WO2002045857A2

WO2002045857A2 - Self-aligning nozzle array for pipette tip array plate

Info

Publication number: WO2002045857A2
Application number: PCT/US2001/046319
Authority: WO
Inventors: Jim E. Stanchfield; Dave J. Wright; David Robinson; Paul B. Robbins; Kenneth J. Christensen
Original assignee: Robbins Scientific Corporation
Priority date: 2000-12-05
Filing date: 2001-12-04
Publication date: 2002-06-13
Also published as: WO2002045857A3; AU2002228777A1

Abstract

An apparatus (10) for dispensing liquid in conjunction with an array of pipette tips (14), where each pipette tip (36) includes a socket portion (42). The liquid dispensing apparatus (10) includes tubes (25), each including a barrel (28) and a lower end (33), and a nozzle (34), each nozzle (34) having a shoulder (68) and a mouth (44) configured of appropriate diameter to enter into the socket portion (42) of each pipette tip (36), and form a liquid-tight seal therewith. A bottom plate (24) includes a number of through-holes (72) through which each of the nozzles passes (34). The through holes (72) are of larger diameter than the nozzles (34) so that limited lateral movement is allowed. A second embodiment (100) is convertible, so that separation of upper (73) and lower boundaries (75) may be decreased such that the upper boundary (73) contacts the shoulders (68) of said nozzles (34), to hold the nozzles (34) in fixed position, for use with pipette tip arrays (96) which are not bound together in fixed spatial relation to each other, but which are themselves allowed limited lateral movement. Both embodiments (10, 100) may further include a shucker plate (50) such that when the shucker plate (50) is made to travel away from the bottom plate (24) by an ejection mechanism (85), the pipette tips (36, 97) are pushed off of the nozzle mouths (44).

Description

SELF-ALIG ING NOZZLE ARRAY FOR PIPETTE TIP ARRAY PLATE

TECHNICAL FIELD The present invention relates generally to dispensing devices used in laboratory analysis and more particularly to devices which dispense multiple samples of liquid onto assay plates and multi-well containers.

BACKGROUND ART The use of pipette tips, which are commonly disposable, is well known. As technology for processing multiple samples of materials becomes more advanced, the capacity to handle larger and larger numbers of samples has steadily increased. It is quite common now that laboratory equipment can deal with an 8 X 12 matrix of samples which are arranged in a standard configuration and which has a standard spacing between the centers of the sample containers. Quite commonly these sample containers are configured as collection plates, which may have deep wells, or may be nearly, or even completely flat, if very minute quantities are to be dispensed onto them, in which case it may be more appropriate to speak of a target area for deposition. Since the configuration and spacing of these wells or target areas are largely standardized, the spacing of the dispensing pipettes or syringe needles has also been standardized as well. A standard of 9mm between centers has been established by the Society for Biomoiecular Screening (SBS), and other data relating to this standard can be referenced at their web site http://www.sbsonline.org/.

Traditionally, individual pipette tips, which are usually disposable, are fitted onto pipettes. As the number of pipettes which are included in a pipette array has grown to 96 and beyond, the practicality of attaching individual pipette tips one-by-one to each pipette has decreased greatly. This becomes a time consuming operation, and large numbers of these pipette tips must be ordered and maintained in appropriate multiples of the number of pipettes. They are also messy to dispose of and do not stack easily with one another.

In answer to these problems, pipette tips have been bound together in arrays that can be handled as a unit, and attached to a corresponding pipette array in one operation. In these arrays of pipettes tips, the center-to-center spacing is maintained by having the pipettes tips joined by a web or plate which thus keeps the pipette tips in constant spatial relationship to each other, and thus in relation to the pipette array and well plate which they address. These pipette tip plates may be disposable, or reusable after cleaning.

A problem has existed with these pipette tip plates, which the present invention and system addresses. The pipette mechanisms which feed fluid samples to the pipette tip plates contain an array of mating parts which must fit into the individual pipette tips of the plate, and must seat in such a way as to form a fluid-tight seal with the inner surface of the pipette tips. These mating parts, which will be referred to as "nozzles" must each form a liquid-tight seal with its respective pipette tip in order to avoid leakage of materials, some of which may be toxic, or contain dangerous materials. The problem exists therefore of having two arrays of parts which must meet to form a liquid-tight seal at the joining portions of each one of its many members. Each array of nozzles may potentially be required to mate with a number of different, though standardized, pipette tip plates, if the pipette tip plates are desired to be interchangeable and perhaps disposable. In computerized, or automated systems, the element of human oversight to the process may be minimized, and it may be impractical to required human inspection of the nozzle-to-pipette seals. Reliability of the seal, and thus of the mating parts is therefore very important.

Though the pipette tip plates are theoretically standardized in dimension and configuration, there will be individual differences due to manufacturing tolerances, and differences in suppliers' manufacturing methods. Consequently, the tolerances in the pipette tip plates traditionally must be very close in order to ensure that an effective seal is produced with the nozzles among all of its members of all the replacement plates. Tight tolerances in the pipette tip plates require more exacting manufacturing procedures, and thus higher costs, which of course, make disposability of the plates less attractive economically.

Thus, there is a great need for a system which will allow alignment of the individual elements in a nozzle array to accommodate small inconsistencies in dimensional spacing among pipettes in a pipette tip array, therefore allowing for less demanding tolerances in the manufacture of the pipette tip plates.

DISCLOSURE OF INVENTION Accordingly, it is an object of the present invention to provide a system in which an array of pipette tips can be changed in unison, while ensuring that the seal to each pipette tip is secure.

Another object of the invention is to provide a system which can use pipette tip array plates which do not need to be manufactured to extremely tight tolerances, and thus are less expensive.

And another object of the invention is to provide a system in which the placement of the connecting nozzles can compensate for small variations in the positions of pipette tips within a pipette tip array.

A further object of the invention is to provide a system in which inexpensive, perhaps disposable, pipette tip array plates can be used. Yet another object of the present invention is to provide an array of nozzles which are self-aligning.

Yet another object of the present invention is to provide a system which. is convertible from use with bound arrays to arrays of pipettes tips which are free floating.

Briefly, one preferred embodiment of the present invention is an apparatus for dispensing liquid in conjunction with an array of pipette tips, where each pipette tip includes a socket portion. The liquid dispensing apparatus includes a number of tubes, where each tube includes a barrel and a lower end. Also included are a number of nozzles, each nozzle having a shoulder and a mouth configured of appropriate diameter to enter into the socket portion of each pipette tip, and form a liquid-tight seal therewith. Each nozzle is attached to the lower end of one of the tubes. Upper and lower boundaries limit the vertical travel of the nozzles, the upper and lower boundaries being preferably variable in separation from each other. A bottom plate includes a number of through-holes through which each of the nozzles passes. The through holes are of larger diameter than the nozzles so that limited lateral movement is allowed when separation of said upper and lower boundaries is great enough such that the upper boundary does not contact the shoulders of the nozzles, for use with pipette tip arrays which are bound together in fixed spatial relation to each other by a web portion.

In a second, convertible embodiment, the separation of the upper and lower boundaries may be decreased such that the upper boundary does contact the shoulders of said nozzles, to hold the nozzles in fixed position, for use with pipette tip arrays which are not bound together in fixed spatial relation to each other, but which are themselves allowed limited lateral movement.

Both embodiments may further include a shucker plate such that when the shucker plate is made to travel away from the bottom plate by an ejection mechanism, the pipette tips are pushed off of the nozzle mouths. An advantage of the present invention is the position of the nozzles is self-aligning so that automated production methods, including computer-controlled systems, can be easily used.

Another advantage of the invention is since the nozzle positions can be aligned to accommodate variations in the pipette tip positions, less precise and thus less expensive pipette tip plates can be used.

And another advantage of the invention is that larger arrays, which would be expected to have larger alignment and parts tolerance problems can be used.

These and other objects and advantages of the present invention will become clear to those skilled in the art in view of the description of the best presently known mode of carrying out the invention and the industrial applicability of the preferred embodiment as described herein and as illustrated in the several figures of the drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

The purposes and advantages of the present invention will be apparent from the following detailed description in conjunction with the appended drawings in which:

FIG. 1 shows a block diagram view of the major components of a liquid dispensing system; FIG. 2 illustrates an isometric view of the tube array assembly and pipette tip array of the present invention;

FIG. 3 shows a partial cross-sectional detail view of the tube array assembly and pipette tip array of the present invention;

FIG. 4 illustrates a side plan view of the tube array assembly of the present invention; FIG. 5 shows a front plan view of the tube array assembly of the present invention;

FIG. 6 shows a top plan view of the tube array assembly of the present invention;

FIG. 7 illustrates a partially exploded perspective view of a second embodiment of the present invention;

FIG. 8 shows a more fully exploded perspective view of the second embodiment of the present invention;

FIG. 9 shows a cut-away view of the second embodiment of the present invention, as taken through section line 9-9 of Fig. 7;

FIG. 10 illustrates a cut-away view of the second embodiment of the present invention, as taken through section line 10-10 of Fig. 7; FIG. 11 shows a detail cut-away view of the convertible liquid dispensing system in floating configuration; and

FIG. 12 shows a detail cut-away view of the convertible liquid dispensing system in fixed configuration.

BEST MODE FOR CARRYING OUT THE INVENTION

A preferred embodiment of the present invention is a liquid dispensing system which uses arrays of pipettes tips which are fixed together in a plate structure, and which has an array of nozzles which is self-aligning with respect to the pipette tip array. As illustrated in the various drawings herein, and particularly in the view of FIG. 1, a form of this preferred embodiment of the inventive device is depicted by the general reference character 10.

FIG. 1 illustrates a block diagram of a system for dispensing liquid 10 which includes a tube array assembly 12, a pipette tip array plate 14 and a multi-well plate 16. The system

10 may also include other elements such as a pick-and-place robot arm 11 which may be computer controlled to direct the movement and positioning of the tube array block 12 as it engages the pipette tip array plate 14, and then moves the joined assembly 18 to its position at the multi-well plate 16. It may also have automated mechanisms (not shown), which act to depress the plungers of the tubes, thus dispensing the liquid contents. It is to be understood that the attachment and positioning may also be done manually or by simpler mechanisms, such as a system of rails, or processing stations.

FIG. 2 shows an exploded view of the tube array assembly 12 and its relationship to the pipette tip array 14 as well as many of the components which are included within the tube array assembly 12.

FIGS. 2 and 3 together show a tube array assembly 12, which has been mated with a pipette tip array plate 14 to form a liquid dispensing assembly 18. The tube array assembly

12 includes an upper plate 20, and a lower plate assembly 22, which includes a bottom plate

24, and a retainer plate 26 (see Fig. 3 only). Also included are a number of tubes 25, each having a barrel 28, a plunger 30, and a plunger head 32.

The tubes 25 are preferably air-liquid displacement tubes, in which a plunger forces liquid from the lower end of the tube when depressed, and which draws liquid into the tubes by creation of a partial vacuum when the plunger head is raised. The term tube 25 thus includes what are thought of as conventional syringes, in which a plunger including a moveable seal moves inside a cylinder, and also include other forms, such as those having a plunger rod which travels through an O-ring seal which remains stationary. The plunger may contact the liquid directly, or there may be a air-space buffer between the liquid and the plunger. All such variations will be obvious to those skilled in the art, and are all contemplated by the present invention.

The tube barrels 28 each have a lower end 33, which is attached, preferably by epoxy, to a nozzle 34, having a number of portions, which will be discussed below. The pipette tip array plate 14 includes a number of pipette tips 36 bound together in fixed spatial relationship to each other by a web portion 38. The upper ends 40 of the pipette tips 36 have a socket portion 42 into which the mouths 44 of the nozzles 34 are fitted. The socket portions 42 of the pipette tips 36 are of sufficient diameter that the nozzle mouths 44 fit easily when pressed into them, but fit tightly enough that an effective liquid-tight seal 46 is formed when the nozzles 34 are engaged with the pipettes tips 36.

The tube array block 12 also includes an optional shucker assembly 48 which includes a shucker plate 50 which is fitted between the bottom plate 24 (see Fig. 3) and the lip portions 60 of the pipette tips 36 and which can be used to force the pipette tip array plate 14 down and away from the nozzles 34, so that a new pipette tip array plate can be mounted. The shucker assembly 48 also may include a linear bearing 52, a housing 54 and an air cylinder bank 56, which cooperate to force the shucker plate 50 downward. Through holes 58 in the shucker plate 50 are of smaller diameter than the outer diameter of the lip portion 60 of the pipette tips 36. When the shucker plate 50 is driven downwards, it catches the lip portions 60 and forces the entire pipette tip array plate 14 off from engagement with the nozzles 34. The shucker plate 50 can then be raised again so that a new pipette tip array plate can be attached, either manually or by use of automated devices.

Each nozzle 34 has a mouth 44, a shank 64, a collar 66 and a shoulder 68. The retainer plate 26 has through holes 70 which are slightly larger in diameter than the nozzle shoulders 68, but may be smaller in diameter than the nozzle collars 66. The bottom plate 24 has through holes 72, and is formed with a cavity space 74 in which the collars 66 are located. The bottom plate through holes 72 are also of smaller diameter than the collars 66, but slightly larger than the nozzle shanks 64. The retainer plate 26 and the bottom plate 24 are attached together with the respective through holes 70, 72 aligned. The nozzle collars 66 are then captured between the retainer plate 26 and the bottom plate 24, and constrained in its vertical movement. It is free to move in the horizontal plane until the shoulder 68 and shank portions 64 contact the sides of the through holes 70,72 of the retainer plate 26 and bottom 24 respectively. Thus, each of the nozzles 34 is free floating in a narrow horizontal range of motion. The tubes 25 are similarly constrained around their barrels 28 by through holes 62 in upper plate 20. These may be fairly close fitting so that the motion is more confined than at the lower end 78, so that there is motion analogous to a pivot point or hinge located at the tube upper end 76. Alternatively, the tube upper end 76 may have a similar range of motion or even greater range of motion than the tube lower end 78 so that the tube upper ends 76 are free floating within a narrow horizontal range as well, resulting in a sideways translational motion of the tube 25 as a whole.

When a new pipette tip array plate 14 is to be attached, it is positioned in approximate alignment with the nozzle mouths 44. The tip array plate 14 is then either raised to mate with the nozzle mouths 44 by raising a platform on which it is seated, or placed by a automated arm, or by manual attachment, or the tube array 12 may be lowered to meet the tip array plate 14. Since the pipette tips 36 in the tip array plate 14 are constrained from movement by the web portion 38 connecting them, they remain stationary as the nozzle mouths 44 each individually float sideways to align and mate with the socket portions 42 of the pipette tips 36. The nozzle mouths 44 are preferably tapered to facilitate insertion and alignment. The floating self alignment of the nozzles 34 thus allows for dimensional tolerances of the nozzles 34 and the pipette tips 36 to be much looser, since a liquid tight seal can be expected in each case, without the stress which results when an array of rigidly positioned parts is forced to mate with another array of rigidly positioned parts. Fig. 3 contains some variations on the basic design, which may be optionally included. In this embodiment, a middle plate 21 is included having through holes 82 which define the range of movement allowed by the upper ends 76 of the tubes 25. Again, it is possible that the through holes 82 may be large enough to allow lateral translational movement, or they may constrain sideways motion, so that they act as a pivot point. An optional end post 84 is shown, which gives structural support to the overall assembly.

Collars 66 may be integrally formed parts of the nozzles 34 or they may be washers which are externally attached onto the shank portion 64 of the nozzles 34. It may be possible that the shucker plate 50 also acts as the bottom plate 24, or that the bottom plate 24 has a number of through holes 72 having a step in diameter so that the collars 66 are given room to float within a larger diameter hole portion and the shank 58 extends through a narrower diameter hole portion, so that there are a series of discrete holes rather than a cavity 74.

The retainer plate 26 may also optionally not be included, as is shown in Fig. 2, so that tubes 25 are not constrained from upward movement, for maintenance or replacement purposes. If the retainer plate 26 is not included, this means that vertical force is transferred to the tube barrels 28, rather than being stopped at the collars 66 as they are prevented from upward movement by the retainer plate 26, as seen in Fig. 3. Thus, if the tube barrels 28 are to be made of glass, there will be definite advantages to having the vertical force stopped by the retainer plate 26, to prevent possible breakage of the barrels 28. However, if metal or certain sturdy plastics, which may easily withstand the vertical force, are to be used in the barrels, the retainer plate 26 may be optionally dispensed with, as seen in Fig. 2.

FIGS. 4, 5 and 6 show front plan, side plan and top plan views of the tube array assembly.

A second embodiment of a liquid dispensing system 100 is shown in FIGS. 7-12. Fig. 7 is a partially exploded view of the tube array assembly 12, and Fig. 8 is a more fully exploded view of the tube array assembly 12. Both figures do not show the pipette tip array to which the nozzles will be mated, but it is to be assumed that they are configured and positioned much as described before. Where elements are used in a similar manner to those in the earlier embodiment, the same numbers will be used. Referring now to Figs. 7 and 8, the tube array assembly 12 includes an upper plate 20, a middle plate 21, and a lower plate assembly 22, which includes a bottom plate 24. There are a number of tubes 25, each having a barrel 28, a plunger 30, and a plunger head 32. The tube barrels 28 each have a lower end 33, which is attached to a nozzle 34 having a mouth 44, a shank 64, a collar 66 and a shoulder 68. The tube array assembly 12 includes a shucker plate 50 which is fitted between the bottom plate 24 and the lip portions of the pipette tips when a new pipette tip array plate is to be mounted. The shucker assembly 48 includes an ejection mechanism 85, in this case a manifold 86, including a number of pistons 90, which cooperate to force the shucker plate 50 downward. Through holes 58 in the shucker plate 50 are of smaller diameter than the outer diameter of the lip portion of the pipette tips. When the shucker plate 50 is driven downwards, it forces the entire pipette tip array plate off from engagement with the nozzles 34. The shucker plate 50 can then be raised again so that a new pipette tip array plate can be attached, either manually or automated devices.

The ejection mechanism 85 can any number of mechanisms including pistons, air cylinders, screw mechanisms, linear motors and solenoids.

The manifold block 87 has through holes 70 which are slightly larger in diameter than the nozzle shoulders 68, but may be smaller in diameter than the nozzle collars 66. The lower side of the manifold block 68 thus performs the same function as the retainer plate 26 (see Fig. 3) of the first embodiment 10, namely preventing the tubes 25 from moving vertically when vertical force is applied to them for pressing them onto the pipette tips.

The bottom plate 24 has through holes 72, and is formed with a cavity space 74 in which the collars 66 are positioned. The bottom plate through holes 72 are also of smaller diameter than the collars 66, but slightly larger than the nozzle shanks 64. The nozzle collars 66 are then captured between the lower surface of the manifold block 87 and the bottom plate

24, and constrained in its vertical movement. They are free to move in the horizontal plane until the shoulder 68 and shank portions 64 contact the sides of the through holes 70,72 of the manifold block 87 and bottom plate 24 respectively. A pad 45 is included to dampen vibration, although still allowing horizontal movement. Thus, each of the nozzles 34 is free floating in a narrow horizontal range of motion.

The cavity 74 is partially bounded by an upper boundary 73 and a lower boundary 75 (see Figs. 10-12). The upper boundary 73 can be a retainer plate 26 or the manifold block 87, and the lower boundary is the bottom plate 24. As described below, it may be advantageous to make the separation between the upper boundary 73 and the lower boundary 75 variously separable, so that the cavity 74 can be changed in size.

Although there are many advantages, as described above, to having the pipette tips bound together into a fixed array, there are occasions in which bound pipette arrays are not available or a user may wish to use up his stock of detached pipettes. These detached pipettes are still commonly handled by arranging them into arrays, usually by placing them in a tray having multiple holes in which they are allowed a limited amount of lateral movement. In such cases, it may be undesirable to have one array of floating nozzles attempting to mate with a second array of pipette tips which are themselves floating. In this case, it is desirable that the nozzle array be convertible to a fixed configuration that the floating pipette tips can then align with. This second embodiment 100 (shown in Figs. 7-12) has been designed to be convertible in its use, meaning that it can be configured both with free-floating, self-aligning nozzles for use with pipette tip array plates, or alternatively, the nozzles can be fixed in position to use with pipette tips which are themselves freely arrayed and not fixed in position by a connecting web. This is accomplished by the insertion of spacers 94 between the bottom plate 24 and the lower surface of the manifold block 87 (see Fig. 8, 11). The cavity space 74 of the bottom plate 24 is designed to be shallow enough that without the use of spacers 94, the nozzles 34 are held in fixed position, and prevented from horizontal movement. This is useful for arrays of pipette tips which are not bound into a regular matrix, and are thus able to "float" sideways to align with the nozzle mouths 44, which are now in fixed array. These arrays of pipettes which are not bound together by a web will be referred to as floating pipette tip arrays 96, and will include pipettes tips 97 held in a tray 98 which includes an array of pipette array through holes 95. This convertible liquid dispensing system

100, is shown in both configurations in Figs. 7-12. For ease of reference, when the nozzles are not held in place, i.e. allowed to float, the system 100 will be said to be in floating configuration 102, in which the spacers 94 are in place. When the spacers have been removed and the nozzles are held in fixed relation to each other and the pipette tips, it will be said to be in fixed configuration 104.

Fig. 9 shows a cut-away view of the convertible liquid dispensing system 100 seen in Fig. 7, as taken through line 9-9 and Fig. 10 shows a cut-away view as taken through line 10-

10. The system 100 is in fixed configuration 104, so that it is used with a floating pipette tip array 96, having pipette tips 97 positioned in through holes 95 fashioned in the pipette tip tray 98. The nozzles 34 are held in position by the lower plate 24 and the manifold block 87, and the pipette tips 97 are then free to align themselves with the nozzles 34 as they descend. Also shown are the plungers 30, plunger heads 32, upper plate 20, side plates 55, middle plate 21, tubes 25 and shucker plate 50.

Figs. 11 and 12 show detail cut-away views of the convertible liquid dispensing system 100 in floating configuration 102 and fixed configuration 104, respectively. In Fig.

11, the spacer 94 is shown in position between the bottom plate 24 and the manifold block 87. The cavity space 74 is thus increased, the nozzle shoulders 68 do not contact the manifold block 87, the nozzle shanks 64 are free to move in the through-holes 58, and the nozzles 34 are able to float. The nozzles 34 are thus able to align with pipette tips 36 in a bound pipette tip array 14, having pipette tips 36 connected by a web portion 38. Both figures also show the plungers 30, plunger heads 32, upper plate 20, side plates 55, middle plate 21, middle plate through holes 82, tubes 25, nozzle shank 64 and shucker plate 50.

In Fig. 12, the spacer has been removed, the cavity 74 is thus decreased and the nozzles 34 fixed in place. This fixed configuration is thus prepared for use with a floating pipette tip array 96, having pipette tips 97 positioned in through holes 95 fashioned in the pipette tip tray 98. When the liquid dispensing system (see Fig. 11) is to be used with pipette tip arrays

14 which are bound into a matrix, and the individual tips 36 fixed in place by a matrix web 38, then the spacers 94 may be inserted. The spacers displace the lower plate 24 vertically downward from the manifold block 87, thus enlarging the cavity space 74. The nozzles are then again allowed to "float" in a horizontal plane, to align with the pipette tips, which are not themselves free to move. The device 100 is thus able to convert easily from one configuration and set of pipette tips to another, and is useable with both.

It will be obvious to one skilled in the art that the features of both embodiments can be combined, so that for example the embodiment 100 shown in Fig. 8 could be made permanently floating as in the first embodiment 10 by configuring a deeper step in the bottom plate 24, so that the cavity 74 is larger, and the nozzles 34 are allowed to float without the use of spacers 94, while still maintaining the same configuration of manifold block, pistons, etc. It is also possible that a retainer plate 26 could be used in addition to the manifold block 87. Also, other types of spacers could be used besides washers, both removable and non- removable, including a screw mechanism, a lever or wedge, or any other mechanical, electromechanical, piezoelectric, etc. mechanism for increasing the cavity space and freeing the nozzles to float.

While various embodiments have been described above, it should be understood that they have been presented by way of example only, and not limitation. Thus, the breadth and scope of a preferred embodiment should not be limited by any of the above described exemplary embodiments, but should be defined only in accordance with the following claims and their equivalents.

ΓNDUSTRIAL APPLICABILITY

The liquid dispensing system 10 of the present invention is designed to be used for many applications involving the testing and analysis of chemical compounds on a micro scale. The many advantages of doing work on a micro-scale include the reduced costs of reagents, solvents and materials due to the reduced amounts needed, and the generation of less waste materials which may be environmentally damaging and costly to dispose of.

Sample containers are commonly configured as collection plates, which may have deep wells, or may be nearly, or even completely flat. Since the configuration and spacing of these wells or target areas are largely standardized, the spacing of the dispensing pipettes or tube needles has also been standardized as well. A standard of 9mm between centers has been established by the Society for Biomoiecular Screening (SBS). Traditionally, individual pipette tips, which are usually disposable, are fitted onto pipettes. As the number of pipettes which are included in a pipette array has grown to 96 and beyond, the practicality of attaching individual pipette tips one-by-one to each pipette has decreased greatly. This becomes a time consuming operation, and large numbers of these pipette tips must be ordered and maintained in appropriate multiples of the number of pipettes. They are also messy to dispose of and do not stack easily with one another.

The present invention 10 is made to allow easy and automated handling of pipette tip plates by allowing the mating parts, the nozzle mouth 44, to self-align with the sockets portions 42 of the pipette tip arrays 14. The pipette tip array plate 14 includes a number of pipette tips 36 bound together in fixed spatial relationship to each other by a web portion 38. The upper ends 40 of the pipette tips 36 have a socket portion 42 into which the mouths 44 of the nozzles 34 are fitted. The socket portions 42 of the pipette tips 36 are of sufficient diameter that the nozzle mouths 44 fit easily when pressed into them, but fit tightly enough that an effective liquid-tight seal 46 is formed when the nozzles 34 are engaged with the pipettes tips 36.

Each nozzle 34 has a mouth 44, a shank 64, a collar 66 and a shoulder 68. The retainer plate 26 has through holes 70 which are slightly larger in diameter than the nozzle shoulders 68, but may be smaller in diameter than the nozzle collars 66. The bottom plate 24 has through holes 72, and is formed with a cavity space 74 in which the collars 66 are located. The bottom plate through holes 72 are also of smaller diameter than the collars 66, but slightly larger than the nozzle shanks 64. The retainer plate 26 and the bottom plate 24 are attached together with the respective through holes 70, 72 aligned. The nozzle collars 66 are then captured between the retainer plate 26 and the bottom plate 24, and constrained in its vertical movement. It is free to move in the horizontal plane until the shoulder 68 and shank portions 64 contact the sides of the through holes 70,72 of the retainer plate 26 and bottom 24 respectively. Thus, each of the nozzles 34 is free floating in a narrow horizontal range of motion.

When a new pipette tip array plate 14 is to be attached, it is positioned in approximate alignment with the nozzle mouths 44. The tip array plate 14 is then either raised to mate with the nozzle mouths 44 by raising a platform on which it is seated, or placed by a automated arm, or by manual attachment, or the tube array 12 may be lowered to meet the tip array plate 14. Since the pipette tips 36 in the tip array plate 14 are constrained from movement by the web portion 38 connecting them, they remain stationary as the nozzle mouths 44 each individually float sideways to align and mate with the socket portions 42 of the pipette tips 36. The nozzle mouths are preferably tapered to facilitate insertion and alignment. The floating self alignment of the nozzles 34 thus allows for dimensional tolerances of the nozzles and the pipette tips 36 to be much looser, since a liquid tight seal can be expected in each case, without the stress which results when an array of rigidly positioned parts is forced to mate with another array of rigidly positioned parts.

The tube array block 12 also includes an optional shucker assembly 48 which includes a shucker plate 50 which is fitted between the bottom plate 24 (see Fig. 3) and the lip portions 60 of the pipette tips 36 and which can be used to force the pipette tip array plate 14 down and away from the nozzles 34, so that a new pipette tip array plate can be mounted. The shucker assembly 48 also may include a linear bearing 52, a housing 54 and an air cylinder bank 56, which cooperate to force the shucker plate 50 downward. Through holes 58 in the shucker plate 50 are of smaller diameter than the outer diameter of the lip portion 60 of the pipette tips 36. When the shucker plate 50 is driven downwards, it catches the lip portions 60 and forces the entire pipette tip array plate 14 off from engagement with the nozzles 34. The shucker plate 50 can then be raised again so that a new pipette tip array plate can be attached, either manually or automated devices.

As mentioned above, the dimensional tolerances on the pipette tip arrays 14 can be greatly relaxed by the use of the present invention. This results in a substantially savings on these parts, especially considering that larger scale processing facilities may use thousands of these pipette tip arrays 14.

A second embodiment 100 has been designed to be convertible in its use, meaning that it can be configured both with free-floating, self-aligning nozzles for use with pipette tip array plates, or alternatively, the nozzles can be fixed in position to use with pipette tips which are themselves freely arrayed and not fixed in position by a connecting web. This is accomplished by the insertion of spacers 94 between the bottom plate 24 and the lower surface of the manifold block 87. The cavity space 74 of the bottom plate 24 is designed to be shallow enough that without the use of spacers 94, the nozzles 34 are held in fixed position, and prevented from horizontal movement. This is useful for arrays of pipette tips which are not bound into a regular matrix, and are thus able to "float" sideways to align with the nozzle mouths 44, which are now in fixed array.

When the liquid dispensing system is to be used with pipette tip arrays 14 which are bound into a matrix, and the individual tips 36 fixed in place by a matrix web 38, then the spacers 94 may be inserted. The spacers displace the lower plate 24 vertically downward from the manifold block 87, thus enlarging the cavity space 74. The nozzles are then again allowed to "float" in a horizontal plane, to align with the pipette tips, which are not themselves free to move. The device 100 is thus able to convert easily from one configuration and set of pipette tips to another, and is useable with both.

For the above, and other reasons, it is expected that the liquid dispensing system 10 will have widespread industrial applicability. Therefore, it is expected that the commercial utility of the present invention will be extensive and long lasting.

Claims

LN THE CLAIMS What is claimed is:

1. An apparatus for dispensing liquid in conjunction preferably with an array of pipette tips which are bound together in fixed spatial relation to each other by a web portion, each pipette tip including a socket portion, the liquid dispensing apparatus comprising: a plurality of tubes, each tube including a barrel and a lower end; a plurality of nozzles, each nozzle having a mouth configured of appropriate diameter to enter into said socket portion of said pipette tip, and form a liquid-tight seal therewith, each nozzle being attached to said lower end of one of said tubes; and a bottom plate including a plurality of through-holes through which each of said plurality of nozzles passes, said through holes being of larger diameter than said nozzles so that limited lateral movement is allowed, said plurality of nozzles being allowed to move laterally when mating with each of said plurality of pipette tips, thus self-aligning with said pipette tips.

2. The apparatus of claim 1, further comprising: an upper boundary which limits the vertical travel of said plurality of nozzles;

3. The apparatus of claim 2, further comprising: a retainer plate which defines said upper boundary.

4. The apparatus of claim 2, further comprising: a manifold block which defines said upper boundary.

5. The apparatus of claim 2, wherein: said lower plate defines a lower boundary: and said upper boundary and said lower boundary form portions of the boundary of a cavity, within which said plurality of nozzles are positioned.

6. The apparatus of claim 5, wherein: said boundaries of said cavity are variable in separation from each other, such that said cavity is variable in size.

7. The apparatus of claim 6, wherein: said boundaries may be positioned to contact said plurality of nozzles, thus preventing movement and placing them in a fixed configuration, which may be used with pipette tips which are not bound together in fixed spatial relation to each other, but which are themselves allowed limited lateral movement.

8. The apparatus of claim 7, wherein: said variation in separation of the boundaries is done by inserting at least one spacer.

9. The apparatus of claim 1, further comprising: a shucker plate interposed between said lower plate and said socket portions of said pipette tips of said shucker plate including a plurality of through-holes through which each of said plurality of nozzles passes, said through holes being of larger diameter than said nozzles but of smaller diameter than said socket portions of said pipette tips, such that when said shucker plate is made to travel away from said bottom plate by an ejection mechanism, said pipette tips are pushed off of said nozzle mouths.

10. The apparatus of claim 9, wherein: an ejection mechanism is at least one piston.

11. The apparatus of claim 9, wherein: an ejection means is at least one air cylinder.

12. The apparatus of claim 1, wherein: said plurality of tubes and the attached array of nozzles are combined to form a tube array; and said pipette tip array is attached to said tube array by raising said pipette tip array to meet said tube array.

13. The apparatus of claim 1, wherein: said plurality of tubes and the attached array of nozzles are combined to form a tube array; and said pipette tip array is attached to said tube array by lowering said tube array to meet said pipette tip array.

14. Apparatus for dispensing liquid in conjunction with an array of pipette tips each pipette tip including a socket portion, the liquid dispensing apparatus comprising: a plurality of tubes, each tube including a barrel and a lower end; a plurality of nozzles, each nozzle having a shoulder and a mouth configured of appropriate diameter to enter into said socket portion of said pipette tip, and form a liquid- tight seal therewith, each nozzle being attached to said lower end of one of said tubes; upper and lower boundaries which limit the vertical travel of said plurality of nozzles, said upper and lower boundaries being variable in separation from each other; a bottom plate including a plurality of through-holes through which each of said plurality of nozzles passes, said through holes being of larger diameter than said nozzles so that limited lateral movement is allowed when separation of said upper and lower boundaries is great enough such that said upper boundary does not contact said shoulders of said nozzles, for use with pipette tip arrays which are bound together in fixed spatial relation to each other by a web portion; and said separation of said upper and lower boundaries may be decreased such that said upper boundary does contact said shoulders of said nozzles, to hold said nozzles in fixed position, for use with pipette tip arrays which are not bound together in fixed spatial relation to each other, but which are themselves allowed limited lateral movement.

15. The liquid dispensing apparatus of claim 14, further comprising: a retainer plate which defines said upper boundary.

16. The liquid dispensing apparatus of claim 14, further comprising: a manifold block which defines said upper boundary.

17. The liquid dispensing apparatus of claim 14, wherein: said lower plate defines said lower boundary.

18. The apparatus of claim 14, wherein: said variation in separation of the boundaries is done by using at least one spacer.

19. The apparatus of claim 14, further comprising: a shucker plate interposed between said lower plate and said socket portions of said pipette tips said shucker plate including a plurality of through-holes through which each of said plurality of nozzles passes, said through holes being of larger diameter than said nozzles but of smaller diameter than said socket portions of said pipette tips, such that when said shucker plate is made to travel away from said bottom plate by an ejection mechanism, said pipette tips are pushed off of said nozzle mouths.

20. The apparatus of claim 19, wherein: an ejection mechanism is at least one piston.

21. The apparatus of claim 19, wherein: an ejection mechanism is at least one air cylinder.

22. A method of attaching and detaching arrays of pipette tips to arrays of tubes, each pipette tip having a socket portion, comprising the steps of: A) providing an apparatus for dispensing liquid comprising an array of tubes, each tube including a barrel and a lower end, a plurality of nozzles, each nozzle having a shoulder and a mouth configured of appropriate diameter to enter into said socket portion of said pipette tip, and form a liquid-tight seal therewith, each nozzle being attached to said lower end of one of said tubes, upper and lower boundaries which limit the vertical travel of said plurality of nozzles, said upper and lower boundaries being variable in separation from each other, a bottom plate including a plurality of through-holes through which each of said plurality of nozzles passes, said through holes being of larger diameter than said nozzles so that limited lateral movement is allowed when separation of said upper and lower boundaries is such that said upper boundary does not contact said shoulders of said nozzles; B) providing an array of pipette tips; and C) pressing said array of tubes and said array of pipette tips together, one of which said arrays includes array elements which are allowed to self-align with elements of the other array.

23. The method of claim 22, wherein said pipette tip arrays are bound together in fixed spatial relation to each other by a web portion, said separation of said upper and lower boundaries may be increased such that said upper boundary does not contact said shoulders of said nozzles, and in step C, elements of said tube array are allowed to self-align with said pipette tips, which are stationary.

24. The method of claim 22, wherein said pipette tip arrays are not bound together in fixed spatial relation, said separation of said upper and lower boundaries may be decreased such that said upper boundary contacts said shoulders of said nozzles, and in step C, elements of said pipette tips arrays are allowed to self-align with said elements of said tube array, which are stationary.

25. The method of claim 22, wherein said apparatus provided in step A further comprises a shucker plate interposed between said lower plate and said socket portions of said pipette tips, said shucker plate including a plurality of through-holes through which each of said plurality of nozzles passes, said through holes being of larger diameter than said nozzles but of smaller diameter than said socket portions of said pipette tips, such that when said shucker plate is made to travel away from said bottom plate by an ejection mechanism, said pipette tips are pushed off of said nozzle mouths, said method further comprising the step of: D) activating said ejection mechanism of said shucker plate to eject said pipette tip array.

26. The method of claim 22, wherein in step C, said pipette tip array is raised to meet said tube array.

27. The method of claim 22, wherein in step C, said tube array is lowered to meet said pipette tip array.