EP1744831B8 - Method and device for collecting suspended particles - Google Patents

Abstract

A description is given of methods for collecting particles (1, 2) which are suspended in a liquid, including the following steps: providing the liquid containing the suspended particles (1, 2) in a compartment (10) having lateral surfaces (11), wherein at least one electrode (21) is arranged on at least one of the lateral surfaces (11), and generating high-frequency electric fields by means of the at least one electrode (21) so as to form at least one circulating flow (30), by means of which the particles (1, 2) are guided to at least one predetermined collecting area (40) in the compartment (10), wherein the flow (30) is formed in such a way that at least one branch of the flow runs along a longitudinal extent of the at least one electrode (21), and the flow (30) circulates about an axis (31) which is oriented perpendicular to the respectively adjacent lateral surface (11) with the electrode (21). Corresponding devices for collecting particles are also described.

Description

 Method and device for collecting suspended particles

The invention relates to a method for collecting particles suspended in a liquid, in particular for collecting suspended biological objects, such as biological cells, in a fluidic microsystem, with the features of the preamble of claim 1. The invention also relates to a device to implement such a method and its applications.

It is known to suspend particles in a liquid in fluidic microsystems in a dielectrophoretic

To catch or collect field cages (see for example publication "Trapping in AC octopole field cages" by T. Schnell et al. In "Journal of Electrostatics", Vol. 50, 2000, pp. 17 to 29). This technique has the disadvantage that only relatively large particles with typical dimensions> 500 nm can be safely caught. With smaller particles, such as viruses, the dielectrophoretic trapping forces can be too low or can be overlaid by thermal disturbances.

With planar electrodes, to which high-frequency alternating voltages are applied, electro-osmosis flows can be generated in a liquid-filled compartment by electro-osmosis. KF Hoettges et. al. describe in the publication "Optimizing Particle Collection for enhanced surface-based biosensors" (see "IEEE ENGINEERING IN MEDICINE AND BIOLOGY MAGAZINE", November / December 2003, p. 68) the use of circulating electrohydrodynamic flows to collect in the liquid suspended particles. In this method, particles 1 ', 2' suspended according to FIG. 9 are collected in a compartment 10 'with a side face 11'. At the edges of electrodes 21 '(partially shown), which are arranged on the side surface 11', there is a vortex flow 30 'which runs around an axis 31' parallel to the orientation of the side surface 11 '. In the middle of the electrodes 21 ', a flow-reduced area is formed, which represents a collection area 40' for the particles brought between the electrodes 21 'by the vortex flow 30'.

K. F. Hoettges et. al. The technology described has several disadvantages, in particular for use in biology, biochemistry and medicine. The circulating vortex flow has a relatively small intake area for the particles to be collected. Furthermore, the particles can only be collected directly adjacent to the electrodes. However, contact with the electrodes can be detrimental to the particles, especially if the particles comprise biological materials. In addition, relatively large-area electrodes are required in order to form correspondingly large collection areas. However, undesired heating occurs on large-area electrodes. Finally, there is a major disadvantage of the Hoettges et al. described technology in that it is based on electroosmosis and positive electrophoresis and is therefore limited to low frequencies and low conductivities of the solutions used. It is therefore not possible to use this method to examine cells in physiological solutions.

It is also known to guide viruses 1 'into the capture region of a funnel-shaped, dielectric field cage 50' using electrohydrodynamic currents 30 ', as shown in FIG. 10 (see publication "Trapping of Viruses in High Frequency Electric Field Cages" by T. Schnell et al. in "Naturwissenschaften" Vol. 83, 1996, pp. 172 to 176; Publication "High Frequency Electric Fields for Trapping of Viruses" by T. Müller et al. in "Biotechnological Technologies", Vol. 10, 1996, pp. 221 to 226; and publication "Trapping of micrometre and sub-micrometre particles by high frequency electric fields and hydrodynamic forces" by T. Müller et al. in "J. Phys. D: Appl. Phys." Vol. 29, 1996, pp. 340 to 349). This technique also has the disadvantage that the collecting flow only detects viruses in the immediate vicinity of the electrodes 21 'used to form the field cage 50' and therefore has a relatively small catchment area. Furthermore, the method mentioned is limited to low conductivities or low-salt solutions and is therefore not suitable for the examination of cells in physiological solutions.

Flows in fluidic micro systems can also be induced by high electrical field strengths (electrical heating). This principle, the z. B. is used in traveling wave pumps in microchips (see publication "A traveling-wave micropump for aqueous solutions: Comparison of 1 g and μg results" by T. Müller et al. In "Electrophoresis", Vol. 14, 1993, p . 764 to 772), but can be disadvantageous in particular for biological particles because of the heat conversion.

The object of the invention is to provide improved methods for the collection of particles suspended in a liquid, in particular for the collection of suspended biological objects, with which the disadvantages of the conventional methods are overcome and which in particular a collection from an enlarged catchment area and without Allowing damage to the collected particles. Another object of the invention is to provide improved devices for Collection of particles suspended in a liquid, in particular for implementing the method according to the invention.

This object is achieved with methods and devices with the features of claims 1 and 25. Advantageous embodiments and applications of the invention result from the dependent claims.

In terms of the method, the invention is based on the general technical teaching of collecting suspended particles in at least one collection area in a compartment with a circulating flow which runs at least partially along a longitudinal extent of at least one electrode on one side surface of the compartment. The collection area is the volume into which the flow leads the particles and in which the particles can collect, in particular through a local flow reduction. The circulating flow generated according to the invention by an interaction of the liquid with high-frequency electrical fields at the electrode advantageously runs in a plane parallel to the respective side surface. The inventors have found that the limitation of the collection effectiveness of the conventional techniques can be overcome and the catchment area of the flow circulating at the electrode can be increased if the flow does not revolve around an axis parallel to the orientation of the side face as before, but a local axis of rotation perpendicular to it Has side surface. Another important advantage of the invention is that even the smallest particles, such as viruses, can be effectively collected with the at least one flow.

The net liquid flow in the circulating flows is zero because there is no source or sink in the collection area exists and the fluid is incompressible. Nevertheless, a net particle flow from the outside in is observed. This can be explained by the fact that negative dielectrophoresis means that the particle concentration between the electrodes (liquid flow directed outwards) is lower than in the vicinity of the electrodes (liquid flow directed inwards).

If, according to a preferred embodiment of the invention, the particles are collected in the collection area without mechanical contact with a wall or another part of the compartment, there may be advantages for the manipulation of biological particles, such as for example biological cells, which are based on mechanical contact with undesired additives. Status changes would react. If a mechanical

However, if contact is just desired, the particles can be arranged according to an alternative embodiment of the invention in the collection area with a touch of a side surface of the compartment. A measurement by a compartment wall can thus advantageously be simplified. Even if the collection is done with a touch of the side surface, in contrast to conventional electro-optical techniques, electrode contact and thus an undesirable electrode reaction can be avoided. In this case, the collection area can be formed by a part of the side surface in which the wall material of the compartment is exposed and there are no electrodes.

According to a particularly preferred embodiment of the invention, a plurality of locally circulating flows are generated on at least one electrode, of which at least one branch of the local circulation is directed towards the at least one collection area. Leave along the electrode for example two currents. This advantageously increases the effectiveness of the collection.

A further enlargement of the collection area of the collection can advantageously be achieved if, according to a variant of the method according to the invention, a plurality of locally circulating flows are generated on several electrodes. In particular, this enables the particles to be guided from several directions to the at least one collection area. If the flows relative to one another are formed such that they are symmetrical, in particular point-symmetrical, to the collection area that the flow is calmed or essentially free of flow, it can advantageously be achieved that the particles conveyed from one side to the collection area move the collection area in a different direction, eg. B. do not leave again on the opposite side.

Since, according to the invention, the flow is generated along the longitudinal extent of the respective electrode, the feed area can advantageously be extended with elongated, band-shaped or strip-shaped electrodes, which preferably extend radially from the collection area in different directions.

According to a further advantageous embodiment of the invention, the particles are collected from a feed area of the compartment, the volume of which is 10 ² to 10 ⁹ times greater than the volume of the collection area. This ratio shows that with the method according to the invention, particles can not only be collected, but concentrated or enriched with a high factor. For example, the catchment area of a single vertebra can have a volume of up to 10 μl and the collection area a volume of 1 distant have toliters up to 50 picoliters, so that the invention can advantageously be implemented with fluidic microsystems.

According to a particularly preferred embodiment of the invention, high-frequency electric fields are also used to directly exert a predetermined dielectrophoretic propulsive force on the particles. Under the action of the high-frequency electric fields, the particles are moved to the collection area by negative dielectrophoresis. Advantageously, the indirect hydrodynamic force effect is thereby increased. It is particularly preferred if, according to the invention, high-frequency electric fields are generated which are used for the electrodynamic flow generation and simultaneously for the dielectrophoretic manipulation of the particles.

The collection effectiveness can be further increased if at least one dielectrophoretic field cage with a potential minimum that is located in the collection area is generated with the high-frequency electric fields. The dielectrophoretic capture forces in the field cage depend on the particle size. Particles which are so small that the catching forces of the field cage would be too weak for effective collection can advantageously be combined with the electrohydrodynamic flows to form larger aggregates in such a way that field forces are achieved which are sufficient for safe catching in the field cage are. According to the invention, the field cage is closed in two (funnel-shaped field cage) or three (all-sided field cage) spatial directions. The field cage can be formed with 6, 8 or more electrodes.

If, according to an advantageous variant of the invention, electrodes are arranged in this way and with high-frequency electrical If voltages are applied so that several field cages are formed, the catchment area of the particle collection according to the invention can advantageously be increased. An inner and an outer field cage are preferably provided, the potential minima of which have the same position in the collection area. The field cages are arranged concentrically to one another, the outer field cage in each case moving particles toward the inner field cage by negative dielectrophoresis.

According to the invention it can be provided that at least one further force acts on the particles in the collection area. This advantageously enables additional holding and / or manipulation of the particles in the collection area to be achieved. The generation of an optically effective force can have advantages when the technique according to the invention is combined with an optical measurement in the collection area and for selective particle manipulation. Generating a dielectrophoretic force can have advantages for effective interaction with a dielectrophoretic

Have a barrier in the field cage. An additional magnetic force offers advantages when manipulating magnetic particles. Finally, the at least one further force can be a force transmitted by ultrasound, for example nodes of an ultrasound field can be formed in the collection area.

To exert another force, there is also the possibility that there is a start object in the collection area, e.g. a bead that can also be functionalized.

With this starting object, the particles are not only influenced by dielectric interactions, but also, if necessary, by a specific bond to the bead or a hydrodynamic partition caused by the starting object. According to a further preferred embodiment of the invention, at least one measurement of the collected particles takes place in the collection area. This can result in particular advantages in the manipulation or evaluation of collected biological particles. The measurement preferably comprises an electrical, electrochemical and / or optical measurement known per se, for example from the field of fluidic microsystems.

According to a preferred application of the invention, the measurement is aimed at the detection of a receptor-ligand binding event. For this measurement, according to the invention, the side surface of the compartment in the area of the at least one collection area can be functionalized with detection spots in the form of receptor molecules (e.g. proteins, antibodies, DNA, viruses (for transfection experiments), etc.), as is the case with conventional microarrays or biochips is known so that a specific receptor-ligand interaction takes place with particles or molecules accumulated in the collection area. The interaction can then be carried out in a known manner e.g. can be demonstrated using electrical, electrochemical or optical readout methods.

The method according to the invention can advantageously increase the concentration of analyte particles or molecules in the vicinity of the detection spots (increase in sensitivity) and accelerate the detection process compared to the purely diffusive transport of analyte particles or molecules to the detection spots.

The functionalized receptor array can e.g. B. be applied to a flat electrode and together with a die The second substrate containing collecting electrodes form a microchamber. After the analyte particles or molecules have been enriched by the method according to the invention and have bound them to the immobilized receptors on the array, the collection structure can then be removed again. Accordingly, it can also be used several times.

If, according to a further modification of the invention, the particles are collected in several compartments in the compartment, there may be advantages for a parallel enrichment of the particles from several catchment areas in the compartment and a parallel manipulation or evaluation of the collected particles.

For use in fluidic microsystems, it is of particular advantage of the invention that the collection can take place not only from a catchment area with a stationary suspension liquid, but even dynamically from a moving suspension liquid. The compartment can be penetrated, for example, by a laminar flow which, according to the invention, is superimposed on the locally circulating flow.

Furthermore, a mutual superimposition of several locally circulating flows can be provided in the compartment. A first circulating flow can lead the particles straight into a collection area which is part of a further, downstream circulating flow. This makes it possible to arrange a large number of circulations in the manner of a cascade, in which particles are led from an extended feed area into a single collection area. The method according to the invention is particularly well suited for collecting particles with a diameter of less than 1 μm. For biological applications, cells, viruses, bacteria, proteins, cell components and / or biological macromolecules, eg. B. DNS can be collected.

According to further variants of the invention, it can be provided that the flows circulating locally on the electrodes are amplified by a local temperature gradient in the liquid. The temperature gradient can be formed by locally heating the liquid, which is preferably carried out by irradiating the liquid and / or side surfaces of the compartment with light and its corresponding absorption and / or by embedded (“buried”) thermocouples in the walls. Alternatively or additionally, the temperature gradient can be formed by local, targeted cooling of the liquid.

The local heating of the liquid can advantageously also be used to stimulate chemical reactions. Due to the locally high temperatures in the collection area, z. B. thermally activated reactions occur, e.g. an aggregation or a precipitation.

In terms of the device, the above-mentioned object of the invention is achieved by a collection device for collecting suspended particles, which in a compartment for receiving a liquid on one side surface has at least one electrode for generating one or more locally circulating flows in the liquid, with the suspended particles can be led to at least one predetermined collection area in the compartment, the collection device being set up to at least generate a flow so that part of the flow extends along the longitudinal extent of the electrode and the

Flow revolves around an axis that is aligned perpendicular to the adjacent side surface with the electrode.

According to advantageous variants of the invention, the collection area can be arranged at a distance from the side faces of the compartment or in such a way that the collection area is in contact with one of the side faces.

The electrode, on which the at least one circulating flow can be generated, is preferably connected to a voltage source for providing predetermined high-frequency electrical voltages. The at least one electrode that is used to generate the circulating flow is also referred to as a collecting electrode. When generating a plurality of circulating flows which are directed to one or more collection areas, the collection device accordingly comprises a plurality of collection electrodes which form a collection electrode array.

If, according to a preferred embodiment of the invention, the collection device is set up to exert not only electrohydrodynamic but also dielectrophoretic forces on the particles to be collected, the collection effect can be improved by the additional force effect. The dielectrophoretic force effect is exerted by the interaction of the particles with high-frequency electric fields, which are generated in the compartment with at least one electrode, which is referred to below as the cage electrode. If the above-mentioned field cages, which are closed on one or all sides, are to be produced, the compartment is equipped with a cage electrode array. According to a particularly preferred variant of the invention, the collecting and cage electrodes are identical. The collecting electrode and cage electrode arrays are formed by a common electrode arrangement. In this case, the structure of the collection device and the control of the electrodes are simplified.

A particular advantage of the collection device according to the invention is that it can be miniaturized. The compartment of the collection device is preferably part of a fluidic microsystem. The collection function according to the invention can advantageously be combined with collection, sorting, evaluation or measurement functions of the microsystem. The collection device is arranged, for example, in the channel of a fluidic microsystem, which forms the named compartment with the flow generator. Surprisingly, the collection device according to the invention can also be used to collect particles in the flow-through channel.

To increase the collection activity, it can be provided according to a modification of the invention that a plurality of collection areas are arranged in rows along a longitudinal direction of the channel.

There are particular advantages for an expanded area of application of the collection device if it is equipped with a magnetic field device for exerting a magnetic holding force in the collection area mentioned and / or a measuring device for detecting electrical, electrochemical or optical properties of particles in the collection area. According to further variants of the invention, the flow generator can additionally comprise a heating device and / or a light source.

Further details and advantages of the invention will become apparent from the following description of exemplary embodiments and the accompanying drawings. Show it:

FIG. 1: a schematic sectional view of an embodiment of a collection device according to the invention,

Figures 2, 3: different phases of the collection of particles with the inventive method,

FIGS. 4A, 4B: illustrations of field and temperature conditions in a collection device according to the invention and of experimental results which were achieved with a collection device according to the invention,

FIG. 5: an embodiment of a collection device according to the invention with a number of collection areas,

FIG. 6: a further embodiment of a collection device according to the invention with a cascade of collection areas,

FIG. 7: a further embodiment of a collection device according to the invention with a cascade of collection areas,

FIG. 8: an illustration of the flow conditions in a collection device according to FIG. 7, and Figures 9, 10: illustrations of conventional collection techniques (prior art).

The exemplary embodiments of the invention are described below with reference to the application of the invention in fluidic microsystems for dielectrophoretic particle manipulation. Such fluidic microsystems, their components and their operating methods are known per se and are therefore not described below. The invention is discussed below by way of example with reference to a design in which electrodes are used both for collecting and for exerting a dielectrophoretic driving force, in which case the collecting and cage electrodes are identical. It is emphasized that the implementation of the invention is not limited to this embodiment. Rather, according to the invention, collecting electrodes can be provided exclusively for generating an electrohydrodynamic flow and cannot form part of a dielectric field cage, as is illustrated, for example, in FIGS. 6 or 7 (see below). Furthermore, it is emphasized that the application of the invention is not limited to the fluidic microsystems for dielectrophoretic particle manipulation, but also in other cases in which, in particular, particles suspended in biochemical tasks in liquid-filled compartments, e.g. B. laboratory vessels to be collected, applied.

FIG. 1 illustrates in an enlarged schematic sectional view a part of a channel or another section of a fluidic microsystem by which the compartment 10 of the collection device according to the invention is formed. An electrode arrangement 20 with eight electrodes 21 is arranged on the channel walls, which represent side surfaces 11 of the compartment 10. It's on the lower side ten surface (bottom surface) and on the upper side surface (top surface) four electrodes 21 each (see also Figures 2, 3). The electrode arrangement 20 is formed as is known per se from electrode arrangements for producing dielectrophoretic field cages.

Each electrode for electrohydrodynamic flow generation has the shape of a strip or tape with a length (see also FIGS. 2, 3) that is substantially larger than the electrode width. The aspect ratio electrode width: electrode length is preferably selected in the range from 1:10 to 1: 100. The dimensions of the electrode 21 are, for example.

10 μm '500 μm. A longitudinal orientation of the electrode 21 is defined by the elongated electrode shape. Each electrode 21 is arranged so that the longitudinal alignment to a collection area 40 is in the middle between the side surfaces

11 or the vertical projection from the collection area onto the respective side surface 11. The electrodes 21 are electrically connected in a manner known per se to a voltage source for generating high-frequency electrical voltages, preferably to predeterminable amplitudes, frequencies and phase relationships. When the electrodes 21 are acted upon by the high-frequency electrical voltages, currents 30 are formed parallel to the side surfaces 11, with which particles 1 are moved to the collection area 40.

Reference numeral 50 relates to a measuring device, for example a microscope with a CCD camera, with which, for example, fluorescence-marked particles in the collection area can be optically measured and evaluated. For this purpose, at least one optically transparent window is provided in the side surface 21 of the channel (see FIG. 5). Alternatively or additionally, at least one further can be used as the measuring device Electrode for impedance measurements can be provided in the collection area 40.

FIG. 2 illustrates the state of the collection device immediately before the start of an electrohydrodynamic collection. In the compartment 10, particles 1 are randomly distributed as long as the electrodes 21 are voltage-free or a relatively low voltage (<1 V) is applied. When the electrodes are subjected to high-frequency voltages of sufficiently high amplitude, the currents 30 form (also shown in FIG. 2 for illustration purposes). One or two locally circulating flows 32, 33 are generated at each electrode. A first flow branch of each flow runs along the longitudinal orientation of the electrode 21 and parallel to the side surface 11 through the compartment 10 essentially in the direction of the collection area 40, as is illustrated in FIGS. 2 and 3. Another branch of the circulating flow 30 leads back over the electrode 21 in the opposite direction. The rotation takes place about an axis 31 which is perpendicular to the plane in which the electrodes are arranged. With the flows 30, the particles 1 are guided from the outside outside the electrode arrangement 20 into the inner collection area 40, where they form an aggregate (FIG. 3).

The cause of the electrohydrodynamic flow 30 is illustrated in FIG. 4A. The left part of FIG. 4A shows the temperatures in the xz plane (according to FIG. 1) and in the xy plane (according to FIG. 2). Without an external flow, there is a temperature profile such that the collection area 40 between the electrodes 21 is warmer than the ambient solution. Since the electrical conductivity and the dielectric constant are temperature-dependent, the medium in the collection area becomes dielectrically inhomogeneous. Thereby The electric field exerts polarizing forces on the liquid, which lead to the formation of the desired flow vortices. Since the flow vortices are formed on all electrodes, there is a symmetrical inflow towards the center of the cage into the collection area 40.

FIG. 4A (left part) shows the temperature conditions in the case of a liquid which is initially at rest in the compartment. Surprisingly, the circulating flows pointing to the collection area also occur if the liquid flows in the compartment. The liquid forms a carrier flow at a speed which is less than the liquid speed in the circulating flows.

Under the action of the high-frequency fields in the compartment 10, dielectrophoretic forces are also exerted on the particles. The electrical field conditions are correspondingly illustrated in the right part of FIG. 4A. It is the square of the electric field strength (E ² ) in the xz plane

(according to FIG. 1) and in the x-y plane (according to FIG. 2). Particles that are to be transported into the interior of the field cage must overcome a relatively high dielectric barrier in the x or y direction. After passing through the barrier under the action of flow forces, the particles experience a dielectrophoretic force acting in the center of the field cage, so that in the center of the cage the collection of aggregates is increased, which are subject to a dimensionally larger volume force.

The voltage amplitude required to generate the electrohydrodynamic flow is selected as a function of the dielectric properties of the suspension liquid and the geometric properties of the electrical dena order. An empirical selection by experiments can also be provided. The high-frequency electric fields are preferably selected so that only negative dielectrophoresis acts on the particles. The collection shown in FIGS. 2 and 3 can be implemented to collect 1 μm particles, for example with the following operating parameters. The particles are suspended in KC1 (concentration: 12.5 mM). A high-frequency electrical voltage (frequency: 8 MHz, amplitude: 3.5 V) is applied to the electrodes 21. The distance between the electrodes lying opposite one another in one plane (tip-tip) is 40 μm.

Under the following operating conditions, it was possible to accumulate hepatitis A viruses (diameter around 30 nm) within 10 minutes. High-frequency AC voltages with frequency: 7.4 MHz, amplitude: 4 V _rms ), electrode spacing: 5 μm. The starting concentration of the viruses in the compartment was approx. 10 ⁹ to 10 ¹⁰ / ml. The accumulation of the fluorescence-labeled hepatitis A viruses is shown in FIG. 4B for different observation times. After 2 minutes, an initially small aggregate was formed from the viruses, which had a diameter of approx. 4 μm (9 min.) Grew. With a catchment area of approx. 100 μm * 100 μm * 10 μm (channel height) corresponds to a concentration of approx. 10 ³ .

FIG. 5 schematically illustrates the formation of a series of collection areas 41, 42, 43, ... in the channel of a fluidic microsystem, only the electrodes 21 of the electrode arrangements on one of the side surfaces of the channel and the associated connecting lines via which the electrodes are shown being shown for reasons of clarity Electrodes 21 are connected to a voltage source. In the left part, the counter-phase control of adjacent electrodes in a single field cage 20 is symbolically illustrated, with which the desired flow vortices can be generated at each collection area 41, 42, 43, ...

Outside the fluidic microsystem there is a measuring device (not shown) with which the particles in the collection areas 41, 42, 43, ... are measured through a window 51 along a scanning line 52. For example, a fluorescence correlation measurement (FCS) is carried out to detect receptor-ligand binding events in the collected particles.

A cascade-like combination of a plurality of circulating flows is illustrated schematically in FIG. 6. In this embodiment of the invention, the electrode arrangement 20 generates a flow directed toward the collection region 40 over a relatively large area. For example, a plurality of collecting electrodes 21, 22 pointing radially to the collecting area 40 are provided. The innermost electrodes 23 simultaneously form collecting and cage electrodes, which form a field cage according to FIG. Outdoor

Particles are transported, for example, with the vortex 34 on the first collecting electrode 21 into the vortex 35 of the second collecting electrode 22, from which the further transport to the vortex 36 of the collecting and cage electrode 23 takes place. With this, the particles are transported into the central collection area 40.

FIG. 6 illustrates that two vortices are formed in each case on a strip-shaped electrode, the axis 31 (shown offset) of the flow circulation being aligned with the electrodes perpendicular to the adjacent side surface. Deviating from the illustrated straight strip shape, the electrodes in the embodiment of the invention shown in FIG. 6 or also in the exemplary embodiments described above can have a conical shape in which the width of the electrode strip widens outwards with increasing radial distance from the collection area. With this design, the catchment area of the collecting currents can be expanded. Alternatively, it is possible for the electrodes to have a straight strip shape and for the electrodes to become larger with a radial distance from the collection area to the outside. For example, narrow, small electrodes and wide, large electrodes are provided on the inside. B. the aspect ratio of the electrodes increases.

FIG. 7 illustrates an embodiment of the collection device according to the invention with an electrode arrangement 20 which has an outer cage 20.1, in the catch area of which an inner cage 20.2 is formed. Each of the inner and outer field cages 20.1 and 20.2 is a closed 8-electrode field cage. The associated electrode arrangements are arranged offset by 45 ° relative to one another, as a result of which the interaction of the two field cages is improved.

FIG. 8 illustrates the flow profiles resulting from the embodiment according to FIG. 7 (numerical simulation). The flow profiles are shaped in such a way that the intake area of the electrode arrangement 20 is enlarged and the central resting or particle collection zone is also expanded. In contrast to the concentric double arrangement, the outer field cage 20.1 alone would provide a lower flow and thus a less effective particle transport, while the inner field cage 20.2 alone would have a smaller catchment area and a smaller quiet zone.

In the electrode arrangements shown in FIGS. 5, 6 and 7, the individual electrodes and their connecting lines to the voltage sources are electrically isolated from one another. profiled. The insulation is carried out by a multi-level structure consisting of electrode and insulation layers.

According to a further modification of the invention, the collecting device can be equipped with a cooling device, e.g. B. be equipped with a Peltier element in order to avoid undesired overall heating of the collecting device.

The features of the invention disclosed in the above description, the drawings and the claims can be of significance both individually and in combination for the implementation of the invention in its various configurations.

Claims

1. A method for collecting particles (1, 2) suspended in a liquid, comprising the steps: - Provision of the liquid with the suspended particles (1, 2) in a compartment (10) with side surfaces (11), at least one electrode (21) being arranged on at least one of the side surfaces (11), and - Generation of high-frequency electrical fields with the at least one electrode (21) to form at least one circulating flow (30) with which the particles (1, 2) are guided to at least one predetermined collection area (40) in the compartment (10) , characterized in that - The flow (30) is formed in such a way that at least one branch of the flow runs along a longitudinal extent of the at least one electrode (21) and the flow (30) rotates around an axis (31) that is perpendicular to the respectively adjacent side surface (11 ) is aligned with the electrode (21). 2. The method according to claim 1, in which the particles are arranged in the collection area (40) without touching the side surface (11) of the compartment (10). 3. The method according to claim 1, wherein the particles in the collection area (40) are arranged so that they touch one of the side surfaces (11) of the compartment (10). 4. The method according to at least one of the preceding claims, in which a plurality of circulating flows (32, 33) are generated on each electrode (21) with which the Particles are led to the at least one collection area (40). 5. The method according to at least one of the preceding claims, in which at least one circulating flow (30) is generated in each case on a plurality of electrodes (21, 22, 23), so that the particles are guided to the at least one collection area (40). 6. The method according to claim 5, wherein the electrodes are arranged on different sides of the collection area (40), of which the particles are guided to the collection area (40) with a plurality of flows. 7. The method of claim 5 or 6, wherein the flows are generated substantially symmetrically relative to the collection area (40). 8. The method according to at least one of the preceding claims, in which the high-frequency electric fields exert forces on the particles by means of negative dielectrophoresis, which are directed towards the collection area (40). 9. The method according to at least one of the preceding claims, in which the high-frequency electric fields are generated with ribbon-shaped electrodes of an electrode arrangement (20) for producing at least one dielectrophoretic field cage, which are arranged on the side faces (11) of the compartment. 10. The method of claim 9, wherein the dielectrophoretic field cage is generated with a potential minimum, which is located in the collection area (40). 11. The method according to claim 10, in which a dielectrophoretic field cage is produced which is closed in at least two spatial directions. 12. The method according to at least one of claims 8 to 11, wherein the high-frequency electric fields with electrodes of an electrode arrangement (20) with an outer dielectrophoretic field cage (20.1) and with an inner dielectrophoretic field cage (20.2) are generated, the electrodes on the Side surfaces (11) of the compartment are arranged. 13. The method according to at least one of the preceding claims, in which the particles are guided into the collection area (40) from an intake area of the compartment (10) whose volume is 10 ² to 10 ⁹ times larger than the volume of the collection area (40 ) is. 14. The method of claim 13, wherein the feed zone up to 1 fl have a volume of up to 50 ul and the collection area (40) ^■ a volume of 40 ul. 15. The method according to at least one of the preceding claims, in which at least one further force acts on the particles in the collection area (40). 16. The method of claim 15, wherein the force is an optically effective, a dielectrophoretic or a magnetic see. 17. The method according to at least one of the preceding claims, in which a measurement is carried out on the collected particles in the collection area (40). 18. The method of claim 17, wherein the measurement comprises an electrical, electrochemical or optical measurement. 19. The method of claim 18, wherein the measurement comprises detection of a receptor-ligand binding event. 20. The method according to at least one of the preceding claims, in which a plurality of collection areas (41, 42, 43, ...) are arranged in the compartment, in which particles are collected. 21. The method according to at least one of the preceding claims, in which a laminar flow or an ultrasound field is generated in the compartment, which overlap with the circulating flow (30). 22. The method according to at least one of the preceding claims, in which a plurality of circulating flows (34, 35, 36) are generated in the compartment (10), which overlap one another. 23. The method according to at least one of the preceding claims, in which particles having a diameter which is less than 1 μm are collected. 24. The method according to claim 23, in which particles are collected which comprise cells, viruses, bacteria, proteins, cell components or biological macromolecules. 25. A collection device for collecting particles suspended in a liquid, comprising: - A compartment (10) delimited by side surfaces (11) for receiving the liquid with the suspended particles, and - At least one electrode (21) which is arranged on at least one of the side surfaces (11) and with which high-frequency electrical fields can be generated in the compartment (10) to form at least one circulating flow (30) with which the particles form at least one predetermined collection area (40) can be guided in the compartment (10), characterized in that - The at least one electrode has an elongated shape and is configured to form the at least one flow (30) such that a branch of the flow (30) runs along the elongated shape, and - At least one axis (31) around which the flow (30) rotates, is aligned perpendicular to the respectively adjacent side surface (11) with the electrode. 26. The apparatus of claim 25, wherein the collection area (40) is arranged at a distance from the side surfaces (11) of the compartment (10). 27. The apparatus of claim 25, wherein the collection area (40) is one of the side surfaces (11) of the compartment (10) touched. 28. The device according to at least one of claims 25 to 27, in which an electrode arrangement (20) with a plurality of electrodes (21, 22, 23) is set up to generate a plurality of circulating flows (32, 33). 29. The device according to at least one of claims 25 to 28, in which on the side surfaces (11) of the compartment Fig electrodes is arranged to produce at least one dielectrophoretic field cage. 30. The apparatus of claim 29, wherein the cage electrodes are part of the electrode arrangement (20). 31. The apparatus of claim 29, wherein the cage electrodes form an outer dielectrophoretic field cage (20.1) and an inner dielectrophoretic field cage (20.2) which is arranged in the outer dielectrophoretic field cage (20.1). 32. Device according to at least one of claims 25 to 29, in which a heating device, cooling device and / or a light source are provided. 33. Device according to at least one of claims 25 to 32, in which the collection area (40) is equipped with a magnetic field device. 34. Device according to at least one of claims 25 to 33, which is equipped with a measuring device (50) for detecting electrical or optical properties of particles in the collection area (40). 35. Device according to at least one of claims 25 to 34, in which at least one of the side surfaces of the compartment in the area of the at least one collection area is functionalized with detection spots in the form of receptor molecules. 36. Device according to at least one of claims 25 to 35, in which several collection areas (41, 42, 43) are provided. 37. Device according to at least one of claims 25 to 36, wherein the compartment is part of a channel of a fluidic microsystem. 38. Device according to claim 37, in which the collection areas (41, 42, 43) are arranged in rows along a longitudinal direction of the channel.