Integrated circuit-based electrochemical sensor for spatially resolved detection of redox-active metabolites in biofilms

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 mm2 area can be captured with a diffusion-limited spatial resolution of 750 mm. We demonstrate that square wave voltammetry can be used to detect, identify and quantify (for concentrations as low as 2.6 mM) 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

A Single-Photon Avalanche Diode Imager for Fluorescence Lifetime Applications

A 64-by-64-pixel CMOS single-photon avalanche diode (SPAD) imager for time-resolved fluorescence detection features actively quenched and reset pixels, allowing gated detection to eliminate pile-up nonlinearities common to most time-correlated single-photon counting (TCSPC) approaches. Timing information is collected using an on-chip time-to-digital converter (TDC) based on a counter and a supply-regulated delay-locked loop (DLL)

Race to the Bottom: Malicious Hardware

Increasingly, hardware design and fabrication has come to resemble that of software: hardware logic modules (resembling software libraries) are licensed from third parties and combined in designs of greater complexity, while the fabrication is outsourced to a low-cost manufacturer or otherwise off-shored

High-density integration of ultrabright OLEDs on a miniaturized needle-shaped CMOS backplane

This work was supported in part by the Defense Advanced Research Projects Agency (DARPA) under Contract N6600117C4012, by the National Institutes of Health under Grant U01NS090596, and by the Leverhulme Trust (RPG-2017-231). C.K.M. acknowledges funding from the European Commission through a Marie Skłodowska Curie individual fellowship (101029807). M.C.G. acknowledges funding from the Alexander von Humboldt Stiftung (Humboldt-Professorship). We thank Aaron Naden for the FIB/STEM measurements (Engineering and Physical Sciences Research Council under grant numbers EP/L017008/1, EP/R023751/1 and EP/T019298/1).Direct deposition of organic light-emitting diodes (OLEDs) on silicon-based complementary metal–oxide–semiconductor (CMOS) chips has enabled self-emissive microdisplays with high resolution and fill-factor. Emerging applications of OLEDs in augmented and virtual reality (AR/VR) displays and in biomedical applications, e.g., as brain implants for cell-specific light delivery in optogenetics, require light intensities orders of magnitude above those found in traditional displays. Further requirements often include a microscopic device footprint, a specific shape and ultrastable passivation, e.g., to ensure biocompatibility and minimal invasiveness of OLED-based implants. In this work, up to 1024 ultrabright, microscopic OLEDs are deposited directly on needle-shaped CMOS chips. Transmission electron microscopy and energy-dispersive X-ray spectroscopy are performed on the foundry-provided aluminum contact pads of the CMOS chips to guide a systematic optimization of the contacts. Plasma treatment and implementation of silver interlayers lead to ohmic contact conditions and thus facilitate direct vacuum deposition of orange- and blue-emitting OLED stacks leading to micrometer-sized pixels on the chips. The electronics in each needle allow each pixel to switch individually. The OLED pixels generate a mean optical power density of 0.25 mW mm−2, corresponding to >40 000 cd m−2, well above the requirement for daylight AR applications and optogenetic single-unit activation in the brain.Publisher PDFPeer reviewe

The Wooster Voice (Wooster, OH), 1997-10-16

This edition of the College of Wooster student run newspaper was published on October 16 of 1997 and it is twelve pages long. Jilted surgeon general calls for more health education, Dr. Jocelyn Elders presents during the Wooster Forum series about health care and education. Ebert to be dedicated this weekend, the Ebert Art Center is going to be formally dedicated. Renowned musical trio combines classical with new, the Cleveland Duo and saxophonist James Umble perform at the Gault Recital Hall. Athletic updates for the past week are highlighted on pages ten to twelve.https://openworks.wooster.edu/voice1991-2000/1177/thumbnail.jp

The Pseudomonas aeruginosa Efflux Pump MexGHI-OpmD Transports a Natural Phenazine that Controls Gene Expression and Biofilm Development

Redox-cycling compounds, including endogenously produced phenazine antibiotics, induce expression of the efflux pump MexGHI-OpmD in the opportunistic pathogen Pseudomonas aeruginosa Previous studies of P. aeruginosa virulence, physiology, and biofilm development have focused on the blue phenazine pyocyanin and the yellow phenazine-1-carboxylic acid (PCA). In P. aeruginosa phenazine biosynthesis, conversion of PCA to pyocyanin is presumed to proceed through the intermediate 5-methylphenazine-1-carboxylate (5-Me-PCA), a reactive compound that has eluded detection in most laboratory samples. Here, we apply electrochemical methods to directly detect 5-Me-PCA and find that it is transported by MexGHI-OpmD in P. aeruginosa strain PA14 planktonic and biofilm cells. We also show that 5-Me-PCA is sufficient to fully induce MexGHI-OpmD expression and that it is required for wild-type colony biofilm morphogenesis. These physiological effects are consistent with the high redox potential of 5-Me-PCA, which distinguishes it from other well-studied P. aeruginosa phenazines. Our observations highlight the importance of this compound, which was previously overlooked due to the challenges associated with its detection, in the context of P. aeruginosa gene expression and multicellular behavior. This study constitutes a unique demonstration of efflux-based self-resistance, controlled by a simple circuit, in a Gram-negative pathogen

Optogenetic stimulation probes with single-neuron resolution based on organic LEDs monolithically integrated on CMOS

Funding: This work was supported in part by the Defense Advanced Research Projects Agency (DARPA) under contract N6600117C4012, by the National Institutes of Health under grant U01NS090596, by the Leverhulme Trust (RPG-2017-231) and by the Alexander von Humboldt Stiftung (Humboldt-Professorship to M.C.G.). This work was performed in part at the Columbia Nano Initiative cleanroom facility, at the CUNY Advanced Science Research Center Nanofabrication Facility, and at the Singh Center for Nanotechnology, part of the National Nanotechnology Coordinated Infrastructure Program, which is supported by the National Science Foundation grant NNCI-2025608. C.-K.M. acknowledges funding from the European Commission through a Marie-Skłodowska Curie Individual Fellowship (101029807).The use of optogenetic stimulation to evoke neuronal activity in targeted neural populations—enabled by opsins with fast kinetics, high sensitivity and cell-type and subcellular specificity—is a powerful tool in neuroscience. However, to interface with the opsins, deep-brain light delivery systems are required that match the scale of the spatial and temporal control offered by the molecular actuators. Here we show that organic light-emitting diodes can be combined with complementary metal–oxide–semiconductor technology to create bright, actively multiplexed emissive elements. We create implantable shanks in which 1,024 individually addressable organic light-emitting diode pixels with a 24.5 µm pitch are integrated with active complementary metal–oxide–semiconductor drive and control circuitry. This integration is enabled by controlled electrode conditioning, monolithic deposition of the organic light-emitting diodes and optimized thin-film encapsulation. The resulting probes can be used to access brain regions as deep as 5 mm and selectively activate individual neurons with millisecond-level precision in mice.Publisher PDFPeer reviewe