Boyan Penkov , David Niedzwiecki , Nicolae Lari, Marija Drndic, Kenneth Shepard, “Time-domain event detection using single-instruction, multiple-thread gpGPU architectures in single-molecule biophysical data, ” Computer Physics Communications 300, 109191 (2024)
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Discrete amplitude levels in ordered, time-domain data often represent different underlying latent states of the system that is being interrogated. Analysis and feature extraction from these data sets generally requires considering the order of each individual point; this approach cannot take advantage of contemporary general-purpose graphics processing units (gpGPU) and single-instruction multiple-data (SIMD) instruction set architectures. Two sources of such data from single-molecule biological measurements are nanopores and single- molecule field effect transistor (smFET) nanotube devices; both generate streams of time-ordered current or voltage data, typically sampled near 1 MS/s, with run times of minutes, yielding terabyte-scale datasets. Here, we present three gpGPU-based algorithms to overcome limitations associated with serial event detection in time series data, resulting in a 250× improvement in the rate with which we can detect salient features in nanopore and smFET datasets. The code is freely available.
Gilhotra, Y., Overhauser, H., Yin, H., Pollmann, E.H., Eichler, G., Cheng, A., Jung, T., Zeng, N., Carloni, L.P., and Shepard, K.L., “A Wireless Subdural Optical Cortical Interface Device with 768 Co-Packaged Micro-LEDs for Fluorescence Imaging and Optogenetic Stimulation“. In 2024 IEEE Custom Integrated Circuits Conference (CICC) (pp. 1-2). IEEE.
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One of the goals of neuroengineering is to establish high-bandwidth, fully implantable, and minimally invasive wireless neural interfaces that help interrogate neural circuits in freely moving and socially behaving animals. Optical interfaces offer advantages over electrophysiological techniques such as cell-type specificity, low cross-talk bidirectionality, and wide field-of-view (FoV). While most optical interfaces to-date have taken the form of bulky “mini-scopes”, recent advances in optical interfaces have shown promise in achieving high-resolution, volume-efficient brain interfacing over large FoVs with devices accommodated entirely within the subdural space [1, 2]. These devices, however, still require wired connection through the skull, negating advantages of their volumetric efficiency.
Ilke Uguz, David Ohayon, Sinan Yilmax, Sophie Griggs, Rajendar Sheelamanthula, Jason Fabbri, Iain McCulloch, Sahika Inal, and K. L. Shepard, Complementary integration of organic electrochemical transistors for front-end amplifier circuits of flexible neural implants. Science Advances 10, eadi9710(2024).
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The development of neural probes, capable of on-site amplification and signal conditioning of neuronal signals, has been an increasingly important focus of neurotechnology research in the past few decades (1–3). However, the current state-of-the-art, silicon-based technology is limited by the rigidity of the implants where the hard electrodes do not match the softness and the constant, dynamic movement of the brain, creating damage upon implantation and chronic inflammation (4). Here, we instead develop integrated circuits for this front-end analog signal processing in neural recording applications using soft, flexible semiconductors with dual ionic-electronic conductivity.
Ilke Uguz, David Ohayon, Volkan Arslan, Rajendar Sheelamanthula, Sophie Griggs, Adel Hama, John William Stanton, Iain McCulloch, Sahika Inal & Kenneth L. Shepard Flexible switch matrix addressable electrode arrays with organic electrochemical transistor and pn diode technology 15 January 2024 Nature Communications
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Due to their effective ionic-to-electronic signal conversion and mechanical flexibility, organic neural implants hold considerable promise for biocompatible neural interfaces. Current approaches are, however, primarily limited to passive electrodes due to a lack of circuit components to realize complex active circuits at the front-end. Here, we introduce a p-n organic electrochemical diode using complementary p- and n-type conducting polymer films embedded in a 15-μm -diameter vertical stack. Leveraging the efficient motion of encapsulated cations inside this polymer stack and the opposite doping mechanisms of the constituent polymers, we demonstrate high current rectification ratios () and fast switching speeds (230 μs). We integrate p-n organic electrochemical diodes with organic electrochemical transistors in the front-end pixel of a recording array. This configuration facilitates the access of organic electrochemical transistor output currents within a large network operating in the same electrolyte, while minimizing crosstalk from neighboring elements due to minimized reverse-biased leakage. Furthermore, we use these devices to fabricate time-division-multiplexed amplifier arrays. Lastly, we show that, when fabricated in a shank format, this technology enables the multiplexing of amplified local field potentials directly in the active recording pixel (26-μm diameter) in a minimally invasive form factor with shank cross-sectional dimensions of only 50×8 .
Yoonhee Lee, Jakob Buchheim, Björn Hellenkamp, David Lynall, Kyungae Yang, Erik F. Young, Boyan Penkov, Samuel Sia, Milan N. Stojanovic & Kenneth L. Shepard Carbon-nanotube field-effect transistors for resolving single-molecule aptamer–ligand binding kinetics. 17 January 2024 Nature Nanotechnology
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Small molecules such as neurotransmitters are critical for biochemical functions in living systems. While conventional ultraviolet–visible spectroscopy and mass spectrometry lack portability and are unsuitable for time-resolved measurements in situ, techniques such as amperometry and traditional field-effect detection require a large ensemble of molecules to reach detectable signal levels. Here we demonstrate the potential of carbon-nanotube-based single-molecule field-effect transistors (smFETs), which can detect the charge on a single molecule, as a new platform for recognizing and assaying small molecules. smFETs are formed by the covalent attachment of a probe molecule, in our case a DNA aptamer, to a carbon nanotube. Conformation changes on binding are manifest as discrete changes in the nanotube electrical conductance. By monitoring the kinetics of conformational changes in a binding aptamer, we show that smFETs can detect and quantify serotonin at the single-molecule level, providing unique insights into the dynamics of the aptamer–ligand system. In particular, we show the involvement of G-quadruplex formation and the disruption of the native hairpin structure in the conformational changes of the serotonin–aptamer complex. The smFET is a label-free approach to analysing molecular interactions at the single-molecule level with high temporal resolution, providing additional insights into complex biological processes.