EP1565266B1 - Fluidic microsystem and method comprising field-forming passivation layers provided on microelectrodes - Google Patents

Fluidic microsystem and method comprising field-forming passivation layers provided on microelectrodes Download PDF

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Publication number
EP1565266B1
EP1565266B1 EP03776918.9A EP03776918A EP1565266B1 EP 1565266 B1 EP1565266 B1 EP 1565266B1 EP 03776918 A EP03776918 A EP 03776918A EP 1565266 B1 EP1565266 B1 EP 1565266B1
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EP
European Patent Office
Prior art keywords
channel
electrode
layer
passivation layer
field
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German (de)
French (fr)
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EP1565266A1 (en
Inventor
Torsten Müller
Thomas Schnelle
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Revvity Cellular Technologies GmbH
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PerkinElmer Cellular Technologies Germany GmbH
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    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/502761Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip specially adapted for handling suspended solids or molecules independently from the bulk fluid flow, e.g. for trapping or sorting beads, for physically stretching molecules
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B03SEPARATION OF SOLID MATERIALS USING LIQUIDS OR USING PNEUMATIC TABLES OR JIGS; MAGNETIC OR ELECTROSTATIC SEPARATION OF SOLID MATERIALS FROM SOLID MATERIALS OR FLUIDS; SEPARATION BY HIGH-VOLTAGE ELECTRIC FIELDS
    • B03CMAGNETIC OR ELECTROSTATIC SEPARATION OF SOLID MATERIALS FROM SOLID MATERIALS OR FLUIDS; SEPARATION BY HIGH-VOLTAGE ELECTRIC FIELDS
    • B03C5/00Separating dispersed particles from liquids by electrostatic effect
    • B03C5/02Separators
    • B03C5/022Non-uniform field separators
    • B03C5/026Non-uniform field separators using open-gradient differential dielectric separation, i.e. using electrodes of special shapes for non-uniform field creation, e.g. Fluid Integrated Circuit [FIC]
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/06Fluid handling related problems
    • B01L2200/0647Handling flowable solids, e.g. microscopic beads, cells, particles
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/06Fluid handling related problems
    • B01L2200/0647Handling flowable solids, e.g. microscopic beads, cells, particles
    • B01L2200/0652Sorting or classification of particles or molecules
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/06Fluid handling related problems
    • B01L2200/0647Handling flowable solids, e.g. microscopic beads, cells, particles
    • B01L2200/0668Trapping microscopic beads
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/06Auxiliary integrated devices, integrated components
    • B01L2300/0627Sensor or part of a sensor is integrated
    • B01L2300/0645Electrodes
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/16Surface properties and coatings
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00Moving or stopping fluids
    • B01L2400/04Moving fluids with specific forces or mechanical means
    • B01L2400/0403Moving fluids with specific forces or mechanical means specific forces
    • B01L2400/0415Moving fluids with specific forces or mechanical means specific forces electrical forces, e.g. electrokinetic

Definitions

  • the invention relates to a fluidic microsystem with the features according to the preamble of claim 1 and a method for field shaping in a channel of said fluidic microsystem.
  • Non-contact particle manipulation eg, move, stop, deflect, join, etc.
  • Non-contact particle manipulation is based on negative dielectrophoresis. It is known to at least partially cover the arranged on channel walls microelectrodes with an electrically insulating thin layer to unwanted interactions between the microelectrodes and the suspension medium or the particles, such as. B. Ohm 'cal losses, electrolysis, induction of transmembrane potentials, etc. to minimize (passivation of the microelectrodes).
  • the fluidic microsystems include spatial electrode arrays.
  • the microelectrodes are at opposite, z. B. lower and upper channel walls with typical distances in the range of 10 .mu.m to 100 .mu.m (s. T. Muller et al. in "Biosensors &Bioelectronics", Vol. 14, 1999, pp. 247-256 ).
  • the microelectrodes must be shaped in a certain way and arranged relative to each other. In spatial electrode arrangements, this is with a high Justieraufwand the Channel walls (chip levels) connected. The accuracy must be better than 5 ⁇ m for typical dimensions of the microsystem in the cm range. Furthermore, problems arise in the production of the microsystem.
  • the structuring consists in the formation of openings or openings in the passivation layer over a planar electrode. Through the openings, the electric field can pass through from the electrode into the channel and form the desired field shape corresponding to the shape of the opening.
  • the openings in the passivation layers have the disadvantage that a contact between the electrode material and the suspension liquid is formed. It may lead to irreversible electrode processes. For example, particles under the field effect can be pulled onto the electrodes and clog the channel. Furthermore, it may lead to a dissolution of the electrode material and thus to a contamination of the suspension liquid. This problem has been addressed by that suspension liquids with a rather low electrolyte content were used. However, this limited the scope of the microsystems. Many biological particles have limited ability to tolerate low electrolyte levels for extended periods of time.
  • field shielding is effected by the passivation layers on microelectrodes. This can be used, for example, to amplify or attenuate field gradients in the channel in accordance with a specific spatial progression (see FIG BT Schnelle et al., S. above and G. Fuhr et al. in "Sensors and Materials", Vol. 7/2, 1995, pp. 131-146 ).
  • a disadvantage is that the attenuating influence of the passivation layer in the suspension liquids with low electrolyte content (low conductivity) is relatively weak.
  • the object of the invention is to provide an improved fluidic microsystem which overcomes the disadvantages of conventional microsystems.
  • the object of the invention is in particular to provide a microsystem with a simplified structure, in particular a simplified electrode arrangement and a simplified contacting, increased reliability and an extended range of application, in particular in the manipulation of biological particles.
  • the object of the invention is also to provide an improved method for field shaping in fluidic microsystems, in particular to provide for the dielectrophoretic manipulation of particles.
  • a feature of the invention is a fluidic microsystem with at least one channel through which a particle suspension can flow, on the channel walls of which electrode devices for generating alternating electrical fields are arranged in the channel, of which a first electrode device for field shaping is provided with a structuring and a second electrode device is planar, unstructured is formed with a passivation layer, in particular to further develop in that the structuring of the first electrode device has characteristic dimensions smaller than the planar electrode layer of the second electrode device and the passivation layer of the second electrode device is a closed, the electrode surface of the second electrode device completely covering layer.
  • the first electrode device which is, for example, a lower electrode device on the lower chip level or bottom surface in the operating position, must be structured for field shaping, while advantageously as a second electrode device, in particular as an upper electrode device
  • a flat, completely passivated electrode layer can be provided, which merely has a single connecting line for connection to a voltage supply or, if the second electrode device is potential-free is operated, no connection cable required.
  • the planar second electrode device can be produced without complex masking steps during the wafer processing.
  • the closed passivation layer on the second electrode device completely avoids undesired electrode processes.
  • first electrode device at the lower chip level and the second electrode device at the upper chip level is not a mandatory feature of the invention, but may in particular be provided in reverse.
  • first and second electrode means may be provided on different channel walls forming the top surfaces, bottom surfaces and / or side surfaces.
  • a further advantage of the combination on the one hand of a structured electrode device (preferably on the bottom surface) and a non-structured, flat electrode device (preferably on the cover surface) is the possibility of realizing the most varied electrode arrangements and system functions, as shown below.
  • the passivation layer of the second (preferably) upper electrode device in turn has layer structures for field shaping in the channel, wherein the layer structures comprise regions which have a changed thickness in the passivation layer or a material other than the surrounding passivation layer.
  • This structuring of the passivation layer is combined with a planar electrode layer.
  • the patterning of the passivation layer may have advantages in terms of field shaping in the channel.
  • the first electrode device may comprise at least one structured electrode layer having individual partial electrodes, which in their entirety constitute the structuring or at least one first structural element, as is known per se from conventional microelectrode arrangements.
  • the provision of a plurality of sub-electrodes may be advantageous in relation to a separate controllability of each sub-electrode.
  • the separate controllability is important, for example, if the fields in the channel are to be varied depending on certain external influences or measurement results.
  • the sub-electrodes preferably comprise individually controllable electrode strips, ie microelectrodes with an elongated line shape with a typical width in the range of 50 nm to 100 ⁇ m and a typical length of up to 5 mm.
  • the sub-electrodes can carry passivation layers, which optionally carry a defined opening corresponding to the position of the sub-electrodes.
  • the layer structures in which the field penetration is modulated into the channel are formed, for example, by regions of changed (reduced or increased thickness) in the passivation layer.
  • these lowered or protruding layer structures can be produced by a simple etching process.
  • the shape of the layer structures can be adjusted by masking. Emerging layer structures are particularly preferred when forming the passivation layer with materials having a relatively high dielectric constant.
  • the layer structures may comprise regions which have at least one other material than the surrounding passivation layer, which is characterized in particular by a changed dielectric constant. Both forms of the layer structures, ie the thickness variation and the material variation can be provided in combination.
  • the passivation layers can be formed of different layer materials in multiple layers.
  • passivation layers are at least partially formed by layer materials whose dielectric properties are reversibly or irreversibly variable ("smart isolation").
  • the coating materials are converted, for example, by a laser treatment between different modifications (eg crystalline ⁇ -> amorphous), which are distinguished by different DK values.
  • changeable materials are for example descriptive or rewritable optical storage (CD) known.
  • CD descriptive or rewritable optical storage
  • polymers can be used whose conductivity can be changed at least once by laser irradiation as in a direct laser writing method.
  • specific prototypes eg for rapid prototyping
  • the channel is equipped with the electrode devices described above with at least one transverse channel, in which a third electrode means for generating electrical DC fields in the transverse channel is arranged.
  • a third electrode means for generating electrical DC fields in the transverse channel is arranged.
  • passivation layers compared to bare electrodes is that the resistance of bare electrodes can already change by orders of magnitude due to the superposition of monolayers. This can be relatively easy during the Chip production or in operation happen and endanger the function of dielectric elements in particular when the layers are not homogeneous. To avoid this problem, additional measures (plasma etching, etc.) had to be implemented so far. On the other hand, additional layers on passivation layers have a significantly less disturbing effect. The functional reliability of the microsystems is thereby improved.
  • Another object of the invention is a method for field shaping in a channel of the fluidic microsystem according to the invention, in particular for the dielectrophoretic manipulation of suspended particles in the fluidic microsystem according to the invention by the field shaping by means of lateral structures in passivation layers on electrodes.
  • FIG. 1A In a schematic perspective view, a part of a fluidic microsystem 100 according to the invention is shown.
  • the microsystem 100 includes at least one channel 10 formed between two plate-shaped chip elements, namely the bottom element or substrate 20 and the cover element 30. Other parts of the microsystem, in particular lateral walls, spacers and the like are not shown for reasons of clarity.
  • the substrate 20 forms a first (lower) channel wall with a bottom surface 21 facing the channel 10, on which a first electrode device, optionally with a passivation layer (see below), is arranged.
  • the cover element 30 forms the second (upper) channel wall with a cover surface 31 facing the channel 10, on which the second electrode device (see below) is arranged accordingly.
  • At least one of the electrode means is for field generation in the channel 10 with an AC voltage source (not shown).
  • a passivation layer is provided.
  • the channel 10 is formed by a free space between the chip elements 20, 30. It is permeable by a liquid, in particular a particle suspension and has a height, for example. In the range of 5 .mu.m to 1 mm and application-dependent selected transverse and longitudinal dimensions in the micrometer to cm range.
  • the chip elements 20, 30 are typically made of glass, silicon or an electrically non-conductive polymer.
  • the layer structure of electrode device and passivation layer is in the right, enlarged section of Figure 1A shown.
  • the first electrode device 40 and a first passivation layer 50 are on the bottom surface 21 of the substrate 20 .
  • the layer structure is formed by per se known planar technology by deposition of the desired materials on the substrate.
  • the electrode device consists of an electrically conductive material, for. As a metal or conductive oxide, for. Sn doped In 2 O 3 , (ITO), indium cadmium oxide (In x Cd 1-x O), Cd 2 SnO 4 , or a conductive polymer (eg, polyaniline, polypyrrole, polythiophene).
  • the thickness of the electrode device is, for example, in the range of 50 nm to 2 microns.
  • the passivation layer 50 is a dielectric insulating layer having a thickness in the range of 0.1 ⁇ m to 10 ⁇ m. It consists, for example, of polyimide or an electrically insulating oxide, for. For example, silicon oxide, silicon nitride.
  • FIGS. 1B and 1C Illustrations of microsystems are illustrated in which the second electrode device carries an unstructured passivation layer (no embodiments of the invention).
  • the above preferred embodiments of the invention are illustrated with schematic plan views of the first (lower) and second (upper) channel walls 21, 31.
  • the first electrode means 40 is formed structured for field formation in the channel. It is generally equipped with at least one first structural element, which in the illustrated example comprises four electrode elements or partial electrodes 41, which are formed in strip-form on the bottom surface 21 in a manner known per se.
  • the partial electrodes 41 may be covered with a passivation layer (not shown), which optionally has openings on the surfaces of the partial electrodes 41 in a manner known per se.
  • the second electrode device 60 on the cover surface 31 comprises a planar electrode layer 61 (shown in dashed lines) with a closed second electrode surface, which is completely covered by a second passivation layer 70.
  • the first structural elements 41 of the first electrode device 40 form a smaller effective electrode area than the second electrode area 61 of the second electrode device 60 (the sum of the individual areas of the first electrode device 40 is smaller than the second electrode area 61).
  • the electrode devices 40, 60 are acted upon by electrical voltages, field line profiles are formed which combine on the bottom surface 21 at the partial electrodes 41 with an enlarged field line density and terminate on the top surface 31 in the electrode layer 61.
  • the electric field in the channel is shaped according to the shape of the sub-electrodes. For example, a field barrier or a field cage is formed, with which the movement of particles in the channel can be influenced or particles can be held.
  • the electrode layer 61 of the second electrode device 60 may be connected to a control device via a connecting line in accordance with a first operating mode.
  • a connecting line for forming the counterelectrode is sufficient, for example for a field cage with a barrier shape corresponding to the partial electrodes 41.
  • the second electrode device may be arranged on the cover surface 31 without being connected to a control device. In this so-called "floating" state, the potential of the second electrode device automatically forms as a function of the surrounding potential conditions. In each case a charge distribution is formed in the electrode layer, which compensates for the field occurring in the channel in the interior of the electrode layer. In this case, advantageously can be completely dispensed with a contact.
  • Figure 1C illustrates a microsystem in which both electrode devices 40, 60 are formed by flat, closed electrode layers 42, 61 which are each covered by closed passivation layers 50, 60.
  • the first (lower) electrode device 40 is equipped with at least one structural element, which in this embodiment is formed by a structure in the first passivation layer 50.
  • the layer structure in the first passivation layer 50 comprises Areas 51 with z. B. reduced thickness and / or in comparison to the remaining passivation layer varied materials.
  • the regions 51 have laterally in the layer plane a geometric shape corresponding to the conventionally formed microelectrodes, that is, for example, a strip shape.
  • the second electrode device 60 is according to Figure 1C as in FIG. 1B formed by an electrode layer with closed, unstructured passivation layer 70.
  • the geometric shape of the passage of the electric field from the electrode layer 42 into the channel is set in a predetermined manner according to the shape of the areas 51.
  • the regions 51 can, for example, be a line-up element with a funnel-shaped field barrier (FIG. Figure 1C ) form.
  • a plurality of structured regions can be realized in a passivation layer which covers a closed electrode layer. This has the advantage that a fluidic microsystem, for. B. a sorting system with a plurality of functional elements with only two, provided on opposite channel walls and with structured passivations electrodes is constructed, possibly only one electrode is driven with a high-frequency voltage and the other electrode is left in the floating state.
  • FIG. 1D is the first electrode device on the bottom surface 21 with a plurality of partial electrodes 41 as in FIG. 1B is constructed while the second electrode means 60 according to the invention with a structured passivation layer 70 is covered.
  • the structured regions 71 in the passivation layer 70 have, for example, a geometric shape according to the orientation of the opposing sub-electrodes 41 to form the field cage.
  • the structuring may be provided on both passivation layers, that is to say both on the bottom surface and on the top surface.
  • FIG. 2 illustrates a section of an electrode device according to the invention with structured passivation layer in an enlarged, exploded perspective view.
  • the electrode layer 40 with a dielectric insulating layer or passivation layer 50 having a structured region 51 processed thereon.
  • the thickness d p of the passivation layer 50 is, for example, 600 nm.
  • the thickness d s is set to a value of z , B. 200 nm or formed with an altered composition having other electrical properties, a modified dielectric constant or an altered specific electrical conductivity.
  • the structuring of the passivation layer 50 can be carried out, for example, by photolithography. If the first and / or second passivation layer is formed at least partially by a layer material whose dielectric properties are reversibly or irreversibly variable, the structuring can be carried out, for example, by laser irradiation in accordance with the geometry of the desired structures.
  • FIGS. 3A to 3D illustrate the effect of the passivation layers structured according to the invention on the basis of the results of model calculations.
  • the structure of the two electrode devices on channel walls with the suspension-flow channel is modeled by a liquid-filled plate capacitor assuming infinitely large capacitor plates in which, for example, an electrode is provided with a passivation layer.
  • the field strength inside the channel (or the plate capacitor) depends on both the frequency and the dielectric and geometric conditions.
  • the modeling takes place with the following parameters: Dielectric constant of the suspension or solution between the capacitor plates: 80, dielectric constant of the passivation layer: 5 and conductivity of the passivation layer: 10 -5 S / m.
  • FIG. 3A illustrates the relative field strength E rel (field strength with passivation layer / field strength without passivation layer) in the channel as a function of the frequency f at different conductivities of the aqueous suspension in the channel.
  • the thickness of the passivation layer is 1% of the distance of the electrode device.
  • FIG. 3A shows that the field coupling into the channel depends on the conductivity of the suspension and the frequency. Surprisingly, it has been found that the insulating effect of the passivation layer depends on the frequency and becomes increasingly strong as the electrolyte content increases.
  • FIG. 3B shows with the same parameters as in FIG. 3A the phase angle ⁇ (in radians) of the electric field.
  • the phase angle ⁇ is also strongly frequency-dependent with increasing conductivity.
  • electric field gradients in the channel can be realized in terms of phase and amplitude with homogeneous electrodes. This can be used, for example, to realize an octupole cage, which conventionally required eight electrodes, with only four electrodes, each one of them Electrode over a suitable passivation two in each case by approx. 90 ° out of phase signals.
  • FIG. 3C shows the relative field strength E rel in the channel as a function of the frequency at different thicknesses of the passivation layer, which is indicated in each case as a% proportion relative to the electrode spacing.
  • the modeling is done with a water-filled channel (conductivity: 0.3 S / m). It turns out that the field penetration is considerably reduced with increasing thickness of the passivation layer and that this effect is frequency-dependent.
  • an increase of the field strength in the channel can be achieved by a reduction in thickness. This effect depends on the frequency. This means that a functional element in the fluidic microsystem can be activated or ineffective depending on the frequency.
  • the results according to FIG. 3 show a particular advantage of the invention in that the modulation of the field in the channel by the structured passivation is particularly effective at lower conductivities of the suspension in the channel.
  • the modulation of the field in the channel by the structured passivation is particularly effective at lower conductivities of the suspension in the channel.
  • the structured passivation layers form frequency filters. Certain field components with certain frequencies are allowed to pass through the structured regions (eg 51) due to high field penetration, while other frequency components are attenuated (s. FIG. 3 ). This effect depends on the thickness and / or composition of the structured regions of the passivation layer. If the electrode devices with high-frequency voltage signals with a z. B. rectangular waveform, which represents a corresponding superposition of a plurality of frequencies, the frequency composition can be modulated in the channel by the passivation layer. Since the dielectrophoretic effect of the electric fields is frequency-dependent in particular, the function of the respective electrode device can be adjusted via the frequency of the control voltage.
  • the structuring of the passivation layer may be formed inhomogeneous in itself.
  • a region 51 of reduced thickness in the passivation layer 50 may be formed according to FIG. 4A have a Dickengradient in itself. At one end 51a with a larger thickness, the field penetration is lower than at the opposite end 51b with the smaller thickness.
  • a filter for different types of particles or sizes are formed. A particle mixture flowing in a partial channel in the direction of the arrow strikes the field barrier which is formed on the structured region 51.
  • the small particles which are relatively unaffected by a strong field, can pass the field barrier at region 51 without deflection, while the larger particles are first deflected into an area with reduced field penetration.
  • the particles of different size follow different paths in the channel.
  • FIG. 5 shows in more detail a non-inventive dielectric filter element, wherein the first electrode means 40 is provided at the upper chip level.
  • the bottom element 20 and the cover element 30 are formed by glass substrates, which are mounted one above the other at a distance from one another and form the upper and lower boundary of the channel 10.
  • the distance h is, for example, in the range of 5 .mu.m to 100 .mu.m.
  • an electrode strip 41 with a passivation layer 50 is provided on the upper cover surface 31, an electrode strip 41 with a passivation layer 50 is provided.
  • the electrode strip 41 is connected via a connecting line 43 to a power supply (not shown).
  • the passivation layer 50 is opened above the electrode strip 41.
  • An unstructured electrode layer 61 is attached to the bottom part 20 as a second electrode device, and a structured passivation layer 70 is applied to this according to the invention.
  • passivation layer 70 is reduced in thickness and / or composition is varied.
  • a passivation layer thickness in the region 71 of 10% of the electrode spacing eg 400 nm to 600 nm
  • the relative field strength at a frequency of 1 MHz increases from 0.1 to 0.7 (see FIG. FIG. 3C ).
  • a sufficiently high field gradient in the flow passing through the channel 10 can be generated locally between the electrodes.
  • the field gradient forms a field barrier, which, for example, restrains large particles and lets small particles through.
  • the acting restraining force scales quadratically with the field strength.
  • the channel 10 is filled with water at 10 mS / m.
  • the electrodes are supplied with sinusoidal signals at a frequency of 10 MHz. Between the opposing electrode devices 40, 60, concentrated field lines form, which form two field barriers for the particles
  • FIGS. 7A and 7B Illustrate in each case from the channel 10 from considered schematic plan views of the upper (A) and lower (B) channel wall of a fluidic system 100 according to the invention with the channel 10, which splits into two sub-channels 11, 12.
  • channel 10 are as dielectric functional elements 80, two deflectors 81, 82, a hook 83 and a switch (switch) 84 arranged, as it is in itself from the fluidic Microsystem technology is known.
  • measuring devices for. B. Particle detectors may be provided.
  • the lower chip level ( FIG. 7B ) is analogous to FIG. 1D constructed in a conventional manner with individually controllable sub-electrodes.
  • the partial electrodes z. B. 41 with different geometric configurations each have a connecting line 43, leading to connection points (bond pads) 44.
  • the electrode areas not required for the dielectric manipulation of the particles are completely passivated. The passivation is opened above the active electrode areas (see eg at 52).
  • the upper chip level ( FIG. 7A ) is simpler. It's analogous to FIG. 1D a single electrode layer (not shown) with a closed electrode surface on which a passivation layer (not shown) with structured regions 71 is formed. For the formation of an electric field between the electrode pairs of the upper and lower chip planes, only the upper level electrode layer and the lower level part electrodes are connected to a power supply (generator).
  • the field-shaping structures may be arranged offset in the channel direction in order to form a channel-driving field.
  • the particles are flowed into the channel 10 in the direction of the arrow and exposed to the electric field barriers at the sub-electrodes.
  • individual partial electrodes can be switched on or off.
  • a lateral electrode spacing in the channel direction which is greater than the channel height.
  • FIG. 8 shows an example of a microsystem 100 according to the invention, in which both the lower and the upper electrode means is completely covered with structured passivation layers and in addition a perpendicular from the channel 10 or diagonally branching transverse channel 13 is provided with a third electrode means 90 for generating a DC voltage field.
  • a liquid or particle transport can take place between the electrodes 91, 92 by electroosmosis or electrophoresis under the effect of the DC voltage field (see double arrow), which remains undisturbed by the passivation of the first and second electrode devices.
  • it is provided to deflect a particle into the transverse channel 13 as a function of the signal of a particle detector.
  • electroporation or electrofusion processes can be triggered when passing through transverse channel 13 when pulsed DC voltages are applied.

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Description

Die Erfindung betrifft ein fluidisches Mikrosystem mit den Merkmalen gemäß dem Oberbegriff von Anspruch 1 und ein Verfahren zur Feldformung in einem Kanal des genannten fluidischen Mikrosystems.The invention relates to a fluidic microsystem with the features according to the preamble of claim 1 and a method for field shaping in a channel of said fluidic microsystem.

Es ist bekannt, suspendierte Partikel (z. B. biologische Zellen, Zellgruppen, Zellbestandteile, Makromoleküle oder synthetische Partikel in Suspensionslösungen) in fluidischen Mikrosystemen mit hochfrequenten elektrischen Feldern zu manipulieren, die mit Mikroelektroden in Kanälen des Mikrosystems erzeugt werden (s. z. B. T. Schnelle et al. in "Langmuir". Bd. 12, 1996, Seite 801-809 ). Die berührungslose Partikelmanipulation (z. B. Bewegen, Anhalten, Ablenken, Zusammenfügen usw.) basiert auf der negativen Dielektrophorese. Es ist bekannt, die auf Kanalwänden angeordneten Mikroelektroden zumindest teilweise mit einer elektrisch isolierenden dünnen Schicht abzudecken, um unerwünschte Wechselwirkungen zwischen den Mikroelektroden und dem Suspensionsmedium oder den Partikeln, wie z. B. Ohm' sche Verluste, Elektrolyse, Induktion von Transmembranpotentialen usw. zu minimieren (Passivierung der Mikroelektroden).It is known to manipulate suspended particles (eg biological cells, cell groups, cell constituents, macromolecules or synthetic particles in suspension solutions) in fluidic microsystems with high-frequency electric fields generated by microelectrodes in channels of the microsystem (cf. BT Schnelle et al. in "Langmuir". Vol. 12, 1996, pages 801-809 ). Non-contact particle manipulation (eg, move, stop, deflect, join, etc.) is based on negative dielectrophoresis. It is known to at least partially cover the arranged on channel walls microelectrodes with an electrically insulating thin layer to unwanted interactions between the microelectrodes and the suspension medium or the particles, such as. B. Ohm 'cal losses, electrolysis, induction of transmembrane potentials, etc. to minimize (passivation of the microelectrodes).

Typischerweise enthalten die fluidischen Mikrosysteme räumliche Elektrodenanordnungen. Die Mikroelektroden sind an einander gegenüberliegenden, z. B. unteren und oberen Kanalwänden mit typischen Abständen im Bereich von 10 µm bis 100 µm angeordnet (s. T. Müller et al. in "Biosensors & Bioelectronics", Bd. 14, 1999, S. 247-256 ). Zur Erzielung definierter Feldwirkungen müssen die Mikroelektroden in bestimmter Weis geformt und relativ zueinander angeordnet sein. Bei räumlichen Elektrodenanordnungen ist dies mit einem hohen Justieraufwand der Kanalwände (Chipebenen) verbunden. Die Genauigkeit muss besser als 5 µm bei typischen Maßen des Mikrosystems im cm-Bereich sein. Des Weiteren ergeben sich Probleme bei der Herstellung des Mikrosystems. Diese erfolgt üblicherweise mit Techniken der Halbleitertechnologie, wobei für die räumliche Elektrodenanordnung mehrere Masken zur Waferprozessierung erforderlich sind. Schließlich besteht ein Problem der räumlichen Elektrodenanordnung mit strukturierten Mikroelektroden auf verschiedenen Kanalwänden in der elektrischen Kontaktierung. In der Regel muss die elektrische Kontaktierung der oberen Kanalwand (obere Chipebene) zu der unteren Kanalwand durchgeführt und von dieser elektrisch getrennt zu einem Steueranschluss geführt werden. Insbesondere mit Blick auf einen massenhaften Einsatz fluidischer Mikrosysteme besteht ein Interesse an Mikrosystemen mit einem vereinfachten Aufbau und einer erhöhten Funktionssicherheit.Typically, the fluidic microsystems include spatial electrode arrays. The microelectrodes are at opposite, z. B. lower and upper channel walls with typical distances in the range of 10 .mu.m to 100 .mu.m (s. T. Muller et al. in "Biosensors &Bioelectronics", Vol. 14, 1999, pp. 247-256 ). To achieve defined field effects, the microelectrodes must be shaped in a certain way and arranged relative to each other. In spatial electrode arrangements, this is with a high Justieraufwand the Channel walls (chip levels) connected. The accuracy must be better than 5 μm for typical dimensions of the microsystem in the cm range. Furthermore, problems arise in the production of the microsystem. This is usually done with semiconductor technology techniques, requiring multiple masks for wafer processing for the spatial electrode array. Finally, there is a problem of the spatial electrode arrangement with structured microelectrodes on different channel walls in the electrical contacting. As a rule, the electrical contacting of the upper channel wall (upper chip level) to the lower channel wall has to be carried out and separated electrically from this to a control connection. In particular, with a view to a mass use of fluidic microsystems, there is an interest in microsystems with a simplified structure and increased reliability.

Es ist bekannt, elektrisch isolierende Passivierungsschichten zu strukturieren, um eine bestimmte Feldformung zu bewirken (s. DE 198 69 117 , DE 198 60 118 ). Die Strukturierung besteht in der Bildung von Öffnungen oder Durchbrüchen in der Passivierungsschicht über einer flächigen Elektrode. Durch die Öffnungen kann das elektrische Feld von der Elektrode in den Kanal durchgreifen und die gewünschte Feldform entsprechend der Form der Öffnung bilden. Die Öffnungen in den Passivierungsschichten besitzen jedoch den Nachteil, dass ein Kontakt zwischen dem Elektrodenmaterial und der Suspensionsflüssigkeit entsteht. Es kann zu ggf. irreversiblen Elektrodenprozessen kommen. Beispielsweise können Partikel unter der Feldwirkung auf die Elektroden gezogen werden und den Kanal verstopfen. Des Weiteren kann es zu einer Auflösung des Elektrodenmaterials und damit zu einer Kontamination der Suspensionsflüssigkeit kommen. Diesem Problem wurde bisher dadurch begegnet, dass Suspensionsflüssigkeiten mit einem eher niedrigen Elektrolytgehalt verwendet wurden. Dadurch wurde jedoch der Anwendungsbereich der Mikrosysteme eingeschränkt. Viele biologische Partikel besitzen nur eine begrenzte Fähigkeit, einen niedrigen Elektrolytgehalt über längere Zeit zu tolerieren.It is known to structure electrically insulating passivation layers in order to effect a specific field shaping (s. DE 198 69 117 . DE 198 60 118 ). The structuring consists in the formation of openings or openings in the passivation layer over a planar electrode. Through the openings, the electric field can pass through from the electrode into the channel and form the desired field shape corresponding to the shape of the opening. However, the openings in the passivation layers have the disadvantage that a contact between the electrode material and the suspension liquid is formed. It may lead to irreversible electrode processes. For example, particles under the field effect can be pulled onto the electrodes and clog the channel. Furthermore, it may lead to a dissolution of the electrode material and thus to a contamination of the suspension liquid. This problem has been addressed by that suspension liquids with a rather low electrolyte content were used. However, this limited the scope of the microsystems. Many biological particles have limited ability to tolerate low electrolyte levels for extended periods of time.

Es ist auch bekannt, dass durch die Passivierungsschichten auf Mikroelektroden eine Feldabschirmung bewirkt wird. Dies kann bspw. verwendet werden, um Feldgradienten im Kanal entsprechend einem bestimmten räumlichen Verlauf zu verstärken oder abzuschwächen (s. z. B. T. Schnelle et al., s. oben und G. Fuhr et al. in "Sensors and Materials", Bd. 7/2, 1995, S. 131-146 ). Nachteilig ist jedoch, dass der abschwächende Einfluss der Passivierungsschicht bei den Suspensionsflüssigkeiten mit niedrigem Elektrolytgehalt (niedrige Leitfähigkeit) relativ schwach ist.It is also known that field shielding is effected by the passivation layers on microelectrodes. This can be used, for example, to amplify or attenuate field gradients in the channel in accordance with a specific spatial progression (see FIG BT Schnelle et al., S. above and G. Fuhr et al. in "Sensors and Materials", Vol. 7/2, 1995, pp. 131-146 ). A disadvantage, however, is that the attenuating influence of the passivation layer in the suspension liquids with low electrolyte content (low conductivity) is relatively weak.

Aus US 6 387 707 B1 und US 2002/0166766 A1 sind weitere fluidische Mikrosysteme bekannt, bei denen auf einer Kanalwand eine strukturierte Elektrode und auf einer gegenüberliegenden Kanalwand eine unstrukturierte Elektrode vorgesehen ist.Out US Pat. No. 6,387,707 B1 and US 2002/0166766 A1 Further fluidic microsystems are known in which a structured electrode is provided on a channel wall and an unstructured electrode is provided on an opposite channel wall.

Die Aufgabe der Erfindung ist es, ein verbessertes fluidisches Mikrosystem bereitzustellen, mit dem den Nachteilen herkömmlicher Mikrosysteme begegnet wird. Die Aufgabe der Erfindung ist es insbesondere, ein Mikrosystem mit einem vereinfachten Aufbau, insbesondere einer vereinfachten Elektrodenanordnung und einer vereinfachten Kontaktierung, einer erhöhten Funktionssicherheit und einem erweiterten Anwendungsbereich, insbesondere bei der Manipulation biologischer Partikel bereitzustellen. Die Aufgabe der Erfindung ist es auch, ein verbessertes Verfahren zur Feldformung in fluidischen Mikrosystemen, insbesondere zur dielektrophoretischen Manipulation von Partikeln bereitzustellen.The object of the invention is to provide an improved fluidic microsystem which overcomes the disadvantages of conventional microsystems. The object of the invention is in particular to provide a microsystem with a simplified structure, in particular a simplified electrode arrangement and a simplified contacting, increased reliability and an extended range of application, in particular in the manipulation of biological particles. The object of the invention is also to provide an improved method for field shaping in fluidic microsystems, in particular to provide for the dielectrophoretic manipulation of particles.

Diese Aufgaben werden durch Mikrosysteme und Verfahren mit den Merkmalen gemäß den Patentansprüchen 1 und 7 gelöst. Vorteilhafte Ausführungsformen und Anwendungen der Erfindung ergeben sich aus den abhängigen Ansprüchen.These objects are achieved by microsystems and methods having the features according to claims 1 and 7. Advantageous embodiments and applications of the invention will become apparent from the dependent claims.

Ein Merkmal der Erfindung ist es, ein fluidisches Mikrosystem mit mindestens einem von einer Partikelsuspension durchströmbaren Kanal, an dessen Kanalwänden Elektrodeneinrichtungen zur Erzeugung elektrischer Wechselspannungsfelder im Kanal angeordnet sind, von denen eine erste Elektrodeneinrichtung zur Feldformung mit einer Strukturierung ausgestattet und eine zweite Elektrodeneinrichtung flächig, unstrukturiert mit einer Passivierungsschicht gebildet ist, insbesondere dahingehend weiterzuentwickeln, dass die Strukturierung der ersten Elektrodeneinrichtung charakteristische Dimensionen kleiner als die flächige Elektrodenschicht der zweiten Elektrodeneinrichtung besitzt und die Passivierungsschicht der zweiten Elektrodeneinrichtung eine geschlossene, die Elektrodenfläche der zweiten Elektrodeneinrichtung vollständig bedeckende Schicht ist. Durch diese Merkmale wird der Aufbau des Mikrosystems erheblich vereinfacht, da lediglich die erste Elektrodeneinrichtung, die bspw. eine untere Elektrodeneinrichtung auf der in Betriebsposition unteren Chipebene oder Bodenfläche ist, zur Feldformung strukturiert sein muss, während vorteilhafterweise als zweite Elektrodeneinrichtung, insbesondere als eine obere Elektrodeneinrichtung an der oberen Chipebene oder Deckfläche des Kanals einfach eine flächige, vollständig passivierte Elektrodenschicht vorgesehen sein kann, die lediglich eine einzige Anschlussleitung zur Verbindung mit einer Spannungsversorgung oder, falls die zweite Elektrodeneinrichtung potentialfrei betrieben wird, keine Anschlussleitung erfordert. Die flächige zweite Elektrodeneinrichtung kann ohne komplizierte Maskierungsschritte bei der Waferprozessierung hergestellt werden. Durch die geschlossene Passivierungsschicht auf der zweiten Elektrodeneinrichtung werden unerwünschte Elektrodenprozesse vollständig vermieden. Die Anordnung der ersten Elektrodeneinrichtung an der unteren Chipebene und der zweiten Elektrodeneinrichtung an der oberen Chipebene ist kein zwingendes Merkmal der Erfindung, sondern kann insbesondere umgekehrt vorgesehen sein. Allgemein können die ersten und zweiten Elektrodeneinrichtungen an verschiedenen Kanalwänden vorgesehen sein, die die Deckflächen, Bodenflächen und/oder Seitenflächen bilden. Ein weiterer Vorteil der Kombination einerseits einer strukturierten Elektrodeneinrichtung (vorzugsweise auf der Bodenfläche) und einer nicht-strukturierten, flächigen Elektrodeneinrichtung (vorzugsweise auf der Deckelfläche) besteht in der Möglichkeit, die verschiedensten Elektrodenanordnungen und Systemfunktionen zu realisieren, wie unten dargestellt wird.A feature of the invention is a fluidic microsystem with at least one channel through which a particle suspension can flow, on the channel walls of which electrode devices for generating alternating electrical fields are arranged in the channel, of which a first electrode device for field shaping is provided with a structuring and a second electrode device is planar, unstructured is formed with a passivation layer, in particular to further develop in that the structuring of the first electrode device has characteristic dimensions smaller than the planar electrode layer of the second electrode device and the passivation layer of the second electrode device is a closed, the electrode surface of the second electrode device completely covering layer. These features considerably simplify the design of the microsystem since only the first electrode device, which is, for example, a lower electrode device on the lower chip level or bottom surface in the operating position, must be structured for field shaping, while advantageously as a second electrode device, in particular as an upper electrode device At the upper chip level or top surface of the channel, a flat, completely passivated electrode layer can be provided, which merely has a single connecting line for connection to a voltage supply or, if the second electrode device is potential-free is operated, no connection cable required. The planar second electrode device can be produced without complex masking steps during the wafer processing. The closed passivation layer on the second electrode device completely avoids undesired electrode processes. The arrangement of the first electrode device at the lower chip level and the second electrode device at the upper chip level is not a mandatory feature of the invention, but may in particular be provided in reverse. Generally, the first and second electrode means may be provided on different channel walls forming the top surfaces, bottom surfaces and / or side surfaces. A further advantage of the combination on the one hand of a structured electrode device (preferably on the bottom surface) and a non-structured, flat electrode device (preferably on the cover surface) is the possibility of realizing the most varied electrode arrangements and system functions, as shown below.

Gemäß der Erfindung weist die Passivierungsschicht der zweiten, (vorzugsweise) oberen Elektrodeneinrichtung ihrerseits Schichtstrukturen zur Feldformung im Kanal auf, wobei die Schichtstrukturen Bereiche umfassen, die eine veränderte Dicke in der Passivierungsschicht oder ein anderes Material als die umgebenden Passivierungsschicht aufweisen. Diese Strukturierung der Passivierungsschicht ist mit einer flächigen Elektrodenschicht kombiniert. Die Strukturierung der Passivierungsschicht kann Vorteile in Bezug auf die Feldformung im Kanal besitzen.According to the invention, the passivation layer of the second (preferably) upper electrode device in turn has layer structures for field shaping in the channel, wherein the layer structures comprise regions which have a changed thickness in the passivation layer or a material other than the surrounding passivation layer. This structuring of the passivation layer is combined with a planar electrode layer. The patterning of the passivation layer may have advantages in terms of field shaping in the channel.

Gemäß einer ersten Ausführungsform der Erfindung kann die erste Elektrodeneinrichtung mindestens eine strukturierte Elektrodenschicht mit einzelnen Teilelektroden aufweisen, die in ihrer Gesamtheit die Strukturierung oder mindestens ein erstes Strukturelement bilden, wie es an sich von herkömmlichen Mikroelektrodenanordnungen bekannt ist. Die Bereitstellung einer Vielzahl von Teilelektroden kann im Bezug auf eine separate Ansteuerbarkeit jeder Teilelektrode vorteilhaft sein. Die separate Ansteuerbarkeit ist bspw. wichtig, wenn die Felder im Kanal in Abhängigkeit von bestimmten äußeren Einflüssen oder Messergebnissen variiert werden sollen. Die Teilelektroden umfassen vorzugsweise einzeln ansteuerbare Elektrodenstreifen, also Mikroelektroden mit einer langgestreckten Linienform mit einer typischen Breite im Bereich von 50 nm bis 100 µm und einer typischen Länge von bis zu 5 mm. Die Teilelektroden können Passivierungsschichten tragen, die ggf. eine definierte Öffnung entsprechend der Position der Teilelektroden tragen.According to a first embodiment of the invention, the first electrode device may comprise at least one structured electrode layer having individual partial electrodes, which in their entirety constitute the structuring or at least one first structural element, as is known per se from conventional microelectrode arrangements. The provision of a plurality of sub-electrodes may be advantageous in relation to a separate controllability of each sub-electrode. The separate controllability is important, for example, if the fields in the channel are to be varied depending on certain external influences or measurement results. The sub-electrodes preferably comprise individually controllable electrode strips, ie microelectrodes with an elongated line shape with a typical width in the range of 50 nm to 100 μm and a typical length of up to 5 mm. The sub-electrodes can carry passivation layers, which optionally carry a defined opening corresponding to the position of the sub-electrodes.

Die Schichtstrukturen, an denen eine Modulierung des Felddurchgriffs in den Kanal erfolgt, werden bspw. durch Bereiche veränderter (verminderter oder erhöhter Dicke) in der Passivierungsschicht gebildet. Vorteilhafterweise können diese abgesenkten oder hervortretenden Schichtstrukturen durch einen einfachen Ätzprozess erzeugt werden. Die Form der Schichtstrukturen kann durch eine Maskierung eingestellt werden. Hervortretende Schichtstrukturen werden insbesondere bei Bildung der Passivierungsschicht mit Materialien mit relativ hoher Dielektrizitätskonstante bevorzugt. Alternativ können die Schichtstrukturen Bereiche umfassen, die mindestens ein anderes Material als die umgebende Passivierungsschicht aufweisen, das sich insbesondere durch eine veränderte Dielektrizitätskonstante auszeichnet. Beide Formen der Schichtstrukturen, also die Dickenvariation und die Materialvariation können in Kombination vorgesehen sein. Des Weiteren können die Passivierungsschichten aus verschiedenen Schichtmaterialien mehrschichtig gebildet sein.The layer structures in which the field penetration is modulated into the channel are formed, for example, by regions of changed (reduced or increased thickness) in the passivation layer. Advantageously, these lowered or protruding layer structures can be produced by a simple etching process. The shape of the layer structures can be adjusted by masking. Emerging layer structures are particularly preferred when forming the passivation layer with materials having a relatively high dielectric constant. Alternatively, the layer structures may comprise regions which have at least one other material than the surrounding passivation layer, which is characterized in particular by a changed dielectric constant. Both forms of the layer structures, ie the thickness variation and the material variation can be provided in combination. Furthermore, the passivation layers can be formed of different layer materials in multiple layers.

Weitere Vorteile können sich für die Gestaltung des Mikrosystems ergeben, wenn Passivierungsschichten zumindest teilweise durch Schichtmaterialien gebildet sind, deren dielektrische Eigenschaften reversibel oder irreversibel veränderlich sind ("smart isolation"). Die Schichtmaterialien werden beispielsweise durch eine Laserbehandlung zwischen verschiedenen Modifikationen (z. B. kristallin <-> amorph) umgestellt, die sich durch verschiedene DK-Werte auszeichnen. Derartig veränderbare Materialien sind beispielsweise von beschreibaren oder wiederbeschreibaren optischen Speichern (CD) bekannt. Alternativ können als veränderliche Schichtmaterialien Polymere verwendet werden, deren Leitfähigkeit wenigstens einmalig wie bei einem Direkt-Laserschreib-verfahren durch Laserbestrahlung geändert werden kann. Vorteilhafterweise können mit dieser Ausführungsform besonders günstig spezifische Prototypen (z.B. für ein "rapid prototyping") hergestellt werden.Further advantages may result for the design of the microsystem if passivation layers are at least partially formed by layer materials whose dielectric properties are reversibly or irreversibly variable ("smart isolation"). The coating materials are converted, for example, by a laser treatment between different modifications (eg crystalline <-> amorphous), which are distinguished by different DK values. Such changeable materials are for example descriptive or rewritable optical storage (CD) known. Alternatively, as a variable layer materials, polymers can be used whose conductivity can be changed at least once by laser irradiation as in a direct laser writing method. Advantageously, specific prototypes (eg for rapid prototyping) can be produced with this embodiment particularly favorably.

Vorteilhafterweise wird der Kanal mit den oben beschriebenen Elektrodeneinrichtungen mit mindestens einem Querkanal ausgestattet, in dem eine dritte Elektrodeneinrichtung zur Erzeugung elektrischer Gleichspannungsfelder im Querkanal angeordnet ist. Durch die Passivierung der ersten und zweiten Elektrodeneinrichtungen bleiben die Transportvorgänge im Querkanal ungestört.Advantageously, the channel is equipped with the electrode devices described above with at least one transverse channel, in which a third electrode means for generating electrical DC fields in the transverse channel is arranged. Through the passivation of the first and second electrode devices, the transport processes in the transverse channel remain undisturbed.

Ein Vorteil von Passivierungsschichten im Vergleich zu blanken Elektroden besteht darin, dass sich der Widerstand blanker Elektroden schon durch Auflagerung von Monolayern um Größenordnungen ändern kann. Dies kann relativ leicht während der Chipherstellung oder im Betrieb passieren und gefährdet insbesondere dann die Funktion dielektrischer Elemente, wenn die Schichten nicht homogen sind. Zur Vermeidung dieses Problems mussten bisher zusätzliche Maßnahmen (Plasmaätzen etc.) realisiert werden. Zusätzliche Schichten auf Passivierungsschichten haben dagegen einen wesentlich weniger störenden Effekt. Die Funktionssicherheit der Mikrosysteme wird dadurch verbessert.An advantage of passivation layers compared to bare electrodes is that the resistance of bare electrodes can already change by orders of magnitude due to the superposition of monolayers. This can be relatively easy during the Chip production or in operation happen and endanger the function of dielectric elements in particular when the layers are not homogeneous. To avoid this problem, additional measures (plasma etching, etc.) had to be implemented so far. On the other hand, additional layers on passivation layers have a significantly less disturbing effect. The functional reliability of the microsystems is thereby improved.

Ein weiterer Gegenstand der Erfindung ist ein Verfahren zur Feldformung in einem Kanal des erfindungsgemäßen fluidischen Mikrosystems, insbesondere zur dielektrophoretischen Manipulation von suspendierten Partikeln in dem erfindungsgemäßen fluidischen Mikrosystem durch die Feldformung mittels lateralen Strukturen in Passivierungsschichten auf Elektroden.Another object of the invention is a method for field shaping in a channel of the fluidic microsystem according to the invention, in particular for the dielectrophoretic manipulation of suspended particles in the fluidic microsystem according to the invention by the field shaping by means of lateral structures in passivation layers on electrodes.

Weitere Vorteile und Einzelheiten der Erfindung werden aus der folgenden Beschreibung der beigefügten Zeichnungen ersichtlich. Es zeigen:

Fign. 1A, 1D und 1E:
schematische Ansichten verschiedener Ausführungsbeispiele erfindungsgemäßer Mikrosysteme (Ausschnitte),
Fign. 1B und 1C:
Ausschnitte von weiteren Mikrosystemen (keine Ausführungsbeispiele der Erfindung),
Fig. 2:
eine weitere schematische Illustration einer Elektrodeneinrichtung mit einer strukturierten Passivierungsschicht,
Fign. 3A-3D:
Kurvendarstellungen zur Illustration der Feldwirkung der erfindungsgemäß vorgesehenen Passivierungsschichten,
Fign. 4A, B:
ein Ausführungsbeispiel der Erfindung mit einer Gradientenstruktur in der Passivierungsschicht,
Fig. 5:
kein erfindungsemäße Ausführungsbeispiel einer Elektrodenanordnung eines Mikrosystems,
Fig. 6:
eine Feldbarriere eines erfindungsgemäßen Mikrosystems,
Fign. 7A, 7B:
schematische Illustrationen eines weiteren Ausführungsbeispiels eines erfindungsgemäßen fluidischen Mikrosystems, und
Fig. 8:
ein weiteres Ausführungsbeispiel eines erfindungsgemäßen fluidischen Mikrosystems.
Further advantages and details of the invention will become apparent from the following description of the accompanying drawings. Show it:
FIGS. 1A, 1D and 1E:
schematic views of various embodiments of microsystems according to the invention (extracts),
FIGS. 1B and 1C:
Cutouts of further microsystems (no embodiments of the invention),
Fig. 2:
a further schematic illustration of an electrode device with a structured passivation layer,
FIGS. 3A-3D:
Graphs illustrating the field effect of the passivation layers provided according to the invention,
FIGS. 4A, B:
an embodiment of the invention with a gradient structure in the passivation layer,
Fig. 5:
no inventive embodiment of an electrode assembly of a microsystem,
Fig. 6:
a field barrier of a microsystem according to the invention,
FIGS. 7A, 7B:
schematic illustrations of another embodiment of a fluidic microsystem according to the invention, and
Fig. 8:
a further embodiment of a fluidic microsystem according to the invention.

In Figur 1A ist in schematischer Perspektivansicht ein Teil eines erfindungsgemäßen fluidischen Mikrosystems 100 gezeigt. Das Mikrosystem 100 enthält mindestens einen Kanal 10, der zwischen zwei plattenförmigen Chipelementen, nämlich dem Bodenelement oder Substrat 20 und dem Deckelement 30 gebildet ist. Weitere Teile des Mikrosystems, insbesondere seitliche Wänden, Spacer und dgl. sind aus Übersichtlichkeitsgründen nicht gezeigt. Das Substrat 20 bildet eine erste (untere) Kanalwand mit einer zum Kanal 10 weisenden Bodenfläche 21, auf der eine erste Elektrodeneinrichtung, ggf. mit einer Passivierungsschicht (siehe unten) angeordnet ist. Das Deckelement 30 bildet die zweite (obere) Kanalwand mit einer zum Kanal 10 weisenden Deckfläche 31, auf der entsprechend die zweite Elektrodeneinrichtung (siehe unten) angeordnet ist. Mindestens einer der Elektrodeneinrichtungen ist zur Felderzeugung im Kanal 10 mit einer Wechselspannungsquelle (nicht dargestellt) verbunden. Mindestens auf der zweiten Elektrodeneinrichtung ist erfindungsgemäß eine Passivierungsschicht vorgesehen.In Figure 1A In a schematic perspective view, a part of a fluidic microsystem 100 according to the invention is shown. The microsystem 100 includes at least one channel 10 formed between two plate-shaped chip elements, namely the bottom element or substrate 20 and the cover element 30. Other parts of the microsystem, in particular lateral walls, spacers and the like are not shown for reasons of clarity. The substrate 20 forms a first (lower) channel wall with a bottom surface 21 facing the channel 10, on which a first electrode device, optionally with a passivation layer (see below), is arranged. The cover element 30 forms the second (upper) channel wall with a cover surface 31 facing the channel 10, on which the second electrode device (see below) is arranged accordingly. At least one of the electrode means is for field generation in the channel 10 with an AC voltage source (not shown). At least on the second electrode device according to the invention a passivation layer is provided.

Der Kanal 10 wird durch einen Freiraum zwischen den Chipelementen 20, 30 gebildet. Er ist von einer Flüssigkeit, insbesondere einer Partikelsuspension durchströmbar und besitzt eine Höhe bspw. im Bereich von 5 µm bis 1 mm und anwendungsabhängig gewählte Quer- und Längendimensionen im µm- bis cm-Bereich. Die Chipelemente 20, 30 bestehen typischerweise aus Glas, Silizium oder einem elektrisch nicht leitenden Polymer.The channel 10 is formed by a free space between the chip elements 20, 30. It is permeable by a liquid, in particular a particle suspension and has a height, for example. In the range of 5 .mu.m to 1 mm and application-dependent selected transverse and longitudinal dimensions in the micrometer to cm range. The chip elements 20, 30 are typically made of glass, silicon or an electrically non-conductive polymer.

Der Schichtaufbau aus Elektrodeneinrichtung und Passivierungsschicht ist im rechten, vergrößerten Ausschnitt von Figur 1A gezeigt. Beispielsweise auf der Bodenfläche 21 des Substrats 20 befindet sich die erste Elektrodeneinrichtung 40 und eine erste Passivierungsschicht 50 (siehe z. B. Figur 1C, (kein Ausführungsbeispiel der Erfindung). Der Schichtaufbau wird mit an sich bekannter Planartechnologie durch Deposition der gewünschten Materialien auf dem Substrat gebildet. Die Elektrodeneinrichtung besteht aus einem elektrisch leitfähigen Material, z. B. einem Metall oder leitfähigen Oxid, z. B. Sn doped In2O3, (ITO), Indium-Cadmium-Oxid (InxCd1-xO), Cd2SnO4, oder einem leitfähigen Polymer (z. B. Polyanilin, Polypyrrol, Polythiophen). Die Dicke der Elektrodeneinrichtung liegt bspw. im Bereich von 50 nm bis 2 µm. Die Passivierungsschicht 50 ist eine dielektrische Isolationsschicht mit einer Dicke im Bereich von 0.1 µm bis 10 µm. Sie besteht bspw. aus Polyimid oder einem elektrisch isolierenden Oxid, z. B. Siliziumoxid, Siliziumnitrid.The layer structure of electrode device and passivation layer is in the right, enlarged section of Figure 1A shown. For example, on the bottom surface 21 of the substrate 20 is the first electrode device 40 and a first passivation layer 50 (see, eg, FIG. Figure 1C , (not an embodiment of the invention). The layer structure is formed by per se known planar technology by deposition of the desired materials on the substrate. The electrode device consists of an electrically conductive material, for. As a metal or conductive oxide, for. Sn doped In 2 O 3 , (ITO), indium cadmium oxide (In x Cd 1-x O), Cd 2 SnO 4 , or a conductive polymer (eg, polyaniline, polypyrrole, polythiophene). The thickness of the electrode device is, for example, in the range of 50 nm to 2 microns. The passivation layer 50 is a dielectric insulating layer having a thickness in the range of 0.1 μm to 10 μm. It consists, for example, of polyimide or an electrically insulating oxide, for. For example, silicon oxide, silicon nitride.

In den Figuren 1B und 1C sind Ausschnitte von Mikrosystemen illustriert, bei denen die zweite Elektrodeneinrichtung eine unstrukturierte Passivierungsschicht trägt (keine Ausführungsbeispiele der Erfindung). In den Figuren 1D und 1E sind die o. g. bevorzugten Ausführungsformen der Erfindung mit schematischen Draufsichten auf die ersten (unteren) und zweiten (oberen) Kanalwände 21, 31 illustriert.In the FIGS. 1B and 1C Illustrations of microsystems are illustrated in which the second electrode device carries an unstructured passivation layer (no embodiments of the invention). In the Figures 1D and 1E For example, the above preferred embodiments of the invention are illustrated with schematic plan views of the first (lower) and second (upper) channel walls 21, 31.

Gemäß Figur 1B (kein Ausführungsbeispiel der Erfindung) ist die erste Elektrodeneinrichtung 40 zur Feldformung im Kanal strukturiert gebildet. Sie ist allgemein mit mindestens einem ersten Strukturelement ausgestattet, das im dargestellten Beispiel vier Elektrodenelemente oder Teilelektroden 41 umfasst, die in an sich bekannter Weise in Streifenform auf der Bodenfläche 21 gebildet sind. Die Teilelektroden 41 können mit einer Passivierungsschicht (nicht gezeigt) bedeckt sein, die ggf. an den Flächen der Teilelektroden 41 in an sich bekannter Weise Durchbrüche aufweist.According to FIG. 1B (Not an embodiment of the invention), the first electrode means 40 is formed structured for field formation in the channel. It is generally equipped with at least one first structural element, which in the illustrated example comprises four electrode elements or partial electrodes 41, which are formed in strip-form on the bottom surface 21 in a manner known per se. The partial electrodes 41 may be covered with a passivation layer (not shown), which optionally has openings on the surfaces of the partial electrodes 41 in a manner known per se.

Die zweite Elektrodeneinrichtung 60 auf der Deckfläche 31 umfasst eine flächige Elektrodenschicht 61 (gestrichelt gezeigt) mit einer geschlossenen zweiten Elektrodenfläche, die von einer zweiten Passivierungsschicht 70 vollständig bedeckt ist.The second electrode device 60 on the cover surface 31 comprises a planar electrode layer 61 (shown in dashed lines) with a closed second electrode surface, which is completely covered by a second passivation layer 70.

Es ist vorgesehen, dass die ersten Strukturelemente 41 der ersten Elektrodeneinrichtung 40 eine kleinere wirksame Elektrodenfläche als die zweite Elektrodenfläche 61 der zweiten Elektrodeneinrichtung 60 bilden (die Summe der einzelnen Flächen der ersten Elektrodeneinrichtung 40 ist kleiner als die zweite Elektrodenfläche 61). Dadurch entstehen bei Beaufschlagung der Elektrodeneinrichtungen 40, 60 mit elektrischen Spannungen Feldlinienverläufe, die sich auf der Bodenfläche 21 an den Teilelektroden 41 mit vergrößerter Feldliniendichte vereinigen und auf der Deckfläche 31 in der Elektrodenschicht 61 enden. Das elektrische Feld im Kanal ist entsprechend der Gestalt der Teilelektroden geformt. Es wird bspw. eine Feldbarriere oder ein Feldkäfig gebildet, mit denen die Bewegung von Partikeln im Kanal beeinflusst oder Partikel festgehalten werden können.It is provided that the first structural elements 41 of the first electrode device 40 form a smaller effective electrode area than the second electrode area 61 of the second electrode device 60 (the sum of the individual areas of the first electrode device 40 is smaller than the second electrode area 61). As a result, when the electrode devices 40, 60 are acted upon by electrical voltages, field line profiles are formed which combine on the bottom surface 21 at the partial electrodes 41 with an enlarged field line density and terminate on the top surface 31 in the electrode layer 61. The electric field in the channel is shaped according to the shape of the sub-electrodes. For example, a field barrier or a field cage is formed, with which the movement of particles in the channel can be influenced or particles can be held.

Die Elektrodenschicht 61 der zweiten Elektrodeneinrichtung 60 kann gemäß einem ersten Betriebsmodus über eine Anschlussleitung mit einer Steuereinrichtung verbunden sein. Im Unterschied zu herkömmlichen Elektrodenanordnungen ist vorteilhafterweise nur eine Anschlussleitung zur Bildung der Gegenelektrode zum Beispiel für einen Feldkäfig mit einer Barriereform entsprechend den Teilelektroden 41 ausreichend. Gemäß einem zweiten Betriebsmodus kann die zweite Elektrodeneinrichtung ohne Verbindung mit einer Steuereinrichtung auf der Deckfläche 31 angeordnet sein. In diesem sog. "floatenden" Zustand bildet sich das Potential der zweiten Elektrodeneinrichtung automatisch in Abhängigkeit von den umgebenden Potentialverhältnissen. In der Elektrodenschicht wird jeweils eine Ladungsverteilung gebildet, die das im Kanal auftretende Feld im Innern der Elektrodenschicht ausgleicht. In diesem Fall kann vorteilhafterweise auf eine Kontaktierung vollständig verzichtet werden.The electrode layer 61 of the second electrode device 60 may be connected to a control device via a connecting line in accordance with a first operating mode. In contrast to conventional electrode arrangements, advantageously only one connecting line for forming the counterelectrode is sufficient, for example for a field cage with a barrier shape corresponding to the partial electrodes 41. In accordance with a second operating mode, the second electrode device may be arranged on the cover surface 31 without being connected to a control device. In this so-called "floating" state, the potential of the second electrode device automatically forms as a function of the surrounding potential conditions. In each case a charge distribution is formed in the electrode layer, which compensates for the field occurring in the channel in the interior of the electrode layer. In this case, advantageously can be completely dispensed with a contact.

Figur 1C (kein Ausführungsbeispiel der Erfindung) illustriert ein Mikrosystem, bei dem beide Elektrodeneinrichtungen 40, 60 durch flächige, geschlossene Elektrodenschichten 42, 61 gebildet werden, die jeweils durch geschlossene Passivierungsschichten 50, 60 abgedeckt sind. Die erste (untere) Elektrodeneinrichtung 40 ist mit mindestens einem Strukturelement ausgestattet, das bei dieser Ausführungsform durch eine Struktur in der ersten Passivierungsschicht 50 gebildet wird. Die Schichtstruktur in der ersten Passivierungsschicht 50 umfasst Bereiche 51 mit z. B. verminderter Dicke und/oder im Vergleich zur restlichen Passivierungsschicht variierten Materialien. Die Bereiche 51 besitzen lateral in der Schichtebene eine geometrische Form entsprechend den herkömmlich gebildeten Mikroelektroden, also bspw. eine Streifenform. Die zweite Elektrodeneinrichtung 60 ist gemäß Figur 1C wie bei Figur 1B durch eine Elektrodenschicht mit geschlossener, unstrukturierter Passivierungsschicht 70 gebildet. Figure 1C (Not an embodiment of the invention) illustrates a microsystem in which both electrode devices 40, 60 are formed by flat, closed electrode layers 42, 61 which are each covered by closed passivation layers 50, 60. The first (lower) electrode device 40 is equipped with at least one structural element, which in this embodiment is formed by a structure in the first passivation layer 50. The layer structure in the first passivation layer 50 comprises Areas 51 with z. B. reduced thickness and / or in comparison to the remaining passivation layer varied materials. The regions 51 have laterally in the layer plane a geometric shape corresponding to the conventionally formed microelectrodes, that is, for example, a strip shape. The second electrode device 60 is according to Figure 1C as in FIG. 1B formed by an electrode layer with closed, unstructured passivation layer 70.

Durch die Verwendung der strukturierten Passivierungsschicht 50 auf der flächigen Elektrodenschicht 42 wird die geometrische Form des Durchtritts des elektrischen Feldes von der Elektrodenschicht 42 in den Kanal entsprechend der Form der Bereiche 51 in vorbestimmter Weise eingestellt. Die Bereiche 51 können bspw. ein Aufreihelement mit einer trichterförmigen Feldbarriere (Figur 1C) bilden. Alternativ können in einer Passivierungsschicht, die eine geschlossene Elektrodenschicht abdeckt, mehrere strukturierte Bereiche (Feldstrukturierungselemente) realisiert sein. Dies besitzt den Vorteil, dass ein fluidisches Mikrosystem, z. B. ein Sortiersystem mit mehreren funktionalen Elementen mit nur zwei, an gegenüberliegenden Kanalwänden und mit strukturierten Passivierungen versehenen Elektroden aufgebaut ist, wobei ggf. nur eine Elektrode mit einer hochfrequenten Spannung angesteuert und die andere Elektrode im floatenden Zustand gelassen wird.By using the patterned passivation layer 50 on the sheet-like electrode layer 42, the geometric shape of the passage of the electric field from the electrode layer 42 into the channel is set in a predetermined manner according to the shape of the areas 51. The regions 51 can, for example, be a line-up element with a funnel-shaped field barrier (FIG. Figure 1C ) form. Alternatively, a plurality of structured regions (field structuring elements) can be realized in a passivation layer which covers a closed electrode layer. This has the advantage that a fluidic microsystem, for. B. a sorting system with a plurality of functional elements with only two, provided on opposite channel walls and with structured passivations electrodes is constructed, possibly only one electrode is driven with a high-frequency voltage and the other electrode is left in the floating state.

Gemäß Figur 1D ist die erste Elektrodeneinrichtung auf der Bodenfläche 21 mit mehreren Teilelektroden 41 wie in Figur 1B aufgebaut ist, während die zweite Elektrodeneinrichtung 60 gemäß der Erfindung mit einer strukturierten Passivierungsschicht 70 bedeckt ist. Die strukturierten Bereiche 71 in der Passivierungsschicht 70 besitzen bspw. eine geometrische Form entsprechend der Ausrichtung der gegenüberliegenden Teilelektroden 41 zur Bildung des Feldkäfigs.According to FIG. 1D is the first electrode device on the bottom surface 21 with a plurality of partial electrodes 41 as in FIG. 1B is constructed while the second electrode means 60 according to the invention with a structured passivation layer 70 is covered. The structured regions 71 in the passivation layer 70 have, for example, a geometric shape according to the orientation of the opposing sub-electrodes 41 to form the field cage.

Schließlich kann gemäß der Ausführungsform in Figur 1E die Strukturierung an beiden Passivierungsschichten, also sowohl an der Bodenfläche als auch an der Deckfläche vorgesehen sein.Finally, according to the embodiment in FIG Figure 1E the structuring may be provided on both passivation layers, that is to say both on the bottom surface and on the top surface.

Figur 2 illustriert einen Ausschnitt einer erfindungsgemäßen Elektrodeneinrichtung mit strukturierter Passivierungsschicht in vergrößerter, auseinandergezogener Perspektivansicht. Auf dem Substrat 20 befindet sich die Elektrodenschicht 40 mit einer darauf prozessierten dielektrischen Isolationsschichtoder Passivierungsschicht 50 mit einem strukturierten Bereich 51. Die Dicke dp der Passivierungsschicht 50 beträgt bspw. 600 nm. Am strukturierten Bereich 51 ist die Dicke ds auf einen Wert von z. B. 200 nm reduziert oder mit einer veränderten Zusammensetzung gebildet, die andere elektrische Eigenschaften, eine veränderte Dielektrizitätskonstante oder einer veränderte spezifisch elektrische Leitfähigkeit besitzt. FIG. 2 illustrates a section of an electrode device according to the invention with structured passivation layer in an enlarged, exploded perspective view. On the substrate 20 there is the electrode layer 40 with a dielectric insulating layer or passivation layer 50 having a structured region 51 processed thereon. The thickness d p of the passivation layer 50 is, for example, 600 nm. At the structured region 51, the thickness d s is set to a value of z , B. 200 nm or formed with an altered composition having other electrical properties, a modified dielectric constant or an altered specific electrical conductivity.

Die Strukturierung der Passivierungsschicht 50 kann bspw. durch Photolithographie erfolgen. Wenn die erste und/oder zweite Passivierungsschicht zumindest teilweise durch ein Schichtmaterial gebildet ist, dessen dielektrischen Eigenschaften reversibel oder irreversibel veränderlich sind, kann die Strukturierung beispielsweise durch eine Laserbestrahlung entsprechend der Geometrie der gewünschten Strukturen erfolgen.The structuring of the passivation layer 50 can be carried out, for example, by photolithography. If the first and / or second passivation layer is formed at least partially by a layer material whose dielectric properties are reversibly or irreversibly variable, the structuring can be carried out, for example, by laser irradiation in accordance with the geometry of the desired structures.

Die Figuren 3A bis 3D illustrieren die Wirkung der erfindungsgemäß strukturierten Passivierungsschichten anhand der Ergebnisse von Modellrechnungen. Der Aufbau der zwei Elektrodeneinrichtungen an Kanalwänden mit dem suspensionsdurchströmten Kanal wird durch einen flüssigkeitsgefüllten Plattenkondensator unter der Annahme unendlich großer Kondensatorplatten modelliert, bei dem bspw. eine Elektrode mit einer Passivierungsschicht versehen ist. Die Feldstärke im Inneren des Kanals (oder des Plattenkondensators) hängt sowohl von der Frequenz als auch von den dielektrischen und geometrischen Verhältnissen ab. Die Modellierung erfolgt mit den folgenden Parametern: Dielektrizitätskonstante der Suspension oder Lösung zwischen den Kondensatorplatten: 80, Dielektrizitätskonstante der Passivierungsschicht: 5 und Leitfähigkeit der Passivierungsschicht: 10-5 S/m.FIGS. 3A to 3D illustrate the effect of the passivation layers structured according to the invention on the basis of the results of model calculations. The structure of the two electrode devices on channel walls with the suspension-flow channel is modeled by a liquid-filled plate capacitor assuming infinitely large capacitor plates in which, for example, an electrode is provided with a passivation layer. The field strength inside the channel (or the plate capacitor) depends on both the frequency and the dielectric and geometric conditions. The modeling takes place with the following parameters: Dielectric constant of the suspension or solution between the capacitor plates: 80, dielectric constant of the passivation layer: 5 and conductivity of the passivation layer: 10 -5 S / m.

Figur 3A illustriert die relative Feldstärke Erel (Feldstärke mit Passivierungsschicht/Feldstärke ohne Passivierungsschicht) im Kanal in Abhängigkeit von der Frequenz f bei verschiedenen Leitfähigkeiten der wässrigen Suspension im Kanal. Die Dicke der Passivierungsschicht beträgt 1 % des Abstandes der Elektrodeneinrichtung. Figur 3A zeigt, dass die Feldeinkopplung in den Kanal von der Leitfähigkeit der Suspension und der Frequenz abhängig ist. Überraschenderweise zeigt sich, dass die Isolationswirkung der Passivierungsschicht von der Frequenz abhängig ist und mit steigendem Elektrolytgehalt immer stärker wird. FIG. 3A illustrates the relative field strength E rel (field strength with passivation layer / field strength without passivation layer) in the channel as a function of the frequency f at different conductivities of the aqueous suspension in the channel. The thickness of the passivation layer is 1% of the distance of the electrode device. FIG. 3A shows that the field coupling into the channel depends on the conductivity of the suspension and the frequency. Surprisingly, it has been found that the insulating effect of the passivation layer depends on the frequency and becomes increasingly strong as the electrolyte content increases.

Figur 3B zeigt mit den gleichen Parametern wie bei Figur 3A die Phasenlage Φ (in rad) des elektrischen Feldes. Auch die Phasenlage Φ ist mit zunehmender Leitfähigkeit stark frequenzabhängig. Entsprechend den in den Figuren 3A und 3B gezeigten Ergebnissen können elektrische Feldgradienten im Kanal in Bezug auf die Phase und die Amplitude mit homogenen Elektroden realisiert werden. Dies kann bspw. dazu benutzt werden, einen Oktupolkäfig, der herkömmlich acht Elektroden erforderte, mit lediglich vier Elektroden zu realisieren, wobei jede Elektrode über einer geeignete Passivierung zwei jeweils um rd. 90° phasenverschobene Signale liefert. FIG. 3B shows with the same parameters as in FIG. 3A the phase angle Φ (in radians) of the electric field. The phase angle Φ is also strongly frequency-dependent with increasing conductivity. According to the in the FIGS. 3A and 3B As shown, electric field gradients in the channel can be realized in terms of phase and amplitude with homogeneous electrodes. This can be used, for example, to realize an octupole cage, which conventionally required eight electrodes, with only four electrodes, each one of them Electrode over a suitable passivation two in each case by approx. 90 ° out of phase signals.

Figur 3C zeigt die relative Feldstärke Erel im Kanal in Abhängigkeit von der Frequenz bei verschiedenen Dicken der Passivierungsschicht, die jeweils als %-Anteil relativ zum Elektrodenabstand angegeben ist. Die Modellierung erfolgt mit einem wassergefüllten Kanal (Leitfähigkeit: 0.3 S/m). Es zeigt sich, dass der Felddurchgriff mit zunehmender Dicke der Passivierungsschicht erheblich reduziert wird und das dieser Effekt frequenzabhängig ist. Entsprechend dem in Figur 3C illustrierten Ergebnis können lokal an den strukturierten Bereichen (z. B. 51 in Figur 1C, E) durch eine Dickenreduzierung eine Erhöhung der Feldstärke im Kanal erzielt werden. Diese Wirkung ist von der Frequenz abhängig. Dies bedeutet, dass ein Funktionselement im fluidischen Mikrosystem je nach der Frequenz aktiviert oder unwirksam sein kann. FIG. 3C shows the relative field strength E rel in the channel as a function of the frequency at different thicknesses of the passivation layer, which is indicated in each case as a% proportion relative to the electrode spacing. The modeling is done with a water-filled channel (conductivity: 0.3 S / m). It turns out that the field penetration is considerably reduced with increasing thickness of the passivation layer and that this effect is frequency-dependent. According to the in FIG. 3C As illustrated, locally at the structured regions (eg 51 in FIGS. 1C, E) an increase of the field strength in the channel can be achieved by a reduction in thickness. This effect depends on the frequency. This means that a functional element in the fluidic microsystem can be activated or ineffective depending on the frequency.

Ein entsprechendes Ergebnis zeigt sich bei Strukturierungen der Passivierungsschicht durch Einbringung von Bereichen mit veränderter Dielektrizitätskonstante. Bei einer Suspensionsleitfähigkeit von 0.3 S/m und einer Dicke der Passivierungsschicht von 1% des Elektrodenabstandes ergibt sich gemäß Figur 3D mit zunehmender Dielektrizitätskonstante ein zunehmender Felddurchgriff auch bei geringeren Frequenzen.A corresponding result can be seen in structurings of the passivation layer by introducing regions with a changed dielectric constant. With a suspension conductivity of 0.3 S / m and a thickness of the passivation layer of 1% of the electrode spacing results according to Figure 3D with increasing dielectric constant an increasing field penetration even at lower frequencies.

Die Ergebnisse gemäß Figur 3 zeigen einen besonderen Vorteil der Erfindung dahingehend, dass die Modulation des Feldes im Kanal durch die strukturierte Passivierung bei geringeren Leitfähigkeiten der Suspension im Kanal besonders wirksam ist. Bei der Manipulation künstlicher Partikel, insbesondere aus Kunststoff, z. B. Latex-Beads, besteht ein Interesse an einer Verwendung niedriger Leitfähigkeiten. Bei einem Salz-Anteil von 1 mM ergibt sich bspw. eine Leitfähigkeit von rd. 14 mS/m. Biologische Zellen werden häufig in Medien mit einer Leitfähigkeit um 1 S/m gehandhabt. Eine kurzzeitige (bis zu 10 min) dielektrische Manipulation in niedriger Leitfähigkeit bis zu 1 mS/m wird gut vertragen. Für die dielektrische Manipulation werden typischerweise 0.05-0.3 S/m eingesetzt.The results according to FIG. 3 show a particular advantage of the invention in that the modulation of the field in the channel by the structured passivation is particularly effective at lower conductivities of the suspension in the channel. In the manipulation of artificial particles, in particular of plastic, for. As latex beads, there is an interest in using low conductivities. With a salt content of 1 mM results, for example, a conductivity of approx. 14 mS / m. Biological cells are often handled in media with conductivity around 1 S / m. Short term (up to 10 min) dielectric conduction in low conductivity up to 1 mS / m is well tolerated. For the dielectric manipulation typically 0.05-0.3 S / m are used.

Gemäß einem besonderen Vorteil der Erfindung bilden die strukturierten Passivierungsschichten Frequenzfilter. Bestimmte Feldanteile mit bestimmten Frequenzen werden aufgrund eines hohen Felddurchgriffs an den strukturierten Bereichen (z. B. 51) durchgelassen, während andere Frequenzanteile gedämpft werden (s. Figur 3). Diese Wirkung hängt von der Dicke und/oder Zusammensetzung der strukturierten Bereiche der Passivierungsschicht ab. Wenn die Elektrodeneinrichtungen mit hochfrequenten Spannungssignalen mit einer z. B. rechteckigen Signalform angesteuert werden, die entsprechend eine Überlagerung einer Vielzahl von Frequenzen darstellt, kann durch die Passivierungsschicht die Frequenzzusammensetzung im Kanal moduliert werden. Da die dielektrophoretische Wirkung der elektrischen Felder insbesondere frequenzabhängig ist, kann die Funktion der jeweiligen Elektrodeneinrichtung über die Frequenz der Steuerspannung eingestellt werden.According to a particular advantage of the invention, the structured passivation layers form frequency filters. Certain field components with certain frequencies are allowed to pass through the structured regions (eg 51) due to high field penetration, while other frequency components are attenuated (s. FIG. 3 ). This effect depends on the thickness and / or composition of the structured regions of the passivation layer. If the electrode devices with high-frequency voltage signals with a z. B. rectangular waveform, which represents a corresponding superposition of a plurality of frequencies, the frequency composition can be modulated in the channel by the passivation layer. Since the dielectrophoretic effect of the electric fields is frequency-dependent in particular, the function of the respective electrode device can be adjusted via the frequency of the control voltage.

Gemäß einer alternativen Ausführungsform der Erfindung kann die Strukturierung der Passivierungsschicht in sich inhomogen ausgebildet sein. Beispielsweise kann ein Bereich 51 verminderter Dicke in der Passivierungsschicht 50 gemäß Figur 4A in sich einen Dickengradient aufweisen. An einem Ende 51a mit einer größeren Dicke ist der Felddurchgriff niedriger als am entgegengesetzten Ende 51b mit der geringeren Dicke. Auf dieser Grundlage kann allein durch eine streifenförmige Passivierungsstruktur gemäß Figur 4B ein Filter für verschiedene Partikelarten oder -größen gebildet werden. Ein in Pfeilrichtung in einem Teilkanal einströmendes Partikelgemisch trifft auf die Feldbarriere, die an dem strukturierten Bereich 51 gebildet ist. Die kleinen Teilchen, die durch ein starkes Feld relativ wenig beeinflusst werden, können die Feldbarriere am Bereich 51 ohne Ablenkung passieren, während die größeren Teilchen zunächst in einen Bereich mit vermindertem Felddurchgriff abgelenkt werden. Entsprechend folgen nach Passage des Bereiches 51 die Teilchen verschiedener Größe verschiedenen Wegen im Kanal.According to an alternative embodiment of the invention, the structuring of the passivation layer may be formed inhomogeneous in itself. For example, a region 51 of reduced thickness in the passivation layer 50 may be formed according to FIG FIG. 4A have a Dickengradient in itself. At one end 51a with a larger thickness, the field penetration is lower than at the opposite end 51b with the smaller thickness. On this basis, only by a strip-shaped passivation according to FIG. 4B a filter for different types of particles or sizes are formed. A particle mixture flowing in a partial channel in the direction of the arrow strikes the field barrier which is formed on the structured region 51. The small particles, which are relatively unaffected by a strong field, can pass the field barrier at region 51 without deflection, while the larger particles are first deflected into an area with reduced field penetration. Correspondingly, after passage of the region 51, the particles of different size follow different paths in the channel.

Figur 5 zeigt mit weiteren Einzelheiten ein nicht erfindungsgemäßes dielektrisches Filterelement, bei dem die erste Elektrodeneinrichtung 40 an der oberen Chipebene vorgesehen ist. Das Bodenelement 20 und das Deckelelement 30 werden durch Glassubstrate gebildet, die mit Abstand voneinander übereinander montiert sind und die obere und untere Begrenzung des Kanals 10 bilden. Der Abstand h liegt bspw. im Bereich von 5 µm bis 100 µm. An der oberen Deckfläche 31 ist ein Elektrodenstreifen 41 mit einer Passivierungsschicht 50 vorgesehen. Der Elektrodenstreifen 41 ist über eine Anschlussleitung 43 mit einer Spannungsversorgung (nicht dargestellt) verbunden. Die Passivierungsschicht 50 ist über dem Elektrodenstreifen 41-geöffnet. FIG. 5 shows in more detail a non-inventive dielectric filter element, wherein the first electrode means 40 is provided at the upper chip level. The bottom element 20 and the cover element 30 are formed by glass substrates, which are mounted one above the other at a distance from one another and form the upper and lower boundary of the channel 10. The distance h is, for example, in the range of 5 .mu.m to 100 .mu.m. On the upper cover surface 31, an electrode strip 41 with a passivation layer 50 is provided. The electrode strip 41 is connected via a connecting line 43 to a power supply (not shown). The passivation layer 50 is opened above the electrode strip 41.

Auf dem Bodenteil 20 ist als zweite Elektrodeneinrichtung eine unstrukturierte Elektrodenschicht 61 und auf dieser gemäß der Erfindung eine strukturierte Passivierungsschicht 70 angebracht. Im Bereich 71 ist die Passivierungsschicht 70 in ihrer Dicke vermindert und/oder Zusammensetzung variiert. Bei einer Dicke der Passivierungsschicht im Bereich 71 von 10 % vom Elektrodenabstand (z. B. 400 nm bis 600 nm) steigt im Kanal über dem strukturierten Bereich 71 die relative Feldstärke bei einer Frequenz von 1 MHz von 0.1 auf 0.7 (s. Figur 3C). Dadurch kann zwischen den Elektroden lokal ein ausreichend hoher Feldgradient in der Strömung, die den Kanal 10 durchsetzt, erzeugt werden. Durch den Feldgradienten wird eine Feldbarriere gebildet, die beispielsweise große Partikel zurückhält und kleine Partikel durchlässt. Vorteilhafterweise kann dabei ausgenutzt werden, dass die wirkende Rückhaltekraft quadratisch mit der Feldstärke skaliert.An unstructured electrode layer 61 is attached to the bottom part 20 as a second electrode device, and a structured passivation layer 70 is applied to this according to the invention. In region 71, passivation layer 70 is reduced in thickness and / or composition is varied. In the case of a passivation layer thickness in the region 71 of 10% of the electrode spacing (eg 400 nm to 600 nm), in the channel above the structured region 71 the relative field strength at a frequency of 1 MHz increases from 0.1 to 0.7 (see FIG. FIG. 3C ). Thereby For example, a sufficiently high field gradient in the flow passing through the channel 10 can be generated locally between the electrodes. The field gradient forms a field barrier, which, for example, restrains large particles and lets small particles through. Advantageously, it can be exploited here that the acting restraining force scales quadratically with the field strength.

Die Simulationsdarstellung in Figur 6 zeigt die Verteilung der Feldstärkequadrate, d. h. der Potentiale für dielektrische Kraftwirkung, bei einem Ausführungsbeispiel mit zwei streifenförmigen Elektrodenstrukturen 40, 60 (Abstand h = 40 µm), die jeweils eine Passivierungsschicht (nicht gezeigt) mit einer Dicke von 5 µm tragen. In jeder Passivierungsschicht sind zwei Streifen mit einer Breite von 50 µm gebildet, die jeweils eine Substanz mit einer erhöhten Dielektrizitätskonstante (DK = 100, z. B. TiO, höhere Werte der DK von bis 12000 sind bei Titanaten wie BaTiO, SrTiO, CaTiO, PbTiO möglich) enthalten, während die übrige Passivierungsschicht jeweils Polyimid (DK = 3.5) oder SiNxOy umfasst. Der Kanal 10 ist mit Wasser bei 10 mS/m gefüllt. Die Elektroden werden mit Sinussignalen mit einer Frequenz von 10 MHz beaufschlagt. Zwischen den gegenüberliegenden Elektrodeneinrichtungen 40, 60 bilden sich konzentrierte Feldlinienverläufe aus, die zwei Feldbarrieren für die im Kanal 10 strömenden Partikel bilden.The simulation representation in FIG. 6 shows the distribution of the field strength squares, ie the potentials for dielectric force effect, in an embodiment with two strip-shaped electrode structures 40, 60 (distance h = 40 microns), each carrying a passivation layer (not shown) with a thickness of 5 microns. In each passivation layer, two strips with a width of 50 μm are formed, each of which is a substance with an increased dielectric constant (DK = 100, eg TiO 2, higher values of DK of up to 12000 are for titanates such as BaTiO, SrTiO, CaTiO, PbTiO possible), while the remaining passivation layer in each case comprises polyimide (DK = 3.5) or SiN x O y . The channel 10 is filled with water at 10 mS / m. The electrodes are supplied with sinusoidal signals at a frequency of 10 MHz. Between the opposing electrode devices 40, 60, concentrated field lines form, which form two field barriers for the particles flowing in the channel 10.

Die Figuren 7A und 7B illustrieren jeweils vom Kanal 10 aus betrachtete schematische Draufsichten auf die obere (A) und untere (B) Kanalwand eines erfindungsgemäßen fluidischen Systems 100 mit dem Kanal 10, der sich in zwei Teilkanäle 11, 12 aufspaltet. Im Kanal 10 sind als dielektrische Funktionselemente 80 zwei Deflektoren 81, 82, ein Haken 83 und ein Schalter (Weiche) 84 angeordnet, wie es an sich aus der fluidischen Mikrosystemtechnik bekannt ist. Des Weiteren können Messeinrichtungen, z. B. Partikeldetektoren vorgesehen sein.The FIGS. 7A and 7B Illustrate in each case from the channel 10 from considered schematic plan views of the upper (A) and lower (B) channel wall of a fluidic system 100 according to the invention with the channel 10, which splits into two sub-channels 11, 12. In channel 10 are as dielectric functional elements 80, two deflectors 81, 82, a hook 83 and a switch (switch) 84 arranged, as it is in itself from the fluidic Microsystem technology is known. Furthermore, measuring devices, for. B. Particle detectors may be provided.

Die untere Chipebene (Figur 7B) ist analog zu Figur 1D in an sich bekannter Weise mit einzeln ansteuerbaren Teilelektroden aufgebaut. Die Teilelektroden z. B. 41 mit verschiedenen geometrischen Gestaltungen besitzen jeweils eine Anschlussleitung 43, die zu Anschlussstellen (Bondpads) 44 führen. Die für die dielektrische Manipulation der Partikel nicht benötigten Elektrodenbereiche sind vollständig passiviert. Über den aktiven Elektrodenbereichen ist die Passivierung geöffnet (siehe z. B bei 52).The lower chip level ( FIG. 7B ) is analogous to FIG. 1D constructed in a conventional manner with individually controllable sub-electrodes. The partial electrodes z. B. 41 with different geometric configurations each have a connecting line 43, leading to connection points (bond pads) 44. The electrode areas not required for the dielectric manipulation of the particles are completely passivated. The passivation is opened above the active electrode areas (see eg at 52).

Die obere Chipebene (Figur 7A) ist einfacher aufgebaut. Es ist analog zu Figur 1D eine einzelne Elektrodenschicht (nicht gezeigt) mit einer geschlossenen Elektrodenfläche vorgesehen, auf der eine Passivierungsschicht (nicht gezeigt) mit strukturierten Bereichen 71 gebildet ist. Für die Ausbildung eines elektrischen Feldes zwischen den Elektrodenpaaren der oberen und unteren Chipebenen werden lediglich die Elektrodenschicht der oberen Ebene und die Teilelektroden der unteren Ebene mit einer Spannungsversorgung (Generator) verbunden.The upper chip level ( FIG. 7A ) is simpler. It's analogous to FIG. 1D a single electrode layer (not shown) with a closed electrode surface on which a passivation layer (not shown) with structured regions 71 is formed. For the formation of an electric field between the electrode pairs of the upper and lower chip planes, only the upper level electrode layer and the lower level part electrodes are connected to a power supply (generator).

Die feldformenden Strukturen (Teilelektroden und Strukturen in Passivierungsschicht) können in Kanalrichtung versetzt angeordnet sein, um ein in Kanalrichtung vorantreibendes Feld zu bilden.The field-shaping structures (sub-electrodes and structures in the passivation layer) may be arranged offset in the channel direction in order to form a channel-driving field.

Die Partikel werden in Pfeilrichtung in den Kanal 10 eingeströmt und an den Teilelektroden den elektrischen Feldbarrieren ausgesetzt. Je nach der gewünschten Funktion können einzelne Teilelektroden ein- oder ausgeschaltet werden. Für eine störungsfreie Trennung der einzelnen Funktionselemente wird vorzugsweise ein lateraler Elektrodenabstand (in Kanalrichtung) eingestellt, der größer als die Kanalhöhe ist.The particles are flowed into the channel 10 in the direction of the arrow and exposed to the electric field barriers at the sub-electrodes. Depending on the desired function, individual partial electrodes can be switched on or off. For a trouble-free separation of the individual functional elements is preferably set a lateral electrode spacing (in the channel direction) which is greater than the channel height.

Figur 8 zeigt ein Beispiel eines erfindungsgemäßen Mikrosystems 100, bei dem sowohl die untere als auch die obere Elektrodeneinrichtung komplett mit strukturierten Passivierungsschichten bedeckt ist und zusätzlich ein vom Kanal 10 senkrecht oder schräg abzweigender Querkanal 13 mit einer dritten Elektrodeneinrichtung 90 zur Erzeugung eines Gleichspannungsfeldes vorgesehen ist. Im Querkanal 13 kann zwischen den Elektroden 91, 92 durch Elektroosmose oder Elektrophorese ein Flüssigkeits- oder Partikeltransport unter Wirkung des Gleichspannungsfeldes erfolgen (siehe Doppelpfeil), der durch die Passivierung der ersten und zweiten Elektrodeneinrichtungen ungestört bleibt. Beispielsweise ist vorgesehen, in Abhängigkeit vom Signal eines Partikeldetektors einen Partikel in den Querkanal 13 abzulenken. Des Weiteren können beim Vorbeitritt am Querkanal 13 bei Anwendung gepulster Gleichspannungen Elektroporations- oder Elektrofusionsvorgänge ausgelöst werden. FIG. 8 shows an example of a microsystem 100 according to the invention, in which both the lower and the upper electrode means is completely covered with structured passivation layers and in addition a perpendicular from the channel 10 or diagonally branching transverse channel 13 is provided with a third electrode means 90 for generating a DC voltage field. In the transverse channel 13, a liquid or particle transport can take place between the electrodes 91, 92 by electroosmosis or electrophoresis under the effect of the DC voltage field (see double arrow), which remains undisturbed by the passivation of the first and second electrode devices. For example, it is provided to deflect a particle into the transverse channel 13 as a function of the signal of a particle detector. Furthermore, electroporation or electrofusion processes can be triggered when passing through transverse channel 13 when pulsed DC voltages are applied.

Die in der vorstehenden Beschreibung, den Zeichnungen und den Ansprüchen offenbarten Merkmale der Erfindung können sowohl einzeln als auch in Kombination für die Verwirklichung der Erfindung in ihren verschiedenen Ausgestaltungen von Bedeutung sein.The features of the invention disclosed in the foregoing description, drawings and claims may be significant to the realization of the invention in its various forms both individually and in combination.

Claims (7)

  1. A fluidic microsystem, comprising:
    - at least one channel (10) through which a particle suspension can flow, and
    - first and second electrode devices (40, 60) which are arranged on first and second channel walls (21, 31) for generating electrical alternating-voltage fields in the channel (10), wherein
    - the first electrode device (40) for field shaping in the channel is provided with first structure elements (41, 51), which are formed by structured partial electrodes (41, 51), wherein the structured partial electrodes (41, 51) comprise individually controllable electrode strips,
    - the second electrode device (60) comprises an area-like second electrode layer (61) with a closed second electrode surface, and
    - the sum of the individual areas of the electrode strips of the first electrode device (40) is smaller than the second electrode area (61),
    characterised in that
    - the area-like second electrode layer (61) carries a passivation layer (70), wherein
    - the passivation layer (70) is a closed layer which completely covers the second electrode layer (61),
    - the passivation layer (70) has at least one second structure element for field shaping in the channel (10), which is formed by layer structures (71) in the passivation layer (70), wherein
    - the layer structures (71) comprise regions, which have a changed thickness in the passivation layer (70) or a material that differs from the material of the surrounding passivation layer (70).
  2. The microsystem according to claim 1, in which the regions of the layer structures (71) are inhomogeneous with a thickness gradient and/or a material gradient.
  3. The microsystem according to any one of the preceding claims, in which the passivation layer (70) comprises several layers.
  4. The microsystem according to any one of the preceding claims, in which the passivation layer (70) is at least partly formed by a layer material whose dielectric characteristics are reversibly or irreversibly changeable.
  5. The microsystem according to any one of the preceding claims, in which a third electrode device (90) is provided for generating electrical direct-voltage fields or direct-voltage pulses in the channel (10) or in a transverse channel (13) which branches off from the channel (10).
  6. The microsystem according to any one of the preceding claims 1 to 4, in which an external electrode device is provided for generating electrical direct-voltage fields or direct-voltage pulses in the channel (10) or in a transverse channel (13) which branches off from the channel (10).
  7. A method for field shaping in a channel (10) of a fluidic microsystem (100) according to any one of the preceding claims, in which the geometric shape of electrical fields in the channel (10) is determined by the geometric shape of layer structures in the passivation layer (70) in which there is a modified field transconductance.
EP03776918.9A 2002-11-29 2003-11-26 Fluidic microsystem and method comprising field-forming passivation layers provided on microelectrodes Expired - Lifetime EP1565266B1 (en)

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