrifuge Chamber [00127] FIG. 19 illustrates centrifuge chamber 2101 in cross section with the housing of tower system 2000 removed. Rotational device 900 (also in cross-section) capable of utilizing 1-omega 2-omega spin technology is positioned within centrifuge chamber 2101.
Rotational device 900 includes a rotating bracket 910 and a bowl holding plate 919 for rotatably securing centrifuge bowl 10 (FIG. 1). Housing 2107 of centrifuge chamber 2101 is preferably made of aluminum or some other lightweight, sturdy metal.
Alternatively, other rotational systems may be used within tower system 2000 such as that described in U.S.
Patent No. 3,986,442, which is expressly incorporated herein by reference in its entirety.
[00128] Leak detection circuit 2106 is provided on back wall 2108 of housing 2107.
Leak detection circuit 2106 is provided to detect any leaks within centrifuge bowl 10 or the connecting tubes during processing. Leak detection circuit 2106 is identical to leak detector circuit 762 described above. An electrical schematic of leak detection circuit 2106 is provided in FIG. 21.
C. Fluid Flow Control Deck [00129] FIG. 22 illustrates control deck 1200 of tower system 2000 (FIG.
17) without a cassette 1100 loaded thereon. Control deck 1200 performs the valving and pumping so as to drive and control fluid flow throughout photopheresis kit 1000. Preferably, deck 1200 is a separate plate 1202 that is secured to base portion 2200 of tower system 2000 via screws or other securing means, such as, for example, bolts, nuts, or clamps. Plate 1202 can be made of steel, aluminum, or other durable metal or material.
[00130] Deck 1200 has five peristaltic pumps, whole blood pump 1301, return pump 1302, recirculation pump 1303, anticoagulant pump 1304, and red blood cell pump 1305 extending through plate 1202. Pumps 1301-1305 are arranged on plate 1202 so that when cassette 1100 is loaded onto deck 1200 for operation, pump loop tubes 1120-1124 extend over and around pumps 1301-1305 (FIG. 25).
1001311 Air bubble sensor assembly 1204 and HCT sensor assembly 1205 are provided on plate 1202. Air bubble sensor assembly 1204 has three trenches 1206 for receiving tubes 1114, 1106, and 1119 (FIG. 25). Air bubble sensor assembly 1204 uses ultrasonic energy to monitor tubes 1114, 1106, and 1119 for differences in density that would indicate the presence of air in the liquid fluids normally passing therethrough. Tubes 1114, 1106, and 1119 are monitored because these lines go to the patient. Air bubble sensor assembly 1204 is operably coupled and transmits data to the system controller for analysis. If an air bubble is detected, the system controller will shut down operation and prohibit fluid flow into the patient by occluding tubes 1114, 1106, and 1109 by moving compression actuators 1240-1242 to a raised position, thereby compressing tubes 1114, 1106, and 1119 against cassette 1100 as discussed above and/or shutting down the appropriate pump. HCT sensor assembly 1205 has trench 1207 for receiving HCT component 1125 of tube 1116. HCT sensor assembly 1205 monitors tube 1116 for the presence of red blood cells by using a photoelectric sensor. HCT sensor assembly 1205 is also operably coupled to and transmits data to the system controller. Upon HCT sensor assembly 1205 detecting the presence of red blood cells in tube 1116, the system controller will take the appropriate action, such as stopping the appropriate pump or activating one of compression actuators 1243-1247, to stop fluid flow through tube 1116.
100132] Deck 1200 also has five compression actuators 1243-1247 and three compression actuators 1240-1242 strategically positioned on plate 1202 so that when cassette 1100 is loaded onto deck 1200 for operation, each of compression actuators 1240-1247 are aligned with corresponding apertures 1137 and 1157. Compression actuators 1240-1247 can be moved between a lowered position and a raised position. As illustrated in FIG. 22, compression actuators 1243-1247 are in the lowered position and compression actuators 1240-1242 are in the raised position. When in a raised position, and when cassette 1100 is loaded onto deck 1200 as illustrated in FIG 25, compression actuators 1240-1247 will extend through the corresponding apertures 1137 or 1157 and compress the portion of flexible tubing that is aligned with that aperture, thereby pinching the flexible tube shut so that fluid can not pass. When in the lowered position, compression actuators 1240-1247 do not extend through apertures 1137 and 1157 and thus do compress the flexible tubing.
[00133] Compression actuators 1243-1247 are spring retracted so that their default position is to move to the lowered position unless activated. Compression actuators 1243-1247 are independently controlled and can be raised r lowered independent of one another.
Compression actuators 1240-1242 on the other hand are coupled together. As such, when one compression actuator 1240-1242 is lowered or raised, the other two compression actuators 1240-1242 are also lowered in raised accordingly. Additionally, compression actuators 1240-1242 are spring loaded so that their default position is to move to the raised position. Thus, if the system loses power during a therapy session, compression actuators 1240-1242 will automatically move to the raised position, occluding tubes 1114, 1106, and 1119 and preventing fluids from entering or leaving the patient.
[001341 Referring now to FIGS. 23 and 24, deck 1200 further includes system controller 1210, cylinder assembly 1211, manifold assemblies 1213, pump cable 1215, pump motor cable 1216, and timing belt assembly 1217. System controller 1210 is a properly programmed integrated circuit that is operably coupled to the necessary components of the system to perform all of the functions, interactions, decisions, and reaction discussed above and necessary to perform a photopheresis therapy according to the present invention.
Cylinder assembly 1211 couples each of compression actuators 1240-1247 to a pneumatic cylinder. Air ports 1212 are provided on the various elements of deck 1200 as necessary to connect air lines to the devices and the appropriate one of manifolds 1213. As such, air can be provided to the devices as necessary to actuate the necessary component, such as compression valves 1240-1247. All of these functions and timing are controlled by system controller 1210. Timing belt assembly 1217 is used to coordinate the rotation of rotating clamps 1203. Finally, plate 1202 includes a plurality of holes 1215, 1219, 1220, 1221, and 1218 so that the various components of deck 1200 can be properly loaded into and so that deck 1200 can be secured to tower system 2000. Specifically, pumps 1301-1305 fit into holes 1314, HCT sensor assembly 1205 fits into hole 1220, air bubble detector assembly 1204 fits into hole 1219, compression actuators 1240-1247 extend through holes 1218, and bolts extend through holes 1221 to secure deck 1200 to tower assembly 2000.

1. Cassette Clamping Mechanism [00135] Referring now to FIGS. 22 and 25, the method by which cassette 1100 is loaded and secured to deck 1200 will now be discussed. In order for system 2000 to perform a photopheresis therapy, cassette 1100 must be properly loaded onto deck 1200.
Because of the compression actuator valving system incorporated in the present invention, it is imperative that cassette 1100 be properly secured to deck 1200 and not shift or become dislodged when compression actuators 1240-1247 occlude portions of the flexible tubing by compressing the flexible tubing against cover 1130 of cassette 1100 (FIG. 3).
However, this requirement competes with the desired goals of ease in loading cassette 1100 onto deck 1200 and reducing operator errors. All of these goals are achieved by the below described cassette clamping mechanism.
1001361 In order to facilitate clamping of cassette 1100 to deck 1200, deck 1200 is provided with two catches 1208 and two rotating clamps 1203 and 1223. Catches 1208 have a slot 1228 near the middle of the top plate. Catches 1208 are secured to plate 1202 at predetermined positions so that the spacing between them is substantially the same as the spacing between tabs 1102 and 1103 on cassette 1100 (FIG. 2). Rotating clamps 1203 and 1223 are illustrated in a closed position. However, rotating clamps 1203 and 1223 can be rotated to an open position (not illustrated) manually or through the automatic actuation of a pneumatic cylinder. Rotating clamps 1203 and 1223 are spring loaded by torque springs so as to automatically return to the closed position when additional torque is not being applied.
Rotating clamps 1203 and 1223 are linked together by timing belt assembly 1217 (FIG. 24).
[00137] Referring now to FIG. 23, timing belt assembly 1217 comprises timing belt 1226, torque spring housings 1224, and tension assembly 1225. Timing belt assembly 1217 coordinates the rotation of rotational clamps 1203 and 1223 so that if one is rotated, the other also rotates in the same direction and the same amount. In other words, rotational clamps 1203 and 1223 are coupled. Tension assembly 1217 ensures that timing belt 1226 is under sufficient tension to engage and rotate the rotational clamp 1203 or 1223 that is being coordinated. Torque spring housings 1224 provide casings for the torque springs that torque rotational clamps 1203 and 1223 to the closed position.
[00138] Referring back to FIGS. 22 and 25, when loading cassette 1100 onto deck 1200, cassette 1100 is placed at an angle to deck 1200 and tabs 1102 and 1103 (FIG. 2) are aligned with catches 1208. Cassette 1100 is moved so that tabs 1102 and 1103 slidably insert into catches 1208. Rotational clamps 1203 and 1223 are in the closed position at this time.

The rear of the cassette 1100 (i.e. the side opposite the tabs 1102 and 1103) contacts rotational clamps 1203 and 1223 as tabs 1102 and 1103 are being inserted in catches 1108.
As force is applied downward on cassette 1100, rotational clamps 1103 and 1123 will be rotated to the open position, allowing the rear of cassette 1100 to move downward to a position below ledges 1231 of rotational clamps 1203 and 1223. Once cassette 1100 is in this position, the rotational clamps 1203 and 1223 spring back from the force applied by the torque springs and rotate back to the closed position, locking cassette 1100 in place. When in the locked position, cassette 1100 can resist upward and lateral forces.
[00139] To remove cassette 1110 after the therapy session is complete, rotational clamps 1203 and 1223 are rotated to the open position either manually or automatically.
Automatic rotation is facilitated by an air cylinder that is coupled to an air line and system controller 1210. Once rotational clamps 1203 and 1223 are in the open position, cassette 1100 is removed by simple lifting and sliding tabs 1102 and 1103 out of catches 1208.
2. Self-Loading Peristaltic Pumps [00140] Referring to FIG. 24, peristaltic pumps 1301-1305 are provided on deck 1200 and are used to drive fluids through photopheresis kit 1000 (FIG. 1) along desired pathways.
The activation, deactivation, timing, speed, coordination, and all other functions of peristaltic pumps 1301-1305 are controlled by system controller 1210. Peristaltic pumps 1301-1305 are identical in structure. However, the placement of each peristaltic pump 1301-1305 on deck 1200 dictates the function of each peristaltic pump 1301-1305 with respect to which fluid is being driven and along which pathway. This is because the placement of peristaltic pumps 1301-1305 dictates which pump loop 1220-1224 will be loaded therein.
[00141] Referring now to FIGS. 28 and 29, whole blood pump 1301 is illustrated in detail. The structure and functioning of whole blood pump will be described with the understanding that peristaltic pumps 1302-1305 are identical. Whole blood pump 1301 has motor 1310, position sensor 1311, pneumatic cylinder 1312, pneumatic actuator 1313, rotor 1314 (best illustrated in FIG. 30), and housing 1315.
[00142] Rotor 1314 is rotatably mounted within housing 1315 and is in operable connection with drive shaft 1316 of motor 1310. Specifically, rotor 1314 is mounted within curved wall 1317 of housing 1315 so as to be rotatable by motor 1310 about axis A-A. When rotor 1314 is mounted in housing 1315, a space 1318 exists between rotor 1314 and curved wall 1317. This space 1318 is the tube pumping region of whole blood pump 1301 into which pump loop tube 1121 (FIG. 33) fits when loaded for pumping. Position sensor 1316 is coupled to drive shaft 1316 of motor 1310 so that the rotational position of rotor 1314 can be monitored by monitoring drive shaft 1316. Position sensor 1311 is operably connected and transmits data to system controller 1210 (FIG. 24). By analyzing this data, system controller 1210, which is also coupled to motor 1310, can activate motor 1310 to place rotor 1314 in any desired rotational position.
[001431 Housing 1315 also includes a housing flange 1319. Housing flange 1319 is used to secure whole blood pump 1310 to plate 1202 of deck 1200 (FIG. 22).
More specifically, a bolt is extended through bolt holes 1320 of housing flange 1319 to threadily engage holes within plate 1202. Housing flange 1319 also includes a hole (not shown) to allow pneumatic actuator 1313 to extend therethrough. This hole is sized so that pneumatic actuator 1313 can move between a raised and lowered position without considerable resistance. Pneumatic actuator 1313 is activated and deactivated by pneumatic cylinder 1312 in a piston-like manner through the use of air. Pneumatic cylinder 1312 comprises air inlet hole 1321 for connecting an air supply line. When air is supplied to pneumatic cylinder 1312, pneumatic actuator extends upward through housing flange 1319 to a raised position.
When air ceases to be supplied to pneumatic cylinder 1312, pneumatic actuator retracts back into pneumatic cylinder 1312, returning to the lowered position. System controller 1210 (FIG. 22) controls the supply of air to air inlet hole 1321.
[001441 Curved wall 1317 of housing 1315 contains two slots 1322 (only one visible).
Slots 1322 are located on substantially opposing sides of curved wall 1317.
Slots 1322 are provided for allowing pump loop tube 1121 (FIG. 33) to pass into tube pumping region 1318.
More specifically, pump inlet portion 1150 and outlet portions 1151 (FIG. 33) of pump loop tube 1121 pass through slots 1322.
1001451 Turning now to FIGS. 30 and 31, rotor 1314 is illustrated as removed from housing 1315 so that its components are more clearly visible. Rotor 1314 has a top surface 1323, angled guide 1324, rotor flange 1325, two guide rollers 1326, two drive rollers 1327, and rotor floor 1328. Guide rollers 1326 and drive rollers 1327 are rotatably secured about cores 1330 between rotor floor 1328 and a bottom surface 1329 of rotor flange 1325. As is best illustrated in FIG. 29, cores 1330 fit into holes 1331 of rotor floor 1328 and recesses 1332 in bottom surface 1329. Guide rollers 1326 and drive rollers 1327 fit around cores 1330 and can rotate thereabout. Preferably, two guide rollers 1326 and two drive rollers 1327 are provided. More preferably, guide rollers 1326 and drive rollers 1327 are provided on rotor 1314 so as to be in an alternating pattern.
[00146] Referring to FIGS. 29 and 31, drive rollers 1327 are provided to compress the portion of pump loop tube 1121 that is loaded into tube pumping region 1318 against the inside of curved wall 1317 as rotor 1314 rotates about axis A-A, thereby deforming the tube and forcing fluids to flow through the tube. Changing the rotational speed of rotor 1314 will correspondingly change the rate of fluid flow through the tube. Guide rollers 1326 are provided to keep the portion of pump loop tube 1121 that is loaded into tube pumping region 1318 properly aligned during pumping. Additionally, guide rollers 1326 help to properly load pump tube loop 1121 into tube pumping region 1318. While guide rollers 1326 are illustrated as having a uniform cross-section, it is preferred that the top plate of the guide rollers be tapered so as to come to a sharper edge near its outer diameter.
Tapering the top plate results in a guide roller with a non-symmetric cross-sectional profile.
The tapered embodiment helps ensure proper loading of the tubing into the tube pumping region.
[001471 Rotor 1314 further includes cavity 1328 extending through its center. Cavity 1328 is designed to connect rotor 1314 to drive shaft 1316 of motor 1310.
[00148] Referring now to FIGS. 30 and 32, rotor flange has opening 1333.
Opening 1333 is defined by a leading edge 1334 and a trailing edge 1335. The terms leading and trailing are used assuming that rotating rotor 1314 in the clockwise direction is the forward direction while rotating rotor 1314 in a counterclockwise direction is the rearward direction.
However, the invention is not so limited and can be modified for counterclockwise pumps.
Leading edge 1334 is beveled downward into opening 1333. Trailing edge 1335 extends upward from the top surface of rotor flange 1325 higher than the leading edge 1334. Leading edge is provide for trailing edge for capturing and feeding pump loop tube 1121 into tube pumping region 1318 upon rotor 1314 being rotated in the forward direction.
[00149] Rotor 1314 also has angled guide 1324 extending upward, at an inverted angle, from rotor flange 1325. Angled guide 1324 is provided for displacing pump loop tube 1121 toward rotor flange 1325 upon rotor 1314 being rotated in the forward direction.
Preferably, angled guide 1324 has elevated ridge 1336 running along top surface 1323 for manual engagement by an operator if necessary. More preferably, angled guide 1314 is located forward of leading edge 1334.
[00150] Referring now to FIGS. 28 and 33, whole blood pump 1301 can automatically load and unload pump lop tube 1121 into and out of tube pumping region 1318.
Using position sensor 1311, rotor 1314 is rotated to a loading position where angled guide 1324 will face cassette 1100 when cassette 1100 is loaded onto deck 1200 (FIG. 25). More specifically, rotor 1314 is preset in a position so that angled guide 1324 is located between inlet portion 1150 and outlet portion 1151 of pump loop 1121 when cassette 1100 is secured to the deck, as is illustrated in FIG. 13. When cassette 1100 is secured to deck 1200, pump lop tube 1121 extends over and around rotor 1314. Pneumatic actuator 1313 is in the lowered position at this time.
[00151] Once cassette 1100 is properly secured and the system is ready, rotor 1314 is rotated in the clockwise direction (i.e., the forward direction). As rotor 1314 rotates, pump tube loop 1121 is contacted by angled guide 1324 and displaces against the top surface of rotor flange 1325. The portions of pump loop tube 1121 that are displaced against rotor flange 1325 are then contacted by trailing edge 1325 and fed downward into tube pumping region 1318 through opening 1333. A guide roller 1326 is provided directly after opening 1333 to further properly position the tubing within tube pumping chamber for pumping by drive rollers 1327. When loaded, inlet portion 1150 and outlet portion 1151 of pump loop tube 1121 pass through slots 1322 of curved wall 1317. One and a half revolutions are needed to fully load the tubing.
[00152] To automatically unload pump tube loop 1121 from whole blood pump after the therapy is complete, rotor 1314 is rotated to a position where opening 1333 is aligned with the slot 1322 through which outlet portion 1151 passes. Once aligned, pneumatic actuator 1313 is activated and extended to the raised position, contacting and lifting outlet portion 1151 to a height above trailing edge 1335. Rotor 1314 is then rotated in the counterclockwise direction, causing trailing edge to 1335 to contact and remove pump loop tube 1121 from tube pumping region 1318 via opening 1333.
D. Infra-Red Communication 100153] Referring to FIG. 34, tower system 2000 (FIG. 17) preferably further includes a wireless infrared ("ER") communication interface (not shown). The wireless IR interface consists of three primary elements, system controller 1210, IRDA protocol integrated circuit, 1381, and IRDA transceiver port 1382. The IR communication interface is capable of both transmitting and receiving data via IR signals from a remote computer or other device having IR capabilities. In sending data, system controller 1210 sends serial communication data to the IRDA protocol chip 1381 to buff the data. IRDA protocol chip 1381 adds additional data and other communication information to the transmit string and then sends it to IRDA
transceiver 1382. Transceiver 1382 converts the electrical transmit data into encoded light pulses and transmits them to a remote device via a photo transmitter.
1001541 In receiving data, IR data pulses are received by a photo detector located on the transceiver chip 1382. The transceiver chip 1382 converts the optical light pulses to electrical data and sends the data stream to IRDA protocol chip 1381 where the electrical signal is stripped of control and additional IRDA protocol content. The remaining data is then sent to the system controller 1210 where the data stream is parsed per the communication protocol.
[00155] By incorporating an IR communication interface on tower system 2000 real time data relating to a therapy session can be transmitted to a remote device for recording, analysis, or further transmission. Data can be sent via IR signals to tower system 2000 to control the therapy or allow protocols to be changed in a blinded state.
Additionally, IR
signals do not interfere with other hospital equipment, like other wireless transmission methods, such as radio frequency.
Photopheresis Treatment Process [00156] Referring together to Fig. 26, a flow chart illustrating an embodiment of the invention which includes photactivation of buffy coat, and Fig. 27, a schematic representation of apparatus which can be employed in such an embodiment, the process starts 1400 with a patient 600 connected by means of a needle adapter 1193 carrying a needle, for drawing blood, and needle adapter 1194 carrying another needle, for returning treated blood and other fragments. Saline bag 55 is connected by connector 1190 and anticoagulant bag 54 is connected by connector 1191. Actuators 1240, 1241, and 1242 are opened, anticoagulant pump 1304 is turned on, and saline actuator 1246 is opened so that the entire disposable tubing set is primed 1401 with saline 55 and anticoagulant 54. The centrifuge 10 is turned on 1402, and blood-anticoagulant mixture is pumped 1403 to the centrifuge bowl 10, with the A/C pump 1304 and WB pump 1301 controlled at a 1:10 speed ratio.
[00157] When the collected volume reaches 150 ml 1404, the return pump 1302 is set 1405 at the collection pump 1301 speed until red cells are detected 1406 at an HCT sensor (not shown) in the centrifuge chamber 1201 (Fig. 19). Packed red cells and buffy coat have at this point accumulated in the spinning centrifuge bowl and are pumped out slowly at a rate, controlled by the processor, which maintains the red cell line at the sensor interface level.

[001581 The red cell pump 1305 is then set 1407 at 35% of the inlet pump speed while controlling 1408 the rate to maintain the cell line at the interface level until the collection cycle volume is reached 1409, at which point the red cell pump 1305 is turned off 1410 and the fluid path to the treatment bag 50 via the HCT sensor 1125 is opened by lowering actuator 1244, and stops when the HCT sensor 1125 detects 1411 red cells.
"Collection cycle volume" is defined as the whole blood processed target divided by the number of collection cycles, for example a white blood process target of 1500 ml may require 6 cycles, and so 1500/6 is a volume of 250 ml. With whole blood continuing at 1410 to be delivered from the patient to the bowl and the red cell pump off, red cells will accumulate and will push out the buffy coat from inside the bowl 10. The red cells are used to push out the buffy coat and will be detected by the effluent hematocrit (HCT) sensor, indicating that the buffy coat has been collected.
[00159] If another cycle is needed 1412, the centrifuge 10 effluent path is returned 1413 to the plasma bag 51 and the red cell pump 1305 rate is increased 1413 to the inlet pump 1301 pump rate until red cells are detected 1414, which is the beginning of the second cycle. If another cycle 1412 is not needed, the centrifuge 10 is turned off 1415 and inlet pump 1301 and anticoagulant pump 1304 are set at KVO rate, 10 ml/hr in this embodiment.
The effluent path is directed 1416 to the plasma bag 51, the red cell pump 1305 rate is set 1417 at 75 ml/min, the recirculation pump 1303 and photoactivation lamps are turned on 1418 for sufficient period to treat the buffy coat, calculated by the controller depending on the volume and type of disease being treated.
[00160] When the bowl 10 is empty 1419, the red cell pump 1305 is turned off 1420 and the plasma bag 51 is emptied 1421 by opening actuator 1247 and continuing return pump 1302. The return pump 1302 is turned off 1422 when the plasma bag 51 is empty and when photoactivation is complete 1423, the treated cells are returned 1424 to the patient from the plate 700 by means of the return pump 1302. Saline is used to rinse the system and the rinse is returned to the patient, completing the process 1425.
[00161] The anticoagulant, blood from patient, and fluid back to patient are all monitored by air detectors 1204 and 1202, and the fluid back to the patient goes through drip chamber and filter 1500. The pumps, 1304, 1301, 1302, 1303, and 1305, the actuators 1240, 1241, 1242, 1243, 1244, 1245, 1246, and 1247, and the spinning of the bowl 10 are all controlled by the programmed processor in the tower.

[00162] The process and related apparatus have significant advantages over prior processes and apparatus in that the invention allow buffy coat to be in the bowl longer since red cells are being drawn off while collecting buffy coat in the bowl while centrifuging, keeping more buffy coat in the bowl until the desired amount of buffy coat cells are collected prior to withdrawing the collected buffy cells. Platelets, leukocytes, and other buffy coat fractions can also be separated, or red cells can be collected rather than returning them with plasma to the patient as the illustrated process does.
[00163] It has been found that increasing the time that buffy coat 810 is subjected to rotational motion in centrifuge bowl 10 yields a "cleaner cut" of buffy coat 820. A "cleaner cut" means that the hematocrit count (HCT%) is decreased. HCT% is the amount of red blood cells present per volume of buffy coat. The amount of time that buffy coat 820 is subjected to rotational motion in centrifuge bowl 10 can be maximized in the following manner. First, whole blood 800 is fed into first bowl channel 420 as centrifuge bowl 10 is rotating. As discussed above, whole blood 800 is separated into buffy coat 820 and RBC's 810 as it moves outwardly atop lower plate 300. Second bowl channel 410 and third bowl channel 740 are closed at this time. The inflow of whole blood 800 is continued until the separation volume 220 is filled with a combination of buffy coat 820 near the top and RBC's 810 near the bottom of centrifuge bowl 10. By removing RBC's 810 from centrifuge bowl via second bowl channel 410 only, additional volume is created for the inflow of whole blood 800 and the unremoved buffy coat 820 is subjected to rotational forces for an extended period of time. As centrifuge bowl 10 continues to rotate, some of the RBC's 810 that may be trapped in buffy coat 820 get pulled to the bottom of centrifuge bowl 10 and away from third bowl channel 740 and buffy coat 820. Thus, when third bowl channel 740 is opened, the buffy coat 820 that is removed has a lower HCT%. By controlling the inflow rate of whole blood 800 and the outflow rates of buffy coat 820 and RBC's 810, a steady state can be reached that yields a buffy coat 820 with an approximately constant HCT%.
[00164] The elimination of batch processing and the improved yields achieved by the current invention, have reduced the treatment time necessary to properly treat patients. For an average sized adult, 90-100 milliliters of buffy coat/white blood cells must be captured in order to conduct a full photopheresis treatment. In order to collect this amount of buffy coat/white blood cells, the present invention needs to process around 1.5 liters of whole blood. The required amount of buffy coat/white blood cells can be removed from the 1.5 liters of whole blood in about 30-45 minutes using the present invention, collecting around 60% or more of the total amount of the buffy coat/white blood cells that are subjected to the separation process. The captured buffy coat/white blood cells have an HCT of 2% or less. In comparison, one existing apparatus, the UVAR XTS, takes around 90 minutes to process 1.5 liters of whole blood to obtain the sufficient amount of buffy coat/white blood cells. The UVAR XTS only collects around 50% of the total amount of the buffy coat/white blood cells that are subjected to the separation process. The HCT of the buffy coat/white blood cells collected by the UVAR XTS is around, but not substantially below, 2%. Another existing apparatus, the Cobe Spectra Tm by Gambro, must process 10 liters of whole blood in order to collect the sufficient amount of buffy coat/white blood cells. This typically takes around 150 minutes, collecting only 10-15% of the total amount of the buffy coat/white blood cells that are subjected to the separation process, and having an HCT of about 2%. Thus, it has been discovered that while existing apparatus and systems require anywhere from 152 to 225 minutes to separate, process, treat, and reinfuse the requisite amount of white blood cells or buffy coat, the present invention can perform the same functions in less than 70 minutes.
These times do not include the patient preparation or prime time. The times indicate only the total time that the patient is connected to the system.

Claims (29)

Claims What is claimed is:

1. A method of collecting a desired blood component comprising:
providing a separator having an inlet, a first outlet, and a second outlet;
adding an anticoagulant fluid to whole blood drawn from a source in a predetermined ratio to form a mixture of whole blood and anticoagulant fluid;
pumping the mixture of whole blood and anticoagulant fluid into the separator via the inlet at a selected inlet rate;
separating the mixture into blood components of different densities;
withdrawing plasma and red blood cells from the separator while continuing to pump the mixture of whole blood and anticoagulant fluid into the separator, the plasma and red blood cells being withdrawn at rates so as to build up buffy coat in the separator, the plasma being withdrawn via the first outlet and the red blood cells being withdrawn via the second outlet; and upon a predetermined amount of buffy coat building up in the separator, collecting the buffy coat from the separator, the method further comprising injecting a photoactivation chemical into the collected buffy coat; and irradiating the collected buffy coat within an irradiation chamber until a predetermined amount of energy has been transferred to the collected buffy coat; and wherein overall treatment time is less than about 70 minutes.

2. The method of claim 1 wherein the step of collecting the buffy coat from the separator comprises discontinuing the withdrawal of red blood cells from the second outlet, thereby causing the red blood cells to push the buffy coat out of the separator via the first outlet.

3. The method of claim 2 further comprising collecting the withdrawn buffy coat in a treatment bag.

4. The method of claim 2 further comprising discontinuing the collecting of buffy coat when red blood cells are detected in an outlet line fluidly connected to the first outlet.

5. The method of claim 1 wherein the step of withdrawing plasma and red blood cells from the separator comprises: withdrawing only the plasma from the separator via the first outlet until a predetermined amount of red blood cells are detected in the separator; and upon the predetermined amount of red blood cells being detected in the separator, withdrawing red blood cells from the separator at a rate so as to maintain the amount of red blood cells present in the separator at approximately the predetermined amount.

6. The method of claim 5 wherein the predetermined amount of red blood cells is detected using a hematocrit sensor.

7. The method of claim 1 further comprising: collecting the withdrawn plasma in a plasma storage bag; mixing the withdrawn plasma with a priming fluid; and upon a selected amount of plasma being collected in the plasma storage bag, returning the mixture of plasma and priming fluid to the source.

8. The method of claim 7 further comprising mixing the withdrawn red blood cells with the plasma and priming fluid mixture from the plasma collection bag and returning the red blood cells-plasma-priming fluid mixture to the source at a rate approximately equal to the inlet rate.

9. The method of claim 1 wherein the step of pumping the mixture into the separator comprises passing the mixture through a cassette for controlling fluid flow before the mixture enters the separator.

10. The method of claim 1 wherein the step of irradiating the buffy coat comprises recirculating the collected buffy coat between a treatment bag and the irradiation chamber.

11. The method of claim 1 further comprising: passing the irradiated buffy coat through a filter; and returning the irradiated buffy coat to the source.

12. The method of claim 1 wherein the overall treatment time is less than about 45 minutes.

13. The method of claim 11 wherein the filter is within a cassette for controlling fluid flow.

14. The method of claim 1 further comprising collecting the withdrawn red blood cells.

15. The method of claim 1 wherein the source is a patient, a whole blood storage bag, or, a blood donor, and wherein the separator is a centrifuge bowl.

16. A system for collecting a desired blood component, the system comprising:
means for combining anticoagulant with whole blood withdrawn from a patient at a selected ratio of anticoagulant to whole blood;

a fluid flow controller;
a pump;
a separator;
means for controlling the pump to:
pump the combination of whole blood and anticoagulant through the fluid flow controller to the separator, wherein the separator is configured to operate until air is displaced; and continue to pump the combined whole blood and anticoagulant into the separator until a selected amount of plasma is collected;
means for mixing plasma with a priming fluid and for returning the mixture of plasma and priming fluid to the patient at the same rate as incoming whole blood until red blood cells are detected;
means for withdrawing red blood cells;
means for controlling the speed of the pump so as to maintain a red blood cell line selected level in the separator while buffy coat is collected in the separator;
means for, at a selected time, when a desired amount of buffy coat cells are collected in the separator, causing the pump to continue to pump whole blood into the separator while discontinuing pumping red blood cells, thereby causing the red blood cells to push buffy coat out of the separator until a desired amount is collected in a buffy coat collector; and means for discontinuing collection of buffy coat when red blood cells have been detected, wherein the separator is configured to separate the mixture of whole blood and anticoagulant into a plurality of blood components according to density, wherein the system further comprises:
means for mixing a photoactivation chemical with at least one of the blood components to form a mixture of the photoactivation chemical and the at least one blood component; and means for irradiating the combination of the at least one blood component and photoactivation chemical to produce an irradiated combination for return to the patient.

17. The system of claim 16, further comprising:

means for mixing the withdrawn red blood cells with plasma from the plasma collection bag for return to the patient;
means for pumping buffy coat to a treatment bag;
means for injecting photoactivation chemical into the buffy coat in the treatment bag;
an irradiation chamber and means for pumping the buffy coat and photoactivation chemical mixture from the treatment bag to the irradiation chamber;
means for recirculating the buffy coat between the treatment bag and the irradiation chamber;
means for irradiating the buffy coat in the irradiation chamber while recirculating;
means for pumping the irradiated buffy coat from the irradiation chamber to the 10 treatment bag;
a filter;
means for pumping irradiated buffy coat from the treatment bag through the filter for return to the patient.

18. The system of claim 17 wherein the priming fluid is a mixture of anticoagulant and saline.

19. The system of claim 17 or claim 18, wherein:
the fluid flow controller is a cassette;
the separator is a centrifuge bowl;
the air is displaced into a plasma bag, and further comprising:
a bowl sensor, at which the red blood cells are detected; and a sensor interface, at which the red blood cell line is detected.

20. The system of any one of claims 17 to 19, further comprising means for separating the buffy coat cells and collecting one or more selected components, the components selected from the group consisting of platelets and leukocytes.

21. The system of any one of claims 17 to 20, further comprising means for priming the separator with anticoagulant and saline mixture.

22. The system of any one of claims 17 to 21, further including means for rinsing the separator, treatment bag, and irradiation chamber with saline to provide a resultant rinse solution for return to the patient.

23. A method of treating blood for photopheresis treatment comprising:
adding an anticoagulant fluid to whole blood withdrawn from a source in a predetermined ratio to form a mixture of whole blood and anticoagulant fluid;
separating the mixture of whole blood and anticoagulant into a plurality of blood components according to density;
mixing a photoactivation chemical with at least one of the blood components to form a mixture of the photoactivation chemical and the at least one blood component;
irradiating the combination of the at least one blood component and photoactivation chemical for return to a patient;
wherein the entire photopheresis treatment is completed in less than about 70 minutes;
and wherein the step of separating the mixture of whole blood and anticoagulant fluid comprises: providing a separator having an inlet, a first outlet, and a second outlet; pumping the mixture of whole blood and anticoagulant fluid into the separator via the inlet at a selected inlet rate; and withdrawing plasma and red blood cells from the separator while continuing to pump the mixture of whole blood and anticoagulant fluid into the separator, the plasma and red blood cells being withdrawn at rates so as to build up buffy coat in the separator, the plasma being withdrawn via the first outlet and the red blood cells being withdrawn via the second outlet; and upon a predetermined amount of buffy coat building up in the separator, collecting the buffy coat from the separator.

24. The method of claim 23 wherein the entire photopheresis treatment is completed in less than about 45 minutes.

25. The method of claim 23 wherein the at least one blood component is buffy coat, a leukocyte, or platelets.

26. The method of claim 23 wherein the at least one blood component is buffy coat.

27. The method of claim 23 wherein the step of collecting the buffy coat from the separator comprises discontinuing the withdrawal of red blood cells from the second outlet, thereby causing the red blood cells to push the buffy coat out of the separator via the first outlet; and discontinuing the collecting of buffy coat when red blood cells are detected in an outlet line fluidly connected to the first outlet.

28. The method of claim 23 wherein the step of withdrawing plasma and red blood cells from the separator comprises: withdrawing only the plasma from the separator via the first outlet until a predetermined amount of red blood cells are detected in the separator; and upon the predetermined amount of red blood cells being detected in the separator, withdrawing red blood cells from the separator at a rate so as to maintain the amount of red blood cells present in the separator at approximately the predetermined amount.

29. The method of claim 23 further comprising irradiating the collected buffy coat within an irradiation chamber until a predetermined amount of energy has been transferred to the collected buffy coat, the predetermined amount of energy being sufficient to induce apoptosis.