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一种基于单克隆抗体 BCMab1 的微流控系统可特异性捕获膀胱癌患者的循环肿瘤细胞。

A microfluidic system based on the monoclonal antibody BCMab1 specifically captures circulating tumor cells from bladder cancer patients.

机构信息

Department of Urology, the First Affiliated Hospital of Shandong First Medical University, Jinan, China ;

Department of Ultrasound, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China.

出版信息

J Biomater Sci Polym Ed. 2020 Jun;31(9):1199-1210. doi: 10.1080/09205063.2020.1748332. Epub 2020 Apr 10.

Abstract

Circulating bladder tumor cells provide significant information for cancer diagnosis, tumor staging and personalized cancer therapy. Previous studies have reported various methods for capturing circulating tumor cells; however, capturing circulating tumor cells remain a challenge. Here, we present a microfluidic chip with high specificity and capture yields that we refer to as a bladder cancer diagnosis chip. We show that this chip can be used to effectively capture circulating bladder cancer cells based on antibody-BCMab1, a monoclonal antibody that binds to aberrantly glycosylated integrin a3b1. This capture platform is composed of a polydimethylsiloxane (PDMS) chip, whose microchannels are functionalized with biotinylated BCMab1. To change the direction of flow to increase cell-substrate contact, we also introduced a herringbone or chevron channel pattern into the chip. Using this system, we were able to capture bladder cancer cells with high specificity. The capture rates of the bladder cancer diagnosis chip were evaluated at different flow rates and cell concentrations. We found that 90% of the cancer cells were successfully captured at flow rates of 10 μL/min and at various cell concentrations. This highly specific microfluidic chip is a novel tool for bladder cancer diagnosis and offers an opportunity for personalized treatment.

摘要

循环膀胱肿瘤细胞为癌症诊断、肿瘤分期和个体化癌症治疗提供了重要信息。先前的研究已经报道了各种捕获循环肿瘤细胞的方法;然而,捕获循环肿瘤细胞仍然是一个挑战。在这里,我们提出了一种具有高特异性和高捕获率的微流控芯片,我们称之为膀胱癌诊断芯片。我们证明,该芯片可以基于结合异常糖基化整合素 a3b1 的单克隆抗体 BCMab1,有效地捕获循环膀胱癌细胞。该捕获平台由聚二甲基硅氧烷 (PDMS) 芯片组成,其微通道用生物素化的 BCMab1 功能化。为了改变流动方向以增加细胞与基底的接触,我们还在芯片中引入了人字形或雪佛龙通道模式。使用该系统,我们能够以高特异性捕获膀胱癌细胞。在不同的流速和细胞浓度下评估了膀胱癌诊断芯片的捕获率。我们发现,在流速为 10 μL/min 和各种细胞浓度下,有 90%的癌细胞被成功捕获。这种高度特异的微流控芯片是膀胱癌诊断的一种新工具,并为个体化治疗提供了机会。

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