Wireless sequential dual light delivery for programmed PDT in vivo.

Using photodynamic therapy (PDT) to treat deep-seated cancers is limited due to inefficient delivery of photosensitizers and low tissue penetration of light. Polymeric nanocarriers are widely used for photosensitizer delivery, while the self-quenching of the encapsulated photosensitizers would impair the PDT efficacy. Furthermore, the generated short-lived reactive oxygen spieces (ROS) can hardly diffuse out of nanocarriers, resulting in low PDT efficacy. Therefore, a smart nanocarrier system which can be degraded by light, followed by photosensitizer activation can potentially overcome these limitations and enhance the PDT efficacy. A light-sensitive polymer nanocarrier encapsulating photosensitizer (RB-M) was synthesized. An implantable wireless dual wavelength microLED device which delivers the two light wavelengths sequentially was developed to programmatically control the release and activation of the loaded photosensitizer. Two transmitter coils with matching resonant frequencies allow activation of the connected LEDs to emit different wavelengths independently. Optimal irradiation time, dose, and RB-M concentration were determined using an agent-based digital simulation method. In vitro and in vivo validation experiments in an orthotopic rat liver hepatocellular carcinoma disease model confirmed that the nanocarrier rupture and sequential low dose light irradiation strategy resulted in successful PDT at reduced photosensitizer and irradiation dose, which is a clinically significant event that enhances treatment safety.

Single body-coupled fiber enables chipless textile electronics.

Intelligent textiles provide an ideal platform for merging technology into daily routines. However, current textile electronic systems often rely on rigid silicon components, which limits seamless integration, energy efficiency, and comfort. Chipless electronic systems still face digital logic challenges owing to the lack of dynamic energy-switching carriers. We propose a chipless body-coupled energy interaction mechanism for ambient electromagnetic energy harvesting and wireless signal transmission through a single fiber. The fiber itself enables wireless visual-digital interactions without the need for extra chips or batteries on textiles. Because all of the electronic assemblies are merged in a miniature fiber, this facilitates scalable fabrication and compatibility with modern weaving techniques, thereby enabling versatile and intelligent clothing. We propose a strategy that may address the problems of silicon-based textile systems.

Harnessing metamaterials for efficient wireless power transfer for implantable medical devices.

Wireless power transfer (WPT) within the human body can enable long-lasting medical devices but poses notable challenges, including absorption by biological tissues and weak coupling between the transmitter (Tx) and receiver (Rx). In pursuit of more robust and efficient wireless power, various innovative strategies have emerged to optimize power transfer efficiency (PTE). One such groundbreaking approach stems from the incorporation of metamaterials, which have shown the potential to enhance the capabilities of conventional WPT systems. In this review, we delve into recent studies focusing on WPT systems that leverage metamaterials to achieve increased efficiency for implantable medical devices (IMDs) in the electromagnetic paradigm. Alongside a comparative analysis, we also outline current challenges and envision potential avenues for future advancements.

Ambient health sensing on passive surfaces using metamaterials.

Ambient sensors can continuously and unobtrusively monitor a person's health and well-being in everyday settings. Among various sensing modalities, wireless radio-frequency sensors offer exceptional sensitivity, immunity to lighting conditions, and privacy advantages. However, existing wireless sensors are susceptible to environmental interference and unable to capture detailed information from multiple body sites. Here, we present a technique to transform passive surfaces in the environment into highly sensitive and localized health sensors using metamaterials. Leveraging textiles' ubiquity, we engineer metamaterial textiles that mediate near-field interactions between wireless signals and the body for contactless and interference-free sensing. We demonstrate that passive surfaces functionalized by these metamaterials can provide hours-long cardiopulmonary monitoring with accuracy comparable to gold standards. We also show the potential of distributed sensors and machine learning for continuous blood pressure monitoring. Our approach enables passive environmental surfaces to be harnessed for ambient sensing and digital health applications.

A Magnetic Particle Imaging Approach for Minimally Invasive Imaging and Sensing With Implantable Bioelectronic Circuits.

Minimally-invasive and biocompatible implantable bioelectronic circuits are used for long-term monitoring of physiological processes in the body. However, there is a lack of methods that can cheaply and conveniently image the device within the body while simultaneously extracting sensor information. Magnetic Particle Imaging (MPI) with zero background signal, high contrast, and high sensitivity with quantitative images is ideal for this challenge because the magnetic signal is not absorbed with increasing tissue depth and incurs no radiation dose. We show how to easily modify common implantable devices to be imaged by MPI by encapsulating and magnetically-coupling magnetic nanoparticles (SPIOs) to the device circuit. These modified implantable devices not only provide spatial information via MPI, but also couple to our handheld MPI reader to transmit sensor information by modulating harmonic signals from magnetic nanoparticles via switching or frequency-shifting with resistive or capacitive sensors. This paper provides proof-of-concept of an optimized MPI imaging technique for implantable devices to extract spatial information as well as other information transmitted by the implanted circuit (such as biosensing) via encoding in the magnetic particle spectrum. The 4D images present 3D position and a changing color tone in response to a variable biometric. Biophysical sensing via bioelectronic circuits that take advantage of the unique imaging properties of MPI may enable a wide range of minimally invasive applications in biomedicine and diagnosis.

Ambient Cardiovascular Monitoring with Metamaterial Textile Sensors.

Contactless sensors embedded in the ambient environment have broad applications in unobtrusive, long-term health monitoring for preventative and personalized healthcare. Microwave radar sensors are an attractive candidate for ambient sensing due to their high sensitivity to physiological motions, ability to penetrate through obstacles and privacy-preserving properties, but practical applications in complex real-world environments have been limited because of challenges associated with background clutter and interference. In this work, we propose a thin and soft textile sensor based on microwave metamaterials that can be easily integrated into ordinary furniture for contactless ambient monitoring of multiple cardiovascular signals in a localized manner. Evaluations of our sensor's performance in human subjects show high accuracy of heartbeat and arterial pulse detection, with ≥ 96.5% sensitivity and < 5% mean absolute relative error (MARE) across all subjects. We demonstrate our sensor's utility for cuffless blood pressure monitoring on a human subject over a continuous 10-minute period. Our results highlight the potential of metamaterial textile sensors in ambient health and wellness monitoring applications.Clinical relevance-The contactless metamaterial textile sensors demonstrated in this paper provide unobtrusive, convenient and long-term monitoring of multiple cardiovascular health metrics, including heart rate, pulse rate and cuffless blood pressure, which can facilitate preventative and personalized healthcare.

Frictionless multiphasic interface for near-ideal aero-elastic pressure sensing.

Conventional pressure sensors rely on solid sensing elements. Instead, inspired by the air entrapment phenomenon on the surfaces of submerged lotus leaves, we designed a pressure sensor that uses the solid-liquid-liquid-gas multiphasic interfaces and the trapped elastic air layer to modulate capacitance changes with pressure at the interfaces. By creating an ultraslippery interface and structuring the electrodes at the nanoscale and microscale, we achieve near-friction-free contact line motion and thus near-ideal pressure-sensing performance. Using a closed-cell pillar array structure in synergy with the ultraslippery electrode surface, our sensor achieved outstanding linearity (R2 = 0.99944 ± 0.00015; nonlinearity, 1.49 ± 0.17%) while simultaneously possessing ultralow hysteresis (1.34 ± 0.20%) and very high sensitivity (79.1 ± 4.3 pF kPa-1). The sensor can operate under turbulent flow, in in vivo biological environments and during laparoscopic procedures. We anticipate that such a strategy will enable ultrasensitive and ultraprecise pressure monitoring in complex fluid environments with performance beyond the reach of the current state-of-the-art.

Synergetic positivity of loss and noise in nonlinear non-Hermitian resonators.

Loss and noise are usually undesirable in electronics and optics, which are generally mitigated by separate ways in the cost of bulkiness and complexity. Recent studies of non-Hermitian systems have shown a positive role of loss in various loss-induced counterintuitive phenomena, while noise still remains a fundamental challenge in non-Hermitian systems particularly for sensing and lasing. Here, we simultaneously reverse the detrimental loss and noise and reveal their coordinated positive role in nonlinear non-Hermitian resonators. This synergetic effect leads to the amplified spectrum intensity with suppressed spectrum fluctuations after adding both loss and noise. We reveal the underlying mechanism of nonlinearity-induced bistability engineered by loss in the non-Hermitian resonators and noise-loss enhanced coherence of eigenfrequency hopping driven by temporal modulation of detuning. Our findings enrich counterintuitive non-Hermitian physics and lead to a general recipe to overcome loss and noise from electronics to photonics with applications from sensing to communication.

Implant-to-implant wireless networking with metamaterial textiles.

Implanted bioelectronic devices can form distributed networks capable of sensing health conditions and delivering therapy throughout the body. Current clinically-used approaches for wireless communication, however, do not support direct networking between implants because of signal losses from absorption and reflection by the body. As a result, existing examples of such networks rely on an external relay device that needs to be periodically recharged and constitutes a single point of failure. Here, we demonstrate direct implant-to-implant wireless networking at the scale of the human body using metamaterial textiles. The textiles facilitate non-radiative propagation of radio-frequency signals along the surface of the body, passively amplifying the received signal strength by more than three orders of magnitude (>30 dB) compared to without the textile. Using a porcine model, we demonstrate closed-loop control of the heart rate by wirelessly networking a loop recorder and a vagus nerve stimulator at more than 40 cm distance. Our work establishes a wireless technology to directly network body-integrated devices for precise and adaptive bioelectronic therapies.

Stochastic Exceptional Points for Noise-Assisted Sensing.

Noise is a fundamental challenge for sensors deployed in daily environments for ambient sensing, health monitoring, and wireless networking. Current strategies for noise mitigation rely primarily on reducing or removing noise. Here, we introduce stochastic exceptional points and show the utility to reverse the detrimental effect of noise. The stochastic process theory illustrates that the stochastic exceptional points manifest as fluctuating sensory thresholds that give rise to stochastic resonance, a counterintuitive phenomenon in which the added noise increases the system's ability to detect weak signals. Demonstrations using a wearable wireless sensor show that the stochastic exceptional points lead to more accurate tracking of a person's vital signs during exercise. Our results may lead to a distinct class of sensors that overcome and are enhanced by ambient noise for applications ranging from healthcare to the internet of things.

Technology Roadmap for Flexible Sensors.

Humans rely increasingly on sensors to address grand challenges and to improve quality of life in the era of digitalization and big data. For ubiquitous sensing, flexible sensors are developed to overcome the limitations of conventional rigid counterparts. Despite rapid advancement in bench-side research over the last decade, the market adoption of flexible sensors remains limited. To ease and to expedite their deployment, here, we identify bottlenecks hindering the maturation of flexible sensors and propose promising solutions. We first analyze challenges in achieving satisfactory sensing performance for real-world applications and then summarize issues in compatible sensor-biology interfaces, followed by brief discussions on powering and connecting sensor networks. Issues en route to commercialization and for sustainable growth of the sector are also analyzed, highlighting environmental concerns and emphasizing nontechnical issues such as business, regulatory, and ethical considerations. Additionally, we look at future intelligent flexible sensors. In proposing a comprehensive roadmap, we hope to steer research efforts towards common goals and to guide coordinated development strategies from disparate communities. Through such collaborative efforts, scientific breakthroughs can be made sooner and capitalized for the betterment of humanity.

Cation-Induced Assembly of Conductive MXene Fibers for Wearable Heater, Wireless Communication, and Stem Cell Differentiation.

Emerging wearable electronics, wireless communication, and tissue engineering require the development of conductive fiber-shaped electrodes and biointerfaces. Ti3C2Tx MXene nanosheets serve as promising building block units for the construction of highly conductive fibers with integrated functionalities, yet a facile and scalable fabrication scheme is highly required. Herein, a cation-induced assembly process is developed for the scalable fabrication of conductive fibers with MXene sheaths and alginate cores (abbreviated as MXene@A). The fabrication scheme of MXene@A fibers includes the fast extrusion of alginate fibers followed by electrostatic assembly of MXene nanosheets, enabling high-speed fiber production. When multiple fabrication parameters are optimized, the MXene@A fibers exhibit a superior electrical conductivity of 1083 S cm-1, which can be integrated as Joule heaters into textiles for wearable thermal management. By triggering reversible de/hydration of alginate cores upon heating, the MXene@A fibers can be repeatedly contracted and generate large contraction stress that is >40 times higher than the ones of mammalian skeletal muscle. Furthermore, the MXene@A springs demonstrate large contraction strains up to 65.5% and are then fabricated into a reconfigurable dipole antenna to wirelessly monitor the surrounding heat sources. In the end, with the biocompatibility of MXene nanosheets, the MXene@A fibers enable the guidance of neural stem/progenitor cells differentiation and the promotion of neurite outgrowth. With a cation-induced assembly process, our multifunctional MXene@A fibers exhibit high scalability for future manufacturing and hold the prospect to inspire other applications.

Bioelectronic devices for light-based diagnostics and therapies.

Light has broad applications in medicine as a tool for diagnosis and therapy. Recent advances in optical technology and bioelectronics have opened opportunities for wearable, ingestible, and implantable devices that use light to continuously monitor health and precisely treat diseases. In this review, we discuss recent progress in the development and application of light-based bioelectronic devices. We summarize the key features of the technologies underlying these devices, including light sources, light detectors, energy storage and harvesting, and wireless power and communications. We investigate the current state of bioelectronic devices for the continuous measurement of health and on-demand delivery of therapy. Finally, we highlight major challenges and opportunities associated with light-based bioelectronic devices and discuss their promise for enabling digital forms of health care.

Needle-integrated ultrathin bioimpedance microsensor array for early detection of extravasation.

Extravasation is a common complication during intravenous therapy in which infused fluids leak into the surrounding tissues. Timely intervention can prevent severe adverse consequences, but early detection remains an unmet clinical need because existing sensors are not sensitive to leakage occurring in small volumes (< 200 µL) or at deep venipuncture sites. Here, an ultrathin bioimpedance microsensor array that can be integrated on intravenous needles for early and sensitive detection of extravasation is reported. The array comprises eight microelectrodes fabricated on an ultrathin and flexible polyimide substrate as well as functionalized using poly(3,4-ethylenedioxythiophene) and multi-walled carbon nanotubes. Needle integration places the array proximity to venipuncture site, and functional coating significantly reduces interface impedance, both enable the microsensors with high sensitivity to detect early extravasation. In vitro and in vivo experiments demonstrate the capability of the microsensors to differentiate various intravenous solutions from different tissue layers as well as identify saline extravasation with detection limit as low as 20 µL.

Topographic design in wearable MXene sensors with in-sensor machine learning for full-body avatar reconstruction.

Wearable strain sensors that detect joint/muscle strain changes become prevalent at human-machine interfaces for full-body motion monitoring. However, most wearable devices cannot offer customizable opportunities to match the sensor characteristics with specific deformation ranges of joints/muscles, resulting in suboptimal performance. Adequate wearable strain sensor design is highly required to achieve user-designated working windows without sacrificing high sensitivity, accompanied with real-time data processing. Herein, wearable Ti3C2Tx MXene sensor modules are fabricated with in-sensor machine learning (ML) models, either functioning via wireless streaming or edge computing, for full-body motion classifications and avatar reconstruction. Through topographic design on piezoresistive nanolayers, the wearable strain sensor modules exhibited ultrahigh sensitivities within the working windows that meet all joint deformation ranges. By integrating the wearable sensors with a ML chip, an edge sensor module is fabricated, enabling in-sensor reconstruction of high-precision avatar animations that mimic continuous full-body motions with an average avatar determination error of 3.5 cm, without additional computing devices.

Wireless interfaces for brain neurotechnologies.

Wireless interfaces enable brain-implanted devices to remotely interact with the external world. They are critical components in modern research and clinical neurotechnologies and play a central role in determining their overall size, lifetime and functionality. Wireless interfaces use a wide range of modalities-including radio-frequency fields, acoustic waves and light-to transfer energy and data to and from an implanted device. These forms of energy interact with living tissue through distinct mechanisms and therefore lead to systems with vastly different form factors, operating characteristics, and safety considerations. This paper reviews recent advances in the development of wireless interfaces for brain neurotechnologies. We summarize the requirements that state-of-the-art brain-implanted devices impose on the wireless interface, and discuss the working principles and applications of wireless interfaces based on each modality. We also investigate challenges associated with wireless brain neurotechnologies and discuss emerging solutions permitted by recent developments in electrical engineering and materials science. This article is part of the theme issue 'Advanced neurotechnologies: translating innovation for health and well-being'.

Digitally-embroidered liquid metal electronic textiles for wearable wireless systems.

Electronic textiles capable of sensing, powering, and communication can be used to non-intrusively monitor human health during daily life. However, achieving these functionalities with clothing is challenging because of limitations in the electronic performance, flexibility and robustness of the underlying materials, which must endure repeated mechanical, thermal and chemical stresses during daily use. Here, we demonstrate electronic textile systems with functionalities in near-field powering and communication created by digital embroidery of liquid metal fibers. Owing to the unique electrical and mechanical properties of the liquid metal fibers, these electronic textiles can conform to body surfaces and establish robust wireless connectivity with nearby wearable or implantable devices, even during strenuous exercise. By transferring optimized electromagnetic patterns onto clothing in this way, we demonstrate a washable electronic shirt that can be wirelessly powered by a smartphone and continuously monitor axillary temperature without interfering with daily activities.

Wirelessly Activated Nanotherapeutics for In Vivo Programmable Photodynamic-Chemotherapy of Orthotopic Bladder Cancer.

Photochemical internalization (PCI) is a promising intervention using photodynamic therapy (PDT) to enhance the activity of chemotherapeutic drugs. However, current bladder cancer treatments involve high-dose chemotherapy and high-irradiance PDT which cause debilitating side effects. Moreover, low penetration of light and drugs in target tissues and cumbersome light delivery procedures hinder the clinical utility of PDT and chemotherapy combination for PCI. To circumvent these challenges, a photodynamic-chemotherapy approach is developed comprising tumor-targeting glycosylated nanocarriers, coloaded with chlorin e6 (Ce6) and gemcitabine elaidate (GemE), and a miniaturized implantable wirelessly powered light-emitting diode (LED) as a light source. The device successfully delivers four weekly light doses to the bladder while the nanocarrier promoted the specific accumulation of drugs in tumors. This approach facilitates the combination of low-irradiance PDT (1 mW cm-2 ) and low-dose chemotherapy (≈1500× lower than clinical dose) which significantly cures and controls orthotopic disease burden (90% treated vs control, 35%) in mice, demonstrating a potential new bladder cancer treatment option.

Electronic textiles for energy, sensing, and communication.

Electronic textiles (e-textiles) are fabrics that can perform electronic functions such as sensing, computation, display, and communication. They can enhance the functionality of clothing in a variety of convenient and unobtrusive ways, thus have garnered significant research and commercial interest in applications ranging from fashion to healthcare. Recent advances in materials science and electronics have given rise to variety of e-textile components, including sensors, energy harvesters, batteries, and antennas on flexible and breathable textiles substrates. In this review, we discuss recent advances in the development of e-textiles for energy, sensing, and communication. In addition, we investigate challenges in the integration of components to realize e-textile systems, and highlight opportunities enabled by innovations in materials science, engineering, and data science.