WO2017206414A1 - Capteur biochimique selon la technologie cmos standard - Google Patents

Capteur biochimique selon la technologie cmos standard Download PDF

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Publication number
WO2017206414A1
WO2017206414A1 PCT/CN2016/102070 CN2016102070W WO2017206414A1 WO 2017206414 A1 WO2017206414 A1 WO 2017206414A1 CN 2016102070 W CN2016102070 W CN 2016102070W WO 2017206414 A1 WO2017206414 A1 WO 2017206414A1
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Prior art keywords
layer
electrode
biochemical sensor
polysilicon
sensor according
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PCT/CN2016/102070
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English (en)
Chinese (zh)
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薛李荣
孙伟
朱春蓉
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张家港万众一芯生物科技有限公司
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Publication of WO2017206414A1 publication Critical patent/WO2017206414A1/fr

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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
    • 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

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  • the invention belongs to the field of biosensors, and in particular relates to a nanoscale biochemical sensor realized by a CMOS standard process.
  • Biosensors are developed in response to the needs of life sciences and information sciences. They are biomaterial-sensitive devices that combine bioactive materials with physicochemical transducers. Compared with traditional chemical sensors and off-line analysis (mass spectrometry and HPLC), it has the characteristics of simple production, time saving, high selectivity, fast analysis speed, simple operation and low cost, and it is also conducive to computer data collection and processing. It is an advanced detection and monitoring method that is essential for the development of biotechnology, and it is also a rapid and microscopic analysis method for the molecular level of substances. It has broad application prospects in health care and clinical diagnosis, industrial control, food testing and drug analysis (including biopharmaceutical research and development), environmental protection, biotechnology, biochip and other research in the national economy.
  • the physical method of realizing the nanowire sensor uses light and electricity technology to evaporate the material in a vacuum or an inert gas, so that atoms or molecules combine to form nanowires, such as thermal evaporation, laser ablation, and the like.
  • Chemical methods generally use a "top-down” or “bottom-up” approach to prepare nanomaterials from molecules and atoms through appropriate chemical reactions, including chemical deposition (CVD), templating, and oxide assist. Law and so on.
  • CVD chemical deposition
  • templating templating
  • oxide assist oxide assist. Law and so on.
  • the above methods are also difficult to prepare for complex microelectrodes that require complex assembly, such as a functional network for fabricating nanowires. Due to the lack of reliability and repeatability of the devices, these technical solutions are difficult to industrialize.
  • a polysilicon gate layer is used as the gate of a CMOS transistor, and a thin layer of dielectric material (such as silicon dioxide) is used to channel the underlying silicon substrate.
  • a bias voltage is provided.
  • the source and drain are of the opposite impurity type to the channel, and the p-n structure is formed to achieve effective current blocking at the gate turn-off.
  • the polysilicon gate layer is generally high-doped, and a silicide is used as a conductor to lower the gate resistance, so that the polysilicon layer no longer has semiconductor characteristics.
  • the present invention proposes a biochemical sensor implemented in a CMOS standard process. Achieve high reliability of biochemical sensors and significantly reduce errors.
  • a biochemical sensor in a CMOS standard process that implements a nanoscale sensor using a layout design rule of a CMOS standard process.
  • the utility model comprises a base, an ion-sensitive field effect transistor, a metal layer, a contact layer and an electrode; the transistor is arranged on the base, comprises a polysilicon channel formed on the polysilicon layer, the top layer of the silicide is removed in the region of the polysilicon channel; The terminals are respectively connected to the source and the drain, and the source and the drain are connected to the metal layer through the contact layer; the polysilicon channel region is exposed to connect the electrolyte solution, and the electrode in contact with the solution provides a gate voltage for the polysilicon channel.
  • the base includes an upper layer and a lower layer, the upper layer is silicon dioxide, the lower layer is a silicon wafer, and the transistor is disposed on the upper layer of the base.
  • a dielectric material is disposed on the polysilicon channel; the dielectric material may be one or more of silicon dioxide, aluminum oxide, hafnium oxide, titanium dioxide, and antimony oxide, or may be other similar inorganic or organic dielectric materials, such as Self-assembled monolayer (SAMS).
  • SAMS Self-assembled monolayer
  • the polysilicon channel is one or more nanowire structures, which are linear or non-linear, and preferably have a meandering shape or a spiral shape.
  • the polysilicon channel is a nanoscale channel with a width ranging from 10 nanometers to 600 nanometers.
  • a silicide layer is disposed on the upper portion of the source and the drain; and the metal layer is connected to the silicide layer through the contact layer.
  • the electrode may be a metal electrode, a silicide electrode or a peripheral wire electrode prepared by a CMOS standard process on a chip; the metal electrode is an on-chip electrode structure formed by a metal layer of a CMOS process; and the silicide electrode is a silicide formed on a CMOS polysilicon layer.
  • the layer forms an electrode; the peripheral wire electrode is a reference electrode, Ag/AgCl or Pt.
  • the senor of the present invention belongs to an ion-sensitive field effect transistor or a nanowire field effect transistor.
  • the dielectric material is provided with a probe which is a selective biomolecule such as a DNA, an antibody, an enzyme, an aptamer, a peptide or a receptor molecule.
  • a probe which is a selective biomolecule such as a DNA, an antibody, an enzyme, an aptamer, a peptide or a receptor molecule.
  • the senor is implemented using a CMOS standard process.
  • the electrode is a silicide or metal layer structure on a chip using a CMOS process.
  • the electrode is designed to realize an on-chip integrated electrode structure directly on the chip by a polysilicon/silicide layer or a metal layer, and the miniaturization of the chip system can be realized without an external electrode material. At the same time, it can also be a variety of external wire electrical grades.
  • the present invention has the following beneficial effects: Compared to the prior art, the present invention implements junctional and non-junction biochemical sensors in a CMOS standard process.
  • the biochemical sensor of the present invention has high sensitivity.
  • the use of CMOS technology greatly improves sensor repeatability, reduces device errors, and reduces production costs.
  • the micro sensor of the invention is suitable for a wide range of applications such as environmental internet of things, agricultural internet of things, and biological detection.
  • FIG. 1 is a structural diagram of a transistor in a conventional standard CMOS process
  • FIG. 2 is a structural diagram of a junction type nanoscale biochemical sensor in a standard CMOS process according to an embodiment of the present invention.
  • FIG. 3 is a structural diagram of a non-junction nanoscale biochemical sensor in a standard CMOS process according to an embodiment of the present invention.
  • FIG. 4 is a structural diagram of a metal electrode prepared on a nanoscale biochemical sensor chip in a standard CMOS process according to an embodiment of the present invention.
  • FIG. 5 is a structural diagram of a silicide electrode prepared on a nanoscale biochemical sensor chip in a standard CMOS process according to an embodiment of the present invention.
  • Embodiment 1 As shown in FIG. 2, a junction type nano-scale biochemical sensor under a CMOS standard process realizes a junction-type nano-scale ion-sensitive field effect transistor sensor by using a layout design rule of a CMOS standard process.
  • the base includes a base, a transistor, a metal layer, a contact layer, and an electrode; the transistor is disposed on the base, and includes a polysilicon channel formed on the polysilicon layer, and the polysilicon channel is a P-type doping of the low doped polysilicon channel.
  • the source and drain are shunted across the polysilicon channel and are highly doped.
  • the doping type is N+ doped opposite to the channel doping, forming a PN junction.
  • a top layer of silicide is removed in the region of the polysilicon channel; an ohmic connection is formed through the contact layer (Contact layer) and the metal layer at the source and drain, and the first layer of the metal layer is the first metal layer M1.
  • the polysilicon channel is a nanoscale channel of one or more nanowire structures ranging in width from 10 nanometers to 600 nanometers.
  • the channel region is linear or non-linear, and preferably has a meandering shape or a spiral shape.
  • the source and drain at both ends are not leaking, the channel region is exposed to connect the electrolyte solution, and the electrode in contact with the solution provides a gate voltage for the polysilicon channel.
  • a dielectric material is disposed on the polysilicon channel; a biochemical probe is disposed on the dielectric material, and the probe is a selective biomolecule such as DNA, an antibody, an enzyme, an aptamer, or a peptide. Or receptor molecule.
  • the dielectric material may be one or more of silicon dioxide, aluminum oxide, hafnium oxide, titanium dioxide, antimony oxide, or other similar inorganic or organic dielectric materials (such as sams self-assembled monomolecular film).
  • a silicide layer is disposed on the upper end of the polysilicon channel at the source and the drain, and the metal layer is connected to the silicide layer through the contact layer.
  • the electrode may be a metal or silicide electrode fabricated on a chip by a CMOS standard process, or may be a peripheral gold
  • the wire electrode includes a reference electrode, Ag/AgCl, Pt, and the like.
  • the sensor is a junction transistor and is an ion-sensitive field effect transistor or a nanowire field effect transistor.
  • Example 2 As shown in Figure 3, a non-junction nanoscale biochemical sensor in a CMOS standard process. The only difference from Example 1 is that the source and drain doping types are the same as the channel doping, the PN junction is not formed, the channel doping is P, and the source and drain doping is P+. That is, the non-junction nanoscale ion-sensitive field effect transistor sensor is realized by the layout design rule of the CMOS standard process.
  • Embodiment 3 As shown in FIG. 4, the electrodes different from the examples 1 and 2 are designed to realize an on-chip integrated electrode structure by using a metal layer in a CMOS standard process on a chip directly through a CMOS process, without an external electrode material. Miniaturize the chip system. In practical applications, a gate voltage can be applied to the sensor by connecting the electrodes.
  • Embodiment 4 As shown in FIG. 5, the difference from Example 3 is that the electrode adopts a polysilicon/silicide layer to realize an on-chip integrated electrode structure directly by a CMOS process, and the miniaturization of the chip system can be realized without an external electrode material. In practical applications, a gate voltage can be applied to the sensor by connecting the electrodes.
  • the electrode is formed by using a silicide layer formed on the polysilicon layer, and the polysilicon layer is disposed on the base. Techniques not covered by the present invention can be implemented by existing techniques.
  • the nanoscale biochemical sensor described in the above example changes the traditional transistor structure, but is fully compatible with CMOS standard processes, enabling production to be industrially engineered, providing a way to achieve high performance nanoscale Biosensors reduce production costs, improve sensor repeatability, reduce device errors, and improve detection sensitivity. It is suitable for a wide range of applications such as environmental Internet of Things, agricultural Internet of Things, and biometrics.

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  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Physics & Mathematics (AREA)
  • Biochemistry (AREA)
  • Pathology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Electrochemistry (AREA)
  • Immunology (AREA)
  • Analytical Chemistry (AREA)
  • Molecular Biology (AREA)
  • General Health & Medical Sciences (AREA)
  • General Physics & Mathematics (AREA)
  • Engineering & Computer Science (AREA)
  • Microelectronics & Electronic Packaging (AREA)
  • Investigating Or Analyzing Materials By The Use Of Electric Means (AREA)
  • Thin Film Transistor (AREA)

Abstract

La présente invention concerne un capteur biochimique selon une technologie CMOS standard, comportant un socle, un transistor à effet de champ sensible aux ions, une couche métallique, une couche de contact et une électrode. Le transistor à effet de champ sensible aux ions est disposé sur le socle et comporte un canal en polysilicium formé sur une couche de polysilicium de technologie CMOS. Deux extrémités du canal en polysilicium sont respectivement connectées à une source et à un drain, et ensuite la source et le drain sont connectés à la couche métallique au moyen de la couche de contact. Une région de canal en polysilicium du canal en polysilicium est exposée pour être en contact avec une solution électrolytique. L'électrode est en contact avec la solution électrolytique pour fournir une tension de grille au canal en polysilicium. Le capteur présente une sensibilité élevée, améliore la reproductibilité du capteur et réduit des erreurs du dispositif et le coût du produit grâce à une technologie CMOS. Le capteur est largement utilisé dans l'Internet des objets de protection environnementale, l'Internet des objets en agriculture, à la détection biologique, et analogues.
PCT/CN2016/102070 2016-06-01 2016-10-14 Capteur biochimique selon la technologie cmos standard WO2017206414A1 (fr)

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CN2016103789812 2016-06-01
CN201610378981.2A CN107449812B (zh) 2016-06-01 2016-06-01 一种在cmos标准工艺下的生物化学传感器

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Cited By (2)

* Cited by examiner, † Cited by third party
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CN110672699A (zh) * 2019-09-18 2020-01-10 天津师范大学 全固态场效应晶体管及应用其的生物传感器和检测方法
EP4047358A4 (fr) * 2019-10-18 2023-11-29 Kuznetsov, Aleksander Evgenevich Système et procédé de mesure dynamique du potentiel redox au cours d'une réaction chimique

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CN110006960A (zh) * 2018-01-05 2019-07-12 张家港万众一芯生物科技有限公司 基于柔性自适应型叉指电容的危险液体检测装置及检测方法
CN108565262A (zh) * 2018-04-17 2018-09-21 重庆第二师范学院 一种用于生化分析的阵列式传感器集成芯片及其制备方法
CN112567238A (zh) * 2018-06-22 2021-03-26 洛桑联邦理工学院 用于感测流体中的离子、分子或生物标志物的场效应晶体管器件或传感器
CN108535470A (zh) * 2018-06-29 2018-09-14 武汉中科志康生物科技有限公司 一种检测重金属的酶生物传感器及其制备方法与应用
CN108535469A (zh) * 2018-06-29 2018-09-14 武汉中科志康生物科技有限公司 一种瘦肉精检测装置
CN112444540B (zh) * 2019-09-04 2023-05-05 张家港万众一芯生物科技有限公司 一种生物传感器和生物传感器的制备方法
CN110646490A (zh) * 2019-09-30 2020-01-03 深圳大学 一种基于二硒化钨的离子敏场效应晶体管传感器及其制备方法
CN110672700B (zh) * 2019-10-18 2022-06-03 广东省半导体产业技术研究院 一种生物电子芯片及其制作方法
CN114280116B (zh) * 2021-12-22 2023-03-17 北京航空航天大学 具有基于cmos工艺的片上参比电极的传感芯片
TWI834353B (zh) * 2022-02-24 2024-03-01 博奧生物科技股份有限公司 積體感測器結構與其製備方法

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Cited By (2)

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Publication number Priority date Publication date Assignee Title
CN110672699A (zh) * 2019-09-18 2020-01-10 天津师范大学 全固态场效应晶体管及应用其的生物传感器和检测方法
EP4047358A4 (fr) * 2019-10-18 2023-11-29 Kuznetsov, Aleksander Evgenevich Système et procédé de mesure dynamique du potentiel redox au cours d'une réaction chimique

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CN107449812A (zh) 2017-12-08

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