Continuous biosensing provides real-time information about biochemical processes and holds great potential for health monitoring. Aptamers have emerged as promising alternatives over traditional biorecognition elements. However, the underlying aptamer-target binding interactions are often poorly understood. Here, we present a technique that can decode aptamer-protein binding interactions at the single-molecule level. We demonstrate that our single-molecule assay is able to decode the underlying binding kinetics of aptamers despite their similar binding affinity. Guided by computational simulations and validated with quartz crystal microbalance experiments, we show that the quantitative insights generated by this single-molecule technique enabled the rational understanding of biosensor performance (i.e., the sensitivity and limit of detection). This capability was demonstrated with thrombin as the analyte and the structurally similar aptamers HD1, RE31, and NU172 as the biorecognition elements. This work decodes aptamer-protein interactions with high temporal resolution, paving the way for the rational design of aptamer-based biosensors.

Ultrasound is a promising technology to address challenges in drug delivery, including limited drug penetration across physiological barriers and ineffective targeting. Here we provide an overview of the significant advances made in recent years in overcoming technical and pharmacological barriers using ultrasound-assisted drug delivery to the central and peripheral nervous system. We commence by exploring the fundamental principles of ultrasound physics and its interaction with tissue. The mechanisms of ultrasonic-enhanced drug delivery are examined, as well as the relevant tissue barriers. We highlight drug transport through such tissue barriers utilizing insonation alone, in combination with ultrasound contrast agents (e.g., microbubbles), and through innovative particulate drug delivery systems. Furthermore, we review advances in systems and devices for providing therapeutic ultrasound, as their practicality and accessibility are crucial for clinical application.

Waterborne polyurethane (WPU) has attracted significant interest as a promising alternative to solvent-based polyurethane (SPU) due to its positive impact on safety and sustainability. However, significant limitations of WPU, such as its weaker mechanical strength, limit its ability to replace SPU. Triblock amphiphilic diols are promising materials to enhance the performance of WPU due to their well-defined hydrophobic-hydrophilic structures. Yet, our understanding of the relationship between the hydrophobic-hydrophilic arrangements of triblock amphiphilic diols and the physical properties of WPU remains limited. In this study, we show that by controlling the micellar structure of WPU in aqueous solution via the introduction of triblock amphiphilic diols, the postcuring efficiency and the resulting mechanical strength of WPU can be significantly enhanced. Small-angle neutron scattering confirmed the microstructure and spatial distribution of hydrophilic and hydrophobic segments in the engineered WPU micelles. In addition, we show that the control of the WPU micellar structure through triblock amphiphilic diols renders WPU attractive in the applications of controlled release, such as drug delivery. Here, curcumin was used as a model hydrophobic drug, and the drug release behavior from WPU-micellar-based drug delivery systems was characterized. It was found that curcumin-loaded WPU drug delivery systems were highly biocompatible and exhibited antibacterial properties in vitro. Furthermore, the sustained release profile of the drug was found to be dependent on the structure of the triblock amphiphilic diols, suggesting the possibility of controlling the drug release profile via the selection of triblock amphiphilic diols. This work shows that by shedding light on the structure-property relationship of triblock amphiphilic diol-containing WPU micelles, we may enhance the applicability of WPU systems and move closer to realizing their promising potential in real-life applications.

With a growing focus on properties of softness, miniaturization, and intelligence, extensive research has been focusing on constructing wearable electronic devices facilitating comfort, wearable health monitoring and diagnosis. Among recent progress in the development of wearable bioelectronics, wearable near-infrared spectroscopy (NIRS) devices demonstrate wide implementation possibilities in multiple health monitoring scenarios. Throughout the years, multiple design strategies have assisted in developing wearable NIRS devices with high wearing comfortability and miniaturized size. This review summarizes the principle of NIRS technology, recent advances in design strategies towards soft, wearable, miniaturized NIRS devices, and the future potential development directions. Based on the discussion of different design strategies, including modular device design, flexible hybrid electronics, and materials innovation, we also pinpoint some development directions for wearable NIRS. The reviewed and proposed research efforts may enhance the applicability and capability of NIRS as an important technology for digital health.

Endotoxin is a deadly pyrogen, rendering it crucial to monitor with high accuracy and efficiency. However, current endotoxin detection relies on multistep processes that are labor-intensive, time-consuming, and unsustainable. Here, we report an aptamer-based biosensor for the real-time optical detection of endotoxin. The endotoxin sensor exploits the distance-dependent scattering of gold nanoparticles (AuNPs) coupled to a gold nanofilm. This is enabled by the conformational changes of an endotoxin-specific aptamer upon target binding. The sensor can be used in an ensemble mode and single-particle mode under dark-field illumination. In the ensemble mode, the sensor is coupled with a microspectrometer and exhibits high specificity, reliability (i.e., linear concentration to signal profile in logarithmic scale), and reusability for repeated endotoxin measurements. Individual endotoxins can be detected by monitoring the color of single AuNPs via a color camera, achieving single-molecule resolution. This platform can potentially advance endotoxin detection to safeguard medical, food, and pharmaceutical products.

Accurate and real-time monitoring of biomarker proteins, such as Tumor Necrosis Factor (TNF) alpha, plays a vital role in early disease diagnosis, effective treatment design, and personalized health management strategies. However, existing detection methods, including enzyme-linked immunosorbent assay (ELISA), radioimmune assays (RIA), and polymerase chain reaction (PCR), have significant drawbacks regarding sensitivity, cost, time, and labor efficiency, emphasizing the urgent need for alternative biosensing techniques. Here, we present a mass-based biosensing approach utilizing aptamers for the real-time detection of proteins, using TNF-alpha as the model analyte. The recognition process is based on the selective binding of the target molecule to the aptamer's unique three-dimensional structure. By utilizing a quartz crystal microbalance (QCM) as the transducing element, real-time detection of target binding is translated into a linear decrease in resonant frequency due to the change in mass upon target binding. The developed aptasensor enabled real-time quantification of TNF-alpha with high reliability, sensitivity, and specificity. The sensitivity of the sensor ranged from 14.5 nM to 115.6 nM, in which a linear correlation between target concentration and frequency decrease rate was found. Successful sensor regeneration demonstrated potential for continuous measurements in solution. By directly monitoring the change in mass during sensor fabrication and upon analyte binding, this platform provides key mechanistic insights in the surface functionalization process during sensor fabrication and analyte binding kinetics during sensor operation. In the future, incorporation of alternative target receptors, by simply changing the aptamer sequence, can broaden the analyte spectrum, making this platform highly versatile. We hereby demonstrate a technology that can be utilized for various biosensing platforms upon minimal modifications, including electrochemical and optical systems, for a wide range of macromolecular analytes.

Flexible and stretchable biosensors have the advantage of enhanced signal validity and patient comfort during physiological signal sensing and biomolecular analysis, crucial for disease diagnosis, treatment and health management. Their lightness, softness and excellent mechanical properties enable effective skin-device interface coupling and skin safety profiles, realizing multi-functional, intelligent real-time sensing. In this review, the basic sensing principles of biosensor systems and their applications are discussed. Moreover, the potential applications and prospective progress of these biosensors are further prospected. Flexible, wearable biosensors have the potential to realize continuous and long-term health monitoring in clinical and daily health care.

Temporary postoperative cardiac pacing requires devices with percutaneous leads and external wired power and control systems. This hardware introduces risks for infection, limitations on patient mobility, and requirements for surgical extraction procedures. Bioresorbable pacemakers mitigate some of these disadvantages, but they demand pairing with external, wired systems and secondary mechanisms for control. We present a transient closed-loop system that combines a time-synchronized, wireless network of skin-integrated devices with an advanced bioresorbable pacemaker to control cardiac rhythms, track cardiopulmonary status, provide multihaptic feedback, and enable transient operation with minimal patient burden. The result provides a range of autonomous, rate-adaptive cardiac pacing capabilities, as demonstrated in rat, canine, and human heart studies. This work establishes an engineering framework for closed-loop temporary electrotherapy using wirelessly linked, body-integrated bioelectronic devices.

Background Current near-infrared spectroscopy (NIRS)-based systems for continuous flap monitoring are highly sensitive for detecting malperfusion. However, the clinical utility and user experience are limited by the wired connection between the sensor and bedside console. This wire leads to instability of the flap-sensor interface and may cause false alarms. Methods We present a novel wearable wireless NIRS sensor for continuous fasciocutaneous free flap monitoring. This waterproof silicone-encapsulated Bluetooth-enabled device contains two light-emitting diodes and two photodetectors in addition to a battery sufficient for 5 days of uninterrupted function. This novel device was compared with a ViOptix T.Ox monitor in a porcine rectus abdominus myocutaneous flap model of arterial and venous occlusions. Results Devices were tested in four flaps using three animals. Both devices produced very similar tissue oxygen saturation (StO 2) tracings throughout the vascular clamping events, with obvious and parallel changes occurring on arterial clamping, arterial release, venous clamping, and venous release. Small interdevice variations in absolute StO 2 value readings and magnitude of change were observed. The normalized cross-correlation at zero lag describing correspondence between the novel NIRS and T.Ox devices was >0.99 in each trial. Conclusion The wireless NIRS flap monitor is capable of detecting StO 2 changes resultant from arterial vascular occlusive events. In this porcine flap model, the functionality of this novel sensor closely mirrored that of the T.Ox wired platform. This device is waterproof, highly adhesive, skin conforming, and has sufficient battery life to function for 5 days. Clinical testing is necessary to determine if this wireless functionality translates into fewer false-positive alarms and a better user experience.

Self-healing soft electronic material composition is crucial to sustain the device long-term durability. The fabrication of self-healing soft electronics exposed to high moisture environment is a significant challenge that has yet to be fully achieved. This paper presents the novel concept of a water-assisted room-temperature autonomous self-healing mechanism based on synergistically dynamic covalent Schiff-based imine bonds with hydrogen bonds. The supramolecular water-assisted self-healing polymer (WASHP) films possess rapid self-healing kinetic behavior and high stretchability due to a reversible dissociation–association process. In comparison with the pristine room-temperature self-healing polymer, the WASHP demonstrates favorable mechanical performance at room temperature and a short self-healing time of 1 h; furthermore, it achieves a tensile strain of 9050%, self-healing efficiency of 95%, and toughness of 144.2 MJ m⁻³. As a proof of concept, a versatile WASHP-based light-emitting touch-responsive device (WASHP-LETD) and perovskite quantum dot (PeQD)-based white LED backlight are designed. The WASHP-LETD has favorable mechanical deformation performance under pressure, bending, and strain, whereas the WASHP-PeQDs exhibit outstanding long-term stability even over a period exceeding one year in a boiling water environment. This paper provides a mechanically robust approach for producing eco-friendly, economical, and waterproof e-skin device components.

Accurate, real-time monitoring of intravascular oxygen levels is important in tracking the cardiopulmonary health of patients after cardiothoracic surgery. Existing technologies use intravascular placement of glass fiber-optic catheters that pose risks of blood vessel damage, thrombosis, and infection. In addition, physical tethers to power supply systems and data acquisition hardware limit freedom of movement and add clutter to the intensive care unit. This report introduces a wireless, miniaturized, implantable optoelectronic catheter system incorporating optical components on the probe, encapsulated by soft biocompatible materials, as alternative technology that avoids these disadvantages. The absence of physical tethers and the flexible, biocompatible construction of the probe represent key defining features, resulting in a high-performance, patient-friendly implantable oximeter that can monitor localized tissue oxygenation, heart rate, and respiratory activity with wireless, real-time, continuous operation. In vitro and in vivo testing shows that this platform offers measurement accuracy and precision equivalent to those of existing clinical standards.

Globally, neonatal mortality remains unacceptability high. Physiological monitoring is foundational to the care of these vulnerable patients to assess neonatal cardiopulmonary status, guide medical intervention, and determine readiness for safe discharge. However, most existing physiological monitoring systems require multiple electrodes and sensors, which are linked to wires tethered to wall-mounted display units, to adhere to the skin. For neonates, these systems can cause skin injury, prevent kangaroo mother care, and complicate basic clinical care. Novel, wireless, and biointegrated sensors provide opportunities to enhance monitoring capabilities, reduce iatrogenic injuries, and promote family-centric care. Early validation data have shown performance equivalent to (and sometimes exceeding) standard-of-care monitoring systems in premature neonates cared for in high-income countries. The reusable nature of these sensors and compatibility with low-cost mobile phones have the future potential to enable substantially lower monitoring costs compared with existing systems. Deployment at scale, in low-income countries, holds the promise of substantial improvements in neonatal outcomes.

The standard of clinical care in many pediatric and neonatal neurocritical care units involves continuous monitoring of cerebral hemodynamics using hard-wired devices that physically adhere to the skin and connect to base stations that commonly mount on an adjacent wall or stand. Risks of iatrogenic skin injuries associated with adhesives that bond such systems to the skin and entanglements of the patients and/or the healthcare professionals with the wires can impede clinical procedures and natural movements that are critical to the care, development, and recovery of pediatric patients. This paper presents a wireless, miniaturized, and mechanically soft, flexible device that supports measurements quantitatively comparable to existing clinical standards. The system features a multiphotodiode array and pair of light-emitting diodes for simultaneous monitoring of systemic and cerebral hemodynamics, with ability to measure cerebral oxygenation, heart rate, peripheral oxygenation, and potentially cerebral pulse pressure and vascular tone, through the utilization of multiwavelength reflectance-mode photoplethysmography and functional near-infrared spectroscopy. Monte Carlo optical simulations define the tissue-probing depths for source-detector distances and operating wavelengths of these systems using magnetic resonance images of the head of a representative pediatric patient to define the relevant geometries. Clinical studies on pediatric subjects with and without congenital central hypoventilation syndrome validate the feasibility for using this system in operating hospitals and define its advantages relative to established technologies. This platform has the potential to substantially enhance the quality of pediatric care across a wide range of conditions and use scenarios, not only in advanced hospital settings but also in clinics of lower- and middle-income countries.