My broad research interests lie in the design of mixed-signal biomedical ICs and high performance biochips. I’m interested in addressing applications such as in-vitro diagnostics, DNA sequencing, proteomics, point-of-care (POC) testing, neuronal detection and stimulation, healthcare monitoring, and smart medical devices. My general strategy is to leverage the advantages of IC design, VLSI systems, nanotechnology, and MEMS to improve the performance of existing technologies or develop new novel devices that can address the various challenges of biotechnology.


My research at Stanford focused on designing interface and readout circuits for giant magnetoresistive spin-valve (GMR SV) biosensors, primarily for ultra-sensitive cancer diagnostics. These sensors are rooted in the hard disk drive industry and operate by transducing a magnetic field into a resistance change. We repurposed these sensors as biosensors and used them to detect biomolecules labeled with a magnetic nanotag (Figure 1). While straightforward conceptually, these sensors present numerous interfacing challenges. For example, the resistance change per magnetic nanotag is only 5 µΩ on a 2.5 kΩ sensor, or a few parts per billion change in the resistance. Furthermore, these sensors have high 1/f noise and are in a dynamic environment where temperature changes of up to 30 °C are possible.

Figure 1 – a) Illustration of concept using a GMR SV as a biosensor to detect the magnetic stray field from a labeled biomarker, b) Array of 64 GMR SV biosensors, c) Sensor interface and acquisition IC for 256 GMR SV biosensors

A High Density Magnetoresistive Biosensor Microarray for Quantitative Proteomics

Microarrays are a vital tool for researchers and laboratories to analyze large-scale gene and protein expression levels in a biological sample. While DNA microarrays have seen prolific success over the past few years, protein microarrays have proved to be much more challenging. Current implementations are often based on bulky optical detection schemes and are not very sensitive. In this work, I designed a highly integrated sensor interface and data acquisition system in a 0.18µm CMOS process to interface an array of 256 GMR SV biosensors. The sensor interface has a remarkably low input referred noise of 50 nT/√Hz which translated to highly multiplexed protein detection at 50 fM, 100 times lower than the previously reported lower limit of detection at the top two integrated circuits conferences (ISSCC and VLSI). Furthermore, I demonstrated an ultra-compact design for a ΣΔ modulator consuming only 0.05 mm2 with a dynamic range of 84 dB.

Point-of-Care Testing

The worldwide research community has made great strides toward developing faster, more sensitive and cost-effective diagnostic technologies. However, despite extensive progress, access to these technologies remains limited to large centralized laboratories in the developed world. I designed a medical diagnostic tool which is cost-effective and will allow individuals to take an active part in their own health care by moving away from costly and complex biomolecular detection. The nanoLAB is a point-of-care testing device capable of rapid detection of HIV and hepatitis C in developing countries. Some of the major accomplishments of this work include the miniaturization of the readout electronics and electromagnet into a handheld, ultraportable device (about the size of a paperback book) as well as re-engineering the bioassay to make it extremely easy to use and wash-free.

Novel Readout Circuits for GMR SV Biosensors

New sensors, and even novel applications of existing sensors, are creating several interesting sensor interface challenges. Throughout my time at Stanford I constantly explored different sensor interfaces, specifically for GMR spin-valve biosensors. These sensors are particularly challenging to interface because the small change in resistance due to the presence of the nanotags is superimposed on a much larger background resistance requiring extremely high dynamic range (> 120 dB). The detection of the nanotags is further complicated by significant process variation, high 1/f noise, and large temperature induced signals. Beyond the ubiquitous Wheatstone bridge, I explored some original sensor interfaces such as integrating the sensor into a CT ΣΔ modulator and designing an all analog signal path that modulates and demodulates the signal to minimize the 1/f noise. I also investigated modulation schemes, such as frequency domain multiplexing (FDM), to reduce the readout time and carrier suppression techniques to reduce the dynamic range requirement. Calibration and correction techniques were developed and patented to improve the reproducibility, enhance the sensitivity, and remove temperature induced signals.

 

Research


Publications

Ph.D. Thesis

 

Drew A. Hall, “GMR Spin-Valve Biochips and Interface Electronics for Ultrasensitive in-vitro Diagnostics,” Ph.D. Thesis, Stanford University, 2011.

Journal Papers (Peer Reviewed)

J7.

Richard S. Gaster, Liang Xu, Shu-Jen Han, Robert J. Wilson, Drew A. Hall, Sebastian J. Osterfeld, Heng Yu, and Shan X. Wang, “Quantification of Protein Interactions and Solution Transport Using High-Density GMR Sensor Arrays,” Nature Nanotechnology, 6, 314-320, 2011.

J6.

R.S. Gaster, D.A. Hall, and Shan X. Wang, “nanoLAB: An ultraportable, hand-held diagnostic laboratory for global health,” Lab on a Chip, 2011, DOI: 10.1039/C0LC00534G. 

These authors contributed equally to this work.

J5.

Richard S. Gaster, Drew A. Hall, Shan X. Wang, “Autoassembly Protein Arrays for Analyzing Antibody Cross-Reactivity,” Nano Letters, 2011, DOI: 10.1021/nl1026056. 

J4.

D.A. Hall, R.S. Gaster, T. Lin, S.J. Osterfeld, S. Han, B. Murmann, and S.X. Wang, “GMR biosensor arrays: a system perspective,” Biosensors and Bioelectronics, 25, 2051-2057, 2010.

J3.

D.A. Hall, R.S. Gaster, S.J. Osterfeld, B. Murmann, and S.X. Wang, “GMR biosensor arrays: correction techniques for reproducibility and enhanced sensitivity," Biosensors and Bioelectronics, 25, 2177-2181, 2010.

J2.

Richard S. Gaster, Drew A. Hall, Carsten Neilson, Sebastian J. Osterfeld, Heng Yu, Kathleen Mach, Robert J. Wilson, Boris Murmann, Joseph C Liao, Sanjiv S. Gambhir, Shan X. Wang, "Matrix-insensitive protein assays push the limits of biosensors in medicine," Nature Medicine, 15, 1327-1332, 2009.

These authors contributed equally to this work.

J1.

S. J. Osterfeld, H. Yu, R. S. Gaster, S. Caramuta, L. Xu, S.-J. Han, D. A. Hall, R. J. Wilson, S. Sun, R. L. White, R. W. Davis, N. Pourmand, and S. X. Wang, “Multiplex Protein Assays Based on Real-Time Magnetic Nanotag Sensing,” PNAS, 105, 20637-20640, 2008.

Conference Papers (Peer Reviewed)

C6.

Drew A. Hall, Richard S. Gaster, Sebastian J. Osterfeld, Kofi Makinwa, Shan X. Wang, and Boris Murmann, “A 256 Channel Magnetoresistive Biosensor Microarray for Quantitative Proteomics,” Symp. VLSI Circuits Dig., Kyoto, Japan, July 15-17, 2011.

C5.

S.X. Wang, R.S.Gaster, D.A. Hall, “Wash-free multiplex protein assay based on magnetic nanotechnology and its applications in cancer research,” Digest of International Magnetics Conf., Taipei, Taiwan, April 25-29, 2011.

C4.

Drew A. Hall, Calvin Chu, Andrew Dotey, Jr., Richard S. Gaster, Kofi Makinwa, Boris Murmann, and Shan X. Wang, “A GMR Spin-Valve Integrated into a Continuous Time ΣΔ Modulator for Quantitative, Real-Time Biosensing,” Digest of International Magnetics Conf., Taipei, Taiwan, April 25-29, 2011.

C3.

Drew A. Hall, Richard S. Gaster, Shan X. Wang, Boris Murmann, "Portable biomarker detection with magnetic nanotags," IEEE International Symposium on Circuits and Systems (ISCAS), June, 2010. 

C2.

D. A. Hall, R. S. Gaster, H. Yu, S. J. Osterfeld, B. Murmann, S. X. Wang, “Multiplexed GMR Biosensor Arrays,” Digest of International Magnetics Conf., Sacramento, CA, May 5-8, 2009.

C1.

Drew A. Hall, Tondra De, “A New Approach to Maze Searching and Solving Techniques for Small Autonomous Mobile Robots,” IEEE Southwest Region Meeting, 2005.

*Best Student Paper Award Winner.

Books and Book Chapters

B2.

Richard S. Gaster, Drew A. Hall, and Shan X. Wang, “Magnetic Nanoparticle Diagnostic Chips,” invited book chapter in Point of Care Diagnostics on a Chip, Springer (Edited by Robert Westervelt and David Issadore), to appear. 

B1.

Drew A. Hall, Richard S. Gaster, and Shan X. Wang, “GMR Biosensors,” invited book chapter in Handbook of Spin Transport and Magnetism, Taylor & Francis (Edited by Evgeny Tsymbal and Igor Žurić), 2011.