+

WO2011076860A1 - Dispositif, procédé, et système de détection quantitative de la présence de multiples analytes cibles - Google Patents

Dispositif, procédé, et système de détection quantitative de la présence de multiples analytes cibles Download PDF

Info

Publication number
WO2011076860A1
WO2011076860A1 PCT/EP2010/070519 EP2010070519W WO2011076860A1 WO 2011076860 A1 WO2011076860 A1 WO 2011076860A1 EP 2010070519 W EP2010070519 W EP 2010070519W WO 2011076860 A1 WO2011076860 A1 WO 2011076860A1
Authority
WO
WIPO (PCT)
Prior art keywords
magnetic
population
paramagnetic material
weight
chamber
Prior art date
Application number
PCT/EP2010/070519
Other languages
English (en)
Inventor
Peter Warthoe
Jens Mikkelsen
Iben Schildt Sørensen
Original Assignee
Atonomics A/S
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 Atonomics A/S filed Critical Atonomics A/S
Publication of WO2011076860A1 publication Critical patent/WO2011076860A1/fr

Links

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
    • B01L3/502715—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 interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
    • 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
    • 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
    • B01L2400/043—Moving fluids with specific forces or mechanical means specific forces magnetic forces

Definitions

  • the present invention relates to a device for the quantitative detection of the presence or absence of two or more target analytes in a liquid sample, and to uses thereof.
  • the invention further relates to a method for the quantitative detection of the presence or absence of two or more target analytes in a liquid sample having a volume of less than 200 ⁇ .
  • the invention further relates to a system for the quantitative detection of the presence or absence of two or more target analytes in a liquid sample having a volume of less than 200 ⁇ .
  • microfluidic systems of reduced dimension and containing magnetic or paramagnetic particles for analytical applications are well-known, and magnetic or para- magnetic nano- and microparticles have become a hot topic in several technical fields of research.
  • Functional nano- and microparticles offer a large specific surface for chemical binding, and a polymer colloid or microsphere solution has a low viscosity compared to solutions having the same amount of solid, giving it special properties.
  • a polymer colloid or microsphere solution has a low viscosity compared to solutions having the same amount of solid, giving it special properties.
  • Such small particles can be advantageously used as a 'mobile substrate' for bio- assays.
  • One of the most prominent advantages of magnetic beads lies in the fact that the particles can be magnetically probed and manipulated using permanent magnets or electromagnets, independent of normal chemical or biological processes.
  • Magnetic or paramagnetic beads coated with labels or capture molecules are widely used for the detection of biomarkers and biological molecules, and the magnetic particle-based assay has become a standard in modern chemical and biological diagnostics.
  • the detection of biological molecules is usually accomplished using biomolecular recognition between the target molecule (analyte) and a specific receptor (e.g. an antibody) that is tagged with a label.
  • the label may for example be a radioisotope, enzyme, fluorescent molecule or a charged molecule or any combination thereof.
  • magnetic beads have been used as labels for bio-sensing. These magnetic and paramagnetic beads are manipulated by use of means generating a magnetic field.
  • the devices and methods disclosed in the field have not been adapted to the quantitative detection of multiple analytes in one single test.
  • An example of a prior art device suitable for manipulating magnetic and paramagnetic beads according to the present invention is disclosed e.g. in PCT/EP2008/066272, PCT/EP2008/066273 PCT/EP2008/066274 and PCT/EP2009/067863.
  • the devices disclosed are not immediately suited for the use according to the present invention, as the paramagnetic material disclosed in these devices is not capable of targeting two or more analytes. Accordingly, when testing for more than one analyte, a test must be run for each specific analyte to be examined for. This situation is inconvenient for several reasons. First, more sample is needed, which naturally is troublesome and not always available. Also, it is time- labour- and material-consuming to run several tests, and hence expensive.
  • one object of the invention is to provide methods and devices to enable the detection of the presence or absence of multiple target analytes in a liquid sample of less than 200 ⁇ .
  • the inventors found that obtaining a highly sensitive, reproducible and fully quantitative assay for quantita- tively detecting the presence or absence of multiple analytes in small liquid samples required the presence and separability of different pools of magnetic material, each pool being capable of capturing specific and mutual different analytes. Furthermore, these different pools of magnetic or paramagnetic material should be allowed to be detected separately.
  • each pool of magnetic particles is capable of capturing a specific and mutually different analyte, thus providing an assay for multiple target analysis.
  • the inventors of the present invention found that they could separate these pools of different particles by displacing an external magnet relative to the chamber device comprising the magnetic particles. The motion of the external magnet allows the different pools of particles containing different amounts of magnetic material relative to the surface area in the chamber device to be released from the magnetic field generated by the external magnet at different times, thus falling to the bottom part of the chamber device in distinct pools. In this way, the different pools are separated in distinct piles at the bottom of the detector part of the chamber device.
  • the amount of analyte can be detected by scanning the area of the detector part of the chamber with suitable means for detection.
  • the invention relates to a method for the quantitative detection of the presence or absence of two or more target analytes in a sample consisting of less than 200 ⁇ liquid, comprising the steps of: a) providing an analyte containing liquid sample consisting of less than 200 ⁇ liquid;
  • the invention relates to a chamber device for the quantitative detection of the presence or absence of two or more target analytes in a liquid sample having a volume of less than 200 ⁇ , the device comprising a reaction chamber comprising a population of magnetic and/or paramagnetic material, said population comprising two or more pools, each pool capable of capturing a specific and mutually different analyte and each pool having a different mean of the ratio of surface area to weight, the weight being the weight of the magnetic of paramagnetic material present in the particle.
  • the invention relates to a system for the quantitative detection of the presence or absence of two or more target analytes in a sample consisting of less than 200 ⁇ liquid, said system comprising a magnet device and a chamber device, said magnet device being capable of moving a magnetic field along side said chamber device so that the magnetic and/or paramagnetic material in the chamber is subjected to the magnetic field.
  • the invention further relates to the use of a population of magnetic and/or paramagnetic material, said population comprising two or more pools, each pool capable of captur- ing a specific and mutually different analyte, and each pool having a different mean of the ratio of surface area to weight, the weight being the weight of the magnetic of par- amagnetic material present in the particle for the quantitative detection of the presence or absence of two or more target analytes in a liquid sample consisting of less than 200 ⁇ liquid. Definitions:
  • unimodal has the conventional mathematical meaning of unimodality, i.e. distributions having only one mode.
  • a function f(x) between two ordered sets is unimodal if for some value m (the mode), it is monoton- ically increasing for x ⁇ m and monotonically decreasing for x ⁇ m. In that case, the maximum value of f(x) is f(m), and there are no other local maxima.
  • bimodal has the conventional mathematical meaning of bimodality, i.e. distributions having two modes. Generally, bimodal distributions are a mixture of two different unimodal distributions.
  • magnetic material or particles includes paramagnetic material or particles.
  • paramagnetic material means mate- rial which is magnetic in the presence of an externally applied magnetic field, but are not magnetic prior to being subjected to a magnetic field.
  • the paramagnetic material according to the invention is preferable paramagnetic particles capable of binding and immobilizing a particular analyte species of interest, e.g. by being coated with a receptor or antibody.
  • displacing an external magnet in a rectilinear movement is meant that one or more magnets are moved relative to the chamber device so that the external magnet applies a magnetic field strong enough to influence or attract the magnetic particles present in the chamber device.
  • the movement is pref- erable unidirectional and may be stepwise alternating between acceleration and deceleration relative to the chamber device.
  • the preferably unidirectional movement may also be at a substantially constant velocity relative to the chamber device.
  • the magnetic influence attracts the magnetic particles present in the chamber device, but due to different size of magnetic material (by weight) the beads move at different velocity through the liquid, and is thus separated.
  • a suitable detector for detecting a signal derived from the captured analytes is arranged in a suitable manner, which enables the discriminated detection of signal derived from the different pools (modus) of magnetic and/or paramagnetic material.
  • point of care system is meant a relatively small transportable, portable, and/or handheld instrument or system.
  • the point of care system or instrument is preferably located at or near the site of patient care, e.g. in the doctors clinic, or located at the hospital such as in the intensive care unit instead of in a central laboratory.
  • An object of the present invention is to develop methods and devices for the quantitative detection of the presence or absence of even very small quantities of multiple target analytes in a sample consisting of less than 200 ⁇ liquid, preferably applying the methods and devices in relatively small handheld "point of care" instruments.
  • the problem of targeting multiple analytes in one single test in a microfluidic system could be solved by providing pools of magnetic particles wherein the amount (by weight) of magnetic material differs and wherein the different pools of particles are capable of capturing a specific analyte present in the liquid.
  • the invention relates in one embodiment to a method for the quantitative detection of the presence or absence of two or more target analytes in a sample consisting of less than 200 ⁇ liquid, comprising the steps of: a) providing an analyte containing liquid sample consisting of less than 200 ⁇ liquid;
  • the method provides a physical separation, in a mi- crofluidic system, of the steps of reacting, immobilising and purifying the analytes (steps a) to e)) from the steps of detecting the analytes (steps f) to h)), thus minimizing the unspecific background signal relating to the first steps a) to e) of the method.
  • the liquid sample of step a) can be any kind of liquid containing analytes to be detected. It is preferred that the liquid is from a mammal, preferably a human.
  • the liquid may be any liquid deriving from the body, such as blood, saliva, urine, peritoneal fluid, gas- trie juice or the like.
  • the reaction chamber of b) may be part of a chamber device suited for a microfluidic system, preferably a point-of-care system.
  • the reaction chamber comprises one or more capillary channels having a volume of less than 200 ⁇ , a sample inlet for the introduction of a liquid sample containing analytes, and a discharge outlet for the dis- charge of waste products.
  • step c) the liquid sample within the reaction chamber is contacted with a population of magnetic and/or paramagnetic material.
  • the population of magnetic and/or paramagnetic material comprises two or more pools of magnetic and/or paramagnetic ma- terial, each being capable of capturing a specific and mutually different analyte. By having two or more pools targeted at different analytes, the method enables the analysis of multiple analytes in the same sample.
  • each pool (being capable of capturing a specific and mutually different analyte) refers to a subpopulation of particles that is essentially normally distributed around a mean in terms of the ratio of surface area to weight, wherein the weight is calculated on the basis of the weight of magnetic or paramagnetic material present in the particle.
  • the population of particles according to the invention may comprise two or more pools or subpopulations of particles, each pool having dif- ferent surface areas and different weights in terms of weight of magnetic or paramagnetic material.
  • the population of particles according to the invention comprises two or more pools of particles made from the same magnetic or paramagnetic material, but differing in mean size.
  • the population of particles according to the invention may have essentially the same weight in terms of magnetic or paramagnetic material, but comprise two or more pools or subpopulations of particles in terms of surface area, wherein each pool or subpopulation has a normally distributed surface area.
  • the population of particles according to the invention may have essentially the same surface area but comprise two or more pools or subpopulations of particles in terms of weight of magnetic or paramagnetic material, wherein each pool or subpopulation has a normally distributed weight in terms of weight of magnetic or paramagnetic material.
  • the population of particles according to the invention may have essentially the same weight in terms of magnetic or paramagnetic material but comprise two or more pools or subpopulations of particles in terms of surface area, wherein each pool or subpopulation has a normally distributed surface area.
  • the population of magnetic and/or paramagnetic material is at least bimodally distributed in terms of weight of magnetic and/or paramagnetic material.
  • each pool constitutes a single modus.
  • the magnetic and/or paramagnetic material according to the invention is selected from the group comprising magnetic particles, paramagnetic particles, magnetic nanoparticles, paramagnetic nanoparticles or superparamagnetic particles.
  • the population of magnetic material may differ in terms of surface area so that the population of magnetic and/or paramagnetic material is at least bimodally distributed in terms of surface area.
  • each pool constitutes a single modus.
  • a population of magnetic material preferably in the form of particles, is provided, wherein the surface area of the material is significantly different, each pool containing material of the overall same surface area, but differing from the surface area of the material in the other pools.
  • pools are provided, wherein the magnetic material of each pool behave differently in a liquid environment. The viscous resistance is small for material with small surface areas and greater for material with larger surface areas.
  • Material with smaller viscous resistance can, all other things being equal, be carried a longer distance in the liquid by the magnetic force applied by an external magnet than material with greater viscous resistance. This is advantageous because it enables a separation of the pools by the displacement of an external magnet relative to the chamber device.
  • Another advantage of applying pools of material with different surface areas is that great differences in the amount of the different analytes to be detected in the sample may be balanced by using material with a greater surface area to capture the analyte present in trace or small amounts, whereas analytes present in greater amount may be captured by magnetic material with a smaller surface area.
  • the signal derived from the trace or small amount analyte may be seen as being amplified in this way so that the signal from both pools can be detected within the same detection window.
  • the separation of the pools of material may be further aided by providing pools wherein the material not only differ in terms of surface area but also in terms of amount by weight of magnetic material.
  • a first pool may contain material with a small surface area and large amount by weight of magnetic material
  • a second pool may contain material with a greater surface area and smaller amount by weight of magnetic material compared to the first pool.
  • the population of magnetic and/or paramagnetic material within the chamber device is unimodal in terms of surface area, but bimodal in terms of weight of the magnetic or paramagnetic material.
  • a population of magnetic material, preferably in the form of particles is provided, wherein the surface area of the material in the population is substantially equal, and wherein the amount of the magnetic material in terms of weight differs be- tween the pools of the population. This is advantageous in a number of applications, especially when quantitatively comparing the ratio between the presences of two or more analytes in a sample.
  • the means for capturing the analytes is provided by coating the magnetic and/or paramagnetic material with a biological material capable of capturing a specific analyte.
  • the biological material comprises but is not limited to monoclonal antibodies, polyclonal antibodies, antigens, receptors, ligands, enzymes, proteins, peptides and nucleic acids. It is preferred that it is antibodies.
  • Each pool of particles is coated with the same biological material so that each pool is specific for a single ana- lyte in the sample. Accordingly, by providing at least two pools of material, the method is capable of detecting the presence or absence of at least two different analytes.
  • the magnetic particles are optionally thoroughly mixed in the liquid contain- ing the analytes by means of a changing magnetic field causing the particles to be stirred, thus facilitating the capturing of analytes by the particles.
  • the changing magnetic field may be generated by displacing an external magnet relative to the reaction chamber.
  • the method further comprises a reaction step wherein the population of magnetic and/or paramagnetic material comprising the captured analytes is contacted with a second biological material linked to a marker, said material being capable of binding to the specific analytes targeted by the coated particles.
  • the analytes are captured in a sandwich between two biological materials specific for the analyte.
  • the marker of the second biological material is selected from the group comprising HRP, ALP, fluorophores and biotin or any combination thereof.
  • the marker is capable of transmitting a signal either by itself or after having reacted with a substrate which may be provided in a subsequent step.
  • the method further comprises a step of contacting the popula- tion of magnetic and/or paramagnetic material comprising the captured analytes with a substance capable of reacting with the marker.
  • the substrate is chosen so that it is a substrate that reacts with the marker to emit some kind of signal that can be quantitatively detected. Since the marker is coupled to a biological material that specifically binds to the analytes to be detected, the amount of analytes can be detected by quanti- tatively detecting the signal emitted from marker/substrate.
  • the reaction of the substance with the marker emits light which is detectable by a suitable light detector.
  • the quantity of bound analyte can be calculated from the amount of emitted light from each pool of material.
  • the second biological material is selected from the group comprising monoclonal antibodies, polyclonal antibodies, antigens, receptors, ligands, enzymes, proteins, peptides and nucleic acids, preferably it is mono- or polyclonal antibodies.
  • the population of magnetic and/or paramagnetic material comprising the captured analytes is immobilized by means of a magnetic field which may be generated by an external magnet.
  • the magnetic field attracts the material, thus gathering the material and allowing for the subsequent purification of magnetic material, e.g. by moving the material from one part of the reaction chamber to another part. This may be achieved by means of a moving magnetic field, e.g. by displacing an external magnet relative to the chamber device.
  • the reaction chamber is preferably divided into a "dirty zone” and a "clean zone", the dirty zone comprising the liquid sample comprising analytes as well as unbound, contaminating material, and the "clean zone” being substantially free from unbound, con- taminating material.
  • the magnetic material is preferably moved from the dirty zone into the clean zone, thus minimizing the contamination from unspecific material in the liquid sample.
  • the preferred separation of the chamber device into a dirty zone and a clean zone provides for a minimal unspecific background signal relating to the unspecific material from the liquid sample.
  • the population of magnetic material preferably within the clean zone, is washed with a washing solution. This step may be repeated several times. Hereby, any contaminating unbound material is removed from the material so that only specifically bound analyte is present at the surface of the magnetic material.
  • the population of magnetic material is transferred to a detection chamber of the chamber device, said detection chamber comprising a detection window.
  • the material may be moved by means of displacing a magnetic field relative to the chamber device.
  • the detection chamber is preferably arranged in a suitable manner to allow a detector to receive the emitted marker/substrate signal relating to the bound analytes. As the signal is proportional to the amount of bound analytes, the quantity of bound analyte can be calculated from the signal intensity.
  • the population of magnetic material is separated into the distinct pools by displacing a magnetic field relative to the detection chamber. Due to the fact that the pools of magnetic material are differing in terms of weight and/or surface area of magnetic material, this displacement of the magnetic field will cause the magnetic material containing substantially the same amount by weight and/or substantially equal surface area of magnetic material, and thus having the same magnetic and viscous characteristics, to be released from the magnetic field at substantially the same time, thus causing the material of one pool to fall to the bottom of the chamber in substantial- ly one group.
  • Material with a greater content by weight of magnetic material has a greater magnetic force and will thus be carried further in the liquid in the direction of the moving magnetic field compared to material having less content by weight of magnetic material and thus less magnetic force, which will travel a shorter way. Accordingly, due to the different magnetic characteristics of the pools of magnetic material, the pools can be separated in the chamber device by applying a moving magnetic field to the chamber device.
  • the magnetic material of each pool may alternatively differ in sur- face area, with or without a difference in amount by weight of magnetic material.
  • the surface area affects the viscous resistance of the magnetic material in a liquid
  • such a difference can also be used to separate the pools of magnetic material.
  • Material with a small surface area will travel a longer way in the liquid in the direction of the moving magnetic field than material with a larger surface area provided that the material con- tains substantially the same magnetic characteristics.
  • Material with a different surface area may be even better separated if the material with a small surface area further contains a larger amount by weight of magnetic material than the magnetic material containing the larger surface area. The characteristics of such material will thus be small viscous resistance and high magnetic force and will travel further in liquid in direction of the moving magnetic field compared to the material of a different pool containing a larger surface area and less magnetic material by weight.
  • the magnetic field is applied so that the magnetic material is attracted to the top part of the detection chamber.
  • the material When the material is released from the magnetic field, the material consequently falls from the top part of the chamber device through the liquid and reaches the bottom part of the detection chamber.
  • the material is released from the magnetic field at different times depending on the magnetic and viscous characteristics and thus, the different pools of material will be separated at the bottom part of the detection chamber. It may be that the pools overlap in the detection chamber, but significant parts of the pools are separated so that the signal from one pool can be discriminated from the signal relating to another pool.
  • the displacement of the magnetic field in g) may be obtained by the displacement of an external magnet relative to the chamber device.
  • the magnetic field is displaced in a rectilinear movement relative to the chamber device preferably by moving an external magnet in a single unidirectional movement.
  • the magnetic field may be moved stepwise alternating between acceleration and deceleration.
  • the single unidirectional movement is performed at a substantially constant velocity, such as between 1 mm/sec and 50 mm/sec, preferably between 3 and 20 mm/sec.
  • the magnetic field is displaced by moving a magnetic field in an angle of between 0 and 90 degrees, such as an angel between 0 and 80 degrees, or such as an angel between 0 and 70 degrees, or such as an angel between 0 and 60 degrees, or such as an angel between 0 and 50 degrees, or such as an angle between 0 and 40 degrees, or such as an angle between 0 and 30 degrees, or such as an angle between 0 and 20 degrees, or such as an angle between 0 and 10 degrees relative to the surface of the detection chamber, so that the magnetic field is moved further away from the chamber as the magnetic field passes over the detection chamber, thus reducing the magnetic force/impact on the magnetic material as the magnetic field passes the detection chamber.
  • the displacement of the magnetic field as described above may be at an increasing velocity, preferably the displacement is performed in a linearly increasing velocity.
  • the direction of the moving magnetic field is preferably arranged so that the magnetic material upon release from the magnetic field is sedimented in the detection part of the chamber device.
  • the emitted signal derived from the marker linked to the second biological material, and if relevant, which marker is reacted with a substrate to emit said signal is detected using conventional detection means.
  • the detection is performed by scanning the area of the detection part of the chamber with suitable means for detection.
  • the scanning of the detection chamber may be performed by moving the chamber device relative to the detector.
  • the signal intensity is proportional to the quantity of bound analyte and thus the quantity of analyte present in the liquid sample can be calculated from the signal intensity.
  • the resulting signal will be bimodal when scanning the detector part of the chamber.
  • a possible correction for overlapping pools may be needed in any given sample.
  • suitable means for detection may be selected from the group comprising surface acoustic wave (SAW) detectors, spectrophotometers, fluo- rometers, CCD sensor chip(s), CCOS sensor chip(s), PMT detector(s), or any other suitable detector.
  • SAW surface acoustic wave
  • the method of the present invention is preferably performed in a point-of-care system.
  • the detection for the presence or absence of the target analytes i.e. diagnostic testing, is brought conveniently and immediately to the patient. This increases the likelihood that the patient will receive the results in a timely manner.
  • the invention relates to a chamber device for the quantitative detection of the presence or absence of two or more target analytes in a liquid sample having a volume of less than 200 ⁇ , the device comprising a reaction chamber comprising a population of magnetic and/or paramagnetic material, said population comprising two or more pools, each pool being capable of capturing a specific and mutually differ- ent analyte and each pool having a different mean of the ratio of surface area to weight, the weight being the weight of the magnetic of paramagnetic material present in the particle.
  • the device is capable of detecting multiple analytes in the same sample at the same time.
  • the chamber is a capillary channel.
  • the chamber has a volume of less than 150 ⁇ . In a more preferred embodiment the chamber has a volume of less than 100 ⁇ . In an even more preferred embodiment the chamber has a volume of less than 90 ⁇ , even more preferred less than 80 ⁇ , even more preferred less than 70 ⁇ , such as less than 60 ⁇ , less than 50 ⁇ or even less than 40 ⁇ . In an even more preferred embodiment, the chamber has a volume of less than 30 ⁇ , even more preferred less than 25 ⁇ , even more preferred less than 20 ⁇ , such as less than 15 ⁇ , less than 10 ⁇ or even less than 5 ⁇ .
  • the method according to the invention is preferably performed in a system comprising a chamber device and a magnetic device.
  • the invention relates to a system for the quantitative detection of the presence or absence of two or more target analytes in a sample consisting of less than 200 ⁇ liquid, said system comprising a magnet device and a chamber device according to the invention, said magnet device being capable of displacing one or more magnetic fields relative to the chamber device so that the magnetic and/or paramagnetic material in the chamber is subjected to the one or more magnetic fields.
  • the system of the present invention is preferably a point-of-care system.
  • the invention further relates to the use of a chamber device according to the invention for the quantitative detection of the presence or absence of two or more target analytes. Further, the invention relates to the use of a population of magnetic and/or paramagnetic material, said population comprising two or more pools, each pool being capable of capturing a specific and mutually different analyte, and each pool having a different mean of the ratio of surface area to weight, the weight being the weight of the magnetic of paramagnetic material present in the particle for the quantitative detection of the presence or absence of two or more target analytes in a liquid sample consisting of less than 200 ⁇ liquid.
  • the invention relates to the use of a population of magnetic and/or paramagnetic material as described above, wherein the population of magnetic and/or para- magnetic material is at least bimodally distributed in terms of weight of magnetic and/or paramagnetic material, each pool constituting a single modus.
  • the invention relates to the use of a population of magnetic and/or paramagnetic material as described above, wherein the population of magnetic and/or para- magnetic material is at least bimodally distributed in terms of surface area, each pool constituting a single modus. Further, the invention relates to the use of a population of magnetic and/or paramagnetic material as described above, wherein the population is unimodal in terms of surface area.
  • Two pools of paramagnetic particles were mixed to form a population of particles consisting of two pools.
  • One pool had a mean particle diameter of 2.8 ⁇ and the other a mean particle diameter of 1 .0 ⁇ . Both pools consisted of paramagnetic material.
  • the population of particles was suspended in a buffer solution within a chamber device.
  • the population of paramagnetic particles was immobilised on the top surface of the capillary device using an external magnet.
  • the magnet was subsequently displaced over the top surface of the capillary device by moving the magnet slowly at a substantially constant velocity in one direction.
  • the population of particles was observed to be released from the magnetic field as the external magnet was displaced and the particles were observed to sediment into two distinct pools at the bottom of the chamber device.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Dispersion Chemistry (AREA)
  • Analytical Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Hematology (AREA)
  • Clinical Laboratory Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Investigating Or Analyzing Materials By The Use Of Magnetic Means (AREA)

Abstract

La présente invention concerne un dispositif, un procédé et un système de détection quantitative de la présence ou de l'absence de deux analytes cibles ou plus dans un échantillon constitué de moins de 200 µL de liquide, ledit procédé comprenant entre autres les étapes consistant à mettre en contact un échantillon contenant un analyte dans une chambre de réaction avec une population de particules magnétiques et/ou paramagnétiques, ladite population comprenant deux ensembles ou plus, chaque ensemble étant capable de capturer un analyte spécifique et mutuellement différent, et chaque ensemble ayant une moyenne différente du rapport de l'aire de surface sur le poids, la séparation de la population de particules magnétiques et/ou paramagnétiques comprenant les analytes capturés dans lesdits deux ensembles ou plus en déplaçant un champ magnétique par rapport à une partie de détecteur de la chambre, l'élimination du champ magnétique, et finalement la détection de la présence ou de l'absence d'analytes cibles dans chaque ensemble de matériel magnétique et/ou paramagnétique en utilisant un moyen de détection conventionnel.
PCT/EP2010/070519 2009-12-23 2010-12-22 Dispositif, procédé, et système de détection quantitative de la présence de multiples analytes cibles WO2011076860A1 (fr)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US28216409P 2009-12-23 2009-12-23
EP09180620A EP2338595A1 (fr) 2009-12-23 2009-12-23 Dispositif, procédé et système pour la détection quantitative de la présence de plusieurs analytes cibles
US61/282,164 2009-12-23
EP09180620.8 2009-12-23

Publications (1)

Publication Number Publication Date
WO2011076860A1 true WO2011076860A1 (fr) 2011-06-30

Family

ID=41683092

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP2010/070519 WO2011076860A1 (fr) 2009-12-23 2010-12-22 Dispositif, procédé, et système de détection quantitative de la présence de multiples analytes cibles

Country Status (2)

Country Link
EP (1) EP2338595A1 (fr)
WO (1) WO2011076860A1 (fr)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
RU2528885C2 (ru) * 2011-10-04 2014-09-20 Общество с ограниченной ответственностью "Инноград Пущино" Способ детекции аналита из раствора на частицах и устройство для его реализации
CN109330420A (zh) * 2018-10-26 2019-02-15 常开喜 一种生抽调味料定量出液装置
CN114011479A (zh) * 2017-06-06 2022-02-08 西北大学 跨界面磁性分离

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1996017686A1 (fr) * 1994-12-05 1996-06-13 Bolt Beranek And Newman, Inc. Separation magnetique de spheres a sensibilite magnetique
WO2007129275A2 (fr) * 2006-05-10 2007-11-15 Koninklijke Philips Electronics N.V. Biocapteur magnétique rapide
WO2009068585A1 (fr) * 2007-11-26 2009-06-04 Atonomics A/S Cartouche de séparation et de détection à l'aide de particules magnétiques avec une distribution granulométrique bimodale

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1996017686A1 (fr) * 1994-12-05 1996-06-13 Bolt Beranek And Newman, Inc. Separation magnetique de spheres a sensibilite magnetique
WO2007129275A2 (fr) * 2006-05-10 2007-11-15 Koninklijke Philips Electronics N.V. Biocapteur magnétique rapide
WO2009068585A1 (fr) * 2007-11-26 2009-06-04 Atonomics A/S Cartouche de séparation et de détection à l'aide de particules magnétiques avec une distribution granulométrique bimodale

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
RU2528885C2 (ru) * 2011-10-04 2014-09-20 Общество с ограниченной ответственностью "Инноград Пущино" Способ детекции аналита из раствора на частицах и устройство для его реализации
CN114011479A (zh) * 2017-06-06 2022-02-08 西北大学 跨界面磁性分离
CN114011479B (zh) * 2017-06-06 2023-05-02 西北大学 跨界面磁性分离
US11673134B2 (en) 2017-06-06 2023-06-13 Northwestern University Trans-interfacial magnetic separation
CN109330420A (zh) * 2018-10-26 2019-02-15 常开喜 一种生抽调味料定量出液装置
CN109330420B (zh) * 2018-10-26 2020-07-03 江苏特味浓生物技术开发有限公司 一种生抽调味料定量出液装置

Also Published As

Publication number Publication date
EP2338595A1 (fr) 2011-06-29

Similar Documents

Publication Publication Date Title
US12253577B2 (en) Rapid magnetic biosensor
JP5000666B2 (ja) 流体を分析する装置
US9528985B2 (en) Discontinuous fluidic systems for point-of-care analyte measurement
JP5595382B2 (ja) 唾液内の検体を検出する装置及び方法
US20110008776A1 (en) Integrated separation and detection cartridge using magnetic particles with bimodal size distribution
JP6013519B2 (ja) 統合された電気化学的免疫測定に基づくマイクロ流体デバイス、及びその基板
RU2456618C2 (ru) Система и способ обнаружения с помощью магнитной и/или электрической метки
JP5423200B2 (ja) 分析チップおよび検体の分析方法
JP2007522435A (ja) 流体力による弁別
MX2008011787A (es) Dispositivos y metodos para detectar celulas y otros analizados.
JP2011525109A (ja) ライブラリ・エレメントを選択するためのシステムおよび方法ならびにマイクロ流体デバイスを製造する方法（ライブラリ・エレメントのマイクロ流体選択）
WO2006130299A2 (fr) Bande de detection de flux laminaire microfluidique
WO2011029794A1 (fr) Mesure multiplexée de concentrations en analytes
WO2009083856A2 (fr) Dosage de particules magnétiques non liées concentré pour biocapteurs
JP6861456B2 (ja) アナライトの検出およびそのための方法
WO2010086772A1 (fr) Système et procédé de détection
WO2011076860A1 (fr) Dispositif, procédé, et système de détection quantitative de la présence de multiples analytes cibles
KR102114446B1 (ko) 랩온어칩, 랩온어칩 제조 방법 및 랩온어칩을 이용한 진단 방법
WO2007072444A2 (fr) Dispositif de bio-capteur
Shao et al. Design, fabrication and test of a pneumatically controlled, renewable, microfluidic bead trapping device for sequential injection analysis applications
JP2007263706A (ja) バイオアッセイ用マイクロチップ
KR102543112B1 (ko) 유체 시료 내에 극미량으로 존재하는 분석 대상 물질의 입자를 검출하기 위한 방법
US20100009465A1 (en) Method for the analysis of circulating antibodies
JP2010008223A (ja) マイクロチップ
Ghonge Point-of-care microfluidic assays for measuring expression level of antigen on blood cells

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 10792949

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 10792949

Country of ref document: EP

Kind code of ref document: A1

点击 这是indexloc提供的php浏览器服务，不要输入任何密码和下载