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用于癌症生物标志物检测的 0.18μm CMOS 技术中的生物传感器-CMOS 平台和集成读出电路。

A Biosensor-CMOS Platform and Integrated Readout Circuit in 0.18-μm CMOS Technology for Cancer Biomarker Detection.

机构信息

Computer, Electrical and Mathematical Science and Engineering Division (CEMSE), King Abdullah University of Science and Technology (KAUST), Thuwal 23955-6900, Saudi Arabia.

Department of Biomedical Engineering, University of Chapel Hill/North Carolina State University, Raleigh, NC 27695, USA.

出版信息

Sensors (Basel). 2017 Aug 23;17(9):1942. doi: 10.3390/s17091942.

DOI:10.3390/s17091942
PMID:28832523
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5620726/
Abstract

This paper presents a biosensor-CMOS platform for measuring the capacitive coupling of biorecognition elements. The biosensor is designed, fabricated, and tested for the detection and quantification of a protein that reveals the presence of early-stage cancer. For the first time, the spermidine/spermine N1 acetyltransferase (SSAT) enzyme has been screened and quantified on the surface of a capacitive sensor. The sensor surface is treated to immobilize antibodies, and the baseline capacitance of the biosensor is reduced by connecting an array of capacitors in series for fixed exposure area to the analyte. A large sensing area with small baseline capacitance is implemented to achieve a high sensitivity to SSAT enzyme concentrations. The sensed capacitance value is digitized by using a 12-bit highly digital successive-approximation capacitance-to-digital converter that is implemented in a 0.18 μm CMOS technology. The readout circuit operates in the near-subthreshold regime and provides power and area efficient operation. The capacitance range is 16.137 pF with a 4.5 fF absolute resolution, which adequately covers the concentrations of 10 mg/L, 5 mg/L, 2.5 mg/L, and 1.25 mg/L of the SSAT enzyme. The concentrations were selected as a pilot study, and the platform was shown to demonstrate high sensitivity for SSAT enzymes on the surface of the capacitive sensor. The tested prototype demonstrated 42.5 μS of measurement time and a total power consumption of 2.1 μW.

摘要

本文提出了一种用于测量生物识别元件电容耦合的生物传感器-CMOS 平台。该生物传感器经过设计、制造和测试,可用于检测和定量检测一种蛋白质,该蛋白质可揭示早期癌症的存在。本文首次在电容传感器表面筛选和定量检测了精脒/精胺 N1 乙酰转移酶(SSAT)酶。传感器表面经过处理以固定抗体,通过将串联的一组电容器连接到分析物上,使生物传感器的基准电容降低。采用大的感测面积和小的基准电容实现了对 SSAT 酶浓度的高灵敏度。使用在 0.18μm CMOS 技术中实现的 12 位高精度逐次逼近电容数字转换器对感测电容值进行数字化。读出电路在近亚阈值区工作,提供了高效的功率和面积利用率。电容范围为 16.137 pF,绝对分辨率为 4.5 fF,足以覆盖 10mg/L、5mg/L、2.5mg/L 和 1.25mg/L 的 SSAT 酶浓度。选择这些浓度作为初步研究,该平台证明了在电容传感器表面对 SSAT 酶具有高灵敏度。测试原型的测量时间为 42.5 μs,总功耗为 2.1 μW。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/180d/5620726/175ef014b135/sensors-17-01942-g012.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/180d/5620726/4df755e4d2a8/sensors-17-01942-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/180d/5620726/114f26d1b4ff/sensors-17-01942-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/180d/5620726/2363e2a9967b/sensors-17-01942-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/180d/5620726/615875111a66/sensors-17-01942-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/180d/5620726/c2f66ce8dad9/sensors-17-01942-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/180d/5620726/15369424f25d/sensors-17-01942-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/180d/5620726/fada4ce22b64/sensors-17-01942-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/180d/5620726/a5bf36869bff/sensors-17-01942-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/180d/5620726/f43f066e6845/sensors-17-01942-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/180d/5620726/64d9011d7196/sensors-17-01942-g011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/180d/5620726/175ef014b135/sensors-17-01942-g012.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/180d/5620726/4df755e4d2a8/sensors-17-01942-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/180d/5620726/0eb6afcc31aa/sensors-17-01942-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/180d/5620726/114f26d1b4ff/sensors-17-01942-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/180d/5620726/2363e2a9967b/sensors-17-01942-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/180d/5620726/615875111a66/sensors-17-01942-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/180d/5620726/c2f66ce8dad9/sensors-17-01942-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/180d/5620726/15369424f25d/sensors-17-01942-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/180d/5620726/fada4ce22b64/sensors-17-01942-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/180d/5620726/a5bf36869bff/sensors-17-01942-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/180d/5620726/f43f066e6845/sensors-17-01942-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/180d/5620726/64d9011d7196/sensors-17-01942-g011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/180d/5620726/175ef014b135/sensors-17-01942-g012.jpg

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