Wearable and implantable biosensors are pioneering new frontiers in precision medicine by enabling continuous biomolecule analysis for fundamental investigation and personalized health monitoring. However, their widespread adoption remains impeded by challenges such as the limited number of detectable targets, operational instability and production scalability. Here, to address these issues, we introduce printable core–shell nanoparticles with built-in dual functionality: a molecularly imprinted polymer shell for customizable target recognition, and a nickel hexacyanoferrate core for stable electrochemical transduction. Using inkjet printing with an optimized nanoparticle ink formulation, we demonstrate the mass production of robust and flexible biosensors capable of continuously monitoring a broad spectrum of biomarkers, including amino acids, vitamins, metabolites and drugs. We demonstrate their effectiveness in wearable metabolic monitoring of vitamin C, tryptophan and creatinine in individuals with long COVID. Additionally, we validate their utility in therapeutic drug monitoring for cancer patients and in a mouse model through providing real-time analysis of immunosuppressants such as busulfan, cyclophosphamide and mycophenolic acid. Current wearable and implantable biosensors still face challenges to improve sensitivity, stability and scalability. Here the authors report inkjet-printable, mass-producible core–shell nanoparticle-based biosensors to monitor a broad range of biomarkers.
The emerging and exciting field of on-body wearable chemical sensing represents a major transition away from common centralized laboratory-based analytical systems involving in-vitro test-tube assays of blood or urine. Such a major revolution has led to a variety of wearable chemical sensors that allow non-invasive continuous monitoring of many important analytes in biofluids, such as sweat, saliva, tears, and interstitial fluid (ISF), instead of blood. These biosensors can detect several metabolites and electrolytes, and their integration with smart devices and the Internet of Things (IoT) will prompt personalized nutrition to a new era. Precision Nutrition powered by biosensors and wearables will be able to accurately predict and prevent diet-related diseases while increasing the life span of the population by promoting healthy aging and lifestyle. The non-invasive nature of these wearable biosensors allows continuous monitoring of various human physiological signals, including nutritional biomarkers, for an improved approach to personalized nutrition recommendations as part of Precision Nutrition.
Wearable sensors hold great potential in empowering personalized health monitoring, predictive analytics, and timely intervention toward personalized healthcare. Advances in flexible electronics, materials science, and electrochemistry have spurred the development of wearable sweat sensors that enable the continuous and noninvasive screening of analytes indicative of health status. Existing major challenges in wearable sensors include: improving the sweat extraction and sweat sensing capabilities, improving the form factor of the wearable device for minimal discomfort and reliable measurements when worn, and understanding the clinical value of sweat analytes toward biomarker discovery. This review provides a comprehensive review of wearable sweat sensors and outlines state-of-the-art technologies and research that strive to bridge these gaps. The physiology of sweat, materials, biosensing mechanisms and advances, and approaches for sweat induction and sampling are introduced. Additionally, design considerations for the system-level development of wearable sweat sensing devices, spanning from strategies for prolonged sweat extraction to efficient powering of wearables, are discussed. Furthermore, the applications, data analytics, commercialization efforts, challenges, and prospects of wearable sweat sensors for precision medicine are discussed.
Wearable sweat sensors can potentially be used to continuously and non-invasively monitor physicochemical biomarkers that contain information related to disease diagnostics and fitness tracking. However, the development of such autonomous sensors faces a number of challenges including achieving steady sweat extraction for continuous and prolonged monitoring and addressing the high power demands of multifunctional and complex analysis. Here we report an autonomous wearable biosensor that is powered by a perovskite solar cell and can provide continuous and non-invasive metabolic monitoring. The device uses a flexible quasi-two-dimensional perovskite solar cell module that provides ample power under outdoor and indoor illumination conditions (power conversion efficiency exceeding 31% under indoor light illumination). We show that the wearable device can continuously collect multimodal physicochemical data—glucose, pH, sodium ion, sweat rate and skin temperature—across indoor and outdoor physical activities for over 12 h.
Wearable sweat sensors have the potential to revolutionize precision medicine as they can non-invasively collect molecular information closely associated with an individual's health status. However, the majority of clinically relevant biomarkers cannot be continuously detected in situ using existing wearable approaches. Molecularly imprinted polymers (MIPs) are a promising candidate to address this challenge but haven't yet gained widespread use due to their complex design and optimization process yielding variable selectivity. Here, QuantumDock is introduced, an automated computational framework for universal MIP development toward wearable applications. QuantumDock utilizes density functional theory to probe molecular interactions between monomers and the target/interferent molecules to optimize selectivity, a fundamentally limiting factor for MIP development toward wearable sensing. A molecular docking approach is employed to explore a wide range of known and unknown monomers, and to identify the optimal monomer/cross-linker choice for subsequent MIP fabrication. Using an essential amino acid phenylalanine as the exemplar, experimental validation of QuantumDock is performed successfully using solution-synthesized MIP nanoparticles coupled with ultraviolet-visible spectroscopy. Moreover, a QuantumDock-optimized graphene-based wearable device is designed that can perform autonomous sweat induction, sampling, and sensing. For the first time, wearable non-invasive phenylalanine monitoring is demonstrated in human subjects toward personalized healthcare applications.
Wearable non-invasive biosensors for the continuous monitoring of metabolites in sweat can detect a few analytes at sufficiently high concentrations, typically during vigorous exercise so as to generate sufficient quantity of the biofluid. Here we report the design and performance of a wearable electrochemical biosensor for the continuous analysis, in sweat during physical exercise and at rest, of trace levels of multiple metabolites and nutrients, including all essential amino acids and vitamins. The biosensor consists of graphene electrodes that can be repeatedly regenerated in situ, functionalized with metabolite-specific antibody-like molecularly imprinted polymers and redox-active reporter nanoparticles, and integrated with modules for iontophoresis-based sweat induction, microfluidic sweat sampling, signal processing and calibration, and wireless communication. In volunteers, the biosensor enabled the real-time monitoring of the intake of amino acids and their levels during physical exercise, as well as the assessment of the risk of metabolic syndrome (by correlating amino acid levels in serum and sweat). The monitoring of metabolites for the early identification of abnormal health conditions could facilitate applications in precision nutrition.
Laser-engraved graphene (LEG) has been applied increasingly in flexible electronics over the past decade owing to its unique physical and chemical properties, and has shown great promise in energy controls, chemical and physical sensing, and telemedicine. In situ laser engraving has empowered graphene with additional versatilities such as miniaturized patterning, tunable composition, controllable morphology, and environmental friendliness. In this review, the technological advances of LEG from synthesis to applications in flexible and wearable electronic devices are summarized. Specifically, the use of LEG in designing next-generation nanogenerators, batteries, supercapacitors, physical sensors, gas sensors, biosensors, and wearable/telemedicine systems is discussed. An outlook related to LEG-based flexible electronics and key technological bottlenecks is identified.
The Martlets Society (www.martlets-society.com) is an independent non-profit organization found and run by young scholars. It aims to build a free and equal community for young scholars to build connections and have interdisciplinary exchanges. It currently holds talks and events with diverse topics to show young scholars the world of academia and beyond. It is also planning more events for the equality in education and academia.
Understanding and assessing endocrine response to stress is crucial to human performance analysis, stress-related disorder diagnosis, and mental health monitoring. Current approaches for stress monitoring are largely based on questionnaires, which could be very subjective. To avoid stress-inducing blood sampling and to realize continuous, non-invasive, and real-time stress analysis at the molecular levels, we investigate the dynamics of a stress hormone, cortisol, in human sweat using an integrated wireless sensing device. Highly sensitive, selective, and efficient cortisol sensing is enabled by a flexible sensor array that exploits the exceptional performance of laser-induced graphene for electrochemical sensing. Here, we report the first cortisol diurnal cycle and the dynamic stress-response profile constructed from human sweat. Our pilot study demonstrates a strong empirical correlation between serum and sweat cortisol, revealing exciting opportunities offered by sweat analysis toward non-invasive dynamic stress monitoring via wearable and portable sensing platforms.
Since the advent of ingestible temperature sensors and capsule endoscopes, rapid advances in electronics, robotics, nanotechnology, and material sciences have opened the door for the development of novel medical ingestible robots. The untethered robots provide direct, non-invasive access to the entire gastrointestinal (GI) tract. Furthermore, the tissues, gases, and fluids of the gastrointestinal lumen contain a multitude of biomarkers indicative of gut diseases and health. Ingestible medical robots equipped with advanced imaging and sensing techniques can enable the diagnosis and monitoring of diseases, while providing a better pathophysiological understanding of gastrointestinal disorders. In addition, various robotic actuation mechanisms in the macro- and microscale can realize enhanced drug delivery and surgical interventions for the treatment of diseases. In this paper, an overview of recent advances in ingestible robots toward imaging, sensing, drug delivery, and surgical applications in the GI tract is provided. Key challenges and strategies for the development of novel ingestible robots and future directions of ingestible robots toward precision medicine are also discussed.
The COVID-19 pandemic is an ongoing global challenge for public health systems. Ultrasensitive and early identification of infection is critical in preventing widespread COVID-19 infection by presymptomatic and asymptomatic individuals, especially in the community and in-home settings. We demonstrate a multiplexed, portable, wireless electrochemical platform for ultra-rapid detection of COVID-19: the SARS-CoV-2 RapidPlex. It detects viral antigen nucleocapsid protein, IgM and IgG antibodies, as well as the inflammatory biomarker C-reactive protein, based on our mass-producible laser-engraved graphene electrodes. We demonstrate ultrasensitive, highly selective, and rapid electrochemical detection in the physiologically relevant ranges. We successfully evaluated the applicability of our SARS-CoV-2 RapidPlex platform with COVID-19-positive and COVID-19-negative blood and saliva samples. Based on this pilot study, our multiplexed immunosensor platform may allow for high-frequency at-home testing for COVID-19 telemedicine diagnosis and monitoring.
Existing electronic skin (e-skin) sensing platforms are equipped to monitor physical parameters using power from batteries or near-field communication. For e-skins to be applied in the next generation of robotics and medical devices, they must operate wirelessly and be self-powered. However, despite recent efforts to harvest energy from the human body, self-powered e-skin with the ability to perform biosensing with Bluetooth communication are limited because of lack of a continuous energy source and limited power efficiency. Here, we report a flexible and fully perspiration-powered integrated electronic skin (PPES) for multiplexed metabolic sensing in situ. The battery-free e-skin contains multimodal sensors and highly efficient lactate biofuel cells that use a unique integration of zero- to three-dimensional nanomaterials to achieve high power intensity and long-term stability. The PPES delivered a record-breaking power density of 3.5 milliwatt-centimeter-2 for biofuel cells in untreated human body fluids (human sweat) and displayed a very stable performance during a 60-hour continuous operation. It selectively monitored key metabolic analytes (e.g., urea, NH4 +, glucose, and pH) and the skin temperature during prolonged physical activities and wirelessly transmitted the data to the user interface using Bluetooth. The PPES was also able to monitor muscle contraction and work as a human-machine interface for human- prosthesis walking.
Wireless wearable sweat biosensors have gained huge traction due to their potential for noninvasive health monitoring. As high energy consumption is a crucial challenge in this field, efficient energy harvesting from human motion represents an attractive approach to sustainably power future wearables. Despite intensive research activities, most wearable energy harvesters suffer from complex fabrication procedures, poor robustness, and low power density, making them unsuitable for continuous biosensing. Here, we propose a highly robust, mass-producible, and battery-free wearable platform that efficiently extracts power from body motion through a flexible printed circuit board (FPCB)-based freestanding triboelectric nanogenerator (FTENG). The judiciously engineered FTENG displays a high power output of ~416 mW m-2 Through seamless system integration and efficient power management, we demonstrate a battery-free triboelectrically driven system that is able to power multiplexed sweat biosensors and wirelessly transmit data to the user interfaces through Bluetooth during on-body human trials.
The recent advances in skin-interfaced wearable sensors have enabled tremendous potential toward personalized medicine and digital health. Compared with traditional healthcare, wearable sensors could perform continuous and non-invasive data collection from the human body and provide an insight into both fitness monitoring and medical diagnostics. In this review, we summarize the latest progress of skin-interfaced wearable sensors along with their integrated systems. We first introduce the strategies of materials selection and structure design that can be accommodated for intimate contact with human skin. Current development of physical and biochemical sensors is then classified and discussed with an emphasis on their sensing mechanisms. System-level integration including power supply, wireless communication, and data analysis are also briefly discussed. We conclude with an outlook of this field and identify the key challenges and opportunities for future wearable devices and systems.
Wearable biosensors have received tremendous attention over the past decade owing to their great potential in predictive analytics and treatment toward personalized medicine. Flexible electronics could serve as an ideal platform for personalized wearable devices because of their unique properties such as light weight, low cost, high flexibility and great conformability. Unlike most reported flexible sensors that mainly track physical activities and vital signs, the new generation of wearable and flexible chemical sensors enables real-time, continuous and fast detection of accessible biomarkers from the human body, and allows for the collection of large-scale information about the individual's dynamic health status at the molecular level. In this article, we review and highlight recent advances in wearable and flexible sensors toward continuous and non-invasive molecular analysis in sweat, tears, saliva, interstitial fluid, blood, wound exudate as well as exhaled breath. The flexible platforms, sensing mechanisms, and device and system configurations employed for continuous monitoring are summarized. We also discuss the key challenges and opportunities of the wearable and flexible chemical sensors that lie ahead.
Tremendous progress in synthetic micro/nanomotors has been made for potential biomedical applications. However, existing micro/nanomotor platforms are inefficient for deep tissue imaging and motion control in vivo. Here, we present a photoacoustic computed tomography (PACT) guided investigation of micromotors in intestines in vivo. The micromotors enveloped in microcapsules exhibit efficient propulsion in various biofluids once released. PACT has visualized the migration of micromotor capsules toward the targeted regions in real time in vivo. The integration of the developed microrobotic system and PACT enables deep imaging and precise control of the micromotors in vivo.
Wearable sweat sensors have the potential to provide continuous measurements of useful biomarkers. However, current sensors cannot accurately detect low analyte concentrations, lack multimodal sensing or are difficult to fabricate at large scale. We report an entirely laser-engraved sensor for simultaneous sweat sampling, chemical sensing and vital-sign monitoring. We demonstrate continuous detection of temperature, respiration rate and low concentrations of uric acid and tyrosine, analytes associated with diseases such as gout and metabolic disorders. We test the performance of the device in both physically trained and untrained subjects under exercise and after a protein-rich diet. We also evaluate its utility for gout monitoring in patients and healthy controls through a purine-rich meal challenge. Levels of uric acid in sweat were higher in patients with gout than in healthy individuals, and a similar trend was observed in serum.
An achromatization method optimized for dual-channel imaging is developed. Dichroic mirrors are employed to split and recombine narrowband signals, and separation between catoptric components is used to minimize the longitudinal chromatic shift. An achromatic system based on this principle could be built from singlet lenses, since refractive element properties such as dispersion and power are not utilized to optimize wavelength-dependent performance. To demonstrate the validity of the proposed solution, a prototype miniature fluorescence microscope optimized for two emission lines of acridine orange (525 and 650 nm) is built. To reduce the cost and accelerate assembly, the system is built from commercially available optical components. The optical train consisted of two plastic singlet lenses combined with a pair of dichroic mirrors. Optical performance of the prototype is evaluated by imaging a bar line target at both design wavelengths. To demonstrate the potential of the proposed design strategy, the achromatic system prototype is used to measure a two-part white blood cells differential count on a venous blood sample. Data from the prototype fluorescence microscope are compared against results from a commercially available blood analyzer, and the difference between both instruments is within 20%. (C) 2019 Society of Photo-Optical Instrumentation Engineers (SPIE)
Synthetic micro/nanomotors (MNMs) are a particular class of micrometer or nanometer scale devices with controllable motion behavior in solutions by transferring various energies (chemical, optical, acoustic, magnetic, electric, etc.) into mechanical energy. These tiny devices can be functionalized either chemically or physically to accomplish complex tasks in a microcosm. Up to now, MNMs have exhibited great potential in various fields, ranging from environmental remediation, nanofabrication, to biomedical applications. Recently, light-driven MNMs as classic artificial MNMs have attracted much attention. Under wireless remote control, they can perform reversible and repeatable motion behavior with immediate photoresponse. Photocatalytic micro/nanomotors (PMNMs) based on photocatalysts, one of the most important light-driven MNMs, can utilize energy from both the external light source and surrounding chemicals to achieve efficient propulsion. Unlike other kinds of MNMs, the PMNMs have a unique characteristic: photocatalytic property. On one hand, since photocatalysts can convert both optical and chemical energy inputs into mechanical propulsion of PMNMs via photocatalytic reactions, the propulsion generated can be modulated in many ways, such as through chemical concentration or light intensity. In addition, these PMNMs can be operated at low levels of optical and chemical energy input which is highly desired for more practical scenarios. Furthermore, PMNMs can be operated with custom features, including go/stop motion control through regulating an on/off switch, speed modulation through varying light intensities, direction control through adjusting light source position, and so forth. On the other hand, as superoxide radicals can be generated by photocatalytic reactions of activated photocatalysts, the PMNMs show great potential in environment remediation, especially in organic pollutant degradation. In order to construct more practical PMNMs for future applications and further extend their application fields, the ideal PMNMs should be operated in a fully environmentally friendly system with strong propulsion. In the past decade, great progress in the construction, motion regulation, and application of PMNMs has been achieved, but there are still some challenges to realize the perfect system. In this Account, we will summarize our recent efforts and those of other groups in the development toward attractive PMNM systems. First, we will illustrate basic principles about the photocatalytic reactions of photocatalysts and demonstrate how the photocatalytic reactions affect the propulsion of PMNMs. Then, we will illustrate the construction strategies for highly efficient and biocompatible PMNMs from two key aspects: (1) Improvement of energy conversion efficiency to achieve strong propulsion of PMNMs. (2) Expansion of the usable wavelengths of light to operate PMNMs in environment-friendly conditions. Next, potential applications of PMNMs have been described. In particular, environment remediation has taken major attention for the applications of PMNMs due to their photocatalytic properties. Finally, in order to promote the development of PMNMs which can be operated in fully green environments for more practical applications, an outlook of key challenges and opportunities in construction of ideal PMNMs is presented.
flexible charge-coupled device can be used to create a sensor capable of measuring the pH of a person’s sweat with high sensitivity.