CN108175415A - 一种可穿戴式微流控芯片在生命监测领域中的应用 - Google Patents

一种可穿戴式微流控芯片在生命监测领域中的应用 Download PDF

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CN108175415A
CN108175415A CN201711351008.2A CN201711351008A CN108175415A CN 108175415 A CN108175415 A CN 108175415A CN 201711351008 A CN201711351008 A CN 201711351008A CN 108175415 A CN108175415 A CN 108175415A
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罗宇
黄文超
吴家慧
李文琪
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Foshan Tak Public Record Technology Co Ltd
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Abstract

可穿戴式微流控芯片在医疗、体育、军事等领域具有广泛的应用潜力,利用可穿戴式微流控芯片对人体体液进行实时监测,可以通过芯片与皮肤的接触,方便地对汗液、泪液、唾液等体液进行采集,并分析和传输数据,可以实时获取汗液p H值以及血糖、乳酸盐、钠/钾离子、钙离子、重金属等的含量的信息,这些体液信息对于个体生命体征的实时监测和疾病诊断有着重要的指示性作用。

Description

一种可穿戴式微流控芯片在生命监测领域中的应用
技术领域
本发明涉及一种可穿戴式微流控芯片在生命监测领域中的应用。
背景技术
作为生命科学、电子科学、材料科学与化学相融合的实用性技术,可穿戴技术近年有了显著的发展和进步,同时也在生命体征监测、疾病检测、运动科学、军事等领域得到了越来越广泛的应用。可穿戴技术及基于可穿戴技术的设备是指可以直接穿在身上,与衣服或者配饰等整合在一起的一种便携式设备。传统的可穿戴技术及其商业化产品使用光电检测的方法,侧重于对物理指标的测量,如心率、体温、运动跟踪、生物电信号和步数等。以此为代表,国外的商业化产品有i Watch手表、Fitbit手环、Google Glass眼镜等可穿戴产品,国内也有以小米手环等为代表的一系列手环和手表类产品。然而,这些侧重于物理指标检测的传统可穿戴技术还不能满足人类健康监测的另外一个重要信息来源,即体液的监测。这里所指的体液包括血液、汗液、组织液、唾液、泪液、尿液等。现有医疗手段在体液检测方面还集中在使用专用设备对与血液和尿液进行成分分析,如原子吸收光谱仪、离子色谱仪、气相色谱仪等。这些检测手段成本相对较高,而且只能做“一次性(One shot)冶的检测,很难实现在一段时间内对个体进行连续性检测。
发明内容
本发明提出一种可穿戴式微流控芯片，解决了现有技术中使用微流控芯片进行体液检测的优越性还在于:
(1)对检测样品的需求量非常小且可以对样品进行精确操控,可以有效减少被检测者的痛苦和负担；
(2)对检测试剂的需求量非常少,通过使用可穿戴式微流控芯片进行体液检测,检测试剂的需求从传统的毫升级别下降到微升甚至纳升级别,大大降低了昂贵检测试剂的消耗,显著降低了检测成本；
(3)可以实现对体液样本的连续检测,传统的检测方法采用的是体外(In vitro)采集-检测的间断过程,通过可穿戴式微流控芯片可以实现对特定指标的实时体内(Invivo)连续监测与无线数据传输；
(4)具有融合各类传感器的天然优势,由于微流控芯片的加工方法继承自微机电系统 (MEMS)的加工技术,而EMS加工技术已被广泛应用在各类传感器的微加工过程中。因此, 可穿戴式微流控芯片可以灵活整合不同类型的传感器,如光传感器、压电传感器、光化学传感器、电化学传感器、生物传感器等,以适应不同体液检测的需求。
附图说明
为了更清楚地说明本发明实施例或现有技术中的技术方案，下面将对实施例或现有技术描述中所需要使用的附图作简单地介绍，显而易见地，下面描述中的附图仅仅是本发明的一些实施例，对于本领域普通技术人员来讲，在不付出创造性劳动性的前提下，还可以根据这些附图获得其他的附图。
图1检测血糖和乳酸的可穿戴式微流控芯片检测系统；(A)检测血糖和乳酸浓度的3D 打印微流控系统；(B)通过微透析探针测量受试者的血糖和乳酸变化情况；(C)监测运动过程中受试者的血糖和乳酸的变化
图2展示了该芯片通过腕带固定图2可穿戴式汗液p H值检测微流控系统。(A)微流控检测芯片的图片(B)微流控芯片的加工过程(C)微流控芯片与腕带结合定在手腕上的效果,在运动过程中,通过观察离子聚合物凝胶的颜色变化就能获知汗液p H值的变化,p H值的检测范围为4.5～8.0,能够完全覆盖不同状态下人体汗液的p H值变化范围。在这项研究的基础上,Curto等又添加了微型的光电传感器,芯片和传感器可同时穿戴在身上,通过对显色反应的光电识别自动读取p H值并进行无线数据传输。
图3基于PDMS材质的可穿戴式的汗液p H检测芯片。(A)微流控传感器的示意图,包括加工在PDMS上的通道、经过改性的蚕丝以及通道的出入口；(B)光流控检测传感器检测原理
图4基于多层聚合物材料的可穿戴式微流控汗液Na+检测系统。(A)在聚对苯二甲酸乙二醇酯基板上通过丝网印刷的两个电极；(B)构成微流控体液采集系统的各层结构；(C)可穿戴式微流控芯片固定在人的上臂Guinovart等利用了棉线的疏松微结构,将其浸没在碳纳米管墨水(CNT)后,棉线有了导电性质,然后将棉线尖端包裹不同种类的离子选择性渗透膜(Ion鄄 selective membrane),可以实现对不同的离子的检测,并以此为基础制成了简易有效的微流控离子浓度检测装置,其对K+的检出限为10滋mol/L。
图5不同种类的微针。(A)金属锥形针(B)中心偏置的火山形针(C)城堡形状的针头(D)锯齿形的针头
图6可穿戴式微流控药物释放装置。(A)内置药物的可穿戴式微流控芯片,通过手指的弯曲完成药物释放(B)内置药物的可穿戴芯片与微针阵列结合
具体实施方式
下面将结合本发明实施例中的附图，对本发明实施例中的技术方案进行清楚、完整地描述，显然，所描述的实施例仅仅是本发明一部分实施例，而不是全部的实施例。基于本发明中的实施例，本领域普通技术人员在没有作出创造性劳动前提下所获得的所有其他实施例，都属于本发明保护的范围。
1.血糖和乳酸检测
人体内的各组织细胞活动所需要的能量大部分来源于血糖中的葡萄糖,为了维持体内各器官的和组织的需要,必须将血糖保持在一定水平。乳酸是糖酵解的终产物,对于运动负荷的控制、高血压糖尿病患者的监护、糖源性疾病检测等方面具有重要的参考意义。目前,最通用的血糖检测方法是采用全自动生化分析仪或小型化的快速血糖仪,而乳酸检测也需要专用的乳酸检测仪。血糖和血乳酸盐的检测方法还多停留在使用侵入性(Invasive)检测方法的阶段, 即需要从人体穿刺采全血或指尖采血。以目前最为广泛使用的小型血糖仪为例,针尖穿刺指尖采血,血液涂抹在试纸后,通过仪器读取血糖含量,使用过程不仅操作步骤多、病人有痛苦、试纸成本高,且仪器需频繁校准,最重要的是,其穿刺采血的方式不可能做到对血糖含量的实时监测(不可能频繁穿刺采血)。而现有的可以实现血糖实时检测和胰岛素注射的可穿戴式动态胰岛素泵系统的体积较大、不方便佩带,且售价高昂(以MiniMed Paradigm 722设备为例,售价约￥9万元)。相比之下,可穿戴式微流控芯片给血糖检测提供了极少侵入和非侵入的检测方法:极少侵入方法指通过微针阵列对皮肤进行穿刺采血,由于微针的长度触及不到内皮神经层,因而被测者几乎感觉不到疼痛；非侵入方法目前集中于通过对组织液中葡萄糖浓度的分析间接反映血糖的浓度。
2.p H值检测
排汗在维持体内环境的稳定性方面发挥着重要作用,排汗还能辅助和部分替代肾脏的功能,参与新陈代谢。汗液中携带丰富的信息,对汗液进行实时检测和分析对掌握生命体征的变化有重要意义。
3.Na+,K+,Ca2+等离子检测
汗液中的Na+、K+的浓度可以直接反映出人皮肤的水合作用程度,通过监测Na+的浓度可以获知在极端环境(如高温高湿)中工作的人员,例如运动员、煤矿工人、士兵的电解质流失和脱水情况。在高温高湿的环境中,排汗是人体散热的最主要方式,然而随着汗液的排出也造成了电解质的流失,如果人体不能有效适应环境,Na+随汗液的排出量过多(>40mmol/L),会造成肌肉痉挛,甚至热射病等严重后果,所以对体液中Na+,K+的实时检测对于极端环境中工作的人员非常重要。另一方面,汗液中的Na+浓度异常也可是一些疾病的特征,如囊性纤维化病等。与Na+类似,Ca2+在血液凝固、神经肌肉的传导等过程中也有非常重要的作用,同时,Ca也占到了人体总重的1％～2％。
在Na+、K+、Ca2+的检测方面,可穿戴技术与微流控芯片的结合主要体现在使用微流控芯片采集和传输体液,之后使用选择性渗透膜或者选择性电极的方法对相应的离子浓度进行检测。需要注意的是,这些检测芯片的成本较低廉但受到检测方法和检测物无法排出的限制,都仅限于一次性使用。可穿戴式微流控芯片为体液检测提供了一个综合性的体液采集、传感、分析控制以及数据传输系统。
4.可穿戴式微流控芯片在药物递送方面
即通过可穿戴的储药装置结合微针或者微针阵列穿刺皮肤送药,由于微针的外形长度精确可控,可以在穿刺皮肤时做到刺透皮肤表层的同时不触及神经层,实现无痛穿刺和精准用量送药。通过微针阵列与微流控芯片的配合,还能做到以微米甚至纳米颗粒包裹药物的形式进行送药。图5展示了各种不同种类的微针,其中空造型可实现穿刺和送药的目的,这些微针采用了金属、硅、聚合物等材料,其加工方法也都是从微机电系统(MEMS)和微流控系统的加工方法中继承和发展的。鉴于中空造型的微针阵列的加工比较困难,实际使用过程中也可以将药物涂在实心微针阵列上进行穿刺后缓慢释放药物或者使用可以生物降解的微针阵列.图6 展示了一种简单易行的可穿戴式微流控药物释放装置,首先将纳米颗粒形态的药物固定在凝胶中,然后将凝胶装载在柔软材质的微流控芯片基片上,并添加一层微针阵列。当需要用药时, 通过手指弯曲时的张力作用微针刺入皮肤,同时压迫凝胶,释放含有药物的纳米颗粒,达到送药的目的。
以上所述仅为本发明的较佳实施例而已，并不用以限制本发明，凡在本发明的精神和原则之内，所作的任何修改、等同替换、改进等，均应包含在本发明的保护范围之内。

Claims (1)

1.一种可穿戴式微流控芯片在生命监测领域中的应用，其特征在于，包括：
(1)血糖和乳酸检测；
(2)p H值检测；
(3)Na+,K+,Ca2+等离子检测。
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CN110618257A (zh) * 2019-08-30 2019-12-27 北京祥为信息技术有限公司 一种生物芯片及其制备方法
WO2020055791A1 (en) * 2018-09-10 2020-03-19 Stc.Unm Color changing detection patch utilizing microneedle sampling of interstitial fluid
CN111938664A (zh) * 2020-08-13 2020-11-17 合肥安时智造科技有限公司 一种基于微流控技术的穿戴式智能无创血糖监测装置
CN115804902A (zh) * 2022-11-22 2023-03-17 复旦大学 一种可载药的心脏贴片

Non-Patent Citations (1)

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范一强 等: "可穿戴式微流控芯片在体液检测和药物递送中的研究进展", 《分析化学》 *

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2020055791A1 (en) * 2018-09-10 2020-03-19 Stc.Unm Color changing detection patch utilizing microneedle sampling of interstitial fluid
CN110618257A (zh) * 2019-08-30 2019-12-27 北京祥为信息技术有限公司 一种生物芯片及其制备方法
CN111938664A (zh) * 2020-08-13 2020-11-17 合肥安时智造科技有限公司 一种基于微流控技术的穿戴式智能无创血糖监测装置
CN115804902A (zh) * 2022-11-22 2023-03-17 复旦大学 一种可载药的心脏贴片

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