WO2018094780A1 - 一种无创血糖检测试纸及其制备方法 - Google Patents

一种无创血糖检测试纸及其制备方法 Download PDF

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Publication number
WO2018094780A1
WO2018094780A1 PCT/CN2016/109439 CN2016109439W WO2018094780A1 WO 2018094780 A1 WO2018094780 A1 WO 2018094780A1 CN 2016109439 W CN2016109439 W CN 2016109439W WO 2018094780 A1 WO2018094780 A1 WO 2018094780A1
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electrode
test paper
blood glucose
invasive blood
thin film
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French (fr)
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林鹏
胡进
宋家俊
严锋
柯善明
曾燮榕
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Shenzhen University
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Shenzhen University
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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
    • G01N27/28—Electrolytic cell components
    • G01N27/30—Electrodes, e.g. test electrodes; Half-cells
    • G01N27/308—Electrodes, e.g. test electrodes; Half-cells at least partially made of carbon

Definitions

  • the invention relates to the field of biosensing technology, in particular to a non-invasive blood glucose detecting test paper and a preparation method thereof.
  • non-invasive blood glucose detection methods mainly include optical and radiation methods, reverse iontophoresis analysis, electromagnetic wave method, ultrasonic method, and tissue fluid extraction method.
  • near-infrared spectroscopy mainly uses the relationship between blood glucose concentration and its near-infrared spectroscopy absorption, illuminates the skin with near-infrared light, and reflects the blood glucose concentration from changes in reflected light intensity.
  • This method has the advantages of fast measurement, no need for chemical reagents and consumables, but because the individual difference of the measured object is large and the obtained signal is very weak, the weak chemistry is extracted in the measurement site selection, measurement condition selection, and overlapping spectrum. Key technical aspects such as information methods still need to be further resolved.
  • the invention provides a non-invasive blood glucose detecting test paper and a preparation method thereof, thereby solving the problem that the non-invasive blood glucose detecting in the prior art has poor accuracy and slow reaction speed.
  • a non-invasive blood glucose detecting test paper for detecting a glucose concentration in a liquid, comprising: a test paper substrate, a first electrode, a second electrode and a third electrode disposed on the test paper substrate, and being disposed on the test paper substrate An organic semiconductor thin film material of an electrode and a second electrode, glucose oxidase immobilized on the third electrode, and an insulating cover sheet disposed on the test paper substrate; the insulating cover sheet is provided with a drop for An open groove of the liquid to be tested is added, and the organic semiconductor thin film material and glucose oxidase are simultaneously exposed in the open groove.
  • the non-invasive blood glucose detecting test paper wherein the glucose oxidase is fixedly modified on the third electrode by an organic polymer.
  • the non-invasive blood glucose detecting test paper wherein the organic polymer comprises perfluorosulfonic acid, chitosan, polyaniline.
  • the non-invasive blood glucose detecting test paper wherein the third electrode is modified by a nano material to improve detection sensitivity of the third electrode.
  • the non-invasive blood glucose detecting test paper wherein the nano material comprises graphene, carbon nanotubes, and platinum nanoparticles.
  • the non-invasive blood glucose detecting test paper wherein the material of the test paper substrate and the insulating cover sheet comprises PET Plastic; the material of the first electrode, the second electrode and the third electrode comprises Pt, Au, Ag, C.
  • the non-invasive blood glucose detecting test paper wherein the organic semiconductor thin film material comprises poly(3,4-ethylenedioxythiophene)- Polystyrenesulfonic acid, polypyrrole, polythiophene, polyaniline, polycarbazole, and poly(3,4-ethylenedioxythiophene)-polystyrenesulfonic acid, polypyrrole, polythiophene, polyaniline, polycarbazole Copolymer.
  • the non-invasive blood glucose detecting test paper wherein the first electrode, the second electrode and the third electrode have a thickness of 50-200 nm
  • the organic semiconductor thin film material has a thickness of 30 to 200 nm.
  • A cleaning the test paper substrate and drying, after which the first electrode, the second electrode and the third electrode are prepared on the test paper substrate;
  • the insulating cover sheet is fixed on the test paper substrate, and the organic semiconductor film material and the glucose oxidase are simultaneously exposed in the open grooves of the insulating cover sheet to prepare the non-invasive blood glucose detecting test paper.
  • the method for preparing a non-invasive blood glucose detecting test paper wherein in the step A, the first electrode, the second electrode and the third electrode pass Prepared by one method of screen printing, vacuum thermal evaporation, magnetron sputtering or vapor deposition;
  • a method of preparing an organic semiconductor thin film material on the test paper substrate is spin coating or ink jet printing.
  • the present invention is based on a thin film transistor for the first time to produce blood glucose detection Test paper to detect low-concentration glucose in body fluids such as saliva, urine, sweat, and tissue fluid.
  • the non-invasive blood glucose detecting test paper of the invention has extremely high detection sensitivity and extremely low detection limit, can truly realize non-invasive blood sugar detection, and has great market potential and commercial value.
  • FIG. 1 is a partial structural view showing a preferred embodiment 1 of a non-invasive blood glucose detecting test paper of the present invention.
  • Fig. 2 is a partial schematic structural view showing a preferred embodiment 1 of the non-invasive blood glucose detecting test paper of the present invention.
  • Fig. 3 is a view showing the overall structure of a preferred embodiment 1 of the non-invasive blood glucose detecting test paper of the present invention.
  • Fig. 4 is a graph showing the I DS -T curve (in the figure, C g is the concentration of glucose) of the non-invasive blood glucose test strip of the present invention tested in a PBS solution containing different concentrations of glucose.
  • Figure 5 is a non-invasive blood glucose test strip of the present invention in PBS containing different concentrations of glucose
  • the channel current obtained in the solution is related to different concentration values.
  • Figure 6 is a non-invasive blood glucose test strip of the present invention Use the non-invasive blood glucose meter to test the blood glucose values in saliva samples (corresponding to different blood glucose values).
  • Fig. 7 is a partial structural view showing a preferred embodiment 2 of the non-invasive blood glucose detecting test paper of the present invention.
  • Fig. 8 is a schematic view showing another partial structure of a preferred embodiment 2 of the non-invasive blood glucose detecting test paper of the present invention.
  • Fig. 9 is a view showing the overall structure of a preferred embodiment 2 of the non-invasive blood glucose detecting test paper of the present invention.
  • Fig. 10 is a partial structural view showing a preferred embodiment 3 of the non-invasive blood glucose detecting test paper of the present invention.
  • Fig. 11 is a partial structural schematic view showing a third preferred embodiment of the non-invasive blood glucose detecting test strip of the present invention.
  • Fig. 12 is a view showing the overall structure of a preferred embodiment 3 of the non-invasive blood glucose detecting test paper of the present invention.
  • the invention provides a non-invasive blood glucose detecting test paper and a preparation method thereof
  • a non-invasive blood glucose detecting test paper and a preparation method thereof
  • the present invention will be further described in detail below. It is understood that the specific embodiments described herein are merely illustrative of the invention and are not intended to limit the invention .
  • the invention provides a non-invasive blood glucose detecting test paper for detecting glucose concentration in a liquid, as shown in FIG. 1 to FIG. 3, the present invention
  • the non-invasive blood glucose detecting test paper of the first embodiment comprises: a test paper substrate 1, a first electrode 2, a second electrode 3 and a third electrode 4 disposed on the test paper substrate 1, and disposed on the test paper substrate 1
  • the insulating cover sheet 7 is provided with an open groove 71 for dropping a liquid to be tested, and the organic semiconductor thin film material 5 and glucose oxidase 6 are simultaneously exposed in the open groove 71.
  • the organic semiconductor thin film material 5 and the glucose oxidase 6 are simultaneously exposed to the open cells 71 Inside, therefore, when a liquid is dropped into the open groove, the liquid is simultaneously contacted with the organic semiconductor thin film material and the glucose oxidase.
  • the position of the open slot 71 can be selected according to actual needs, for example, as shown in FIG. As shown, it can be placed at the end of the insulating cover sheet 7.
  • the non-invasive blood glucose detecting test paper of the invention is based on the principle of thin film transistor (TFT)
  • TFT thin film transistor
  • a test strip is prepared and combined with a blood glucose meter to achieve non-invasive detection of glucose in body fluids.
  • Thin film transistors have many advantages such as low operating voltage, high detection sensitivity, and low detection limit.
  • the first electrode 2 and the second electrode 3 of the present invention That is, it corresponds to the source electrode and the drain electrode of the thin film transistor, and the third electrode 4 corresponds to the gate electrode of the thin film transistor.
  • the liquid to be tested according to the present invention includes saliva, urine, sweat, tissue fluid and the like. Studies have shown that the concentration of glucose in body fluids such as saliva has a good correlation with blood glucose concentration, so the blood glucose concentration can be indirectly reflected by detecting the concentration of glucose in body fluids such as saliva. By using the high sensitivity characteristic of the non-invasive blood glucose detecting test paper of the invention, the detection of low glucose concentration in saliva can be realized, and the non-invasive blood glucose detection can be truly realized.
  • the present invention creatively proposes a high-sensitivity non-invasive blood glucose detection test paper based on a thin film transistor, which has a signal amplification function and has a glucose detection function. Higher sensitivity and lower detection limits. Because salivary glucose concentration is only blood glucose concentration 1/50 to 1/100, traditional test strips cannot be detected due to insufficient detection limits.
  • the technique of the present invention utilizes the principle of transistor signal amplification to reduce the detection limit of glucose for glucose compared to conventional electrochemical techniques. 2-3 An order of magnitude for detection of salivary glucose.
  • the invention also utilizes the method of electrical detection, and thus has better accuracy and repeatability than the method of optics in the non-invasive detection technology, and has higher reliability and stability.
  • the glucose oxidase is fixedly modified on the third electrode by an organic polymer.
  • the organic polymer comprises perfluorosulfonic acid, chitosan, polyaniline.
  • the third electrode is modified by the nano material to improve the detection sensitivity of the third electrode.
  • the nano material comprises graphene, carbon nanotubes, and platinum nanoparticles.
  • the materials of the test paper substrate and the insulating cover sheet include but are not limited to PET (polyethylene terephthalate) plastic.
  • the test paper substrate and the insulating cover sheet may be selected from all flexible substrates including PET plastic.
  • materials of the first electrode, the second electrode, and the third electrode include Pt, Au, Ag, C and other conductive materials.
  • the organic semiconductor thin film material comprises poly(3,4-ethylenedioxythiophene)- Polystyrenesulfonic acid, polypyrrole, polythiophene, polyaniline, polycarbazole, and poly(3,4-ethylenedioxythiophene)- A copolymer of polystyrenesulfonic acid, polypyrrole, polythiophene, polyaniline, polycarbazole, or a new material obtained by modifying the above materials.
  • the first electrode, the second electrode and the third electrode have a thickness of 50-200 nm.
  • the thickness of the organic semiconductor thin film material is 30-200 nm.
  • the embodiment of the invention further provides a preparation method of the non-invasive blood glucose detecting test paper as described above, which comprises the steps of:
  • the insulating cover sheet is fixed on the test paper substrate, and the organic semiconductor film material and the glucose oxidase are simultaneously exposed in the open grooves of the insulating cover sheet to prepare the non-invasive blood glucose detecting test paper.
  • the method for preparing the non-invasive blood glucose detecting test paper of the present invention that is, preparing the first electrode, the second electrode and the third electrode on the test paper substrate, in the first electrode and the second electrode (source, drain electrode)
  • An organic semiconductor thin film material is prepared, glucose oxidase is prepared on the third electrode (gate electrode) to form a thin film transistor, and finally an insulating cover sheet is added to expose the organic semiconductor thin film material and glucose oxidase to the open slot at the end.
  • the first electrode, the second electrode and the third electrode are passed It is prepared by one of screen printing, vacuum thermal evaporation, magnetron sputtering or vapor deposition.
  • the method for preparing the organic semiconductor thin film material is spin coating or ink jet printing, and the annealing temperature is 100-160 ° C for 5-30 min.
  • this invention For the first time, it was proposed to use a thin film transistor to make test paper to achieve high sensitivity and low concentration detection of saliva samples, and to achieve non-invasive blood glucose detection.
  • the non-invasive blood glucose meter can be matched with the first electrode 2 and the second electrode 3
  • An operating voltage (source/drain voltage) is applied between the electrodes, and the current (channel current) passing through the organic semiconductor thin film material 5 is measured while being on the first electrode 2 and the third electrode 4
  • another working voltage (gate voltage) is applied between them
  • the channel current of the thin film transistor can be regulated by the gate voltage, and when the liquid to be tested is dropped into the open groove of the test paper, the organic semiconductor thin film material 5 and glucose oxidase 6
  • the glucose in the liquid to be tested electrochemically reacts with the glucose oxidase on the gate electrode, and electron gain and loss are formed on the gate electrode, so that the interface potential of the gate electrode changes, thereby causing the channel current of the thin film transistor to occur.
  • the change value of the channel current has a certain relationship with the concentration of glucose contained in the liquid to be tested, so the first electrode can be measured 2.
  • the current between the second electrodes 3 reflects the concentration of glucose contained in the liquid to be tested. Due to the use of the principle of transistor signal amplification, TFTs have higher detection sensitivity and lower detection limits.
  • the working voltage applied between the first electrode 2 and the second electrode 3 can be selected to be 0.05V-0.1V. .
  • the working voltage applied between the first electrode 2 and the third electrode 4 can be selected to be 0.1V-1.0V. .
  • the portable non-invasive blood glucose detecting of the household can be realized simply and conveniently.
  • the present invention is based on a thin film transistor for the first time to produce blood glucose detection.
  • Test paper to detect low-concentration glucose in body fluids such as saliva, urine, sweat, and tissue fluid.
  • the non-invasive blood glucose detecting test paper of the invention has extremely high detection sensitivity and extremely low detection limit, can truly realize non-invasive blood sugar detection, and has great market potential and commercial value.
  • Figure 4 is a graph showing the I DS -T curve of the non-invasive blood glucose test strip of the present invention tested in a solution of PBS (phosphate buffer) containing different concentrations of glucose. It can be seen from the figure that as the glucose concentration increases, the channel current of the thin film transistor (non-invasive blood glucose detecting test paper) decreases, and a better step gradient change appears with the change of different magnitudes.
  • Figure 5 shows the relationship between the corresponding channel currents and the values of different glucose concentrations. The linear relationship is good. This result indicates that the minimum detection concentration of glucose in the test paper of the present invention is 10 -8 M, and the linear relationship between 10 -6 M and 10 -3 M is good, due to glucose in saliva samples of normal humans and diabetic patients. The concentration is approximately 3 ⁇ 10 -6 M to 210 ⁇ 10 -6 M. Therefore, the present invention can cover the glucose detection range of the saliva sample, and the actual non-invasive detection of the saliva sample can be realized.
  • PBS phosphate buffer
  • FIG. 6 is the non-invasive blood glucose test strip of the present invention.
  • the blood glucose level measured in the saliva sample (corresponding to different blood glucose values) in combination with the non-invasive blood glucose meter.
  • the abscissa represents the blood glucose value measured for the corresponding blood sample when the patient's saliva sample is taken, and the ordinate represents the blood glucose reading obtained when the saliva sample is measured with the non-invasive blood glucose meter.
  • the non-invasive blood glucose detecting test paper of the present invention can realize actual detection of saliva samples, and has higher sensitivity and lower detection limit in glucose detection.
  • the invention has the following beneficial effects: the invention non-invasive blood glucose detecting test paper
  • the detection liquid can select saliva, urine, sweat, tissue fluid, etc., without causing pain to the patient, and avoid cross-infection easily caused during blood detection;
  • the non-invasive blood glucose test strip of the present invention is based on The principle design of the thin film transistor, the thin film transistor has the function of sensing and signal amplification, and can amplify the weak signal change on the gate electrode, so the non-invasive blood glucose detecting test paper of the invention Extremely high sensitivity and extremely low detection limits.
  • the non-invasive blood glucose detecting test paper of the invention has the advantages of simple structure, simple preparation process and suitable for large-scale mass production.
  • non-invasive blood glucose detecting test paper of the present invention can be made into different shapes under the teaching of the design principle of the present invention.
  • the size, shape, and order of the electrodes can also be changed differently, as shown in Figure 7 to Figure 9, Figure 10 to Figure 12. All similar non-substantial changes are intended to fall within the scope of the present invention.
  • the present invention is based on a thin film transistor for the first time to produce blood glucose detection.
  • Test paper to detect low-concentration glucose in body fluids such as saliva, urine, sweat, and tissue fluid.
  • the non-invasive blood glucose detecting test paper of the invention has extremely high detection sensitivity and extremely low detection limit, can truly realize non-invasive blood sugar detection, and has great market potential and commercial value.

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Abstract

一种无创血糖检测试纸及其制备方法，无创血糖检测试纸包括：试纸基片(1)，设置在试纸基片(1)上的第一电极(2)、第二电极(3)和第三电极(4)，设置在试纸基片(1)上连接第一电极(2)和第二电极(3)的有机半导体薄膜材料(5)，固定在第三电极(4)上的葡萄糖氧化酶(6)，及覆盖设置在试纸基片(1)之上的绝缘盖片(7)；绝缘盖片(7)上设置有用于滴加待测液体的开口槽(71)，有机半导体薄膜材料(5)和葡萄糖氧化酶(6)同时暴露在开口槽(71)内。首次基于薄膜晶体管制作出血糖检测试纸，来实现对唾液、尿液、汗液、组织液等体液中的低浓度葡萄糖的检测。无创血糖检测试纸，具有极高的检测灵敏度和极低的检测极限，能够真正实现无创血糖检测。

Description

一种无创血糖检测试纸及其制备方法
技术领域
本发明涉及生物传感技术领域，尤其涉及一种无创血糖检测试纸及其制备方法。
背景技术
随着生活水平的不断提高，糖尿病已成为严重影响人类身体健康的一种世界性的第三大疾病。为了有效监控糖尿病患者的血糖浓度，家用便携式血糖仪及血糖试纸得到了广泛的使用。目前市场上对血糖的检测，主要是针对采集血样的有创伤或微创伤检测，给患者带来极大的痛苦，而且存在病毒通过血液感染的危险。因此，无创伤血糖检测成为治疗糖尿病的迫切需求。国内外围绕无痛无伤害的无创血糖检测技术已展开了广泛的研究，但市场上极少出现成熟的产品，偶尔有产品上市即因为测量准确性和可靠性的问题而很快下架，相关技术还有待进一步完善。
目前无创血糖检测的方法主要有光学和辐射方法、反向离子电渗分析法、电磁波法、超声波法以及组织液提取法等。例如，近红外光谱检测法主要利用血糖浓度与其近红外光谱吸收之间的关系，用近红外光照射皮肤，并从反射光强度变化来反映出血糖浓度。这种方法具有测量快速、无需化学试剂及消耗品等优点，但是由于被测对象的个体差异大，且取得的信号又非常微弱，因此在测量部位选择、测量条件选取、重叠光谱中提取微弱化学信息的方法等关键性技术方面还有待进一步解决。还有皮下组织液检测法，通过测量皮下渗出的组织液的葡萄糖浓度来反映血糖浓度。根据此原理可制成检测葡萄糖的手表，并可实时连续监控血糖浓度，然而这种方法准确性较差，且反应速度慢，因此很难替代现有的血糖仪。
因此，现有技术还有待于改进和发展。
发明内容
鉴于上述现有技术的不足，本发明的目的 在于提供一种无创血糖检测试纸及其制备方法，从而解决现有技术中的无创血糖检测准确性较差，反应速度慢的问题。
本发明的技术方案如下：
一种 无创血糖检测试纸，用于检测液体内的葡萄糖浓度，其包括：试纸基片，设置在所述试纸基片上的第一电极、第二电极和第三电极，设置在所述试纸基片上连接第一电极和第二电极的有机半导体薄膜材料，固定在所述第三电极上的葡萄糖氧化酶，及覆盖设置在所述试纸基片之上的绝缘盖片；所述绝缘盖片上设置有用于滴加待测液体的开口槽，所述有机半导体薄膜材料和葡萄糖氧化酶同时暴露在所述开口槽内。
所述的无创血糖检测试纸，其中，通过有机聚合物在所述第三电极上固定修饰所述葡萄糖氧化酶。
所述的无创血糖检测试纸，其中，所述有机聚合物包括全氟磺酸、壳聚糖、聚苯胺。
所述的无创血糖检测试纸，其中，通过纳米材料修饰所述第三电极以提高第三电极的检测灵敏度。
所述的无创血糖检测试纸，其中，所述纳米材料包括石墨烯、碳纳米管、铂纳米颗粒。
所述的无创血糖检测试纸，其中，所述试纸基片和所述绝缘盖片的材质包括 PET 塑料；所述第一电极、所述第二电极和所述第三电极的材质包括 Pt 、 Au 、 Ag 、 C 。
所述的无创血糖检测试纸，其中，所述有机半导体薄膜材料包括聚 (3,4- 乙烯二氧噻吩 )- 聚苯乙烯磺酸、聚吡咯、聚噻吩、聚苯胺、聚咔唑以及聚 (3,4- 乙烯二氧噻吩 )- 聚苯乙烯磺酸、聚吡咯、聚噻吩、聚苯胺、聚咔唑的共聚物。
所述的无创血糖检测试纸，其中，所述第一电极、所述第二电极和所述第三电极的厚度为 50-200nm ；所述有机半导体薄膜材料的厚度为 30-200nm 。
一种如以上任一项所述的无创血糖检测试纸的制备方法，包括步骤：
A 、清洗试纸基片并干燥，之后，在试纸基片上制备第一电极、第二电极和第三电极；
B 、在第一电极和第二电极之间制备有机半导体薄膜材料，在第三电极上固定葡萄糖氧化酶；
C 、将绝缘盖片固定在试纸基片上，使有机半导体薄膜材料和葡萄糖氧化酶同时暴露在绝缘盖片的开口槽内，制得所述无创血糖检测试纸。
所述的无创血糖检测试纸的制备方法，其中，所述步骤 A 中，所述第一电极、第二电极和第三电极是通过 丝网印刷、真空热蒸镀、磁控溅射或气相沉积中的一种方法制备 ；
所述步骤 B 中，在所述试纸基片上 制备有机半导体薄膜材料的方法为旋涂或喷墨印刷 。
有益效果：本发明首次基于薄膜晶体管制作出 血糖检测 试纸，来实现对唾液、尿液、汗液、组织液等体液中的低浓度葡萄糖的检测。本发明无创血糖检测试纸，具有极高的检测灵敏度和极低的检测极限，能够真正实现无创血糖检测，具有巨大的市场潜力和商业价值。
附图说明
图 1 是本发明 无创血糖检测试纸较佳实施例一的局部结构示意图 。
图 2 是本发明 无创血糖检测试纸较佳实施例一的另一局部结构示意图 。
图 3 是本发明 无创血糖检测试纸较佳实施例一的整体结构示意图 。
图 4 是本发明 无创血糖检测试纸 在含不同浓度葡萄糖的 PBS 溶液中测试得到的 IDS-T 曲线（图中 Cg 为葡萄糖的浓度）。
图 5 是本发明 无创血糖检测试纸 在含不同浓度葡萄糖的 PBS 溶液中测试得到的沟道电流随不同浓度值的关系。
图 6 是本发明 无创血糖检测试纸 配合无创血糖仪在唾液样品（对应不同的血糖值）中测试得到的血糖数值。
图 7 是本发明 无创血糖检测试纸较佳实施例二的局部结构示意图 。
图 8 是本发明 无创血糖检测试纸较佳实施例二的另一局部结构示意图 。
图 9 是本发明 无创血糖检测试纸较佳实施例二的整体结构示意图 。
图 10 是本发明 无创血糖检测试纸较佳实施例三的局部结构示意图 。
图 11 是本发明 无创血糖检测试纸较佳实施例三的另一局部结构示意图 。
图 12 是本发明 无创血糖检测试纸较佳实施例三的整体结构示意图 。
具体实施方式
本发明提供 一种无创血糖检测试纸及其制备方法 ，为使本发明的目的、技术方案及效果更加清楚、明确，以下对本发明进一步详细说明。 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 。
本发明提供一种 无创血糖检测试纸，用于检测液体内的葡萄糖浓度，如图 1 至图 3 所示，本发明 较佳实施例一的无创血糖检测试纸， 包括：试纸基片 1 ，设置在所述试纸基片 1 上的第一电极 2 、第二电极 3 和第三电极 4 ，设置在所述试纸基片 1 上连接第一电极 2 和第二电极 3 的有机半导体薄膜材料 5 ，固定在所述第三电极 4 上的葡萄糖氧化酶 6 ，及覆盖设置在所述试纸基片 1 之上的绝缘盖片 7 ；所述绝缘盖片 7 上设置有用于滴加待测液体的开口槽 71 ，所述有机半导体薄膜材料 5 和葡萄糖氧化酶 6 同时暴露在所述开口槽 71 内。
本发明实施例中，由于有机半导体薄膜材料 5 和葡萄糖氧化酶 6 同时暴露在开口槽 71 内，因此当液体滴加到所述开口槽内时，液体与所述有机半导体薄膜材料和所述葡萄糖氧化酶同时接触。开口槽 71 的设置位置可以根据实际需要选择，例如，如图 3 所示，可以设置在绝缘盖片 7 的末端。
本发明无创血糖检测试纸，是 基于薄膜晶体管 （ TFT ） 的原理 制成试纸，并结合血糖仪来实现对体液中葡萄糖的无创检测。薄膜晶体管具有工作电压低、检测灵敏度高、检测极限低等诸多优点。本发明所述第一电极 2 、第二电极 3 也即相当于 薄膜晶体管的 源电极和漏电极，所述第三电极 4 也即相当于 薄膜晶体管的 栅电极。
进一步的，本发明实施例中，本发明所述待测液体包括唾液、尿液、汗液、组织液等。研究表明，唾液等体液中的葡萄糖浓度与血糖浓度具有很好的相关性，因此可利用检测唾液等体液中的葡萄糖浓度来间接反应血糖浓度。利用本发明无创血糖检测试纸的高灵敏特性，可以实现唾液中的低葡萄糖浓度检测，真正实现无创血糖检测。
与现有的基于传统电化学检测方法的血糖试纸相比，本发明创造性的提出了一种基于薄膜晶体管的高灵敏的无创血糖检测试纸，由于薄膜晶体管具有信号放大的功能，在葡萄糖检测中具有更高的灵敏度和更低的检测极限。由于唾液葡萄糖浓度只有血糖浓度的 1/50 ～ 1/100 ，传统的试纸因检测极限不够而无法检测到。本发明的技术利用了晶体管信号放大的原理，使 TFT 对葡萄糖的检测极限比传统电化学技术降低了 2-3 个数量级，可实现对唾液葡萄糖的检测。本发明同样利用电学检测的方法，因此比无创检测技术中的光学等方法具有更好的准确性和重复性，且可靠性和稳定性更高。
进一步的，本发明实施例中，通过有机聚合物在所述第三电极上固定修饰所述葡萄糖氧化酶。其中，所述有机聚合物包括全氟磺酸、壳聚糖、聚苯胺。
进一步的，本发明实施例中，通过纳米材料修饰所述第三电极以提高第三电极的检测灵敏度。其中，所述纳米材料包括石墨烯、碳纳米管、铂纳米颗粒。
进一步的，本发明实施例中，所述试纸基片和所述绝缘盖片的材质包括但不限定 PET （聚对苯二甲酸乙二醇酯）塑料。具体的，所述试纸基片和绝缘盖片可选择包括 PET 塑料在内的所有柔性基片。
进一步的，本发明实施例中，所述第一电极、所述第二电极和所述第三电极的材质包括 Pt 、 Au 、 Ag 、 C 等各种导电材料。
进一步的，本发明实施例中，所述有机半导体薄膜材料包括聚 (3,4- 乙烯二氧噻吩 )- 聚苯乙烯磺酸、聚吡咯、聚噻吩、聚苯胺、聚咔唑、及聚 (3,4- 乙烯二氧噻吩 )- 聚苯乙烯磺酸、聚吡咯、聚噻吩、聚苯胺、聚咔唑的共聚物，或者由以上材料改性后得到的新材料。
进一步的，本发明实施例中，所述第一电极、所述第二电极和所述第三电极的厚度为 50-200nm 。
进一步的，本发明实施例中，所述有机半导体薄膜材料的厚度为 30-200nm 。
本发明实施例还提供了一种如以上所述的无创血糖检测试纸的制备方法，其包括步骤：
S100 、清洗试纸基片并干燥，之后，在试纸基片上制备第一电极、第二电极和第三电极；
S200 、在第一电极和第二电极之间制备有机半导体薄膜材料，在第三电极上固定葡萄糖氧化酶；
S300 、将绝缘盖片固定在试纸基片上，使有机半导体薄膜材料和葡萄糖氧化酶同时暴露在绝缘盖片的开口槽内，制得所述无创血糖检测试纸。
具体实施时，本发明所述无创血糖检测试纸的制备方法，也就是在试纸基片上制备第一电极、第二电极和第三电极，在第一电极、第二电极（源、漏电极）之间制备一层有机半导体薄膜材料，在第三电极（栅电极）上制备葡萄糖氧化酶，组成一个薄膜晶体管，最后加上绝缘盖片，把有机半导体薄膜材料和葡萄糖氧化酶暴露在末端的开口槽内。
优选地，本发明实施例中，所述步骤 S100 中，所述第一电极、第二电极和第三电极是通过 丝网印刷、真空热蒸镀、磁控溅射或气相沉积中的一种方法制备 。
优选地，本发明实施例中，所述步骤 S200 中，在所述试纸基片上 制备有机半导体薄膜材料的方法为旋涂或喷墨印刷 ，退火温度为 100-160 ℃，时间为 5-30min 。
本发明 第一次提出利用有薄膜晶体管制作成试纸来实现对唾液样品的高灵敏、低浓度检测，实现无创血糖检测目的。
本发明无创血糖检测试纸具体使用时，可以配合配套的无创血糖仪，在第一电极 2 、第二电极 3 之间加一个工作电压（源漏电压），测量通过有机半导体薄膜材料 5 的电流（沟道电流），同时在第一电极 2 、第三电极 4 之间加另外一个工作电压（栅电压），薄膜晶体管的沟道电流可以受到栅电压的调控，当待测液体滴加到试纸的开口槽内时，与有机半导体薄膜材料 5 和葡萄糖氧化酶 6 同时接触，此时待测液体中的葡萄糖与栅电极上的葡萄糖氧化酶发生电化学反应，在栅电极上形成电子得失，使得栅电极的界面电势发生改变，从而导致薄膜晶体管的沟道电流发生变化。沟道电流的变化值与待测液体中含有的葡萄糖浓度呈一定的关系，因此可以通过测量第一电极 2 、第二电极 3 之间的电流来反映待测液体内含有的葡萄糖浓度。由于利用了晶体管信号放大的原理， TFT 具有更高的检测灵敏度和更低的检测极限。
进一步的，本发明实施例中，在第一电极 2 、第二电极 3 之间加的工作电压可选择为 0.05V-0.1V 。
进一步的，本发明实施例中，在第一电极 2 、第三电极 4 之间加的工作电压可选择为 0.1V-1.0V 。
采用本发明无创血糖检测试纸，结合配套的无创血糖仪，即可简单方便的实现家用便携式无创血糖检测。
本发明首次基于薄膜晶体管制作出 血糖检测 试纸，来实现对唾液、尿液、汗液、组织液等体液中的低浓度葡萄糖的检测。本发明无创血糖检测试纸，具有极高的检测灵敏度和极低的检测极限，能够真正实现无创血糖检测，具有巨大的市场潜力和商业价值。
下面以具体实施例对本发明作详细说明：
图 4 是本发明 无创血糖检测试纸 在含不同浓度葡萄糖的 PBS （磷酸盐缓冲液） 溶液中测试得到的 IDS-T 曲线。 从图中可以看到，随着葡萄糖浓度的增加，薄膜晶体管（无创血糖检测试纸）的沟道电流下降，并且随不同量级的变化呈现较好的台阶梯度变化。图 5 为对应的沟道电流随不同葡萄糖浓度值的变化关系，线性关系较好。此结果表明，本发明试纸对葡萄糖的最低检测浓度为 10-8M ，并且在 10-6M 到 10-3M 之间的线性关系较好，由于正常人及糖尿病患者的唾液样品中的葡萄糖浓度大概在 3 × 10-6M ～ 210 × 10-6M ，因此本发明可覆盖到唾液样品的葡萄糖检测范围，可实现对唾液样品的实际无创检测。
配合自制的无创血糖仪，把测量得到的沟道电流通过一定的拟合关系换算成血糖值，并通过血糖仪的屏幕读数读出。 图 6 是本发明 无创血糖检测试纸 配合无创血糖仪在唾液样品（对应不同的血糖值）中测试得到的血糖数值。 横坐标代表取患者的唾液样品时对应的血液样品测量得到的血糖值，纵坐标代表用无创血糖仪测量唾液样品时得到的血糖读数。从图中可以看出，实际测到的唾液血糖值跟血液的真实血糖值仅存在微量的误差，大概的变化趋势基本一致，也就是随着血液血糖值的增加，唾液血糖值也是增加的趋势，因此本发明无创血糖检测试纸可以实现对唾液样品的实际检测，且在葡萄糖检测中具有更高的灵敏度和更低的检测极限。
本发明具有以下有益效果：本发明 无创血糖检测试纸 ，检测液体可选择唾液、尿液、汗液、组织液等，不会给患者带来痛苦，同时避免血液检测过程中容易引起的交叉感染；本发明 无创血糖检测试纸基于 薄膜晶体管的原理设计，薄膜晶体管兼具传感和信号放大的作用，可对栅电极上微弱的信号变化进行放大，因此本发明 无创血糖检测试纸 具有极高的灵敏度和极低的检测极限。本发明 无创血糖检测试纸的 结构简单，制备工艺简单，适合大规模批量生产。
需要强调的是，在本发明设计原理的教导下， 可以将本发明 所述 无创血糖检测试纸做成不同的形状， 电极的尺寸、形状、以及排列顺序等也都可以进行不同的改变，如图 7 至图 9 、图 10 至图 12 所示，所有类似的非实质性的改变都应落在本发明的保护范围之内。
综上所述，本发明首次基于薄膜晶体管制作出 血糖检测 试纸，来实现对唾液、尿液、汗液、组织液等体液中的低浓度葡萄糖的检测。本发明无创血糖检测试纸，具有极高的检测灵敏度和极低的检测极限，能够真正实现无创血糖检测，具有巨大的市场潜力和商业价值。
应当理解的是，本发明的应用不限于上述的举例，对本领域普通技术人员来说，可以根据上述说明加以改进或变换，所有这些改进和变换都应属于本发明所附权利要求的保护范围。

Claims (10)

  1. 一种无创血糖检测试纸，用于检测液体内的葡萄糖浓度，其特征在于，所述无创血糖检测试纸包括：试纸基片，设置在所述试纸基片上的第一电极、第二电极和第三电极，设置在所述试纸基片上连接第一电极和第二电极的有机半导体薄膜材料，固定在所述第三电极上的葡萄糖氧化酶，及覆盖设置在所述试纸基片之上的绝缘盖片；
    所述绝缘盖片上设置有用于滴加待测液体的开口槽，所述有机半导体薄膜材料和葡萄糖氧化酶同时暴露在所述开口槽内。
  2. 根据权利要求 1 所述的无创血糖检测试纸，其特征在于，通过有机聚合物在所述第三电极上固定修饰所述葡萄糖氧化酶。
  3. 根据权利要求 2 所述的无创血糖检测试纸，其特征在于，所述有机聚合物包括全氟磺酸、壳聚糖、聚苯胺。
  4. 根据权利要求 1 所述的无创血糖检测试纸，其特征在于，通过纳米材料修饰所述第三电极以提高第三电极的检测灵敏度。
  5. 根据权利要求 4 所述的无创血糖检测试纸，其特征在于，所述纳米材料包括石墨烯、碳纳米管、铂纳米颗粒。
  6. 根据权利要求 1 所述的无创血糖检测试纸，其特征在于，所述试纸基片和所述绝缘盖片的材质包括 PET 塑料；所述第一电极、所述第二电极和所述第三电极的材质包括 Pt 、 Au 、 Ag 、 C 。
  7. 根据权利要求 1 所述的无创血糖检测试纸，其特征在于，所述有机半导体薄膜材料包括聚 (3,4- 乙烯二氧噻吩 )- 聚苯乙烯磺酸、聚吡咯、聚噻吩、聚苯胺、聚咔唑以及聚 (3,4- 乙烯二氧噻吩 )- 聚苯乙烯磺酸、聚吡咯、聚噻吩、聚苯胺、聚咔唑的共聚物。
  8. 根据权利要求 1 所述的无创血糖检测试纸，其特征在于，所述第一电极、所述第二电极和所述第三电极的厚度为 50-200nm ；所述有机半导体薄膜材料的厚度为 30-200nm 。
  9. 一种如权利要求 1-8 任一项所述的无创血糖检测试纸的制备方法，其特征在于，包括步骤：
    A 、清洗试纸基片并干燥，之后，在试纸基片上制备第一电极、第二电极和第三电极；
    B 、在第一电极和第二电极之间制备有机半导体薄膜材料，在第三电极上固定葡萄糖氧化酶；
    C 、将绝缘盖片固定在试纸基片上，使有机半导体薄膜材料和葡萄糖氧化酶同时暴露在绝缘盖片的开口槽内，制得所述无创血糖检测试纸。
  10. 根据权利要求 9 所述的无创血糖检测试纸的制备方法，其特征在于，所述步骤 A 中，所述第一电极、第二电极和第三电极是通过 丝网印刷、真空热蒸镀、磁控溅射或气相沉积中的一种方法制备 ；
    所述步骤 B 中，在所述试纸基片上 制备有机半导体薄膜材料的方法为旋涂或喷墨印刷 。
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