CN105411607B - Micro Interventional subcutaneous glucose sensor and method of preparation - Google Patents

Micro Interventional subcutaneous glucose sensor and method of preparation Download PDF

Info

Publication number
CN105411607B
CN105411607B CN201510783645.1A CN201510783645A CN105411607B CN 105411607 B CN105411607 B CN 105411607B CN 201510783645 A CN201510783645 A CN 201510783645A CN 105411607 B CN105411607 B CN 105411607B
Authority
CN
China
Prior art keywords
layer
electrode
lead
portion
sensor
Prior art date
Application number
CN201510783645.1A
Other languages
Chinese (zh)
Other versions
CN105411607A (en
Inventor
高春燕
Original Assignee
杭州亿信网络科技有限公司
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by 杭州亿信网络科技有限公司 filed Critical 杭州亿信网络科技有限公司
Priority to CN201510783645.1A priority Critical patent/CN105411607B/en
Publication of CN105411607A publication Critical patent/CN105411607A/en
Application granted granted Critical
Publication of CN105411607B publication Critical patent/CN105411607B/en

Links

Abstract

本发明是一种微型传感器,特别涉及一种皮下组织介入式葡萄糖微型传感器及其制备方法。 The present invention is a micro sensor, particularly to a subcutaneous glucose microsensor intrusive method for its preparation. 包括底座,所述的底座中设有向外延伸的引线部分,所述的引线部分的末端与传感器部分相连接,所述的传感器部分与引线部分分别设在绝缘基层上。 Comprising a base, said base is provided with a lead portion extending outwardly of said tip portion and sensor portion of the lead is connected to said sensor portion and the lead portions are provided on the insulating base layer. 皮下组织介入式葡萄糖微型传感器及其制备方法结构紧凑,提高操作性能,提升使用寿命。 Micro Interventional subcutaneous glucose sensor and its preparation method compact structure, improve operational performance, improve service life.

Description

皮下组织介入式葡萄糖微型传感器及其制备方法 Micro Interventional subcutaneous glucose sensor and method of preparation

技术领域 FIELD

[0001] 本发明是一种微型传感器,特别涉及一种皮下组织介入式葡萄糖微型传感器及其制备方法。 [0001] The present invention is a micro sensor, particularly to a subcutaneous glucose microsensor intrusive method for its preparation.

背景技术 Background technique

[0002] 糖尿病是一种全球范围内的严重危害人类健康的常见内分泌代谢疾病。 [0002] Diabetes is a common endocrine and metabolic diseases serious harm to human health within a global range. 近年来全球糖尿病患病率呈现明显上升趋势。 In recent years, the global prevalence of diabetes showed significant upward trend. 对于糖尿病患者而言,血糖监测至关重要,必须要根据血糖高低制定相应治疗方案。 For diabetes patients, glucose monitoring is essential, we must develop appropriate treatment programs based on blood glucose level. 由于影响人体血糖水平的因素很多,血糖有较大波动,传统单点血糖测量存在明显不足,不能获得准确全面的获得血糖信息,无法制定科学的个性化治疗方案,导致患者血糖波动,频繁出现高、低血糖,影响患者健康,严重时甚至危及生命。 Since the factors that affect blood sugar levels much greater fluctuations in blood sugar, there are obvious shortcomings of the traditional single-point blood glucose measurements, can not get access to accurate and comprehensive information on blood sugar, can not make scientific individualized treatment programs, leading to fluctuations in blood glucose in patients with frequent high , low blood sugar, affecting the health of patients, serious or even life-threatening.

[0003] 针对上述问题,近年来国内外公司研究开发出能够连续测量血糖的生物传感器,如美国专利US 7153265提及生物传感器,该传感器埋植在皮下组织,连续监测组织液葡萄糖。 [0003] In response to these problems, researches in recent years has developed a biosensor capable of continuous measurement of blood glucose, as described in US Patent No. US 7153265 mentioned biosensor, the sensor implanted in the subcutaneous tissue, tissue fluid continuous monitoring of glucose. 国内专利如CN200410101080.6提及皮下植入式生物传感器。 As mentioned domestic patent CN200410101080.6 subcutaneously implanted biosensor.

[0004]当前用于连续葡萄糖监测的生物传感器,基本都是利用葡萄糖氧化酶,该酶具有对葡萄糖高选择性的特点。 [0004] Current biosensors for continuous glucose monitoring, basically using the glucose oxidase enzyme having the characteristics of a high selectivity for glucose.

[0005] 考虑到植入可行性和工作稳定性,皮下植入传感器体积要求尽可能小,这样植入时痛感较小,植入后引起人体排斥反应也会较小,有利于传感器正常工作。 [0005] Considering the working stability and viability implanted subcutaneously implantable sensors required volume as small as possible, so that when implanted in a small pain, rejection after implantation will cause the body less conducive sensor is working properly. 当前用于人体植入葡萄糖微型传感器有两类,一类是需要导针植入传感器,基材一般为微型塑料片,除去作为载体的部分,还需要考虑电路导体引线排布,因而传感器体积较大,植入过程痛感较强,传感器的有效传感面积非常有限,会导致灵敏度较低,信噪比不佳,植入后稳定性不好。 Current implantable glucose microsensor for humans there are two types, one is the need for the guide pin implantable sensors, micro plastic sheet substrate is generally removed as part of the carrier, also we need to consider the circuit conductor wire arrangement, thus the volume of more sensors large, strong pain implantation procedure, the effective sensing area of ​​the sensor is very limited, results in a lower sensitivity, poor signal to noise ratio, good stability after implantation. 传感器工作电压一般在0.5V (Ag/AgCL参比)以上,在此电位上人体内小分子干扰物包括抗坏血酸、儿茶酚胺等会被氧化从而产生干扰信号,严重影响准确性。 Usually the sensor operating voltage 0.5V (Ag / AgCL reference) or more, the potential of this molecule in vivo Master small interferent include ascorbic acid, catecholamines, etc. may be oxidized to produce an interference signal, to affect the accuracy. 对此有些传感器在设计上增加一层高分子膜来阻挡干扰物,这往往导致传感器灵敏度下降,影响整体性能。 Some of this additional layer of polymer film sensor designed to block interferents, which often results in decreased sensitivity of the sensor, affect the overall performance. 此外传感器葡萄糖氧化酶氧化酶活性会随工作时间延长损失,酶活损失到一定程度,传感器无法正常工作,通常人体植入时间一般在72小时。 Further sensor glucose oxidase oxidase activity will work over prolonged loss, loss of enzyme activity to a certain extent, the sensor does not work, usually implanted human time is normally 72 hours.

[0006]未使用的葡萄糖氧化酶传感器,酶的活性会随保存时间衰减,活性损失到一定程度,传感器就不能提供稳定可用的信号,无法使用,因此葡萄糖氧化酶传感器都有有效期,一般有效期仅有6个月,使用不便。 [0006] Glucose oxidase unused sensor, the enzyme activity will decay over storage time, the loss of activity to a certain extent, the sensor can not provide a stable signal is available, can not be used, thus there is valid glucose oxidase sensor, generally valid only six months, inconvenient to use.

[0007] 不需要导针植入传感器,基材一般为金属,虽然电极有效面积得到提升,但是产品稳定性差,工艺流程非常规,无法实现大规模工业生产。 [0007] The guide pin does not need to implantable sensors, typically a metal substrate, although the effective area of ​​the electrode may be raised, but poor product stability, non-conventional processes, large scale industrial production can not be achieved.

[0008] 此外上述两种传感器都需要考虑电路导通问题,需要设计比较复杂的电路结构,需要设计非通用细小电路引线以及微型接插结构,而这些结构往往可靠性不佳,会出现引线或接插件故障引起的断路问题,从而导致传感器无法正常工作。 [0008] Also to be considered are both turned sensor circuit problem, the need to design more complex circuit configuration, a small circuit need to design non-universal connector leads and micro structures, and these structures are often poor reliability, will lead or open circuit connector failure caused the problem, leading to the sensor does not work.

发明内容 SUMMARY

[0009] 本发明主要是解决现有技术中存在的不足,结构紧凑度高,传感器体积小,有效面积大,相应信号高,抗干扰性能好,有效期长,可以比较好的解决电路导通问题,稳定可靠,容易大批量工业生产的皮下组织介入式葡萄糖微型传感器及其制备方法。 [0009] The present invention is to solve the problem present in the prior art, high structure compact, small volume sensor, a large effective area, high signal corresponding, anti-jamming performance, long shelf life, a better solution may be turned on circuit problem , reliable, easy to mass industrial production subcutaneous tissue glucose microsensor intrusive method for its preparation.

[0010] 本发明的上述技术问题主要是通过下述技术方案得以解决的: [0010] The technical problem of the present invention is mainly solved by the following technical scheme:

[0011] —种皮下组织介入式葡萄糖微型传感器,包括底座,所述的底座中设有向外延伸的引线部分,所述的引线部分的末端与传感器部分相连接,所述的传感器部分与引线部分分别设在绝缘基层上; [0011] - glucose species involved subcutaneous micro-sensor, comprising a base, said base is provided with a lead portion extending outwardly of said tip portion and sensor portion of the lead is connected to said sensor portion and the lead portions are provided on the insulating base layer;

[0012] 所述的传感器部分包括工作电极、参比电极、对电极和空白电极,所述的工作电极设在绝缘基层正面的左端,所述的参比电极设在绝缘基层正面的右端,所述的对电极设在绝缘基层正面的左端,所述的空白电极设在绝缘基层正面的右端,所述的工作电极与参比电极呈间隔状分布,所述的对电极与空白电极呈间隔状分布,构成四电极体系; [0012] The sensor portion includes a working electrode, reference electrode, counter electrode and a blank electrode, the working electrode disposed on the front surface of the left end of the insulating base layer, the reference electrode is provided on the front surface of the right end of the insulating base layer, the the electrode of said blank is provided on the front surface of the insulating base layer left end, the right end is disposed in front of the insulating base layer, the working electrode and the reference electrode was spaced-shaped profile, the blank electrode and counter electrode in a spaced-like distribution, constituting four-electrode system;

[0013]或, [0013] or,

[0014] 所述的传感器部分包括工作电极、对电极和参比电极,所述的工作电极设在绝缘基层一端面的左端,所述的对电极设在绝缘基层一端面的右端,所述的工作电极上端的内壁与对电极上端的内壁间设有参比电极,所述的工作电极、对电极和参比电极呈间隔状分布,构成三电极体系; [0014] The sensor portion includes a working electrode, counter electrode and reference electrode, the working electrode disposed on one end face of the left end of the insulating base layer, a counter electrode provided in a right end surface of the insulating base layer, said the upper end of the inner wall of the working electrode and the counter electrode between the inner wall of the upper end is provided with a reference electrode, the working electrode, counter electrode and reference electrode were spaced like distribution, constituting a three-electrode system;

[0015]或, [0015] or,

[0016] 所述的传感器部分包括工作电极、参比电极和对电极,所述的工作电极设在绝缘基层正面的左端,所述的参比电极设在绝缘基层正面的右端,所述的对电极设在绝缘基层背面的左端,所述的工作电极与参比电极呈间隔状分布,构成三电极体系; Sensor portion [0016] comprises the working electrode, a reference electrode and a counter electrode, the working electrode disposed on the front surface of the left end of the insulating base layer, the reference electrode is provided on the front surface of the right end of the insulating base layer, according to electrodes provided on the back surface of the left end of the insulating base layer, the working electrode and the reference electrode in a spaced-shaped profile constituting the three-electrode system;

[0017]或, [0017] or,

[0018] 所述的传感器部分包括工作电极和参比电极,所述的工作电极设在绝缘基层的正面,所述的参比电极设在绝缘基层的背面,构成两电极体系; [0018] The sensor includes a working electrode and a front portion of the reference electrode, the working electrode disposed on the insulating base layer, the reference electrode is provided on the back surface of the insulating base layer constituting the two-electrode system;

[0019] 所述的工作电极包括粘结层,所述的粘结层覆在绝缘基层的上部,所述的粘结层的上部的覆有导电层,所述的导电层的上部覆有惰性金属层,所述的惰性金属层的上部的覆有催化层,所述的催化层的上部的覆有酶层,所述的酶层的上部的覆有高分子层; [0019] The working electrode comprises an adhesive layer, the adhesive layer overlying the upper portion of the insulating base layer, an upper portion of the adhesive layer is coated with a conductive layer, an upper portion of the conductive layer is coated with an inert a metal layer, an upper portion of the inert metal layer is coated with a catalytic layer, an upper portion of the catalyst layer is coated with an enzyme layer, an upper portion of the enzyme layer is covered with a polymer layer;

[0020] 所述的参比电极包括参比电极粘结层,所述的粘结层覆在绝缘基层的上部,所述的粘结层的上部覆有参比电极导电层,所述的导电层的上部覆有惰性金属层,所述的惰性金属层的上部覆有银/氯化银层,所述的参比银/氯化银层的上部覆有参比高分子层; [0020] The reference electrode is a reference electrode comprising an adhesive layer, the adhesive layer overlying the upper portion of the insulating base layer, an upper portion of said adhesive layer is coated with a conductive layer, a reference electrode, said conductive the upper layer is coated with a layer of inert metal, inert metal layer, the upper portion is coated with silver / silver chloride layer, said upper reference silver / silver chloride reference layer is coated with a polymer layer;

[0021] 所述的对电极包括粘结层,所述的粘结层设在绝缘基层的底部,所述的粘结层的表面覆有导电层,所述的导电层的表面覆有惰性金属层,所述的惰性金属层的表面覆有催化层,所述的催化层的表面覆有高分子层; Said electrode comprising [0021] an adhesive layer, the adhesive layer is provided on the bottom of the insulating base layer, the surface of the adhesive layer is coated with a conductive layer, the surface of the conductive layer is coated with an inert metal layer, the surface layer of inert metal coated with a catalyst layer, the catalyst layer surface is coated with a polymer layer;

[0022] 所述的空白电极包括粘结层,所述的电极粘结层设在绝缘基层的底部,所述的粘结层的表面覆有导电层,所述的导电层的表面覆有惰性金属层,所述的惰性金属层的表面覆有催化层,所述的催化层的表面覆有高分子层; Blank electrode [0022] The adhesive layer comprises an adhesive layer provided on the electrode bottom insulating base layer, the surface of the adhesive layer is coated with a conductive layer, the surface of the conductive layer is coated with an inert a metal layer, the surface layer of inert metal coated with a catalyst layer, the catalyst layer surface is coated with a polymer layer;

[0023] 所述的引线部分由至少一个引线组件组成,所述的引线组件包括覆在绝缘基层表面的引线第一粘结层,所述的引线第一粘结层的表面覆有引线导电层,所述的引线导电层的表面覆有引线第二粘结层,所述的引线第二粘结层的表面覆有引线保护层。 Lead parts [0023] by at least one lead of said components, said assembly comprising a lead wire substrate surface overlying the first insulating adhesive layer, the surface of the first adhesive layer of the lead wire is coated with a conductive layer the surface of the lead wire is coated with the conductive layer of the second adhesive layer, the surface of the adhesive layer of the second lead wire covered with a protective layer.

[0024]作为优选,所述的引线组件设有4个,引线组件分别设在绝缘基层上表面的左端、绝缘基层上表面的右端、绝缘基层下表面的左端和绝缘基层下表面的右端,各引线组件间呈间隔状分布; [0024] Advantageously, the assembly is provided with a lead 4, the lead assembly are disposed on the left end surface of the insulating base layer, an insulating base layer on the right end of the right end surface of the left end of the lower insulating base layer and the insulating surface of the base surface, each between lead assembly in spaced-shaped distribution;

[0025]或, [0025] or,

[0026] 所述的引线组件设有3个,3个引线组件均分在绝缘基层的一个端面上; Lead assembly [0026] The provided 3, 3-average lead assembly in one end face of the insulating base layer;

[0027]或, [0027] or,

[0028] 所述的引线组件设有3个,其中二个引线组件均分在绝缘基层的上表面,另一个引线组件设在绝缘基层上表面的中间位; Lead assembly [0028] according to features 3, wherein the two lead assembly on the average surface of the insulating base, the other lead assembly disposed in the intermediate position on the insulating surface of the base layer;

[0029]或, [0029] or,

[0030] 所述的引线组件设有2个,一个引线组件设在绝缘基层上表面的中间位,另一个引线组件设在绝缘基层下表面的中间位。 Lead assembly [0030] according to features 2, a lead assembly is provided in an intermediate position on the surface of the insulating base layer, the other lead assembly disposed in the middle position of the lower insulating substrate surface.

[0031] 皮下组织介入式葡萄糖微型传感器的制备方法,按以下步骤进行: [0031] The method of preparing the subcutaneous tissue glucose invasive microsensors, perform the following steps:

[0032] (I)、绝缘基层的选择: [0032] (I), the insulating base layer selection:

[0033] 绝缘基层采用可挠曲的聚酰亚胺绝缘薄膜或聚酯薄膜作为载体,具有良好的物理和化学性能; [0033] an insulating base layer using an insulating flexible polyimide film or a polyester film as a carrier, has good physical and chemical properties;

[0034]具高度曲柔性,可立体配线,依空间限制改变形状;耐高低温,耐燃;可折叠而不影响讯号传递功能,可防止静电干扰;化学变化稳定,安定性、可信赖度高;利于相关产品的设计,可减少装配工时及错误,并提尚有关广品的使用寿命;良好的绝缘性能,体积电阻率达到1015 Ω.cm;对常用基体、金属和介电材料的粘结性优良;该层厚度控制在7.5-12.5微米; [0034] Qu highly flexible, three-dimensional wiring, by changing the shape of the space limit; high temperature resistance, fire; foldable without affecting the signal transmission, which prevents static; stable chemical changes, stability, and high reliable ; conducive related product design, assembly work can be reduced and mistakes, and still provide about the product life wide; good insulating properties, the volume resistivity reached 1015 Ω.cm; commonly used adhesive matrix metal and a dielectric material excellent; in the 7.5-12.5 micron layer thickness control;

[0035] (2)、粘结层材质选择: [0035] (2), the tie layer material selection:

[0036] 粘结层包括传感器部分和引线部分中各粘结层; [0036] The adhesive layer including the adhesive layer and the lead portion of the sensor portion;

[0037] 绝缘基层的正反两面涂布粘结层,该层性能直接影响到电极的性能,由于粘结剂与绝缘基层之间在制造过程中存在化学反应,因此对于不同的绝缘基层还应选择相对应的粘结剂体系,粘结剂的性能必须与绝缘基层相适应; [0037] both sides of the insulating base layer adhesive coating layer which directly affects the performance properties of the electrode, due to the presence of a chemical reaction between the binder in the manufacturing process and the insulating base layer, an insulating base layer thus also for different corresponding to the selected binder system, the binder must be adapted to the performance of the insulating base layer;

[0038] 所用的粘结层必须能够承受各种工艺条件和在制造中所使用的化学药品的侵蚀,并没有分层或降解的现象,考虑到人体植入粘结剂必需有较好的生物相容性,粘结层采用环氧树脂或丙烯酸树脂类,该层厚度控制在5-15微米; [0038] The adhesive layer used must be able to withstand the processing conditions and chemicals used in the production of corrosion and no delamination or degradation phenomena, taking into account the human implants binder must have good biological compatible, adhesive layer or an acrylic epoxy resin, controlling the thickness of the layer 5 to 15 microns;

[0039] (3)、导电层的选择: [0039] (3), the conductive layer is selected:

[0040] 导电层包括传感器部分和引线部分中各导电层; [0040] The conductive layer comprises a conductive layer of each sensor part and the lead portion;

[0041] 粘结层的表面为导电层,导电层采用压延铜箔,厚度控制在5-20微米; [0041] surface of the adhesive layer is a conductive layer, a conductive layer using a rolled copper foil, in 5-20 micron thickness control;

[0042]引线部分需要在导电层上制备引线第二粘结层和引线保护层,层间可通过滚压法增加层间结合力,电极部分不需要第二粘结层和保护层,按照不同要求制备相应功能层; [0042] The lead of the second lead portion needs to lead the protective layer and the adhesive layer was prepared on the conductive layer, the interlayer roll method may be increased by inter-layer adhesion, it does not require a second electrode portion adhesive layer and the protective layer, in different required to prepare the corresponding functional layer;

[0043] ⑷、引线第二粘结层的选择: [0043] ⑷, lead of the second adhesive layer is selected:

[0044]后端引线部分的导电层外是引线第二粘结层,粘结剂采用环氧树脂或丙烯酸树脂类,该层厚度控制在5-15微米; [0044] The rear end of the outer lead portion of the conductive layer is a lead of the second adhesive layer, an adhesive epoxy or acrylic resin, the layer thickness control in the 5-15 micron;

[0045] 前端电极部分需要裸漏的不涂该层粘结剂,层间可通过滚压法增加层间结合力; [0045] The front end of the bare drain electrode portion need not coated with the layer of adhesive, an interlayer may be increased interlayer bonding force by a rolling method;

[0046] (5)、保护层的选择: [0046] (5), the protective layer is selected:

[0047]后端引线部分的引线第二粘结层外是聚酰亚胺绝缘薄膜,保护膜先进行切割加工,露出前段电极部位的铜箔,电极引线覆盖保护膜; [0047] The rear end of the lead wire portion of the outer layer is a second adhesive polyimide insulating film, a protective film for cutting to expose part of the preceding electrode foil, a protective film covering the electrode lead;

[0048]该层厚度控制在5-15微米;可通过滚压法增加层间结合力; [0048] In the 5-15 micron layer thickness control; interlayer bonding force can be increased by the rolling method;

[0049] ⑶、电极部分功能层制备: [0049] ⑶, the functional layer portion of the electrode preparation:

[0050] 电极部分可以根据需要分为工作电极、对电极、参比电极、空白电极; [0050] The electrode portion may be divided into the required working electrode, counter electrode, reference electrode, the electrode blank;

[0051] ①、工作电极: [0051] ①, working electrode:

[0052] 工作电极铜箔上的功能层组成如下:惰性金属层、催化层、酶层、高分子层; [0052] The functional layer on the working electrode foil composed as follows: inert metal layer, a catalyst layer, an enzyme layer, a polymer layer;

[0053] 惰性金属层在电极部位的铜箔上制备,通过电镀、溅射的方法制备,可选用金、铂的惰性金属,该层厚度为10-15微米; [0053] The inert metal electrode layer prepared on the copper foil portions, by plating, sputtering production method, the choice of gold, platinum, inert metal, the layer thickness is 10-15 microns;

[0054] 催化层为铂黑,可以通过电镀方法制备; [0054] The platinum black catalyst layer may be prepared by a plating method;

[0055] 酶层通过喷雾、浸渍、涂布的方式将酶溶液转移到工作电极上,浸渍时间为5-15分钟; [0055] the enzyme layer by spraying, dipping, coating the enzyme solution was transferred way to the working electrode, the immersion time of 5-15 minutes;

[0056] 然后用浓度为5%-20%的戊二醛溶液将转移到工作电极的葡萄糖氧化酶交联固定,交联温度在25-35摄氏度,采用液相浸渍交联或气相交联,交联时间为30-60min; [0056] and a glutaraldehyde solution with a concentration of 5% to 20% will be transferred to the working electrode and cross-linked glucose oxidase, the crosslinking temperature 25-35 ° C, a liquid phase impregnation crosslinking or crosslinked to gas, crosslinking time is 30-60 min;

[0057] 所用酶溶液制备过程如下:在磷酸盐缓冲液中加入葡萄糖氧化酶和人重组白蛋白,葡萄糖氧化酶加入量为每毫升50-100毫克,人重组白蛋白加入量为每毫升50-100毫克;溶解充分后,添加1-5%的纳米金混匀,最后加入1-5 %的PVB,PVB指聚乙烯醇缩丁醛,混合均匀; [0057] The enzyme preparation was as follows: addition of glucose oxidase and recombinant human albumin in phosphate buffer, the glucose oxidase is added in an amount of 50-100 mg per ml, recombinant human albumin was added in an amount of 50 ml per 100 mg; fully dissolved after addition of 1-5% of gold nanoparticles mixing, and finally adding 1-5% of PVB, PVB refers to polyvinyl butyral, mixed;

[0058]纳米金利用AOT与环己烷体系形成的反胶束体系中制备,AOT是指琥玻酸二异辛酯璜酸钠,通过柠檬酸钠还原氯金酸盐水溶液,调节水、电解质、表面活性剂的浓度比例,制备不同直径的纳米金颗粒,纳米金颗粒直径在5-30nm ; [0058] Gold Nanoparticles prepared using reversed micelles of AOT formed cyclohexane system, AOT amber glass refers sodium dioctyl Juan, by reducing chloroauric acid salt sodium citrate solution, adjusting water electrolyte , the ratio of the concentration of surfactant, the preparation of gold nanoparticles with different diameters of 5-30 nm diameter gold nanoparticles;

[0059] 葡萄糖氧化酶交联完成后,可以通过浸渍、涂布的方式在电极固定一层高分子膜,以增强传感器生物相容性,提高体内性能; [0059] After the completion of cross-linking glucose oxidase, by dipping, coating manner fixed electrode layer of polymer film, to enhance the biocompatibility of the sensor, to improve the performance in vivo;

[0060]由于纳米金具有良好的生物相容性,可以较长时间植入人体内,而不引起不良反应; [0060] Since the nano-gold has good biocompatibility, may be implanted in the human body for a long time without causing adverse reactions;

[0061]纳米金有良好的导电性,可以提高酶电极的灵敏度,缩短酶电极对葡萄糖响应时间,延长酶电极使用寿命; [0061] Nano Jinyou Liang good electrical conductivity, can improve the sensitivity of the enzyme electrode, an enzyme electrode glucose shorten response time, to extend the service life of the enzyme electrode;

[0062] 葡萄糖氧化酶电极氧化葡萄糖的反应由两步酶反应组成: [0062] Glucose Glucose Oxidase Electrode oxidation reaction of two-step enzyme reaction composition:

[0063] D-glucose+GOD (FAD) -^glucose-lactone+GOD (FADH2) [0063] D-glucose + GOD (FAD) - ^ glucose-lactone + GOD (FADH2)

[0064] GOD (FADH2) +O2—GOD (FAD) +H2O2 [0064] GOD (FADH2) + O2-GOD (FAD) + H2O2

[0065] glucose-lactone+H20^glucose-acid [0065] glucose-lactone + H20 ^ glucose-acid

[0066] 上述过程中,还原态葡萄糖氧化酶GOD (FADH2)稳定性较差,比较容易发生结构改变,无法被氧化变成常态葡萄糖氧化酶,这是常见葡萄糖氧化酶电极酶活丧失的原因之一;而在酶层加入纳米金颗粒后,纳米金颗粒具有从环境吸收电子的特性,可以迅速将还原态葡萄糖氧化酶GOD (FADH2)氧化成稳态葡萄糖氧化酶GOD (FAD),减少电极反应过程中还原态葡萄糖氧化酶GOD (FADH2)的数量以及存在时间,减少酶活性损失,延长电极寿命;此外纳米金颗粒加入还大幅度提高酶电极响应应速度,缩短酶电极相应时间,改善了皮下葡萄糖传感器测量时信号延迟,提高实时监测准确度; [0066] The above-described process, the reduced state of glucose oxidase GOD (FADH2) poor stability, more prone to structural changes, can not be oxidized to normal glucose oxidase, which is glucose oxidase electrode common cause loss of activity a; and after addition of the enzyme layer of gold nanoparticles, gold nanoparticles having a property of absorbing electrons from the environment, can be quickly reduced state of glucose oxidase GOD (FADH2) is oxidized to the steady-state glucose oxidase GOD (FAD), reduced electrode reaction reducing the number of processes of glucose oxidase GOD (FADH2) and the present time, reduce loss of enzyme activity, prolong electrode life; gold nanoparticles added in addition also be greatly improved in response speed of the enzyme electrode, an enzyme electrode to shorten the response time, improved subcutaneous when the glucose sensor measurement signal delay, improve the accuracy of the real-time monitoring;

[0067]高分子层,用以提供传感器植入人体所需生物相容性,提高体内性能;可以通过浸渍、涂布的方式在电极固定一层高分子膜,所用到高分子材料是硅橡胶聚合物、聚氨酯、聚亚安酯、聚乙二醇其中的一种或多种混合;溶剂采用无水乙醇、四氢呋喃,可以通过喷雾、浸渍、涂布的方式制备; [0067] polymer layer, to provide the desired biocompatible implantable sensor body, to improve the performance in vivo; by dipping, coating manner fixed electrode layer of polymer film, the polymer material used is a silicone rubber polymers, polyurethanes, polyurethane, polyethylene glycol, wherein the one or more mixed; the solvent using ethanol, tetrahydrofuran, can be prepared by spraying, dipping, coating methods;

[0068] ②、对电极: [0068] ②, counter electrode:

[0069] 对电极铜箔上的功能层包括对惰性金属层、对催化层、对高分子层;其制备方法与工作电极基本相同,不需制备酶层; [0069] The inert metal layer, a functional layer including copper on the electrode catalyst layer, the polymer layer; prepared in substantially the same manner as the working electrode thereof, prepared without the enzyme layer;

[0070] ③、空白电极: [0070] ③, blank electrode:

[0071]空白电极铜箔上的功能层包括惰性金属层、催化层、高分子层;其制备方法与工作电极相同,不需制备酶层; [0071] The functional layer comprises an inert foil electrode blank metal layer, catalyst layer, polymer layer; the same preparation method of the working electrode, was prepared without the enzyme layer;

[0072] ④、参比电极: [0072] ④, reference electrode:

[0073] 参比电极铜箔上的功能层包括惰性金属层、参比银/氯化银层、高分子层; [0073] Reference inert metal layer, a reference silver / silver chloride layer, a functional polymer layer than the layer on the electrode comprises a copper foil;

[0074] 惰性金属层制备方法与工作电极相同,惰性金属层制备完成后,通过电镀、真空溅射的方法制备银/氯化银层,电化学氯化后制备银/氯化银层,最后制备高分子外膜; [0074] The inert metal layer and the working electrode prepared in the same method, after completion of the preparation of an inert metal layer by electroplating, vacuum sputtering method for preparing a silver / silver chloride layer, electrochemical chloride after preparation of silver / silver chloride layer, and finally preparation of outer membrane polymer;

[0075] 上述制备工艺完成后,最后根据单元电路进行切割,得到传感器,三电极和四电极传感器尺寸如下:植入人体部分长度不大于15_,宽不大于0.6mm,厚不大于0.4mm; [0075] After the above preparation process is completed, the final cut unit circuit according to obtain the sensor, three-electrode and four-electrode sensor dimensions are as follows: the implant body portion length is not greater than 15_, width is not greater than 0.6mm, a thickness of not greater than 0.4mm;

[0076] 两电极尺寸如下:植入人体部分长度不大于15mm,宽不大于0.3mm,厚不大于0.4mm; [0076] The two electrodes following dimensions: a length no greater than the implant portion body 15mm, width is not greater than 0.3mm, a thickness of not greater than 0.4mm;

[0077]由上述工作电极、对电极、参比电极、空白电极,四电极组成传感器,不需要在酶层添加纳米金,传感器正常工作电压0.55V,空白电极用于检测背景信号和干扰信号,提高传感器准确性; [0077] by the working electrode, counter electrode, reference electrode, blank electrode, an electrode composed of four sensors, no need to add the enzyme in the nano-gold layer, the sensor normal operating voltage 0.55V, blank electrode for detecting the background signal and interference signals, improve the accuracy of the sensor;

[0078] 两电极和三电极传感器,制备过程需在酶层增加纳米金; [0078] The two electrodes and three-electrode sensors, need to increase the preparation of gold nanoparticles in the enzyme layer;

[0079] 传感器可以通过导针植入皮下,然后退出导针,传感器留在皮下组织开始工作。 [0079] The sensor may be implanted subcutaneously by a guide pin and guide pin exit, leaving the sensor in the subcutaneous tissue to work.

[0080] 本发明采取传感器制备方法,没有任何非通用电路引线以及微型接插结构,传感器本身就在柔性线路上,从根本上解决了电路导通问题,可以实现长期稳定信号采集,不会出现由于电路断路引起故障。 [0080] The present invention takes the preparation of the sensor, there is no non-universal micro circuit wiring and connector structures, sensors on the flexible circuit itself, solve the problem of conduction from the fundamental circuit, signal acquisition can achieve long-term stable, does not appear Since the circuit breaker due to a fault.

[0081] 本传感器制备方法,由于电极引线是铜箔,而且有保护膜,电路引线可弯曲、扭转而不会损坏,引线可以体积更小,排布方式更灵活,因而可以给铜箔电极提供更大的空间。 [0081] The preparation method of the sensor, since the electrode lead wire is a copper foil, and a protective film, circuit wiring can be bent, twisted without damage, the lead can be smaller, more flexible arrangement, it is possible to provide a copper foil electrode more space. 传感器体积可以做到,双面传感器工作电极有效面积可以做到,相比常见传感器体积更小,电极工作面积更大,有利于提高传感器体内性能。 Volume sensor can be done, a double-sided sensor active area of ​​the working electrode can be done, as compared to the common sensor is smaller and larger working electrode area, help to improve the in vivo performance of the sensor.

[0082] 本传感器制备方法借鉴较为成熟电子工业电路制备工艺,工艺成熟稳定,易于实现批量化生产,提高传感器稳定性,同时大大降低单个传感器成本。 [0082] The present method for preparing mature reference sensor producing an electronic circuit industrial processes, of mature stable, easy to achieve mass production, to improve the stability of the sensor, while significantly reducing the cost of a single sensor.

[0083]因此,本发明提供的皮下组织介入式葡萄糖微型传感器及其制备方法,结构紧凑,提尚操作性能,提升使用寿命。 [0083] Accordingly, the present invention provides the subcutaneous tissue glucose microsensor intervention and its preparation method, compact, yet provide operation performance, improve service life.

附图说明 BRIEF DESCRIPTION

[0084]图1是本发明中的结构示意图; [0084] FIG. 1 is a schematic view of the present invention;

[0085]图2是本发明的制备过程示意图; [0085] FIG. 2 is a schematic diagram of preparation process of the present invention;

[0086]图3本发明中电极的正面示意图; [0086] Figure 3 a front electrode of the present invention in a schematic view;

[0087]图4本发明中电极的反面示意图; [0087] Figure 4 a schematic back electrode of the present invention;

[0088] 图5是图4中AA剖视结构示意图; [0088] FIG. 5 is a schematic cross-sectional view AA structure of Figure 4;

[0089] 图6是图4中BB剖视结构示意图; [0089] FIG. 6 is a schematic cross-sectional view BB structure of Figure 4;

[0090]图7是本发明中其中一种电极形态的示意图; [0090] FIG. 7 is a schematic view of an electrode aspect of the present invention;

[0091]图8本发明中另一种电极形态的正面示意图; [0091] The schematic diagram of another aspect of a positive electrode of the present invention in Figure 8;

[0092]图9是图8的反面结构示意图; [0092] FIG. 9 is a structural diagram of the reverse side of FIG. 8;

[0093]图10本发明中另外一种电极形态的正面示意图; [0093] Further aspect of a front view showing an electrode 10 in the present invention;

[0094]图11是图10的反面结构示意图; [0094] FIG. 11 is a schematic configuration diagram of the reverse side of the 10;

[0095]图12是本发明的传感器在溶液中测试性能的表格图; [0095] FIG. 12 is a sensor of the present invention in solution form in FIG performance tests;

[0096]图13是本发明的传感器在溶液中测试性能的性能图; [0096] FIG 13 is a sensor of the present invention in solution Performance FIG performance tests;

[0097]图14是本发明植入人体后传感器性能图。 [0097] FIG. 14 is a rear sensor performance of the present invention implanted in the body FIG.

具体实施方式 Detailed ways

[0098]下面通过实施例,并结合附图,对本发明的技术方案作进一步具体的说明。 [0098] The following Examples, in conjunction with the accompanying drawings, technical solutions of the present invention will be further specifically described.

[0099] 实施例1:如图1、图2、图3、图4、图5、图6、图7、图8、图9、图10、图11、图12、图13和图14所示,一种皮下组织介入式葡萄糖微型传感器,包括底座I,所述的底座I中设有向外延伸的引线部分2,所述的引线部分2的末端与传感器部分3相连接,所述的传感器部分3与引线部分2分别设在绝缘基层4上; [0099] Example 1: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 and 14 in FIG. illustrating a subcutaneous glucose interventional micro sensor comprising a base I, I, said base is provided with an outwardly extending portion of the lead 2, of the lead terminal portion 2 and the sensor portion 3 is connected to the sensor portion 3 and the lead portion 2 are provided on the insulating base layer 4;

[0100] 所述的传感器部分3包括工作电极5、参比电极6、对电极7和空白电极8,所述的工作电极5设在绝缘基层4正面的左端,所述的参比电极6设在绝缘基层4正面的右端,所述的对电极7设在绝缘基层4正面的左端,所述的空白电极8设在绝缘基层4正面的右端,所述的工作电极5与参比电极6呈间隔状分布,所述的对电极7与空白电极8呈间隔状分布,构成四电极体系; [0100] The sensor portion 5 includes a working electrode 3, reference electrode 6, counter electrode 7 and the electrode gap 8, the working electrode 5 is provided on the front surface of the left end of the insulating base layer 4, the reference electrode 6 is provided in front of the right end of the insulating base layer 4, the counter electrode 7 provided on the front surface of the left end of the insulating base layer 4, the blank electrode 8 provided in the insulating base layer 4 of the front right, the working electrode 5 and reference electrode 6 was spaced-like distribution, to form electrodes 7 and the electrode gap-like distribution of the spacer 8, constituting the four-electrode system;

[0101]或, [0101] or,

[0102] 所述的传感器部分3包括工作电极5、对电极7和参比电极6,所述的工作电极5设在绝缘基层4 一端面的左端,所述的对电极7设在绝缘基层4 一端面的右端,所述的工作电极5上端的内壁与对电极7上端的内壁间设有参比电极6,所述的工作电极5、对电极7和参比电极6呈间隔状分布,构成三电极体系; [0102] The sensor portion 3 includes a working electrode 5, counter electrode 7 and the reference 6, the working electrode 5 provided on the insulating base layer 4 is a left end surface of the electrode, the counter electrode 7 provided on the insulating base layer 4 a right end surface, between the inner wall of the upper end of the working electrode 5 with the inner wall of the upper end of the reference electrode 7 is provided with 6, the electrode of the working electrode 5, as a gap-like distribution of the reference electrode 7 and the electrode 6, composed of three-electrode system;

[0103]或, [0103] or,

[0104] 所述的传感器部分3包括工作电极5、参比电极6和对电极7,所述的工作电极5设在绝缘基层4正面的左端,所述的参比电极6设在绝缘基层4正面的右端,所述的对电极7设在绝缘基层4背面的左端,所述的工作电极5与参比电极6呈间隔状分布,构成三电极体系; [0104] The sensor portion 5 includes a working electrode 3, reference electrode 6 and counter electrode 7, the working electrode 5 is provided on the front surface of the left end of the insulating base layer 4, the reference electrode 6 is provided on the insulating base layer 4 front right end of the counter electrode 7 provided on the back surface of the left end of the insulating base layer 4, the working electrode 5 as a reference electrode 6 and the spacer profile shaped to form a three-electrode system;

[0105]或, [0105] or,

[0106] 所述的传感器部分3包括工作电极5和参比电极6,所述的工作电极5设在绝缘基层4的正面,所述的参比电极6设在绝缘基层4的背面,构成两电极体系; [0106] The sensor portion 3 includes a back surface of the working electrode 5 and reference electrode 6, the working electrode 5 is provided on the front surface of the insulating base layer 4, the reference electrode 6 is provided on the insulating base layer 4 constitutes two electrode system;

[0107] 所述的工作电极5包括粘结层9,所述的粘结层9覆在绝缘基层4的上部,所述的粘结层9的上部的覆有导电层10,所述的导电层10的上部覆有惰性金属层11,所述的惰性金属层11的上部的覆有催化层12,所述的催化层12的上部的覆有酶层13,所述的酶层13的上部的覆有高分子层14; [0107] The working electrode 5 comprises an adhesive layer 9, the adhesive layer 9 overlying the upper insulating base layer 4, the upper portion of the adhesive layer 9 is coated with 10, a conductive layer of the conductive the upper layer 10 is coated with an inert metal layer 11, an upper portion of the inert metal layer 11 is coated with a catalyst layer 12, the upper portion of the catalyst layer 12 is coated with an enzyme layer 13, an upper layer 13 of the enzyme It is coated with a polymer layer 14;

[0108] 所述的参比电极包括参比电极粘结层15,所述的粘结层15覆在绝缘基层4的上部,所述的粘结层15的上部覆有参比电极导电层16,所述的导电层16的上部覆有惰性金属层17,所述的惰性金属层17的上部覆有银/氯化银层18,所述的参比银/氯化银层18的上部覆有参比高分子层19; [0108] The reference electrode comprises a reference electrode 15 adhesive layer, the adhesive layer 15 overlying the upper insulating base layer 4, an upper portion of the adhesive layer 15 is covered with a reference electrode in the conductive layer 16 upper portion of the conductive layer 16 is coated with an inert metal layer 17, an upper portion of the inert metal layer 17 is coated with silver / silver chloride layer 18, an upper portion of said reference silver / silver chloride layer 18 overlying there reference polymer layer 19;

[0109] 所述的对电极包括粘结层20,所述的粘结层20设在绝缘基层4的底部,所述的粘结层20的表面覆有导电层21,所述的导电层21的表面覆有惰性金属层22,所述的惰性金属层22的表面覆有催化层23,所述的催化层23的表面覆有高分子层24; Said electrode comprising [0109] 20 adhesive layer, the adhesive layer 20 provided on the bottom of the insulating base layer 4, the surface of the adhesive layer 20 is coated with a conductive layer 21, the conductive layer 21 a surface coated with an inert metal layer 22, the surface of the inert metal layer 22 is coated with a catalyst layer 23, the surface of the catalyst layer 23 is coated with a polymer layer 24;

[0110] 所述的空白电极8包括粘结层25,所述的电极粘结层25设在绝缘基层4的底部,所述的粘结层25的表面覆有导电层26,所述的导电层26的表面覆有惰性金属层27,所述的惰性金属层27的表面覆有催化层28,所述的催化层28的表面覆有高分子层29; Blank electrode according to [0110] 8 comprises an adhesive layer 25, the adhesive layer 25 is an electrode provided at the bottom of the insulating base layer 4, the surface of the adhesive layer 25 is coated with a conductive layer 26, the conductive the surface layer 26 is coated with an inert metal layer 27, the surface of the inert metal layer 27 is coated with a catalytic layer 28, the surface of the catalyst layer 28 is coated with a polymer layer 29;

[0111] 所述的引线部分2由至少一个引线组件30组成,所述的引线组件30包括覆在绝缘基层4表面的引线第一粘结层31,所述的引线第一粘结层31的表面覆有引线导电层32,所述的引线导电层32的表面覆有引线第二粘结层33,所述的引线第二粘结层33的表面覆有引线保护层34。 Lead [0111] 2 portion of the at least one lead assembly 30 composed of the lead wire assembly 30 comprises a first adhesive layer overlying the surface of the insulating base layer 31 4, the lead 31 of the first adhesive layer a lead layer coated with conductive surface 32, the surface of the conductive layer 32 of the lead wire is coated with a second adhesive layer 33, the surface of the adhesive layer 33 of the second lead is covered with a protective layer 34 lead.

[0112] 所述的引线组件30设有4个,引线组件30分别设在绝缘基层4上表面的左端、绝缘基层4上表面的右端、绝缘基层4下表面的左端和绝缘基层4下表面的右端,各引线组件30间呈间隔状分布; Lead assembly [0112] 30 is provided with four of the lead assemblies 30 are disposed on the left end surface of the insulating base layer 4, the right end surface of the insulating base layer 4, 4 4 and the lower surface of the left end surface of the insulating base layer an insulating base layer right, each of the lead assemblies 30 in spaced-shaped distribution;

[0113]或, [0113] or,

[0114] 所述的引线组件30设有3个,3个引线组件30均分在绝缘基层4的一个端面上; Lead assembly [0114] 30 is provided with the three, sharing one end face 30 of the insulating base layer 4 of the lead assembly 3;

[0115]或, [0115] or,

[0116] 所述的引线组件30设有3个,其中二个引线组件30均分在绝缘基层4的上表面,另一个引线组件30设在绝缘基层4上表面的中间位; Lead assembly [0116] 30 is provided with the three, two of which lead assembly 30 on the average surface of the insulating base layer 4, the other lead assembly 30 is provided in the intermediate position on the surface 4 of the insulating base layer;

[0117]或, [0117] or,

[0118] 所述的引线组件30设有2个,一个引线组件30设在绝缘基层4上表面的中间位,另一个引线组件30设在绝缘基层4下表面的中间位。 Lead assembly [01] of claim 30 with 2, a lead assembly 30 is provided on the surface of the insulating base layer meditope 4, the other lead assembly 30 is provided at an intermediate position of the lower surface of the insulating base layer 4.

[0119] 皮下组织介入式葡萄糖微型传感器的制备方法,按以下步骤进行: [0119] The method of preparing the subcutaneous tissue glucose invasive microsensors, perform the following steps:

[0120] (I)、绝缘基层的选择: [0120] (I), the insulating base layer selection:

[0121] 绝缘基层采用可挠曲的聚酰亚胺绝缘薄膜或聚酯薄膜作为载体,具有良好的物理和化学性能; [0121] an insulating base layer using an insulating flexible polyimide film or a polyester film as a carrier, has good physical and chemical properties;

[0122]具高度曲柔性,可立体配线,依空间限制改变形状;耐高低温,耐燃;可折叠而不影响讯号传递功能,可防止静电干扰;化学变化稳定,安定性、可信赖度高;利于相关产品的设计,可减少装配工时及错误,并提尚有关广品的使用寿命;良好的绝缘性能,体积电阻率达到1015 Ω.Cm;对常用基体、金属和介电材料的粘结性优良;该层厚度控制在7.5微米; [0122] Qu highly flexible, three-dimensional wiring, by changing the shape of the space limit; high temperature resistance, fire; foldable without affecting the signal transmission, which prevents static; stable chemical changes, stability, and high reliable ; conducive related product design, assembly work can be reduced and mistakes, and still provide about the product life wide; good insulating properties, the volume resistivity reached 1015 Ω.Cm; commonly used adhesive matrix metal and a dielectric material excellent; control of the layer thickness of 7.5 microns;

[0123] ⑷、粘结层材质选择: [0123] ⑷, the adhesive layer material selection:

[0124] 粘结层包括传感器部分和引线部分中各粘结层; [0124] the adhesive layer including the adhesive layer and the lead portion of the sensor portion;

[0125] 绝缘基层的正反两面涂布粘结层,该层性能直接影响到电极的性能,由于粘结剂与绝缘基层之间在制造过程中存在化学反应,因此对于不同的绝缘基层还应选择相对应的粘结剂体系,粘结剂的性能必须与绝缘基层相适应; [0125] both sides of the insulating base layer adhesive coating layer which directly affects the performance properties of the electrode, due to the presence of a chemical reaction between the binder in the manufacturing process and the insulating base layer, an insulating base layer thus also for different corresponding to the selected binder system, the binder must be adapted to the performance of the insulating base layer;

[0126] 所用的粘结层必须能够承受各种工艺条件和在制造中所使用的化学药品的侵蚀,并没有分层或降解的现象,考虑到人体植入粘结剂必需有较好的生物相容性,粘结层采用环氧树脂或丙烯酸树脂类,该层厚度控制在5微米; [0126] The adhesive layer used must be able to withstand the processing conditions and chemicals used in the production of corrosion and no delamination or degradation phenomena, taking into account the human implants binder must have good biological compatible, adhesive layer or an acrylic epoxy resin, the layer thickness control at 5 [mu] m;

[0127] (5)、导电层的选择: [0127] (5), the conductive layer is selected:

[0128] 导电层包括传感器部分和引线部分中各导电层; [0128] each conductive layer comprises a conductive layer and the lead portion of the sensor portion;

[0129] 粘结层的表面为导电层,导电层采用压延铜箔,厚度控制在5微米; [0129] surface of the adhesive layer is a conductive layer, a conductive layer using a rolled copper foil, in a thickness of 5 microns control;

[0130]引线部分需要在导电层上制备引线第二粘结层和引线保护层,层间可通过滚压法增加层间结合力,电极部分不需要第二粘结层和保护层,按照不同要求制备相应功能层; [0130] required lead portion and the lead wire of the second adhesive layer was prepared in the protective layer on the conductive layer, the interlayer roll method may be increased by inter-layer adhesion, it does not require a second electrode portion adhesive layer and the protective layer, in different required to prepare the corresponding functional layer;

[0131] ⑷、引线第二粘结层的选择: [0131] ⑷, lead of the second adhesive layer is selected:

[0132]后端引线部分的导电层外是引线第二粘结层,粘结剂采用环氧树脂或丙烯酸树脂类,该层厚度控制在5微米; [0132] the rear end of the outer lead portions of the conductive layer is a lead of the second adhesive layer, an adhesive epoxy or acrylic resin, the layer thickness control at 5 [mu] m;

[0133] 前端电极部分需要裸漏的不涂该层粘结剂,层间可通过滚压法增加层间结合力; [0133] The front end of the bare drain electrode portion need not coated with the layer of adhesive, an interlayer may be increased interlayer bonding force by a rolling method;

[0134] (5)、保护层的选择: [0134] (5), the protective layer is selected:

[0135]后端引线部分的引线第二粘结层外是聚酰亚胺绝缘薄膜,保护膜先进行切割加工,露出前段电极部位的铜箔,电极引线覆盖保护膜; [0135] lead a rear end of the outer lead portion of the second insulating adhesive layer is a polyimide film, a protective film for cutting to expose part of the preceding electrode foil, a protective film covering the electrode lead;

[0136]该层厚度控制在5微米;可通过滚压法增加层间结合力; [0136] The layer thickness was controlled at 5 microns; interlayer bonding force can be increased by the rolling method;

[0137] ⑶、电极部分功能层制备: [0137] ⑶, the functional layer portion of the electrode preparation:

[0138] 电极部分可以根据需要分为工作电极、对电极、参比电极、空白电极; [0138] The electrode portion may be divided into the required working electrode, counter electrode, reference electrode, the electrode blank;

[0139] ①、工作电极: [0139] ①, working electrode:

[0140] 工作电极铜箔上的功能层组成如下:惰性金属层、催化层、酶层、高分子层; [0140] a functional layer on the working electrode foil composed as follows: inert metal layer, a catalyst layer, an enzyme layer, a polymer layer;

[0141] 惰性金属层在电极部位的铜箔上制备,通过电镀、溅射的方法制备,可选用金、铂的惰性金属,该层厚度为10微米; [0141] inert metal electrode layer prepared on the copper foil portions, by plating, sputtering production method, the choice of gold, platinum, inert metal, the layer thickness is 10 m;

[0142] 催化层为铂黑,可以通过电镀方法制备; [0142] platinum black catalyst layer may be prepared by a plating method;

[0143] 酶层通过喷雾、浸渍、涂布的方式将酶溶液转移到工作电极上,浸渍时间为5分钟; [0143] the enzyme layer by spraying, dipping, coating the enzyme solution was transferred way to the working electrode, the immersion time of 5 minutes;

[0144] 然后用浓度为5%的戊二醛溶液将转移到工作电极的葡萄糖氧化酶交联固定,交联温度在25摄氏度,采用液相浸渍交联或气相交联,交联时间为30-60min; [0144] and a glutaraldehyde solution with a concentration of 5% will be transferred to the working electrode and cross-linked glucose oxidase, the crosslinking temperature of 25 ° C, a liquid phase impregnation VAPOR crosslinking or crosslinking time of 30 -60min;

[0145] 所用酶溶液制备过程如下:在磷酸盐缓冲液中加入葡萄糖氧化酶和人重组白蛋白,葡萄糖氧化酶加入量为每毫升50毫克,人重组白蛋白加入量为每毫升50毫克;溶解充分后,添加I %的纳米金混匀,最后加入I %的PVB,PVB指聚乙烯醇缩丁醛,混合均匀; [0145] The enzyme solution was prepared with the following procedure: addition of glucose oxidase and recombinant human albumin in phosphate buffer, the glucose oxidase is added in an amount of 50 mg per ml, recombinant human albumin was added in an amount of 50 mg per ml; dissolved after sufficient, I% of gold nanoparticles added mixed and finally I% of PVB, PVB refers to polyvinyl butyral, mixed;

[0146]纳米金利用AOT与环己烷体系形成的反胶束体系中制备,AOT是指琥玻酸二异辛酯璜酸钠,通过柠檬酸钠还原氯金酸盐水溶液,调节水、电解质、表面活性剂的浓度比例,制备不同直径的纳米金颗粒,纳米金颗粒直径在5nm ; [0146] Gold Nanoparticles prepared using reversed micelles of AOT formed cyclohexane system, AOT amber glass refers sodium dioctyl Juan, by reducing chloroauric acid salt sodium citrate solution, adjusting water electrolyte , the ratio of the concentration of surfactant, the preparation of gold nanoparticles with different diameters, gold nanoparticles 5 nm in diameter;

[0147] 葡萄糖氧化酶交联完成后,可以通过浸渍、涂布的方式在电极固定一层高分子膜,以增强传感器生物相容性,提高体内性能; [0147] After the completion of cross-linking glucose oxidase, by dipping, coating manner fixed electrode layer of polymer film, to enhance the biocompatibility of the sensor, to improve the performance in vivo;

[0148]由于纳米金具有良好的生物相容性,可以较长时间植入人体内,而不引起不良反应; [0148] Since the nano-gold has good biocompatibility, may be implanted in the human body for a long time without causing adverse reactions;

[0149]纳米金有良好的导电性,可以提高酶电极的灵敏度,缩短酶电极对葡萄糖响应时间,延长酶电极使用寿命; [0149] Nano Jinyou Liang good electrical conductivity, can improve the sensitivity of the enzyme electrode, an enzyme electrode glucose shorten response time, to extend the service life of the enzyme electrode;

[0150] 葡萄糖氧化酶电极氧化葡萄糖的反应由两步酶反应组成: [0150] Glucose Glucose Oxidase Electrode oxidation reaction of two-step enzyme reaction composition:

[0151] D-glucose+GOD (FAD) -^glucose-lactone+GOD (FADH2) [0151] D-glucose + GOD (FAD) - ^ glucose-lactone + GOD (FADH2)

[0152] GOD (FADH2) +O2^GOD (FAD) +H2O2 [0152] GOD (FADH2) + O2 ^ GOD (FAD) + H2O2

[0153] glucose-lactone+H20^glucose-acid [0153] glucose-lactone + H20 ^ glucose-acid

[0154] 上述过程中,还原态葡萄糖氧化酶GOD (FADH2)稳定性较差,比较容易发生结构改变,无法被氧化变成常态葡萄糖氧化酶,这是常见葡萄糖氧化酶电极酶活丧失的原因之一;而在酶层加入纳米金颗粒后,纳米金颗粒具有从环境吸收电子的特性,可以迅速将还原态葡萄糖氧化酶GOD (FADH2)氧化成稳态葡萄糖氧化酶GOD (FAD),减少电极反应过程中还原态葡萄糖氧化酶GOD (FADH2)的数量以及存在时间,减少酶活性损失,延长电极寿命;此外纳米金颗粒加入还大幅度提高酶电极响应应速度,缩短酶电极相应时间,改善了皮下葡萄糖传感器测量时信号延迟,提高实时监测准确度; [0154] In the above process, the reduced state of glucose oxidase GOD (FADH2) poor stability, more prone to structural changes, can not be oxidized to normal glucose oxidase, which is glucose oxidase electrode common cause loss of activity a; and after addition of the enzyme layer of gold nanoparticles, gold nanoparticles having a property of absorbing electrons from the environment, can be quickly reduced state of glucose oxidase GOD (FADH2) is oxidized to the steady-state glucose oxidase GOD (FAD), reduced electrode reaction reducing the number of processes of glucose oxidase GOD (FADH2) and the present time, reduce loss of enzyme activity, prolong electrode life; gold nanoparticles added in addition also be greatly improved in response speed of the enzyme electrode, an enzyme electrode to shorten the response time, improved subcutaneous when the glucose sensor measurement signal delay, improve the accuracy of the real-time monitoring;

[0155]高分子层,用以提供传感器植入人体所需生物相容性,提高体内性能;可以通过浸渍、涂布的方式在电极固定一层高分子膜,所用到高分子材料是硅橡胶聚合物、聚氨酯、聚亚安酯、聚乙二醇其中的一种或多种混合;溶剂采用无水乙醇、四氢呋喃,可以通过喷雾、浸渍、涂布的方式制备; [0155] polymer layer, to provide the desired biocompatible implantable sensor body, to improve the performance in vivo; by dipping, coating manner fixed electrode layer of polymer film, the polymer material used is a silicone rubber polymers, polyurethanes, polyurethane, polyethylene glycol, wherein the one or more mixed; the solvent using ethanol, tetrahydrofuran, can be prepared by spraying, dipping, coating methods;

[0156] ②、对电极: [0156] ②, counter electrode:

[0157] 对电极铜箔上的功能层包括对惰性金属层、对催化层、对高分子层;其制备方法与工作电极基本相同,不需制备酶层; [0157] The inert metal layer, a functional layer including copper on the electrode catalyst layer, the polymer layer; prepared in substantially the same manner as the working electrode thereof, prepared without the enzyme layer;

[0158] ③、空白电极: [0158] ③, blank electrode:

[0159]空白电极铜箔上的功能层包括惰性金属层、催化层、高分子层;其制备方法与工作电极相同,不需制备酶层; [0159] The functional layer comprises an inert metal foil blank electrode layer, a catalyst layer, a polymer layer; the same preparation method of the working electrode, was prepared without the enzyme layer;

[0160] ④、参比电极: [0160] ④, reference electrode:

[0161] 参比电极铜箔上的功能层包括惰性金属层、参比银/氯化银层、高分子层; [0161] Reference inert metal layer, a reference silver / silver chloride layer, a functional polymer layer than the layer on the electrode comprises a copper foil;

[0162] 惰性金属层制备方法与工作电极相同,惰性金属层制备完成后,通过电镀、真空溅射的方法制备银/氯化银层,电化学氯化后制备银/氯化银层,最后制备高分子外膜; [0162] inert metal layer and the working electrode prepared in the same method, after completion of the preparation of an inert metal layer by electroplating, vacuum sputtering method for preparing a silver / silver chloride layer, electrochemical chloride after preparation of silver / silver chloride layer, and finally preparation of outer membrane polymer;

[0163] 上述制备工艺完成后,最后根据单元电路进行切割,得到传感器,三电极和四电极传感器尺寸如下:植入人体部分长度不大于15_,宽不大于0.6mm,厚不大于0.4mm; [0163] After the above preparation process is completed, the final cut unit circuit according to obtain the sensor, three-electrode and four-electrode sensor dimensions are as follows: the implant body portion length is not greater than 15_, width is not greater than 0.6mm, a thickness of not greater than 0.4mm;

[0164] 两电极尺寸如下:植入人体部分长度不大于15mm,宽不大于0.3mm,厚不大于0.4mm; [0164] two electrodes following dimensions: a length no greater than the implant portion body 15mm, width is not greater than 0.3mm, a thickness of not greater than 0.4mm;

[0165]由上述工作电极、对电极、参比电极、空白电极,四电极组成传感器,不需要在酶层添加纳米金,空白电极用于检测背景信号和干扰信号,提高传感器准确性; [0165] by the working electrode, counter electrode, reference electrode, blank electrode, an electrode composed of four sensors, do not need the addition of nano gold, enzyme blank electrode layer for detecting the background signal and interference signal to improve the accuracy of the sensor;

[0166] 两电极和三电极传感器,制备过程需在酶层增加纳米金; [0166] two electrodes and three-electrode sensors, need to increase the preparation of gold nanoparticles in the enzyme layer;

[0167] 传感器可以通过导针植入皮下,然后退出导针,传感器留在皮下组织开始工作。 [0167] Sensors may be implanted subcutaneously by a guide pin and guide pin exit, leaving the sensor in the subcutaneous tissue to work.

[0168] 实施例2:皮下组织介入式葡萄糖微型传感器的制备方法,按以下步骤进行: [0168] Example 2: preparation of the subcutaneous tissue glucose invasive microsensors, perform the following steps:

[0169] (I)、绝缘基层的选择: [0169] (I), the insulating base layer selection:

[0170] 绝缘基层采用可挠曲的聚酰亚胺绝缘薄膜或聚酯薄膜作为载体,具有良好的物理和化学性能; [0170] an insulating base layer using an insulating flexible polyimide film or a polyester film as a carrier, has good physical and chemical properties;

[0171]具高度曲柔性,可立体配线,依空间限制改变形状;耐高低温,耐燃;可折叠而不影响讯号传递功能,可防止静电干扰;化学变化稳定,安定性、可信赖度高;利于相关产品的设计,可减少装配工时及错误,并提尚有关广品的使用寿命;良好的绝缘性能,体积电阻率达到1015 Ω.Cm;对常用基体、金属和介电材料的粘结性优良;该层厚度控制在1微米; [0171] Qu highly flexible, three-dimensional wiring, by changing the shape of the space limit; high temperature resistance, fire; foldable without affecting the signal transmission, which prevents static; stable chemical changes, stability, and high reliable ; conducive related product design, assembly work can be reduced and mistakes, and still provide about the product life wide; good insulating properties, the volume resistivity reached 1015 Ω.Cm; commonly used adhesive matrix metal and a dielectric material excellent; controlling the thickness of the layer 1 micron;

[0172] ⑶、粘结层材质选择: [0172] ⑶, the adhesive layer material selection:

[0173] 粘结层包括传感器部分和引线部分中各粘结层; [0173] the adhesive layer including the adhesive layer and the lead portion of the sensor portion;

[0174] 绝缘基层的正反两面涂布粘结层,该层性能直接影响到电极的性能,由于粘结剂与绝缘基层之间在制造过程中存在化学反应,因此对于不同的绝缘基层还应选择相对应的粘结剂体系,粘结剂的性能必须与绝缘基层相适应; [0174] both sides of the insulating base layer adhesive coating layer which directly affects the performance properties of the electrode, due to the presence of a chemical reaction between the binder in the manufacturing process and the insulating base layer, an insulating base layer thus also for different corresponding to the selected binder system, the binder must be adapted to the performance of the insulating base layer;

[0175] 所用的粘结层必须能够承受各种工艺条件和在制造中所使用的化学药品的侵蚀,并没有分层或降解的现象,考虑到人体植入粘结剂必需有较好的生物相容性,粘结层采用环氧树脂或丙烯酸树脂类,该层厚度控制在10微米; [0175] The adhesive layer used must be able to withstand the processing conditions and chemicals used in the production of corrosion and no delamination or degradation phenomena, taking into account the human implants binder must have good biological compatible, adhesive layer or an acrylic epoxy resin, the layer thickness control 10 microns;

[0176] (7)、导电层的选择: [0176] (7), the conductive layer is selected:

[0177] 导电层包括传感器部分和引线部分中各导电层; [0177] each conductive layer comprises a conductive layer and the lead portion of the sensor portion;

[0178] 粘结层的表面为导电层,导电层采用压延铜箔,厚度控制在15微米; [0178] surface of the adhesive layer is a conductive layer, a conductive layer using a rolled copper foil, 15 m in thickness control;

[0179]引线部分需要在导电层上制备引线第二粘结层和引线保护层,层间可通过滚压法增加层间结合力,电极部分不需要第二粘结层和保护层,按照不同要求制备相应功能层; [0179] required lead portion and the lead wire of the second adhesive layer was prepared in the protective layer on the conductive layer, the interlayer roll method may be increased by inter-layer adhesion, it does not require a second electrode portion adhesive layer and the protective layer, in different required to prepare the corresponding functional layer;

[0180] ⑷、引线第二粘结层的选择: [0180] ⑷, lead of the second adhesive layer is selected:

[0181]后端引线部分的导电层外是引线第二粘结层,粘结剂采用环氧树脂或丙烯酸树脂类,该层厚度控制在10微米; [0181] the rear end of the outer lead portions of the conductive layer is a lead of the second adhesive layer, an adhesive epoxy or acrylic resin, the layer thickness control 10 microns;

[0182] 前端电极部分需要裸漏的不涂该层粘结剂,层间可通过滚压法增加层间结合力; [0182] the front end of the bare drain electrode portion need not coated with the adhesive layer, the interlayer may be increased interlayer bonding force by a rolling method;

[0183] (5)、保护层的选择: [0183] (5), the protective layer is selected:

[0184]后端引线部分的引线第二粘结层外是聚酰亚胺绝缘薄膜,保护膜先进行切割加工,露出前段电极部位的铜箔,电极引线覆盖保护膜; [0184] lead a rear end of the outer lead portion of the second insulating adhesive layer is a polyimide film, a protective film for cutting to expose part of the preceding electrode foil, a protective film covering the electrode lead;

[0185]该层厚度控制在10微米;可通过滚压法增加层间结合力; [0185] The layer thickness is controlled to 10 microns; interlayer bonding force may be increased by the rolling method;

[0186] ⑶、电极部分功能层制备: [0186] ⑶, the functional layer portion of the electrode preparation:

[0187] 电极部分可以根据需要分为工作电极、对电极、参比电极、空白电极; [0187] The electrode portion may be divided into the required working electrode, counter electrode, reference electrode, the electrode blank;

[0188] ①、工作电极: [0188] ①, working electrode:

[0189] 工作电极铜箔上的功能层组成如下:惰性金属层、催化层、酶层、高分子层; [0189] a functional layer on the working electrode foil composed as follows: inert metal layer, a catalyst layer, an enzyme layer, a polymer layer;

[0190] 惰性金属层在电极部位的铜箔上制备,通过电镀、溅射的方法制备,可选用金、铂的惰性金属,该层厚度为12微米; [0190] inert metal electrode layer prepared on the copper foil portions, by plating, sputtering production method, the choice of gold, platinum, inert metal, the layer having a thickness of 12 microns;

[0191] 催化层为铂黑,可以通过电镀方法制备; [0191] platinum black catalyst layer may be prepared by a plating method;

[0192] 酶层通过喷雾、浸渍、涂布的方式将酶溶液转移到工作电极上,浸渍时间为10分钟; [0192] the enzyme layer by spraying, dipping, coating the enzyme solution was transferred way to the working electrode, the immersion time of 10 minutes;

[0193] 然后用浓度为15 %的戊二醛溶液将转移到工作电极的葡萄糖氧化酶交联固定,交联温度在30摄氏度,采用液相浸渍交联或气相交联,交联时间为30-60min; [0193] and a glutaraldehyde solution with a concentration of 15% will be transferred to the working electrode and cross-linked glucose oxidase, the crosslinking temperature at 30 ° C, a liquid phase impregnation VAPOR crosslinking or crosslinking time of 30 -60min;

[0194] 所用酶溶液制备过程如下:在磷酸盐缓冲液中加入葡萄糖氧化酶和人重组白蛋白,葡萄糖氧化酶加入量为每毫升70毫克,人重组白蛋白加入量为每毫升70毫克;溶解充分后,添加2 %的纳米金混匀,最后加入2 %的PVB,PVB指聚乙烯醇缩丁醛,混合均匀; [0194] The enzyme solution was prepared with the following procedure: addition of glucose oxidase and recombinant human albumin in phosphate buffer, the glucose oxidase is added in an amount of 70 mg per ml, recombinant human albumin was added in an amount of 70 mg per ml; dissolved after sufficient, 2% of gold nanoparticles mixed and finally 2% PVB, PVB refers to polyvinyl butyral, mixed;

[0195]纳米金利用AOT与环己烷体系形成的反胶束体系中制备,AOT是指琥玻酸二异辛酯璜酸钠,通过柠檬酸钠还原氯金酸盐水溶液,调节水、电解质、表面活性剂的浓度比例,制备不同直径的纳米金颗粒,纳米金颗粒直径在20nm ; [0195] Gold Nanoparticles prepared using reversed micelles of AOT formed cyclohexane system, AOT amber glass refers sodium dioctyl Juan, by reducing chloroauric acid salt sodium citrate solution, adjusting water electrolyte , the ratio of the concentration of surfactant, the preparation of gold nanoparticles with different diameters, gold nanoparticles 20 nm in diameter;

[0196] 葡萄糖氧化酶交联完成后,可以通过浸渍、涂布的方式在电极固定一层高分子膜,以增强传感器生物相容性,提高体内性能; [0196] After the completion of cross-linking glucose oxidase, by dipping, coating manner fixed electrode layer of polymer film, to enhance the biocompatibility of the sensor, to improve the performance in vivo;

[0197]由于纳米金具有良好的生物相容性,可以较长时间植入人体内,而不引起不良反应; [0197] Since the nano-gold has good biocompatibility, may be implanted in the human body for a long time without causing adverse reactions;

[0198]纳米金有良好的导电性,可以提高酶电极的灵敏度,缩短酶电极对葡萄糖响应时间,延长酶电极使用寿命; [0198] Nano Jinyou Liang good electrical conductivity, can improve the sensitivity of the enzyme electrode, an enzyme electrode glucose shorten response time, to extend the service life of the enzyme electrode;

[0199] 葡萄糖氧化酶电极氧化葡萄糖的反应由两步酶反应组成: [0199] Glucose Glucose Oxidase Electrode oxidation reaction of two-step enzyme reaction composition:

[0200] D-glucose+GOD (FAD) -^glucose-lactone+GOD (FADH2) [0200] D-glucose + GOD (FAD) - ^ glucose-lactone + GOD (FADH2)

[0201] GOD (FADH2) +O2^GOD (FAD) +H2O2 [0201] GOD (FADH2) + O2 ^ GOD (FAD) + H2O2

[0202] glucose-lactone+H20^glucose-acid [0202] glucose-lactone + H20 ^ glucose-acid

[0203] 上述过程中,还原态葡萄糖氧化酶GOD (FADH2)稳定性较差,比较容易发生结构改变,无法被氧化变成常态葡萄糖氧化酶,这是常见葡萄糖氧化酶电极酶活丧失的原因之一;而在酶层加入纳米金颗粒后,纳米金颗粒具有从环境吸收电子的特性,可以迅速将还原态葡萄糖氧化酶GOD (FADH2)氧化成稳态葡萄糖氧化酶GOD (FAD),减少电极反应过程中还原态葡萄糖氧化酶GOD (FADH2)的数量以及存在时间,减少酶活性损失,延长电极寿命;此外纳米金颗粒加入还大幅度提高酶电极响应应速度,缩短酶电极相应时间,改善了皮下葡萄糖传感器测量时信号延迟,提高实时监测准确度; [0203] In the above process, the reduced state of glucose oxidase GOD (FADH2) poor stability, more prone to structural changes, can not be oxidized to normal glucose oxidase, which is glucose oxidase electrode common cause loss of activity a; and after addition of the enzyme layer of gold nanoparticles, gold nanoparticles having a property of absorbing electrons from the environment, can be quickly reduced state of glucose oxidase GOD (FADH2) is oxidized to the steady-state glucose oxidase GOD (FAD), reduced electrode reaction reducing the number of processes of glucose oxidase GOD (FADH2) and the present time, reduce loss of enzyme activity, prolong electrode life; gold nanoparticles added in addition also be greatly improved in response speed of the enzyme electrode, an enzyme electrode to shorten the response time, improved subcutaneous when the glucose sensor measurement signal delay, improve the accuracy of the real-time monitoring;

[0204]高分子层,用以提供传感器植入人体所需生物相容性,提高体内性能;可以通过浸渍、涂布的方式在电极固定一层高分子膜,所用到高分子材料是硅橡胶聚合物、聚氨酯、聚亚安酯、聚乙二醇其中的一种或多种混合;溶剂采用无水乙醇、四氢呋喃,可以通过喷雾、浸渍、涂布的方式制备; [0204] polymer layer, to provide the desired biocompatible implantable sensor body, to improve the performance in vivo; by dipping, coating manner fixed electrode layer of polymer film, the polymer material used is a silicone rubber polymers, polyurethanes, polyurethane, polyethylene glycol, wherein the one or more mixed; the solvent using ethanol, tetrahydrofuran, can be prepared by spraying, dipping, coating methods;

[0205] ②、对电极: [0205] ②, counter electrode:

[0206] 对电极铜箔上的功能层包括对惰性金属层、对催化层、对高分子层;其制备方法与工作电极基本相同,不需制备酶层; [0206] The inert metal layer, a functional layer including copper on the electrode catalyst layer, the polymer layer; prepared in substantially the same manner as the working electrode thereof, prepared without the enzyme layer;

[0207] ③、空白电极: [0207] ③, blank electrode:

[0208]空白电极铜箔上的功能层包括惰性金属层、催化层、高分子层;其制备方法与工作电极相同,不需制备酶层; [0208] The functional layer comprises an inert metal foil blank electrode layer, a catalyst layer, a polymer layer; the same preparation method of the working electrode, was prepared without the enzyme layer;

[0209] ④、参比电极: [0209] ④, reference electrode:

[0210] 参比电极铜箔上的功能层包括惰性金属层、参比银/氯化银层、高分子层; [0210] Reference inert metal layer, a reference silver / silver chloride layer, a functional polymer layer than the layer on the electrode comprises a copper foil;

[0211] 惰性金属层制备方法与工作电极相同,惰性金属层制备完成后,通过电镀、真空溅射的方法制备银/氯化银层,电化学氯化后制备银/氯化银层,最后制备高分子外膜; [0211] inert metal layer and the working electrode prepared in the same method, after completion of the preparation of an inert metal layer by electroplating, vacuum sputtering method for preparing a silver / silver chloride layer, electrochemical chloride after preparation of silver / silver chloride layer, and finally preparation of outer membrane polymer;

[0212] 上述制备工艺完成后,最后根据单元电路进行切割,得到传感器,三电极和四电极传感器尺寸如下:植入人体部分长度不大于15_,宽不大于0.6mm,厚不大于0.4mm; [0212] After the above preparation process is completed, the final cut unit circuit according to obtain the sensor, three-electrode and four-electrode sensor dimensions are as follows: the implant body portion length is not greater than 15_, width is not greater than 0.6mm, a thickness of not greater than 0.4mm;

[0213] 两电极尺寸如下:植入人体部分长度不大于15mm,宽不大于0.3mm,厚不大于0.4mm; [0213] two electrodes following dimensions: a length no greater than the implant portion body 15mm, width is not greater than 0.3mm, a thickness of not greater than 0.4mm;

[0214]由上述工作电极、对电极、参比电极、空白电极,四电极组成传感器,不需要在酶层添加纳米金,空白电极用于检测背景信号和干扰信号,提高传感器准确性; [0214] by the working electrode, counter electrode, reference electrode, blank electrode, an electrode composed of four sensors, do not need the addition of nano gold, enzyme blank electrode layer for detecting the background signal and interference signal to improve the accuracy of the sensor;

[0215] 两电极和三电极传感器,制备过程需在酶层增加纳米; [0215] two electrodes and three-electrode sensors, in preparation for an increased quantity of nano enzyme layer;

[0216] 传感器可以通过导针植入皮下,然后退出导针,传感器留在皮下组织开始工作。 [0216] Sensors may be implanted subcutaneously by a guide pin and guide pin exit, leaving the sensor in the subcutaneous tissue to work.

[0217] 实施例3:皮下组织介入式葡萄糖微型传感器的制备方法,按以下步骤进行: [0217] Example 3: preparation of the subcutaneous tissue glucose invasive microsensors, perform the following steps:

[0218] (I)、绝缘基层的选择: [0218] (I), the insulating base layer selection:

[0219] 绝缘基层采用可挠曲的聚酰亚胺绝缘薄膜或聚酯薄膜作为载体,具有良好的物理和化学性能; [0219] an insulating base layer using an insulating flexible polyimide film or a polyester film as a carrier, has good physical and chemical properties;

[0220] 具高度曲柔性,可立体配线,依空间限制改变形状;耐高低温,耐燃;可折叠而不影响讯号传递功能,可防止静电干扰;化学变化稳定,安定性、可信赖度高;利于相关产品的设计,可减少装配工时及错误,并提尚有关广品的使用寿命;良好的绝缘性能,体积电阻率达到1015 Ω.Cm;对常用基体、金属和介电材料的粘结性优良;该层厚度控制在12.5微米; [0220] Qu highly flexible, three-dimensional wiring, by changing the shape of the space limit; high temperature resistance, fire; foldable without affecting the signal transmission, which prevents static; stable chemical changes, stability, and high reliable ; conducive related product design, assembly work can be reduced and mistakes, and still provide about the product life wide; good insulating properties, the volume resistivity reached 1015 Ω.Cm; commonly used adhesive matrix metal and a dielectric material excellent; the 12.5 micron layer thickness control;

[0221] ⑶、粘结层材质选择: [0221] ⑶, the adhesive layer material selection:

[0222] 粘结层包括传感器部分和引线部分中各粘结层; [0222] the adhesive layer including the adhesive layer and the lead portion of the sensor portion;

[0223] 绝缘基层的正反两面涂布粘结层,该层性能直接影响到电极的性能,由于粘结剂与绝缘基层之间在制造过程中存在化学反应,因此对于不同的绝缘基层还应选择相对应的粘结剂体系,粘结剂的性能必须与绝缘基层相适应; [0223] both sides of the insulating base layer adhesive coating layer which directly affects the performance properties of the electrode, due to the presence of a chemical reaction between the binder in the manufacturing process and the insulating base layer, an insulating base layer thus also for different corresponding to the selected binder system, the binder must be adapted to the performance of the insulating base layer;

[0224] 所用的粘结层必须能够承受各种工艺条件和在制造中所使用的化学药品的侵蚀,并没有分层或降解的现象,考虑到人体植入粘结剂必需有较好的生物相容性,粘结层采用环氧树脂或丙烯酸树脂类,该层厚度控制在10微米; [0224] The adhesive layer used must be able to withstand the processing conditions and chemicals used in the production of corrosion and no delamination or degradation phenomena, taking into account the human implants binder must have good biological compatible, adhesive layer or an acrylic epoxy resin, the layer thickness control 10 microns;

[0225] (9)、导电层的选择: [0225] (9), the conductive layer is selected:

[0226] 导电层包括传感器部分和引线部分中各导电层; [0226] each conductive layer comprises a conductive layer and the lead portion of the sensor portion;

[0227] 粘结层的表面为导电层,导电层采用压延铜箔,厚度控制在20微米; [0227] surface of the adhesive layer is a conductive layer, a conductive layer using a rolled copper foil, 20 m in thickness control;

[0228]引线部分需要在导电层上制备引线第二粘结层和引线保护层,层间可通过滚压法增加层间结合力,电极部分不需要第二粘结层和保护层,按照不同要求制备相应功能层; [0228] required lead portion and the lead wire of the second adhesive layer was prepared in the protective layer on the conductive layer, the interlayer roll method may be increased by inter-layer adhesion, it does not require a second electrode portion adhesive layer and the protective layer, in different required to prepare the corresponding functional layer;

[0229] ⑷、引线第二粘结层的选择: [0229] ⑷, lead of the second adhesive layer is selected:

[0230]后端引线部分的导电层外是引线第二粘结层,粘结剂采用环氧树脂或丙烯酸树脂类,该层厚度控制在15微米; [0230] the rear end of the outer lead portions of the conductive layer is a lead of the second adhesive layer, an adhesive epoxy resin or an acrylic resin, controlling the thickness of the layer 15 microns;

[0231] 前端电极部分需要裸漏的不涂该层粘结剂,层间可通过滚压法增加层间结合力; [0231] the front end of the bare drain electrode portion need not coated with the adhesive layer, the interlayer may be increased interlayer bonding force by a rolling method;

[0232] (5)、保护层的选择: [0232] (5), the protective layer is selected:

[0233]后端引线部分的引线第二粘结层外是聚酰亚胺绝缘薄膜,保护膜先进行切割加工,露出前段电极部位的铜箔,电极引线覆盖保护膜; [0233] lead a rear end of the outer lead portion of the second insulating adhesive layer is a polyimide film, a protective film for cutting to expose part of the preceding electrode foil, a protective film covering the electrode lead;

[0234]该层厚度控制在15微米;可通过滚压法增加层间结合力; [0234] The layer thickness is controlled to 15 m; can increase the interlayer bonding force by a rolling method;

[0235] ⑶、电极部分功能层制备: [0235] ⑶, the functional layer portion of the electrode preparation:

[0236] 电极部分可以根据需要分为工作电极、对电极、参比电极、空白电极; [0236] The electrode portion may be divided into the required working electrode, counter electrode, reference electrode, the electrode blank;

[0237] ①、工作电极: [0237] ①, working electrode:

[0238] 工作电极铜箔上的功能层组成如下:惰性金属层、催化层、酶层、高分子层; [0238] a functional layer on the working electrode foil composed as follows: inert metal layer, a catalyst layer, an enzyme layer, a polymer layer;

[0239] 惰性金属层在电极部位的铜箔上制备,通过电镀、溅射的方法制备,可选用金、铂的惰性金属,该层厚度为15微米; [0239] inert metal electrode layer prepared on the copper foil portions, by plating, sputtering production method, the choice of gold, platinum, inert metal, the layer thickness is 15 m;

[0240] 催化层为铂黑,可以通过电镀方法制备; [0240] platinum black catalyst layer may be prepared by a plating method;

[0241] 酶层通过喷雾、浸渍、涂布的方式将酶溶液转移到工作电极上,浸渍时间为15分钟; [0241] the enzyme layer by spraying, dipping, coating the enzyme solution was transferred way to the working electrode, was immersed for 15 minutes;

[0242] 然后用浓度为20%的戊二醛溶液将转移到工作电极的葡萄糖氧化酶交联固定,交联温度在35摄氏度,采用液相浸渍交联或气相交联,交联时间为30-60min; [0242] and a glutaraldehyde solution with a concentration of 20% will be transferred to the working electrode and cross-linked glucose oxidase, the crosslinking temperature at 35 ° C, a liquid phase impregnation VAPOR crosslinking or crosslinking time of 30 -60min;

[0243] 所用酶溶液制备过程如下:在磷酸盐缓冲液中加入葡萄糖氧化酶和人重组白蛋白,葡萄糖氧化酶加入量为每毫升100毫克,人重组白蛋白加入量为每毫升100毫克;溶解充分后,添加5 %的纳米金混匀,最后加入5 %的PVB,PVB指聚乙烯醇缩丁醛,混合均匀; [0243] The enzyme solution was prepared with the following procedure: addition of glucose oxidase and recombinant human albumin in phosphate buffer, the glucose oxidase is added in an amount of 100 mg per ml, recombinant human albumin was added in an amount of 100 mg per ml; dissolved after sufficient, 5% of gold nanoparticles mixing, and finally 5% of PVB, PVB refers to polyvinyl butyral, mixed;

[0244]纳米金利用AOT与环己烷体系形成的反胶束体系中制备,AOT是指琥玻酸二异辛酯璜酸钠,通过柠檬酸钠还原氯金酸盐水溶液,调节水、电解质、表面活性剂的浓度比例,制备不同直径的纳米金颗粒,纳米金颗粒直径在30nm ; [0244] Gold Nanoparticles prepared using reversed micelles of AOT formed cyclohexane system, AOT amber glass refers sodium dioctyl Juan, by reducing chloroauric acid salt sodium citrate solution, adjusting water electrolyte , the ratio of the concentration of surfactant, the preparation of gold nanoparticles with different diameters, gold nanoparticles 30 nm in diameter;

[0245] 葡萄糖氧化酶交联完成后,可以通过浸渍、涂布的方式在电极固定一层高分子膜,以增强传感器生物相容性,提高体内性能; [0245] After the completion of cross-linking glucose oxidase, by dipping, coating manner fixed electrode layer of polymer film, to enhance the biocompatibility of the sensor, to improve the performance in vivo;

[0246]由于纳米金具有良好的生物相容性,可以较长时间植入人体内,而不引起不良反应; [0246] Since the nano-gold has good biocompatibility, may be implanted in the human body for a long time without causing adverse reactions;

[0247]纳米金有良好的导电性,可以提高酶电极的灵敏度,缩短酶电极对葡萄糖响应时间,延长酶电极使用寿命; [0247] Nano Jinyou Liang good electrical conductivity, can improve the sensitivity of the enzyme electrode, an enzyme electrode glucose shorten response time, to extend the service life of the enzyme electrode;

[0248] 葡萄糖氧化酶电极氧化葡萄糖的反应由两步酶反应组成: [0248] Glucose Glucose Oxidase Electrode oxidation reaction of two-step enzyme reaction composition:

[0249] D-glucose+GOD (FAD) -^glucose-lactone+GOD (FADH2) [0249] D-glucose + GOD (FAD) - ^ glucose-lactone + GOD (FADH2)

[0250] GOD (FADH2) +O2^GOD (FAD) +H2O2 [0250] GOD (FADH2) + O2 ^ GOD (FAD) + H2O2

[0251] glucose-lactone+H20^glucose-acid [0251] glucose-lactone + H20 ^ glucose-acid

[0252] 上述过程中,还原态葡萄糖氧化酶GOD (FADH2)稳定性较差,比较容易发生结构改变,无法被氧化变成常态葡萄糖氧化酶,这是常见葡萄糖氧化酶电极酶活丧失的原因之一;而在酶层加入纳米金颗粒后,纳米金颗粒具有从环境吸收电子的特性,可以迅速将还原态葡萄糖氧化酶GOD (FADH2)氧化成稳态葡萄糖氧化酶GOD (FAD),减少电极反应过程中还原态葡萄糖氧化酶GOD (FADH2)的数量以及存在时间,减少酶活性损失,延长电极寿命;此外纳米金颗粒加入还大幅度提高酶电极响应应速度,缩短酶电极相应时间,改善了皮下葡萄糖传感器测量时信号延迟,提高实时监测准确度; [0252] In the above process, the reduced state of glucose oxidase GOD (FADH2) poor stability, more prone to structural changes, can not be oxidized to normal glucose oxidase, which is glucose oxidase electrode common cause loss of activity a; and after addition of the enzyme layer of gold nanoparticles, gold nanoparticles having a property of absorbing electrons from the environment, can be quickly reduced state of glucose oxidase GOD (FADH2) is oxidized to the steady-state glucose oxidase GOD (FAD), reduced electrode reaction reducing the number of processes of glucose oxidase GOD (FADH2) and the present time, reduce loss of enzyme activity, prolong electrode life; gold nanoparticles added in addition also be greatly improved in response speed of the enzyme electrode, an enzyme electrode to shorten the response time, improved subcutaneous when the glucose sensor measurement signal delay, improve the accuracy of the real-time monitoring;

[0253]高分子层,用以提供传感器植入人体所需生物相容性,提高体内性能;可以通过浸渍、涂布的方式在电极固定一层高分子膜,所用到高分子材料是硅橡胶聚合物、聚氨酯、聚亚安酯、聚乙二醇其中的一种或多种混合;溶剂采用无水乙醇、四氢呋喃,可以通过喷雾、浸渍、涂布的方式制备; [0253] polymer layer, to provide the desired biocompatible implantable sensor body, to improve the performance in vivo; by dipping, coating manner fixed electrode layer of polymer film, the polymer material used is a silicone rubber polymers, polyurethanes, polyurethane, polyethylene glycol, wherein the one or more mixed; the solvent using ethanol, tetrahydrofuran, can be prepared by spraying, dipping, coating methods;

[0254] ②、对电极: [0254] ②, counter electrode:

[0255] 对电极铜箔上的功能层包括对惰性金属层、对催化层、对高分子层;其制备方法与工作电极基本相同,不需制备酶层; [0255] The inert metal layer, a functional layer including copper on the electrode catalyst layer, the polymer layer; prepared in substantially the same manner as the working electrode thereof, prepared without the enzyme layer;

[0256] ③、空白电极: [0256] ③, blank electrode:

[0257]空白电极铜箔上的功能层包括惰性金属层、催化层、高分子层;其制备方法与工作电极相同,不需制备酶层; [0257] The functional layer comprises an inert metal foil blank electrode layer, a catalyst layer, a polymer layer; the same preparation method of the working electrode, was prepared without the enzyme layer;

[0258] ④、参比电极: [0258] ④, reference electrode:

[0259] 参比电极铜箔上的功能层包括惰性金属层、参比银/氯化银层、高分子层; [0259] Reference inert metal layer, a reference silver / silver chloride layer, a functional polymer layer than the layer on the electrode comprises a copper foil;

[0260] 惰性金属层制备方法与工作电极相同,惰性金属层制备完成后,通过电镀、真空溅射的方法制备银/氯化银层,电化学氯化后制备银/氯化银层,最后制备高分子外膜; [0260] inert metal layer and the working electrode prepared in the same method, after completion of the preparation of an inert metal layer by electroplating, vacuum sputtering method for preparing a silver / silver chloride layer, electrochemical chloride after preparation of silver / silver chloride layer, and finally preparation of outer membrane polymer;

[0261] 上述制备工艺完成后,最后根据单元电路进行切割,得到传感器,三电极和四电极传感器尺寸如下:植入人体部分长度不大于15_,宽不大于0.6mm,厚不大于0.4mm; [0261] After the above preparation process is completed, the final cut unit circuit according to obtain the sensor, three-electrode and four-electrode sensor dimensions are as follows: the implant body portion length is not greater than 15_, width is not greater than 0.6mm, a thickness of not greater than 0.4mm;

[0262] 两电极尺寸如下:植入人体部分长度不大于15mm,宽不大于0.3mm,厚不大于 [0262] two electrodes following dimensions: a length no greater than the implant portion body 15mm, width is not greater than 0.3mm, a thickness of no greater than

0.4mm; 0.4mm;

[0263]由上述工作电极、对电极、参比电极、空白电极,四电极组成传感器,不需要在酶层添加纳米金,空白电极用于检测背景信号和干扰信号,提高传感器准确性; [0263] by the working electrode, counter electrode, reference electrode, blank electrode, an electrode composed of four sensors, do not need the addition of nano gold, enzyme blank electrode layer for detecting the background signal and interference signal to improve the accuracy of the sensor;

[0264] 两电极和三电极传感器,制备过程需在酶层增加纳米金; [0264] two electrodes and three-electrode sensors, need to increase the preparation of gold nanoparticles in the enzyme layer;

[0265] 传感器可以通过导针植入皮下,然后退出导针,传感器留在皮下组织开始工作。 [0265] Sensors may be implanted subcutaneously by a guide pin and guide pin exit, leaving the sensor in the subcutaneous tissue to work.

[0266] 实施例3:皮下组织介入式葡萄糖微型传感器的制备方法,按以下步骤进行: [0266] Example 3: preparation of the subcutaneous tissue glucose invasive microsensors, perform the following steps:

[0267] (I)、绝缘基层的选择: [0267] (I), the insulating base layer selection:

[0268] 绝缘基层采用可挠曲的聚酰亚胺绝缘薄膜或聚酯薄膜作为载体,具有良好的物理和化学性能; [0268] an insulating base layer using an insulating flexible polyimide film or a polyester film as a carrier, has good physical and chemical properties;

[0269]具高度曲柔性,可立体配线,依空间限制改变形状;耐高低温,耐燃;可折叠而不影响讯号传递功能,可防止静电干扰;化学变化稳定,安定性、可信赖度高;利于相关产品的设计,可减少装配工时及错误,并提尚有关广品的使用寿命;良好的绝缘性能,体积电阻率达到1015 Ω.Cm;对常用基体、金属和介电材料的粘结性优良;该层厚度控制在12.5微米; [0269] Qu highly flexible, three-dimensional wiring, by changing the shape of the space limit; high temperature resistance, fire; foldable without affecting the signal transmission, which prevents static; stable chemical changes, stability, and high reliable ; conducive related product design, assembly work can be reduced and mistakes, and still provide about the product life wide; good insulating properties, the volume resistivity reached 1015 Ω.Cm; commonly used adhesive matrix metal and a dielectric material excellent; the 12.5 micron layer thickness control;

[0270] (2)、粘结层材质选择: [0270] (2), the tie layer material selection:

[0271] 粘结层包括传感器部分和引线部分中各粘结层; [0271] the adhesive layer including the adhesive layer and the lead portion of the sensor portion;

[0272] 绝缘基层的正反两面涂布粘结层,该层性能直接影响到电极的性能,由于粘结剂与绝缘基层之间在制造过程中存在化学反应,因此对于不同的绝缘基层还应选择相对应的粘结剂体系,粘结剂的性能必须与绝缘基层相适应; [0272] both sides of the insulating base layer adhesive coating layer which directly affects the performance properties of the electrode, due to the presence of a chemical reaction between the binder in the manufacturing process and the insulating base layer, an insulating base layer thus also for different corresponding to the selected binder system, the binder must be adapted to the performance of the insulating base layer;

[0273] 所用的粘结层必须能够承受各种工艺条件和在制造中所使用的化学药品的侵蚀,并没有分层或降解的现象,考虑到人体植入粘结剂必需有较好的生物相容性,粘结层采用环氧树脂或丙烯酸树脂类,该层厚度控制在15微米; [0273] The adhesive layer used must be able to withstand the processing conditions and chemicals used in the production of corrosion and no delamination or degradation phenomena, taking into account the human implants binder must have good biological compatible, adhesive layer or an acrylic epoxy resin, controlling the thickness of the layer 15 microns;

[0274] (3)、导电层的选择: [0274] (3), the conductive layer is selected:

[0275] 导电层包括传感器部分和引线部分中各导电层; [0275] each conductive layer comprises a conductive layer and the lead portion of the sensor portion;

[0276] 粘结层的表面为导电层,导电层采用压延铜箔,厚度控制在20微米; [0276] surface of the adhesive layer is a conductive layer, a conductive layer using a rolled copper foil, 20 m in thickness control;

[0277]引线部分需要在导电层上制备引线第二粘结层和引线保护层,层间可通过滚压法增加层间结合力,电极部分不需要第二粘结层和保护层,按照不同要求制备相应功能层; [0277] required lead portion and the lead wire of the second adhesive layer was prepared in the protective layer on the conductive layer, the interlayer roll method may be increased by inter-layer adhesion, it does not require a second electrode portion adhesive layer and the protective layer, in different required to prepare the corresponding functional layer;

[0278] ⑷、引线第二粘结层的选择: [0278] ⑷, lead of the second adhesive layer is selected:

[0279]后端引线部分的导电层外是引线第二粘结层,粘结剂采用环氧树脂或丙烯酸树脂类,该层厚度控制在15微米; [0279] the rear end of the outer lead portions of the conductive layer is a lead of the second adhesive layer, an adhesive epoxy resin or an acrylic resin, controlling the thickness of the layer 15 microns;

[0280] 前端电极部分需要裸漏的不涂该层粘结剂,层间可通过滚压法增加层间结合力; [0280] the front end of the bare drain electrode portion need not coated with the adhesive layer, the interlayer may be increased interlayer bonding force by a rolling method;

[0281] (5)、保护层的选择: [0281] (5), the protective layer is selected:

[0282]后端引线部分的引线第二粘结层外是聚酰亚胺绝缘薄膜,保护膜先进行切割加工,露出前段电极部位的铜箔,电极引线覆盖保护膜; [0282] lead a rear end of the outer lead portion of the second insulating adhesive layer is a polyimide film, a protective film for cutting to expose part of the preceding electrode foil, a protective film covering the electrode lead;

[0283]该层厚度控制在15微米;可通过滚压法增加层间结合力; [0283] The layer thickness is controlled to 15 m; can increase the interlayer bonding force by a rolling method;

[0284] ⑶、电极部分功能层制备: [0284] ⑶, the functional layer portion of the electrode preparation:

[0285] 电极部分可以根据需要分为工作电极、对电极、参比电极、空白电极; [0285] The electrode portion may be divided into the required working electrode, counter electrode, reference electrode, the electrode blank;

[0286] ①、工作电极: [0286] ①, working electrode:

[0287] 工作电极铜箔上的功能层组成如下:惰性金属层、催化层、酶层、高分子层; [0287] a functional layer on the working electrode foil composed as follows: inert metal layer, a catalyst layer, an enzyme layer, a polymer layer;

[0288] 惰性金属层在电极部位的铜箔上制备,通过电镀、溅射的方法制备,可选用金、铂的惰性金属,该层厚度为15微米; [0288] inert metal electrode layer prepared on the copper foil portions, by plating, sputtering production method, the choice of gold, platinum, inert metal, the layer thickness is 15 m;

[0289] 催化层为铂黑,可以通过电镀方法制备; [0289] platinum black catalyst layer may be prepared by a plating method;

[0290] 酶层通过喷雾、浸渍、涂布的方式将酶溶液转移到工作电极上,浸渍时间为15分钟; [0290] the enzyme layer by spraying, dipping, coating the enzyme solution was transferred way to the working electrode, was immersed for 15 minutes;

[0291] 然后用浓度为20 %的戊二醛溶液将转移到工作电极的葡萄糖氧化酶交联固定,交联温度在35摄氏度,采用液相浸渍交联或气相交联,交联时间为30-60min; [0291] and a glutaraldehyde solution with a concentration of 20% will be transferred to the working electrode and cross-linked glucose oxidase, the crosslinking temperature at 35 ° C, a liquid phase impregnation VAPOR crosslinking or crosslinking time of 30 -60min;

[0292] 所用酶溶液制备过程如下:在磷酸盐缓冲液中加入葡萄糖氧化酶和人重组白蛋白,葡萄糖氧化酶加入量为每毫升100毫克,人重组白蛋白加入量为每毫升100毫克;溶解充分后,添加5 %的纳米金混匀,最后加入5 %的PVB,PVB指聚乙烯醇缩丁醛,混合均匀; [0292] The enzyme solution was prepared with the following procedure: addition of glucose oxidase and recombinant human albumin in phosphate buffer, the glucose oxidase is added in an amount of 100 mg per ml, recombinant human albumin was added in an amount of 100 mg per ml; dissolved after sufficient, 5% of gold nanoparticles mixing, and finally 5% of PVB, PVB refers to polyvinyl butyral, mixed;

[0293]纳米金利用AOT与环己烷体系形成的反胶束体系中制备,AOT是指琥玻酸二异辛酯璜酸钠,通过柠檬酸钠还原氯金酸盐水溶液,调节水、电解质、表面活性剂的浓度比例,制备不同直径的纳米金颗粒,纳米金颗粒直径在30nm ; [0293] Gold Nanoparticles prepared using reversed micelles of AOT formed cyclohexane system, AOT amber glass refers sodium dioctyl Juan, by reducing chloroauric acid salt sodium citrate solution, adjusting water electrolyte , the ratio of the concentration of surfactant, the preparation of gold nanoparticles with different diameters, gold nanoparticles 30 nm in diameter;

[0294] 葡萄糖氧化酶交联完成后,可以通过浸渍、涂布的方式在电极固定一层高分子膜,以增强传感器生物相容性,提高体内性能; [0294] After the completion of cross-linking glucose oxidase, by dipping, coating manner fixed electrode layer of polymer film, to enhance the biocompatibility of the sensor, to improve the performance in vivo;

[0295]由于纳米金具有良好的生物相容性,可以较长时间植入人体内,而不引起不良反应; [0295] Since the nano-gold has good biocompatibility, may be implanted in the human body for a long time without causing adverse reactions;

[0296]纳米金有良好的导电性,可以提高酶电极的灵敏度,缩短酶电极对葡萄糖响应时间,延长酶电极使用寿命; [0296] Nano Jinyou Liang good electrical conductivity, can improve the sensitivity of the enzyme electrode, an enzyme electrode glucose shorten response time, to extend the service life of the enzyme electrode;

[0297] 葡萄糖氧化酶电极氧化葡萄糖的反应由两步酶反应组成: [0297] Glucose Glucose Oxidase Electrode oxidation reaction of two-step enzyme reaction composition:

[0298] D-glucose+GOD (FAD) -^glucose-lactone+GOD (FADH2) [0298] D-glucose + GOD (FAD) - ^ glucose-lactone + GOD (FADH2)

[0299] GOD (FADH2) +O2^GOD (FAD) +H2O2 [0299] GOD (FADH2) + O2 ^ GOD (FAD) + H2O2

[0300] glucose-lactone+H20^glucose-acid [0300] glucose-lactone + H20 ^ glucose-acid

[0301] 上述过程中,还原态葡萄糖氧化酶GOD (FADH2)稳定性较差,比较容易发生结构改变,无法被氧化变成常态葡萄糖氧化酶,这是常见葡萄糖氧化酶电极酶活丧失的原因之一;而在酶层加入纳米金颗粒后,纳米金颗粒具有从环境吸收电子的特性,可以迅速将还原态葡萄糖氧化酶GOD (FADH2)氧化成稳态葡萄糖氧化酶GOD (FAD),减少电极反应过程中还原态葡萄糖氧化酶GOD (FADH2)的数量以及存在时间,减少酶活性损失,延长电极寿命;此外纳米金颗粒加入还大幅度提高酶电极响应应速度,缩短酶电极相应时间,改善了皮下葡萄糖传感器测量时信号延迟,提高实时监测准确度; [0301] In the above process, the reduced state of glucose oxidase GOD (FADH2) poor stability, more prone to structural changes, can not be oxidized to normal glucose oxidase, which is glucose oxidase electrode common cause loss of activity a; and after addition of the enzyme layer of gold nanoparticles, gold nanoparticles having a property of absorbing electrons from the environment, can be quickly reduced state of glucose oxidase GOD (FADH2) is oxidized to the steady-state glucose oxidase GOD (FAD), reduced electrode reaction reducing the number of processes of glucose oxidase GOD (FADH2) and the present time, reduce loss of enzyme activity, prolong electrode life; gold nanoparticles added in addition also be greatly improved in response speed of the enzyme electrode, an enzyme electrode to shorten the response time, improved subcutaneous when the glucose sensor measurement signal delay, improve the accuracy of the real-time monitoring;

[0302]高分子层,用以提供传感器植入人体所需生物相容性,提高体内性能;可以通过浸渍、涂布的方式在电极固定一层高分子膜,所用到高分子材料是硅橡胶聚合物、聚氨酯、聚亚安酯、聚乙二醇其中的一种或多种混合;溶剂采用无水乙醇、四氢呋喃,可以通过喷雾、浸渍、涂布的方式制备; [0302] polymer layer, to provide the desired biocompatible implantable sensor body, to improve the performance in vivo; by dipping, coating manner fixed electrode layer of polymer film, the polymer material used is a silicone rubber polymers, polyurethanes, polyurethane, polyethylene glycol, wherein the one or more mixed; the solvent using ethanol, tetrahydrofuran, can be prepared by spraying, dipping, coating methods;

[0303] ②、对电极: [0303] ②, counter electrode:

[0304] 对电极铜箔上的功能层包括对惰性金属层、对催化层、对高分子层;其制备方法与工作电极基本相同,不需制备酶层; [0304] The inert metal layer, a functional layer including copper on the electrode catalyst layer, the polymer layer; prepared in substantially the same manner as the working electrode thereof, prepared without the enzyme layer;

[0305] ③、空白电极: [0305] ③, blank electrode:

[0306]空白电极铜箔上的功能层包括惰性金属层、催化层、高分子层;其制备方法与工作电极相同,不需制备酶层; [0306] The functional layer comprises an inert metal foil blank electrode layer, a catalyst layer, a polymer layer; the same preparation method of the working electrode, was prepared without the enzyme layer;

[0307] ④、参比电极: [0307] ④, reference electrode:

[0308] 参比电极铜箔上的功能层包括惰性金属层、参比银/氯化银层、高分子层; [0308] Reference inert metal layer, a reference silver / silver chloride layer, a functional polymer layer than the layer on the electrode comprises a copper foil;

[0309] 惰性金属层制备方法与工作电极相同,惰性金属层制备完成后,通过电镀、真空溅射的方法制备银/氯化银层,电化学氯化后制备银/氯化银层,最后制备高分子外膜; [0309] inert metal layer and the working electrode prepared in the same method, after completion of the preparation of an inert metal layer by electroplating, vacuum sputtering method for preparing a silver / silver chloride layer, electrochemical chloride after preparation of silver / silver chloride layer, and finally preparation of outer membrane polymer;

[0310] 上述制备工艺完成后,最后根据单元电路进行切割,得到传感器,三电极和四电极传感器尺寸如下:植入人体部分长度不大于15_,宽不大于0.6mm,厚不大于0.4mm; [0310] After the above preparation process is completed, the final cut unit circuit according to obtain the sensor, three-electrode and four-electrode sensor dimensions are as follows: the implant body portion length is not greater than 15_, width is not greater than 0.6mm, a thickness of not greater than 0.4mm;

[0311] 两电极尺寸如下:植入人体部分长度不大于15mm,宽不大于0.3mm,厚不大于 [0311] two electrodes following dimensions: a length no greater than the implant portion body 15mm, width is not greater than 0.3mm, a thickness of no greater than

0.4mm; 0.4mm;

[0312]由上述工作电极、对电极、参比电极、空白电极,四电极组成传感器,不需要在酶层添加纳米金,空白电极用于检测背景信号和干扰信号,提高传感器准确性; [0312] by the working electrode, counter electrode, reference electrode, blank electrode, an electrode composed of four sensors, do not need the addition of nano gold, enzyme blank electrode layer for detecting the background signal and interference signal to improve the accuracy of the sensor;

[0313] 两电极和三电极传感器,制备过程需在酶层增加纳米金; [0313] two electrodes and three-electrode sensors, need to increase the preparation of gold nanoparticles in the enzyme layer;

[0314] 传感器可以通过导针植入皮下,然后退出导针,传感器留在皮下组织开始工作。 [0314] Sensors may be implanted subcutaneously by a guide pin and guide pin exit, leaving the sensor in the subcutaneous tissue to work.

Claims (2)

1.一种皮下组织介入式葡萄糖微型传感器,其特征在于:包括底座(I),所述的底座(I)中设有向外延伸的引线部分⑵,所述的引线部分⑵的末端与传感器部分⑶相连接,所述的传感器部分⑶与引线部分⑵分别设在绝缘基层⑷上; 所述的传感器部分⑶包括工作电极⑶、对电极(7)和参比电极⑶,所述的工作电极(5)设在绝缘基层(4) 一端面的左端,所述的对电极(7)设在绝缘基层(4) 一端面的右端,所述的工作电极(5)上端的内壁与对电极⑵上端的内壁间设有参比电极(6),所述的工作电极⑶、对电极⑵和参比电极(6)呈间隔状分布,构成三电极体系; 所述的工作电极(5)包括粘结层(9),所述的粘结层(9)覆在绝缘基层(4)的上部,所述的粘结层⑶的上部的覆有导电层(10),所述的导电层(10)的上部覆有惰性金属层(11),所述的惰性金属层(11)的上部的覆有催化层(12),所述的催化 A subcutaneous micro-invasive glucose sensor comprising: a base (I), the base (I) is provided with a lead portion extending outwardly ⑵, the lead end portion of the sensor ⑵ ⑶ connecting portion, said sensor portion and the lead portion ⑵ ⑶ respectively disposed on the insulating base layer ⑷; said sensor includes a working electrode portion ⑶ ⑶, the counter electrode (7) and a reference electrode ⑶, the working electrode (5) provided on the insulating base layer (4) a left end surface of the counter electrode (7) provided on the insulating base layer (4) a right end surface of the inner wall of the working electrode (5) and the upper electrode ⑵ is provided between the inner wall of the upper end of the reference electrode (6), said working electrode ⑶, ⑵ counter electrode and a reference electrode (6) in a spaced-shaped profile constituting the three-electrode system; the working electrode (5) comprises a stick junction layer (9), said adhesive layer (9) covering the upper insulating base layer (4), the upper portion of the adhesive layer is coated with a conductive layer ⑶ (10), said conductive layer (10 ) is coated with an inert metal layer upper portion (11), an upper portion of the inert metal layer (11) is coated with a catalyst layer (12), the catalytic (12)的上部的覆有酶层(13),所述的酶层(13)的上部的覆有高分子层(14); 所述的参比电极包括参比电极粘结层(15),所述的粘结层(15)覆在绝缘基层(4)的上部,所述的粘结层(15)的上部覆有参比电极导电层(16),所述的导电层(16)的上部覆有惰性金属层(17),所述的惰性金属层(17)的上部覆有银/氯化银层(18),所述的参比银/氯化银层(18)的上部覆有参比高分子层(19); 所述的对电极包括粘结层(20),所述的粘结层(20)设在绝缘基层(4)的底部,所述的粘结层(20)的表面覆有导电层(21),所述的导电层(21)的表面覆有惰性金属层(22),所述的惰性金属层(22)的表面覆有催化层(23),所述的催化层(23)的表面覆有高分子层(24); 所述的引线部分⑵由3个引线组件(30)组成,3个引线组件(30)均分在绝缘基层⑷的一个端面上,所述的引线组件(30)包括覆在绝缘基层⑷表面的引线第一粘结层(31),所 The upper portion (12) is coated with an enzyme layer (13), an upper portion of said enzyme layer (13) is coated with a polymer layer (14); said reference electrode reference electrode comprising an adhesive layer (15) said adhesive layer (15) overlying the upper portion of the insulating base layer (4), the upper portion of said adhesive layer (15) is coated with a reference (16), a conductive electrode layer, said conductive layer (16) the upper portion of the inert metal coated with a layer (17), an upper portion of the inert metal layer (17) is coated with silver / silver chloride layer (18), said upper reference silver / silver chloride layer (18) reference is coated with a polymer layer (19); said pair of electrodes comprises an adhesive layer (20), said adhesive layer (20) disposed in the bottom of the insulating base layer (4), said adhesive layer ( surface 20) is coated with a conductive layer (21), the surface of the conductive layer (21) is coated with an inert metal layer (22), the surface of an inert metallic layer (22) is coated with a catalyst layer (23), the surface of the catalyst layer (23) is coated with a polymer layer (24); ⑵ the lead portions of the three lead assembly (30), with the three lead assembly (30) in a sharing of the insulating base layer ⑷ an end surface of the lead assembly (30) comprising an insulating base layer leads overlying ⑷ surface of the first adhesive layer (31), the 述的引线第一粘结层(31)的表面覆有引线导电层(32),所述的引线导电层(32)的表面覆有引线第二粘结层(33),所述的引线第二粘结层(33)的表面覆有引线保护层(34); (I)、绝缘基层的选择: 绝缘基层采用可挠曲的聚酰亚胺绝缘薄膜或聚酯薄膜作为载体,体积电阻率达到1015Ω.cm;该层厚度控制在7.5-12.5微米; ⑵、粘结层材质选择: 粘结层包括传感器部分和引线部分中各粘结层; 绝缘基层的正反两面涂布粘结层,粘结层采用环氧树脂或丙烯酸树脂类,该层厚度控制在5-15微米; (3)、导电层的选择: 导电层包括传感器部分和引线部分中各导电层;粘结层的表面为导电层,导电层采用压延铜箔,厚度控制在5-20微米;引线部分需要在导电层上制备引线第二粘结层和引线保护层,层间通过滚压法增加层间结合力,电极部分不需要第二粘结层和保护层,按照不同要求制备相 Surface of the lead of the first adhesive layer (31) of said lead is coated with a conductive layer (32), the surface of the conductive layer of the lead (32) is coated with lead of the second adhesive layer (33), said first lead surface of the two adhesive layer (33) is coated with a lead protective layer (34); (I), the insulating base selected: an insulating base layer of polyimide insulating films or polyester films can be flexible as a carrier, the volume resistivity reaches 1015Ω.cm; layer thickness control in the 7.5 to 12.5 micron; ⑵, material selection adhesive layer: adhesive layer including the adhesive layer and the lead portion of the sensor portion; coating both sides of the insulating base layer adhesive layer, epoxy adhesive layer or the acrylic resin, the layer thickness control in the 5-15 micron; (3), selected conductive layer: the conductive layer comprises a conductive layer of each sensor part and the lead portion; surface of the adhesive layer is a conductive layer, a conductive layer using a rolled copper foil, in 5-20 micron thickness control; required lead portion and the lead wire of the second adhesive layer was prepared in the protective layer on the conductive layer, the interlayer roll method by increasing the inter-layer adhesion, electrode The second part of the adhesive layer does not need and the protective layer, prepared in accordance with the requirements of the different 功能层; ⑷、引线第二粘结层的选择: 后端引线部分的导电层外是引线第二粘结层,粘结剂采用环氧树脂或丙烯酸树脂类,该层厚度控制在5-15微米;前端电极部分需要裸漏的不涂该层粘结剂,层间可通过滚压法增加层间结合力; ⑶、保护层的选择: 后端引线部分的引线第二粘结层外是聚酰亚胺绝缘薄膜,保护膜先进行切割加工,露出前段电极部位的铜箔,电极引线覆盖保护膜;该层厚度控制在5-15微米;通过滚压法增加层间结合力; (6)、电极部分功能层制备: ①、工作电极: 工作电极铜箔上的功能层组成如下:惰性金属层、催化层、酶层、高分子层; 惰性金属层在电极部位的铜箔上制备,通过电镀、溅射的方法制备,用金、铂的惰性金属,该层厚度为10-15微米; 催化层为铂黑,可以通过电镀方法制备; 酶层通过喷雾、浸渍、涂布的方式将酶溶液转移到 A functional layer; selecting ⑷, lead of the second adhesive layer: the conductive layer of the rear end of the outer lead portion of the lead is a second tie layer, an adhesive epoxy or acrylic resin, the layer thickness control 5-15 microns; distal electrode portion does not need to bare the drain layer of the adhesive coating, the interlayer roll method may be increased by inter-layer adhesion; selecting ⑶, the protective layer: the outer lead portion of the rear end of the lead is a second adhesive layer polyimide insulating film, a protective film for cutting to expose the copper foil electrodes preceding parts of the protective film covering the electrode lead; in the 5-15 micron layer thickness control; rolling method by increasing the inter-layer adhesion; (6 ), an electrode layer prepared some features: ①, working electrode: a functional layer on the working electrode foil composed as follows: inert metal layer, a catalyst layer, an enzyme layer, a polymer layer; inert metal layer prepared on the copper foil of the electrode portion, by plating, sputtering prepared, gold, platinum metals inert, the layer thickness is 10-15 microns; platinum black catalyst layer may be prepared by a plating method; enzyme layer by spraying, dipping, coating manner enzyme solution is transferred to 作电极上,浸渍时间为5-15分钟;然后用浓度为5%-20%的戊二醛溶液将转移到工作电极的葡萄糖氧化酶交联固定,交联温度在25-35摄氏度,采用液相浸渍交联或气相交联,交联时间为30-60min; 所用酶溶液制备过程如下:在磷酸盐缓冲液中加入葡萄糖氧化酶和人重组白蛋白,葡萄糖氧化酶加入量为每毫升50-100毫克,人重组白蛋白加入量为每毫升50-100毫克;溶解充分后,添加1-5 %的纳米金混匀,最后加入1-5 %的聚乙烯醇缩丁醛,混合均匀; 纳米金利用AOT与环己烷体系形成的反胶束体系中制备,AOT是指琥玻酸二异辛酯璜酸钠,通过柠檬酸钠还原氯金酸盐水溶液,调节水、电解质、表面活性剂的浓度比例,制备不同直径的纳米金颗粒,纳米金颗粒直径在5-30nm; 葡萄糖氧化酶交联完成后,通过浸渍、涂布的方式在电极固定一层高分子膜,以增强传感器生物相容性,提 As the upper electrode, the immersion time of 5-15 minutes; followed by a solution of glutaraldehyde at a concentration of 5% -20% will be transferred to the working electrode and cross-linked glucose oxidase, the crosslinking temperature 25-35 ° C, by liquid gas phase impregnation crosslinked or crosslinked to the crosslinking time is 30-60 min; enzyme preparation used was as follows: addition of glucose oxidase and recombinant human albumin in phosphate buffer, the glucose oxidase is added in an amount of 50 ml per 100 mg, recombinant human albumin was added in an amount of 50-100 mg per ml; after dissolving sufficiently, adding 1-5% of gold nanoparticles mixing, and finally adding 1-5% of polyvinyl butyral, mixed; nano preparation of gold using cyclohexane AOT reverse micelles formed in the system, AOT amber glass refers sodium dioctyl Juan, by reducing chloroauric acid salt sodium citrate solution, adjusting water, electrolytes, surfactant concentration ratio, the nano gold particles of different diameters prepared, gold nanoparticles 5-30 nm in diameter; the complete glucose oxidase crosslinked by dipping, coating manner fixed electrode layer of polymer film, in order to enhance the biological sensor phase capacitive, mention 高体内性能; 葡萄糖氧化酶电极氧化葡萄糖的反应由两步酶反应组成: D-glucose+GOD (FAD) -^glucose-lactone+GOD (FADH2) GOD (FADH2) +O2^GOD (FAD) +H2O2 glucose-lactone+H20^glucose-acid 高分子层,通过浸渍、涂布的方式在电极固定一层高分子膜,所用到高分子材料是硅橡胶聚合物、聚氨酯、聚酰亚胺、聚乙二醇其中的二种或多种混合;溶剂采用无水乙醇、四氢呋喃,通过喷雾、浸渍、涂布的方式制备; ②、对电极: 对电极铜箔上的功能层包括对惰性金属层、对催化层、对高分子层;其制备方法与工作电极基本相同,不需制备酶层; ③、参比电极: 参比电极铜箔上的功能层包括惰性金属层、参比银/氯化银层、高分子层; 惰性金属层制备方法与工作电极相同,惰性金属层制备完成后,通过电镀、真空溅射的方法制备银/氯化银层,电化学氯化后制备银/氯化银层,最后制备高分子外 High in vivo performance; glucose oxidase electrode of a two-step oxidation of glucose by the reaction of the enzyme composition of the reaction: D-glucose + GOD (FAD) - ^ glucose-lactone + GOD (FADH2) GOD (FADH2) + O2 ^ GOD (FAD) + H2O2 glucose-lactone + H20 ^ glucose-acid polymer layer by dipping, coating manner fixed electrode layer of polymer film, the polymer material used is a silicone rubber polymer, polyurethane, polyimide, polyethylene wherein the alcohol mixture of two or more; solvents using ethanol, tetrahydrofuran, prepared by spraying, dipping, coating manner; ②, counter electrode: electrode layer on the functional copper foil comprises an inert metal layer, the catalytic layer, the polymer layer; the preparation method of the working electrode is substantially the same, was prepared without the enzyme layer; ③, reference electrode: the reference electrode layer on the functional copper foil comprises an inert metal layer, a reference silver / silver chloride layer , the polymer layer; preparation inert metal layer and the working electrode the same method, after completion of the preparation of an inert metal layer, by electroplating, vacuum sputtering method for preparing a silver / silver chloride layer, electrochemical chloride after preparation of silver / silver chloride layer Finally, to prepare a polymer outer 膜; 上述制备工艺完成后,最后根据单元电路进行切割,得到传感器,传感器尺寸如下:植入人体部分长度不大于15mm,宽不大于0.6mm,厚不大于0.4mm。 Film; after the completion of the above-described manufacturing process, the final cut unit circuit according to obtain the sensor, the sensor dimensions are as follows: not more than implanted in the body portion length 15mm, width is not greater than 0.6mm, a thickness of not greater than 0.4mm.
2.根据权利要求1所述的一种皮下组织介入式葡萄糖微型传感器的制备方法,其特征在于:按以下步骤进行: (I)、绝缘基层的选择: 绝缘基层采用可挠曲的聚酰亚胺绝缘薄膜或聚酯薄膜作为载体,体积电阻率达到1015Ω.cm;该层厚度控制在7.5-12.5微米; ⑵、粘结层材质选择: 粘结层包括传感器部分和引线部分中各粘结层; 绝缘基层的正反两面涂布粘结层,粘结层采用环氧树脂或丙烯酸树脂类,该层厚度控制在5-15微米; (3)、导电层的选择: 导电层包括传感器部分和引线部分中各导电层;粘结层的表面为导电层,导电层采用压延铜箔,厚度控制在5-20微米;引线部分需要在导电层上制备引线第二粘结层和引线保护层,层间通过滚压法增加层间结合力,电极部分不需要第二粘结层和保护层,按照不同要求制备相应功能层; ⑷、引线第二粘结层的选择: 后端引线部分 The involvement of subcutaneous glucose production method according to claim 1 micro-sensor, characterized in that: the following steps performed: (the I), the insulating base selected: an insulating base layer using the flexible polyimide amine insulating film or a polyester film as a support, the volume resistivity reached 1015Ω.cm; layer thickness control in the 7.5 to 12.5 micron; ⑵, material selection adhesive layer: adhesive layer of each adhesive layer and the lead portion of the sensor portion comprises ; coating both sides of the insulating base layer adhesive layer, the adhesive layer using an epoxy resin or acrylic resin, the layer thickness control in the 5-15 micron; selecting (3), a conductive layer: the conductive layer comprises a sensor section and each conductive layer of the lead portion; surface of the adhesive layer is a conductive layer, a conductive layer using a rolled copper foil, in 5-20 micron thickness control; required lead portion and the lead wire of the second adhesive layer was prepared in the protective layer on the conductive layer, the interlayer rolling method by increasing the inter-layer bonding force, does not require a second electrode portion adhesive layer and protective layer, prepared in accordance with the respective functional layers different requirements; selecting ⑷, lead of the second adhesive layer: the rear end portion of the lead 导电层外是引线第二粘结层,粘结剂采用环氧树脂或丙烯酸树脂类,该层厚度控制在5-15微米;前端电极部分需要裸漏的不涂该层粘结剂,层间可通过滚压法增加层间结合力; ⑶、保护层的选择: 后端引线部分的引线第二粘结层外是聚酰亚胺绝缘薄膜,保护膜先进行切割加工,露出前段电极部位的铜箔,电极引线覆盖保护膜;该层厚度控制在5-15微米;通过滚压法增加层间结合力; (6)、电极部分功能层制备: ①、工作电极: 工作电极铜箔上的功能层组成如下:惰性金属层、催化层、酶层、高分子层; 惰性金属层在电极部位的铜箔上制备,通过电镀、溅射的方法制备,用金、铂的惰性金属,该层厚度为10-15微米; 催化层为铂黑,通过电镀方法制备; 酶层通过喷雾、浸渍、涂布的方式将酶溶液转移到工作电极上,浸渍时间为5-15分钟;然后用浓度为5%-20%的戊二 An outer lead of the second conductive layer is a tie layer, an adhesive epoxy or acrylic resin, the layer thickness control in the 5-15 micron; distal electrode portion need not coat the bare drain adhesive layer, interlayer may be combined by inter-layer rolling method to increase the force; selecting ⑶, the protective layer: the rear end of the lead outer lead portion of the second adhesive layer is a polyimide insulating film, a protective film for cutting to expose part of the preceding electrode copper foil, the protective film covering the electrode lead; in the 5-15 micron layer thickness control; interlayer bonding force is increased by the rolling method; (6), the electrode portion of the functional layer was prepared: ①, working electrode: copper foil on the working electrode functional layers as follows: inert metal layer, a catalyst layer, an enzyme layer, a polymer layer; inert metal electrode layer prepared on the copper foil portions, by plating, sputtering production method, inert metals gold, platinum, this layer having a thickness of 10-15 microns; platinum black catalyst layer, prepared by a plating method; enzyme layer by spraying, dipping, coating the enzyme solution was transferred way to the working electrode, the immersion time of 5-15 minutes; followed by concentration 5% -20% of glutaric 醛溶液将转移到工作电极的葡萄糖氧化酶交联固定,交联温度在25-35摄氏度,采用液相浸渍交联或气相交联,交联时间为30-60min; 所用酶溶液制备过程如下:在磷酸盐缓冲液中加入葡萄糖氧化酶和人重组白蛋白,葡萄糖氧化酶加入量为每毫升50-100毫克,人重组白蛋白加入量为每毫升50-100毫克;溶解充分后,添加1-5 %的纳米金混匀,最后加入1-5 %的聚乙烯醇缩丁醛,混合均匀; 纳米金利用AOT与环己烷体系形成的反胶束体系中制备,AOT是指琥玻酸二异辛酯璜酸钠,通过柠檬酸钠还原氯金酸盐水溶液,调节水、电解质、表面活性剂的浓度比例,制备不同直径的纳米金颗粒,纳米金颗粒直径在5-30nm; 葡萄糖氧化酶交联完成后,通过浸渍、涂布的方式在电极固定一层高分子膜,以增强传感器生物相容性,提高体内性能; 葡萄糖氧化酶电极氧化葡萄糖的反应由两步 The aldehyde solution is transferred to the working electrode and cross-linked glucose oxidase, the crosslinking temperature 25-35 ° C, liquid phase impregnation, or VAPOR crosslinking, the crosslinking time is 30-60 min; of the enzyme solution was prepared as follows: in phosphate buffer was added glucose oxidase and recombinant human albumin, glucose oxidase is added in an amount of 50-100 mg per ml, recombinant human albumin was added in an amount of 50-100 mg per ml; fully dissolved, was added 1 5% of the gold nano mixing, and finally adding 1-5% of polyvinyl butyral, uniformly mixed; preparation of gold nanoparticles using cyclohexane system AOT reverse micelles formed, AOT amber glass refers to diethyl Huang isooctyl sodium, sodium citrate by reducing chloroauric acid salt solution, adjusting water electrolyte, the ratio of the concentration of surfactant, the preparation of gold nanoparticles with different diameters of 5-30 nm diameter gold nanoparticles; glucose oxidase after the completion of crosslinking, by dipping, coating manner fixed electrode layer of polymer film, to enhance the biocompatibility of the sensor, to improve the performance in vivo; glucose oxidase electrode of a two-step oxidation of glucose by the reaction of 反应组成: D-glucose+GOD (FAD) -^glucose-lactone+GOD (FADH2) GOD (FADH2) +O2^GOD (FAD) +H2O2 glucose-lactone+H20^glucose-acid 高分子层,通过浸渍、涂布的方式在电极固定一层高分子膜,所用到高分子材料是硅橡胶聚合物、聚氨酯、聚酰亚胺、聚乙二醇其中的二种或多种混合;溶剂采用无水乙醇、四氢呋喃,通过喷雾、浸渍、涂布的方式制备; ②、对电极: 对电极铜箔上的功能层包括对惰性金属层、对催化层、对高分子层;其制备方法与工作电极基本相同,不需制备酶层; ③、参比电极: 参比电极铜箔上的功能层包括惰性金属层、参比银/氯化银层、高分子层; 惰性金属层制备方法与工作电极相同,惰性金属层制备完成后,通过电镀、真空溅射的方法制备银/氯化银层,电化学氯化后制备银/氯化银层,最后制备高分子外膜; 上述制备工艺完成后,最后根据单元电路进行切割, Reaction composition: D-glucose + GOD (FAD) - ^ glucose-lactone + (FADH2) + O2 ^ GOD (FAD) + H2O2 glucose-lactone + H20 ^ glucose-acid polymer layer GOD (FADH2) GOD, by dipping, the coated electrodes are fixed in one embodiment the polymer film, the polymer material used is a silicone rubber polymer, polyurethane, polyimide, polyethylene glycol in which two or more kinds; using ethanol solvent, tetrahydrofuran, prepared by spraying, dipping, coating manner; ②, counter electrode: electrode layer on the functional copper foil comprises an inert metal layer, on the catalyst layer, the polymer layer; substantially the same preparation method and the working electrode, prepared without the enzyme layer; ③, reference electrode: the reference electrode layer on the functional copper foil comprises an inert metal layer, a reference silver / silver chloride layer, a polymer layer; inert metal layer, the same method of preparation and the working electrode, an inert after the completion of the preparation of the metal layer by electroplating, vacuum sputtering method for preparing a silver / silver chloride layer, electrochemical chloride after preparation of silver / silver chloride layer, and finally to prepare a polymer outer membrane; prepared as described above after the process is completed, according to the final cutting unit circuit, 到传感器,传感器尺寸如下:植入人体部分长度不大于15mm,宽不大于0.6mm,厚不大于0.4mm。 To the sensor, the sensor dimensions are as follows: the implant body portion length is not greater than 15mm, width is not greater than 0.6mm, a thickness of not greater than 0.4mm.
CN201510783645.1A 2015-11-16 2015-11-16 Micro Interventional subcutaneous glucose sensor and method of preparation CN105411607B (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201510783645.1A CN105411607B (en) 2015-11-16 2015-11-16 Micro Interventional subcutaneous glucose sensor and method of preparation

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201510783645.1A CN105411607B (en) 2015-11-16 2015-11-16 Micro Interventional subcutaneous glucose sensor and method of preparation

Publications (2)

Publication Number Publication Date
CN105411607A CN105411607A (en) 2016-03-23
CN105411607B true CN105411607B (en) 2017-03-01

Family

ID=55490495

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201510783645.1A CN105411607B (en) 2015-11-16 2015-11-16 Micro Interventional subcutaneous glucose sensor and method of preparation

Country Status (1)

Country Link
CN (1) CN105411607B (en)

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1644157A (en) * 2004-12-08 2005-07-27 圣美迪诺医疗科技(湖州)有限公司 Endermic implantating biological sensors
CN102905621A (en) * 2009-12-30 2013-01-30 马奎特急救护理股份公司 Sensor arrangement for continuously measuring analytes in a biological fluid
CN102920465A (en) * 2012-10-26 2013-02-13 浙江大学 The glucose sensor
CN104799866A (en) * 2009-07-23 2015-07-29 雅培糖尿病护理公司 The analyte monitoring device

Family Cites Families (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6932894B2 (en) * 2001-05-15 2005-08-23 Therasense, Inc. Biosensor membranes composed of polymers containing heterocyclic nitrogens
US7153265B2 (en) * 2002-04-22 2006-12-26 Medtronic Minimed, Inc. Anti-inflammatory biosensor for reduced biofouling and enhanced sensor performance
US8583204B2 (en) * 2008-03-28 2013-11-12 Dexcom, Inc. Polymer membranes for continuous analyte sensors
US20110082356A1 (en) * 2009-10-01 2011-04-07 Medtronic Minimed, Inc. Analyte sensor apparatuses having interference rejection membranes and methods for making and using them
US20110230735A1 (en) * 2010-03-16 2011-09-22 Medtronic Minimed, Inc. Analyte sensor apparatuses having improved electrode configurations and methods for making and using them
EP2653868A1 (en) * 2012-04-18 2013-10-23 NovioSense B.V. Process for making biosensor
CN205215238U (en) * 2015-11-16 2016-05-11 杭州亿信网络科技有限公司 Hypodermics intervenes formula glucose microsensor

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1644157A (en) * 2004-12-08 2005-07-27 圣美迪诺医疗科技(湖州)有限公司 Endermic implantating biological sensors
CN104799866A (en) * 2009-07-23 2015-07-29 雅培糖尿病护理公司 The analyte monitoring device
CN102905621A (en) * 2009-12-30 2013-01-30 马奎特急救护理股份公司 Sensor arrangement for continuously measuring analytes in a biological fluid
CN102920465A (en) * 2012-10-26 2013-02-13 浙江大学 The glucose sensor

Also Published As

Publication number Publication date
CN105411607A (en) 2016-03-23

Similar Documents

Publication Publication Date Title
Wang et al. Needle-type dual microsensor for the simultaneous monitoring of glucose and insulin
Sanz et al. Development of a tyrosinase biosensor based on gold nanoparticles-modified glassy carbon electrodes: Application to the measurement of a bioelectrochemical polyphenols index in wines
Si et al. Nanomaterials for electrochemical non-enzymatic glucose biosensors
JP4912489B2 (en) How to prepare a test piece having a sample receiving chamber formed flared
ES2235795T3 (en) Biosensor.
Moscone et al. Construction and analytical characterization of Prussian blue-based carbon paste electrodes and their assembly as oxidase enzyme sensors
US8641618B2 (en) Method and structure for securing a monitoring device element
US20040238359A1 (en) Biosensor
EP2071331A2 (en) Biosensors with porous chromatographic membranes
Kumar et al. Immobilization of cholesterol oxidase and potassium ferricyanide on dodecylbenzene sulfonate ion‐doped polypyrrole film
Cao et al. Nickel oxide microfibers immobilized onto electrode by electrospinning and calcination for nonenzymatic glucose sensor and effect of calcination temperature on the performance
CA2245941C (en) Disposable test strips for determination of blood analytes, and methods and compositions for making same
KR890004367B1 (en) Enzyme sensor
US20050096520A1 (en) Extracting device, extracting method, analyzer and analyzing method
Wiegand et al. Extracellular potassium activity changes in the canine myocardium after acute coronary occlusion and the influence of beta-blockade
US7112265B1 (en) Disposable test strips with integrated reagent/blood separation layer
Guinovart et al. Bandage‐based wearable potentiometric sensor for monitoring wound pH
JP3389106B2 (en) The electrochemical analysis element
EP0759553B1 (en) Amperometric biosensor
CN2372689Y (en) Current biological sensor
Owens et al. Organic electronics at the interface with biology
US7882611B2 (en) Method of making an analyte sensor
US7842012B2 (en) Guidewire with chemical sensing capabilities
Wang et al. Enzyme microelectrode array strips for glucose and lactate
Cogan et al. Sputtered iridium oxide films for neural stimulation electrodes

Legal Events

Date Code Title Description
C06 Publication
C10 Entry into substantive examination
GR01
TR01