EP1973661A1

EP1973661A1 - Electric field cage and associated operating method

Info

Publication number: EP1973661A1
Application number: EP07702841A
Authority: EP
Inventors: Thomas Schnelle; Torsten Müller
Original assignee: Evotec Technologies GmbH
Current assignee: PerkinElmer Cellular Technologies Germany GmbH
Priority date: 2006-01-18
Filing date: 2007-01-17
Publication date: 2008-10-01
Also published as: WO2007082738A1; US20100155246A1; DE102006002462A1

Abstract

The invention relates to an electric field cage (6) for spatially fixing particles (2, 3) which are suspended in a carrier liquid, in particular in a microfluidic system, comprising a plurality of cage electrodes (7, 8), which can be electrically driven, for generating a capture field. It is proposed that at least one of the cage electrodes (8) is annular and surrounds the other cage electrode (7). The invention also covers an associated operating method.

Description

DESCRIPTION

Electric field cage and associated operating method

The invention relates to an electric field cage and an associated operating method according to the preamble of the dependent claims.

From Muller, T. et al. : "A 3D Microelectrode for Handling and Caging Single Cells and Particles", Biosensors and Bioelectronics 14, 247-256, 1999 microfluidic systems with dielectrophoretic field cages are known, which allow a spatial fixation of the suspended particles in the current bearing fluid, so that these electrode arrangements are also referred to according to their function as Feldkafig (English, "cage"). The known Feldkafige have a three-dimensional electrode configuration with, for example, eight cubically arranged Kafigelektroden.

A disadvantage of these known three-dimensional Feldkafigen addition to the necessary accurate assembly of the three-dimensional electrode assembly, the unsatisfactory ratio of fixing force, the required electrical voltage for driving the Feldkafige and the thermal heating of the fixed particles due to the electrical control of Feldkafigs. In this way, the particles are captured centrally between the electrode planes, where, on the one hand, the capture forces are lowest and, on the other hand, the flow velocity in the channel and thus the deflecting forces are greatest. Although a voltage increase in the control of the conventional Feldkafige leads to a desired Increase the fixation force. However, this is associated with an undesirable increase in the heating of the fixed particles, in particular in physiological or more highly conductive media.

From Fuhr, G. et al. : "Levitation, holding, and rotation of cells within traps made by high-frequency fields", Biochimica et Biophysica Acta, 1108 (1992) 215-223 are still known Planar field cages in which the cage electrodes are arranged in a common electrode plane ,

A disadvantage of these planar electrode arrangements is the fact that the particles to be fixed are repelled at right angles to the electrode plane in the case of negative dielectrophoresis, so that these electrode arrangements alone are not suitable for fixing and holding particles. However, the known planar electrode arrangements can be used as field cages, if an additional force is utilized, such as the gravitational force or the force generated by a laser tweezer.

The invention is therefore based on the object to provide a correspondingly improved field cage.

This object is achieved by a field cage and an associated operating method according to the independent claims.

The invention comprises the general technical teaching that at least one of the cage electrodes surrounds the other cage electrode in an annular manner.

The term used in the invention of an annular cage electrode is geometrically not limited to circular cage electrodes, but closes different shapes. For example, the annular cage electrodes may be polygonal, rectangular, elliptical or generally round.

In a preferred embodiment, the outer ring electrode surrounds an inner ring electrode. In a further preferred embodiment, these two ring electrodes surround a third, for example, circular electrode. Both arrangements are particularly well suited for the manipulation of particles by means of negative dielectrophoresis.

The term used in the invention of a ring electrode comprises on the one hand ring electrodes in the strict sense, which are not filled inside. On the other hand, this term also includes electrodes in which only the circumference is annular, while the electrodes are filled inside.

Furthermore, the invention comprises the general technical teaching to use a substantially planar electrode structure as a field cage instead of the known three-dimensional field cages described above.

The term "planar field cage" used in the context of the invention is preferably to be understood as meaning that the individual cage electrodes are arranged only on one side with respect to the particle to be fixed, whereas the particles to be fixed are fixed within the field cage in the case of the conventional three-dimensional field cages described above that the individual cage electrodes surround the fused particles on different sides.

The cage electrodes are thus preferably located on a substrate (ie a surface), which may be, for example, glass, plastic or silicon. The sub strat with the cage electrodes may for example be arranged on an upper channel wall of the carrier flow channel or on a lower channel wall of the carrier flow channel.

Preferably, the individual cage electrodes have a vertical electrode spacing which is smaller than the lateral electrode spacing, whereas the electrode spacing in the case of the conventional three-dimensional field cages described above is substantially greater.

In a preferred embodiment, the field cage according to the invention has exactly two cage electrodes, but the invention is not limited in terms of the number of cage electrodes to exactly two cage electrodes for the spatial fixation of the suspended particles. Rather, it is also possible, for example, for the field cage according to the invention to have three, four, six or eight cage electrodes or a different number of cage electrodes.

Furthermore, the individual cage electrodes of the field cage are preferably each planar and preferably aligned parallel to one another.

In a variant of the invention, all the cage electrodes are arranged in a common electrode plane, so that the entire electrode arrangement is exactly planar.

In another variant of the invention, the Käfigelekt ^¬ are clear, however, in two parallel and arranged in mutually offset planes. However, this variant also can be in the scope of the invention as a planar electrode arrangement referred ^¬, since the individual electrodes of the cage in power to fixie ^¬ particle are arranged only on one side with respect to the. In addition, the vertical electrode spacing is preferably substantially smaller than the lateral electrode extent. Here, the inner annular Kafig- electrodes may optionally be disposed above or below the outer annular Kafigelektrode.

The annular cage electrodes can be arranged concentrically or eccentrically to one another within the scope of the invention, but a concentric arrangement of the cage electrodes is preferred.

In a preferred embodiment of the invention with two annular cage electrodes, the inner annular cage electrode encloses an opening in a channel wall of a carrier flow channel, whereby the suspended particles can enter or exit through this opening in the channel wall. Through the opening in the channel wall of the carrier flow channel, the suspended particles can be transferred, for example, into fluidic quiet zones (for example storage reservoirs) or into other channels.

Furthermore, it is possible within the scope of the invention for at least one of the annular cage electrodes to be open on one side and / or to have a passivation layer on one side in order to weaken the electrode arrangement in a specific direction. The use of passivation layers for weakening the field cage has the advantage that the relative weakening of the field barrier generated by the field cage can be controlled via the frequency of the field. In this case, cell biologically used molecules such as lamin, serve as an insulating layer. This exploits the fact that the coupling of the field into the carrier solution over the given passivation layer is frequency- and medium-dependent. So takes the field docking into the carrier solution with the frequency and decreases with the ratio of the conductivities of the medium and passivation layer and the thickness of the passivation layer.

By applying a lower frequency, the field cage opens in directions of the passivation layers. The Feild cage can do this at the same time if all passivations are the same. However, it is also possible that different passivation layers are applied and the field cage is then deposited at these locations e.g. one after the other / selectively opens.

Alternatively, the inflow of another medium (for example, with a different conductivity) can be used as a switch. This procedure can both fill the nDEP ring arrays

(which can be simplified via upstream deflectors or funnels) as well as facilitate discharge in defined directions. In addition to this, specific line growth directions can be specifically favored. This can be used, for example, to set up a defined neural network. For this purpose, an array of nDEP ring structures on an eg rectangular grid is initially filled with individual neurons. The growth of the axons can be allowed / switched according to the predefined passivations. For individually addressable nDEP ring structures, this can also be done individually. Alternatively, the openings can also be realized via a laser by ablation of electrode material after the growth of the cells. Furthermore, nDEP-Rmg arrays can be used for collecting and, if appropriate, subsequent cryopreservation of, in particular, particulate material from suspensions. In the context of the invention, there is also the possibility that the individual Kafigelektroden are either the same or different shapes.

Furthermore, the Feldkafig invention has a certain snap point (minimum of the electric field in negative dielectrophoresis), in which the particles are spatially fixed, the snap point is either directly to a channel wall of Tragerstromkanals or spaced to the channel walls of Tragerstromkanals. The close-to-wall fixation of the suspended particles offers the advantage that the flow velocity is significantly lower there than in the middle of the carrier flow channel, so that smaller holding forces are sufficient for the spatial fixation of the suspended particles.

Furthermore, it is within the scope of the invention, the possibility that the substrate is provided with a passivation layer, a biochemical coating and / or a nanolayer. The biochemical coating of the substrate can, for example, modify the adhesion properties of the substrate for the particles to be fixed and / or set differentiation signals for the particles to be fixed.

In a variant of this different within the inner annular Kafigelektrode and outside the inner annular Kafigelektrode coatings are applied to the sub ^¬ strat, wherein the coating within the inner annular Kafigelektrode the acts to be fixed adhesively particle kel (attracting), while the coating au ^¬ ßerhalb the inner annular Kafigelektrode on the particles to be fixed repulsive (repulsive) acts. In a further variant of the invention, the substrate with the Kafxgelektroden the Feldkafigs is not arranged on a channel wall of Tragerstromkanals, but the substrate passes through the Tragerstromkanal in the direction of flow in the middle m shape of a membrane, so that the substrate divides the Tragerstromkanal into two sub-channels. This is particularly advantageous if there is an opening in the substrate through which particles can pass from one partial channel into the other partial channel of the carrier flow channel.

The field cage according to the invention is preferably a dielectrophoretic field cage, wherein optionally positive dielectrophoresis or negative dielectrophoresis can be used in order to spatially fix the suspended particles.

Furthermore, the invention includes a variant with a plurality of Feldkafigen each having preferably two or three Kafigelektroden, wherein the individual Feldkafige each allow a spatial fixation of one or more suspended particles. In this case, the individual field cells are arranged in a matrix-like manner in a plurality of columns and a plurality of rows, with the electrical control of the field cells being effected by a plurality of column control lines and a plurality of row control lines. For each column of the Feldkafige here in each case a common column control line for all Feldkafige the respective column is provided, wherein the column control line is connected at each electrode arrangement of the respective column in each case with the first Kafigelektrode. In the same way, a common row control line for all field cells of the respective row is provided for each row of the field cells, the row control line being connected to the second cage electrode for each electrode arrangement of the respective row. In the variant with three cages electrodes, one of the cage electrodes can optionally be controlled electrically separately or lie on an electrically floating potential.

It should also be mentioned that the invention comprises not only the Feldkafig described above, but also a microfluidic system with such Feldkafig and a cell biology device with such a microfluidic system, such as a Zeilsortierer, a ZeIl-Screenmg device or the like.

Furthermore, the invention also encompasses the use of a microfluidic system according to the invention in such a cell biological device.

Furthermore, the invention also encompasses a microamplulator for manipulating suspended particles, wherein the micromorphulator according to the invention has a field cage according to the invention in order to fix the suspended particles. For example, the micromultiplier can be designed as dielectrophoretic forceps.

Suitable electrode materials besides metals and doped semiconductors are also conductive polymers, such as, for example, polyanilm, polypyrrole or polythiophene. Also advantageous is the use of laser-modiflzierbaren polymers, such as polybisalkylthioacetylene. In the laser direct writing process, electrodes can be written into a polymer chip in this way, which is advantageous in particular for prototype construction.

Finally, the invention also relates to a corresponding operating method for the above-described erfmdungs- according microfluidic system. In this case, it is possible for the field cage to be controlled for the spatial fixation of the particles and for the subsequent release of the fixed particles with different frequencies. Thus, the control for the spatial fixation of the suspended particles is preferably carried out with a frequency which is sufficiently large to form a trapping field. The subsequent electrical control for releasing the fixed particles, however, takes place with a smaller frequency, which is sufficiently small to open the catch field at least in the region of the opening or the passivation layer.

The above-described opening of the annular cage electrodes on one side can be achieved, for example, by irradiating the cage electrodes by a laser, so that electrode material is removed from the irradiated cage electrodes, whereby the desired opening is formed.

Furthermore, in the operating method according to the invention, a preferably optical test can also be carried out as to whether or not particles are fixed in the individual field cages. Such an occupancy test is particularly advantageous if the microfluidic system has numerous electrode ^arrangements for fixing particles. In this case, the microfluidic system is first charged with particles until all field cages are coated with suspended particles. Subsequently, the loading phase can be terminated and it can be followed by further operating phases. The occupancy test thus allows a time minimization of the loading phase with simultaneous full occupancy of all electrode cages. Furthermore, in the case of a plurality of field cages, a chemical gradient can be generated between the individual field cages by influencing the flow accordingly. For example, chemical additives with the carrier flow can be fed into the microfluidic system for this purpose, it being possible to vary the inflow of the additives in terms of time and / or space within the carrier flow.

Furthermore, the electrode assembly used for particle fixing can additionally be used for a further purpose. For example, the electrode arrangement can be electrically controlled in order to trigger a stimulus on the particle fixed therein and / or to carry out an electrical measurement (for example impedance).

Finally, it should be mentioned that the particles to be suspended are preferably biological cells. However, with regard to the particles to be fixed, the invention is not restricted to biological cells, but instead also makes it possible, for example, to fix cell aggregates or other particles.

Other advantageous developments of the invention are characterized in the subclaims or are explained in more detail below together with the description of the preferred exemplary embodiments of the invention with reference to the figures. Show it:

FIG. 1A shows a preferred exemplary embodiment of a microfluidic system according to the invention with a field cage with two concentric annular cage electrodes attached to the lower channel wall of the carrier flow channel are and allow a spatial fixation of the suspended particles,

FIG. 1B, IC shows the field distribution in the field cage from FIG. 1A,

FIG. 1D shows the field distribution in a double-ring-force field cage, in which the ring electrodes are opened in a cross-shaped manner,

FIG. 2 shows an alternative exemplary embodiment, in which the field cage is arranged on the upper channel wall of the carrier flow channel,

FIG. 3 shows a substrate which carries a field cage, wherein the substrate can be arranged in the carrier flow channel, for example in the middle of the channel, and allows a passage of the suspended particles,

FIG. 4 shows an alternative exemplary embodiment of such a substrate with another configuration of the field cage,

FIG. 5A shows an alternative exemplary embodiment of a microfluidic system according to the invention with a field cage, the field cage consisting of two annular concentric cage electrodes on the lower channel wall, which have passivation layers on one side,

FIG. 5B shows a modification of the exemplary embodiment according to FIG. 5A, wherein the passivation layer cause weakening in four directions,

FIG. 5C shows a modification of the exemplary embodiment according to FIG. 5A, wherein the passivation layers cause a weakening m in three directions,

FIG. 6 shows an alternative exemplary embodiment with a matπxformigen arrangement of a plurality of Feldkafigen for particle fixation,

FIG. 7 shows the operating method according to the invention in the form of a flowchart,

FIG. 8 shows a dielectrophoretic forceps according to the invention,

FIG. 9 shows a further exemplary embodiment of a dielectrophoretic forceps according to the invention,

FIG. 10A shows a further exemplary embodiment of a microfluidic system according to the invention with a field cage with three concentric annular cage electrodes, FIG.

FIG. 10B shows the field distribution in the field cage according to FIG. 10A,

FIG. 11A shows a further exemplary embodiment of a microfluidic system with a flat counterelectrode, FIG. IIB the field distribution in the microfluidic

System according to Figure IIA, as well

Figures 12A-12I different exemplary embodiments of inventive dungsgemaßen Feldkafigen.

FIG. 1A shows, in a simplified form, an exemplary embodiment of a microfluidic system according to the invention with a carrier flow channel 1, through which a carrier liquid with particles 2, 3 suspended therein flows in the X direction.

The carrier flow channel 1 in this case has a lower channel wall 4 and an upper channel wall 5, wherein on the lower channel wall 4 a Feldkafig 6 is arranged, which consists of two circular, concentric annular electrodes 7, 8, which can be controlled independently and a allow spatial fixing of the particle 3 in the current Tragerflus- sigkeit by the Feldkafig 6 generates an electric capture field, which is shown in perspective in Figures IB and IC.

The two ring electrodes 7, 8 are in this case arranged coplanar in a common electrode plane, so that the snap point is likewise located directly on the lower channel wall 4 in the common electrode plane. This near-wall fixation of the particle 3 is advantageous because the flow velocity is smaller there than in the middle of the Tragerstromkanals 1, so that relatively low holding forces sufficient to fix the particles 3 to spatially. This in turn allows a relatively weak electrical actuation of the field cage 6, so that the fixed particle 3 is only slightly impaired by field effects. In addition, the particles can 3 by Liche zusätz ^¬ forces (eg. Inertial forces and the gravitational force ^¬ g) are fixed at the bottom under lopping FIGS. IB and IC show the field profile in the field box 6 according to FIG. 1A in a central vertical section through (FIG. 1B) and in a horizontal plane above the electrode structure (FIG. 1C).

Furthermore, FIG. 1D shows the field profile in a horizontal plane above the electrode structure for a modified field cage in which the annular cage electrodes 7, 8 are not open but open in a cruciform manner.

The alternative exemplary embodiment shown in FIG. 2 corresponds largely to the exemplary embodiment described above and shown in FIG. 1, so that reference is made to FIG. 1 to avoid repetition, the same reference numerals being used for corresponding components.

A special feature of this exemplary embodiment is that the Feldkafig 6 is not arranged on the lower channel wall 4, but on the upper channel wall 5 of the Tragerstromkanals 1. By overlaying with additional forces, for example, inertia forces or the gravitational force g, the snap point can also be shifted from the channel wall into the solution.

FIG. 3 shows a simplified perspective view of a substrate 9 made of glass, plastic or silicon with the field cage 6, as already described above with reference to FIGS. 1 and 2. In order to avoid repetition, reference is therefore made to the above description of FIG. 1 with regard to field box 6. In the substrate 9 there is a cylindrical opening 10 through which the particles 2, 3 can pass from the one side of the substrate 9 to the other side of the substrate 9, as is illustrated schematically by the dashed arrow lines. The substrate 9 thus acts as a partition and, for example in the microfluidic system according to FIG. 1, can be arranged as a membrane in the means of the carrier flow channel 1 and extend in the longitudinal direction of the carrier flow channel 1, so that the substrate 9 in the carrier flow channel 1 has two adjacent subchannels separates each other.

FIG. 4 shows an alternative exemplary embodiment of a substrate 9, which largely corresponds to the exemplary embodiment described above and in FIG. 3, so that reference is made to FIG. 3 in order to avoid repetition, the same reference numbers being used for corresponding parts in the following ,

A special feature here is that the opening 10 in the substrate 9 tapers conically upwards, wherein the two ring electrodes 7, 8 are arranged in different electrode planes. In this case, the two electrode planes are aligned parallel to one another and spaced apart from one another, as a result of which the snap point is lifted out of the electrode plane. However, the field cage 6 can also be referred to herein as a planar electrode arrangement, since the individual cage electrodes, with reference to the particle to be fixed, are arranged only on one side. In this case too, the distance of the electrode planes may preferably be smaller than the lateral electrode extension, ie the electrode extension in the Y direction. FIG. 5A shows a further exemplary embodiment of a microfluidic system according to the invention that largely corresponds to the embodiment described above and illustrated in FIG. 1, so that reference is made to FIG. 1 to avoid repetition, with the same reference numerals being used for corresponding parts become.

A special feature of this embodiment is that the two ring electrodes 7, 8 each have a passivation layer 11, 12 on the downstream side. The passivation layers 11, 12 weaken the capture field generated by the field cage 6 in the region of the passivation layer 11 or 12.

It should be mentioned that a weakening in the respective direction can also be achieved by applying a passivation only on the inner ring or only on the outer ring. Applications for the embodiments according to FIGS. 5B and 5C are, for example, neuron networks or triangular gratings.

In this case, there is the possibility electrode within the inner ring ^¬ 7 to arrange a further electrode which may have a sivierungsschicht Pas-.

FIG. 5B shows a corresponding exemplary embodiment with four weakening points, while FIG. 5C shows a further exemplary embodiment with three weakening points.

Further, Figure 6 shows an alternative embodiment of a microfluidic system with numerous arrayed field cages, each consisting of two concentrically ordered at ^¬ ring electrodes 13, 14th The individual field cages are arranged in matrix form in four rows and four columns and are electrically driven by four column control lines 15 and four row control lines 16. The individual column control lines 15 are in each case connected to the outer ring electrode 13 of all field cages of the respective column. In the same way, the individual row control lines 16 are each connected to the inner ring electrode 14. If, for example, all line control lines with signals of one phase and all column control lines are driven in opposite phase, particles can be fixed in all field cages. A single particle may then be released by grounding the corresponding row and column control lines.

The flowchart in FIG. 7 shows the operating method of a microfluidic system with the matrix-shaped electrode arrangement shown in FIG.

The operating method essentially consists of a charging phase 17, a consolidation phase 18, a growth / differentiation phase 19 and an investigation phase 20, which are described in detail below.

In the loading phase 17, first all field cages arranged in matrix form are switched off and biological cells are flushed in. Subsequently, the FeId- cages are connected to fix the flushed cells and dielectrophoretically driven, starting with the downstream field cages. As a result, biological cells are spatially fixed in the individual field cages. An optical occupancy test of the Individual field cages and unfixed cells are ejected as soon as whole field cages are covered with biological cells.

In the subsequent consolidation phase 18, the fixed cells then attach themselves. Depending on the degree of adhesion or flow conditions, the electric field can be reduced or completely switched off.

In the subsequent growth / differentiation phase 19, the field cages used for the spatial fixation of the cells are then electrically driven in a special way in order to structure the forming cell structure.

In addition, during the growth / differentiation phase 19, a chemical gradient can be generated between the individual feeder cells by correspondingly influencing the flow conditions.

Finally, an investigation of the formed Zeilverbande then takes place in the investigation phase. For this purpose, the cage electrodes are switched off and the desired measurements are carried out, wherein, for example, optical or electronic measurements are possible.

This operating method can also be used to set up a defined neural network. ι

FIG. 8 shows a simplified illustration of a dielectrophoretic forceps 21 which can be used to remove suspended particles from a suspension fluid. At its distal end, the forceps 21 has a hemispherical tip, the two annular cage electrodes 22,

23 carries, which can be electrically controlled independently of each other and allow a fixation of the suspended particles, so that the fixed particles can be manipulated together with the forceps 21 in the carrier liquid and removed from it.

FIG. 9 shows an alternative exemplary embodiment of a forceps 21 according to the invention, which largely corresponds to the embodiment described above, so that reference is made to the above description to avoid repetition, the same reference numerals being used for corresponding components.

A special feature of this embodiment is that the forceps 21 at its distal end a recess

24, in which a particle 25 can be fixed.

The illustrated in Figure 10A alternative embodiment of a microfluidic system is largely consistent with the embodiment described above and shown in Figure 1, so that reference is made to avoid repetition of the above description of Figure 1, wherein the same reference numerals are used for corresponding components.

A special feature of this embodiment is that the field cage 6 has three cage electrodes 7, 8, 26, wherein the outer cage electrodes 7, 8 can be electrically controlled independently of each other, as already described above. On the other hand, the inner cage electrode 26 can optionally be at an electrically floating potential or can also be driven electrically, as indicated by the dashed line.

Finally, FIG. 10B shows the field distribution of the field cage 6 according to FIG. 10A in a central vertical section through the electrode structure, wherein the electrodes 7 and 8 are driven in phase opposition and the electrode 26 is grounded.

Figure IIA shows a simplified perspective view of a further embodiment of a microfluidic system according to the invention, which largely matches the microfluidic systems described above, so reference is made to the above description to avoid repetition, the same reference numerals being used for corresponding details hereinafter.

A special feature of this embodiment is that the upper channel wall 5 of the carrier flow channel 1 is formed here as a planar counter electrode. The counterelectrode in this case consists of a transparent material in order to allow undisturbed optical observation through the upper channel wall 5. For example, the planar counterelectrode may be made of indium tin oxide (ITO) on the upper channel wall 5, but other materials are possible.

In contrast, the field cage 6 is arranged on the lower channel wall 4 in this exemplary embodiment and thus lies opposite the planar counterelectrode on the upper channel wall 5. With this arrangement, it is possible to realize nDEP field cages with simple circular-ring structures, which can hold the particles 2 in free solution, which is of particular interest for arrays.

FIG. IIB shows the field distribution E ² in the microfluidic system according to FIG. IIA in the zy plane, which cuts the field cage 6 in the middle.

The central ring electrode 7 in this case has the same electrical potential as the counter electrode on the upper channel wall 5, while the outer ring electrode 8 is at the opposite electrical potential, which is achieved by a phase shift of 180 °.

Alternatively, the inner ring electrode 7 and the counter electrode 5 are grounded or are at a free potential, while the ring electrode 8 is driven with an alternating field.

Figures 12A-12I show alternative embodiments of field cages according to the invention.

In the exemplary embodiment according to FIG. 12A, the two ring electrodes 7, 8 are each of square shape and are arranged with their edges parallel to one another.

In the embodiment shown in Figure 12B, the two ring electrodes I ₁ 8 are also each square shaped, but the ring electrode 7 is rotated relative to the ring electrode 8 by an angle of 45 °. In the exemplary embodiment according to FIG. 12C, the ring electrode 8 is square, while the ring electrode 7 is hexagonally shaped.

In the exemplary embodiments according to FIGS. 12D to 12F, the outer ring electrode 8 has the shape of an equilateral triangle. The inner ring electrode 7 is circular or elliptical in these embodiments, wherein the figures 12D and 12E by a centric (Figure 12D) and eccentric (Figure 12E) arrangement of the inner

Ring electrode 7 differ within the outer ring electrode 8.

In the field cage according to FIG. 12G, the two ring electrodes 7, 8 are each circular and concentric, wherein a triangular further electrode is arranged centrally within the inner ring electrode 7.

In the exemplary embodiment shown in FIG 12H, the outer ring electrode 8, the shape of a pentagon on, while the nere in ^¬ ring electrode 7 is arranged in a circle and centered within the outer annular electrode. 8 In addition, in this exemplary embodiment within the inner ring ^¬ electrode 7, a further ring electrode is arranged.

In the exemplary embodiment according to FIG. 121, the outer ring electrode 8 is star-shaped, while the inner ring electrode 7 is arranged in a circular centric manner within the outer ring electrode 8.

The invention is not limited to the above-described be ^¬ preferred exemplary embodiments. Rather, a multiplicity of variants and modifications is possible which also if make use of the idea of the invention and therefore fall within the scope.

Reference sign list:

1 carrier flow channel

2 particles

3 particles

4 Lower channel wall

5 Upper channel wall

6 field cage

7 ring electrode

8 ring electrode

9 substrate

10 opening

11 Passing Layer 2 Passing Layer 3 Ring Electrodes 4 Ring Electrodes 5 Column Control Line 6 Line Control Line 7 Feed Phase 8 Consolidation Phase 9 Growth / Differentiation Phase 0 Examination Phase 1 Tweezers 2 Kafig Electrode 3 Kafig Electrode 4 Well 5 Particles 6 Kafig Electrode

Claims

1. Electric Feldkafig (6) for spatial fixation of particles (2, 3) suspended in exner Tragerflussigkeit, especially in a microfluidic system, with a plurality of electrically controllable Kafigelektroden (7, 8) for generating a trapping field, characterized in that at least one of the cage electrodes (7, 8) is annular and surrounds the other cage electrode.

2. Feldkafig (6) according to claim 1, characterized in that exactly two or exactly three Kafigelektroden (7, 8) are provided.

3. Feldkafig (6) according to any one of the preceding claims, characterized in that the lateral electrode extension of Kafigelektroden (7, 8) is greater than the electrode spacing transverse to the flow direction.

4. Feldkafig (6) according to any one of the preceding claims, characterized in that the individual Kafigelektroden

(7, 8) are arranged only on one side with respect to the particle to be fixed.

5. Feldkafig (6) according to any one of the preceding claims, characterized in that the Kafigelektroden (7, 8) are each planar.

6. Feldkafig (6) according to any one of the preceding claims, characterized in that the Kafigelektroden (7, 8) are arranged in a common electrode plane or on a surface.

7. Feldkafig (6) according to one of claims 1 to 5, characterized in that the Kafigelektroden (7, 8) are arranged in two parallel and mutually offset planes.

8. Feldkafig (6) according to any one of the preceding claims, characterized in that the Kafigelektroden (7, 8) are arranged concentrically to each other.

9. Feldkafig (6) according to one of claims 1 to 7, characterized in that the Kafigelektroden (7, 8) are arranged eccentrically to one another.

10. Feldkafig (6) according to any one of the preceding claims, characterized in that the annular Kafig electrode are elliptical, circular, polygonal or rectangular.

11. Feldkafig (6) according to any one of the preceding claims, characterized in that at least one of the annular Kafigelektroden (7, 8) is open on one side and / or on one side of a passivation layer (11, 12).

12. Feldkafig (6) according to any one of the preceding claims, characterized in that the Kafigelektroden (7, 8) are shaped differently.

13. Feldkafig (6) according to any one of the preceding claims, characterized in that at least one of the Kafigelektroden (7, 8) on a substrate (9) is arranged.

14. Feldkafig (6) according to claim 13, characterized in that the substrate (9) glass, plastic or silicon.

15. Feldkafig (6) according to claim 13 or 14, characterized in that the substrate (9) with a passivation Layer (11, 12), a biochemical coating and / or a nano-layer is provided.

16. Feldkafig (6) according to claim 15, characterized in that the biochemical coating, the adhesion properties of the substrate (9) for the fixed particles (2, 3) modified and / or differentiation signals for the fixed particles (2, 3) sets.

17. Feldkafig according to one of claims 15 to 16, characterized in that a) that within the inner annular Kafigelektrode (7) and outside the inner annular Kafigelekt- rode (7) different coatings are applied to the substrate (9), b ) that the coating within the inner annular Kafigelektrode (7) on the particles to be fixed (2, 3) acts adhesive, c) that the coating outside the inner πngformi- Kafig electrode (7) on the particles to be fixed

(2, 3) acts repulsively.

18. Feldkafig (6) according to any one of the preceding claims, characterized in that the Feldkafig (6) is a dielectrophoretic Feldkafig (6).

19. Feldkafig (6) according to claim 18, characterized in that the Feldkafig (6) is either a positive dielectrophoretic Feldkafig (6) or a negative-dielectrophoretic Feldkafig (6).

20. Feldkafig according to one of the preceding claims, characterized by a counter electrode (5), wherein the counter electrode (5) on the one hand and the annular Kafigelektroden (7, 8) are arranged on the other hand in parallel, mutually spaced electrode planes.

21. Microfluidic system with a) a carrier flow channel (1) for receiving a carrier stream with particles (2, 3) suspended therein and b) an electrically controllable field cage (6) with a plurality of cage electrodes (7, 8) for spatially fixing the particles (2 , 3) in the carrier stream, characterized in that c) the field cage (6) is designed according to one of the preceding claims.

22. Microfluidic system according to claim 21, characterized in that the inner annular cage electrode (7) encloses an opening (10) in a channel wall of the carrier flow channel (1), wherein the suspended particles (2, 3) through the opening (10 ) can enter or leave.

23. Microfluidic system according to one of claims 21 to

22, characterized in that the field cage (6) has a specific snap point, in which the particles (2, 3) are spatially fixed, wherein the snap point is located directly on a channel wall (4, 5) of the carrier flow channel (1).

24. Microfluidic system according to one of claims 21 to

23, characterized in that the field cage (6) has a specific snap point, in which the particles (2, 3) cavities ^¬ be fixed Lich, wherein the catching point of the channel walls (4, 5) of the carrier flow channel (1) is spaced apart.

25. Microfluidic system according to one of claims 21 to

24, characterized in that the substrate (9) with the cheese figelektroden (7, 8) on a channel wall (4, 5) of the carrier flow channel (1) is arranged.

26. Microfluidic system according to claim 25, character- ized in that the substrate (9) with the cage electrodes

(7, 8) on the upper channel wall (5) of the carrier flow channel (1) is arranged.

27. Microfluidic system according to claim 25, character- ized in that the substrate (9) with the cage electrodes

(7, 8) on the lower channel wall (4) of the carrier flow channel (1) is arranged.

28. Microfluidic system according to claim 25, character- ized in that the substrate (9) with the cage electrodes

(7, 8) is arranged on a lateral channel wall of the carrier flow channel (1).

29. Microfluidic system according to one of claims 21 to 28, characterized in that the substrate (9) with the cage electrodes (7, 8) in the carrier flow channel (1) to the Ka ^¬ cal walls (4, 5) of the carrier flow channel (1). spaced apart and extending in the longitudinal direction of the carrier flow channel (1).

30. Microfluidic system according to claim 21, characterized in that a) a plurality of field cages is provided, each with two cage electrodes (13, 14), wherein the individual field cages each have a spatial fixation of the suspended particles (2, 3), b) that the field cages are arranged in matrix form in several columns and several rows, c) that for each column of the field cages in each case a common column control line (15) is provided for all field cages of the respective column, wherein the column control line (15) in each field cage (6) of the respective column in each case with the first cage electrode (13), d) that for each row of the field cages in each case a common row control line (16) is provided for all field cages of the respective row, wherein the row control line (16) at each field cage (6) of the respective row respectively is connected to the second cage electrode (14).

31. The microfluidic system is provided according to one of claims 21 to 28, characterized in that a) a plurality of field cages, each with three Kä ^¬ figelektroden, wherein the single field ^¬ cages each spatial fixation of the suspending ^¬ th particle (2, 3 c) that the field cages are arranged in matrix form in a plurality of columns and a plurality of rows, d) that for each column of the field cages each have a common Column control line is provided for all field cages of the respective column, wherein the column control line at each field cage (6) of each column is connected to the second cage electrode, e) that for each row of field cages each have a common ^¬ same row control line is provided for all 'field cages of the respective row, wherein the line Steuerleitu ng at each field cage (6) of the respective Row is in each case connected to the third Kafigelektrode.

32. The microfluidic system according to claim 21, wherein: a) the cage electrodes are arranged on a channel wall of the carrier current channel, and b) a flat counterelectrode is arranged on the opposite channel wall of the carrier current channel.

33. The microfluidic system according to claim 32, characterized in that the counterelectrode is transparent.

34. The microfluidic system according to claim 21, wherein the cage electrodes and / or the counter electrode consist of one of the following materials: a) metal, b) semiconductors, c) electrically conductive polymers, in particular polyaniline, polypyrrole or Polythiophene, d) laser-modifiable polymers, in particular polybisalkylthioacetylene.

35. Micromanipulator, in particular tweezers (21), for manipulating particles (2, 3) which are suspended in a suspension fluid, characterized by a field cage (6) according to one of claims 1 to 19 for spatially fixing the particles (2, 3 ).

36. Use of a Feldkafigs (6) according to any one of claims 1 to 20 or a microfluidic system according to any one of claims 21 to 34 or a micromanipulator according to claim 35 in a zellbiologischen Gerat.

37. Operating method for a microfluidic system with a carrier flow channel (1) for receiving a carrier stream with particles suspended therein (2, 3) and an electrically controllable field cage (6) for spatially fixing the particles (2, 3), wherein the field cage (6 ) comprises a plurality of cage electrodes (7, 8), characterized in that at least one of the cage electrodes (7, 8) is annular and surrounds the other cage electrode.

38. Operating method according to claim 37, characterized in that at least one of the annular cage electrodes (7, 8) on one side has an opening and / or a passivation layer, wherein the field cage (6) is driven by the following steps: a ) Electric control of the field cage with a first frequency for spatial fixation of the suspended particles (2, 3), wherein the first frequency is sufficiently large to form a trapping field, b) then electrical control of the field cage with a second frequency for releasing the trapped particles (2, 3), wherein the second frequency is smaller than the first frequency and sufficiently small to open the capture field in the region of the opening or the passivation layer.

39. Operating method according to one of claims 37 to 38, characterized by the following step:

Irradiation of at least one of the cage electrodes (7, 8) by a laser, so that the electrode electrode material is removed from the irradiated cage electrode and thereby an opening in the cage electrode is generated.

40. Operating method according to one of claims 37 to 39, wherein the microfluidic system comprises a plurality of Feldkafi- gene, characterized by the following steps: a) turning off the Feldkafige (6), b) rewinding the Tragerflussigkeit with the particles suspended therein (2, 3) in the carrier flow channel (1), c) electrical control of the Feldkafige (6), so that the individual Feldkafige (6) each spatially fix suspended particles (2, 3), d) unwinding of not fixed in the Feldkafigen particles (2 , 3) from the carrier flow channel (1), e) switching off or weakening the flow in the carrier flow channel (1) for consolidation of the particles (2, 3) fixed in the field cage, f) electrical control of the field cage, so that the be structured in fixed particle (2, 3) forming cell networks.

41. Operating method according to claim 40, characterized by the following step:

Optical verification of whether particles (2, 3) are fixed in the individual field cages (6).

42. Operating method according to claim 40 or 41, characterized by the following step:

Generation of a chemical gradient between the individual Feldkafigen (6) by influencing the flow in the Tragerstromkanal (1).

43. Operating method according to one of claims 40 to 42, characterized by the following step:

Examination of the spatially fixed particle in at least one of the field cages (6).

44. Operating method according to one of claims 40 to 43, characterized by the following step:

Electrical control of at least one of the field cages for triggering stimulus on the particles (2, 3) fixed therein.

45. Operating method according to one of claims 40 to 43, characterized by the following step:

Electrical control of at least one of the field cages for measuring at least one electrical characteristic on the particles (2, 3) fixed therein or its immediate surroundings.