WO1990000251A1 - Appareil et procede d'analyse a pression - Google Patents

Appareil et procede d'analyse a pression Download PDF

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Publication number
WO1990000251A1
WO1990000251A1 PCT/US1989/002914 US8902914W WO9000251A1 WO 1990000251 A1 WO1990000251 A1 WO 1990000251A1 US 8902914 W US8902914 W US 8902914W WO 9000251 A1 WO9000251 A1 WO 9000251A1
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WO
WIPO (PCT)
Prior art keywords
filter
analyte
reaction chamber
labeled
ligand
Prior art date
Application number
PCT/US1989/002914
Other languages
English (en)
Inventor
Brian W. Lee
Peter Nash
Michelle M. Krenz
Stephen J. Chudzik
Original Assignee
Bio-Metric Systems, Inc.
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 Bio-Metric Systems, Inc. filed Critical Bio-Metric Systems, Inc.
Publication of WO1990000251A1 publication Critical patent/WO1990000251A1/fr

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Classifications

    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/569—Immunoassay; Biospecific binding assay; Materials therefor for microorganisms, e.g. protozoa, bacteria, viruses
    • G01N33/571—Immunoassay; Biospecific binding assay; Materials therefor for microorganisms, e.g. protozoa, bacteria, viruses for venereal disease, e.g. syphilis, gonorrhoea
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/543—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
    • G01N33/54366—Apparatus specially adapted for solid-phase testing
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/569—Immunoassay; Biospecific binding assay; Materials therefor for microorganisms, e.g. protozoa, bacteria, viruses
    • G01N33/56911—Bacteria
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/569—Immunoassay; Biospecific binding assay; Materials therefor for microorganisms, e.g. protozoa, bacteria, viruses
    • G01N33/56961—Plant cells or fungi
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
    • G01N33/6854—Immunoglobulins
    • G01N33/686—Anti-idiotype

Definitions

  • the present invention relates to an apparatus and method for determining the presence of microorganisms, chemicals, and other analytes in physiological, biological and environmental specimens.
  • the traditional methods of detecting and identifying microorganisms in physiological and biological fluids require cell culturing on laboratory media (sometimes followed by susceptibility testing to determine resistance to a particular antibiotic) , identification of the organism by detection of serum antibodies against the organism, or isolation of the organism from infected tissues. These methods may require from 24 hours to ten days to perform and therefore do not necessarily contribute toward patient management and diagnosis. In some cases the microorganism cannot be isolated or cultured. Development of rapid detection methods which are sensitive enough to determine if a particular microorganism (viable or non-viable) is present in a biological specimen and which can be easily and rapidly performed in a clinic or doctor's office would greatly aid in the diagnosis of illnesses induced by such organisms.
  • Membranes and filters have been used in a number of devices and in procedures for determining the presence of an analyte in a sample. These devices, however, are dependent on a specific sample size, typically utilize bound reagents and are dependent upon the rate of diffusion of liquid sample through an absorbent material to define the time limitations of the assay.
  • U.S. Patent 4,632,901 discloses an apparatus having a membrane or filter to which an antibody is bound and which is in liquid contact with an absorbent material. The sample size is limited by the absorbancy of the material.
  • U.S. Patent 4,623,461 also discloses a membrane device having an absorbent material in fluid contact with the membrane. In this device, however, the absorbent material contacts only the periphery of the membrane thus causing liquid to diffuse transversely. The device is useful for only a .limited number of sample types.
  • the present invention provides apparatus and methods for use in determining, in a liquid sample, the presence of an analyte which is one member of a ligand-receptor pair; the method using filter means and superatmospheric pressure.
  • filter means we have found that the use of superatmospheric pressure with the apparatus and methods of the invention to create a pressure differential .across the filter means provides substantially better results than are obtained with use of a vacuum to create the pressure differential.
  • the apparatus of the invention comprises a reaction chamber having at least one open end, a predetermined quantity of a labeled member of the ligand-receptor pair of which the analyte is the other member, the labeled ligand-receptor pair member being chosen to bind to the analyte in relation to the quantity of analyte in the sample and being disposed within the chamber, means for applying superatmospheric pressure to the contents of the reaction chamber, and filter means communicating with the open end of the reaction chamber for preventing passage through the filter means of a labeled ligand-receptor pair member when it is bound to an analyte while permitting unbound labeled ligand-receptor pair member to pass therethrough when supe atmospheric pressure is applied to the chamber to force the contents of the chamber through the filter means.
  • the filter means comprises a porous filter or membrane communicating with the open end of the reaction chamber, the filter having pores sized to prevent passage therethrough of the labeled ligand-receptor pair member when it is bound to analyte while permitting unbound labeled ligand-receptor pair member to pass therethrough when superatmospheric pressure is applied to the reaction chamber.
  • the filter is desirably made of a low protein binding material having pores sized no larger than about lOOum in diameter and preferably in the range of .45um-15um.
  • the apparatus provides a substantially enclosed system comprising a .cylindrical chamber having a plunger received snugly therein for providing superatmospheric pressure to the contents of the reaction chamber when the assay is performed, a filter, and support means for supporting the filter between an upper and lower housing, the upper housing being made of a clear material so that the surface of the filter is visible through the housing wall.
  • the upper and lower housings are removably attachable to the reaction chamber and to a collection chamber that is positioned to collect fluid and other material that passes through the filter during the performance of an assay.
  • the invention comprises a method of determining, in a liquid sample, the presence of an analyte which is one member of a ligand-receptor pair.
  • the method comprises the steps of reacting the liquid sample with a predetermined quantity of a labeled member of the ligand-receptor pair chosen to bind to the analyte in the sample in relation to the quantity of analyte present in the sample, forcing the resulting reaction mixture under superatmospheric through a porous filter having pores sized to substantially prevent passage therethrough of the labeled ligand-receptor pair member when it is bound to an analyte while permitting unbound labeled ligand-receptor pair member to pass therethrough, and determining the presence of analyte in the sample by detecting the presence of labeled ligand-receptor pair member in and on the filter.
  • Figure 1 is an exploded front view of an apparatus of the invention
  • Figure 2 is a cross-sectional view of the apparatus of Figure 1;
  • Figure 3 is a bro en-away, front view of a plunger part -.of the apparatus of Figure 1.
  • ligand-receptor pair refers to a pair of compounds of which one, a “receptor” is capable of recognizing a particular spacial and polar organization of the other ("ligand") or portion thereof, and is capable of binding to that compound.
  • illustrative receptors forming the other half of a ligand-receptor pair include antibodies, enzymes, lectins, antibody fragments, complementary nucleic acids, protein A, anti-idiotype antibodies, avidin, and the like. Commonly, the receptor will be an antibody and the ligand will act as an antigen or hapten.
  • the analyte or an analyte derivative will be the ligand.
  • analyte derivative means a chemical derivative of an analyte that retains the capacity to bind to the other member of a ligand-receptor pair as does the analyte.
  • labeled member of a ligand-receptor pair is meant a conjugate of a ligand-receptor pair member with a chemical label such as an enzyme, a fluorescent compound or other detectable chemical species, the conjugate retaining the capacity to bind to the other member of the ligand-receptor pair, and the enzyme or other detectable label continuing to have a capacity of being detected by a detector system (which may be a separate chemical reaction system) to provide a perceptible signal.
  • a detector system which may be a separate chemical reaction system
  • Detector refers to a chemical system that provides perceptible signals, commonly electromagnetic radiation or absorption of the same leading to perceptible fluorescense, color changes and the like, when contacted with a specific enzyme or other label and desirably with substrate and chromogen.
  • chromogens which produce visible color when added to their specific enzymes and substrates.
  • o-phenylenediamine and o-dianisidine have been used a ⁇ peroxidase and glucose oxidase chromogens.
  • Napthol-MX-phosphate and the chromogen Fast Red TR salt are used for detecting alkaline phosphatase.
  • Yolken, R.N. "Solid-Phase Enzyme Immunoassays for the Detection of Microbial Antigens in Body Fluids," in Manual of Clinical Microbiology, pgs. 949-957 (1985) contains a more detailed description of these chromogens.
  • the invention is useful in detecting a broad range of analytes.
  • U.S. Patents 4,374,925 and 3,817,837 set out excellent lists of analytes which are part of specific binding pairs, the teachings of which patents are incorporated herein by reference.
  • Analytes of particular interest include viruses, bacteria, fungi and other analytes of similar size. Examples of analytes that can be assayed with this invention include Chlamydia, Salmonella, Bordetella, Candida and Asperqillus.
  • a preferred embodiment of the apparatus of the invention is shown as 10.
  • a reaction chamber typified as a transparent hollow col mn of plastic or the like 11 has an upper opening 12 and a lower opening 13.
  • the reaction chamber may be sized and shaped to hold any volume of sample sufficient for performing an immunoassay; preferably, the chamber will hold approximately 3 ml of sample. It may be made of glass or any suitable plastic material.
  • the sidewalls of the chamber at its lower end desirably slope inwardly to form a constriction 14.
  • the sloping structure of the reaction chamber walls provide an integral funnel to facilitate the exposure of liquid sample and wash solutions to the walls of the vessel when an assay is performed.
  • a labeled ligand-receptor pair member chosen to bind to the analyte in relation to the amount of analyte in a liquid sample.
  • the labeled ligand-receptor pair member may be dried onto the inner wall of the reaction chamber, placed in the chamber in a dry pellet or as a powder or dissolved in a liquid in the chamber.
  • the labeled ligand receptor pair member is in a pellet form and may be mixed with other inert ingredients, such as stabilizers and solubilizers.
  • the apparatus also has filter means for preventing the passage therethrough of labeled ligand receptor pair member bound to analyte while permitting unbound labeled pair member to pass therethrough when superatmospheric pressure is applied to the reaction chamber.
  • the filter means may be any of a variety of membranes or filters that separate materials by size, charge and the like.
  • the filter means is a porous filter or membrane having pores sized to prevent the passage therethrough of the labeled pair member when it is bound to the analyte while permitting unbound labeled pair member to pass therethrough when superatmospheric pressure is applied to it.
  • the filter is desirably made of a low protein binding material, such as derivatized nylon, polysulfone and the like.
  • a low protein binding material binds less than about
  • PBS phosphate buffered saline
  • HSA tritiated human serum albumin
  • the filter is then washed by forcing 5 mis of a wash solution (PBS with 0.05%, polyoxyethylene sorbitan monolaurate (Tween 20, a trademarked product of Sigma Chemical)) through it.
  • the filter is removed and placed in 4 mis of scintillation cocktail.
  • the amount of tritiated HSA bound to the filter is calculated using disintegrations per minute measured over five minutes. Using this procedure, cellulose acetate, polysulfone and derivatized nylon 66 filters bound less than 0.1% of the HSA.
  • the filter material is also desirably deformable or compressible in the direction of fluid flow.
  • the pore size of the filter used in this invention will vary according to the analyte being assayed for and the type of sample.
  • the pores should be sized according to the particular analyte for which the assay is being performed so that when the analyte is bound to the labeled ligand receptor pair member the resulting complex is prevented from passing through the filter.
  • the pore size of the filter may be larger than the average diameter of the organism being assayed in order to obtain adequate sensitivity of the assay the pore size is desirably no more than 2.5 times as large as the analyte being assayed.
  • Filters with pore sizes ranging from 0.lum in diameter to lOOum in diameter have been used with this invention.
  • filters having pores sized no larger than about 15um are used.
  • pore size of .the filter may influence the selection of pore size of .the filter besides analyte size.
  • the type of specimen being assayed may contain biological agents and/or debris which may clog the filter pores and thus interfere with the assay. It is desirable to select a pore size that will allow such agents and/or debris to pass through the filter when superatmospheric pressure is applied but still prevents the passage of bound labeled ligand receptor pair member therethrough.
  • the size of the labeled ligand receptor pair member selected to bind the analyte is also important. The pores must be large enough to allow unbound labeled ligand receptor pair member to pass through the filter when superatmospheric pressure is applied.
  • the porous filter or membrane 25 is placed between upper and lower housings 26 and 27 on a filter support 28.
  • the filter communicates with the reaction chamber through constriction 14.
  • the upper housing 26 desirably forms a compartment 29 above the filter 25 and is sealingly engaged to the outer sidewalls of the reaction chamber.
  • the constriction 14 of the reaction chamber is sized and shaped so that if the filter is wetted to make it substantially airtight when liquid is added to the reaction chamber, an "airlock" will form that will prevent passage of the reaction mixture into compartment 29 until superatmospheric pressure is applied.
  • this "airlock" is positioned directly above the filter surface during the assay, nonspecific adsorption of the labeled ligand receptor-pair member and potentially interfering substances is significantly minimized by decreasing the length of time those agents contact the filter surface.
  • the walls of the upper housing desirably slope outwardly as .shown in Figures 1 and 2 to provide even dispersion of solutions over the filter surface during performance of the assay.
  • the walls of the lower housing slope inwardly to provide a funnel for directing the flow of materials passing through the filter.
  • the upper housing is desirably made of a clear material so that color change occuring on the filter surface can be observed by the user without the necessity of removing the filter.
  • the upper and lower housings are removably attached so that the filter may be removed from the apparatus after the assay has been performed and retained a ⁇ a record of the assay results.
  • the apparatus of the invention further includes means for applying superatmospheric pressure to the reaction mixture in the reaction chamber.
  • the pressure means may be any of a variety of conventional means but preferably comprises a plunger slidingly received within the upper opening 12 of the reaction chamber 11.
  • Other means that may be used with this invention include a bellows that sealingly connected with the reaction chamber or a source of compressed gas which when opened, releases a specific amount of gas at a specific rate to apply pressure to the reaction mixture disposed in the reaction chamber.
  • the means should be able to.provide at least 1-5 psi (gauge pressure) to the contents of the reaction chamber so that liquid passes through the filter at a rate of about 1 milliliter in 12-25 seconds.
  • the plunger comprises a piston 21 having sealing rings 22, 23 that sealingly engage the inner sidewalls of the reaction chamber when received therein and a handle for sliding the piston upwardly and downwardly within the chamber.
  • the piston desirably includes one-way valve means for allowing air to escape from the reaction-chamber when the plunger is moved upwardly to prevent disturbance of reactants lying on the filter surface.
  • valve means is typified as a flexible flap 30 normally covering an axially extending hole 31 formed in the piston 21, so that when the the piston is moved upwardly the flap 30 opens allowing passage of air through the piston hole and when the piston is moved downwardly the flap remains in its normal position covering the hole in the piston.
  • the apparatus of the invention is substantially enclosed to protect the user from exposure to undesirable elements in the liquid sample.
  • a collection chamber 35 is positioned below the lower filter support in liquid communication with the reaction chamber to collect liquid and unbound ligand-receptor pair member that passes through the filter when superatmospheric pressure i ⁇ applied to the reaction chamber.
  • the collection chamber may be of any variety of size and shape and may be attached to the reaction chamber or filter housings by any of a variety of means.
  • the collection chamber is removably attached to the lower filter housing with complimentary screw threads.
  • the collection chamber desirably includes means for releasing gas from within the chamber and desirably comprises a hole 36 formed in the wall of the collection chamber a ⁇ shown in Figure 1.
  • the gas releasing means may further compri ⁇ e filter means which substantially prevents the release of particles or liquid from the collection chamber.
  • the filter means may be an absorbent material placed within the collection chamber that absorbs liquid as it passes through the filter or it may simply be porous filter attached to the wall of the collection chamber covering the gas releasing means.
  • This apparatus comprises means for allowing the introduction of liquid sample into the reaction chamber.
  • Sample introducing means is typified in Figures 1 and 2 as a tubular port 32, although it may be any variety of conventional means, such as a hole formed in the wall of the reaction chamber.
  • the sample introducing means is designed to prevent escape of liquid sample out of the reaction chamber.
  • This may be accomplished by covering the opening into the reaction chamber with a diaphram 41 that may be penetrated by a needle and which will then reseal itself after removal of the needle or it may be a valve which may be selectively opened or closed, such as a stopcock.
  • the opening of the sample introducing means into the reaction chamber should be positioned so that a cushion of air can be trapped in the reaction chamber between the reaction mixture and the means for applying superatmospheric pressure.
  • the cushion of air is useful in pushing all liquid through the filter to ensure that traces of unbound labeled ligand receptor pair member do not remain trapped in liquid on the filter surface.
  • the method of this invention comprises reacting liquid sample suspected of containing analyte, the analyte being a member of a ligand-receptor pair, with a predetermined quantity of a labeled member of the ligand-receptor pair chosen to bind to the analyte in the sample in relation to the quantity of analyte present in the sample, forming a reaction mixture.
  • liquid sample is added to the reaction chamber of the apparatus described above in which a predetermined quantity of the labeled member of the ligand-receptor pair is present.
  • the reaction mixture remains in the reaction chamber a predetermined length of time to allow the labeled pair member to bind to analyte in the sample.
  • This "incubation" time is typically 5-10 minutes.
  • the resulting reaction mixture is then forced under pressure through a filter having pores sized to substantially prevent passage therethrough of the labeled ligand-receptor pair member when it i ⁇ bound to analyte while permitting unbound labeled pair member to pass therethrough.
  • a wash solution such as PBS or PBS/ 0.05% Tween 20 is added to the reaction chamber and superatmospheric pressure applied to force the solution through the filter to wash through any remaining unbound labeled ligand-receptor pair member.
  • the presence of analyte in the sample is detected by detecting the presence of labeled ligand-receptor pair member in and on the filter.
  • the presence of analyte may be determined using any of a number of detection means.
  • a liquid detection system responsive to the label in the ligand-receptor pair member is forced through the filter. If analyte is present, color appears on the filter surface.
  • the filter may be removed and the filter checked for the appearance of color at predetermined intervals or it may be left in the apparatus and viewed through the clear wall of the upper housing.
  • the labeled ligand receptor pair member used is horseradish peroxidase ("HRP") labeled polyclonal antibody to Chlamydia.
  • HRP horseradish peroxidase
  • the antibody, . conjugate preparation used comprises a polyclonal antibody, monoclonal or monospecific antibodies or combinations may also be used. Techniques for polyclonal, monoclonal, or monospecific antibody preparation are well known.
  • the conjugate was prepared as follows. Periodate activation of 4 mgs HRP involved the oxidation of the carbohydrate moiety with 0.2 ml of 0.1 M sodium meta-periodate to form free aldehyde groups. The solution was stirred for 20 minutes at room temperature.
  • the purified antibody (8mgs of IgG) was added to the peroxidase solution at a slightly alkaline pH (pH 9.5) followed by reduction of the resulting Schiff base by addition of 0.1 ml of 4 mg/ml sodium cyano borohydride to stabilize covalent bonds between the primary amino groups on the antibody and aldehyde groups of the peroxidase (stirred at 4°C for 2 hours) .
  • conjugate preparation was purified on a Sephacryl S-200 gel permeation chromatography column to separate uncoupled proteins from conjugated proteins.
  • the assay was conducted using a derivatized nylon 66 filter (LoProdyne, a trademarked product of Pall) having .45um sized pores.
  • the filter was wetted and then inserted into the apparatus shown in Figure 1 by unscrewing the upper housing from the lower housing and placing the filter on the filter support carried by the lower housing.
  • the filter housings were screwed together and attached to the reaction chamber and collection chambers.
  • the plunger was placed in the upper opening of the reaction chamber and pushed down until the piston rested just above the opening of the sample introducing arm.
  • Each positive unit received 300 ul of PBS and each control unit received 400ul of PBS through the sample introducing arm.
  • lOOul of a 1:100 stock culture dilution of Chlamydia was added to the reaction chamber of each positive unit through the sample introducing arm.
  • 100 ul of 9mgs/ml HRP-anti-Chiamydia was already present in the reaction chamber of each unit.
  • the reaction mixture of each unit was incubated in the chamber for approximately ten minutes.
  • the plunger in each unit was then pressed downwardly with about 1-5 psi (gauge pressure) to cause the reaction mixture to pass through the filter at a rate of about 1ml per 12 to 25 seconds.
  • a positive test is recorded as a plus 1 or greater using a color chart (such as a Pantone chart selector #534 produced by Pantone, Inc.); or a reading of 10 or above using a reflectance spectrophotpmeter.
  • a color chart such as a Pantone chart selector #534 produced by Pantone, Inc.
  • the total color difference (DE) was measured by the L, a, b coordinate system, and was recorded in units.
  • the total color difference value depends on the standard illuminant and observer used.
  • the total color difference data obtained is a composite unit and depends upon the a) dark/light difference; b) red/green difference; c) yellow/blue difference; and d) chromaticity difference (chromaticity and hue). The higher the value of DE, the more saturated and chromatic was the color.
  • the total assay time was about 25 minutes including the time for final readout at 10 minutes.
  • the units to which Chlamydia was added gave a positive colored signal while the negative controls were white or negative even after 10 minutes.
  • the labeled ligand receptor-pair member was a 1:75 dilution of 11.08mgs/ml HRP-labeled polyclonal antibody to Candida.
  • the conjugate was prepared according to the procedure described in Example 1. The same type of filter was used and the apparatus assembled as described in Example 1.
  • Candida organisms (10 5 - 107 organisms) were added to urine and added to a buffer solution. Urine without Candida and a buffer solution without Candida were used as negative controls.
  • the assay was carried out as previously described except the wash solution used was PBS not PBS/Tween.

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Abstract

On a mis au point un appareil et des procédés d'analyse d'une substance d'éssai, utilisant un moyen de filtration (25) et une pression supra-atmosphérique. Ledit appareil comprend une chambre de réaction (11) comportant une extrémité ouverte (13), un filtre poreux (25) communiquant avec l'extrémité ouverte (13), ledit filtre (25) ayant des pores dimensionnés pour empêcher le passage à travers ledit filtre d'un complexe d'anticorps et d'analyte marqués; la chambre de réaction (11) est cylindrique; un plongeur (20) y est logé, afin de fournir une pression supra-atmosphérique au contenu de la chambre de réaction (11) pendant l'utilisation.
PCT/US1989/002914 1988-06-30 1989-06-30 Appareil et procede d'analyse a pression WO1990000251A1 (fr)

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US21333388A 1988-06-30 1988-06-30
US213,333 1988-06-30

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Cited By (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0419168A2 (fr) * 1989-09-18 1991-03-27 La Mina Ltd. Appareil de collection d'essais d'échantillons de fluides
WO1991017441A1 (fr) * 1990-04-27 1991-11-14 Genzyme Corporation Determination d'analytes dans des fluides biologiques en presence de substances perturbant les analyses
US5077012A (en) * 1989-01-10 1991-12-31 La Mina Ltd. Device for detecting disease markers
US5358690A (en) * 1989-01-10 1994-10-25 Lamina, Ltd. Environmental sample collection and membrane testing device
EP0654972A1 (fr) * 1992-07-28 1995-05-31 GUIRGUIS, Raouf A. Procede et appareil permettant d'obtenir des monocouches cytologiques
FR2735400A1 (fr) * 1995-06-16 1996-12-20 Nosenzo Michel Dispositif pour tester des elements biologiques a partir d'une operation de filtration
EP0755719A2 (fr) * 1990-11-09 1997-01-29 Ortho Diagnostic Systems Inc. Essai d'agglutination en colonnes et dispositif
EP0924991A1 (fr) * 1996-07-02 1999-06-30 Bioseq, Inc. Association par pression de complexes biomoleculaires
WO2001011359A2 (fr) * 1999-08-06 2001-02-15 Imi International Medical Innovations Inc. Mesure spectrophotometrique dans des dosages biochimiques et immunologiques chromatiques
US7348055B2 (en) 2001-12-21 2008-03-25 Surmodics, Inc. Reagent and method for providing coatings on surfaces
US7816142B1 (en) 2008-04-29 2010-10-19 Emsl Analytical, Inc. Lead testing system

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