技术领域technical field
本发明涉及一种葡萄糖传感器。特别是涉及一种可实现组织液透皮抽取和测量抽取的组织液中葡萄糖浓度的一体化的柔性差分式阵列电化学葡萄糖传感器及使用方法。The present invention relates to a glucose sensor. In particular, it relates to an integrated flexible differential array electrochemical glucose sensor capable of realizing the transdermal extraction of interstitial fluid and measuring the glucose concentration in the extracted interstitial fluid and its use method.
背景技术Background technique
随着人们生活水平的提高，饮食结构的变化以及生活方式的改变，人口老龄化以及肥胖发生率的增加，糖尿病的发病率呈逐年上升趋势。连续血糖监测对糖尿病诊治的重要意义越来越被人们所认识。如果能对患者进行无痛而又不间断的连续血糖监测，提供更为密切的血糖浓度连续变化的数据，就能够反映患者的血糖“全貌”，测量出那些被忽略的血糖信息，揭示出隐藏的血糖状态，发现那些无自觉症状的反复低血糖发作、黎明现象和高血糖的峰值等，为拟定更加合理﹑个体化的降糖治疗方案，提供有价值的临床依据，从而更好地指导糖尿病的治疗。With the improvement of people's living standards, changes in diet structure and lifestyle, population aging and the increase in the incidence of obesity, the incidence of diabetes is increasing year by year. The importance of continuous blood glucose monitoring in the diagnosis and treatment of diabetes has been increasingly recognized by people. If painless and uninterrupted continuous blood glucose monitoring can be performed on patients and more closely data on continuous changes in blood glucose concentration can be provided, it will be able to reflect the "full picture" of the patient's blood glucose, measure those neglected blood glucose information, and reveal the hidden The state of blood sugar, to find those repeated episodes of hypoglycemia, the dawn phenomenon and the peak of hyperglycemia without subjective symptoms, etc., to provide a valuable clinical basis for formulating a more reasonable and individualized hypoglycemic treatment plan, so as to better guide diabetes Treatment.
目前的血糖监测多采用快速指尖采血来检测血糖。由于检测方法的限制，血糖监测只能在孤立的时间点完成，其结果反映的是一天中某几个时刻的瞬间血糖。然而，瞬间血糖浓度容易受运动、饮食、药物、情绪波动等诸多因素的影响，存在着一定的片面性和不准确性。为了更全面地反映人体血糖浓度的变化，就必须实现血糖浓度的连续检测。无创和微创检测技术使得血糖浓度的连续检测成为可能。无创血糖检测技术不需要提取血液等体内物质，不需要将传感器植入皮下，依靠光与人体特定部位组织的相互作用来检测病人体内血糖浓度的变化，是最理想的人体血糖检测方法。微创血糖浓度检测技术是通过将传感器植入皮下或通过组织液透皮抽取的方法来测量人体组织液中葡萄糖浓度，再根据组织液中葡萄糖浓度与血液中葡萄糖浓度的关系得到血液中葡萄糖浓度。微创血糖检测技术在最大限度地减少创伤的基础上，可实现人体血糖浓度的动态、连续监测，技术原理相对简单，具有可实现性强、使用方便、测量速度快等特点。Current blood sugar monitoring mostly uses quick fingertip blood sampling to detect blood sugar. Due to the limitations of detection methods, blood glucose monitoring can only be done at isolated time points, and the results reflect the instantaneous blood glucose at certain times of the day. However, the instantaneous blood sugar concentration is easily affected by many factors such as exercise, diet, drugs, mood swings, etc., and there is a certain one-sidedness and inaccuracy. In order to more comprehensively reflect the changes of blood glucose concentration in the human body, continuous detection of blood glucose concentration must be realized. Non-invasive and minimally invasive detection technology makes continuous detection of blood glucose concentration possible. Non-invasive blood sugar detection technology does not need to extract blood and other body substances, does not need to implant sensors under the skin, and relies on the interaction between light and specific parts of the human body to detect changes in blood sugar concentration in the patient's body. It is the most ideal human blood sugar detection method. The minimally invasive blood glucose concentration detection technology is to measure the glucose concentration in the human tissue fluid by implanting the sensor under the skin or through the transdermal extraction of the tissue fluid, and then obtain the blood glucose concentration according to the relationship between the glucose concentration in the tissue fluid and the glucose concentration in the blood. Minimally invasive blood glucose detection technology can realize dynamic and continuous monitoring of human blood glucose concentration on the basis of minimizing trauma.
近年来有人发明制作了植入式的血糖连续监测设备，通过将葡萄糖传感器植入皮下，在皮下组织实现对组织液中葡萄糖浓度的检测，来计算得到血糖的浓度。但是这种设备的使用有一系列的问题，例如，植入式传感器不可避免的给人体带来创伤，使人体产生不舒服的感觉；而植入的传感器由于是在复杂的生物环境中使用，随着时间的推移，在传感器表面会不断的吸附蛋白质等物质，这些物质会阻碍传感器对葡萄糖的检测，使得检测得到的结果发生漂移，这就需要不断的采用采血校准的方法来矫正传感器的检测结果，加深了被检测者的痛苦，而蛋白质的吸附会不断进行，直至传感器完全不能工作，而这个过程最多也就几天，这大大限制了传感器的使用寿命，影响了传感器的检测精度。In recent years, someone has invented and produced an implantable continuous blood glucose monitoring device. By implanting a glucose sensor under the skin, the glucose concentration in the interstitial fluid can be detected in the subcutaneous tissue to calculate the blood glucose concentration. But the use of this device has a series of problems, for example, the implanted sensor will inevitably bring trauma to the human body, making the human body feel uncomfortable; and the implanted sensor is used in a complex biological environment. As time goes by, substances such as proteins will be continuously adsorbed on the surface of the sensor. These substances will hinder the detection of glucose by the sensor and cause the detection results to drift. This requires constant blood sampling to correct the detection results of the sensor. , which deepens the pain of the person being detected, and the adsorption of protein will continue until the sensor cannot work at all, and this process will only take a few days at most, which greatly limits the service life of the sensor and affects the detection accuracy of the sensor.
现在还有人利用微流控芯片来实现对组织液的透皮抽取，然后利用各种方法来实现对抽取的组织液的葡萄糖浓度的测量。这种方法虽然也能够得到血糖浓度，但是存在很多问题。首先其抽取得到的组织液是以液滴的形式存在于皮肤表面，很难收集，通常需要用缓冲液对其进行稀释，然后再进行测量，这就需要知道所抽取的组织液的体积，才能计算得到相应的葡萄糖浓度，增加了测量的复杂程度和误差；其次用微流控芯片抽取组织液，需要将液体转移后才能完成测量，在液体的转移过程中，不可避免的会损失一些，这就会造成测量结果出现较大的误差。At present, some people use microfluidic chips to realize the transdermal extraction of interstitial fluid, and then use various methods to realize the measurement of the glucose concentration of the extracted interstitial fluid. Although this method can also obtain the blood sugar concentration, there are many problems. First of all, the extracted interstitial fluid exists in the form of droplets on the skin surface, which is difficult to collect. Usually, it needs to be diluted with a buffer solution, and then measured. This requires knowing the volume of the extracted interstitial fluid to be calculated. The corresponding glucose concentration increases the complexity and error of the measurement; secondly, the microfluidic chip is used to extract the tissue fluid, and the measurement needs to be completed after the liquid is transferred. During the transfer process of the liquid, some will inevitably be lost, which will cause There are large errors in the measurement results.
发明内容Contents of the invention
本发明所要解决的技术问题是，提供一种测量精度高、体积小的柔性差分式阵列电化学葡萄糖传感器及使用方法。The technical problem to be solved by the present invention is to provide a flexible differential array electrochemical glucose sensor with high measurement accuracy and small volume and its use method.
本发明所采用的技术方案是：一种柔性差分式阵列电化学葡萄糖传感器，包括有并排设置有7个结构完全相同的传感器单元，每一个传感器单元都包括有柔性基底，以及设置在所述柔性基底上的第一个三电极单体和第二个三电极单体，所述的第一个三电极单体和第二个三电极单体结构完全相同，均包括有参比电极、辅助电极和工作电极。The technical solution adopted in the present invention is: a flexible differential array electrochemical glucose sensor, including 7 sensor units with identical structures arranged side by side, each sensor unit includes a flexible substrate, and is arranged on the flexible substrate. The first three-electrode monomer and the second three-electrode monomer on the substrate, the structure of the first three-electrode monomer and the second three-electrode monomer is exactly the same, and both include a reference electrode and an auxiliary electrode and working electrode.
所述的参比电极的结构为由柔性基底至上依次设置的一层铬、一层惰性金属铂和一层Ag/AgCl电极，所述的辅助电极和工作电极结构相同，均为由柔性基底至上依次设置的一层铬、一层惰性金属铂。The structure of the reference electrode is a layer of chromium, a layer of inert metal platinum, and a layer of Ag/AgCl electrode arranged sequentially from the flexible base up. The auxiliary electrode and the working electrode have the same structure, both from the flexible base up. A layer of chromium and a layer of inert metal platinum are arranged in sequence.
所述参比电极、辅助电极和工作电极为弧形或条形形状。The reference electrode, auxiliary electrode and working electrode are in the shape of arcs or strips.
所述的工作电极上固化有用于对葡萄糖分子的特异性进行检测的葡萄糖氧化酶。Glucose oxidase for detecting the specificity of glucose molecules is immobilized on the working electrode.
所述的第一个三电极单体中的工作电极和第二个三电极单体中的工作电极一起构成抽取电极对，当给两个工作电极加上直流电压时，其中第一个三电极单体中的工作电极处为用于聚集透皮抽取组织液的葡萄糖分子的负极，第二个三电极单体中的工作电极处为用于聚集不包括葡萄糖分子的组织液的正极。The working electrode in the first three-electrode monomer and the working electrode in the second three-electrode monomer together form an extraction electrode pair. When a DC voltage is applied to the two working electrodes, the first three-electrode The working electrode in the monomer is a negative electrode for gathering glucose molecules from transdermally extracted interstitial fluid, and the working electrode in the second three-electrode monomer is a positive pole for gathering interstitial fluid not including glucose molecules.
所述工作电极在结合作为抽取电极的同时，第一个三电极单体中的工作电极、辅助电极和参比电极一起构成一个电化学传感器，第二个三电极单体中的工作电极、辅助电极和参比电极一起构成另一个电化学传感器，从而实现在工作电极处组织液抽取点的葡萄糖分子的原位测量。When the working electrode is combined as an extraction electrode, the working electrode, auxiliary electrode and reference electrode in the first three-electrode monomer form an electrochemical sensor together, and the working electrode, auxiliary electrode and reference electrode in the second three-electrode monomer Together, the electrode and the reference electrode constitute another electrochemical sensor, enabling in situ measurement of glucose molecules at the point of interstitial fluid extraction at the working electrode.
所述的第一个三电极单体用于检测抽取的组织液中的葡萄糖浓度，第二个三电极单体用于检测背景组织液以及环境对传感器结果产生的影响，所述的第一个三电极单体和第二个三电极单体一起构成差分测量体系，用以消除测量过程中由环境变化而引起的误差。The first three-electrode monomer is used to detect the glucose concentration in the extracted interstitial fluid, the second three-electrode monomer is used to detect the background interstitial fluid and the influence of the environment on the sensor results, and the first three-electrode The monomer and the second three-electrode monomer together form a differential measurement system to eliminate errors caused by environmental changes during the measurement process.
一种柔性差分式阵列电化学葡萄糖传感器的使用方法，由7个传感器单元构成的阵列电化学葡萄糖传感器，每天使用1个传感器单元，达到实现7天的连续测量，利用换位测量的方式来降低由于组织液的长时间抽取而导致的皮肤过敏现象。A method for using a flexible differential array electrochemical glucose sensor. The array electrochemical glucose sensor consists of 7 sensor units. One sensor unit is used every day to achieve continuous measurement for 7 days, and the method of transposition measurement is used to reduce the Skin allergies due to prolonged extraction of interstitial fluid.
本发明的一种柔性差分式阵列电化学葡萄糖传感器及使用方法，具有体积小、精度高的优点，可以原位测量，实现了组织液透皮抽取和测量抽取的组织液中葡萄糖浓度的一体化，并解决抽取过程中传感器与皮肤的粘合问题以及长时间抽取造成的皮肤过敏等问题，去除环境因素对传感器测量结果的影响，同时实现对低浓度葡萄糖的检测。本发明具有如下优点：A flexible differential array electrochemical glucose sensor of the present invention and its use method have the advantages of small size and high precision, can be measured in situ, realize the integration of transdermal extraction of interstitial fluid and measurement of glucose concentration in the extracted interstitial fluid, and Solve the problem of adhesion between the sensor and the skin during the extraction process and skin allergies caused by long-term extraction, remove the influence of environmental factors on the measurement results of the sensor, and realize the detection of low-concentration glucose at the same time. The present invention has the following advantages:
1、将传感器是制作在柔性衬底上，利用柔性衬底的性质，让传感器随着皮肤的形变而形变，使传感器与皮肤紧密相连，从而让传感器能够稳定的工作，获得准确的测量结果。1. The sensor is made on a flexible substrate. Using the properties of the flexible substrate, the sensor deforms with the deformation of the skin, so that the sensor is closely connected with the skin, so that the sensor can work stably and obtain accurate measurement results.
2、传感器利用一个传感器单元中的两个工作电极形成组织液抽取电极对，以此来实现对于组织的透皮抽取，又通过两组三电极来实现对抽取的组织液中的葡萄糖浓度的测量，实现了组织液透皮抽取和测量抽取的组织液中葡萄糖浓度的一体化。2. The sensor uses two working electrodes in one sensor unit to form a pair of interstitial fluid extraction electrodes to realize the transdermal extraction of tissue, and to realize the measurement of the glucose concentration in the extracted interstitial fluid through two sets of three electrodes. The integration of transdermal extraction of interstitial fluid and measurement of glucose concentration in the extracted interstitial fluid is realized.
3、传感器在测量过程中利用了差分的原理，通过传感器单元中的两组三电极在相同条件下的共同测量实现差分(测量对象一个有葡萄糖，一个没有)，可去除在测量过程中由环境变化而引起的测量结果的误差。同时这里利用原位测量的方法，有利于更准确地获得葡萄糖的浓度。3. The sensor utilizes the principle of difference in the measurement process. The difference is realized through the common measurement of two groups of three electrodes in the sensor unit under the same conditions (one measurement object has glucose, and the other does not), which can eliminate the environmental influence during the measurement process. The error in the measurement result caused by the change. At the same time, the method of in-situ measurement is used here, which is beneficial to obtain the concentration of glucose more accurately.
4、传感器是由七个传感器单元形成的阵列式传感器，每天使用1个传感器单元，第二天撕下第一天已使用过的单元，利用新的传感器单元进行测量，能实现7天的连续测量。这相当于每天的测试位置不同，这种不同即可形容为利用换位测量的方式，这种方式可以有效的降低由于长时间抽取组织液而导致的皮肤过敏现象。4. The sensor is an array sensor formed by seven sensor units. One sensor unit is used every day, and the unit that has been used on the first day is torn off the next day, and the new sensor unit is used for measurement, which can achieve continuous 7 days Measurement. This is equivalent to different test locations every day. This difference can be described as the method of transposition measurement, which can effectively reduce skin allergies caused by long-term extraction of interstitial fluid.
附图说明Description of drawings
图1是本发明第一实施例的整体结构示意图；Fig. 1 is the overall structure schematic diagram of the first embodiment of the present invention;
图2是本发明第二实施例的整体结构示意图；Fig. 2 is a schematic diagram of the overall structure of the second embodiment of the present invention;
图3是本发明第一实施例传感器单元的结构示意图；3 is a schematic structural view of a sensor unit according to a first embodiment of the present invention;
图4是本发明第二实施例传感器单元的结构示意图；4 is a schematic structural view of a sensor unit according to a second embodiment of the present invention;
图5是本发明第一实施例中第一、第二三电极单体的结构示意图；5 is a schematic structural view of the first and second three-electrode monomers in the first embodiment of the present invention;
图6是本发明第二实施例中第一、第二三电极单体的结构示意图。Fig. 6 is a schematic structural view of the first and second three-electrode monomers in the second embodiment of the present invention.
图中in the picture
1：传感器单元 2：第一个三电极单体1: Sensor unit 2: The first three-electrode unit
3：第二个三电极单体 4：柔性基底3: Second three-electrode cell 4: Flexible substrate
21、31：参比电极 22、32：辅助电极21, 31: Reference electrode 22, 32: Auxiliary electrode
23、33：工作电极23, 33: Working electrode
具体实施方式Detailed ways
下面结合实施例和附图对本发明的一种柔性差分式阵列电化学葡萄糖传感器及使用方法做出详细说明。A flexible differential array electrochemical glucose sensor and its usage method of the present invention will be described in detail below with reference to the embodiments and drawings.
如图1、图2、图3、图4所示，本发明的一种柔性差分式阵列电化学葡萄糖传感器，包括有并排设置有7个结构完全相同的传感器单元1，每一个传感器单元1都包括有柔性基底4，以及设置在所述柔性基底4上的第一个三电极单体2和第二个三电极单体3，所述的柔性基底4为柔性PET基底，利用柔性衬底的性质来使传感器与皮肤很好的粘合，从而让传感器稳定的工作。所述的第一个三电极单体2和第二个三电极单体3结构完全相同，均包括有参比电极21、31、辅助电极22、32和工作电极23、33。所述参比电极21、31、辅助电极22、32和工作电极23、33为弧形或条形形状。As shown in Fig. 1, Fig. 2, Fig. 3 and Fig. 4, a flexible differential array electrochemical glucose sensor of the present invention includes seven sensor units 1 with identical structures arranged side by side, and each sensor unit 1 has Including a flexible substrate 4, and the first three-electrode monomer 2 and the second three-electrode monomer 3 arranged on the flexible substrate 4, the flexible substrate 4 is a flexible PET substrate, using the flexible substrate The properties make the sensor adhere to the skin well, so that the sensor can work stably. The first three-electrode unit 2 and the second three-electrode unit 3 have the same structure, and both include reference electrodes 21 , 31 , auxiliary electrodes 22 , 32 and working electrodes 23 , 33 . The reference electrodes 21, 31, auxiliary electrodes 22, 32 and working electrodes 23, 33 are arc-shaped or strip-shaped.
所述的参比电极21、31的结构为由柔性基底4至上依次设置的一层铬、一层惰性金属铂和一层Ag/AgCl电极，所述的辅助电极22、32和工作电极23、33结构相同，均为由柔性基底4至上依次设置的一层铬构成粘附层、一层惰性金属铂构成基底电极，所述的工作电极23、33上还固定葡萄糖氧化酶。The structure of the reference electrodes 21, 31 is a layer of chromium, a layer of inert metal platinum, and a layer of Ag/AgCl electrodes arranged sequentially from the flexible base 4, the auxiliary electrodes 22, 32 and the working electrode 23, 33 have the same structure, and they are all composed of a layer of chromium on the flexible substrate 4 to form an adhesion layer, and a layer of inert metal platinum to form a base electrode. Glucose oxidase is also immobilized on the working electrodes 23 and 33 .
所述的第一个三电极单体2中的工作电极23和第二个三电极单体3中的工作电极33一起构成抽取电极对，当给两个工作电极23，33加上直流电压时，其中第一个三电极单体2中的工作电极23处为用于聚集透皮抽取组织液的葡萄糖分子的负极，第二个三电极单体3中的工作电极33处为用于聚集不包括葡萄糖分子的组织液的正极。The working electrode 23 in the first three-electrode cell 2 and the working electrode 33 in the second three-electrode cell 3 together form an extraction electrode pair. When a DC voltage is applied to the two working electrodes 23 and 33 , where the working electrode 23 in the first three-electrode unit 2 is the negative electrode for gathering glucose molecules extracted from the tissue fluid transdermally, and the working electrode 33 in the second three-electrode unit 3 is for gathering glucose molecules that do not include Positive pole of interstitial fluid for glucose molecules.
在所述工作电极23、33在结合作为抽取电极的同时，第一个三电极单体2中的工作电极23、辅助电极22和参比电极21一起构成一个电化学传感器，第二个三电极单体3中的工作电极33、辅助电极32和参比电极31一起构成另一个电化学传感器，从而实现在工作电极23，33处组织液抽取点的葡萄糖分子的原位测量。When the working electrodes 23 and 33 are combined as extraction electrodes, the working electrode 23, the auxiliary electrode 22 and the reference electrode 21 in the first three-electrode unit 2 form an electrochemical sensor together, and the second three-electrode The working electrode 33 , the auxiliary electrode 32 and the reference electrode 31 in the cell 3 together form another electrochemical sensor, so as to realize the in-situ measurement of glucose molecules at the tissue fluid extraction point at the working electrodes 23 and 33 .
所述的第一个三电极单体2用于检测抽取的组织液中的葡萄糖浓度，第二个三电极单体3用于检测背景组织液以及环境对传感器结果产生的影响，所述的第一个三电极单体2和第二个三电极单体3一起构成差分测量体系，用以消除测量过程中由环境变化而引起的误差。The first three-electrode monomer 2 is used to detect the glucose concentration in the extracted interstitial fluid, the second three-electrode monomer 3 is used to detect the background tissue fluid and the influence of the environment on the sensor results, and the first three-electrode monomer 3 is used to detect the background tissue fluid and the environment. The three-electrode unit 2 and the second three-electrode unit 3 together form a differential measurement system to eliminate errors caused by environmental changes during the measurement process.
本发明的一种柔性差分式阵列电化学葡萄糖传感器的使用方法是，由7个传感器单元1构成的阵列电化学葡萄糖传感器，每天使用1个传感器单元1进行测量，第二天换下一个传感器单元进行测量，达到能够实现7天的连续测量，利用换位测量的方式来降低由于组织液的长时间抽取而导致的皮肤过敏现象。A method of using a flexible differential array electrochemical glucose sensor of the present invention is that the array electrochemical glucose sensor is composed of seven sensor units 1, and one sensor unit 1 is used for measurement every day, and the next sensor unit is replaced the next day The measurement is carried out to achieve continuous measurement for 7 days, and the method of transposition measurement is used to reduce skin allergies caused by long-term extraction of interstitial fluid.
本发明的一种柔性差分式阵列电化学葡萄糖传感器的制作是：首先利用磁控溅射或3D打印的方式在PET基底上依次溅射一层铬和一层惰性金属铂，其中铬层作为粘附层，即形成基底电极。然后利用电镀的方式在基底电极上电镀银，并利用三氯化铁溶液对银电极进行氯化处理，得到参比电极21、31。接着用电化学沉积或者层层分子自组装的方法在工作电极23、33上固定葡萄糖氧化酶，即完成整个电极的加工。The fabrication of a flexible differential array electrochemical glucose sensor of the present invention is as follows: first, a layer of chromium and a layer of inert metal platinum are sequentially sputtered on a PET substrate by means of magnetron sputtering or 3D printing, wherein the chromium layer is used as an adhesive The attached layer is to form the base electrode. Then electroplate silver on the base electrode by means of electroplating, and chlorinate the silver electrode with ferric chloride solution to obtain reference electrodes 21 and 31 . Next, glucose oxidase is immobilized on the working electrodes 23 and 33 by means of electrochemical deposition or layer-by-layer molecular self-assembly, that is, the processing of the entire electrode is completed.
如图5、图6所示，所述的参比电极21、31包括有一体形成且依次连接的第一接线端子21a、31a、第一衔接部21b、31b和第一电极端21c、31c，所述的第一衔接部21b、31b和第一电极端21c、31c之间形成有大于130度的夹角。所述的辅助电极22、32包括有一体形成且依次连接的第二接线端子22a、32a、第二衔接部22b、32b和第二电极端22c、32c，所述的第二电极端22c、32c为半圆弧形状。所述的工作电极23、33包括有一体形成且依次连接的第三接线端子23a、33a、第三衔接部23b、33b和第三电极端23c、33c，所述的23c、33c为圆形片形状。As shown in FIG. 5 and FIG. 6, the reference electrodes 21, 31 include first connection terminals 21a, 31a, first connecting parts 21b, 31b and first electrode terminals 21c, 31c, which are integrally formed and connected in sequence, An included angle greater than 130 degrees is formed between the first engaging portions 21b, 31b and the first electrode ends 21c, 31c. The auxiliary electrodes 22, 32 include second connection terminals 22a, 32a, second connecting parts 22b, 32b, and second electrode ends 22c, 32c, which are integrally formed and connected in sequence. The second electrode ends 22c, 32c It is in the shape of a semicircle. The working electrodes 23, 33 include third connection terminals 23a, 33a, third connecting parts 23b, 33b, and third electrode terminals 23c, 33c, which are integrally formed and sequentially connected, and the above-mentioned 23c, 33c are circular pieces shape.
如图6所示，所述的参比电极21、31和工作电极23、33均包括有一体形成且依次连接的第四接线端子21a′、31a′、第四衔接部21b′、31b′和第四电极端21c′、31c′，所述的第四电极端21c′为条形片形状。所述的辅助电极22、32包括有一体形成且依次连接的第五接线端子22a′、32a′、第五衔接部22b′、32b′和第五电极端22c′、32c′，所述的第五电极端22c′、32c′为矩形片形状。As shown in FIG. 6, the reference electrodes 21, 31 and the working electrodes 23, 33 all include integrally formed and sequentially connected fourth connection terminals 21a', 31a', fourth connecting parts 21b', 31b' and The fourth electrode terminals 21c', 31c', the fourth electrode terminal 21c' is in the shape of a strip. The auxiliary electrodes 22, 32 include fifth connection terminals 22a', 32a', fifth connecting parts 22b', 32b', and fifth electrode ends 22c', 32c', which are integrally formed and sequentially connected. The five-electrode terminals 22c', 32c' are in the shape of rectangular plates.
本发明的一种柔性差分式阵列电化学葡萄糖传感器及使用方法，通过在工作电极上固定葡萄糖氧化酶的方式来实现对葡萄糖的特异性检测。The flexible differential array electrochemical glucose sensor and its use method of the present invention realize the specific detection of glucose by immobilizing glucose oxidase on the working electrode.
本发明利用了两组由第一个三电极单体2和第二个三电极单体3构成的电化学葡萄糖传感器进行差分测量，其中一个(如第一个三电极单体2)电化学葡萄糖传感器测量的组织液中有葡萄糖，另一个(如第二个三电极单体3)电化学葡萄糖传感器3没有葡萄糖，以此来消除测量过程中由环境变化而引起的误差；同时实现了对抽取点即工作电极23，33组织液葡萄糖浓度的原位测量，有利于更准确地获得葡萄糖的浓度。The present invention utilizes two groups of electrochemical glucose sensors composed of the first three-electrode monomer 2 and the second three-electrode monomer 3 for differential measurement, one of which (such as the first three-electrode monomer 2) electrochemically glucose There is glucose in the interstitial fluid measured by the sensor, and the other (such as the second three-electrode monomer 3) electrochemical glucose sensor 3 has no glucose, so as to eliminate the error caused by environmental changes during the measurement process; That is, the in-situ measurement of the glucose concentration in the interstitial fluid by the working electrodes 23 and 33 is beneficial to obtaining the glucose concentration more accurately.
本发明的一种柔性差分式阵列电化学葡萄糖传感器及使用方法的工作过程是：第一天使用第一个传感器单元，首先利用单元中的两个工作电极23、33对组织液进行透皮抽取，其次利用单元中的第一个三电极单体2和第二个三电极单体3对抽取的组织液中的葡萄糖进行检测；第二天撕掉前一天用过的传感器单元，用新的传感器单元实现对组织液的抽取和对抽取的组织液中的葡萄糖浓度的检测；以次类推直到完成7天的连续检测。The working process of a flexible differential array electrochemical glucose sensor and its usage method of the present invention is as follows: the first sensor unit is used on the first day, and the tissue fluid is transdermally extracted by using the two working electrodes 23 and 33 in the unit, Secondly, use the first three-electrode monomer 2 and the second three-electrode monomer 3 in the unit to detect the glucose in the extracted interstitial fluid; tear off the sensor unit used the day before the next day, and use a new sensor unit Realize the extraction of interstitial fluid and the detection of the glucose concentration in the extracted interstitial fluid; and so on until the continuous detection of 7 days is completed.
通过传感器单元中的两个工作电极实现对组织液的透皮抽取：如图3、图4所示，将传感器与皮肤粘合好后，给传感器单元的工作电极23、33加上0.3mA的电流，即对组织液进行恒流抽取，使得葡萄糖分子随组织液聚集到负极23表面，不含葡萄糖分子的组织液聚集到正极33表面，每次抽取时间为3分钟。The transdermal extraction of interstitial fluid is realized through the two working electrodes in the sensor unit: as shown in Figure 3 and Figure 4, after the sensor is bonded to the skin, a current of 0.3mA is applied to the working electrodes 23 and 33 of the sensor unit , that is, the interstitial fluid is extracted with a constant flow, so that the glucose molecules gather on the surface of the negative electrode 23 along with the interstitial fluid, and the interstitial fluid without glucose molecules gathers on the surface of the positive electrode 33, and the extraction time is 3 minutes each time.
对抽取组织液中的葡萄糖浓度的检测：这里的检测体系是传感器单元中的第一个三电极单体2和第二个三电极单体3，如图3、图4所示，抽取过程完成之后，给工作电极23加上相对于参比电极21为-0.6V的电压，并使得工作电极23与辅助电极22之间形成测量回路，葡萄糖氧化酶特异性催化葡萄糖的分解，在恒电势下电化学反应中电子的转移速率即电化学反应中的电流与待测液中葡萄糖的浓度成正比，通过检测该电流(即23与22之间的电流)的大小就可以获得待测液中葡萄糖的浓度。这里的差分主要体现在：对于电极23与33、22与32、21与31上所施加的条件分别对应完全相同，在检测时的唯一差别就是23处有葡萄糖而33处没有葡萄糖，故而工作电极23所检测到的电流的变化即环境变化对电极的影响，通过工作电极23与工作电极33的差分，即可消除环境变化对葡萄糖测量结果的影响。Detection of glucose concentration in the extracted interstitial fluid: the detection system here is the first three-electrode monomer 2 and the second three-electrode monomer 3 in the sensor unit, as shown in Figure 3 and Figure 4, after the extraction process is completed , add a voltage of -0.6V to the working electrode 23 relative to the reference electrode 21, and form a measurement circuit between the working electrode 23 and the auxiliary electrode 22. Glucose oxidase specifically catalyzes the decomposition of glucose. The transfer rate of electrons in the chemical reaction, that is, the current in the electrochemical reaction is proportional to the concentration of glucose in the test solution, and the glucose concentration in the test solution can be obtained by detecting the magnitude of the current (ie, the current between 23 and 22). concentration. The difference here is mainly reflected in: the conditions imposed on electrodes 23 and 33, 22 and 32, and 21 and 31 are exactly the same, and the only difference in detection is that there is glucose at 23 and no glucose at 33, so the working electrode The change of the current detected by 23 is the influence of the environment change on the electrode, and the influence of the environment change on the glucose measurement result can be eliminated by the difference between the working electrode 23 and the working electrode 33 .
本发明的一种柔性差分式阵列电化学葡萄糖传感器及使用方法，对传统的传感器结构进行了改进，将电极制作在柔性衬底上，通过柔性衬底的性质，使得传感器随着皮肤的形变而形变，让传感器与皮肤紧密粘合，从而让传感器能够稳定的工作，获得准确的测量结果。传感器利用一个传感器单元中的两个工作电极形成组织液抽取电极对，以此来实现对于组织的透皮抽取，又通过两组三电极单体来实现对抽取的组织液中的葡萄糖浓度的测量，实现了组织液透皮抽取和测量抽取的组织液中葡萄糖浓度的一体化。传感器在测量过程中利用了差分的原理，通过传感器单元中的两组三电极单体在相同条件下(差别仅为一个三电极测量对象有葡萄糖，一个没有)的共同测量实现差分，可去除在测量过程中由环境变化而引起的测量结果的误差。同时这里还运用了原位测量的原理，这里的原位测量表现在：在完成对组织液的透皮抽取之后，不需要收集转移抽取的组织液，就在工作电极23处原位实现对所抽取的组织液中的葡萄糖浓度的检测。传感器是由七个传感器单元形成的阵列式传感器，每天使用1个传感器单元，第二天撕下第一天已使用过得单元，利用新的传感器单元进行测量，能实现7天的连续测量。这相当于每天的测试位置有细微的差别，这种细微的差别即可形容为利用换位测量的方式，这种方式可以有效的降低由于长时间抽取组织液而导致的皮肤过敏现象。A flexible differential array electrochemical glucose sensor and its use method of the present invention improve the structure of the traditional sensor, the electrodes are made on the flexible substrate, and through the properties of the flexible substrate, the sensor can be deformed with the deformation of the skin. The deformation allows the sensor to adhere closely to the skin, so that the sensor can work stably and obtain accurate measurement results. The sensor uses two working electrodes in one sensor unit to form a pair of interstitial fluid extraction electrodes to achieve transdermal extraction of tissue, and uses two sets of three-electrode monomers to realize the measurement of the glucose concentration in the extracted interstitial fluid. The integration of transdermal extraction of interstitial fluid and measurement of glucose concentration in the extracted interstitial fluid is realized. The sensor uses the principle of difference in the measurement process. The difference is realized through the common measurement of two groups of three-electrode monomers in the sensor unit under the same conditions (the difference is only that one three-electrode measurement object has glucose and one does not). Errors in measurement results caused by environmental changes during the measurement process. At the same time, the principle of in-situ measurement is also used here. The in-situ measurement here is as follows: after the transdermal extraction of tissue fluid is completed, it is not necessary to collect and transfer the extracted tissue fluid, and the extracted tissue fluid can be measured in situ at the working electrode 23. Detection of glucose concentration in interstitial fluid. The sensor is an array sensor formed by seven sensor units. One sensor unit is used every day, and the unit that has been used on the first day is torn off the next day, and the new sensor unit is used for measurement, which can realize continuous measurement for 7 days. This is equivalent to a slight difference in the test position every day. This slight difference can be described as a method of transposition measurement, which can effectively reduce skin allergies caused by long-term extraction of interstitial fluid.
本发明公开和揭示的所有组合可以通过借鉴本文公开内容产生，尽管本发明的组合已通过详细实施过程进行了描述，但是本领域技术人员明显能在不脱离本发明内容、精神和范围内对本文所述的装置进行拼接或改动，或增减某些部件，更具体地说，所有相类似的替换和改动对本领域技术人员来说是显而易见的，他们都被视为包括在本发明精神、范围和内容之中。All the combinations disclosed and disclosed in the present invention can be produced by referring to the disclosure herein. Although the combination of the present invention has been described in detail, those skilled in the art can clearly understand the present invention without departing from the content, spirit and scope of the present invention. The described device is spliced or changed, or some parts are added or subtracted, more specifically, all similar replacements and changes are obvious to those skilled in the art, and they are all considered to be included in the spirit and scope of the present invention and content.
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