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GMR 生物传感器阵列:系统视角。

GMR biosensor arrays: a system perspective.

机构信息

Department of Electrical Engineering, Stanford University, Stanford, CA 94305, USA.

出版信息

Biosens Bioelectron. 2010 May 15;25(9):2051-7. doi: 10.1016/j.bios.2010.01.038. Epub 2010 Feb 6.


DOI:10.1016/j.bios.2010.01.038
PMID:20207130
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2855856/
Abstract

Giant magnetoresistive biosensors are becoming more prevalent for sensitive, quantifiable biomolecular detection. However, in order for magnetic biosensing to become competitive with current optical protein microarray technology, there is a need to increase the number of sensors while maintaining the high sensitivity and fast readout time characteristic of smaller arrays (1-8 sensors). In this paper, we present a circuit architecture scalable for larger sensor arrays (64 individually addressable sensors) while maintaining a high readout rate (scanning the entire array in less than 4s). The system utilizes both time domain multiplexing and frequency domain multiplexing in order to achieve this scan rate. For the implementation, we propose a new circuit architecture that does not use a classical Wheatstone bridge to measure the small change in resistance of the sensor. Instead, an architecture designed around a transimpedance amplifier is employed. A detailed analysis of this architecture including the noise, distortion, and potential sources of errors is presented, followed by a global optimization strategy for the entire system comprising the magnetic tags, sensors, and interface electronics. To demonstrate the sensitivity, quantifiable detection of two blindly spiked samples of unknown concentrations has been performed at concentrations below the limit of detection for the enzyme-linked immunosorbent assay. Lastly, the multiplexing capability and reproducibility of the system was demonstrated by simultaneously monitoring sensors functionalized with three unique proteins at different concentrations in real-time.

摘要

巨磁电阻生物传感器在敏感、可量化的生物分子检测方面变得越来越流行。然而,为了使磁生物传感能够与当前的光学蛋白质微阵列技术竞争,有必要在保持较小阵列(1-8 个传感器)的高灵敏度和快速读取时间特性的同时,增加传感器的数量。在本文中,我们提出了一种可扩展到更大传感器阵列(64 个可单独寻址的传感器)的电路架构,同时保持高读取速率(在不到 4 秒的时间内扫描整个阵列)。该系统利用时域多路复用和频域多路复用来实现这一扫描速度。对于实现,我们提出了一种新的电路架构,该架构不使用经典的惠斯通电桥来测量传感器的小电阻变化。相反,采用了一种围绕跨阻放大器设计的架构。对该架构进行了详细的分析,包括噪声、失真和潜在的误差源,然后提出了一个包括磁性标签、传感器和接口电子设备的整个系统的全局优化策略。为了演示灵敏度,我们对两个未知浓度的盲目添加样本进行了可量化的检测,其浓度低于酶联免疫吸附测定的检测限。最后,通过实时同时监测功能化有三种不同浓度的独特蛋白质的传感器,展示了系统的多路复用能力和可重复性。

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本文引用的文献

[1]
GMR biosensor arrays: correction techniques for reproducibility and enhanced sensitivity.

Biosens Bioelectron. 2010-2-6

[2]
Matrix-insensitive protein assays push the limits of biosensors in medicine.

Nat Med. 2009-11

[3]
Femtomolar limit of detection with a magnetoresistive biochip.

Biosens Bioelectron. 2009-4-15

[4]
Multiplex protein assays based on real-time magnetic nanotag sensing.

Proc Natl Acad Sci U S A. 2008-12-30

[5]
Rapid DNA multi-analyte immunoassay on a magneto-resistance biosensor.

Biosens Bioelectron. 2009-3-15

[6]
Sensitive and rapid immunoassay for parathyroid hormone using magnetic particle labels and magnetic actuation.

J Immunol Methods. 2008-9-30

[7]
Giant magnetoresistive biochip for DNA detection and HPV genotyping.

Biosens Bioelectron. 2008-9-15

[8]
Magnetic labeling, detection, and system integration.

Biosens Bioelectron. 2008-9-15

[9]
An integrated and sensitive detection platform for magneto-resistive biosensors.

Biosens Bioelectron. 2007-4-15

[10]
The BARC biosensor applied to the detection of biological warfare agents.

Biosens Bioelectron. 2000-1

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