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
  • B01L3/502738—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 integrated valves
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
  • B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
  • B01F31/00—Mixers with shaking, oscillating, or vibrating mechanisms
  • B01F31/65—Mixers with shaking, oscillating, or vibrating mechanisms the materials to be mixed being directly submitted to a pulsating movement, e.g. by means of an oscillating piston or air column
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
  • B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
  • B01F33/00—Other mixers; Mixing plants; Combinations of mixers
  • B01F33/30—Micromixers
• • F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
  • F15—FLUID-PRESSURE ACTUATORS; HYDRAULICS OR PNEUMATICS IN GENERAL
  • F15C—FLUID-CIRCUIT ELEMENTS PREDOMINANTLY USED FOR COMPUTING OR CONTROL PURPOSES
  • F15C1/00—Circuit elements having no moving parts
  • F15C1/02—Details, e.g. special constructional devices for circuits with fluid elements, such as resistances, capacitive circuit elements; devices preventing reaction coupling in composite elements ; Switch boards; Programme devices
  • F15C1/04—Means for controlling fluid streams to fluid devices, e.g. by electric signals or other signals, no mixing taking place between the signal and the flow to be controlled
• • 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
  • B01L2200/0605—Metering of fluids
• • 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
  • B01L2200/0673—Handling of plugs of fluid surrounded by immiscible fluid
• • 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
  • B01L2300/0809—Geometry, shape and general structure rectangular shaped
  • B01L2300/0816—Cards, e.g. flat sample carriers usually with flow in two horizontal directions
• • 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
  • B01L2400/0442—Moving fluids with specific forces or mechanical means specific forces thermal energy, e.g. vaporisation, bubble jet
• • 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
  • B01L2400/06—Valves, specific forms thereof
• • 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
  • B01L2400/06—Valves, specific forms thereof
  • B01L2400/0688—Valves, specific forms thereof surface tension valves, capillary stop, capillary break

Definitions

• the present invention relates to a fluidic device comprising or associated with an operating cavity of the reactor type, allowing, without any mechanical or moving part, on the one hand to isolate the contents of said cavity, and on the other hand to isolate with agitation. of the contents of this cavity.
• the invention relates to a fluidic device of the microfluidic type, usable by way of example in systems or device of the "laboratory on chip” type (in English "lab-on-a-chip”).
• microfluidics is a developing technical field. To simplify, it is a question of treating liquids, gases, and solids if necessary, in devices or structures whose volume unit is between 1 nano liter and 1 microliter. On this scale, it is therefore required or preferred to exclude any part of the mechanical type, in particular with a moving part, and by way of example the thermo-pneumatic is retained as the actuation or motor principle, in particular for the circulation of liquid in such systems.
• valves or valves As regards first of all valves or valves, or more generally means allowing any control of the flow rate of a liquid, various solutions using gas or vapor microbubbles have been proposed.
• a fluidic device has been described making it possible to form and transport predetermined volumes of a liquid.
• a fluid section comprising, in series, a reserve chamber, a first storage cavity, a portion of capillary conduit, and a second storage cavity.
• the reserve chamber and the two storage cavities are in communication with an external pressure source.
• the portion of capillary conduit is filled with liquid, through the first storage cavity, and stopping at the second storage cavity; the portion of capillary conduit between the two storage cavities defines the predetermined volume of liquid,
• the liquid is returned to the reserve chamber, by isolating the predetermined volume of liquid between two menisci situated respectively at the level of the two storage cavities, - by increasing the pressure in the first storage cavity, the predetermined and isolated volume of liquid is transferred beyond and through the second storage cavity.
• a microfluidic device consisting of an arrangement of capillary conduits, comprising different capillary valves, without moving part, each arranged to generate an overpressure at the interface between a control gas and a liquid of interest, or meniscus.
• a control gas By external control of the control gas, to or from the fluidic device, at the level of the various capillary valves, it is possible to circulate, or "pump", the liquid of interest according to any predetermined process.
• a microfluidic device has been described making it possible to dispense predetermined volumes of a liquid of interest, from a single inlet conduit, thanks to an external source gas, injected into said device to move said predetermined volumes.
• the present invention relates specifically to the following function, namely the isolation in an operating cavity of a volume of liquid filling it, possibly with agitation of said volume in said cavity.
• the object of the present invention is to achieve this function with particularly simple fluidic means.
• a fluidic device arranged from one or more components, for example from a support comprises: - an operating cavity
• conduits for example inlet and outlet of a liquid of interest, communicating with the operating cavity, respectively by means of two bodies without moving part, of the valve type, allowing the control of the cavity operating - two trapping chambers for a gas, for example air, communicating only and respectively with the two conduits, by two separate connection channels respectively of the two said conduits
• an inlet or outlet conduit and a connecting channel with a trapping chamber communicate, directly or indirectly, with the same member without moving part, of the valve type, placed on the operating cavity.
• a said connecting channel is connected to an inlet or outlet conduit, for example by means of an expansion chamber, as described or defined below.
• the conduits considered by the present invention are capillary, in the sense that, with respect to a predetermined liquid, they are capable of containing the latter according to a certain height against gravity.
• such conduits have a section whose transverse dimension (or diameter) does not exceed 1.5 mm, for example of the order of 500 ⁇ m.
• a "cavity” or “chamber” When, according to the present invention, a “cavity” or “chamber” is envisaged, the shape and / or the dimensions of the latter differentiate it from a duct, in the sense that by following a dimension, for example in the direction liquid circulation, or the other dimensions of the cavity or chamber are greater than that, for example transverse, of a conduit.
• a device constitutes, by means of the trapping chambers, a thermo-pneumatic system, in the sense that only thermal actuations make it possible to control the pressure and / or the volume of the gas in the trapping chambers.
• the device comprises, on either side of the operating cavity, two isolation means disposed respectively on the two conduits, for example inlet and outlet, each arranged to take two positions, namely a position establishing a communication of a said conduit with the outside, and another position isolating said conduit from the outside.
• two isolation means disposed respectively on the two conduits, for example inlet and outlet, each arranged to take two positions, namely a position establishing a communication of a said conduit with the outside, and another position isolating said conduit from the outside.
• a device comprises two expansion chambers each disposed between said operating cavity and each conduit, each chamber communicating on one side with said conduit by a first capillary valve with no moving part, opposing any liquid passage capillary, opposing any liquid passage to said chamber, and on the other side with said cavity by a second capillary valve, opposing any liquid passage to said chamber.
• each connecting channel each connect a trapping chamber with an expansion chamber.
• each expansion chamber constitutes the junction between an inlet or outlet conduit and a connecting channel with a trapping chamber, on each side of the operating cavity.
• the means for controlling the pressure and / or the volume of the gas in one and / or the other trapping chamber are: - two hot sources in heat exchange relationship with the two trapping chambers respectively, - or one only hot source, in heat exchange relationship with the two trapping chambers.
• hot source any source capable of delivering and / or receiving heat.
• Each of these hot springs can be a resistance integrated on the cover of the fluidic device, for example a platinum resistance produced by photolithography, on a glass cover, aligned opposite one or the other of the trapping when assembling the cover with the support.
• This resistance can be of the order of 25 to 50 ohms.
• Each of these hot sources can be an emitter of radiation, for example infrared radiation, capable of being absorbed by the gas present in the trapping chambers.
• FIG. 1 schematically represents a fluidic device in accordance with the present invention
• Figures 2 and 3 show, still schematically, two phases of use of the device according to Figure 1, to isolate or confine a volume of a liquid of interest in the operating cavity, belonging to said device
• - Figures 4 to 6 show schematically respectively three embodiments of any capillary valve belonging to a device according to the invention, and by way of example disposed at the junction between a connecting channel and an expansion chamber belonging to the device according to FIG. 1;
• FIG. 7 and 8 respectively represent two phases of use of the device shown in Figure 1, to agitate the contents of the operating cavity belonging to said device.
• FIG. 9 to 11 show another embodiment called “threshold", of an expansion chamber belonging to a device according to Figure 1, Figures 9 to 11 schematically and respectively representing three phases of thermal control d 'such an expansion chamber;
• FIG. 12 shows an embodiment of the operating cavity of a fluidic device according to the present invention
• FIG. 14 represents a device according to the present invention, modified to implement the immunoassay format shown diagrammatically in FIG. 13.
• a device according to the invention is produced by means of micro-technologies, making it possible to obtain, in any flat support, for example a hollow structure represented schematically on a large scale in FIG. 1.
• micro-technologies one can cite chemical etching or with a plasma of a silicon or glass support, machining, hot molding ("hot-embossing"), and injection or ablation by laser beam d 'a flat support, for example plastic, such as polycarbonate.
• hot-embossing hot molding
• injection or ablation by laser beam d 'a flat support for example plastic, such as polycarbonate.
• the hollow structure defines in the support (12) a fluidic device (1) comprising:
• the two connecting channels (91, 92) each connecting a trapping chamber (81) or (82) with an expansion chamber (61) or (62), - two capillary valves (101) and (102) such as defined above, by which the connecting channels (91, 92) communicate respectively with the corresponding expansion chambers (61) and (62), these two capillary valves opposing any liquid passage towards the trapping chambers (81 ) and (82) respectively, - two isolation means (201 and 202), disposed respectively on the two conduits (41 and 42), on either side of the operating cavity (3), each arranged to take two positions, namely an open position establishing communication of a said conduit with the outside, and a closed position isolating said conduit from the outside.
• capillary valve By “capillary valve”, and by reference by way of example to the valve represented in an enlarged manner under the reference (71) in FIG. 3, is meant a valve without moving part, constituted by a capillary type restriction, opposing at any liquid passage in a given direction, for example towards the expansion chamber (61) relating to the valve (71), in FIG. 3.
• a capillary valve is arranged to generate an interface between a gas, for example residual air, and a liquid, for example the liquid of interest, interface called in meniscus practice, the latter generating an overpressure generally opposing any liquid passage beyond the valve, of course below a given pressure, or pressure threshold.
• the obtaining and the reproducibility of such a meniscus depend on many factors, among which may be mentioned: - the geometry of the edges or walls at which the meniscus is obtained,
• any appropriate treatment of the latter for example of the hydrophobic or hydrophilic type, being in particular capable of modifying the above-mentioned properties. -vis liquid.
• the operating cavity (3) constitutes for example a micro-reactor, having a volume of the order of 0.1 ⁇ l, the expansion chambers (61) and ( 62) having a volume of the order of 0.03 ⁇ l, as well as the trapping chambers (81) and (82) having a volume of the order of 0.03 ⁇ l to 0.15 ⁇ l.
• a fluidic device 1 as described above is also suitable (but not shown) for working in a technical environment providing it:
• a source of pressure or load at the inlet of the device, for example in the duct (41), generally greater than the outlet pressure, for example in the duct (42), and this by any appropriate means, such as that a height of liquid higher than the height of liquid at the outlet of said device, for example in the case of filling under pressure, or by a syringe, itself mounted on a syringe pump.
• a device During the active operating phase of a device according to the invention, that is to say the isolation of the operating cavity filled with the liquid of interest, with or without agitation, said device is isolated from the outside by means 201 and 202, in the closed position, and constitutes a closed system in heat exchange with the sources 21 and / or 22.
• the geometry and the size of the fluidic device (1) the person skilled in the art will retain and adjust numerous parameters, in order to obtain stable and reproducible operation of said device. These parameters include: - the wettability of the liquid or liquids used relative to the internal surface of the device, considered in particular by its geometry and its surface characteristics,
• the shape of the operating cavity (3) can be optimized depending on the intended application.
• the capillary shape, shown in Figure 12 may be of interest for certain chemical reactions; this form appears to be suitable for good stirring of the liquid of interest, in order to obtain a more homogeneous or more complete reaction.
• the previously described device is now used to isolate or confine the contents of an operating cavity (3), according to the operation described below.
• the device (1) is empty, and the isolation means
• Figures 4 to 6 describe different possible forms of capillary valve.
• Figures 4 and 5 illustrate a narrowing of the capillary section in the case of a wetting liquid. Conversely, in the case of a non-wetting liquid, it is a widening of the section of the capillary which allows blocking of the meniscus at the level of the valve (cf. FIG. 6).
• the capillary valve (101) or (102) can be arranged according to one of the embodiments shown schematically in Figures 4 and 5 respectively.
• a baffle (95) is arranged obliquely at the base of the connecting channel (91) and (92), directed towards the corresponding trapping chamber (81) or (82).
• a restriction is provided at the base of the connecting channel (91) or (92).
• the state of the device shown in FIG. 2 is therefore obtained, in which the conduits (41) and (42), the expansion chambers (61, 62) and the operating cavity (3 ) are met.
• the device is then isolated, by placing the isolation means (201 and 202) in the closed position, as shown in FIG. 3.
• the residual gas in the two trapping chambers (81) and (82) is brought to a so-called isolation temperature, higher than the previously called filling temperature, in order to bring the pressure in the trapping chambers (81) and ( 82) at a value sufficient to completely evacuate the liquid of interest from the two expansion chambers (61) and (62), by the two conduits (41) and (42) respectively. Consequently, the expansion chambers (61) and (62) are filled with two bubbles of residual gas, isolating the operating cavity (3), from any leakage of the liquid of interest, and / or of any diffusion of the particles contained in said liquid of interest, towards the conduits (41) and (42), or from said conduits (41) and (42) towards said cavity (3).
• particle means any discrete element, for example an element carrying biological information, such as an electrically charged, magnetic, or non-magnetic particle, supporting a biological molecule.
• This isolation step can be carried out in different ways:
• the trapping chambers (81) and (82) are dimensioned so as to initially contain a volume of the residual gas, which, heated to the so-called isolation temperature, completely or partially occupies the expansion chambers ( 61) and (62) respectively. Furthermore, these same chambers (81) and (82) have a compensating role, when the liquid rises naturally towards them, when the device cools, to a temperature possibly lower than the filling temperature. As soon as the temperature increases, the liquid returns, without capture inside the chambers (81) and (82), to the expansion chambers (61) and (62) respectively.
• the use of the fluidic device (1) for the purpose of isolating or confining an operating cavity (3), described above, can be made without expansion chambers (61) and (62).
• thermodynamic of the device it is therefore possible to isolate a reaction mixture against the diffusion towards the outside of any particles or species which it contains. Thanks to this confinement, the concentration of the reaction mixture is not modified, which may be essential for the yield and the integrity of the reaction carried out.
• the two expansion chambers (61) and (62) are substantially identical, in particular in volume
• - the two trapping chambers (81) and (82) are substantially identical, in particular in volume
• the two trapping chambers (81) and (82) are heated locally and independently thanks to the hot springs (21, 22) respectively.
• the operating cavity (3) is filled and the two expansion chambers (61) and (62), retaining the residual gas in the two trapping chambers (81) and (82), at a predetermined temperature, previously called filling.
• the device is therefore in the state shown schematically in FIG. 2.
• the device (1) is isolated with the means (201 and 202) in the closed position.
• the temperature of the residual gas in one (81) and in the other (82) of the trapping chambers is increased to a reference temperature; this increase in temperature in the chambers (81) and (82) is preferably simultaneous.
• the reference temperature in the trapping chamber (82) has a high value, greater than the so-called low value, in the other trapping chamber (81). Due to this difference in reference temperatures, respectively in the chambers (81) and (82), the expansion chamber (62) is completely filled with a bubble of the residual gas, while the expansion chamber (61 ) is partially filled with the same residual gas.
• the volume of liquid of interest displaced has flowed to the inlet (41) and / or outlet (42) conduits. If necessary, the residual gas present in the trapping chamber (81) can be heated, then the residual gas present in the trapping chamber (82), which facilitates the evacuation of the liquid towards the outlet conduit (42).
• the operations described above can be generated an integer number of times, to generate oscillations of the discrete portion (20) on either side of the operating cavity (3). These oscillations can be obtained at frequencies from 0.5 Hz to 25 Hz. They can be caused over a period of the order of an hour, corresponding to the duration of the chemical (or other) reaction in the operating cavity ( 3).
• the fluidic device (1) according to FIG. 1 can be used, to isolate or confine and stir all or part of a liquid of interest at the level of the operating cavity (3), according to the following operating steps: a) beforehand, by circulation of the liquid of interest, from an inlet conduit (41) to the other outlet conduit (42), the operating cavity (3) and the expansion chambers ( 61, 62), retaining a residual gas in the two trapping chambers (81, 82), b) after circulation of the liquid of interest, the residual gas is brought in the two trapping chambers, to a temperature called isolation, to bring the pressure in said trapping chambers to a value called equilibrium pressure, sufficient to evacuate all or part of the liquid of interest from the two expansion chambers (61, 62) by at least one of the two conduits ( 41, 42), and fill all or part of said chambers with two bubbles of the residual gas, isolating the operating cavity from any leakage of the liquid of interest and / or from any diffusion of the particles contained in said liquid interest towards said conduits (41, 42),
• the pressure obtained in step (d) is the equilibrium pressure.
• steps (c) and (d) are repeated.
• the operations described above can be generated an integer number of times, to generate oscillations of the discrete portion (20) on either side of the operating cavity (3), through the latter, the residual gas being compressed in each direction, or in the expansion chamber (62) or in the expansion chamber (61), and exerting each time a return action in the opposite direction.
• a stirring function is obtained, but also an isolation function, since the volume of the liquid of interest, present in the operating cavity (3 ) is isolated, with the discrete portion (20) of the same liquid, generally representing a few% of the volume of the operating cavity (3).
• the capillary valves (71, 72, 51, 52, 101 and 102) play exactly the same role in the agitation function as in the pure isolation function.
• the residual gas is compressed, without being able to flow, either towards the inlet duct (41) or towards the outlet duct (42).
• the residual gas can play a damping role in the agitation function described above.
• the proportion (20) of the liquid of interest is determined by the association of the geometry of the expansion chambers (61) and (62), and the choice of the so-called stirring temperatures previously exposed. As shown in Figures 9-11, the expansion chambers (61) and (62), and the choice of the so-called stirring temperatures previously exposed. As shown in Figures 9-11, the expansion chambers
• (61) or (62) can have a predetermined geometry, in order to obtain a so-called "threshold" structure.
• each expansion chamber (61) or (62) comprises, in the direction of the operating cavity (3), two successive narrowing A and B, towards diameters or sections respectively smaller than one another. Consequently, from a complete filling of the expansion chamber (61) according to FIG. 9, in order to pass to a complete evacuation, it is necessary to increase the temperature in a non-linear manner, according to two stages or thresholds, taking into account the increase in the capillary force from one narrowing to the other, at the interface or meniscus between the liquid of interest and the residual gas. These allow a discrete volume variation, or in stages, and therefore a more flexible thermal control of the fluidic device according to the invention, either in isolation, or in agitation or both.
• the agitation previously described with reference to Figures 7 and 8 can be obtained with amplitudes and frequencies previously selected. It intervenes locally in the device, and does not require the introduction of particles or other means, since only the residual gas, trapped passively during filling with the liquid of interest is the only means used for this purpose, and this on the periphery or outside of the isolated liquid of interest.
• a fluidic device as previously described or defined is particularly well suited for the implementation of a method, of ELISA or ELOSA type, for determining a target species, or analyte, described schematically below with reference to the figure 13.
• the method comprises the following steps: a) there is a support (Mi) functionalized with the first ligand (Li) placed by example in liquid medium, in an incubation chamber (not shown), b) always in liquid medium, in the incubation chamber, the functionalized support (Mi, L1) is brought into contact, successively or simultaneously, l target species (C) or ana lyte, and the second labeled ligand (L 2 , E), to obtain a complex 300 associating the support (Mi), the first ligand (Li), the target species (C) and the second labeled ligand (L 2 , E ), c) there is, for example in a liquid medium or in contact with a liquid medium, another support (M 2 ) functionalized 303 with a third ligand (L 3 ), capable of binding to the target species (C), d) the complex 300 is associated in an oriented manner, to separate a conjugate 301 associating the target species (C) and the second label
• This generally defined process of the immunoassay type can be subject to various adaptations or supplements, in particular depending on the analyte (C), or the device allowing its implementation.
• the third ligand (L 3 ) can be identical to or different from the first ligand (Li)
• step e) can be carried out in an identical or different enclosure from the incubation enclosure, making it possible to obtain the intial complex 300,
• the support (M1) and / or the other support (M2) may be in divided form, for example of particles, which may contain or contain, if necessary, a magnetic material,
• a fraction enriched in complex 300 is separated from the liquid medium obtained, after contacting,
• step (b) various washes can be carried out, on the one hand to remove the second labeled ligand (L2, E) in excess, and on the other hand to remove this same reagent, weakly adsorbed , functionalized support (Mi, Li),
• target species or “analyte” means any entity, in particular biological, that we want to determine, that is to say detect qualitatively and / or quantitatively; by way of example, it is an antibody or an antigen, or also a polynucleotide;
• ligand means any entity capable of binding, for example specifically, by weak bonds, for example of hydrogen type, with a site, called ligation, belonging to the target species; it is for example an antibody or an antigen, or also a polynucleotide, partly complementary to a target polynucleotide;
• support is meant any substrate, in divided or undivided form, generally having an inert nature with respect to the analyte and / or a ligand, making it possible by functionalization to attach an editorial entity, for example a ligand;
• the operating cavity 12 comprises, in the form of filling in the manner of a chromatography column, particles 303 as defined above, that is to say the support (M 2 ) functionalized with the third ligand (L 3 ), - a means 307, for example of heating, of oriented dissociation is arranged in relation to the conduit entry 41, at the exit of the incubation enclosure 305, and this so as to allow the dissociation of the complex 300, previously defined, between the support (Mi) the first ligand (Li), and the target species (C), and the second labeled ligand (Mi, L 2 ); this means 307 can be associated, where appropriate, with a means for concentrating complex "300,
• a means 308 for retaining particles for example of the magnetic type, is disposed downstream of the dissociation means 307, still in relation to the inlet conduit 41, for retaining the particles of the functionalized support 302, dissociated from the complex 300 .
• the conjugate 301 can circulate towards the operating cavity 3, and bind in the latter with the particles of the functionalized support 303 (M 2 , L 3 )

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• 2003
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  • 2003-06-24 JP JP2004514986A patent/JP2005530608A/ja active Pending
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