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GMR spin-valve biochips and interface electronics for ultrasensitive in-vitro diagnostics [electronic resource] / Drew Alexander Hall.



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Hall, Drew Alexander.
Publication date:
  • Book, Thesis
  • 1 online resource.
Submitted to the Department of Electrical Engineering.
Thesis (Ph. D.)--Stanford University, 2011.
Nanotechnology has had a transformative effect on medical diagnostics due to the influx of new sensing modalities and transducers. Magnetic nanotechnologies, in particular, have shown significant potential in several areas of nanomedicine such as imaging, therapeutics, and early disease detection. Giant magnetoresistive spin-valve (GMR SV) sensors, commonly used in hard disk drives, coupled with magnetic nanotags have shown great promise as biosensors. In this work, we present several custom designed circuit interface and readout systems tailored to specific application spaces and their unique needs. Taken together, we have demonstrated that innovative electronic circuits play an indispensable role in unlocking the tremendous potential of nanosensors in the biomedical arena. The first system was designed for ultrasensitive early cancer diagnostics and built using off-the-shelf components for an 8x8 array of GMR SV sensors. At the core of this design, we demonstrate a new circuit architecture based on a transimpedance amplifier (TIA) with a carrier suppression technique to reduce the dynamic range requirement and a multiplexing scheme to reduce the readout time. This system is capable of real-time, multiplex detection with a detection limit of 5 femtomolar (fM) and over 6 orders of linear dynamic range. The second system is a miniaturized, portable platform called the nanoLAB. Although there is a growing need for point-of-care (POC) testing for global health, the current options are bulky, slow, expensive, and often not sensitive. The nanoLAB addresses these needs and pushes the state of the art with sensitive 8-plex detection using a wash-free assay that can be run by anyone, anywhere. This platform was tested and validated using human immunodeficiency virus (HIV) biomarkers with detection down to 50 fM in as little as 15 minutes. We also show how a GMR SV biosensor can be integrated into a continuous time sigma delta modulator. This proof-of-concept hybrid sigma delta modulator has a peak SNR of 99.3 dB and a dynamic range of over 92 dB in a 1 kHz bandwidth using the sensor as part of the first integrator. The carrier suppression and multiplexing concepts were also incorporated into the hybrid sigma delta modulator. Lastly, we conclude by describing an integrated platform for a large 16x16 array of GMR SV sensors implemented in a 0.18 [mu]m CMOS technology. Arranged like an imager chip, each of the 16 column level readout channels contains an analog front-end and an analog-to-digital converter. Each readout channel occupies less than 0.2 mm^2 of chip area and consumes 3.4 mW of power. This system is designed as a replacement for optical protein microarrays while being fully quantitative and providing real-time readout.
Murmann, Boris, primary advisor.
Wang, Shan, primary advisor.
Wooley, Bruce A., 1943-, advisor.
Stanford University. Department of Electrical Engineering

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