Classifications

• • G—PHYSICS
  • G01—MEASURING; TESTING
  • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
  • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
  • G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
  • G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
  • G01N21/65—Raman scattering
• • 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
  • B01F33/301—Micromixers using specific means for arranging the streams to be mixed, e.g. channel geometries or dispositions
  • B01F33/3012—Interdigital streams, e.g. lamellae
• • 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
  • 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
  • B01L2400/0403—Moving fluids with specific forces or mechanical means specific forces
  • B01L2400/0406—Moving fluids with specific forces or mechanical means specific forces capillary forces
• • G—PHYSICS
  • G01—MEASURING; TESTING
  • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
  • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
  • G01N21/01—Arrangements or apparatus for facilitating the optical investigation
  • G01N21/03—Cuvette constructions
  • G01N21/05—Flow-through cuvettes
  • G01N2021/058—Flat flow cell

Definitions

• the present invention relates to a method and an installation for determining the characteristics representative of a physical and / or chemical transformation occurring in a micro-reactor.
• transformation is meant in particular a reaction of chemical and / or physical type, such as for example any type of conventional chemical reaction, as well as also crystallization or precipitation, or else a modification of a liquid / vapor balance, etc.
• the determination of the characteristics representative of the transformation may firstly consist in determining the parameters specific to this transformation. The latter designate in particular the kinetic, thermodynamic or other parameters. The determination of these parameters is of major interest, insofar as it provides in-depth knowledge of the transformation considered.
• the determination of the characteristics representative of the transformation may also consist in determining the parameters for carrying out this transformation, within the framework of the process, on a pilot or industrial scale, in which the aforementioned transformation takes place. .
• These control parameters include modifications to the temperature, flow rates and concentrations at the input of the products involved in this transformation.
• Micro-reactors are tools used in particular in the fields of analytical chemistry, biochemistry, clinical diagnosis, medical chemistry and the chemical industry.
• the characteristic dimension of micro-reactors, targeted by the invention is between ten micrometers and one millimeter. -A microreactor is described, typically, for example in EP-A-0 616 218.
• a process for determining the characteristics representative of a physical and / or chemical transformation, in particular of a reaction, this transformation occurring in a medium, in particular reaction, flowing within at least one micro-reactor in which: - a steady state flow of the medium is carried out in at least one region of the micro-reactor; - you access, via an analysis means, at least one point of the permanent flow; - At least one measurement of at least one characteristic quantity of the medium is carried out, at the or at each point, by means of the analysis means; and - characteristics representative of the transformation are determined, as a function of the result of the or each measurement.
• the or each characteristic quantity of the medium, measured by the analysis means is for example the concentration in one and / or the other of the reagents, reactants and / or products intervening within the transformation, or the temperature or the density.
• the permanent regime can be defined, in a conventional manner, as a regime for which are substantially constant over time, on the one hand, the different magnitudes of the transformation occurring in the medium at the same point thereof and, on the other hand, the various parameters relating to the flow of this medium, such as in particular the flow rate.
• the establishment of such a permanent flow, in the micro-reactor is carried out in a manner known per se by those skilled in the art.
• an analysis means is the active element of an analysis apparatus, which extends between the body of this apparatus and the medium to be analyzed.
• an analysis means can be a laser beam in the case of a Raman spectrum, an ultra-violet or infrared ray in the case of a spectrophotometer, or even a temperature, an online density determination device or even more simply the view.
• the invention makes it possible in particular to achieve the objectives mentioned above. Indeed, it authorizes monitoring "in situ", namely in the micro-reactor itself, as opposed to monitoring which was carried out in the prior art, at the outlet of this micro-reactor.
• the determination of the characteristics representative of the transformation is of a significantly increased precision compared to this prior art.
• the invention makes it possible to determine all of the chemical and / or physical parameters chosen, by means of the implementation of a single transformation, without it being necessary to repeat the same transformation several times by performing successive quenches or tests with variable passage times. It should be noted that the determination of the characteristics of a transformation, implemented in standard reactors, cannot be easily transposed to the micro-reactors targeted by the invention. Thus, a reactor, even a small one, cannot be assimilated to a micro-reactor, given that these two types of tool have significantly different specificities.
• microreactors are all the more notable on a pilot or industrial scale. Indeed, these two types of reactors are accompanied by totally different, even opposite, extrapolations. So in the. In the case of standard type reactors, extrapolation is used, namely a change in the size of the reactor.
• This is to be compared with replication, implemented in the field of micro-reactors, which consists in placing several of these micro-reactors in parallel, without significantly varying their dimensions.
• micro-reactors allow more easily the study of transformations whose kinetics are very fast, allowing transformations under high, even very high pressures, with less risk of explosion. They also have a high resistance to high temperatures, which reduces the risk of thermal runaway.
• micro-reactors because of their size, are also very advantageous from an economic point of view and from the point of view of the toxicity of the various products of the transformation implemented.
• the small quantities of said products used make these micro-reactors very safe and efficient tools compared to standard reactors.
• the methods implemented in the state of the art by means of microfluidic type systems cannot be transposed, in a simple manner, to the field targeted by the present invention, for the same reasons as those mentioned above.
• thermal transfer problems as well as shortcomings in terms of resistance to pressure, which make it possible to remedy the microreactors.
• the latter therefore have a much greater versatility than that of microfluidic systems, while having a very limited size.
• the object of the invention clearly differs from a process, in which one would be satisfied with verifying the parameters of a transformation within the micro-reactor, while these parameters would have been determined beforehand.
• the flow of the medium within the micro-reactor allows, not a validation step, but an additional determination step, allowing access to characteristics not yet known a priori.
• different points of the permanent flow are accessed, which are distinct from each other in time and / or in space. This allows for a deeper and faster knowledge of the transformation whose representative characteristics we seek to determine.
• one accesses different points distinct from each other in space.
• a relative movement takes place between the analysis means and the permanent flow of the medium.
• this micro-reactor it is first of all possible to move this micro-reactor while keeping the analysis means stationary.
• the means of analysis is non-destructive with respect to the medium, in which the transformation takes place.
• the analysis means is invasive. This therefore means that it penetrates, physically, through at least one wall of the microreactor. In this case, it is for example a temperature sensor.
• the steady-state flow is accessed through an area of the micro-reactor which is permeable by means of analysis. In other words, the means of analysis is able to cross the aforementioned zone, without altering its own characteristics. This permeable zone may form substantially the entire " body of the - micro-reactor or, as a variant; - be added.
• the permeable zone varies as a function of the very nature of the means of analysis.
• this zone can be permeable to waves, in particular be permeable to visible radiation, to ultraviolet radiation, or again to any electromagnetic radiation.
• the transformation, the parameters of which it is proposed to determine by means of the invention is in particular a reaction, for example of chemical and / or physical type, or else a crystallization.
• the flow rate of the permanent flow is between 1 ml / h and 1 1 / h, preferably between 0.1 1 / h and 1 1 / h.
• parameters specific to the transformation are, for example, the concentration of one and / or the other of the reactants, reactants and / or products involved in the transformation, or even the temperature or the density.
• parameters for conducting this transformation are determined, as characteristics representative of this transformation.
• control parameters include modifications to the temperature, the flow rate and the input concentration of the products involved in the processing.
• the or each micro-reactor is advantageously arranged, within which the parameters for controlling the transformation are determined, * in parallel with other micro-reactors, and these different micro-reactors are fed reactors using the same media, having the same flow rates and under the same operating conditions.
• these different micro-reactors form a single reactor, capable of having a pilot, even industrial, scale.
• the other micro-reactors are of the conventional type, that is to say that they are in particular devoid of means for accessing the flow in steady state.
• these different micro-reactors placed in parallel are supplied by means of a single upstream supply line.
• At least one instantaneous value of at least one characteristic quantity of the medium is obtained, the or each instantaneous value is compared with a reference value of the or each characteristic quantity and the behavior is modified. of the transformation, as a function of the value of the ratio between this measured value and this set value.
• the subject of the invention is also an installation for determining the parameters of a physical and / or chemical transformation, in particular of a reaction, for the implementation of the process as defined above, this transformation occurring in a medium, in particular reaction, • comprising: at least a first micro-reactor, within which said medium is able to flow; - a means of analysis; - Means of access to at least one point of a steady state flow of the medium, in at least one region of the first micro-reactor; - Means for carrying out at least one measurement of at least one quantity characteristic of the medium at the or each point; and means for determining characteristics representative of the transformation, as a function of the result of the or each measurement.
• - means of displacement are provided, suitable for displacing one with respect to the other the analysis means and the micro-reactor; the means of analysis is non-destructive with respect to the reaction medium; the analysis means is intrusive, in particular the sensor of a probe; the access means comprise an area of the micro-reactor which is permeable to the analysis means, in particular a window transparent to visible light; the means of determining the characteristic characteristics of the transformation are means of determination of parameters specific to this transformation; the means for determining the parameters specific to this transformation include a computer; the means for determining the characteristics representative of the transformation are means for determining the parameters for carrying out this transformation; the means for determining the parameters for conducting the transformation include a regulation loop; the regulation loop has a measurement line placed in communication with the analysis means / capable of supplying at least one instantaneous value of at least one characteristic quantity, a reference line capable of supplying at least one reference value d 'at least one characteristic quantity, as well as an output line linked to means for conducting the transformation
• FIG. 1 illustrates a micro-reactor, designated as a whole by the reference 1.
• the latter comprises a body 2, made for example of metal or stainless steel, in which are provided, in a manner known per se, two inlets 3, in which can be introduced two different reagents.
• a different number of inputs can be provided, for example between 1 and 10, preferably between 2 and 3. Downstream of these inputs 3 are formed different upstream channels 4, produced in parallel. As an indication, these channels are provided for example 124, their cross section being for example 0.005 mm 2 . However, as a variant, a different number of channels can be provided, for example between 1 and 10 000, advantageously between 10 and 1 000, the cross section of which is different from the example above. Downstream of these upstream channels 4 extends a throttling zone 5, which opens into a downstream channel 6, called main, whose length is for example 40 mm and whose section is for example 0.25 mm 2 .
• channel 6 can be given a length different from that mentioned above, for example between 1 mm and 1 m, preferably between 15 and 50 mm, as well as a section different from that mentioned above. above.
• this channel 6, which has been shown in rectilinear form, may also have different profiles, such as in particular sinusoidal.
• the different channels 4 are made for example within a first plate, which can be made detachably, in relation to • another plate in which is formed the main channel 6.
• this main channel 6 opens into an outlet 7, for example connected to a conventional effluent treatment system.
• the micro-reactor 1 also comprises a cover (not shown), in which a transparent window 8 is integrated, by any suitable fixing means. 'Once the cover covers the body 2, the window 8 extends above at least one part of the main channel 6. For the sake of clarity, the contours of this window 8 are shown in lines mixed in FIG. 1. Means (not shown, for example electrical or pneumatic) are also provided, intended to drive the reagents in a known manner from the inputs 3 to the output 7, via the channels 4, the throttle 5 and the main channel 6.
• the installation, represented in this FIG. 1, further comprises an analysis apparatus 10, which in this case is of the Raman type. In service, this analyzer 10 takes advantage of a laser beam 11, forming an analysis means.
• this mixture formed by A and B constitutes a medium, in this case reaction, capable of undergoing a transformation, in this case a chemical reaction.
• the products of this reaction are denoted C and D.
• the beam 11 is moved along the channel 6, in the downstream direction of the latter, according to the arrow F '. This beam is then directed to another point in the reaction medium, denoted 6 2 , which corresponds to a position P + ⁇ P of this beam, denoted 11, which relates to a residence time t s + ⁇ t s of the reaction medium.
• the beam 11 then proceeds to a second measurement of at least one quantity representative of the reaction medium, analogously to what has been described with reference to the first position III.
• concentrations [A] 2 , [B] 2 , [C] 2 and [D] 2 are for example the concentrations [A] 2 , [B] 2 , [C] 2 and [D] 2 .
• the beam 11 downstream of the channel 6 so that it proceeds to a series of measurements of at least one quantity representative of the reaction medium.
• knowledge of these different quantities makes it possible to access, in a manner known per se, the different parameters of the reaction. This determination is for example implemented using a computer 10 ′, which is integrated into the analyzer 10.
• FIG. 3 illustrates an alternative embodiment of the invention.
• the micro-reactor 1, associated with the analysis apparatus 10 is integrated within an installation, which includes (n-1) other micro-reactors, assigned references 1 2 to I n - It should be noted that these other micro-reactors are generally identical to that referenced 1. However, they lack a zone permeable to an analysis means, such as the transparent pane 8 of FIG. 1.
• n micro-reactors 1 to l n are supplied by an upstream main line L, which is divided into n upstream secondary lines, referenced L], at L n . Downstream of these micro-reactors are provided for downstream secondary lines L'i to L ' n , which are grouped together in a single main downstream line L'. It should be noted that, in the main lines L and L ', the reaction medium has a flow rate noted Q. Furthermore, in each of the secondary lines, respectively Li to L n and L' i to L ' n , this medium has the same bit rates, i.e. Q / n. It should be noted that the installation of FIG.
• micro-reactor 3 forms a single reactor, capable of presenting a pilot or industrial scale, formed by replication of the micro-reactors, which can be provided in a very large number, for example of the order in this regard, even if the flow rate Q / n within each micro-reactor is relatively low, the overall flow rate Q is likely to have high values, since a very large number of micro-reactors can be placed in parallel.
• the various transformations occurring within micro-reactors 1 to l n are all identical, as regards their nature and their progress. Indeed, these different micro-reactors are supplied by means of the same products, with - the same flow rates, while being placed under the same operating conditions.
• the parameters specific to the transformation itself are not determined by the analysis apparatus itself, since they are already known beforehand.
• the analysis apparatus therefore makes it possible, at each instant, to compare the instantaneous quantities, characteristics of the environment in which the transformation takes place, with reference values. This allows, if necessary, to modify in real time the general parameters of the overall reactor, formed by the various micro-reactors in parallel, so as to bring the instantaneous quantities closer to the predefined set values.
• measurements can be made such as those carried out at the level of the microreactor 1, on several of these micro-reactors.
• the various instantaneous measured values are then compared with each other, for example to provide an average value which is then compared with a set value. This allows verification of the proper functioning of the various micro-reactors and, consequently, of the correct parallelization of the input flow.

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• 2003
  • 2003-12-24 FR FR0315396A patent/FR2864625B1/fr not_active Expired - Fee Related
• 2004
  • 2004-12-22 EP EP04817583A patent/EP1708807A1/de not_active Withdrawn
  • 2004-12-22 US US10/584,210 patent/US20070214609A1/en not_active Abandoned
  • 2004-12-22 WO PCT/FR2004/003356 patent/WO2005063378A1/fr active Application Filing

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