Pharmacology and optogenetics are widely used in neuroscience research to study the central and peripheral nervous systems. While both approaches allow for sophisticated studies of neural circuitry, continued advances are, in part, hampered by technology limitations associated with requirements for physical tethers that connect external equipment to rigid probes inserted into delicate regions of the brain. The results can lead to tissue damage and alterations in behavioral tasks and natural movements, with additional difficulties in use for studies that involve social interactions and/or motions in complex 3-dimensional environments. These disadvantages are particularly pronounced in research that demands combined optogenetic and pharmacological functions in a single experiment. Here, we present a lightweight, wireless, battery-free injectable microsystem that combines soft microfluidic and microscale inorganic light-emitting diode probes for programmable pharmacology and optogenetics, designed to offer the features of drug refillability and adjustable flow rates, together with programmable control over the temporal profiles. The technology has potential for large-scale manufacturing and broad distribution to the neuroscience community, with capabilities in targeting specific neuronal populations in freely moving animals. In addition, the same platform can easily be adapted for a wide range of other types of passive or active electronic functions, including electrical stimulation.

The clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas) systems have recently received notable attention for their applications in nucleic acid detection. Despite many attempts, the majority of current CRISPR-based biosensors in infectious respiratory disease diagnostic applications still require target preamplifications. This study reports a new biosensor for amplification-free nucleic acid detection via harnessing the trans-cleavage mechanism of Cas13a and ultrasensitive graphene field-effect transistors (gFETs). CRISPR Cas13a-gFET achieves the detection of SARS-CoV-2 and respiratory syncytial virus (RSV) genome down to 1 attomolar without target preamplifications. Additionally, we validate the detection performance using clinical SARS-CoV-2 samples, including those with low viral loads (Ct value > 30). Overall, these findings establish our CRISPR Cas13a-gFET among the most sensitive amplification-free nucleic acid diagnostic platforms to date.

Electrolytes play a pivotal role in regulating cardiovascular functions, hydration, and muscle activation. The current standards for monitoring electrolytes involve periodic sampling of blood and measurements using laboratory techniques, which are often uncomfortable/inconvenient to the subjects and add considerable expense to the management of their underlying disease conditions. The wide range of electrolytes in skin interstitial fluids (ISFs) and their correlations with those in plasma create exciting opportunities for applications such as electrolyte and circadian metabolism monitoring. However, it has been challenging to monitor these electrolytes in the skin ISFs. In this study, we report a minimally invasive microneedle-based potentiometric sensing system for multiplexed and continuous monitoring of Na+ and K+ in the skin ISFs. The potentiometric sensing system consists of a miniaturized stainless-steel hollow microneedle to prevent sensor delamination and a set of modified microneedle electrodes for multiplex monitoring. We demonstrate the measurement of Na+ and K+ in artificial ISFs with a fast response time, excellent reversibility and repeatability, adequate selectivity, and negligible potential interferences upon the addition of a physiologically relevant concentration of metabolites, dietary biomarkers, and nutrients. In addition, the sensor maintains the sensitivity after multiple insertions into the chicken skin model. Furthermore, the measurements in artificial ISFs using calibrated sensors confirm the accurate measurements of physiological electrolytes in artificial ISFs. Finally, the skin-mimicking phantom gel and chicken skin model experiments demonstrate the sensor’s potential for minimally invasive monitoring of electrolytes in skin ISFs. The developed sensor platform can be adapted for a wide range of other applications, including real-time monitoring of nutrients, metabolites, and proteins.

The real-time monitoring of neurochemical release in vivo plays a critical role in understanding the biochemical process of the complex nervous system. Current technologies for such applications, including microdialysis and fast-scan cyclic voltammetry, suffer from limited spatiotemporal resolution or poor selectivity. Here, we report a soft implantable aptamer-graphene microtransistor probe for real-time monitoring of neurochemical release. As a demonstration, we show the monitoring of dopamine with nearly cellular-scale spatial resolution, high selectivity (dopamine sensor >19-fold over norepinephrine), and picomolar sensitivity, simultaneously. Systematic benchtop evaluations, ex vivo experiments, and in vivo studies in mice models highlight the key features and demonstrate the capability of capturing the dopamine release dynamics evoked by pharmacological stimulation, suggesting the potential applications in basic neuroscience studies and studying neurological disease-related processes. The developed system can be easily adapted for monitoring other neurochemicals and drugs by simply replacing the aptamers functionalized on the graphene microtransistors.

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