EP1778976B1 - Electrode addressing method - Google Patents

Abstract

A device for addressing an electrode array of 2n lines of an electro-fluidic device, each line having N electrodes (n@N). The device includes, on each line, n selection electrodes, all of the line selection electrodes being connected to 2n line selection conductors, 2n-1 line selection electrodes of 2n-1 lines being connected to each line selection conductor, and selection devices for selecting one or more line selection conductors.

Description

TECHNICAL FIELD AND PRIOR ART

The invention relates to electro-fluidic multiplexing for the manipulation of several drops in a microsystem.

The invention is particularly well suited to the lab-on-a-chip requiring the control of a large number of different liquids, for example, for high-throughput analysis or combinatorial chemistry applications.

The reaction volumes are drops manipulated by electrowetting on sets of electrodes.

One of the most used modes of movement or manipulation is based on the principle of electrowetting on a dielectric, as described in the article of MG Pollack, AD Shendorov, RB Fair, entitled "Electro-wetting-based actuation of droplets for integrated microfluidics", Lab Chip 2 (1) (2002) 96-101 .

The forces used for displacement are electrostatic forces.

The document FR-2 841 063 describes a device implementing a catenary facing electrodes activated for displacement.

The principle of this type of displacement is synthesized on the Figures 1A - 1C .

A drop 2 rests on a network 4 of electrodes, from which it is isolated by a dielectric layer 6 and a hydrophobic layer 8 ( Figure 1A ).

Each electrode is connected to a common electrode via a switch, or rather an individual electrical relay control system 11.

Initially, all the electrodes as well as the counter electrode are placed at a reference potential V0.

When the electrode 4 - 1 located near the drop 2 is activated (placed at a potential V1 different from V0 by actuation of the relay 11), the dielectric layer 6 and the hydrophobic layer 8 between this activated electrode and the drop, polarized by the counter-electrode 10, act as a capacitance, the electrostatic charge effects induce the displacement of the drop on the activated electrode. The counter-electrode 10 can be either a catenary as described in FR - 2 841 063 ( Figure 2A ) a buried wire, or a planar electrode on a hood in the case of a confined system.

The hydrophobic layer thus becomes locally more hydrophilic.

The drop can thus be moved step by step ( figure 1C ), on the hydrophobic surface 8, by successive activation of the electrodes 4 - 1, 4 - 2, ... etc. and along the catenary 10.

The documents cited above give examples of implementations of adjacent electrode series for handling a drop in a plane.

There are two families of realization of this type of device.

In a first case, the drops rest on the surface of a substrate comprising the matrix of electrodes, as illustrated in FIG. Figure 1A and as described in the document FR 2 841 063 .

A second family of embodiments consists in confining the droplet between two substrates, as explained, for example, in the document by M.G. POLLAK et al, already mentioned above.

In the first case we speak of an open system, in the second case we speak of a confined system.

The system generally consists of a chip and a control system.

The chips have electrodes as described above.

The electrical control system comprises a set 11 of relays and a PLC or a PC for programming relay switching.

The chip is electrically connected to the control system, so each relay can control one or more electrodes.

Thanks to the relays, all the electrodes can be placed at a potential V0 or V1.

Generally the number of electrical connections between the control system and the chip is equal to that of the number of relays.

To move a drop on a line of electrodes, simply connect all the electrodes to relays and activate them successively as described on Figures 1A - 1C .

The figure 2 illustrates the case of a matrix of N electrode lines.

It is then desired to move simultaneously (in parallel) N drops on these N lines.

For this, the electrodes are connected in columns, each column of electrodes being connected to a relay, said parallel relay 20.

The operation of the lines is dissociated in order, for example, to bring a single drop given to one end, and to leave the other drops at the beginning of the line.

To dissociate the lines, at least one column of electrodes, called line selection electrodes, is defined, each of the electrodes of this column being connected, via a conductor 21 - i, to a relay 22 - i which is independent of the relays to which connected the other electrodes of this same column. These various relays are designated by the references 22 - 1, 22 - 6, 22 - 7, 22 - 8 on the figure 2 and are called line selection relays.

All the drops are displaced on the N lines by the parallel relays 20 to the column of electrodes that precedes the row selection electrode column ESL.

By controlling the various line selection relays 22- i, the drops that are to be stopped and those that must continue to move along one or other line of electrodes are chosen.

The drops thus selected can then continue their movement by controlling the relays 20.

In this implementation the number of electrical conductors 21 - i and relay 22 - i is proportional to the number of lines. For a large number of lines (N = 20, 50, 100 ....), the large number of drivers and relays makes this technology complex and very expensive.

There is therefore the problem of finding a method and a device for simplifying the electrical connections while maintaining the possibility of selection for each line of electrodes.

STATEMENT OF THE INVENTION

• sur chaque ligne, n électrodes dites de sélection, l'ensemble de ces électrodes de sélection de ligne étant reliées à 2n conducteurs de sélection de lignes, 2^n-1 électrodes de sélection de lignes de 2^n-1 lignes étant connectées à chaque conducteur de sélection de lignes,
• des moyens de sélection, pour sélectionner un ou plusieurs conducteurs de sélection de ligne.

The invention first relates to a device for addressing an array of electrodes with 2 ⁿ lines of an electro-fluidic device, each line having N electrodes (n <N ), this device comprising:

• on each line, n said selection electrodes, all of these line selection electrodes being connected to 2n line selection conductors, 2 ^{n-1 line} selection electrodes of 2 ^n-1 lines being connected to each conductor line selection,
• selection means for selecting one or more line selection conductors.

The invention makes it possible to reduce the number of line selection conductors, and therefore of simplifying the line selection means in an electro-fluidic addressing matrix.

Thanks to the invention, it is therefore possible to handle 2 ⁿ drops for only 2 ⁿ input signals.

The invention thus makes it possible to drive line selection electrodes with only 2 n relays.

By way of example, the invention makes it possible to drive 8, 16, 32, 64, 128, 256, 512, 1024 line selection electrodes with respectively 6, 8, 10, 12, 14, 16, 18, 20 conductors. line selection and the same number of line selection relays.

The invention is particularly well suited when the number of lines is large (> 16 or 32 for example).

The ESL-k electrodes for selecting the different lines can be connected to two line selection conductors for a given value of "k", the ESL-k electrodes being connected in packets of 2 ^k-1 alternatively to the conductor Ck. and the driver Ck '.

The selection means for selecting one or more line selection conductors may comprise selective electrical relays.

According to one embodiment, in such a device, the line selection lead selection means comprise 2n electrical selection relay, each relay being connected to a single line selection conductor.

According to one embodiment, in such a device, the line selection lead selection means comprising n electrical selection relays, each relay being connected to two line selection conductors.

Each line selection relay can then be combined with means for generating, in addition to an input signal, a complementary signal.

The line selection electrodes are arranged successively along each line, or non-sequentially along at least one line.

The line selection electrodes of at least one line may be rectangular in shape, the long side of each rectangle being arranged perpendicular to the line.

The line selection electrodes of at least one line may alternatively be square.

According to a particular embodiment, at least one electrode line of the matrix has a cut-off electrode (Ec).

Digital line selection means may be provided for controlling a device according to the invention.

These digital line selection means may be programmed to select the rows of the electrode array in a binary code.

According to the invention, a combinatorial logic obtained using an appropriate method is then used. interconnections between several electrodes at the chip or the device.

These digital line selection means may comprise means for selecting one or more lines of the matrix, and means for forming instructions for controlling the line selection conductors according to the selected line or lines.

These digital line selection means may furthermore comprise means for consecutively activating the line selection electrodes of a selected line and / or for simultaneously activating the line selection electrodes of a selected line.

The invention also relates to a device for forming drops of liquids, comprising a device as described above, and means forming reservoirs for liquids, each line of the matrix being connected to a reservoir.

Such a device according to the invention may also comprise means forming 2 ⁿ reservoirs for liquids, each line of the matrix being connected to a single reservoir.

Each line can be connected to a common line of electrodes, to mix drops of liquids formed on the different lines.

The invention also relates to a device for addressing an array of electrodes of p lines, with 2 ⁿ <p <2 ^{n + 1} lines, of an electrofluidic device, comprising a device with 2 ⁿ lines as described herein. -above.

• le déplacement d'un volume de fluide la long d'au moins une ligne de la matrice par activation des électrodes de ladite ligne.

The invention also relates to a method for moving at least one volume of liquid, using a device as described above, comprising:

• moving a volume of fluid along at least one line of the matrix by activating the electrodes of said line.

The line selection electrodes of said line can be activated consecutively, or successively.

The invention also relates to a method of forming a drop of liquid comprising the displacement of a volume of liquid as described above, the spreading of this volume on several electrodes of said line by simultaneous selection of these electrodes, and breaking the spread volume using a cutoff electrode (Ec).

The implementation of the invention makes it possible to control a very large number of drops with a simple technology for manufacturing the chip, a minimization of the number of electrical connections between the chip and the control system, a simplification of the electrical control system and thus minimization of the manufacturing costs of the chip, the electrical connections, and the control system.

BRIEF DESCRIPTION OF THE DRAWINGS

• The Figures 1A - 1C illustrate the principle of manipulation of drop by electrowetting on insulation,
• the figure 2 represents the manipulation of a drop column by Rp relays and the selection of drops by Rsl relays,
• the figure 3 is an example of electro-fluidic multiplexing with 8 electrode lines,
• the figure 4 is an exemplary embodiment of the invention, implementing a binary coding with 8 electrode lines.
• the figure 5 is an example embodiment of ESL electrodes,
• the Figures 6A - 6D represent steps to make a drop on a line of electrodes,
• the Figures 7A - 7D illustrate examples of fluidic processors using the invention,
• the figure 8 represents a device with 16 lines, connected according to the invention,
• the figure 9 represents a confined device,
• the figure 10 represents an electrode structure of which one of the profiles is in the form of sawtooth,
• the Figures 11A and 11B illustrate examples of series of matrices of electrodes according to the invention,
• the figure 12 is an example of a chip for various operations on drops of liquid, from different tanks,
• the Figures 13A - 13D illustrate various aspects of a fluidic processor,
• the Figures 14A - 14D represent various steps of a drop mixing process according to the invention,
• the figure 15 is an example of a microfluidic processor or chip, with various reservoirs containing fluids at different levels of dilution or concentration,
• the figure 16 is a detailed view of four tanks containing fluids at different levels of dilution or concentration,
• the figure 17 is another embodiment of the invention,
• the Figures 18 - 24D explain how to constitute a microfluidic contactor that can be implemented in the context of the invention.

DETAILED PRESENTATION OF PARTICULAR EMBODIMENTS

An exemplary embodiment of the invention will be given in connection with the figure 3 .

In this example, the device comprises 8 lines (No. 0 to No. 7) of electrodes, or 2 ³ lines.

Each line has at least 3 electrodes, 6 in the example of the figure 3 .

Among the electrodes of each line are selected 3 electrodes Es11, Es12, Es13, said selection. More generally, for N = 2 ⁿ lines, n selection electrodes Esl-i are selected, i = 1-n on each line, n> 0.

The line selection electrodes Esl-i are connected to line selection relays, as explained in more detail below, or to line selection conductors C1, C1 ', C2, C2', C3, C3 'which are themselves connected to line selection relays.

On the figure 3 , are implemented 6 (= 2 x 3) line selection conductors. These conductors are, in this figure, grouped in pairs.

In general, for N = 2 ⁿ lines, 2n line selection conductors are available.

The n line selection electrodes of each line, and therefore the 2 ⁿ x ⁿ line selection electrodes, are connected to one or the other of the conductors of the n pairs of conductors Ck, Ck '(k = 1,. ..n and k '= 1, ... n) line selection.

Each line selection conductor is controlled by a line selection relay, Rs1 - k, Rs1 - k '(k = 1-3, k' = 1 - 3). There is therefore, in total, in this embodiment, 2n line selection relays.

The other electrodes, which are not line selection electrodes, are connected to parallel relays 30, as already explained above: each electrode column is connected to a parallel relay.

For a given line, the electrodes Es1 - i are not necessarily consecutive: there may be, for at least one line, a "normal" electrode (which is not a selection electrode) between two selection electrodes Es1 - i. We will see moreover an example of use of such a device.

On the other hand, it is preferable to adopt, by convention, a numbering direction common to all the lines: for example, it is appropriate that, on each line, the rightmost selection electrode on the line is Esl - 1, Esl - 2 being the left selection electrode of Esl - 1 (even if it is not juxtaposed to it) and, more generally, Esl - k being the left selection electrode of Esl - (k - 1 ), even if it is not juxtaposed with it.

On the figure 3 are represented Esl-1, Esl-2 and Esl-3 for each of the lines j = 0 and 1. But this arrangement, as explained above, is not the only one possible.

For i = 1, the electrodes Esl - 1 of the different lines are connected to C1 and C1 '(then to Rs1 - 1 and to Rs1 - 1') alternately: in other words, the electrodes Esl - 1 are alternately connected to C1 and C1 '(so there is change every 2 ^(1-1) lines, that is to say at every line).

For i = 2, the electrodes Esl - 2 of the different lines are connected to C2 and C2 '(then to Rsl - 2 and Rsl - 2'), again alternately, but every 2 ^(2-1) = 2 ¹ , every two lines. In other words, they are groups of 2 ¹ electrodes Esl - 2 which are connected alternately on C2 then on C2 '.

For i = 3, the electrodes Esl - 3 of the different lines are connected to C3 and C3 '(then to Rsl - 3 and Rsl - 3'), again alternately, but every 2 ^(3-1) = 2 ² lines. In other words, this are groups of 2 ² electrodes Esl - 3 which are alternately connected to C3 then C3.

More generally, for N = 2 ⁿ lines, 2 ^k-1 electrodes Esl-k (k = 1, .... N) out of all the 2 ⁿ xn electrodes Esl-k of all the lines are connected to the selection conductor line Ck (connected to the relay Rs1 - k), the following 2 ^k-1 being on the line selection conductor Ck '(connected to the relay Rsl - k'). If there are still electrodes Esl - k after these two assignments, they can be assigned again to Ck (and therefore to Rsl - k) for the next 2 ^{k - 1} , then back to Ck '(so at Rsl - k ') for the following 2 ^k-1s . If there remains only one group of less than 2 ^k-1 electrodes, these will be assigned to either Ck or Ck ', depending on whether the preceding electrodes Esl-k are connected to Ck' or Ck.

For a given value of "k", the ESL-k electrodes of the different lines can be connected to two line selection conductors Ck
or Ck '(and corresponding RSL-k or RSL-k' relays), the ESL-k electrodes being connected in a 2 ^k-1 packet, alternately on the conductor Ck and on the conductor Ck '.

For a given line, the line selection electrodes of this line are assigned to different pairs Ck, Ck 'and therefore, in the configuration of the figure 3 , to different relay pairs Rs1-k, Rs1-k '. In addition, where, as on the figure 3 , the line selection electrodes are paired, two line selection electrodes of the same line are not assigned to the same pair Ck (Rs1 - k), Ck '(Rs1 - k').

Finally, for the general case of 2 ⁿ lines, each line selection conductor Ck is assigned or connected 2 ^{n-1 line} selection electrodes of 2 ^n-1 lines.

In the case of figure 3 the addressing of the ESL-k electrodes by the RSL-k and RSL-k 'relays for k = 1, 2, 3 is summarized in the following Table I. The addressing of the conductors Ck, Ck ', respectively connected to Rsl-k and Rsl-k', follows. Table I Line j Relay connected to ESL-3 Relay connected to ESL-2 Relay connected to ESL-1 0 RSL-3 ' RSL-2 ' RSL-1 ' 1 RSL-3 ' RSL-2 ' RSL-1 2 RSL-3 ' RSL-2 RSL-1 ' 3 RSL-3 ' RSL-2 RSL-1 4 RSL-3 RSL-2 ' RSL-1 ' 5 RSL-3 RSL-2 ' RSL-1 6 RSL-3 RSL-2 RSL-1 ' 7 RSL-3 RSL-2 RSL-1

For example, for the line j = 0, Esl - 3 is activated if Rs1-3 'is activated too, and therefore also the driver C3' ( figure 3 ).

Regardless of the number of lines and line selection electrodes, each line selection conductor and relay may have two different states.

A first state is said state "0". The conductor Ck and the electrodes that this relay controls are then connected to the potential V0 (or to a floating potential): the electrowetting does not act on these electrodes, there is no displacement or spreading of the drops on these electrodes.

A second state is said state "1". The conductors Ck and the electrodes that this relay controls are then connected to the potential V1: the electrowetting can act on these electrodes to move or spread the drops on these electrodes.

In order for a droplet to cross the different electrodes ESL1, ESL2 ..., ESLn, line selection of the same line, all line selection conductors and relays to which these different electrodes are connected must be at the same time. state "1".

If only one of these line selection conductors or relays is in state "0", there is no possible crossing of the liquid on the electrode lines connected to the line selection conductor and the relay in the state "0".

If all the drivers Ci and Ci 'and all the relays RSLi and RSLi', for i = 1 to 2n are in the state "0", there is no possible crossing of liquid on any of the lines.

On the other hand, if all the RSLi and RSLi 'relays are in state "1", all the drops can move or stretch, on each line, on all ESL-1 electrodes to ESL-n.

This embodiment of the invention makes it possible to work only with 2n line selection conductors, and as many control relays, 2 ⁿ xn line selection electrodes. the set of lines, these row selection electrodes being in number n on each line.

On the contrary, the known devices implement, at best, 2 ⁿ row selection electrodes, but with 2 ⁿ conductors and as many relays (see FIG. figure 2 ). The gain provided by the invention, in terms of the number of conductors and relays, is therefore significant, especially if the number of lines is of the order of 2 ^n. With n ≥ 4, or 8, or 16 ... etc.

Means 40 for controlling the relays may be provided, for example programmable digital means (PC or other) to which the relays are connected and which can drive these relays.

These means may be provided with a screen 42 allowing the user to select a line on which a drop must be able to be transferred. For example, the matrix is represented on this screen and the user selects one or more drop transfer lines, using a cursor or a stylus to designate the line or lines retained directly on the screen .

Or an automatic program can select the lines and send the corresponding control signals to the electrodes.

Means for memorizing the means 40 make it possible to memorize the information making it possible to select this or that line. This information is for example that of Table I for the case of an addressing matrix of 8 lines, they are stored or stored in the form of Table I or in another form.

On instruction of an operator, for example on selection as described above, or on instruction of an automatic program, the digital means select, in the storage means, the data for opening or closing the relays Rs1 -k, Rsl-k 'necessary, and thus activate the electrodes Ck, Ck' necessary.

In the previous embodiment, the line selection conductors Ck, Ck 'are connected to as many line selection relays Rs1-k, Rs1-k'.

It is possible, according to another embodiment, to reduce this number of line selection relays.

Thus, according to another aspect of the invention, illustrated on the figure 4 the 2n relays can be further reduced to a number n if each pair of relays Rs1 - k, Rs1 - k 'is replaced by a single relay and logic gate type means for forming, for each relay Rs1 - k an output to a first state (state "1") and an output to a complementary state (the state "0").

Each combination of the n inputs of the relays Rs1-k, and therefore a corresponding combination of the line selection conductors Ck, Ck ', leads to the selection or opening of one or more lines of the matrix for a transfer of a drop on this line.

For example, in the embodiment of the figure 3 , the two RSL-i and RSL-i 'relays are replaced by a single RSL-i' relay using a complementary logic function ( figure 4 ). This allows the number of relays to be divided by 2.

In this embodiment, there are only n relays left.

It is also possible to encode or locate the 2 ⁿ rows of the matrix by an n-digit binary code, each line being selectable by assignment, at the input of the n relays Rs1-k, of the coding for this line.

In this case, it is therefore possible to implement a logic for coding the lines in binary numbers, and to assign this coding to the control of the line selection relays, and therefore to the selection of the lines themselves. To select a line, its binary code is assigned to the input of the line selection relays.

For example we can refer to the figure 4 , corresponding to the case of 8 electrode lines, comprising 3 line selection electrodes per line, 6 line selection conductors C1 - C6, but only 3 line selection relays.

In this example, the coding of the lines using the state of the relays is summarized in the following Table II: Table II Line Binary number State of the RSL3 relay State of the RSL-2 relay State of the RSL1 relay 0 000 0 0 0 1 001 0 0 1 2 010 0 1 0 3 011 0 1 1 4 100 1 0 0 5 101 1 0 1 6 110 1 1 0 7 111 1 1 1

For a given binary digit, a single line will have the 3 line selection electrodes at potential V1, and only one line will be selected.

For example, the number 101 makes it possible to define the state of the 3 relays allowing the 3 electrodes ESL-1, ESL-2, ESL-3 of line 5 to be at potential V1.

Only the drops placed on this line will be able to circulate.

The other drops will not be able to cross the ESL electrodes because at least one of them is at potential V0.

The assignments or connections of the line selection electrodes to line selection conductors Ck, Ck 'are, in this embodiment, the same as in the first embodiment.

Likewise, in this embodiment also, means 40 for controlling the relays can be provided, for example programmable digital means (PC or other) to which the n relays are connected and which can drive these relays.

These means may be provided with a screen 42 allowing the user to select a line on which a drop must be able to be transferred. For example, the matrix is represented on this screen and the user selects a drop transfer line, using a cursor or a stylus to designate the line or lines retained directly on the screen.

Or an automatic program can select the lines and send the corresponding control signals to the electrodes.

Means for storing the means 40 make it possible to store the information making it possible to select one or another line, for example the information in Table II as above, in the form of this table or in an equivalent form.

On instruction of an operator, for example on selection as described above, or on instruction of an automatic program, the digital means select, in the storage means, the data for opening or closing the relays Rs1 -k necessary, and thus activate the necessary Ck electrodes.

In general, whatever the embodiment envisaged, two operating modes can be distinguished.

In a first case, for a given line, a drop spreads simultaneously on all line selection electrodes of this line, in a second case the drop moves successively on the line selection electrodes of this line.

With the first operating mode, the different row selection electrodes of the same line are activated simultaneously. For example, the control means 40 are specifically programmed to simultaneously activate these line selection electrodes. Or an operator can choose, on a case-by-case basis, between simultaneous activation and subsequent activation.

For this, the liquids and technologies used (confined system or open system) allow the drops to spread over the entire series of these line selection electrodes.

This is usually the case of confined systems. A confined system includes, in addition to the substrate as illustrated on the figure 1 , a second substrate 11, which faces the first, as illustrated on the figure 9 or as described in the MG Pollack document cited in the introduction to this application. On the figure 9 , references 13 and 15 respectively denote a hydrophobic layer and an underlying electrode. The reference 17 designates an orifice made in the upper substrate 11 (or cover) and serves as a well for introducing a liquid.

For an open system, liquids with a low surface tension (for example water with surfactants) are preferably used.

Depending on the surface tensions of the liquids and the dimensions of the electrodes, it may be difficult to obtain a complete spread of the liquid on all the n line selection electrodes of the same line, activated simultaneously, when the number n is high (by example: n> 3 or 4).

To circumvent this problem, it is possible to modify the geometry of the electrodes in order to minimize the total length of the different line selection electrodes, and thus to limit the spreading length of the drop.

This is achieved, for example by using rectangular line selection electrodes, as illustrated in FIG. figure 5 . The long side of each rectangle is arranged perpendicular to the direction of the line.

With the second operating mode, the row selection electrodes are driven consecutively.

Indeed, for some configurations, (for example in an open system with drops with high surface tension), it may be difficult to spread a drop, simultaneously on all line selection electrodes of the same line.

By driving consecutively the line selection electrodes of the same line (ESL-1 then ESL-2, until ESP-n, or the reverse if the electrodes are numbered in the opposite direction) we move step by step the selected drop along a line, on the different line selection electrodes placed consecutively to the potential V1.

If one of the line selection electrodes is placed at potential VO, the drop is stopped.

To select a new drop is carried out a reset, which is to replace at the beginning of line all drops stopped on one of the line selection electrodes. For example, the electrodes preceding the one on which the drop is located are reactivated in order to raise the drop along the line.

Variants for the formation of a drop will be described.

It is possible to form drops from a reservoir R through a line of electrodes which is connected to this reservoir and which itself is part of an electrode matrix.

For this purpose, a series of electrodes E1 - E4 of a line of a matrix is activated, this line being connected to a reservoir R as shown in FIG. Figure 6A , which leads to the spreading of a drop, and therefore to a liquid segment 50 as shown in FIG. Figure 6B .

Then, the liquid segment obtained is cut off by deactivating one of the activated electrodes (electrode Ec on the Figure 6C ). A drop 52 is thus obtained, as shown in FIG. Figure 6D .

The method according to the invention can be applied by inserting the selection electrodes between the reservoir R and one or more electrodes Ec ( Figure 6C ) said breaking electrode.

According to the invention, the selection electrodes make it possible to select the lines where the drops are to be formed, to stretch the liquid up to the cutoff electrodes to form a drop.

An example of an application will now be described in connection with the Figures 7A to 7D .

It is a fluidic processor for combinatorial chemistry.

In this example, the chip has 2 x 2 ⁿ reservoirs Rk, k = 1, ..., 2 ^{n + 1} , and a corresponding number of electrode lines.

Each reservoir is associated with a line of electrodes for the manufacture of a drop. The set of lines thus forms a matrix as already described above.

n line selection electrodes, as previously described, are located on each line.

The Figure 7B represents the first line, with its line selection electrodes Esl and the reservoir R1. The other lines have a similar structure.

All electrode lines from the reservoirs result in a common electrode line 60, which may also include line selection electrodes. The various reagents are brought onto this line 60, in the form of drops, to be mixed.

The structure of the Figure 7A is symmetrical with respect to this line 60, and for this reason has 2 x 2 ⁿ lines. But a structure according to the invention can also be asymmetrical and comprise only 2 ⁿ lines, all located on one side,
or at 90 °, with respect to the common line 60.

The line selection conductors, arranged according to one of the embodiments of the invention, are not represented on the Figures 7A and 7B but are underlying a hydrophobic insulating layer, as illustrated on the Figure 1A .

These line selection conductors are connected to control means such as the means 40, 42 of the figure 4 .

According to a variant, it is possible to arrange the lines, each provided with line selection electrodes and connected to a tank R1,... Rk, R '1, ... R' k ', in a perpendicular architecture, according to a scheme such as that of the Figure 7C . The lines are perpendicular to common lines 160, 162.

According to another variant, it is possible to arrange the lines, each provided with line selection electrodes and connected to a tank R1,... Rk, R'1,... R 'k', R1, .. .Rj, R '1, ... R' j 'in a square architecture, according to a diagram such as that of the Figure 7D . The lines are perpendicular to common lines 260, 262, which form a square.

Other arrangements are possible and allow to perform any type of circuit or fluidic processor.

The line selection conductors, arranged according to one of the embodiments of the invention, are not represented on the Figures 7C and 7D but are underlying a hydrophobic insulating layer, as illustrated on the Figure 1A .

These line selection conductors are connected to control means such as the means 40, 42 of the figure 4 .

Thanks to the invention it is possible to program a large number of possible combinations of mixtures between the different reagents.

For the analysis of the results, the chip may comprise a detection zone (not shown in the figure) in which detection can be carried out, for example by colorimetry,
or by fluorescence, or electrochemistry.

The chip may optionally include other inputs / outputs or reservoirs 62 for injecting a sample to be mixed with, successively, a combination of the different reagents, each one coming from a reservoir connected to a line of electrodes, or to a zone 64, called the trash zone, to evacuate the liquids after analysis.

The invention applies not only to matrices with 2 ⁿ lines (n> 0 or 1), but also to any matrix of p lines (p integer), with 2 ⁿ <p <2 ^{n + 1} , n integer . In this case, a matrix of 2 ^{n + 1} lines is processed according to one of the embodiments described above, and the excess lines are then eliminated in this scheme.

The figure 8 gives an example of matrix with 16 lines (j = 0, ... 15), with connections to 8 line selection conductors according to the invention.

The switches or relays are schematized by 4 blocks Rs1-i (i = 1-4), which can take one or the other of the forms described above in connection with one of the embodiments of the invention. .

The deletion of, for example, 3 lines is symbolized by the broken line 70. The lines j = 13, 14, 15 being eliminated, there remains a configuration comprising 15 lines, whose 8 lines j = 0 - 7, each of these 8 lines comprising at least 3 (actually: 4) line selection electrodes Es1 - 1, 2, 3, connected to the conductors C1, C1 ', C2, C2', C3, C3 'according to the invention (block 72 of the figure 8 groups these connections).

The device then furthermore comprises two additional line selection conductors C4 and C4 'which, for the lines 0 to 7 are respectively completely occupied or empty, and therefore do not intervene in the marking of the lines.

A device comprising p lines, with 2 ⁿ <p <2 ^{n + 1} therefore comprises a device with 2 ⁿ lines according to the invention. Each of these lines has no more n line selection electrodes, but n + 1, of which n are connected as already described above in connection with the figures 3 or 4 .

The invention therefore makes it possible to produce a method and a system for addressing an electro-fluidic matrix having any number of lines.

A device according to the invention can be realized in a structure such as that illustrated on the Figures 1A - 1C the electrodes, arranged in a matrix, being situated under an insulating layer 6 and a hydrophobic layer 8.

The substrate 1 is for example silicon
or glass or plastic.

Typically, the distance between the conductor 10 ( Figures 1A - 1C ) on the one hand and the hydrophobic surface 8 on the other hand is for example between 1 micron and 100 microns or 500 microns.

The conductor 10 is for example in the form of a wire diameter between 10 microns and a few hundred microns, for example 200 microns. This wire may be a gold or aluminum wire or tungsten or other conductive materials.

When two substrates 1, 11 are used, in the case of a confined structure ( figure 9 ), they are separated by a distance of, for example, 10 μm and 100 μm or 500 μm.

In this case, the second substrate comprises a hydrophobic layer 13 on its surface intended to be in contact with the liquid of a drop. A counter electrode 15 may be buried in the second substrate, or a planar electrode may cover a large part of the hood surface. A catenary can also be used.

Whatever the embodiment considered, a drop of liquid 2 will have a volume between, for example, 1 nanolitre and a few microliters, for example between 1 nl and 5 .mu.l.

In addition, each of the electrodes of a row of the matrix will have for example a surface of the order of a few tens of μm2 (for example 10 μm2) up to 1 mm 2, depending on the size of the drops to be transported, the spacing between neighboring electrodes being for example between 1 .mu.m and 10 .mu.m.

The structuring of the electrodes of the matrix can be obtained by conventional methods of micro-technologies, for example by photolithography, the electrodes being for example made by depositing a metal layer (AU, or AL, or ITO, or Pt, or Cr, or Cu) and then photolithography.

The substrate is then covered with a dielectric layer of Si3N4 or SiO2. Finally, a hydrophobic layer may be deposited, for example a teflon deposit made by spinning.

The same techniques apply to the realization of the second substrate of the figure 9 in the case of a confined device.

Methods for producing chips incorporating a device according to the invention can also be directly derived from the methods described in the document FR - 2 841 063 .

Whatever the embodiment, the electrodes of at least one line preferably have a sawtooth profile like that illustrated in FIG. figure 10 . The saw teeth of the consecutive electrodes fit into each other. This makes it easier to move the menisci from one electrode to another.

An alternative embodiment of a device according to the invention will be exposed in connection with the figure 11A

This is an array of electrodes, or a series of multiplexing series.

It is indeed possible to put in series several electrode systems as described above in connection with one of the figures 3 , 4 or 8 or one of the variants of the invention already described above. A matrix structure is obtained. This configuration makes it possible to selectively move drops between two parallel electrode columns EPI, EP2, EP3, etc. EPn. In addition, one or more column (s) 200 of electrodes can be placed at one or more points of the matrix making it possible to pass a drop from one electrode line to the other.

Line selection electrodes Es1-i (i = 1 - 3), Esl-i '(i' = 1-3), Esl-i "(i" = 1-3) are arranged on each line of electrodes . The number of 3 line selection electrodes is given as an example and could be any.

The other electrodes, which are not line selection electrodes, are connected to parallel relays 300, as already explained above: each electrode column is connected to a parallel relay.

The conductors Ci, Ci 'can be arranged as illustrated on the Figure 11B : there are then as many of these drivers as on the figure 3 or 4 , and as many relays (not shown on the Figure 11B ) than on the figures 3 or 4 . Each line selection electrode Esl-1, Esl-2, Esl-3 is connected to these conductors as on the figure 3 or 4 . The same is true for the electrodes Esl-1 ', Esl-2', Esl-3 ', - Esl-1 ", Esl-2", Esl-3 ".

In this case, the electrodes Esl-1, Esl-1 ', and Esl-1 "of one and the same line are activated at the same time, a drop, placed on one of the lines, will advance step by step, of a system electrodes to another arranged in series therewith.

According to a variant, not shown in the figures, to each set of electrodes as described above in connection with one of the figures 3 , 4 or 8 or with one of the variants of the invention already described above, is associated a set of 6 conductors C _k , C _k , (k = 1,2,3). For the entire device of the figure 11A we have 3x6 conductors, and as many relay means Rsl-i (i = 1 - 3) to control.

• sur chaque ligne, n électrodes dites de sélection (Esl - i), l'ensemble de ces électrodes de sélection de ligne étant reliées à 2n conducteurs (C1, C1', C2, C2', C3, C3') de sélection de lignes, 2^n-1 électrodes de sélection de lignes de 2^n-1 lignes étant connectées à chaque conducteur de sélection de lignes,
• des moyens (Rsl-k, Rsl-k') de sélection, pour sélectionner un ou plusieurs conducteurs de sélection de ligne.

Serialization of several electrode systems, preferably having the same number of line selection electrodes, applies not only to 3 electrode systems, each having 8 lines, as described above in connection with the example of Figures 11A , 11B , but also at k (k any integer) system of 2 ⁿ lines of an electro-fluidic device according to the invention, each line having N electrodes (n <N ), this device comprising:

• on each line, n selection said electrodes (Esl - i), all of these line selection electrodes being connected to 2n conductors (C1, C1 ', C2, C2', C3, C3 ') of lines selection , 2 ^{n-1 line} selection electrodes of 2 ^n-1 lines being connected to each line selection conductor,
• selection means (Rs1-k, Rs1-k ') for selecting one or more line selection conductors.

This type of serialization can also be applied to an addressing device of a matrix of electrodes of p lines, with 2 ⁿ <p <2 ^{n + 1} lines, of an electro-fluidic device, comprising a 2 ⁿ line device according to the invention.

Another example of a chip according to the invention, for carrying out storage operations, and / or mixing, and / or dilution will be described in connection with the figure 12 .

• deux réservoirs principaux R₁ et R₁₆ ouverts sur l'extérieur par des puits 317 et 417, par exemple similaires au puits 17 de la figure 9,
• et 14 réservoirs secondaires R₂ à R₁₅.

It has n reservoirs (here: n = 16 by way of example, one can also have any number n of reservoirs, with n ≥ 2) R ₁ - R ₁₆ distributed as follows in the represented configuration:

• two main tanks R ₁ and R ₁₆ open on the outside by wells 317 and 417, for example similar to the well 17 of the figure 9 ,
• and 14 secondary tanks R ₂ to R ₁₅ .

The n tanks communicate with each other (that is to say that liquid volumes can be moved between these tanks) by a bus 301 consisting of a line of electrodes. The drops are placed or dispensed on this bus 301 by means of lines of line selection electrodes Esl-i, Esl-i 'according to the invention. The steering of these lines is for example one of the driving modes described above in the context of the present invention. The conductors C _k , C _{k '} and the relays Rs1 are not shown in this figure for the sake of clarity. Various modes of operation of a reservoir with one or more electrode lines have also been described above in connection with the Figures 6A - 7D and are applicable to the present embodiment.

With this device the figure 12 , a drop of a liquid from the tank R ₁ or R ₁₆ can be selected, as well as at least one drop of one of the secondary tanks R ₂ - R ₁₅ and these drops can be mixed by electrowetting on the path of electrodes 301.

An example of mask design used for photolithography of the electrical level of electrodes is reported on the figure 13A . This figure clearly shows the structure of the electrodes, in particular those leading from each tank to the bus line 301. The chip here comprises 16 tanks, which requires 8 electrical connections (as in figure 8 ) not shown on the figure 13A .

The bus 301 consists of an activated electrode line 3 to 3. Three relays make it possible to move a drop across the entire bus. The bus and its connection to the relay-controlled conductors 330, 331, 332 is illustrated in more detail on the Figure 13B the electrodes 301-1, 301-4, 301-7 will be activated simultaneously; then the electrodes 301-2, 301-5, ... etc will be activated simultaneously, ... etc.

References 320, 321 of the figure 13A represent the passages of the connection line of an electrode of the bus 301 to the conductor 330. The line passes under the conductors 331, 332, which explains that it passes into the substrate at 320, then leaves at 321 to come to driver contact 330. The same principle applies to all other connections in this figure. A second electrical level (not shown on the figure 13A ) is thus realized in order to electrically interconnect certain connection lines. Only the connections to the nearest conductor (for example the connection of the electrodes of the bus 301 to the conductor 332) do not require this passage under the other conductors.

Reference 400 designates another connection, from a line selection electrode 411 to a conductor 410 via a conductor 401.

A comb 340 gathers all the contacts. References 341, 342 designate electrodes for making contact at a lid.

All line selection conductors are not shown in this figure for the sake of clarity.

Moreover, conductive lines 343 come from the comb 340 to connect the line selection conductors (represented or not) but also conductors providing other functions on the chip. Again for the sake of clarity of the figure, the conductors 343 are not shown completely, but interrupted (they end in the dashed figure).

In total with a control system working with a limited number of relays, here only 16 relays, we can control a hundred electrodes to handle liquids in the 16 tanks. The number of relays actually depends not only on the number of tanks, but also the other functions to activate on the chip.

The electrodes are formed of a conductive layer (eg gold) with a thickness of 0.3 μm. The patterns of the electrodes and connection lines are etched by conventional photolithography techniques. A deposit of an insulating layer is made, for example silicon nitride 0.3 μm thick. This layer is locally etched to resume the electrical contacts.

For the second electrical level mentioned above, the technology used is the same as for the electrode level, ie a metal deposit and a photolithography. The interconnections (some of them only) are designated by the 400 marks on the figure 13A .

For example, the chip is silicon and measures 4 to 5 cm ² . The area of each electrode of the bus 301 and the electrodes of the tanks R ₂ to R ₁₅ is 1.4 mm ² square. The area of each ESL selection electrode is 0.24mm ² .

In one or more tanks, and in particular in the tanks R1 and R16, the liquid can be moved by electrowetting to the outlet of the tank, or to one of the electrodes of the electrode line connected to this tank.

In particular, on the figure 13A the reservoir R1 (respectively R2) has two electrowetting electrodes 448, 448 '(respectively 449, 449').

On the figure 13A it may be noted that the shape of the electrodes 448 and 449, respectively corresponding to the tanks R ₁ and R ₁₆ , is star. This form of the reservoir electrodes makes it possible to constantly plating or attracting the liquid towards the drop formation electrodes, the first of which at the outlet of the reservoirs are, respectively, the electrodes 450 and 451. This allows the initiation of the finger formation process to take place. liquid when dispensing drop, as explained above in connection with the Figures 6A - 6D .

According to a variant, represented in figure 13C it is possible to use an electrode 448 (and possibly an electrode 449 of the same shape) in the form of a comb, which guarantees, as in the case of the half-star, an electrode surface gradient. Indeed, electrowetting on insulation has the effect of spreading the liquid at the activated electrodes, which is reflected here by a liquid position to maximize the surface facing the electrode. This results in a "collecting" effect of the liquid near the first drop forming electrode 450.

This improvement also makes it possible to empty the tank completely.

Note that the fingers of the comb ( figure 3C ) or the half-star ( figure 13A ) can be square or pointed.

The figure 13D , which shows schematically the chip during operation, in section at the level of the tank R1, summarizes the technological stack. References 460, 461, 462, 463 designate electrowetting electrodes.

Reference 470 designates an interconnection of the electrowetting electrodes between different lines. Reference 471 designates an electrode of the comb 340 ( figure 13A ).

A thick resin (100 μm thick for example) is laminated and then structured by photolithography, and a hydrophobic treatment is performed (Teflon AF example from Dupont). This resin film is used to define the spacing 350, 351 between the lower plate 1 and the upper plate 11 ( figures 9 and 13D ). In addition, this resin film makes it possible to confine the reservoirs and to avoid the risks of contamination or coalescence between the drops placed in the different reservoirs. The chip is glued and then electrically wired onto a printed circuit board. The chip is covered with a polycarbonate lid (substrate 11) with an ITO electrode (indium-titanium oxide) and a thin hydrophobic layer 13. The fluidic component thus formed is filled with silicone oil.

An example of operation of this device, or fluidic protocol, will be given.

With the previously described chip, it is possible to carry out a protocol making it possible to carry out successive dilutions. The liquid containing the solution to be diluted (liquid containing a reagent, and / or one or more biological samples, and / or beads, and / or cells, etc.) is dispensed into the reservoir R ₁₆ . The purpose of the protocol is to dilute the reagent, (respectively: sample, beads, cells). For this, the tank R ₁ is filled with the dilution buffer (water, biological buffer, etc.). The chip is driven by means such as the means 40, 42 of the figures 3 and 4 (typically: a PC programmed to implement a method according to the invention) and an instruction list, which corresponds to the dilution method to be implemented, is executed. Each instruction corresponds to an elementary operation.

• OUT 1 ou OUT 16: Dispense d'une goutte à partir d'un réservoir R₁ ou R₁₆.
• BUS(m,n) Déplacement d'une goutte sur le bus 301; m et n correspondent au numéro du réservoir de départ et au numéro de réservoir d'arrivée.
• STOCK(n): Stockage d'une goutte dans l'un des réservoirs R₂ à R₁₅.
• DISP (n) : Dispense d'une goutte depuis l'un des réservoirs R₂ à R₁₅ par les électrodes de sélection de ce réservoir, conformément à l'invention.

There may be for example 4 types of basic instructions:

• OUT 1 or OUT 16: Dispense of a drop from a tank R ₁ or R ₁₆ .
• BUS (m, n) Moving a drop on the bus 301; m and n correspond to the number of the start tank and the arrival tank number.
• STOCK (n): Storage of a drop in one of the tanks R ₂ to R ₁₅ .
• DISP (n): Dispense of a drop from one of the tanks R ₂ to R ₁₅ by the selection electrodes of this tank, in accordance with the invention.

So ( Figures 14A - 14D ) to form a drop of liquid containing the entity to be diluted, the instruction OUT (16) is executed. To store this drop in the tanks R _2, the instructions BUS (16,2) and STOCK (2) are successively executed. Then, a droplet "g2" is dispensed from the tank R2 ( Figure 14B ). Drop g2 is manufactured on the last line selection electrode ( Figure 14B ), on the bus side; a drop "g 1" is also formed from the tank R ₁ . This drop g1 is brought by the bus 301 facing the tank R2 ( figure 14C ). g1 and g2 are therefore placed on two adjacent electrodes, which naturally causes the coalescence of the two drops g1 and g2 in a drop g3 ( figure 14D ). Due to the geometry of the electrodes, g1 is larger than g2; for example, the volumes of g1 and g2 are respectively 141 nl and 24 nl. A dilution ratio of (144 + 24) / 24 is thus obtained, ie approximately 7.

The new drop G3 thus formed can be stored, for example in the tank R3. The dilution operation is repeated by forming a droplet g4 from R2 and a new drop from R1, the result being stored in the tank R4. This operation is repeated until, in each tank R2 to Rn, concentrations C1, C1 / 7, C1 / 49, Ci / ⁷ⁿ .

This situation is represented in figure 15 , which schematically represents the device of the figures 12 and 13A , and at which various concentrations in the tanks R ₂ - R ₆ are indicated.

In summary, the instructions to be provided to the control system 40, 42 of the fluid component to achieve 4 successive dilutions with storage of liquids in the tanks R2 to R16 are given in the following table. OUT16 Dispense of a drop of the R16 tank BUS (16.2) Move to the R2 tank STOCK (2) The drop is stored in the R2 tank DISP (2) Dispense of a droplet "g2" from R2 on the last electrode OUT (1) Exemption of a drop 'g1' from the tank R1 BUS (1,3) Move to the R3 tank (on the way the coalescing drops g1 and g2) STOCK (3) The drop is stored in the tank R3 DISP (3) Exemption of a droplet g4 from R3 on the last ES electrode OUT (1) Exemption of a new drop g5 from the tank R1 BUS (1.4) Move to the R4 tank (on the way the drops g4 and g5 coalescent) STOCK (4) The drop is stored in the R4 tank DISP (4) Exemption of a droplet g6 from R4 on the last ES electrode OUT (1) Dispense of a new drop g7 from the tank R1 BUS (1.5) Moving to the R5 tank (on the way, the g1 and g4 coalescing drops) STOCK (5) The drop is stored in the tank R5 DISP (5) Exemption of a droplet g8 from R5 on the last ES electrode OUT (1) Dispense of a new drop g9 from the tank R1 BUS (1.6) Move to the R6 tank (on the way the g1 and g9 coalescing drops) STOCK (6) The drop is stored in the R4 tank

The process can be repeated on all 14 tanks R2 to R15. Several drops can also be formed with equivalent concentrations.

For example, one can carry out 4 successive dilutions to obtain a C1 / 2401 concentration and then repeat the dilutions but still from the same tank R5. Thus, the other tanks R7 R8, R9 ... will be filled with a volume of liquid with the same concentration C1 / 2401.

After coalescence, the drop can be moved on the bus 301 to homogenize and / or mix the liquids. Typically 12 to 20 displacements on the bus electrodes are sufficient for efficient mixing. The line selection electrodes can also be used to make back-and-forth drops between the reservoirs and the bus 301 for stirring the liquids.

The figure 16 corresponds to a dilution carried out with fluorescent beads (Diameter 20 μm in water). With 4 dilutions one goes to a high concentration of balls (tank R2: 400 balls for 140nl) to a few balls (tank R3: 80 balls, tank R4: 27 balls, tank R5: 8 balls, each time for 140 nl).

The same protocol can be performed with cells. Thanks to the implementation of the invention it is possible to handle drops containing only a few cells, or even a single cell. One can then apply a biological protocol on this drop to study and / or analyze the behavior of the cell. This protocol can be performed in parallel on a very large number of droplets. One of the applications is the "screening" of drugs.

The figure 17 represents a variant or an improvement of the device of the figure 4 in which only one relay device Rs1-k is required for two electrode lines Ck, Ck '. The references are identical to those of the figure 4 .

A microfluidic switching device 501, 502, 503 is used in combination with each relay.

Such a microfluidic switching device operates on the following principles, which will first be explained in the context of an open configuration. So we consider the case, illustrated on the figure 18 , and close derivative of the case illustrated in Figures 1A - 1C , where the driver 10 is interrupted. The end 33 of a second conductor 12, which may be at a floating potential, is situated at a short distance from the end 11 of the first conductor 10. This distance is such that, if, by simultaneous activation of the electrodes 4-1, 4-2, 4-3, the drop 2, after being brought to the end 11 of the conductor 10, is stretched, it puts, in its position 2 'shown in broken lines on the figure 18 both ends 11 and 33 in contact and carries the conductor 12 at the same potential as the conductor 10.

The reverse operation can then be performed, the drop then returns to its initial position 2 and the driver 12 is no longer at the potential of the driver 10.

In this operation, the drop 2 is stretched, but not displaced. In addition, the contact is made by stretching the drop on the flat surface 8. A switching or a change of state therefore results from a stretching of the drop in order to bring into contact two lines 10, 12.

In the initial state, the drop 2 may be formed on a reservoir electrode and stretched on another adjacent electrode 4-3.

From the logical point of view, it will be assumed that the potential 0 of the electrodes 4 causes the drop to spread.

As we see on the figure 19A the state of the line 12 is modified by the command Va on the electrode 4-3. If Va = 1, the drop does not spread on this electrode. Line 12 is therefore at a floating potential. If Va = 0, then the drop spreads over two electrodes 4-2 and 4-3 and the drop connects the line 12, whose state becomes identical to the catenary 10 which is the state "1" ( figure 19B ).

This produces a logic switch in micro-fluidics.

Another embodiment is illustrated on the figure 19C the switching of the drop towards a second conductor 12, 12 'varies according to the direction of deformation imposed on the drop by the activation of the electrowetting electrodes.

A device according to the invention may also be of closed configuration, of the type illustrated in FIG. figure 9 .

In this case, illustrated in figure 20 , the drop 2 goes, by stretching or deformation as in the previous case, to be switched between a first state and a second state. It is preferable, in this case, to have a low or zero voltage difference between the conductors 15 and the conductors 10 and 12, to avoid any risk of reaction or heating of the drop 2.

In the embodiments already described, the drop is, by stretching or deformation, brought into contact with two conductors located parallel to the substrate 1 or located between the substrate 1 and the cover 11.

According to another embodiment of the invention ( figure 21 ), in the closed configuration, the second substrate or the cover 11 comprises two electrodes or two conductors 11-2, 11-2 '. For each of these conductors, the layer 13 of hydrophobic material has a zone 107, 107 'for which the layer of hydrophobic material is either zero (the corresponding conductor 11-2, 11-2' of the cover is then apparent from the cavity), or low enough to pass a current or loads .

A portion 107, respectively 107 ', of the layer 13 of the cover 11 is for example etched, so that a drop 2 of conductive liquid makes it possible to make contact with the conductor 11-2, respectively 11-2' (drop in stretched position 2 ') of the hood. It is also possible to leave in zone 107 and / or zone 107 'a very fine hydrophobic layer, for example of the order of a few tens of nm for teflon; it is then porous to electrical charges. In this case, it is not necessary to completely etch the hydrophobic layer 13 in this zone.

The hydrophobic layer thickness allowing a certain porosity to the charges, sufficient to ensure a flow of the current with the counter electrode 11-2, respectively 11-2 ', will depend on the material of the layer 13. In the case of Teflon, we find indications on this subject in the document of S.-K. Cho et al., "Spliting a liquid droplet for electrowetting - based microfluidics," Proceedings of 2001 ASME International Mechanical Engineering Congress and Exhibition, Nov. 11 - 16, New York. With regard to Teflon, a layer of 20 nm, or for example less than 30 nm, is sufficient to pass charges. For each hydrophobic and / or insulating material, a test may be performed according to the thickness deposited to determine if the desired potential is achieved with respect to the electrode 15.

According to the invention the passage from one state to another can be controlled by the passage of a contact of the drop with a zone of the layer 13 where the latter is non-existent or weak, at a contact of the drop with two zones of this layer where the latter is non-existent or weak.

According to yet another embodiment of the invention ( figure 22 ), in open configuration (but which could be both in closed configuration), two electrodes 4-2 and 4-4 of the substrate 1 are non-passivated and not covered by the hydrophobic layer 8. The non-passivated areas of the first substrate are designated by references 17 and 17 '.

The two electrodes 4-2 and 4-4 are therefore used as contact zones for two states, one in which the droplet 2 is in contact only with the electrode 4-2, and the other in which the drop 2 is in contact with the two electrodes 4-2 and 4-4. The passage from one to the other is effected by electrowetting by activation of electrodes located between the elongated electrodes.

Finally it is possible to combine the various embodiments above. For example, in figure 23 a device according to the invention combines a cover, with an electrode 13 whose area or portion 107 is without a hydrophobic layer, or has a hydrophobic layer of very thin thickness, and two conductors 10, 12 arranged in the cavity between the two. substrates, parallel to the surfaces of these two substrates which delimit said cavity.

Thus the switching can take place between the zone 107 and the conductor 12.

Complex functions can be developed from one of the basic configurations discussed above.

The figure 24A represents a function "complement", so that the output 12 is never at a floating potential.

In this figure, at least 4 electrodes 4-1, 4-2, 4-1 ', 4-2' are concerned. The electrodes 4-1 and 4-1 'are respectively at the state 1 and 0, while the electrodes 4-2 and 4-2' are at an initially potential potential Va.

Each of the two catenaries 10 and 10 'plays the same role, respectively for the electrode 4-1, and for the electrode 4-1', as already explained above for the catenary 10 vis-à-vis the electrode 4-1.

Two states are then possible.

When Va = 1 ( figure 24B ), the drop 2 ₁ , located on the electrode 4-1, remains on this electrode, while the drop 2 ₁ 'stretches to the branch 12 ₁ of the catenary 12. The catenary 12 is then at potential Vc = 0, complementary to Va = 1.

When Va = 0 ( figure 24C ), the drop 2 _{1 '} , located on the electrode 4-1', remains on this electrode, while the drop 2 ₁ stretches to the branch 12 ₁ of the catenary 12. The catenary 12 is then at potential Vc = 1, complementary to Va = 0.

The complement function explained above in connection with the Figures 24A - 24C can be symbolized by a single block I, as illustrated in figure 24D which thus transforms a voltage V _a into its complement V _a .

This device can advantageously be used in a device according to the present invention.

In the diagram of the figure 17 , the use of a block I 501, 502, 503 on each conductor Ck 'makes it possible to assign to this conductor a complementary or inverse state of the state assigned to the conductor Ck. Relays Rsl-1, Rsl-2, Rsl-3, have the same function as in the case of the figure 4 . But the use of the micro-fluidic switching component makes it possible to simplify the structure of the figure 4 . The control of the electrodes to activate each microfluidic component can again be provided by the means 40, 42.

• des moyens de déplacement d'une goutte de liquide par électromouillage, comportant un substrat hydrophobe 8 et au moins deux électrodes d'électromouillage 4-1, 4-2, 4-3, 4-4,
• un premier et au moins un deuxième conducteurs 10, 31, 12, 107, 107', 17, 17', dits conducteurs de contact, avec lesquels une goutte 2 de liquide conducteur peut entrer en contact électrique, dans un premier état dans lequel la goutte est en contact électrique avec seulement le premier conducteur et dans un deuxième état dans lequel la goutte est en contact électrique avec le premier et le deuxième conducteurs,
• des moyens pour commuter par électromouillage une goutte entre le premier état et le deuxième état.

Each block 501, 502, 503, is a device for forming a complementary function of a voltage, called input voltage. Such a device comprises two switching devices, each switching device comprising:

• means for moving a drop of liquid by electrowetting, comprising a hydrophobic substrate 8 and at least two electrowetting electrodes 4-1, 4-2, 4-3, 4-4,
• a first and at least a second conductor 10, 31, 12, 107, 107 ', 17, 17', said contact conductors, with which a drop 2 of conductive liquid can come into electrical contact, in a first state in which the drop is in electrical contact with only the first conductor and in a second state in which the drop is in electrical contact with the first and second conductors,
• means for electrowetting a drop between the first state and the second state.

At least one of the two contact conductors of a switching device may include an elongated electrowetting electrode 4-2, 4-4.

A switching device may further comprise a cover 11 with a hydrophobic surface 13 facing the hydrophobic layer of the substrate, at least one of the two contact conductors comprising an electrode 11-2, 11-2 'arranged in the cover, a portion 107, 107 'of the hydrophobic surface of this cover being either etched or having a sufficiently small thickness to pass electric charges.

The means for switching a drop may comprise means for switching a voltage applied to at least one electrowetting electrode, called the switching electrode, between a first value, for which the drop is not in contact with the second conductor, and a second value, for which the drop is in contact with the second conductor.

• un premier et un deuxième dispositif de commutation tel que décrit ci-dessus, les deux deuxièmes conducteurs 12₁, 12'₁ étant reliés à un conducteur unique 12, dit conducteur de sortie,
• des moyens pour appliquer la tension d'entrée (Va) aux deux électrodes de commutation 4-2, 4-2' des deux dispositifs de commutation.

A device for forming a function complementary to a voltage (Va), called the input voltage, therefore comprises:

• a first and a second switching device as described above, the two second conductors 12 ₁ , 12 ' ₁ being connected to a single conductor 12, said output conductor,
• means for applying the input voltage (Va) to the two switching electrodes 4-2, 4-2 'of the two switching devices.

The conductive liquid used for the drops 2 ', 2 ₁ used in a switching device can be a liquid conductive gel, or a low temperature fuse material (for example: lead, or tin, or indium or silver or alloy of at least two of these materials) which, by phase change, induces definitive or temporarily fixed contact (the phase change may indeed be reversible), or a conductive adhesive (hardening or solidifying by polymerization for example). The realization of a definitive contact, or the blocking of a switch, can indeed be useful, not to electrically power the contactor or logic functions while maintaining the spreading of the drop. Thus the switch or the logic function consumes energy only during the change of state.

Claims (37)

1. Device for addressing an electrode array of 2ⁿ lines of an electro-fluidic device, each line having N electrodes (n<N), comprising:

   - on each line, n so-called selection electrodes (Esl-i), all of these line selection electrodes being connected to 2n line selection conductors (C1, C1', C2, C2', C3, C3'), 2^n-1 line selection electrodes of 2^n-1 lines being connected to each line selection conductor,

   - selection means (Rsl-k, Rsl-k'), for selecting one or more line selection conductors.
2. Device according to claim 1, the electrodes ESL-k for selecting the different lines being, for a given value of "k", connected to two line selection conductors, the electrodes ESL-k being connected by packets of 2^k-1 alternatively to conductor Ck and to conductor Ck'.
3. Device according to claim 1 or 2, the selection means for selecting one or more line selection conductors comprising electrical selection relays.
4. Device according to one of claims 1 to 3, the means for selecting line selection conductors comprising 2n electrical selection relays (Rsl-1, Rsl-2, Rsl-3), each relay being connected to a single line selection conductor.
5. Device according to one of claims 1 to 3, the means for selecting line selection conductors comprising n electrical selection relays (Rsl-1, Rsl-2, Rsl-3), each relay being connected to two line selection conductors.
6. Device according to claim 5, each line selection relay being combined with means (31, 33, 35, 501, 502, 503) for generating, in addition to an input signal, a complementary signal.
7. Device according to claim 6, the means (31, 33, 35) for generating, by electrowetting, in addition to input signal, a complementary signal.
8. Device according to one of claims 1 to 7, the line selection electrodes being arranged successively along each line.
9. Device according to one of claims 1 to 8, the line selection electrodes being arranged non-successively along each line.
10. Device according to one of claims 1 to 9, the line selection electrodes of at least one line being in rectangular form, with the large side of each rectangle being arranged perpendicularly to the line.
11. Device according to one of claims 1 to 9, the line selection electrodes of at least one line being in square form.
12. Device according to one of claims 1 to 11, at least one electrode line of the array having a cutting electrode (Ec).
13. Device for addressing an electrode array comprising a plurality of addressing devices according to one of claims 1 to 12, called basic devices, arranged in series, each line of one of these devices being in series with a line of at least one second such device.
14. Device according to claim 13, the line selection conductors of one of the basic devices being common to all of the basic devices arranged in series.
15. Device according to one of claims 1 to 14, also comprising digital line selection means (40).
16. Device according to the previous claim, the digital line selection means (40) being programmed to select the lines of the electrode array according to a binary code.
17. Device according to claim 15 or 16, the digital line selection means (40) comprising means for selecting one or more lines of the array, and means for forming instructions for controlling line selection conductors according to the line(s) selected.
18. Device according to one of claims 15 to 17, the digital line selection means (40) comprising means for consecutively activating the line selection electrodes of a selected line.
19. Device according to one of claims 15 to 17, the digital line selection means (40) comprising means for simultaneously activating the line selection electrodes of a selected line.
20. Device for forming liquid drops, comprising a device according to one of claims 1 to 19, and means (R1, Rk) forming containers for liquids, each line of the array being connected to a container.
21. Device according to claim 20, 2ⁿ means forming 2ⁿ containers for liquids, each line of the array being connected to a single container.
22. Device according to claim 20 or 21, each line being connected to a common line (60, 301) of electrodes, in order to mix the liquid drops formed on the different lines.
23. Device according to claim 21 or 22, comprising a plurality of common lines (160, 162, 260, 262, 301), arranged perpendicularly to one another or in a square.
24. Device according to one of claims 20 to 23, at least one of the containers comprises electrowetting electrodes (448, 448', 449, 449') for bringing a liquid drop, from the container, to the corresponding electrode line.
25. Device according to the previous claim, one of the electrodes (448, 449) of the container being in the form of a comb or a star.
26. Device according to the previous claim, the star or the comb having fingers of which the ends are square or pointed.
27. Device according to one of claims 1 to 26, at least one of the lines comprising electrodes with a saw tooth profile.
28. Device for addressing an electrode array of p lines, with 2ⁿ<p<2ⁿ⁺¹ lines, of an electro-fluidic device, comprising a device with 2ⁿ lines according to one of claims 1 to 27.
29. Method for moving at least one liquid volume, using a device according to one of claims 1 to 28, comprising:

    - the movement of a fluid volume along at least one line of the array by activation of the electrodes of said line.
30. Method according to claim 29, the line selection electrodes of said line being activated consecutively.
31. Method according to claim 29, the line selection electrodes of said line being activated successively.
32. Method for forming a liquid drop, comprising the movement of a liquid volume according to one of claims 29 to 31, the spreading of this volume on a plurality of electrodes of said line by simultaneous selection of these electrodes, and the cutting of the spread volume by means of a cutting electrode (Ec).
33. Method for modifying the dilution of a first liquid, containing a first solution with a first concentration, using a device according to one of claims 1 to 28, means forming at least one first and one second container, respectively for said liquid and for at least one second liquid or a buffer, each container being connected to a line of the electrode array, which method comprises:

    - the formation of a drop of the first liquid, from the first container,

    - the formation of a drop of the second liquid, from the second container,

    - the mixing of the two drops to form a drop, with a second concentration different from the first.
34. Method according to the previous claim, the modification of the dilution of a first liquid being a reduction of this dilution, the second concentration being lower than the first.
35. Method according to one of claims 33 or 34, the first liquid containing a reagent, and/or biological samples, and/or beads, and/or cells.
36. Method according to one of claims 33 to 35, the second liquid or the buffer comprising water or a biological buffer.
37. Method according to one of claims 33 to 36, the device comprising a common electrode line (301) that connects the lines of the electro-fluidic device, and on which the drops are moved by electrowetting.

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