Harsh Bais, PhD



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  • 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.