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CN115161177A - 一种基于尺寸匹配的生物芯片及其检测方法 - Google Patents

一种基于尺寸匹配的生物芯片及其检测方法 Download PDF

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CN115161177A
CN115161177A CN202210568675.0A CN202210568675A CN115161177A CN 115161177 A CN115161177 A CN 115161177A CN 202210568675 A CN202210568675 A CN 202210568675A CN 115161177 A CN115161177 A CN 115161177A
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李铁
魏擅红
王跃林
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Shanghai Institute of Microsystem and Information Technology of CAS
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Abstract

本发明涉及一种基于尺寸匹配的生物芯片及其检测方法，所述生物芯片为根据检测需求，由数个零维传感器、一维传感器或二维传感器中的一种或几种组成的多维度传感器。本发明利用与待测物尺寸相匹配的多维度传感器进行检测，得到的检测结果具有高灵敏度；使用多维度的传感器对待测物进行并行检测，可提高检测结果的精确度，进而使检测结果更加可靠。

Description

一种基于尺寸匹配的生物芯片及其检测方法
技术领域
本发明属于生物芯片领域，特别涉及一种基于尺寸匹配的生物芯片及其检测方法。
背景技术
检测单元与核酸、蛋白质、细菌与病毒等从纳米级到微米级的待测生物物质在尺寸不匹配时难以实现高灵敏检测。在现有的对不同生物物质的检测系统中，聚合酶链式反应、环介导等温扩增技术、酶联免疫吸附法、微生物培养等检测方法，经过长时间的发展已经建立起成熟的检测技术，并在医学、食品、环境、生化等领域进行样品分析与检测等广泛应用，但是现有生物检测方法有检测对象单一、检测周期长、仪器设备复杂、操作人员专业技术要求高、检测成本高或检测结果不准确等缺点。因此，十分有必要开发一种可高灵敏、精准通用的检测方法。
发明内容
本发明所要解决的技术问题是提供一种基于尺寸匹配的生物芯片及其检测方法，利用与待测物尺寸相匹配的多维度传感器进行检测，得到的检测结果具有高灵敏度；使用多维度的传感器对待测物进行并行检测，可提高检测结果的精确度，进而使检测结果更加可靠。
本发明提供了一种基于尺寸匹配的生物芯片，所述生物芯片为根据检测需求，由数个零维传感器、一维传感器或二维传感器中的一种或几种组成的多维度传感器。
所述零维传感器的敏感单元为硅纳米粒子、金纳米粒子、磁珠、量子点中的至少一种。
所述一维传感器的敏感单元为硅纳米线、碳纳米管中的至少一种。
所述二维传感器的敏感单元为石墨烯、二硫化钼中的至少一种。
所述零维传感器、一维传感器、二维传感器的敏感单元上修饰有特异性识别待测物中不同生物物质的相应探针。
所述生物物质包括离子、小分子、蛋白、核酸、激素、细胞、真菌、细菌和病毒中的至少一种。
进一步的，所述零维传感器对小尺寸生物物质进行检测，所述小尺寸生物物质为核酸、离子、小分子或激素；所述一维传感器对中尺寸生物物质进行检测，所述中尺寸生物物质为蛋白质或病毒；二维传感器对大尺寸生物物质进行检测，所述大尺寸生物物质为细菌、细胞或真菌。
进一步的，所述组合方式包括：传感器均为零维传感器组合，均为一维传感器组合，均为二维传感器组合，零维传感器与一维传感器组合，零维传感器与二维传感器组合，一维传感器与二维传感器组合或者零维传感器、一维传感器与二维传感器组合。
进一步的，所述数个零维传感器、一维传感器或二维传感器是指零维传感器、一维传感器或二维传感器是指传感器可以为一个以上。
本发明还提供了一种基于尺寸匹配的生物芯片的检测方法，包括如下步骤：
首先获取生物样本，对所述样本进行生物物质提取；根据所述生物物质的尺寸大小，利用尺寸匹配原则，使用与生物物质尺寸相匹配的传感器对其进行联合检测；最后综合传感器对生物物质检测的数据，得到所述生物样本的检测结果。
所述尺寸相匹配是指待测生物物质的尺寸与某维度的传感器敏感元件尺寸比值为0.001～1，则待测生物物质与该维度的传感器成功匹配。
有益效果
(1)本发明利用与待测物尺寸相匹配的多维度传感器进行检测，得到的检测结果具有高灵敏度；使用多维度的传感器对待测物进行并行检测，可提高检测结果的精确度，进而使检测结果更加可靠。
(2)本发明采用能够识别待测物的探针，特异性强，灵敏度高，检测快速稳定；同时，不同的探针能够特异性识别不同靶标物，只需要在多维度的传感器功能化过程中将抗体或偶联物更换，即可实现不同抗原或分子的检测，通用性高，应用范围广泛。
附图说明
图1为本发明检测方法的流程示意图。
图2为本发明生物芯片结构示意图之一；其中，1为样品池，2为阀门，3为微流控芯片，4为裂解池，5为零维传感器，6为一维传感器，7为二维传感器，8为废液池。
具体实施方式
下面结合具体实施例，进一步阐述本发明。应理解，这些实施例仅用于说明本发明而不用于限制本发明的范围。此外应理解，在阅读了本发明讲授的内容之后，本领域技术人员可以对本发明作各种改动或修改，这些等价形式同样落于本申请所附权利要求书所限定的范围。
实施例1
示例性的，本实施例提供了一种基于尺寸匹配的生物芯片，结构如图2所示，所述生物芯片包括样品池1和废液池8，通过阀门2控制生物样本进入裂解池4，裂解反应完成后进入微流控芯片3分离检测，多维度传感器由零维传感器5、一维传感器6与二维传感器7组成。
图1是可选的流程示意图，以下将结合图1示出的步骤进行说明。
1.获取生物样本。
所述生物样本可以是人体、动物或环境中采集到的待测样本，将其溶于缓冲液中。
示例性的，本实施例以对河道水体中的大肠杆菌进行检测为例，则在河道中取少量河水，静置一段时间，固液分离后取上清液。
2.对生物样本进行生物物质提取与分离。
本发明中生物物质可以是离子、小分子、蛋白、核酸、激素、细胞、真菌、细菌和病毒等，在生物样本中对生物物质提取可采用离心法等方式。
示例性的，本实施例选择上述河道中分离的上清液，将其置于生物芯片的样品池中，打开样品池后的三通阀，使该样本中的大肠杆菌分别进行裂解与非裂解处理。进行裂解处理的样品流向裂解池中进行大肠杆菌裂解，而后与非裂解处理的样品共同通过2号三通阀进入微流控芯片中进行不同尺寸的生物物质分离。
3.根据所述生物物质的尺寸大小，利用尺寸匹配原则，使用与生物物质尺寸相匹配的传感器对其进行联合检测。
本发明中，生物芯片中的微流控芯片依据生物物质的尺寸大小对其进行分离，将生物物质分为如离子、小分子、核酸、激素等小尺寸的生物物质，如蛋白质、病毒等中尺寸的生物物质，如真菌、细菌、细胞等大尺寸的生物物质。匹配原则是零维传感器对核酸或离子或小分子或激素等小尺寸生物物质进行检测、一维传感器对蛋白质或病毒等中尺寸生物物质进行检测、二维传感器对细菌或细胞或真菌等大尺寸生物物质进行检测。
示例性的，上述河道中提取与分离得到的生物物质，依据其尺寸被生物芯片中的微流控芯片分离为核酸等小尺寸生物物质，蛋白质等中尺寸生物物质，细菌等大尺寸生物物质。对零维传感器修饰上大肠杆菌的特异性核酸序列探针，一维传感器修饰上大肠杆菌的特异性蛋白质抗体，二维传感器修饰上大肠杆菌的抗体。被分离后的生物物质分别在相应的传感器中同时检测。
4.综合多维度的传感器对生物物质检测的数据，得到所述生物样本的检测结果。
将得到的多维度的传感器的检测数据进行分析，如有至少大于两个维度的传感器产生信号变化，其他维度的传感器无信号变化，则样本中有待测生物物质；如传感器均无信号变化，则样本中无待测生物物质。
示例性的，如上述河道样本中含有大肠杆菌，则在多维度的传感器中零维传感器、一维传感器与二维传感器有信号变化，检测结果为河道中有大肠杆菌；如河道样本中无大肠杆菌，则多维度的传感器均无信号响应，检测结果为河道中无大肠杆菌。

Claims (10)

1.一种基于尺寸匹配的生物芯片，其特征在于：所述生物芯片包括根据检测需求，由数个零维传感器、一维传感器或二维传感器中的一种或几种组成的多维度传感器。
2.根据权利要求1所述的生物芯片，其特征在于：所述零维传感器的敏感单元为硅纳米粒子、金纳米粒子、磁珠、量子点中的至少一种。
3.根据权利要求1所述的生物芯片，其特征在于：所述一维传感器的敏感单元为硅纳米线、碳纳米管中的至少一种。
4.根据权利要求1所述的生物芯片，其特征在于：所述二维传感器的敏感单元为石墨烯、二硫化钼中的至少一种。
5.根据权利要求1所述的生物芯片，其特征在于：所述零维传感器、一维传感器、二维传感器的敏感单元上修饰有特异性识别待测物中不同生物物质的相应探针。
6.根据权利要求5所述的生物芯片，其特征在于：所述生物物质包括离子、小分子、蛋白、核酸、激素、细胞、真菌、细菌和病毒中的至少一种。
7.根据权利要求6所述的生物芯片，其特征在于：所述零维传感器对小尺寸生物物质进行检测，所述小尺寸生物物质为核酸、离子、小分子或激素；所述一维传感器对中尺寸生物物质进行检测，所述中尺寸生物物质为蛋白质或病毒；二维传感器对大尺寸生物物质进行检测，所述大尺寸生物物质为细菌、细胞或真菌。
8.根据权利要求1所述的生物芯片，其特征在于：所述组合方式包括：传感器均为零维传感器组合，均为一维传感器组合，均为二维传感器组合，零维传感器与一维传感器组合，零维传感器与二维传感器组合，一维传感器与二维传感器组合或者零维传感器、一维传感器与二维传感器组合；所述数个零维传感器、一维传感器或二维传感器是指零维传感器、一维传感器或二维传感器是指传感器为一个以上。
9.一种如权利要求1所述的基于尺寸匹配的生物芯片的检测方法，包括如下步骤：
首先获取生物样本，对所述样本进行生物物质提取；根据所述生物物质的尺寸大小，利用尺寸匹配原则，使用与生物物质尺寸相匹配的传感器对其进行联合检测；最后综合传感器对生物物质检测的数据，得到所述生物样本的检测结果。
10.根据权利要求9所述的检测方法，其特征在于：所述尺寸相匹配是指待测生物物质的尺寸与某维度的传感器敏感元件尺寸比值为0.001～1，则待测生物物质与该维度的传感器成功匹配。
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