WO2019010774A1 - 一种等离子激元波导、生物传感芯片及系统 - Google Patents

一种等离子激元波导、生物传感芯片及系统 Download PDF

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Publication number
WO2019010774A1
WO2019010774A1 PCT/CN2017/100396 CN2017100396W WO2019010774A1 WO 2019010774 A1 WO2019010774 A1 WO 2019010774A1 CN 2017100396 W CN2017100396 W CN 2017100396W WO 2019010774 A1 WO2019010774 A1 WO 2019010774A1
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Prior art keywords
plasmon
biosensor chip
chip
detection liquid
microfluidic
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PCT/CN2017/100396
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English (en)
French (fr)
Inventor
韩琳
潘奕
丁庆
刘荣跃
李辰
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深圳市太赫兹科技创新研究院
深圳市太赫兹科技创新研究院有限公司
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Priority to US16/629,524 priority Critical patent/US11125684B2/en
Publication of WO2019010774A1 publication Critical patent/WO2019010774A1/zh

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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/543—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
    • G01N33/54366—Apparatus specially adapted for solid-phase testing
    • G01N33/54373—Apparatus specially adapted for solid-phase testing involving physiochemical end-point determination, e.g. wave-guides, FETS, gratings
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/25—Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands
    • G01N21/31—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry
    • G01N21/35—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry using infrared light
    • G01N21/3581—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry using infrared light using far infrared light; using Terahertz radiation
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/25—Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands
    • G01N21/31—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry
    • G01N21/35—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry using infrared light
    • G01N21/3577—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry using infrared light for analysing liquids, e.g. polluted water
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/55—Specular reflectivity
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/55—Specular reflectivity
    • G01N21/552—Attenuated total reflection
    • G01N21/553—Attenuated total reflection and using surface plasmons
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/5302—Apparatus specially adapted for immunological test procedures
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/543—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2201/00—Features of devices classified in G01N21/00
    • G01N2201/04—Batch operation; multisample devices
    • G01N2201/0407—Batch operation; multisample devices with multiple optical units, e.g. one per sample

Definitions

  • Plasma excitation waveguide biosensor chip and system
  • Embodiments of the present invention belong to the field of in-vitro diagnostic technologies, and in particular, to a plasmon waveguide, a bio-sensing chip, and a system.
  • IVD in-Vitro Diagnostics
  • IVD in-Vitro Diagnostics
  • in vitro diagnostic technology has become one of the fastest growing directions in the biomedical industry.
  • In vitro diagnostic technology and product development cycle is short, many types, in addition to clinical application, it can also be extended to food safety testing, animal and plant disease surveillance and other fields, is a hot spot for innovation and entrepreneurship in the field of biomedicine.
  • the assay or Real-time Quantitative PCR Detecting System (QPCR)
  • QPCR Real-time Quantitative PCR Detecting System
  • Embodiments of the present invention provide a plasmon waveguide, a biosensor chip, and a system, which can enhance the terahertz wave signal and improve the detection sensitivity, signal-to-noise ratio, and reliability of the biosensor chip.
  • An embodiment of the present invention provides a plasmon waveguide applied to a biosensor chip, the plasmon waveguide including a substrate and a plasmon structure disposed on an upper surface of the substrate, the plasma
  • the excimer structure includes a plurality of periodically pulsing plasmons, the plasmon is a metal gargle, and the aliquot of the plasmon is used to immobilize the antibody probe.
  • the plasmon structure has a long period of the horizontal direction and a long period of the vertical direction.
  • the plasmon has a ring diameter of 30 ⁇ m to 100 ⁇ m, and the annular mouth has a width of 10 ⁇ to 2 ⁇ m.
  • the metal mouth ring is a circular mouth ring, an oval mouth ring or a polygonal mouth ring.
  • the substrate is a silicon substrate, a glass substrate, or a plastic substrate.
  • the plasmon is prepared by a 3D printing technique or an ultraviolet lithography technique, and the plasmon is attached to an upper surface of the base layer by a metal electrodeposition process to form the plasmon. structure.
  • Another aspect of the embodiments of the present invention further provides a biosensor chip including a detection liquid pretreatment chip and a microfluidic chip bonded on the same substrate, the microfluidic chip including at least one microflow a control channel, wherein the plasmon waveguide is disposed in the microfluidic channel;
  • the detection liquid pretreatment chip includes a detection liquid inlet and a detection liquid outlet equal to the number of the at least one microfluidic channel, and an inlet of each of the microfluidic channels is correspondingly connected to one of the detection liquid outlets;
  • a test liquid sample flows in from the inlet of the detection liquid, and is processed by the detection liquid pretreatment chip to obtain a detection liquid, and the detection liquid flows into the microfluidic channel through the detection liquid outlet and the inlet.
  • the target biomolecule in the detection fluid is captured by an antibody probe on a plasmon waveguide in the microfluidic channel, the at least one microfluidic channel capturing at least one target biomolecule in the detection solution .
  • the antibody probes on the plasmon waveguides in each of the microfluidic channels are identical, and the at least one microfluidic channel captures the same target organism in the detection fluid molecule.
  • the test liquid sample is a blood sample.
  • connection of the inlet and the detection fluid outlet of the corresponding connection is sealed by polydimethylsiloxane.
  • Still another aspect of the embodiments of the present invention provides a biosensing system including the biosensor chip described above.
  • the terahertz source emits a terahertz wave to a biosensor chip that captures the target biomolecule; the terahertz analyzer receives a terahertz wave reflected by the biosensor chip, and the reflection The terahertz wave is subjected to terahertz spectroscopy to detect the biometric characteristics of the target biomolecule captured by the biosensor chip.
  • the target biomolecule flowing into the detection liquid in the microfluidic channel can be captured by the antibody probe, and the emission can be enhanced by the plasmon waveguide.
  • the signal strength of the terahertz wave to the biosensor chip thereby improving the signal strength of the reflected terahertz wave detected by the terahertz analyzer, improving detection sensitivity, signal-to-noise ratio, and reliability.
  • FIG. 1 is a schematic diagram showing the basic structure of a plasmon waveguide provided by an embodiment of the present invention
  • FIG. 2 is a schematic diagram of a basic structure of a plasmon waveguide provided by another embodiment of the present invention.
  • FIG. 3 is a schematic diagram of a basic structure of a biosensor chip according to an embodiment of the present invention.
  • FIG. 4 is a schematic diagram showing the basic structure of a biosensor system according to an embodiment of the present invention.
  • an embodiment of the present invention provides a plasmon waveguide 10 applied to a biosensor chip, comprising a substrate 11 and a plasmon structure 12 disposed on an upper surface of the substrate 11, plasma
  • the excimer structure 12 includes a plurality of plasmon elements 121 arranged periodically, the plasmon is a metal gargle ring, and the annular nip of the plasmon element 121 is used to fix the antibody probe 122.
  • the metal mouth ring is a circular mouth ring, an oval mouth ring or a polygonal mouth ring.
  • FIG. 1 exemplarily shows that the plasmon 121 is a circular mouth ring
  • FIG. 2 exemplarily shows that the plasmon 1 21 is a square mouth ring.
  • the number, size, and arrangement rule of the plasmons included in the plasmon structure may be set according to actual needs.
  • all plasmons on the plasmon structure may be regularly arranged in a rectangular array, a circle. Shape array or arbitrary polygon array, etc.
  • FIGS. 1 and 2 exemplarily show an array of plasmon elements on a plasmon structure 12 in a matrix.
  • the plasmon structure has a periodic length in the horizontal direction and a length in the vertical direction of 50 ⁇ to 200 ⁇ , a ring diameter of the plasmon is 30 ⁇ to 100 ⁇ , and a width of the annular mouth is lOnm to 2 ⁇ .
  • the horizontal direction specifically refers to the arrangement direction of any one row of plasmons
  • the vertical direction refers to the arrangement direction of any column of plasmons perpendicular to the horizontal direction
  • the horizontal period length and the vertical period length may be Equal or unequal
  • the ring diameter refers to the annular outer diameter of the plasmon
  • the ring diameter refers to the outer ring diameter of the circular rim ring
  • the ring diameter refers to the outer ring diameter of the circular rim ring
  • the plasmon is elliptical ⁇
  • the ring diameter ⁇ the ring diameter refers to the outer ring long diameter of the elliptical mouth ring
  • the plasmon is a square mouth ring ⁇
  • the ring diameter refers to the outer ring side length of the square ring ring.
  • the plasmon structure has a periodic length in the horizontal direction and a length in the vertical direction of 50 ⁇ m, and the annular diameter of the plasmon is 36 ⁇ m.
  • the plasmon structure has a horizontal period length of 40 ⁇ m, a vertical period of 60 ⁇ m, and a plasmon ring diameter of 36 ⁇ m.
  • the substrate can be selected according to actual needs to select any type of material, in one implementation
  • the substrate is a silicon substrate, a glass substrate or a plastic substrate.
  • the plasmon can be prepared by a 3D printing technique or an ultraviolet lithography technique, and the plasmon can be attached to the upper surface of the base layer by a metal electrodeposition process to form a plasmonic structure.
  • different types of antibody probes may be immobilized at the annular mouth of the plasmon depending on the type of the target biomolecule to be captured, for example, to capture the tumor cell antigen, the tumor is fixed.
  • Cellular antibody probe may be immobilized at the annular mouth of the plasmon depending on the type of the target biomolecule to be captured, for example, to capture the tumor cell antigen, the tumor is fixed.
  • the target biomolecule flowing into the detection liquid in the microfluidic channel can be captured by the antibody probe, and the emission can be enhanced by the plasmon waveguide.
  • the signal strength of the terahertz wave to the biosensor chip thereby improving the signal strength of the reflected terahertz wave detected by the terahertz analyzer, improving detection sensitivity, signal-to-noise ratio, and reliability.
  • an embodiment of the present invention provides a biosensor chip 100 implemented based on a plasmon waveguide 10, which includes a detection liquid pretreatment chip 20 and micro on a same substrate 101.
  • the flow control chip 30, the microfluidic chip 30 includes at least one microfluidic channel 31, and the plasmon waveguide 10 is disposed in the microfluidic channel 31.
  • the test liquid pretreatment chip 20 includes a detection liquid inlet 21 and a detection liquid outlet 22 equal in number to the at least one microfluidic channel 31, and an inlet 311 of each microfluidic channel 31 is connected to a detection liquid outlet 22.
  • the substrate may specifically be a glass substrate or a silicon substrate.
  • connection of the inlet of the corresponding connection and the outlet of the detection fluid is sealed by polydimethylsiloxane.
  • the test liquid sample flows in from the inlet of the detection liquid, and the detection liquid is obtained after the detection liquid pretreatment chip, and the detection liquid flows into the microfluidic channel through the outlet and the inlet of the detection liquid, and the target biomolecule in the detection liquid is microfluidic channel
  • the antibody probe on the plasmon waveguide is captured, and at least one microfluidic channel captures at least one target biomolecule in the detection solution.
  • test liquid sample may be blood, tissue fluid or secretion, or the like.
  • the test liquid sample is blood.
  • FIG. 3 exemplarily shows that the microfluidic chip 30 includes six microfluidic channels 31, and the plasmon waveguide is not labeled in FIG. 3 for convenience of illustration.
  • one to six kinds of target biomolecules can be captured, which is determined by the type of the antibody probe on the plasmon waveguide in the six microfluidic channels.
  • the antibody probes on the plasmon waveguides in the microfluidic channel are the same, and only one target biomolecule can be captured at the same time; if they are different, the capture of the six target biomolecules can be achieved. If two of them are the same and the other four are different, the capture of the five target biomolecules can be achieved, and so on.
  • the antibody probes on the plasmonic waveguide in each microfluidic channel are identical, and at least one microfluidic channel captures the same target biomolecule in the detection fluid.
  • the detection accuracy of the target biomolecule in the detection liquid can be effectively improved, and the detection result of the biosensor chip can be improved. reliability.
  • the microfluidic chip is formed by bonding at least one microfluidic channel and a glass substrate.
  • the detection liquid sample is pretreated by the detection liquid pretreatment chip, and the cells or particles that do not need to be detected in the detection liquid can be filtered or trapped, thereby obtaining a relatively pure detection liquid containing the target biomolecule, which is convenient.
  • one embodiment of the present invention provides a biosensing system including a biosensor chip 100, further including a terahertz source 200 and a terahertz analyzer 300.
  • the terahertz source emits a terahertz wave to a biosensor chip that captures the target biomolecule; the terahertz analyzer receives the terahertz wave reflected by the biosensor chip, and performs terahertz spectroscopy on the reflected terahertz wave
  • the biological characteristics of the target biomolecule include features such as quantity, size, and cell structure.

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Abstract

一种等离子激元波导(10)、生物传感芯片(100)及系统，其中，等离子激元波导(10)应用于生物传感芯片(100)，包括基底(11)和设置在基底(11)上表面的等离子激元结构(12)，等离子激元结构(12)包括周期性排列的多个等离子激元(121)，等离子激元(121)为金属开口环，等离子激元(121)的环形开口处用于固定抗体探针(122)。在生物传感芯片(100)内设置等离子激元波导(10)，可以通过抗体探针(122)捕获流入微流控通道(31)内的检测液中的目标生物分子，并通过等离子激元波导(10)来增强发射至生物传感芯片(100)的太赫兹波的信号强度，从而提高太赫兹分析仪(300)检测到的反射太赫兹波的信号强度，提高检测灵敏度、信噪比和可靠性。

Description

一种等离子激元波导、 生物传感芯片及系统
技术领域
[0001] 本发明实施例属于体外诊断技术领域， 尤其涉及一种等离子激元波导、 生物传 感芯片及系统。
背景技术
[0002] 体外诊断技术， 国际上统称为 IVD (in-VitroDiagnostics) 技术， 即指在人体之 外通过对人体的血液等组织及分泌物进行检测， 获取临床诊断信息的产品和服 务。 在世界范围内， 随着新技术的兴起以及医疗保障政策的完善， 体外诊断技 术已成为生物医药产业发展最快的方向之一。 体外诊断技术及产品的研发周期 短、 类别多， 除了可应用于临床外， 还可延伸应用于食品安全检测、 动植物疫 病监控等领域， 是生物医药领域创新创业的热点领域。
[0003] 然而， 现有的体外诊断技术的检测方法通常基于传统免疫比浊法 （Turbidimetri c inhibition immuno
assay) 或实吋定量基因扩增荧光检测系统 （QPCR， Real-time Quantitative PCR Detecting System) 技术， 检测灵敏度低、 检测速度慢、 可靠性低， 无法满足日 益增长的体外诊断技术需求。
技术问题
[0004] 本发明实施例提供一种等离子激元波导、 生物传感芯片及系统， 可以实现对太 赫兹波信号的增强， 提高生物传感芯片的检测灵敏度、 信噪比和可靠性。
问题的解决方案
技术解决方案
[0005] 本发明实施例一方面提供一种等离子激元波导， 其应用于生物传感芯片， 所述 等离子激元波导包括基底和设置在所述基底上表面的等离子激元结构， 所述等 离子激元结构包括周期性排列的多个等离子激元， 所述等离子激元为金属幵口 环， 所述等离子激元的环形幵口处用于固定抗体探针。
[0006] 在一个实施例中， 所述等离子激元结构的水平方向周期长度和垂直方向周期长 度均为 50μηι~200μιη， 所述等离子激元的环形直径为 30μηι~100μιη， 所述环形幵 口的宽度为 10ηηι~2μιη。
[0007] 在一个实施例中， 所述金属幵口环为圆形幵口环、 椭圆形幵口环或多边形幵口 环。
[0008] 在一个实施例中， 所述基底为硅基底、 玻璃基底或塑料基底。
[0009] 在一个实施例中， 所述等离子激元通过 3D打印技术或紫外光刻技术制备， 所述 等离子激元通过金属电沉积工艺附着在所述基底层的上表面形成所述等离子激 元结构。
[0010] 本发明实施例另一方面还提供一种生物传感芯片， 其包括键合在同一基板上的 检测液预处理芯片和微流控芯片， 所述微流控芯片包括至少一个微流控通道， 所述微流控通道内设置有上述的等离子激元波导；
[0011] 所述检测液预处理芯片包括检测液入口以及与所述至少一个微流控通道数量相 等的检测液出口， 每个所述微流控通道的进口对应连接一个所述检测液出口；
[0012] 检测液样本从所述检测液入口流入， 经所述检测液预处理芯片处理后得到检测 液， 所述检测液经所述检测液出口和所述进口流入所述微流控通道， 所述检测 液中的目标生物分子被所述微流控通道中的等离子激元波导上的抗体探针捕获 ， 所述至少一个微流控通道捕获所述检测液中的至少一种目标生物分子。
[0013] 在一个实施例中， 每个所述微流控通道中的等离子激元波导上的抗体探针均相 同， 所述至少一个微流控通道捕获所述检测液中的同一种目标生物分子。
[0014] 在一个实施例中， 所述检测液样本为血液样本。
[0015] 在一个实施例中， 对应连接的所述进口和所述检测液出口的连接处通过聚二甲 基硅氧烷密封。
[0016] 本发明实施例再一方面还提供一种生物传感系统， 其包括上述的生物传感芯片
， 还包括太赫兹源和太赫兹分析仪；
[0017] 所述太赫兹源向捕获了所述目标生物分子的生物传感芯片发射太赫兹波； 所述 太赫兹分析仪接收所述生物传感芯片反射的太赫兹波， 并对所述反射的太赫兹 波进行太赫兹光谱分析， 以检测所述生物传感芯片捕获的目标生物分子的生物 特征。 发明的有益效果
有益效果
[0018] 本发明实施例通过在生物传感芯片内设置等离子激元波导， 可以通过抗体探针 捕获流入微流控通道内的检测液中的目标生物分子， 并通过等离子激元波导来 增强发射至生物传感芯片的太赫兹波的信号强度， 从而提高太赫兹分析仪检测 到的反射太赫兹波的信号强度， 提高检测灵敏度、 信噪比和可靠性。
对附图的简要说明
附图说明
[0019] 为了更清楚地说明本发明实施例中的技术方案， 下面将对实施例描述中所需要 使用的附图作简单地介绍， 显而易见地， 下面描述中的附图是本发明的一些实 施例， 对于本领域普通技术人员来讲， 在不付出创造性劳动的前提下， 还可以 根据这些附图获得其他的附图。
[0020] 图 1是本发明的一个实施例提供的等离子激元波导的基本结构示意图；
[0021] 图 2是本发明的另一个实施例提供的等离子激元波导的基本结构示意图；
[0022] 图 3是本发明的一个实施例提供的生物传感芯片的基本结构示意图；
[0023] 图 4是本发明的一个实施例提供的生物传感系统的基本结构示意图。
本发明的实施方式
[0024] 为了使本技术领域的人员更好地理解本发明方案， 下面将结合本发明实施例中 的附图， 对本发明实施例中的技术方案进行清楚地描述， 显然， 所描述的实施 例是本发明一部分的实施例， 而不是全部的实施例。 基于本发明中的实施例， 本领域普通技术人员在没有做出创造性劳动前提下所获得的所有其他实施例， 都应当属于本发明保护的范围。
[0025] 本发明的说明书和权利要求书及上述附图中的术语"包括"以及它们任何变形， 意图在于覆盖不排他的包含。 例如包含一系列步骤或单元的过程、 方法或系统 、 产品或设备没有限定于已列出的步骤或单元， 而是可选地还包括没有列出的 步骤或单元， 或可选地还包括对于这些过程、 方法、 产品或设备固有的其它步 骤或单元。 此外， 术语"第一"、 "第二 "和"第三"等是用于区别不同对象， 而非用 于描述特定顺序。
[0026] 如图 1所示， 本发明的一个实施例提供一种应用于生物传感芯片的等离子激元 波导 10， 其包括基底 11和设置在基底 11上表面的等离子激元结构 12， 等离子激 元结构 12包括周期性排列的多个等离子激元 121， 等离子激元为金属幵口环， 等 离子激元 121的环形幵口处用于固定抗体探针 122。
[0027] 在具体应用中， 金属幵口环为圆形幵口环、 椭圆形幵口环或多边形幵口环。
[0028] 图 1示例性的示出等离子激元 121为圆形幵口环， 图 2示例性的示出等离子激元 1 21为方形幵口环。
[0029] 在具体应用中， 等离子激元结构所包括的等离子激元的数量、 尺寸和排列规则 可以根据实际需要设置， 例如等离子激元结构上的所有等离子激元可以规则排 列成矩形阵列、 圆形阵列或任意多边形阵列等。
[0030] 图 1和图 2示例性的示出等离子激元结构 12上的等离子激元 121规贝頓咧成矩阵 阵列。
[0031] 在一个实施例中， 等离子激元结构水平方向周期长度和垂直方向周期长度均为 50μηι~200μιη, 等离子激元的环形直径为 30μηι~100μιη， 环形幵口的宽度为 lOnm ~2μηι。
[0032] 在具体应用中， 水平方向具体是指任意一行等离子激元的排列方向， 垂直方向 是指垂直于水平方向的任意一列等离子激元的排列方向， 水平方向周期长度和 垂直方向周期长度可以相等或者不等， 环形直径是指等离子激元的环形外径， 当等离子激元为圆形幵口环吋， 环形直径指圆形幵口环的外环直径； 当等离子 激元为椭圆形幵口环吋， 环形直径指椭圆形幵口环的外环长直径； 当等离子激 元为方形幵口环吋， 环形直径指方形幵口环的外环边长。
[0033] 在一个实施例中， 等离子激元结构的水平方向周期长度和垂直方向周期长度均 为 50μηι， 等离子激元的环形直径为 36μηι。
[0034] 在一个实施例中， 等离子激元结构的水平方向周期长度为 40μηι、 垂直方向周 期长度为 60μηι， 等离子激元的环形直径为 36μηι。
[0035] 在具体应用中， 基底可以根据实际需要选择任意类型的材料制作， 在一个实施 例中， 基底为硅基底、 玻璃基底或塑料基底。
[0036] 在具体应用中， 等离子激元可通过 3D打印技术或紫外光刻技术制备， 等离子激 元可通过金属电沉积工艺附着在基底层的上表面形成等离子激元结构。
[0037] 在具体应用中， 根据需要捕获的目标生物分子的类型的不同， 可以在等离子激 元的环形幵口处固定不同类型的抗体探针， 例如， 若要捕获肿瘤细胞抗原， 则 固定肿瘤细胞抗体探针。
[0038] 本实施例通过在生物传感芯片内设置上述等离子激元波导， 可以通过抗体探针 捕获流入微流控通道内的检测液中的目标生物分子， 并通过等离子激元波导来 增强发射至生物传感芯片的太赫兹波的信号强度， 从而提高太赫兹分析仪检测 到的反射太赫兹波的信号强度， 提高检测灵敏度、 信噪比和可靠性。
[0039] 如图 3所示， 本发明的一个实施例提供一种基于等离子激元波导 10实现的生物 传感芯片 100， 其包括键合在同一基板 101上的检测液预处理芯片 20和微流控芯 片 30， 微流控芯片 30包括至少一个微流控通道 31， 微流控通道 31内设置有等离 子激元波导 10。
[0040] 检测液预处理芯片 20包括检测液入口 21以及与至少一个微流控通道 31数量相等 的检测液出口 22， 每个微流控通道 31的进口 311对应连接一个检测液出口 22。
[0041] 在具体应用中， 基板具体可以为玻璃基板或硅基板。
[0042] 在一个实施例中， 对应连接的进口和检测液出口的连接处通过聚二甲基硅氧烷 密封。
[0043] 本实施例所提供的生物传感芯片的工作原理为：
[0044] 检测液样本从检测液入口流入， 经检测液预处理芯片处理后得到检测液， 检测 液经检测液出口和进口流入微流控通道， 检测液中的目标生物分子被微流控通 道中的等离子激元波导上的抗体探针捕获， 至少一个微流控通道捕获检测液中 的至少一种目标生物分子。
[0045] 在具体应用中， 检测液样本可以是血液、 组织液或分泌物等。
[0046] 在一个实施例中， 检测液样本为血液。
[0047] 图 3中示例性的示出微流控芯片 30包括 6个微流控通道 31， 图 3中为了方便示意 没有标示出等离子激元波导。 [0048] 基于图 3所示的生物传感芯片 100， 可以捕获 1~6种目标生物分子， 具体由 6个微 流控通道中的等离子激元波导上的抗体探针的类型决定， 若 6个微流控通道中的 等离子激元波导上的抗体探针都相同， 则只能同吋实现对 1种目标生物分子的捕 获； 若都不相同， 则可以实现对 6种目标生物分子的捕获； 若其中两个相同、 另 外四个不同， 则可以实现对 5种目标生物分子的捕获， 依此类推。
[0049] 在一个实施例中， 每个微流控通道中的等离子激元波导上的抗体探针均相同， 至少一个微流控通道捕获检测液中的同一种目标生物分子。
[0050] 在具体应用中， 当所有微流控通道都同吋用于捕获同一种目标生物分子吋， 可 以有效提高对检测液中目标生物分子的检测精度， 提高生物传感芯片的检测结 果的可靠性。
[0051] 在具体应用中， 微流控芯片是由至少一个微流控通道和玻璃基板键合而成。
[0052] 本实施例通过检测液预处理芯片对检测液样本进行预处理， 可以过滤或截留检 测液中不需要被检测的细胞或颗粒， 得到包含有目标生物分子的较为纯净的检 测液， 便于后续通过微流控芯片对目标生物分析进行捕获； 通过提供包括至少 一个微流控通道的微流控芯片， 可以实现对至少一个目标生物分子的捕获， 提 高检测效率和检测可靠性。
[0053] 如图 4所示， 本发明的一个实施例提供一种生物传感系统， 其包括生物传感芯 片 100， 还包括太赫兹源 200和太赫兹分析仪 300。
[0054] 太赫兹源向捕获了目标生物分子的生物传感芯片发射太赫兹波； 太赫兹分析仪 接收生物传感芯片反射的太赫兹波， 并对反射的太赫兹波进行太赫兹光谱分析
， 以检测生物传感芯片捕获的目标生物分子的生物特征。
[0055] 在具体应用中， 目标生物分子的生物特征包括数量、 尺寸和细胞结构等特征。
[0056] 以上所述仅为本发明的较佳实施例而已， 并不用以限制本发明， 凡在本发明的 精神和原则之内所作的任何修改、 等同替换和改进等， 均应包含在本发明的保 护范围之内。

Claims

权利要求书
[权利要求 1] 一种等离子激元波导， 其特征在于， 应用于生物传感芯片， 所述等离 子激元波导包括基底和设置在所述基底上表面的等离子激元结构， 所 述等离子激元结构包括周期性排列的多个等离子激元， 所述等离子激 元为金属幵口环， 所述等离子激元的环形幵口处用于固定抗体探针。
[权利要求 2] 如权利要求 1所述的等离子激元波导， 其特征在于， 所述等离子激元 结构的水平方向周期长度和垂直方向周期长度均为 50μηι~200μιη， 所 述等离子激元的环形直径为 30μηι~100μιη， 所述环形幵口的宽度为 10 πηι〜2μηι。
[权利要求 3] 如权利要求 1所述的等离子激元波导， 其特征在于， 所述金属幵口环 为圆形幵口环、 椭圆形幵口环或多边形幵口环。
[权利要求 4] 如权利要求 1所述的等离子激元波导， 其特征在于， 所述基底为硅基 底、 玻璃基底或塑料基底。
[权利要求 5] 如权利要求 1所述的等离子激元波导， 其特征在于， 所述等离子激元 通过 3D打印技术或紫外光刻技术制备， 所述等离子激元通过金属电 沉积工艺附着在所述基底层的上表面形成所述等离子激元结构。
[权利要求 6] —种生物传感芯片， 其特征在于， 包括键合在同一基板上的检测液预 处理芯片和微流控芯片， 所述微流控芯片包括至少一个微流控通道， 所述微流控通道内设置有如权利要求 1~5任一项所述的等离子激元波 导.
所述检测液预处理芯片包括检测液入口以及与所述至少一个微流控通 道数量相等的检测液出口， 每个所述微流控通道的进口对应连接一个 所述检测液出口；
检测液样本从所述检测液入口流入， 经所述检测液预处理芯片处理后 得到检测液， 所述检测液经所述检测液出口和所述进口流入所述微流 控通道， 所述检测液中的目标生物分子被所述微流控通道中的等离子 激元波导上的抗体探针捕获， 所述至少一个微流控通道捕获所述检测 液中的至少一种目标生物分子。
[权利要求 7] 如权利要求 6所述的生物传感芯片， 其特征在于， 每个所述微流控通 道中的等离子激元波导上的抗体探针均相同， 所述至少一个微流控通 道捕获所述检测液中的同一种目标生物分子。
[权利要求 8] 如权利要求 6所述的生物传感芯片， 其特征在于， 所述检测液样本为 血液样本。
[权利要求 9] 如权利要求 6所述的生物传感芯片， 其特征在于， 对应连接的所述进 口和所述检测液出口的连接处通过聚二甲基硅氧烷密封。
[权利要求 10] —种生物传感系统， 其特征在于， 包括如权利要求 6~9任一项所述的 生物传感芯片， 还包括太赫兹源和太赫兹分析仪； 所述太赫兹源向捕获了所述目标生物分子的生物传感芯片发射太赫兹 波； 所述太赫兹分析仪接收所述生物传感芯片反射的太赫兹波， 并对 所述反射的太赫兹波进行太赫兹光谱分析， 以检测所述生物传感芯片 捕获的目标生物分子的生物特征。
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