US3784826A - Apparatus for analysing continuously discrete biological liquid samples - Google Patents

Apparatus for analysing continuously discrete biological liquid samples Download PDF

Info

Publication number
US3784826A
US3784826A US00118426A US3784826DA US3784826A US 3784826 A US3784826 A US 3784826A US 00118426 A US00118426 A US 00118426A US 3784826D A US3784826D A US 3784826DA US 3784826 A US3784826 A US 3784826A
Authority
US
United States
Prior art keywords
containers
incubation
sample
dilution
container
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
Application number
US00118426A
Other languages
English (en)
Inventor
K Bagshawe
D Marchant
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.)
EDM Ltd AN ISLE OF MAN Co
POST NATAL CHORIONEPIPHELIOMA TRUST A CHARITABLE TRUST OF GREAT BRITAIN
HAYWARD FOUNDATION
Original Assignee
HAYWARD FOUNDATION
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 HAYWARD FOUNDATION filed Critical HAYWARD FOUNDATION
Application granted granted Critical
Publication of US3784826A publication Critical patent/US3784826A/en
Assigned to POST NATAL CHORIONEPIPHELIOMA TRUST, THE, A CHARITABLE TRUST OF GREAT BRITAIN, EDM LIMITED , AN ISLE OF MAN COMPANY reassignment POST NATAL CHORIONEPIPHELIOMA TRUST, THE, A CHARITABLE TRUST OF GREAT BRITAIN ASSIGNMENT OF ASSIGNORS INTEREST. Assignors: PICKER INTERNATIONAL INC.
Assigned to PICKER INTERNATIONAL, INC. reassignment PICKER INTERNATIONAL, INC. CHANGE OF NAME (SEE DOCUMENT FOR DETAILS). EFFECTIVE JULY 10, 1981 Assignors: PICKER CORPORATION
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

Links

Images

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
    • G01N35/02—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor using a plurality of sample containers moved by a conveyor system past one or more treatment or analysis stations
    • G01N35/025—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor using a plurality of sample containers moved by a conveyor system past one or more treatment or analysis stations having a carousel or turntable for reaction cells or cuvettes
    • 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
    • G01N2035/00346—Heating or cooling arrangements
    • G01N2035/00356—Holding samples at elevated temperature (incubation)
    • G01N2035/00386—Holding samples at elevated temperature (incubation) using fluid heat transfer medium
    • 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
    • G01N2035/00346—Heating or cooling arrangements
    • G01N2035/00435—Refrigerated reagent storage

Definitions

  • ABSTRACT Analysis apparatus primarily for carrying out biological analyses using radioimmunoassay techniques includes a turntable disc for carrying a plurality of specimens.
  • a delivery arm delivers successive samples to a row of dilution containers and simultaneously supplies a diluent.
  • a transfer arm controlled by a code on the turntable disc picks a selected diluted sample and transfers it to one of a long series of incubation chambers each of which contains a reagent.
  • a second rea gent is added at the time of transfer and the mixture is incubated prior to removal by an appropriate device. After removal the active constituents are filtered and measured quantitatively by a counter.
  • FIGHA FIGMD FIGMG FIGMB FIG.
  • radioimmunoassay Numerous analysis methods for biological samples are available of which radioimmunoassay has particular application where the sample includes, or may include hormones, enzymes or other substances produced by normal or cancerous cells.
  • the technique of radioimmunoassay serves to measure accurately the quantity of a specific species of a protein and/or a specific species of a polypeptide in a sample, for example urine, blood or plasma, by reaction with specific anti-bodies produced in an animal in response to injections with the protein or polypeptide to be measured. Further, isotopically labelled protein or polypeptide of the specific species to be measured is added to the sample and this competes with the specific protein or polypeptide of the unknown sample for binding sites on the antibody.
  • isotopically labelled protein or isotopically labelled polypeptide bound to an antibody can be effected by filtration, centrifuging or electrophoresis.
  • analysis apparatus comprising means for successively delivering discrete biological samples to successive containers at a station at which each sample is diluted to produce a plurality of diluted samples, means for diluting the samples at the dilution station, means for transferring a selected said diluted sample to an incubation container, an incubator for incubating the selected diluted sample in the container and analysis means for analysing components of the diluted incubated sample.
  • liquid analysis apparatus incorporating a plurality of remotely controlled peristaltic pumps for delivering and/or transferring quantities of liquid to and- /or from containers of the apparatus, at least one of the pumps incorporating bellows means, operable at the end of each delivery cycle of the pump to produce a suck-back action preventing the formation of drips.
  • FIG. 1 is a perspective view of analysis apparatus in accordance with the invention
  • FIG. 2 is a plan view ofa turntable for carrying original, undiluted samples and forming part of the apparatus shown in FIG. 1;
  • FIG. 3 is a side elevation of a device for disposing of unwanted diluted samples
  • FIG. 4 is a plan view illustrating a specimen dilution arm and a sample selection arm
  • FIG. 4A is a side elevation of the sample selection arm of FIG. 4;
  • FIG. 5 is a side elevation of a device for cleaning certain parts of the arms shown in FIG. 4;
  • FIG. 6 is a fragmentary plan view of an incubation container web and one of the pulleys on which it is mounted;
  • FIG. 7 is a side elevation of a device for capping the individual containers of the incubation container strip conveyor and part of the drive for the incubation con tainer web;
  • FIG. 8 is a vertical sectionthrough an incubator of the apparatus
  • FIG. 9A is a vertical section of an arrangement for removing the contents of successive incubation containers
  • FIG. 98 illustrates a detail of the arrangement of FIG. 9A
  • FIG. 9C is a diagram of an associated peristaltic P p
  • FIG. 10 is a diagram illustrating a pump used for certain fluid supply and withdrawal operations in the apparatus
  • FIG. 11 is a section of the pump illustrated in FIG. 10;
  • FIG. 12 is a section of another pump used in the apparatus.
  • FIGS. 13A to 13C illustrate a device for adjusting the operation of one of the pumps.
  • FIG. 14 is a circuit diagram of the control system of the apparatus.
  • the apparatus as illustrated in FIG. 1 includes a turntable disc or other carrier means which has two rings of apertures 101, 102 each containing a pot 103 or other specimen container which is preferably disposable but is, in any event, readily removable from the turntable disc.
  • the turntable disc 100 has a plurality of sets of pegs I04 selectively engaged in holes, or notches, the rows of holes or notches extending radially inwardly from the rings of apertures 101, 102.
  • the position of thepeg 104 in any given radial row dictates the required dilution or neat specimen from which a sample is taken.
  • Each sample is withdrawn from its pot 103 by delivery means 109 and diluted to a series of dilutions in a row of depressions 110 or other dilution containers in a plastics band 111 and a selected diluted or undiluted sample is transferred by transfer means 112 to an incubation train which includes a row of disposable plastics containers 131.
  • the incubation train is initially stored in a refrigerated compartment 140.
  • One reagent is already contained in each container 131 and another is added preferably simultaneously with transfer to the container 131, and the biological reactions are allowed to proceed with the aid of thorough mixing by agitation at the time of transfer and for about three minutes thereafter.
  • the incubation train then follows an elongate path through an incubator 150.
  • the length of this path through the incubator and the speed of the incubation train is such that the elapsed time from the addition of the reagents to the separation of the constituent to be measured corresponds to the required incubation time (say 2 hours at 37 C), for the reagents and sample in question.
  • the incubation train is indexed forward at one minute intervals.
  • the samples are removed from the containers 131 by an incubatedsample removal means 160 and the molecular complexes in the incubated material are separated into the antibody-bound and antibody-free phases either by filtration, centrifuging or electrophoresis as is conventional in radioimmunoassay techniques.
  • a vacuum filtration process is employed, the mixture being released on to a filter material by successively withdrawing the incubated sample from each container of the incubation train and washing out the whole of the contents on to the filter material by gelatin or other washing agent dispensed by the removal means 160.
  • the filter bed material moves past or through an isotopic counter and the whole bed, including sample solids, is passed to waste.
  • the output of the isotopic counter is supplied to a pulse-height analyser (not shown) which, in turn passes its output to a rate meter. If desired, the signals from the rate meter are recorded on a chart recorder.
  • the output of the multiplication stage is fed via a scaler to a data processor which correlates the result with sample identification information and the selected degree of dilution in order to produce comprehensive digital information at a final print-out.
  • any one analysis apparatus more than one disc 100 and set of pots 103 will be provided, since, when one set of samples is being processed another set is being loaded with fresh sample-containing pots.
  • the specimens to be tested are arranged in the moulded plastics pots 103 which are lipped to enable them to engage the periphery of appropriately sized apertures 101, 102 in the turntable disc 100 which is rotatable about a vertical axis.
  • the two annular rows 101, 102 of apertures are arranged with the individual apertures of one row 101 alternating in the circumferential sense with individual apertures of the other row 102. In other words, no one aperture has its centre line on the same radial line as another.
  • Radially inwardly of each pot-receiving aper ture there is a radially extending line of eight holes 105 (FIG. 2) of smaller diameter than the pot-receiving apertures.
  • control apertures 105 serve as a part of the control system of the apparatus, and each denotes a different degree of dilution required for the portion ofthe sample (or next specimen) to be deposited in the incubation train.
  • the radial rows of control apertures 105 also form eight annular rows and a micro-switch (not shown) is associated with and lies below each circular row so that a peg 104 inserted in one of the apertures 105 trips a micro-switch appropriate to the final degree of dilution (or non-dilution) selected and this in turn controls the operation of the transfer means 112 and pump hereinafter described in greater detail.
  • the pegs 104 are held in place by a circular plate 106 (FIG. 1) and the disc as a whole is readily removable from the apparatus.
  • a horizontally extending flange 106A (broken lines) upon which the disc 100 is mounted by keying also actuates by means of an annular row of recesses 107, two indexing micro-switches 107.
  • These position-control micro-switches 107' serve to control the indexing movements of the disc 100 through positions in which pots of the outer row 102 are available for sample delivery and on completion of pots of this row a switch 107" engages a recess 10613 and thus causes the flange to be indexed initially through one half of the pitch of the recesses 107 so that the other one of the switches 107' becomes operative.
  • the flange is then indexed as before until the recess 1068 which actuates the switch 107" again actuates the switch to stop the apparatus when all the specimens have been dealt with.
  • the switch 107 also initiates a change in operation of the delivery and dilution arm, in that the transverse movement is extended to cover the inner row.
  • the turntable disc 100 is driven intermittently by an electric motor (not shown) and is stopped exactly in each indexed position by a brake (likewise not shown) under control of the indexing switches 107. Alternatively if a synchronous motor is used, the brake can be omitted.
  • FIG. 14 Details of the control system have been omitted from the general description but are illustrated by FIG. 14, however, at this stage attention is drawn to the timers arranged conveniently in a bank T and the relays in a bank R.
  • a power supply input is indicated at S and a control panel C lies between the timer bank T and the turntable 100.
  • a vacuum gauge V indicates the vacuum applied to the filter process in the analysis counter.
  • the turntable 100 lies adjacent the delivery means and the transfer means 109, 112,
  • the band 111 is vacuum-formed to provide the continuous series of transverse rows of depressions 110, seven in each row. To reduce interruption in the operation of the machine, it is clearly desirable to have a supply of dilution containers in the band which will last for at least one day of continuous operation.
  • each dilution container (FIG. 3) is formed with a flat bottom A and a frustoconical side wall 1108.
  • the side wall 110B extends at an angle of 92 r to the plane of the bottom 110A.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Physics & Mathematics (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Analytical Chemistry (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • General Physics & Mathematics (AREA)
  • Immunology (AREA)
  • Pathology (AREA)
  • Automatic Analysis And Handling Materials Therefor (AREA)
  • Investigating Or Analysing Biological Materials (AREA)
US00118426A 1970-03-03 1971-02-24 Apparatus for analysing continuously discrete biological liquid samples Expired - Lifetime US3784826A (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
GB1002370 1970-03-03

Publications (1)

Publication Number Publication Date
US3784826A true US3784826A (en) 1974-01-08

Family

ID=9960026

Family Applications (1)

Application Number Title Priority Date Filing Date
US00118426A Expired - Lifetime US3784826A (en) 1970-03-03 1971-02-24 Apparatus for analysing continuously discrete biological liquid samples

Country Status (5)

Country Link
US (1) US3784826A (enrdf_load_stackoverflow)
DE (1) DE2110221A1 (enrdf_load_stackoverflow)
FR (1) FR2084155A5 (enrdf_load_stackoverflow)
GB (1) GB1353014A (enrdf_load_stackoverflow)
IT (1) IT943523B (enrdf_load_stackoverflow)

Cited By (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3923463A (en) * 1972-10-09 1975-12-02 Kenneth Dawson Bagshawe Apparatus for performing chemical and biological analysis
US3999068A (en) * 1975-06-16 1976-12-21 Union Carbide Corporation Apparatus for measuring the radioactivity of the contents of tube like receptacles
US4021669A (en) * 1976-03-15 1977-05-03 The United States Of America As Represented By The United States Energy Research And Development Administration Nuclear fuel microsphere gamma analyzer
EP0074102A1 (en) * 1981-09-04 1983-03-16 Hitachi, Ltd. Chemical analyzer equipped with reagent cold-storage chamber
EP0109613A1 (en) * 1982-11-09 1984-05-30 Mitsubishi Kasei Corporation Automatic analytical apparatus
EP0445616A3 (en) * 1990-03-03 1992-03-04 Hitachi, Ltd. Automatic analysis method and apparatus of the same
EP0571034A1 (en) * 1992-05-22 1993-11-24 Johnson & Johnson Clinical Diagnostics, Inc. Mixing mechanism for analyzers
US5360597A (en) * 1993-03-22 1994-11-01 Eastman Kodak Company Ribbed mechanism for mixing sample by vibration
US20050260768A1 (en) * 2000-07-18 2005-11-24 Cawse James N Sequential high throughput screening method and system
US20090035867A1 (en) * 2007-07-31 2009-02-05 Kenichi Yagi Automatic analyzer and method for using the same
CN109311012A (zh) * 2016-06-17 2019-02-05 株式会社生物基石 管开闭装置及包含该装置的分装系统

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2521304A1 (fr) * 1982-02-09 1983-08-12 Rhone Poulenc Sa Appareil automatise pour la realisation de dosages biologiques, biochimiques ou physico-chimiques
GB2124707B (en) * 1982-07-06 1985-07-31 Mk Refrigeration Limited Liquid-dispensing outlet
DE102004043399A1 (de) * 2004-09-03 2006-03-09 Bioplan Consulting Gmbh Anlage zur Behandlung mikrobiologischer Proben
IT1395679B1 (it) * 2009-07-31 2012-10-16 Cps Color Equipment Spa Dispositivo di erogazione di prodotti fluidi o simili

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3614434A (en) * 1968-07-17 1971-10-19 Lofstrom James E Automatic agitating and sample device

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3614434A (en) * 1968-07-17 1971-10-19 Lofstrom James E Automatic agitating and sample device

Cited By (18)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3923463A (en) * 1972-10-09 1975-12-02 Kenneth Dawson Bagshawe Apparatus for performing chemical and biological analysis
USRE30627E (en) * 1972-10-09 1981-05-26 Picker Corporation Apparatus for performing chemical and biological analysis
US3999068A (en) * 1975-06-16 1976-12-21 Union Carbide Corporation Apparatus for measuring the radioactivity of the contents of tube like receptacles
US4021669A (en) * 1976-03-15 1977-05-03 The United States Of America As Represented By The United States Energy Research And Development Administration Nuclear fuel microsphere gamma analyzer
EP0074102A1 (en) * 1981-09-04 1983-03-16 Hitachi, Ltd. Chemical analyzer equipped with reagent cold-storage chamber
EP0109613A1 (en) * 1982-11-09 1984-05-30 Mitsubishi Kasei Corporation Automatic analytical apparatus
EP0445616A3 (en) * 1990-03-03 1992-03-04 Hitachi, Ltd. Automatic analysis method and apparatus of the same
EP0571034A1 (en) * 1992-05-22 1993-11-24 Johnson & Johnson Clinical Diagnostics, Inc. Mixing mechanism for analyzers
US5360597A (en) * 1993-03-22 1994-11-01 Eastman Kodak Company Ribbed mechanism for mixing sample by vibration
US20050260768A1 (en) * 2000-07-18 2005-11-24 Cawse James N Sequential high throughput screening method and system
US7052659B1 (en) * 2000-07-18 2006-05-30 General Electric Company Sequential high throughput screening method and system
US20090035867A1 (en) * 2007-07-31 2009-02-05 Kenichi Yagi Automatic analyzer and method for using the same
US9063106B2 (en) * 2007-07-31 2015-06-23 Hitachi High-Technologies, Corporation Automatic analyzer and method for using the same
CN109311012A (zh) * 2016-06-17 2019-02-05 株式会社生物基石 管开闭装置及包含该装置的分装系统
JP2019527339A (ja) * 2016-06-17 2019-09-26 バイオインフラ、カンパニー、リミテッドＢｉｏｉｎｆｒａ Ｃｏ．， Ｌｔｄ． チューブ開閉装置、及びそれを含む分注システム
EP3473339A4 (en) * 2016-06-17 2019-11-13 Bioinfra Co., Ltd. PIPE OPENING AND CLOSING DEVICE AND DISCHARGE SYSTEM THEREWITH
CN109311012B (zh) * 2016-06-17 2021-08-27 株式会社生物基石 管开闭装置及包含该装置的分装系统
US11572263B2 (en) 2016-06-17 2023-02-07 Bioinfra Co., Ltd. Tube opening and closing device and dispensing system including same

Also Published As

Publication number Publication date
DE2110221A1 (de) 1971-10-14
GB1353014A (en) 1974-05-15
IT943523B (it) 1973-04-10
FR2084155A5 (enrdf_load_stackoverflow) 1971-12-17

Similar Documents

Publication Publication Date Title
US3784826A (en) Apparatus for analysing continuously discrete biological liquid samples
CA1167437A (en) Apparatus and method for the controlled, non-invasive mixing of substances
US4837159A (en) Method and apparatus for effecting immunological analysis
EP0089346B1 (en) Automated immunoassay system
US3883308A (en) Apparatus for analysing liquid substances likely to form agglutinates
US3679367A (en) Apparatus for determining the pack volume of particulates in liquid mixtures
JPH07505476A (ja) 自動連続ランダム・アクセス分析システム及びその構成要素
GB2199407A (en) Automated patient sample analysis instrument
US4837160A (en) Biological fluid assay system and method
CA1259554A (en) Clinical analysis systems and methods
EP1417494A2 (en) Method for automatically storing and reprocessing patient specimen's in an automatic clinical analyzer
JPH0118383B2 (enrdf_load_stackoverflow)
US5324479A (en) Analyzer for the determination of the phenotype and the ABO blood group
US20020064884A1 (en) Method for automatically storing and reprocessing patient specimen's in an automatic clinical analyzer
EP0336309A2 (en) A selective or sequential access analyzer for clinico-chemical analyses and for immunological tests
JPS6230377B2 (enrdf_load_stackoverflow)
JPH05172828A (ja) 自動分析装置
Marschner et al. A modular analyzer system for double antibody radioimmunoassays
JPH0577981B2 (enrdf_load_stackoverflow)
JPS6249259A (ja) 自動分析装置
JPH0656383B2 (ja) 酵素免疫学的自動分析装置
JPS61118662A (ja) 免疫学的自動分析方法
JPH0471182B2 (enrdf_load_stackoverflow)
JPH04194752A (ja) 免疫測定装置のｂ／ｆ分離システム
JPH0364834B2 (enrdf_load_stackoverflow)

Legal Events

Date Code Title Description
AS Assignment

Owner name: EDM LIMITED , SARK,CHANNEL ISLANDS, AN ISLE OF MA

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST.;ASSIGNOR:PICKER INTERNATIONAL INC.;REEL/FRAME:004103/0578

Effective date: 19830105

Owner name: PICKER INTERNATIONAL, INC.

Free format text: CHANGE OF NAME;ASSIGNOR:PICKER CORPORATION;REEL/FRAME:004103/0597

Effective date: 19810617

Owner name: POST NATAL CHORIONEPIPHELIOMA TRUST, THE, 62 THE P

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST.;ASSIGNOR:PICKER INTERNATIONAL INC.;REEL/FRAME:004103/0578

Effective date: 19830105