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血液中癌症DNA生物标志物的芯片上波长复用检测。

On-chip wavelength multiplexed detection of cancer DNA biomarkers in blood.

作者信息

Cai H, Stott M A, Ozcelik D, Parks J W, Hawkins A R, Schmidt H

机构信息

School of Engineering, University of California , Santa Cruz. 1156 High Street, Santa Cruz, California 95064, USA.

Department of Electrical and Computer Engineering, Brigham Young University , 459 Clyde Building, Provo, Utah 84602, USA.

出版信息

Biomicrofluidics. 2016 Dec 15;10(6):064116. doi: 10.1063/1.4968033. eCollection 2016 Nov.

Abstract

We have developed an optofluidic analysis system that processes biomolecular samples starting from whole blood and then analyzes and identifies multiple targets on a silicon-based molecular detection platform. We demonstrate blood filtration, sample extraction, target enrichment, and fluorescent labeling using programmable microfluidic circuits. We detect and identify multiple targets using a spectral multiplexing technique based on wavelength-dependent multi-spot excitation on an antiresonant reflecting optical waveguide chip. Specifically, we extract two types of melanoma biomarkers, mutated cell-free nucleic acids -BRAFV600E and NRAS, from whole blood. We detect and identify these two targets simultaneously using the spectral multiplexing approach with up to a 96% success rate. These results point the way toward a full front-to-back chip-based optofluidic compact system for high-performance analysis of complex biological samples.

摘要

我们开发了一种光流体分析系统,该系统从全血开始处理生物分子样本,然后在基于硅的分子检测平台上分析和识别多个目标。我们使用可编程微流控电路展示了血液过滤、样本提取、目标富集和荧光标记。我们在反谐振反射光波导芯片上,基于波长依赖的多点激发,使用光谱复用技术检测和识别多个目标。具体而言,我们从全血中提取了两种黑色素瘤生物标志物,即突变的游离核酸——BRAFV600E和NRAS。我们使用光谱复用方法同时检测和识别这两个目标,成功率高达96%。这些结果为基于芯片的全前端到后端光流体紧凑型系统用于复杂生物样本的高性能分析指明了方向。

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本文引用的文献

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Clinical Application of Liquid Biopsies.液体活检的临床应用
JAMA Oncol. 2016 Aug 1;2(8):1003-5. doi: 10.1001/jamaoncol.2016.0240.
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Optofluidic wavelength division multiplexing for single-virus detection.用于单病毒检测的光流控波分复用技术。
Proc Natl Acad Sci U S A. 2015 Oct 20;112(42):12933-7. doi: 10.1073/pnas.1511921112. Epub 2015 Oct 5.
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Lab Chip. 2013 Oct 21;13(20):4118-23. doi: 10.1039/c3lc50818h. Epub 2013 Aug 23.
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PLoS One. 2012;7(11):e49843. doi: 10.1371/journal.pone.0049843. Epub 2012 Nov 27.
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Cell-free nucleic acids as biomarkers in cancer patients.细胞游离核酸作为癌症患者的生物标志物。
Nat Rev Cancer. 2011 Jun;11(6):426-37. doi: 10.1038/nrc3066. Epub 2011 May 12.

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