Design and validation of a low-cost photomodulator for in vivo photoactivation of a mGluR5 inhibitor.

Purpose: Severe side effects prevent the utilization of otherwise promising drugs in treatments. These side effects arise when drugs affect untargeted tissues due to poor target specificity. In photopharmacology, light controls the timing and the location of drug delivery, improving treatment specificity and pharmacokinetic control. Photopharmaceuticals have not seen widespread adoption in part because researchers do not always have access to reliable and reproducible light delivery devices at prices which fit within the larger research budget. Method: In this work, we present a customizable photomodulator for use in both wearable and implantable devices. For experimental validation of the photomodulator, we photolyse JF-NP-26 in rats. Results: We successfully drive in vivo photopharmacology with a tethered photomodulator and demonstrate modifications which enable the photomodulator to operate wirelessly. Conclusion: By documenting our photomodulator development, we hope to introduce researchers to a simple solution which significantly lowers the engineering barriers to photopharmacology research. Graphical abstract: Researchers present a photomodulator, a device designed to facilitate in vivo photopharmacology. They demonstrate the in vivo capabilities of the photomodulator by photoreleasing raseglurant, an mGluR5 inhibitor, to treat pain in an acute rat model and follow this study by showing how to reconfigure the photomodulator to work wirelessly and interface with other biomedical devices. Supplementary Information: The online version contains supplementary material available at 10.1007/s13534-023-00334-3.

Smart capsule for monitoring inflammation profile throughout the gastrointestinal tract.

Inflammatory bowel disease (IBD) has become alarmingly prevalent in the last two decades affecting 6.8 million people worldwide with a starkly high relapse rate of 40% within 1 year of remission. Existing visual endoscopy techniques rely on subjective assessment of images that are error-prone and insufficient indicators of early-stage IBD, rendering them unsuitable for frequent and quantitative monitoring of gastrointestinal health necessary for detecting regular relapses in IBD patients. To address these limitations, we have implemented a miniaturized smart capsule (2.2 cm × 11 mm) that allows monitoring reactive oxygen species (ROS) levels as a biomarker of inflammation for quantitative and frequent profiling of inflammatory lesions throughout the gastrointestinal tract. The capsule is composed of a pH and oxidation reduction potential (ORP) sensor to track the capsule's location and ROS levels throughout the gastrointestinal tract, respectively, and an optimized electronic interface for wireless sensing and data communication. The designed sensors provided a linear and stable performance within the physiologically relevant range of the GI tract (pH: 1-8 and ORP: -500 to +500 mV). Additionally, systematic design optimization of the wireless interface electronics offered an efficient sampling rate of 10 ms for long-running measurements up to 48 h for a complete evaluation of the entire gastrointestinal tract. As a proof-of-concept, the capsule the capsule's performance in detecting inflammation risks was validated by conducting tests on in vitro cell culture conditions, simulating healthy and inflamed gut-like environments. The capsule presented here achieves a new milestone in addressing the emerging need for smart ingestible electronics for better diagnosis and treatment of digestive diseases.

Ground and excited electronic state analysis of PrF²âº and PmF²âº.

The ground state and excited state manifolds are computed for PrF(2+) and PmF(2+) at the CASSCF (n,8) level of theory where the active space spans the Ln 4f orbitals as well as the F 2pz orbital. Dynamical correlation is included using second-order multireference quasidegenerate perturbation theory (MCQDPT2). The spin-orbit multiplets for each of the excited states are resolved, and spin-orbit coupling constants are computed using the Breit-Pauli spin-orbit operator. Equilibrium geometries for each of the ground and excited states are computed, and the nature of the Ln-F bond is examined. Potential energy curves for the lowest four triplet states and lowest two quintet states are computed for PrF(2+), which split into 14 levels upon application of the spin-orbit Hamiltonian. Likewise, the lowest six quintet states are computed for PmF(2+) as well as the lowest triplet state and the lowest two septet states. These nine states split into 43 terms upon application of the spin-orbit Hamiltonian.