Confined spaces in the human body pose substantial challenges for biomedical procedures. Navigating these ultrasmall environments is essential for precise drug delivery, improving treatment outcomes and reducing adverse effects. Microrobots offer a promising approach to accessing these complex microenvironments. Here, we show a biohybrid microrobot based on picoeukaryotes, engineered as a cargo carrier for active delivery in tight in vivo spaces. The microrobot exhibits strong in vitro motility through narrow two-dimensional and complex three-dimensional networks and, in vivo, achieves outstanding kidney penetration, uniform distribution, and >48-hour retention while resisting flow shear and immune clearance, with excellent biosafety. Their ability to retain functionality and sustain propulsion within the confined and complex kidney vasculatures and interstitial spaces underscore their potential for long-term, active delivery in confined biological environments. The picoeukaryote-based biohybrid microrobot system represents a major advancement in active drug delivery, especially tailored to the challenging microenvironments of the kidney.

In a recent paper from Device, Hu and co-workers developed a reusable, wearable uric acid (UA) sensor that enables continuous, non-invasive monitoring via iontophoresis-induced sweat sampling and ratiometric electrochemical sensing. This system offers stable, accurate UA detection over 150 uses, paving the way for personalized hyperuricemia management and broader chronic disease monitoring.

Accurate health analysis demands real-time tracking of multiple biomarkers and vital signs under dynamic physiological conditions. Current multimodal hybrid platforms provide biochemical and biophysical data but are limited by active sweat collection for biochemical sensing and bulky designs for biophysical sensing. Here a touch-enabled platform is presented that simultaneously monitors vitals and metabolic markers. With a simple tri-finger touch, the platform measures mean arterial pressure and heart rate using photoplethysmography, and glucose, uric acid, and cortisol at rest by leveraging the natural perspiration at the fingertip. Extended studies involving diverse activities reveal strong dynamic interplay among the metabolic and vital profiles, with mean arterial pressure showing the highest sensitivity to cortisol fluctuations. The platform delivers comprehensive health information linking diet, lifestyle, metabolism, and serves as an early metabolic or hormonal stress indicator. Valuable insights gained through the platform position it as a promising tool for personalized health and wellness management.

The development of closed-loop systems towards effective management of diabetes requires the inclusion of additional chemical and physical inputs that affect disease pathophysiology and reflect cardiovascular risks in patients. Comprehensive glycaemic control information should account for more than a single glucose signal. Here, we describe a hybrid flexible wristband sensing platform that integrates a microneedle array for multiplexed biomarker sensing and an ultrasonic array for blood pressure, arterial stiffness and heart-rate monitoring. The integrated system provides a continuous evaluation of the metabolic and cardiovascular status towards improving glycaemic control and alerting patients to cardiovascular risks. The multimodal platform offers continuous glucose, lactate and alcohol monitoring, along with simultaneous ultrasonic measurements of blood pressure, arterial stiffness and heart rate, to support understanding of the interplay between interstitial fluid biomarkers and physiological parameters during common activities. By expanding the continuous monitoring of patients with diabetes to additional biomarkers and key cardiac signals, our integrated multiplexed chemical–physical health-monitoring platform holds promise for addressing the limitations of existing single-modality glucose-monitoring systems towards enhanced management of diabetes and related cardiovascular risks. A wristband combines continuous glucose monitoring with real-time detection of physiological signals to track glucose metabolism.

Significant advances have been made in the management of diabetes through the development of wearable biomedical monitoring and drug-delivery devices. Technologies such as continuous glucose monitors (CGMs) and insulin pumps have particularly transformed diabetes care over the past two decades. However, most current efforts largely focus on glucose and insulin regulation, limiting a broader understanding of metabolic health and the interplay of various biomarkers. Comprehensive diabetes management requires a more holistic approach encompassing diverse biomarkers to address the full spectrum of metabolic health. Adequate response to glycemic variability thus requires continuous monitoring of additional chemical and physical parameters that affect insulin sensitivity. Leveraging recent advances in wearable microneedle (MN) platforms, such systems have received considerable attention for biomedical applications, ranging from continuous multiplexed monitoring to transdermal drug delivery. This review article provides a thorough analysis of the use of MNs for enhanced diabetes management, emphasizing their unique capabilities for simultaneous monitoring of multiple key diabetes biomarkers beyond glucose and for autonomous transdermal delivery of insulin and glucagon based on novel glucose-responsive MN materials and addressing literature gaps regarding the integration of such diagnostic and treatment technologies onto single MN arrays. Representative applications of key MN sensing and delivery devices are highlighted, underscoring their capabilities to revolutionize disease management. We conclude with a forward-looking vision of next-generation AI-guided MN-based closed-loop "Sense-Release" artificial pancreas systems for enhanced glycemic control and improved patient outcomes.

Considering the extremely high toxicity of lead (Pb), early detection of atmospheric Pb levels is paramount for the implementation of preventive measures, to contain sources of emission, to minimize both human and plant exposure and to prevent accumulation in the biosphere. This work demonstrates a wearable "on-plant" sensor for electrochemical Pb detection in atmospheric aerosol samples. The sensor is screen-printed onto a flexible selfadhesive vinyl-based matte substrate which enables its attachment on plant leaves. It features a bismuth/ Nafion-coated carbon working electrode transducer covered with a polyvinyl alcohol (PVA) membrane which serves as a passive in-situ gas collection layer and as an electrolyte-containing matrix. The Pb collected at the interface between the sample in the gas phase and the acetate buffer solution (ABS) embedded within the PVA membrane is measured by square wave anodic stripping voltammetry (SWASV). Different steps of the fabrication process were optimized and the detection of on plant leaves was demonstrated. Simulation experiments were conducted with a Pb-containing aerosol sprayed on the leaves to evaluate the effect of various operational parameters such as long-term stability, spraying time, accumulation time, or sensor/leaf bending. The "on-plant" sensor allows remote near real-time monitoring of Pb levels as low as 50 mu g L- 1 in ambient air using a portable miniaturized potentiostat, and can be expanded to other target metals, forming the basis of an early warning system for atmospheric heavy metals exposure.

Wearable technology has the potential to advance health monitoring by enabling continuous, multimodal sensing. A major bottleneck that hampers the adoption of such advanced health monitoring systems is the need for continuous power supply. Integrated energy-autonomous wearable microgrids offer a compelling solution to support the growing power demands of long-term health care and wellness monitoring. However, wearable microgrid systems require optimal energy management, tailored to changing environmental conditions and dynamic user demands. This Perspective highlights the transformative role of artificial intelligence (AI) in optimizing and guiding the development of powerful wearable microgrids. Leveraging intelligent, accurate prediction of future energy needs, AI empowers autonomous, on-demand, continuous power supply, able to dynamically adapt to fluctuating energy needs in diverse everyday scenarios. AI’s key roles in guiding wearable microgrids include data processing, energy budgeting, sustainable energy harvesting and tailoring systems to behavioural patterns and environmental factors. The developmental trends of AI-enabled wearable microgrids are categorized into three proposed generations, with an in-depth analysis of their advanced functions and intelligent operations. The resulting microgrids balance in real-time energy production, storage and demand to achieve greater efficiency, autonomy and sustained performance, as desired for supporting continuous health monitoring. Wearable multimodal monitoring systems deliver continuous insight into patients’ health status but are constrained by power needs. Next-generation artificial intelligence-enabled wearable microgrids can drive sustainable energy harvesting, intelligent budgeting and adaptive management for autonomous, on-demand power delivery for wearable devices.

The emergence of biohybrid microrobots offers a promising platform for environmental remediation; however, their potential for neurotoxin decontamination remains largely unexplored. Neurotoxins, such as tetrodotoxin (TTX), pose acute threats to aquatic biodiversity with far-reaching consequences for public health. The removal of TTX from aquatic environments presents a critical challenge, necessitating innovative and adaptive strategies. Here, we present a neuronal membrane-functionalized algae-based microrobot platform for the autonomous and selective detoxification of TTX in various aquatic environments. By integrating the natural long-lasting motility of green algae Micromonas pusilla with neuronal membranes with intrinsic TTX-binding receptors, this self-propelled biohybrid microrobot acts as a motile neuron decoy that enables dynamic "on-the-fly" interactions with TTX, significantly enhancing neutralization efficiency in natural river and seawater environments. Moreover, the active penetration abilities of the biohybrid microrobots allow for effective toxin removal from confined complex three-dimensional (3D) microporous networks, such as riverbeds and seabeds, where diffusion-based methods are often ineffective. The microrobot platform further demonstrates exceptional adaptability, maintaining robust detoxification performance across diverse environmental conditions including fluctuations in pH, temperature, and dissolved oxygen levels. By leveraging biohybrid intelligence and environmental adaptability, this work establishes an innovative strategy for sustainable, efficient, and versatile neurotoxin remediation in dynamic aquatic environments.

A fundamental goal in modern biology and precision medicine is to acquire rich, multi-omics-style information from cells, including transcriptomic, proteomic, metabolic and electrophysiological data, in real time and at single-cell resolution. However, current techniques often rely on destructive endpoint assays that require cell lysis, losing spatial, temporal and dynamic context. Nanoscale sensors offer a transformative solution by enabling minimally invasive, continuous monitoring of intracellular activities. Here we propose a spatial classification of intracellular sensing technologies-near cell, on cell and in cell-and use this framework to evaluate the sensing modalities on the basis of their invasiveness, signal fidelity and resolution. We highlight emerging sensor platforms that are capable of detecting ions, metabolites, electrical signals and mechanical changes, as well as artificial intelligence-driven strategies for decoding complex cellular data streams. We further consider the integration of these nanosensors into three-dimensional, physiologically relevant models such as organoids to create 'smart organoids' that report on their internal state autonomously and in real time. Finally, we discuss the major challenges in achieving intelligent intracellular sensing, including issues of sensor miniaturization, biocompatibility, multiplexing and three-dimensional integration. Together, these advances set the stage for a new era of dynamic, high-resolution cell profiling that can accelerate drug discovery, disease modelling and personalized medicine.

Rapid drug delivery is critical in emergency medical circumstances where delays can result in adverse or life-threatening outcomes. The sublingual route holds significant promise for the swift systemic delivery of drugs, but is limited by slow passive diffusion mechanisms that hinder efficient drug transport. To address these challenges, we introduce here a novel sublingual microrobotic pill platform designed for rapid and efficient drug delivery. Our system incorporates magnesium-based microstirrers that accelerate pill disintegration and drug release via an active propulsion mechanism. Such bubble-propelled microstirrers generate strong hydrodynamic flows, enhancing local mixing and drug transport, allowing them to overcome the limitations of traditional diffusion-dominated delivery systems. Optimized through in vitro studies, this platform demonstrated robust motion capabilities in complex human saliva and accelerated drug release kinetics. In a rabbit model, using epinephrine as the model drug, the sublingual microrobotic pill achieved significantly faster drug delivery speed, efficiency, and bioavailability compared to a conventional pill. Moreover, when compared against the gold standard intramuscular injections, the microstirring pill provides competitive delivery speed and enhanced absorption profile, demonstrating its potential for use in the treatment of conditions like anaphylactic shock. Such user-friendly, non-invasive sublingual microrobotic pills can be readily employed for delivering a wide range of drugs, offering a versatile solution for acute conditions requiring rapid therapeutic onset or when enteral absorption is not feasible.

Accurate, non-invasive monitoring of creatinine is essential for assessing kidney function, with elevated levels indicative of chronic kidney disease (CKD). Sweat creatinine serves as a promising biomarker for kidney health. Similarly, sweat glucose monitoring is critical for detecting metabolic imbalances, particularly in diabetic kidney disease (DKD). Simultaneous detection of these biomarkers is vital for early and effective kidney disease management. This study introduces a novel touch-based biosensing platform for real-time, non-invasive self-screening of creatinine and glucose in sweat. The platform utilizes Prussian blue-modified screen-printed carbon electrodes, enhanced with carboxylated multiwalled carbon nanotubes (MWCNTs-COOH) and enzyme mixtures, fabricated through a simplified one-step drop-casting process. A polyvinyl alcohol (PVA) hydrogel ensures efficient passive sweat collection. The biosensor demonstrates a wide linear detection range (20-1000 mu M creatinine, 0.05-1 mM glucose), high selectivity against common sweat interferents, and strong correlation with standard blood assays, validating its potential for reliable, non-invasive kidney disease screening.

Over the past two decades, nanotechnology has made significant progress toward the development and applications of micromotors (MMs) and nanomotors (NMs). Characterized by their capability to self-propel and swim in fluids, they have emerged as promising tools in various fields, particularly in biomedicine. This Review presents an overview of the current state of MMs and NMs, their motion in viscous media and complex environments, their interaction with biological barriers, and potential therapeutical applications. We identify the choice of appropriate administration routes to reach their target location as a key aspect of the success of MMs and NMs in biomedical applications. Looking ahead, we envision NMs playing a key role in treating diverse medical disorders, as recent proof-of-concept in vivo studies demonstrate their distinct capabilities and versatility. However, addressing regulatory, scalability, biocompatibility, and safety concerns remains imperative for the successful translation of NMs into clinical trials and industrial-scale production. This work provides a guideline for researchers, guiding them through the current landscape, challenges, and prospects of using MMs and NMs in biomedicine, thereby encouraging their responsible development and positioning in the future of nanomedicine. Furthermore, we outline critical areas for further research, including studies on biocompatibility, safety, and methods to overcome physical obstacles.

Timely and precise monitoring of inflammatory biomarkers is essential for the effective management of sepsis and related acute conditions. Current monitoring strategies depend mostly on centralized, benchtop systems. Here, we present compact in vitro and in vivo bioelectronic sensor platforms capable of rapid and simultaneous detection of lactate and interleukin-6 (IL-6) in human serum and interstitial fluid. The dual-analyte sensor integrates an enzymatic amperometric lactate sensor with an aptamer-based voltammetric IL-6 sensor on single microchips and microneedle arrays toward rapid decentralized and on-body testing, respectively. Lactate is measured via a first-generation enzymatic oxidation strategy, while IL-6 is quantified using a methylene blue-tagged aptamer through square wave voltammetry. These compact systems address key challenges in combining distinctly different surface chemistries, assay formats, and electrochemical transduction mechanisms, enabling simultaneous real-time and crosstalk-free detection. The resulting platforms demonstrate robust analytical performance and represent a significant step toward rapid, continuous, and decentralized monitoring of sepsis biomarkers. Furthermore, the underlying aptamer-enzyme integration strategy along with the multiplexed capabilities of both platforms offers broad potential for simultaneous measurements of a wide range of inflammatory and metabolic biomarkers in various clinical diagnostic applications.

The human ear has emerged as a bidirectional gateway to the brain's and body's signals. Recent advances in around-the-ear and in-ear sensors have enabled the assessment of biomarkers and physiomarkers derived from brain and cardiac activity using ear-electroencephalography (ear-EEG), photoplethysmography (ear-PPG), and chemical sensing of analytes from the ear, with ear-EEG having been taken beyond-the-lab to outer space. Parallel advances in non-invasive and minimally invasive brain stimulation techniques have leveraged the ear's access to two cranial nerves to modulate brain and body activity. The vestibulocochlear nerve stimulates the auditory cortex and limbic system with sound, while the auricular branch of the vagus nerve indirectly but significantly couples to the autonomic nervous system and cardiac output. Acoustic and current mode stimuli delivered using discreet and unobtrusive earables are an active area of research, aiming to make biofeedback and bioelectronic medicine deliverable outside of the clinic, with remote and continuous monitoring of therapeutic responsivity and long-term adaptation. Leveraging recent advances in ear-EEG, transcutaneous auricular vagus nerve stimulation (taVNS), and unobtrusive acoustic stimulation, we review accumulating evidence that combines their potential into an integrated earable platform for closed-loop multimodal sensing and neuromodulation, towards personalized and holistic therapies that are near, in- and around-the-ear.

We used disposable biosensors to measure capillary blood levodopa concentration in Parkinson's disease (PD) after participants ingested oral carbidopa/levodopa, with the goal of correlating levodopa levels with motor symptoms.

The administration of therapeutics for long-term chronic disease management or treatment faces considerable challenges, such as the need for precise dosage control, timely delivery and adherence to medication regimens. Traditional drug delivery methods often result in suboptimal therapeutic outcomes owing to variable responses, fluctuating drug concentrations and lack of feedback from real-time monitoring. Smart closed-loop systems (CLSs) could address these limitations by integrating real-time biosensing with automated drug delivery, thereby personalizing treatments to individual needs. This Review explores the current landscape of CLSs, highlighting recent advancements in wearable and implantable technologies that facilitate continuous monitoring of biomarkers and offer responsive therapeutic interventions. We discuss the implications of device design and the trade-offs between wearable and implantable systems. In addition, we highlight the potential of artificial intelligence enhancement of CLS control algorithms by enabling systems to learn from and predict responses to achieve more effective and adaptive optimal therapies. Ultimately, this Review charts a path towards next-generation CLSs, emphasizing the integration of synthetic biology and engineered cells into implantable devices.

Malnutrition poses a significant burden on the global healthcare system, in both loss of life and economic toll. Of particular interest is monitoring the regular intake of water-soluble vitamins, such as vitamin C, due to the body's inability to store them for extended periods. However, existing vitamin C monitoring conventionally relies on inconvenient, infrequent, and costly lab visits. Here, we describe an integrated touch-based disposable battery-free Smart Cup platform that harvests energy via a biofuel cell (BFC) that captures and converts metabolites naturally present on finger tips into electrical energy without requiring subject exertion or heating, and boosts the BFC's output voltage to a higher level needed to run on-board electronics that are used to sense, digitize, and wirelessly transmit data from an integrated potentiometric vitamin C sensor. Human subject testing was performed to validate the system's ability to monitor the temporal profile of vitamin C levels in natural perspiration, observing increased levels in response to an oral vitamin C supplement. The novel disposable cup-based system offers a unique opportunity for low-cost, unobtrusive, and regular real-time monitoring of vitamins, enabling individuals from all socioeconomic backgrounds to better optimize their diet and health.

Amidst the rising prevalence of respiratory diseases, the importance of effective lung treatment modalities is more critical than ever. However, current drug delivery systems face significant limitations that impede their efficacy and therapeutic outcome. Biohybrid microrobots have shown considerable promise for active in vivo drug delivery, especially for pulmonary applications via intratracheal routes. However, the invasive nature of intratracheal administration poses barriers to its clinical translation. Herein, we report on an efficient non-invasive inhalation-based method of delivering microrobots to the lungs. A nebulizer is employed to encapsulate picoeukaryote algae microrobots within small aerosol particles, enabling them to reach the lower respiratory tract. Post nebulization, the microrobots retain their motility ( 55 μm s-1) to help achieve a homogeneous lung distribution and long-term retention exceeding five days in the lungs. Therapeutic efficacy is demonstrated in a mouse model of acute methicillin-resistant Staphylococcus aureus pneumonia using this pulmonary inhalation approach to deliver microrobots functionalized with platelet membrane-coated polymeric nanoparticles loaded with vancomycin. These promising findings underscore the benefits of inhalable biohybrid microrobots in a setting that does not require anesthesia, highlighting the substantial translational potential of this delivery system for routine clinical applications. Reaching the depths of the respiratory tract is hard even with vapor-based drug delivery. Here, the authors devise inhalable biohybrid microrobots that, thanks to their motility, reach deeper regions of the lungs.

Tuberculosis is a severe contagious disease caused by Mycobacterium tuberculosis (Mtb), whose epidemic has persisted since its discovery in 1882. Despite global efforts to combat tuberculosis, which include financial support for prevention, diagnosis, and treatment, relapses of latent patients and an increase in cases of multidrug-resistant tuberculosis contribute to the non-eradication of the disease. Therefore, overcoming the difficulties in developing assays for point-of-care diagnosis has become a necessary priority in the fight against this pathogen. In this sense, substantial research efforts have been devoted to advancing electrochemical biosensors for detecting Mycobacterium tuberculosis and diagnosing Tuberculosis in centralized and decentralized settings. Thus, this work sought to address the main Mycobacterium tuberculosis antigens that have been screening targets during the development of immunosensors and electrochemical genosensors for diagnosing tuberculosis, analyzing the manufacturing strategies, validation, and analytical characteristics of these devices. Here, an in-depth discussion is provided in pursuit of understanding the main advances and challenges in overcoming limitations in tuberculosis diagnosis, including cases of latent tuberculosis or co-infected patients. Finally, we present a technological prospection, where the main patents filed, and technological products related to tuberculosis diagnosis were evaluated. Therefore, this study’s scientific and technological survey revealed that biosensors aimed at diagnosing tuberculosis still need to overcome some difficulties for practical and safe use. Furthermore, the new insights described in this work reveal valuable information about monitoring biointeractions that can support the development of new methods for diagnosis of tuberculosis.