CN115266870A - 基于凝胶的可穿戴微流控准固态生物芯片的制备方法及其产品和应用 - Google Patents
基于凝胶的可穿戴微流控准固态生物芯片的制备方法及其产品和应用 Download PDFInfo
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Abstract
本发明公开了基于凝胶的可穿戴微流控准固态生物芯片的制备方法及其产品和应用，生物芯片由含有导电性好的纳米仿生酶材料的导电水凝胶，调整粘度后印刷在柔性基底上制得；发明的芯片构建方法简单、操作性强且成本低。由于芯片中导电凝胶含有特异性检测生物分子的纳米仿生酶材料，使该微流控芯片对特定的生物分子表现出很好的催化性能，含有不同纳米仿生酶材料的微通道能够同时对人体汗液中的多种生物分子进行实时高灵敏监测；通过全印刷技术构建的柔性可穿戴微流控准固态生物芯片具有很好的溶胀性和吸水性，可快速吸收人体汗液实现对汗液中葡萄糖、尿酸、乳酸、氨基酸、尿素等多种生物分子的同时实时高灵敏电化学监测。
Description
技术领域
本发明涉及生物检测领域，具体涉及基于凝胶的可穿戴微流控准固态生物芯片，还涉及可穿戴微流控准固态生物芯片的制备方法和应用。
背景技术
即时检测技术(POCT)是现代医学检验领域极具潜力的新型检测技术。与传统临床检验相比，具有检测快速、操作简便、成本低、样品用量少等优点。随着各种生物传感技术如丝网印刷电极、免疫标记、酶联技术、生物芯片技术等在POCT中广泛应用，与传统的生化分析仪相比极大的缩短了分析时间并降低了检测成本，也为患者提供了自身随时监测的方便。目前主要开发公司有瑞士罗氏、德国拜耳、美国雅培、日本京都等。市场容量大的主要产品为血糖试纸条、尿酸试纸条，但市售的大部分血糖、尿酸等检测试纸条都是利用酶生物传感器与丝网印刷技术制造。酶的成本高、固定非常复杂、稳定性较差，且其活性很容易受pH、温度、湿度和有毒化学品等因素的影响，因此，市售的试纸条成本较高且保质期较短，通常要放置在4℃冰箱内进行储存，尤其是在启封后试纸条的保质期仅有三个月。此外，这类试纸条需要病人进行针刺采血测试且不能实现连续动态监测，这都使其在日常生活中的应用受到一定的限制。
因此，针对目前酶电化学试纸条在实际应用中存在的问题和挑战，急需开发新一代高性能、低成本、非针刺采血的仿生酶电化学传感芯片。
发明内容
有鉴于此，本发明的目的之一在于提供一种基于凝胶的可穿戴微流控准固态生物芯片的制备方法；本发明的目的之二在于提供由方法制得的可穿戴微流控准固态生物芯片；本发明的目的之三在于提供所述可穿戴微流控准固态生物芯片在检测人体排出汗液生物分子中的应用。
为达到上述目的，本发明提供如下技术方案：
1、基于凝胶的可穿戴微流控准固态生物芯片的制备方法，具体方法如下：将含有导电性好的纳米仿生酶材料的导电水凝胶，调整粘度后印刷在柔性基底上制得工作电极，然后与对电极获得生物芯片。
本发明优选的，所述纳米仿生酶材料为检测人体排出汗液中生物分子的仿生酶。
本发明优选的，所述人体排出汗液中生物分子为葡萄糖、尿酸、乳酸、氨基酸或尿素。
本发明优选的，所述导电水凝胶为用明胶制成的水凝胶。
本发明优选的，所述导电性好的纳米仿生酶材料的浓度为1-10mg/mL。
本发明优选的，所述柔性基底为PET膜或PE膜。
2、由所述基于凝胶的可穿戴微流控准固态生物芯片的制备方法制得的可穿戴微流控准固态生物芯片。
3、所述可穿戴微流控准固态生物芯片在检测人体排出汗液生物分子中的应用。
优选的，所述人体排出汗液中生物分子为葡萄糖、尿酸、乳酸、氨基酸或尿素。
本发明的有益效果在于：本发明基于生物相容性好的水凝胶结合导电性好的纳米仿生酶材料开发新型导电凝胶，通过全印刷技术在柔性基底上构建可穿戴微流控准固态生物芯片。该可穿戴微流控准固态生物芯片的不同微通道含有不同纳米仿生酶材料，且其具有很好的溶胀性和吸水性，因此能够贴敷在皮肤上通过快速吸收人体汗液实现对人体汗液中葡萄糖、尿酸、乳酸、氨基酸、尿素等多种生物分子的同时实时高灵敏电化学监测。基于导电凝胶的可穿戴微流控芯片灵敏度高、特异性强、稳定性好，且可以在室温非密封条件下储存1-2年仍保持较高的灵敏度，能够极大的降低生产成本。此外，这种可穿戴的微流控准固态生物芯片可以有效避免针刺采血及其带来的感染风险，对于病人日常检测来讲实用性和适用性更强，突出显示了其在临床诊断和日常疾病监测中的潜在应用。
附图说明
为了使本发明的目的、技术方案和有益效果更加清楚，本发明提供如下附图进行说明：
图1为修饰有不同仿生酶纳米材料的可穿戴微流控准固态生物芯片示意图(图中心黑点为对电极，***黑点为工作电极)。
图2为生物分子检测结果(a：葡萄糖；b：尿酸；c：胆固醇；d：芯片结构)。
具体实施方式
下面结合附图和具体实施例对本发明作进一步说明，以使本领域的技术人员可以更好的理解本发明并能予以实施，但所举实施例不作为对本发明的限定。
实施例1、基于凝胶的可穿戴微流控准固态生物芯片的构建
基于凝胶的可穿戴微流控准固态生物芯片的制备方法，具体步骤如下：
(1)将明胶等生物相容性好的材料制成水凝胶；
(2)将导电性好的纳米仿生酶材料，添加到制备好的水凝胶中使纳米仿生酶终浓度为1-10mg/mL形成导电凝胶，调整黏度然后通过印刷等技术在柔性基底，如PET膜或PE膜上等)上构建得到工作电极，然后与对电极获得可穿戴微流控准固态生物芯片。
进一步对其进行冷冻干燥得到可穿戴微流控准固态生物芯片，结构如图1所示。
分别在不同微通道含有不同纳米仿生酶材料，如葡萄糖的纳米仿生酶材料选择铜纳米花复合碳材料或铂纳米花复合碳材料等；尿酸的纳米仿生酶材料选择普鲁士蓝复合氮掺杂碳材料、单原子钴修饰氮掺杂碳材料等；胆固醇的纳米仿生酶材料选择纳米金复合碳纳米材料包裹胆固醇酶。
其中碳材料为但不限于石墨烯、碳纳米管、Mxene、生物炭等导电性好的碳纳米材料)；
本实施例中微流控芯片的形状大小、通道粗细及微电极的数量等可以根据具体实验的需求进行设计。
实施例2、基于凝胶的可穿戴微流控准固态生物芯片在生物分子检测中的应用
(1)将制备好的柔性可穿戴微流控芯片贴敷在人体易出汗的部位；
(2)采用计时电流法对糖尿病人和痛风病人排出的汗液中的葡萄糖、尿酸和胆固醇。
结果如图2所示。结果显示，能够检测出汗液中的葡萄糖、尿酸和胆固醇，且葡萄糖最低检出浓度为5mM，尿酸最低检出浓度为0.3mM，胆固醇最低检出浓度为3mM。
按照同样的原理，使用不同的纳米仿生酶材料检测出其他生物分子，如乳酸、氨基酸、尿素等。
综上所述，基于凝胶的可穿戴微流控准固态生物芯片可以通过上述构建方法1得到，该构建方法简单、操作性强且成本低。此外，该导电凝胶含有特异性检测生物分子的纳米仿生酶材料，使该微流控芯片对特定的生物分子表现出很好的催化性能，含有不同纳米仿生酶材料的微通道能够同时对人体汗液中的多种生物分子进行实时高灵敏监测。与传统的试纸条相比，本发明结合生物相容性好的水凝胶和导电性好的纳米仿生酶材料开发新型导电凝胶，该导电凝胶特异性好、灵敏度高、易储存且成本低。通过全印刷技术构建的柔性可穿戴微流控准固态生物芯片具有很好的溶胀性和吸水性，可快速吸收人体汗液实现对汗液中葡萄糖、尿酸、乳酸、氨基酸、尿素等多种生物分子的同时实时高灵敏电化学监测。
以上所述实施例仅是为充分说明本发明而所举的较佳的实施例，本发明的保护范围不限于此。本技术领域的技术人员在本发明基础上所作的等同替代或变换，均在本发明的保护范围之内。本发明的保护范围以权利要求书为准。
Claims (9)
1.基于凝胶的可穿戴微流控准固态生物芯片的制备方法，其特征在于，具体方法如下：将含有导电性好的纳米仿生酶材料的导电水凝胶，调整粘度后印刷在柔性基底上制得工作电极，然后与对电极获得生物芯片。
2.根据权利要求1所述基于凝胶的可穿戴微流控准固态生物芯片的制备方法，其特征在于：所述纳米仿生酶材料为检测人体排出汗液中生物分子的仿生酶。
3.根据权利要求2所述基于凝胶的可穿戴微流控准固态生物芯片的制备方法，其特征在于：所述人体排出汗液中生物分子为葡萄糖、尿酸、乳酸、氨基酸或尿素。
4.根据权利要求2所述基于凝胶的可穿戴微流控准固态生物芯片的制备方法，其特征在于：所述导电水凝胶为用明胶制成的水凝胶。
5.根据权利要求2所述基于凝胶的可穿戴微流控准固态生物芯片的制备方法，其特征在于：所述导电性好的纳米仿生酶材料的浓度为1-10mg/mL。
6.根据权利要求2所述基于凝胶的可穿戴微流控准固态生物芯片的制备方法，其特征在于：所述柔性基底为PET膜或PE膜。
7.由权利要求1～6任一项所述基于凝胶的可穿戴微流控准固态生物芯片的制备方法制得的可穿戴微流控准固态生物芯片。
8.权利要求7所述可穿戴微流控准固态生物芯片在检测人体排出汗液生物分子中的应用。
9.根据权利要求8所述的应用，其特征在于：所述人体排出汗液中生物分子为葡萄糖、尿酸、乳酸、氨基酸或尿素。
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