Yonggang Huang

Human organoids represent promising models for studies of significance to the biology and medical communities. Of the existing approaches for monitoring organoids, none offers the ability to apply programmable mechanical forces while simultaneously recording multi-modal physiological responses, of relevance to phenomena spanning from traumatic brain injuries to cardiac rhythm disorders. Here, we present a mesoscale soft robotic organoid interface that enables programmable delivery of forces to organoids of diverse shapes, and to map electrophysiological activity and mechanical responses. The platform combines actuation elements with integrated sensors for quantitative measurement and control. Studies using this technology reveal that spheroidal cortical organoids exhibit distinct responses to mechanical trauma, including silencing, recovery, and changes in neuronal firing patterns. Additional experiments on cardiac ring tissues demonstrate that sustained stretching induces beat-to-beat rhythm variability and altered conduction. The results establish a framework for investigating force-triggered transitions between physiological and disease-like states in human tissue models. HIGHLIGHTS: ◦ A mesoscale soft robotic interface delivers programmable forces to human organoids ◦ Versatile geometries deliver compression, stretch, and shear to varied tissue shapes ◦ Real-time recording captures trauma-induced silencing and recovery in organoids ◦ Multimodal readout tracks rhythmic changes in engineered heart tissue under loading

Effective modeling of chronic human diseases in vivo requires precise spatiotemporal regulation of molecular processes at defined tissue locations. Optogenetic and optoelectronic tools can provide such control but targeting internal organs such as the lungs remain challenging. To address this, we developed E-LightR-Cre recombinase, enabling precise, spatially restricted gene activation with no dark-state activity and robust blue light responsiveness. To achieve local activation of E-LightR-Cre in specific organ sites, we engineered wireless, fully implantable optoelectronic devices enabling focal illumination of murine lungs with no discernible organ damage. The size of the activated area is controlled by modulating light intensity and duration. Using implanted optoelectronic devices, we activated E-LightR-Cre in a selected area of mouse lungs and achieved local regulation of targeted genes. Light-regulated expression of the oncogenic KRas-G12D mutant in mouse lungs induced local formation of oncogenic lesions. These results show that our protein engineering and adaptable optoelectronic approaches enable facile application of optogenetic tools for locally controlled disease modeling in vivo.

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 noncontact, 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 of infected and noninfected wounds on diabetic mice 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 noncontact sensing scheme as a distinct and clinically translatable paradigm for wound monitoring, with broad implications for noninvasive surveillance of disease states in which tissue metabolic activity and skin barrier integrity serve as actionable physiological readouts.

In vivo fluorescence signals provide physiological and pathological insights for the interpretation of biological states associated with anatomical abnormalities or disease. Conventional methods for measuring fluorescence signals rely on bulky, costly instrumentation for imaging or for localized sensing. Here, we report a compact, wireless fluorimeter system for continuous, real-time measurements of the dynamics of fluorescence signals at locations of interest across the body. The approach represents a type of wearable that enables quantitative, interpretable fluorescence readouts and automatic data streaming to standard smart devices. The platform is compatible with injectable fluorescent species of medical relevance, such as indocyanine green, fluorescein, and methylene blue. Measurements from ischemic rodent and healthy porcine models, as well as those associated with limb amputation/replantation studies in rodents, demonstrate physiologically meaningful fluorescence profiles, with validation against ex situ blood analysis. These conceptual and technical advances offer the potential for convenient, continuous monitoring of fluorescence signals to support disease management and long-term patient care.

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.

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.

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. Significance Statement: Limited capabilities in continuous, quantitative assessment of a wound make early diagnosis and effective management challenging, particularly in cases of infection that rapidly progress before symptoms appear. Non-contact approaches for wound monitoring that preserve fragile tissue can transform wound care. In this context, gaseous flux from the wound bed provides an integrative measure of microbial activity and barrier restoration. This study establishes a wearable sensing platform that quantifies these fluxes in real time, enabling early infection detection and temporal tracking of wound healing. These results highlight a path toward personalized treatment strategies and reduced reliance on episodic clinical evaluation.

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.

Accurate measurement of biofluid flow rate is critical for clinical diagnostics and physiological monitoring, such as in cerebrospinal fluid shunt assessment and vascular blood flow evaluation. Thermal flow sensors, particularly hot‐film and calorimetric types, are widely used in biomedical settings due to their broad dynamic range and long‐term stability. However, their performance declines at high flow rates. To overcome this drawback, we propose a transient heating method that applies a short‐duration thermal pulse and tracks the peak temperature response. This method, validated by experiments using artificial blood and vessels, significantly improves sensitivity to the flow rate change at high flow rates and reduces energy consumption. There exists an optimal heating time to maximize sensitivity to the flow rate. A contour plot of flow rate sensitivity vs. the heating time and flow rate is obtained to guide the selection of optimal heating time for different flow conditions.