Raudel Avila

Miniaturized implantable optoelectronic technologies for in vivo biomedical applications are gaining interest, but require strict thermal management for safe operation. Here, we introduce a comprehensive framework combining analytical solutions and numerical modeling to estimate and manage thermal effects of optoelectronic devices. We propose Green's functions to analytically solve temperature distributions in tissue from a point source with coupled thermal-optical power, capturing the influence of critical tissue properties and spatiotemporal parameters. Integrating the Green's function derives temperature distributions for sources with definable geometry. Numerical modeling defines scaling factors to account for variations in radiation patterns and material designs, enabling direct performance comparisons across systems. Guided by this framework, iterative optimization of a filamentary optogenetic probe for deep brain stimulation significantly reduces thermal loads while preserving typical behaviors in freely moving mice. Experimental validation through in vitro and in vivo characterization demonstrates scalable strategies to overcome thermal challenges in advanced bio-optoelectronic systems.

Abstract Precise spatial regulation of site-specific DNA recombination (SSR) in vivo remains a challenge due to limited tunability of current platforms. Here, we present an optogenetic approach that overcome these limitations by employing engineered light-regulated recombinase E-LightR-Cre and tunable wireless implantable optoelectronic devices. E-LightR-Cre meets the key criteria for spatial regulation of SSR in vivo , showing no detectable activity in the dark, while demonstrating robust activation upon blue-light illumination. To achieve local E-LightR-Cre activation in murine lungs, we developed wireless, fully-implantable optoelectronic devices enabling focal illumination with no discernible organ damage. By modulating illumination intensity and duration, we can control the size of the activated area. Local expression of oncogenic KRas-G12D in a photoactivated subpopulation of cells in vitro revealed rapid reprogramming of the mutant expressing cells and their non-activated neighbors. Light-guided activation of E-LightR-Cre in mouse lungs resulted in focal expression of a reporter gene and allowed us to induce local formation of oncogenic lesions in vivo .

Wireless bioresorbable electrical stimulators have broad potential as therapeutic implants. Such devices operate for a clinically relevant duration and then harmlessly dissolve, eliminating the need for surgical removal. A representative application is in treating peripheral nerve injuries through targeted stimulation at either proximal or distal sites, with operation for up to one week. This report introduces enhanced devices with additional capabilities: (1) simultaneous stimulation of both proximal and distal sites, and (2) robust operation for as long as several months, all achieved with materials that naturally resorb by hydrolysis in surrounding biofluids. Systematic investigations of the materials and design aspects highlight the key features that enable dual stimulation and with enhanced stability. Animal model studies illustrate beneficial effects in promoting peripheral nerve regeneration, as quantified by increased total muscle and muscle fiber cross-sectional area and compound muscle action potentials. These findings expand the clinical applications of bioresorbable stimulators, particularly for long-term nerve regeneration and continuous neuromodulation-based monitoring. Wireless bioresorbable stimulators are promising therapeutic implants that naturally dissolve after use. Here, the authors developed a device that operates for months and enables simultaneous multi-site stimulation, preventing early muscle atrophy and accelerating reinnervation in nerve injury models.

Summary Neurotechnologies and genetic tools for dissecting neural circuit functions have advanced rapidly over the past decade, although the development of complementary pharmacological methodologies has comparatively lagged. Understanding the precise pharmacological mechanisms of neuroactive compounds is critical for advancing basic neurobiology and neuropharmacology, as well as for developing more effective treatments for neurological and neuropsychiatric disorders. However, integrating modern tools for assessing neural activity in large-scale neural networks with spatially localized drug delivery remains a major challenge. Here, we present a dual microfluidic-photometry platform that enables simultaneous intracranial drug delivery with neural dynamics recording in the rodent brain. The integrated platform combines a wireless, battery-free, miniaturized fluidic microsystem with optical probes, allowing for spatially and temporally restricted drug delivery while sensing activity-dependent fluorescence using genetically encoded calcium indicators (GECIs), neurotransmitter sensors, and neuropeptide sensors. We demonstrate the performance of this platform for investigating neuropharmacological mechanisms in vivo in behaving mice.

Real-time monitoring of hydration biomarkers in tandem with biophysical markers can offer valuable physiological insights about heat stress and related thermoregulatory response. These metrics have been challenging to achieve with wearable sensors. Here we present a closed-loop electrochemical/biophysical wearable sensing device and algorithms that directly measure whole-body sweat loss, sweating rate, sodium concentration, and sodium loss with electrode arrays embedded in a microfluidic channel. The device contains two temperature sensors for skin temperature and thermal flux recordings, and an accelerometer for real-time monitoring of activity level. An onboard haptic module enables vibratory feedback cues to the wearer once critical sweat loss thresholds are reached. Data is stored onboard in memory and autonomously transmitted via Bluetooth to a smartphone and cloud portal. Field studies conducted in physically demanding activities demonstrate the key capabilities of this platform to inform hydration interventions in highly challenging real-world settings.

Sensations of heat and touch produced by receptors in the skin are of essential importance for perceptions of the physical environment, with a particularly powerful role in interpersonal interactions. Advances in technologies for replicating these sensations in a programmable manner have the potential not only to enhance virtual/augmented reality environments but they also hold promise in medical applications for individuals with amputations or impaired sensory function. Engineering challenges are in achieving interfaces with precise spatial resolution, power-efficient operation, wide dynamic range, and fast temporal responses in both thermal and in physical modulation, with forms that can extend over large regions of the body. This paper introduces a wireless, skin-compatible interface for thermo-haptic modulation designed to address some of these challenges, with the ability to deliver programmable patterns of enhanced vibrational displacement and high-speed thermal stimulation. Experimental and computational investigations quantify the thermal and mechanical efficiency of a vertically stacked design layout in the thermo-haptic stimulators that also supports real-time, closed-loop control mechanisms. The platform is effective in conveying thermal and physical information through the skin, as demonstrated in the control of robotic prosthetics and in interactions with pressure/temperature-sensitive touch displays.

Abstract Neurotechnologies and genetic tools for dissecting neural circuit functions have advanced rapidly over the past decade, although the development of complementary pharmacological method-ologies has comparatively lagged. Understanding the precise pharmacological mechanisms of neuroactive compounds is critical for advancing basic neurobiology and neuropharmacology, as well as for developing more effective treatments for neurological and neuropsychiatric disorders. However, integrating modern tools for assessing neural activity in large-scale neural networks with spatially localized drug delivery remains a major challenge. Here, we present a dual microfluidic-photometry platform that enables simultaneous intracranial drug delivery with neural dynamics monitoring in the rodent brain. The integrated platform combines a wireless, battery-free, miniaturized fluidic microsystem with optical probes, allowing for spatially and temporally specific drug delivery while recording activity-dependent fluorescence using genetically encoded calcium indicators (GECIs), neurotransmitter sensors GRAB NE and GRAB DA , and neuropeptide sensors. We demonstrate the performance this platform for investigating neuropharmacological mechanisms in vivo and characterize its efficacy in probing precise mechanistic actions of neuroactive compounds across several rapidly evolving neuroscience domains.

Continuous monitoring of biomarkers at locations adjacent to targeted internal organs can provide actionable information about postoperative status beyond conventional diagnostic methods. As an example, changes in pH in the intra-abdominal space after gastric surgeries can serve as direct indicators of potentially life-threatening leakage events, in contrast to symptomatic reactions that may delay treatment. Here, we report a bioresorbable, wireless, passive sensor that addresses this clinical need, designed to locally monitor pH for early detection of gastric leakage. A pH-responsive hydrogel serves as a transducer that couples to a mechanically optimized inductor-capacitor circuit for wireless readout. This platform enables real-time monitoring of pH with fast response time (within 1 hour) over a clinically relevant period (up to 7 days) and timely detection of simulated gastric leaks in animal models. These concepts have broad potential applications for temporary sensing of relevant biomarkers during critical risk periods following diverse types of surgeries.

Wireless Wearables In article number 2302256, John A. Rogers, Ralph G. Nuzzo, Yonggang Huang, and co-workers report a miniaturized, wireless mechanoacoustic sensor, encapsulated with a self-healing, dynamic covalent elastomer, embedded with chemistries that provide colorimetric responses, strain-adaptive stiffening, and thermal insulation properties relevant to the safety of wireless, skin-interfaced bioelectronic device use and operation. These multifunctional materials design strategies can immediately apply to wide ranging classes of devices, and also inspire the development of additional, complementary materials strategies for safe operation of bioelectronic systems.

Abstract Many recently developed classes of wireless, skin‐interfaced bioelectronic devices rely on conventional thermoset silicone elastomer materials, such as poly(dimethylsiloxane) (PDMS), as soft encapsulating structures around collections of electronic components, radio frequency antennas and, commonly, rechargeable batteries. In optimized layouts and device designs, these materials provide attractive features, most prominently in their gentle, noninvasive interfaces to the skin even at regions of high curvature and large natural deformations. Past studies, however, overlook opportunities for developing variants of these materials for multimodal means to enhance the safety of the devices against failure modes that range from mechanical damage to thermal runaway. This study presents a self‐healing PDMS dynamic covalent matrix embedded with chemistries that provide thermochromism, mechanochromism, strain‐adaptive stiffening, and thermal insulation, as a collection of attributes relevant to safety. Demonstrations of this materials system and associated encapsulation strategy involve a wireless, skin‐interfaced device that captures mechanoacoustic signatures of health status. The concepts introduced here can apply immediately to many other related bioelectronic devices.

Peripheral nerve injuries cause various disabilities related to loss of motor and sensory functions. The treatment of these injuries typically requires surgical operations for improving functional recovery of the nerve. However, capabilities for continuous nerve monitoring remain a challenge. Herein, a battery-free, wireless, cuff-type, implantable, multimodal physical sensing platform for continuous in vivo monitoring of temperature and strain from the injured nerve is introduced. The thin, soft temperature, and strain sensors wrapped around the nerve exhibit good sensitivity, excellent stability, high linearity, and minimum hysteresis in relevant ranges. In particular, the strain sensor integrated with circuits for temperature compensation provides reliable, accurate strain monitoring with negligible temperature dependence. The system enables power harvesting and data communication to wireless, multiple implanted devices wrapped around the nerve. Experimental evaluations, verified by numerical simulations, with animal tests, demonstrate the feasibility and stability of the sensor system, which has great potential for continuous in vivo nerve monitoring from an early stage to complete regeneration.

Many recently developed classes of wireless, skin-interfaced bioelectronic devices rely on conventional thermoset silicone elastomer materials, such as poly(dimethylsiloxane) (PDMS), as soft encapsulating structures around collections of electronic components, radio frequency antennas and, commonly, rechargeable batteries. In optimized layouts and device designs, these materials provide attractive features, most prominently in their gentle, noninvasive interfaces to the skin even at regions of high curvature and large natural deformations. Past work, however, overlooks opportunities for developing variants of these materials for multimodal means to enhance the safety of the devices against failure modes that range from mechanical damage to thermal runaway. This paper presents a self-healing PDMS dynamic covalent matrix embedded with chemistries that provide thermochromism, mechanochromism, strain-adaptive stiffening, and thermal insulation, as a collection of attributes relevant to safety. Demonstrations of this materials system and associated encapsulation strategy involve a wireless, skin-interfaced device that captures mechanoacoustic signatures of health status. The concepts introduced here can apply immediately to many other related bioelectronic devices.

Chronic wounds, particularly those associated with diabetes mellitus, represent a growing threat to public health, with additional notable economic impacts. Inflammation associated with these wounds leads to abnormalities in endogenous electrical signals that impede the migration of keratinocytes needed to support the healing process. This observation motivates the treatment of chronic wounds with electrical stimulation therapy, but practical engineering challenges, difficulties in removing stimulation hardware from the wound site, and absence of means to monitor the healing process create barriers to widespread clinical use. Here, we demonstrate a miniaturized wireless, battery-free bioresorbable electrotherapy system that overcomes these challenges. Studies based on a splinted diabetic mouse wound model confirm the efficacy for accelerated wound closure by guiding epithelial migration, modulating inflammation, and promoting vasculogenesis. Changes in the impedance provide means for tracking the healing process. The results demonstrate a simple and effective platform for wound site electrotherapy.

Abstract Individuals who are unable to walk independently spend most of the day in a wheelchair. This population is at high risk for developing pressure injuries caused by sitting. However, early diagnosis and prevention of these injuries still remain challenging. Herein, we introduce battery-free, wireless, multimodal sensors and a movable system for continuous measurement of pressure, temperature, and hydration at skin interfaces. The device design includes a crack-activated pressure sensor with nanoscale encapsulations for enhanced sensitivity, a temperature sensor for measuring skin temperature, and a galvanic skin response sensor for measuring skin hydration levels. The movable system enables power harvesting, and data communication to multiple wireless devices mounted at skin-cushion interfaces of wheelchair users over full body coverage. Experimental evaluations and numerical simulations of the devices, together with clinical trials for wheelchair patients, demonstrate the feasibility and stability of the sensor system for preventing pressure injuries caused by sitting.

colorimetric assays for precise assessments of sweat rate, sweat loss and concentrations of wide-ranging types of biomarkers in sweat. This paper presents a set of findings that enhances the performance of these systems through the use of microfluidic networks, integrated valves and microscale optical cuvettes formed by three dimensional printing in hard/soft hybrid materials systems, for accurate spectroscopic and fluorometric assays. Field studies demonstrate the capability of these microcuvette systems to evaluate the concentrations of copper, chloride, and glucose in sweat, along with the pH of sweat, with laboratory-grade accuracy and sensitivity.