US20060006061A1 - Electrical microhydraulic multiplex system and use thereof - Google Patents

Electrical microhydraulic multiplex system and use thereof Download PDF

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Publication number
US20060006061A1
US20060006061A1 US10/515,884 US51588405A US2006006061A1 US 20060006061 A1 US20060006061 A1 US 20060006061A1 US 51588405 A US51588405 A US 51588405A US 2006006061 A1 US2006006061 A1 US 2006006061A1
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United States
Prior art keywords
electrodes
groups
group
electric
microfluidics
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Abandoned
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US10/515,884
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English (en)
Inventor
Uwe Tangen
Thomas Maeke
John McCaskill
Ruedi Fuchslin
Harald Mathis
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Fraunhofer Gesellschaft zur Forderung der Angewandten Forschung eV
Protolife SRL
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Fraunhofer Gesellschaft zur Forderung der Angewandten Forschung eV
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Assigned to PROTOLIFE SRL. reassignment PROTOLIFE SRL. ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: MCCASKILL, JOHN S., FUECHSLIN, RUEDI, MAEKE, THOMAS, TANGEN, UWE
Assigned to FUECHSLIN, RUEDI, MAEKE, THOMAS, MCCASKILL, JOHN S., TANGEN, UWE reassignment FUECHSLIN, RUEDI ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: MATHIS, HARALD
Publication of US20060006061A1 publication Critical patent/US20060006061A1/en
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    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5025—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures for parallel transport of multiple samples
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027—Containers 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
    • B01L3/502761—Containers 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
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N27/00—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
    • G01N27/26—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating electrochemical variables; by using electrolysis or electrophoresis
    • G01N27/416—Systems
    • G01N27/447—Systems using electrophoresis
    • G01N27/44756—Apparatus specially adapted therefor
    • G01N27/44773—Multi-stage electrophoresis, e.g. two-dimensional electrophoresis
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00277—Apparatus
    • B01J2219/00497—Features relating to the solid phase supports
    • B01J2219/005—Beads
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00277—Apparatus
    • B01J2219/00497—Features relating to the solid phase supports
    • B01J2219/00527—Sheets
    • B01J2219/00529—DNA chips
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00583—Features relative to the processes being carried out
    • B01J2219/00603—Making arrays on substantially continuous surfaces
    • B01J2219/00646—Making arrays on substantially continuous surfaces the compounds being bound to beads immobilised on the solid supports
    • B01J2219/00648—Making arrays on substantially continuous surfaces the compounds being bound to beads immobilised on the solid supports by the use of solid beads
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00583—Features relative to the processes being carried out
    • B01J2219/00603—Making arrays on substantially continuous surfaces
    • B01J2219/00653—Making arrays on substantially continuous surfaces the compounds being bound to electrodes embedded in or on the solid supports
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/0068—Means for controlling the apparatus of the process
    • B01J2219/00686—Automatic
    • B01J2219/00689—Automatic using computers
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/06—Fluid handling related problems
    • B01L2200/0647—Handling flowable solids, e.g. microscopic beads, cells, particles
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/04—Moving fluids with specific forces or mechanical means
    • B01L2400/0403—Moving fluids with specific forces or mechanical means specific forces
    • B01L2400/0415—Moving fluids with specific forces or mechanical means specific forces electrical forces, e.g. electrokinetic
    • B01L2400/0421—Moving fluids with specific forces or mechanical means specific forces electrical forces, e.g. electrokinetic electrophoretic flow

Definitions

  • the invention describes a device and several methods for the highly parallel, electrically controllable processing of molecules (especially biopolymers) in an integrated microstructured hybrid component (combination of microfluidics and electronics).
  • the controlling is mediated via electrodes by the known electrophoretic drift of molecules in an electric field.
  • This way of controlling is designed to the effect that the active control of the molecular movement in different units (e.g. channels) of the microfluidics can be carried out in a highly parallel manner independent for each unit.
  • the electric transport control of biomolecules by use of a moderate number of electrodes belongs to the current state of the art. Particularly in electrophoresis (e.g. gel electrophoresis and capillary electrophoresis), considerably less electrodes are driven individually and analogously, inclusive of voltage and current monitoring. In microstructures, electrolysis will limit the maximum allowable potential value at the electrodes due to gas generation. The use of gels for better discrimination during transport entails problems because of restricted reusability and cross contamination.
  • Some present-day microreactors already use electric fields to convey molecules to specific sites (DNA chips), or to prevent them from diffusing away from a site.
  • these sites are provided with specific substances, e.g. short DNA strings, to thus allow for conclusions on the substances contained in the liquid on the basis of the site information.
  • Active movements of molecules in solutions have been described (e.g. by Fuhr) but are not yet economically utilizable.
  • the reactors, arranged in parallel are not controlled individually. Further documented uses of electric fields relate to electroporation and the sorting of cells. In all of these examples, there is reached only a limited parallelism of the control.
  • each group of the thus interconnected electrodes has an output of the control electronics assigned thereto.
  • this control signal will be present on all electrodes of this group.
  • the arrangement of electrodes of two respective groups is selected in such a manner that both groups together include at least one pair of electrodes, with the distance of the electrodes being minimum.
  • control signals are applied to both groups of electrodes, an electric field will be generated between the electrodes of the above mentioned pair of electrodes, which field has a sufficient strength to cause the desired manipulation (e.g. the transport of a molecule).
  • the desired manipulation e.g. the transport of a molecule
  • the output of a digital component can assume only three states: 0, 1, tristate ⁇ Z, i.e. about 0 Volts, 3.3 or 5 Volts (V cc ) or high-ohmic (inactive).
  • the control for a pair of electrodes in a solution with charged molecules represents—under the aspect of electricity—an arrangement comprising at least resistors (the conduction is performed via charge carriers existing in the liquid, normally ions) and capacitors (local barrier layers may build up, which will then further increase the already existing capacities).
  • the technical expenditure for control is considerably reduced.
  • the actually effective electric field between two electrodes controlled in this way can vary in strength and direction almost in any desired manner between zero and the maximum.
  • the effect of the field on the molecules can be set in virtually every desired manner.
  • n output drivers By the use of highly integrated commercial digital components comprising several hundreds of output drivers (n output drivers), it now becomes possible to drive electrode bundles in the magnitude of n 2 independently from each other and thereby provide several thousands of reaction chambers with molecules or to remove molecules from the reaction chambers in any desired manner. In this regard, it is irrelevant whether these reaction chambers are formed as spatial chambers or merely are generated spatially-temporally within moving liquid streams. Because of the ionic double layers which are in the process of being generated and because of the associated field shielding, the electrode control processes can be interleaved in time in such a manner (similar to the annular-core-type storage devices from the early years of computer technology) that several thousands of electrodes can be operated although merely several hundreds of active drivers of digital components exist.
  • the output drivers of the digital components can be integrated directly into the carrier material. This will be advisable especially if silicon is used as a carrier material.
  • the silicon surface required for the additional logic inclusive of the corresponding drivers can be easily made available among the electrodes.
  • these microstructured bioreactors are disposable articles and thus should be inexpensive in manufacture.
  • the advantages achievable with the invention relate to the now possible highly parallel integration of thousands of electrodes and the thus accomplished availability of a combinatorial variety in the reaction paths.
  • the described invention makes it possible to carry out, within a microfluidics system, a large number (10 3 -10 6 ) of different reactions or separation methods with parallel and mutually independent control.
  • the highly parallel electrode control can be utilized to configure—i.e. to program—a microfluidics system for various purposes.
  • the desired molecular processing need not be known in advance and need not be identical for all samples but can be made dependent from intermediate results.
  • the now possible provision of thousands of independently controlled electrodes will open up novel fields of application in chemical or biochemical reaction systems, e.g.
  • the pulse and duty cycles can be adapted to the particle types so that “electric filters” and “amplifiers” can be produced which allow for a preferred transportation of specific particle types.
  • the fields can be formed to be very inhomogeneous so that also molecules which have dipole characteristics can be transported and manipulated.
  • the duration, the frequencies and the duty cycles of the applied digital potentials allow not only for the avoidance of electrolysis effects on the electrodes but also allow for the above mentioned multiplex operation, notably because of the relaxation behavior of mobile charge carriers in the solution.
  • FIG. 1 left-hand part, there is shown a matrix with respectively six traces in the x- and y-directions (x 1 -x 6 and y 1 -y 6 ).
  • Liquid channels can be laid diagonally across the 36 electrodes driven by these traces.
  • the electrodes have rectangular pulses assigned thereto.
  • a plurality of reference electrodes distributed in the liquid channel have assigned thereto a rectangular voltage of a higher frequency which is selected to the effect that the medium voltage level will be set e.g. exactly at V cc /2.
  • FIG. 2 shows a possible realization of the above two-dimensional array.
  • the electrodes are connected diagonally in order to allow for horizontal and vertical channel structures.
  • the electrode connections are configured to the effect that electrodes which are no direct neighbors are arranged at least four electrodes apart from each other.
  • the fields which then act across the four electrodes can be neglected because of the strong decrease of the field strengths.
  • it can be accomplished in many cases that even the more remote electrode pairs, although active, will have no influence at all due to the absence of molecules. Nonetheless, of course, it should be kept in mind that the reasonable number of simultaneously active electrode pairs must be much smaller than x y since the forces integrally exerted on the biomolecules would otherwise become too small.
  • FIG. 2 The design illustrated in FIG. 2 is however subject to the precondition that a two-layered trace layout is allowable. It is of no relevance whether these two layers are arranged on the selfsame side of the basic material (e.g. silicone) or each of the sides is provided with a layer comprising the corresponding vias.
  • FIG. 3 shows a test example for the case that only a one-layered trace layout is possible. However, the scaling work suffers considerably from this restriction to a merely one-layered trace layout and can be reasonably performed only in one dimension.

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  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Analytical Chemistry (AREA)
  • Molecular Biology (AREA)
  • Physics & Mathematics (AREA)
  • Clinical Laboratory Science (AREA)
  • Hematology (AREA)
  • Biochemistry (AREA)
  • Dispersion Chemistry (AREA)
  • Electrochemistry (AREA)
  • Fluid Mechanics (AREA)
  • General Physics & Mathematics (AREA)
  • Immunology (AREA)
  • Pathology (AREA)
  • Physical Or Chemical Processes And Apparatus (AREA)
  • Control Of Eletrric Generators (AREA)
  • Centrifugal Separators (AREA)
  • Remote Monitoring And Control Of Power-Distribution Networks (AREA)
  • Automatic Analysis And Handling Materials Therefor (AREA)
US10/515,884 2002-05-24 2003-05-23 Electrical microhydraulic multiplex system and use thereof Abandoned US20060006061A1 (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
DE10223127A DE10223127C1 (de) 2002-05-24 2002-05-24 Elektrisches Mikrofluidik-Multiplex-System und dessen Verwendung
DE10223127.3 2002-05-24
PCT/EP2003/005418 WO2003100375A2 (de) 2002-05-24 2003-05-23 Elektrisches mikrofluidik-multiplex-system und dessen verwendung

Publications (1)

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US20060006061A1 true US20060006061A1 (en) 2006-01-12

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US10/515,884 Abandoned US20060006061A1 (en) 2002-05-24 2003-05-23 Electrical microhydraulic multiplex system and use thereof

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US (1) US20060006061A1 (de)
EP (1) EP1556166B1 (de)
AT (1) ATE428501T1 (de)
AU (1) AU2003247289A1 (de)
DE (1) DE10223127C1 (de)
WO (1) WO2003100375A2 (de)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN112175815A (zh) * 2019-07-05 2021-01-05 京东方科技集团股份有限公司 Pcr基板、芯片、系统及液滴拉出方法
WO2021123259A1 (de) * 2019-12-20 2021-06-24 Leibniz-Institut Für Photonische Technologien E.V. Probenträger zur elektrischen manipulation von flüssigen proben und zur schwingungsspektroskopie an den proben

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7309410B2 (en) 2003-12-03 2007-12-18 Palo Alto Research Center Incorporated Traveling wave grids and algorithms for biomolecule separation, transport and focusing
DE102008062620B4 (de) * 2008-12-10 2012-12-27 Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung e.V. Vorrichtung und Verfahren zur Detektion von in flüssigen Proben enthaltenen Analytmolekülen

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5846396A (en) * 1994-11-10 1998-12-08 Sarnoff Corporation Liquid distribution system
US6033546A (en) * 1994-08-01 2000-03-07 Lockheed Martin Energy Research Corporation Apparatus and method for performing microfluidic manipulations for chemical analysis and synthesis
US6046056A (en) * 1996-06-28 2000-04-04 Caliper Technologies Corporation High throughput screening assay systems in microscale fluidic devices
US6361671B1 (en) * 1999-01-11 2002-03-26 The Regents Of The University Of California Microfabricated capillary electrophoresis chip and method for simultaneously detecting multiple redox labels

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4737251A (en) * 1985-09-27 1988-04-12 Washington University Field-inversion gel electrophoresis
HUT54236A (en) * 1988-02-02 1991-01-28 Inst Molekularnojj Biolog Akad Device for separating macromolecular dns-s embedded into gel by means of electrophoresis
DE19860117A1 (de) * 1998-12-23 2000-07-13 Evotec Biosystems Ag Elektrodenanordnung zur dielektrophoretischen Partikelablenkung

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6033546A (en) * 1994-08-01 2000-03-07 Lockheed Martin Energy Research Corporation Apparatus and method for performing microfluidic manipulations for chemical analysis and synthesis
US5846396A (en) * 1994-11-10 1998-12-08 Sarnoff Corporation Liquid distribution system
US6046056A (en) * 1996-06-28 2000-04-04 Caliper Technologies Corporation High throughput screening assay systems in microscale fluidic devices
US6361671B1 (en) * 1999-01-11 2002-03-26 The Regents Of The University Of California Microfabricated capillary electrophoresis chip and method for simultaneously detecting multiple redox labels

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN112175815A (zh) * 2019-07-05 2021-01-05 京东方科技集团股份有限公司 Pcr基板、芯片、系统及液滴拉出方法
WO2021123259A1 (de) * 2019-12-20 2021-06-24 Leibniz-Institut Für Photonische Technologien E.V. Probenträger zur elektrischen manipulation von flüssigen proben und zur schwingungsspektroskopie an den proben

Also Published As

Publication number Publication date
AU2003247289A8 (en) 2003-12-12
EP1556166A2 (de) 2005-07-27
EP1556166B1 (de) 2009-04-15
ATE428501T1 (de) 2009-05-15
DE10223127C1 (de) 2003-10-02
WO2003100375A2 (de) 2003-12-04
AU2003247289A1 (en) 2003-12-12
WO2003100375A3 (de) 2005-05-26

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