EP3817859A1

EP3817859A1 - Device for dielectrophoretic capture of particles

Info

Publication number: EP3817859A1
Application number: EP19735269.3A
Authority: EP
Inventors: Samir KADIC; Christoph FAIGLE
Original assignee: Robert Bosch GmbH
Current assignee: Robert Bosch GmbH
Priority date: 2018-07-04
Filing date: 2019-06-27
Publication date: 2021-05-12
Also published as: US20210260602A1; CN112334234A; WO2020007703A1; DE102018211001A1

Abstract

The invention relates to a device (1) for dielectrophoretic capture of particles (2, 3), at least comprising one or more layers (4) and electrical contacting (5), the layers (4) each having a layer upper side (6), a layer underside (7) and an obstacle structure (8). A fluid including the particles (2, 3) can flow through the obstacle structure (8). The obstacle structure (8) is arranged on the layer upper side (6), and the obstacle structure (8) distances the layer upper side (6) from the layer underside (7) of the same layer (4) or of a further one of the layers (4).

Description

description

title

Device for dielectrophoretic capture of particles

The invention relates to a device for dielectrophoretic capture of particles and a method for producing a corresponding device.

State of the art

Circulating tumor cells (CTC ^' s) and cell-free tumor DNA (Circulating Tumor DNA, ctDNA) have established themselves in recent years as promising and clinically relevant biomarkers for the diagnosis and adapted therapy of malignant tumors and metastases. Their early and reliable detection in the human body, especially from blood or other suitable body fluids, has therefore long been one of the main research focuses of modern oncology (liquid biopsy).

This form of tumor analysis offers significant advantages, especially for the patient, compared to conventional invasive tissue biopsies. Last but not least, the integration of emerging analysis technologies into highly developed microsystems and the unification of all necessary ones

Processing steps to form a chain in a single compact device (lab-on-a-chip) make this investigation approach seem consistently attractive due to its potentially very short processing time, high precision, reproducibility, flexibility, simplicity and enormous cost-effectiveness.

In this context, the urgent need for reliable isolation of tumor material with regard to these requirements has so far been expressed in a large number of different approaches. In addition to simple mechanical filters, hydrodynamic variants or antibody-based methods for the separation of circulating tumor cells in microfluidic channels based on corresponding physical properties such as size, density or

Deformability used. However, decisive restrictions were observed in each case, and practical use remained

largely difficult.

Disclosure of the invention

Here, a device is proposed according to claim 1

dielectrophoretic capture of particles, at least comprising one or more layers and electrical contacting, the layers each having a top layer, a bottom layer and an obstacle structure. A fluid comprising the particles can flow through the obstacle structure. Furthermore, the obstacle structure is arranged on the top side of the layer, the obstacle structure spacing the top side of the layer from the bottom side of the same layer or a further one of the layers.

The solution proposed here is based in particular on the approach of manipulating particles according to their dielectric properties. This approach has the particular advantages that it can be scaled independently of markers and on a large scale, as well as being simple, non-contact, versatile, and very easy to integrate into modern MEMS and microfluidic technologies. A particularly preferred component of the solution proposed here is the superimposition of a layer that can be caught by D EP force, in particular

Foil structure, to a multi-layer overall catch system. The at least one layer is also referred to below as the so-called “DEP band”.

The device is used for (targeted) dielectrophoretic capture of

(certain) particles or is set up for this. In other words, this means in particular that the device serves for the targeted dielectrophoretic capture of particles of a certain type or type (target cells) or

is set up. The solution presented here advantageously allows at least one specific type of particle to be specifically captured from a medium guided in the channel and thus to be made removable or removable. The type of particle or type of particle (target particle / target cell) is determined in particular by its dielectric properties. By way of example, tumor cells circulating in the blood (advantageous target cells) differ in their

electrical permittivity of normal white blood cells. The particles to be captured are in particular circulating

Tumor cells.

Each cell usually has its own unique morphology. Among other things, it is a function of the cell type, the complexity of the cell interior and the phase in the cell cycle. The cell membrane of most cell types is still not smooth, but is actually littered with wrinkles and microvilli.

Unlike healthy blood cells, tumor cells form a solid tissue from which in the course of tumor growth single circulating tumor cells (so-called. ^CTC's) can be detached. Because of the increased packing density in the original tissue, their actual cell membrane area is therefore larger than that of the healthy blood cells freely present in the blood and increases with increasing disorder due to the progressive growth of the tumor.

Together with the cell size, the cell membrane area is the morphological property that is evident in the different transition frequencies of the two cell types: When examining the frequency behavior of over 80 different types of solid tumors, it was found that in comparison to healthy blood cells between 50% and 300% larger standardized surface capacity and an average larger cell radius for tumor cells lead to transition frequencies between 20 kHz and 75 kHz. With the same conductivity of 0.03 S / m, the were for all of the 15 subpopulations of healthy mononuclear blood cells examined

Crossover frequencies more than 120 kHz. The transition frequencies for five types of leukemia cells were between 60 kHz and 100 kHz.

Based on these findings and the fact that the

Crossover frequencies of the most abundant subpopulations of healthy blood cells - namely lymphocytes and granulocytes - have very low standard deviations and are at least 5 to 7 standard deviations away from the crossover frequencies of most tumor types Dielectrophoresis suitable for the reliable isolation of all types of solid tumors and - albeit with lower efficiencies - applicable for (highly concentrated) leukemia populations.

The DEP sorting of ^CTC's from healthy blood cells based (in this context), in particular on an opposite movement of the two

Particle types: Especially when the operating frequency lies between the respective transition frequencies, tumor cells can be attracted by pDEP and healthy blood cells can be rejected by nDEP. The obstacle structure and / or the electrical contacting is or are in particular set up such that corresponding operating frequencies can be set here.

The mechanism of so-called dielectrophoresis (DEP) is at the basis of dielectrophoretic capture. This describes the movement of (also uncharged) polarizable particles in a non-homogeneous electric field. A dipole induced in the particle as a result of an external electrical alternating field interacts with this external field and leads to a dielectrophoretic force effect on the particle. This force effect can be used here to hold back the particle and thus its dielectrophoretic capture.

The two different architectures and principles of particle capture that can be present here, mDEP and iDEP, are explained in more detail below.

Principle of the iDEP: With this variant, electrical field lines are generated with a DC signal or AC signal of low frequency (there may even be a superposition of two different signal components) and on insulating (obstacle) structures (polymers, glass, etc.) curved within the fluid channel. The strongest curvature takes place in the area of the

Constriction instead, in which particles can be captured using pDEP. In iDEP applications using electroosmosis, a DC voltage can often also cause a flow of the fluid at the same time.

Principle of the mDEP: The field is usually generated by directly applying an electrical voltage to obstacle structures (Electrode structures), especially metal (obstacle) structures

(usually an alternating microelectrode arrangement). The largest field gradient usually occurs at the edges of the electrodes.

The device further comprises one or more layers. Preferably, the device comprises exactly or only one layer, for example if the layer is e.g. B. is wound into a so-called winding cylinder. Alternatively, the device can have a plurality of layers, for example if the layers are stacked one above the other to form a stack.

The layers preferably each comprise at least one (electrically insulating) insulator layer or insulation layer. In other words, this means in particular that the layers can each comprise at least one (flat) layer which is set up in such a way that it has an electrically insulating effect. This insulator layer can be formed, for example, with a film. The (insulator) films can be, for example, (thin, spin-coated) polyimide films, in particular with a thickness of, for example, up to 25 μm. The layers particularly preferably each comprise at least two (flat) insulator layers arranged one above the other, which can include an (flat and / or meandering) electrode between them.

Furthermore, the device comprises an electrical contact. The electrical contacting is in particular set up to form an electrical field within the fluid channel and in particular in the area of the obstacle structures. For this purpose, the electrical contact can generally be connected or connected to a voltage supply.

For iDEP applications, the contacting can be two, for example

Have contact arms that extend opposite one another, at least partially along one of the layers. Each other (immediately)

opposite contact arms in particular overlap (only) partially. The contact arms preferably extend on the top side of the layer and / or in the region of the obstacle structure (formed as an isolator structure for iDEP applications). Furthermore, contact arms can preferably be formed both on the top side of the layer and on the underside of the layer. The contact arms are preferably in particular on the top of the layer and / or

Layer underside (flat) conductor tracks formed. Here one can the contact arms form a positive pole and the other contact arm form a negative pole. A particularly inhomogeneous electric field can thus be set between the contact arms, the field lines of which can be curved or deflected by the obstacle structure (insulator structure).

For mDEP applications, the contacting can be set up, for example, to form the electrodes of the electrodes

To connect the obstacle structure and / or the electrode extending along (and / or in) the layer to a voltage supply. In this case too, the contact can have contact arms which, for example, connect some of the electrodes of the electrode structure to a positive pole and others of the electrodes of the electrode structure to a negative pole. A particularly inhomogeneous electric field can thus be set between the electrodes of the electrode structure. In addition, the contacting can connect the electrode extending along and / or in position, for example with a positive pole or negative pole.

The layers each have a top side and a bottom side. The layers are preferably each flat. As a rule, these each have a flat top side and a flat bottom side. If several layers are provided, these are preferably formed identically. The layers can each be constructed with a plurality of layers arranged one above the other and / or flat.

Furthermore, the layers each have an obstacle structure. The

A fluid comprising the particles can flow through the obstacle structure. The fluid is usually blood. That is further

Obstacle structure arranged on top of the layer. In addition, it can also be provided that an obstacle structure is arranged on the top of the layer and an obstacle structure on the underside of the layer. The obstacle structure is configured to face the top of the layer from the underside of the same layer (for example, if only one layer is provided that is wound into a cylinder) or another of the layers (for example if there are several layers that are stacked into a stack) spacing.

The obstacle structures extend in particular along at least one (longitudinal) section of the position and / or (in a developed state of the Location) on one level. At least one of the obstacle structures preferably has a plurality of (electrically insulating and / or electrically insulated or in the form of rod electrodes) posts. Each obstacle structure particularly preferably has a plurality of posts. An obstacle structure can, for example, run along one

Longitudinal section of the layer extend that in the longitudinal direction of the layer (which may relate to a development direction of the layer) several posts of the

Obstacle structure are arranged side by side. In addition, multiple posts of the obstacle structure (transverse to the longitudinal direction)

be arranged one behind the other.

The obstacle structures are preferably each set up in such a way that they set a (certain, in particular predefined) spatial one

Contribute to inhomogeneity of an electric field. The electrical field is formed in particular within the fluid channel and in particular in the area of the obstacle structures (possibly (in the case of mDEP) even from the obstacle structures). The obstacle structures (in particular in cooperation with the electrical contacting) are particularly preferably set up to form particle-type-specific energetic minima in the fluid channel. The meaning of the term "energetic minima" is explained in more detail below. This advantageously allows certain (or only) certain particles or particles of a certain type to be captured in the fluid channel. In this

Context, it is further preferred if the obstacle structures are dimensioned specifically for the particle type. In other words, this means in particular that the obstacle structures are dimensioned according to the partial chart (target cell) that is to be captured.

According to a preferred embodiment, it is proposed that at least one of the layers is wound. In this context, it is preferred if only one layer is provided. This layer is also preferably wound into a so-called winding cylinder. The layer is particularly preferably wound spirally. In this context, it is particularly preferred if the layer is wound in such a way that a (microfluidic) fluid channel is formed between the top side and the bottom side of the same layer, in which the

Obstacle structure is arranged. According to a preferred embodiment, it is proposed that several of the layers are stacked. In other words, this means in particular that at least two of the layers are provided and stacked to form a stack. These layers each have an obstacle structure. In addition, at least one (smooth) layer can be provided in the stack or stack, which has no obstacle structure, for example as

Intermediate layer or top layer. In this context, it is particularly preferred if several of the layers are stacked in such a way that one of the layers and one of the layers underneath one between the top of the layer

adjacent layer a (microfluidic) fluid channel is formed, in which one of the obstacle structures is arranged.

According to a preferred embodiment, it is proposed that the

Obstacle structure is an isolator structure. In other words, this means in particular that the obstacle structures are formed with or from an electrically insulating material. Such obstacle structures are used in particular when implementing an iDEP system (insulator based dielectrophoresis, iDEP). The insulating material protrudes into the channel in the manner of posts, possibly even spanning at least part of a channel cross section.

According to a preferred embodiment, it is proposed that the

Obstacle structure is an electrode structure. In other words, this means in particular that the obstacle structures are formed with or from an electrically conductive material. Such obstacle structures are used in particular when implementing an mDEP system (metal based dielectrophoresis, mDEP). The electrically conductive material protrudes into the channel in the manner of posts in particular, possibly even spanning at least part of a channel cross section. In this context, it is further preferred if the electrode structures are each formed with a large number of microelectrodes. Those are preferred

Electrically contacted electrode structures so that the obstacle structures (each) include both cathodes and anodes. At least one of the obstacle structures particularly preferably comprises the same number of cathodes as anodes. In mDEP systems, the (necessary) (micro) electrodes could e.g. B. structured with lithographic methods directly on the top of the layer. In particular, thermally vapor-deposited or galvanically applied metal, such as gold or copper, is suitable for this. In the case of iDEP applications, the (required) isolator obstacle structures or isolator structures made of the same material as well as the location,

in particular an insulator layer of the layer itself and / or also structured lithographically (possibly together with the layer).

According to a preferred embodiment, the device further comprises at least one electrical passivation or electrical insulation. The layer preferably comprises electrical passivation, in particular over the entire surface, preferably on the top side of the layer. The electrical passivation can also cover at least part of the surface of the obstacle structure that is arranged on the layer. The electrical passivation can be formed, for example, with a chemically inert but electrically transparent material. The electrical insulation can be formed, for example, with one or more insulator layers of one layer.

According to a preferred embodiment, the device further comprises at least one electrode that extends at least partially along (and / or in) one of the layers. The electrode preferably extends within the (flat) material of the layer, which can be achieved, for example, by arranging the electrode between two one above the other

Layers layers, especially foils. In this case, the layer is preferably formed with a sandwich arrangement of two insulator layers and a metal electrode embedded therein over the entire surface. In other words, this means in particular that an insulator layer is provided as the upper layer and an insulator view as the lower layer, which between them

Include metal electrode.

According to a further aspect, a method for producing a device proposed here is also proposed, at least comprising one

Providing one or more of the layers and wrapping at least one of the layers or stacking several of the layers. The details, features and advantageous configurations discussed in connection with the device can accordingly also occur in the method presented here and vice versa. In this respect, full reference is made to the explanations given there for the more detailed characterization of the features.

The solution presented here and its technical environment are explained in more detail below with reference to the figures. It should be pointed out that the invention is not intended to be limited by the exemplary embodiments shown. In particular, unless explicitly stated otherwise, it is also possible to extract partial aspects of the facts explained in the figures and to combine them with other components and / or knowledge from other figures and / or the present description. They show schematically:

1: a position for a device proposed here in one

Sectional view

2: a device proposed here in a sectional view,

3: a position according to FIG. 1 or from FIG. 2 in a perspective

View,

4: a further position for a device proposed here in a perspective view,

5: a detailed view of the embodiment of FIG. 4,

6: a sequence of a method proposed here,

Fig. 7: an illustration of a step of the proposed here

process

8: an illustration of a further step of the here

proposed method

9: a further device proposed here in a perspective view, and

10: a further device proposed here in a perspective view.

The technical environment of the solution presented here, which is also a

Device for dielectrophoretic capture of particles can be: The underlying mechanism, the so-called dielectrophoresis (DEP), describes the movement (also uncharged) of polarizable particles in a non-homogeneous electric field. In this case, a dipole induced in the particle as a result of an external electrical alternating field interacts with this external field and leads to a dielectrophoretic

Force effect on the particle.

If only the first-order dipole moment is taken into account and all other higher-order terms and the force effect on charged particles in the form of the Coulomb term (electrophoresis) are disregarded, the time-average dielectrophoretic force on a particle can in the most general case be used for a spatially stationary E- Field as

Be formulated. Here G denotes the geometry factor of the particle,

£ _m the (absolute) real electrical permittivity of the surrounding medium,

E _{RMS is} the effective value of the E field vector (root mean square,

RMS) and Reifem) the real part of the so-called "Clausius-Mosotti factor" (CM factor).

For the simplest case of a spherical particle, representative of a tumor cell, for and

G = 27ÜÄ ³ this expression too rewrite. Here R stands for the radius of the cell under consideration as well as i _p and i _m for the (absolute) complex electrical permittivity of particles and the surrounding medium with / = - I as a complex unit, s as electrical conductivity and w as angular frequency of the applied electric field.

Depending on the sign of Re {f _M ) (depending on the operating point of the electrical field and the relative coordination between frequency-dependent (absolute) real electrical permittivity e and electrical conductivity s between medium and material), either an attractive (positive dielectrophoresis, pDEP) can be used for manipulation. or repulsive (negative dielectrophoresis, nDEP) force effect on particles.

This is particularly interesting if, for example, by external

Limitations such as undefined flow conditions in microfluidic channels or lack of space in the DEP system no continuous separation

(Equilibrium approaches) realized in a flowing fluid, but instead only the capture (imbalance approaches) of target particles in this can be tracked either by metal electrodes (mDEP) or insulating posts (iDEP). The latter approach is based on the basic principle that particles to be isolated are addressed and held by electrodes against the flow forces of the flowing medium using pDEP, while at the same time undesired particles are repelled by nDEP.

For the functioning of a DEP manipulation, especially in the interpretation of the

- f. - f .2

Concept, the last factor \ E _RMS \ in the above expression for (F _DEP ) is particularly important, which occurs regardless of the material, shape and size of the target particle. In addition to the amplitude and the temporal distribution of the E field, it expresses its spatial inhomogeneity. This spatial

Inhomogeneity in a microfluidic channel can be achieved, for example, by suitable structuring of microelectrodes in the channel and direct application of an appropriate electrical signal to them (metal based

dielectrophoresis, mDEP) or (alternatively) by suitably designed Isolator structures in the channel and outside of the created E-field (insulator based dielectrophoresis, iDEP) are generated. With mDEP, a deformation of the E-field at the almost planar electrode edges would be observed, with iDEP as a result of a deformation around the insulating extruded structures.

If the DEP system should not (only) be designed for continuous separation in a flowing fluid, but (as here) for capturing target particles in it (assumption: operating point by E field is set in such a way that all target particles have a sufficiently high level pDEP can work), both variants set themselves the goal, by appropriate dimensioning of V | E _{R 5} | to design the spatial energy landscape for particles in such a way that energetic minima

(Energy minimum for particles, since pDEP) only target particles contrary to any other energies occurring in the system within the framework of fixed

Capture boundary conditions (throughput, cell destruction, recovery and purity rates of separation, etc.) while everyone else is in the medium

occurring species remain largely unaffected by this effect (force effect through DEP either positive and very small or even negative).

The meaning of the term "energetic minima" is explained in more detail below: With pDEP (attractive force), particles are usually moved in the direction of the maxima of the electric field strength. In an energy landscape, however, these areas correspond to minima, so to speak “potential pots”. In other words, this can also be described in such a way that with pDEP the particles move in the direction of the higher field strength, but fall into a "potential well" or "potential wells". “Energetic minima” are to be understood here in particular as the minima described in the energy landscape or the potential pots described. In other words, this means in particular that the energetic minima are minima in the energy landscape and / or potential pots.

The (previously described) principle of particle trapping by means of pDEP is an attractive manipulation approach that is preferably pursued in the context of the solution presented here.

The following could be observed with conventional implementations of mDEP or iDEP trapping separators: Due to the generally very short range of the dielectrophoretic force, however, maximum distances between the electrodes and the particles should generally be observed when trapping the particles (up to 100 mhh), which, however, limited, at least in the vertical direction, in reverse

Channel dimensions and thus comparatively small throughputs. These can only be increased to a limited extent by increasing the flow rate, since the resulting flow forces should in no way dominate the dielectrophoretic forces (in the pN range) or damage the cells (corresponds in conventional DEP systems as the equivalent of maximum flow rates up to about 100 pm / s). An instant one

This would wash away the captured particles and a drastic drop in separation efficiency would be expected.

Alternatively, in order to increase the cross-section and thus the throughput in conventional implementations, a widening of the channel in the horizontal direction could also be considered, but here too the expansion of such a channel is severely limited by the usually limited size of the DEP system.

Against this background, a brief calculation example for conventional DEP trapping filtering is to be presented below (which is compared below with a calculation example for an embodiment of the solution presented here):

For liquid biopsy applications, for example, a 10 ml blood sample would have to be taken in a channel with a height of 50 pm within one hour

If the fluid velocity is 100 pm / s, an effective channel width of more than 55 cm would have to be accepted (the cross-sectional area through which flow is then around 28 mm ² without obstacles), which would be far too unwieldy from a microfluidic point of view.

Proceeding from this, an object of the invention is, in particular, to achieve a

necessarily very flat and wide channel, which conventionally has an otherwise too large base area for filter operation in the form of a

dielectrophoretic particle capture at a sufficiently high throughput in Would take up a volume that is as manageable as possible

redistribute. In this case, for example, the expansion of a quasi-planar DEP structure can be expanded by a third spatial dimension, so that compression flows through as large as possible

Cross-sectional area can be made available. The arrangement is in particular able to keep the target cells as small as possible

Interaction distance (high gradients of the E-field or high DEP forces) but to allow a sufficiently long interaction path with the D EP electrodes at otherwise advantageously low flow rates but advantageously sufficiently high throughput.

Fig. 1 shows schematically a layer 4 for a device proposed here in a sectional view. The layer 4 has a layer top 6, one

Layer underside 7 and an obstacle structure 8. The obstacle structure 8 is made of a fluid comprising the particles 2, 3 (not shown here)

flow through. In addition, the obstacle structure 8 is arranged on the top side 6 of the layer.

1, the layer 4 is formed, for example, in the manner of a DEP film. Here, the layer 4 has a sandwich arrangement made up of two insulator layers 13 and one which is embedded over the entire surface thereof

Metal electrode 12 formed. The insulator layers 13 represent an example of how the layer 4 can have electrical insulation 11. The

Counter electrodes form extruded metal posts, which are applied to one of the two insulator layers 13 and are connected to one another on the bottom by flat conductor tracks 14 (not shown here, see FIG. 3) (for example, there is a change of polarities in the checkerboard pattern between the posts) , The extruded metal posts represent an example of how the obstacle structure 8 can be designed as an electrode structure.

In addition, the layer 4, as shown in FIG. 1, has, for example, a full-area electrical passivation 10 of the strip. This electrical passivation 10 can be formed, for example, with a chemically inert, but electrically as transparent as possible material. Furthermore, the layer 4 in FIG. 1 has, for example, a thin adhesive layer 15 on the back of the tape or on the bottom 7 of the layer. This adhesive layer 15 could stacking for ultimate strength and later in operation for tightness of the microchannels.

FIG. 2 schematically shows a device 1 proposed here in a sectional illustration. The reference symbols are used uniformly, so that reference can be made in full to the above explanations relating to FIG. 1.

The device 1 is set up for the dielectrophoretic capture of particles 2, 3 (not shown here). The device 1 comprises one or more layers 4 and an electrical contact 5 (not shown here). The layers 4 each have a layer top 6, a layer bottom 7 and one

Obstacle structure 8. A fluid comprising the particles 2, 3 (not shown here) can flow through the obstacle structure 8. The obstacle structure 8 is arranged on the top side 6 of the layer. Also spaced the

Obstacle structure 8 the top layer 6 of the bottom layer 7 of the same layer 4 or a further one of the layers 4.

The arrangement according to FIG. 2 can be formed, for example, by stacking several layers 4 according to FIG. 1 or alternatively by winding a layer 4 according to FIG. 1. In this context, the arrangement can resemble a coplanar line. The effective cross-sectional area of an imaginary microfluidic channel can be defined via the distances and heights of the individual posts. The obstacle structure 8 or the layer with the metal posts is rolled up and is insulated on both sides by two layers 4 of a planar one

Enclosed electrode 12 and thus opposite neighboring

Obstacle structures 8 or (obstacle structure) layers are completely shielded - winding or stacking is thus made possible in a particularly advantageous manner. This manifests itself in particular in a symmetrical and uniform electrical field 16, which can be found in each of the “cages” (partial microfluidic channels 17).

If, however, cross-talk between two layers 4 of the DEP band were negligible in operation, the shielding could also be omitted for simplified manufacture and operation. For example, only one insulator layer 13 could remain, on which the metal posts

(Obstacle structure 8) together with conductor tracks 14 (not shown here, see FIG. 3) and contacting 5 (not shown here, see FIG. 3) could be applied.

In all cases, inflowing particles (target cells) could pass through the stacked obstacle structures 8 and thereby advantageously interact as strongly as possible with the inhomogeneous E field 16. The summation of many imaginary small partial microfluidic channels 17 over the width of an entire band results in a stacked state in parallel connection to a channel with an acceptable effective cross-sectional area.

In FIG. 2 it can also be seen that a fluid channel 9, in which the obstacle structure 8 is arranged, is formed between the top side 6 of the bottom 7 facing the layer. The sum of these fluid channels 9 or the partial microfluidic channels 17 results in a flowable (total) cross-sectional area of the device, which previously also was effective

Cross-sectional area was designated.

FIG. 3 schematically shows a layer 4 according to FIG. 1 or from FIG. 2 in a perspective view. The reference numerals are used uniformly, so that reference can be made in full to the above statements relating to the preceding FIGS. 1 and 2.

FIG. 4 schematically shows a further layer 4 for a device proposed here in a perspective view. The reference numerals are used uniformly, so that reference can be made in full to the above statements relating to the previous figures.

4 differs in particular from that according to FIGS. 1 to 3 in that the obstacle structure 8 does not exist

Electrode structure, but an insulator structure. Instead of the metal posts, insulating spacers (posts) are used as the obstacle structure 8 with planar metal electrodes 12 applied (on one or both sides). It is particularly advantageous here if (because of possible

Crosstalk from fields of neighboring layers 4) is now additionally paid for an exact adjustment when stacking or winding. FIG. 5 schematically shows a detailed view of the exemplary embodiment according to FIG.

4. The associated detail section is marked in Fig. 4 with IV. The

Reference symbols are used uniformly, so that reference can be made in full to the above explanations regarding the previous figures.

6 schematically shows a sequence of a method proposed here. The method is used to manufacture a device proposed here. The sequence of the method steps shown with the blocks 110 and 120 results in a regular operating sequence. A occurs in block 110

Deploy one or more of the layers. In block 120, at least one of the layers is wrapped or several of the layers are stacked.

7 schematically shows an illustration of a step of the method proposed here. The reference symbols are used uniformly, so that reference can be made in full to the above explanations regarding the previous figures.

In this context, FIG. 7 illustrates the provision of a layer 4. The layer 4 is held on a carrier roller 19 by way of example with a fastening means 18. For this purpose, the fastening means 18 is simultaneously formed, for example, in the manner of a spacer.

8 schematically shows an illustration of a further step of the method proposed here. The reference numerals are used uniformly, so that reference can be made in full to the above statements relating to the previous figures.

In this context, FIG. 8 illustrates a winding of the layer 4 provided according to FIG. 7. Here, for example, a layer 4 (suitably structured film arrangement) is wound onto a carrier roll 19 and electrically contacted at the end. The effective cross-sectional area of such a "DEP winding cylinder" can be determined from the top surfaces of the

rolled-up tape and the carrier contained therein are calculated and varies depending on the layout. The diameter of the carrier 19 can be minimized in favor of a maximum throughput. Such a cylinder would be integrable into a likewise cylindrical channel (see FIG. 9) without major difficulties.

9 schematically shows a further device 1 proposed here in a perspective view. The reference symbols are used uniformly, so that reference can be made in full to the above explanations regarding the previous figures.

The device 1 could have been manufactured, for example, using the method steps illustrated in FIGS. 7 and 8. In other words, this means in particular that the device 1 is formed in the manner of a “winding cylinder” according to the division of darts according to FIG. 9.

Some advantages of this embodiment are to be discussed below using a calculation example for a winding cylinder:

A layer 4 (DEP tape), for example according to FIG. 1, with a thickness of 100 pm (50 pm substrate thickness and 50 pm post height with a ratio of post width to post spacing of 1: 1) and about 1 m length could have over 35 turns on a roll 19 with a diameter of 6 mm are rolled into a cylinder with a total diameter of less than 13 mm. The length of such a winding cylinder could be chosen individually (e.g. 1 cm). A 10 ml blood sample could then also be processed at a maximum flow rate of 100 pm / s within about an hour, with the big difference (compared to the calculation example given above for conventional DEP trapping filtering) that such a filter would then could be installed relatively easily in lab-on-chip systems.

Such a filter could be manufactured using microfabrication technology: the insulator layers 13 could be made with insulator foils. The insulator films could be thin, spin-on polyimide films with a thickness of, for example, up to 25 μm. A carrier roll 19 from z. B. Plastic could have a bend radius of up to one millimeter or less. Sheets and rolls could be connected to each other with an adhesive tape of a suitable height, which could also serve as a spacer and protection of the posts (obstacle structure 8) during a first winding. A metal, such as copper, could be used as the electrode material or gold, which (previously) for example by photolithography,

Sputtering method and / or electroplating, in particular at different heights for conductor tracks 14 and metal posts (an exemplary one

Obstacle structure 8) was structured and applied. Conductor tracks 14 could have thicknesses between a few nanometers to a few micrometers and posts of an exemplary obstacle structure 8) heights of possibly up to 100 pm. Solder contacts would be conceivable for the electrical contact 5 of the layer 4. If one wanted to passivate the metal electrodes electrically with chemically inert material (as exemplary passivation 10), aluminum oxide could be evaporated for this purpose.

A similar effect could also be achieved by stacking several layers 4 to form a “DEP stack” with a defined cross-section.

10 schematically shows a further device 1 proposed here in a perspective view. The reference symbols are used uniformly, so that reference can be made in full to the above explanations regarding the previous figures.

FIG. 10 exemplifies the previously mentioned embodiment as a “DEP stack”. In other words, this relates in particular to a device 1 in which a plurality of the layers 4 are stacked.

Layers or “DEP tapes”, as previously presented, could in principle be produced in any width and length and, consequently, individually to form cylinders and stacks with any diameter, length, width and height.

The solution proposed here has in particular one or more of the following advantages:

• High degree of parallelization of individual microfluidic channels with precisely adjustable dimensions and field strengths, which enables efficient use of the dielectrophoretic capture volume:

Increase in the cross-sectional area effectively flowed through or

The relative flow velocity in the fluidic channel can be reduced in a compact form, with particles keeping a maximum distance from the electrodes • Versatile layout options, as a very large selection of design parameters is available (especially with regard to the length and width of the D EP tapes used, which would be easily adjustable)

• Processes are potentially very cost-effective because mass production is conceivable

• Principle relatively simple and good in MEMS or. Microfluidic technologies can be integrated

• Optional operation with passivated metal electrodes (possibly, double-sided and extruded) can be easily implemented: Generation of high field strength gradients even at high frequencies with comparatively low ones

Operating voltages possible without, for example, blistering due to chemical reactions, etc.

Claims

Expectations

1. Device (1) for the dielectrophoretic capture of particles (2, 3), at least comprising one or more layers (4) and an electrical contact (5), the layers (4) each having a layer top (6), a layer underside ( 7) and have an obstacle structure (8), wherein the obstacle structure (8) can be flowed through by a fluid comprising the particles (2, 3), the obstacle structure (8) being arranged on the top side of the layer (6) and the obstacle structure (8 ) the top layer (6) from the bottom layer (7) of the same layer (4) or a further one of the layers (4) spaced.

2. Device according to claim 1, wherein at least one of the layers (4)

is wrapped.

3. Device according to claim 2, wherein the layer (4) is wound such that a fluid channel (9) is formed between the top side (6) and the bottom side (7) of the same layer (4), in which the obstacle structure (8) is arranged.

4. The device according to claim 1, wherein a plurality of the layers (4) are stacked.

5. The device according to claim 4, wherein a plurality of the layers (4) are stacked in such a way that a fluid channel (9) is formed between the top side (6) of one of the layers (4) and the bottom side (7) of an adjacent layer (4) in which one of the obstacle structures (8) is arranged.

6. Device according to one of the preceding claims, wherein the

Obstacle structure (8) is an insulator structure.

7. Device according to one of claims 1 to 4, wherein the obstacle structure (8) is an electrode structure.

8. Device according to one of the preceding claims, further

comprising at least one electrical passivation (10) or electrical insulation (11).

9. Device according to one of the preceding claims, further comprising at least one electrode (12) which extends at least partially along one of the layers (4).

10. A method for producing a device according to one of the

preceding claims, at least comprising providing one or more of the layers (4) and winding at least one of the layers (4) or stacking several of the layers (4).