Harsh Bais, PhD



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  • Bellin, Daniel L.; Warren, Steven B.; Rosenstein, Jacob K.; Shepard, Kenneth L. Interfacing CMOS electronics to biological systems: from single molecules to cellular communities, Biomedical Circuits and Systems Conference (BioCAS), 2014 IEEE

    irect electronic interfaces between biological systems and solid-state devices offer considerable advantages over traditional optical interfaces by reducing system costs and affording increased signal levels. Integrating sensor transduction onto a complementary metal-oxide-semiconductor (CMOS) chip provides further advantages by enabling reduction of parasitics and improved sensor density. We present two sensing platforms that demonstrate the range of capabilities of CMOS-based bioelectronics. The first platform electrochemically images signaling molecules in multicellular communities, while the second focuses on single-molecule, high-bandwidth sensing using carbon nanotube field-effect transistors.

  • Jaebin Choi, Eyal Aklimi, Jared Roseman, David Tsai, Harish Krishnaswamy, Kenneth L. Shepard Matching the power density and potentials of biological systems: a 3.1-nW, 130-mV, 0.023-mm3 pulsed 33-GHz radio transmitter in 32-nm SOI CMOS, Custom Integrated Circuits Conference, 2014

    A 3.1 nJ/bit pulsed millimeter-wave transmitter, 300μm by 300μm by 250μm in size, designed in 32-nm SOI CMOS, operates on an electric potential of 130mV and 3.1nW of dc power. These achieved power levels and potentials are comparable to those present across cellular and intracellular membranes. Far-field data transmission at 33 GHz is achieved by supply-switching an LC-oscillator with a duty cycle of 10-6. The time interval between pulses carries information on the amount of power harvested by the radio, supporting a data rate of ~1bps. The inductor of the oscillator also acts as an electrically small (~λ/30) on-chip antenna, enabling the extremely small form factor.

  • Haig Norian, Ryan M. Field, Ioannis Kymissis and Kenneth L. Shepard An integrated CMOS quantitative-polymerase-chain-reaction lab-on-chip for point-of-care diagnostics, Lab Chip, 2014, Advance Article.

    Considerable effort has recently been directed toward the miniaturization of quantitative-polymerasechain-reaction (qPCR) instrumentation in an effort to reduce both cost and form factor for point-of-care applications. Considerable gains have been made in shrinking the required volumes of PCR reagents, but resultant prototypes retain their bench-top form factor either due to heavy heating plates or cumbersome optical sensing instrumentation. In this paper, we describe the use of complementary-metal-oxide semiconductor (CMOS) integrated circuit (IC) technology to produce a fully integrated qPCR lab-on-chip. Exploiting a 0.35 μm high-voltage CMOS process, the IC contains all of the key components for performing qPCR. Integrated resistive heaters and temperature sensors regulate the surface temperature of the chip to an accuracy of 0.45 °C. Electrowetting-on-dielectric microfluidics are actively driven from the chip surface, allowing for droplet generation and transport down to volumes less than 1.2 nanoliter. Integrated single-photon avalanche diodes (SPADs) are used for fluorescent monitoring of the reaction, allowing for the quantification of target DNA with more than four-orders-of-magnitude of dynamic range and sensitivities down to a single copy per droplet. Using this device, reliable and sensitive real-time proof-of-concept detection of Staphylococcus aureus (S. aureus) is demonstrated.

  • R.M. Field, S. Realov, and K.L. Shepard A 100-fps, Time-Correlated Single-Photon-Counting-Based Fluorescence-Lifetime Imager in 130-nm CMOS, IEEE Journal of Solid-State Circuite, vol.49, no.4 (2014) advanced online version.

    A fully-integrated single-photon avalanche diode (SPAD) and time-to-digital converter (TDC) array for high-speed fluorescence lifetime imaging microscopy (FLIM) in standard 130-nm CMOS is presented. This imager is comprised of an array of 64-by-64 SPADs each with an independent TDC for performing time-correlated single-photon counting (TCSPC) at each pixel. The TDCs use a delay-locked-loop-based architecture and achieve a 62.5-ps resolution with up to a 64-ns range. A data-compression datapath is designed to transfer TDC data to off-chip buffers, which can support a data rate of up to 42 Gbps. These features, combined with a system implementation that leverages a x4 PCIe-cabled interface, allow for demonstrated FLIM imaging rates at up to 100 frames per second.

  • D.L. Bellin, H. Sakhtah, J.K. Rosenstein, P.M. Levine, J. Thimot, K. Emmet, L.E.P. Dietrich, and K.L. Shepard Integrated circuit-based electrochemical sensor for spatially resolved detection of redox-active metabolites in biofilms, Nature Communications 5:3256 (2014) doi:10.1038/ncomms4256

    Despite advances in monitoring spatiotemporal expression patterns of genes and proteins with fluorescent probes, direct detection of metabolites and small molecules remains challenging. A technique for spatially resolved detection of small molecules would benefit the study of redox-active metabolites that are produced by microbial biofilms and can affect their development. Here we present an integrated circuit-based electrochemical sensing platform featuring an array of working electrodes and parallel potentiostat channels. ‘Images’ over a 3.250.9mm2 area can be captured with a diffusion-limited spatial resolution of 750 μm. We demonstrate that square wave voltammetry can be used to detect, identify and quantify (for concentrations as low as 2.6 μm) four distinct redox-active metabolites called phenazines. We characterize phenazine production in both wild-type and mutant Pseudomonas aeruginosa PA14 colony biofilms, and find correlations with fluorescent reporter imaging of phenazine biosynthetic gene expression.