Advances in Medical Wearable Biosensors: Design,Fabrication and Materials Strategies in Healthcare Monitoring

In the past decade, wearable biosensors have radically changed our outlook on contemporary medical healthcare monitoring systems. These smart, multiplexed devices allow us to quantify dynamic biological signals in real time through highly sensitive, miniaturized sensing platforms, thereby decentralizing the concept of regular clinical check-ups and diagnosis towards more versatile, remote, and personalized healthcare monitoring. This paradigm shift in healthcare delivery can be attributed to the development of nanomaterials and improvements made to non-invasive biosignal detection systems alongside integrated approaches for multifaceted data acquisition and interpretation. The discovery of new biomarkers and the use of bioaffinity recognition elements like aptamers and peptide arrays combined with the use of newly developed, flexible, and conductive materials that interact with skin surfaces has led to the widespread application of biosensors in the biomedical field. This review focuses on the recent advances made in wearable technology for remote healthcare monitoring. It classifies their development and application in terms of electrochemical, mechanical, and optical modes of transduction and type of material used and discusses the shortcomings accompanying their large-scale fabrication and commercialization. A brief note on the most widely used materials and their improvements in wearable sensor development is outlined along with instructions for the future of medical wearables.     

Environmental significance of wearable sensors based on MXene and graphene

Conductive layered materials such as MXenes (e.g., transition metal carbides, nitrides, and carbonitrides), graphene and their derivatives have attracted tremendous research interests in diverse fields of research for their unique structured merits and outstanding physical and chemical properties. Benefitting from their unique layered structures and fascinating multifunctional characteristic, MXenes and graphene serve as vital components in a variety of wearable devices. Especially, due to their large surface area and high electrocatalytic activity, these materials have also demonstrated great promise in biophysical and biochemical sensing systems. Following an introduction into the field, we summarize the recent progress in wearable sensors that can be accomplished by using layered materials, with a specific focus on kinematic, mechanical, thermal, pressure and strain sensors. A further large section underscores the recent progress in MXenes and graphene based wearable biochemical sensors including electrolyte monitoring, glucose monitoring, micro/mcromolecular organics metabolite, volatile gases monitoring and humidity sensors. The next section covers the sensing of small biomolecules serving as biomarkers, which are of great significance for early diagnosis and treatment of a spectrum of diseases. This review underscores the recent progress in wearable sensors to be used in different physiological and environmental signals. Finally, the review concludes with a debate on current challenges being faced and future perspectives.     

柔性印刷可穿戴电化学传感器

实现对人体的健康监测和慢性病监测是包括材料科学、信息技术、电子技术、分析化学等科学领域在内的世界前沿课题。通过连续获取温度、压力、应力等物理信号来实现对人体活动情况和心率、血压、脑电图、心电图等实时监测的可穿戴设备已实现商业化,但连续监测人体体液、呼出气中的各类化学物质的可穿戴传感器仍面临许多问题,比如传感器的柔韧性、灵敏度、准确性以及与人体皮肤的贴合性等。针对这些问题,本文以柔性印刷技术为出发点,综述了各类柔性基底在电化学传感器/生物传感器领域的应用,同时对可穿戴传感器的发展方向提出了建议。     

Wearable self-powered biosensors

Wearable self-powered biosensors are devices that operate without an external electronic power source or onboard battery and that use a biorecognition detection element to relay sensing information. Such devices are becoming more widespread following the larger trend of more ubiquitous wearable devices in general. Self-powering can be a particularly important characteristic in situations where replacing/recharging a battery is either impossible or impractical. Most wearable self-powered biosensors rely primarily on enzymatic reactions to supply the energy required for operation, but there are also other innovative approaches that combine multiple signal transduction techniques to simultaneously provide power and produce a detection signal. Areas of needed research include developing higher power energy harvesting techniques and more wearable self-powered biosensor devices that have integrated low-power wireless electronics.     

Sensing nanomaterials of wearable glucose sensors

The metabolic disorder of glucose in human body will cause diseases such as diabetes and hyperglycemia.Hence the determination of glucose content is very important in clinic diagnosing.In recent years,researchers have proposed various non-invasive wearable sensors for rapid and real-time glucose monitoring from human body fluids.Unlike those reviews which discussed performances,detection environments or substrates of the wearable glucose sensor,this review focuses on the sensing nanomaterials since they are the key elements of most wearable glucose sensors.The sensing nanomaterials such as carbon,metals,and conductive polymers are summarized in detail.And also the structural characteristics of different sensing nanomaterials and the corresponding wearable glucose sensors are highlighted.Finally,we prospect the future development requirements of sensing nanomaterials for wearable glucose sensors.This review would give some insights to the further development of wearable glucose sensors and the modern medical treatment.     

Paper-based Wearable Electrochemical Sensors: A New Generation of Analytical Devices

Over the past few years, the emergence of electrochemical wearable sensors has attracted considerable attention because of their promising application in point-of-care testing due to some features such as high sensitivity, simplicity, miniaturization, and low fabrication cost. Recent developments in new fabrication approaches and innovative substrates have resulted in sensors able to real-time and on-body measurements. Wearable electrochemical sensors have also been combined with paper-based substrates and directly used on human skin for different applications for non-invasive analyses. Furthermore, wearable electrochemical sensors enable monitoring analytes in different biofluids without complex procedures, such as pre-treatment or sample manipulation. The coupling of IoT to various wearable sensors has also attracted attention due to real-time data collection and handling in remote and resource-limited conditions. This mini-review presents the significant advances in developing wearable electrochemical devices, such as sampling, data collection, connection protocols, and power sources, and discusses some critical challenges for higher performance in this field. We also present an overview of the application of paper as an intelligent substrate for electrochemical wearable sensors and discuss their advantages and drawbacks. Lastly, conclude by highlighting the future advances in wearable sensors and diagnostics by coupling real-time and on-body measurements to multiplexed detection of different biomarkers simultaneously, reducing the cost and time of classical analysis to provide fast and complete overall physiological conditions to the wearer.     

Recent developments in textile based polymeric smart sensor for human health monitoring: A review

In the modern age, the most important and prevailing issue is the monitoring of human health. To address this, several devices have been developed and a need new materials investigated. The idea of textile-based smart sensors is emerging rapidly. In this regard, ICPs and ECPs have attracted the attention of researchers due to their mechanical adaptability to suit the characteristics of textile fabric. The lighter weight, stretchability and wearability, etc. are considered an advantage while selecting the material for developing sensors not only in health monitoring but also in biomedical, sports, and military fields. The idea behind wearable sensing devices is to enable easy integration of the sensor device into daily life routines. Such wearable sensors also have the potential for real time and online monitoring of human health and integrate with smart monitoring devices. The purpose of this review is to discuss the recent developments in smart monitoring sensors.     

An Overview of Wearable and Implantable Electrochemical Glucose Sensors

Electrochemical glucose sensors have garnered considerable attention because of their attractive prospect in point-of-care testing (POCT). In this review, we firstly introduce the principles and challenges of electrochemical glucose sensors. Subsequently, we present an overview of the application of electrochemical glucose sensors and discuss their advantages and drawbacks. Wearable and implantable devices based on diverse target biofluid and platforms provide a considerable prospect of accurate and continuous monitoring. Thus, we believe that the future development direction of electrochemical glucose sensors is non-invasive, wearable devices and implantable devices with minimally invasive for continuous glucose monitoring in real time.     

Application of MXene in Electrochemical Sensors: A Review

Electroanalysis has obtained considerable progress over the past few years, especially in the field of electrochemical sensors. Broadly speaking, electrochemical sensors include not only conventional electrochemical biosensors or non-biosensors, but also emerging electrochemiluminescence (ECL) sensors and photoelectrochemical (PEC) sensors which are both combined with optical methods. In addition, various electrochemical sensing devices have been developed for practical purposes, such as multiplexed simultaneous detection of disease-related biomarkers and non-invasive body fluid monitoring. For the further performance improvement of electrochemical sensors, material is crucial. Recent years, a kind of two-dimensional (2D) nanomaterial MXene containing transition metal carbides, nitrides and carbonitrides, with unique structural, mechanical, electronic, optical, and thermal properties, have attracted a lot of attention form analytical chemists, and widely applied in electrochemical sensors. Here, we reviewed electrochemical sensors based on MXene from Nov. 2014 (when the first work about electrochemical sensor based on MXene published) to Mar. 2021, dividing them into different types as electrochemical biosensors, electrochemical non-biosensors, electrochemiluminescence sensors, photoelectrochemical sensors and flexible sensors. We believe this review will be of help to those who want to design or develop electrochemical sensors based on MXene, hoping new inspirations could be sparked.     

Electrochemical biosensors based on Ti3C2Tx MXene: future perspectives for on-site analysis

MXenes are recently developed two-dimensional layered materials composed of early transition metal carbides and/or nitrides that provide unique characteristics for biosensor applications. This review presents the recent progress made on the usage and applications of MXenes in the field of electrochemical biosensors, including microfluidic biosensors and wearable microfluidic biosensors, and highlights the challenges with possible solutions and future needs. The multilayered configuration and high conductivity make these materials as an immobilization matrix for the biomolecule immobilization with activity retention and to be explored in the fabrication of electrochemical sensors, respectively. First, how the MXene nanocomposite as an electrode modifier affects the sensing performance of the electrochemical biosensors based on enzymes, aptamer/DNA, and immunoassays is well described. Second, recent developments in MXene nanocomposites as wearable biosensing platforms for the biomolecule detection are highlighted. This review pointed out the future concerns and directions for the use of MXene nanocomposites to fabricate advanced electrochemical biosensors with high sensitivity and selectivity. Specifically, possibilities for developing microfluidic electrochemical sensors and wearable electrochemical microfluidic sensors with integrated biomolecule detection are emphasized.     

Wearable electrochemical sensors for noninvasive monitoring of health—a perspective

Global problems today such as aging society and rising health costs have made preventive care and health monitoring increasingly important, so research on wearable electrochemical sensors for noninvasive monitoring of health has become very popular during the past several years. But the new technologies cannot be some dues ex machine who wrought changes overnight. Problems about fundamentals of electrochemistry under wearable conditions, software algorithms to treat signal artifacts in the real wearable detection, reliable sensors for prolonged wearable sensing in body fluid, platforms for tests of newly developed sensors, validation of test results, reproducible and standardized sampling methods, as well as clinical significance of wearable testing data still require to be addressed. The short review is not to include all important works recently published or reach any conclusion but to focus on the challenges as well as some of the promising approaches that help to overcome these challenges.     

S‐Click Reaction for Isotropic Orientation of Oxidases on Electrodes to Promote Electron Transfer at Low Potentials

Electrochemical sensors are essential for point‐of‐care testing (POCT) and wearable sensing devices. Establishing an efficient electron transfer route between redox enzymes and electrodes is key for converting enzyme‐catalyzed reactions into electrochemical signals, and for the development of robust, sensitive, and selective biosensors. We demonstrate that the site‐specific incorporation of a novel synthetic amino acid (2‐amino‐3‐(4‐mercaptophenyl)propanoic acid) into redox enzymes, followed by an S‐click reaction to wire the enzyme to the electrode, facilitates electron transfer. The fabricated biosensor demonstrated real‐time and selective monitoring of tryptophan (Trp) in blood and sweat samples, with a linear range of 0.02–0.8 mm . Further developments along this route may result in dramatic expansion of portable electrochemical sensors for diverse health‐determination molecules.     

Sensing at Your Fingertips: Glove‐based Wearable Chemical Sensors

In this review, we detail the evolution and recent progress of glove‐based wearable electrochemical sensors with focus on forensic, security, and defense applications. Glove‐based wearable sensors offer the ability to have rapid, on‐site chemical and biological threat assessment, ranging from explosive and gunshot residues to drugs of abuse and pesticides, critical for timely and informed incident management and investigation. Additionally, these field deployable systems offer the ability for law enforcement to complete on‐the‐spot qualitative chemical testing for immediate forensic evidence collection in connection to mechanical ‘swipe’ sampling. Recent advances have been made for translation of this class of wearable electrochemical sensors to increase the sensory perspective of robotics, demonstrating the progression to robotic skin with chemical analysis capability suitable for translation to remote chemical analysis in hazardous scenarios. Critical to such progress have been advances in flexible electrochemically‐compatible materials and design, with increasing functionality, leveraging from advances in wearable biosensors and electronic miniaturization. Indeed, the customization potential of these wearable systems is great, yet challenges remain for advancing these systems from prototypes to more ubiquitous devices readily deployed in the field. With significant attention these challenges can be overcome, creating new opportunities for further decentralization of electrochemical analyses using these flexible and intuitive glove‐based wearable sensing systems for significant impact on fields such as forensics, defense, biomedical, robotics and beyond.     

Monitoring Cardiac Biomarkers with Aptamer-Based Molecular Pendulum Sensors

Reagent-free electronic biosensors capable of analyzing disease markers directly in unprocessed body fluids will enable the development of simple & affordable devices for personalized healthcare monitoring. Here we report a powerful and versatile nucleic acid-based reagent-free electronic sensing system. The signal transduction is based on the kinetics of an electrode-tethered molecular pendulum—a rigid double stranded DNA with one of the strands displaying an analyte-binding aptamer and the other featuring a redox probe—that exhibits field-induced transport modulated by receptor occupancy. Using chronoamperometry, which enables the sensor to circumvent the conventional Debye length limitation, the binding of an analyte can be monitored as these species increase the hydrodynamic drag. The sensing platform demonstrates a low femtomolar quantification limit and minimal cross-reactivity in analyzing cardiac biomarkers in whole blood collected from patients with chronic heart failure.     

Wearable Electrochemical Sensors Based on Nanomaterials for Healthcare Applications

Wearable electrochemical sensors have attracted great interest in health care applications because of their flexibility, biocompatibility, low cost and light weight. This review briefly focuses on the main concepts and methods that are related to the application of nanoparticles (NPs) in wearable electrochemical sensors. Moreover, attempts to bring together different perspectives and terms that are commonly used in NPs-based wearable electrochemical sensors along with the introduction and discussion of common manufacturing methods and recent achievements. In the end, future challenges and prospects are also discussed on the development of wearable electrochemical sensors based on nanoparticles.     

The review of Lab-on-PCB for biomedical application

Prevention of infectious diseases, diagnosis of diseases, and determination of treatment options all rely on biosensors to detect and analyze biomarkers, which are usually divided into four parts: cell analysis, biochemical analysis, immunoassay, and molecular diagnosis. However, traditional biosensing devices are expensive, bulky, and require a lot of time to detect, which also limited its application in resource-limited areas. In recent years, Lab-on-PCB, which combines biosensing technology and PCB technology, has been widely used in biomedical applications due to its high integration, personalized design, and easy mass production. Among these Lab-on-PCB sensing devices, the PCB circuit plays an important role. It can be directly used as a resistance sensor to count cells, and also used as a control device to automatically control the detection device. Flexible PCBs can be used to make wearable medical biosensors. In addition, due to the high degree of integration of the PCB circuit, Lab-on-PCB can perform multiple inspections on the same platform, which reduces the inspection time equivalently. Therefore, in this review paper, we discuss the application of Lab-on-PCB in four analysis methods of cell analysis, biochemical analysis, immunoassay, and molecular diagnosis, and give some suggestions for improvement and future development trends at the end.     

Wearable Sweat Sensors: Background and Current Trends

Sweat‐related physiology research has been well established over the years. However, it has only been around ten years that sweat‐based sensing devices started to be explored. With the recent advancements in wearable activity and physiology monitoring devices, sweat was investigated for its contents similar to blood and corresponding wearable devices were studied intensively. This article provides a thorough review on sweating mechanisms, sweat sensing devices, and electronic technologies for sweat sensor implementations. Potential future directions and recommendations based on current research trends were provided in each section. This review aims to offer a unique perspective from both physiology and engineering point‐of‐view to draw a complete landscape of the sweat sensing research.     

Application of Nanoparticles in Electrochemical Sensors and Biosensors

The unique chemical and physical properties of nanoparticles make them extremely suitable for designing new and improved sensing devices, especially electrochemical sensors and biosensors. Many kinds of nanoparticles, such as metal, oxide and semiconductor nanoparticles have been used for constructing electrochemical sensors and biosensors, and these nanoparticles play different roles in different sensing systems. The important functions provided by nanoparticles include the immobilization of biomolecules, the catalysis of electrochemical reactions, the enhancement of electron transfer between electrode surfaces and proteins, labeling of biomolecules and even acting as reactant. This minireview addresses recent advances in nanoparticle‐based electrochemical sensors and biosensors, and summarizes the main functions of nanoparticles in these sensor systems.     

Recent advances in nanoscale metal-organic frameworks biosensors for detection of biomarkers

Early and precise diagnosis are propitious to timely treatment and simultaneously increase the chance of successful treatments. It is of critical importance to develop rapid, sensitive, and reliable sensing techniques of physiological biomarkers for disease diagnosis. Due to the advantages of structural designability and property tunability, nanoscale metal-organic frameworks(nMOFs) have been widely applied in the field of biomedicine in recent years. Particularly, enhanced stability, more modif...     

Recent advances of multidimensional sensing: from design to applications

Recently, multidimensional(or multi-channel) sensing methodology has attracted broad attention in the field of analytical chemistry due to its fascinating merits. A variety of multidimensional sensors based on sensor arrays, lab-on-a-molecule/nanoparticle and smart chip strategies have been designed to differentiate chemical structure and property similar analytes and complex samples. Pattern recognition algorithms are usually used and allow these sensors to fulfill such proposes. In this review,the recent advances of multidimensional sensor devices were firstly summarized, and particularly focused on their design strategies and applications in monitoring of biological active molecules, biomarkers, microbes, foods and beverages, etc. Then,some limitations and possible solutions of multidimensional sensors were discussed. And finally, potential applications of this technique in the future were proposed. This review would help the readers who are interested in multidimensional sensing methodology to understand the research progresses and trends.