WO2021169242A1 - Dual-channel electrochemical biosensor and method for measuring heme concentration - Google Patents

Dual-channel electrochemical biosensor and method for measuring heme concentration Download PDF

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WO2021169242A1
WO2021169242A1 PCT/CN2020/114236 CN2020114236W WO2021169242A1 WO 2021169242 A1 WO2021169242 A1 WO 2021169242A1 CN 2020114236 W CN2020114236 W CN 2020114236W WO 2021169242 A1 WO2021169242 A1 WO 2021169242A1
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electrode group
electrode
reagent layer
dual
channel
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Chinese (zh)
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危亮
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江苏鱼跃医疗设备股份有限公司
江苏鱼跃信息系统有限公司
南京鱼跃软件技术有限公司
苏州医疗用品厂有限公司
苏州鱼跃医疗科技有限公司
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Priority to DE212020000534.6U priority Critical patent/DE212020000534U1/en
Publication of WO2021169242A1 publication Critical patent/WO2021169242A1/en

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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
    • G01N27/416—Systems
    • G01N27/4163—Systems checking the operation of, or calibrating, the measuring apparatus
    • 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
    • G01N27/28—Electrolytic cell components
    • G01N27/30—Electrodes, e.g. test electrodes; Half-cells
    • G01N27/327—Biochemical electrodes, e.g. electrical or mechanical details for in vitro measurements
    • G01N27/3271—Amperometric enzyme electrodes for analytes in body fluids, e.g. glucose in blood
    • G01N27/3272—Test elements therefor, i.e. disposable laminated substrates with electrodes, reagent and channels
    • 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
    • G01N27/27—Association of two or more measuring systems or cells, each measuring a different parameter, where the measurement results may be either used independently, the systems or cells being physically associated, or combined to produce a value for a further parameter
    • 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
    • G01N27/28—Electrolytic cell components
    • G01N27/30—Electrodes, e.g. test electrodes; Half-cells
    • G01N27/327—Biochemical electrodes, e.g. electrical or mechanical details for in vitro measurements
    • G01N27/3271—Amperometric enzyme electrodes for analytes in body fluids, e.g. glucose in blood
    • G01N27/3274—Corrective measures, e.g. error detection, compensation for temperature or hematocrit, calibration

Definitions

  • the invention belongs to the technical field of biosensing, and specifically relates to a dual-channel electrochemical biosensor and a method for measuring heme concentration.
  • Biosensors have been widely used in the fields of medical testing, environmental analysis and food testing. Electrochemical biosensors chemically react with the analyte to be tested in a certain way, and convert the reaction signal into an electrical signal that can be analyzed and measured. A technique for qualitative or quantitative analysis of an object. This type of sensor has the characteristics of simple operation, small sample size, high accuracy, low production cost, and can be used for real-time detection. However, the current electrochemical biosensor is easily affected by hematocrit when testing the concentration of analyte in blood samples. , Thereby causing interference to the test analyte concentration results. The existing hematocrit test methods mostly use the blood flow rate method, the conductance method or the impedance method, and correct the analyte concentration. These methods are greatly affected by the stability of the printed electrode of the sensor and the properties of the hydrophilic layer film material. Therefore, the development of new detection methods to improve the sensitivity and accuracy of the detection means is a major problem that needs to be solved urgently.
  • the hematocrit level causes a large deviation in the detection of the component concentration in the blood.
  • the higher hematocrit hinders the electron transfer between the electron enzyme mediator and the reaction component, and the signal value obtained is low.
  • the test result will be higher.
  • the current hematocrit correction technology is susceptible to the influence of the enzyme layer on blood components, resulting in unstable detection signals, it is difficult to accurately determine the actual hematocrit level of the blood, and accurate detection results cannot be obtained.
  • the invention provides a dual-channel electrochemical biosensor and a method for measuring heme concentration, which can be used to eliminate the influence of hematocrit on the measurement of analyte concentration and improve the accuracy of detection.
  • a dual-channel electrochemical biosensor includes a base layer.
  • the lower end of the base layer is provided with a first electrode group, a second electrode group, the first electrode group, and the second electrode group are all provided with a counter electrode, a working electrode, and an electrode output terminal
  • the first electrode group, the second electrode group share the counter electrode, the first electrode group, the counter electrode of the second electrode group, the working electrode and the electrode output terminal are connected with conductive lines
  • the substrate layer is provided with two reaction channels, two A counter electrode of a fixed area is exposed in each reaction channel, and the working electrodes of the first electrode group and the second electrode group are respectively exposed;
  • the reaction channel is provided with a hydrophilic layer;
  • the front end of the reaction channel is provided with an inlet for the liquid to be tested.
  • the hydrophilic layer at the rear end of the reaction channel may be respectively provided with pores.
  • the two reaction channels are respectively provided with a first reagent layer and a second reagent layer; the first reagent layer includes a hemolytic agent, a first electronic mediator, and a first stabilizer; the second reagent layer includes a surfactant and a second electronic mediator Body, enzyme, second stabilizer.
  • the buffer solution in the first reagent layer is used to maintain the pH value in the range of 6 to 8
  • the buffer solution in the second reagent layer is used to maintain the pH value in the range of 5 to 8.
  • the first electron mediator includes one of potassium ferricyanide, ferrocene, dimethylferrocene, and ferrocene dicarboxylate.
  • the second electron mediator includes one of potassium ferricyanide, ruthenium hexaammonium trichloride, tetrathiafulvalene, ferrocene, dimethylferrocene, and ferrocene dicarboxylate.
  • the hemolytic agent in the first reagent layer includes one or a combination of saponin, dodecyl sulfuric acid, cetyltrimethylammonium bromide, and triton.
  • the surfactant in the second reagent layer includes one or a combination of saponin, dodecylsulfuric acid, cetyltrimethylammonium bromide, and triton.
  • the first electrode group and the second electrode group adopt: gold electrode, carbon electrode, silver electrode or any combination between them.
  • the invention also discloses a method for measuring the heme concentration by using the above-mentioned electrochemical biosensor.
  • test conditions are as follows: the first reaction channel and the second reaction channel are respectively applied to conduct the reaction under constant potential between 0.2 and 1 volt; the buffer solution in the first reagent layer is used to maintain the pH value in the range of 6 to 8. The buffer solution in the second reagent layer is used to maintain the pH value in the range of 5-8.
  • the first electron mediator includes one of potassium ferricyanide, ferrocene, dimethylferrocene, and ferrocene dicarboxylate.
  • the second electron mediator includes one of potassium ferricyanide, ruthenium hexaammonium trichloride, tetrathiafulvalene, ferrocene, dimethylferrocene, and ferrocene dicarboxylate.
  • the hemolytic agent in the first reagent layer includes one or a combination of saponin, dodecyl sulfuric acid, cetyltrimethylammonium bromide, and triton.
  • the surfactant in the second reagent layer includes one or a combination of saponin, dodecylsulfuric acid, cetyltrimethylammonium bromide, and triton.
  • the present invention has the following technical solution features:
  • the present invention provides a brand-new electrochemical test strip structure, which has multiple functions, a small amount of blood used, fast blood inflow, and convenient operation.
  • the electrochemical test strip of the present invention can be divided into two circuit structures and two reagent layer printing structures, which can meet multi-purpose test requirements.
  • the electrochemical test strip of the present invention can save a large production cost and has a good industrial application prospect.
  • Fig. 1 is a schematic structural diagram of a dual-channel electrochemical biosensor according to an embodiment of the present invention.
  • FIG. 1 is a schematic structural diagram of a dual-channel electrochemical biosensor with hematocrit correction according to this embodiment.
  • the figure includes a base layer 13, a conductive layer disposed on the base layer 13, and an insulating layer 11 above the conductive layer.
  • the upper end of the conductive layer includes electrode output terminals 1 to 5, and the lower end of the conductive layer includes a first working electrode 6 and a second working electrode 7, and a counter electrode 8 shared by the first working electrode 6 and the second working electrode 7.
  • a conductive circuit 16 is connected between the first working electrode 6, the second working electrode 7, the counter electrode 8 and the electrode output terminals 1 to 5.
  • the first working electrode 6 and the counter electrode 8 constitute a first electrode group, and the second working electrode 7 and the counter electrode 8 constitute a second electrode group.
  • the insulating layer 11 covers the part above the pins of the detection electrode group, and two inverted Y-shaped reaction channels are arranged according to the arrangement of the conductive layer electrodes, namely the first channel 9 (first reagent layer) and the second channel 10 (second Reagent layer).
  • a hydrophilic layer 12 is provided in the reaction channel.
  • the front end of the hydrophilic layer 12 is provided with an inlet 14 for the liquid to be tested; the hydrophilic layer 12 at the rear end of the reaction channel is provided with pores 15 respectively.
  • the first electrode group and the second electrode group adopt silver and carbon electrodes.
  • the test conditions are: the first reaction channel and the second reaction channel are respectively applied to the first reaction channel and the second reaction channel under constant potential conditions of 0.2 to 1 volt for reaction; the first reagent layer
  • the buffer solution in 9 is used to maintain the pH value in the range of 6 to 8
  • the buffer solution in the second reagent layer 10 is used to maintain the pH value in the range of 5 to 8.
  • the first reagent layer 9 includes a hemolytic agent, a first electron mediator, and a first stabilizer
  • the second reagent layer 10 includes a surfactant, a second electron mediator, an enzyme, and a second stabilizer.
  • the first electron mediator includes one of potassium ferricyanide, ferrocene, dimethylferrocene, and ferrocene dicarboxylate.
  • the second electron mediator includes one of potassium ferricyanide, ruthenium hexaammonium trichloride, tetrathiafulvalene, ferrocene, dimethylferrocene, and ferrocene dicarboxylate.
  • the hemolytic agent in the first reagent layer includes one or a combination of saponin, dodecyl sulfate, cetyltrimethylammonium bromide, and triton.
  • the surfactant in the second reagent layer includes one or a combination of saponin, dodecyl sulfuric acid, cetyltrimethylammonium bromide, and triton.
  • the biosensor and method of this embodiment can be used for hematocrit correction.
  • determine the hematocrit value of the blood sample and use the measured hematocrit value to analyze
  • the concentration of the analyte is corrected to eliminate the influence of the hematocrit on the determination of the analyte concentration and improve the accuracy of the analyte concentration test.

Abstract

A dual-channel electrochemical biosensor and a method for measuring heme concentration by using a dual-channel electrochemical biosensor. The dual-channel electrochemical biosensor comprises a substrate layer (13), a first electrode group and a second electrode group being provided at the lower end of the substrate layer (13); each of the first electrode group and the second electrode group is provided with a counter electrode, working electrodes and electrode output ends; the first electrode group and the second electrode group share a counter electrode (8); the counter electrode (8), the working electrodes (6, 7) and the electrode output ends (1, 2, 3, 4, 5) of the first electrode group and the second electrode group are connected to a conductive circuit (16); two reaction channels (9, 10) are provided on the substrate layer; the counter electrode, having a fixed area, is exposed in the two reaction channels, and the working electrodes of the first electrode group and the second electrode group are each exposed; a hydrophilic layer (12) is provided on the reaction channels; a liquid inlet (14) to be detected is disposed at the front end of the reaction channels; and a first reagent layer and a second reagent layer are provided on the two reaction channels, respectively.

Description

一种双通道电化学生物传感器及测量血红素浓度的方法Double-channel electrochemical biosensor and method for measuring heme concentration 技术领域Technical field
本发明属于生物传感技术领域，具体涉及一种双通道电化学生物传感器及测量血红素浓度的方法。The invention belongs to the technical field of biosensing, and specifically relates to a dual-channel electrochemical biosensor and a method for measuring heme concentration.
背景技术Background technique
生物传感器已经广泛应用在医药检测、环境分析及食品检测等领域，电化学生物传感器是通过一定的方式与待测分析物发生化学反应，并将反应信号转化成可分析测量的电信号，从而对待测物进行定性或定量分析的一种技术。该类传感器具有操作简单、样本量少，准确度高、制作成本低以及能用于实时检测等特点，但目前电化学生物传感器在测试血样中分析物浓度时很容易受到血液红细胞压积的影响，从而对测试分析物浓度结果造成干扰。现有的红细胞压积测试方法多是利用血液流速法、电导法或阻抗法，并对分析物浓度进行校正。这些方法受传感器印刷电极稳定性、亲水层薄膜材料性质的影响较大，所以发展新的检测方法，提高检测手段的灵敏度、准确性，是急需解决的主要问题。Biosensors have been widely used in the fields of medical testing, environmental analysis and food testing. Electrochemical biosensors chemically react with the analyte to be tested in a certain way, and convert the reaction signal into an electrical signal that can be analyzed and measured. A technique for qualitative or quantitative analysis of an object. This type of sensor has the characteristics of simple operation, small sample size, high accuracy, low production cost, and can be used for real-time detection. However, the current electrochemical biosensor is easily affected by hematocrit when testing the concentration of analyte in blood samples. , Thereby causing interference to the test analyte concentration results. The existing hematocrit test methods mostly use the blood flow rate method, the conductance method or the impedance method, and correct the analyte concentration. These methods are greatly affected by the stability of the printed electrode of the sensor and the properties of the hydrophilic layer film material. Therefore, the development of new detection methods to improve the sensitivity and accuracy of the detection means is a major problem that needs to be solved urgently.
在电化学生物传感器中，红细胞压积水平使血液中成分浓度的检测产生较大的偏差，红细胞压积较高阻碍电子酶介体和反应成分之间的电子传递，得到的信号值偏低，红细胞压积较低时又会使检测结果偏高。目前红细胞压积校正技术中容易受到酶层对血液成分的影响，导致检测信号不稳定，很难准确判断血液的实际红细胞压积水平，无法得到准确的检测结果。In electrochemical biosensors, the hematocrit level causes a large deviation in the detection of the component concentration in the blood. The higher hematocrit hinders the electron transfer between the electron enzyme mediator and the reaction component, and the signal value obtained is low. When the hematocrit is low, the test result will be higher. The current hematocrit correction technology is susceptible to the influence of the enzyme layer on blood components, resulting in unstable detection signals, it is difficult to accurately determine the actual hematocrit level of the blood, and accurate detection results cannot be obtained.
发明内容Summary of the invention
本发明提供一种双通道电化学生物传感器，以及一种测定血红素浓度的方法，可用于消除血液红细胞压积对分析物浓度测量的影响，提高检测的准确度。The invention provides a dual-channel electrochemical biosensor and a method for measuring heme concentration, which can be used to eliminate the influence of hematocrit on the measurement of analyte concentration and improve the accuracy of detection.
一种双通道电化学生物传感器，包括基底层，基底层的下端设有第一电极组，第二电极组，第一电极组，第二电极组都设置有对电极、工作电极、电极输出端；其中第一电极组，第二电极组共用对电极，第一电极组，第二电极组的对电极、工作电极与电极输出端连接有导电线路，基底层上设有两个反应通道，两个反应通道中均暴露固定面积的对电极，并分别暴露第一电极组、第二电极组的工作电极；反应通道上设有亲水层；反应通道前端设置有待测液入口，优选方式中反应通道后端亲水层上可以分别设有气孔。两个反应通道上分别设有第一试剂层、第二试剂层；第一试剂层包括溶血剂，第一电子媒介体，第一稳定剂；第二试剂层包括表面活性剂、第二电子媒介体、酶、第二稳定剂。A dual-channel electrochemical biosensor includes a base layer. The lower end of the base layer is provided with a first electrode group, a second electrode group, the first electrode group, and the second electrode group are all provided with a counter electrode, a working electrode, and an electrode output terminal Wherein the first electrode group, the second electrode group share the counter electrode, the first electrode group, the counter electrode of the second electrode group, the working electrode and the electrode output terminal are connected with conductive lines, the substrate layer is provided with two reaction channels, two A counter electrode of a fixed area is exposed in each reaction channel, and the working electrodes of the first electrode group and the second electrode group are respectively exposed; the reaction channel is provided with a hydrophilic layer; the front end of the reaction channel is provided with an inlet for the liquid to be tested. The hydrophilic layer at the rear end of the reaction channel may be respectively provided with pores. The two reaction channels are respectively provided with a first reagent layer and a second reagent layer; the first reagent layer includes a hemolytic agent, a first electronic mediator, and a first stabilizer; the second reagent layer includes a surfactant and a second electronic mediator Body, enzyme, second stabilizer.
进一步的，第一试剂层中缓冲溶液用于使pH值维持在6至8的范围，第二试剂层中缓冲溶液用于使pH值维持在5至8的范围。Further, the buffer solution in the first reagent layer is used to maintain the pH value in the range of 6 to 8, and the buffer solution in the second reagent layer is used to maintain the pH value in the range of 5 to 8.
作为优选的，第一电子媒介体包括铁氰化钾、二茂铁、二甲基二茂铁、二甲酸二茂铁中的一种。Preferably, the first electron mediator includes one of potassium ferricyanide, ferrocene, dimethylferrocene, and ferrocene dicarboxylate.
作为优选的，第二电子媒介体包括铁氰化钾、三氯六铵合钌、四硫富瓦烯、二茂铁、二甲基二茂铁、二甲酸二茂铁中的一种。Preferably, the second electron mediator includes one of potassium ferricyanide, ruthenium hexaammonium trichloride, tetrathiafulvalene, ferrocene, dimethylferrocene, and ferrocene dicarboxylate.
作为优选的，第一试剂层中溶血剂包括皂素、十二烷基硫酸、十六烷基三甲基溴化铵、曲拉通中的一种或者多种的组合。Preferably, the hemolytic agent in the first reagent layer includes one or a combination of saponin, dodecyl sulfuric acid, cetyltrimethylammonium bromide, and triton.
作为优选的，第二试剂层中表面活性剂包括皂素、十二烷基硫酸、十六烷基三甲基溴化铵、曲拉通中的一种或者多种的组合。Preferably, the surfactant in the second reagent layer includes one or a combination of saponin, dodecylsulfuric acid, cetyltrimethylammonium bromide, and triton.
上述的带红细胞压积校正的双通道电化学生物传感器，第一电极组和第二电极组采用：金电极、碳电极、银电极或它们之间任意组合。In the above-mentioned dual-channel electrochemical biosensor with hematocrit correction, the first electrode group and the second electrode group adopt: gold electrode, carbon electrode, silver electrode or any combination between them.
本发明还公开一种利用上述的电化学生物传感器测量血红素浓度的方法。The invention also discloses a method for measuring the heme concentration by using the above-mentioned electrochemical biosensor.
测试条件为：分别施加在第一反应通道和第二反应通道介于0.2至1伏的恒电位条件下进行反应；第一试剂层中缓冲溶液用于使pH值维持在6至8的范围，第二试剂层中缓冲溶液用于使pH值维持在5至8的范围。The test conditions are as follows: the first reaction channel and the second reaction channel are respectively applied to conduct the reaction under constant potential between 0.2 and 1 volt; the buffer solution in the first reagent layer is used to maintain the pH value in the range of 6 to 8. The buffer solution in the second reagent layer is used to maintain the pH value in the range of 5-8.
作为优选的，第一电子媒介体包括铁氰化钾、二茂铁、二甲基二茂铁、二甲酸二茂铁中的一种。Preferably, the first electron mediator includes one of potassium ferricyanide, ferrocene, dimethylferrocene, and ferrocene dicarboxylate.
作为优选的，第二电子媒介体包括铁氰化钾、三氯六铵合钌、四硫富瓦烯、二茂铁、二甲基二茂铁、二甲酸二茂铁中的一种。Preferably, the second electron mediator includes one of potassium ferricyanide, ruthenium hexaammonium trichloride, tetrathiafulvalene, ferrocene, dimethylferrocene, and ferrocene dicarboxylate.
作为优选的，第一试剂层中溶血剂包括皂素、十二烷基硫酸、十六烷基三甲基溴化铵、曲拉通中的一种或者多种的组合。Preferably, the hemolytic agent in the first reagent layer includes one or a combination of saponin, dodecyl sulfuric acid, cetyltrimethylammonium bromide, and triton.
作为优选的，第二试剂层中表面活性剂包括皂素、十二烷基硫酸、十六烷基三甲基溴化铵、曲拉通中的一种或者多种的组合。Preferably, the surfactant in the second reagent layer includes one or a combination of saponin, dodecylsulfuric acid, cetyltrimethylammonium bromide, and triton.
相对现有技术，本发明具有如下技术方案特色：Compared with the prior art, the present invention has the following technical solution features:
(1)本发明提供了一种全新的电化学测试条结构，该结构功能多样、使用血液量少、进血速度快、操作便捷。(1) The present invention provides a brand-new electrochemical test strip structure, which has multiple functions, a small amount of blood used, fast blood inflow, and convenient operation.
(2)本发明电化学测试条可以分为两种电路结构，两种试剂层印刷结构，可以满足多用途测试要求。(2) The electrochemical test strip of the present invention can be divided into two circuit structures and two reagent layer printing structures, which can meet multi-purpose test requirements.
(3)本发明电化学测试条可以节省较大的生产成本，具有很好地工业应用前景。(3) The electrochemical test strip of the present invention can save a large production cost and has a good industrial application prospect.
附图说明Description of the drawings
图1为本发明实施例的双通道电化学生物传感器的结构示意图。Fig. 1 is a schematic structural diagram of a dual-channel electrochemical biosensor according to an embodiment of the present invention.
具体实施方式Detailed ways
为了本相关领域的技术人员能够理解本发明方案，结合本发明实施例中附图，对本发明实施例中的技术方案进行完整明确地描述，显然，所描述的实施例仅仅是本发明部分实施例，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。In order for those skilled in the art to understand the solutions of the present invention, the technical solutions in the embodiments of the present invention are described completely and clearly in conjunction with the accompanying drawings in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention. , Not all examples. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative work shall fall within the protection scope of the present invention.
图1为本实施例的带红细胞压积校正的双通道电化学生物传感器的结构示意图，图中包括基底层13，设置在基底层13上的导电层，以及导电层上方的绝缘层11。导电层上端包括电极输出端1～5，导电层下端包括第一工作电极6和第二工作电极7，以及第一工作电极6和第二工作电极7共用的对电极8。第一工作电极6、第二工作电极7、对电极8与电极输出端1～5之间连接有导电线路16。第一工作电极6和对电极8构成第一电极组，第二工作电极7和对电极8构成第二电极组。绝缘层11覆盖检测电极组接脚以上的部分，并且根据导电层电 极排列方式设置倒Y型的两个反应通道，分别为第一通道9(第一试剂层)、第二通道10(第二试剂层)。反应通道内设置亲水层12。亲水层12的前端设置有待测液入口14；反应通道后端亲水层12上分别设有气孔15。本实施例的带红细胞压积校正的双通道电化学生物传感器，第一电极组和第二电极组采用银、碳电极。1 is a schematic structural diagram of a dual-channel electrochemical biosensor with hematocrit correction according to this embodiment. The figure includes a base layer 13, a conductive layer disposed on the base layer 13, and an insulating layer 11 above the conductive layer. The upper end of the conductive layer includes electrode output terminals 1 to 5, and the lower end of the conductive layer includes a first working electrode 6 and a second working electrode 7, and a counter electrode 8 shared by the first working electrode 6 and the second working electrode 7. A conductive circuit 16 is connected between the first working electrode 6, the second working electrode 7, the counter electrode 8 and the electrode output terminals 1 to 5. The first working electrode 6 and the counter electrode 8 constitute a first electrode group, and the second working electrode 7 and the counter electrode 8 constitute a second electrode group. The insulating layer 11 covers the part above the pins of the detection electrode group, and two inverted Y-shaped reaction channels are arranged according to the arrangement of the conductive layer electrodes, namely the first channel 9 (first reagent layer) and the second channel 10 (second Reagent layer). A hydrophilic layer 12 is provided in the reaction channel. The front end of the hydrophilic layer 12 is provided with an inlet 14 for the liquid to be tested; the hydrophilic layer 12 at the rear end of the reaction channel is provided with pores 15 respectively. In the dual-channel electrochemical biosensor with hematocrit correction in this embodiment, the first electrode group and the second electrode group adopt silver and carbon electrodes.
利用本实施例的电化学生物传感器测量血红素浓度的方法，测试条件为：分别施加在第一反应通道和第二反应通道介于0.2至1伏的恒电位条件下进行反应；第一试剂层9中缓冲溶液用于使pH值维持在6至8的范围，第二试剂层10中缓冲溶液用于使pH值维持在5至8的范围。第一试剂层9包括溶血剂，第一电子媒介体，第一稳定剂；第二试剂层10包括表面活性剂、第二电子媒介体、酶、第二稳定剂。Using the electrochemical biosensor of this embodiment to measure the concentration of heme, the test conditions are: the first reaction channel and the second reaction channel are respectively applied to the first reaction channel and the second reaction channel under constant potential conditions of 0.2 to 1 volt for reaction; the first reagent layer The buffer solution in 9 is used to maintain the pH value in the range of 6 to 8, and the buffer solution in the second reagent layer 10 is used to maintain the pH value in the range of 5 to 8. The first reagent layer 9 includes a hemolytic agent, a first electron mediator, and a first stabilizer; the second reagent layer 10 includes a surfactant, a second electron mediator, an enzyme, and a second stabilizer.
第一电子媒介体包括铁氰化钾、二茂铁、二甲基二茂铁、二甲酸二茂铁中的一种。第二电子媒介体包括铁氰化钾、三氯六铵合钌、四硫富瓦烯、二茂铁、二甲基二茂铁、二甲酸二茂铁中的一种。第一试剂层中溶血剂包括皂素、十二烷基硫酸、十六烷基三甲基溴化铵、曲拉通中的一种或者多种的组合。第二试剂层中表面活性剂包括皂素、十二烷基硫酸、十六烷基三甲基溴化铵、曲拉通中的一种或者多种的组合。The first electron mediator includes one of potassium ferricyanide, ferrocene, dimethylferrocene, and ferrocene dicarboxylate. The second electron mediator includes one of potassium ferricyanide, ruthenium hexaammonium trichloride, tetrathiafulvalene, ferrocene, dimethylferrocene, and ferrocene dicarboxylate. The hemolytic agent in the first reagent layer includes one or a combination of saponin, dodecyl sulfate, cetyltrimethylammonium bromide, and triton. The surfactant in the second reagent layer includes one or a combination of saponin, dodecyl sulfuric acid, cetyltrimethylammonium bromide, and triton.
本实施例的生物传感器及方法可用于红细胞压积校正。首先建立不同红细胞压积与血液样本中血红素浓度电流相关性曲线，根据已确定的电流与红细胞压积的相关性曲线，确定血样的红细胞压积值，用已测定血液红细胞压积值对分析物浓度进行校正，消除红细胞压积对分析物浓度测定的影响，提高分析物浓度测试准确度。The biosensor and method of this embodiment can be used for hematocrit correction. First, establish the current correlation curve between different hematocrit and heme concentration in the blood sample. According to the determined correlation curve between current and hematocrit, determine the hematocrit value of the blood sample, and use the measured hematocrit value to analyze The concentration of the analyte is corrected to eliminate the influence of the hematocrit on the determination of the analyte concentration and improve the accuracy of the analyte concentration test.
上述实施例只为说明本发明的技术方案和特征，其目的在于让熟悉此项技术的专业人员能够了解到本发明的内容并据以实施，并不能以此限制本发明的保护范围。凡基于本发明的原理对本发明所做出的各种改动或修改同样落入本发明权利要求书所限定。The above-mentioned embodiments are only to illustrate the technical solutions and features of the present invention, and their purpose is to enable professionals familiar with the technology to understand the content of the present invention and implement them accordingly, and should not limit the protection scope of the present invention. Any changes or modifications made to the present invention based on the principles of the present invention also fall within the scope of the claims of the present invention.

Claims (10)

  1. 一种双通道电化学生物传感器，其特征在于：包括基底层，基底层的下端设有第一电极组、第二电极组；第一电极组、第二电极组都设置有对电极、工作电极、电极输出端；其中第一电极组，第二电极组共用对电极，第一电极组，第二电极组的对电极、工作电极与电极输出端连接有导电线路，基底层上设有两个反应通道，两个反应通道中均暴露固定面积的对电极，并分别暴露第一电极组、第二电极组的工作电极；反应通道上设有亲水层；反应通道前端设置有待测液入口；两个反应通道上分别设有第一试剂层、第二试剂层；第一试剂层包括溶血剂，第一电子媒介体，第一稳定剂；第二试剂层包括表面活性剂、第二电子媒介体、酶、第二稳定剂。A dual-channel electrochemical biosensor, characterized in that it comprises a base layer, the lower end of the base layer is provided with a first electrode group and a second electrode group; both the first electrode group and the second electrode group are provided with a counter electrode and a working electrode , Electrode output terminal; wherein the first electrode group, the second electrode group share the counter electrode, the first electrode group, the second electrode group counter electrode, working electrode and the electrode output terminal are connected with a conductive circuit, the base layer is provided with two Reaction channel, in both reaction channels, a fixed area of the counter electrode is exposed, and the working electrodes of the first electrode group and the second electrode group are respectively exposed; the reaction channel is provided with a hydrophilic layer; the front end of the reaction channel is provided with a test liquid inlet ; The two reaction channels are respectively provided with a first reagent layer and a second reagent layer; the first reagent layer includes a hemolytic agent, a first electron mediator, and a first stabilizer; the second reagent layer includes a surfactant and a second electron Mediator, enzyme, second stabilizer.
  2. 根据权利要求1所述的双通道电化学生物传感器，其特征在于：The dual-channel electrochemical biosensor according to claim 1, wherein:
    第一试剂层中缓冲溶液用于使pH值维持在6至8的范围，第二试剂层中缓冲溶液用于使pH值维持在5至8的范围。The buffer solution in the first reagent layer is used to maintain the pH value in the range of 6 to 8, and the buffer solution in the second reagent layer is used to maintain the pH value in the range of 5 to 8.
  3. 根据权利要求1所述的双通道电化学生物传感器，其特征在于：The dual-channel electrochemical biosensor according to claim 1, wherein:
    第一电子媒介体包括铁氰化钾、二茂铁、二甲基二茂铁、二甲酸二茂铁中的一种。The first electron mediator includes one of potassium ferricyanide, ferrocene, dimethylferrocene, and ferrocene dicarboxylate.
  4. 根据权利要求1所述的双通道电化学生物传感器，其特征在于：The dual-channel electrochemical biosensor according to claim 1, wherein:
    第二电子媒介体包括铁氰化钾、三氯六铵合钌、四硫富瓦烯、二茂铁、二甲基二茂铁、二甲酸二茂铁中的一种。The second electron mediator includes one of potassium ferricyanide, ruthenium hexaammonium trichloride, tetrathiafulvalene, ferrocene, dimethylferrocene, and ferrocene dicarboxylate.
  5. 根据权利要求1所述的双通道电化学生物传感器，其特征在于：The dual-channel electrochemical biosensor according to claim 1, wherein:
    第一试剂层中溶血剂包括皂素、十二烷基硫酸、十六烷基三甲基溴化铵、曲拉通中的一种或者多种的组合。The hemolytic agent in the first reagent layer includes one or a combination of saponin, dodecyl sulfate, cetyltrimethylammonium bromide, and triton.
  6. 根据权利要求1所述的双通道电化学生物传感器，其特征在于：The dual-channel electrochemical biosensor according to claim 1, wherein:
    第二试剂层中表面活性剂包括皂素、十二烷基硫酸、十六烷基三甲基溴化铵、曲拉通中的一种或者多种的组合。The surfactant in the second reagent layer includes one or a combination of saponin, dodecyl sulfuric acid, cetyltrimethylammonium bromide, and triton.
  7. 一种利用权利要求1所述的双通道电化学生物传感器测量血红素浓度的方法，其特征在于：分别施加在第一反应通道和第二反应通道介于0.2至1伏的恒电位条件下进行反应；第一试剂层中缓冲溶液用于使pH值维持在6至8的范围，第二试剂层中缓冲溶液用于使pH值维持在5至8的范围。A method for measuring hemoglobin concentration using the dual-channel electrochemical biosensor according to claim 1, characterized in that: the first reaction channel and the second reaction channel are respectively applied under constant potential conditions of 0.2 to 1 volt. Reaction; the buffer solution in the first reagent layer is used to maintain the pH value in the range of 6 to 8, and the buffer solution in the second reagent layer is used to maintain the pH value in the range of 5 to 8.
  8. 根据权利要求7所述的测量血红素浓度的方法，其特征在于：The method for measuring hemoglobin concentration according to claim 7, characterized in that:
    第一电子媒介体包括铁氰化钾、二茂铁、二甲基二茂铁、二甲酸二茂铁中的一种；The first electron mediator includes one of potassium ferricyanide, ferrocene, dimethylferrocene, and ferrocene dicarboxylate;
    第二电子媒介体包括铁氰化钾、三氯六铵合钌、四硫富瓦烯、二茂铁、二甲基二茂铁、二甲酸二茂铁中的一种。The second electron mediator includes one of potassium ferricyanide, ruthenium hexaammonium trichloride, tetrathiafulvalene, ferrocene, dimethylferrocene, and ferrocene dicarboxylate.
  9. 根据权利要求7所述的测量血红素浓度的方法，其特征在于：The method for measuring hemoglobin concentration according to claim 7, characterized in that:
    第一试剂层中溶血剂包括皂素、十二烷基硫酸、十六烷基三甲基溴化铵、曲拉通中的一种或者多种的组合。The hemolytic agent in the first reagent layer includes one or a combination of saponin, dodecyl sulfate, cetyltrimethylammonium bromide, and triton.
  10. 根据权利要求7所述的测量血红素浓度的方法，其特征在于：The method for measuring hemoglobin concentration according to claim 7, characterized in that:
    第二试剂层中表面活性剂包括皂素、十二烷基硫酸、十六烷基三甲基溴化铵、曲拉通中的一种或者多种的组合。The surfactant in the second reagent layer includes one or a combination of saponin, dodecyl sulfuric acid, cetyltrimethylammonium bromide, and triton.
PCT/CN2020/114236 2020-02-24 2020-09-09 Dual-channel electrochemical biosensor and method for measuring heme concentration WO2021169242A1 (en)

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