WO2003079017A2 - Dispositif et procede pour determiner des particules specifiques dans un echantillon de liquide - Google Patents

Dispositif et procede pour determiner des particules specifiques dans un echantillon de liquide Download PDF

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Publication number
WO2003079017A2
WO2003079017A2 PCT/NL2003/000192 NL0300192W WO03079017A2 WO 2003079017 A2 WO2003079017 A2 WO 2003079017A2 NL 0300192 W NL0300192 W NL 0300192W WO 03079017 A2 WO03079017 A2 WO 03079017A2
Authority
WO
WIPO (PCT)
Prior art keywords
binding surface
liquid sample
along
particles
flow
Prior art date
Application number
PCT/NL2003/000192
Other languages
English (en)
Other versions
WO2003079017A3 (fr
Inventor
Gerardus Henricus Maria Engbers
Richard Bernardus Maria Schasfoort
Original Assignee
Ibis Technologies B.V.
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 Ibis Technologies B.V. filed Critical Ibis Technologies B.V.
Priority to AU2003220768A priority Critical patent/AU2003220768A1/en
Publication of WO2003079017A2 publication Critical patent/WO2003079017A2/fr
Publication of WO2003079017A3 publication Critical patent/WO2003079017A3/fr

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Classifications

    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/50273—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by the means or forces applied to move the fluids
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
    • G01N15/06—Investigating concentration of particle suspensions
    • 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
    • G01N33/54393—Improving reaction conditions or stability, e.g. by coating or irradiation of surface, by reduction of non-specific binding, by promotion of specific binding
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/06—Fluid handling related problems
    • B01L2200/0636—Focussing flows, e.g. to laminate flows
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/06—Auxiliary integrated devices, integrated components
    • B01L2300/0627—Sensor or part of a sensor is integrated
    • B01L2300/0636—Integrated biosensor, microarrays
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/089—Virtual walls for guiding liquids
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/04—Moving fluids with specific forces or mechanical means
    • B01L2400/0403—Moving fluids with specific forces or mechanical means specific forces
    • B01L2400/0415—Moving fluids with specific forces or mechanical means specific forces electrical forces, e.g. electrokinetic
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/04—Moving fluids with specific forces or mechanical means
    • B01L2400/0475—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure
    • B01L2400/0487—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure fluid pressure, pneumatics
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
    • G01N15/06—Investigating concentration of particle suspensions
    • G01N15/075—Investigating concentration of particle suspensions by optical means

Definitions

  • the invention relates to a device for determining particles of at least one specific type in at least one liquid sample, comprising: a binding surface for binding particles of the specific type, first initiating means for causing at least a part of the liquid sample to flow along the binding surface, and detection means for detecting particles of the specific type bound to the binding surface.
  • the invention also relates to a method for determining particles of at least one specific type in at least one liquid sample using such a device, comprising the steps of: A) causing at least a part of the liquid sample to flow along the binding surface, and B) detecting particles of the specific type bound to the binding surface.
  • Bio-diagnostic techniques are known based on affinity reactions, for instance antibody/antigen and receptor/ligand reactions. These techniques are used in biochemical analyses of bodily fluids such as blood, serum and urine. Much used is the "sandwich technique" wherein a specific ligand is adsorbed to a solid carrier. A particle for determining binds itself selectively to this ligand. The particles for determining can be marked, for example with fluorescent particles, whereafter the presence of the particle in question can be established qualitatively and/or quantitatively, for example with a fluorescence microscope.
  • micro-globules in (bio) chemical analyses. These micro- globules are available in many types and sizes, marked or unmarked. Many micro- globules can bind specific ligands such as proteins and antibodies to their surface. These proteins can in turn also be marked, for example by means of a colour, a fluorescent or radioactive particle or through conjugation with gold. A particular ligand can enter into a selective binding with a (bio) chemical particle to be specifically determined in a sample. A so-called “reporter molecule” that is also marked can in turn bind selectively to the particle for determining.
  • micro-globules and the reporter molecules are generally mixed with the sample, whereafter the markings are determined qualitatively and quantitatively, from which the presence and concentration of one or more particles for determining can be inferred.
  • a significant advantage of this "micro-globule" technology is the enormous diversity of markings of the micro-globules, ligands and reporter molecules, whereby the (bio) chemical determination of a large number of particles in a sample can take place simultaneously.
  • flow cytometry wherein particles flow through a channel.
  • particles can be cells, but also micro-globules such as used in (bio) chemical analyses, or large molecules.
  • the particles can herein be urged by means of "control flows” or 'focussing flows” to for instance the middle of the channel or, conversely, to one of the sides, see for example WO 00/70080.
  • a device for determining at least one specific type of particle in a liquid sample, wherein the device comprises a binding surface along which a liquid can flow.
  • Binding surface is always understood to mean, here and hereinbelow, a surface which is suitable to be provided with, or is already provided with binding sites, wherein at each binding site a selective binding can take place with a particle of a specific type.
  • the binding surface For guiding of the liquid flows along the binding surface, use is made of a hydraulic network with channels. In many cases this method of directing and controlling the liquid movements by means of such a rigid and fixed network of channels will suffice well. In the case it is wished to determine a plurality of types of particle and/or to measure subject to time and/or to perform serial or parallel analysis of a plurality of samples, the binding surface can then be divided into a number of separate portions, each provided with one or more types of specific binding site. It must then be possible to direct liquid (partial) flows individually to and guide them along a determined portion of the binding surface.
  • the invention fulfills said need and provides for this purpose a device of the type stated in the preamble of claim 1 , characterized in that the device further comprises second initiating means for initiating at least one control flow, by means of which control flow the flowing part of the liquid sample can be directed along an intended part of the binding surface.
  • Applying one or more control flows makes it possible in controlled and efficient manner to direct and guide the liquid (partial) flow to and along a determined portion of the binding surface, where a specific binding reaction can take place between a specific type of particle and a determined type of binding site.
  • the first and/or second initiating means can herein be at least partly hydraulic in nature.
  • hydraulic is understood to mean either hydrostatic by means of a static pressure difference or height difference, or hydrodynamic by means of a kinetic pressure difference, or a combination of the two.
  • the device can for instance be provided with one or more pumps wherein the liquid flows can be controlled by means of valves.
  • the first and/or second initiating means are preferably at least partly electrokinetic in nature.
  • electrokinetic is understood to mean relating to a phenomenon wherein transport of matter takes place under the influence of an electric field, in particular electro-osmosis.
  • the device can for instance be provided with one or more electrodes for generating and controlling electro-osmotic liquid flows by applying electronic potential differences.
  • the second initiating means are adapted to initiate a plurality of control flows enclosing the part of the liquid sample flowing along the binding surface. In this way the efficiency and the accuracy of the directing of the liquid sample along the binding surface can be further enhanced compared to directing of the liquid flow with a single control flow.
  • the invention further provides a method of the type stated in the preamble of claim 1, characterized in that the method also comprises the step of: C) directing the flowing part of the liquid sample along an intended part of the binding surface by at least one control flow during the performing of step A).
  • a liquid sample can thus be analysed, wherein for example many types of particles can be simultaneously determined by causing individual parts of the sample to flow along separate parts of a binding surface, or a time-dependent analysis can be performed. Or a plurality of liquid samples can for instance be analysed serially or in parallel by guiding the individual samples or parts thereof along determined portions of the binding surface.
  • At least a part of the flow along the binding surface and/or the control flow can herein be brought about hydraulically. Pumps can be utilized for this purpose wherein the liquid flows can for example be controlled by means of valves. At least a part of the flow along the binding surface and/or the control flow is preferably brought about electrokinetically. Electrokinetic inducement and control of the liquid movements is possible with great precision by applying electrical voltages at the appropriate positions and at the correct times.
  • the surfaces which only come into contact with the "clean" control flows will in principle have a constant zeta potential, whereby electrokinetic transport or electro- osmotic flow is better manageable and contamination of these surfaces, for example by protein adsorption, will in principle not occur.
  • a plurality of control flows is applied which enclose the part of the liquid sample flowing along the binding surface. In this way the liquid flow can be guided with increased precision along the binding surface in efficient and effective manner when compared to the directing of the liquid flow using a single control flow.
  • figure 1 shows a schematic top view of a first embodiment of a device according to the invention
  • figure 2 shows a schematic top view of a second embodiment of a device according to the invention
  • figure 3 shows a schematic top view of a third embodiment of a device according to the invention.
  • Figure 1 shows a first basic embodiment of a device 1 according to the invention, comprising a surface 11 and a reservoir 13. It is possible to initiate a liquid flow 17 from reservoir 13 to surface 11. Control flows 16a, 16b can further be initiated whereby the width of the liquid stream 18 displacing along surface 11 can be regulated. This width will decrease with the strength of control flows 16a, 16b.
  • Figure 2 shows a second device 2 according to the invention comprising a binding surface 21 divided into a plurality of tracks 21a-21 v, in this embodiment each provided with micro-globules 22 with binding sites where a selective binding can take place with particles of a specific type.
  • Reservoirs 23 contain for instance one or more samples, washing- liquids or marking particles.
  • Buffer reservoirs 24a, 24b contain for instance a buffer solution for electrokinetic generation of control flows 26a, 26b.
  • Reservoir 25 serves for storage of waste liquid.
  • One or more liquid flows 27a-27j are initiated by one or more of the reservoirs 23 to binding surface 21.
  • the "mechanical grids" 29 serve to rectify small deviations in the liquid flow and to equalize the flow profile.
  • the liquid flow 28 is directed along a determined track, 21e in the case shown in figure 2, of binding surface 21.
  • Particles of a specific type if present, can there be bound to the relevant binding sites.
  • a washing liquid can then be carried along binding surface 21 and for instance fluorescent marking particles, whereafter binding surface 21 can be examined with a "fluorescence imaging microscope".
  • the presence and/or concentration of a specific type of particle in a determined sample can thus be determined.
  • Other detection methods can also be employed such as SPR (surface plasmon resonance), laser technology or digital imaging technology, see for example NL 1019446 or NL 1019875 in the name of the present applicant. In this way one or more samples can each be examined qualitatively and /or quantitatively for one or more specific types of particle.
  • Figure 3 shows a third device according to the invention, comprising a binding surface 31 which is divided into two mutually perpendicular directions in tracks 31a-31p, 31'a- 3 l'p.
  • first control flows 36a, 36b a first liquid flow 38 can be directed and guided along a determined track in the first direction, 31m in the case shown in figure 3.
  • second control flows 36'a, 36'b a second liquid flow 38' can subsequently be directed and guided along a determined track in the second direction, 31'f in the case shown in figure 3. It is thus possible to go through a number of successive steps in a particular analysis, wherein a given intended portion of binding surface 31 is addressed in each case.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Immunology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Hematology (AREA)
  • General Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Analytical Chemistry (AREA)
  • Biomedical Technology (AREA)
  • Dispersion Chemistry (AREA)
  • Pathology (AREA)
  • Molecular Biology (AREA)
  • Urology & Nephrology (AREA)
  • General Physics & Mathematics (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Physics & Mathematics (AREA)
  • Biochemistry (AREA)
  • Biotechnology (AREA)
  • Medicinal Chemistry (AREA)
  • Food Science & Technology (AREA)
  • Microbiology (AREA)
  • Cell Biology (AREA)
  • Clinical Laboratory Science (AREA)
  • Investigating Or Analysing Biological Materials (AREA)
  • Analysing Materials By The Use Of Radiation (AREA)

Abstract

Cette invention concerne un dispositif qui permet de déterminer des particules d'au moins un type spécifique dans au moins un échantillon de liquide. Le dispositif comprend une surface de liaison pour attacher les particules de type spécifique; un premier moyen de déclenchement pour amener au moins une partie de l'échantillon de liquide à s'écouler le long de la surface de liaison; et un moyen de détection pour détecter des particules du type spécifique attachées à la surface de liaison. L'invention concerne en outre un procédé qui met en oeuvre ledit dispositif pour déterminer des particules d'au moins un type spécifique dans au moins un échantillon de liquide.
PCT/NL2003/000192 2002-03-16 2003-03-14 Dispositif et procede pour determiner des particules specifiques dans un echantillon de liquide WO2003079017A2 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU2003220768A AU2003220768A1 (en) 2002-03-16 2003-03-14 Device and method for determining specific particles in a liquid sample

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
NL1020187A NL1020187C2 (nl) 2002-03-16 2002-03-16 Inrichting en werkwijze voor het bepalen van deeltjes in een vloeibaar monster.
NL1020187 2002-03-16

Publications (2)

Publication Number Publication Date
WO2003079017A2 true WO2003079017A2 (fr) 2003-09-25
WO2003079017A3 WO2003079017A3 (fr) 2004-02-26

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AU (1) AU2003220768A1 (fr)
NL (1) NL1020187C2 (fr)
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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
NL1027633C2 (nl) * 2004-12-01 2006-06-02 Stichting Tech Wetenschapp Werkwijzen en mengsel voor (bio)chemische analyse en synthese.
WO2008133698A1 (fr) * 2007-04-25 2008-11-06 Whalen Christopher D Procédé et appareil d'isolement hydrodynamique

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2261283A (en) * 1991-11-11 1993-05-12 Bunce Roger A Liquid transfer device for diagnostic assays
WO1993020449A1 (fr) * 1992-03-27 1993-10-14 Perseptive Biosystems, Inc. Systeme d'immunodetection par ecoulement rapide et hypersensible
WO1996002837A1 (fr) * 1994-07-20 1996-02-01 Sios, Inc. Appareil et procede pour la detection et le dosage de molecules organiques
EP0851230A1 (fr) * 1996-12-30 1998-07-01 Diagnostic Products Corporation Procédé et appareil pour le dosage immunologique utilisant la résonance plasmonique de surface induite par fluorescence

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2261283A (en) * 1991-11-11 1993-05-12 Bunce Roger A Liquid transfer device for diagnostic assays
WO1993020449A1 (fr) * 1992-03-27 1993-10-14 Perseptive Biosystems, Inc. Systeme d'immunodetection par ecoulement rapide et hypersensible
WO1996002837A1 (fr) * 1994-07-20 1996-02-01 Sios, Inc. Appareil et procede pour la detection et le dosage de molecules organiques
EP0851230A1 (fr) * 1996-12-30 1998-07-01 Diagnostic Products Corporation Procédé et appareil pour le dosage immunologique utilisant la résonance plasmonique de surface induite par fluorescence

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
NL1027633C2 (nl) * 2004-12-01 2006-06-02 Stichting Tech Wetenschapp Werkwijzen en mengsel voor (bio)chemische analyse en synthese.
WO2008133698A1 (fr) * 2007-04-25 2008-11-06 Whalen Christopher D Procédé et appareil d'isolement hydrodynamique
US7858372B2 (en) 2007-04-25 2010-12-28 Sierra Sensors Gmbh Flow cell facilitating precise delivery of reagent to a detection surface using evacuation ports and guided laminar flows, and methods of use

Also Published As

Publication number Publication date
WO2003079017A3 (fr) 2004-02-26
NL1020187C2 (nl) 2003-09-19
AU2003220768A1 (en) 2003-09-29

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