K.L. Shepard

Columbia University, New York, New York, United States

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Publications (174)594.05 Total impact

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    Matthew L Johnston, Erik F Young, Kenneth L Shepard
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    ABSTRACT: The current state of the art in high-throughput minimally invasive radiation biodosimetry involves the collection of samples in the field and analysis at a centralized facility. We have developed a simple biological immunoassay for radiation exposure that could extend this analysis out of the laboratory into the field. Such a forward placed assay would facilitate triage of a potentially exposed population. The phosphorylation and localization of the histone H2AX at double-stranded DNA breaks has already been proven to be an adequate surrogate assay for reporting DNA damage proportional to radiation dose. Here, we develop an assay for phosphorylated H2AX directed against minimally processed sample lysates. We conduct preliminary verification of H2AX phosphorylation using irradiated mouse embryo fibroblast cultures. Additional dosimetry is performed using human blood samples irradiated ex vivo. The assay reports H2AX phosphorylation in human blood samples in response to ionizing radiation over a range of 0-5 Gy in a linear fashion, without requiring filtering, enrichment, or purification of the blood sample.
    Biophysik 05/2015; DOI:10.1007/s00411-015-0595-4 · 1.58 Impact Factor
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    ABSTRACT: In this paper, we present a compact model for graphene resonant channel transistors (G-RCTs) that uses extracted electrical and mechanical parameters to provide an accurate simulation of dc, RF, noise, and frequency-tuning characteristics of the device. The model is validated with measurements on fabricated G-RCTs, which include what we believe to be the first noise measurements conducted on any resonant transistor. The noise model, which considers both electrical and mechanical sources, is used to demonstrate the fundamental differences in the noise behavior of active and passive resonator technologies, and to show how optimization of device parameters can be used to improve the noise performance of RCTs.
    IEEE Transactions on Electron Devices 03/2015; PP(99):1. DOI:10.1109/TED.2015.2405540 · 2.36 Impact Factor
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    ABSTRACT: Third-order intermodulation distortion (IM3) is an important metric for electromechanical resonators used in radio frequency signal processing applications since it characterizes the nonlinearity of the device, and the amount of in-band interference it generates when subject to unwanted, out-of-band signals. In this letter, we measure and model IM3 in a strain-engineered graphene mechanical resonator operated as a graphene resonant channel transistor (G-RCT). The device analyzed in this work has a voltage third-order intercept point (VIIP 3) of 69.5 dBm V at a gate-to-source DC bias (Vgs ) of 2.5 V, which drops to 52.1 dBm V at Vgs = 4.5 V when driven with two out-of-band input tones spaced 5 and 10 MHz from the resonant frequency. The decrease in the VIIP 3 with Vgs coincides with an increase in the transmission response (S 21) of the device, illustrating a trade-off between transduction efficiency and linearity. In addition, we find that conventional micro-electro-mechanical systems theory for IM3 calculation does not accurately describe our measurement data. To resolve this discrepancy, we develop a model for IM3 in G-RCTs that takes into account all of the output current terms present in the embedded transistor structure, as well as an effective Duffing parameter (αeff ).
    Applied Physics Letters 02/2015; 106(7):073504. DOI:10.1063/1.4913462 · 3.52 Impact Factor
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    ABSTRACT: Flexible radio-frequency (RF) electronics require materials which possess both exceptional electronic properties and high-strain limits. While flexible graphene field-effect transistors (GFETs) have demonstrated significantly higher strain limits than FETs fabricated from thin films of Si and III-V semiconductors, to date RF performance has been comparatively worse, limited to the low GHz frequency range. However, flexible GFETs have only been fabricated with modestly scaled channel lengths. In this paper, we fabricate GFETs on flexible substrates with short channel lengths of 260 nm. These devices demonstrate extrinsic unity-power-gain frequencies, fmax, up to 7.6 GHz and strain limits of 2%, representing strain limits an order of magnitude higher than the flexible technology with next highest reported fmax.
    01/2015; 3(1):44-48. DOI:10.1109/JEDS.2014.2363789
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    ABSTRACT: DNA sequencing using solid-state nanopores is, in part, impeded by the relatively high noise and low bandwidth of the current state-of-the-art translocation measurements. In this Letter, we measure the ion current noise through sub 10 nm thick Si3N4 nanopores at bandwidths up to 1 MHz. At these bandwidths, the input-referred current noise is dominated by the amplifier's voltage noise acting across the total capacitance at the amplifier input. By reducing the nanopore chip capacitance to the 1-5 pF range by adding thick insulating layers to the chip surface, we are able to transition to a regime in which input-referred current noise (∼117-150 pArms at 1 MHz in 1 M KCl solution) is dominated by the effects of the input capacitance of the amplifier itself. The signal-to-noise ratios (SNRs) reported here range from 15 to 20 at 1 MHz for dsDNA translocations through nanopores with diameters from 4 to 8 nm with applied voltages from 200 to 800 mV. Further advances in bandwidth and SNR will require new amplifier designs that reduce both input capacitance and input-referred amplifier noise.
    Nano Letters 12/2014; 14(12):7215-20. DOI:10.1021/nl504345y · 12.94 Impact Factor
  • Jacob K. Rosenstein, Serge G. Lemay, Kenneth L. Shepard
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    ABSTRACT: Experimental techniques that interface single biomolecules directly with microelectronic systems are increasingly being used in a wide range of powerful applications, from fundamental studies of biomolecules to ultra-sensitive assays. In this study, we review several technologies that can perform electronic measurements of single molecules in solution: ion channels, nanopore sensors, carbon nanotube field-effect transistors, electron tunneling gaps, and redox cycling. We discuss the shared features among these techniques that enable them to resolve individual molecules, and discuss their limitations. Recordings from each of these methods all rely on similar electronic instrumentation, and we discuss the relevant circuit implementations and potential for scaling these single-molecule bioelectronic interfaces to high-throughput arrayed sensing platforms.For further resources related to this article, please visit the WIREs website.Conflict of interest: The authors have declared no conflicts of interest for this article.
    Wiley Interdisciplinary Reviews Nanomedicine and Nanobiotechnology 12/2014; 7(4). DOI:10.1002/wnan.1323 · 4.24 Impact Factor
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    ABSTRACT: Direct 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.
    Biomedical Circuits and Systems Conference (BioCAS), 2014 IEEE, Lausanne, Switzerland; 10/2014
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    ABSTRACT: Considerable effort has recently been directed toward the miniaturization of quantitative-polymerase-chain-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.
    Lab on a Chip 08/2014; 14(20). DOI:10.1039/C4LC00443D · 5.75 Impact Factor
  • 1 edited by Eric Lagally, 05/2014; CRC Press., ISBN: 9781466594906
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    R.M. Field, Simeon Realov, K.L. Shepard
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    ABSTRACT: 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.
    IEEE Journal of Solid-State Circuits 04/2014; 49(4):867-880. DOI:10.1109/JSSC.2013.2293777 · 3.11 Impact Factor
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    ABSTRACT: 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 3.25 × 0.9 mm(2) 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.
    Nature Communications 02/2014; 5:3256. DOI:10.1038/ncomms4256 · 10.74 Impact Factor
  • Biophysical Journal 01/2014; 106(2):812a. DOI:10.1016/j.bpj.2013.11.4453 · 3.83 Impact Factor
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    ABSTRACT: This paper presents a compact virtual source (VS) model to describe carrier transport valid in both unipolar and ambipolar transport regimes in quasi-ballistic graphene field-effect transistors (GFETs). The model formulation allows for an easy extension to bilayer graphene transistors, where a bandgap can be opened. The model also includes descriptions of intrinsic terminal charges/capacitances obtained self-consistently with the transport formulation. The charge model extends from drift-diffusive transport regime to ballistic transport regime, where gradual-channel approximation (GCA) fails. The model is calibrated exhaustively against DC and S-parameter measurements of GFETs. To demonstrate the model capability for circuit-level simulations, the Verilog-A implementation of the model is used to simulate the dynamic response of frequency doubling circuits with GFETs operating in the ambipolar regime.
    2013 IEEE International Electron Devices Meeting (IEDM); 12/2013
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    ABSTRACT: Oscillators, which produce continuous periodic signals from direct current power, are central to modern communications systems, with versatile applications including timing references and frequency modulators. However, conventional oscillators typically consist of macroscopic mechanical resonators such as quartz crystals, which require excessive off-chip space. Here, we report oscillators built on micrometre-size, atomically thin graphene nanomechanical resonators, whose frequencies can be electrostatically tuned by as much as 14%. Self-sustaining mechanical motion is generated and transduced at room temperature in these oscillators using simple electrical circuitry. The prototype graphene voltage-controlled oscillators exhibit frequency stability and a modulation bandwidth sufficient for the modulation of radiofrequency carrier signals. As a demonstration, we use a graphene oscillator as the active element for frequency-modulated signal generation and achieve efficient audio signal transmission.
    Nature Nanotechnology 11/2013; DOI:10.1038/nnano.2013.232 · 33.27 Impact Factor
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    ABSTRACT: Heterostructures based on layering of two-dimensional (2D) materials such as graphene and hexagonal boron nitride represent a new class of electronic devices. Realizing this potential, however, depends critically on the ability to make high-quality electrical contact. Here, we report a contact geometry in which we metalize only the 1D edge of a 2D graphene layer. In addition to outperforming conventional surface contacts, the edge-contact geometry allows a complete separation of the layer assembly and contact metallization processes. In graphene heterostructures, this enables high electronic performance, including low-temperature ballistic transport over distances longer than 15 micrometers, and room-temperature mobility comparable to the theoretical phonon-scattering limit. The edge-contact geometry provides new design possibilities for multilayered structures of complimentary 2D materials.
    Science 11/2013; 342(6158):614-7. DOI:10.1126/science.1244358 · 31.48 Impact Factor
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    ABSTRACT: Graphene-based photodetectors have attracted strong interest for their exceptional physical properties, which include an ultrafast response1, 2, 3 across a broad spectrum4, a strong electron–electron interaction5 and photocarrier multiplication6, 7, 8. However, the weak optical absorption of graphene2, 3 limits its photoresponsivity. To address this, graphene has been integrated into nanocavities9, microcavities10 and plasmon resonators11, 12, but these approaches restrict photodetection to narrow bands. Hybrid graphene–quantum dot architectures can greatly improve responsivity13, but at the cost of response speed. Here, we demonstrate a waveguide-integrated graphene photodetector that simultaneously exhibits high responsivity, high speed and broad spectral bandwidth. Using a metal-doped graphene junction coupled evanescently to the waveguide, the detector achieves a photoresponsivity exceeding 0.1 A W−1 together with a nearly uniform response between 1,450 and 1,590 nm. Under zero-bias operation, we demonstrate response rates exceeding 20 GHz and an instrumentation-limited 12 Gbit s−1 optical data link.
    Nature Photonics 09/2013; 7(11):883-887. DOI:10.1038/nphoton.2013.253 · 29.96 Impact Factor
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    ABSTRACT: Four-turn coupled (flux-closed) inductor structures have been fabricated and tested for use in high-power-density integrated voltage regulator (IVR) applications. Our solenoid-like structure is comprised of a laminated magnetic core of four rungs surrounded by four Cu windings creating four coupled inductors. The magnetic core is made of laminations of ultra-high-vacuum-sputtered [5 nm Ta/200 nm Ca91.5Zr4.0Ta4.5 (CZT)/7 nm SiO2] repeated 20 times. Individual CZT layers are deposited under a magnetic bias to induce uniaxial anisotropy. The quad-coupled inductor shows a frequency response with a measured self-inductance of 7.4 nH for one inductor sustained up to 100 MHz and roll-off to half this low-frequency value at similar to 450 MHz. This inductance is more than 65x higher than what would be calculated from an air-core inductor of equivalent geometry.
    IEEE Transactions on Magnetics 07/2013; 49(7):4009-4012. DOI:10.1109/TMAG.2013.2237892 · 1.21 Impact Factor
  • Jacob K Rosenstein, Kenneth L Shepard
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    ABSTRACT: Here we discuss the limits to temporal resolution in nanopore sensor recordings, which arise from considerations of both small-signal frequency response and accumulated noise power. Nanopore sensors have strong similarities to patch-clamp ion channel recordings, except that the magnitudes of many physical parameters are substantially different. We will present examples from our recent work developing high-speed nanopore sensing platforms, in which we physically integrated nanopores with custom low-noise complementary metal-oxide-semiconductor (CMOS) circuitry. Close physical proximity of the sensor and amplifier electronics can reduce parasitic capacitances, improving both the signal-to-noise ratio and the effective temporal resolution of the recordings.
    Conference proceedings: ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Conference 07/2013; 2013:4110-4113. DOI:10.1109/EMBC.2013.6610449
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    ABSTRACT: The performance of graphene field-effect transistors (GFETs) strongly depends on the interfaces between the graphene layer and the supporting and top gate dielectrics. In this study, we combine our simulation approach [1] with new and existing experimental data to provide the first detailed analysis and comparison of the high-field properties of graphene on BN [2], on HfO2 (examined here for the first time) and on SiO2 [3]. These substrates each present unique scenarios because they have different (remote) phonons and different thermal conductivities, all of which influence high-field transport in GFETs.
    2013 71st Annual Device Research Conference (DRC); 06/2013

Publication Stats

5k Citations
594.05 Total Impact Points


  • 1998–2015
    • Columbia University
      • Department of Electrical Engineering
      New York, New York, United States
  • 2008
    • University of Virginia
      Charlottesville, Virginia, United States
  • 2004
    • Cadence Design Systems, Inc.
      San Jose, California, United States
  • 1999
    • Microcosm, Inc.
      Hawthorne, California, United States