CN113977829A - 一种空心微针阵列生物传感器的制备方法 - Google Patents

一种空心微针阵列生物传感器的制备方法 Download PDF

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CN113977829A
CN113977829A CN202111049444.0A CN202111049444A CN113977829A CN 113977829 A CN113977829 A CN 113977829A CN 202111049444 A CN202111049444 A CN 202111049444A CN 113977829 A CN113977829 A CN 113977829A
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庄俭
赵泽伟
吴大鸣
高小龙
杨振洲
黄尧
孙靖尧
朱龙
林龙
康婷婷
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Abstract

本发明公开了一种空心微针阵列生物传感器的制备方法，包括：制备实心微针阵列；在所述的实心微针阵列上利用脉冲激光打孔得到空心微针阵列；在所述的空心微针阵列的内壁上沉积一层铂薄膜；在所述的空心微针阵列的内壁上电聚合一层生物识别分子膜。本发明中微针阵列的空心结构，有助于生物识别分子被电聚合捕获在空心微针阵列的内壁上，并且在穿刺过程中生物识别分子与皮肤无直接接触，实现了对生物识别分子的最大保护，防止生物识别分子被破坏脱落。本发明无需采血即可完成生物传感，提高了顺从感，实现穿刺与检测一体化，简化了设备要求和传感过程。

Description

一种空心微针阵列生物传感器的制备方法
技术领域
本发明涉及生物医学工程领域，具体地，涉及一种空心微针阵列生物传感器的制备方法。
背景技术
为了实现用于对体内监测微型装置的临床转化，微创电化学生物传感器的发展越来越受重视。在这方面，由于无痛生物传感和高度集成的生物兼容性优势，微针阵列在生物医学界引起了很大的关注。
目前市场上常见的生物检测装置如血糖仪在进行血糖检测时,患者需要进行指尖取血,但是指尖取血时不仅会产生痛感,容易造成感染，这种方式也不适用于身体上的连续监测。
微针阵列生物传感器是在微针阵列的表面沉积一层生物识别分子，当微针阵列生物传感器刺入人体时，微针阵列上的生物识别分子会与组织液中的生物分子进行反应并产生电子，将目标浓度以电信号表示出来。微针阵列生物传感器在进行人体检测时不会碰到皮下的痛觉神经，具有无痛、操作简单与安全无感染等优势。而且相比于现有的生物检测装置,微针阵列生物传感器不需要进行采血,可直接检测组织液中的目标含量,显著提高了患者服从性与安全性。
但是在现有的微针阵列生物传感器中，生物识别分子并不易于聚合在微针阵列的表面，而且当微针阵列生物传感器刺入人体时表面的生物识别分子层很容易被破坏脱落。
发明内容
因此，本发明提供了一种空心微针阵列生物传感器的制备方法。本发明中微针阵列的空心结构，有助于生物识别分子被电聚合捕获在空心微针阵列的内壁上，并且在穿刺过程中生物识别分子与皮肤无直接接触，实现了对生物识别分子的最大保护，防止生物识别分子被破坏脱落。本发明无需采血即可完成生物传感，提高了顺从感，实现穿刺与检测一体化，简化了设备要求和传感过程。
本发明提供的一种空心微针阵列生物传感器的制备方法，包括如下步骤，包括如下步骤，
S1、将液态聚合物材料浇注在微针模具上，脱模后得到实心微针阵列，实心微针阵列的微针高度为300～1000μm。
S2、在所述的实心微针阵列上用脉冲激光打孔得到空心微针阵列，脉冲激光打孔的孔直径在10～100μm。
S3、利用分子激光器在室温下进行脉冲激光沉积，在空心微针阵列的孔内壁上沉积一层可导电薄膜。
S4、在所述的可导电薄膜上电聚合一层生物识别分子膜。
进一步地，所述的空心微针阵列上有一个由脉冲激光打的孔；在所述的空心微针阵列的孔内壁上沉积一层可导电薄膜；在所述的可导电薄膜上电聚合一层生物识别分子膜。
进一步地，所述的实心微针阵列的材料为聚合物材料。
进一步地，所述的空心微针阵列的制备材料为聚丙烯、聚乳酸、聚碳酸酯、光敏(UV)树脂、聚四氟乙烯、聚乙烯或聚氯乙烯等聚合物材料。
进一步地，所述的空心微针阵列制备方法为3D打印、光刻刻蚀、浇注成型或注塑成型。
进一步地，所述的实心微针阵列是将聚合物材料浇注在微针模具上，后脱模得到。
进一步地，所述的空心微针阵列的微针高度为50～1000μm。
进一步地，所述的孔是用脉冲激光在实心微针阵列上打孔得到。
进一步地，所述的脉冲激光打孔直径在10～200μm。
进一步地，所述的孔的形状为倾斜圆台或圆柱或长方体。
进一步地，所述的可导电薄膜可为铝、银、铂、金、参杂石墨烯或炭黑的可导电材料。
进一步地，所述的可导电薄膜是利用分子激光器在室温下进行1～10min脉冲激光沉积，压力保持在5～30m torr，最终在空心微针阵列孔的内壁上沉积了一层可导电薄膜。
进一步地，所述的生物识别分子膜是以电聚合方法沉积在可导电薄膜上。
相对于传统的微针阵列生物传感器，本发明基于空心微针阵列，将生物识别分子沉积在在空心微针阵列的内壁上，不仅有助于生物识别分子被电聚合捕获在空心结构上，并且在穿刺过程中生物识别分子与皮肤无直接接触，实现了对生物识别分子的最大保护，防止生物识别分子被破坏脱落。本发明无需采血即可完成生物传感，提高了顺从感，实现穿刺与检测一体化，简化了设备要求和传感过程。
附图说明
图1是空心微针阵列生物传感器的平面示意图；
图2是空心微针阵列生物传感器的立体示意图；
图3是空心微针阵列生物传感器的工艺流程图。
具体实施方式
以下是结合附图对具体的实施例的描述，是对本发明所述的一种双组分微针阵列生物传感器的制备方法作的进一步说明，但本发明的保护范围并不限于这几个实施例。
实施例1
本实施例提供了一种检测谷氨酸的空心微针阵列生物传感器的制备方法，制备方法包括以下步骤：
S1、将液态聚合物材料浇注在微针模具上，后脱模得到实心微针阵列，微针阵列的微针高度为300～1000μm。。
S2、在所述的实心微针阵列上用脉冲激光打孔得到空心微针阵列，孔直径在 10～100μm，孔的形状为倾斜圆台。
S3、利用分子激光器在室温下进行1～10min脉冲激光沉积，压力保持在 5～30mtorr，最终在空心微针阵列内壁上沉积了一层铂薄膜。
S4、在室温下用氮气吹扫含有5mM硫酸钠和100U/mL谷氨酸氧化酶的 0.1M磷酸盐缓冲液(pH 7.40)的溶液。然后将微针阵列、Ag/AgCl参比电极和铂对电极浸入溶液中，随后施加0.75V的电势20分钟，在铂薄膜上电聚合得到谷氨酸氧化酶膜。
将依照上述步骤得到的空心微针阵列生物传感器用于在体检测,空心微针阵列不仅有助于生物识别分子被电聚合捕获在空心结构上，当在微针穿刺皮肤时，生物识别分子与皮肤无直接接触，实现了对生物识别分子的最大保护，防止生物识别分子被破坏脱落。微针穿刺皮肤后，空心微针阵列中的谷氨酸氧化酶会与组织液进行接触，从而会产生电信号。
实施例2
本实施例提供了一种检测葡萄糖的空心微针阵列生物传感器的制备方法，制备方法包括以下步骤：
S1、将液态聚合物材料浇注在微针模具上，后脱模得到实心微针阵列，微针阵列的微针高度为300～1000μm。。
S2、在所述的实心微针阵列上用脉冲激光打孔得到空心微针阵列，孔直径在 10～100μm，孔的形状为倾斜圆台。
S3、利用分子激光器在室温下进行1～10min脉冲激光沉积，压力保持在 5～30mtorr，最终在空心微针阵列内壁上沉积了一层铂薄膜。
S4、在室温下用氮气吹扫含有5mM硫酸钠和4U葡萄糖氧化酶的0.1M磷酸盐缓冲液(pH 7.40)的溶液。然后将微针阵列、Ag/AgCl参比电极和铂对电极浸入溶液中，随后施加0.75V的电势20分钟，在铂薄膜上电聚合得到葡萄糖氧化酶膜。
将依照上述步骤得到的空心微针阵列生物传感器用于在体检测,空心微针阵列不仅有助于生物识别分子被电聚合捕获在空心结构上，当在微针穿刺皮肤时，生物识别分子与皮肤无直接接触，实现了对生物识别分子的最大保护，防止生物识别分子被破坏脱落。微针穿刺皮肤后，空心微针阵列中的葡萄糖氧化酶膜会与组织液进行接触，从而会产生电信号。
显然，上述实施例仅仅是为清楚地说明所作的举例，而并非对实施方式的限定。对于所属领域的普通技术人员来说，在上述说明的基础上还可以做出其它不同形式的变化或改动，这些变化或改动仍处于本发明专利要求的保护范围之内。

Claims (10)

1.一种空心微针阵列生物传感器的制备方法，其特征在于：包括如下步骤，
S1、将液态聚合物材料浇注在微针模具上，脱模后得到实心微针阵列，实心微针阵列的微针高度为300～1000μm；
S2、在所述的实心微针阵列上用脉冲激光打孔得到空心微针阵列，脉冲激光打孔的孔直径在10～100μm；
S3、利用分子激光器在室温下进行脉冲激光沉积，在空心微针阵列的孔内壁上沉积一层可导电薄膜；
S4、在所述的可导电薄膜上电聚合一层生物识别分子膜。
2.根据权利要求1所述的一种空心微针阵列生物传感器的制备方法，其特征在于：所述的空心微针阵列上有一个由脉冲激光打的孔；在所述的空心微针阵列的孔内壁上沉积一层可导电薄膜；在所述的可导电薄膜上电聚合一层生物识别分子膜。
3.根据权利要求1所述的一种空心微针阵列生物传感器的制备方法，其特征在于：所述的实心微针阵列的材料为聚合物材料。
4.根据权利要求1所述的一种空心微针阵列生物传感器的制备方法，其特征在于：所述的空心微针阵列的制备材料为聚丙烯、聚乳酸、聚碳酸酯、光敏树脂、聚四氟乙烯、聚乙烯或聚氯乙烯。
5.根据权利要求1所述的一种空心微针阵列生物传感器的制备方法，其特征在于：所述的空心微针阵列制备方法为3D打印、光刻刻蚀、浇注成型或注塑成型。
6.根据权利要求1所述的一种空心微针阵列生物传感器的制备方法，其特征在于：所述的脉冲激光打孔直径在10～200μm。
7.根据权利要求1所述的一种空心微针阵列生物传感器的制备方法，其特征在于：所述的孔的形状为倾斜圆台或圆柱或长方体。
8.根据权利要求1所述的一种空心微针阵列生物传感器的制备方法，其特征在于：所述的可导电薄膜可为铝、银、铂、金、参杂石墨烯或炭黑的可导电材料。
9.根据权利要求1所述的一种空心微针阵列生物传感器的制备方法，其特征在于：所述的可导电薄膜是利用分子激光器在室温下进行1～10min脉冲激光沉积，压力保持在5～30mtorr，最终在空心微针阵列孔的内壁上沉积了一层可导电薄膜。
10.根据权利要求1所述的一种空心微针阵列生物传感器的制备方法，其特征在于：所述的生物识别分子膜是以电聚合方法沉积在可导电薄膜上。
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