US3764041A - Microdispensing process and apparatus - Google Patents

Microdispensing process and apparatus Download PDF

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Publication number
US3764041A
US3764041A US00083967A US3764041DA US3764041A US 3764041 A US3764041 A US 3764041A US 00083967 A US00083967 A US 00083967A US 3764041D A US3764041D A US 3764041DA US 3764041 A US3764041 A US 3764041A
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United States
Prior art keywords
dispensing
liquid
reagent
flushing
casing
Prior art date
Legal status (The legal status 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 status listed.)
Expired - Lifetime
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US00083967A
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English (en)
Inventor
H Noll
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
TM ANALYTIC Inc AN IL CORP
GD Searle LLC
Tracor Instruments Austin Inc
Original Assignee
GD Searle LLC
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Assigned to TM ANALYTIC, INC. AN IL CORP reassignment TM ANALYTIC, INC. AN IL CORP ASSIGNMENT OF ASSIGNORS INTEREST. Assignors: TRACOR ANALYTIC, INC., A TX CORP
Assigned to TRACOR INSTRUMENTS AUSTIN reassignment TRACOR INSTRUMENTS AUSTIN ASSIGNMENT OF ASSIGNORS INTEREST. Assignors: TRACOR INC
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    • 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
    • G01N35/1009—Characterised by arrangements for controlling the aspiration or dispense of liquids
    • G01N35/1016—Control of the volume dispensed or introduced

Definitions

  • the resolution often is determined by the smallness of the fractions that can be collected with precision. This applies to all procedures in which the detection and quantitative analysis of the substances that have been separated into narrow and closely spaced bands or zones must be carried out by discontinuous sampling. Thus, the separation into two closely spaced bands will only be detectable if a sufficient number of small fractions can be collected for analysis.
  • Fractionation into smaller volumes can be achieved by pipetting (as in manual laboratory practice) by touching the tip of the pipette to the surface of the receiving vessel or tube or by immersing the tip below the surface of a diluent fluid present in the receiving vessel.
  • My invention comprises a novel configuration of components providing for the precise dispensing of very small volumes of liquids or gels, thereby overcoming the limitations of automatic and manual fraction collecting mentioned above.
  • the apparatus and process of my invention achieves this precision by removing even fractional drops from the tip of the tube or needle delivering the liquid or gel to the collection ves sels by flushing this tip with asmall volume of a suitable rinsing liquid added on command from a supply reservoir, immediately preceding the advance of the delivery tip to the next vessel.
  • the rinsing liquid may comprise any liquid physically and chemically compatible with the fraction such as distilled water or suitable organic solvents. Where subsequent procedures require the addition of chemical reagents, the rinsing liquid may comprise or include such reagents.
  • My invention also comprises a delivery spout which may be operated so that reagents necessary for the liquid scintillation assay of collected'fractions are dispensed simultaneously with the fractions, thereby eliminating time-consuming and inefficient separate addition thereof.
  • the invention is adaptable for automated or manual collection systems and, when used in conjunction with a commercial moving fraction collector, timers, and commercial pumps, makes possible a completely automatic system capable of processing a liquid or gel for radioassay or chemical testing. Substantial economies of time are thus achieved as well as greater accuracy and improved radioassay resolution, since resolution increases with the smaller size fractions obtainable by use of my invention.
  • Typical applications of the automatic microdispensing fractionation and processing system made possible by my. invention are the processing of liquid density gradients and acrylamide electrophoresis gels for radioassay and the automatic chemical testing of fractions obtained from chromatographic columns, density gradients or acrylamide gels.
  • the fractionation of gels by existing techniques is similar to the collection of liquids and subject to the same limitations.
  • FIG. 1 is a front elevation view of a liquid or gel microdispensing and reagent dispensing apparatus embodying the invention
  • FIG. 2 is an enlarged vertical cross section view of the dispensing assembly of my microdispensing apparatus.
  • my liquid or gel microdispensing reagent dispensing apparatus comprises an L-shaped retainer block 10, that attaches by means of a baseplate 70 to the lower portion of any known liquid or gel delivery head (not shown).
  • the baseplate 70 has suitable slits for accommodating set screws 71 to enable adjustments of the apparatus in the direction of travel and laterally with respect to the center of the collection vessels, as required.
  • the retainer block has a vertical bore 12 whose upper portion is open-sided to afford a vertical channel 14 and an open-topped channel l6 communicating therewith to form an open acute-angle joint. The bore and two channels cooperate to removably support therein the liquid dispensing assembly 18.
  • Dispensing assembly 18 comprises a hollow needle or small-diameter conduit 20 which is connectable at its upper end, as by suitable tubing 22, to a liquid or gel supply and which terminates at its bottom in a dispensing tip 24.
  • a cylindrical tube or casing having an internal diameter greater than the external diameter of the needle 20 is positioned in sheath-like manner over the needle 20 to provide an annular passageway 32 therearound.
  • Passageway 32 is closed at its upper end by a removable cap member 34 having a central aperture 36 which supports the needle 20 coaxially within the passageway 32.
  • the open bottom end 38 of the easing 30 is positioned above the dispensing tip 24 for reasons which will subsequently become apparent.
  • a tubular side arm 40 projects at an acute angle from the casing 30 and communicates with the passageway 32, said side arm being connectable, as by suitable tubing 42, with a rinsing liquid supply and flushing pump. It should thus be noted that the entire assembly 18 is supported by the contour-accommodating bore 12 and channels 14 and 16 so that the same may be readily removed for purposes of cleaning, maintenance and replacement.
  • the foot of the L-shaped block is formed with a vertical channel or cut-out defined by a vertical wall 44 and opening to the facing edge 45 of the foot.
  • This channel spout 50 is adjustable by means of a set screw 56 adapted to track in a horizontal groove 58 formed in a side wall of inset block 46, while verticaland radial positioning of the spout is adjustable by means of a set screw 60 carried by the inset block and adapted to bear against vertical section 52 of the spout.
  • the spout thus may be positioned precisely with relation to dispensing tip 24 and the receiving vessels as dictated by the particular conditions obtaining.
  • the flushing pump is activated to pump a charge of rinsing liquid through the side arm to and into the passageway 32 where it flows downwardly and circulates around the needle 20 to emerge at the casing bottom 38.
  • the rinsing liquid surrounds and flows down the protruding dispensing tip 24 of the needle 20 in a stream, flushing from the tip the drop or fractional drop formed thereat.
  • the relative diameters of the needle 20 and passageway 32 are in some measure a function of the surface tension of the rinsing liquids and are determined to prevent unwanted flow of the rinsing liquids between flushing actions.
  • the microdispensing and reagent dispensing apparatus is combined with a commercial fraction collector, which moves the collecting vessels relative to a stationary delivery system or which moves the delivery head over a rack of collecting vessels.
  • the microdispensing apparatus will be interposed between the delivery system and the collecting vessels.
  • such known elements as a reagent supply and a reagent pump, a rinsing liquid supply and pump, a first timing means regulating the collecting interval, and a second timing means regulating the delivery of the rinsing liquid and the scintillation reagent, when required.
  • the rinsing liquid may contain, or comprise solely, the reagent or reagents required.
  • the flushing and reagent pumps are of the oneshot repetitive-action type.
  • the action of the pumps is synchronized with the advancement of the delivery head or collecting vessels depending on the fraction collector used in such a way that the pumping action is triggered and the liquid addition completed immediately before advancement to the next collection vessel.
  • the slave timer is set for an interval that is a few seconds shorter than the collection interval. Hence, with each advancement to the next collecting vessel, the slave timer is started. At the end of the interval, or a few seconds before the next advancement, the slave timer actuates the pumps and the rinsing liquid and/or reagent are introduced into the microdispensing and reagent dispensing apparatus.
  • the retainer block and inset block preferably are constructed of a rigid, lightweight, easily shaped or cut material such as metal, plastic or wood in order to properly support and maintain in position the various dispensing means.
  • the dispensing assembly 18 may be made of any suitable non-reactive and easily cleanable material such as stainless steel or glass.
  • Apparatus for dispensing precise volumes of a fluid which is a member of the group consisting of a liquid anda gel comprising:
  • a dispensing conduit connectable to a reservoir of said fluid and terminating in a dispensing tip
  • dispensing pump means communicating with said dispensing conduit for delivering a predetermined volume of said fluid dropwise through said dispensing tip
  • discontinuous flushing pump means communicating with said passageway for delivering a rinsing liquid at said dispensing tip and adapted to be actuated when delivery of said predetermined volume is substantially complete so as to flush from said dispensing tip fluid collected thereon; whereby the rinsing liquid flushes from the dispensing tip any fluid collected externally thereon to reproducibly complete the volume of fluid dispensed.
  • conduit comprises a hollow needle and said firstmentioned means comprises a cylindrical tubular casing having an inner diameter greater than the outer diameter of said needle,
  • said needle being positioned within said casing so that at least the dispensing tip extends outwardly from the bottom thereof.
  • Apparatus according to claim 2 in which the flushing pump means delivers the rinsing liquid under pressure and the difference between the inner diameter of the casing and outer diameter of the needle is such as to be effective to prevent flow of the flushing liquid between flushing cycles.
  • Apparatus according to claim 4 comprising further a cap member sealing the top portion of said passageway and accommodating said needle therethrough to maintain the same coaxially within the cas- Apparatus according to claim 2 and comprising further reagent dispensing means for dispensing a reagent during the dispensing cycle of the liquid or gel responsive to a pre-determined signal.
  • the rinsing liquid comprises a reagent for use in chemical analysis of the test fraction.
  • an apparatus for continuously and automatically obtaining precise test fractions from a liquid or gel reservoir for further analysis including a rack containing a plurality of collection vessels, a delivery head mounted above said vessels and means for moving delivery of liquid or gel from one vessel to the next at a pre-determined dispensing cycle, the improvement comprising:
  • a small-diameter conduit having a dispensing tip
  • timer means for automatically actuating the pump means at a pre-determined time in each dispensing cycle
  • Apparatus according to claim 10 in which the difference between the inner diameter of the casing and the outer diameter of the conduit is such as to be effective to prevent flow of the flushing liquid between flushing cycles.
  • the flushing liquid comprises a reagent for use in chemical analysis of the test fractions.
  • said timer means automatically actuating said second pump means to dispense into the test fraction simultaneously with the delivery of the flushing liquid a fixed amount of the liquid scintillation reagent for use in radioactive assay of the test fractions.

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  • General Health & Medical Sciences (AREA)
  • General Physics & Mathematics (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Analytical Chemistry (AREA)
  • Biochemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Immunology (AREA)
  • Physics & Mathematics (AREA)
  • Pathology (AREA)
  • Automatic Analysis And Handling Materials Therefor (AREA)
  • Sampling And Sample Adjustment (AREA)
  • Feeding, Discharge, Calcimining, Fusing, And Gas-Generation Devices (AREA)
  • Investigating Or Analysing Biological Materials (AREA)
  • Treatment Of Liquids With Adsorbents In General (AREA)
US00083967A 1970-10-26 1970-10-26 Microdispensing process and apparatus Expired - Lifetime US3764041A (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
US8396770A 1970-10-26 1970-10-26

Publications (1)

Publication Number Publication Date
US3764041A true US3764041A (en) 1973-10-09

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ID=22181815

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Application Number Title Priority Date Filing Date
US00083967A Expired - Lifetime US3764041A (en) 1970-10-26 1970-10-26 Microdispensing process and apparatus

Country Status (7)

Country Link
US (1) US3764041A (enrdf_load_stackoverflow)
JP (1) JPS547235B1 (enrdf_load_stackoverflow)
CA (1) CA974204A (enrdf_load_stackoverflow)
CH (1) CH535429A (enrdf_load_stackoverflow)
DE (1) DE2153090A1 (enrdf_load_stackoverflow)
FR (1) FR2111843B1 (enrdf_load_stackoverflow)
GB (1) GB1321568A (enrdf_load_stackoverflow)

Cited By (21)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3869068A (en) * 1974-06-06 1975-03-04 Hyperion Inc Diluter probe assembly
US3891121A (en) * 1972-08-04 1975-06-24 Mead Corp Method of operating a drop generator that includes the step of pre-pressurizing the liquid manifold
US3960020A (en) * 1974-12-30 1976-06-01 Technicon Instruments Corporation Liquid aspirating probe assembly of a supply analyzer
US3971420A (en) * 1973-12-11 1976-07-27 F. Kuppersbusch & Sohne Aktiengesellschaft Dosing device for industrial cooking apparatus
FR2354555A1 (fr) * 1976-06-08 1978-01-06 Technicon Instr Pipette pour aspirer des liquides pour l'analyse d'echantillons
US4090475A (en) * 1976-05-19 1978-05-23 S. E. Rykoff & Co. Self-cleaning fluid injection system
US4528161A (en) * 1981-08-31 1985-07-09 American Hospital Supply Corp. Probe for automated liquid dispenser
US4534494A (en) * 1982-11-15 1985-08-13 Societe Anonyme Dite: Etude De Realisation De Chaines Automatiques Erca Cleaning system for filler
US4574850A (en) * 1985-01-17 1986-03-11 E. I. Du Pont De Nemours And Company Method of and apparatus for dispensing liquid
US4610170A (en) * 1983-11-30 1986-09-09 Labsystems Oy Method for the dilution of liquid samples
US4670219A (en) * 1985-02-27 1987-06-02 Fisher Scientific Company Liquid handling
US4820497A (en) * 1986-06-23 1989-04-11 E. I. Du Pont De Nemours And Company Movable cleaning assembly for an aspirating needle
US4905871A (en) * 1986-06-06 1990-03-06 Dutertre Donald F Handling device for agricultural chemicals and the like
US5188255A (en) * 1990-09-07 1993-02-23 Du Benjamin R Method and apparatus for facilitating the cleaning of a spray aperture in a mixing chamber of a nozzle
US5261566A (en) * 1981-02-16 1993-11-16 Tokyo Ohka Kogyo Co., Ltd. Solution-dropping nozzle device
US5332311A (en) * 1991-10-09 1994-07-26 Beta Raven Inc. Liquid scale and method for liquid ingredient flush thereof
US5650122A (en) * 1986-10-31 1997-07-22 Pasteur Sanofi Diagnostics Automated patient sample analysis instrument having tubes and reaction wells washing apparatus
US6463611B1 (en) * 1999-04-02 2002-10-15 Ecolab, Inc. Apparatus for dispensing incompatible chemicals to a common utilization point
US20050269362A1 (en) * 2004-06-02 2005-12-08 Guerrero Arturo F Device and method for hygienically delivering a liquid food
US20050281713A1 (en) * 2004-06-18 2005-12-22 Bioanalytical Systems, Inc. (An Indiana Company) System and method for sample collection
CN110418967A (zh) * 2017-06-30 2019-11-05 深圳迈瑞生物医疗电子股份有限公司 反应组件、样本分析仪及混合方法

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2482310A1 (fr) * 1980-05-09 1981-11-13 Prioux Alain Dispositif de transfert de liquide pour un appareil de prelevement ou de fourniture d'echantillons liquides
DE4432599C2 (de) * 1994-09-13 1996-10-31 Thomae Gmbh Dr K Probenahmeverfahren für die Bioprozeßanalytik

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR1114735A (fr) * 1953-12-12 1956-04-16 Naamlooze Vennootschap Unstzij Dispositif de distribution de petites quantités de liquide

Cited By (26)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3891121A (en) * 1972-08-04 1975-06-24 Mead Corp Method of operating a drop generator that includes the step of pre-pressurizing the liquid manifold
US3971420A (en) * 1973-12-11 1976-07-27 F. Kuppersbusch & Sohne Aktiengesellschaft Dosing device for industrial cooking apparatus
US3869068A (en) * 1974-06-06 1975-03-04 Hyperion Inc Diluter probe assembly
US3960020A (en) * 1974-12-30 1976-06-01 Technicon Instruments Corporation Liquid aspirating probe assembly of a supply analyzer
US4090475A (en) * 1976-05-19 1978-05-23 S. E. Rykoff & Co. Self-cleaning fluid injection system
FR2354555A1 (fr) * 1976-06-08 1978-01-06 Technicon Instr Pipette pour aspirer des liquides pour l'analyse d'echantillons
US5261566A (en) * 1981-02-16 1993-11-16 Tokyo Ohka Kogyo Co., Ltd. Solution-dropping nozzle device
US4528161A (en) * 1981-08-31 1985-07-09 American Hospital Supply Corp. Probe for automated liquid dispenser
US4534494A (en) * 1982-11-15 1985-08-13 Societe Anonyme Dite: Etude De Realisation De Chaines Automatiques Erca Cleaning system for filler
US4610170A (en) * 1983-11-30 1986-09-09 Labsystems Oy Method for the dilution of liquid samples
US4574850A (en) * 1985-01-17 1986-03-11 E. I. Du Pont De Nemours And Company Method of and apparatus for dispensing liquid
EP0188265A3 (en) * 1985-01-17 1987-06-10 E.I. Du Pont De Nemours And Company Method of and apparatus for dipsensing liquid
US4670219A (en) * 1985-02-27 1987-06-02 Fisher Scientific Company Liquid handling
US4905871A (en) * 1986-06-06 1990-03-06 Dutertre Donald F Handling device for agricultural chemicals and the like
US4820497A (en) * 1986-06-23 1989-04-11 E. I. Du Pont De Nemours And Company Movable cleaning assembly for an aspirating needle
US5650122A (en) * 1986-10-31 1997-07-22 Pasteur Sanofi Diagnostics Automated patient sample analysis instrument having tubes and reaction wells washing apparatus
US5188255A (en) * 1990-09-07 1993-02-23 Du Benjamin R Method and apparatus for facilitating the cleaning of a spray aperture in a mixing chamber of a nozzle
US5332311A (en) * 1991-10-09 1994-07-26 Beta Raven Inc. Liquid scale and method for liquid ingredient flush thereof
US6463611B1 (en) * 1999-04-02 2002-10-15 Ecolab, Inc. Apparatus for dispensing incompatible chemicals to a common utilization point
US20050269362A1 (en) * 2004-06-02 2005-12-08 Guerrero Arturo F Device and method for hygienically delivering a liquid food
US20080061081A1 (en) * 2004-06-02 2008-03-13 Nestec S.A. Device and method for hygienically deliverying a liquid
US7347345B2 (en) * 2004-06-02 2008-03-25 Nestec S.A. Device and method for hygienically delivering a liquid food
US7694850B2 (en) 2004-06-02 2010-04-13 Nestec S.A. Device and method for hygienically delivering a liquid
US20050281713A1 (en) * 2004-06-18 2005-12-22 Bioanalytical Systems, Inc. (An Indiana Company) System and method for sample collection
CN110418967A (zh) * 2017-06-30 2019-11-05 深圳迈瑞生物医疗电子股份有限公司 反应组件、样本分析仪及混合方法
CN110418967B (zh) * 2017-06-30 2024-02-06 深圳迈瑞生物医疗电子股份有限公司 反应组件、样本分析仪及混合方法

Also Published As

Publication number Publication date
FR2111843B1 (enrdf_load_stackoverflow) 1975-10-10
CH535429A (de) 1973-03-31
DE2153090A1 (de) 1972-07-27
CA974204A (en) 1975-09-09
FR2111843A1 (enrdf_load_stackoverflow) 1972-06-09
GB1321568A (en) 1973-06-27
JPS547235B1 (enrdf_load_stackoverflow) 1979-04-05

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Legal Events

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AS Assignment

Owner name: TM ANALYTIC, INC. AN IL CORP

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST.;ASSIGNOR:TRACOR ANALYTIC, INC., A TX CORP;REEL/FRAME:004220/0818

Effective date: 19830701

AS Assignment

Owner name: TRACOR INSTRUMENTS AUSTIN

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST.;ASSIGNOR:TRACOR INC;REEL/FRAME:004188/0869

Effective date: 19830901