Classifications

• • G—PHYSICS
  • G01—MEASURING; TESTING
  • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
  • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
  • G01N35/08—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor using a stream of discrete samples flowing along a tube system, e.g. flow injection analysis
  • G01N35/085—Flow Injection Analysis
• • 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
  • 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
  • B01L3/502769—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 multiphase flow arrangements
  • B01L3/502784—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 multiphase flow arrangements specially adapted for droplet or plug flow, e.g. digital microfluidics
• • 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
  • B01L2300/00—Additional constructional details
  • B01L2300/08—Geometry, shape and general structure
  • B01L2300/0861—Configuration of multiple channels and/or chambers in a single devices
  • B01L2300/0867—Multiple inlets and one sample wells, e.g. mixing, dilution
• • 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
• • 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
  • B01L2400/0633—Valves, specific forms thereof with moving parts
  • B01L2400/0655—Valves, specific forms thereof with moving parts pinch valves
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
  • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
  • B01L7/00—Heating or cooling apparatus; Heat insulating devices
  • B01L7/54—Heating or cooling apparatus; Heat insulating devices using spatial temperature gradients
• • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
  • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
  • Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
  • Y10T436/00—Chemistry: analytical and immunological testing
  • Y10T436/11—Automated chemical analysis
  • Y10T436/117497—Automated chemical analysis with a continuously flowing sample or carrier stream
• • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
  • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
  • Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
  • Y10T436/00—Chemistry: analytical and immunological testing
  • Y10T436/11—Automated chemical analysis
  • Y10T436/117497—Automated chemical analysis with a continuously flowing sample or carrier stream
  • Y10T436/118339—Automated chemical analysis with a continuously flowing sample or carrier stream with formation of a segmented stream
• • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
  • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
  • Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
  • Y10T436/00—Chemistry: analytical and immunological testing
  • Y10T436/25—Chemistry: analytical and immunological testing including sample preparation
  • Y10T436/25625—Dilution
• • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
  • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
  • Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
  • Y10T436/00—Chemistry: analytical and immunological testing
  • Y10T436/25—Chemistry: analytical and immunological testing including sample preparation
  • Y10T436/25875—Gaseous sample or with change of physical state

Definitions

• FLUID FLOW DEVICE ASSEMBLY FOR DETERMINING AT LEAST ONE CHARACTERISTIC OF A PHYSICO-CHEMICAL SYSTEM COMPRISING SUCH A DEVICE, METHOD OF
• the present invention relates to a fluid flow device, a set of determination of at least one characteristic of a physico-chemical system comprising such a device, a determination method implementing this set, as well as a screening method. corresponding.
• a physicochemical system which is intended to determine at least one characteristic, may be a pure body, but also a compound, such as for example one or more solute (s) dissolved in a solvent or a mixture of several pure bodies.
• a characteristic of this physico-chemical system is in particular a characteristic curve of such a system, in particular a thermodynamic limit, in particular a phase diagram, such as a solubility curve, or even the miscibility limit for a mixture of two liquids.
• the present invention aims more particularly, but not exclusively, the study of the solubility of such a physicochemical system. It is recalled that the solubility of a solute in a solvent is the maximum concentration of this solute that can be dissolved in this solvent at a given temperature. The solubility curve of this solute, which therefore forms a physicochemical system according to the invention, corresponds to the variation of this solubility as a function of temperature.
• the methods conventionally used to determine this solubility curve are various. They involve different measures, during which at least one parameter is changed, especially the solute concentration and / or the temperature. In general, the methods used in the state of the art are of a systematic nature, so that they prove to be particularly lengthy to implement.
• the invention proposes to remedy this drawback. It aims in particular to provide a solution for reliably determining at least one characteristic of a physicochemical system, which is accompanied by a significantly reduced handling time compared to the prior art.
• the invention also relates to a set of determination of at least one characteristic of a physico-chemical system according to claim 13 attached.
• the invention also relates to a method for determining at least one characteristic of a physico-chemical system according to claim 14 attached.
• FIG. 1 is a front view, schematically illustrating a set of determination according to 1;
• FIGS. 2A and 2B are side views, illustrating two positions of a valve fitted to the determination assembly of FIG. 1;
• FIG. 3 is a graph illustrating a solubility curve that the invention proposes to determine
• FIG. 5 is a view on a larger scale of FIG. 4.
• FIG. 1 illustrates a determination assembly according to the invention, which firstly comprises a fluid flow device, designated as a whole by reference numeral 1.
• a fluid flow device designated as a whole by reference numeral 1.
• This latter comprises a wafer 2, which is produced in a known manner in FIG. for example PDMS (poly (dimethylsiloxane)).
• PDMS poly (dimethylsiloxane)
• it may be provided to form it in any other suitable material, such as glass, silicon, PMMA (polymethyl methacrylate), or a photoresist of SU-8 type MicroChem company, or NOA type from Nordland.
• the invention also finds application in millifluidic flow channels, ie whose cross-section is greater than the values mentioned above.
• the cross section of these millifluidic channels may reach a value close to 9 mm 2 , for example 3 mm by 3 mm, or even close to 25 mm 2 , for example 5 mm by 5 mm.
• FIG. 1 illustrates more particularly the design of the microchannels, which are etched on the wafer 2.
• microchannels 4 and 6 for supplying two first components, which are associated with two inputs 8 and 10. the latter is adapted to receive a first end of a nonrepresented tube, the other end is connected to a syringe also not shown.
• the flow rate of the component administered by each syringe is controlled by means of a syringe pump, also not shown.
• a microchannel 12 associated with an inlet 14 which cooperates with a tube, with a syringe, and with a not shown syringe driver.
• This microchannel 12 is divided into two branches 16, affecting approximately a square shape, which meet at an intersection 18.
• a microchannel 19 mixing in which open the downstream ends of the two microchannels 4 and 6, is put in communication with this intersection 18.
• This connecting channel 20 is provided with an output 20 ', which will be noted that it is optional. It is put in communication with several so-called storage channels 22 ⁇ to 22 ⁇ .
• the term "several" means "at least two".
• these storage microchannels extend horizontally, namely that they are parallel to each other, while being perpendicular to the connecting channel 20.
• these storage channels are not perpendicular to the link channel and are not parallel to each other.
• the connecting channel 20 and the various storage channels 22i 22 6 define a comb, whose base is formed by the connecting channel and the teeth are formed by the storage channels.
• this link channel and these storage channels define a quadrilateral, one side of which is formed by the link channel 20, two additional sides are defined by the end storage channels 22 ⁇ and 22 ⁇ , and one The last side is defined by a segment parallel to the link channel 20, which connects the downstream outputs of the different storage channels.
• the aforementioned quadrilateral is a rectangle.
• the storage microchannels 22i to 22 ⁇ are represented in number of six. However, in practice, a number of these channels is advantageously used which is between two and fifteen, preferably between five and ten. One can also consider using a single microchannel storage.
• the storage microchannels cooperate with valves V 1 to V 6 , illustrated in a schematic manner, one of which V 1 is shown more precisely in FIGS. 2A and 2B.
• the outlet 22 'x of the microchannel 22 ⁇ is placed in communication with a rigid tube 24, made for example of ethylene-propylene fluorinate (Teflon FEP) or Polyetheretherketone (PEEK ® ), namely that it does not deform substantially radially. during the flow of a fluid.
• this rigid tube 24 opens into a flexible tube 26, made for example of PVC or silicone, which is associated with the valve Vi.
• the latter is a tube-clamping solenoid valve of a type known per se.
• the tubes 24 and 26 form a connecting member, connecting the outlet 22 'i of the microchannel 22i with the valve Vi.
• This connecting member is independent of the wafer, namely that it can be reported, including removably, on the walls of the aforementioned outlet. This is advantageous, insofar as it is possible to make the wafer 2 of any material, regardless of the nature of the valve and its connecting member.
• This solenoid valve Vi is conventionally provided with a piston 28 adapted to be actuated by a not shown coil, capable of crushing the tube 26 against a support 30. It should be noted that the length 1 of the flexible tube 26, between its connection with the rigid tube 24 and the pinching zone by the piston 28, is very small, for example close to 2 mm. This makes it possible to limit the parasitic displacements of the fluid in the different channels during the maneuvers of the valve.
• valve shown in Figures 2A and 2B is advantageous. Indeed, this valve is physically isolated, thanks to the presence of the flexible tube 26, relative to the fluid present in the microchannel storage. Furthermore, this valve is reliable, while having a relatively low cost.
• the invention provides for imposing two gradients according to the two dimensions x and y, respectively defined by the storage microchannels 22 and the connecting microchannel 20.
• a gradient of operating condition including temperature, humidity, illumination, or concentration of another compound.
• each of these modules 32 ⁇ and 32 2 may constitute a hot source or a cold source, .according to the steps of the method according to the invention.
• the determination unit is provided with means capable of analyzing the contents of the different microchannels formed in the wafer 2.
• these are means of visual analysis, namely a microscope 34 shown
• the microscope 34 which is associated with an unrepresented camera, is connected in a conventional manner to a processing computer 36.
• this solute A constitutes a physicochemical system that the invention proposes to study, which can be introduced into the microchannel 4. Furthermore, the abovementioned solvent B can be admitted via the microchannel 6, so that the mixture of the solute and the solvent forms a physicochemical set within the meaning of the invention. Finally, a carrier phase P, such as oil, which is not miscible with the solute mixture • and solvent, is admitted by the microchannel 12.
• a succession of drops Gi which are directed towards the first storage channel 22i, is formed in a manner known per se.
• Each drop is formed by the mixture of solute A and solvent B, namely the physicochemical set defined above.
• these drops Gi are separated from each other by sections of oil, forming a carrier phase P immiscible with these drops. It will be noted that, during this step, a sufficiently high temperature is imposed so that the solute is entirely in liquid form in the drops Gi, that is, at the bottom and to the right of the curve CS of the figure 3.
• the sum of the flow rates of the solute and the solvent is between 0.1 mL / hr and 5 mL / hr, in particular between 0.5 and 1 mL / hr.
• the oil flow admitted by the microchannel 12 is between 0.5 and 10 mL / hr, especially between 1 and 5 mL / hr.
• the filling of the various microchannels 22 has been performed at a high temperature, so that the different drops Gi to G 6 are in the fully liquid state. Then it is a question of lowering the temperature prevailing in these microchannels 22, so as to move towards the part situated at the top left of the curve C of FIG. 3, and so as to crystallize the solute present in all of these drops.
• This change in temperature is obtained by modifying, as appropriate, the electric current supplied to the Peltier modules 32 2 and 32 2.
• the left Peltier module 32 X is controlled so as to generate a relatively low temperature on its surface, for example around 10 0 C, while the right module 322 is controlled so as to generate a relatively high temperature for example of the order of 60 ° C.
• the application of these different temperatures leads to a substantially linear gradient along each microchannel 22.
• the temperature is close to that imposed by the module 32i while at the downstream end, the temperature is close to that imposed by the module 322-
• this analysis is conducted visually through the microscope 34.
• this microscope 34 has a wide field of view, to observe at the same time time the entire wafer. This is for example a binocular microscope.
• an observation can be made through a crossed analyzer and polarizer to easily detect the presence of crystals that are birefringent. If the crystals are large enough, it is possible not to use birefringence.
• Ti (Ti '+ T 1 ") / 2.
• the computer 36 places, on the graph of FIG. 6, the different values Ti to T ⁇ thus obtained for the concentrations Ci to C 6 . From these different points, we thus obtain a solubility curve CS ', represented in FIG. 6, which is close to that CS of FIG.
• the solubility curve a been plotted from six points, corresponding to six microchannels of storage. It will be understood that, if it is desired to improve the accuracy of the method of the invention, it is a question of increasing the number of microchannels of storage, which will make it possible to correspondingly increase the number of points from which performed the solubility curve. It is also possible to increase the number of drops present in the same storage channel, which contributes to reducing the distance between two adjacent drops. This improves the accuracy of the solubility temperature.
• the concentration of impurities in the drops tends to vary.
• the temperature was varied along the different storage channels, namely along the x axis.
• another operating condition such as the hygrometric degree, the illumination or the concentration variation of another compound.
• the analysis is of a visual type, thanks to the use of the microscope 34.
• other types of analysis may be provided, especially of the Rar ⁇ an spectroscopy type, spectroscopy. infrared, UV or visible spectroscopy.
• a succession of drops, forming plugs are directed in the different microchannels of storage.
• the invention achieves the previously mentioned objectives.
• the filling operations of the various storage channels, made according to the invention are reveal significantly faster than successive manipulations, which should be carried out in the state of the art. Furthermore, it is possible, thanks to the invention, to perform a direct reading of the desired characteristic, including a simple visual analysis.
• drops of particularly small volume are advantageous .
• these drops are real microreactors which, given their scale, are homogeneous and therefore do not require agitation, as might be the case for macroscopic systems.
• This size of drops also ensures a rapid thermal equilibrium.
• the use of this microscopic scale makes it possible to limit the inadvertent presence of impurities, which confers great precision on the determination thus made.
• plugs is advantageous in terms of the accuracy of the determination of the desired characteristic.
• the various plugs present in the storage channels are individual entities, likely to retain their original properties, especially their initial concentration.

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• 2006
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