Highly efficient circulating tumor cell isolation from whole blood and label-free enumeration using polymer-based microfluidics with an integrated conductivity sensor

Highly efficient circulating tumor cell isolation from whole blood and label-free enumeration using polymer-based microfluidics with an integrated conductivity sensor
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DOI:
10.1021/ja8015022
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发表时间:
2008-07-09
影响因子:
15
通讯作者:
Soper, Steven A.
Soper, Steven A.
中科院分区:
化学1区
文献类型:
--
作者:
Adams, Andre A.;Okagbare, Paul I.;Soper, Steven A.

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一种新型的微流体装置,其可以通过单克隆抗体(mAB)介导的过程,通过设计具有适当宽度和高度的捕获通道,在短时间内(97%)直接采样大输入体积(>= 1 mL)的全血,选择性和特异性地分离极少量的循环肿瘤细胞(CTC)。使用胰蛋白酶将分离的CTC容易地从mAB捕获表面释放。然后使用能够检测通过检测电极的单个肿瘤细胞的新型无标记溶液电导率途径在设备上对释放的CTC进行计数。由于比例因子和潜在干扰(红细胞或白细胞)的非最佳电特性,电导率读数提供了接近100%的检测效率和CTC的精确特异性。该装置的制造简单性及其易于操作性使其对于需要一次性使用操作的临床应用具有吸引力。
A novel microfluidic device that can selectively and specifically isolate exceedingly small numbers of circulating tumor cells (CTCs) through a monoclonal antibody (mAB) mediated process by sampling large input volumes (>= 1 mL) of whole blood directly in short time periods (97%) by designing capture channels with the appropriate widths and heights. The isolated CTCs were readily released from the mAB capturing surface using trypsin. The released CTCs were then enumerated on-device using a novel, label-free solution conductivity route capable of detecting single tumor cells traveling through the detection electrodes. The conductivity readout provided near 100% detection efficiency and exquisite specificity for CTCs due to scaling factors and the nonoptimal electrical properties of potential interferences (erythrocytes or leukocytes). The simplicity in manufacturing the device and its ease of operation make it attractive for clinical applications requiring one-time use operation.