Method And Apparatus For The Manipulation And/Or The Detection Of Particles

• US 20090205963A1
• Filed: 07/19/2006
• Published: 08/20/2009
• Est. Priority Date: 07/19/2005
• Status: Active Grant

• Current Assignee: Menarini Silicon Biosystems S.P.A
• Original Assignee: Silicon Biosystems, S.p.A.
• Inventors: Medoro, Gianni, Manaresi, Nicolo
• Granted Patent: US 8,641,880 B2
• Time in Patent Office: Days
• US Class Current: 204/547
• CPC Class Codes: B03C 2201/24 for measuring or calculating of parameters, e.g. efficiency
• CPC Class Codes: B03C 5/026 using open-gradient differential dielectric separation, i.e. using electrodes of special shapes for non-uniform field creation, e.g. Fluid Integrated Circuit [FIC]
• CPC Class Codes: G01N 15/1031 by measuring electrical or magnetic effects
• CPC Class Codes: G01N 15/1459 the analysis being performed on a sample stream
• CPC Class Codes: G01N 27/44756 Apparatus specially adapted therefor

Abstract

Method and apparatus for the manipulation and/or control of the position of particles by means of time-variable fields of force. The fields of force can be of dielectrophoresis (positive or negative), electrophoresis, electrohydrodynamic or electrowetting on dielectric, characterized by a set of stable points of equilibrium for the particles.

Claims

1. A method for the manipulation of particles (BEAD) by means of an at least two-dimensional array of groups (BLOCK_i,j) of electrodes, comprising the steps of:

i. generating a first configuration of field of force (F_i), which presents at least one first point (CAGE_i,j) and at least one second point (CAGE_i,j+1) of stable equilibrium for said particles (BEAD), said points being positioned, respectively, on a first group (BLOCK_i,j) and on a second group (BLOCK_i,j+1) of said array immediately adjacent to the first, and being such that at least one particle (BEAD) is entrapped in said first point of stable equilibrium (CAGE_i,j);

ii. generating at least one second configuration of field of force (F_ii) such that a particle (BEAD) is pushed within a basin of attraction of said at least one second point of stable equilibrium (CAGE_i,j+1); and

iii. generating again said first configuration of field of force (F_i), such that said particle (BEAD) is attracted towards the second point of stable equilibrium (CAGE_i,j+1);

said method being characterized in that said first configuration (F_i) and said second configuration (F_ii) of field of force are generated by means of at least two different configurations of first voltages (Vrow_i[p] and Vcol_j[q]) applied to the electrodes of the first group of the array (BLOCK_i,j) and of second voltages (Vrow_i[p] and Vcol_j+l[q]) applied to the electrodes of the second group of the array (BLOCK_i,j+1).

2. The method according to claim 1, comprising an iterative execution of steps i) to iii) on a plurality of said groups of electrodes of said array arranged adjacent to one another two by two so as to displace at least one particle (BEAD) present in at least one of said groups of electrodes (BLOCK_i,j) along paths constituted by a succession of said adjacent groups of electrodes.

3. The method according to claim 1, characterized in that each group of electrodes (BLOCK_i,j) of the array is constituted by:

at least one first set of electrodes connected to voltages (Vphip, Vphin) by means of row signals (Vrow_i[p]);

at least one second set of electrodes connected to voltages (Vphip, Vphin) by means of column signals (Vcol_j[q]); and

at least one electrode connected to voltages (Vphip, Vphin) by means of a signal (Vcore) common to all the groups of electrodes of the array and such that each pair of adjacent groups of electrodes (BLOCK_i,j and BLOCK_i,j+1) can assume said at least one second configuration of field of force (F_ii) whilst all the other groups of electrodes of the array maintain said first configuration (F_i), by means of modification of the voltages applied via said row signals (Vrow_i[p]) and column signals (Vcol_j[q]) connected to said pair of adjacent groups (BLOCK_i,j and BLOCK_i,j+1) of electrodes.

4. The method according to claim 1, characterized in that each group of electrodes (BLOCK_i,j) of the array is constituted by at least one first set of electrodes connected to voltages (Vphip, Vphin) by means of electronic circuits (MUX_i,j and AND_i,j) controlled by means of a first set of digital row signals (row_i) and column signals (col_j) and by at least one electrode connected to voltages (Vphip, Vphin) by means of a second set of signals (Vcore) common to all the groups of electrodes (BLOCK_i,j) of the array such that each pair of adjacent groups of electrodes (BLOCK_i,j and BLOCK_i,j+1) can assume said second configuration of field of force (F ii) whilst all the other groups of electrodes of the array maintain said first configuration (F_i), by means of modification of the voltages applied to said pair of adjacent groups (BLOCK_i,j and BLOCK_i,j+1) of electrodes via said first set of row signals (row_i) and column signals (col_j), which are connected to the electronic circuits (MUX_i,j and AND_i,j) of said groups (BLOCK_i,j and BLOCK_i,j+1) of electrodes.

10. The method according to claim 1, characterized in that it comprises, in sequence, a plurality of steps of entrapping of said particles in points of stable equilibrium and of displacement of said points of stable equilibrium combined in such a way as to select one or more particles (BEAD).

11. The method according to claim 1, characterized in that it comprises, in sequence, a plurality of steps of entrapping of said particles in points of stable equilibrium and of displacement of said points of stable equilibrium combined in such a way as to reorder the arrangement of two or more particles (BEAD).

12. The method according to claim 1, characterized in that it comprises, in sequence, a plurality of steps of entrapping of said particles in points of stable equilibrium and of displacement of said points of stable equilibrium combined in such a way as to displace one or more particles (BEAD) present on one and the same group of electrodes (BLOCK_i,j).

13. The method according to claim 1, characterized in that it comprises, in sequence, a plurality of steps of entrapping of said particles in points of stable equilibrium and of displacement of said points of stable equilibrium combined in such a way as to separate and/or move away two or more particles (BEAD) positioned on one and the same group of electrodes (BLOCK_i,j) towards at least two different positions.

14. The method according to claim 1, characterized in that said field of force (F) comprises at least one of the following forces:

i. positive dielectrophoresis (PDEP);

ii. negative dielectrophoresis (NDEP);

iii. electrophoresis (EF);

iv. electrohydrodynamic flows (EHD); and

v. electrowetting on dielectric (EWOD)

5. A method for the manipulation of particles (BEAD) by means of an array of first groups of electrodes that form at least one lane (C_STORE;

VRCHJ), comprising the steps of;

i. generating a first configuration of field of force designed to create at least one point of stable equilibrium (CAGE_i,j) for said particles (BEAD), said point being positioned on at least one lane (C_STORE;

VRCHJ) and being such that at least one particle (BEAD) is entrapped in said at least one point of stable equilibrium (CAGE_i,j); and

ii. displacing by one or more positions, each defined by at least one electrode or by a first group of electrodes, all of said points of stable equilibrium previously generated along said at least one lane (C_STORE;

VRCHJ);

said method being characterized in that the points of stable equilibrium present on said lanes are generated and moved by means of the application to the electrodes of the first groups of electrodes forming said at least one lane (C_STORE;

VRCHJ) of at least three different configurations of voltages (V1_j, V2_j, V3_j).

6. The method according to claim 5, characterized in that it envisages manipulation of said particles (BEAD) by means of a plurality of lanes and by means of second groups of electrodes of said array that form parking cells (BLOCK_i,j) arranged alongside one another and/or alongside said lanes, said method comprising the steps of:

i. generating a second configuration of field of force designed to create at least one point of stable equilibrium (CAGE_i,j) for said particles (BEAD), which is positioned on a parking cell (BLOCK_i,j) and is such that at least one particle (BEAD) is entrapped in said at least one point of stable equilibrium (CAGE_i,j);

ii. generating a third configuration of field of force such that a particle (BEAD) entrapped in a parking cell (BLOCK_i,j) can be pushed into a basin of attraction of a point of stable equilibrium adjacent to the parking cell and formed by means of the electrodes of said lanes (VRCHJ); and

iii. displacing by one or more positions all the points of stable equilibrium present in said lanes (VRCHJ) along them;

where the points of stable equilibrium of said lanes are generated and moved by means of at least three different configurations of voltages (V1_j, V2_j, V3_j) applied to the electrodes of said lanes (VRCHJ); and

in which the different field configurations for pushing a particle (BEAD) from the point of stable equilibrium of one parking cell (BLOCK_i,j) to one of the points of stable equilibrium of the lanes (VRCHJ) or vice versa are generated by means of row voltages (Vrow_i) and column voltages (Vcol_j and Vcage_j) applied to the electrodes of the second groups (BLOCK_i,j) and by means of voltages (V1_j, V2_j, V3_j) applied to the electrodes of the first groups of electrodes forming said lanes (VRCHJ).

7. The method according to claim 6, comprising the further step of:

generating a fourth configuration of field of force such that a said particle (BEAD) can be pushed from a lane into a basin of attraction (CAGE_i+1) of a point of stable equilibrium belonging to a parking cell (BLOCK_i+1,j) different from the one in which said particle was before being displaced on the lane.

8. The method according to claim 7, characterized in that said movements of points of stable equilibrium and said field configurations necessary for pushing the particle (BEAD) from the point of stable equilibrium of a parking cell (BLOCK_i,j) to one of the points of stable equilibrium of the lanes (VRCHJ) and vice versa act on any number of particles simultaneously, to displace each particle along a different path.

9. The method according to claim 5, characterized in that for the manipulation of said particles (BEAD) by means of said array of first groups of electrodes, the latter are pre-arranged for providing at least two lanes (C_STORE and C_TEMP);

and in that it comprises the steps of;

i. generating at least one point of stable equilibrium (CAGE_i,j) for said particles (BEAD), which is positioned on at least one first lane (C_STORE) and is such that at least one particle (BEAD) is entrapped in said at least one point of stable equilibrium (CAGE_i,j);

ii. displacing by one or more positions all the points of stable equilibrium along one or more lanes (C_STORE) so that said at least one point of stable equilibrium (CAGE_i,j) can be shared by at least one second lane (C_TEMP); and

iii. displacing by one or more positions all the points of stable equilibrium along one or more lanes (C_STORE) so that said particle (BEAD) is entrapped in at least one point of stable equilibrium (CAGE_i,j) belonging to said at least one second lane (C_TEMP);

in which said points of stable equilibrium of said lanes are generated and moved by applying to the electrodes of said first groups of electrodes of the array at least three different configurations of voltages (V1_j, V2_j, V3_j) for each of said lanes.

15. A method for detection and/or characterization and/or quantification and/or recognition of cells or particles (BEAD) in aqueous suspension or aggregated in tissues comprising a measurement of impedance between at least one first electrode connected to at least one first row signal and at least one second electrode adjacent to said first electrode, said second electrode being connected to at least one first column signal, said method being characterized in that said measurement between said at least two adjacent electrodes is made by evaluating the impedance between said first row signal and said first column signal.

16. The method according to claim, characterized in that it is carried out further a detection and/or characterization and/or quantification and/or recognition of cells or particles (BEAD) in aqueous suspension comprising a measurement of impedance between at least one first electrode connected to at least one first row signal and at least one second electrode adjacent to said first electrode, said second electrode being connected to at least one first column signal, said method being characterized in that said measurement between said at least two adjacent electrodes is made by evaluating the impedance between said first row signal and said first column signal.

17. An apparatus for the manipulation of particles (BEAD), characterized in that it comprises:

i. an array of electrodes forming an array of blocks of groups (BLOCK_i,j) of electrodes arranged in rows and columns, each block comprising;

a first group of electrodes connected to column signals (Vcol_j[q]) common to all the first groups of the same column of blocks;

a second group of electrodes connected to row signals (Vrow_i[p]) common to all the second groups of the same row of blocks; and

a third group of electrodes connected to signals common to all the blocks of groups of electrodes (BLOCK_i,j) of the array of electrodes;

ii. means for generating at least two different voltages (Vphin, Vphip); and

iii. means for distributing said voltages (Vphin, Vphip) to said row signals (Vrow_i[p]) and to said column signals (Vcol_j[q]) and to said common signals;

in which said means for distributing said voltages (Vphin, Vphip) are such that for each pair formed by a first block (BLOCK_i,j) of groups of electrodes and by a second block (BLOCK_i,j+1) of groups of electrodes adjacent to the first block, at least one first configuration (F_i) and one second configuration (F_ii) of field of force are generated obtained by applying two different configurations of said two voltages (Vphin, Vphip) to the row signals (Vrow_i[p]) and column signals (Vcol_j[q] and Vcol_j+1[q]);

said first configuration (F_i) of field of force being designed to create at least one first point (CAGE_i,j) and at least one second point (CAGE_i,j+1) of stable equilibrium for said particles (BEAD), said points being positioned, respectively, on said first block (BLOCK_i,j) and on said second block (BLOCK_i,j+1) of groups of electrodes of the array; and

said second configuration (F_ii) of field of force being designed to push said particle (BEAD) possibly entrapped in said first point of stable equilibrium (CAGE_i,j) into a basin of attraction of said at least one second point of stable equilibrium (CAGE_i,j+1).

18. The apparatus according to claim 17, characterized in that said first group of electrodes of each said block (BLOCK_i,j) comprises at least one first electrode (ring_i,j_1) connected to a column signal (Vcol_j) common to all the groups of the same column;

said second group of electrodes of each block comprises at least one second electrode (ring_i,j_2) connected to a row signal (Vrow_i) common to all the groups of the same row; and

said third group of electrodes of each block comprises at least one third electrode (EL_i,j) connected to a common signal (Vcore), in which said third electrode (EL_i,j) is surrounded by said first electrode (ring_i,j_1) and said third electrode (EL_i,j) and said first electrode (ring_i,j_1) are surrounded by said second electrode (ring_i,j_2);

19. The apparatus according to claim 17, characterized in that said first group of electrodes of each said block (BLOCK_i,j) comprises at least one first electrode (elle_j) connected to a column signal (Venable_j) common to all the groups of the same column;

said second group of electrodes of each block comprises at least one second electrode (wallx_i) connected to a row signal (Vrow_i[x]) common to all the groups of the same row; and

said third group of electrodes of each block comprises at least one third electrode (EL_i,j) connected to a common signal (Vcore);

in which said second group of electrodes of each block moreover comprises at least one fourth electrode (wally_i) connected to a row signal (Vrow_i[y]) common to all the groups of the same row; and

where said third electrode (EL_i,j) is flanked in two directions adjacent by said first electrode (elle_j), and said first electrode (elle_j) is flanked by said second electrode (wallx_i) and said fourth electrode (wally_i).

20. The apparatus according to claim 17, characterized in that said first group of electrodes of each said block (BLOCK_i,j) is distinguished into electrodes with even column index and odd column index, whilst said second group of electrodes of each said block (BLOCK_i,j) is distinguished into electrodes with even row index and odd row index;

in which said third group of each block comprises at least one third electrode (EL_i,j) connected to a common signal (Vcore); and

in which said first group comprises at least one first electrode connected to a column signal (Vcol_i[D1]) common to the blocks of the same column with even column index or to a column signal (Vcol_i[D2]) common to the blocks of the same column with odd column index; and

at least one second electrode connected to a column signal (Vcol_i[U1]) common to the blocks of the same column with even column index or to a column signal (Vcol_i[U2]) common to the blocks of the same column with odd column index; and

in which said second group comprises at least one fourth electrode connected to a row signal (Vrow_i[R1]) common to the blocks of the same row with even row index or to a row signal (Vrow_i[R2]) common to the blocks of the same row with odd row index and at least a fifth electrode connected to a row signal (Vrow_i[L1]) common to the blocks of the same row with even row index or to a row signal (Vrow_i[L2]) common to the blocks of the same row with odd row index.

33. The apparatus according to claim 17, characterized in that it comprises at least two microchambers and in that it presents an arrangement of said electrodes of said array of electrodes such that it is possible to displace said particles (BEAD) from one microchamber to the other and vice versa by driving said electrodes with appropriate signals.

34. The apparatus according to claim 17, characterized in that said electrodes are made on a substantially planar substrate (SUB);

and in that it comprises a further electrode (ITO) made on a further substrate (LID) set at a distance from and facing said first substrate (SUB), said further electrode (ITO) being electrically connected to a further electrical signal.

21. An apparatus for the manipulation of particles (BEAD), comprising:

i. an array of electrodes forming an array of blocks of groups (BLOCK_i,j) of electrodes arranged in rows and columns, each block comprising;

a first group of at least one first electrode (EL_i,j) connected to a signal common to all the blocks; and

a second group of at least one second electrode (ring_i,j) connected to an output signal of a circuit (MUX_i,j), driven by at least one second circuit (AND_i,j);

ii. means for generating at least two different voltages (Vphin, Vphip); and

iii. means generating row signals (row_i) common to all the blocks (BLOCK_i,j) of the same row and column signals (col_j) common to all the blocks (BLOCK_i,j) of the same column for driving said circuits (AND_i,j) and by means of which the voltage (Vphin, Vphip) to connect to said at least one second electrode (ring_i,j) of each block (BLOCK_i,j) is selected;

where for each pair formed by a first block (BLOCK_i,j) and a second block (BLOCK_i,j+1) adjacent to the first block said means for generation of signals determine the creation of at least one first configuration (F_i) and one second configuration (F_ii) of field of force by applying two different configurations of values to the row signals (Vrow_i) and column signals (Vcol_j and Vcol_j+1) such that said first configuration (F_i) of field of force presents at least one first point (CAGE_i,j) of stable equilibrium and at least one second point (CAGE_i,j+1) of stable equilibrium for said particles (BEAD), said points being positioned, respectively, on said first block (BLOCK_i,j) and on said second block (BLOCK_i,j+1) of the array, and being such that said second configuration (F_ii) of field of force is designed to push said particle (BEAD) that is possibly entrapped in said first point of stable equilibrium (CAGE_i,j) into a basin of attraction of said at least one second point of stable equilibrium (CAGE_i,j+1).

22. The apparatus according to claim 21, characterized in that said first group of electrodes of each said block (BLOCK_i,j) comprises at least one first electrode (EL_i,j) connected to a signal common to all the blocks constituted by one (Vphin) of said different voltages;

and in that said second group of electrodes comprises at least one second electrode (ring_i,j) connected to the output signal of a circuit that constitutes a deviator (MUX_i,j), such that just one of two different signals (Vphin, Vphip) at input to the deviator can be connected at output from the deviator according to the value of the output signal of a further circuit (AND_i,j), which performs a logic function between the values of the row signals (row_i) and column signals (col_j); and

in which said first electrode (EL_i,j) is surrounded by said second electrode (ring_i,j).

23. An apparatus for the manipulation of particles (BEAD), comprising:

i. an array of electrodes comprising first groups of electrodes, each of which is constituted by at least one first electrode connected to a first signal (V1_j;

S1), by at least one second electrode connected to a second signal (V2_j;

S2) and by at least one third electrode connected to a third signal (V3_j;

S3) such that the set of said first groups of electrodes forms at least one first lane (VRCHJ;

C_STORE), designed to move said particles (BEAD) in a chosen direction;

ii. means for generating at least two different voltages (Vphin, Vphip); and

iii. means for distributing said voltages (Vphin, Vphip) to said at least one first signal (V1_j;

S1), second signal (V2_j;

S2) and third signal (V3_j;

S2);

so that each lane (VRCHJ;

C_STORE) can generate at least one first configuration (F_i) of field of force designed to create at least one first point of stable equilibrium (CAGE_i,j) for said particles (BEAD), which is positioned on said at least one first lane (VRCHJ;

C_STORE) and is such that at least one particle (BEAD) is entrapped in said at least one point of stable equilibrium (CAGE_i,j) and can be displaced along said first lane (VRCHJ;

C_STORE), simultaneously displacing all of said first points of stable equilibrium present on the first lane by applying to the electrodes of said first groups of electrodes at least three different configurations of voltages on said signals (V1_j, V2_j, V3_j;

S1, S2, S3).

24. The apparatus according to claim 23, characterized in that said array of electrodes moreover comprises an array of blocks (BLOCK_i,j) of groups of electrodes arranged in rows and columns for the manipulation of said particles (BEAD), each block (BLOCK_i,j) of the array comprising:

i. a second group of electrodes of said array connected to column signals (Vcage_j, Vcol_j) common to all the blocks (BLOCK_i,j) of the same column;

ii. a third group of electrodes of said array connected to row signals (Vrow_i) common to all the groups of the same row; and

iii. and a fourth group of electrodes of said array connected to signals (Vp_j) common to all the blocks (BLOCK_i,j);

such that each block (BLOCK_i,j) can constitute a parking cell (CAGE_i,j) for said particles arranged alongside one another and/or alongside said at least one first lane;

said apparatus comprising moreover means for distributing said voltages (Vphin, Vphip) to said row signals (Vrow_i) and to said column signals (Vcage_j, Vcol_j) and to said common signals (Vp_j) so that each block (BLOCK_i,j) of the array can generate at least one first configuration (F_i) and one second configuration (F_ii) of field of force by applying two different configurations of voltages (Vphin, Vphip) to the row signals (Vrow_i) and column signals (Vcage_j, Vcol_j) such that said first configuration (F_i) of field of force presents at least one second point of stable equilibrium (CAGE_i,j) for said particles (BEAD) positioned on said block (BLOCK_i,j) and such that said second configuration (F_ii) of field of force pushes said particle (BEAD) into a basin of attraction of said at least one first point of stable equilibrium formed by means of the electrodes of said at least one first lane (VRCH_j) and displaceable along said lane (VRCH_j).

25. The apparatus according to claim 24, characterized in that said means for distributing said voltages (Vphin, Vphip) to said row signals (Vrow_i) and/or to said column signals (Vcage_j, Vcol_j) and/or to said common signals (Vp_j) are constituted by signal-conditioning circuits and/or memory elements.

26. The apparatus according to claim 25, characterized in that said means for distributing said voltages (Vphin, Vphip) to said at least one first signal (V1_j), one second signal (V2_j), and one third signal (V3_j) are constituted by signal-conditioning circuits and/or memory elements.

27. The apparatus according to claim 23, characterized in that said array of electrodes moreover comprises:

i. second groups of electrodes, each of which is constituted by at least one first electrode connected to a fourth signal (T1), by at least one second electrode connected to a fifth signal (T2), and by at least one third electrode connected to a sixth signal (T3) such that the set of said second groups of electrodes forms at least one second lane (C_TMP), designed to move said particles (BEAD) in a chosen direction;

ii. at least one point of exchange formed by means of adjacent electrodes belonging to said first and, respectively, said second at least one lane; and

iii. means for distributing said voltages (Vphin, Vphip) to said at least one fourth signal (T1), fifth signal (T2) and sixth signal (T3);

so that each at least one first and second lanes (C_STORE and C_TEMP) is designed to generate selectively at least one first configuration (F_i) and one second configuration (F_ii) of field of force such that said first configuration (F_i) of field of force presents at least one first and one second point of stable equilibrium on said first and second lane (C_STORE or C_TEMP), respectively, said points being such that at least one particle (BEAD) is entrapped in said at least one first or second point of stable equilibrium and can be displaced along said lanes (C_STORE or C_TEMP), simultaneously displacing all of said first or second points of stable equilibrium present on the first or second lane by applying to the electrodes of said first and second groups of electrodes at least three different configurations of voltages on said signals (S1 and/or S2 and/or S3 and/or T1 and/or T2 and/or T3) and such that said second configuration (F_ii) of field of force is formed at said point of exchange and is designed to push said particle (BEAD) into a basin of attraction of said at least one second point of stable equilibrium obtained by means of the electrodes of the second lane (C_TEMP).

28. The apparatus according to claim 27, characterized in that it comprises at least one first microchamber (MCH) comprising:

one or more first lanes (VC_1), driven by at least three voltages (V1, V2 and V3), and at least one second (HCONV) lane, driven by at least three signals (H1, H2 and H3) with at least one first point of exchange between said first lane (VC_1) and said second lane (HCONV); and

at least one second microchamber (RCH);

characterized in that it comprises at least one third lane (RCONV), driven by at least three signals (R1, R2 and R3) and at least one second point of exchange between said second lane (HCONV) and said third lane (RCONV) such that it is possible to bring a particle from said first microchamber (MCH) into said second microchamber (RCH) through a said first (VC_1) and said second lane (HCONV), and said at least one first and at least one second point of exchange.

29. The apparatus according to claim 27, characterized in that it comprises at least one first microchamber (MCH) comprising at least one first lane (VC_1), driven by at least three signals (V1, V2 and V3) and at least one second (HCONV) lane driven by at least three signals (H1, H2 and H3) with a first point of exchange between said first lane (VC_1) and said second lane (HCONV), and at least one second microchamber (RCH);

characterized in that it comprises at least one third lane (RCONV) synchronous with said first lane and driven by said at least three signals (V1, V2 and V3) and at least one second point of exchange between said second lane (HCONV) and said third lane (RCONV) obtained by means of an electrode driven by a signal (THR) such that it is possible to bring a particle from said first microchamber (MCH) into said second microchamber (RCH) through said first lane (VC_1) and said second lane (HCONV) and said first and said second points of exchange.

30. The apparatus according to claim 27, characterized in that said means for distributing said voltages (Vphin, Vphip) to said signals are obtained by means of signal-conditioning circuits and/or memory elements.

31. The apparatus according to claim 27, characterized in that it is divided by a diaphragm (CHW) made of polymeric material into two microchambers (MCH, RCH), a first microchamber (MCH) comprising:

a. a first multiplicity and a second multiplicity of lanes forming a vertical closed loop (VC1<sub>—

1</sub> . . . VC1_NCV and VC2_1 . . . VC2_NCV), designed to form each a plurality (NI) of said points of stable equilibrium (CAGES) for entrapping said particles (BEAD), by means of three phases (V1, V2 and V3), connected repeatedly at respective iterations (I_1 . . . I_NI) of groups of three electrodes on each lane;

b. a first horizontal lane and a second horizontal lane (HCONV_UP, HCONV_DOWN), respectively, an upper one and a lower one, driven by four phases (H1, H2, H3 and H4) and comprising a plurality (NCV) of points of exchange with the vertical lanes, active in one of said phases (V2+H3), so that it will be possible to transfer simultaneously the contents of at least one point of stable equilibrium from the vertical lanes to the first horizontal lane or second horizontal lane;

c. a third horizontal lane (HCONV_AUX), driven by four phases (AUX1, AUX2, AUX3 and AUX4), which comprises a plurality (NCAUX1) of points of exchange with the upper horizontal lane (HCONV_UP) and an identical number (NCAUX2) of points of exchange with the lower horizontal lane (HCONV_DOWN), situated in positions corresponding to one another;

d. a completely programmable array of electrodes designed to form in use an array of individually programmable attraction cages for said particles defined by points of stable equilibrium of a field of force generated via said electrodes;

e. a first vertical dump lane and a second vertical dump lane (VCW_UP and VCW_DOWN), driven by three phases in a way substantially similar to said vertical lanes (VC1_i and VC2_j), which have the function of removing undesired particles from the array; and

f. a vertical long dump lane (VCW_LONG), having a dimension approximately twice that of the other said vertical lanes (VC1_i and VC2_j) set in a portion of said first microchamber (MCH) situated on the opposite side with respect to the array.

32. The apparatus according to claim 31, characterized in that said second microchamber (RCH) comprises:

an exit lane (RCONV), driven by four phases (R1, R2, R3 and R4), for conveying particles of interest leaving said array into the second microchamber, through a discontinuity of said diaphragm made of polymeric material (CHW) constituting a passage of communication between the two microchambers; and

a horizontal feedback lane (HCONV_FB), driven by four phases (FB1, FB2, FB3 and FB4), lying substantially on one and the same straight line identified by said auxiliary horizontal lane, by means of which it is possible to bring a particle back from the exit lane (RCONV), and hence from the second microchamber (RCH), into the array, once again through the aforesaid passage in the diaphragm (CHW).

35. An apparatus for detection and/or characterization and/or quantification and/or recognition of cells or particles (BEAD) in aqueous suspension or aggregated in tissues, comprising:

i. an array of groups of electrodes comprising a first group of electrodes connected to column signals (Cj) common to all the groups of the same column and at least one second group of electrodes connected to row signals (R1) common to all the groups of the same row;

ii. means for generating at least one voltage (Vin);

iii. at least one circuit for reading the impedance (Zcage_i,j) given by the intersection of a row (Ri) and a column (Cj); and

iv. means (MRi) for distributing said voltage (Vin) to said row signals (Ri) and means (MCj) for distributing said column signals (Cj) to said at least one read circuit;

in which by connecting said read circuit to a column (Cj) and by applying said voltage to a row, (Ri) the output signal (Vout and/or out) of said read circuit is affected by the value of the impedance (Zcage_ij) between that column and that row.

36. The apparatus according to claim 35, characterized in comprising means for reading the variation of impedance at one or more potential holes (CAGE) due to the presence of one or more particles (BEAD).

37. The apparatus according to claim 36, characterized in that said means for reading the variation of impedance are obtained by means of row signals (Ri) and column signals (Cj) such that at least one or more particles (BEAD) alter the value of impedance due to the intersection between at least one row (Ri) and at least one column (Cj).

38. The apparatus according to claim 37, characterized in that said column signals (Cj) are obtained on a first substantially planar substrate (SUB) and in that said row signals (Ri) are obtained on a further substrate (LID) set at a distance from and facing said first substrate (SUB).

39. The apparatus according to claim 36, characterized in that said means for reading the variation of impedance are obtained by means of the same signals used for the creation of the distributions of said fields of force (F).

40. An apparatus for the manipulation of particles (BEAD) comprising:

i. means for generating at least one voltage (Vphin); and

ii. at least one electrode (EL) connected to said electrical signal (Vphin);

said apparatus being characterized in that said at least one electrode comprises holes such as to form a grid and, as a consequence of the application of said electrical signal to said electrode, points of stable equilibrium (CAGE_i,j) for said particles (BEAD).

41. The apparatus for the manipulation and detection and/or identification of particles (BEAD) according to claim 40, characterized in that it comprises means for reading the variation in intensity of a light (LIGHT) reflected and/or transmitted to one or more of said points of stable equilibrium due to the presence of one or more particles (BEAD) entrapped therein.

42. The apparatus according to claim 41, characterized in that said means for reading the variation in intensity of the reflected and/or transmitted light comprise an array of one or more optical sensors (pixel) arranged on a mobile head (SENSHEAD) and separate from the substrate (SUB) such that reading of the variation of reflected and/or transmitted light (LIGHT) at each point of equilibrium can be obtained by aligning said head with respect to said point of equilibrium by means of a relative motion between head and substrate.

43. The apparatus according to claim 41, characterized in that said means for reading the variation of the intensity of the light reflected and/or transmitted comprise an array of one or more optical sensors (pixel) integrated within said substrate (SUB).

44. The apparatus according to claim 41, characterized in that said means for reading the variation in intensity of the light comprise an array of one or more external optical sensors (pixel) positioned in a further substrate (OPTISENS) set underneath said first substrate (SUB) or on top of said second substrate (LID).

45. The apparatus according to claim 43, characterized in that it comprises an array of lenses (MICROLENSES), each of which concentrates the incident light in a position corresponding to each electrode or group of electrodes (BLOCK_i,j) in which a said point of stable equilibrium (CAGE_i,j) for said particles (BEAD) can be provided.