CN106179546A - 一种具有特异构型微通道的poct芯片 - Google Patents

一种具有特异构型微通道的poct芯片 Download PDF

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CN106179546A
CN106179546A CN201610569113.2A CN201610569113A CN106179546A CN 106179546 A CN106179546 A CN 106179546A CN 201610569113 A CN201610569113 A CN 201610569113A CN 106179546 A CN106179546 A CN 106179546A
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李经民
刘子扬
王帅
梁超
刘冲
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Dalian University of Technology
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Abstract

本发明提供了一种具有特异构型微通道的POCT芯片，属于免疫分析、即时检测等领域。采用不同形状的边缘为“锯齿”状的微通道，集成于POCT芯片上，用于免疫分析、即时检测等众多生物医疗领域。规律分布的“锯齿”状边缘，改变了流体通道的局部微尺度特性，进而改变样品的流速、流型等流动特性。当样品流经该特异构型微通道时，为了满足流体与通道壁的动态接触角，“锯齿”结构使流动前沿弯液面由凹状转变为凸状，抑制气阻的产生，消除了边缘效应。通过调整特异构型微通道的波长w，路径比r、扩张角α、相位P四个结构参数可以精确控制流动前沿弯液面的形状及其曲率大小。

Description

一种具有特异构型微通道的POCT芯片
技术领域
本发明提供了一种具有特异构型微通道的POCT芯片，采用不同形状的边缘为“锯齿”状微通道，可集成于POCT检测芯片，用于免疫分析、即时检测等领域。
背景技术
即时检测(POCT，Point-of-CareTest)是一种新型的医学检测技术。它是在传统实验室以外，由临床医疗人员或患者本人进行的一种快速疾病诊断技术。相比传统的实验室检测，POCT优势明显，如直接使用无需抗凝的全血，试剂用量少，标本周转时间(TurnAround Time，TAT)短，仪器小型化，操作简便化，结果报告即时化等。目前最成熟的POCT应用是侧流试纸条检测法，它使用一个薄膜或纸带指示蛋白质标记物如抗原或抗体的存在，已广泛应用于妊娠检测及链球菌、流感感染等的检测。尽管侧流试纸条检测法易于操作，但其检测结果精度低、重现差，因此常常只能用于定性检测，不能进行高精密度的定量检测，这些缺点限制了该方法的进一步应用。
近年来，LOC(lab-on-a-chip，芯片实验室)技术的出现给POCT指明了新的发展方向。LOC在几英寸芯片上集成各种生化反应，减少了试剂消耗、缩短了反应时间，实现高通量、大规模的检测。基于芯片实验室的即时检测被广泛认为是实现POCT产业升级最有潜力的技术，已成为生物医疗领域的研究热点。
基于芯片实验室技术的POCT检测在小分子、早期癌症、艾滋病、心脏病等的快速检测方面具有较大优势。如雅培公司(Abbott)的i－STAT利用电化学测定法检测血液中的钠、钾、氯化物、葡萄糖、血细胞比容等小分子物质；Epocal公司开发的SmartCard可定量检测血液中pH、pCO2、pO2、Na+、K+、Ca++、Glu、Lac、Hct等物质的含量；Alere公司开发的The AlerePimaTMAnalyser只需注入25mL血液至检测芯片即可在20分钟内检测出血液中CD4细胞的数量，这对HIV/AIDS的确诊具有重要意义；博适公司的Triage MeterPlus手提式荧光计，可同时定量测定cTnI、CK-MB和Mb，采用荧光标记技术，可产生高达85％的荧光效率，通过储存在仪器中的标准曲线最终换算出待测物的浓度。
微流体控制是即时检测芯片的操作核心，芯片中所涉及的进样、混合、反应、分离等过程无一不是在可控流体中完成的。微通道网络是即时检测微流控芯片的重要组成部分。当使用POCT微流控芯片进行检测时,流体媒介流经微通道，与固着于其上的物质混合并发生反应，达到生物或医学检测目的。亲水通道因利于样品引入而广泛应用于即时检测微流控芯片。但另一方面，当通道表面亲水时，在表面张力作用下靠近通道壁面的样品输运速率比通道中间更快，使流体前沿液面呈凹状而不是凸状或平面状，这就是边缘效应。凹状液面容易在通道中引入气泡，导致定量分析出现偏差。例如定量(或半定量)检测样品中的某种抗原，只有精确控制流体前沿在通道中位置才能定量分析样品中抗原浓度。凹状液面会导致抗原与抗体的反应不充分。此外，样品在边缘流动过快会导致空气不能及时排出通道而引入气泡，使通道堵塞或被分析物与抗体的不均匀混合，影响最终定量分析精度。
发明内容
本发明提供了一种具有特异构型微通道的POCT芯片。
本发明的技术方案：
一种具有特异构型微通道的POCT芯片，将传统POCT芯片的直线形微通道改为“锯齿”波浪形微通道，即为特异构型微通道；特异构型微通道的长度取决于其宽度w，即“锯齿”波浪形微通道的每个波长l＝1/100～1/10w；路径比r是“锯齿”波浪形微通道的宽度与长度之比，其取值为1～10；扩张角α是液面流动方向与通道边缘切线的夹角，且通道截面扩大时取为正值，减小时取为负值，其变动范围是﹣90°～90°；
构成“锯齿”波浪形微通道的“锯齿”形状是三角形、矩形、梯形、半圆形或组合；
所述的特异构型微通道材质为聚甲基丙烯酸甲酯(PMMA)、聚对苯二甲酸乙二酯醇(PET)、聚四氟乙烯(特富龙PTFE)、聚碳酸酯(PC)、聚苯乙烯(PS)、聚乙烯(PE)聚丙烯(PP)、聚氯乙烯(PVC)、尼龙、聚氨酯(PU)、苯乙烯二甲基丙烯酸甲酯共聚物(SMMA)等热塑性聚合物。
本发明的有益效果：使得液体在通道内流动时前沿始终保持“凸面”形状，抑制气阻，有效解决了液体在芯片内流动的边缘效应和因此而产生的气泡现象。
附图说明
图1是本发明的POCT产品整体俯视图。
图2(a)是本发明特异构型微通道的宽度w。
图2(b)是本发明特异构型微通道的扩张角α。
图2(c)本发明特异构型微通道同相位。
图2(d)本发明特异构型微通道异相位。
图中：1“锯齿”结构；2通道。
具体实施方式
以下结合附图和技术方案，进一步说明本发明的具体实施方式。
本发明提供了一种特异构型微通道，有效解决了POCT检测芯片内的边缘效应问题。在“锯齿”通道内，由于通道侧壁不断的扩张－收缩，流动前沿弯液面形状会产生周期性变化，水头始终保持“凸面”形状，可有效消除边缘流动，抑制气阻的产生；通过调整参数路径比r、波长w及扩张角α可以比较精确控制气－液界面曲率，调整相位P则可调整液面分布的对称性。
下面以一种典型尺寸的特异构型微通道，集成于POCT微流控芯片在心梗检测的应用，作为实施例，对血清或全血与荧光物质的混合液体在三维波浪形控流微结构控制单元作用下的流动控制加以说明。结合附图如下。
实施例
该POCT芯片由基片与盖片键合而成。其中基片包括进样区、混合区、特异构型微通道、废液区。进样区用于样品的滴加，混合区表面均匀涂覆一层抗原，流经此处的样品与这些抗原混合并反应；特异构型微通道是检测通道，“锯齿”状侧壁结构使流动前沿弯液面始终保持为“凸”状，消除了边缘效应，保证检测精度。
本发明的特异构型微通道是一种侧壁边缘为“锯齿”状的微通道。集成了此结构的基片通过与盖片的键合形成密闭通道。
特异微通道深度70um，宽度2mm，长30mm。侧壁边缘为半圆状“锯齿”结构，其参数为波长l＝0.2mm，路径比r＝π/2，扩张角α在﹣π/2～π/2范围变动，且两个侧壁对称分布，即为同相位。
血清或全血通过进样区加样后，在毛细力作用下流入混合区。样品与预先在混合区表面均匀涂覆的一层荧光物质发生混合，接着这些混合液流入特异构型微通道－半圆状“锯齿”通道。为了满足流体与通道侧壁的动态接触角，“锯齿”结构使流动前沿弯液面由凹状转变为凸状，从而抑制气阻的产生，消除了边缘效应。在特异构型微通道的下壁面表面均匀涂覆有心梗的蛋白质标记物，经荧光标记的样品在“锯齿”通道中与这些蛋白充分反应并发生特异性结合，过量样品流入废液区；最后利用荧光检测装置对流过特异构型微通道的混合液体进行荧光检测，得出检测结果。医务人员对检测结果进行分析判断，如果检测数据超出正常范围，说明存在患有心梗的风险。

Claims (3)

1.一种具有特异构型微通道的POCT芯片，其特征在于，将传统POCT芯片的直线形微通道改为“锯齿”波浪形微通道，即为特异构型微通道；特异构型微通道的长度取决于其宽度w，即“锯齿”波浪形微通道的每个波长l＝1/100～1/10w；路径比r是“锯齿”波浪形微通道的宽度与长度之比，其取值为1～10；扩张角α是液面流动方向与通道边缘切线的夹角，且通道截面扩大时取为正值，减小时取为负值，其变动范围是﹣90°～90°。
2.根据权利要求1所述的POCT芯片，其特征在于，构成“锯齿”波浪形微通道的“锯齿”形状是三角形、矩形、梯形、半圆形或组合。
3.根据权利要求1或2所述的POCT芯片，其特征在于，所述的特异构型微通道材质为聚甲基丙烯酸甲酯、聚对苯二甲酸乙二酯醇、聚四氟乙烯、聚碳酸酯、聚苯乙烯、聚乙烯、聚丙烯、聚氯乙烯、尼龙、聚氨酯或苯乙烯二甲基丙烯酸甲酯共聚物。
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