WO2016127457A1 - 用于检测生物标志物浓度的生物传感系统及其检测方法 - Google Patents

用于检测生物标志物浓度的生物传感系统及其检测方法 Download PDF

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Publication number
WO2016127457A1
WO2016127457A1 PCT/CN2015/073835 CN2015073835W WO2016127457A1 WO 2016127457 A1 WO2016127457 A1 WO 2016127457A1 CN 2015073835 W CN2015073835 W CN 2015073835W WO 2016127457 A1 WO2016127457 A1 WO 2016127457A1
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Prior art keywords
biomarker
concentration
detecting
light intensity
organic electroluminescent
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English (en)
French (fr)
Inventor
张贯京
陈兴明
葛新科
张少鹏
方静芳
高伟明
梁艳妮
周荣
梁昊原
周亮
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Shenzhen Qianhai AnyCheck Information Technology Co Ltd
E Techno Information Technologies Co Ltd
Bio Tech Academy China Co Ltd
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Shenzhen Qianhai AnyCheck Information Technology Co Ltd
E Techno Information Technologies Co Ltd
Bio Tech Academy China Co Ltd
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Publication of WO2016127457A1 publication Critical patent/WO2016127457A1/zh
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    • 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
    • G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
    • G01N21/66—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light electrically excited, e.g. electroluminescence

Definitions

  • the invention relates to the field of biological detection technology, in particular to a biosensor system for detecting biomarker concentration and a detection method thereof.
  • Organic electroluminescent materials have been used in display, imaging and other fields due to their special luminescent properties.
  • biomarkers DNA, antibodies, viruses, microorganisms, enzymes, pesticides and other biological macromolecules
  • the detection method is constantly updated.
  • the existing detection methods usually use detection instruments, but these detection instruments have the disadvantages of large volume, low detection sensitivity, high price, and narrow application fields.
  • the main object of the present invention is to provide a biosensor system for detecting the concentration of a biomarker and a detection method thereof, which can improve the detection sensitivity to biomacromolecules.
  • the present invention provides a biosensor system for detecting a concentration of a biomarker, the biosensor system for detecting a concentration of a biomarker comprising an organic electroluminescence element, a light receiving module, and a photoelectric Signal conversion module, and processing module:
  • the light receiving module is configured to receive a light intensity signal emitted by the organic electroluminescent element, and send the light intensity signal to the photoelectric signal conversion module;
  • the photoelectric signal conversion module is connected to the light receiving module, configured to amplify and convert the light intensity signal into an electrical signal, and convert the electrical signal into a digital signal and output the signal to the processing module;
  • the processing module is connected to the photoelectric signal conversion module, and configured to determine a concentration of the biomarker to be tested according to the change of the digital signal;
  • the organic electroluminescent element comprises a light-emitting body, the light-emitting body comprising a light-emitting layer, the light-emitting layer being made of an organic electroluminescent material; the organic electroluminescent material being represented by the following general formula (I):
  • A represents an organic electroluminescent compound molecule
  • B represents a functional group
  • AB represents a product after A is functionalized by B
  • C represents an antibody
  • C is bonded to A through B to obtain an organic electroluminescent material.
  • the A is a macrocyclic conjugated organic compound molecule
  • the B is one or more of -OH, -SH, -CHO, -COOH, -SO3H, -NH2, -CH2-, RCO- Carbon chain structure.
  • the light receiving module is a fluorescence detector or a phosphorescent detector.
  • the A is a macrocyclic conjugated organic compound molecule
  • the B is one or more of -OH, -SH, -CHO, -COOH, -SO3H, -NH2, -CH2-, RCO- Carbon chain structure.
  • the biosensor system for detecting a concentration of a biomarker further comprises:
  • a concentrating module is disposed at a front end of the light receiving module for collecting a light intensity signal emitted by the organic electroluminescent element.
  • the A is a macrocyclic conjugated organic compound molecule
  • the B is one or more of -OH, -SH, -CHO, -COOH, -SO3H, -NH2, -CH2-, RCO- Carbon chain structure.
  • a microchannel for carrying a biomarker to be tested is disposed in the luminescent layer, and the biomarker to be tested flows in the microchannel.
  • the A is a macrocyclic conjugated organic compound molecule
  • the B is one or more of -OH, -SH, -CHO, -COOH, -SO3H, -NH2, -CH2-, RCO- Carbon chain structure.
  • the antigen in the biomarker to be tested binds to C in the general formula (I).
  • the present invention also provides a method for detecting a concentration of a biomarker by a biosensor system for detecting a concentration of a biomarker, the method comprising the following steps:
  • the light receiving module receives the light intensity signal emitted by the light emitting layer of the organic electroluminescent element and the biomarker to be tested, and sends the light intensity signal to the photoelectric signal conversion module;
  • the photoelectric signal conversion module amplifies and converts the light intensity signal into an electrical signal, and converts the electrical signal into a digital signal and outputs the signal to the processing module;
  • the processing module determines the concentration of the biomarker to be tested based on the digital signal and an initial light intensity signal emitted by the organic electroluminescent element.
  • the method for detecting the concentration of the biomarker further comprises the steps of:
  • the concentrating module collects the light intensity signal emitted by the organic electroluminescent element.
  • the step of the light receiving module receiving and detecting the light intensity signal emitted by the light emitting layer of the organic electroluminescent element combined with the biomarker to be tested comprises:
  • the biomarker to be tested flows in a microchannel in the luminescent layer of the organic electroluminescent element, and the antigen in the biomarker to be tested is bound to the antibody on the luminescent layer;
  • the light receiving module receives the light intensity signal after the antigen in the biomarker to be tested emitted by the organic electroluminescent element is combined with the antibody on the luminescent layer.
  • the method for detecting the concentration of the biomarker further comprises the steps of:
  • the concentrating module collects the light intensity signal emitted by the organic electroluminescent element.
  • the step of determining, by the processing module, the concentration of the biomarker to be tested according to the digital signal and an initial light intensity signal emitted by the organic electroluminescent element comprises:
  • the processing module acquires an initial light intensity signal emitted by the organic electroluminescent element, and a corresponding initial concentration value
  • the processing module determines the concentration of the biomarker to be tested according to the initial light intensity signal, the initial concentration value, the digital signal output by the photoelectric signal conversion module, and the correspondence between the light intensity signal and the concentration value.
  • the method for detecting the concentration of the biomarker further comprises the steps of:
  • the concentrating module collects the light intensity signal emitted by the organic electroluminescent element.
  • the invention receives the light intensity signal emitted by the organic electroluminescent element through the light receiving module, sends the light intensity signal to the photoelectric signal conversion module, and amplifies and converts the light intensity signal into an electrical signal through the photoelectric signal conversion module, and the electrical signal
  • the digital signal is converted to a processing module, and the processing module determines the concentration of the biomarker to be tested according to the change of the digital signal.
  • the luminescent property of the organic electroluminescent material is applied to the field of biological macromolecule detection, and the concentration of the biomarker to be tested is detected, thereby broadening the application field of the organic electroluminescent material, and achieving high selectivity and high specificity detection. And improve the detection sensitivity of biological macromolecules.
  • FIG. 1 is a schematic diagram of functional modules of a first embodiment of a biosensing system for detecting biomarker concentration according to the present invention
  • FIG. 2 is a schematic structural view of a biosensing system for detecting a concentration of a biomarker according to the present invention
  • FIG. 3 is a schematic diagram of functional modules of a second embodiment of a biosensing system for detecting biomarker concentration according to the present invention
  • FIG. 4 is a schematic flow chart of a first embodiment of a method for detecting a concentration of a biomarker according to the present invention
  • FIG. 5 is a schematic diagram showing the refinement flow of S10 in FIG. 4;
  • FIG. 6 is a schematic diagram showing the refinement flow of S30 in FIG. 4;
  • Fig. 7 is a schematic flow chart showing the second embodiment of the method for detecting the concentration of the biomarker of the present invention.
  • the main object of the present invention is to solve the defects of the detection method of the existing biomacromolecules, such as high detection cost, low detection sensitivity, narrow application field, etc.
  • the innovation of the present invention is to provide a biotransfer for detecting the concentration of biomarkers.
  • the sensing system can apply the luminescent properties of the organic electroluminescent material to the field of biological macromolecule detection, thereby achieving the above object.
  • FIG. 1 is a schematic diagram of functional modules of a first embodiment of a biosensing system for detecting biomarker concentration according to the present invention
  • FIG. 2 is a biosensing system for detecting biomarker concentration according to the present invention. Schematic diagram of the structure.
  • a biosensing system for detecting biomarker concentration includes an organic electroluminescent element 10, a light receiving module 20, an optoelectronic signal conversion module 30, and a processing module 40, wherein:
  • the light receiving module 20 is configured to receive the light intensity signal emitted by the organic electroluminescent element 10, and send the light intensity signal to the photoelectric signal conversion module 30;
  • the photoelectric signal conversion module 30 is connected to the light receiving module 20 for amplifying and converting the light intensity signal into an electrical signal, and converting the electrical signal into a digital signal output to the processing module 40;
  • the processing module 40 is connected to the photoelectric signal conversion module 30 for determining the concentration of the biomarker to be tested according to the change of the digital signal;
  • the organic electroluminescent element 10 includes a light emitting body 100, the light emitting body 100 includes a light emitting layer 101, and the light emitting layer 101 is made of an organic electroluminescent material; the organic electroluminescent material is represented by the following general formula (I):
  • A represents an organic electroluminescent compound molecule
  • B represents a functional group
  • AB represents a product obtained by B functionalization with B
  • C is bonded to A by B to obtain an organic electroluminescent material.
  • A is a macrocyclic conjugated organic compound molecule
  • B is a functional group contained on A, and -OH, -SH can be selected.
  • C represents an antibody, and an antigen in a biomarker to be tested, such as a biological macromolecule such as a virus, a bacterium, an enzyme, or a biomarker protein, selectively binds to C, and a corresponding biochemical reaction occurs; when the biomarker to be tested is When flowing in the organic electroluminescent element 10, the biomacromolecule therein selectively binds to C.
  • a biomarker to be tested such as a biological macromolecule such as a virus, a bacterium, an enzyme, or a biomarker protein
  • the light receiving module 20 can be configured as a fluorescence detector or a phosphorescent detector.
  • the light-receiving module 20 is provided as a fluorescence detector that can receive fluorescence;
  • the phosphorescent material is contained in the light-emitting layer 101, the light-receiving module 20 is provided as a phosphorescent detector that can receive phosphorescence.
  • the biomarker to be tested flows in the organic electroluminescent element 10 and is combined with the illuminating body 100, and the light receiving module 20 receives the light intensity signal emitted by the organic electroluminescent element 10,
  • the light intensity signal is sent to the photoelectric signal conversion module 30;
  • the photoelectric signal conversion module 30 amplifies the received light intensity signal and converts it into an electrical signal, and then further converts the electrical signal into a corresponding digital signal, and the digital signal Output to the processing module 40;
  • the processing module 40 determines the concentration of the biomarker to be tested based on the change in the digital signal and the correspondence between the intensity signal and the concentration of the biomarker.
  • the light intensity signal emitted by the biomarker is an initial light intensity signal
  • an initial density value corresponding to the initial light intensity signal is preset.
  • the processing module 40 acquires an initial light intensity signal emitted by the organic electroluminescent element 10 and a corresponding initial concentration value according to the light intensity signal and the biomarker. The corresponding relationship of the concentrations determines the concentration of the biomarker to be tested.
  • the correspondence relationship between the intensity signal and the concentration of the biomarker is a linear relationship, and since the initial light intensity signal, the initial density value, and the light intensity signal corresponding to the currently output digital signal are known, The above linear relationship determines the concentration of the biomarker to be tested.
  • the light intensity signal emitted by the organic electroluminescent element 10 is received by the light receiving module 20, the light intensity signal is sent to the photoelectric signal conversion module 30, and the light intensity signal is amplified and converted into an electrical signal by the photoelectric signal conversion module 30. And converting the electrical signal into a digital signal output to the processing module 40, the processing module 40 determining the concentration of the biomarker to be tested based on the change in the digital signal.
  • the luminescent property of the organic electroluminescent material is applied to the field of biological macromolecule detection, and the concentration of the biomarker to be tested is detected, thereby broadening the application field of the organic electroluminescent material, and achieving high selectivity and high specificity detection. And improve the detection sensitivity of biological macromolecules.
  • the light-emitting body 100 of the organic electroluminescent element 10 includes the light-emitting layer 101. Further, the light-emitting body 100 further includes a cathode layer 102 above the light-emitting layer 101 and an anode layer 103 under the light-emitting layer. among them:
  • the anode layer 103 undertakes the task of injecting holes into the hole transport layer or the light-emitting layer, using 4.5 eV.
  • the anode of the above work function is effective.
  • the anode material indium tin oxide alloy (ITO), tin oxide (NESA), indium zinc oxide, gold, silver, platinum, copper, or the like can be selected.
  • the anode can be produced by forming a film of these electrode materials by a vapor deposition method, a sputtering method, or the like.
  • the light emitted from the light-emitting layer is taken out from the anode, it is preferably 10% larger than the transmittance of light in the visible region of the anode.
  • the film thickness of the anode varies depending on the material, and is usually selected from the range of 10 nm to 1 ⁇ m, preferably 10 nm to 200 nm.
  • the cathode layer 102 is responsible for injecting electrons into the electron injection layer, the electron transport layer, or the light-emitting layer, and is preferably formed of a material having a small work function.
  • the cathode material is not particularly limited, and specifically, a metal material such as indium, aluminum, magnesium, magnesium-indium alloy, magnesium-aluminum alloy, aluminum-lithium alloy, aluminum-niobium-lithium alloy, or magnesium-silver alloy can be used.
  • the cathode can be produced by forming a film by a method such as a vapor deposition method or a sputtering method. Further, the emitted light can be taken out from the cathode side as needed.
  • the light-emitting layer 101 functions as an organic layer having a light-emitting function, and includes a host material and a dopant material when a doping system is employed.
  • the host material mainly has a function of promoting recombination of electrons and holes, and closing excitons in the light-emitting layer
  • the dopant material has a function of efficiently emitting excitons obtained by recombination.
  • the light-emitting layer 101 may be a double body in which the carrier balance in the light-emitting layer is adjusted by, for example, combining an electron-transporting body and a hole-transporting body.
  • Host also known as host-cohost).
  • the luminescent layer 101 may include a fluorescent luminescent material and/or a phosphorescent luminescent material, preferably a fluorescent luminescent material.
  • the organic electroluminescent element in this embodiment may be a fluorescent or phosphorescent illuminating monochromatic luminescent element. It may be a fluorescent/phosphorescent hybrid white light-emitting element, and may be a single type having a single light-emitting unit or a tandem type having a plurality of light-emitting units, and among them, a fluorescent light-emitting type is preferable.
  • the organic electroluminescent element is provided as a concave lens structure.
  • a plurality of micro via holes are disposed in the light emitting layer 101, and the plurality of micro through holes constitute the microchannel 1011.
  • the microchannel is used.
  • the biomarker to be tested can carry the biomarker to be tested, and the biomarker to be tested can flow in the microchannel.
  • FIG. 3 there is shown a functional block diagram of a second embodiment of a biosensing system for detecting biomarker concentrations in accordance with the present invention.
  • the biosensor system for detecting the concentration of the biomarker further comprises:
  • the concentrating module 50 is disposed at the front end of the light receiving module 20 for collecting the light intensity signal emitted by the organic electroluminescent element 10.
  • the concentrating module 50 is disposed at the front end of the light receiving module 20, and collects the light intensity signals emitted by the organic electroluminescent element 10, so that the scattered light intensity signals are gathered to overcome the problems of light scattering and interference of the light intensity signals, so that the measurement is made.
  • the maximum amount of light intensity signal is received by the light receiving module 20 to improve the accuracy of the measurement system.
  • the concentrating module 50 can use a concentrating device such as a condensing mirror, a lenticular lens, and an LED lamp cup.
  • the concentrating module 50 is integrated with the light receiving module 20.
  • the invention also provides a method for detecting the concentration of a biomarker.
  • FIG. 4 is a schematic flow chart of a first embodiment of a method for detecting a concentration of a biomarker according to the present invention.
  • the method for detecting the concentration of a biomarker comprises:
  • Step S10 the light receiving module receives the light intensity signal emitted by the light emitting layer of the organic electroluminescent element and the biological marker to be tested;
  • Step S11 the light receiving module sends the light intensity signal to the photoelectric signal conversion module
  • Step S20 the photoelectric signal conversion module amplifies and converts the light intensity signal into an electrical signal, and converts the electrical signal into a digital signal and outputs the signal to the processing module;
  • Step S30 the processing module determines the concentration of the biomarker to be tested according to the digital signal and the initial light intensity signal emitted by the organic electroluminescent element.
  • the organic electroluminescent element comprises a light emitting body, the light emitting body comprises a light emitting layer, and the light emitting layer is made of an organic electroluminescent material;
  • the organic electroluminescent material is represented by the following general formula (I):
  • A represents an organic electroluminescent compound molecule
  • B represents a functional group
  • AB represents a product obtained by B functionalization with B
  • C is bonded to A by B to obtain an organic electroluminescent material.
  • A is a macrocyclic conjugated organic compound molecule
  • B is a functional group contained in A, and -OH, -SH, One or more of -CHO, -COOH, -SO3H, -NH2, -CH2, RCO-.
  • C represents an antibody, and the antigen in the biomarker to be tested binds to C, such as a biological macromolecule such as a virus, a bacterium, an enzyme, or a biomarker protein; when the biomarker to be tested flows in the organic electroluminescent element, Biomacromolecules selectively bind to C.
  • the light receiving module can be configured as a fluorescence detector or a phosphorescent detector.
  • the light receiving module is provided as a fluorescence detector that can receive fluorescence;
  • the phosphor layer is included in the light emitting layer, the light receiving module is provided as a phosphorescent detector that can receive phosphorescence.
  • the biomarker to be tested flows in the organic electroluminescent element and is combined with the illuminating body, and the light receiving module receives the light intensity signal emitted by the organic electroluminescent element, and the light intensity is The signal is sent to the photoelectric signal conversion module; the photoelectric signal conversion module amplifies the received light intensity signal and converts it into an electrical signal, and then further converts the electrical signal into a corresponding digital signal, and outputs the digital signal to the processing module; The module determines the concentration of the biomarker to be tested based on the change in the digital signal and the correspondence between the intensity signal and the concentration of the biomarker.
  • the light intensity signal sent by the organic electroluminescent element is received by the light receiving module, the light intensity signal is sent to the photoelectric signal conversion module, and the light intensity signal is amplified and converted into an electrical signal by the photoelectric signal conversion module, and the electricity is generated.
  • the signal is converted into a digital signal output to the processing module, and the processing module determines the concentration of the biomarker to be tested according to the change of the digital signal.
  • the luminescent property of the organic electroluminescent material is applied to the field of biological macromolecule detection, and the concentration of the biomarker to be tested is detected, thereby broadening the application field of the organic electroluminescent material, and achieving high selectivity and high specificity detection. And improve the detection sensitivity of biological macromolecules.
  • FIG. 5 is a schematic diagram of the refinement flow of S10 in FIG.
  • step S10 specifically includes:
  • Step S101 in the energized state, the biomarker to be tested flows in the microchannel in the luminescent layer of the organic electroluminescent element, and the antigen in the biomarker to be tested is combined with the antibody on the luminescent layer;
  • Step S102 the light receiving module receives the light intensity signal after the antigen in the biomarker to be tested emitted by the organic electroluminescent element is combined with the antibody on the luminescent layer.
  • the organic electroluminescent element starts to emit light, and when the biomarker to be tested flows in the microchannel in the luminescent layer of the organic electroluminescent element, the antigen in the biomarker to be tested, such as viruses, bacteria, Biomacromolecules such as enzyme or biomarker protein binding selectively bind to antibodies in the organic electroluminescent material constituting the luminescent layer, and a corresponding biochemical reaction occurs, thereby affecting the light intensity of the organic electroluminescent element.
  • the antigen in the biomarker to be tested such as viruses, bacteria, Biomacromolecules such as enzyme or biomarker protein binding selectively bind to antibodies in the organic electroluminescent material constituting the luminescent layer, and a corresponding biochemical reaction occurs, thereby affecting the light intensity of the organic electroluminescent element.
  • the organic electroluminescent element transmits the light intensity signal of the biomarker to be tested and the antibody, virus, bacteria, enzyme or biomarker protein on the luminescent layer to the light receiving module, so that the light receiving module further performs the light intensity signal Process and determine the concentration of the biomarker to be tested.
  • FIG. 6 is a schematic diagram of the refinement flow of S30 in FIG.
  • step S30 specifically includes:
  • Step S301 the processing module acquires an initial light intensity signal emitted by the organic electroluminescent element, and a corresponding initial concentration value
  • Step S302 the processing module determines the concentration of the biomarker to be tested according to the initial light intensity signal, the initial concentration value, the digital signal output by the photoelectric signal conversion module, and the correspondence between the light intensity signal and the density value.
  • the light intensity signal emitted by the biomarker is an initial light intensity signal
  • an initial concentration value corresponding to the initial light intensity signal is preset.
  • the processing module After receiving the light intensity signal corresponding to the digital signal output by the photoelectric signal conversion module, the processing module first obtains the initial light intensity signal emitted by the organic electroluminescent element and the corresponding initial concentration value when determining the concentration of the biological marker to be tested.
  • the concentration of the biomarker to be tested is determined according to the correspondence between the intensity signal and the concentration of the biomarker.
  • the correspondence relationship between the intensity signal and the concentration of the biomarker is a linear relationship, and since the initial light intensity signal, the initial density value, and the light intensity signal corresponding to the currently output digital signal are known, The linear relationship determines the concentration of the biomarker to be tested.
  • FIG. 7 is a schematic flow chart of a second embodiment of a method for detecting a concentration of a biomarker according to the present invention.
  • the method further includes:
  • step S40 the concentrating module collects the light intensity signal emitted by the organic electroluminescent element.
  • the light intensity signal Before receiving the light intensity signal emitted by the organic electroluminescent element through the spectrum receiving module, the light intensity signal is concentrated by the concentrating module disposed at the front end of the spectrum receiving module, so that the scattered light intensity signals are gathered to overcome the light intensity signal Problems such as light scattering and interference make the maximum amount of measured light intensity signal received by the light receiving module, improving the accuracy of the measurement system.
  • the concentrating module can adopt a concentrating device such as a condensing mirror, a lenticular lens, and an LED lamp cup.
  • the concentrating module is integrated with the light receiving module.

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Abstract

一种用于检测生物标志物浓度的生物传感系统及相应的检测方法，该系统包括：光接收模块（20），用于接收有机电致发光元件（10）所发出的光强信号，将光强信号发送至光电信号转换模块（30）；光电信号转换模块（30），用于将光强信号放大并转换成电信号，将电信号转换成数字信号输出至处理模块（40）；处理模块（40），用于根据数字信号的变化确定待测生物标志物的浓度；有机电致发光元件（10）包括发光本体（100），发光本体（100）包括发光层（101），发光层（101）由有机电致发光材料制成。将有机电致发光材料的发光特性应用于生物大分子检测领域，检测待测生物标志物的浓度，拓宽了有机电致发光材料的应用领域，实现了高选择性、高特异性的检测，并且提高了对生物大分子的检测灵敏度。

Description

用于检测生物标志物浓度的生物传感系统及其检测方法
技术领域
本发明涉及生物检测技术领域，尤其涉及一种用于检测生物标志物浓度的生物传感系统及其检测方法。
背景技术
有机电致发光材料因其特殊的发光特性，已经应用于显示、成像等领域，随着生物技术的发展，生物标记物蛋白、DNA、抗体、病毒、微生物、酶、农药等多种生物大分子的检测方法不断更新。现有的检测方法通常是使用检测仪器，但是这些检测仪器存在体积大、检测灵敏度低、价格昂贵、应用领域窄等缺点。目前，如何将生物分子转化为可级数放大的波动电信号，如何实现高灵敏度、高选择性、高特异性、高通量复合型的检测是生物分子检测的关键，因此，有必要将有机电致发光材料的发光特性应用于对生物大分子的检测领域，来解决现有的检测方法存在检测成本高、检测灵敏度低、应用领域窄等缺点。
发明内容
本发明的主要目的在于提供一种用于检测生物标志物浓度的生物传感系统及其检测方法，能够提高对生物大分子的检测灵敏度。
为实现上述目的，本发明提供了一种用于检测生物标志物浓度的生物传感系统，所述用于检测生物标志物浓度的生物传感系统包括有机电致发光元件、光接收模块、光电信号转换模块，以及处理模块：
所述光接收模块，用于接收所述有机电致发光元件所发出的光强信号，将所述光强信号发送至所述光电信号转换模块；
所述光电信号转换模块，与所述光接收模块连接，用于将所述光强信号放大并转换成电信号，并将所述电信号转换成数字信号输出至所述处理模块；
所述处理模块，与所述光电信号转换模块连接，用于根据所述数字信号的变化确定待测生物标志物的浓度；
所述有机电致发光元件包括发光本体，所述发光本体包括发光层，所述发光层由有机电致发光材料制成；所述有机电致发光材料由以下通式（Ⅰ）表示：
AB C （Ⅰ）
式（Ⅰ）中，A表示有机电致发光化合物分子，B表示官能团，AB表示A经B官能团化后的产物；C表示抗体，C通过B与A结合以获得有机电致发光材料。
优选地，所述A为大环共轭有机化合物分子；所述B为含-OH、-SH、-CHO、-COOH、-SO3H、-NH2、-CH2-、RCO-中一种或几种的碳链结构。
优选地，所述光接收模块为荧光检测器或磷光检测器。
优选地，所述A为大环共轭有机化合物分子；所述B为含-OH、-SH、-CHO、-COOH、-SO3H、-NH2、-CH2-、RCO-中一种或几种的碳链结构。
优选地，所述用于检测生物标志物浓度的生物传感系统还包括：
聚光模块，设置在所述光接收模块前端，用于聚集所述有机电致发光元件所发出的光强信号。
优选地，所述A为大环共轭有机化合物分子；所述B为含-OH、-SH、-CHO、-COOH、-SO3H、-NH2、-CH2-、RCO-中一种或几种的碳链结构。
优选地，所述发光层内设置有用于承载待测生物标志物的微通道，所述待测生物标志物在所述微通道中流动。
优选地，所述A为大环共轭有机化合物分子；所述B为含-OH、-SH、-CHO、-COOH、-SO3H、-NH2、-CH2-、RCO-中一种或几种的碳链结构。
优选地，所述待测生物标志物中的抗原与所述通式（Ⅰ）中的C结合。
此外，为实现上述目的，本发明还提供一种用于检测生物标志物浓度的生物传感系统检测生物标志物浓度的检测方法，所述检测方法包括如下步骤：
光接收模块接收有机电致发光元件的发光层与待测生物标志物结合后所发出的光强信号，将所述光强信号发送至光电信号转换模块；
光电信号转换模块将所述光强信号放大并转换成电信号，并将所述电信号转换成数字信号输出至处理模块；
处理模块根据所述数字信号以及所述有机电致发光元件发出的初始光强信号，确定所述待测生物标志物的浓度。
优选地，所述生物标志物浓度的检测方法还包括步骤：
聚光模块聚集所述有机电致发光元件所发出的光强信号。
优选地，所述光接收模块接收并检测有机电致发光元件的发光层与待测生物标志物结合后所发出的光强信号的步骤包括：
在通电状态下，待测生物标志物在所述有机电致发光元件的发光层中的微通道中流动，所述待测生物标志物中的抗原与所述发光层上的抗体结合；
光接收模块接收有机电致发光元件发出的待测生物标志物中的抗原与发光层上的抗体结合后的光强信号。
优选地，所述生物标志物浓度的检测方法还包括步骤：
聚光模块聚集所述有机电致发光元件所发出的光强信号。
优选地，所述处理模块根据所述数字信号以及所述有机电致发光元件发出的初始光强信号，确定所述待测生物标志物的浓度的步骤包括：
处理模块获取有机电致发光元件发出的初始光强信号，以及对应的初始浓度值；
处理模块根据所述初始光强信号、初始浓度值、光电信号转换模块输出的数字信号以及光强信号与浓度值的对应关系，确定所述待测生物标志物的浓度。
优选地，所述生物标志物浓度的检测方法还包括步骤：
聚光模块聚集所述有机电致发光元件所发出的光强信号。
本发明通过光接收模块接收有机电致发光元件所发出的光强信号，将光强信号发送至光电信号转换模块，通过光电信号转换模块将光强信号放大并转换成电信号，并将电信号转换成数字信号输出至处理模块，处理模块根据数字信号的变化确定待测生物标志物的浓度。将有机电致发光材料的发光特性应用于生物大分子检测领域，检测待测生物标志物的浓度，从而拓宽了有机电致发光材料的应用领域，实现了高选择性、高特异性的检测，并且提高了对生物大分子的检测灵敏度。
附图说明
图1为本发明用于检测生物标志物浓度的生物传感系统第一实施例的功能模块示意图；
图2为本发明用于检测生物标志物浓度的生物传感系统的结构示意图；
图3为本发明用于检测生物标志物浓度的生物传感系统第二实施例的功能模块示意图；
图4为本发明生物标志物浓度的检测方法第一实施例的流程示意图；
图5为图4中S10的细化流程示意图；
图6为图4中S30的细化流程示意图；
图7为本发明生物标志物浓度的检测方法第二实施例的流程示意图。
本发明目的的实现、功能特点及优点将结合实施例，参照附图做进一步说明。
具体实施方式
应当理解，此处所描述的具体实施例仅仅用以解释本发明，并不用于限定本发明。
本发明的主要目的在于解决现有的生物大分子的检测方法存在检测成本高、检测灵敏度低、应用领域窄等缺点，本发明的创新点在于提供一种用于检测生物标志物浓度的生物传感系统，能够将有机电致发光材料的发光特性应用于生物大分子检测领域，从而实现上述目的。
参照图1和图2，图1为本发明用于检测生物标志物浓度的生物传感系统第一实施例的功能模块示意图；图2为本发明用于检测生物标志物浓度的生物传感系统的结构示意图。
在一实施例中，用于检测生物标志物浓度的生物传感系统包括有机电致发光元件10、光接收模块20、光电信号转换模块30，以及处理模块40，其中：
光接收模块20，用于接收有机电致发光元件10所发出的光强信号，将光强信号发送至光电信号转换模块30；
光电信号转换模块30，与光接收模块20连接，用于将光强信号放大并转换成电信号，并将电信号转换成数字信号输出至处理模块40；
处理模块40，与光电信号转换模块30连接，用于根据数字信号的变化确定待测生物标志物的浓度；
有机电致发光元件10包括发光本体100，发光本体100包括发光层101，发光层101由有机电致发光材料制成；有机电致发光材料由以下通式（Ⅰ）表示：
AB C （Ⅰ）
式（Ⅰ）中，A表示有机电致发光化合物分子，B表示官能团，AB表示A经B官能团化后的产物；C通过B与A结合以获得有机电致发光材料。
本实施例中，构成有机电致发光元件10的有机电致发光材料的上述通式中，A为大环共轭有机化合物分子；B为包含于A上的官能团，可选择-OH、-SH、-CHO、-COOH、-SO3H、-NH2、-CH2、RCO-中的一种或几种。C表示抗体，待测生物标志物中的抗原，例如病毒、细菌、酶、或生物标记蛋白等生物大分子会选择性地与C结合，发生相应的生物化学反应；当待测生物标志物在有机电致发光元件10中流动时，其中的生物大分子会选择性的与C结合。
光接收模块20可设置为荧光检测器或磷光检测器。当发光层101中包含荧光发光材料时，光接收模块20设置为可接收荧光的荧光检测器；当发光层101中包含磷光发光材料时，光接收模块20设置为可接收磷光的磷光检测器。
在检测待测生物标志物的浓度时，待测生物标志物在有机电致发光元件10中流动，并与发光本体100结合，光接收模块20接收有机电致发光元件10发出的光强信号，将该光强信号发送至光电信号转换模块30；光电信号转换模块30对接收到的光强信号进行放大并将其转换为电信号，然后进一步将电信号转换成对应的数字信号，将数字信号输出至处理模块40；处理模块40根据数字信号的变化，以及光强信号与生物标志物的浓度的对应关系确定待测生物标志物的浓度。
具体地，在待测生物标志物未与发光本体100结合时，其所发出的光强信号为初始光强信号，并预先设置对应于该初始光强信号对应的初始浓度值。处理模块40接收到光电信号转换模块30输出的数字信号对应的光强信号后，获取有机电致发光元件10发出的初始光强信号以及对应的初始浓度值，根据光强信号与生物标志物的浓度的对应关系，确定待测生物标志物的浓度。本实施例中，光强信号与生物标志物的浓度的对应关系为一线性关系，由于初始光强信号、初始浓度值和当前输出的数字信号对应的光强信号为已知，因此便可根据上述线性关系确定待测生物标志物的浓度。
本实施例通过光接收模块20接收有机电致发光元件10所发出的光强信号，将光强信号发送至光电信号转换模块30，通过光电信号转换模块30将光强信号放大并转换成电信号，并将电信号转换成数字信号输出至处理模块40，处理模块40根据数字信号的变化确定待测生物标志物的浓度。将有机电致发光材料的发光特性应用于生物大分子检测领域，检测待测生物标志物的浓度，从而拓宽了有机电致发光材料的应用领域，实现了高选择性、高特异性的检测，并且提高了对生物大分子的检测灵敏度。
在上述实施例中，有机电致发光元件10的发光本体100包括发光层101，此外，发光本体100还包括位于发光层101上方的阴极层102和位于发光层下方的阳极层103。其中：
阳极层103承担将空穴注入空穴传输层或发光层的任务，使用具有4.5eV 以上的功函数的阳极是有效果的。作为阳极材料，可选择氧化铟锡合金（ITO）、氧化锡（NESA）、氧化铟锌氧化物、金、银、铂、铜等。阳极可以通过用蒸镀法、溅射法等方法使这些电极物质形成薄膜来制作。将由发光层发出的光从阳极取出时，优选比阳极的可见区域的光的透射率大10%。阳极的膜厚因材料而异，通常在10nm~1μm、优选在10nm~200nm的范围内选择。
阴极层102承担向电子注入层、电子传输层或发光层注入电子的任务，优选由功函数小的材料形成。阴极材料没有特别限定，具体而言，可以使用铟、铝、镁、镁-铟合金、镁-铝合金、铝-锂合金、铝-钪-锂合金、镁-银合金等金属材料。阴极也与阳极同样地可以通过用蒸镀法、溅射法等方法形成薄膜来制作。另外，根据需要也可以从阴极侧取出所发出的光。
发光层101作为具有发光功能的有机层，在采用掺杂系统时，包含主体材料和掺杂材料。此时，主体材料主要具有促进电子与空穴的再结合、将激子关闭在发光层内的功能，掺杂材料具有使再结合而得到的激子有效地发光的功能。发光层101也可以采用例如将电子传输性的主体与空穴传输性的主体组合等来调整发光层内的载流子平衡的双重主体（double host）（也称为主体－共主体（host-cohost））。本实施例中，发光层101中可含有荧光发光材料和/或磷光发光材料，优选含有荧光发光材料；另外，本实施例中有机电致发光元件可以是荧光或磷光发光型的单色发光元件，也可以是荧光/磷光混合型的白色发光元件，可以是具有单独的发光单元的单型，也可以是具有多个发光单元的串联型，其中，优选为荧光发光型。
在上述实施例中，有机电致发光元件设置为凹透镜结构。
参照图2，在上述实施例中，在发光层101中设置多个微通孔，多个微通孔组成微通道1011，在检测待测生物标志物中的生物大分子时，该微通道用于承载待测生物标志物，待测生物标志物可在微通道中流动。
参照图3，图3为本发明用于检测生物标志物浓度的生物传感系统第二实施例的功能模块示意图。
基于上述本发明用于检测生物标志物浓度的生物传感系统第一实施例，在第二实施例中，用于检测生物标志物浓度的生物传感系统还包括：
聚光模块50，设置在光接收模块20前端，用于聚集有机电致发光元件10所发出的光强信号。
聚光模块50设置在光接收模块20前端，对有机电致发光元件10发出的光强信号进行聚集，使得散射的光强信号聚拢，以克服光强信号的光线散射和干涉等问题，使测量的光强信号最大量的被光接收模块20接收，提高测量系统的精确度。该聚光模块50可以采用聚光镜、凹凸透镜和LED灯杯等具有聚光作用的装置，优选地，聚光模块50与光接收模块20集成于一体。
本发明还提供一种生物标志物浓度的检测方法。
参照图4，图4为本发明生物标志物浓度的检测方法第一实施例的流程示意图。
在一实施例中，用于生物标志物浓度的检测方法包括：
步骤S10，光接收模块接收有机电致发光元件的发光层与待测生物标志物结合后所发出的光强信号；
步骤S11，光接收模块将光强信号发送至光电信号转换模块；
步骤S20，光电信号转换模块将光强信号放大并转换成电信号，并将电信号转换成数字信号输出至处理模块；
步骤S30，处理模块根据数字信号以及有机电致发光元件发出的初始光强信号，确定待测生物标志物的浓度。
本实施例中，有机电致发光元件包括发光本体，发光本体包括发光层，发光层由有机电致发光材料制成；有机电致发光材料由以下通式（Ⅰ）表示：
AB C （Ⅰ）
式（Ⅰ）中，A表示有机电致发光化合物分子，B表示官能团，AB表示A经B官能团化后的产物；C通过B与A结合以获得有机电致发光材料。
本实施例中，构成有机电致发光元件的有机电致发光材料的上述通式中，A为大环共轭有机化合物分子；B为包含于A上的官能团，可选择-OH、-SH、-CHO、-COOH、-SO3H、-NH2、-CH2、RCO-中的一种或几种。C表示抗体，待测生物标志物中的抗原与C结合，例如病毒、细菌、酶、或生物标记蛋白等生物大分子；当待测生物标志物在有机电致发光元件中流动时，其中的生物大分子会选择性的与C结合。
光接收模块可设置为荧光检测器或磷光检测器。当发光层中包含荧光发光材料时，光接收模块设置为可接收荧光的荧光检测器；当发光层中包含磷光发光材料时，光接收模块设置为可接收磷光的磷光检测器。
在检测待测生物标志物的浓度时，待测生物标志物在有机电致发光元件中流动，并与发光本体结合，光接收模块接收有机电致发光元件发出的光强信号，将该光强信号发送至光电信号转换模块；光电信号转换模块对接收到的光强信号进行放大并将其转换为电信号，然后进一步将电信号转换成对应的数字信号，将数字信号输出至处理模块；处理模块根据数字信号的变化，以及光强信号与生物标志物的浓度的对应关系确定待测生物标志物的浓度。
本实施例通过光接收模块接收有机电致发光元件所发出的光强信号，将光强信号发送至光电信号转换模块，通过光电信号转换模块将光强信号放大并转换成电信号，并将电信号转换成数字信号输出至处理模块，处理模块根据数字信号的变化确定待测生物标志物的浓度。将有机电致发光材料的发光特性应用于生物大分子检测领域，检测待测生物标志物的浓度，从而拓宽了有机电致发光材料的应用领域，实现了高选择性、高特异性的检测，并且提高了对生物大分子的检测灵敏度。
参照图5，图5为图4中S10的细化流程示意图。
在上述实施例中，步骤S10具体包括：
步骤S101，在通电状态下，待测生物标志物在有机电致发光元件的发光层中的微通道中流动，待测生物标志物中的抗原与发光层上的抗体结合；
步骤S102，光接收模块接收有机电致发光元件发出的待测生物标志物中的抗原与发光层上的抗体结合后的光强信号。
在通电状态下，有机电致发光元件开始发光，当待测生物标志物在有机电致发光元件的发光层中的微通道中流动时，待测生物标志物中的抗原，例如病毒、细菌、酶或生物标记蛋白结合等生物大分子，便会选择性的与组成发光层的有机电致发光材料中的抗体结合，发生相应的生物化学反应，从而影响到有机电致发光元件的光强。有机电致发光元件将待测生物标志物与发光层上的抗体、病毒、细菌、酶或生物标记蛋白结合后的光强信号发送至光接收模块，以供光接收模块进一步对光强信号进行处理，并确定待测生物标志物的浓度。
参照图6，图6为图4中S30的细化流程示意图。
在上述实施例中，步骤S30具体包括：
步骤S301，处理模块获取有机电致发光元件发出的初始光强信号，以及对应的初始浓度值；
步骤S302，处理模块根据初始光强信号、初始浓度值、光电信号转换模块输出的数字信号以及光强信号与浓度值的对应关系，确定待测生物标志物的浓度。
在待测生物标志物未与发光本体结合时，其所发出的光强信号为初始光强信号，并预先设置对应于该初始光强信号对应的初始浓度值。处理模块接收到光电信号转换模块输出的数字信号对应的光强信号后，在确定待测生物标志物的浓度时，首先获取有机电致发光元件发出的初始光强信号以及对应的初始浓度值，根据光强信号与生物标志物的浓度的对应关系，确定待测生物标志物的浓度。本实施例中，光强信号与生物标志物的浓度的对应关系为一线性关系，由于初始光强信号、初始浓度值和当前输出的数字信号对应的光强信号为已知，因此便可根据线性关系确定待测生物标志物的浓度。
参照图7，图7为本发明生物标志物浓度的检测方法第二实施例的流程示意图。
在上述本发明生物标志物浓度的检测方法第一实施例的基础上，第二实施例中，在执行步骤S10之前，该方法还包括：
步骤S40，聚光模块聚集有机电致发光元件所发出的光强信号。
在通过光谱接收模块接收有机电致发光元件所发出的光强信号之前，通过设置在光谱接收模块前端的聚光模块对光强信号进行聚集，使得散射的光强信号聚拢，以克服光强信号的光线散射和干涉等问题，使测量的光强信号最大量的被光接收模块接收，提高测量系统的精确度。该聚光模块可以采用聚光镜、凹凸透镜和LED灯杯等具有聚光作用的装置，优选地，聚光模块与光接收模块集成于一体。
以上仅为本发明的优选实施例，并非因此限制本发明的专利范围，凡是利用本发明说明书及附图内容所作的等效结构或等效流程变换，或直接或间接运用在其他相关的技术领域，均同理包括在本发明的专利保护范围内。

Claims (11)

  1. 一种用于检测生物标志物浓度的生物传感系统，其特征在于，所述用于检测生物标志物浓度的生物传感系统包括有机电致发光元件、光接收模块、光电信号转换模块，以及处理模块：
    所述光接收模块，用于接收所述有机电致发光元件所发出的光强信号，将所述光强信号发送至所述光电信号转换模块；
    所述光电信号转换模块，与所述光接收模块连接，用于将所述光强信号放大并转换成电信号，并将所述电信号转换成数字信号输出至所述处理模块；
    所述处理模块，与所述光电信号转换模块连接，用于根据所述数字信号的变化确定待测生物标志物的浓度；
    所述有机电致发光元件包括发光本体，所述发光本体包括发光层，所述发光层由有机电致发光材料制成；所述有机电致发光材料由以下通式（Ⅰ）表示：
    AB C （Ⅰ）
    式（Ⅰ）中，A表示有机电致发光化合物分子，B表示官能团，AB表示A经B官能团化后的产物；C表示抗体，C通过B与A结合以获得有机电致发光材料。
  2. 如权利要求1所述的用于检测生物标志物浓度的生物传感系统，其特征在于，所述A为大环共轭有机化合物分子；所述B为含-OH、-SH、-CHO、-COOH、-SO3H、-NH2、-CH2-、RCO-中一种或几种的碳链结构。
  3. 如权利要求1所述的用于检测生物标志物浓度的生物传感系统，其特征在于，所述光接收模块为荧光检测器或磷光检测器。
  4. 如权利要求3所述的用于检测生物标志物浓度的生物传感系统，其特征在于，所述A为大环共轭有机化合物分子；所述B为含-OH、-SH、-CHO、-COOH、-SO3H、-NH2、-CH2-、RCO-中一种或几种的碳链结构。
  5. 如权利要求1所述的用于检测生物标志物浓度的生物传感系统，其特征在于，所述用于检测生物标志物浓度的生物传感系统还包括：
    聚光模块，设置在所述光接收模块前端，用于聚集所述有机电致发光元件所发出的光强信号。
  6. 如权利要求5所述的用于检测生物标志物浓度的生物传感系统，其特征在于，所述A为大环共轭有机化合物分子；所述B为含-OH、-SH、-CHO、-COOH、-SO3H、-NH2、-CH2-、RCO-中一种或几种的碳链结构。
  7. 如权利要求1所述的用于检测生物标志物浓度的生物传感系统，其特征在于，所述发光层内设置有用于承载待测生物标志物的微通道，所述待测生物标志物在所述微通道中流动。
  8. 如权利要求7所述的用于检测生物标志物浓度的生物传感系统，其特征在于，所述A为大环共轭有机化合物分子；所述B为含-OH、-SH、-CHO、-COOH、-SO3H、-NH2、-CH2-、RCO-中一种或几种的碳链结构。
  9. 如权利要求8所述的用于检测生物标志物浓度的生物传感系统，其特征在于，所述待测生物标志物中的抗原与所述通式（Ⅰ）中的C结合。
  10. 一种利用如权利要求1所述的用于检测生物标志物浓度的生物传感系统检测生物标志物浓度的检测方法，其特征在于，所述检测方法包括如下步骤：
    光接收模块接收有机电致发光元件的发光层与待测生物标志物结合后所发出的光强信号，将所述光强信号发送至光电信号转换模块；
    光电信号转换模块将所述光强信号放大并转换成电信号，并将所述电信号转换成数字信号输出至处理模块；
    处理模块根据所述数字信号以及所述有机电致发光元件发出的初始光强信号，确定所述待测生物标志物的浓度。
  11. 如权利要求10所述的生物标志物浓度的检测方法，其特征在于，所述生物标志物浓度的检测方法还包括步骤：
    聚光模块聚集所述有机电致发光元件所发出的光强信号。
PCT/CN2015/073835 2015-02-11 2015-03-07 用于检测生物标志物浓度的生物传感系统及其检测方法 Ceased WO2016127457A1 (zh)

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