[Show abstract][Hide abstract]ABSTRACT: Monitoring spatial distribution of metabolites in multicellular structures can enhance understanding of the biochemical processes and regulation involved in cellular community development. Here we report on an electrochemical camera chip capable of simultaneous spatial imaging of multiple redox-active phenazine metabolites produced by Pseudomonas aeruginosa PA14 colony biofilms. The chip features an 8 mm × 8 mm array of 1,824 electrodes multiplexed to 38 parallel output channels. Using this chip, we demonstrate potential-sweep-based electrochemical imaging of whole-biofilms at measurement rates in excess of 0.2 s per electrode. Analysis of mutants with various capacities for phenazine production reveals distribution of phenazine-1-carboxylic acid (PCA) throughout the colony, with 5-methylphenazine-1-carboxylic acid (5-MCA) and pyocyanin (PYO) localized to the colony edge. Anaerobic growth on nitrate confirms the O 2 -dependence of PYO production and indicates an effect of O 2 availability on 5-MCA synthesis. This integrated-circuit-based technique promises wide applicability in detecting redox-active species from diverse biological samples.
Full-text · Article · Jan 2016 · Nature Communications
[Show abstract][Hide abstract]ABSTRACT: There is enormous potential in combining the capabilities of the biological and the solid state to create hybrid engineered systems. While there have been recent efforts to harness power from naturally occurring potentials in living systems in plants and animals to power complementary metal-oxide-semiconductor integrated circuits, here we report the first successful effort to isolate the energetics of an electrogenic ion pump in an engineered in vitro environment to power such an artificial system. An integrated circuit is powered by adenosine triphosphate through the action of Na+/K+ adenosine triphosphatases in an integrated in vitro lipid bilayer membrane. The ion pumps (active in the membrane at numbers exceeding 2 x 10(6)mm -(2)) are able to sustain a short-circuit current of 32.6 pA mm -(2) and an open-circuit voltage of 78mV, providing for a maximum power transfer of 1.27 pW mm -(2) from a single bilayer. Two series-stacked bilayers provide a voltage sufficient to operate an integrated circuit with a conversion efficiency of chemical to electrical energy of 14.9%.
Full-text · Article · Dec 2015 · Nature Communications
[Show abstract][Hide abstract]ABSTRACT: We present the characterization of ballistic graphene field-effect transistors (GFETs) with an effective oxide thickness of 3.5 nm. Graphene channels are fully encapsulated within hexagonal boron nitride, and self-aligned contacts are formed to the edge of the single-layer graphene. Devices of channel lengths (LG) down to 67 nm are fabricated, and a virtual-source transport model is used to model the resulting current-voltage characteristics. The mobility and source-injection velocity as a function of LG yields a mean-free-path, ballistic velocity, and effective mobility of 850 nm, 9.3 x 10⁷ cm/s, and 13,700 cm²/Vs, respectively, which are among the highest velocities and mobilities reported for GFETs. Despite these best-in-class attributes, these devices achieve transconductance (gm) and output conductance (gds) of only 600 and 300 μS/μm, respectively, due to the fundamental limitations of graphene's quantum capacitance and zero-bandgap. gm values, which are less than those of comparable ballistic silicon devices, benefit from the high ballistic velocity in graphene but are degraded by an effective gate capacitance reduced by the quantum capacitance. The gds values, which limit the effective power gain achievable in these devices, are significantly worse than comparable silicon devices due to the properties of the zero-bandgap graphene channel.
No preview · Article · Oct 2015 · IEEE Transactions on Electron Devices
[Show abstract][Hide abstract]ABSTRACT: Flexible graphene field-effect transistors (GFETs) are fabricated with graphene channels fully encapsulated in hexagonal boron nitride (hBN) implementing a self-aligned fabrication scheme. Flexible GFETs fabricated with channel lengths of 2 μm demonstrate exceptional room-temperature carrier mobility (μFE = 10000 cm2 V-1s-1), strong current saturation characteristics (peak output resistance, ro = 2000 Ω), and high mechanical flexibility (strain limits of 1%). These values of μFE and ro are unprecedented in flexible GFETs. Flexible radio-frequency FETs (RF-FETs) with channel lengths of 375 nm demonstrate μFE = 2200 cm2 V-1s-1 and ro = 132.5 Ω. Unity-current-gain frequencies, fT, and unity-power-gain frequencies, fmax, reach 12.0 GHz and 10.6 GHz, respectively. The corresponding ratio of cutoff frequencies approaches unity (fmax/fT = 0.9), a record value for flexible GFETs. Intrinsic fT and fmax are 29.7 GHz and 15.7 GHz, respectively. The outstanding electronic characteristics are attributed to the improved dielectric environment provided by full hBN-encapsulation of the graphene channel in conjunction with an optimized, self-aligned device structure. These results establish hBN as a mechanically robust dielectric that can yield enhanced electronic characteristics to a diverse array of graphene-based flexible electronics.
[Show abstract][Hide abstract]ABSTRACT: This paper explores the extent to which a solid-state transmitter can be miniaturized, while still using RF for wireless information transfer and working with power densities and operating voltages comparable to what could be harvested from a living system. A 3.1 nJ/bit pulsed millimeter-wave transmitter, 300 by 300 by 250 in size, designed in 32-nm SOI CMOS, operates on an electric potential of 130 mV and 3.1 nW of dc power. Far-field data transmission at 33 GHz is achieved by supply-switching an LC-oscillator with a duty cycle of . The time interval between pulses carries information on the amount of power harvested by the radio, supporting a data rate of 1 bps. The inductor of the oscillator also acts as an electrically small on-chip antenna, which, combined with millimeter-wave operation, enables the extremely small form factor.
No preview · Article · Aug 2015 · Circuits and Systems I: Regular Papers, IEEE Transactions on
[Show abstract][Hide abstract]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.
[Show abstract][Hide abstract]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.
No preview · Article · Mar 2015 · IEEE Transactions on Electron Devices
[Show abstract][Hide abstract]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
No preview · Article · Feb 2015 · Applied Physics Letters
[Show abstract][Hide abstract]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.
No preview · Article · Jan 2015 · IEEE Journal of the Electron Devices Society
[Show abstract][Hide abstract]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.
[Show abstract][Hide abstract]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.
No preview · Article · Dec 2014 · Wiley Interdisciplinary Reviews Nanomedicine and Nanobiotechnology
[Show abstract][Hide abstract]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.
[Show abstract][Hide abstract]ABSTRACT: 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.
[Show abstract][Hide abstract]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.
[Show abstract][Hide abstract]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.
[Show abstract][Hide abstract]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.
Full-text · Article · Feb 2014 · Nature Communications