WO1987007377A1

WO1987007377A1 - Fluid dispensing apparatus

Info

Publication number: WO1987007377A1
Application number: PCT/GB1987/000347
Authority: WO
Inventors: Christopher John Hammond
Original assignee: Boots-Celltech Diagnostics Limited
Priority date: 1986-05-20
Filing date: 1987-05-20
Publication date: 1987-12-03
Also published as: GB8612261D0

Abstract

An apparatus for simultaneously dispensing fluid to a plurality of separate locations comprising: a reservoir for the fluid (11), a plurality of outlets (15) for dispensing fluid from the reservoir (11) and a valve means (3) for interrupting fluid flow from the reservoir (11) to the outlets (15), the valve means (3) being responsive to increases in fluid pressure within the reservoir (11) to open and permit fluid flow from the reservoir (11) through the outlets (15). The apparatus is particularly suited for use in assay procedures in which it is required to dispense substantially equal aliquots of fluid simultaneously to a plurality of containers.

Description

FLUID DISPENSING APPARATUS

Field of the Invention

This invention relates to apparatus for dispensing fluid, in particular to apparatus for simultaneously dispensing a plurality of substantially equal aliquots of fluid.

Background to the Invention

There are numerous applications in which it is required to dispense substantially equal aliquots of fluid simultaneously to a plurality of containers. One particular area of application is in the field of diagnostic assays where, for efficiency of sample handling, a plurality of samples may be assayed at one time. In such assay procedures it may be required to dispense aliquots of liquid assay reagents simultaneously to each of a plurality of samples. An example is heterogeneous binding assay procedures, as described in the specification of British Patent No. 1566098, in which a sucrose layering step is employed to separate solid and liquid components of the assay incubate. In such procedures it is desirable to dispense equal aliquots of sucrose solution simultaneously to a plurality of assay samples.

A simple form of apparatus for dispensing a plurality of fluid aliquots comprises a manifold having a fluid inlet and a plurality of tubular outlets, through which the fluid is dispensed. However, such apparatus is not altogether satisfactory because between dispensing operations, air may enter the manifold through one or more of the tubular outlets, causing liquid to vent from the manifold.

This may lead to a reduction in the volume of liquid delivered during subsequent dispensing operations and possible variations in the volume of liquid dispensed from one tubular outlet to another. This problem arises, in particular, if the manifold is moved between dispensing operations or if the tubular outlets are likely to be knocked or otherwise disturbed during use. This problem can have very far reaching consequences in assay applications where variations in the volumes of reagents delivered may give rise to erroneous assay results. The problem is particularly exacerbated in automated clinical assay apparatus where venting of the manifold may go undetected and potentially may give rise to incorrect patient diagnoses.

We have now devised an improved fluid dispensing apparatus for simultaneously dispensing a plurality of aliquots of fluid. The improved apparatus overcomes or at least substantially reduces the problem of air entry associated with simple manifold apparatus.

Summary of the Invention

Accordingly, the present invention provides apparatus for simultaneously dispensing fluid to a plurality of separate locations comprising: a reservoir for the fluid;

a plurality of outlets for dispensing fluid from the reservoir, and

a valve means for interrupting fluid flow from the reservoir to the outlets, the valve means being responsive to increases in fluid pressure within the reservoir to open and permit fluid flow from the reservoir through the outlets.

The apparatus of the invention provides a simple and convenient solution to the problem of air entry and consequent fluid venting as described above in relation to simple manifold apparatus. During a dispensing operation, the valve means opens in response to increased fluid pressure within the reservoir consequent upon supply of fluid thereto and fluid is dispensed from the reservoir through the outlets. Between dispensing operations the valve means is closed, isolating the outlets from one another and the reservoir, preventing entry of air into the reservoir and venting of fluid therefrom. Thus the valve means provides a convenient self-sealing function and operates 'automatically' in response to variations in fluid pressure within the reservoir.

The apparatus may be used in any fluid dispensing application where it is required to simultaneously dispense fluid to a plurality of locations. The apparatus is particularly suited, however, to the simultaneous dispensing of aliquots of liquid of substantially equal volume. In a particularly preferred application the apparatus may be used to dispense liquid assay reagents to assay samples. For example, the apparatus may be used to dispense substantially equal volumes of sucrose solution simultaneously to a plurality of binding assay samples as required for the sucrose layering separation procedure described in British Patent No. 1566098.

Preferably the fluid outlets comprise tubular probes through which fluid may be dispensed conveniently at a plurality of separate locations. For example, the tubular probes may be arranged in a regular two dimensional matrix array (e.g. a 4 x 5 matrix) corresponding to a similar array of racked assay tubes or assay plate wells such that the probes may be lowered into the tubes or wells to deliver separate aliquots of assay reagents thereto. Such tubular probes are preferably of relatively narrow internal diameter e.g. 1 - 2mm or less, so that liquid advantageously does not tend to run out of the probes when the valve is closed. The tubular probes are usually of the same internal diameter so that equal volumes of liquid are dispensed from each outlet during a dispensing operation. Preferably the outlet ends of the tubular probes are slightly constricted, e.g. of internal diameter less than 1mm. It has been found that constriction of the tubular probe outlets is desirable for uniform priming of all the tubular probes with liquid prior to use of the apparatus.

Typically the reservoir has at least one fluid inlet through which fluid is supplied thereto. Preferably the fluid volume of the reservoir is relatively large with respect to the sum of the fluid volumes of the outlets, e.g. tubular probes. In applications where it is required to dispense substantially equal volumes of liquid from each of the outlets, it is important to ensure that the cross-sectional area of the reservoir inlet(s) is greater than or equal to the sum of the cross-sectional areas of the outlets and that the cross-sectional areas of the outlets are equal to one another. Any suitable means may be employed to supply fluid, e.g. liquid to the reservoir. A pump, such as a peristaltic pump may be used and dispensing of fluid may be controlled, for instance by timed operation of the pump, by delivering a desired volume of liquid to the reservoir which is then dispensed evenly through the outlets, e.g. substantially equal volumes of liquid are dispensed through each of the outlets. Conveniently the reservoir may additionally contain an air bleed valve to permit venting of air from the reservoir during priming thereof with liquid.

Any suitable fluid pressure responsive valve means may be used in the present apparatus to interrupt fluid flow from the reservoir to the outlets. Typically the valve means comprises a moveable sealing member which at rest, i.e. between dispensing operations, closes the outlets and which, as a result of increased fluid pressure in the reservoir during dispensing, is displaced from its rest position permitting fluid flow from the reservoir through the outlets. The moveable sealing member is typically biassed into its rest position by suitable biassing means, such as springs, and is displaced against this biassing means during the dispensing operation. Preferably the moveable sealing member comprises a flexible resilient membrane, made of rubber or other suitable elastic material. Such a flexible resilient membrane may be biassed into its rest position by appropriate tensioning of the membrane. The use of a flexible resilient membrane advantageously appears to damp down variations in fluid delivery rate when a variable delivery pump, such as a peristaltic pump, is used to supply fluid to the reservoir.

Preferably the apparatus comprises one or more valve seats e.g. one for each of the outlets, against which the sealing member or membrane is biassed when at rest. In one arrangement the apparatus is in the form of a two part housing divided internally by a flexible resilient membrane into reservoir and head space sections. The head space section provides a space into which the membrane may be displaced during the dispensing operation. Preferably the head space has a vent to permit displacement of air when the membrane moves into the head space. It has been found that such a vent is desirable to ensure benefit from the damping effect of the membrane described above. In this arrangement the membrane not only provides the sealing member for closing the outlets but advantageously may also provide a seal between the two parts of the housing of the apparatus the membrane being clamped in position between the two parts of the housing. In an alternative form of this arrangement the head space may be sealed and in particular may contain pressurised gas to provide for or enhance biassing of the membrane into its rest position.

When the valve means comprises a flexible resilient membrane the membrane is usually reinforced or otherwise suitably stiffened. This is desirable to ensure that when the membrane is displaced by increased fluid pressure in the reservoir it is displaced uniformly across its area opening each outlet at substantially the same time. This may be important to ensure uniform dispensing of fluid across all of the outlets. Any suitable reinforcing or stiffening may be used, both internal or external. Preferably, however, a reinforcing plate, e.g. a metal plate is used, moulded within the membrane or preferably bonded to one of the surfaces thereof, especially the surface remote from the outlets. When a reinforcing plate is used, the plate is preferably suitably apertured or slotted in the regions of the membrane which correspond to the outlets, e.g. outlet valves seats, so that the membrane is suitably flexible in these regions to permit effective sealing of the outlets.

The invention includes processes in which a plurality of aliquots of fluid are dispensed simultaneously using the apparatus of the invention. Dispensing is initiated by delivery of fluid to the reservoir e.g. by means of an electrically-driven pump. Fluid entering the reservoir increases the fluid pressure therein causing the valve to open and fluid is dispensed simultaneously through the plurality of outlets. For instance, increased fluid pressure lifts the reinforced flexible membrane simultaneously from all of the fluid outlets valve seats and fluid flows out through all of the outlets. At the end of the dispensing operation the pump is switched off and the membrane settles back under tension into its rest position cutting off fluid flow from the reservoir to the outlets. In a preferred embodiment the pump may be reversed at the end of the dispensing operation to 'suck' the membrane down into its rest position ensuring a complete cut off of fluid flow to the outlets.

The apparatus of the invention provides a simple solution to the problems of air entry to and liquid venting from manifold apparatus. The valve means isolates the outlets from one another and from the reservoir, advantageously preventing air entering the reservoir and loss of liquid by syphoning effects between dispensing operations. The only liquid which may be lost from the apparatus is the very small quantity of liquid present in the tubular probes, for instance if the apparatus is subjected to a violent disturbance. In most circumstances, the loss of this small volume of liquid will not have unacceptable consequences.

Brief Description of the Drawings

The invention is further described by way of example only with reference to the accompanying diagrams:

Figure 1 is a side view of a vertical section through an apparatus according to the invention;

Figure 2 is an enlarged view of part of the section of Figure 1;

Figure 3 is a plan view from above of the lower portion of the apparatus of the invention; Figure 4 is a plan view from above of flexible resilient membrane and reinforcing plate of the apparatus of the invention, and

Figure 5 is a plan view from above of the reinforcing plate shown in Figure 4.

Detailed Description of the Embodiments

With reference to Figures 1 and 2 apparatus according to the invention comprises a two part housing having upper 1 and lower 2 portions made of machined plastics material. A flexible resilient rubber membrane 3 is clamped between the upper 1 and lower 2 portions, the membrane having an apertured metal reinforcing plate 4 bonded to its upper surface.

The upper portion 1 is in the form of an oblong plate having angled surfaces 6 and 7 around its circumference and an oblong recess 8 machined into its bottom surface. The corners of this recess are radiused and the outer corners of the upper portion 1 have bore holes to accommodate bolts used to clamp the upper 1 and lower 2 portions together (not shown). The recess is provided with a vent to the exterior via bore hole 9.

With reference also to Figure 3 the lower portion 2 is in the form of a similar oblong plate, having bore holes 10 at the corners thereof to accommodate bolts used to clamp the upper 1 and lower 2 portions together. The top surface of portion 2 has an oblong recess 11 machined into it, the recess having radiused corners. The recess 11 has an inner wall 12 and outer groove 13 machined around its circumference and is surrounded by an outer wall 14. A 5 x 4 array of twenty tubular stainless steel probes 15 (internal diameter ~ 1mm) are firmly located in tubular recesses 16 machined into the bottom surface of the lower portion 2. The bottom ends of these probes 15 are nipped in to constrict the outlets therefrom. The tubular recesses 16 communicate with the top surface of the portion 2 via bore holes 17 which exit at the centre of the annular top surfaces 19 of raised cylindrical portions 21. The height of the outer wall 14 is slightly higher (~.1mm) than the height of the cylindrical portions 21 which in turn are slightly higher (~.1mm) than the height of the inner wall 12. The body of the portion 2 has a horizontal bore hole 23 extending from the centre of one edge and communicating with the interior of the recess 11 via the outlet. A stainless steel tubular boss 25 is firmly located in the outer end of bore hole 23.

With reference to Figures 4 and 5, the flexible reinforced rubber membrane 3 which is clamped between the upper 1 and lower 2 portions is similarly oblong in shape and has radiused corners. The membrane 3 has a down-turned lip 30 around the circumference of its lower surface which locates in the outer circumferential groove 13 of portion 2. Metal reinforcing plate 4 is bonded to the top surface of membrane 3 and has circular apertures 32. These apertures 32 coincide with and are of larger diameter than the annular surfaces 19 of raised cylindrical portions 21. The resultant circular portions 34 of membrane 3 are thus flexible and able to provide a good seal When biassed against the annular surfaces 19. When the membrane 3 is clamped between the upper 1 and lower 2 portions as shown in Figures 1 and 2, the discrepancy in height of the circumferential inner wall 12 and the raised cylindrical portions tensions the membrane 3 and biasses the circ.ular portions 34 against the annular surfaces 19 sealing the outlets 17 to the tubular probes 15.

In use the recess 11 in the top surface of the lower portion 2 acts as the reservoir and the recess 8 in the bottom surface of the top portion 1 acts as the head space. When the apparatus has been primed with liquid, supply of additional liquid to the reservoir 11 via the inlet 23 raises the fluid pressure and displaces the reinforced membrane 3 upward into the head space 8 from which air is displaced through vent 9. The reinforcing plate 4 ensures that the membrane 3 is displaced upward uniformly across its area simultaneously opening all of the outlets 17 and dispensing liquid through all of the tubular probes 15. When liquid supply to the reservoir ceases the tensioned membrane 3 is biassed downward and the flexible circular portions 34 lay across and seal the valve seat surfaces 19. Sealing of the valve may be enhanced by running the pump backwards to add suction to the tensioning of the- membrane 3. Additionally the recess 11 may be provided with an air bleed valve (not shown) to permit venting of air from the reservqir during priming thereof with liquid.

The apparatus is primed by supplying liquid to the reservoir 11 through inlet 23, raising the membrane 3 and displacing air via the tubular probes 15. Any air bubbles remaining in the reservoir may be vented therefrom by means of an air bleed valve (not shown). If one or more probes 15 fill with liquid before the rest the resistance to liquid flow caused by the 'nipped in' constrictions at the bottom outlets of the probes 15 causes air to be displaced in preference to liquid and all of the tubular probes become primed with liquid.

In use, if the probes 15 are knocked or the apparatus otherwise disturbed, liquid may escape from the tubular probes 15 but not from the reservoir 11. During the subsequent delivery operation any such emptied probe will prime with liquid and the variation in volume of liquid dispensed from one probe to another will be relatively insignificant.

Claims

1. Apparatus for simultaneously dispensing fluid to a plurality of separate locations comprising:

a reservoir for the fluid;

a plurality of outlets for dispensing fluid from the reservoir, and

2. Apparatus according to Claim 1 wherein the fluid outlets comprise tubular probes, and the reservoir has at least one fluid inlet.

3. An apparatus according to Claim 2 wherein the cross-sectional area of the reservoir inlet(s) is greater than or equal to the sum of the cross-sectional areas of the outlets and the cross-sectional areas of the outlets are equal to one another.

4. An apparatus according to Claim 1 wherein the valve means comprises a moveable sealing member.

5. An apparatus according to Claim 4 wherein the moveable sealing member is biassed into its rest position by biassing means and is displaced against the biassing means during the dispensing operation.

6. An apparatus according to Claim 5 wherein the moveable sealing member comprises a flexible resilient membrane.

7. An apparatus according to Claim 6 wherein the flexible resilient membrane is reinforced or stiffened.

8. An apparatus according to any of the previous Claims in the from of a two part housing divided internally by a flexible fesilient membrane into reservoir and head space sections.

9. An apparatus according to Claim 8 wherein the head space has a vent to permit displacement of air when the membrane moves into the head space.

10. An apparatus according to Claim 8 wherein the head space is sealed and contains pressurised gas.