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用于实时蛋白质和 DNA 检测的完全集成单片光电传感器:NEMOSLAB 方法。

Fully integrated monolithic optoelectronic transducer for real-time protein and DNA detection: the NEMOSLAB approach.

机构信息

Institute of Microelectronics, N.C.S.R. Demokritos, GR-15310 Aghia Paraskevi, Athens, Attiki, Greece.

出版信息

Biosens Bioelectron. 2010 Dec 15;26(4):1528-35. doi: 10.1016/j.bios.2010.07.104. Epub 2010 Aug 3.

DOI:10.1016/j.bios.2010.07.104
PMID:20729053
Abstract

The development and testing of a portable bioanalytical device which was capable for real-time monitoring of binding assays was demonstrated. The device was based on arrays of nine optoelectronic transducers monolithically integrated on silicon chips. The optocouplers consisted of nine silicon avalanche diodes self-aligned to nine silicon nitride waveguides all converging to a single silicon detector. The waveguides were biofunctionalized by appropriate recognition molecules. Integrated thick polymer microchannels provided the necessary fluidic functions to the chip. A single sided direct contact scheme through a board-to-board receptacle was developed and combined with a portable customized readout and control instrument. Real-time detection of deleterious mutations in BRCA1 gene related to predisposition to hereditary breast/ovarian cancer was performed with the instrument developed using PCR products. Detection was based on waveguided photons elimination through interaction with fluorescently labeled PCR products. Detection of single biomolecular binding events was also demonstrated using nanoparticles as labels. In addition, label-free monitoring of bioreactions in real time was achieved by exploiting wavelength filtering on photonic crystal engineered waveguides. The proposed miniaturized sensing device with proper packaging and accompanied by a portable instrument can find wide application as a platform for reliable and cost effective point-of-care diagnosis.

摘要

展示了一种可实时监测结合分析的便携式生物分析设备的开发和测试。该设备基于九个光电晶体管阵列,这些阵列整体集成在硅芯片上。光耦合器由九个硅雪崩二极管组成,这些雪崩二极管与九个氮化硅波导自对准,全部汇聚到单个硅探测器上。波导通过适当的识别分子进行生物功能化。集成的厚聚合物微通道为芯片提供了必要的流体功能。通过板对板插座开发了一种单面直接接触方案,并与便携式定制读出和控制仪器相结合。使用开发的仪器,对与遗传性乳腺癌/卵巢癌易感性相关的 BRCA1 基因的有害突变进行实时检测,该仪器使用 PCR 产物进行检测。检测基于与荧光标记的 PCR 产物相互作用时导波光子的消除。还使用纳米颗粒作为标记物演示了单生物分子结合事件的检测。此外,通过在光子晶体工程波导上进行波长滤波,实现了生物反应的实时无标记监测。这种经过适当封装的小型化传感设备与便携式仪器配套使用,可以广泛应用于可靠且具有成本效益的即时护理诊断平台。

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