ABSTRACT The kidney epithelium’s pivotal role in molecular filtration, metabolism, and excretion highlights the crucial importance of understanding kidney physiology in drug development. However, our knowledge is largely derived from non-human or non-physiological models, potentially limiting its applicability to humans. To address this significant gap, we have pioneered a human kidney epithelial microphysiological analysis platform (Epi-MAP) designed to establish, mature, and monitor renal functions of the human collecting epithelium within a physiologically relevant microenvironment. We first demonstrate the highly mature collecting duct physiology derived from human stem cells, enabled by the Epi-MAP’s microenvironments that recapitulate in vivo asymmetries in fluidic and biochemical conditions. The integrated biosensors of the Epi-MAP provide long-term, time-resolved epithelial maturation trajectories, revealing advanced integrity and functional maturity with transepithelial metrics. Furthermore, Epi-MAP’s electrophysiological analytics for measuring water flux, in conjunction with transepithelial potential and resistance, allow for real-time decoding of intricate epithelial responses to substance stimulation, showcasing its effectiveness as a robust pharmacological test model. This human cell-derived, physiologically advanced model on a chip stands as a robust in vitro tool, offering comprehensive insights into human kidney biology and significantly enhancing drug discovery process based on human physiology.
Abstract Zebrafish are a popular vertebrate model for human neurological disorders and drug discovery. Although fecundity, breeding convenience, genetic homology and optical transparency have been key advantages, laborious and invasive procedures are required for electrophysiological studies. Using an electrode-integrated microfluidic system, here we demonstrate a novel multichannel electrophysiology unit to record multiple zebrafish. This platform allows spontaneous alignment of zebrafish and maintains, over days, close contact between head and multiple surface electrodes, enabling non-invasive long-term electroencephalographic recording. First, we demonstrate that electrographic seizure events, induced by pentylenetetrazole, can be reliably distinguished from eye or tail movement artifacts, and quantifiably identified with our unique algorithm. Second, we show long-term monitoring during epileptogenic progression in a scn1lab mutant recapitulating human Dravet syndrome. Third, we provide an example of cross-over pharmacology antiepileptic drug testing. Such promising features of this integrated microfluidic platform will greatly facilitate high-throughput drug screening and electrophysiological characterization of epileptic zebrafish.
The importance of the photothermal effect in surface enhanced Raman scattering (SERS) measurements is addressed. Strong temperature gradient (≈106 K m−1) induced by photothermal effect can force molecules to move. Finally, redistributed molecules can result in a nonuniform SERS intensity. Detailed facts of importance to specialist readers are published as "Supporting Information". Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Recent outbreaks of deadly infectious diseases, such as Ebola and Middle East respiratory syndrome coronavirus, have motivated the research for accurate, rapid diagnostics that can be administered at the point of care. Nucleic acid biomarkers for these diseases can be amplified and quantified via polymerase chain reaction (PCR). In order to solve the problems of conventional PCR--speed, uniform heating and cooling, and massive metal heating blocks--an innovative optofluidic cavity PCR method using light-emitting diodes (LEDs) is accomplished. Using this device, 30 thermal cycles between 94 °C and 68 °C can be accomplished in 4 min for 1.3 μL (10 min for 10 μL). Simulation results show that temperature differences across the 750 μm thick cavity are less than 2 °C and 0.2 °C, respectively, at 94 °C and 68 °C. Nucleic acid concentrations as low as 10(-8) ng μL(-1) (2 DNA copies per μL) can be amplified with 40 PCR thermal cycles. This simple, ultrafast, precise, robust, and low-cost optofluidic cavity PCR is favorable for advanced molecular diagnostics and precision medicine. It is especially important for the development of lightweight, point-of-care devices for use in both developing and developed countries.
Precisely constructed nanoscale devices and nanoarchitectures with high spatial resolution are critically needed for applications in high-speed electronics, high-density memory, efficient solar cells, optoelectronics, plasmonics, optical antennas, chemical sensors, biological sensors, and nanospectroscopic imaging. Current methods of classical optical lithography are limited by the diffraction effect of light for nanolithography, and the state of art of e-beam or focused ion beam lithography limit the throughput and further reduction less than few nanometers for large-area batch fabrication. However, these limits can be surpassed surprisingly by utilizing the overlap of two shadow images. Here we present shadow overlap of ion-beam lithography (SOIL), which can combine the advantages of parallel processing, tunable capability of geometries, cost-effective method, and high spatial resolution nanofabrication technique. The SOIL method relies on the overlap of shadows created by the directional metal deposition and etching angles on prepatterned structures. Consequently, highly tunable patterns can be obtained. As examples, unprecedented nanoarchitectures for optical antennas are demonstrated by SOIL. We expect that SOIL can have a significant impact not only on nanoscale devices, but also large-scale (i.e., micro and macro) three-dimensional innovative lithography.
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