Effective management of prenatal nutrient concentrations, such as those associated with folate, is critical for the health of the prospective mother and child, but quantifying them currently requires frequent blood tests and specialized laboratories. Human sweat is a non-invasive alternative to blood that is well suited for point-of-care biosensing. Here we present a skin-interfaced microcapsule that enables collection and storage of pristine, microlitre volumes of sweat and supports an efficient interface to a portable lab-on-a-disc platform for folate quantification. This platform automates an entire enzyme-linked immunoassay sequence for measuring folate in sweat, including incubation, washing, mixing and detection, and facilitates wireless data transmission. A series of tests in human participants reveal a dose-response relationship between oral intake of folate supplements and sweat folate levels, with a strong correlation in levels between sweat and serum. In addition, daily tracking of sweat folate concentrations shows clear differences between control periods without supplementation and daily intake periods. This technology creates possibilities for the routine use of sweat for precise point-of-care assessment of prenatal nutrient bioavailability.
Conventional strategies for the management of acute pain have significant limitations. Pharmaceutical approaches carry risks for addiction and misuse. Standard implantable devices require secondary surgeries for removal and physical tethers to external systems for power and control. Recent work on bioresorbable electrical stimulators overcomes certain of these drawbacks, but existing versions still depend on transcutaneous leads. Here, we introduce a platform that employs thermal mechanisms for nerve block to bypass some of these limitations. The system integrates both a Joule heating element and a resistive temperature sensor in a soft cuff structure as a nerve interface, in which most of the materials are bioresorbable over a clinically relevant timeframe. This design enables precise control of nerve temperature within a safe range (<= 45 degrees C) for effective nerve block through a feedback-guided strategy that continuously monitors temperature and adjusts current in real time. Options for wireless power delivery eliminate the need for external interfaces. Small animal model studies confirm the reversible and non-invasive operation of this system. The results demonstrate effective suppression of compound nerve action potentials in response to thermal stimulation, with recovery of nerve conduction upon cooling. These findings highlight the potential of this platform as a safe and effective solution to acute pain management.
Human neural organoids are essential platforms for fundamental and applied research due partly to their complex, three-dimensional neuronal circuit geometries. Standard and recently developed neural interface technologies have shortcomings in their ability to electrically characterize and control neural activity in these systems, owing to their limited accessibility to neuron populations and microelectrode densities. Here we report a shape-matched, soft, three-dimensional mesoscale framework with nearly full surface coverage to neural organoids that supports high channel count interfaces for precision electrophysiology and programmed electrical stimulation. The neural interface is designed via inverse modelling techniques and self-assembles three-dimensionally around the organoids. Three-dimensional reconstruction of neural activities allows high-resolution spatial electrophysiology to reveal network-level characteristics in neural organoids. The porous framework offers options for simultaneous fluorescence imaging, localized optogenetic neuromodulation, longitudinal monitoring, pharmacological evaluations and modelling of neural disease phenotypes, demonstrating broad applicability for studies of human-derived cortical and spinal organoids.
Mechanical forces act throughout the body across multiple scales, from organs and tissues to cells and molecules, playing a vital role in maintaining tissue integrity, regulating cellular functions and supporting physiological performance. Importantly, alterations in mechanical forces and properties can be hallmarks of tissue injury and disease, and can thus serve as valuable biomarkers for disease monitoring and diagnostics and can be harnessed to modulate biological processes for therapeutic benefit. This concept, termed mechanomedicine, offers an important strategy in disease diagnosis and therapy. In this Review, we first introduce biomechanics and mechanobiology as the underlying principles of mechanomedicine and outline the properties and measurements of key mechanical signatures in health and disease. We then explore the application of mechanomedicine across scales, from organ-level and tissue-level diagnostics to cellular and molecular mechanotherapeutics, including strategies for tissue regeneration and rehabilitation. Finally, we highlight challenges and opportunities in the clinical translation of mechanomedicine approaches, in particular with regards to the innovation of materials and devices, the manufacturing of cells and organoids, the definition and standardization of mechanical biomarkers, and the integration of artificial intelligence. Mechanical forces are crucial regulators of biological functions in health and disease, offering measurable biomarkers and therapeutic targets. This Review introduces the principles of mechanomedicine and highlights its translational potential across scales, from tissue diagnostics to molecular mechanotherapeutics.
Evaluating soft tissue elasticity provides critical biomechanical insights essential for the precise characterization of various physiological and pathological conditions. Here, we present the clinical validation of a wireless, compact wearable system designed for direct, location-specific monitoring of the elastic modulus of the skin and underlying tissues via vibro-rotational biomechanical dynamics. Validated by computational models and experiments, the device uses a tunable skin interface to enable depth-controlled measurements across diverse anatomical sites. Two human subject studies, one involving patients with cancer-related lymphedema and the other involving patients with systemic scleroderma, yield data that correlate with standard clinical metrics. This technology offers the potential for longitudinal assessments in these and other contexts, in both clinical and home settings.
Neural organoids are emerging as advanced three-dimensional (3D) in vitro models for recapitulating human development and pathology, but they lack dedicated mass-transport pathways that perfuse interior regions, limiting control over solute concentrations in deep tissues. Microfluidic technologies hold promise for intra-organoid delivery, yet creating high-resolution 3D transport architectures spanning arteriole-to-venule scales while integrating them with minimal disruption to morphogenesis remains challenging. Here, we introduce a multiscale 3D microfluidic delivery platform that embeds lithographically defined, flexible, thread-like microchannels into organoids during growth. The nanoporous interface along the embedded microchannels enables controlled diffusive transport of biomolecules into localized regions with ~100 μm spatial resolution and to depths of ~400 μm from the organoid center, with minute-scale temporal precision, as demonstrated with dyes, morphogens, and MRI contrast agents. Delivery of growth factor-supplemented media leads to reduced apoptosis near the microchannels and improved neural tissue integrity. This platform offers a robust means to interrogate deep, site-specific microenvironments and to advance studies of organoid viability, structural organization, and functional maturation.
Capabilities for quantitative monitoring of chronic wounds remain an unmet clinical need, as existing diagnostic approaches rely on semiquantitative evaluation of symptoms that lack sensitivity especially during early stages of infection. Here we present a scheme for tracking wound physiology that leverages a miniature, wireless skin-interfaced device for non-contact, transient measurements of the flux of volatile organic compounds (VOCs) and water vapor from the wound microenvironment. Unlike emerging smart bandage platforms that rely on physical contact with the fragile wound bed to interrogate liquid-phase biomarkers, this strategy uses an engineered microclimate and suspended suite of sensors to measure the diffusive transport of wound-derived gases across the wound surface but separated from it. The result enables quantitative evaluation of metabolic activity and healing progression without perturbing the healing tissues. In biofilm growth models of Staphylococcus aureus, measurements demonstrate that trends in VOC flux correlate strongly with bacterial growth kinetics and precede any visible biofilm formation. Longitudinal monitoring in infected murine wound healing models shows that concurrent measurements of water vapor and VOC flux provide complementary physiological insights, capturing both the trajectory of barrier restoration and the dynamics of bacterial burden. The findings establish this non-contact sensing scheme as a distinct and clinically translatable paradigm for wound monitoring, with broad implications for non-invasive surveillance of disease states in which tissue metabolic activity and skin barrier integrity serve as actionable physiological readouts.
Real-time continuous measurement of tissue oxygenation (StO2) can provide insight into organ transplant health and disease progression and provide feedback after medical interventions. However, existing optical oximetry approaches typically assume stable blood volume, limiting their usefulness in real-world scenarios involving vasoconstriction, vasodilation, or acute blood loss. Here, we leverage miniaturized optical sensors and Bluetooth microprocessors to create a fully implantable oximeter that measures subdermal tissue oxygenation and accounts for varying levels of blood volume. The device utilizes a wireless radiofrequency (RF) power transfer scheme that allows high bandwidth Bluetooth data transmission from three wavelength channels: green (537 nm), red (660 nm), and near-infrared (NIR) (880 nm). Results show that the addition of a green wavelength improves tissue oxygenation estimation in the presence of varying blood volumes. In silico and in vivo validation of the device and tissue oxygenation algorithm is performed in rats during hypoxia, hypercapnia, and occlusion on a variety of tissues such as paw, subdermal muscle, and kidney. Miniaturized, wireless, battery-free, implantable devices such as these that support mechanisms to compensate for varying blood volumes for StO2 calculations offer the potential for continuous, real-time, physiologically consistent monitoring of blood hemodynamics under dynamic physiological conditions.
ABSTRACT We propose a non‐invasive pulse wave monitoring system that integrates a fully printed, partially stretchable ferroelectric electronic tattoo (e‐tattoo) sensor with a soft, elastomer‐encapsulated, partially stretchable data transmission unit (DTU). The DTU includes a rechargeable battery, Bluetooth‐enabled wireless data transmission, and optimized signal conditioning circuitry for the e‐tattoo sensor. We demonstrate: 1) a simple, printing‐based fabrication process for the e‐tattoo sensor and its integration with the DTU; 2) significant improvement in pulse wave index accuracy through optimized electrode material selection used in the e‐tattoo sensor (e.g., reduction in relative error of relative crest time index from 56.3% to 0.2%); 3) enhanced sensitivity via integration of the e‐tattoo on the DTU's soft encapsulation (increased from 25 pC/N to 1277 pC/N); and 4) successful extraction of clinically relevant pulse indices from radial artery of a human study subject.
Skin-interfaced biomedical devices require adhesives that provide strong attachment during use while enabling gentle removal with minimized subsurface skin deformation. Conventional medical adhesives lack mechanisms for on-demand adhesion modulation, often causing skin irritation and damage during detachment, particularly in vulnerable populations. Here, we present a thermally triggered shape memory polymer (SMP) adhesive that achieves reversible, high-contrast adhesion switching through programmable pyramidal structure recovery. The adhesive incorporates an array of pyramidal structures that remain flattened in a dormant state to ensure robust skin adhesion, but rapidly recover upon mild heating above the glass transition temperature, significantly reducing effective contact area and enabling low-force detachment. Adhesion switchability performances are supported by quantitative mechanical measurements, including reductions in peel force and adhesion energy after activation, as well as three-dimensional digital image correlation (3D-DIC) analyses demonstrating minimal subsurface skin deformation during detachment. Mechanical testing demonstrates up to ~99% reduction in adhesion energy upon activation, while maintaining stable load-bearing performance during use. 3D-DIC shows that the actuated SMP suppresses stress concentrations and minimizes subsurface skin deformation during detachment, unlike the dormant SMP. A kirigami structural design further enhances conformability on both singly and doubly curved anatomical surfaces while improving water vapor permeability. Finite element analysis and 3D-DIC measurements reveal substantial reductions in effective stiffness and enhanced bending accommodation enabled by the kirigami geometry. Integration with wireless mechano-acoustic sensors confirms reliable physiological signal acquisition in the dormant state and controlled detachment upon activation. This work establishes a thermally switchable SMP adhesive platform for low-force removal of skin-interfaced devices. Skin interfaced devices require strong attachment, though adhesives lack mechanism for on-demand adhesion. Here the authors design a thermally triggered shape memory polymer for reversible adhesion for onskin devices.
Feet provide essential sensory input, supporting body awareness for safe movement. The impairment of plantar sensation, arising in conditions such as stroke and spinal cord injury, has a major impact on mobility, balance, and quality of life. Substituting the sensation of plantar pressure to another area on the body with intact somatosensory abilities requires capabilities for fast, programmable delivery of haptic feedback. Here, we introduce a wireless network of skin-conformable, multimodal haptic arrays that deliver high-density thermal and vibrotactile patterns anywhere on the body. Central to this approach is a hybrid motor unit that independently controls thermal and mechanical stimulation, enabling 128 degrees of freedom across 64 addressable nodes. Electromechanical characterization establishes precise, simultaneous, and safe modulation of both modalities. Psychophysical experiments demonstrate reliable spatial discrimination of colocated heat and vibration. These haptic arrays form the receivers in a sensory substitution system that delivers patterns of vibrotactile stimulation to mirror the distribution of pressure recorded from an insole-based array of pressure sensors. Exploratory case studies in individuals with spinal cord injury and stroke demonstrate feasibility and suggest improved performance during standing balance and walking tests. Altogether, this work highlights the potential of information-rich cutaneous interfaces to substitute plantar sensation, expanding the scope of somatosensory engagement for rehabilitation, entertainment, and education.
Bioaerosols comprise an array of airborne particles that can be benign, contain irritants (i.e., allergens), or disseminate pathogens. Current fieldable devices are incapable of discriminating between benign bioaerosols and pathogenic bioaerosols. Thus, rapid on-site detection and identification at the point of exposure of the components comprising bioaerosols is critical to assess health risks; elimination of both false positives and false negatives is essential to ensure that the correct countermeasures are deployed. The sandwich enzyme-linked immunosorbent assay (sandwich ELISA) remains a gold standard technique for accurate, sensitive detection of proteins, bacteria, and viruses. ELISAs require recognition of the target by two biorecognition elements (BREs) and thus effectively eliminate false positives. The sandwich ELISA, however, suffers from laborious manual processes, which severely impacts its utility in point-of-care (POC). Centrifugal microfluidics offers an automated solution to execute multi-step ELISAs. Here, we introduce a centrifugal microfluidic device that operates based on passive capillary and siphon valving networks to detect human serum albumin (HSA) concentrations in collected bioaerosol samples. We investigate key aspects for minimizing the assay operation time by investigating siphon valve mechanisms, co-incubation time for HSA with a capture antibody and detection antibody conjugated with streptavidin-horse radish peroxidase (strep-HRP), and incubation time for tetramethylbenzidine with strep-HRP for electrochemical amperometric detection. The fully integrated device quantifies HSA concentrations in 15 minutes based on a small sample volume of 12.5 μL. Using the device, we successfully quantify HSA concentrations in bioaerosol samples and obtain results similar to standard 96 well plate-based ELISA.
Wireless bioresorbable systems for electrical stimulation can deliver electrotherapy over clinically relevant timeframes, and then subsequently dissolve away in a harmless fashion. Such systems have previously been used in neuroregeneration and cardiac pacing, delivering monophasic pulses to a targeted site. Here we report a wirelessly powered system with programmable control of the stimulation waveforms using tissue-penetrating near-infrared light. The approach relies on a bioresorbable silicon phototransistor that is designed to optically modulate current flows at critical nodes in electrical circuits. We show that the approach can offer precise control over stimulation pulses-allowing monophasic, biphasic and polyphasic waveforms to be delivered to single or multiple sites-and all with power wirelessly delivered to a single receiver unit. Using small and large animal models, we further show that the technology enables single- and dual-chamber cardiac pacing, as well as phrenic neuromuscular stimulation for inducing and blocking diaphragmatic excursion.
Accurate, continuous monitoring of psychophysiological states is central to understanding stress and autonomic dysfunction across diverse medical contexts. Current approaches such as polygraphy and polysomnography rely on cumbersome, wired sensors that limit real-world utility and burden patients, particularly vulnerable populations such as infants. Here, we introduce a wireless, skin-interfaced multimodal sensing system capable of simultaneously recording cardiac, respiratory, electrodermal, and thermal signals in a time-synchronized manner. Leveraging compact and soft designs, the technology enables unobtrusive monitoring across controlled, clinical, and naturalistic settings. Validation studies performed in parallel with gold standard systems demonstrate high fidelity in quantifying stress responses during polygraph interviews, cognitive load tasks, and cold pressor tests. In pediatric sleep studies, the data reliably identify arousals, hypopnea, and apnea while revealing disease-specific autonomic signatures in infants with Down syndrome. Real-world deployment during emergency simulation training shows that multimodal stress signatures correlate inversely with performance, underscoring translational value in medical education. Machine learning analyses across all studies confirm that multimodal features outperform single-signal approaches in detecting stress and clinical events with high sensitivity and specificity. Collectively, these findings establish the technology as a next-generation wearable platform that bridges engineering innovation and clinical practice, offering mechanistic insight and diagnostic potential in stress medicine, sleep medicine, and beyond.
Cortisol is a key regulator of stress and circadian physiology, yet current monitoring relies on invasive blood sampling or saliva assays that are prone to contamination and provide limited temporal resolution. Wearable sweat cortisol sensors are promising, but require electronic sensing systems and have limited capability for long-term, time-sequenced monitoring. Here we present a wearable paper-based microfluidic platform that integrates plasmonic-gold-nanoflower-based colorimetric assays to enable non-invasive tracking of cortisol in eccrine sweat. Sweat is induced by carbachol iontophoresis and directed through collection channels using either electronically timed sequential activation or paper-based delay valves with self-powered electrochromic indicators. In human studies, the system resolved circadian variations, acute stress responses to cold pressor challenges, and jet-lag-associated disruptions, with the results closely matching those from saliva and serum assays. This wearable lateral flow technology establishes sweat as a viable medium for real-time hormone monitoring and may enable personalized management of stress, sleep and circadian misalignment. A wearable paper-based microfluidic device tracks cortisol in sweat via gold nanoflower colorimetric assays and captures circadian rhythms, stress responses and jet lag disruptions.
Stable mounting is a central requirement for skin-interfaced wearable biomedical devices, because accurate and long-term measurements with clinical utility typically demand intimate contact with the skin, whereas practical use also requires gentle removal to minimize skin irritation and damage. Existing mounting strategies often struggle to satisfy these competing requirements simultaneously, especially under prolonged wear or in the presence of sweat and moisture. Suction-based mounting has recently emerged as a promising alternative because it can provide strong, reversible, and adhesive-free attachment, yet its underlying mechanics remain insufficiently understood. Here, we establish analytical models for the deformation and force of suction cups in a fully explicit form, covering both the cone suction cup and an optimized ring suction cup design. Unlike previous approaches that rely on indirect quantities such as the pressure difference and contact radius, which are not available before experiments and therefore cannot serve as controllable design variables, the present framework yields direct relations between suction performance and geometry parameters, material properties, and loading conditions, including the maximum push down displacement and the subsequent pull up displacement. The resulting formulas agree closely with accurate numerical solutions and lead to compact scaling laws that clearly identify how geometry and material parameters govern suction performance. These results provide a quantitative and physically transparent foundation for the design of suction-based mounting strategies in wearable devices.