WO1987007377A1 - Systeme de distribution de fluides - Google Patents

Systeme de distribution de fluides Download PDF

Info

Publication number
WO1987007377A1
WO1987007377A1 PCT/GB1987/000347 GB8700347W WO8707377A1 WO 1987007377 A1 WO1987007377 A1 WO 1987007377A1 GB 8700347 W GB8700347 W GB 8700347W WO 8707377 A1 WO8707377 A1 WO 8707377A1
Authority
WO
WIPO (PCT)
Prior art keywords
reservoir
fluid
outlets
membrane
dispensing
Prior art date
Application number
PCT/GB1987/000347
Other languages
English (en)
Inventor
Christopher John Hammond
Original Assignee
Boots-Celltech Diagnostics Limited
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Boots-Celltech Diagnostics Limited filed Critical Boots-Celltech Diagnostics Limited
Publication of WO1987007377A1 publication Critical patent/WO1987007377A1/fr

Links

Classifications

    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
    • G01N35/1095—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices for supplying the samples to flow-through analysers
    • G01N35/1097—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices for supplying the samples to flow-through analysers characterised by the valves
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N1/00—Sampling; Preparing specimens for investigation
    • G01N1/02—Devices for withdrawing samples
    • G01N1/10—Devices for withdrawing samples in the liquid or fluent state
    • G01N1/18—Devices for withdrawing samples in the liquid or fluent state with provision for splitting samples into portions
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00277—Apparatus
    • B01J2219/00351—Means for dispensing and evacuation of reagents
    • B01J2219/00364—Pipettes
    • B01J2219/00367—Pipettes capillary
    • B01J2219/00369—Pipettes capillary in multiple or parallel arrangements
    • C—CHEMISTRY; METALLURGY
    • C40—COMBINATORIAL TECHNOLOGY
    • C40B—COMBINATORIAL CHEMISTRY; LIBRARIES, e.g. CHEMICAL LIBRARIES
    • C40B60/00—Apparatus specially adapted for use in combinatorial chemistry or with libraries
    • C40B60/14—Apparatus specially adapted for use in combinatorial chemistry or with libraries for creating libraries

Definitions

  • This invention relates to apparatus for dispensing fluid, in particular to apparatus for simultaneously dispensing a plurality of substantially equal aliquots of fluid.
  • 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.
  • a manifold having a fluid inlet and a plurality of tubular outlets, through which the fluid is dispensed.
  • air may enter the manifold through one or more of the tubular outlets, causing liquid to vent from the manifold.
  • the improved apparatus overcomes or at least substantially reduces the problem of air entry associated with simple manifold apparatus.
  • the present invention provides apparatus for simultaneously dispensing fluid to a plurality of separate locations comprising: a reservoir for the fluid;
  • 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.
  • 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.
  • 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.
  • 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.
  • the apparatus may be used to dispense liquid assay reagents to assay samples.
  • 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.
  • the fluid outlets comprise tubular probes through which fluid may be dispensed conveniently at a plurality of separate locations.
  • 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.
  • 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.
  • the reservoir has at least one fluid inlet through which fluid is supplied thereto.
  • 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.
  • 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.
  • the reservoir may additionally contain an air bleed valve to permit venting of air from the reservoir during priming thereof with liquid.
  • valve means may be used in the present apparatus to interrupt fluid flow from the reservoir to the outlets.
  • 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.
  • 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.
  • a variable delivery pump such as a peristaltic pump
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • apparatus 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.

Abstract

Système de distribution simultanée de fluides à une pluralité d'emplacements séparés comprenant: un réservoir pour le fluide (11), une pluralité d'orifices de sortie (15) permettant de distribuer le fluide à partir du résevoir (11) et un organe de vanne (3) servant à interrompre l'écoulement du fluide allant du réservoir (11) aux orifices de sortie (15), l'organe de vanne (3) s'ouvrant en réaction aux augmentations de la pression du fluide dans le réservoir (11), de manière à permettre l'écoulement du fluide depuis le réservoir (11) à travers les orifices de sortie (15). Ce système est particulièrement indiqué pour être utilisé dans des procédures d'analyses dans lesquelles il est nécessaire de distribuer simultanément vers une pluralité de récipients des quantités essentiellement égales de fluide.
PCT/GB1987/000347 1986-05-20 1987-05-20 Systeme de distribution de fluides WO1987007377A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GB8612261 1986-05-20
GB868612261A GB8612261D0 (en) 1986-05-20 1986-05-20 Fluid dispensing apparatus

Publications (1)

Publication Number Publication Date
WO1987007377A1 true WO1987007377A1 (fr) 1987-12-03

Family

ID=10598140

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/GB1987/000347 WO1987007377A1 (fr) 1986-05-20 1987-05-20 Systeme de distribution de fluides

Country Status (2)

Country Link
GB (1) GB8612261D0 (fr)
WO (1) WO1987007377A1 (fr)

Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1991017420A1 (fr) * 1990-05-07 1991-11-14 MAX-PLANCK-Gesellschaft zur Förderung der Wissenschaften e.V. Dispositif de dosage avec agencement radial des vannes
US5779147A (en) * 1995-10-24 1998-07-14 Nestec S.A. Dosing nozzle assembly and process for dosing liquid
EP1129008A2 (fr) * 1998-07-07 2001-09-05 Cartesian Technology Inc. Modele de pointe et matrice a acces selectif pour transfert micro-fluidique
EP1157737A2 (fr) * 2000-05-26 2001-11-28 Yokogawa Electric Corporation Procédé et dispositif pour la production de biopuces
EP1204479A1 (fr) * 1999-05-27 2002-05-15 Orchid BioSciences, Inc. Processeur d'echantillons multiples et systeme
EP1218180A1 (fr) * 1999-05-04 2002-07-03 Orchid BioSciences, Inc. Appareil de traitement d'echantillons a fluides multiples a adressabilite par puits unique
US6551557B1 (en) 1998-07-07 2003-04-22 Cartesian Technologies, Inc. Tip design and random access array for microfluidic transfer
US7690325B2 (en) 2004-04-30 2010-04-06 Bioforce Nanosciences, Inc. Method and apparatus for depositing material onto a surface

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE832076C (de) * 1949-05-01 1952-02-21 Dr Georg Roeder Serienabmessgeraet
FR1561307A (fr) * 1968-01-24 1969-03-28
US3999689A (en) * 1976-01-07 1976-12-28 Ciantro Steven V Device for simultaneously delivering equal amounts of liquid
US4304257A (en) * 1980-07-01 1981-12-08 Instrumentation Laboratory Inc. Valve with flexible sheet member
DE3208414A1 (de) * 1981-03-11 1982-09-16 Landstingens inköpscentral LIC, ekonomisk förening, 17141 Solna Ventil zur entleerung einer fluessigkeitsleitung

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE832076C (de) * 1949-05-01 1952-02-21 Dr Georg Roeder Serienabmessgeraet
FR1561307A (fr) * 1968-01-24 1969-03-28
US3999689A (en) * 1976-01-07 1976-12-28 Ciantro Steven V Device for simultaneously delivering equal amounts of liquid
US4304257A (en) * 1980-07-01 1981-12-08 Instrumentation Laboratory Inc. Valve with flexible sheet member
DE3208414A1 (de) * 1981-03-11 1982-09-16 Landstingens inköpscentral LIC, ekonomisk förening, 17141 Solna Ventil zur entleerung einer fluessigkeitsleitung

Cited By (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1991017420A1 (fr) * 1990-05-07 1991-11-14 MAX-PLANCK-Gesellschaft zur Förderung der Wissenschaften e.V. Dispositif de dosage avec agencement radial des vannes
US5779147A (en) * 1995-10-24 1998-07-14 Nestec S.A. Dosing nozzle assembly and process for dosing liquid
EP1129008A2 (fr) * 1998-07-07 2001-09-05 Cartesian Technology Inc. Modele de pointe et matrice a acces selectif pour transfert micro-fluidique
US7736591B2 (en) 1998-07-07 2010-06-15 Biodot, Inc. Method and apparatus for liquid dispensing
EP1129008A4 (fr) * 1998-07-07 2001-12-05 Cartesian Technology Inc Modele de pointe et matrice a acces selectif pour transfert micro-fluidique
US6551557B1 (en) 1998-07-07 2003-04-22 Cartesian Technologies, Inc. Tip design and random access array for microfluidic transfer
EP1218180A4 (fr) * 1999-05-04 2005-06-22 Orchid Biosciences Inc Appareil de traitement d'echantillons a fluides multiples a adressabilite par puits unique
EP1218180A1 (fr) * 1999-05-04 2002-07-03 Orchid BioSciences, Inc. Appareil de traitement d'echantillons a fluides multiples a adressabilite par puits unique
EP1204479A4 (fr) * 1999-05-27 2005-06-22 Orchid Biosciences Inc Processeur d'echantillons multiples et systeme
EP1204479A1 (fr) * 1999-05-27 2002-05-15 Orchid BioSciences, Inc. Processeur d'echantillons multiples et systeme
EP1157737A3 (fr) * 2000-05-26 2003-07-09 Yokogawa Electric Corporation Procédé et dispositif pour la production de biopuces
EP1157737A2 (fr) * 2000-05-26 2001-11-28 Yokogawa Electric Corporation Procédé et dispositif pour la production de biopuces
US7690325B2 (en) 2004-04-30 2010-04-06 Bioforce Nanosciences, Inc. Method and apparatus for depositing material onto a surface

Also Published As

Publication number Publication date
GB8612261D0 (en) 1986-06-25

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