EP3086879A1

EP3086879A1 - Microfluidic device for handling immiscible fluids

Info

Publication number: EP3086879A1
Application number: EP14824016.1A
Authority: EP
Inventors: Axel HUERRE; Vincent MIRALLES; Marie-Caroline Jullien; Bastien FOURNIE; Hannah WILLIAMS; Bertrand SELVA
Original assignee: Ecole Superieure de Physique et Chimie Industrielles de Ville Paris
Current assignee: Ecole Superieure de Physique et Chimie Industrielles de Ville Paris
Priority date: 2013-12-24
Filing date: 2014-12-24
Publication date: 2016-11-02
Also published as: WO2015097300A1; FR3015310B1; US20160367989A1; FR3015310A1

Abstract

The process (1200) for handling an element consisting of a first fluid transported by a second fluid that is immiscible with the first fluid in a cavity, at least one wall of which is made of a deformable material, characterized in that it comprises: a step (1205) of introducing the second fluid and the element of the first fluid into the cavity, - a step (1210) of ordering a local deformation of the deformable material of the cavity, at least one other portion of the deformable material of the cavity not being deformed, - a step (1215) of locally deforming a portion of the deformable material forming the cavity in order to at least partially obstruct the passage of the element introduced into the cavity without obstructing the passage of the second fluid and - a step (1220) of moving the element in the cavity to the outside of the deformed portion of the cavity.

Description

MICROFLUIDIC DEVICE FOR HANDLING NON-MISCIBLE FLUIDS

TECHNICAL FIELD OF THE INVENTION

The present invention aims to:

- a handling device,

a generation device,

- a sorting device and

- a storage device

an element consisting of a first fluid transported in a second fluid immiscible with the first fluid and a device for melting two elements consisting of miscible first fluids transported in a second fluid immiscible with each first fluid. It applies, in particular, to biological diagnosis and chemical and biochemical analyzes. The invention applies to two main configurations, ie the element of the first fluid is transported by a flow of the second fluid, or the flow of the second fluid is zero. STATE OF THE ART

One element of a fluid will be called a drop of a liquid or an air bubble, as an example.

In current biological diagnostic systems based on liquid samples of limited volumes using, for example, digital microfluidic systems based on the manipulation of bubbles / drops of a first fluid in a second fluid, the optimal manipulation of the amount of sample available is a major constraint. Today's most advanced systems focus on controlling the flow of an element of the sample in an optimal way.

In this type of system, the functions to be performed are in particular, in the case of systems with a flow of the second fluid: - generate an element,

- move an element,

- isolate an element,

- break an element,

- sort an element,

- store an item,

- force the contact between two elements,

- merge elements and,

- retain an element in the manner of a valve,

The functions to be performed are in particular, in the case of systems without flows of the second fluid:

- move an element,

- isolate an element,

- break an element,

- sort an element,

- store an item,

- force the contact between two elements and

- merge elements.

However, there is currently no system for performing all of these functions independently of the presence of a stream of the second fluid optimally.

In "EWOD" (Electrowetting On Dielectrics) type systems, the manipulation functions of an element can be realized. These systems consist in modifying the wetting properties, by application of an electric field, of a functionalized substrate making it possible to perform the manipulation, generation, sorting, melting and storage functions described above.

However, these systems have the disadvantage of having a triple line at the element level. This element being in direct contact with the substrate, that is to say without lubrication of the substrate, the handling of the element is made complex. On the other hand, these systems require a high electrical potential, of the order of 100 Volts, to operate, which makes these systems energetically less optimal. To overcome this energy constraint, it is possible to reduce the thickness of the layer of the dielectric material, which in this case makes the manufacture of these systems complex.

Other systems use dielectrophoresis, ie the application of an electromagnetic field to manipulate an element. These systems only make it possible to perform a sorting function with flow or isolation without flow.

In particular, systems implementing the teaching of patent application WO 2008/150210 are known. In such systems, a micro-pump is produced by the implementation of two diaphragms actuated by phase change actuators. These systems notably have integration difficulties.

For all these reasons, the current systems do not make it possible to satisfactorily meet the constraints:

- energy optimization,

- ease of manufacture,

- absence of triple line likely to pollute a sample or the substrate and

- Realization of all the desired manipulation functions.

OBJECT OF THE INVENTION

The present invention aims to remedy all or part of these disadvantages. For this purpose, the present invention aims, in a first aspect, a method of handling an element consisting of a first fluid carried by a second fluid immiscible with the first fluid in a cavity, at least one wall is made of material deformable, which comprises:

a step of introducing the second fluid and the element of the first fluid into the cavity,

a step of controlling a local deformation of a part of the deformable material of the cavity, at least one other part of the deformable material of the cavity being not deformed,

a step of locally deforming a portion of the deformable material of the cavity to at least partially obstruct the passage of the element introduced into the cavity without obstructing the passage of the second fluid and

a step of moving the element in the cavity towards the outside of the deformed portion of the cavity. Thanks to these provisions, it is possible to achieve the movement of an element or the manipulation of this element by the exercise of a physical pressure on the element so as to force its displacement. In addition, the presence of the second fluid, wetting the wall of the cavity, prevents the element from coming into contact with the wall, limiting the risk of pollution of the elements.

In embodiments, the method that is the subject of the present invention comprises a step of determining the positioning of an element of the cavity as a function of the positioning of a deformed part of the cavity.

These embodiments make it possible to make a prediction of the positioning of the element in the cavity, this positioning information being able to be used for the control of a deformation of another part made of deformable material of the cavity.

In embodiments, the method that is the subject of the present invention comprises a step of detecting the positioning of an element in the cavity, the control step controlling the deformation of a portion of the deformable material of the cavity selected as a function of the detected positioning of the element.

These embodiments make it possible to use this positioning information for controlling a deformation of another portion of deformable material of the cavity.

In embodiments, the deformation of a portion of the deformable material is achieved by local heating of the deformable material, the deformed part of the deformable material being deformed by thermomechanical effect.

In embodiments, the deformation of a portion of the deformable material is achieved by pneumatic deformation means.

In embodiments, the deformation of a portion of the deformable material is achieved by a piezoelectric deformation means.

The present invention aims, in a second aspect, a device for handling an element consisting of a first fluid transported in a second fluid immiscible with the first fluid, which comprises:

a cavity, configured to receive at least one element constituted by the first fluid and the second fluid, which comprises at least one wall made of thermomechanically deformable material, at least one local heating means configured to deform at least a portion of the deformable material of the cavity by thermomechanical effect so that, when the local heating means heats up, each part of the heated deformable material at least partially obstructs a section of the cavity to allow the passage of the second fluid and to block the passage of each element of the first fluid, at least one other part of the deformable material of the cavity being not deformed,

a means for moving the element constituted by the first fluid configured to move the element towards the outside of the deformed part of the deformable material and

- Control means configured to independently control heating of at least one local heating means.

With these provisions, it is possible to achieve the displacement of an element by using a physical pressure on the element so as to force its displacement. The electrical voltage required to achieve the deformation is small compared to the voltages applied, for example, with the EWOD. In addition, the presence of the second fluid, wetting the wall of the cavity, prevents the element from coming into contact with the wall, limiting the risk of pollution of the elements.

In embodiments, the heat transfers are very fast, of the order of a few hundred milliseconds, which ensures a quasi-instantaneous heating of the deformable material heated by a local heating means.

In embodiments, the moving means is a thermal rail, comprising at least one local heating means, configured to deform at least a portion of the deformable material of the cavity by thermomechanical effect so that, when the local heating means heats, each portion of heated deformable material at least partially obstructing a section of the cavity to allow the passage of the second fluid and to block the passage of each element of the first fluid.

These embodiments have the advantage of allowing, in the case of a small local heating zone with respect to the length of the cavity, a local manipulation of at least one element according to the manipulation to be carried out. In embodiments, the control means is configured to control successive heating of the successive heating means of the thermal rail so as to move the element along the cavity.

These embodiments have the advantage of allowing to move an element in the cavity without requiring an external flow. In addition, it is possible to force two elements to come into contact by pushing each element towards each other.

In embodiments, the cavity comprises at least one lateral portion of material that is not deformable by the heat emitted by at least one local heating means.

These embodiments have the advantage of facilitating the manufacture of the device object of the present invention.

In embodiments, the moving means includes means for generating a flow of the second fluid to move at least one element.

These embodiments make it possible to perform a capillary valve function by blocking an element set in motion by a flow.

In embodiments, the device that is the subject of the present invention comprises means for detecting the content of an element of the first fluid.

The advantage of these embodiments is that they allow, depending on the detected content, to perform a treatment to the element such as a displacement or on the contrary an isolation of the element.

In embodiments, the device which is the subject of the present invention comprises means for detecting the position of at least one element in the cavity in order to supply a position signal to the control means.

These embodiments have the advantage of allowing optimization of the processing performed on an element as a function of the detected position of the element.

In embodiments:

the cavity comprises at least one translucent part,

the means for detecting the position of at least one element in the cavity comprises an image capture means and a captured image processing means configured to determine the position of an element according to the processed image . The advantage of these embodiments is that they make it possible, with only one detection means, to detect a plurality of elements in the case of a complex device comprising a plurality of cavities and / or devices that are the subject of the present invention. invention.

In embodiments, the detection means is configured to detect an element of the first fluid as a function of a disturbance of an electromagnetic field near the cavity.

These embodiments have the advantage of making it possible to detect the position of an element without brightness constraints, for example

In embodiments, the control means is configured to cause at least two adjacent portions of the deformable material to heat up at the sensed position of the member to isolate the member in a portion of the obstructed cavity at each end. by a deformation of the cavity.

The advantage of these embodiments is that they allow to retain an element in a channel thinned at each end by a deformation of the cavity.

In embodiments, the control means is configured to control heating of a portion of the deformable material of the cavity to the sensed position of the member to divide said member into two members positioned outwardly of the portion of the material. deformable heated.

These embodiments have the advantage of making it possible to optimize the breaking of an element whose dimensions are large relative to the dimension of the deformed part of the deformable material by the heat emitted by a local heating means.

In embodiments, the device that is the subject of the present invention comprises a substrate, comprising at least one local heating means, secured to the cavity.

The advantage of these embodiments is that they make it possible to recover each local heating means in the substrate by detaching the substrate from the cavity.

According to a third aspect, the present invention provides an element generating device consisting of a first fluid transported in a second fluid immiscible with the first fluid, which comprises a device for handling an object of the present invention, including: an opening of the cavity towards at least one secondary cavity is traversed by at least one continuous phase flow,

the moving means is configured to move a flow of first fluid in the cavity to the secondary cavity to form an element of the first fluid in the secondary cavity and

- Local heating means heating the deformable material positioned at the intersection of the two cavities so as to block or force, during heating of the portion of the deformable material, the passage of elements from the cavity to the secondary cavity.

With these provisions, it is possible to control the size of a generated element in the secondary cavity by dividing this element by deforming the cavity at the intersection.

Without the action of a local heating means, an element can form naturally, but its size is then determined by the ratios of flow rates and by the geometry of the junction between the two cavities. With the generation device object of the present invention, it is possible to control the size of the generated elements.

According to a fourth aspect, the present invention aims at a device for sorting at least one element consisting of a first fluid transported in a second fluid immiscible with the first fluid, which comprises:

means for actuating a control means of a device for manipulating an element which is the subject of the present invention,

the device for manipulating an element which comprises:

at least two openings of the cavity located downstream of a direction of movement of the moving means each giving into a secondary cavity and

- Local heating means heating the deformable material positioned at each intersection so as to block the passage of an element from the cavity to at least one secondary cavity.

Thanks to these provisions, it is possible to sort elements of different natures in particular to separate these elements. According to a fifth aspect, the present invention is directed to a storage / retrieval device for an element consisting of a first fluid transported in a second fluid immiscible with the first fluid, which comprises:

a handling device according to the present invention, a part of the deformable material of which is configured, during deformation, to block the passage of an element in a primary cavity and to direct this element towards a storage / retrieval structure and

- The storage / retrieval structure configured for, during heating of a portion of the deformable material of the structure, by means of local heating of the secondary device, destocking the element.

Thanks to these arrangements, it is possible to store an element present in the first cavity. In addition, these provisions make it possible to rearrange a sequence of elements of the first fluid.

In embodiments, the device that is the subject of the present invention comprises a portion of deformable material located at the junction between the primary cavity and the storage / retrieval structure.

These embodiments make it possible to isolate a stored item.

In embodiments, the portion of the deformable material located at the junction between the primary cavity and the storage / retrieval structure is configured to be heated when an element is stored in the structure.

These embodiments have the advantage of automating the isolation of a stored item.

In embodiments, the storage / retrieval structure comprises a conduit configured to feed the primary cavity with the second fluid contained in the structure.

These embodiments make it possible to store an element in the storage structure more easily when the primary cavity is blocked.

According to a sixth aspect, the present invention provides a device for melting two elements consisting of miscible first fluids transported in a second fluid immiscible with each first fluid, which comprises a manipulation device object of the present invention, comprising a plurality of parts deformed configured to force in contact the two elements by successive displacement of at least one of the two elements. Thanks to these arrangements, it is possible to force the contact between two elements made of different fluids.

According to a seventh aspect, the present invention aims at a matrix device for manipulating an element consisting of a first fluid transported in a second fluid immiscible with the first fluid, which comprises a device for handling an element consisting of a first fluid transported in a second fluid immiscible with the first fluid of the present invention, whose cavity extends in two directions and which comprises:

at least one box having at least three exits and

- At least one heating means for deforming a portion of the deformable material positioned opposite at least one outlet.

These embodiments have the advantage of making it possible to carry out a matrix movement if the cavity comprises a plurality of boxes. The following 3 cases can be envisaged: the whole of the matrix is subjected to a flow, no flow passes through the matrix, and a flow passes only a part of the matrix. In this mastering can realize all the features previously proposed. In variants, these features are assisted by a detection and / or identification system. To do this stamping, it suffices to make a network of local heating means having an angle. In this geometry, the device makes it possible to perform an obstacle bypass function. In this geometry, the device makes it possible to reorganize the sequences of elements of first fluids, or even the other functionalities described hereinafter.

BRIEF DESCRIPTION OF THE FIGURES

Other advantages, aims and particular characteristics of the invention will emerge from the following nonlimiting description of at least one particular embodiment of the method and devices that are the subject of the present invention, with reference to the appended drawings, in which:

FIG. 1 represents, schematically, a sectional view of a particular embodiment of the device for manipulating an element which is the subject of the present invention,

FIG. 2 represents, schematically, a particular embodiment of the device for manipulating an element that is the subject of the present invention, FIG. 3 represents, schematically, a sectional view of a particular embodiment of a displacement of an element by the device forming the subject of the present invention,

FIG. 4 schematically represents a sectional view of a particular embodiment of an isolation of an element by the device that is the subject of the present invention,

FIG. 5 represents, schematically, a sectional view of a particular embodiment of a capillary valve by the device that is the subject of the present invention,

FIG. 6 schematically represents a view from above of a particular embodiment of the device for generating an element which is the subject of the present invention,

FIG. 7 schematically represents a view from above of a particular embodiment of the device for sorting an element which is the subject of the present invention,

FIG. 8 represents, schematically, a view from above of a particular embodiment of the storage / retrieval device that is the subject of the present invention,

FIG. 9 represents, schematically, a view from above of a particular embodiment of the device that is the subject of the present invention in which the cavity extends in two dimensions,

FIG. 10 is a diagrammatic representation of a particular embodiment of a manipulation network of an element which is the subject of the present invention,

FIG. 11 schematically represents a sectional view of a particular embodiment of the device for manipulating an element that is the subject of the present invention,

FIG. 12 schematically represents a particular flow diagram of the process of the present invention and

- Figure 13 shows schematically a sectional view of the cavity object of the present invention.

DESCRIPTION OF EXAMPLES OF EMBODIMENT OF THE INVENTION

The present description is given in a non-limiting manner. As of now, we note that the figures are not to scale.

In the remainder of the description, will be called "element of a fluid" a drop of a liquid or a bubble of air, for example. However, the present invention is not limited to these cases alone.

FIG. 1 shows a sectional view of a particular embodiment of the device 10 for manipulating an element that is the subject of the present invention. This device 10 comprises:

a cavity 105, configured to receive at least one element of a fluid, which comprises:

a part 1 10 of the deformable material deformed by thermomechanical effect;

a part 125 of electrically insulating material;

a translucent part 1;

two openings 130 and

a means 135 for generating a flow of a carrier fluid passing through the two openings 130;

a means 120 for controlling at least one local heating means 1 15,

a thermal rail 160 comprising a plurality of local heating means 1 15,

in variants, a means 140 for detecting the position of at least one element in the cavity 105 which comprises:

a means 145 for image capture and

a captured image processing means 150 configured to determine the position of an element according to the processed image and

a substrate 1 65, comprising the thermal rail 160, secured to the cavity 105.

The cavity 105 is, for example, a pipe of rectangular section, along a transverse axis of the cavity 105, placed on the substrate 1 65. This cavity 105 may also have a section of any other geometric shape. This conduit comprises a portion 125 of electrically insulating material, in contact with the substrate 1 65. This portion 125 of electrically insulating material, such as PDMS for example. This part 125 is of small thickness compared to the thickness of the part 1 10. The conduit comprises a part 1 10 of deformable material, such as PDMS. The thickness of this portion 10 of deformable material is, for example, ten times greater than a dimension of the section of the cavity 105 along a transverse axis of the cavity 105. This conduit is, for example, configured to receive elements 80 micrometers in diameter. The conduit has, for example, a diameter of 100 micrometers. The conduit further comprises a translucent portion 1 corresponding to the deformable portion 1. In variants, the cavity 105 does not have a translucent part. This duct further comprises two openings 130 located at both ends of the duct. These openings 130 allow the injection or ejection of an element in the conduit. In particular, one of these openings 130 may be associated with means 135 for generating a flow passing through the two openings 130.

In variants, one of these openings is constituted by pores in the part 125 or in the part 1 10 of deformable material.

In variants, the portion 125 is of non-deformable material.

In variants, the device 10 has a single opening 130 allowing an element to enter the cavity 105.

The means 135 for generating a flow of a carrier fluid is, for example, a syringe or pressure controller for injecting a fluid into an opening 130 so that the injected fluid exits through the other opening 130 of the fluid. leads. In variants, this generation means 135 is configured to inject a multiphasic fluid containing at least one fluid element to be handled. This flow of a carrier fluid allows to move at least one element. In variants, the device 10 does not include means 135 for generating flows.

The control means 120 of at least one local heating means 1 15 is, for example, a controller connected to each local heating means 1 15 of the device 10. This control means 120 is configured to issue a control of local heating independently to at least one local heating means 1 to manipulate an element in the cavity 105. The control means 120 is configured to cause successive heating of at least two adjacent local heating means 1 of the thermal rail 1 60 so as to move the element along the cavity 105. Indeed, the deformation of a portion 1 10 of the deformable material of the cavity 105 generated by heating of a first local heating means 1 15 causes displacement of the element in the cavity 105. If a second local heating means 1 15 is heated to the new location where the element is located, a new displacement of the element is achieved . Each local heating means 1 positioned along the cavity 105 may be heated to move an element from one end to the other of the path formed by the local heating means 1 along the cavity 105. In variants, the control means 120 is controlled by the detection means 140. In these variants, when the device 10 does not include a flow generating means 135, the detection means 140 commands the control means 120 to heat up. successive local heating means 1 15 adjacent to an element according to the detected position of this element.

The control means 120 is also configured to control heating of two local heating means 1 adjacent to the detected position of the element so as to retain the element in a conduit. When the device includes flow generation means 135, the control means 120 may be configured to control heating of a local heating means adjacent to the detected position of the element so as to retain the element against the part 1 10 deformable deformed material. This embodiment is more particularly observed in FIG.

The control means 120 is, finally, configured to control heating of a means 1, one element of which is positioned between the means 1 and a deformed portion 1 of the cavity 105 so as to divide the element into at least two elements. elements smaller than the divided element.

Each local heating means 1 15 is integrated with a thermal rail 1 60 controlled by the control means 120 and integrated into the substrate 1 65. This thermal rail 1 60 is positioned along the cavity 105 so that each means for local heating 1 15 of the thermal rail 1 60 is facing a deformed portion of the deformable material 1 10 of the cavity 105. The presence of a lubricating film of the second fluid present between the element and a portion 125 guarantees that there is no element-substrate cross-pollution. Each local heating means 1 15 is configured, during a heating, to cause deformation by thermomechanical effect of a portion of the deformable material 1 10, the cavity 105. This deformation causes an at least partial obstruction of the cavity 105 blocking the passage of an element instead of obstruction. The dimension of each local heating means 1 15 facing a part of deformable material 1 10 is much smaller, at least an order of magnitude, to the total length of the cavity 105. This difference in size makes it possible to locally deform the cavity 105 without causing deformation throughout the cavity 105 and allows, thus, a controlled control of the handling of an element. The power required to effect the deformation of a portion of deformable material 1 10 is, for example, of the order of 150 mW and the voltage across each means is less than 10 V.

Variations of local heating means are described in FIG. 11, below.

This local heating means heats the cavity 105 on a surface whose largest dimension is of similar size to the largest dimension of a fluid element passing through the cavity. This local heating allows a local manipulation and fine drops in an otherwise larger cavity.

The relationship between the dimensions of the deformed part, the element and the cavity are illustrated in FIG. 13.

In this figure 13, there is a cavity 1300 having a wall of deformable material 1310, an element 1305 of the first fluid being introduced into the cavity 1300.

It is observed, in particular, that the largest dimension L2 of the deformed portion 1310 is an order of magnitude smaller than the largest dimension L1 of the cavity 1300. Preferably, the deformed portion 1310 is two orders of magnitude lower than the Largest dimension L1 of the cavity 1300.

The dimension L2 of the deformable material part 1310 is chosen so that, during the deformation of this part of the deformable material 1310, the smallest dimension L4 of the section of the deformed cavity 1300 does not allow the passage of the element 1305. but allows the flow of the second fluid. This dimension L4 is smaller than the smallest dimension L5 of the element 1305, the largest dimension of the drop being greater than the dimension L3 of the cavity.

For example, the section of the cavity 1300 is rectangular, the element 1305 having a wafer shape and the portion of deformable material 1310 has a dimension L2 of the portion of deformable material similar to the section of the element 1305 and therefore of the cavity 1300. For example, an obstruction formed in the section of the cavity by a portion of the deformable material measures two micrometers.

The detection means 140, illustrated in FIG. 1, of an element is, for example, an assembly formed of the image capture means 145 and the image processing means 150 captured. The image capturing means 145 is, for example, a camera positioned so as to capture an image of each translucent portion 10 of the device 10. The image processing means 150 is, for example, a controlled electronic circuit by a computer program configured to establish, by detection of shapes, the presence or absence of an element at a location of the cavity 105 according to the captured image. This detection means 140 is configured to transmit a position signal to the control means 120. This position signal is used by the control means 120 to determine which local heating means 1 are to be heated. In variants, this detection means 140 is an electronic circuit, connected to a coil at least partially surrounding the cavity, configured to detect an element of the first fluid as a function of a disturbance of an electromagnetic field near the cavity 105. .

The substrate 1 65 comprising the thermal rail 1 60, secured to the cavity 105, can be detached from the portion 125, which recycles the heat rail 160 that the substrate 1 65 comprises.

FIG. 2 diagrammatically shows a particular embodiment of the device 20 of the present invention. This device 20 comprises a control means 205 which independently addresses a control signal, via an independent control channel 215, to each local heating means 210 of the device 20. The detection system 220, comprising, for example, a detection system 230 and a system for detecting the content 235 of the elements in the device 20, is connected to the control means 205 via another control channel 225.

FIG. 3 shows a sectional view of a particular embodiment of the device 30 for displacing an element 315 by the device 10 which is the subject of the present invention. In this embodiment, the device 10 does not include flow generation means. The movement of an element 315 is carried out when an element 315 is present in a cavity 320 facing the deformable material 310 of the cavity 320. If a movement control of the element 315 is received by a control means, not shown, of the local heating means 305, this control means control heating of the means 305 local heating. This local heating means 305 causes the deformable material part 310 to expand in the cavity 320. When the part of deformable material 310 bears on the element 315, the element 315 is pushed into the cavity 320 so as to make a longitudinal displacement. In variants, a plurality of means is implemented so as to cause a displacement of close to the element 315. These embodiments allow to move at least one element without flow of the second fluid.

FIG. 4 shows a sectional view of a particular embodiment of the device 40 for isolating an element 415 by the device 10 which is the subject of the present invention. This element isolation 415 is achieved by simultaneously heating two heating means 405 placed opposite the deformable material causing deformation 410 adjacent to the position of an element 415 located in a cavity 420. The element 415 is then found trapped between two deformable parts 410 deformed by thermomechanical effect. In variants, the element 415 is positioned between two deformable parts of the cavity 410, non-adjacent deformed by the action of two means 405 local heating.

FIG. 5 shows a sectional view of a particular embodiment of the device 50 of a capillary valve by the device 10 which is the subject of the present invention. This capillary valve is produced when a deformed part 510 of the deformable material of a cavity 520 is deformed by thermomechanical effect by the actuation of a local heating means 505 while an element 515 is pushed towards the deformation by a flow 525 of a fluid for example. This stream 525 is generated by a means 530 for generating a flow of the second fluid. This valve is open when the means 505 for local heating does not heat up, and therefore that the portion of deformable material 510 does not obstruct the passage of the element 515. Conversely the valve is closed when the means 505 heats and the part of the deformable deformed material prevents an element 515 from passing into the cavity 520. FIG. 6 shows, seen from above, a particular embodiment of the device 60 for generating an element that is the subject of the present invention. This device 60 comprises:

a cavity 605 traversed by a longitudinal flow 610 of a first fluid, which will be dispersed in a secondary cavity 620, which comprises a junction 615 located downstream of the flow 610, entering the secondary cavity 620 through which a flow 625 of a second fluid and

a local heating means positioned facing the deformable material at the intersection 615 of the two cavities, 605 and 620, so as to block the passage of the first fluid from the cavity 605 towards the secondary cavity 620, thus blocking the formation of elements.

The cavity 605 is, for example, similar to the cavity 105 described in FIG. This cavity 605 is traversed by a flow 610 of a first immiscible fluid with the second fluid carried by the stream 625.

In order to generate an element, not shown, of the first fluid, the local heating means is heated so as to block the passage of an element injected by the flow 610. When an element generation command is received by the device 60, the local heating means ceases to heat so as to allow the first fluid to enter the secondary cavity 620. After a predetermined time, the local heating means is heated again so as to break the element passing between the local heating means and a portion of deformable material 630 of the cavity 605. The portion of the first fluid having thus passed the means is thus injected into the cavity 620 and generates an element of the first fluid that can be used according to different needs.

Without the action of a local heating means, an element can form naturally, but its size is then determined by the ratios of flow rates, 610 and 625, and by the geometry of the junction 615 between the two cavities , 605 and 620. With the embodiment of the device 60 described in Figure 6, it is possible to control the size of the generated elements. There are therefore two possible variants when the local heating means is deactivated:

- Or let the element form freely and activates the local heating means to block the formation of a new element or the local heating means is activated after a predetermined time to generate elements of controlled size.

In variants, the junction 615 connects upstream a plurality of cavities 605 and a plurality of streams 625, opening downstream in at least one cavity 620 single.

In other variants, a plurality of cavities 605, each cavity 605 carries an element of at least one secondary fluid transported in a first fluid. At least two secondary fluids are miscible with each other. Thus, the elements generated and moved in at least one cavity 620 unique from at least two cavities 605 can mix to become an "element of a second fluid" as described in the description of the figures. Thus, the generation device 60 may include a plurality of cavities 605 carrying a fluid for generating an element and a plurality of cavities 620 carrying a generated element.

FIG. 7 shows, seen from above, a particular embodiment of the device 70 for sorting an element which is the subject of the present invention. This device 70 comprises:

a means 705 for identifying the nature of an element

a means 710 for actuating a means 715 for controlling a device 10 as described in FIG. 1,

the device 10 for manipulating an element of which:

the cavity 720 is traversed by a longitudinal flow 725 comprising elements of a first fluid dispersed in the second fluid;

two openings 730 of the cavity 720 situated downstream of the flow 725 each enter a secondary cavity 735 and

a local heating means is positioned facing the deformable material 740 at each intersection so as to block the passage of an element from the cavity 720 to a secondary cavity 735.

The identification means 705 of an element is, for example, a coil surrounding a location of the cavity 720 configured to measure the impedance of the fluid of the element and to determine the nature of the fluid as a function of the measured impedance. .

In preferred embodiments, the device 70 does not include identification means 705. The actuating means 710 is, for example, an electronic circuit configured to control the control means 715 heating of the local heating means positioned at the opening 730 of the secondary cavity 735 in which it is not desired to enter the fluid element identified. Conversely, the control means 715 controls the heating stop of the local heating means positioned at the opening 730 of the secondary cavity 735 in which it is desired to enter the identified fluid element, if this means of local heating. is heating up. In this way, it is possible to sort the elements entering the device 70 by selectively opening a secondary cavity 735 in which the sorted element is directed.

FIG. 8, seen from above, shows a particular embodiment of the device 80 for storing / retrieving an element of a first immiscible fluid. This device 80 comprises a main cavity 825 traversed by a stream 820 of dispersed first fluid elements. This device 80 also comprises a secondary cavity 815 towards which the elements can be directed and therefore stored. The control means activates local heating means heating the deformable portions 835 during the passage of at least one element detected by the detection means, directing the elements in the secondary cavity 815 for storage. A bypass cavity 830 allows free circulation of a second fluid carrying the elements of the first fluid. In variants, the device 80 does not have a bypassing cavity 830. In variants, the cavity 815 is isolated from the secondary cavity 825 by activation of a local heating means, heating a portion of the deformable material 840 of the cavity, controlled by the control means. In the destocking phase:

a local heating means configured to heat a portion of the deformable material 835 of the main cavity 825 so as to block the passage of an element in this cavity 825, is deactivated and

- Local heating means, heating deformable parts 845, are activated by the control means so as to propel at least one element of the secondary cavity 815 to the main cavity 825.

In the variants comprising a local heating means 840, the destocking phase is carried out by the following sequence: the local heating means, heating the part of the deformable material 840, isolating the secondary cavity 815 is deactivated,

the local heating means configured to heat a portion of the deformable material 835 of the main cavity 825 so as to block the passage of an element in this cavity 825, is deactivated and

- The local heating means, heating the deformable portions of the cavity 845, are activated by the control means so as to propel at least one element of the secondary cavity 815 to the main cavity 825 and

the cavity 815 is isolated by actuating the local heating means heating the deformed part of the deformable material 840.

In variants, the deformed part of the deformable material opposite the local heating means, heating the part of deformable material 840 located at the junction between the primary cavity and the secondary cavity is configured to be heated when an element is stored in the structure.

Another embodiment of the storage / retrieval device 80 makes it possible to reorganize a sequence of immiscible fluid elements. In these embodiments, the device 80 comprises at least one secondary cavity in which elements are stored. In variants, storage is performed according to their nature detected by a detection means. As a function of an element sequence command received by a means for controlling the heating of the local heating means, the destocking of at least one element is caused sequentially in at least one secondary cavity. In this way, it is possible to rearrange a sequence of elements by independently storing each element at first and then selectively releasing the stored elements according to their nature.

FIG. 9 shows, seen from above, a particular embodiment of the device 90 which is the subject of the present invention. In this figure, a cavity 945 of the device 90 extends along two axes. This cavity 945 is formed of boxes 935 delimited by four links between pads 915 distributed in the cavity 945, positioned to form four corners of a square.

In variants, boxes of any polygonal geometry having at least three sides are used. In variants, these boxes are delimited by deformed parts, whose function is similar to that of the pads described above, the cavity causing deformation of the cavity.

The accumulation of boxes makes it possible to create a two-dimensional matrix making it possible to perform a plurality of functions. A deformed part of the deformable material 920 is positioned opposite each edge of the square thus delimited. It is possible, during heating of at least a portion of the deformable material 920, to:

block access to a box when each deformed part of the deformable material 920 is heated by a local heating means,

creating a unidirectional cavity when two opposite deformed parts 920 are heated simultaneously,

creating a bend for a unidirectional cavity connected to the box when two adjacent deformed parts 920 are heated simultaneously, propelling an element towards an adjacent cavity and facing a part of the deformable material 920.

This device 90 further comprises a cavity 925 serving as input to elements of a first immiscible fluid transported by a flow 930 of a second fluid. This device 90 comprises an outlet cavity 940 positioned facing the inlet cavity 925 so that the flow 930 of the second fluid is directed towards the outlet cavity 940. On the flow path 930 between the inlet cavity 925 and the outlet cavity 940, deformed portions 920 are positioned. In this way, when the local heating means heats up, an element pushed by the flow 930 is oriented towards a box of the matrix by the deformation of a portion of the deformable material 920. Inside the cavity 935 in two dimensions, it is possible to perform all the functions detailed in Figures 1 to 8, namely, for example:

- capillary valve,

- generation of an element,

- breaking of an element,

- isolation of an element,

- sorting an element,

- fusion of two or more elements, - moving an element and

- reorganization of a sequence of elements.

FIG. 10 diagrammatically shows a particular embodiment of a network 1000 for handling immiscible fluid elements. This network comprises four element generators 1005 as described in FIG. 6 producing, from one generator to the other, elements of composition and volumes that may be different. These elements are conveyed into a cavity 1010 comprising a capillary valve system as described in FIG. 5. These capillary valves allow, in this embodiment, to predefine the number of elements of each nature for a sequence of elements given to junction 1055.

Each sequence of elements is routed, via a channel 1015, into a cavity 1020 having a two-dimensional matrix system as in FIG. 9. In one embodiment, the order of the elements of the sequence entering the matrix can be to be modified at the output.

One or more elements of the sequence can be stored in one or more storage cavities 1030 via the device described in FIG. 8 so as to possibly merge them into a fusion device 1025. This operation makes it possible to generate elements of moreover large size containing various elements from successive sequences. The advantage of fusing elements is to enable high-throughput screening, ie to test a large number of combinations of possible elements.

These elements can be expelled from the cavity 1030 via the destocking system as described in FIG. 8. These elements are then conveyed to a sorting device 1035 as described in FIG. 7, comprising a detection means and three output branches. 1060, 1065 and 1070.

The elements routed into the branch 1060 are directly routed to a junction 1085. The elements routed to a junction 1065 are divided into at least two smaller elements in the cavity 1045 having an element splitter.

The elements resulting from the division are conveyed to a sorting device 1035, as described in FIG. 7, comprising a detection means and two branches of Outputs 1075 and 1080. The elements routed through the 1080 branch are routed directly to a junction 1090.

The elements conveyed by the branch 1075 are blocked by a device 1050 as described in FIG. 5 in order to be brought into contact with the elements coming from the branch 1060 via the junction 1085. The elements thus brought into contact can be released by the device 1050, then fused via another fusion device 1025.

The element resulting from the melting is conveyed in a cavity comprising a thermal rail 1040, via a storage device 1030 as described in FIG. 8. In the thermal rail, as described in FIG. 1, the element is conveyed in any position of the rail. The chosen position makes it possible, for example, to observe an evolution of the nature of the element as a function of time. If the item is not stored, this item is routed directly to a 1090 junction.

The elements conveyed in the branch 1070 are transported to a cavity comprising a thermal rail 1040, via a storage device 1030 as described in FIG. 8. In the thermal rail, as described in FIG. 1, the element is conveyed in any position of the rail. If the element is not stored, this element is routed directly to the junction 1090. All the elements arriving at the junction 1090 are evacuated via an output 1095.

FIG. 11 shows a particular embodiment of the device

1,100 object of the present invention. This device 1100 is similar to the device 10 described in FIG. In this device 1 100, the local heating means is an assembly comprising a laser 1 105 and a mirror 1 120, the mirror 1 120 being configured to orient the laser beam 1 105 towards a portion of deformable material 1 1 10 of the cavity 1 1 15 according to a local heating command issued by the control means, not shown. In variants, the device 1 100 does not include a mirror 1 120 and the laser 1 105 comprises a matrix shutter configured to allow the passage of the beam of the laser 1 105 according to a local heating command issued by the control means. In other variants, the laser 1 105 is mounted on a pivoting device for directing the beam of the laser 1 105 according to a local heating command issued by the control means. In other variants, the local heating means implements any known transmission means of a wave In other embodiments, other local heating techniques may be employed, such as, for example, devices using the Joule effect, preheated fluids, microwaves, and the like. waves, an infra-red signal. The differences between these techniques lie in the transient time of establishing temperature and integration.

FIG. 12 shows a particular flow diagram of the process of the present invention. This method 1200 for manipulating an element consisting of a first fluid transported by a second fluid immiscible with the first fluid in a cavity of which at least one wall is made of deformable material, comprises:

a step 1205 for introducing the second fluid and the element of the first fluid into the cavity,

a step 1210 for controlling a local deformation of a portion of the deformable material of the cavity, at least one other portion of deformable material of the cavity being not deformed,

a step 1215 of local deformation of a portion of the deformable material of the cavity to at least partially block the passage of the element introduced into the cavity without obstructing the passage of the second fluid and

a step 1220 of setting the element in motion in the cavity towards the outside of the deformed part of the cavity.

The introduction step 1205 is performed, for example, by the implementation of a supply of elements of the first fluid transported by the second fluid. This diet pushes into the cavity these elements.

The control step 1210 is performed, for example, by a control means as described with reference to one of Figures 1 to 1 1.

The local deformation step 1215 is carried out, for example, by:

local heating of a portion of the deformable material, the portion of deformable material being deformed by thermomechanical effect,

a means of pneumatic deformation and / or

a piezoelectric deformation means.

The local heating is similar to the heating described with reference to one of Figures 1 to 1 1 above. The pneumatic deformation means is, for example, a pipe contained in the wall of the cavity, the pressure of a fluid inside this pipe being increased so that the pipe extends and partially obstructs the cavity .

The piezoelectric deformation means is a piezoelectric material whose application of an electric current on this material causes a deformation partially obstructing the cavity.

The setting step 1220 depends on the type of manipulation performed, the different types of manipulation being described with reference to Figures 1 to 1 1.

In particular embodiments, the method 1200 comprises a step 1230 for determining the positioning of an element of the cavity as a function of the positioning of a deformed part of the cavity.

This determination step 1230 is carried out, for example, during the implementation of a thermal rail as described above, as a function of the thermal element of the actuated rail allowing a prediction of the positioning of the element in the cavity.

In particular embodiments, the method 1200 includes a step 1225 for detecting the positioning of an element in the cavity, the control step 1210 controlling the deformation of a portion of the deformable material of the cavity selected according to the positioning detected from the element.

This detection step 1225 is performed, for example, by an optical sensor, inductive, capacitive or resistive positioned opposite the portion of the cavity and configured to detect the passage of an element.

Claims

1. Method (1200) for handling an element constituted by a first fluid transported by a second fluid immiscible with the first fluid in a cavity of which at least one wall is made of deformable material, characterized in that it comprises:

a step (1205) for introducing the second fluid and the element of the first fluid into the cavity,

a step (1210) of controlling a local deformation of the deformable material of the cavity, at least one other part of the deformable material of the cavity being not deformed,

a step (1215) of local deformation of a portion of the deformable material forming the cavity to at least partially block the passage of the element introduced into the cavity without obstructing the passage of the second fluid and

a step (1220) of setting the element in motion in the cavity towards the outside of the deformed part of the cavity.

2. Method (1200) according to claim 1, which comprises a step (1230) for determining the positioning of an element of the cavity as a function of the positioning of a deformed portion of the cavity.

3. Method (1200) according to one of claims 1 or 2, which comprises a step (1225) for detecting the positioning of an element in the cavity, the control step (1210) controlling the deformation of a part deformable material of the selected cavity according to the detected positioning of the element.

4. Process (1200) according to one of claims 1 to 3, wherein the deformation of a portion of the deformable material is achieved by local heating of the deformable material, the deformed portion of the deformable material being deformed by thermomechanical effect.

5. Method (1200) according to one of claims 1 to 4, wherein the deformation of a portion of the deformable material is performed by a pneumatic deformation means.

6. Method (1200) according to one of claims 1 to 5, wherein the deformation of a portion of the deformable material is performed by a piezoelectric deformation means.

7. Device (10) for handling an element consisting of a first fluid transported in a second fluid immiscible with the first fluid to implement the method according to one of claims 1 to 6, characterized in that it comprises :

a cavity (105), configured to receive at least one element constituted by the first fluid and the second fluid, which comprises at least one wall (1 10) of thermomechanically deformable material,

at least one local heating means (1 15) configured to deform at least a portion of the deformable material of the cavity by thermomechanical effect so that, when the local heating means heats up, each part of the heated deformable material at least partially obstructing a section of the cavity to allow the passage of the second fluid and to block the passage of each element of the first fluid, at least one other part of the deformable material of the cavity being not deformed,

means (135, 1 60) for moving the element constituted by the first fluid configured to move the element towards the outside of the deformed part of the deformable material and

- Control means (120) configured to independently control heating of at least one local heating means.

8. Device (10) according to claim 7, wherein the means (1 60) for moving is a rail (1 60) thermal, comprising at least one means (1 15) of local heating, configured to deform at the at least a portion of the deformable material of the cavity by thermomechanical effect so that when the local heated heating means, each deformed portion of the heated deformable material at least partially obstructs a section of the cavity to allow the passage of the second fluid and to block the passage of each element of the first fluid.

9. Device (10) according to claim 8, wherein the means (120) for controlling is configured to control successive heating of the successive local heating means of the rail (1 60) heat so as to move the element along the the cavity.

10. Device (10) according to one of claims 7 to 9, wherein the cavity comprises at least one side portion (125) of non-deformable material by the heat emitted by at least one local heating means.

1 1. Device (50) according to one of claims 7 to 10, wherein the means (530) for setting in motion comprises means (535) for generating a flow of the second fluid to move at least one element.

12. Device (70) according to one of claims 7 to 11, which comprises means (710) for detecting the contents of an element of the first fluid.

13. Device (10) according to one of claims 7 to 12, which comprises means (140) for detecting the position of at least one element in the cavity to provide a position signal to the control means (120). .

The device (10) of claim 13, wherein:

the cavity (105) comprises at least one translucent part (1 10),

the means (140) for detecting the position of at least one element in the cavity comprises an image capturing means (145) and a captured image processing means (150) configured to determine the position of an element according to the processed image.

15. Device (10) according to claim 13, wherein the means (140) for detecting is configured to detect an element of the first fluid as a function of a disturbance of an electromagnetic field near the cavity.

16. Device (10) according to one of claims 13 to 15, wherein the means (120) for controlling is configured to cause heating of at least two parts of the deformable material adjacent to the detected position of the element so that isolating the element in a portion of the cavity obstructed at each end by a deformation of the cavity (105).

17. Device (10) according to one of claims 13 to 1 6, wherein the means (120) for controlling is configured to control heating of a portion of the deformable material of the cavity to the detected position of the element for dividing said element into two elements positioned towards the outside of the portion of the heated deformable material.

18. Device (10) according to one of claims 7 to 17, which comprises a substrate (1 65) comprising at least one means (1 15) of local heating, secured to the cavity (105).

19. Device (60) for generating an element consisting of a first fluid transported in a second fluid immiscible with the first fluid, characterized in that it comprises a device for handling an element according to one of the claims. 7 to 18 of which:

an opening (615) of at least one cavity (605) towards a secondary cavity (620) is traversed by at least one flow (625) with a continuous phase,

the moving means (610) is configured to move a flow of first fluid in the cavity to the secondary cavity to form an element of the first fluid in the secondary cavity and

20. Device (70) for sorting at least one element consisting of a first fluid transported in a second fluid immiscible with the first fluid, characterized in that it comprises:

means (710) for actuating a means (715) for controlling an element handling device according to claims 7 to 18,

the device for manipulating an element which comprises:

at least two openings (730) of the cavity located downstream of a direction of movement of the moving means each giving into a secondary cavity (735) and

21. Device (80) for storing / releasing an element consisting of a first fluid transported in a second fluid immiscible with the first fluid, characterized in that it comprises:

- A handling device according to claim 1 1 and one of claims 7 to 10 and / or 12 to 28, a portion of the deformable material (835) is configured, during deformation, to block the passage of a element in a primary cavity (825) and directing this element to a storage / retrieval structure (815) and

- The storage / retrieval structure configured for, during heating of a portion of the deformable material of the structure by a local heating means of the secondary device, destocking the element.

22. Device (80) according to claim 21, which comprises a deformed portion of the deformable material (840) located at the junction between the primary cavity (825) and the structure (815) storage / retrieval.

23. Device (40) for melting two elements consisting of miscible first fluids transported in a second immiscible fluid with each first fluid, characterized in that it comprises a handling device according to one of claims 7 to 18, comprising a plurality of deformed portions (410) configured to force in contact the two elements by successive displacement of at least one of the two elements.

24. Device (90) for manipulating a matrix consisting of a first fluid transported in a second fluid immiscible with the first fluid, which comprises a device for handling an element consisting of a first fluid transported in a first fluid second fluid immiscible with the first fluid according to one of claims 7 to 18, the cavity (925) extends in two directions and which comprises:

at least one box (935) comprising at least three outputs (945) and

at least one portion (920) deformed of the deformable material is positioned facing at least one outlet.