DE19500660B4 - Device and method for manipulating microscopic particles and their use - Google Patents
Device and method for manipulating microscopic particles and their use Download PDFInfo
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- DE19500660B4 DE19500660B4 DE19500660A DE19500660A DE19500660B4 DE 19500660 B4 DE19500660 B4 DE 19500660B4 DE 19500660 A DE19500660 A DE 19500660A DE 19500660 A DE19500660 A DE 19500660A DE 19500660 B4 DE19500660 B4 DE 19500660B4
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- antenna
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- microelectrode
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N13/00—Treatment of microorganisms or enzymes with electrical or wave energy, e.g. magnetism, sonic waves
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B03—SEPARATION 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
- B03C—MAGNETIC OR ELECTROSTATIC SEPARATION OF SOLID MATERIALS FROM SOLID MATERIALS OR FLUIDS; SEPARATION BY HIGH-VOLTAGE ELECTRIC FIELDS
- B03C5/00—Separating dispersed particles from liquids by electrostatic effect
- B03C5/02—Separators
- B03C5/022—Non-uniform field separators
- B03C5/028—Non-uniform field separators using travelling electric fields, i.e. travelling wave dielectrophoresis [TWD]
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
- C12M33/00—Means for introduction, transport, positioning, extraction, harvesting, peeling or sampling of biological material in or from the apparatus
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
- C12M47/00—Means for after-treatment of the produced biomass or of the fermentation or metabolic products, e.g. storage of biomass
- C12M47/02—Separating microorganisms from the culture medium; Concentration of biomass
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- Life Sciences & Earth Sciences (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Chemical & Material Sciences (AREA)
- Wood Science & Technology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Organic Chemistry (AREA)
- Zoology (AREA)
- Biotechnology (AREA)
- Genetics & Genomics (AREA)
- General Health & Medical Sciences (AREA)
- Microbiology (AREA)
- Biochemistry (AREA)
- General Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Molecular Biology (AREA)
- Sustainable Development (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Electrochemistry (AREA)
- Apparatus Associated With Microorganisms And Enzymes (AREA)
Abstract
Vorrichtung zur Manipulation mikroskopisch kleiner Partikel durch hochfrequente Wechselfelder, die eine Mikroelektrodenanordnung aufweist, die eine oder mehrere Elektroden eines Ultramikroelektrodensystems mit typischen Elektrodenenden im Mikrometer- und/oder Submikrometerbereich umfasst, welche die Spitze einer massefreien Antenne für hochfrequente Wechselspannungs-Signale bilden, die mit einem Höchfrequenzsignal von einem Generator beaufschlagt wird, dadurch gekennzeichnet, dass die Mikroelektrodenanordnung mit nur einer einpoligen Leitung als elektrischer Zufühurung mit dem Generator elektrisch verbunden ist.contraption for the manipulation of microscopic particles by high-frequency Alternating field having a microelectrode arrangement, the one or several electrodes of an ultramicroelectrode system with typical Includes micron and / or submicron electrode ends, which is the tip of a mass-free antenna for high-frequency AC signals form with a maximum frequency signal is acted upon by a generator, characterized in that the microelectrode arrangement with only a single-pole line as electrical supply is electrically connected to the generator.
Description
Die vorliegende Erfindung betrifft eine Vorrichtung und ein Verfahren zur Manipulation, Bewegung, Sammlung, Separation, Abstoßung, Formung und Aggregatbildung mikroskopisch kleiner Partikel in einer Ultramikroelektrodenanordnung durch HF-Wechselfelder.The The present invention relates to an apparatus and a method for manipulation, movement, collection, separation, repulsion, shaping and Aggregate formation of microscopic particles in an ultramicroelectrode array by HF alternating fields.
Dem Stand der Technik entsprechen Anordnungen, die hochfrequente elektrische Signale an mindestens 2 Elektroden benutzen, um Mikropartikel und Zellen in flüssigen Medien zu sammeln, zu separieren oder zu Aggregaten zusammenzufügen (POHL, Dielectrophoresis; Cambridge University Press, 1978). Die Kräfte, die diese Teilchenbewegungen bewirken, entstehen aus der Wechselwirkung der Oberflächenpolarisationsladungen mit dem zwischen den Elektroden erzeugten Feld. Entsprechend der Polarität unterscheidet man anziehende (positive Dielektrophorese) und abstoßende (negative Dielektrophorese) Kräfte (POHL, ebenda). In der Regel werden 2 oder mehr Elektroden mit einem Generatorausgang verbunden, so daß zumindest auch 2 Zuleitungen und bei Multielektrodenanordnungen elektrische Zwischenverknüpfungen erforderlich sind. Die elektrisch induzierten Kräfte sind um so wirksamer, je stärkere Inhomogenitäten der elektrischen Felder in den Mikropartikelsuspensionen erzeugt werden können. Das kann besonders gut erreicht werden, wenn ultraminiaturisierte Elektroden, insbesondere solche, die mit den Methoden der Halbleiterstrukturierungstechnologien hergestellt werden, benutzt werden (SCHNELLE, TH. et al., Biochim. Biophys. Acta 1157 (1993) 127–140, FUHR, G. et al., Sensors & Actuators A, 41–42 (1994) 230–239). Für viele Aufgaben, z.B. Implantation oder in schwierigen Umgebungslösungen (Sensoren der Umwelttechnik) werden die Vorteile der Miniaturisierung durch die kaum zu miniaturisierenden elektrischen Zuleitungskabel wieder aufgehoben.the State of the art arrangements correspond to the high-frequency electrical Use signals on at least 2 electrodes to make microparticles and Cells in liquid Collecting, separating or assembling media (POHL, dielectrophoresis; Cambridge University Press, 1978). The forces that These particle movements cause, arise from the interaction of Surface polarization charges with the field generated between the electrodes. According to the polarity A distinction is made between attractive (positive dielectrophoresis) and repulsive (negative Dielectrophoresis) forces (POHL, ibid.). In general, 2 or more electrodes with a Generator output connected, so that at least 2 leads and in multi-electrode arrays, electrical interconnections required are. The electrically induced forces are all the more effective, the stronger the inhomogeneities of the electric fields are generated in the microparticle suspensions can. This can be achieved especially well when ultraminiaturized Electrodes, in particular those using the methods of semiconductor patterning technologies (SCHNELLE, TH. et al., Biochim. Biophys. Acta 1157 (1993) 127-140, Fuhr, G. et al., Sensors & Actuators A, 41-42 (1994) 230-239). For many Tasks, e.g. Implantation or in difficult environmental solutions (sensors Environmental Technology) will realize the benefits of miniaturization the hardly be miniaturized electrical supply cable repealed.
Einen Ausweg bieten Sender- und Empfängersysteme, wie sie von KÜPPERS & ZIMMERMANN, FEBS 1009, 323–329 (1983) bzw. KÜPPERS, DIETRICH und ZIMMERMANN, Z. Naturforsch. 39c, 973–980 (1984) beschrieben wurden. Hier wird der Generator an eine Antenne ausgekoppelt und die eigentliche Elektrodenanordnung wird an eine Empfangsantenne angeschlossen. Die Autoren haben mit dieser Anordnung versucht zu beweisen, daß Zellen im Urozean durch in Erzblöcken aufgenommene elektrische Wellen nach Blitzeinschlag fusionieren können. Der Nachteil der Elektrodenverknüpfung und des mehrpoligen Anschlusses der Mikroelektrodenanordnung an die Empfangsantenne bleibt auch bei dieser Anordnung erhalten. Hinzu kommt, daß eine Anpassung der Antennen an die Frequenzen der elektromagnetischen Wellen zusätzlichen Aufwand und feste Elektrodengeometrien erfordern. Frequenzen im kHz- und niederen MHz-Bereich lassen sich aufgrund ihrer Wellenlänge (einige 100 m bis zu einigen 10 m) nur sehr uneffektiv übertragen.a Way out offer transmitter and receiver systems, as described by KÜPPERS & ZIMMERMANN, FEBS 1009, 323-329 (1983) or KÜPPERS, DIETRICH and ZIMMERMANN, Z. Naturforsch. 39c, 973-980 (1984) have been described. Here the generator is decoupled to an antenna and the actual electrode assembly is connected to a receiving antenna connected. The authors have tried with this arrangement too prove that cells in the Urozean through in Erzblöcken fuse absorbed electric waves after lightning strike can. The disadvantage of the electrode connection and the multi-pole terminal of the microelectrode assembly the receiving antenna is retained even with this arrangement. Come in addition, that one Adaptation of the antennas to the frequencies of the electromagnetic Waves extra Require effort and solid electrode geometries. Frequencies in the kHz and low MHz range can be due to their wavelength (some 100 m up to some 10 m) transmitted very inefficient.
Durch die immer kleiner werdenden Chips, die zunehmend für Zellmanipulationszwecke, aber auch zum Freihalten von kleinen Oberflächen von Sensoren eingesetzt werden, besteht ein wachsender Bedarf, die Frage der elektrischen Zuführungskabel zu vereinfachen.By the ever shrinking chips, increasingly used for cell manipulation purposes, but also used for keeping small surfaces of sensors There is a growing need, the question of electric feeder cable to simplify.
Die
Aufgabe der vorliegenden Erfindung ist es, ein Verfahren und eine Vorrichtung zu entwickeln, die starke Kräfte in Ultramikroelektrodenanordnungen erzeugen, dies allerdings mit nur einer elektrischen Zuführung und ohne Sender-Empfänger-Anpassung. Die Anordnung soll geeignet sein, die üblicherweise verwendeten Multielektrodenanordnungen zu betreiben und auf diesem Weg über dielektrophoretische Kräfte Mikropartikel zu separieren, zu bewegen oder zu task It is the object of the present invention to provide a method and an apparatus to develop the strong forces in ultramicroelectrode arrays, but with only one electrical feeder and without transmitter-receiver adaptation. The order should be suitable, the commonly used To operate multi-electrode arrangements and in this way via dielectrophoretic forces microparticles to separate, to move or to
Aggregaten zu formieren. Diese Aufgabe wird durch ein Verfahren und eine Vorrichtung gemäß der unabhängigen Ansprüche gelöst. Dabei wird die Ultramikroelektrodenanordnung als Spitze einer Sendeantenne benutzt, so daß das System ohne kabelförmigen Erdanschluß mit Frequenzen im kHz- und MHz-Bereich betrieben werden kann.aggregates to form. This object is achieved by a method and a device solved according to the independent claims. there the ultramicroelectrode arrangement becomes the tip of a transmitting antenna used, so that the System without cable-shaped Ground connection with Frequencies in the kHz and MHz range can be operated.
Die Vorrichtung und das Verfahren umfassen die Bewegung mikroskopischer Teilchen, ihre Separation, Formung zu Aggregaten, Freihaltung von elektrodennahen Bereichen und das Trapping von Mikropartikeln. Unter Mikropartikeln werden auch Moleküle, Zellen und Viren verstanden.The The device and method include microscopic movement Particles, their separation, forming into aggregates, freeing of electrodes close to the electrode Areas and the trapping of microparticles. Under microparticles also become molecules, Understood cells and viruses.
Vorteilhafte Ausführungsformen ergeben sich aus dem Anschluß nur einer Elektrode aus einem Multielektrodenarray oder dem Zusammenschluß mehrerer Elektroden an nur eine Zuleitung. Die extreme Miniaturisierung der Elektroden (Mikrometer- oder sogar Submikrometerabmessungen in mindestens 2 Dimensionen) führt zu einer starken Bündelung der Feldlinien an den Elektrodenenden, die die Antennenspitze bilden. Neu ist, daß kein Erdanschluß oder eine Rückführung zur Antenne oder dem Generator notwendig ist. Da die anderen, nicht angeschlossenen Elektroden je nach Anordnung eine virtuelle Masse bilden, die auf einem vom Generator unterschiedlichen Potential liegen kann, lassen sich stark inhomogene Felder in analoger Weise nutzen, wie in den konventionellen Systemen. Es ist offensichtlich, daß auch kein Sender-Empfänger-Prinzip angewendet wird, da in diesem Sinne gar kein Empfänger existiert. Demzufolge ist auch eine Anpassung der Antenne in weiten Bereichen unkritisch. Die Zuführung zur Ultramikroelektrodenanordnung muß deshalb auch nicht einer konventionellen Elektrode entsprechen, sondern kann eine normale, auch isolierte Kabelzuführung sein.Advantageous embodiments result from the connection of only one electrode from a multi-electrode array or the combination of multiple electrodes to only one supply line. The extreme miniaturization of the electrodes (micrometer or even submicrometer dimensions in at least 2 dimensions) leads to a strong bundling of the field lines at the electrode ends, which form the antenna tip. What is new is that no ground connection or a return to the antenna or the generator is necessary. Since the other unconnected electrodes, depending on the arrangement, form a virtual mass which can be at a potential different from the generator, it is possible to use strongly inhomogeneous fields in an analogous manner, as in conventional systems. It is of Obvious that no transmitter-receiver principle is applied, since in this sense no receiver exists. Consequently, an adaptation of the antenna is not critical in many areas. The supply to the Ultramikroelektrodenanordnung must therefore not correspond to a conventional electrode, but may be a normal, even insulated cable feed.
Beschreibung der Figuren:Description of the figures:
In
Claims (15)
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE19500660A DE19500660B4 (en) | 1994-12-10 | 1995-01-12 | Device and method for manipulating microscopic particles and their use |
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE9420739 | 1994-12-10 | ||
DEG9420739.9 | 1994-12-10 | ||
DE19500660A DE19500660B4 (en) | 1994-12-10 | 1995-01-12 | Device and method for manipulating microscopic particles and their use |
Publications (2)
Publication Number | Publication Date |
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DE19500660A1 DE19500660A1 (en) | 1996-06-13 |
DE19500660B4 true DE19500660B4 (en) | 2007-12-27 |
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DE19500660A Expired - Fee Related DE19500660B4 (en) | 1994-12-10 | 1995-01-12 | Device and method for manipulating microscopic particles and their use |
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DE (1) | DE19500660B4 (en) |
Cited By (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US8992754B2 (en) | 2005-10-26 | 2015-03-31 | Silicon Biosystems S.P.A. | Method and apparatus for the characterizing and counting particles, in particular, biological particles |
US9719960B2 (en) | 2005-07-19 | 2017-08-01 | Menarini Silicon Biosystems S.P.A. | Method and apparatus for the manipulation and/or the detection of particles |
US10234447B2 (en) | 2008-11-04 | 2019-03-19 | Menarini Silicon Biosystems S.P.A. | Method for identification, selection and analysis of tumour cells |
US10376878B2 (en) | 2011-12-28 | 2019-08-13 | Menarini Silicon Biosystems S.P.A. | Devices, apparatus, kit and method for treating a biological sample |
US10648897B2 (en) | 2007-10-29 | 2020-05-12 | Menarini Silicon Biosystems S.P.A. | Method and apparatus for the identification and handling of particles |
US10895575B2 (en) | 2008-11-04 | 2021-01-19 | Menarini Silicon Biosystems S.P.A. | Method for identification, selection and analysis of tumour cells |
Families Citing this family (15)
Publication number | Priority date | Publication date | Assignee | Title |
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DE19653659C1 (en) * | 1996-12-20 | 1998-05-20 | Guenter Prof Dr Fuhr | Electrode arrangement for field cages |
DE19653661C1 (en) * | 1996-12-20 | 1998-05-20 | Guenter Prof Dr Fuhr | Method and device for microparticle positioning in field cages |
CA2283641A1 (en) * | 1997-03-18 | 1998-09-24 | Introgene B.V. | Methods and compositions for genetically modifying primate bone marrow cells |
US7070684B1 (en) | 1998-06-26 | 2006-07-04 | Evotec Technologies Gmbh | Electrode arrangement for generating functional field barriers in microsystems |
DE10059152C2 (en) * | 2000-11-29 | 2003-03-27 | Evotec Ag | Microsystem for the dielectric and optical manipulation of particles |
DE10116211A1 (en) * | 2001-03-27 | 2002-10-10 | Eppendorf Ag | Chamber for the treatment of cells contained in a suspension in an electrical field |
ITBO20040420A1 (en) | 2004-07-07 | 2004-10-07 | Type S R L | METAL CUTTING AND FORMING MACHINE |
ITBO20050643A1 (en) * | 2005-10-24 | 2007-04-25 | Si Bio S R L | METHOD AND APPARATUS FOR HANDLING PARTICLES IN CONDUCTIVE SOLUTIONS |
JP2009516198A (en) * | 2005-11-18 | 2009-04-16 | プレジデント・アンド・フエローズ・オブ・ハーバード・カレツジ | Dielectrophoretic tweezers apparatus and method |
ITTO20060226A1 (en) | 2006-03-27 | 2007-09-28 | Silicon Biosystem S P A | METHOD AND APPARATUS FOR PROCESSING AND OR ANALYSIS AND OR SELECTION OF PARTICLES, IN PARTICULAR BIOLOGICAL PARTICLES |
US8021532B2 (en) | 2008-02-26 | 2011-09-20 | President And Fellows Of Harvard College | Dielectrophoretic tweezers apparatus and methods |
CA2782123C (en) | 2009-03-17 | 2017-05-02 | Silicon Biosystems S.P.A. | Microfluidic device for isolation of cells |
IT1403518B1 (en) | 2010-12-22 | 2013-10-31 | Silicon Biosystems Spa | MICROFLUID DEVICE FOR PARTICLE HANDLING |
ITTO20110990A1 (en) | 2011-10-28 | 2013-04-29 | Silicon Biosystems Spa | METHOD AND APPARATUS FOR OPTICAL ANALYSIS OF LOW TEMPERATURE PARTICLES |
GB2591406B (en) | 2018-09-05 | 2023-03-01 | Ihsan Dogramaci Bilkent Univ | Enrichment of samples inside the microchannels by using magnetic particles |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE4434883A1 (en) * | 1994-02-24 | 1995-08-31 | Stefan Fiedler | Forming microparticles in electrical field cages |
-
1995
- 1995-01-12 DE DE19500660A patent/DE19500660B4/en not_active Expired - Fee Related
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE4434883A1 (en) * | 1994-02-24 | 1995-08-31 | Stefan Fiedler | Forming microparticles in electrical field cages |
Cited By (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US9719960B2 (en) | 2005-07-19 | 2017-08-01 | Menarini Silicon Biosystems S.P.A. | Method and apparatus for the manipulation and/or the detection of particles |
US8992754B2 (en) | 2005-10-26 | 2015-03-31 | Silicon Biosystems S.P.A. | Method and apparatus for the characterizing and counting particles, in particular, biological particles |
US10648897B2 (en) | 2007-10-29 | 2020-05-12 | Menarini Silicon Biosystems S.P.A. | Method and apparatus for the identification and handling of particles |
US10234447B2 (en) | 2008-11-04 | 2019-03-19 | Menarini Silicon Biosystems S.P.A. | Method for identification, selection and analysis of tumour cells |
US10895575B2 (en) | 2008-11-04 | 2021-01-19 | Menarini Silicon Biosystems S.P.A. | Method for identification, selection and analysis of tumour cells |
US10376878B2 (en) | 2011-12-28 | 2019-08-13 | Menarini Silicon Biosystems S.P.A. | Devices, apparatus, kit and method for treating a biological sample |
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Publication number | Publication date |
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DE19500660A1 (en) | 1996-06-13 |
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