Nitric Oxide Release for Enhanced Biocompatibility and Analytical Performance of Implantable Electrochemical Sensors

The real-time, continuous monitoring of glucose/lactate, blood gases and electrolytes by implantable electrochemical sensors holds significant value for critically ill and diabetic patients. However, the wide-spread use of such devices has been seriously hampered by implant-initiated host responses (e. g., thrombus formation, inflammatory responses and bacterial infection) when sensors are implanted in blood or tissue. As a result, the accuracy and usable lifetime of in vivo sensors are often compromised. Nitric oxide (NO) is an endogenous gas molecule able to inhibit platelet adhesion/activation, inflammatory responses and bacterial growth. As such, the release of NO from the surfaces of in vivo sensors is a promising strategy for enhancement of their biocompatibility and analytical performance. In this review, the physiological functions of NO to improve the biocompatibility of implantable electrochemical sensors are introduced, followed by a brief analysis of chemical approaches to realize NO release from such devices. A detailed summary of the various types of NO releasing electrochemical sensors reported to date and their performance in benchtop and/or in vivo testing are also provided. Finally, the prospects of future developments to further advance NO releasing sensor technology for clinical use are discussed.     

Implantable application of polymer-based biosensors

Implantable sensors offer a great opportunity to extract physiological information from inside the body by real-time monitoring. With the demand for personal healthcare and point-of-care treatment, a long-term stable sensor of excellent mechanical and biological compatibility with human organs is urgently required. In contrast to rigid electronic devices using silicon or metallic materials, soft sensors are realized by flexible polymers in a simple way, endowing the implantable sensor with a tissue-mimetic structure. In this article, we systematically review the development of implantable electronic sensors based on polymer materials. The unique properties of polymers are introduced, followed by their applications in implantable device fabrication. Strategies to integrate polymers with implantable sensors, encompassing device interface, geometry, and integration, are also summarized. Furthermore, biosensing applications of polymer-based implantable devices are described, ranging from physical stimulus monitoring to biochemical analysis in vivo. Finally, we envision how advances in polymer materials may facilitate the development of intelligent sensors with broader applications in vivo.     

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.     

Smart Design of Sensor-Coated Surgical Sutures for Bacterial Infection Monitoring

Virtually, all implantable medical devices are susceptible to infection. As the main healthcare issue concerning implantable devices is the elevated risk of infection, different strategies based on the coating or functionalization of biomedical devices with antiseptic agents or antibiotics are proposed. In this work, an alternative approach is presented, which consists of the functionalization of implantable medical devices with sensors capable of detecting infection at very early stages through continuous monitoring of the bacteria metabolism. This approach, which is implemented in surgical sutures as a representative case of implantable devices susceptible to bacteria colonization, is expected to minimize the risk of worsening the patient's clinical condition. More specifically, non-absorbable polypropylene/polyethylene (PP/PE) surgical sutures are functionalized with conducting polymers using a combination of low-pressure oxygen plasma, chemical oxidative polymerization, and anodic polymerization, to detect metabolites coming from bacteria respiration. Functionalized suture yarns are used for real-time monitoring of bacteria growth, demonstrating the potential of this strategy to fight against infections.     

The Application of Engineered Glucose Dehydrogenase to a Direct Electron–Transfer‐Type Continuous Glucose Monitoring System and a Compartmentless Biofuel Cell

Abstract

Continuous glucose monitoring (CGM) is expected to become an ideal way to monitor glycemic levels in diabetic patients. On the other hand, biofuel cells can be used as an alternative energy source in future implantable devices, such as implantable glucose sensors in the artificial pancreas. Glucose dehydrogenase from Acinetobacter calcoaceticus, which harbors pyrroloquinoline quinone as the prosthetic group (PQQGDH), is one of the enzymes most attractive as a glucose sensor constituent and as the anode enzyme in biofuel cells, due to its high catalytic activity and insensitivity to oxygen. However, the application of PQQGDH for these purposes is inherently limited because an electron mediator is required for the electron transfer to the electrode.

We have recently reported on the development of an engineered enzyme, quinohemoprotein glucose dehydrogenase (QH‐GDH), in which the cytochrome c domain of the quinohemoprotein ethanol dehydrogenase (QH‐EDH) was fused with PQQGDH, to enable electron transfer to the electrode in the absence of an artificial mediator. In this study, we constructed a direct electron‐transfer‐type CGM system employing QH‐GDH. This CGM system showed sufficient current response and high operational stability. Furthermore, we successfully constructed a compartmentless biofuel cell employing QH‐GDH.     

基于功能性纳米材料的新型电化学界面的构筑以及相关应用(英文)

由于独特的光、电、磁以及催化性质,功能性纳米材料的研究已经渗透到各个学科并在不同领域展示出潜在的应用前景,尤其是利用纳米材料构建功能性电极界面、研究其电化学行为并发展新颖的电化学纳米器件引起了了人们的广泛关注. 本篇综述中,主要介绍作者研究小组在以功能性纳米材料构建新颖的电化学界面的最新进展,集中关注其在电化学传感器、燃料电池以及光谱电化学中的应用. 这些纳米材料的应用极大地增强了电子转移、提高了电化学传感器的灵敏度以及燃料电池的催化效率. 作者也通过合成一些光谱匹配的荧光以及电致变色纳米材料构建新颖的荧光光谱电化学器件,同时在材料的合成组装、多重刺激响应体系以及多功能化进行探索. 最后,作者对这类基于纳米材料的电化学器件的发展和应用予以展望.     

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.     

Thin Films and Composites Based on Graphene for Electrochemical Detection of Biologically‐relevant Molecules

Graphene is one of the most studied materials ever, owing to its exceptional electronic, mechanical and thermal properties, which allow for many different types of application. In this review, we shall concentrate on the use of graphene and derivatives for electrochemical sensors and biosensors, where emphasis is placed on the importance of surface functionalization as this permits synergistic combinations with other nanomaterials and biomolecules. In addition to describing recent advances in graphene‐based electroanalytical applications, we discuss a few examples of their use in detecting small biomolecules and in immunosensing for a few diseases using films and composites. Also discussed are the possible methods for mass production of graphene, which is key to low‐cost biosensors for implantable devices and portable systems in point‐of‐care diagnosis.     

Development of Prototype Wireless Transmission Measurement for Glucose in Subcutaneous and Brain Striatum

Monitoring of glucose in subcutaneous and brain striatum have been extensively studied in the past. While biocompatibility was one of the limitations, others included the messy measuring equipments preclude monitoring in a complex environment. This study tried to establish an amperometric measurement of glucose in pre‐ and post‐insulin‐administration on diabetic and hyperglycemia rats via wireless. The results have indicated that the wireless sensing kit used was capable of monitoring glucose in both subcutaneous and brain. The physiological data have also shown a new insight on the fabrication of implantable glucose sensors.     

Electrochromic sensors: Innovative devices enabled by spectroelectrochemical methods

Electrochromic sensors are electrochemical devices exploiting colour changes as a means to simplify device construction and instrumentation requirements. Despite their advantages, electrochromic sensors have begun to emerge only recently. Mainly based on the works appeared in the literature over the past 2 years, we describe the construction and operation of these devices. A simple framework is proposed to understand and classify these devices more easily. This is based on the sensor architecture, their power source, and how information is displayed. Despite being new, electrochromic sensors are already demonstrated in a number of applications, mostly related to health and point-of-care devices.     

Electrochemical Sensing in Contact Lenses

Electrochemical sensors embedded in hydrogel-based contact lenses provide valuable health-related information, enabling non-invasive and real-time continuous monitoring. Recently, considerable progress has been made in tear based electrochemical sensors. The scope of reported analytes is continuously expanding. This review identifies key chemical biomarkers (including metabolites, ions, proteins) that can be electrochemically detected in tears. The working principles of i) amperometric enzymatic biosensors, ii) ion-selective sensors for pH and ions, iii) voltammetric sensors and iv) affinity sensors are summarized. This review provides guidelines for the future development of contact lens based electrochemical sensors.     

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.     

Stamp transfer electrodes for electrochemical sensing on non-planar and oversized surfaces

This article describes a new alternative approach to the fabrication of printed electrochemical sensors and biosensors based on the transfer of electrode patterns comprising common conductive and insulating inks from elastomeric stamps to a wide variety of rigid and flexible substrates. This simple, low cost, yet robust methodology is demonstrated to be well-suited for the formation of electrochemical sensors on non-planar substrates and large objects/structures, which have traditionally been off-limits to conventional screen printing techniques. Furthermore, the stamped electrode devices are shown to exhibit electrochemical performance that rivals that of their screen printed counterparts and display resilience against severe mechanical deformation. The stamp transfer approach is further extended to the demonstration of epidermal electrochemical sensors through the transfer of the electrode patterns directly onto the skin. The resulting sensors demonstrate a wide range of usability, from the detection of various physiological analytes, including uric acid on the skin, to the identification of residues originating from the handling of munitions and explosives. The migration of printable electrochemical sensors to non-conventional (non-planar and/or oversized) surfaces provides new opportunities within the personal healthcare, fitness, forensics, homeland security, and environmental monitoring domains.     

Miniaturized electrochemical sensors and their point-of-care applications

Most of the current analytical methods depend largely on laboratory-based analytical techniques that require expensive and bullky equipment,potentially incur costly testing,and involve lengthy detection processes.With increasing requirements for point-of-care testing(POCT),more attention has been paid to miniaturized analytical devices.Miniaturized electrochemical(MEC)sensors,including different material-based MEC sensors(such as DNA-,paper-,and screen electrode-based),have been in strong demand in analytical science due to their easy operation,portability,high sensitivity,as well as their short analysis time.They have been applied for the detection of trace amounts of target through measuring changes in electrochemical signal,such as current,voltage,potential,or impedance,due to the oxidation/reduction of chemical/biological molecules with the help of electrodes and electrochemical units.MEC sensors present great potential for the detection of targets including small organic molecules,metal ions,and biomolecules.In recent years,MEC sensors have been broadly applied to POCT in various fields,including health care,food safety,and environmental monitoring,owing to the excellent advantages of electrochemical(EC)technologies.This review summarized the state-of-the-art advancements on various types of MEC sensors and their applications in POCT.Furthermore,the future perspectives,opportunities,and challenges in this field are also discussed.     

Electrochemical non-enzymatic glucose sensors

The electrochemical determination of glucose concentration without using enzyme is one of the dreams that many researchers have been trying to make come true. As new materials have been reported and more knowledge on detailed mechanism of glucose oxidation has been unveiled, the non-enzymatic glucose sensor keeps coming closer to practical applications. Recent reports strongly imply that this progress will be accelerated in ‘nanoera’. This article reviews the history of unraveling the mechanism of direct electrochemical oxidation of glucose and making attempts to develop successful electrochemical glucose sensors. The electrochemical oxidation of glucose molecules involves complex processes of adsorption, electron transfer, and subsequent chemical rearrangement, which are combined with the surface reactions on the metal surfaces. The information about the direct oxidation of glucose on solid-state surfaces as well as new electrode materials will lead us to possible breakthroughs in designing the enzymeless glucose sensing devices that realize innovative and powerful detection. An example of those is to introduce nanoporous platinum as an electrode, on which glucose is oxidized electrochemically with remarkable sensitivity and selectivity. Better model of such glucose sensors is sought by summarizing and revisiting the previous reports on the electrochemistry of glucose itself and new electrode materials.     

Metallized electrospun polymeric fibers for electrochemical sensors and actuators

Electrospun polymeric fibers present an emerging alternative for the development of flexible electronics, enabling applications in wearable sensors and biosensors for continuous monitoring, and actuators for tissue engineering. The possibility to prepare sub-micrometric polymeric scaffolds, their processing for increasing the conductivity, their modification with different materials, conductive polymers and biomolecules in order to obtain functional flexible electrodes, allows the development of innovative devices for healthcare, and biomedical applications. In this review, the impact of metallized electrospun polymeric fibers in electrochemical (bio)sensors and actuators is discussed. A relation between their structure and functionality is provided, alongside with an overview of the different methods to obtain functional conductive fibers.     

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.     

2D Material Chemistry: Graphdiyne-based Biochemical Sensing

The modern internet-of-things era has witnessed an increasing growth in the demand for advanced sensors to collect precise information. To meet this demand, extensive efforts have been devoted to exploring competent materials and designing rational architectures for the fabrication of sensing devices. Graphdiyne represents a promising material due to the attractive electronic, optical and electrochemical properties deriving from its unique molecular structure. In this review, we firstly provide the points of view on the architectures and work principles of the graphdiyne-based sensing devices with respect to resistive, electrochemical, photoelectrochemical and fluorescent categories. Secondly, we present the promising applications on biochemical sensing, such as the detection of DNA, microRNA, and glucose. Finally, the challenges and prospects of graphdiyne-based biochemical sensing platforms are also discussed, in order to provide a cornerstone for understanding this rapidly developing area.     

Fiber-shaped organic electrochemical transistors for biochemical detections with high sensitivity and stability

Precise and continuous monitoring of biochemicals by biosensors assists to understand physiological functions for various diagnostics and therapeutic applications. For implanted biosensors, small size and flexibility are essential for minimizing tissue damage and achieving accurate detection. However, the active surface area of sensor decreases as the sensor becomes smaller,which will increase the impedance and decrease the signal to noise ratio, resulting in a poor detection limit. Taking advantages of local amplification effect, organic electrochemical transistors(OECTs) constitute promising candidates for high-sensitive monitoring. However, their detections in deep tissues are rarely reported. Herein, we report a family of implantable, fiber-shaped all-in-one OECTs based on carbon nanotube fibers for versatile biochemical detection including H_2O_2, glucose, dopamine and glutamate. These fiber-shaped OECTs demonstrated high sensitivity, dynamical stability in physiological environment and antiinterference capability. After implantation in mouse brain, 7-day dopamine monitoring in vivo was realized for the first time.These fiber-shaped OECTs could be great additions to the "life science" tool box and represent promising avenue for biomedical monitoring.     

Neuromorphic bioelectronics based on semiconducting polymers

The recent development of neuromorphic devices with low power consumption and rapid response has been driven primarily by the growing demand for brain-inspired computing in human-like machines and human-machine interfaces. Remarkable progress has been made in developing neuromorphic bioelectronics that combine neuromorphic devices with electronic sensors. In this review, we provide an overview of semiconducting polymer-based neuromorphic devices and their applications in neuromorphic bioelectronics. We focus on recent advances in semiconducting polymer-based three-terminal artificial synapses that mimic neural communication behaviors. Various types of semiconducting polymers and synaptic platforms have been investigated, allowing significant improvement in their performance and expansion of their functionality. Proper selection of materials and device structures can help artificial sensory synapses to react to various external stimuli and to further modulate electrical signals. Advances in semiconducting polymer-based neuromorphic bioelectronics will accelerate the commercialization of human–machine interfacial systems, including intelligent prosthetics and implantable diagnostic devices.