DE19860118C1 - System for dielectrophoretical manipulation of particles suspended in a liquid - Google Patents

Abstract

The electrodes for use in a micro-system, for dielectrophoretical manipulation of particles suspended in a liquid, are deployed with at least one micro-electrode on a side wall of the channel to generate a field barrier along a reference surface, which passes through the channel at least partially. The micro-electrode has a given curvature or angle in relation to the channel flow direction, so that the reference surface has a determined curvature in relation to the flow direction. At least two micro-electrodes are at facing channel walls, of the same design and orientation, each as a curved strip. The micro-electrodes have a curvature so that, according to the flow profile, the force applied to the particles in each zone of the field barrier is directed upstream in relation to the micro-electrode. The two electrodes form a downstream closed angle section. Four micro-electrodes can be used as focus electrodes to form a particle funnel. They are curved so that the force acting on a particle moves it from one end of the electrode to the other end, in a direction change between the upstream and downstream zones flanking the electrode. The electrodes can have a sorting action with the field barrier acting with the flow profile of the suspension through the channel, so that particles with different passive electrical characteristics are directed into different paths by the electrodes. Trap electrodes can be deployed as a group across the channel. The micro-electrodes can be positioned in pairs at the bottom and top surfaces of the channel, and the electrodes at facing channel walls can have different geometric shapes. The channel has a rectangular cross section, with the electrodes at the narrower walls, with a flat electrode at one wall and a strip electrode at the facing wall. The flat electrodes are not earthed. The channel can be divided by a wall into two part-channels. An opening in the dividing wall is at the facing micro-electrodes. Two micro-electrodes can be at the bottom and top surfaces of the channel as focus electrodes, and a third auxiliary electrode is at the center of the channel at a gap from the top and bottom surfaces. The opening in the dividing wall is upstream of the auxiliary electrode. A cube-shaped gathering electrode can be in one channel wall, with a number of reservoirs, working with a deflection electrode at the facing channel wall to deflect the particles in the reservoirs. A number of cube-shaped electrodes can be at one channel wall, with facing deflection electrodes at the opposite wall to deflect the particles in the gaps between the cube electrodes. Independent claims are also included for (1) a technique to manipulate particles in a liquid suspension in a fluid micro-system (24). The micro-system (24) is closed at the end in the reference direction. The particles are moved at a given speed by centrifugal and/or gravity forces on a parallel line to the reference direction. Deflection forces are applied to divert the particles from the reference direction. (2) an appts. with a micro-system (24) to be fitted to the rotor of a centrifuge. The centrifugal forces act on the particles in the channel (21), in parallel to the channel alignment. The ends of the channel are closed or can be closed when subjected to centrifugal forces. Preferred Features:The micro-system (24) is fitted to a swing rotor centrifuge appts. so that the particles settle as a sediment by gravity when the rotor is at rest, and a moved by the centrifugal forces when the rotor is operating. The deflection forces are applied by electrical polarizing forces, optical forces, magnetic forces or ultrasonic forces. The centrifugal forces acting on the particles are equal to or weaker than the deflection forces. The centrifugal force moves the particles sufficiently slowly that they can be deflected out of the reference direction. The centrifuge is controlled by an electrical or optic sensor which registers the particle movement speeds. The centrifugal forces move the particles in a number of movements through separate centrifugal steps, with adjustments to the micro-system between the steps to alter the alignment in relation to the centrifugal forces. The rotary speed of the centrifuge is set according to the dimensions or density of the particles. Rising forces are applied to the particles, against the direction of the centrifugal and/or gravity forces. The micro-electrodes (10-12) are structured to generate field barriers in the micro-system, at facing longitudinal sides of the channel. The electrodes are supplied with a high frequency alternating voltage. The micro-electrodes are strip electrodes, at an angle to the channel alignment, to generate field barriers in the channel. The micro-system is in a swing mounting at the centrifuge rotor. An electronic control is at the centrifuge rotor for the micro-system.

Description

The invention relates to electrode arrangements for production functional field barriers in microsystems leading to manipulation suspended particles are set up, in particular functional microelectrodes for dielectrophoretic deflection kung of microscopic particles, and microsystems with such electrode arrangements are equipped and their Uses.

Manipulating suspended particles in fluidic micro systems is well known and is used for example by G. Fuhr et al. in "Naturwissenschaften", vol. 81, 1994, p. 528 ff., described. The microsystems in particular form a channel structures from a suspension liquid to the manipulating particles are flowed through. Usually be these channel structures have a rectangular cross-sectional area che, with the lower and upper channel in operating position walls (floor and top surfaces) a greater width than that have side channel walls (side surfaces). In the canal structures are attached to the channel walls of microelectrodes brings that entrusted with high-frequency electrical fields be hit. Under the effect of high-frequency electri fields are in the suspended particles on the Ba sis negative or positive dielectrophoresis polarization Forces generated a repulsion from the electrodes and in Interaction with flow forces in the suspension river allow manipulation of the particles in the channel. The Microelectrodes of conventional microsystems are usually on the wider channel walls than straight electrodes tapes attached.  

To generate the high frequency effective for dielectrophoresis Quent electric fields each have two electrode banks the together, each on opposite channel walls because the same shape and orientation are appropriate. The straight electrode strips run parallel to, for example Channel orientation or flow direction of the suspension rivers liquid in the respective channel section or under a agreed angles at an angle to the channel orientation. The electrodes have straps for effective and safe training of the bottom forces on the particles to be manipulated a length ge, which is the characteristic dimension of the particles by one Multiple (factor about 20 to 50) exceeds.

The conventional microsystems have disadvantages with regard to the effectiveness of generating polarizing forces that Stability and lifespan of the microelectrodes and the on limited ability to gradient forces within the channel generate structure. These disadvantages are particularly related the formed over relatively long lengths in the channel Electrode strips together. The longer an electrode band is, the longer there is a flowing particle in the Area of effect of the electrode strip, so that the effective speed of the respective microelectrode or that generated by it field barrier rises. On the other hand, the long ones are electric the tapes also more prone to failure. Due to manufacturing defects or mechanical stresses can occur interruptions, which lead to electrode failure. Furthermore, the microelec tread so far to achieve the same over the channel length lasting and therefore reproducible force effect on the ge just called electrode design limited.

Because of the disadvantages mentioned, the area of application is also said fluidic microsystems with dielectrophoreti particle manipulation on the guidance of the particles in  the channel structure or the deflection of particles from a given current flow.

The object of the invention is to provide an improved electrode arrangement solutions for microsystems with dielectrophoretic particles to create distraction with the disadvantages of conventional Microsystems are overcome and the particular one he own and enable broader scope, too to create effective field barriers over shorter canal sections gen. The object of the invention is also novel Mikrosy steme that with such improved electrode arrangements are permitted to use such microsystems give.

This task is accomplished through electrode arrangements with the characteristics len solved according to claim 1. Advantageous execution Forms and applications of the invention result from the dependent claims.

An electrode arrangement according to the invention is particularly there to set up in a microsystem along field barriers generate predetermined reference surfaces, which are at least partly over the width of a channel in the microsystem stretch and predetermined curvatures relative to the longitudinal extent channel, to the direction of flow of the suspension liquid speed in the channel or to the direction of movement of the (not distracted ten) have particles. The term "reference surface" is used in this context not just a two-dimensional structure designated, but a spatial area on which the Feldwir kung of the respective microelectrodes and in which the Field barrier for dielectric influencing of the microscopy is formed in the microsystem. This room rich essentially corresponds to an area of the Field lines of the effective microelectrodes is interspersed, and extends with interacting microelectrode pairs as  curved hypersurface between the microelectrodes or at single acting microelectrodes as a hypersurface, which the Field line distribution of the single-acting microelectrode tense. The reference surfaces define the places where Pola forces of risk in the microscopic particles can be witnessed. The microelectrodes are thus trained det that the reference areas depending on the intended function of the respective microelectrodes has a predetermined curvature in Relation to the direction of movement of the particles in the microsystem have so that an optimal interaction of the Polarisati forces and mechanical forces is achieved. Hence who which the field barriers also serve as functional field barriers designated. The term "curvature" used here refers not on the curvature of field lines on straight micro-electro by the emergence of the field lines in the adjacent Room. Rather, the curvature denotes the design of the Microelectrode trained field barriers.

The field barriers with the cover curved according to the invention areas are preferably according to one of the following three Basic shapes designed. According to a first variant, there is ei ne electrode arrangement according to the invention from at least one ribbon-shaped, curved microelectrode located on the wider channel wall (floor and / or top surface) at least partially extends across the channel width. With a second Variant, at least one microelectrode is provided, which is connected to the narrower duct wall (side surface) is attached. At The third variant has at least one microelectrode the bottom and / or top surface of the channel and at least one Auxiliary electrode at a distance from the bottom or side surface of the channel attached. The auxiliary electrode provides a defor tion of the microelectrode or the microelectrodes field lines going out from the bottom or side surfaces of the channel s, so that the curved reference surfaces according to the invention be det. In all variants, the respective electrical  the (microelectrodes, auxiliary electrodes) per se band or be punctiform or flat. The electrodes orders of the second and third variants are also called referred to as three-dimensional electrode arrangements because of this Microelectrodes are used, which from the levels of Bo protrude from or from the side of the channel are arranged at a distance.

The invention thus relates to the optimization of micro electrodes in relation to their effect on suspended part that can include natural or synthetic particles NEN, e.g. B. to generate maximum forces at the same time minimized electrical losses.

The invention has the following advantages. The design the microelectrodes can e.g. B. the flow profile in the Suspension liquid can be adjusted. This provides the advantage partly that the microelectrodes are made shorter and can be designed to produce lower barriers, depending but the same effectiveness as conventional microelectrodes in the form of straight ribbons. This has an advantageous effect on the lifespan and functionality of the microelectro and thus the entire microsystem. In addition, the space available in a microsystem can be used more effectively the. Electrode arrangements are also provided, with those gradients and thus depending on the respective Channel area different forces can be generated. It is provided, for example, that the field barriers Microelectrodes are designed so that the particles in the Greater polarizing forces are exerted in the middle of the channel than on the edge of the channel.

The formation of field barriers according to the invention along ge curved reference surfaces also enable the creation of new art applications of microsystems, in particular for steering  suspended particles in certain channel areas, for sorting ren of suspended particles according to their passive electri properties or for suspending or collecting ter particles in certain channel sections. To the latter The microelectrodes are used with a geometri form for holding the particles in a solution current or to generate a particle formation. All of the applications mentioned provide one over the other Microsystem non-contact manipulation of the suspended Particles, which is particularly essential for manipulating bio logical cells or cell components.

Preferred applications are in microsystem technology Separation, manipulation, loading, fusion, permeation, pair chenbildung and aggregate formation of microscopic Particles.

Details and advantages of the invention will be apparent from the the drawings described below can be seen. Show it:

FIG. 1a to 1d are schematic perspective views of a channel structure with micro-electrodes for generating field barriers in a microchannel and examples according to the invention curved reference surfaces;

Fig. 2 is a schematic plan view of ribbon-shaped, curved microelectrodes;

FIG. 3 shows a schematic plan view of a modified design of band-shaped, curved microelectrodes;

FIG. 4a to 4c are schematic views for illustrating tion of sorting electrodes for Teilchensortie;

FIGS. 5a and 5b are schematic views of microelectrodes for generating field gradients;

FIG. 6a through 6e are schematic views of inventive band-shaped trapping electrodes;

Fig. 7a to 7c show further embodiments of inventive trapping electrodes;

Fig. 8: a plan view of various electrode arrangements for generating curved field barriers;

Fig. 9: a schematic view of an electrode assembly on the side walls of a channel;

Figs. 10 to 12: Various embodiments of three-dimen sional electrode assemblies; and

Fig. 13 is a schematic plan view of a segmented electrode assembly.

Fig. 1a shows a schematic example of the execution of microelectrodes for generating field barriers in micro channels. The fluidic microsystem 20 is shown in exaggerated perspective side view of a channel structure. The channel 21 is formed by two spacers 23 arranged at a distance on a substrate 22 and carrying a cover part 24 . The channel width and height are approx. 200 µm or 40 µm, but can also be smaller. Structures of this type are produced, for example, using the processing techniques known per se in semiconductor technology. The substrate 22 forms the bottom surface 21 a of the channel 21 . Accordingly, the cover surface 21 b (not shown separately for reasons of clarity) is formed by the cover part 24 . The electrode arrangement 10 consists of microelectrodes 11 , 12 which are attached to the bottom surface 21 a or on the top surface 21 b. Each of the microelectrodes 11 , 12 consists of curved electrode strips, which are described in more detail below.

In FIG. 1a, the electrode strips form an electrode structure, which is explained in detail below with reference to FIG. 2. The other embodiments of the electrode arrangements according to the invention described below can be brought accordingly on the bottom, top and / or side surfaces of the channel 21 . The microchannel 21 is flowed through by a suspension liquid (in the image from right to left) in which particles 30 are suspended. The electrode arrangement 10 shown in FIG. 1 a has, for example, the task of guiding the particles 30 from different trajectories within the channel to a middle trajectory according to arrow A. To this end, the microelectrodes 11 , 12 are subjected to such electrical potentials that electrical field barriers form in the channel, which force the particles flowing from the right toward the center of the channel (arrow directions B).

The typical dimensions of the microelectrodes 11 , 12 range from 0.1 to a few tens of micrometers (typically 5... 10 .mu.m), a thickness of 100 nm to a few micrometers (typically 200 nm) and a length of up to several hundred micrometers. The inside of the channel 21 is not restricted by the electrodes processed on the top and bottom of the parts 23 , 24 due to the small thickness of the electrodes. The part 23 is a spacer, the structure of which forms the side channel walls.

The microelectrodes 11 , 12 are driven by means of high-frequency electrical signals (typically with a frequency in the MHz range and an amplitude in the volt range). The respective opposite electrodes 11 a, 11 b form a control pair, although the electrodes lying in one plane can also work together in their control (phase, frequency, amplitude). The high-frequency electrical field generated by the channel 21 , ie perpendicular to the direction of flow, has a polarizing effect on suspended particles 30 (which can also be living cells or viruses). At the abovementioned frequencies and suitable conductivity of the suspension liquid surrounding the particles, the particles are repelled by the electrodes. In this way, the hydrodynamically open channel 21 can be structured via the electric fields so that it can be switched on and off, it can be divided or the movement paths of the particles in the passive flow field can be influenced. Furthermore, it is possible to retard the particles despite permanent flow or to position them in a stable position without touching a surface. The type and design of the electrode arrangements formed therefor is also the subject of the invention.

In the following design forms are described dena orders according to the invention electric, for reasons of clarity in Figs. 2 to 13, if necessary, only one planar electrode driving voltage North (or parts thereof), for example. B. is shown on the bottom surface of the channel.

The Fig. 1b to 1c show the basic types of barriers or electromagnetic field limits that the above variants are reali Siert with electrode assemblies according to the invention according to. The illustrations are basic representations of the reference surfaces on which the field barriers are formed with microelectrodes according to the invention. For reasons of clarity, only parts of the side surface (spacer 23 ) and the bottom surface 21 a of the channel, the microelectrodes 11 , 12 and the course of the reference surfaces (hatched) are shown.

According to the above-mentioned first variant, the field barrier is formed in the channel between two curved microelectrodes 11 , 12 on the bottom and top surfaces of the channel ( FIG. 1b). The reference surface of the field barrier (shown hatched) runs accordingly as a curved surface that is perpendicular to the floor and top surfaces. If the microelectrodes 11 , 12 are curved for example according to a certain hyperbolic flow profile (see below), the reference surface forms the cutout of the outer surface of a hyperbolic cylinder. If the microelectrodes 11 , 12 are not arranged exactly one above the other, the reference surface will also be skewed with respect to the bottom and top surfaces of the channel.

Referring to FIG. 1c, the Bezugsflä hatched che spans a region of space, which is traversed by the field lines running surface of a micro-electrode 11 on a side surface of the channel to a micro-electrode 12 on the opposite sides. In the example shown, he ste microelectrode 11 has a larger area than the second microelectrode 12 , so that a field line concentration occurs in the latter. As a result, the polarization forces acting on the suspended particles from the field barrier are greater near the second microelectrode 12 than near the first microelectrode 11 (see also FIG. 9).

The above-mentioned third variant with a three-dimensional electrode arrangement is illustrated in FIG. 1d. The microelectrodes 11 , 12 are located on the bottom or top surfaces of the channel, while the auxiliary electrode 13 is arranged with a suitable holder in the center of the channel (see also FIG. 10). By means of the auxiliary electrode 13 , the field lines between the microelectrodes 11 , 12 are distorted, so that there is the hatched, curved reference surface (partially shown).

The illustrated reference surfaces only represent the position the field barriers, without also those in the corresponding Be rich acting forces, d. H. the height of the field barriers, too illustrate. The acting forces essentially depend on the field line density and the passive electrical property th of the particles to be manipulated in the respective channel area from. The functional field barriers according to the invention thus by the geometric shape of the interacting Microelectrodes both in terms of their shape (curvatures etc.), since the dielectrophoretic repulsive forces in the we stand substantially perpendicular to the reference surfaces, as well as in Affected in relation to their areas (field line density).

An electrode arrangement 10 according to the invention corresponding to the above-mentioned first variant is shown in FIG. 2. On the bottom surface 21 a of the laterally limited by the spacer 23 th channel of a microsystem, micro electrodes 11 a, 11 b are arranged. The microelectrodes 11 a, 11 b are opened via the control lines 14 with high-frequency electrical potentials and act together to form a so-called particle funnel as follows.

The electrode arrangement 10 is intended to focus on the center line of the channel without contact, initially in the entire channel width or the entire channel volume of flowing particles 30 a, as is illustrated by the position of the part 30 b. The advantage of this arrangement is the optimization of the electrode strips with respect to the safety of the deflection (focusing) of the suspended particles, the shortening of the electrode arrangement in the longitudinal direction of the channel and the reduction in electrical losses at the microelectrodes.

In this embodiment of the invention, the basic idea is the design of the microelectrodes in it, the curvature of the reference surfaces formed by the field barrier to the currents adapting forces in the sewer. In microsystems with channel diodes dimensions below 500 µm takes place because of the these dimensions, the low Reynolds numbers the training la mineral flows with predetermined flow profiles. The Flow velocity near the canal walls is low lower than in the middle of the channel (flow velocity immediately bar on the duct wall equals zero). This will kick close flow forces lower than in the middle of the channel on. This enables manipulation of the particles on the channel edge with lower polarization forces or with a steep ge polarization forces directed against the flow forces as in the middle of the canal. The interaction of the flow and pola Risks are explained below. Are along the ge The entire length of the microelectrodes is essentially the same pola trained risk forces, it is enough for a safe exit steering that the particles to be manipulated on the edge of the channel microelectrodes projecting steeper into the channel than in the middle of the canal. This allows a substantial shortening of the Microelectrodes (see below).

The forces acting on the particles are illustrated in FIG. 2 by way of example in individual sections of the microelectrode 11 a. The respective total force is composed of the electrically induced repulsive force F _P (polarization force) and the driving force F _S , which is exerted by the flow of the suspension liquid or from outside (e.g. in centrifugal systems as a centrifugal force). The resulting total force F _R results from the vector addition of the forces F _P and F _S. If the vector of the total force F _R does not intersect the field barrier of the microelectrode 11 a, a particle is reliably deflected. The force diagrams in FIG. 2 illustrate that the driving force F _{S increases} towards the center of the channel. To meet the above-mentioned condition for safe particle deflection, the angle between the alignment of the microelectrode 11 a and the channel longitudinal direction changes accordingly from a steeper angle at the channel edge to a small angle (almost parallelism) in the center of the channel.

The microelectrodes 11 a, 11 b are thus curved depending on the flow profile. In the illustrated embodiment, each of the ribbon-shaped microelectrodes consists of a plurality of straight electrode sections. In a modified embodiment, a continuous curvature course can also be provided. The course of curvature is also correspondingly parabolic or hyperbolic in accordance with the parabolic or hyperbolic flow profiles occurring in laminar flows.

According to the invention, the microelectrodes 11 a, 11 b form the field barriers along a curved reference surface.

The micro-electrodes 11 c, 11 d are not vorgese in practice hen and used in the representation of the comparison of a proper arrangement of polygonal OF INVENTION dung curved Microelectric the same straight electrode bands deflection power. It can be seen that the microelectrodes 11 a, 11 b according to the invention are significantly shorter.

The narrow electrode strips shown in Fig. 2 are very sensitive to manufacturing errors and local interruptions. A hairline crack at the base of a ribbon-shaped microelectrode leads to failure of the entire microelectrode. This can be remedied with an electrode design, which is shown schematically in Fig. 3. The structuring and covering technology described in relation to FIG. 3 can also be implemented in the other embodiments of the invention.

Fig. 3 shows a microelectrodes 11 with a control line 14. The electrode 11 consists of an electrically conductive layer 15 which carries an electrically non-conductive insulation or cover layer 16 . The insulation layer 16 has a structuring in the form of recesses through which the layer 15 is exposed. In FIG. 3, the insulation layer 16 is hatched and the (eg metallic) layer 15 is drawn in black. The insulation layer is structured in accordance with the desired shape of microelectrodes, which in the example shown are set up to form a particle funnel as in FIG. 2. The electrical field lines occur from the metallic layer 15 in the channel only in the areas of the recesses, so that in turn field barriers are formed with application-dependent curved reference surfaces. This Gestal device has the advantage that a slight interruption of the exposed portions of the metallic layer 15 (ie the microelectrode) means no failure, since the rest of the metallic layer 15 also the other exposed areas of the microelectrode are opened with the respective potentials . The layer 15 has a thickness of approx. 50 nm up to a few µm, typically approx. 200 nm. The thickness of the insulation layer is approx. 100 nm down to a few µm. The insulation layer preferably consists of biocompatible materials (e.g. oxides, SiO ₂ , SiNO ₃ and the like, polymers, tantalum compounds or the like).

Another embodiment of an electrode assembly 10 according to the invention corresponding to the above-mentioned first variant is explained below with reference to FIGS . 4a to 4c. An important application of fluidic microsystems is the sorting of the suspended particles depending on their passive electrical properties (hereinafter also referred to as polarization properties with negative dielectrophoresis). The polarization properties depend on the dielectric properties of the particles and their dimensions. The dielectric properties of biological cells are a sensitive indicator of certain cell properties or changes, which in themselves would not be detectable by observing the size.

Particle sorting depending on its passive electrical properties is based on the following principle. Whether a particle can pass through the field barrier formed by a sorting electrode depends on whether or not the resulting force from the driving force F _S and the polarizing force F _P (see above) crosses the field barrier. If the resulting total force F _R passes through the field barrier, the particle moves in this direction, ie the sorting electrode is passed. However, if the resulting force F _R is in an area upstream of the sorting electrode, the particle will move in this direction and will not be able to pass through the sorting electrode. The resulting force F _R depends, as explained above, on the flow velocity of the channel and thus on the x position of the particle. The flow velocity increases towards the middle of the channel. Thus particles with a relatively large polarizability, which could not pass the sorting electrodes at the edge of the channel, are exposed to a stronger driving force F _S towards the center of the channel, so that it is then possible to pass the sorting electrode. The change in flow velocity in the x direction follows the flow profile and is usually non-linear. This would result in a non-linear separation behavior when using a straight sorting electrode. This is compensated for by the implementation of curved field barriers according to the invention. For this purpose, microelectrodes 41 a, 41 b with a curvature depending on the flow profile are used according to the principles explained with reference to FIG. 2.

FIG. 4a shows two examples of curved micro-electrodes 41 a, 41 b on the bottom surface 21a of a channel between lateral spacers 23rd The flow in the y direction is from left to right, with the arrows v representing the speed-flow profile in the channel. Upstream in front of the actual sorting electrode 41 a or 41 b there is a rectilinear microelectrode 47 , the task of which is to focus the particles 30 flowing from the left onto a starting line s. The microelectrode 47 can also be referred to as a focus electrode. It is (as shown) leads straight, conventional deflection or curved. Downstream of the focusing electrode 47 is one of the sorting electrodes 41 a or 41 b, the task of which is to transfer the incoming particles 30 depending on their polarization properties in different paths in the channel with respect to the x-direction. The particles with a high polarizability 30 a should move further in different directions from the particles with a low polarizability 30 b in the y-direction.

The sorting electrode 41 a is set up for a linear force effect. For this purpose, the curvature of the microelectrode is designed accordingly to the flow profile. At low flow velocities, a strong angle of attack between the microelectrode and the y direction and at higher flow velocities, a smaller angle of attack is formed. The microelectrode 41 a thus has an S shape with an inflection point in the center of the channel. After passing through the sorting electrode de 41 a, there is a linear relationship between the x coordinate of the particle and its polarizability. Is a nonlinear sorting effect intended, the microelectrode may be curved b as the sorting electrode. 11 The curvature is weaker than in the case of the sorting electrode 11 a, so that the influence of the driving force F _S is not compensated for by the speed of the flow. Depending on the adjusted conditions, there is a non-linear relationship between the x-position of the particles and their polarizability after passage of the sorting electrode 11 b. This design can be used in particular to separate two types of particles with different polarizabilities.

Experimental results have shown that with a sorting arrangement according to FIG. 4a erythrocytes can be cleanly separated from so-called Jurkart cells, whether both cells have the same size.

If the flow profile in the channel is not shown in Fig. 4a Darge presented pronounced parabolic shape, but a plateau shape, as are c sorting electrodes 41, 41 are provided d accelerator as Fig. 4b. The flow rate initially increases from the channel edge and then remains essentially constant in a central region of the channel. To achieve a linear sorting effect, the sorting electrode 41 a has a straight band shape in the central region and curvatures at the ends to take into account the changing drive force F _S. For a non-linear sorting effect, the sorting electrode 41 d is curved. From the approach of the sorting electrode 41 d at the control connection 14 to the end thereof, there is an increasing effect of the field barrier.

The shape of the sorting electrodes can also be adapted to more complicated flow profiles, as shown in Fig. 4c. In the microsystem 20 , a first channel 211 with a high flow rate and a second channel 212 with a lower flow rate open into a common channel 21 . Due to the laminarity of the flow, the flow profile is initially retained even in the common flow course. Correspondingly, the sorting electrodes 41 e and 41 f are curved in order to achieve a certain linear or non-linear sorting effect. The lower the flow rate, the greater the angle of attack between the direction of the microelectrode (orientation of the reference surface) and the longitudinal direction of the channel (y direction).

In Figs. 4b and 4c is for clarity of the focusing electrode 17 according to Fig. 4a not shown.

The sorting explained above takes place on the assumption of a potential that is constant over the entire length of the microelectrode. In reality, however, there are slight electrical losses along the microelectrode, so that the field barrier from the start of the microelectrode (at the control line) towards its end is getting smaller and smaller. This phenomenon can be taken into account in the curvature of the sorting electrodes by providing a larger electrode curvature on the control line side of the channel than at the end of the sorting electrodes. However, the phenomenon mentioned can also be used deliberately for additional, non-linear separation effects. The drop in potential towards the end of the microelectrodes can, in the case of modified embodiments, be reinforced in particular by measures for the formation of field gradients. This means that the height of the field barrier formed by the microelectrode increases or decreases in the course of the curved electrode strip. Such gradient electrodes can be constructed with a shape according to FIG. 5.

For particle sorting in relation to different feature groups, a plurality of sorting electrodes according to FIG. 4 can be arranged in succession in the channel direction. Each sorting electrode is subjected to a characteristic potential or potential curve at a predetermined frequency. For example, relatively low frequencies (in the range of around 10 kHz) can be used for sorting in relation to various dielectric membrane properties and high frequencies (above 100 kHz) for sorting depending on the cytoplasmic conductivity of biological cells.

Fig. 5 shows gradient electrodes 51 a, 51 b for reasons of clarity with straight electrode strips. To set field barriers designed according to the invention with curved reference surfaces, the gradient electrodes shown additionally have a characteristic, application-dependent curvature in accordance with the principles explained above.

The gradient electrode 51 a is formed by a closed electrode band guided around a triangular surface. With increasing distance from the control line 14 , the Feldli line density corresponding to the fanning out of the triangle is low. The same applies to the gradient electrode 51 b with two diverging subbands 511 b and 512 b.

Another important application of fluidic microsystems is the collection and at least temporary arrangement of particles or groups of particles in the suspension liquid through the channel. For this purpose, electrode arrangements according to the invention are designed as catch electrodes, as will be explained in the following with reference to FIGS . 6 to 8.

FIG. 6a shows the basic form of a collecting electrode. Again, only one microelectrode is shown on the bottom or top surface of a channel, which interacts with a second microelectrode on the opposite side of the channel. A catch electrode 61 a consists of an electrode strip with a win kelabschnitt 611 a and a feed section 612 a. The Win kelabschnitt 611 a forms an angle in the flow direction (x direction). The opening angle of the Winkelab section 611 a is selected depending on the shape of the particles to be captured and is preferably less than 90 °, z. B. in the range of 20 to 60 °. The opposite angular sections of interacting electrodes form a barrier for the particles 30 to be captured even under the effect of the driving force due to the flow. This barrier remains for the duration of the triggering of the capture electrodes. The feed section 612 a is electrically ineffective due to an insulation layer 16 . Fig. 6b shows a modified form of a catch electrode 61 b, which is made according to the covering technique explained above with reference to FIG. 3. The electrically effective angle section 611 b is formed by a recess in the insulation layer 16 , through which a deeper metallic layer 15 is exposed to the suspension liquid with the particles.

Figs. 6c and 6d show corresponding catch electrodes 61 c and 61 d respectively with a plurality of angular portions 611 c and 611 d. These angular sections are in turn set up to catch inflowing particles 30 . By lining up the angular sections 611 c and 611 d transversely to the longitudinal direction of the channel (x direction), the particles flowing into the different channel areas can be selectively collected. A collecting electrode 61 c and 61 is advantageously bined with one of the sorting electrode according to FIGS. 4a to 4c kom d. The sorted particles are collected separately in the individual capture areas of the capture electrodes. The catch electrode 61 d corresponds essentially to the catch electrode 61 c, the masking technique mentioned being implemented.

The target electrodes 61 c and 61 d are particularly well suited to form a line-up of particles in the suspension flow in the manner of a starting line, from which the particles flow away simultaneously when the control potentials of the target electrodes are switched off.

Fig. 6e shows a further embodiment of a catch electrode 61 e, in which a plurality of angular sections 611 e are also provided, which, however, are set up for the collection or collection of different sized particles or different sized collections of these.

The collection of a particle group 300 with a Fangelektro de 71 a is illustrated in Fig. 7a. This embodiment of a catch electrode differs from the catch electrode according to FIG. 6a only in terms of its dimensions. This design is particularly suitable for the formation of particle aggregates. Again, a combination with a sorting arrangement according to FIGS. 4a to 4c is preferably implemented.

The electrode arrangement according to FIG. 7b is collected to separate particles or particle groups on of suspension from the flow in the channel set, the x-direction differ with respect to their flow path in. The Mikroelektro denanodnung 71 b includes several partial target electrodes each with an angular section 711 b, which can be controlled separately. When such a catch electrode arrangement is combined with a sorting arrangement according to FIGS . 4a to 4c, the following procedure can be implemented with particular advantage.

First, a mixture of particles that flows through the channel in the micro system is sorted depending on the passive electrical properties of the particles and is thus directed to different paths that are spaced apart in the x direction. Then the particle-type-specific collection of the incoming particles in the individual lanes takes place with a catch electrode according to FIG. 7b. Through a sequential release of the partial target electrodes (in each case by switching off the control potentials), the previously sorted particles can continue to flow in groups in the microsystem. In the further course of the channel, for example, a division into several subchannels can take place, into which the groups of the particle types are specifically directed.

Fig. 7c shows a further collecting electrode 71 c for generating ei ner predetermined particle formation.

The angular sections of the capture electrodes shown in FIGS. 6 and 7 can extend, depending on the application, over the entire channel width or only over parts of the channel. Within an electrode arrangement, catch electrodes for an individual particle and / or for particle groups can be provided.

Further embodiments of combined sorting and collecting electrodes are illustrated in the top view of the bottom surface 21 a of a channel delimited by the spacers 23 according to FIG. 8. The channel is traversed in the y direction by the suspension liquid with suspended particles. Referring to FIG. 8a is a planar microelectrode 81 a acts on the bottom surface 21a together with a straight, belt-shaped micro electrode 82 a (gestri smiles shown) on the opposite top face of the channel. The flat microelectrode 81 a is produced by the covering technique explained above. A metallic layer carries an insulation layer 86 with a recess corresponding to the shape of the microelectrode 81 a (black ge). The field lines between the microelectrodes 81 a and 82 a run inhomogeneously across the flow direction, so that an asymmetrical field barrier or, in turn, a reference surface curved according to the invention results. In the middle of the channel, the field line density is greatest, so that the elec trically generated forces are in the range of the highest flow rate. As a result, a substantially constant equilibrium between the driving force by the flow and the electrical polarization force's rule is formed in the x-direction across the channel width. According to Fig. 8b is formed as a field barrier derum curved reference surface. The microelectrodes 81 b, 82 b are both linear or band-shaped and not opposed, but arranged offset from one another.

An electrode arrangement for forming particle aggregates is shown in FIG. 8c. The microelectrodes 81 c, 82 c form a series of juxtaposed funnel-shaped Parti catcher. Each particle catcher 11 is formed by a field barrier which initially narrows in a funnel shape in the direction of flow and then opens into a straight channel section 812 . The channel section is dimensioned so that two particles can be arranged one behind the other in the direction of flow. By forming adhesive forces, the particles form an aggregate (so-called couple loading in the direction of flow). The embodiment according to FIG. 8d has been modified such that a couple loading takes place transversely to the direction of flow. The individual catcher elements 811 d are formed with input-side electrode tips 813 d, with which an additional barrier effect or filter effect is achieved and already existing aggregates or larger particles 30 d are excluded from an arrangement in the catch electrode 81 d.

Another embodiment of an electrode assembly according to the invention according to the above-mentioned second variant is shown in FIG. 9. A channel 21 is formed in the microsystem 20 between the spacers 23 and is divided into subchannels 211 and 212 by a partition 231 . The partition 231 be sits an opening 232 , in the area on the side surfaces of the channel 21, the microelectrodes 91 and 92 are attached.

The microelectrodes 91 and 92 are so-called three-dimensional or high electrodes, which protrude on the side surfaces from the levels of the bottom and top surfaces of the channel 21 . The manufacture of the microelectrodes 91 and 92 is carried out using known semiconductor processing techniques (e.g. using the LIGA method). The microelectrode 91 is flat. The field lines extend to the opposite microelectrode 92 , which is made in the form of a band, and thus form a curved capture region with the reference surface illustrated in FIG. 1c.

If the microelectrodes 91 , 92 are driven with electrical high frequency potentials, the particles 30 are pressed with negative dielectrophoresis through the opening 232 into the adjacent subchannel. This particle deflection can in turn take place selectively as a function of the passive electrical properties of the suspended particles. Particles with low polarizability remain in the output channel, while particles with high polarizability are deflected in the adjacent channel.

In the design according to FIG. 9, it is not necessarily erfor sary that the micro-electrode is wired 91st It can be floating (floating) or omitted entirely. In the latter case, the microelectrode 92 acts as an antenna. The microelectrodes 91 , 92 preferably extend over the entire height of the side surfaces of the channel.

An embodiment of an electrode arrangement according to the above-mentioned third variant is illustrated in Fig. 10 (accordingly Fig. 1d). In a microsystem, in turn, two subchannels 211 , 212 run parallel to one another and are separated from one another by a partition 231 with an opening 232 . The electrode arrangement according to the invention consists of the microelectrodes on the bottom and top surfaces in the form of focusing electrodes 101 , 102 and the auxiliary electrode 103 . The auxiliary electrode is disposed on the partition 231 adjacent to the opening 232 on the downstream side of the opening 232 . The auxiliary electrode 103 does not have a control line. It only serves to shape the reference surface of the field barriers formed by the electrode arrangement. The microelectrodes interact as follows.

The focusing electrodes 101 and 102 each serve the focussing of the particles flowing into the subchannels 211 and 212, respectively, parts 30 a, 30 b on a center line corresponding to the position of the opening 232 in the partition 231 . Analogous to the deflection principle explained with reference to FIG. 9, the particles are deflected by the field barrier between the focusing electrode 101 and the auxiliary electrode 103 or between the focusing electrode 102 and the auxiliary electrode 103 through the opening 232 into the adjacent subchannel or in the given subchannel . According to a preferred procedure, the focusing electrodes 101 , 102 are operated at different frequencies in order to act in a particle-selective manner. Accordingly, a selective particle sorting into the subchannels or a deflection of predetermined particles into a neighboring subchannel for carrying out a specific active ingredient treatment with the suspension liquid given there can be achieved.

Another three-dimensional electrode arrangement is shown in FIG. 11. A channel 21 is flowed through in the y direction with a suspension liquid. On the bottom surface 21 a, a group of microelectrodes 111 is arranged which protrude into the channel 21 and are oriented at a distance from one another in the flow direction (y direction). Each microelectrode 111 has the shape of a cuboid. The microelectrodes 111 are made of metal or have a metallic surface coating without being provided with a control line itself.

On the opposite channel wall (top surface, not shown), a flat electrode arrangement 112 (deflection electrode) is provided which interacts with the microelectrodes 111 as follows. The flowing in the y-direction particles 30 a who exposed to the field barriers, which are characterized by the field-forming microelectrodes 111 asymmetrically and by curved reference surfaces. Again, the particles are deflected depending on the passive electrical properties. Weakly polarizable particles 31 a continue to flow in the y direction, while more polarizable particles 30 b are deflected into the distances between the field-forming electrodes 111 . The deflected particles 30 b are accordingly collected or collected and no longer transported with the flow in the y direction.

According to a preferred embodiment, the electrode arrangement according to FIG. 11 is seen at an intersection of two channels. The channel 21 in the y direction is crossed by a (not shown) channel through which a suspension liquid flows in the x direction (arrows A). This lateral additional flow continuously transports the deflected particles 30 b from the spaces between the field-forming electrodes 111 into the transverse channel.

The geometry of the field-forming microelectrodes 111 can be adapted to the flow conditions and the field course in the electrical spaces and the shape of the opposite electrode arrangement 112 .

The embodiment according to FIG. 11 can be modified by providing a volumetric field-forming electrode 121 instead of the field-forming electrodes 111 according to FIG. 12. The volumetric microelectrode is also referred to as a collective electrode de 121 . The collecting electrode 121 is located for example on the bottom surface of a channel (not shown) and consists of a cuboid block made of metallic or metallic coated material with a large number of columns and rows arranged bores or reservoirs 121 a. The collecting electrode is shown cut on the front, so that the reservoirs 121 a can be seen. The collecting electrode 121 a acts as follows with the flat electrode arrangement 122 (deflection electrode) on the opposite channel wall. An asymmetrical field barrier is generated between the microelectrodes 122 , 121 , which is set up to selectively deflect particles into the reservoirs 121 a. The particles 30 flow in the y direction through the channel. Particles, which are deflected downward into the collecting electrode 121 by the field effect, reach the reser voire 121 a and are fixed there. After all Reser voire 121 a are filled, the control can take place of the electrode arrangement that the particles are simultaneously transferred from the reservoirs 121 a in the flow and transported further as a particle or aggregate formation in this in such a manner. For this purpose, a further flat electrode arrangement (not shown) can be provided below the collecting electrode 121 , which is essentially designed like the flat electrode arrangement 122 .

According to a particular aspect of the invention, the microelectrodes can be segmented per se in the individual design forms. In this case, each microelectrode consists of a number of electrode segments which are arranged in accordance with the desired electrode function. A particularly versatile microelectrode 131 is shown in FIG. 13 as an array of a plurality of matrix-like, pixel-shaped electrode segments. The electrode segments are arranged over the entire width of the bottom surface 21 a between the spacers 23 and can be controlled individually. This enables the formation of the desired curved field barriers, in particular in accordance with the above-mentioned first variant, depending on the specific application, in particular as a function of the particles to be manipulated, the flow conditions and the task of the microsystem. In Fig. 13 the currently driven pixels are drawn in black and the non-driven pixels are drawn in white. In this case, the segmented microelectrode 131 takes over the function of a particle funnel according to FIG. 2, with which the particles 30 are focused in the center of the channel.

The pixel-shaped electrode segments allow loss minimizing focus, sorting or collection of part chen. Each electrode segment can have its own pot tialwert (voltage) or its own frequency become. This allows an arbitrary dielectric to be specified form a force field along the channel. So z. B. leaves compensate for the influence of the flow profile, that the pixels arranged transversely to the longitudinal direction of the channel with a voltage corresponding to the square root of the profile of the Flow rate can be controlled.

The size of the electrode segments and distances between the Electrode segments are preferably smaller than charak teristic dimensions of the particles to be manipulated, can also be larger.

All particle manipulations take place without contact, see above that microsystems according to the invention are particularly suitable for mani biological cells or cell components.

Claims (20)

1. Electrode arrangement in a microsystem, which is set up for dielek trophoretic manipulation of particles in a suspension liquid in a channel, wherein at least one microelectrode is arranged on a wall of the channel to produce a field barrier along a reference surface which at least partially penetrates the channel , characterized in that the microelectrode has a predetermined curvature or predetermined angle with respect to the direction of flow in the channel, so that the field effect caused by the microelectrode has predetermined curvatures. 2. Electrode arrangement according to claim 1, wherein the electro the arrangement at least two on opposite channel walls attached microelectrodes of the same shape and orientation comprises, each having the shape of a curved band. 3. Electrode arrangement according to claim 2, wherein the micro electrodes curved depending on the flow profile are that in each section of the field barrier the microelectr the resulting force acting on a particle has an area upstream of the micro electrode is located. 4. Electrode arrangement according to claim 3, wherein the four micro electrodes as focusing electrodes to form a particle funnels are arranged.   5. An electrode arrangement according to claim 2, wherein the micro electrodes are so curved that the one acting on a particle resulting force from one end of the microelectrode to undergoes a change in direction at the other end, Direction in a downstream with respect to the microelectrode located area to a direction in relation to the Microelectrode leads upstream area. 6. Electrode arrangement according to claim 5, wherein the two micro electrodes are provided as sorting electrodes, their field barrier with the flow profile of the suspension liquid in the Channel interacts so that suspended particles with ver various passive electrical properties electrodes depending on their properties on separate tracks can happen. 7. Electrode arrangement according to claim 2, in the opposite lying channel walls at least two microelectrodes of the same Shape and orientation are provided, each one have a closed angular section downstream. 8. An electrode arrangement according to claim 7, wherein the micro electrodes work together as target electrodes. 9. Electrode arrangement according to claim 7 or 8, in which one Group of trapping electrodes arranged in the transverse direction of the channel are. 10. Electrode arrangement according to one of the preceding claims che, in which the microelectrodes in pairs on the Bo the and top surfaces of the channel are arranged. 11. The electrode arrangement according to claim 1, wherein the two micro electrodes are provided on opposite channel walls, that have different geometric shapes.   12. An electrode assembly according to claim 11, wherein the channel has a rectangular cross-sectional shape and the micro electrodes are attached to the narrower side surfaces and a flat microelectrode on one side surface and one ribbon-shaped microelectrode on the opposite side cover area. 13. The electrode arrangement according to claim 12, wherein the surface ge microelectrode is arranged floating. 14. The electrode arrangement according to claim 12 or 13, wherein the Channel is separated into two sub-channels by a partition, the partition being arranged in the area opposite th microelectrode has an opening. 15. The electrode arrangement according to claim 1, wherein the three micro electrodes are provided, two of which are micro-electrodes Focus electrodes on the bottom and top surfaces of the channel attached and a third microelectrode as an auxiliary electrode at a distance from the floor and top surfaces in the middle of the Channel is arranged. 16. The electrode assembly of claim 15, wherein the channel through a partition into two sub-channels with one opening is divided upstream with respect to the auxiliary electrode. 17. Electrode arrangement according to claim 1, in which on a Ka nalwand a cuboid collecting electrode with a variety of reservoirs is arranged with a deflection electrode on the opposite channel wall to distract part interacts in the reservoirs. 18. Electrode arrangement according to claim 1, in which on a Ka wall a plurality of cuboid, spaced apart  stood sub-electrodes are provided with a the deflection electrode arranged on the opposite channel wall to deflect particles into the distances between the qua the shaped partial electrodes is set up. 19. Microsystem for the dielectrophoretic manipulation of Particle with an electrode arrangement according to one of the preceding claims. 20. Use of an electrode arrangement according to one of the An sayings 1 to 18 for distraction, sorting, collecting and / or Formation of microscopic particles.