Publications by authors named "Yu-Hwa Lo"

Back-end-of-line (BEOL)-compatible complementary field-effect transistor (CFET), which vertically integrates p-channel and n-channel thin-film transistors (TFT) in a 3D architecture on Si-CMOS, is critical for next-generation electronics, enabling higher functionality and improved energy efficiency. However, the absence of a high-performance BEOL-compatible p-channel TFT, the counterpart of n-channel oxide-TFT, continues to pose a significant challenge for the development of wafer-scale CFET technology. Tellurium (Te) has recently emerged as a promising candidate for p-channel TFT, but its device performance is not yet satisfactory.

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As an emerging platform gaining significant attention from the biomedical community, multiplexed fluorescent imaging from imaging flow cytometry enables simultaneous detection of numerous biological targets within a single cell. Due to the spectral overlap, signals from one fluorophore can bleed into other detection channels, leading to spillover artifacts, which cause erroneous results and false discoveries. Existing color compensation algorithms use special samples to calibrate the fluorophores individually, a time-consuming and laborious process that is cumbersome and hard to scale.

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Predicting the properties of tissues or organisms from the genomics data is widely accepted by the medical community. Here we ask a question: can we predict the properties of each individual cell? Single-cell genomics does not work because the RNA sequencing process destroys the cell, not allowing us to verify our predictions. To test the hypothesis, we investigate the approach of using AI to analyze single-cell images obtained from a 3D imaging flow cytometer.

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Quantitative optical phase information provides an alternative method to observe biomedical properties, where conventional phase imaging fails. Phase retrieval typically requires multiple intensity measurements and iterative computations to ensure uniqueness and robustness against detection noise. To increase the measurement speed, we propose a single-shot quantitative phase imaging method with metasurface optics that can be conveniently integrated into conventional imaging systems with minimal modification.

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In this study, we present ultrasensitive infrared photodiodes based on PbS colloidal quantum dots (CQDs) using a double photomultiplication strategy that utilizes the accumulation of both electron and hole carriers. While electron accumulation was induced by ZnO trap states that were created by treatment in a humid atmosphere, hole accumulation was achieved using a long-chain ligand that increased the barrier to hole collection. Interestingly, we obtained the highest responsivity in photo-multiplicative devices with the long ligands, which contradicts the conventional belief that shorter ligands are more effective for optoelectronic devices.

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A primary challenge of high-throughput imaging flow cytometry (IFC) is to analyze the vast amount of imaging data, especially in applications where ground truth labels are unavailable or hard to obtain. We present an unsupervised deep embedding algorithm, the Deep Convolutional Autoencoder-based Clustering (DCAEC) model, to cluster label-free IFC images without any prior knowledge of input labels. The DCAEC model first encodes the input images into the latent representations and then clusters based on the latent representations.

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Colloidal quantum dots (CQDs) are finding increasing applications in optoelectronic devices, such as photodetectors and solar cells, because of their high material quality, unique and attractive properties, and process flexibility without the constraints of lattice match and thermal budget. However, there is no adequate device model for colloidal quantum dot heterojunctions, and the popular Shockley-Quiesser diode model does not capture the underlying physics of CQD junctions. Here, we develop a compact, easy-to-use model for CQD devices rooted in physics.

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Sample preparation is essential for nucleic acid assays, affecting their sensitivity and reliability. However, this process often results in a significant loss or dilution of the analyte, which becomes a bottleneck that limits downstream assay performance, particularly for assays that accept a limited input sample volume. To overcome this challenge, we present an evaporative-based sample enrichment method that uses an airjet to concentrate analytes within a small, defined volume by reversing the coffee-ring effect.

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Evaluation of Gastrointestinal Stromal Tumors (GIST) during initial clinical staging, surgical intervention, and postoperative management can be challenging. Current imaging modalities (, PET and CT scans) lack sensitivity and specificity. Therefore, advanced clinical imaging modalities that can provide clinically relevant images with high resolution would improve diagnosis.

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Classification and sorting of cells using image-activated cell sorting (IACS) systems can bring significant insight to biomedical sciences. Incorporating deep learning algorithms into IACS enables cell classification and isolation based on complex and human-vision uninterpretable morphological features within a heterogeneous cell population. However, the limited capabilities and complicated implementation of deep learning-assisted IACS systems reported to date hinder the adoption of the systems for a wide range of biomedical research.

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In this paper, we investigate the temperature sensitivity of gain and breakdown voltage of detectors based on cycling excitation process (CEP), an internal signal amplification mechanism found in amorphous silicon (a-Si). Changes in gain and breakdown voltage with temperature can result in pixel-to-pixel signal variation in a focal plane array and variations in photon detection efficiency for single photon detectors. We have demonstrated athermalized CEP detectors with their gain and breakdown voltage being nearly temperature independent from 200 K to 350 K, covering the temperature range for practical applications.

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Compared with their three-dimensional (3D) counterparts, low-dimensional metal halide perovskites (2D and quasi-2D; BAMX, such as B = R-NH, A = HC(NH), Cs; M = Pb, Sn; X = Cl, Br, I) with periodic inorganic-organic structures have shown promising stability and hysteresis-free electrical performance. However, their unique multiple-quantum-well structure limits the device efficiencies because of the grain boundaries and randomly oriented quantum wells in polycrystals. In single crystals, the carrier transport through the thickness direction is hindered by the layered insulating organic spacers.

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To improve the understanding of the complex biological process underlying the development of non-alcoholic steatohepatitis (NASH), 3D imaging flow cytometry (3D-IFC) with transmission and side-scattered images were used to characterize hepatic stellate cell (HSC) and liver endothelial cell (LEC) morphology at single-cell resolution. In this study, HSC and LEC were obtained from biopsy-proven NASH subjects with early-stage NASH (F2-F3) and healthy controls. Here, we applied single-cell imaging and 3D digital reconstructions of healthy and diseased cells to analyze a spatially resolved set of morphometric cellular and texture parameters that showed regression with disease progression.

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The global pandemic caused by the SARS-CoV-2 virus has underscored the need for rapid, simple, scalable, and high-throughput multiplex diagnostics in non-laboratory settings. Here we demonstrate a multiplex reverse-transcription loop-mediated isothermal amplification (RT-LAMP) coupled with a gold nanoparticle-based lateral flow immunoassay (LFIA) capable of detecting up to three unique viral gene targets in 15 min. RT-LAMP primers associated with three separate gene targets from the SARS-CoV-2 virus (Orf1ab, Envelope, and Nucleocapsid) were added to a one-pot mix.

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We develop a high-throughput technique to relate positions of individual cells to their three-dimensional (3D) imaging features with single-cell resolution. The technique is particularly suitable for nonadherent cells where existing spatial biology methodologies relating cell properties to their positions in a solid tissue do not apply. Our design consists of two parts, as follows: recording 3D cell images at high throughput (500 to 1,000 cells/s) using a custom 3D imaging flow cytometer (3D-IFC) and dispensing cells in a first-in-first-out (FIFO) manner using a robotic cell placement platform (CPP).

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Non-invasive measurement of the arterial blood speed gives important health information such as cardio output and blood supplies to vital organs. The magnitude and change in arterial blood speed are key indicators of the health conditions and development and progression of diseases. We demonstrated a simple technique to directly measure the blood flow speed in main arteries based on the diffused light model.

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Vision loss from diseases of the outer retina, such as age-related macular degeneration, is among the leading causes of irreversible blindness in the world today. The goal of retinal prosthetics is to replace the photo-sensing function of photoreceptors lost in these diseases with optoelectronic hardware to electrically stimulate patterns of retinal activity corresponding to vision. To enable high-resolution retinal prosthetics, the scale of stimulating electrodes must be significantly decreased from current designs; however, this reduces the amount of stimulating current that can be delivered.

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This paper presents an 8-channel array of low-noise (30.3 fA/√Hz) current sensing front-ends with on-chip microelectrode electrochemical sensors. The analog front-end (AFE) consists of a 1-order continuous-time delta-sigma (CT ΔΣ) modulator that achieves 123 fA sensitivity over a 10 Hz bandwidth and 139 dB cross-scale dynamic range with a 2-bit programmable current reference.

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Article Synopsis
  • Microfluidic paper-based analytical devices (μPADs) are crucial for point-of-care testing but often lack sensitivity and handling of complex assays.
  • A new airflow-based evaporative method enhances μPAD functionality by increasing sensitivity 100-1000 times through fluid manipulation on paper membranes.
  • This technique has successfully improved multistep assays like LAMP for COVID-19 detection and ELISA, achieving remarkable sensitivity enhancements and clearer results.
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The microfluidic-based, label-free image-guided cell sorter offers a low-cost, high information content, and disposable solution that overcomes many limitations in conventional cell sorters. However, flow confinement for most microfluidic devices is generally only one-dimensional using sheath flow. As a result, the equilibrium distribution of cells spreads beyond the focal plane of commonly used Gaussian laser excitation beams, resulting in a large number of blurred images that hinder subsequent cell sorting based on cell image features.

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Organic-inorganic hybrid perovskites have electronic and optoelectronic properties that make them appealing in many device applications. Although many approaches focus on polycrystalline materials, single-crystal hybrid perovskites show improved carrier transport and enhanced stability over their polycrystalline counterparts, due to their orientation-dependent transport behaviour and lower defect concentrations. However, the fabrication of single-crystal hybrid perovskites, and controlling their morphology and composition, are challenging.

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Understanding the binding affinities and kinetics of protein-ligand interactions using a label-free method is crucial for identifying therapeutic candidates in clinical diagnostics and drug development. In this work, the IGZO-TFT (thin-film transistor) biosensor integrated with a tailored microfluidic chip was developed to explore binding kinetics of protein-ligand biochemical interactions in the real-time manner. The IGZO-TFT sensor extracts the binding characteristics through sensing biomolecules by their electrical charges.

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Quantitative information about protein-ligand interactions is central to drug discovery. To obtain the quintessential reaction dissociation constant, ideally measurements of reactions should be performed without perturbations by molecular labeling or immobilization. The technique of transient induced molecular electrical signal (TIMES) has provided a promising technique to meet such requirements, and its performance in a microfluidic environment further offers the potential for high throughput and reduced consumption of reagents.

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Organometallic halide perovskites attract strong interests for their high photoresponsivity and solar cell efficiency. However, there was no systematic study of their power- and frequency-dependent photoresponsivity. We identified two different power-dependent photoresponse types in methylammonium lead iodide perovskite (MAPbI) photodetectors.

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Optoelectronic retinal prostheses transduce light into electrical current for neural stimulation. We introduce a novel optoelectronic pixel architecture consisting of a vertically integrated photo junction-field-effect transistor (Photo-JFET) and neural stimulating electrode. Experimental measurements demonstrate that optically addressed Photo-JFET pixels utilize phototransistive gain to produce a broad range of neural stimulation current and can effectively stimulate retinal neurons in vitro.

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