DE102013012145A1 - Protein transistor based on anti-silicon antibody - Google Patents
Protein transistor based on anti-silicon antibody Download PDFInfo
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- DE102013012145A1 DE102013012145A1 DE102013012145.0A DE102013012145A DE102013012145A1 DE 102013012145 A1 DE102013012145 A1 DE 102013012145A1 DE 102013012145 A DE102013012145 A DE 102013012145A DE 102013012145 A1 DE102013012145 A1 DE 102013012145A1
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- 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
- G01N27/403—Cells and electrode assemblies
- G01N27/414—Ion-sensitive or chemical field-effect transistors, i.e. ISFETS or CHEMFETS
- G01N27/4146—Ion-sensitive or chemical field-effect transistors, i.e. ISFETS or CHEMFETS involving nanosized elements, e.g. nanotubes, nanowires
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
- C12Q1/6869—Methods for sequencing
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- 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
- G01N27/403—Cells and electrode assemblies
- G01N27/414—Ion-sensitive or chemical field-effect transistors, i.e. ISFETS or CHEMFETS
- G01N27/4145—Ion-sensitive or chemical field-effect transistors, i.e. ISFETS or CHEMFETS specially adapted for biomolecules, e.g. gate electrode with immobilised receptors
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- H—ELECTRICITY
- H10—SEMICONDUCTOR DEVICES; ELECTRIC SOLID-STATE DEVICES NOT OTHERWISE PROVIDED FOR
- H10K—ORGANIC ELECTRIC SOLID-STATE DEVICES
- H10K10/00—Organic devices specially adapted for rectifying, amplifying, oscillating or switching; Organic capacitors or resistors having a potential-jump barrier or a surface barrier
- H10K10/40—Organic transistors
- H10K10/46—Field-effect transistors, e.g. organic thin-film transistors [OTFT]
- H10K10/462—Insulated gate field-effect transistors [IGFETs]
- H10K10/484—Insulated gate field-effect transistors [IGFETs] characterised by the channel regions
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- H—ELECTRICITY
- H10—SEMICONDUCTOR DEVICES; ELECTRIC SOLID-STATE DEVICES NOT OTHERWISE PROVIDED FOR
- H10K—ORGANIC ELECTRIC SOLID-STATE DEVICES
- H10K85/00—Organic materials used in the body or electrodes of devices covered by this subclass
- H10K85/761—Biomolecules or bio-macromolecules, e.g. proteins, chlorophyl, lipids or enzymes
Abstract
Für die Kombination integrierter Schaltkreise auf Wafern mit biologischen Molekülen (BioChips) ist die Kopplung der biologischen Moleküle an die Siliziumstrukturen der integrierten Schaltkreise von entscheidender Bedeutung. Grundlage der vorliegenden Erfindung ist ein Silizium basierter Wafer an den Antikörper binden, die gegen Silizium Nanopartikel gerichtet sind. Entsprechende Silizium Nanopartikel sind als Elektrodenmaterial an Source und Drain Elektrode von Feld-Effekt Transistoren auf dem Silizium Wafer aufgebracht und bilden zusammen mit dem biologischen Molekül (Antikörper) einen Protein Transistor.For the combination of integrated circuits on wafers with biological molecules (BioChips), the coupling of the biological molecules to the silicon structures of the integrated circuits is of crucial importance. Basis of the present invention is a silicon-based wafer bind to the antibodies that are directed against silicon nanoparticles. Corresponding silicon nanoparticles are applied as electrode material to source and drain electrodes of field effect transistors on the silicon wafer and together with the biological molecule (antibody) form a protein transistor.
Description
Die Kopplung von biologischem Molekül und integriertem Schaltkreis auf Siliziumbasis ist entscheidend für die Konstruktion von Bio-Chips. Mit diesen Bio-Chips können die Konzentrationen von Substanzen in biologischen Materialien (z. B. Vollblut oder Serum) bestimmt werden. Außerdem eignen sich solche Bio-Chips zur Bestimmung der DNA-Sequenz (zur DNA-Sequenzierung). Dies gelingt, indem die Leitfähigkeit der biologischen Moleküle mittels der Schaltungen des integrierten Schaltkreises gemessen wird. Zu diesem Zweck ist der Kontakt zwischen Schaltkreis auf Silizium Basis und biologischem Molekül von entscheidender Bedeutung.The coupling of biological molecule and silicon-based integrated circuit is critical to the design of bio-chips. With these bio-chips, the concentrations of substances in biological materials (eg whole blood or serum) can be determined. In addition, such bio-chips are suitable for determining the DNA sequence (for DNA sequencing). This is achieved by measuring the conductivity of the biological molecules by means of the circuits of the integrated circuit. For this purpose, the contact between silicon-based circuit and biological molecule is of crucial importance.
Hier wird folgende Lösung des Problems des Kontakts zwischen Silizium auf der einen Seite und biologischem Molekül auf der anderen Seite beschrieben: Durch den Einsatz von Anti-Silizium Antikörpern kann eine feste und stabile Verbindung von biologischem Molekül und elektonischem Schaltkreis erreicht werden. Die Antikörper können dabei durch Immunisierung eines Tieres mittels Silizium Nanopartikel erzeugt werden. Eine weitere Möglichkeit zur Erzeugnung der Antikörper liegt in der Produktion monoklonaler Antikörper mittels Hybridomazellen. Durch Kopplung eines Anti-Silizium Antikörpers an einen weiteren Antikörper kann dieser bivalente Antikörper Komplex dann verwendet werden um Konzentrationen von Analyten direkt elektronisch zu bestimmen. Durch Kopplung eines Anti-Silizium-Antikörers an eine DNA-Polymerase kann der Komplex aus Anti-Silizium Antikörper und DNA-Polymerase verwendet werden um die Sequenz von DNA zu bestimmen. Zu diesem Zeck werden die Antikörper-Antikörper Konjugate bzw. die Polymerase Antikörper Konjugate in einem Mikrochip mit Silizium-Nanopartikeln oder Silizium Nanopartikel ähnlichen Strukturen als Kopplungsstellen für die Einbindung des biologischen Komplexes in die Transistoren auf einem Mikrochip eingesetzt. Das neue an der hier vorgestellten Erfindung liegt in der Art des Kontakts zwischen biologischem Molekül (Antikörper) und Elektrode des Transistors. Dabei kommen entsprechend vorliegender Erfindung dotierte Silizium Nanopartikel oder diesen ähnliche Siliziumstrukturen auf der einen Seite und Anti-Silizium Antikörper auf der anderen Seite zur Anwendung. Dies hat den Vorteil der einfachen technischen Realisierbarkeit. Außerdem kann der resultierende Chip in wässriger Umgebung eingesetzt werden. Dies ist von einiger Bedeutung beim geplanten Einsatz zum Messen biologischer Stoffmengen-Konzentrationen. Damit es nicht zu unerwünschten Kurzschlüssen kommt, aber auch damit es nicht zu ungewünschten und unspezifischen Bindungen der Antikörper an die Silizium Oberfläche des Chips kommt, wird der Chip an allen nicht bindenenden Oberflächen mit einer Schicht Siliziumdioxid überzogen. Der Siliziumdioxid Überzug erfüllt dabei zwei Funktionen auf einmal: Zum Einen verhindert er unspezifische Bindungen der Anti-Silizium Antikörper und zum Anderen ermöglicht der Überzug das Eintauchen oder Benetzen des Chips mit wässriger Lösung, was wesentliche Vorraussetzung ist für ein effektives Messen einer biologischen Stoffmengenkonzentration oder für ein effektives Sequenzieren der DNA. Damit ein leitfähiger Kontakt zwischen biologischem Molekül einerseits und Silizium-Chip andererseits zustande kommt, muss das Silizium des Elektroden Materials dotiert sein. Auf diese Weise wird sichergestellt, daß eine leitfähige Verbindung zwischen Schaltkreis und biologischem Molekül besteht.Here, the following solution to the problem of contact between silicon on the one hand and biological molecule on the other hand is described: By using anti-silicon antibodies, a firm and stable connection of biological molecule and electronic circuit can be achieved. The antibodies can be generated by immunizing an animal using silicon nanoparticles. Another possibility for generating the antibodies is the production of monoclonal antibodies by means of hybridoma cells. By coupling an anti-silicon antibody to another antibody, this bivalent antibody complex can then be used to directly determine concentrations of analytes electronically. By coupling an anti-silicon antibody to a DNA polymerase, the complex of anti-silicon antibody and DNA polymerase can be used to determine the sequence of DNA. For this purpose, the antibody-antibody conjugates or the polymerase antibody conjugates are used in a microchip with silicon nanoparticles or silicon nanoparticle-like structures as coupling sites for the integration of the biological complex into the transistors on a microchip. The new feature of the present invention is the nature of the contact between the biological molecule (antibody) and the electrode of the transistor. In this case, according to the present invention, doped silicon nanoparticles or similar silicon structures on one side and anti-silicon antibodies on the other side are used. This has the advantage of simple technical feasibility. In addition, the resulting chip can be used in an aqueous environment. This is of some importance in the planned use for measuring biological substance concentrations. So that it does not come to unwanted short circuits, but also so that it does not come to unwanted and unspecific binding of the antibodies to the silicon surface of the chip, the chip is coated on all non-bonding surfaces with a layer of silicon dioxide. The silicon dioxide coating fulfills two functions at once: On the one hand, it prevents non-specific binding of the anti-silicon antibodies and on the other hand, the coating allows the immersion or wetting of the chip with aqueous solution, which is essential for the effective measurement of a biological molar concentration or an effective sequencing of the DNA. For a conductive contact between biological molecule on the one hand and silicon chip on the other hand, the silicon of the electrode material must be doped. This ensures that there is a conductive connection between the circuit and the biological molecule.
Beschreibung der Zeichnungen/schematischen AbbildungenDescription of the drawings / schematic illustrations
- 1) Die Abbildung zeigt schematisch einen Anti-Silizium Antikörper, der an die Elektroden eines integrierten Schaltkreises gebunden hat.1) The figure shows schematically an anti-silicon antibody bound to the electrodes of an integrated circuit.
- 2) Die Abbildung zeigt schematisch einen Anti-Silizium Antikörper, der an die Elektroden eines integrierten Schaltkreises gebunden hat. An diesen Antikörper ist wieder ein zweiter Antikörper kovalent gebunden, der aufgrund seiner Spezifität die Analyt Moleküle detektieren kann.2) The figure shows schematically an anti-silicon antibody bound to the electrodes of an integrated circuit. Again, a second antibody is covalently bound to this antibody, which due to its specificity can detect the analyte molecules.
- 3) Die Abbildung zeigt schematisch einen Anti-Silizium Antikörper, der an die Elektroden eines integrierten Schaltkreises gebunden hat. An diesen Antikörper wiederum ist DNA-Polymerase kovalent gebunden. Auf diese Weise wird es möglich die Aktivität der DNA-Polymerase zu verfolgen.3) The figure shows schematically an anti-silicon antibody bound to the electrodes of an integrated circuit. In turn, DNA polymerase is covalently bound to this antibody. In this way it becomes possible to follow the activity of the DNA polymerase.
Claims (10)
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DE102013012145.0A DE102013012145A1 (en) | 2013-07-20 | 2013-07-20 | Protein transistor based on anti-silicon antibody |
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Cited By (12)
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WO2018200687A1 (en) | 2017-04-25 | 2018-11-01 | Roswell Biotechnologies, Inc. | Enzymatic circuits for molecular sensors |
JP2019503485A (en) * | 2016-01-14 | 2019-02-07 | ロズウェル バイオテクノロジーズ,インコーポレイテッド | Molecular sensors and related methods |
US10508296B2 (en) | 2017-04-25 | 2019-12-17 | Roswell Biotechnologies, Inc. | Enzymatic circuits for molecular sensors |
US10526696B2 (en) | 2016-07-26 | 2020-01-07 | Roswell Biotechnologies, Inc. | Multi-electrode molecular sensing devices and methods of making the same |
US10597767B2 (en) | 2016-02-22 | 2020-03-24 | Roswell Biotechnologies, Inc. | Nanoparticle fabrication |
US10648941B2 (en) | 2017-05-09 | 2020-05-12 | Roswell Biotechnologies, Inc. | Binding probe circuits for molecular sensors |
US10712334B2 (en) | 2016-01-28 | 2020-07-14 | Roswell Biotechnologies, Inc. | Massively parallel DNA sequencing apparatus |
US10737263B2 (en) | 2016-02-09 | 2020-08-11 | Roswell Biotechnologies, Inc. | Electronic label-free DNA and genome sequencing |
US10902939B2 (en) | 2017-01-10 | 2021-01-26 | Roswell Biotechnologies, Inc. | Methods and systems for DNA data storage |
US11100404B2 (en) | 2017-10-10 | 2021-08-24 | Roswell Biotechnologies, Inc. | Methods, apparatus and systems for amplification-free DNA data storage |
US11624725B2 (en) | 2016-01-28 | 2023-04-11 | Roswell Blotechnologies, Inc. | Methods and apparatus for measuring analytes using polymerase in large scale molecular electronics sensor arrays |
US11656197B2 (en) | 2017-01-19 | 2023-05-23 | Roswell ME Inc. | Solid state sequencing devices comprising two dimensional layer materials |
-
2013
- 2013-07-20 DE DE102013012145.0A patent/DE102013012145A1/en active Pending
Cited By (21)
Publication number | Priority date | Publication date | Assignee | Title |
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JP2019503485A (en) * | 2016-01-14 | 2019-02-07 | ロズウェル バイオテクノロジーズ,インコーポレイテッド | Molecular sensors and related methods |
EP3403079A4 (en) * | 2016-01-14 | 2019-09-04 | Roswell Biotechnologies, Inc | Molecular sensors and related methods |
JP7109785B2 (en) | 2016-01-14 | 2022-08-01 | ロズウェル バイオテクノロジーズ,インコーポレイテッド | Molecular sensors and related methods |
US10712334B2 (en) | 2016-01-28 | 2020-07-14 | Roswell Biotechnologies, Inc. | Massively parallel DNA sequencing apparatus |
US11448639B2 (en) | 2016-01-28 | 2022-09-20 | Roswell Biotechnologies, Inc. | Massively parallel DNA sequencing apparatus |
US11624725B2 (en) | 2016-01-28 | 2023-04-11 | Roswell Blotechnologies, Inc. | Methods and apparatus for measuring analytes using polymerase in large scale molecular electronics sensor arrays |
US11440003B2 (en) | 2016-02-09 | 2022-09-13 | Roswell Biotechnologies, Inc. | Electronic label-free DNA and genome sequencing |
US10737263B2 (en) | 2016-02-09 | 2020-08-11 | Roswell Biotechnologies, Inc. | Electronic label-free DNA and genome sequencing |
US10597767B2 (en) | 2016-02-22 | 2020-03-24 | Roswell Biotechnologies, Inc. | Nanoparticle fabrication |
US10584410B2 (en) | 2016-07-26 | 2020-03-10 | Roswell Biotechnologies, Inc. | Multi-electrode molecular sensing devices and methods of making the same |
US10526696B2 (en) | 2016-07-26 | 2020-01-07 | Roswell Biotechnologies, Inc. | Multi-electrode molecular sensing devices and methods of making the same |
US10902939B2 (en) | 2017-01-10 | 2021-01-26 | Roswell Biotechnologies, Inc. | Methods and systems for DNA data storage |
US11656197B2 (en) | 2017-01-19 | 2023-05-23 | Roswell ME Inc. | Solid state sequencing devices comprising two dimensional layer materials |
EP3615685A4 (en) * | 2017-04-25 | 2021-01-20 | Roswell Biotechnologies, Inc | Enzymatic circuits for molecular sensors |
US11268123B2 (en) | 2017-04-25 | 2022-03-08 | Roswell Biotechnologies, Inc. | Enzymatic circuits for molecular sensors |
US10913966B2 (en) | 2017-04-25 | 2021-02-09 | Roswell Biotechnologies, Inc. | Enzymatic circuits for molecular sensors |
WO2018200687A1 (en) | 2017-04-25 | 2018-11-01 | Roswell Biotechnologies, Inc. | Enzymatic circuits for molecular sensors |
US10508296B2 (en) | 2017-04-25 | 2019-12-17 | Roswell Biotechnologies, Inc. | Enzymatic circuits for molecular sensors |
US11143617B2 (en) | 2017-05-09 | 2021-10-12 | Roswell Biotechnologies, Inc. | Binding probe circuits for molecular sensors |
US10648941B2 (en) | 2017-05-09 | 2020-05-12 | Roswell Biotechnologies, Inc. | Binding probe circuits for molecular sensors |
US11100404B2 (en) | 2017-10-10 | 2021-08-24 | Roswell Biotechnologies, Inc. | Methods, apparatus and systems for amplification-free DNA data storage |
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