WO2009024678A2

WO2009024678A2 - Device and method for separation of the components of a suspension in particular of blood

Info

Publication number: WO2009024678A2
Application number: PCT/FR2008/000961
Authority: WO
Inventors: Hervé ROSTAING; Jean-Luc Achard; Patrick Pouteau
Original assignee: Commissariat A L'energie Atomique; Centre National De La Recherche Scientifique
Priority date: 2007-07-18
Filing date: 2008-07-04
Publication date: 2009-02-26
Also published as: WO2009024678A3; FR2918900A1

Abstract

Device for the separation of a liquid suspension (S), comprising a continuous liquid phase (PL) and at least one dispersed phase (GB, GR), said phases having different densities. Said device comprises a first duct (C1) with at least one curved section, at least one second duct (C2), also with a curved section, running parallel to said first duct on the outside of the curve of the latter and at least one chamber (CL), separating said first and second ducts and in turn being curved. A longitudinal slot (F) is arranged in said chamber running along the curved section of the chamber and communicating between said first and second ducts such as to permit the exchange of material between them, said slot (F) being essentially arranged at the mid-point of said chamber (CL). The invention further relates to a method for separation of a liquid suspension using said device.

Description

DEVICE AND METHOD FOR SEPARATING THE COMPONENTS OF A SUSPENSION AND PARTICULARLY BLOOD

The invention relates to a device and a method for separating the components of a liquid suspension, in particular blood. The term "liquid suspension" is intended to mean a suspension comprising a liquid continuous phase and at least one dispersed phase which may be either liquid (droplets immiscible with the continuous phase) or solid (particles, such as blood cells), the overall mechanical properties of the suspension being essentially those of a liquid. The separation of the components of a suspension is most often by centrifugation, using mechanical centrifuges. The principle of centrifugation is that, when a sample of the suspension to be separated is rotated rapidly, the centrifugal force tends to entrain the densest component (for example, the blood cells dispersed in the plasma) towards the outside.

Alternatively, but only for suspensions having a solid dispersed phase, filtering may be used.

However, conventional centrifugation or filtering devices do not lend themselves to being miniaturized; this is particularly true for centrifuges, which have moving parts.

It would be desirable to have separation devices, particularly for blood, which can be miniaturized, and preferably integrated with a microfluidic device.

The article by Wei Wang et al. "Microfluidic centrifugation in a spiral microchannel", Proceedings of the ^10th 'International Conference on

Miniaturized Systems for Chemistry and Life Sciences "- μTAS2006, November 5-9, 2006, Tokyo, Japan, describes a microfluidic centrifugation process. The principle of this method is to circulate blood in a spiral wound conduit; the centrifugal acceleration can reach 2000g (g is the acceleration of gravity at sea level, about 9.81 m / s ² ), which leads to a concentration of blood cells in the outer part of the duct. However, this process is unsatisfactory because white blood cells are concentrated by a factor of 6 while red blood cells, lighter because smaller, are virtually not concentrated.

The separation of the suspensions in microfluidic devices known from the prior art is likely to be hindered by the appearance of secondary flows which tend to stir the suspension that one would like to separate. Among these secondary flows, particular mention should be made of Dean vortices (or cells), which appear in the curved ducts under the effect of centrifugal force, viscous (or possibly turbulent) resistant forces and the engine pressure gradient. . The Dean vortices are characterized by a secondary motion, superimposed on the axial main flow, which consists of two counter-rotating cells in the section plane of the main flow.

These vortices, known from the prior art, are used in microfluidics to improve the mixing of different liquids; therefore, they are generally considered harmful when one seeks to perform the reverse operation, namely the separation of the components of a heterogeneous mixture.

The article by Shinichi Ookawara et al., "Chemical Engineering Science 61, 2006, pages 3714-3724 studies the influence of Dean cells on the separation of particles contained in a suspension flowing in a circular arc-shaped conduit. As a result of this study, when the suspension is very diluted, the particles tend to concentrate in the center of the Dean cells. As the centrifugal force shifts the centers of the cells towards the outside of the duct, this allows a certain separation, less for particles of relatively large size (equivalent diameter d of more than 10 μm). The authors reached by simulation a maximum concentration of a factor 15 for particles of 20 μm in diameter having a density of 1.19 g / cm ³ in a dilute suspension in which the volume fraction of the dispersed phase relative to the continuous phase is in the range of 6-10 ⁴ . But the efficiency of the separation decreases rapidly in increasing the concentration of the suspension and decreasing the size of the particles. The method implemented by these authors can not therefore be applied to the separation of blood cells, whose volume fraction is of the order of 0.45.

An object of the invention is to overcome at least some of the disadvantages of the prior art and provide a device for separating the components of a liquid suspension, and in particular blood cells, which can be easily miniaturized. Advantageously, the device of the invention must have a simple structure and be able to be manufactured economically.

Such an object can be achieved by a device for separating a liquid suspension consisting of a liquid continuous phase and at least one dispersed phase, said phases having different densities, said device comprising: a first conduit having at least one curved portion ; at least one second duct, also having a curved portion, extending parallel to said first duct on the outside of the curved portion thereof; and at least one partition separating said first and second conduits and having in turn a curved portion; characterized in that said partition has a continuous or discontinuous longitudinal slot, extending along the curved portion of the partition and putting in communication said first and second conduits so as to allow exchanges of material between them, said slot being located substantially at mid-height of said partition and having a height, measured perpendicular to the radius of curvature of the latter, substantially less than that of the partition.

According to particular embodiments of the invention:

The device may further comprise at least a third conduit, also having a curved portion, extending parallel to said second conduit on the outer side of the curved portion thereof; and at least one second partition, separating said second and third conduits and having in turn a curved portion; said second partition having a second continuous or discontinuous longitudinal slot, extending along the curved portion thereof and placing said second and third conduits in communication, the dimensions of said second slot being smaller than that of the slot placing in communication said first and second conduits; said second slot being located substantially at mid-height of said second partition and having a height, measured perpendicularly to the radius of curvature of the latter, substantially lower than that of said partition. The dimensions of said or each slot may be sufficient to allow exchanges of said or at least one dispersed phase between the two conduits that it puts in communication. In particular said or each slot may have a height h, measured perpendicularly to the radius of curvature of the partition, between 0.05 microns and 2 mm.

Alternatively, the dimensions of said slot may be small enough to prevent the exchange of said or at least one dispersed phase between the two ducts. In particular said slot may have a height h, measured perpendicularly to the radius of curvature of the partition, between 0.05 microns and 15 microns.

Said or at least one of said slots may be a discontinuous slot constituted by a plurality of elementary openings aligned along the curved portion of said partition, said elementary openings having a funnel shape so as to promote the unidirectional passage of at least a phase dispersed between the conduits that it puts in communication.

Alternatively, said or each slot may be a continuous slot.

The curved portion of said or each partition wall may have a radius of curvature of between 50 microns and 20 cm, and preferably between 2 mm and 50 mm. Said or each slot may extend over a length L of between 10 mm and 20 m.

Said ducts may have a maximum height H, H ', measured perpendicularly to the radius of curvature of the partition, between 20 μm and 10 mm and a width, measured parallel to the radius of curvature, between 0.05 and 10 times said height. .

Said ducts may have a substantially rectangular section, or have convergent walls in the direction of said or one of said slots, or a substantially cylindrical section.

Said conduits may have, at one of their ends, a common inlet section for the introduction of said suspension to be separated.

As a variant, only one of said ducts may have, at one of its ends, an inlet section for the introduction of said suspension to be separated, the other or the other ducts being closed at the end. corresponding. In this case, the closed conduit (s) at the inlet end may also be closed at the opposite end, and / or have a discontinuous structure. Said ducts and partitions may be spirally wound, or may be curled on themselves so as to form a closed ring.

The device may have a planar structure, or be constituted by a stack of elementary devices (having a planar structure). Advantageously, said planar device or each planar elementary device can be produced by etching from at least one planar substrate. More particularly, said device or each elementary device can be made by placing face to face two planar substrates etched to define said ducts and said slot or slots. The device of the invention may also comprise means for injecting said suspension to be separated in at least one of said ducts.

The device of the invention may also comprise means for imparting to said suspension an axial flow velocity in at least one of said ducts. This means may be an injection pump of said suspension in said or each conduit or a micropump integrated in the device. In any case, said means may be adapted to impart to said suspension a flow rate of between 0.1 mm / s and 10 m / s, and preferably between 10 cm / s and 1 m / s.

At least one of said conduits may also include a set of electrodes adapted to generate an electric field whose lines of force converge towards said slot or diverge from the latter. - At least one of said ducts may have, on its inner wall, grooves extending obliquely with respect to an axial direction of said duct, said grooves being adapted to promote the establishment of secondary vortices when a liquid s' flows into said conduit. - At least one of said conduits may also comprise an electrode assembly for generating an electric field configuration adapted to promote, by electroosmotic effect, the introduction of secondary vortices when a suspension flows in said conduit.

The device may also comprise means for rotating the assembly constituted by said conduits and the closions or closions separating them, the axis of rotation being substantially perpendicular to the radius of curvature of said or each partition.

Another subject of the invention is a process for separating a liquid suspension consisting of a liquid continuous phase and at least one dispersed phase, said phases having different densities, said process being characterized in that it comprises the steps comprising introducing said liquid suspension into a device according to one of previous claims; imparting to said suspension an axial flow velocity sufficient to allow the development of secondary flows; and extracting, in correspondence of an output section of at least one of said channels, a fraction of said enriched suspension in at least one of said phases.

According to particular embodiments of the method of the invention:

The device may have at least one slot of sufficient size to allow exchanges of the said or at least one dispersed phase of the suspension to be separated between the two conduits put in communication by said slot; and the rate of flow of the slurry to be separated in the device may be sufficient to allow the transfer of the denser phase of the conduit from the inner side of said slit to the outermost conduit under the combined effect. centrifugal force and secondary flows.

The flow of the suspension to be separated can be characterized by a Dean number of between 1 and 100 and preferably between 10 and 50.

Said device can be rotated about an axis substantially perpendicular to the radius of curvature of said or each partition.

Said dispersed phase, or at least one of said dispersed phases, of the suspension to be separated may consist of solid particles having a density greater than that of said continuous liquid phase. In particular, said suspension to be separated can be blood.

Other features, details and advantages of the invention will emerge on reading the description made with reference to the appended drawings given by way of example and which represent, respectively: FIGS. 1 and 2, sectional views, respectively longitudinal and transverse, of a device of the invention comprising two parallel ducts; Figure 3A, a cross-sectional view of this device, applied to the separation of blood cells; Figure 3B, a cross-sectional view of a device of the invention comprising three parallel conduits, also applied to the separation of blood cells; Figures 4A and 4B, longitudinal sectional views of devices of the invention in which the outer conduit is closed at both ends; FIGS. 5A to 5D, cross-sectional views of devices of the invention comprising ducts of different shapes; FIGS. 6A, 6B and 6C are detailed views of the device partition wall according to various embodiments of the invention; Figure 7A, a longitudinal sectional view of a device of the invention having a planar structure and a spiral shape; Figure 7B, a longitudinal sectional view of a device of the invention having a planar structure and a ring shape; - Figure 8, a sectional view of a device according to Figure 7A or 7B, highlighting its structure formed by the assembly of two planar substrates etched; and Figure 9, an elevational view of a device consisting of a superposition of planar type elementary devices; FIG. 10, a means that can be used to impart a flow rate to a liquid in a device of the invention; Figures 11, 12 and 13 cross-sectional views of devices having electrical or hydraulic means for separation assistance; and FIG. 14, a device according to a variant of the invention in which the assembly consisting of the ducts and the partition (s) separating them can be rotated. Before describing in detail the various embodiments of the invention, it is appropriate to provide some details on the cells (vortices) of Dean.

In a straight duct in which a fluid flows, the axial velocity profile of said fluid decreases from the center of the duct to the wall, where it vanishes. This profile, called Poiseuille, results in every point from an equilibrium between the viscous (or possibly turbulent) resistant forces and the motor pressure gradient, which is axial and uniform in the section plane of the flow. In order to oppose the centrifugal force of the fluid, which is proportional to the square of the axial velocity, in a curved pipe, a radial pressure gradient is also produced, directed towards the center of the curvature and therefore of the outer part. duct to its internal part. Axial velocity being important in the center of the flow, it is primarily in this central zone that establishes this equilibrium. At the periphery, on the other hand, where the centrifugal forces decrease, the pressure gradient which has been created in the center can only be compensated for by the viscous forces. These then put in motion the fluid that runs along the upper and lower walls of the duct, from the outside to the inside. Following mass conservation considerations, the fluid returns from the inside to the outside via the median plane of the conduit. Overall, this results in a secondary movement (in the section plane of the main flow) consisting of two counter-rotating cells which is superimposed on the axial flow.

The development of secondary flows can be characterized by a numberless number called Dean number and defined by, _Wc

being the mean axial velocity of the flow, D _h the hydraulic diameter of the duct, R _c its radius of curvature and v the kinematic viscosity of the suspension. In general, a Dean number of between 1 and 100, and preferably between 10 and 50, is adequate for the implementation of the invention. A device according to the invention is shown, in its simplest form, in FIGS. 1, 2 and 3A. Such a device consists essentially of two parallel conduits C1 and C2, each having a curved portion C'1, C'2 respectively. In a conventional manner, the term "first conduit" C1 the conduit located on the inner side of the curvature, and "second conduit" C2 the conduit located on the outer side.

The conduits C1, C2 are separated by a partition CL ₁ having in turn a curved portion CL '. A slot F extends along the curved portion CL 'of this partition, placing the two ducts C1, C2 in communication so as to allow exchanges of material between them. The term "slot" should be understood in a general manner: it may be a continuous slot, but also a discontinuous slot constituted by a plurality of elementary openings aligned along the partition.

Figure 1 shows a longitudinal section of the device along the line 1-l of Figure 2; Figure 2 shows a cross section of the device along the line H-II of Figure 1.

In the example considered here, the two ducts C1 and C2 have a constant section of rectangular shape, whose height H, H 'can be between 20 microns and 10 mm and the width L, L "between 0.05 and 10 Once said height, the term "height" means the dimension measured perpendicular to the radius of curvature.In the case of Figure 2, the two ducts are identical: H = H ', L = L'; choice among others and does not constitute an essential characteristic of the invention.The slot F, of the continuous type, has a height h between

0.05 μm and 2 mm, a length L in the direction of flow between 10 mm and 20 m and a radial dimension I, equal to the width of the partition CL, between 1 μm and 1 mm. The ratio h / H or h / H 'is generally between 2.5-10 ^"3 and 0.2 Figure 2 shows that the slot F divides the partition CL into an upper part and a lower part of height α and β respectively, with α + β + h = H. For reasons that will become clear subsequently, it is preferable that the slot F is located approximately halfway up the partition CL; more generally, the ratio α / β is preferably between 0.1 and 0.9.

The curved portion CL 'of the partition CL has a radius of curvature R ₀ which is generally between 50 μm and 20 cm, and preferably between 2 and 50 mm.

As explained above, when a liquid flows in the conduits C1 and C2, for example in the direction indicated by the arrows E, secondary flows appear, and more particularly Dean VD vortices. It can be seen that in each duct two symmetrical vortices develop, one in the upper part of the duct and the other in the lower part. The secondary flow is directed outwards at the middle section of the ducts (at mid-height), and inward at the upper and lower walls of the ducts. The suspension to be separated is introduced into the device at its input end EX1 with a suitable speed. The introduction of the suspension can be done in particular using a syringe pump.

Figure 3A illustrates the principle of operation of the device of Figures 1 and 2, applied to blood fractionation. The blood is a suspension comprising a continuous liquid phase, the plasma PL, and a plurality of solid dispersed phases denser than said continuous phase, the cells; for the sake of simplicity, only two dispersed phases are considered, the "white blood cells" GB (which, in reality, are in their turn diversified) and the "red blood cells", GR, more numerous and of smaller dimensions. The cumulative volume fraction of the dispersed phases is about 0.45. It is important to note that the white and red RBCs, GR, (not shown in scale) have a diameter d less than the height h of the slit: they can therefore pass from a duct to the other via the latter.

According to the invention, blood S is injected into the two ducts C1 and C2 at the input end EX1 of the device, and Dean vortices appear within its laminar flow. In the first duct C1, arranged on the inside, these vortices of Dean have the effect of bringing the blood cells GB, GR, closer to the slot F. Then the centrifugal force FC pushes the latter outwards, and therefore to the second duct C2 through the slot F. In the second duct C2, disposed on the outside, the centrifugal force and the vortex entrainment of Dean contribute to move the GB, GR cells away from the slot F and to prevent them diffusion towards the first conduit C1. Finally, at the outlet end EX2 of the device, a concentration of the cells in the second channel C2 is obtained.

It is observed that the current directed towards the slot F induced by the vortices of Dean in the first conduit is located halfway up the latter. For this reason it is generally preferable that the slot F is located halfway up the partition CL. We now consider in more detail the operating principle of the device of Figure 3A.

The axial pressure gradient common to the two ducts C1 and C2 extends indeed inside the slot F of height h and width I. The average speed flow w _f (axial velocity) which is manifest is a flow of Poiseuille whose local velocity decreases from the center to connect with that the axial flows in the adjacent ducts. Thus, within the slot and also in its vicinity, it appears that a particle of diameter d is subjected to a centrifugal force to which a drag force opposes. The transit speed V _t from one channel to another (perpendicular to the axial speed w _f ), resulting from the equilibrium of these two forces and for a radially immobile carrier liquid, is

Vt oc (d / h) ² (R k) ² [(ρ _g / pc) -l] (v / Rc) wherein R ^f _e is the Reynolds number associated with the slot, Rj. = Wf h / v, v being the kinematic viscosity of the continuous phase of the suspension, p _c its density and p _g the density of the particles forming the dispersed phase. The transfer of a particle from the first path C1 to the second C2 is performed if pg is greater than p _c . This first conduit is said transmitter and the second receiver. Simultaneously a particle in the second conduit can not be transferred in the first. The inverse propositions are true if p _c is greater than P ₃ .

To estimate the trajectory of the particle, it is also necessary to take into account a driving effect if the carrier liquid is mobile. However, secondary flows occur in the slot, as in adjacent ducts. With regard to the slot, these flows whose scale V _s is given by Vs oc (R ^) ³ (v / R _c ) are disturbances. So that

V ₅ remains negligible compared to V _t , we see that one way is to reduce the Reynolds number R ^f _e below unity. Another more advantageous means is that (d / h) ² is as large as possible, which means that the height h of the slot F must vary between a fraction of d (the globules are deformable) and sometimes d; typically, h may range from 0.1d to 10d. The device of FIG. 3B differs from that of the figures

1 to 3A in that it also comprises a third duct C3 disposed outside the duct C2 and separated from the latter by a second partition CL2, along which runs a second slot F2. The second slot F2 has a height h2 which is smaller than the height h of the slot F placing the first and second ducts in communication, and which is even smaller than the diameter of the white blood cells GB, but greater than that of the red RBCs. As explained above, the combined effect of centrifugal force and Dean vortex entrainment induces GB, GR cell migration from the first to the second conduit. These same forces would tend to induce a migration of cells from the second to the third duct, but only the red blood cells can pass through the second slot F2. This results in a complete fractionation of the blood: the plasma PL remains predominantly in the first conduit C1, the white blood cells GB are concentrated in the second conduit C2 and RBC red blood cells in the third conduit C3. A device according to the invention can also be used for the partial separation of a suspension in which the particles constituting the dispersed phase are too large to be able to pass through the slot F. In this case, the suspension is injected into the internal pipe C1, and the centrifugal force pushes the continuous phase toward the outer conduit C2, while the slot F acts as a filter to retain said particles. In this embodiment of the invention, the Dean cells essentially function to prevent the accumulation of particles at the slot, which could interfere with the continuous phase transfer from the internal conduit to the external conduit.

In the devices of Figures 1 to 3B, the conduits have a constant section and the suspension to be separated is introduced into a common input section SX1. These characteristics are not essential, however. Thus, for example, it is possible to introduce the suspension in only one inlet section of a single conduit, for example the first, while the other conduits are closed at their corresponding end. Especially in this case, it is appropriate that the ducts section is not constant. Thus, the conduit into which the suspension is injected may gradually shrink, while the conduits having a closed end, which are initially empty and gradually fill through the corresponding slots, may have an increasing section.

According to another embodiment of the invention, the introduction of the suspension to be separated can be done at the input end EXV of a single conduit, while the other or the other conduits are closed. at both ends EX1 ", EX2" to form kinds of collection pockets for the separate phases. This is particularly the case of the device of FIG. 4A, in which the blood S is introduced into the first duct C1, the cells GB, GR are concentrated in the second duct C2, closed at its ends and at the exit EX2 ' the first conduit is recovered essentially pure PL plasma. In the variant of FIG. 4B, the second conduit C2 is discontinuous, being segmented by radial partitions CLR.

A common point between the different embodiments is the use of a structure comprising a plurality of curved conduits communicating via slots. This structure prevents the secondary flows induce a general stirring of the suspension that would oppose the separation. Localized in each duct, the secondary flows can therefore have a beneficial role by cooperating with the centrifugal force to bring closer or move away, depending on the embodiment considered, the dispersed phase of the suspension slots connecting the ducts between them.

Specifically, Dean's cells perform three distinct functions:

- They sweep all the particles in the particle emitter duct (C1, in the case of particles denser than the continuous phase of the suspension, C2 in the opposite case) and drive them in front of the slot F;

- They have the particles in front of the slot in an area where the carrier liquid is immobilized gradually so that the centrifugal force is preponderant vis-a-vis the driving forces; and

in the receiving duct, they move the particles away from slot F.

The cross section of the ducts of a device according to the invention does not necessarily have to be rectangular. Other shapes may be advantageous, especially for directing the particles towards the slot. Thus, in the embodiments of FIGS. 5A and 5B, the first duct has walls PC1, PC2 which converge towards the slot F. Thus the unidirectional transfer of particles from the first to the second duct is favored by a funnel effect. A similar result can be obtained by using ducts having a cylindrical section, such as the duct C1 of the device of FIG. 5C and the ducts C1 and C2 of the device of FIG. 5D. Figures 6A, 6B and 6C show three possible embodiments of the CL partition. More specifically, each of these figures represents the lower part of a partition of a device according to one embodiment of the invention. In the case of FIG. 6A, each part of the partition CL consists of a continuous wall, CL, of height β (for the lower part) or α (for the upper part). This results in a continuous slit of height h = H-α-β.

In the case of Figure 6B ₁ each part of the partition CL consists of a continuous wall, CL _A of height β (for the lower part) or α (for the upper part). This wall is surmounted by parallelepiped shaped crenellations C _B , of height h / 2, with h = H-α-β. In the complete device, the peaks of the crenellations of the lower part (only represented) come into contact with the tops of the crenellations of the upper part. This results in a discontinuous slot constituted by a succession of rectangular openings O of height h.

In the case of FIG. 6C, the slots have a trapezoidal-shaped prism shape. This results in a discontinuous slot consisting of a succession of openings O 'having a funnel shape which promotes the unidirectional passage of particles from the first to the second duct (or vice versa).

Whatever the embodiment chosen, it is generally necessary that the separation of the components of the suspension continues over a sufficient length. The (axial) separation length must be at least equal to L = (IΛ / _t ) W _f where I is the radial dimension of the slot, V _t the transit velocity of the particles in the slot and w _f the mean axial velocity of the suspension. In addition, the conduit must be of sufficient length to allow the establishment of the desired secondary flows; for this it takes a length of the order of D _h - R _e ^c I 16. Specifically, the separation length is at least 10 mm, and can reach several meters.

Figure 7A shows a first embodiment of a device of the invention, having a spiral shape. The suspension to be separated can be introduced via an input port PE located in the center of the device and the separated components can be recovered at the outer end, via output ports PS1, PS2, solution shown in the figure, or vice versa. The advantage of this solution is to be particularly compact, because the separation is continuous over the entire length of the ducts. This length can be very important, even in a device of relatively small dimensions: a conduit with a diameter of 1 mm and a length of 20 m can be wound into a spiral of only 20 cm in diameter.

Figure 7B shows an alternative embodiment, in which the conduits C1 and C2 are looped on themselves so as to form a ring structure. Ports P1, P2 are provided in the walls of said conduits to introduce the suspension and recover its separate components.

The devices of Figures 7A and 7B have only two ducts, but this is not a limitation of the invention.

Advantageously, a device according to the invention can be made in planar form, so as to form a microfluidic chip. FIG. 8 shows a sectional view of a device of the same type as that of FIGS. 1 and 2, in which the ducts C1, C2 and the slot F are defined by etching of two substrates SUB1, SUB2. The etched substrates are then placed face to face and interconnected using a CLI bonding layer. The substrates SUB1, SUB2 may be, for example, silicon or glass, and be etched by conventional photolithographic techniques. A device according to the invention may also consist of a superposition of planar-type elementary devices D1, D2, D3, D4, D5, as shown in FIG. 9. The figure shows a view of elevation of such a device, as well as a plan view of the elementary device D5. In the embodiment shown in the figure, each elementary device has two ducts C1, C2 forming an open ring, in which the partially separated suspension enters, from the previous elementary device, by two input ports PE1, PE2 and out in the direction of the next elementary device, by two output ports PS1, PS2. The device of the invention must have a means, external or internal, for moving the liquid suspension in at least one of said conduits. The movement of the suspension S can be carried out during its introduction at its inlet end, in particular using a syringe pump SE, as shown in FIG. 10A. Alternatively, the movement of the suspension can be done after its introduction, using an integrated device. Note that this solution is required in the case of a ring device such as that of Figure 7B.

Such an integrated device can be constituted by a micropump: see in this regard the Woias article, "Micropumps - Past, Progress and Future Prospects", Sensors and Actuators B 105, 2005, pages 28-38.

Whatever the actuation means used, the average velocity w _c of the suspension S in each duct is preferably such that W _f / w _c oc (h / D _h ) ² where Dh is the hydraulic diameter of the duct considered. Preferably, this speed must be between 0.1 mm / s and 10 m / s. In any case, the speed w _c must be sufficient for the flow to have a Dean number greater than or equal to 1, and preferably greater than or equal to 10, and in particular between 10 and 50. Indeed, once the geometry of the ducts and the physical properties of the suspension, the

number of Dean D _e = depends exclusively on the speed w _c

Figures 11 to 14 show variants of the invention comprising auxiliary means for promoting the separation of the suspension S.

The device of FIG. 11 comprises a set of electrodes EL1, EL2 adapted to generate an electric field whose lines of force LF1 start from the side wall of the emitter duct C1, converge towards the slot F and extend inside. from the latter until it opens into the receiver channel C2. Advantageously, the electric field preserves the symmetry of Dean flows. The electric field generated by the electrodes EL1, EL2 induces dielectrophoretic forces that suck the particles of the emitter duct to the receiver duct, advantageously combining with the centrifugal force. The device of FIG. 11 is adapted to the case of particles undergoing a positive dielectrophoretic effect; for particles undergoing a negative dielectrophoretic effect, the roles of the conduits C1 and C2 are reversed.

The device of FIG. 12 comprises a set of electrodes EL'1-EL'8 adapted to generate in each duct C1, C2 an electric field CEL oriented parallel to the radius of curvature of said ducts and having a maximum intensity at the level of the upper walls. and lower ducts, and minimal in the median plane. Such a configuration is adapted to promote, by electroosmotic effect, the introduction of secondary vortices when a suspension flows in said ducts. The Dean vortices may also be "amplified" by hydraulic means, such as R-grooves present on the inner walls of the conduits and extending obliquely to the axial direction. This solution is represented in FIG. 13.

FIG. 14 shows a variant of the device of the invention, in which the assembly D "consisting of the ducts C1, C2 and the partition (s) CL separating them is disposed on a turntable of a rotary actuator AR. in rapid rotation of the assembly D 'about an axis of rotation substantially perpendicular to the radius of curvature of said ducts and partition (s) generates a centrifugal force which is superimposed on that due to the flow of the suspension in the curved ducts, and which therefore contributes to the separation. It should be noted that if the conduits C1, C2 have a spiral shape, their rotation can cause actuation by inertial effect of the fluid they contain. Different ways to facilitate separation

(Shape of the ducts and the partition, sets of electrodes, grooves, etc.) have been presented separately from each other, but it should be understood that several of them can advantageously be combined in the same device.

Claims

Apparatus for separating a liquid suspension (S) constituted by a liquid continuous phase (PL) and at least one dispersed phase (GB, GR), said phases having different densities, said device comprising: a first conduit ( C1) having at least one curved portion (CV); at least one second conduit (C2), also having a curved portion (C2 ¹ ), extending parallel to said first conduit on the outer side of the curved portion thereof; and at least one partition (CL), separating said first and second conduits and having in turn a curved portion (CL '); characterized in that said partition has a longitudinal slot (F) continuous or discontinuous, extending along the curved portion of the partition and putting in communication said first and second conduits so as to allow exchanges of material between them, said slot (F) being located substantially halfway up the said partition (CL) and having a height, measured perpendicularly to the radius of curvature of the latter, substantially lower than that of the partition.

2. Device according to claim 1 further comprising at least a third conduit (C3), also having a curved portion, extending parallel to said second conduit on the outer side of the curved portion thereof; and at least one second partition (CL2) separating said second and third conduits and having in turn a curved portion; wherein said second partition has a second continuous or discontinuous longitudinal slot (F2) extending along the curved portion thereof and communicating said second and third conduits, the dimensions of said second slot being smaller than that of the slot (F) placing said first and second conduits in communication; said second slot (F2) being located substantially halfway up said second partition (CL2) and having a height, measured perpendicularly to the radius of curvature of the latter, substantially lower than that of said partition.

3. Device according to one of the preceding claims, wherein the dimensions of said or each slot are sufficient to allow exchanges of said or at least one dispersed phase (GB, GR) between the two ducts that it puts into operation. communication.

4. Device according to one of the preceding claims, wherein said or each slot (F) has a height (h, h2), measured perpendicularly to the radius of curvature of the partition, between 0.05 microns and 2 mm.

5. Device according to claim 1, wherein the dimensions of said slot are small enough to prevent the exchange of said or at least one dispersed phase (GB) between the two ducts.

6. Device according to claim 5, wherein said slot has a height (h2), measured perpendicularly to the radius of curvature of the partition, between 0.05 microns and 15 microns.

7. Device according to one of the preceding claims, wherein said or at least one of said slots (F) is a discontinuous slot constituted by a plurality of elementary openings (O ¹ ) aligned along the curved portion of said partition, said elementary openings having a funnel shape so as to promote the unidirectional passage of at least one dispersed phase between the conduits that it communicates.

8. Device according to one of claims 1 to 6, wherein said or each slot (F) is a continuous slot.

9. Device according to one of the preceding claims, wherein the curved portion of said or each partition (CL, CL2) has a radius of curvature of between 50 microns and 20 cm, and preferably between 2 mm and 50 mm .

10. Device according to one of the preceding claims, wherein said or each slot (F, F2) extends over a length of between 10 mm and 20 m.

11. Device according to one of the preceding claims, wherein said ducts have a maximum height (H ₁ H '), measured perpendicularly to the radius of curvature of the partition, between 20 microns and 10 mm and a width (L, L '), measured parallel to the radius of curvature, between 0.05 and 10 times said height.

12. Device according to one of the preceding claims, wherein said ducts have a substantially rectangular section.

13. Device according to one of claims 1 to 11, wherein at least one of said conduits has converging walls (PC1, PC2) towards said or one of said slots.

14. Device according to claim 13, wherein at least one of said ducts has a substantially cylindrical section.

15. Device according to one of the preceding claims, wherein said conduits have, at one of their ends, a common inlet section (EX1) for the introduction of said suspension to be separated.

16. Device according to one of claims 1 to 14, wherein only one of said conduits has, at one of its ends (EX1 '), an input section for the introduction of said suspension to be separated, the other one or the other conduits being closed at the corresponding end (EX1 ").

The device of claim 16, wherein the at least one closed conduit at the input end is also closed at the opposite end (EX2 ").

18. Device according to claim 17, wherein the conduit or conduits closed at their ends have a discontinuous structure.

19. Device according to one of the preceding claims, wherein said ducts (C1, C2) and partition or partitions (CL) are wound in the form of a spiral.

20. Device according to one of claims 1 to 18, wherein said ducts (C1, C2) and partition or partitions (CL) are looped on themselves to form a closed ring.

21. Device according to one of the preceding claims, having a planar structure.

22. Device according to one of claims 1 to 20, constituted by a stack of elementary devices (D1, D2, D3) having a planar structure.

23. Device according to one of claims 21 or 22, said device or each elementary device (D1, D2, D3) being produced by etching from at least one planar substrate (SUB1, SUB2).

24. Device according to claim 22, said device or each elementary device being made by disposing face to face two planar substrates (SUB1, SUB2) etched so as to define said ducts (C1, C2) and said slot or slots (F).

25. Device according to one of the preceding claims, also comprising a means (SY) for injecting said suspension to be separated in at least one of said conduits (C1, C2).

26. Device according to one of the preceding claims, also comprising a means (SY, P) for imparting to said suspension an axial flow velocity in at least one of said ducts.

27. Device according to claim 26, wherein said means (SY, P) for imparting to said suspension a flow velocity in at least one of said ducts is an injection pump of said suspension in said or each duct.

28. Device according to claim 26, wherein said means (SY, P) for imparting to said suspension a flow velocity in at least one of said ducts is a micropump integrated in the device.

29. Device according to one of claims 26 to 28, wherein said means (SY, P) is adapted to impart to said suspension a flow rate of between 0.1 mm / s and 10 m / s, and of preferably between 10 cm / s and 1 m / s.

30. Device according to one of the preceding claims wherein at least one of said ducts also comprises a set of electrodes adapted to generate an electric field whose lines of force converge towards said slot or diverge from the latter.

31. Device according to one of the preceding claims wherein at least one of said conduits has, on its inner wall, grooves extending obliquely with respect to an axial direction of said duct, said grooves being adapted to favor the establishment of secondary vortices when a liquid flows in said conduit.

32. Device according to one of the preceding claims wherein at least one of said conduits also comprises a set of electrodes for generating an electric field configuration adapted to promote, by electroosmotic effect, the introduction of secondary vortices when a suspension flows in said conduit.

33. Apparatus according to one of the preceding claims also comprising means for rotating the assembly constituted by said conduits and the partition or partitions separating them, the axis of rotation being substantially perpendicular to the radius of curvature of said or each partition.

34. Process for separating a liquid suspension (S) constituted by a liquid continuous phase (PL) and at least one dispersed phase (GB, GR), said phases having different densities, said process being characterized in that it comprises the steps of: introducing said liquid suspension into a device according to one of the preceding claims; - imparting to said suspension an axial flow velocity sufficient to allow the development of secondary flows; and extracting, in correspondence of an output section (EX2, EX2 ') of at least one of said channels, a fraction of said enriched suspension in at least one of said phases.

35. The method of claim 34, wherein: the device has at least one slot (F) of sufficient size to allow exchanges of said or at least one dispersed phase (GB, GR) of the suspension to be separated between the two conduits put in communication by said slot; and the flow velocity of the suspension to be separated in the device is sufficient to allow the transfer of the denser phase of the duct located on the inside (C1) of said slot to the duct located on the outside (C2) under the combined effect of centrifugal force (FC) and secondary flows (VD).

36. Method according to one of claims 34 or 35, wherein the flow of the suspension to be separated (S) is characterized by a Dean number of between 1 and 100 and preferably between 10 and 50.

37. Method according to one of claims 34 to 36, wherein said device is rotated about an axis substantially perpendicular to the radius of curvature of said or each partition.

38. Method according to one of claims 34 to 39, wherein said dispersed phase (GB, GR), or at least one of said dispersed phases, of the suspension to be separated is constituted by solid particles having a density greater than that of said liquid continuous phase (PL).

39. The method of claim 38, wherein said suspension to be separated is blood (S).