技术领域technical field
本发明涉及植入式生物传感器技术领域，特别涉及一种植入式生物传感器及其制备方法。The invention relates to the technical field of implantable biosensors, in particular to an implantable biosensor and a preparation method thereof.
背景技术Background technique
植入式生物传感器是一种用于检测化学物质的分析设备，它将生物成分与物理化学检测器结合在一起。植入式生物传感器是由固定化的生物活性分子作感应元件(包括酶、抗体、抗原、微生物、细胞、组织、核酸等生物活性物质)、适当的理化换能器(如氧电极、光敏管、场效应管、压电晶体等等)及信号放大装置构成的分析工具或系统。An implantable biosensor is an analytical device for the detection of chemicals that combines biological components with physicochemical detectors. Implantable biosensors are composed of immobilized bioactive molecules as sensing elements (including enzymes, antibodies, antigens, microorganisms, cells, tissues, nucleic acids and other biologically active substances), appropriate physical and chemical transducers (such as oxygen electrodes, photosensitive tubes, etc.) , field effect transistor, piezoelectric crystal, etc.) and an analysis tool or system composed of a signal amplification device.
植入式生物传感器采用固体电极作基础电极，将生物活性分子固定在电极表面，然后通过生物分子间的特异性识别作用，生物活性分子能选择性地识别目标分子并将目标分子捕获到电极表面，发射器将电极表面发生的识别反应信号导出，变成可以测量的电信号，从而实现对分析目标物进行定量或定性分析的目的。Implantable biosensors use solid electrodes as basic electrodes, immobilize bioactive molecules on the electrode surface, and then through specific recognition between biomolecules, bioactive molecules can selectively recognize target molecules and capture target molecules on the electrode surface , the transmitter derives the recognition reaction signal that occurs on the electrode surface and turns it into a measurable electrical signal, so as to achieve the purpose of quantitative or qualitative analysis of the analysis target.
植入式生物传感器具有连续测定体内某些随时间变化的重要生理或病理参数的优点，例如氧、葡萄糖、乳酸的浓度等，从而获得全面而准确的诊断或治疗的效果。Implantable biosensors have the advantage of continuously measuring some important physiological or pathological parameters in the body that change over time, such as the concentration of oxygen, glucose, and lactic acid, so as to obtain comprehensive and accurate diagnosis or treatment effects.
现有技术中，由于植入式生物传感器需要长久佩戴，传感器的感应元件容易脱落，影响测试的灵敏度。而且发射器位于人体组织外部，传感器在长期使用过程中，发射器会因人体活动而被外部的物件触碰或拉扯，从而使得与感应元件电连接的信号输出端和与发射器电连接的信号接收端的连接处断裂，造成信号传输不良。因此，需要开发一种耐用且稳定的植入式生物传感器。In the prior art, since the implanted biosensor needs to be worn for a long time, the sensing element of the sensor is easy to fall off, which affects the sensitivity of the test. Moreover, the transmitter is located outside the human body tissue. During the long-term use of the sensor, the transmitter will be touched or pulled by external objects due to human activities, so that the signal output terminal electrically connected to the sensing element and the signal electrically connected to the transmitter The connection at the receiving end is broken, causing poor signal transmission. Therefore, there is a need to develop a durable and stable implantable biosensor.
发明内容Contents of the invention
本发明的目的在于提供一种植入式生物传感器及其制备方法，以解决上述问题。The object of the present invention is to provide an implantable biosensor and its preparation method to solve the above problems.
为解决上述技术问题，本发明的实施方式提供了一种植入式生物传感器，包括：In order to solve the above technical problems, an embodiment of the present invention provides an implantable biosensor, including:
柔性载体，所述柔性载体沿第一方向延伸，且沿所述第一方向包括相互连接的感应段和输出段；a flexible carrier extending along a first direction and including an interconnected sensing section and an output section along the first direction;
感应元件，所述感应元件位于所述感应段的表面并可操作地与目标生物分子反应并产生信号；a sensing element positioned on the surface of the sensing segment and operable to react with a target biomolecule and generate a signal;
信号输出端，所述信号输出端与所述输出段连接，并与所述感应元件电连接；以及a signal output terminal, the signal output terminal is connected to the output section and electrically connected to the inductive element; and
发射器，所述发射器具有信号接收端，所述信号接收端与所述信号输出端通过柔性连接组件电连接，所述柔性连接组件具有弹性。A transmitter, the transmitter has a signal receiving end, the signal receiving end is electrically connected to the signal output end through a flexible connection component, and the flexible connection component has elasticity.
在一个实施例中，所述柔性连接组件为导电胶。In one embodiment, the flexible connection component is conductive glue.
在一个实施例中，所述柔性连接组件包括：In one embodiment, the flexible connection assembly includes:
嵌段共聚物复合材料，所述嵌段共聚物复合材料与所述信号接收端和所述信号输出端连接；以及a block copolymer composite material connected to the signal receiving end and the signal output end; and
导电金属材料，所述导电金属材料分布于所述嵌段共聚物内部并与所述信号接收端和所述信号输出端电连接。A conductive metal material, the conductive metal material is distributed inside the block copolymer and electrically connected to the signal receiving end and the signal output end.
在一个实施例中，所述嵌段共聚物复合材料包括苯乙烯共聚物、乙烯丙烯共聚物、氢化苯乙烯、异戊二烯共聚物、聚乙二醇或乙烯丁烯共聚物中的至少一种，所述导电金属材料包括金、银、铜、钯、钛或铂中的至少一种。In one embodiment, the block copolymer composite material comprises at least one of styrene copolymer, ethylene propylene copolymer, hydrogenated styrene, isoprene copolymer, polyethylene glycol or ethylene butene copolymer species, the conductive metal material includes at least one of gold, silver, copper, palladium, titanium or platinum.
在一个实施例中，所述感应元件通过喷印方式印刷至所述感应段的表面。In one embodiment, the sensing element is printed on the surface of the sensing segment by jet printing.
在一个实施例中，所述感应元件包括：In one embodiment, the sensing element includes:
交联层，所述交联层粘结至所述感应段的表面；a crosslinked layer bonded to the surface of the sensing segment;
导电材料，所述导电材料一部分位于所述交联层内，另一部分位于所述交联层远离所述感应段的表面；以及A conductive material, a part of the conductive material is located in the cross-linked layer, and another part is located on the surface of the cross-linked layer away from the sensing segment; and
感应层，所述感应层覆盖所述交联层远离所述感应段的表面，并可操作地与所述目标生物分子反应并产生电信号。a sensing layer, the sensing layer covers the surface of the cross-linking layer away from the sensing segment, and is operable to react with the target biomolecules and generate electrical signals.
在一个实施例中，所述感应段为亲水性材料，所述感应层包括葡萄糖催化酶，所述交联层包括1,9-壬二硫醇和1-硫代甘油，且所述1,9-壬二硫醇和所述1-硫代甘油的含量比范围为20:1-50:1。In one embodiment, the sensing segment is a hydrophilic material, the sensing layer includes glucose catalytic enzyme, the cross-linking layer includes 1,9-nonanedithiol and 1-thioglycerol, and the 1, The content ratio range of 9-nonanedithiol to the 1-thioglycerol is 20:1-50:1.
在一个实施例中，所述导电材料包括石墨烯、碳纳米管、金、银或铂中的至少一种。In one embodiment, the conductive material includes at least one of graphene, carbon nanotubes, gold, silver or platinum.
在一个实施例中，所述交联层的厚度范围0.5um-40um。In one embodiment, the thickness of the cross-linked layer ranges from 0.5um to 40um.
在一个实施例中，所述感应层的厚度范围为0.1um-80um。In one embodiment, the sensing layer has a thickness ranging from 0.1um to 80um.
在一个实施例中，所述感应元件沿所述第一方向的长度范围1mm-3mm，沿第二方向的宽度范围为1mm-3mm，所述第二方向与所述第一方向垂直。In one embodiment, the sensing element has a length ranging from 1 mm to 3 mm along the first direction, and a width ranging from 1 mm to 3 mm along the second direction, and the second direction is perpendicular to the first direction.
在一个实施例中，所述信号输出端的长度沿所述第一方向的长度范围0.5mm-3mm，沿所述第二方向的宽度范围0.3mm-2mm。In one embodiment, the length of the signal output end along the first direction ranges from 0.5 mm to 3 mm, and the width along the second direction ranges from 0.3 mm to 2 mm.
在一个实施例中，所述信号输出端与所述信号接收端通过导电层电连接，所述导电层可导电并与所述柔性载体的表面连接。In one embodiment, the signal output terminal is electrically connected to the signal receiving terminal through a conductive layer, and the conductive layer is conductive and connected to the surface of the flexible carrier.
在一个实施例中，所述发射器与所述输出段卡接。In one embodiment, the transmitter is engaged with the output section.
本发明还涉及一种植入式生物传感器的制备方法，包括步骤：The present invention also relates to a method for preparing an implantable biosensor, comprising the steps of:
S1、准备柔性载体、感应元件、发射器和柔性连接组件，所述柔性载体包括相互连接的感应段和输出段，所述输出段具有信号输出端；所述柔性载体的表面设有导电层，所述导电层从所述感应段延伸至所述输出段，并与所述输出段的信号输出端电连接；所述发射器具有信号接收端；S1. Prepare a flexible carrier, a sensing element, an emitter and a flexible connection assembly, the flexible carrier includes an interconnected sensing segment and an output segment, the output segment has a signal output end; the surface of the flexible carrier is provided with a conductive layer, The conductive layer extends from the sensing section to the output section, and is electrically connected to the signal output end of the output section; the transmitter has a signal receiving end;
S2、将所述感应元件连接至所述感应段的表面并与所述导电层电连接；S2. Connect the sensing element to the surface of the sensing segment and electrically connect to the conductive layer;
S3、将所述柔性连接组件包括第一连接组件和第二连接组件，将所述第一连接组件粘结至所述信号输出端，将所述第二连接组件粘结至所述信号接收端，并将所述第一连接组件远离所述信号输出端的表面和第二连接组件远离所述信号接收端的表面朝向彼此按压粘合，从而使得所述信号输出端和所述信号连接端弹性电连接。S3. The flexible connection assembly includes a first connection assembly and a second connection assembly, bonding the first connection assembly to the signal output end, and bonding the second connection assembly to the signal receiving end , and press and bond the surface of the first connection component away from the signal output end and the surface of the second connection component away from the signal receiving end toward each other, so that the signal output end and the signal connection end are elastically electrically connected .
在一个实施例中，所述第一连接组件和所述第二连接组件分别包括：In one embodiment, the first connection component and the second connection component respectively include:
嵌段共聚物复合材料，所述第一连接组件的所述嵌段共聚物复合材料粘结至所述信号输出端，所述第二连接组件的所述嵌段共聚物复合材料粘结至所述信号接收端；以及a block copolymer composite material, the block copolymer composite material of the first connection component is bonded to the signal output terminal, and the block copolymer composite material of the second connection component is bonded to the the signal receiving end; and
导电金属材料，所述第一连接组的所述导电金属材料一部分位于所述嵌段共聚物复合材料内部并与所述信号输出端电连接，另一部分覆盖所述嵌段共聚物复合材料远离所述信号输出端的表面；所述第二连接组的所述导电金属材料一部分位于所述嵌段共聚物复合材料内部并与所述信号接收端电连接，另一部分覆盖于所述嵌段共聚物复合材料远离所述信号接收端的表面。A conductive metal material, a part of the conductive metal material of the first connection group is located inside the block copolymer composite material and electrically connected to the signal output end, and the other part covers the block copolymer composite material and is away from the The surface of the signal output end; a part of the conductive metal material of the second connection group is located inside the block copolymer composite material and electrically connected to the signal receiving end, and the other part covers the block copolymer composite material The material is remote from the surface of the signal receiving end.
在一个实施例中，步骤S2之前，包括步骤：对所述柔性载体进行亲水处理；在所述柔性载体和所述导电层的表面涂硅烷类化合物。In one embodiment, before step S2, steps include: performing hydrophilic treatment on the flexible carrier; coating silane compounds on the surface of the flexible carrier and the conductive layer.
在一个实施例中，所述第一连接组件连接至所述信号输出端的步骤包括：先将所述嵌段共聚物复合材料粘结至所述信号输出端，再将所述导电金属材料分布至所述嵌段共聚物复合材料的内部和表面。In one embodiment, the step of connecting the first connection component to the signal output terminal includes: first bonding the block copolymer composite material to the signal output terminal, and then distributing the conductive metal material to the signal output terminal. The interior and surface of the block copolymer composite.
在一个实施例中，所述第二连接组件连接至所述信号接收端的步骤包括：先将所述嵌段共聚物复合材料粘结至所述信号接收端，再将所述导电金属材料分布在所述嵌段共聚物复合材料的内部和表面。In one embodiment, the step of connecting the second connection component to the signal receiving end includes: first bonding the block copolymer composite material to the signal receiving end, and then distributing the conductive metal material on the signal receiving end The interior and surface of the block copolymer composite.
在一个实施例中，所述硅烷类化合物包括氯硅烷、硅溴化物、硅碘化物、硫化硅中的至少一种。In one embodiment, the silane compound includes at least one of chlorosilane, silicon bromide, silicon iodide, and silicon sulfide.
在一个实施例中，所述第一连接组件的嵌段共聚物复合材料的厚度范围为10um-500um，位于所述第一连接组件的所述嵌段共聚物复合材料表面的所述导电金属材料厚度范围10nm-1000nm。In one embodiment, the block copolymer composite material of the first connection component has a thickness ranging from 10um to 500um, and the conductive metal material on the surface of the block copolymer composite material of the first connection component The thickness range is 10nm-1000nm.
在一个实施例中，将所述第一连接组件粘结至所述信号输出端前，还需要对所述柔性载体冲洗；In one embodiment, before bonding the first connection component to the signal output end, the flexible carrier needs to be rinsed;
将所述第一连接组件粘结至所述信号输出端后，还需对所述第一连接组件50°加热10min。After bonding the first connection component to the signal output end, it is necessary to heat the first connection component at 50° for 10 minutes.
在一个实施例中，将所述感应元件通过喷印至所述感应段的表面。In one embodiment, the sensing element is spray-printed onto the surface of the sensing segment.
在一个实施例中，所述感应元件包括交联层、导电材料和感应层，In one embodiment, the sensing element includes a cross-linked layer, a conductive material and a sensing layer,
所述感应元件喷印所述感应段的步骤包括：将混合导电材料的交联剂喷射至所述感应段的表面并形成混合有所述导电材料的交联层，再将感应剂喷射至所述交联层的表面并形成所述感应层；The step of spray printing the sensing section of the sensing element includes: spraying a cross-linking agent mixed with a conductive material onto the surface of the sensing section to form a cross-linked layer mixed with the conductive material, and then spraying the sensing agent onto the surface of the sensing section the surface of the cross-linked layer and form the sensing layer;
或，所述感应元件喷印所述感应段的步骤包括：将导电材料和感应剂喷射至所述感应段的表面并形成感应层，再将交联剂喷射至所述感应层和所述柔性材料，固化形成交联层。Or, the step of printing the sensing segment on the sensing element includes: spraying a conductive material and a sensing agent onto the surface of the sensing segment to form a sensing layer, and then spraying a cross-linking agent onto the sensing layer and the flexible material, curing to form a cross-linked layer.
或，所述感应元件喷印所述感应段的步骤包括：将导电材料喷印至所述感应段，再将感应剂添加至所述导电材料并形成所述感应层，再将交联剂喷射至所述感应层和所述柔性材料，固化形成交联层。Alternatively, the step of printing the sensing segment on the sensing element includes: spraying a conductive material onto the sensing segment, adding a sensing agent to the conductive material to form the sensing layer, and spraying a cross-linking agent The sensing layer and the flexible material are cured to form a cross-linked layer.
本发明通过喷印方式将感应剂喷印至柔性载体的电极工作区，并通过交联剂和感应剂中葡萄糖催化酶交联的效果，将葡萄糖催化酶通过共价键牢固均匀的固定在特定位置，同时增强传感器检测性能，并且无需复杂的工艺处理电极工作区平面，保证植入式生物传感器性能的一致性。而且，通过喷印方式可以快速将感应剂分布在电极工作区，还可以提高感应剂的吸附牢固，并且导电材料还可以增强电极工作区的灵敏度。信号输出端和信号接收端通过柔性连接组件快速高效电连接，减少了电气组件的占用面积、降低了接触应力、提高拉伸力和连接可靠性。In the present invention, the sensing agent is spray-printed to the electrode working area of the flexible carrier by means of jet printing, and through the cross-linking effect of the cross-linking agent and the glucose-catalyzing enzyme in the sensing agent, the glucose-catalyzing enzyme is firmly and evenly fixed on a specific surface through covalent bonds. position, while enhancing the detection performance of the sensor, and does not require complex processes to process the plane of the electrode working area, ensuring the consistency of the performance of the implanted biosensor. Moreover, the sensing agent can be quickly distributed in the working area of the electrode by means of spray printing, which can also improve the firm adsorption of the sensing agent, and the conductive material can also enhance the sensitivity of the working area of the electrode. The signal output end and the signal receiving end are electrically connected quickly and efficiently through the flexible connection component, which reduces the occupied area of the electrical component, reduces contact stress, and improves tensile force and connection reliability.
附图说明Description of drawings
图1是本发明的一个实施例的植入式生物传感器的示意图。Fig. 1 is a schematic diagram of an implantable biosensor according to an embodiment of the present invention.
图2和图3是图1所示实施例中植入式生物传感器的感应段的示意图。2 and 3 are schematic diagrams of the sensing section of the implantable biosensor in the embodiment shown in FIG. 1 .
图4是图3所示实施例中感应元件位于感应段的截面图。Fig. 4 is a cross-sectional view of the sensing element located in the sensing section in the embodiment shown in Fig. 3 .
图5是图1所示实施例中植入式生物传感器的输出段的示意图。FIG. 5 is a schematic diagram of the output section of the implantable biosensor in the embodiment shown in FIG. 1 .
图6是图1所示实施例中植入式生物传感器的输出段的侧视图。FIG. 6 is a side view of the output section of the implantable biosensor in the embodiment shown in FIG. 1 .
图7是图6所示实施例中柔性连接组件位于输出段的信号输出端的截面图。Fig. 7 is a cross-sectional view of the flexible connection assembly located at the signal output end of the output section in the embodiment shown in Fig. 6 .
图8是本发明的一个实施例的植入式生物传感器中第一连接组件粘结至信号输出段的制备流程示意图。Fig. 8 is a schematic diagram of the preparation process of bonding the first connection component to the signal output section in the implantable biosensor according to an embodiment of the present invention.
图9是本发明的一个实施例的发射器的示意图。Figure 9 is a schematic diagram of a transmitter according to one embodiment of the present invention.
图10是本发明的一个实施例的植入式生物传感器中的感应元件喷印至感应段的制备流程示意图。Fig. 10 is a schematic diagram of the preparation process of spray printing the sensing element to the sensing segment in the implantable biosensor according to an embodiment of the present invention.
图11是本发明的一个实施例的植入式生物传感器中第二连接组件与发射器的信号接收端的加工流程示意图。Fig. 11 is a schematic diagram of the processing flow of the second connection component and the signal receiving end of the transmitter in the implantable biosensor according to an embodiment of the present invention.
图12是本发明的一个实施例的发射器和输出段加工后的截面图。Figure 12 is a fabricated cross-sectional view of the emitter and output section of one embodiment of the present invention.
图13是本发明的一个实施例的植入式生物传感器中柔性载体的组装流程示意图。Fig. 13 is a schematic diagram of the assembly process of the flexible carrier in the implantable biosensor according to an embodiment of the present invention.
图14是采用现有技术的植入式生物传感器和本发明的植入式生物传感器检测10天的葡萄糖监测数据对比图。Fig. 14 is a comparison chart of glucose monitoring data detected by the implanted biosensor of the prior art and the implanted biosensor of the present invention for 10 days.
附图标记：100、植入式生物传感器；1、柔性载体；11、感应段；12、输出段；13、导电层；14、卡槽；2、感应元件；21、交联层；22、导电材料；23、感应层；3、信号输出端；4、发射器；41、塑胶件；42、电路板；43、镀层区；45、信号接收端；44、卡块；5、柔性连接组件；51、第一连接组件；52、嵌段共聚物复合材料；53、导电金属材料。Reference signs: 100, implantable biosensor; 1, flexible carrier; 11, sensing section; 12, output section; 13, conductive layer; 14, card slot; 2, sensing element; 21, cross-linked layer; 22, Conductive material; 23. Induction layer; 3. Signal output terminal; 4. Transmitter; 41. Plastic parts; 42. Circuit board; 43. Plating area; 45. Signal receiving end; 44. Block; 5. Flexible connection components ; 51, the first connection component; 52, the block copolymer composite material; 53, the conductive metal material.
具体实施方式Detailed ways
为使本发明的目的、技术方案和优点更加清楚，下面将结合附图对本发明的各实施方式进行详细的阐述。然而，本领域的普通技术人员可以理解，在本发明各实施方式中，为了使读者更好地理解本申请而提出了许多技术细节。但是，即使没有这些技术细节和基于以下各实施方式的种种变化和修改，也可以实现本申请各权利要求所要求保护的技术方案。In order to make the purpose, technical solutions and advantages of the present invention clearer, various embodiments of the present invention will be described in detail below in conjunction with the accompanying drawings. However, those of ordinary skill in the art can understand that, in each implementation manner of the present invention, many technical details are provided for readers to better understand the present application. However, even without these technical details and various changes and modifications based on the following embodiments, the technical solution claimed in each claim of the present application can be realized.
除非语境有其它需要，在整个说明书和权利要求中，词语“包括”和其变型，诸如“包含”和“具有”应被理解为开放的、包含的含义，即应解释为“包括，但不限于”。Unless the context requires otherwise, throughout the specification and claims, the word "comprise" and variations thereof, such as "comprising" and "having" are to be read in an open, inclusive sense, i.e., "including, but not limited to".
以下将结合附图对本发明的各实施例进行详细说明，以便更清楚理解本发明的目的、特点和优点。应理解的是，附图所示的实施例并不是对本发明范围的限制，而只是为了说明本发明技术方案的实质精神。Various embodiments of the present invention will be described in detail below in conjunction with the accompanying drawings, so as to better understand the purpose, features and advantages of the present invention. It should be understood that the embodiments shown in the drawings are not intended to limit the scope of the present invention, but only to illustrate the essence of the technical solutions of the present invention.
在整个说明书中对“一个实施例”或“一实施例”的提及表示结合实施例所描述的特定特点、结构或特征包括于至少一个实施例中。因此，在整个说明书的各个位置“在一个实施例中”或“在一实施例”中的出现无需全都指相同实施例。另外，特定特点、结构或特征可在一个或多个实施例中以任何方式组合。Reference throughout this specification to "one embodiment" or "an embodiment" means that a particular feature, structure, or characteristic described in connection with the embodiments is included in at least one embodiment. Thus, appearances of "in one embodiment" or "in an embodiment" in various places throughout the specification are not necessarily all referring to the same embodiment. In addition, particular features, structures or characteristics may be combined in any manner in one or more embodiments.
如该说明书和所附权利要求中所用的单数形式“一”和“所述”包括复数指代物，除非文中清楚地另外规定。应当指出的是术语“或”通常以其包括“和/或”的含义使用，除非文中清楚地另外规定。As used in this specification and the appended claims, the singular forms "a" and "the" include plural referents unless the context clearly dictates otherwise. It should be noted that the term "or" is generally employed in its sense including "and/or" unless the context clearly dictates otherwise.
在以下描述中，为了清楚展示本发明的结构及工作方式，将借助诸多方向性词语进行描述，但是应当将“前”、“后”、“左”、“右”、“外”、“内”、“向外”、“向内”、“上”、“下”等词语理解为方便用语，而不应当理解为限定性词语。In the following description, in order to clearly show the structure and working method of the present invention, many directional words will be used to describe, but "front", "rear", "left", "right", "outer", "inner" should be used Words such as ", "outward", "inward", "upper" and "lower" are to be understood as convenient terms, and should not be understood as restrictive terms.
本发明涉及一种植入式生物传感器100，该植入式生物传感器100包括柔性载体1、感应元件2、信号输出端3和发射器4，其中，柔性载体1具有一定的柔软度，例如可以采用聚醚胺材质或其他具有一定柔性的材质，本发明不选择柔性载体1的材质。柔性载体1沿第一方向延伸，如图1所示，且沿第一方向包括相互连接的感应段11和输出段12，其中，感应段11用于埋入人体组织内感应目标生物分子，而输出段12位于人体组织外部，用于方便与外部的发射器4连接。The present invention relates to an implantable biosensor 100. The implantable biosensor 100 includes a flexible carrier 1, an inductive element 2, a signal output terminal 3 and a transmitter 4, wherein the flexible carrier 1 has a certain degree of softness, for example, it can be used Polyetheramine material or other materials with certain flexibility, the material of the flexible carrier 1 is not selected in the present invention. The flexible carrier 1 extends along a first direction, as shown in FIG. 1 , and includes an interconnected sensing segment 11 and an output segment 12 along the first direction, wherein the sensing segment 11 is used for embedding in human tissue to sense target biomolecules, and The output section 12 is located outside the human tissue for easy connection with the external transmitter 4 .
感应段11的表面具有电极工作区，感应元件2位于感应段11的电极工作区并被设置成可与人体内的目标生物分子反应并产生信号，感应元件2与目标生物分子反应可产生化学变化、热变化或光变化或者电信号变化等。感应元件2可选但不限于酶、抗体、抗原、微生物、细胞、组织、核酸等生物活性物质，可根据需要检测的目标生物分子设置需要的感应元件2，只要能够与目标生物分子反应即可，不限制感应元件2的具体类型。信号输出端3位于输出段12并与感应元件2电连接，信号输出端3用于传输感应元件2感应的信号。发射器4与输出段12连接并具有信号接收端45，该信号接收端45与信号输出端3通过柔性连接组件5电连接，该柔性连接组件5不仅可导电且具有弹性。The surface of the sensing section 11 has an electrode working area, and the sensing element 2 is located in the electrode working area of the sensing section 11 and is configured to react with target biomolecules in the human body and generate signals, and the sensing element 2 can react with target biomolecules to produce chemical changes , thermal changes or light changes or electrical signal changes, etc. The sensing element 2 can be optional but not limited to enzymes, antibodies, antigens, microorganisms, cells, tissues, nucleic acids and other biologically active substances, and the required sensing element 2 can be set according to the target biomolecules to be detected, as long as it can react with the target biomolecules , does not limit the specific type of the sensing element 2 . The signal output end 3 is located in the output section 12 and electrically connected to the inductive element 2 , and the signal output end 3 is used to transmit the signal sensed by the inductive element 2 . The transmitter 4 is connected to the output section 12 and has a signal receiving end 45, the signal receiving end 45 is electrically connected to the signal output end 3 through a flexible connection component 5, and the flexible connection component 5 is not only conductive but also elastic.
现有工艺需要的感应元件2容易脱落，会影响使用过程中的稳定性和灵敏度。而本发明的植入式生物传感器100在使用过程中，随着人体不断活动，发射器4被触碰或者拉扯，该信号接收端45可产生一定的弹性，并不会被拉扯断，可使得信号接收端45和信号输出端3的稳定连接，保证信号正常输出，经久耐用。而且柔性连接组件5占用面积小、接触应力小、拉伸力高和连接更加可靠。The sensing element 2 required by the existing technology is easy to fall off, which will affect the stability and sensitivity during use. However, during the use of the implantable biosensor 100 of the present invention, as the human body continues to move, the transmitter 4 is touched or pulled, and the signal receiving end 45 can generate a certain degree of elasticity, and will not be pulled off, which can make The stable connection between the signal receiving end 45 and the signal output end 3 ensures the normal output of the signal and is durable. Moreover, the flexible connection component 5 occupies a small area, has small contact stress, high tensile force and more reliable connection.
在一个实施例中，柔性连接组件5可以为导电胶，该导电胶具有粘弹性且可导电，可以使得信号输出端3和信号连接端弹性连接。In one embodiment, the flexible connection component 5 may be conductive glue, which is viscoelastic and conductive, and can make the signal output terminal 3 and the signal connection terminal elastically connected.
在另一个实施例中，柔性连接组件5也导电金属制成的簧丝，该簧丝具有弹性且可导电，也可以使得信号输出端3和信号连接端弹性连接。In another embodiment, the flexible connection component 5 is also a spring wire made of conductive metal, which is elastic and conductive, and can also make the signal output end 3 and the signal connection end elastically connected.
作为优选方案，柔性连接组件5包括嵌段共聚物复合材料52和导电金属材料53，嵌段共聚物复合材料52具有延展性且与信号接收端45和信号输出端3连接，而导电金属材料53分布于嵌段共聚物内部，且与信号接收端45和信号输出端3分别电连接。即嵌段共聚物复合材料52用于提供弹性以及粘结性，而位于嵌段共聚物复合材料52内部的导电金属材料53彼此连接，具有稳定的导电性能，可以使得感应元件2的信号稳定地从信号输出端3传输至信号接收端45。As a preferred solution, the flexible connection assembly 5 includes a block copolymer composite material 52 and a conductive metal material 53, the block copolymer composite material 52 has ductility and is connected with the signal receiving end 45 and the signal output end 3, and the conductive metal material 53 Distributed inside the block copolymer, and electrically connected to the signal receiving end 45 and the signal output end 3 respectively. That is, the block copolymer composite material 52 is used to provide elasticity and cohesiveness, and the conductive metal materials 53 inside the block copolymer composite material 52 are connected to each other, have stable electrical conductivity, and can make the signal of the sensing element 2 stably From the signal output terminal 3 to the signal receiving terminal 45 .
可选地，嵌段共聚物复合材料52可选但不限于苯乙烯共聚物、乙烯丙烯共聚物、氢化苯乙烯、异戊二烯共聚物、聚乙二醇或乙烯丁烯共聚物中的一种或几种混合物，优选乙烯丁烯共聚物，不限制嵌段共聚物符合材料的具体材质。而导电金属材料53可选但不限于金、银、铜、钯、钛或铂中的一种或几种，导电金属材料53优选金。Optionally, the block copolymer composite material 52 can be selected from but not limited to one of styrene copolymer, ethylene propylene copolymer, hydrogenated styrene, isoprene copolymer, polyethylene glycol or ethylene butene copolymer One or several mixtures, preferably ethylene-butylene copolymer, does not limit the block copolymer to meet the specific material of the material. The conductive metal material 53 can be selected but not limited to one or more of gold, silver, copper, palladium, titanium or platinum, and the conductive metal material 53 is preferably gold.
感应元件2优选通过喷印方式印刷至感应段11的表面，喷印的形状或尺寸可以根据需求设置。具体地，感应元件2包括交联层21、导电材料22和感应层23，其中，交联层21由交联剂通过喷印方式粘结至感应段11的表面，用于粘结至柔性载体1上并与柔性载体1的导电层13连接。导电材料22的一部分分布于交联层21内，另一部分位于交联层21远离感应段11的表面，导电材料22可选但不限制于石墨烯、碳纳米管、金、银或铂中的至少一种，优选为金。导电材料22可与导电层13电连接。感应层23由感应剂通过喷印方式覆盖交联层21远离感应段11的表面，感应剂可与目标生物分子反应并产生电信号，并可通过导电材料22和导电层13将信号传输至发射器4。The sensing element 2 is preferably printed on the surface of the sensing segment 11 by jet printing, and the shape or size of the jet printing can be set according to requirements. Specifically, the sensing element 2 includes a cross-linked layer 21, a conductive material 22 and a sensing layer 23, wherein the cross-linked layer 21 is bonded to the surface of the sensing segment 11 by a cross-linking agent by spray printing for bonding to a flexible carrier 1 and connected to the conductive layer 13 of the flexible carrier 1. A part of the conductive material 22 is distributed in the crosslinked layer 21, and the other part is located on the surface of the crosslinked layer 21 away from the sensing section 11. The conductive material 22 can be selected but not limited to graphene, carbon nanotubes, gold, silver or platinum. At least one, preferably gold. The conductive material 22 may be electrically connected to the conductive layer 13 . The sensing layer 23 covers the surface of the cross-linked layer 21 away from the sensing segment 11 by spray printing with a sensing agent. The sensing agent can react with the target biomolecules and generate an electrical signal, and can transmit the signal to the emitter through the conductive material 22 and the conductive layer 13. device 4.
在本实施例中，植入式生物传感器100用于监测血糖值，该感应段11需采用亲水性材料，而感应层23包括葡萄糖催化酶，还可以包括二氮杂菲醌和二茂钌的混合物。交联层21包括1,9-壬二硫醇和1-硫代甘油。In this embodiment, the implantable biosensor 100 is used to monitor the blood glucose level. The sensing section 11 needs to be made of a hydrophilic material, while the sensing layer 23 includes a glucose catalytic enzyme, and may also include phenanthrenequinone and ruthenocene mixture. The cross-linked layer 21 includes 1,9-nonanedithiol and 1-thioglycerol.
人体中含有葡萄糖的组织部位较多，可以通过监测相关组织部位的葡萄糖值进而换算到人体血液中的血糖值，达到监测血糖值的目的。植入式生物传感器100是通过在组织中埋入感应段11，基于电化学原理，感应剂中葡萄糖催化酶可与葡萄糖发生反应，接着换算组织中葡萄糖的数值跟血糖值之间的关系，获得血糖值。信号输出端3可将感应剂的信号传输至发射器4的电子元器件，发射器4内的电子元器件可收集感应剂的信号，还可以传递电信号给感应剂以进行电化学检测。There are many tissue parts containing glucose in the human body, and the purpose of monitoring the blood sugar value can be achieved by monitoring the glucose value of the relevant tissue parts and then converting it to the blood sugar value in human blood. The implantable biosensor 100 embeds the sensing section 11 in the tissue. Based on the electrochemical principle, the glucose catalytic enzyme in the sensing agent can react with glucose, and then convert the relationship between the glucose value in the tissue and the blood sugar level to obtain Blood sugar level. The signal output terminal 3 can transmit the signal of the sensing agent to the electronic components of the transmitter 4, and the electronic components in the transmitter 4 can collect the signal of the sensing agent, and can also transmit an electrical signal to the sensing agent for electrochemical detection.
对于检测血糖的生物传感器来说，1,9-壬二硫醇和1-硫代甘油的混合比为20:1-50:1，优选20:1，而交联层21的厚度范围0.5um-40um，优选5um。感应层23的厚度范围为0.1um-80um，优选5um。For the biosensor for detecting blood sugar, the mixing ratio of 1,9-nonanedithiol and 1-thioglycerol is 20:1-50:1, preferably 20:1, and the thickness of the cross-linked layer 21 is in the range of 0.5um- 40um, preferably 5um. The thickness range of the sensing layer 23 is 0.1um-80um, preferably 5um.
在图2所示的实施例中，三个感应元件2沿第一方向间隔线性排列，应理解，也可以仅设置一个感应元件2或更多个感应元件2。此外，在图2所示的实施例中，感应元件2为长方形的薄片层，且沿第一方向的长度范围1mm-3mm，沿第二方向的宽度范围为1mm-3mm，其中，第二方向与第一方向垂直。In the embodiment shown in FIG. 2 , three sensing elements 2 are linearly arranged at intervals along the first direction. It should be understood that only one sensing element 2 or more sensing elements 2 may also be provided. In addition, in the embodiment shown in FIG. 2 , the sensing element 2 is a rectangular sheet layer, and the length range along the first direction is 1mm-3mm, and the width range along the second direction is 1mm-3mm, wherein the second direction perpendicular to the first direction.
导电材料22含有的基团可吸引感应剂中的葡萄糖催化酶，可与葡萄糖催化酶中的葡萄糖催化酶和交联剂发生交联反应，方便地通过化学键固定了感应剂含有的基团，进而限制感应剂均匀分布在交联层21的表面，避免感应剂无规则的流淌，实现图案化固定感应剂。同时，导电材料22增强的吸附力能够有效地改善感应剂在产品使用过程中脱落的问题，解决产品寿命短、长期使用时灵敏度变化不一致、无法有效监测葡萄糖值等问题，同时功能材料提高了产品的灵敏度。The group contained in the conductive material 22 can attract the glucose catalytic enzyme in the sensory agent, and can undergo a crosslinking reaction with the glucose catalytic enzyme in the glucose catalytic enzyme and the crosslinking agent, and conveniently fix the group contained in the sensory agent through chemical bonds, and then Limiting the uniform distribution of the sensing agent on the surface of the cross-linked layer 21, avoiding the irregular flow of the sensing agent, and realizing patterned immobilization of the sensing agent. At the same time, the enhanced adsorption force of the conductive material 22 can effectively improve the problem of sensor falling off during product use, solve the problems of short product life, inconsistent sensitivity changes during long-term use, and inability to effectively monitor glucose values. sensitivity.
在图5和图9所示的实施例中，信号输出端3和信号接收端45均为长方形，且信号输出端3沿第一方向的长度范围0.5mm-3mm，沿第二方向的宽度范围0.3mm-2mm，在图5所示的实施例中，信号输出端3长为1.5mm，宽为0.5mm。信号接收端45沿第一方向的长度范围0.5mm-1.1mm，沿第二方向的宽度范围为0.3mm-0.9mm。In the embodiment shown in Figure 5 and Figure 9, the signal output end 3 and the signal receiving end 45 are rectangular, and the length range of the signal output end 3 along the first direction is 0.5mm-3mm, and the width range along the second direction 0.3mm-2mm. In the embodiment shown in FIG. 5 , the length of the signal output terminal 3 is 1.5mm and the width is 0.5mm. The length of the signal receiving end 45 along the first direction ranges from 0.5mm to 1.1mm, and the width along the second direction ranges from 0.3mm to 0.9mm.
信号输出端3与信号接收端45通过导电层13电连接，导电层13可导电并与柔性载体1的表面连接，导电层13铺设至柔性载体1的表面并由感应段11延伸至输出段12，导电层13的两端分别与信号输出端3和信号接收端45电连接。The signal output terminal 3 and the signal receiving terminal 45 are electrically connected through the conductive layer 13, the conductive layer 13 is conductive and connected to the surface of the flexible carrier 1, the conductive layer 13 is laid on the surface of the flexible carrier 1 and extends from the induction segment 11 to the output segment 12 , both ends of the conductive layer 13 are electrically connected to the signal output terminal 3 and the signal receiving terminal 45 respectively.
导电层13由导电浆料粘结至柔性载体1的表面形成，具体可以通过丝网印刷、化学镀、气相沉积或电沉积的方式粘结至柔性载体1的表面。应理解，也可以通过其他方式将导电层13设置于柔性载体1内，例如可以将导电丝植入柔性载体1的表面或者缝制柔性载体1表面，不限制导电层13的具体实施方式。The conductive layer 13 is formed by bonding conductive paste to the surface of the flexible carrier 1 , specifically, it can be bonded to the surface of the flexible carrier 1 by screen printing, electroless plating, vapor deposition or electrodeposition. It should be understood that the conductive layer 13 can also be disposed in the flexible carrier 1 in other ways, such as implanting conductive threads on the surface of the flexible carrier 1 or sewing the surface of the flexible carrier 1 , without limiting the specific implementation of the conductive layer 13 .
发射器4用于接收感应元件2的信号并该将信号发射至外部的接收端。发射器4设有凸出的多个卡块44，如图5所示，而输出段12设有容纳多个卡块44的卡槽14，如图1和图5所示，发射器4与输出段12卡接，进一步防止发射器4脱离输出段12或相对于输出段12错位。在图5所示的实施例中，两个卡槽14位于输出段12沿第二方向的一个侧面，并位于相邻的两个信号输出端3之间，可以增强发射器4和输出段12的连接牢度和稳定性。The transmitter 4 is used to receive the signal of the inductive element 2 and transmit the signal to an external receiving end. The transmitter 4 is provided with a plurality of protruding blocks 44, as shown in Fig. 5, and the output section 12 is provided with a slot 14 for accommodating a plurality of blocks 44, as shown in Fig. The output section 12 is clamped to further prevent the transmitter 4 from being separated from the output section 12 or misaligned relative to the output section 12 . In the embodiment shown in FIG. 5, two card slots 14 are located on one side of the output section 12 along the second direction, and are located between two adjacent signal output terminals 3, which can strengthen the transmitter 4 and the output section 12. connection fastness and stability.
发射器4包括电路板42和塑胶件41，电路板42上设有多个电子元器件，用于接收感应元件2的信号。塑胶件41包裹于电路板42的外部，可以防止水和空气进入电路板42内并对电路板42造成损坏。此外，塑胶件41设有镀层区43，如图9所示，镀层区43由塑胶件41的表面凹陷形成。信号接收端45位于镀层区43内并与电路板42电连接，感应元件2的信号可经过信号接收端45传输至电子元器件，电子元器件也可以发射信号指令至感应元件2，也可以将信号发射至外部的终端设备。在图9所示的实施例中，信号接收端45大致成长方形且其长度范围为0.5mm-1.1mm，宽度范围0.3mm-0.9mm，优选长为1.5mm，宽为0.5mm。The transmitter 4 includes a circuit board 42 and a plastic part 41 . The circuit board 42 is provided with a plurality of electronic components for receiving signals from the sensing element 2 . The plastic part 41 is wrapped around the circuit board 42 to prevent water and air from entering the circuit board 42 and causing damage to the circuit board 42 . In addition, the plastic part 41 is provided with a coating area 43 , as shown in FIG. 9 , the coating area 43 is formed by the depression on the surface of the plastic part 41 . The signal receiving end 45 is located in the coating area 43 and is electrically connected with the circuit board 42. The signal of the inductive element 2 can be transmitted to the electronic component through the signal receiving end 45, and the electronic component can also transmit a signal command to the inductive element 2, or the The signal is transmitted to an external end device. In the embodiment shown in FIG. 9 , the signal receiving end 45 is roughly rectangular with a length ranging from 0.5 mm to 1.1 mm and a width ranging from 0.3 mm to 0.9 mm, preferably 1.5 mm long and 0.5 mm wide.
在图9所示的实施例中，三个信号接收端45沿第一方向呈线性间隔排列，三个信号接收端45分别与三个信号输出端3分别通过柔性连接组件5电连接，三个信号输出端3分别通过三个导电层13与三个感应元件2电连接。应理解，在其他实施例中，也可以只设置一个信号接收端45或更多个信号接收端45，多个信号接收端45也可以以其他方式排列，本发明并不限制信号接收端45的数量以及排列方式。In the embodiment shown in FIG. 9, three signal receiving ends 45 are arranged at linear intervals along the first direction, and the three signal receiving ends 45 are respectively electrically connected to the three signal output ends 3 through the flexible connection assembly 5, and the three The signal output terminals 3 are electrically connected to the three inductive elements 2 through the three conductive layers 13 respectively. It should be understood that in other embodiments, only one signal receiving end 45 or more signal receiving ends 45 may be provided, and multiple signal receiving ends 45 may also be arranged in other ways, and the present invention does not limit the number of signal receiving ends 45 number and arrangement.
本发明还涉及上述植入式生物传感器100的制备方法，具体包括步骤：The present invention also relates to a method for preparing the above-mentioned implantable biosensor 100, which specifically includes the steps of:
S1、准备柔性载体1、感应元件2、发射器4和柔性连接组件5，其中，柔性载体1包括相互连接的感应段11和输出段12，输出段12具有信号输出端3；柔性载体1的表面设有导电层13，导电层13从感应段11延伸至所述输出段12，并与输出段12的信号输出端3电连接。发射器4具有信号接收端45；S1, prepare the flexible carrier 1, the sensing element 2, the transmitter 4 and the flexible connection assembly 5, wherein the flexible carrier 1 includes a sensing segment 11 and an output segment 12 connected to each other, and the output segment 12 has a signal output terminal 3; the flexible carrier 1 A conductive layer 13 is provided on the surface, and the conductive layer 13 extends from the sensing section 11 to the output section 12 and is electrically connected to the signal output terminal 3 of the output section 12 . The transmitter 4 has a signal receiving end 45;
S2、将感应元件2连接至感应段11的表面并与导电层13电连接；S2, connecting the sensing element 2 to the surface of the sensing segment 11 and electrically connecting it to the conductive layer 13;
S3、将柔性连接组件5可导电并分成第一连接组件51和第二连接组件，将第一连接组件51粘结至信号输出端3，将第二连接组件粘结至信号接收端45，并将第一连接组件51远离信号输出端3的表面和第二连接组件远离信号接收端45的表面朝向彼此按压粘合，如图13所示，从而使得信号输出端3和信号连接端弹性电连接。S3, the flexible connection component 5 is electrically conductive and divided into a first connection component 51 and a second connection component, the first connection component 51 is bonded to the signal output end 3, the second connection component is bonded to the signal receiving end 45, and The surface of the first connection component 51 away from the signal output end 3 and the surface of the second connection component away from the signal receiving end 45 are pressed and bonded toward each other, as shown in FIG. 13 , so that the signal output terminal 3 and the signal connection end are elastically connected .
其中，第一连接组件51和所述第二连接组件分别包括嵌段共聚物复合材料52和导电金属材料53，第一连接组件51的嵌段共聚物复合材料52粘结至信号输出端3，第二连接组件的嵌段共聚物复合材料52粘结至所述信号接收端45。第一连接组的导电金属材料53一部分位于嵌段共聚物复合材料52内部，另一部分覆盖嵌段共聚物复合材料52远离信号输出端3的表面。第二连接组的导电金属材料53一部分位于嵌段共聚物复合材料52内部，另一部分覆盖于嵌段共聚物复合材料52远离信号接收端45的表面。第一连接组件51和第二连接组粘合后形状一体的楼下连接组件，且第一连接组件51的导电金属材料53和第二连接组件的导电金属材料53彼此电连接，从而使得信号输出端3和信号连接端电连接。Wherein, the first connection component 51 and the second connection component respectively include a block copolymer composite material 52 and a conductive metal material 53, and the block copolymer composite material 52 of the first connection component 51 is bonded to the signal output terminal 3, The block copolymer composite 52 of the second connection component is bonded to the signal receiving end 45 . A part of the conductive metal material 53 of the first connection group is located inside the block copolymer composite material 52 , and another part covers the surface of the block copolymer composite material 52 away from the signal output terminal 3 . A part of the conductive metal material 53 of the second connection group is located inside the block copolymer composite material 52 , and another part covers the surface of the block copolymer composite material 52 away from the signal receiving end 45 . The first connection assembly 51 and the second connection group are bonded to form an integrated downstairs connection assembly, and the conductive metal material 53 of the first connection assembly 51 and the conductive metal material 53 of the second connection assembly are electrically connected to each other, so that the signal output Terminal 3 is electrically connected to the signal connection terminal.
第一连接组件51的嵌段共聚物复合材料52的厚度范围10um-500um，优选90um。第一连接组件51的导电金属材料53一部分在嵌段共聚物复合材料52的内部，另一部分位于在嵌段共聚物复合材料52的表面，位于嵌段共聚物复合材料52的表面的导电金属材料53的厚度范围10nm-1000nm，优选为80nm。嵌段共聚物复合材料52具有柔韧性，从而使得柔性连接组件5发生形变时，能有效保证导电性能。The block copolymer composite material 52 of the first connection component 51 has a thickness ranging from 10 um to 500 um, preferably 90 um. A part of the conductive metal material 53 of the first connection component 51 is inside the block copolymer composite material 52, and the other part is positioned on the surface of the block copolymer composite material 52, and the conductive metal material positioned on the surface of the block copolymer composite material 52 The thickness of 53 is in the range of 10nm-1000nm, preferably 80nm. The block copolymer composite material 52 has flexibility, so that when the flexible connection component 5 is deformed, the electrical conductivity can be effectively ensured.
在人体活动时，感应段11也会被人体组织带动发生移动，进而使输出段12出现拉伸等偏移现象，因此柔性连接组件5的可拉伸性、粘度、发生拉伸时导电性能对产品的性能有关键性影响。若柔性连接组件5在保持有效导电性的情况下的拉伸率均较差，这会导致产品在使用时容易发生断路，进而导致产品无法使用。When the human body is active, the sensing section 11 will also be driven by the human body tissue to move, and then the output section 12 will be stretched and shifted. Therefore, the stretchability, viscosity, and electrical conductivity of the flexible connection component 5 will affect the Product performance has a critical impact. If the elongation rate of the flexible connection component 5 is poor while maintaining effective electrical conductivity, it will cause the product to be easily disconnected during use, and then the product cannot be used.
步骤S2之前，还包括步骤：如图8所示，对柔性载体1进行亲水处理，亲水处理采用离子体处理，处理时间1min-20min，压力为6mbar。再在柔性载体1和导电层13的表面涂硅烷类化合物，硅烷类化合物包括氯硅烷、硅溴化物、硅碘化物、硫化硅中的至少一种。Before step S2, a step is also included: as shown in FIG. 8 , perform hydrophilic treatment on the flexible carrier 1 , the hydrophilic treatment adopts plasma treatment, the treatment time is 1min-20min, and the pressure is 6mbar. Then, silane compounds are coated on the surfaces of the flexible carrier 1 and the conductive layer 13, and the silane compounds include at least one of chlorosilane, silicon bromide, silicon iodide, and silicon sulfide.
第一连接组件51连接至信号输出端3的步骤包括：先将嵌段共聚物复合材料52粘结至信号输出端3，再将部分导电金属材料53添加至所述嵌段共聚物的内部和表面。The step of connecting the first connection component 51 to the signal output terminal 3 includes: first bonding the block copolymer composite material 52 to the signal output terminal 3, and then adding a part of conductive metal material 53 to the inside of the block copolymer and surface.
第二连接组件连接至信号接收端45的步骤包括：先将所述嵌段共聚物复合材料52粘结至信号接收端45，再将部分导电金属材料53添加至嵌段共聚物的内部和表面。The step of connecting the second connection component to the signal receiving end 45 includes: first bonding the block copolymer composite material 52 to the signal receiving end 45, and then adding a part of conductive metal material 53 to the interior and surface of the block copolymer .
将第一连接组件51粘结至信号输出端3前，还需要对柔性载体1冲洗。将第一连接组件51粘结至信号输出端3后，还需对第一连接组件51进行50°加热10min。Before bonding the first connection component 51 to the signal output terminal 3 , the flexible carrier 1 needs to be rinsed. After bonding the first connection component 51 to the signal output terminal 3 , it is necessary to heat the first connection component 51 at 50° for 10 minutes.
感应元件2通过喷印技术打印至感应段11的表面，如图10所示，具体地步骤包括：将混合导电材料22的交联剂喷射至感应段11的表面并形成混合有导电材料22的交联层21，再将感应剂喷射至交联层21的表面并形成感应层23。该步骤也可以换成：将导电材料22和感应剂喷射至感应段11的表面并形成感应层23，再将交联剂喷射至感应层23和所述柔性材料，并形成交联层21。该步骤还可以换成：将导电材料22喷印至感应段11，再将感应剂添加至导电材料22并形成感应层23，再将交联剂喷射至感应层23和柔性材料，固化形成交联层21。The sensing element 2 is printed onto the surface of the sensing segment 11 by jet printing technology, as shown in FIG. The cross-linked layer 21 , and then the sensing agent is sprayed onto the surface of the cross-linked layer 21 to form the sensing layer 23 . This step can also be replaced by: spraying the conductive material 22 and the sensing agent to the surface of the sensing segment 11 to form the sensing layer 23 , and then spraying the crosslinking agent to the sensing layer 23 and the flexible material to form the crosslinking layer 21 . This step can also be changed to: spray-print the conductive material 22 onto the sensing section 11, then add the sensing agent to the conductive material 22 to form the sensing layer 23, then spray the cross-linking agent to the sensing layer 23 and the flexible material, and solidify to form a cross-linking agent. Joint layer 21.
喷印设备的压电喷墨头的孔径为10um-100um，优选40um。喷溅频率为200Hz-700Hz，优选45Hz。喷溅速度为0.5m/s-7m/s，优选3m/s。The piezoelectric inkjet head of the jet printing device has an aperture of 10um-100um, preferably 40um. Sputtering frequency is 200Hz-700Hz, preferably 45Hz. The spraying speed is 0.5m/s-7m/s, preferably 3m/s.
在本实施例中，可以先将导电材料22喷印在柔性载体1上，再添加葡萄糖催化酶，通过交联剂固化葡萄糖催化酶，防止葡萄糖催化酶无规则流淌。也可以现将葡萄糖催化酶、金属导电材料22和交联剂直接喷印至柔性载体1上，该金属导电材料22优选二氮杂菲醌和二茂钌的混合物。In this embodiment, the conductive material 22 can be spray-printed on the flexible carrier 1 first, and then the glucose catalytic enzyme is added, and the glucose catalytic enzyme is solidified by a cross-linking agent to prevent the glucose catalytic enzyme from flowing irregularly. It is also possible to spray-print the glucose catalyzing enzyme, metal conductive material 22 and crosslinking agent directly onto the flexible carrier 1, and the metal conductive material 22 is preferably a mixture of phenanthrocenequinone and ruthenocene.
发射器4的塑胶件41外部的镀层区43长度5.5mm，宽度2.5mm。三个第二连接组件分别为正方体，且边长范围0.5mm-3mm，优选1.5mm。The coating area 43 outside the plastic part 41 of the transmitter 4 has a length of 5.5mm and a width of 2.5mm. The three second connecting components are cubes respectively, and the side length ranges from 0.5 mm to 3 mm, preferably 1.5 mm.
发射器4的加工步骤如图11所示，包括：先利用塑胶件41将电路板42密封，在对镀层区43亲水处理，再涂硅烷类化合物，硅烷类化合物包括氯硅烷、硅溴化物、硅碘化物、硫化硅中的至少一种。最后再将第二连接组粘结至信号接收端45。The processing steps of the emitter 4 are shown in Figure 11, including: firstly use the plastic part 41 to seal the circuit board 42, treat the coating area 43 to be hydrophilic, and then coat the silane compound, the silane compound includes chlorosilane, silicon bromide , silicon iodide, silicon sulfide at least one. Finally, the second connection group is bonded to the signal receiving end 45 .
第一连接组件51和第二连接组件按压的工艺可以是手按压、机器按压等，优选机器按压。按压时间为1s-600s，优选为20s。The process of pressing the first connecting component 51 and the second connecting component may be hand pressing, machine pressing, etc., preferably machine pressing. The pressing time is 1s-600s, preferably 20s.
采用现有技术的植入式生物传感器和本发明的植入式生物传感器100检测10天的葡萄糖监测数据对比图，很明显，利用现有技术的植入式生物传感器检测10天后，灵敏度基本消失，而采用本发明的植入式生物传感器100在第10天仍保持良好的灵敏度，产品更为稳定可靠。Using the implantable biosensor of the prior art and the implantable biosensor 100 of the present invention to compare the glucose monitoring data for 10 days, it is obvious that the sensitivity basically disappears after 10 days of detection using the implantable biosensor of the prior art , while the implantable biosensor 100 of the present invention still maintains good sensitivity on the 10th day, and the product is more stable and reliable.
本发明通过喷印方式将感应剂喷印至柔性载体1的电极工作区，并通过交联剂和感应剂中葡萄糖催化酶交联的效果，将葡萄糖催化酶通过共价键牢固均匀的固定在特定位置，增强传感器检测性能，并且无需复杂的工艺处理电极工作区平面，保证植入式生物传感器100性能的一致性。而且，通过喷印方式可以快速将感应剂分布在电极工作区，还可以提高感应剂的吸附牢固，并且导电材料22还可以增强电极工作区的灵敏度。信号输出端45和信号接收端45通过柔性连接组件5快速高效电连接，减少了电气组件的占用面积、降低了接触应力、提高拉伸力和连接可靠性。In the present invention, the sensing agent is spray-printed onto the electrode working area of the flexible carrier 1 by spray printing, and the glucose catalytic enzyme is firmly and evenly fixed on the flexible carrier 1 through the cross-linking effect of the cross-linking agent and the glucose catalytic enzyme in the sensing agent. The specific position enhances the detection performance of the sensor, and does not require complex processes to process the plane of the electrode working area, so as to ensure the consistency of the performance of the implantable biosensor 100 . Moreover, the sensing agent can be quickly distributed in the working area of the electrode by means of jet printing, which can also improve the firm adsorption of the sensing agent, and the conductive material 22 can also enhance the sensitivity of the working area of the electrode. The signal output terminal 45 and the signal receiving terminal 45 are electrically connected quickly and efficiently through the flexible connection component 5 , which reduces the occupied area of electrical components, reduces contact stress, and improves tensile force and connection reliability.
以上已详细描述了本发明的较佳实施例，但应理解到，若需要，能修改实施例的方面来采用各种专利、申请和出版物的方面、特征和构思来提供另外的实施例。The preferred embodiments of the present invention have been described in detail above, but it should be understood that aspects of the embodiments can be modified, if desired, to employ aspects, features and concepts of various patents, applications and publications to provide further embodiments.
考虑到上文的详细描述，能对实施例做出这些和其它变化。一般而言，在权利要求中，所用的术语不应被认为限制在说明书和权利要求中公开的具体实施例，而是应被理解为包括所有可能的实施例连同这些权利要求所享有的全部等同范围。These and other changes can be made to the embodiments in light of the above detailed description. In general, in the claims, the terms used should not be construed as limited to the specific embodiments disclosed in the specification and claims, but rather should be understood to include all possible embodiments, along with all equivalents to which such claims are entitled. scope.
本领域的普通技术人员可以理解，上述各实施方式是实现本发明的具体实施例，而在实际应用中，可以在形式上和细节上对其作各种改变，而不偏离本发明的精神和范围。Those of ordinary skill in the art can understand that the above-mentioned embodiments are specific examples for realizing the present invention, and in practical applications, various changes can be made to it in form and details without departing from the spirit and spirit of the present invention. scope.
| Application Number | Priority Date | Filing Date | Title |
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| CN202310546819.7ACN116626132A (en) | 2023-05-15 | 2023-05-15 | Implantable biosensor and preparation method thereof |
| PCT/CN2023/125112WO2024234547A1 (en) | 2023-05-15 | 2023-10-18 | Implantable biosensor and preparation method therefor |
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| CN202310546819.7ACN116626132A (en) | 2023-05-15 | 2023-05-15 | Implantable biosensor and preparation method thereof |
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| CN116626132Atrue CN116626132A (en) | 2023-08-22 |
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| CN202310546819.7APendingCN116626132A (en) | 2023-05-15 | 2023-05-15 | Implantable biosensor and preparation method thereof |
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