Wireless bioelectronic interfaces are increasingly used to control tissue-engineered biohybrid robotic systems. However, a unifying engineering framework linking device design to system-level control remains underdeveloped. Here, we propose that wireless control in biohybrid robotics can be formulated as a coupled co-design problem of integrating signal delivery, spatial selectivity, scalability, and interface stability. We analyze three representative control strategies, wireless electrical stimulation, wireless optoelectronic stimulation, and neuromuscular integration, which operates within a distinct regime with characteristic trade-offs. Across these modalities, the tissue-device interface emerges as a key constraint, governing the interplay between electromagnetic coupling, circuit performance, and biomechanical response. Based on this framework, we outline practical design principles spanning electromagnetic field distribution, circuit architecture, and actuator mechanics. We further propose a transition from open-loop stimulation to closed-loop biohybrid autonomy enabled by organoid-integrated bioelectronics and bidirectional microelectrode interfaces. This work establishes
Continuous long-term monitoring and diagnosis of biomedical signals, such as electrocardiograms (ECGs), can help mitigate an increasing threat to public health. Artificial Intelligence (AI) models, such as Convolutional Neural Networks (CNNs), provide accurate monitoring and classification for relevant diseases; however, they require more computational resources than conventional AI hardware can typically afford, especially for a resource-constrained environment on the edge. In this work, we present BenDi, an energy-efficient quasi-stochastic systolic architecture for bioelectronic systems on the edge. BenDi leverages multiple levels of energy and power optimization, ranging from circuits to software quantization, including low supply voltage, the \underline{Ben}t-Pyramid data format for quasi-stochastic multiplication, the \underline{Di}P systolic dataflow, and hardware-aware quantization, to handle CNNs with high accuracy on the edge within limited hardware budgets. The hardware implementation results, using a commercial 22nm technology, show that BenDi architecture, at 0.5 Voltage and 100 MHz, offers 3.35x smaller area and 5x higher energy efficiency, compared to state-of-the-ar
Thin-film self-assembly of three-dimensional (3D) microsystems presents a compelling route to integrate complex functionalities into ultra-compact volumes, yet strategies for incorporating tunable ion-conducting elements remain limited. Here, we introduce a strain-induced self assembly platform that transforms lithographically patterned multilayer thin films into functional 3D coaxial Swiss-roll microtubes with total active volumes below 1 uL. A key innovation is the monolithic integration of a chemically tunable polyimide proton-exchange membrane, enabling post-fabrication optimization of ionic transport that balances proton transport with mediator blocking. We further implement a dual-mode operational scheme that decouples microbial metabolism from electrochemical power generation, revealing biofouling, not chemical fouling or membrane degradation, as the dominant failure mechanism in conventional architectures. Critically, optimally treated polyimide membranes exhibit excellent recoverability after fouling, while cell-free mode operation maintains stable performance by physically excluding microorganisms from the microelectronic environment. This integrated bio-electronic micros
Over the past years, rapid progress has been made on soft-matter electronics for wearable and implantable devices, for bioelectronics and optogenetics. Liquid Metal (LM) based electronics were especially popular, due to their long-term durability, when subject to repetitive strain cycles. However, one major limitation has been the need for tethering bioelectronics circuits to external power, or the use of rigid bulky batteries. This has motivated a growing interest in wireless energy transfer, which demands circuit miniaturization. However, miniaturization of LM circuits is challenging due to low LM-substrate adhesion, LM smearing, and challenges on microchip-interfacing. In this article, we address these challenges by high-resolution laser-assisted micropatterning of biphasic LM composites and vapor-assisted LM microchip soldering. Through development of a search algorithm for optimization of the biphasic ink coil performance, we designed and implemented micro coils with trace spacing of 50 μm that can harvest a significant amount of energy (178 mW/cm2) through near field inductive coupling. We show miniaturized soft-matter circuits with integrated SMD chips such as NFC chips, cap
Recent advances in manufacturing of flexible and conformable microelectronics have opened opportunities for health monitoring and disease treatment. Other material engineering advances, such as the development of conductive, skin-like hydrogels, liquid metals, electric textiles, and piezoelectric films provide safe and comfortable means of interfacing with the human body. Together, these advances have enabled the design and engineering of bioelectronic devices with integrated multimodal sensing and stimulation capabilities to be worn nearly anywhere on the body. Of particular interest here, the external ear (auricle) offers a unique opportunity to design scalable bioelectronic devices with a high degree of usability and familiarity given the broad use of headphones. This perspective article discusses recent design and engineering advances in the development of auricular bioelectronic devices capable of physiological and biochemical sensing, cognitive monitoring, targeted neuromodulation, and control for human-computer interactions. Stemming from this scalable foundation, there will be increased growth and competition in research and engineering to advance auricular bioelectronics.
Organoids offer a promising alternative in biomedical research and clinical medicine, with better feature recapitulation than 2D cultures. They also have more consistent responses with clinical results when compared to animal models. However, major challenges exist in the longevity of culture, the reproducibility of organoid properties, and the development of non-disruptive monitoring methods. Recent advances in materials and microfabrication methods, such as 3D printing and compressive buckling, have enabled three-dimensional (3D) interfaces of microfluidics and bioelectronics to manipulate and monitor these biological models in exciting ways. These advanced systems have great potential for applications in drug delivery, personalized medicine, and disease modelling. We conclude with important future considerations to generate longevity using further technological development in organoid and spheroid models.
Bioelectronic implants with soft mechanics, biocompatibility, and excellent electrical performance enable biomedical implants to record electrophysiological signals and execute interventions within internal organs, promising to revolutionize the diagnosing, monitoring, and treatment of various pathological conditions. However, challenges remain in improving excessive impedance at the bioelectronic-tissue interface and thus the efficacy of electrophysiological signaling and intervention. Here, we devise orbit symmetry breaking in MXene (a low-cost scalability, biocompatible, and conductive 2D layered material, that we refer to as OBXene), that exhibits low bioelectronic-tissue impedance, originating from the out-of-plane charge transfer. Furthermore, the Schottky-induced piezoelectricity stemming from the asymmetric orbital configuration of OBXene facilitates interlayered charge transport in the device. In this study, we report an OBXene-based cardiac patch applied on the left ventricular epicardium of both rodent and porcine models to enable spatiotemporal epicardium mapping and pacing, while coupling the wireless and battery-free operation for long-term real-time recording and clo
Integrating biology with complementary metal-oxide-semiconductor (CMOS) sensors can enable highly parallel measurements with minimal parasitic effects, significantly enhancing sensitivity. However, realizing this potential often requires overcoming substantial barriers related to design, fabrication, and heterogeneous integration. In this context, we present a comprehensive suite of tools and methods designed for wafer-scale biosensor prototyping that is sensitive, highly parallelizable, and manufacturable. A central component of our approach is a new initiative that allows for open-source multi-project wafers (MPW), giving all participants access to the designs submitted by others. We demonstrate that this strategy not only promotes design reuse but also facilitates advanced back-end-of-line (BEOL) fabrication techniques, improving the manufacturability and process yield of CMOS biosensors. Developing CMOS-based biosensors also involves the challenge of heterogeneous integration, which includes external electrical, mechanical, and fluid layers. We demonstrate simple modular designs that enable such integration for sample delivery and signal readout. Finally, we showcase the effect
Symmetry lies at the heart of 2D bioelectronics, determining material properties at the fundamental level. Breaking the symmetry allows emergent functionalities and effects. However, symmetry modulation in 2D bioelectronics and the resultant applications have been largely overlooked. Here we devise an oxidized architectural MXene, referred as OXene, that couples orbit symmetric breaking with inverse symmetric breaking to entitle the optimized interfacial impedance and Schottky-induced piezoelectric effects. The resulting OXene validates applications ranging from microelectrode arrays, gait analysis, active transistor matrix, and wireless signaling transmission, which enables highly-fidelity signal transmission and reconfigurable logic gates. Further OXene interfaces are investigated in both rodent and porcine myocardium, featuring high-quality and spatiotemporally resolved physiological recordings, while accurate differentiated predictions, enabled via various machine learning pipelines.
Autonomous implantable bioelectronics rely on wireless connectivity, necessitating highly efficient electromagnetic (EM) radiation systems. However, limitations in power, safety, and data transmission currently impede the advancement of innovative wireless medical devices, such as tetherless neural interfaces, electroceuticals, and surgical microrobots. To overcome these challenges and ensure sufficient link and power budgets for wireless implantable systems, this study explores the mechanisms behind EM radiation and losses, offering strategies to enhance radiation efficiency in wireless implantable bioelectronics. Using analytical modeling, the EM waves emitted by the implant are expanded as a series of spherical harmonics, enabling a detailed analysis of the radiation mechanisms. This framework is then extended to approximate absorption losses caused by the lossy and dispersive properties of tissues through derived analytical expressions. The radiation efficiency and in-body path loss are quantified and compared in terms of three primary loss mechanisms. The impact of various parameters on the EM efficiency of implantable devices is analyzed and quantified, including operating fr
Wireless minimally invasive bioelectronic implants enable a wide range of applications in healthcare, medicine, and scientific research. Magnetoelectric (ME) wireless power transfer (WPT) has emerged as a promising approach for powering miniature bio-implants because of its remarkable efficiency, safety limit, and misalignment tolerance. However, achieving low-power and high-quality uplink communication using ME remains a challenge. This paper presents a pulse-width modulated (PWM) ME backscatter uplink communication enabled by a switched-capacitor energy extraction (SCEE) technique. The SCEE rapidly extracts and dissipates the kinetic energy within the ME transducer during its ringdown period, enabling time-domain PWM in ME backscatter. Various circuit techniques are presented to realize SCEE with low power consumption. This paper also describes the high-order modeling of ME transducers to facilitate the design and analysis, which shows good matching with measurement. Our prototyping system includes a millimeter-scale ME implant with a fully integrated system-on-chip (SoC) and a portable transceiver for power transfer and bidirectional communication. SCEE is proven to induce >5
Stretchable electronics capable of conforming to nonplanar and dynamic human body surfaces are central for creating implantable and on-skin devices for high-fidelity monitoring of diverse physiological signals. While various strategies have been developed to produce stretchable devices, the signals collected from such devices are often highly sensitive to local strain, resulting in inevitable convolution with surface strain-induced motion artifacts that are difficult to distinguish from intrinsic physiological signals. Here we report all-printed super stretchable strain-insensitive bioelectronics using a unique universal gradient interface (UGI) to bridge the gap between soft biomaterials and stiff electronic materials. Leveraging a versatile aerosol-based multi-materials printing technique that allows precise spatial control over the local stiffnesses with submicron resolution, the UGI enables strain-insensitive electronic devices with negligible resistivity changes under a 180% stretch ratio. We demonstrate various stretchable devices directly printed on the UGI for on-skin health monitoring with high signal quality and near perfect immunity to motion artifacts, including semicon
A central endeavour in bioelectronics is the development of logic elements to transduce and process ionic to electronic signals. Motivated by this challenge, we report fully monolithic, nanoscale logic elements featuring n- and p-type nanowires as electronic channels that are proton-gated by electron-beam patterned Nafion. We demonstrate inverter circuits with state-of-the-art ion-to-electron transduction performance giving DC gain exceeding 5 and frequency response up to 2 kHz. A key innovation facilitating the logic integration is a new electron-beam process for patterning Nafion with linewidths down to 125 nm. This process delivers feature sizes compatible with low voltage, fast switching elements. This expands the scope for Nafion as a versatile patternable high-proton-conductivity element for bioelectronics and other applications requiring nanoengineered protonic membranes and electrodes.
Piezoionic hydrogels offer a route to mechanically driven bioelectronic interfaces, but their output is limited by rapid, symmetric ion redistribution that dissipates charge gradients. In biological electrocytes, efficient signal generation arises from the coupling of ion selectivity with spatial confinement that regulates transport. Here, we introduce a confinement-connectivity design strategy for piezoionic hydrogels, implemented through a supramolecular poly(vinyl alcohol)-glycerol-cucurbit[5]uril (PVA-glycerol-CB[5]) mesoporous network with a layered Negative-Neutral-Positive architecture that simultaneously increases pore fraction while reducing characteristic pore size. This architecture constrains ionic redistribution while maintaining a large mobile-ion reservoir, enabling deformation-driven charge separation. Compression generates peak outputs of ~180 mV and ~9 mA and elicits synchronized electromyographic responses in the mouse sciatic nerve without external power. These results establish confinement-connectivity coupling, rather than bulk conductivity, as a materials design framework in which coupling pore connectivity and confinement governs piezoionic transduction.
Closed-loop bioelectronic regulation of engineered secretory cell systems is challenging because electric-field (EF) stimulation acts indirectly through transcription-factor activation, in the presence of delayed, nonlinear, and noisy intracellular dynamics, sparse measurements, and constrained burst-based actuation. We develop a framework for robust closed-loop endocrine regulation in electrically stimulated engineered cell factories, illustrated through extracellular thyroid hormone \(T_4\) production in engineered thyroid-like cells. The plant is modeled by a control-oriented ODE formulation combining a reduced mechanistic \(T_4\) pathway, an EF-responsive Hill module, and a linear-chain Erlang cascade representing distributed intracellular delay. On this basis, we design a sampled-data adaptive proportional-integral-derivative (PID) controller with derivative filtering, anti-windup, saturation and rate limits, and hysteretic band-locking, together with a robust adaptive extension that accounts for parameter mismatch, sensor noise and bias, actuator mismatch, delay/jitter, and exogenous rhythmic disturbance through a scenario-based risk-aware update. We provide local sampled-dat
To facilitate rational molecular and materials design, this research proposes an integrated computational framework that combines stochastic simulation, ab initio quantum chemistry, and molecular docking. The suggested workflow allows systematic investigation of structural stability, binding affinity, and electronic properties across biological and materials science domains by utilizing complementary tools like Avogadro for molecular construction and visualization, AutoDock for docking and interaction analysis, and ORCA for high-level electronic structure computations. Uncertainty, configurational sampling, and optimization in high-dimensional chemical spaces are addressed by combining Monte Carlo-based and annealing-inspired techniques. The work shows how materials science ideas such as polymer design, thin films, crystalline lattices, and bioelectronic systems can be applied to drug development. On-device, open-source computational methods are viable, scalable, and economical, as demonstrated by comparative platform analysis. All things considered, the findings highlight the need of an integrated, repeatable computational pipeline for speeding up de novo molecule assembly and mat
Understanding how electric fields destabilize biological membranes is important for electroporation-based technologies and bioelectronic interfaces. However, theoretical descriptions of this phenomenon remain fragmented. Existing theories treat either electrostatics in membranes of finite thickness or electrohydrodynamic flows at idealized zero-thickness interfaces, leaving unresolved a unified description that simultaneously incorporates finite membrane thickness, surface charge, and bulk electrohydrodynamics. Here, we apply a recently-developed, dimension-reduction framework that captures the coupled electrohydrodynamic and mechanical effects governing height fluctuations of a charged lipid bilayer of thickness $δ$ in an electrolyte characterized by Debye screening length $λ$. We derive voltage- and charge-dependent renormalizations of the effective surface tension and bending rigidity, along with a dispersion relation governing undulatory instabilities. A wide range of prior theoretical results arise as limiting cases of our more general theory when finite-thickness effects are neglected or screening is asymptotically strong. The key new contribution arises from traction moments
In this article, we attempt to make a conceptual bridge between the research in biology, pre-biotic chemistry, biomimetics, and the tools used in organic bioelectronics in terms of materials and devices. The goal is discussing how materials and devices of organic bioelectronics can be exploited and used at the interface with biology, but also how, and at what extent, they can be adapted to mimicking nature-inspired properties, herein including unconventional computing strategies. The idea is to provide new hints and solid hypotheses for designing niche experiments that could benefit from a proper interaction, even at a basic communicative level, between materials science and biotechnology. The finale long-term vision goal being the vision of collecting experimental data that may help to made a step forward toward the implementation of the transition from inanimate objects to animated beings. The mathematical model canonically considered in this work is the Navier-Stokes-Nernst-Planck (NPNS) Model which is often used to model a charged continuum system such as the organic electrochemical transistors.
Bacteria sense a diverse range of environmental analytes with high sensitivity and temporal resolution. Engineering and synthetic biology approaches enabled harnessing this capability through development of whole-cell biosensors that respond to specific molecules of interest. However, converting these responses into electrical signals in real time, across different environmental conditions, in miniaturized, field-deployable microelectronic devices, remains challenging. Here we present a bioelectronic platform that directly couples engineered bacteria to an integrated circuit (IC) chip through custom on-chip microelectrodes, enabling real-time, electronic readout of analyte sensing through bacterial flagellar motor dynamics. Using non-Faradaic electrochemical impedance measurements the device resolves both the direction and speed of motor rotation with a signal-to-noise ratio (SNR) of 15 dB. The IC is further integrated with a microfluidic system that enables controlled delivery and removal of analytes, nutrients and bacteria. When combined with whole-cell biosensors engineered to detect specific analytes, this work provides a miniature, portable platform for continuous monitoring i
Three-dimensional (3D) printing of bioelectronics offers a versatile platform for fabricating personalized and structurally integrated electronic systems within biological scaffolds. Biodegradable electronics, which naturally dissolve after their functional lifetime, minimize the long-term burden on both patients and healthcare providers by eliminating the need for surgical retrieval. In this study, we developed a library of 3D-printable, biodegradable electronic inks encompassing conductors, semiconductors, dielectrics, thereby enabling the direct printing of fully functional, multi-material, customizable electronic systems in a single integrated process. Especially, conjugated molecules were introduced to improve charge mobility, energy level alignment in semiconducting inks. This ink platform supports the fabrication of passive/active components and physical/chemical sensors making it suitable for complex biomedical applications. Versatility of this system was demonstrated through two representative applications: (i) wireless pressure sensor embedded within biodegradable scaffolds, (ii) wireless electrical stimulators that retain programmable electrical functionality in vivo and