CA2109837C - Apheresis method and device - Google Patents

Abstract

A simplified fluid separation method and device usable for various apheresis procedures, including plasmapheresis. At least one pump is utilized to draw a first fluid (e.g. whole blood) into a separation device. The separation device then operates to separate the fluid (e.g. whole blood) into first and second fluid fractions (e.g.
a cell concentrate and blood plasma). The first and second fluid fractions are pumped from the separation device to separation first and second fluid fraction containers, both of which are positioned on a single weighing device, such as an electronic load cell. At least one of the fluid fractions is subsequently removed from its fluid fraction container and returned to the human subject or other fluid source. Weights recorded by the single weighing device are then utilized to calculate the actual weights of fluid and/or fluid fractions pumped by at least one pump during the procedure. Such actual weights of fluid and/or fluid fractions are then utilized to calculate new pump flow constants, thereby enabling the calibration of the pump(s) to be corrected, on the basis of such new pump flow constants, prior to subsequent utilization of the pump(s) for pumping the fluid and/or fluid fractions. The single weighing device may also be utilized to monitor the weight change or rate of weight change occurring as the fluid fractions are pumped into and/or out of the fluid fraction containers, thereby providing a means for monitoring and verifying the pressures and flow rates within the system.

Description

. 0 2~ 03837 i . ~

,..
APH~RESIS METHOD AND D m CE

F~ e! ~ ~ f ~he Tnv~n~t or~ ~
The present invention pertains generally to fluid procesolng egulpment ana more ~artl¢ularly to a method and devtce for effectlng apheres~ 8 proceaure~.

Rl~rounA of ~h~ Tnv~nt~ on In current ~ractlce, there exi~t numerous situatlons in which it 18 de~lrable to efficiently separate fluids such as whole blood lnto two or more 6pec~fic ¢omponents (e.g. plas~a, red blood cells, leukocytes, platelets, etc.). Tn co~mer¢lal appl~cations, it is often nece~sary ~to separate whole blood into two or more constituents in order that a speciflc blood const~tuent may be harvested and utilized for the preparation of medically useful blood derlvative~ or preparation~ ~e.g. packed red blood cells, fresh frozon pla~a, specific blood factor~, etc.). Also, 20 ln th-rapeutlc ~ettl~gs lt is often d~slrable to separate whole blood into two or ~ore constltuentg for purposes of - treatlng or removlng a speciflc con~tituent(~) of the blood ln accordance with cortaln thorapeuti~ protocols.
~ n al~o~t ail blood constituent separation procedures, whothor com~erclal or therapeutic, guantities of whole blooA are witharawn fro~ a hu~an sub~ect, the whole blood i~ the~ ~eparatQd lnto two or ~ore con~tituent fract~on~
an~ ~at l~a-t one of the con~tltuent fracttons i8 ~ubs-guently transfusea back into the human ~ub~ect. The 0 nonrelnfu8ed constltuont fraction~s) ~ay be retA1ne~ for u~ i~ the ~ep-rAtlon of varloug blood pla¢ma product~
(e.g. fr--h froz-n pla-~a, albu~in, or Factor VIII) or, ln ~' the th-r4peutlc applloatlon~, may be di~carded and replaced by pla~a fron a hoalthy donor or may be sub~ected to 0 !~ ~ 3 7 physical pharmacologic or radiologic treatment and sub~e~uently returned to the human sub~ect.
The ~eneral term ~apheresis~ used to describe three-step proeedures wherein whole blood is a) withdrawn, b) separated into fractions and c) at lea~t one of the fraetions i~ retransfused into the human sub~ect. Speeifie types of apheresis proeedures inelude: ~plasmapheresi6~
(for the eollection of blood plasma), ~leukapheresis~ (for the collection of leukocytes), ~thrombocytapheresis~ (for the eolleetlon of platelets), therap~utie plasma exchange (wherein a portion of the subject~ 8 blood plasma i8 replaced with other fluids, such as plasma obtained from another human), and therapeutie plasma processing wherein -~ a portion of the subject's plasma is separated, treated or - 15 processed and then returned to the sub~ect.
Prior to the 1970'8, when it was desired to separate ~: whole blood into ~pecific blood c~nstituent(s), it was generally neeessary to draw, on a unit by unit basis, quantitles of whole blood from a human donor. Eaeh unit of ,~ .
whole blood withdrawn was manually eentrifuged to effeet separatlon of the desired blood constituent or component and, there~fter, the remaining portions of the blood were manually reinfused into the donor. It was typically -necessary to repeat such a procedure, on the ~ame donor, '~ 25 several tl~es (i.e. unit after unit) until the maximum ~-~ allowable ~olume of pla~ma or other blood con~tituent had been eoileoted.
More recently, automated apheresi~ maehines been developed to minimize the degree of manual endeavor required whèn separating and eolleetlng speeifie blood eonstituents. These automated apheresis maehines typieally eompri~e a eentral eomputer eleetrieally oonnected to, and programmed to control, a ~ystem of tubes, vessels, filters and at least one blood separation device. The blood . ~
~-35 separation device is typically a rotating centrifugal ~J
~ , .

.:
h e ~lV9837 filter or membrane which operates to separate the desired specific blood constituent(61 (e.g. plasma, cellfi, platelets, etc.). ~he typical automated apheresis maQhines of the prior art incorporate one or more ~peristaltic pumps~ or ~tubing pumps~ for moving blood, blood con6tituents and/or reagent solutions through the machine.
Such ~peristaltic pumps~ or ~tubing pumps~ generally consist of a 6eries of rotatlng rollers or cams over which a length of plastic tubing i~ stretched. Rotation of the cams or rollers then serve~ to dynamically compress regions of the tubing 80 as to move the desired fluids through the tubing at a desired rate. The u~e of such peristaltic pumps is particularly suitable in automated apheresis eguipment because the mechanical working components of such pumps do not come in contact with the blood or other fluids being pumped, thereby preventing contamination of such ~ fluids. Moreover, the use of peristaltic pumps permits lntermittent disposal and replacement of the attendant tubing, as i8 commonly done to maintain sterile and hygienic oonditions during each blood donation procedure.
These peristaltic pumps are, however, given to a great deal of uncertainty or ~drift" in calibration. Such uncertainty ~; or ~drift~ in the pump c~ ration occurs because of variations in the size and material consistency of the pump tubing, variations in the rotational speed of the pump aam or rollers, otretching and/or wear of the pu~p tubing, etc.
The re8ultant varlations in the throughput of the peri8t~1tic pu~ps complicates the operation of automated apheresi8 machines because 8uch variation~ in pump throughout render lt dlfficult to accurately control volume - of bIood or blood constituents collected ~n a particular ;~ procedure. Strict aontrol of the volumes of blood or blood -~ constituent~ withdrawn ~8 required by governmental re~ulation intended to prevent inadvertent or purposeful 3S over-withdrawal of blood or specific blood constituents o ~lu9837 from.the human sub~ect, as may result ln in~ury to the human ~ub~ect. Furthermore, variations in throughput of the pumps is problematic because many steps ~n automated apheresis procedures reguire precise knowledge of âctual S fluid flow rates. Also, certsin system com~one~ts, such as the separator device 20 reguire pres~ure and flow control in order to operate safely and efficiently.
In view of the above-stated shortcomings of the prior - art automated apheresis machines, there exists a-need for new apheresls machines and/or methods whlch minimize the expense and/or complexity of apheresis procedures, without any prohibitive diminution in the ability t~ monitor and - maintain accurate control of the c~l~hration ana throughput of the blood a~d other fluids being extracted from the human su_ject and processed by the aphere~is machine.
~:
~ry of ~hol T.~ ol~
The present invention comprises a simplified fluid separation method and device.
In aocordance w$t_ the prQgent invention, there is 7~ provlded a fluid separation or apheresis ~ethod wherein at least one pump is utilized to draw fluld ~e.g. blood) from a source (e.g. a human subject) and to move such fluid into a fluld separation device. Thereafter, the separation de~ice ls utilized to separatQ the fluid (è.g. blood) into at least a~first ~l~o~ fractisn (e.g. cell concentrate) and a secon~ hl~oA ~raotion (e.g. pla~ma). A single welghing device ls operati~ely connected to a flrst fluld fractlon ~con~D-r (e.g. a cell bag) and a ~econd fluid fract$on cont~t~r (e.g. ~ plasm~ ~essel) 80 ~8 to measure the combined we~ght o~ such first fluia fraction cont~ner and econd fluld fractlon cont~ne~ along with the contents thereof. Inltlally, the weight on the weighing device is that of the empty first fluid fraction container and the empty second fluid fraction container, and such weight may be recorded or stored. After the fir~t and second fluid fractions have been collected in the respective containers, a second weight on the weighing device may be recorded. Such second weight includes the first and second fluid fraction containers as well as the first and second fluid fractions contained therein. Thereafter, the first fluid fraction is removed from the first fluid fraction container and reinfused into the human subject. Following such reinfusion, a third weight on the weighing device (i.e. the weight of the empty first blood fraction container and the weight of the second blood fraction container plus its contents) may be recorded. The weights recorded on the weighing device may then be utilized to calculate new flow constants for the pump(s) utilized in drawing and/or reinfusing the fluid and/or fluid fraction(s). The calibration of the pump(s) may then be adjusted in accordance with the newly calculated flow constants.
Another aspect of this invention is as follows:
An apheresis method comprising the steps of:
(a) fluidly connecting a blood separation device to the vasculature of a human subject;
(b) operating at least one pump to withdraw whole blood from the human subject and to move said whole blood into said separation device;
(c) providing a single weighing device having a first blood fraction container and a second blood fraction container po~itioned thereon, such that said weighing device will measure the combined weight of the said first blood fraction container and said second blood fraction container, along with any material contained therein;
(d) recording an initial weight on said weighing device when said first blood fraction container and said second blood fraction container are empty;

~ CA 02109837 1997-12-22 -5a-(e) operating said separation device to fraction the whole blood into at least a first blood fraction and a second blood fraction;
(f) recording a second weight on said weighing device after said first blood fraction and said second blood fraction have been collected in said first blood fraction container and said second blood fraction container;
(g) providing a fluid connection between said first blood fraction container and said human subject;
(h) operating at least one pump to reinfuse said first blood fraction, through said fluid connection, into said human subject; and (i) recording a third weight on said weighing device after said first blood fraction has been removed from said first blood fraction container reinfused into said human subject.
Further in accordance with the invention, weights recorded by the single weighing device may be continuously or periodically used to monitor the flow of first fluid fraction during reinfusion. The monitored weight, or change in weight, is then compared to an n expected" weight based on the expected throughput of the pump being utilized to effect such reinfusion. If the monitored weight, or change in weight, is found to differ more than an allowable amount from the "expected" weight, such is taken to be an indicator of either (a) depletion of the first blood fraction from the first blood fraction container or (b) a malfunction in the system. At such point, the reinfusion pump(s) is stopped.
Still further in accordance with the invention, there is provided an automated fluid processing or apheresis machine having at least one pump, a fluid or blood separator and a single weighing device with separate fluid fraction collection vessels (e.g. a plasma vessel and a flexible eell coneentrate bag) positioned thereon. This automated maehine may be utilizedeto oarry out the method of the present invention as described herein.
Still further in aeeordanee with the invention, an automated apheresls maehine may comprise a plurality of pump~ te.g. a whole blood pump and a eell eoncentrate pump) whieh operate, in eombination, to effeet the withdrawal, ~eparation and reinfusion of the blood and/or blood eomponents. A 8ingle weighing deviee is utilized to simultaneously weigh at least two of the separated blood eomponents, at various points in the proeedure. The weights reeorded by the ~ingle weighlng device may, thereafter, be utilized to ealculate actual flow constants for the pumps and/or to monitor and verify quantities or dynamies of fluid movement(s) within the machine.

Rrl Qf De~er~p~on of ~he nraw~gs Figure 1 i8 a sehematie diagram of a plasmapheresis method and device of the prior art, during a typieal eolleetion eyele;
Flgure 2 18 a ~chematic diagram $11ustrating a plasmapheresls method and device of the present inventlon, during a typioai eolleetion eyele;
Figure 3 i~ a sehematie diagram illustrating a pla~mapheres;is method and deviee of the prior art during a ~;~ typieal reinfu~ion eyele;
Pigure~ 4 i8 a sohematie diagram illustrating a plasmapheres1~ method and deviee of the pre6ent~ invention during a typleal reinfusion eyele;
- 30 Pigur- Sa i6 a flow diagram illu8trating a plasmaph-re'sls methoa in aeeord~nee with the pre~ent - invention;
Figure Sb is a continuation of the flow diagram of Figure Sa;
'~ ~

' ~i~9837 , -7-Figure 6 is a frontal perspective view of an automated plasmapheres~ B machine of the prior art;
' Flgure 7 i8 a frontal perspective view o~ an automated -. plasmapheresis machine of the pre~ent invention; -~~
! 5 Figure 7a is a frontal per~pective view of an ,~ automated plasmapheresis machine of the present invention, ? with darkened areas showing the portions of the machine which contain fluid during the initiat~on of a priming cycle;
Figure 7b i~ a frontal per~pective view of a plasmapheres~s machine of the present invention with darkened areas showing the portions of the machine which contain fluid at the end of a priming cycle;
Figure 7c is a frontal perspective view of a plasmapheresi~ machine of the present invention with darkened aseas showing the portions of t~.e machine which ~ contain fluid during the beg~ nni ng of a collection cycle;
: Figure 7d is a frontal per6pective view of a plasmaphere~is machine of the present invention with ~: ~ 20 dar~e~e~ areas 8howing the portions of the mach~ne which contaln fluid at the end of a collectlon eycle;
Figure 7e is a frontal perspective view of a : plasmapheresis machine of the present invention with ~a r~e~e~ areas ~howing the portions of the ~achine which :25 contain fluid during the begin~ing of a reinfusion cyele;
and :Figure 7f i8 a frontal perspeetive view of a @ ~::plasmapheresis ~achine of the present invention with darkened areas showing the portions of the machlne which oontain fluid at the end of a relnfusion cyele.
Figure 8 i~ a perspective view of a presently preferred blood fllter/bubble trap usable as a component ~n the deviee of the pre8ent invention;
Figure 8a i8 a perspectlve view of a portion of the -35 blood filter/bubble trap shown in Pigure 8;

. . . ~, . ..
- ,. . .

o i 1)9837 Figure 8b is a partial longitudinal sectional view through line b-b' of Figure 8;
Figure 8c is a cross-sectional view through line c-c' of Figure 8;
Figure 9a is an illustration of that whieh eonstitutes the ~DRY TARE~ measurement taken in aceordance with the method of the present invention;
Figure 9b is an illu8tration of that which constitutes the ~PRIMED TARE~ (fir~t eycle~ measurement taken in aceordanee with the method of the present invention;
Figure 9e is an illustration of that which eonstitutes the UEMPTY CELL BAG TARE~ measurement taken in aeeordanee with the method of the presént invention;
Figure 9d i8 an illustration of that whieh eonstitutes the UPRIMED TAREU (later eyeles) measurement taken in aceordanee with the method of the present invention;
Figure 10 i8 an illustration of that whieh constitutes the ealeulated predieted plasma weight (Ppr~) in aeeordanee with the methoa of the present invention;
Figure 11 i8 an illustration of that which eonstitutes the POST CQT-T-FCTION WEIGHT determined in aeeordanee with the method of the present ~nvention; and ~:~ Figure 12 i8 an illustration of that whieh eon8titutes ~; the POST REINFUSION WEIGHT determined in aecordance with the method of the pre~ent invention.

a~l~A r~cr1~ nn of l-h~ Tl ~ rA1~1v~

i. The 8yste~ of the Present I~ on The followlng detailed de~eription and the a¢oompanying drawlngs are provided for purposes of llu6trating eerta~n em~odiment6 of the present invention and are not intended to limit the ~cope of the invention ~n any way.

:~:
~ ~ .

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o "' ~109S37 ~ he present invention i8 particularly applicable to automated plasmapheresis equipment and, thus, will be described herein with particular reference to plasmaphere~ls procedures. It will be appreciated, h~e~er~ that the lnvention 18 egually appllcable to other fluld processing and apheresis procedures, includ~ng but not limited to, leukapheresis, thrombocytapheresis, therapeutic plasma exchange, therapeutic plasma processing, etc.
Flgures 1 through 4 are comparative, schematic illu~trations of a prior art apheresis method and device tFigure~ 1 and 3) and an embodiment of the method and device of the present invention (F$gures 2 and 4).
- Generally, the apheresis systems of the prior art and lS those of the present invention incorporate certain common : components. A venipuncture needle 10, lOa is percutaneously insertable into a peripheral vein of a human plasma donox. A bag or other cont~ner of anticoagulant . ~olution 12, 12a is fluidly connected, by tube 16, lSa, to : 20 a ~ixing chamber 14, 14a which i~ proximal to needle 10.
: An antlcoagulant pump 18, 18a is positioned on tube 16, 16a to draw anticoagulant solution from bag 12, 12a through tube 16, 16a, into the mixing chamber 14, 14a.
Anticoagulant ~olution entering the mixing chamber 14, 14a ~:: 25 will ~oin with, and will become dispersed in, blood which has been extr~cted proximally through nes~e 10.
: ~ blood ~eparation apparatus 20, 20a is fluidly oonn r ~ea to the mixing chamber 14, 14a by tube 22, 22a.
A bidirectional blood pump 24, 24a, preferably a ~:~ 30 peri~t~ltic pump, i~ positioned on tube 22, 22a for alternate withdrawal of blood and infusion of cell 'concentrate through needle 10, lOa. Movement of the blood pump 24, 24a in a clockwise direction will move blood in the direction of arrow A (withdraw), while movement of blood pump 24, 24a in a counter-clockwise direction will r ~ 10 ~ 9 ~ 3 7 i~ move fluids (e.g. cell concentrate from line 60) in the F~ direction of arrow B, back to the human subject.
A cell pump 44, 44a is positioned on line 42, 42a to move cell ooncentrate out of the ~eparation dev~ce 20, 20a 5 at a controlled rate. Close control of the calibration of : the cell pump 44, 44a is critical in that there exists strict limits on the amount of oxygen transporting red blood cells which may be held in the extracorporeal circuit at any point in time. Thus, close control of the amount of 10 cell concentrate being pumped by the cell pump 44, 44a is necèssary to ensure that such limits are not exceeded.
Also, the calibration and throughput of the cell pump directly affects the transmembrane pressure within the separ~tion device 20, 20a. If the calibration and 15 throughput of the cell pump 44, 44a is not closely controlled, errant pressures within the separation device 20, 20a may result in hemolysis of the blood cells, incomplete separatlon of the blood and~or an automatic error signal and shut down of the machine. A plasma 20 cont~ne~ 26, 26a ~ oonnected to t~e plasma outlet port of blood separator 20, 20a by way of tube 28, 28a. A s~ e bag or container 30, 30a is connected to blood line 22, 22a -~; at a point near the inlet port of blood separation device 20, 20a. A saline valve 34, 34a is alternately 25 positionable in an open po~ition whereby flow through line ; 32, 32a, ls permltted ana a closed po~ition whereby flow through llne 32, 32a ~s prohibited.
A blood valve 36, 36a ~ positioned on blood line 22, 22a. Blood valve 36, 36a ~s alternatQly pos~t~onable in an open poslt~on whereby flow through line 22, 22a is perm~tted, ~nd a closea posit~on whereby flow through line 22, 22a is blocked.
A plasma valve 38, 38a is po~itioned in line 28, 28a.
The plasma valve 38, 38a ls alternately positionable in an open position whereby flow through line 28, 28a is ,' .. . .

permitted and a closed position whereby flow through line 28, 28a i# prohibited.
In the typical apheresis maeh~ne of the prior art (Figures 1 and 3), a cell eone~ntrate reservo~r io ls loeated remotely from th~ ~eparate plasma vessel 26.
Separate, diserete systems are employed to monitor the relative weights and/or volumes of a) ~ell eoncentrate colleeted in the eell reservoir 40 and b) plasma eollected in the plasma vessel 26. As shown, the plasma vessel 26 is attached to weighing device 64, sueh as an electronic balance, 80 as to continuously monitor the weight of the plasma eontainer 26 and. its .eontents.. The level of eell eoneentrate in the eell reservoir 40 is, on the other hand, often mea~ured by a series of eleetronie sensors or other measuring device(s) loeated in or ad~aeent to the eell reservoir 40. Thus, the weighing deviee 64 and the sensors or other measuring device(s) associated to the eell : reservoir 40, are ~eparately eonneeted to, and provide ..separate si~nal~ to a eentral eomputer 65, 65a. The .:~ 20 eomputer 65, 65a may inelude an eleetronie mieroproees~or, ~: t~ing and logie eireuits, program memory, eo~munieation busses and power supply eonnections.
The eell eoneentrate re~ervoir o~ the prior art maehine 40 (Figures 1, 3) is fluidly eo~neeted to the eell eoneentrate output port of the blood separation deviee 20 by way o~~a flexible tube 42. A eell pump 44, sueh as a peri~taltle pump, is positioned on tube 42 80 as to pump -' the eell eoncentrate from the eell eoneentrate outlet port ::~ of the blood separation device 20 through l~ne 42 into the eell eoneentrate reservoir 40. The outl~t port of eell :eoneentrate re:servoir 40 i~ eo~ns~ed to the lower portio~
:~ of the blood line 22 by way of a flexible tube or line 46.
Cell eoneentrate valve 48 is positioned on line 46. The eell concentrate valve 48 is alternately pos~tionable in an ;~

.' '~lOg837 ~ -12-open position whereby flow through line 46 is permitted, a clo~ed po~ition whereby flow through line is prohibited.
As ~hown ln the diagrams .of Figs 2 and 4, the ~ystem of the present invention differs from the prior art system shown in Flgures I and 3 in that the concentrate outlet port of the blood 6epar~tion device 20a i8 connected to the top inlet port of a blood filter/bubble trap 50 by way of a flexible tube or line 52. ~he cell pump 44a i8 po8itioned on line 42a to pump cell concentrate -from the cell concentrate output port of blood separator device 20a into the top port of blood filter/bubble trap 50. Another ~ flexible tube or l~ne 56 conne¢ts the right--side bottom port .of blood filter/bubblé trap 50 to a bottom fill port of cell bag 58. A left side bottom port of cell filter/bubble trap 50 i~ connected to a point on line 22a, as shown, by way of a flexible tube or line 60. A cell concsntrate valve 62 i8 positioned on line or tube 60.
Cell concentrate valve 62 i8 alternately positionable in an open po8ition whereby flow t~rough line 60 i~ permitted, ~20 and a closed position whereby flow through line 60 i8 : blocked.
The darkened tubes and components (shown in Figures 1 and 2) lndicate the respective flow paths of fluids w~thln a typical prior art apheresis ~ystem during collection (Figure 1) and reinfu~ion lFigure 3).
As speci~10ally lllustrated in Figure 1, the collection of plasma by a prior art plas~aphere~i~ machine was generally accompllshed with valves 36 and 38 in their open po~itions and valves 34 and 48 in their closed position8. Antiooagulant pu~p 18, blood pu~p 24 and cell :pump 44 are conco~itantly actuated during colle¢tion, so a~
to pump flulds ln the dlre¢tion~ indicated by the arrows of Figure 1. Specifi¢ally, an anticoagulant pump 18 turns in a clockwise direction to pump dilute anticoagulant sol~tion from anticoagulant reservoir 12, through line 16, into the ,:
~' ~ "
-13- 21~37 mixing chamber 14 which is positioned proxlmal to venipuncture ~eedle ~0. Blood pump 24 rotates in a clockwise direction and operates to withdraw blood through needle 10 ~uch th~t blood will become mixed with anticoagulant solution as the blood is drawn through the mixing chamber 14. Whole blood (mixed with anticoagulant solution) i~ then withdrawn by blood pump 24, through line 22, lnto tbe separation device 20. The separatlon device substantially separates blood plasma from a cell concentrate which contains the formed elements of t~e blood (i.e. red cells, white cells and platelets). The cell pump 44 operates to withdraw the cell concentrate from the cell concentrate outlet port of blood geparation device 20, through 11ne 42 and deposits the cell concentrate in cell lS concentrate reservoir 4~. Since valve 48 is in its closed~ position, the cell concentrate is prevented from moving past valve 48 when the devlce is in the depicted collection mode. Air di~placed from the interior of the reser~oir is vented through a hydrophobic filter/vent port 41 formed in the top of the reservoir 40. Blood plasma flowing from the plasma outlet port of the blood separation device 20 is permitted to drain through line 28 lnto plasma colleotion vessel 26.
In the device of the present invention (~igures 2 and 4) a i~n~!e we~g~n~ ~ev~ce 64a, uch ~as an electronic ~l~nce or load cell, is utilized to concomitantly weigh ~ a) ~he plasma conta~er 26a and its contents, and b) the' -- cell conce~trate bag 58 and its contents. The use of this ~ingle weighing dev~ce 64a for both the plasma cont~ner 68a ~na tbe cell bag 58 eliminate6 the need for a separate system for colleqtin~ and measuring the cell concentrate at a locatlon remote from the pla~ma contA~ner. Also, the use - of the ~ingle weighing device 64a, in accordance with the method of the present invention, provides ~or highly accurate measurement of the throughput, of the blood pump ~10983~

24, 24a and cell pump 44, 54, thereby permittlng accurate and frequent recalibratlons thereof. Addltionally, this invention enables continuous, redundant monitorlng of the blood/cell concentrate flow during withdrawal ~ and S reinfusion by providing a continual lndicatlon of flow rate ~ based on the changes of weight being recorded by the single ; weighing device 64a as the withdrawal or reinfu~ion occurfi.
'5 The change in weight or rate of change in weight recorded by welghing device 64a is then continuously or periodically compared to the calculated flow rate or actual rotations of pump 44a. If the actual or expected flow through pump 44a differs more than a certaln amount (e.g. 25%) from the flow rate indicated by the chan~e in weight being recorded by the weighing device, such will indicate a problem with the sy~tem, such as a tubing leak, vessel fracture or improperly rigged or malfunotioning pump. Thus, this redundant, comparative flow monitoring capability provided ~y the single weighing device 64a, is also an advantage of the present invention. Additionally, the invention provides for the use of an inexpensive pla~tic cell ,~ concentrate contA~er bag 58 and inexpensive blood filter/bubble trap S0 a~ opposed to the more expensive components u~ed in ~ome prior art devices, such as the ~~ rigid, vented cell reservoir 40 with attendant electronic (LED) volume monitoring used in the prior art ~ystem shown in Figures 1 and 3.
The general method by which the aphere8is system of the present invention operatès i8 shown in Figures 5a-Sb.
This method i8 more fully de~cribed herebelow with specific' reference to the ~chematic diagrams of Figures 2 and 4.

ii. The Nethod of the Pre8ent Invention Initially, the empty plasma reservoir 26a and cell concentrate bag 58 are placed on a ~ingle weighing device - 35 84a. A ~DRY TARE" is then measured by the weighing device ~, .

~, ~1~983 64a. The ~DRY ~ARE~ value is communicated to the computer 65a wherein the ~DRY TARE~ value i8 stored. The ~DRY TAREU
rvalue is the combined weight of a) the empty plasma container 26a, and b) the empty cell bag 58. This ~DRY
5 TARE~ step ifi carried out at the beg~nn~n~ of the procedure, prior to the initial priming of the system, as illustrated in Figure 9a. The ~DRY TARE~ value is the combined weight of the empty plasma vessel 26, ~6a, 234, 234a and the empty cell bag 58, 237. In subseguent cycles 10 after the initial cycle, an ~EMPTY CELL BAG TARE~ 105 is determined and stored instead of the UDRY TARE" determined and stored at initiation o~ the first cycle. The ~M~-Y
CELL BAG TARE~ 105 differs from the ~DRY TARE~ in that it includes the weig~t of plasma collected in previous 15 collection cycles, as illustrated in ~igure 9c Thereafter, a portion of the system (e.g., the blood tube 22a, b~ood ~eparator device 20a, tube 52, blood filter/bubble trap 50, tube 56 and blood bag 58 ) is initially ~rimed witk a guantity of anticoagulated whole 20 hlooA withdrawn through ven$puncture needle lOa. Such prim~ng of the system 110 will typically result in a small amount of whole blood being disposed in the bottom of the cell concentrate bag 58. At thls point, a ~PRIMED TARE~ i8 measured ~12 by the weighing device 64a. ~he ~PRIMED T~RE~
25 value i~ communicated to the computer 65a wherein such ~PRIMED TARE~ value is stored. The ~PRIMED TARE~ value is the comb~ed weight of the a) empty plasma cont~i~er, and b) cell bag containing the small amount of pri~ing blood as illu~trated in Figure 9b.
After the ~PRIMED TARE~ has been recorded 112, an lnitial collection cycle is begun 114. During such collection cycle, the blood valve 36a is in its ~openU
position, the infusion yalve 62 is in its ~closed~
position, plasma valve 38a is in it~ ~open~ posit~on and blood pump 24a and cell pump 44a are operated in their - ' ~ o ~ lVt~37 rQ~pective, clockwise and counter-clockw~se directions, at specifically controlled rates, as dictated by the program of the computer 65a. The ~et rates of the pumps 24a and S4 are calculated by the computer 65a on the basls of the desired pressures to be maint~e~ within the attendant tubing 22, 52, 28a and the blood separation device 20a.
The rate of the blood pump 24a i8 also determined, to some degree, in view of the volume and pressure of blood available to be withdrawn from the blood vessel of the human subject.
The total volume of blood to be withdrawn into the extracorporeal circuit in any given collection cycle is controlled by preeetting the number of rotations to be made by the cell pump 44a during the next collection cycle. The numbers of rotations that the pumps 24a and 44a will undergo, in each given collection cycle, is controlled by computer 65a on the basis of a preset Upump flow constant"
for each pump (BP and CP). The de~ired number of rotations ~ for any given collection cycle i8 ~enerally determined on the basis of the following eguation:
~.~
t;o~ No. 1 Weight of Material Counted Pltm~ ~m~~r of Pl-m~ Rev~. (Rev.) 8p.Gr. of Material (g/ml) Flow Constant (Rev./ml) ~ .
~
To control the volume to be pumped during the f ~ rst or ~tart-up collectlon cycle (step 114-116), the desired - rotatlons for the cell pump 44a wlll be preset by th~
computer 65a on the basi~ of an ~initial~ flow con~t~nt for each pump. Thereafter, for each repetitive collection cycle, an ~ad~u~ted~.flow constant will be determined and stored in the computer 65a. Each such ~adjusted~ flow g837 constant will be based on actual measurement~ made during the prev~ou~ collection cycle. Such frequent ad~ustment of the desired rotations of the blood pump and cell pump helps to insure that accurate fluid volumes are maint~ined throughout the procedure.
The collection is accomplished by r~nn~n~ the blood pump 24a and cell pump 54 in their respective ~collection~
directions or modes. Typically, such will require that the blood pump 24a be rotated in a clockwi~e direction while the cell pump 54 be rotated in a counter-clockwlse direction. Typically, the cell pump 44a is utilized to precisely gage and control the amount of red cells withdrawn in a single collection cycle and the blood pump 24a continues to run in conjunction with the cell pump 44a until the cell pump is stopped (i.e. where it has undergone a present number of rotations. Thus, in any collection cycle prior to the final collection cycle of a given procedure, the cell pump 54 will undergo a predetermined number of rotations as preset in the computer 65a or as selected or overridden by the operator. The present number of rotations will achiove a precalculated guantity of cell concentrate pumped by cell pump 44a. Such precalculated quantity of blood cell concentrate withdrawal is generally related to a ~pecific weight of cell concentrate cont~ne~
within the cell bag 58 and 18 below the maximum allowable -~- extracorporeal red cell volume permitted by applicable government regulations.
In order to insure that the maximum allowable plasma collection is not exceeded, it i8 desirable to continuously or periodically calculate the current predicted or - calculated plasma wt. (Pp~) and to continuously, or at di~crete time points during each colloction cycle, compase' such predi¢ted plasma volume to the maximum allowable volume of~plasma withdrawal (P~x) 116. The Pm~X~ in most instances, is determined from generally published data ~, . ~ .

~109837 tabies or nomograms, based on the height and/or weight of a generally healthy blood donor and in accordance with governmental regulations. In certain therapeutic instances ~ however, the Pm~ will be determlned and ~et by the operator or medical practitioner t~ g ~nto account the general health of the patient and~or other facts relating to the therapeutic procedure being performed.
In a preferred embodiment of the present invention, the computer 65a continuously monitors the P~" in compari~on to P~. The predicted plasma (Pp~ determined by the following formula:

F.~1A t~o~ No.2 Primed Cell Bag ~ z Primed Tare - Empty Cell Bag Tare ~ t~ on No . 3 Pp" = Current Weight - Dry Tare- Primed Cell Bag - Current Cell ~.~ Coast Bias When P~" i8 determined to equal Pm~X, the collection i8 immediately terminated by the computer 65a and the device moves directly.into the final reinfus~on cycle of the procedure, as will be fully described hereinafter.
In a typical prefinal collection cycle (a full ¢ollection cycle whlch yields a final volume of plasma collectea which 18 less than P~l) prlor to the flnal collection cycle dur~ng which the procedure is terminated, the end of collection will be marked by a weight of red cell con¢entrate w~t~in the cell bag 58 and an attenAant weight of separated plasm~ wlthln the plasma contalner 26a.
After the particular collection cycle has been ended 118, the weigher 64a will take a ~post-collectlon weight~ 122, as illustrated in Figure 11 and will transmit such weight ~, . . .

.. ..

o -19- ~1~9837 to the computer 65a wherein it will be stored. The "post-collect~on weight~ 122 is the combined weight of a) the p~asma cont~e~ plus all pla6ma contained therein, and b) the cell bag plu8 all cell concentrate (and any priming S blood) collected therein plu8 any pri~ing blood, pr~i~e~
cell bag ~, 324, contained therein.
After the ~post-colleotion weight" has been recorded 122, the blood valve 36a will move to its ~closed~ position and reinfusion valve 62 will move to its ~opened~ positlon.
The blood pu~p 24a will then be operated in its counter-clockwise direction to effect reinfusion of the cell concentrate (and/or any priming blood) from the cell bag 58. through~tube 56, through blood filter/bubble trap 50, through tube 60, through mixing chamber 14a, and distally through needle lOa, into the blood vessel of the human donor. It is desirable that such reinfusion cycle ef~ect complete reinfusion of all cell concentrate (and/or priming ~ blood) contained in the cell bag 58a. Thus, the computer j 65a may be capable of continuously or periodically monitoring the flow of fluid through the reinfusion system : in order to detect when the cell bag 58a has been fully emptied and to automatically stop the counter-clockwise movement of the blood pump 24 at such point. The actual number of revolutions made by the blood pump 24 during each reinfu~ion of cell concentrate i~ counted 128 and stored in co~puter 65a. If a subseguent collection cycle is to be co~pleted, (i.e. if the volume of plasma collected thus far has not reached P~), then the weighing device 64a wi 11 determine and ~tore 134 a ~post-re~nfugion weight~. ~he ~po~t-reinfusion weight~ is the combined wetght of a) the plasma oon~n~r plu8 all pl~sma cont~n~d t~ere~n, and b) - the empty cell bag~
After the ~pogt-reinfugion weightU has been ~tored 134 in the oomputer 65a, the computer 65a will proceed to calculate the ~weight of cells reinfused~ 136. The ~weight of cells reinfused" is determined on the basis of the ' following formula:

~uat~on No. 4 Wt. of Cell Concentrate Reinfusedtg) -, (Post-Coll.Wt.(g~ - Post-Reinf.Wt.(g)~

t ~dditionally, the computer will calculate the "weight 10 f actual plasma collected" 138 as of the end of the ~ust-ended collection cycle. The "we~ght of actual plasma collectedN, ~wt. of blood pu~ped during collectionl' and the wt. of cell concentrate pumped during collection~ are then calculated by the following equations nos. 5, 6, and 7:
~uation No. 5 Wt. of Pla6ma = Post-Reinfusion W~.(g) Collected (g) - EMPTY CELL BAG TARE (g) .
~ t~on No. 6 Wt. of Blood = Post-Collection Wt.(g) Pumped dur$ng ( see Fig. 11) Collection - Cycle (g) - PRIMED TARE (g) (see Fi~. 9d) ; ~uat~on No. 7 Wt. of Cell Concentrate - Po6t Collection Pumped During Collection Wt. (g) Cycle.(g) (see F$g. 11) 'r ' ~ Post Reinfusion Wt. (g) t8ee Figure 12) - PRIMED
CELL BAG

' ~ 2109837 The eomputer 65a will also ealeulate new eo~lect flow eonstants for the blood pump 24a and eell pump 44a.
Also, the eomputer 65a will automatieally, on the ba~ls of sueh new flow eon~tants, reset the deslred number of rotations for the blood pump ~nd eell pump for the next eollection eycle. Sueh resetting of the desired pump rotation~ prior to each eollection cyele serves to ensure that during the next eolleetion eyele, there ~ill be aeeurate eontrol of the volumes of fluids pumped by the blood pump 24a and cell pump 44a.
Thevealeulation of the collectlon flow constants for the blood pump and cell pump are ba#ed on the following equations nos; 8 and 9:

~u~t~o~ No. 8 Blood Pump No. of Pump Colleetion Flo.Con. - S~.~r. of Rloo~ t~/mlL X revs. during (Rev/ml) Wt of Blood eollection 20Pumped (g) (Re~s) R~-~t~o~ No, 9 Cell Pump No. of Pump Colleetion Flo.Con. = ~.Rr. of Cel~ (~/mlL X rev~. during Rev/ml) Wt. of Cell collection Coneent. Pumped(~) (Revs) , ~he welght of eell~ reinfused will subsequently be utilized n~the ealeulation of a rev~ed ~e~n~.~Q~n flow eonstant for the blood pump 24a by applieation of Equation l and the newly ealeulated reinfus1on flow eonstant for sueh pump ~-~ will be re8et in the computer for subsequent reinfusion , ~ -~- ~ 35 ey~les.~
The ealeulation of the relnfusion flow eonstant for the blood pu~p lc based on the following formula:

~ ~ .

: ' 210~837 ;

P~-~tl oll No . 10 Blood Pump Sp.Gr. of Cell No. of Pump - Reinfus. ~lo.Con. = Co~c. (~ml ) X revs. during (Rev/ml) Wt. of Cell Reinfu~ion (Revs) Conc. Reinfused(g) ;

After the new flow constants have been calculated and ~tored in computer 65a, and, the desired number~ of rotations of the cell pumps 44a has been ad~ustea (steps 140 and 142), a new collection cycle i8 begun. Steps 105-142 are repeated until ~uch time as the computer 65a determines, during step 116 (i.~. monitoring of Pp" versus Pm~) that, the Ppr~ is equal to P~x~ When it i8 determined that Pp~ eguals P~, the collection i8 automatically terminated by the computer 65a, and the final reinfusion ~tep i8 carried out.
After the fi~l reinfusion step has been completed, the actual total amount of pla~a collected will be etermined by the weighlng device 65a. Such Total Plasma Collected (Actual) will be stored by the computer 65a. The Total Plasma Collected (Actual) is determined by the following formula:
' uat~on No. 11 Total Pla~ma Collected (Actual) (g?
(Post-Reinfu~ion Wt. (g) - D~Y TARE (g)) f lii. A 8pecific Plasmapheresis H~ch~e ~ah~l~ent of The Present Invention In accordance with the genesal ~y~tem and method :
described above, the following detailed description of a - specific plasmapheresi~ machine embodiment of the present invention is provided.
~ ' :
f~ .

i ~
~ 2~9837 ,.

A blood line 180, 180a is fluldly connected to a venipuncture needle which resides within a perlpheral voin of a human donor (not shown). The proximal end of the blood llne 180, 180a bifurcates into a left ~enous pres~ure transducer line 182, 182a and a right blood pump tube 184, 184a. The left venous pressure transducer line is connected to a venous pressure transducer located within the hou~ing 200 80 as to provide to the computer (not shown) cont~ or di~crete monitoring of the pos-itive or negative pressure within the blood line 180, 180a. The blood pump tube 184 is operatively positioned within a peristaltic blood pump 186, 186a. The opposite end of blood pump line 184a is concom~tantly connected, by way of a Y connector, to a reinfusion line 188, 188a and a first 6eparator feed line 190, 190a bifurcates into a second separator feed line 192, 192a and a transmembrane pressure transducer line 194, 194a. The transme~brane pressure transaucer line 194, 194a is connected to a transmembrane pre~sure transducer (not shown) which, in turn, is cQ~ ec~ed to the system computer (not ~hown) ~uch that the computer may continuously or discretely monitor the junction of the first ~eparator feed line 190, 190a and the second separator~feed line 192, 192a.
A presently preferred, automated plasmapheresis mao~e of the present invention is shown in Flgures 7-7f.
Figur- 6 shows a similar ~achine of the pr~or art, which do-s not incorporate the ~ethod or aev~ce of the prefient invention.
Referring to Figures 6 and 7, the prior art machine (Figure 6) and the machine of the pre~ent invent~on (Figure 7) ~hare certain common components~ Both of these machines comprise a housing 200, 200a wherein a central computer~, wiring, electrical connections and other general components of the device (all not ~hown) are ~ounted. On the frontal ; 35 surface of the housing 200, 200a, there is provided a ~ ,~ , ~ ' ~ 21~837 ~y~tem of tubes, pumps, reser~oirs and components for effecting the desired a) withdrawal, b) ~eparation, and c) ; reinfu~ion of blood and~or blood component~. Generally, a 6aline line 202, 202a leads from an attendant bâg or cont~ner of phy~ologlcal 0.9% ~aline solutlon and an antieoagulant line 204, 204a leads from an attendant bag or eGntA~ner of antieoagulant solution. The ~aline line 202, 202a passes through a power actuated elamp 206, 206a and is eonnected to a Y adaptor 208, 20Ba. The oppo~lte side of the Y adaptor 208, 208a i~ concomitantly eonnected to the inlet port 210, 210a of a blood ~eparation device 212, 212a. ~he blood 6eparation device may eonsist of any type of device capsble of effectuating the de6ired 6eparation of blood eonstituents. In a preferred embodiment, ~eparation device 212, 212a eomprises a disposable, rotational plasma separator having an internal rotatable membrane which i~
driven rotationally by an external magnetic motor drive (not shown). Sueh rotation of the inner membrane causes blood plasma to geparate from the eell eoneentrate (a eombination of red blood cells, blood whlte eell~, platelets and a small amount of plasma). The eell eoneentrate flows out of the separation device 212, 212a through eell eoneentrate outlet port 214, 214a. The plasma flows out of the separation device 212, 212a through plasma 25 outlet port 216, 216a.
- A eoneentratea eell llne 220, 220a i8 eonneeted to the eell eoneentrate outl~t port 214, 214a of the blood separation deviee 212, 212a. The eoneentrated eell line 220, 220a is mounted within a peristaltie eell pump 222, ~: 30 222a. the p~rista:ltic cell pump 222, 222a may be ub~tantially identieal to the previously des¢ribed blood pump 186, 186a, or ~ay eompri6e any other type of pump eapable of effeeting the desired movement of eell coneentrate through eoneentrated eell line 220, 220a.

~09837 In the prior art device (Figure 6), the concentrated cel~ line ~20 carries cell concentrate from the blood separation device 212, through cell pump 222 and into the inlet port 224 of a rigid cell collection reservoir 226 having a cap~city of approxim~tely 300 milliliters. Such 300 ml capacity allow~ adequate extra space in the cell bag 237 when a usual collection amount limit of 180 ml of cell concentrate is observed. ~ cell concentrate outlet 228 is located at the bottom of the ce~l concentrate re~ervoir 226. The cell concentrate reinfusion line 188 i~ connected to the cell concentrate outlet 228 of the cell concentrate re~ervoir 226 80 as to permit reinfusion of the cell concentrate into the human donor when the clamp 189 is open, clamp 191 is closed and the blood pump 186 is operated in its ~reinfusion~ direction (counter-clockwise).
Also on the device of the prior invention (Figure 6) a pla~ma line 230 extends downwardly from the plasma outlet port 216 of the blood ~eparat~on device 212, passing through plasma cla~p 232 and le~ng directly into the top of pla~ma collection ve~sel 234.
~In contrast, the device of the present invention ;(F1gure 7) is configured 80 a~ to eliminate the need for a rigla cell reservoir and to collect the cell concentrate in - a low co~t flexIble cell bag 236 which hangs from the same we~ghing ~evice 235a as the plasma collection ve~sel 234a.
Also, in the device of the pregent invention~(Figure 7) the ;cono-ntrated cell line 220a~ i~ conneoted to one of the ~nlet/outlet ports of a blood filter/bubble trap 240. The ~loo~ filter/bubble trap 240 contains a ~creen or quantity of fibrous filtration ~aterial so as to trap bubbles, foreign ob~ects, e~boli, etc. (A specifio preferred e~bo~ment of the blood fllter/bubble tra~ 240 i~ ~hown in Flgure~ 8a through 8d and will be ~ore fully described hereinafter.) ~ .

~::

~1()9837 ,' Al80 fluidly connected to the blood filter/bubble trap ,S, 240, opposite the inlet of the concentrated cell line 220a is a lower cell line extension 242. Such lower cell--line extension 242 fluidly connects the blood filter/bubble trap 240 to the inlet/outlet port 244 po~itioned at the bottom of the cell collection bag 237.
A preferred mode of operation of the device shown in ~igure 7 is illustrated in Figures 7a through 7f.
Specifically, Figure 7a shows a preferred plasmapheresis machine of the present invention during the initial priming of the system. Such priming of the system is effecting by closing clamp l91a, opening, clamp 189a and operating blood pump 186a in it8 ~collectionU direction (clockwise) while anticoagulant pump 205a operates relatively slowly in its operative direction (clockwise). The combination of such ,~: will result in withdrawal of whole blood (containing a mall amount of anticoagulant) through the blood l,ine 180a, : ~ blood pump line 184a, opening clamp 189a, through blood ~ filter/bubble trap 240, down the lower cell line 242 and :: 20 into the very bottom of the cell bag 237. This initial ~:~ pri~ing ~tep i8 illustrated by the darkened and shaded areas shown in Figure 7a. Generally, it is predetermined, - ~ based on the calculated dead space of the tubing and comr~nents, that approximately 32 ml of whole blood mu~t be pumped by~the bloo~ pu~p ln order to ef~ec~ this ini~ial ~ primlng step;ana to bring whole blood through to the bottom '.~: of the c~ll bag 237. ..... Thu8, the computer (not shown) signals tl~e blood pump 186a to rotate ~n a cloclcwise diré¢tion. The blood pu-np 186a stops after a mass of 12 30 - gram- i~ a-t-ctea on'the welghing aevi¢e 235a, a~ generally provides for initial priming of the lower portlon of the ~: system as ~hown in Fiçlure 7a.
~; After the initial priming step has been completed, the device moves on to a secondary priming step known as the ~' 35 "filter prime~ he "filter prime~ step is illustrated by ~109837 the darkened and shaded areas in ~igure 7b. During the filter prime step, the clamp l91a i8 opened, clamp 189a is allowed to remain open, and the blood pump 186a is operated in its ~collectionU direction tclockwise) for a sufficient 5 number of rotations to pass whole blood upwardly through line 192a and to generally fill the concentrated cell line 220a, and the remainder of blood filter/bubble trap 240.
'This will also result in the flow of some additional whole sblood into the lower concentrated cell line 242 and the 10 entry of a slight additional amount of blood into the bottom of the cell bag 237. Based on the initial, .. .
empirically determined or otherwise chosen pump ~low constants, the blood pump 186a and the cell pump 222a are commanded by the computer (not 6hown) to pump sufficient amounts of blood to fill the tubes, blood separator and blood filter/bubble trap, as shown in Figure 7b. ~he computer (not shown) permits the blood pump 186a to undergo a preset nu~ber of revolutions determined to deliver that decired volume of blood and thereby effecting the desired filter prime without aspirating more than the necessary amount of blood from the patien~.
After the "filter primeU step has been completed, the ~PRIMED TARE~ ~tep 112 as lllustrated in Figure 9d, is carried out. Thereafter, the ~nit~al collection cycle 114 is begun.
The collection 6tep, as appl$ed to the presently preferred device, is illustrated in Figure 7c. Dur~ng collection, the anticoagulant pump 205a, blood pùmp 186a and cell pump 222a are all operative in their ~collection"
directions. Valve 191a is opened and valve 189a i8 closed.
Whole blood, along with a small amount of anticoagulant solution, is drawn by blood pump 186a, through the attendant tubing, into the blood separation device 212a.
Plasma çlamp 232a is opened and cell pump 222a operates to withdraw cell concentrate 220a from the blood ,' ,, .,, . . ~ " . . .

' ~la~s37 ; separation device 212a. The cell concentrate passes through blood filter/bubble trap 240, down the lower cell concentrate line 242 and is collected ~n the cell bag 237.
It will be appreciated that, while the collection process is cont~n~ g, the computer may continually monitor the plasma predicted (P~") versus pla~ma maxlmum (P~x) in accordance with step 116 of the inventive method (Flgure 3a). If, at any point, the Ppr~ becomes equal to P~,~, the computer will immediately stop the blood pump 186a, anticoagulant pump 205a, and cell pump 222a, thereby terminating the collection at P~x~ The device will, upon detection of Pp" eguals P~,~, move into reinfusion mode in accordance with step 124 of the inventive method (Figure 3a). However, if Ppr~ does not become egual to P~x during the collection cycle, that collection cycle will be permitted to continue to full completion (e.g. collection of 180 milliliters of cell concentrate) where the cell pump 222a has undergone its preset number of rotations based on the precaloulation of necessary rotations to obtain the desired amount (e.g. approximately 180 milliliters) of cell ~- ~ concentrate in the cell bag 237. When the cell pump 222a has undergone lts preset number of rotations, the computer will stop the movement of all pumps 184a, 205a, 222a, thereby ~n~ ~ ng that collection cycle. Of course, during the collection, the computer will continually monitor the instant predlcted plasma volume (P~) and will contlnuously or periodically compare Ppr~ to the maximum allowable plasma volume, in accordance with ~tep 118 of the inventive method (Figure 3a).
The end of the collection cycle is lllu8trated ln Figure 7d.
Prior to beg~ nn1 n~ reinfusion, the weighing device 235a will measure the ~post-collection weight~ and ~uch value will be stored in-the computer. Thereaf~er, the ~ ~ ' . .

'~109837 device will begin relnfusion of the cell concentrate into the donor.
Reinfusion of the ¢ell concentrate i6 effected by opening cla~p 189a, closing clamp l91a, and r~)nn~ng the blood pump 186a in it~ ~reinfusionU direction (counter-clockwise) until the entlre amount of cell concentrate contained in the cell bag 237 has been reinfused into the human donor. In a preferred embodiment, the computer will ~onitor the flow of cell concentrate through the device ln order to determine when the dynamics of reinfusion flow indicate that the entire volume of red cell concentrate (approximately 180 ~l) has been reinfused. Thls may be achieved by cont~m~lly monitoring the rate at which the weight on weighing device 235a change~ with respect to lS blood pump flow rate and determining from the detected change in weight on weighing device 235a, when the cell bag 237 has been emptied by applying the function, such as:
2g < Mag ¦Current weight on - Past weight on < 6g ¦weighing device (g) weighing device (g) where1n: ~past weight~ i8 the weight which ~ was on the weighing device at the - ti~e when the expected ml. of pump flow was 4 ml. less that the pre8ent expected ml. of pump flow.

Additionally, during both collection and reinfusion, the co~puter will cont~u~lly verlfy the functionlng of the pump~ by app}ylng a function #uch a~ the above-~et-forth funct~on~ and, lf at any point, the magnitude of difference between current wt. and past wt. exceed~ the allowable range, the device will ~hut down and the operator will be '" . ~ 30 ~ 2~98~7 .. . .
signaled to check for possible malfunctions (e.g. leaks in the system). Detecting an empty cell bag can be distin~~ e~ from a system malfunction b~D~ upon a predicted expected time o~ ence of the emptying.
;
During the reinfusion, the computer will count and store the number of rotations undergone by blood pump 186a in its "reinfusion" direction. This number will be subsequently -utilized in recalculating and adjusting the reinfusion pump (i.e. reverse direction) flow constant of the blood pump 186a, in accordance with the method of this invention.
At the end of reinfusion, the cell bag 237 will be completely empty as shown in Figure 7f. At ~hat point, the weighing device 235a will obtain the post-reinfusion weight ; in accordance with step 134 of the method (Figure 3b).
Thereafter, the computer will calculate the a) weight of cell concentrate reinfused (step 136), b) weight of actual plasma collected (step 138), c) collection flow constants for th~e blood pump and cell pump (step 140), and d) a reinfusion flow constant for the blood pump (step 142).
The desired number of cell pump rotations for the next collection cycle will be recalculated by the computer on the basi~ of the newly calculated flow constants and, the ~r--~t number of cell pump rotations will be accordingly reset for the next collection/reinfusion cycle.
The blood filter/bubble trap 240 of the device may consist of any type of outer housing or shell having positioned therein one or more materials operative to effect filtration of the blood and/or trapping of h~hhles as the blood p~ 's through the blood filter/bubble trap 240.
iii. A Preferred 8100d Filter/Bubble Trap U~able in the Device of the ~ nt Invention One presently preferred type of blood filter/bubble trap ~- is shown separately in Figure 8. This preferred blood filter/bubble trap 300 comprises an outer plastic shell 302 .. ,, . . .. , . . ., . ~ .. ... .. . . . .

~1~9~337 of generally cylindrical configuration. The shell is compressed to a flat, closed configuration at its top end 304 a~d bottom end 306. A filtration bag formed of a material approved for use in blood pathway and ~lood processing, (e.g. certain fabrics, filtration media or fine mesh materials, such as a nylon mesh) is positioned inside the shell 302. The opening size or mesh size of the mesh material or fabric or filtration material is preferably about 220 microns. Second 312 and third 314 inlet tubes 10 pa88 through the closed bottom end 306 of the shell 302.
A ~tand pipe 314 is fluidly connected to the third input tube 312 and extends upwardly therefrom with the confines of the shell 302.
' In its preferred embodiment, the filter 300 is approximately 12 centimeters in lengthffrom the top edge 304 of the shell to the bottom edge 306. The stand pipe 314 is approximately 2 centimeters in length.
In normal operation, the preferred blood filter/bubble trap device shown ln Figure 8 is mounted in the device of the present lnvention (Figure 7) such that the cell concentrate line 220 i8 connected to the fir~t inlet tube 308, the reinfusion line 188 ls connected to the second inlet tube 312 and the lower cell concentrate line is connected to the third inlet tube 314. When 80 mounted in the device of the present invention, the filter bag 310 ; will operate to strain or f~lter c~ll concentrate flowing into the blood filter~bubble trap 300 from the blood s~paration device 212a. Additlonally, the pre~ence of the stand pipe 314 within the blood filter/bubbl~ trap 300 will - 30 lnsure that a guant~ty of blood or cell concentrate pools -in the bottom of the inner chamber of the blood filter/bubble trap 300 before such blood or cell concentrate begins to flow down the lower cell concentrate line 242. The opening of the second inlet tube 312 which is connected to the reinfusion line 188a is generally flush , .

~109837 ., with the inner floor or bottom of the interior of the ~hell 302. Thus, the opening into the seeond inlet tube 312 will routinely be mainta~ned below an approximate 2 eenti~eter head of blood or eell eoneentrate. By this arrangement, eell eoneentrate flowing through the f~ltor bag 310 will fall lnto the bottom of the ehamber and will rise to the level of the top of the stand pipe 314 before flowing down the lower eell concentrate line 242. This will help to prevent turbulent eell eoneentrate eontA~n~ aberrant bubbles from entering the lower cell concentrate line 242.
Sueh pooling of the cell eoneentrate in the lower 2 centimeters of the blood filter/bubble trap 240 will a'llow the eell eoneentrate an opportunity to dega~ before ~, beg~nn~ng to flow down the lower cell concentrate line 242.
Sueh will help to prevent the introduction of air or ~: bubbles into the cell bag 237.
The foregoing detailed deseription has discussed only several illustrative embodiments or examples of the present lnvention. ~hose 6killed in the art will reeognize that numerou~ other emho~ents, or additions, modlficatlons, deletions and variations of the deseribed embodiment, may be made without ellminating the novel and unobvious features and advàntages of the present invent~on. It is :; intended that all sueh other embodiments, modifications, deletions and variations be ineluded within the seope of the following o1aims.

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Claims (14)

WHAT IS CLAIMED IS:

1. An apheresis method comprising the steps of:
(a) fluidly connecting a blood separation device to the vasculature of a human subject;
(b) operating at least one pump to withdraw whole blood from the human subject and to move said whole blood into said separation device;
(c) providing a single weighing device-having a first blood fraction container and a second blood fraction container positioned thereon, such that said weighing device will measure the combined weight of the said first blood fraction container and said second blood fraction container, along with any material contained therein;
(d) recording an initial weight on said weighing device when said first blood fraction container and said second blood fraction container are empty;
(e) operating said separation device to fraction the whole blood into at least a first blood fraction and a second blood fraction;
(f) recording a second weight on said weighing device after said first blood fraction and said second blood fraction have been collected in said first blood fraction container and said second blood fraction container;
(g) providing a fluid connection between said first blood fraction container and said human subject;
(h) operating at least one pump to reinfuse said first blood fraction, through said fluid connection, into said human subject; and (i) recording a third weight on said weighing device after said first blood fraction has been removed from said first blood fraction container reinfused into said human subject.

2. The method of Claim 1 further comprising the step of:
utilizing the weights recorded in steps (d) and (f) to calculate a new "collection" flow constant for said at least one pump based on the actual weight of blood pumped from the human subject into the separation device; and utilizing the new collection flow constant to adjust the calibration of said at least one pump.

3. The method of Claim 1 further comprising the steps of:
utilizing the weights recorded by the single weighing device to determine the actual weight of first blood fraction pumped by said at least one pump during reinfusion step (h);
utilizing the actual weight of first blood fraction pumped during reinfusion to calculate a new reinfusion flow constant for the at least one pump;
and, thereafter;
adjusting the calibration of said at least one pump on the basis of the new reinfusion flow constant calculated therefore.

4. The method of Claim 1 further comprising the step of:
continually monitoring the change in weight on the weighing device as said first blood fraction is being reinfused into said human subject; and periodically comparing the change of weight on said weighing device to an expected change in weight calculated on the basis of the expected throughput of said at least one pump utilized for reinfusing said first blood faction; and determining whether the change in weight on said weighing device differs from the expected change in weight by more than a predetermined allowable amount and, if such differing is greater than said allowable amount, stopping said at least one pump, thereby stopping the reinfusion of said first blood fraction at that point.

5. The method of Claim 1 wherein said first blood fraction comprises cell concentrate and said second blood fraction comprises plasma.

6. The method of Claim 1 wherein the step (b) of operating at least one pump further comprises:
operating one blood pump for pumping blood from the human donor into the separation device; and operating a separate first blood fraction collection pump for pumping said first blood fraction out of the separation device and into the first blood fraction container.

7. The method of Claim 6 wherein the step of operating the first blood fraction collection pump further comprises initially setting the first blood fraction pump to pump a desired volume of first blood fraction into said first blood fraction containing such initial setting of the cell pump being based on an "initial" pump flow constant.

8. The method of Claim 7 wherein the "initial" pump flow constant is a coarse setting selected by the operator based on an estimated pump throughout.

9. The method of Claim 6 wherein the "initial" pump flow constant is an empirically determined value.

10. The method of Claim 6 further comprising the steps of:
utilizing the weights recorded by the single weighing device to determine the actual weight of first blood fraction pumped from the separation device into the first blood fraction container by the first blood fraction collection pump;
utilizing the actual weight of first blood fraction pumped by said first blood fraction collection pump to calculate a new collection flow constant for said first blood fraction pump; and, thereafter, adjusting the calibration of the first blood fraction pump in accordance with the new collection flow constant calculated therefore.

11. The method of Claim 6 further comprising the steps of:
utilizing the weights recorded by the single weighing device to determine the actual weight of whole blood pumped by said blood pump from said human subject into said separation device;
utilizing the actual weight of whole blood pumped by said blood pump to calculate a new collection flow constant for said blood pump; and, thereafter, adjusting the calibration of said blood pump in accordance with the new collection flow constant calculated therefore.

12. The method of Claim 6 further comprising the steps of:
operation a reinfusion pump for reinfusing the first blood fraction from said first blood fraction container into said human subject:
utilizing the weights recorded by the single weighing device to determine the actual weight of first blood fraction pumped by said reinfusion pump from said first blood fraction container into said human subject;
utilizing the actual weight of first blood fraction pumped by said reinfusion pump to calculate a new reinfusion flow constant for said reinfusion pump; and, thereafter, adjusting the calibration of said reinfusion pump in accordance with the new reinfusion flow constant calculated therefore.

13. The method of Claim 12 wherein the steps of "operating one blood pump" and "operating a reinfusion pump" further comprise:
positioning a single collection/reinfusion pump relating to the fluid connection between the human subject and the fluid connection between the first blood fraction container and the human subject such that said single collection/reinfusion pump may be alternately operated in a "collection" mode whereby whole blood is pumped from the human subject into the blood separation device and a "reinfusion" mode whereby the first blood fraction is pumped from the first blood fraction container into the human subject.
operating the single collection/reinfusion pump to initially effect "collection" mode pumping of whole blood from the human subject into the blood separation device and to subsequently, effect "reinfusion" mode pumping of the first blood fraction from the first blood fraction container into the human subject.

14. The method of Claim 1 wherein "providing a single weighing device having a first blood fraction container and a second blood fraction container positioned thereon further comprises:
providing a single weighing device having positioned thereon a flexible plastic bag for collecting the first blood fraction and a separate container for collecting the second blood fraction.