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Abstract The development of wearable bioelectronic systems is a promising approach for optimal delivery of therapeutic treatments. These systems can provide continuous delivery of ions, charged biomolecules, and an electric field for various medical applications. However, rapid prototyping of wearable bioelectronic systems for controlled delivery of specific treatments with a scalable fabrication process is challenging. We present a wearable bioelectronic system comprised of a polydimethylsiloxane (PDMS) device cast in customizable 3D printed molds and a printed circuit board (PCB), which employs commercially available engineering components and tools throughout design and fabrication. The system, featuring solution-filled reservoirs, embedded electrodes, and hydrogel-filled capillary tubing, is assembled modularly. The PDMS and PCB both contain matching through-holes designed to hold metallic contact posts coated with silver epoxy, allowing for mechanical and electrical integration. This assembly scheme allows us to interchange subsystem components, such as various PCB designs and reservoir solutions. We present three PCB designs: a wired version and two battery-powered versions with and without onboard memory. The wired design uses an external voltage controller for device actuation. The battery-powered PCB design uses a microcontroller unit to enable pre-programmed applied voltages and deep sleep mode to prolong battery run time. Finally, the battery-powered PCB with onboard memory is developed to record delivered currents, which enables us to verify treatment dose delivered. To demonstrate the functionality of the platform, the devices are used to deliver H $$^+$$ + in vivo using mouse models and fluoxetine ex vivo using a simulated wound environment. Immunohistochemistry staining shows an improvement of 35.86% in the M1/M2 ratio of H $$^+$$ + —treated wounds compared with control wounds, indicating the potential of the platform to improve wound healing.

Electrical signaling plays a crucial role in the cellular response to tissue injury in wound healing and an external electric field (EF) may expedite the healing process. Here, we have developed a standalone, wearable, and programmable electronic device to administer a well-controlled exogenous EF, aiming to accelerate wound healing in an in vivo mouse model to provide pre-clinical evidence. We monitored the healing process by assessing the re-epithelization rate and the ratio of M1/M2 macrophage phenotypes through histology staining. Following three days of treatment, the M1/M2 macrophage ratio decreased by 30.6% and the re-epithelization in the EF-treated wounds trended towards a non-statically significant 24.2% increase compared to the control. These findings provide point towards the effectiveness of the device in shortening the inflammatory phase by promoting reparative macrophages over inflammatory macrophages, and in speeding up re-epithelialization. Our wearable device supports the rationale for the application of programmed EFs for wound management in vivo and provides an exciting basis for further development of our technology based on the modulation of macrophages and inflammation to better wound healing.

Precision medicine endeavors to personalize treatments, considering individual variations in patient responses based on factors like genetic mutations, age, and diet. Integrating this approach dynamically, bioelectronics equipped with real-time sensing and intelligent actuation present a promising avenue. Devices such as ion pumps hold potential for precise therapeutic drug delivery, a pivotal aspect of effective precision medicine. However, implementing bioelectronic devices in precision medicine encounters formidable challenges. Variability in device performance due to fabrication inconsistencies and operational limitations, including voltage saturation, presents significant hurdles. To address this, closed-loop control with adaptive capabilities and explicit handling of saturation becomes imperative. Our research introduces an enhanced sliding mode controller capable of managing saturation, adept at satisfactory control actions amidst model uncertainties. To evaluate the controller's effectiveness, we conducted in silico experiments using an extended mathematical model of the proton pump. Subsequently, we compared the performance of our developed controller with classical Proportional Integral Derivative (PID) and machine learning (ML)-based controllers. Furthermore, in vitro experiments assessed the controller's efficacy using various reference signals for controlled Fluoxetine delivery. These experiments showcased consistent performance across diverse input signals, maintaining the current value near the reference with a relative error of less than 7% in all trials. Our findings underscore the potential of the developed controller to address challenges in bioelectronic device implementation, offering reliable precision in drug delivery strategies within the realm of precision medicine.

Bioelectronic devices that interface electronics with biological systems can actuate and control biological processes. The potassium ion plays a vital role in cell membrane physiology, maintaining the cell membrane potential (Vmem) and generating action potentials. In this work, we present two bioelectronic ion pumps that use an electronic signal to modulate the potassium ion concentration in solution. The first ion pump is designed to integrate directly with six-well cell culture plates for optimal ease of integration with in vitro cell culture, and the second on-chip ion pump provides high spatial resolution. These pumps offer increased ease of integration with in vitro systems and demonstrate K+ concentration distribution with high spatial resolution. We systematically investigate the ion pump’s performance using electrical characterization and computational modeling, and we explore closed-loop control of K+ concentration using fluorescent dyes as indicators. As a proof-of-concept, we study the effects of modulating K+ concentration on Vmem of THP-1 macrophages.

Traditional wired interconnects in multicore multichip (MCMC) systems can be replaced with chip-integrated switched beam antenna arrays to provide reconfigurable chip-to-chip communications. By simply switching the directive beams of the arrays, the chips can be made to dynamically communicate with their surrounding neighbors. Radiation from the arrays in the unintended direction, however, causes interference when multiple pairs of chips are simultaneously communicating. In this paper, the noise and interference limitations of such concurrent chip-to-chip communication systems are analyzed at 60 GHz for the channels defined in the IEEE 802.11ay standard. Each array consists of eight substrate integrated waveguide (SIW) horn elements printed on a thin dielectric substrate. The elements can be individually excited to produce eight directive endfire beams, providing full 360° coverage, in the horizontal plane. The substrate acts as a hybrid space-surface wave interconnect (HSSW-I) that allows near-field, space and surface wave coupling to occur between the arrays, and thus, increases interchip transmission. The antenna and link parameters that dictate the signal-to-noise-plus-interference ratio (SNIR) of such systems are established by considering all the major components. The maximum achievable data rates are then determined based on the SNIR, calculated from the measured and simulated transmission coefficients between the arrays.