While over half a century has passed since the introduction of enzyme glucose biosensors by Clark and Lyons, this important field has continued to be the focus of immense research activity. Extensive efforts during the past decade have led to major scientific and technological innovations towards tight monitoring of diabetes. Such continued progress toward advanced continuous glucose monitoring platforms, either minimal- or non-invasive, holds considerable promise for addressing the limitations of finger-prick blood testing toward tracking glucose trends over time, optimal therapeutic interventions, and improving the life of diabetes patients. However, despite these major developments, the field of glucose biosensors is still facing major challenges. The scope of this review is to present the key scientific and technological advances in electrochemical glucose biosensing over the past decade (2010-present), along with current obstacles and prospects towards the ultimate goal of highly stable and reliable real-time minimally-invasive or non-invasive glucose monitoring. After an introduction to electrochemical glucose biosensors, we highlight recent progress based on using advanced nanomaterials at the electrode-enzyme interface of three generations of glucose sensors. Subsequently, we cover recent activity and challenges towards next-generation wearable non-invasive glucose monitoring devices based on innovative sensing principles, alternative body fluids, advanced flexible materials, and novel platforms. This is followed by highlighting the latest progress in the field of minimally-invasive continuous glucose monitoring (CGM) which offers real-time information about interstitial glucose levels, by focusing on the challenges toward developing biocompatible membrane coatings to protect electrochemical glucose sensors against surface biofouling. Subsequent sections cover new analytical concepts of self-powered glucose sensors, paper-based glucose sensing and multiplexed detection of diabetes-related biomarkers. Finally, we will cover the latest advances in commercially available devices along with the upcoming future technologies.

Electrochemical glucose sensors in diabetes management: an updated review (2010-2020).

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.

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SARS-CoV-2 RapidPlex: A Graphene-Based Multiplexed Telemedicine Platform for Rapid and Low-Cost COVID-19 Diagnosis and Monitoring.

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.

Wireless battery-free wearable sweat sensor powered by human motion

Background SARS-CoV-2 antigen rapid diagnostic tests (Ag-RDTs) are increasingly being integrated in testing strategies around the world. Studies of the Ag-RDTs have shown variable performance. In this systematic review and meta-analysis, we assessed the clinical accuracy (sensitivity and specificity) of commercially available Ag-RDTs. Methods and findings We registered the review on PROSPERO (registration number: CRD42020225140). We systematically searched multiple databases (PubMed, Web of Science Core Collection, medRvix, bioRvix, and FIND) for publications evaluating the accuracy of Ag-RDTs for SARS-CoV-2 up until 30 April 2021. Descriptive analyses of all studies were performed, and when more than 4 studies were available, a random-effects meta-analysis was used to estimate pooled sensitivity and specificity in comparison to reverse transcription polymerase chain reaction (RT-PCR) testing. We assessed heterogeneity by subgroup analyses, and rated study quality and risk of bias using the QUADAS-2 assessment tool. From a total of 14,254 articles, we included 133 analytical and clinical studies resulting in 214 clinical accuracy datasets with 112,323 samples. Across all meta-analyzed samples, the pooled Ag-RDT sensitivity and specificity were 71.2% (95% CI 68.2% to 74.0%) and 98.9% (95% CI 98.6% to 99.1%), respectively. Sensitivity increased to 76.3% (95% CI 73.1% to 79.2%) if analysis was restricted to studies that followed the Ag-RDT manufacturers’ instructions. LumiraDx showed the highest sensitivity, with 88.2% (95% CI 59.0% to 97.5%). Of instrument-free Ag-RDTs, Standard Q nasal performed best, with 80.2% sensitivity (95% CI 70.3% to 87.4%). Across all Ag-RDTs, sensitivity was markedly better on samples with lower RT-PCR cycle threshold (Ct) values, i.e., <20 (96.5%, 95% CI 92.6% to 98.4%) and <25 (95.8%, 95% CI 92.3% to 97.8%), in comparison to those with Ct ≥ 25 (50.7%, 95% CI 35.6% to 65.8%) and ≥30 (20.9%, 95% CI 12.5% to 32.8%). Testing in the first week from symptom onset resulted in substantially higher sensitivity (83.8%, 95% CI 76.3% to 89.2%) compared to testing after 1 week (61.5%, 95% CI 52.2% to 70.0%). The best Ag-RDT sensitivity was found with anterior nasal sampling (75.5%, 95% CI 70.4% to 79.9%), in comparison to other sample types (e.g., nasopharyngeal, 71.6%, 95% CI 68.1% to 74.9%), although CIs were overlapping. Concerns of bias were raised across all datasets, and financial support from the manufacturer was reported in 24.1% of datasets. Our analysis was limited by the included studies’ heterogeneity in design and reporting. Conclusions In this study we found that Ag-RDTs detect the vast majority of SARS-CoV-2-infected persons within the first week of symptom onset and those with high viral load. Thus, they can have high utility for diagnostic purposes in the early phase of disease, making them a valuable tool to fight the spread of SARS-CoV-2. Standardization in conduct and reporting of clinical accuracy studies would improve comparability and use of data.

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Accuracy of novel antigen rapid diagnostics for SARS-CoV-2: A living systematic review and meta-analysis.

Internet of medical things (IoMT)-integrated biosensors for point-of-care testing of infectious diseases.

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.

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Biofuel-powered soft electronic skin with multiplexed and wireless sensing for human-machine interfaces

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. Herein, 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.

https://www.cell.com/matter/pdfExtended/S2590-2385(20)30021-7

Investigation of Cortisol Dynamics in Human Sweat Using a Graphene-Based Wireless mHealth System

The management of the COVID-19 pandemic has relied on cautious contact tracing, quarantine, and sterilization protocols while we await a vaccine to be made widely available. Telemedicine or mobile health (mHealth) is well-positioned during this time to reduce potential disease spread and prevent overloading of the healthcare system through at-home COVID-19 screening, diagnosis, and monitoring. With the rise of mass-fabricated electronics for wearable and portable sensors, emerging telemedicine tools have been developed to address shortcomings in COVID-19 diagnostics, monitoring, and management. In this Perspective, we summarize current implementations of mHealth sensors for COVID-19, highlight recent technological advances, and provide an overview on how these tools may be utilized to better control the COVID-19 pandemic.

Emerging Telemedicine Tools for Remote COVID-19 Diagnosis, Monitoring, and Management.

The recent advances in skin-interfaced wearable sensors have enabled tremendous potential towards 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.

Changhao Xu

Papers

Biofuel-powered soft electronic skin with multiplexed and wireless sensing for human-machine interfaces

SARS-CoV-2 RapidPlex: A Graphene-Based Multiplexed Telemedicine Platform for Rapid and Low-Cost COVID-19 Diagnosis and Monitoring.

Investigation of Cortisol Dynamics in Human Sweat Using a Graphene-Based Wireless mHealth System

Emerging Telemedicine Tools for Remote COVID-19 Diagnosis, Monitoring, and Management.

Skin-interfaced sensors in digital medicine: from materials to applications.