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.     

Point-of-care testing of proteins

Point-of-care testing (POCT) is a fast developing area in clinical diagnostics that is considered to be one of the main driving forces for the future in vitro diagnostic market. POCT means decentralized testing at the site of patient care. The most important POCT devices are handheld blood glucose sensors. In some of these sensors, after the application of less than 1 μl whole blood, the results are displayed in less than 10 s. For protein determination, the most commonly used devices are based on lateral flow technology. Although these devices are convenient to use, the results are often only qualitative or semiquantitative. The review will illuminate some of the current methods employed in POCT for proteins and will discuss the outlook for techniques (e.g., electrochemical immunosensors) that could have a great impact on future POCT of proteins.     

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.     

Electrochemical Biosensors Based on Micro-fabricated Devices for Point-of-Care Testing: A Review

Point-of-care testing (POCT) is becoming a hot research topic that allows rapid, on-site, and non-professional measurements outside the central laboratory. The micro-fabricated devices prepared by various micro-machining technologies have shown the advantages of low reagent consumption, high-throughput samples, and wearability. This review presents the recent progress of electrochemical biosensors based on various micro-fabricated devices for POCT and the corresponding electrochemical techniques. Signal amplification strategies based on enzyme and nanotechnology are also illustrated for the more sensitive POCT applications of these micro-fabricated devices. Consequently, the trends and challenges of electrochemical biosensors based on micro-fabricated devices in POCT diagnosis are discussed.     

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 sensors and biosensors based on redox polymer/carbon nanotube modified electrodes: A review

The aim of this review is to present the contributions to the development of electrochemical sensors and biosensors based on polyphenazine or polytriphenylmethane redox polymers together with carbon nanotubes (CNT) during recent years. Phenazine polymers have been widely used in analytical applications due to their inherent charge transport properties and electrocatalytic effects. At the same time, since the first report on a CNT-based sensor, their application in the electroanalytical chemistry field has demonstrated that the unique structure and properties of CNT are ideal for the design of electrochemical (bio)sensors. We describe here that the specific combination of phenazine/triphenylmethane polymers with CNT leads to an improved performance of the resulting sensing devices, because of their complementary electrical, electrochemical and mechanical properties, and also due to synergistic effects. The preparation of polymer/CNT modified electrodes will be presented together with their electrochemical and surface characterization, with emphasis on the contribution of each component on the overall properties of the modified electrodes. Their importance in analytical chemistry is demonstrated by the numerous applications based on polymer/CNT-driven electrocatalytic effects, and their analytical performance as (bio) sensors is discussed.     

基于纳米材料的电化学免疫传感器在传染性病原体POCT中的应用

传染性病原体POCT对于及时有效控制传染病尤为关键。相比于传统检测方法,基于电化学免疫传感器的传染性病原体检测具有快速、灵敏、准确、易于小型化和集成化等优势,尤其适用于传染病POCT。新兴的纳米材料因其独特的理化性质可用于修饰传感器界面或作为生物分子的固载基质以及信号标记物等,有助于构建出高选择性和高灵敏度的电化学免疫传感器。在本文中,我们着重阐述了不同结构的纳米材料修饰的电化学免疫传感器在传染性病原体POCT检测中的应用,进一步介绍了基于纳米材料的电化学免疫传感器与不同检测技术联用在传染性病原体POCT中的应用,并对其发展前景做出了展望。     

Application of molecularly imprinted polymers for electrochemical detection of some important biomedical markers and pathogens

The determination of biomedical markers and pathogens using electrochemical sensors is a well-established technique in which the transducer and the recognition element are used to detect the target molecule. There is a growing interest in molecularly imprinted polymer (MIPs) applications as promising recognition elements. The use of MIPs as recognition elements in electrochemical sensors offers the advantages of being fast, low cost, and, at the same time, provides accurate and selective results compared with other commonly applied routine methods for biomedical markers and pathogen detection. Compared with other nanomaterials and aptamer-based biosensors, MIP-based sensors offered excellent selectivity for low-priced reagents to be used. The aim of the current review is to discuss the most recent applications of MIP-based electrochemical sensors (2019–2021) as promising detection devices for some important biomarkers, enzymes, and pathogens, such as viruses, bacteria, and toxins.     

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.     

Simultaneous electrochemical detection in paper-based analytical devices

The growing need for reliable analytical tools to perform measurements at the point-of-need has prompted the development of novel sensors that are low cost, portable, sensitive, easy to use, and capable of multiplexed analysis. Miniaturization of the sensors into microfluidic platforms has become a promising approach to achieve these self-contained sensors. However, traditional microfluidics often require relatively expensive and complicated pumping mechanisms that increase the cost and limit the portability of the sensors. From a material perspective, paper is an attractive substrate for constructing point-of-need sensors because of its affordability, vast availability, and self-pumping ability, particularly when combined with electrochemical detection. In this mini-review, we discuss various strategies to achieve multiplexing or simultaneous detection of multiple analytes in electrochemical paper-based devices and provide a brief guide on selecting the detection strategy based on the electrochemical property of the analytes.     

Fluorescence immunoassay based on alkaline phosphatase-induced in situ generation of fluorescent non-conjugated polymer dots

Alkaline phosphatase (ALP) activity assay is not only significant to the clinical diagnosis of some related disease, but also momentous to the construction of ALP-based enzyme-linked immunosorbent assay (ELISA). Herein, for the first time, we have discovered that ascorbic acid (AA) can specially react with N-methylethylenediamine (N-MEDA) to generate fluorescent non-conjugated polymer dots (NCPDs) under mild conditions. On the basis of the AA-responsive emission and ALP-catalyzed hydrolysis of ascorbic acid 2-phosphate (AA2P) to AA, we have exploited a fluorometric ALP activity assay with high sensitivity and selectivity. Furthermore, by means of conventional ALP-based ELISA platform, a conceptual fluorescent ELISA has been constructed and applied in the potential clinical diagnosis, during which cardiac troponin I (cTnI), a well-established biomarker of acute myocardial infarction, has been chosen as the model target. We envision that such original fluorescent NCPDs generation-enabled ELISA could become a versatile tool in biochemical sensing and medical diagnosis in the future.     

Layer double hydroxides (LDHs)- based electrochemical and optical sensing assessments for quantification and identification of heavy metals in water and environment samples: A review of status and prospects

One of the most severe environmental problems is heavy metal contamination, putting the world's sustainability at risk. Much effort has been put into developing sensors that can be taken anywhere to detect the environmental effects of heavy metals. Sensitivity, selectivity, multiplexed detection ability, and mobility enhance significantly when nanoparticles and nanostructures are incorporated into sensors. LDHs (layered double hydroxides) have gotten much attention in analytical chemistry in recent years because of their benefits, including their large specific surface area, ease of synthesis, low cost, and high catalytic efficiency and biocompatibility. LDHs are often manufactured as nanomaterial composites or created with specialized three-dimensional structures depending on the application. However, in these settings, LDHs (as color indicators, extracting sorbents, and electrochemical sensing) are usually restricted. Upcoming signs of progress and development possibilities of LDHs in analytical chemistry are reviewed in this paper to assist overcome these problems. Furthermore, the approaches used in the design of LDHs, including structural aspects, are defined and assessed in preparation for future analytical applications. The latest advances in optical and electrochemical sensors to detect heavy metals are described in this review. The sorts and characteristics of LDHs will be explored first. We will then go into microelectrode (or nanoelectrode) arrays, nanoparticle-modified electrodes, and microfluidic optical and electrochemical sensing assays in detail. This paper also discusses design strategies for LDH-based nanostructured sensors and the advantages of using nanomaterials and nanostructures.     

Cardiac markers: a clear cause for point-of-care testing

Point-of-care testing (POCT) in patients with ischemic heart disease is driven by the time-critical need for fast, specific, and accurate results to initiate therapy instantly. According to current guidelines, the results of the cardiac marker testing should be available to the physician within 30 min (“vein-to-brain” time) to initiate therapy within 60–90 min (“door-to-needle” time) after the patient has arrived at the emergency room or intensive care unit. This article reviews the current efforts to meet this goal (1) by implementing POCT of established biochemical markers such as cardiac troponins, creatine kinase MB, and myoglobin, in accelerated diagnosis and management workflow schemes, (2) by improving current POCT methods to obtain more accurate, more specific, and even faster tests through the integration of optical and electrochemical sensor technology, and (3) by identifying new markers for the very early and sensitive detection of myocardial ischemia and necrosis. Furthermore, the specific requirements for cardiac POCT in regard to analytical performance, comparability, and diagnostic sensitivity/specificity are discussed. For the future, the integration of new immunooptical and electrochemical chip technology might speed up diagnosis even further. However, every new development will have to meet the stringent method validation criteria set for corresponding central laboratory testing.     

A novel electrochemical immunosensor based on colabeled silica nanoparticles for determination of total prostate specific antigen in human serum

A novel electrochemical immunosensor using functionalized silica nanoparticles (Si NPs) as protein tracer has been developed for the detection of prostate specific antigen (PSA) in human serum. The immunosensor was carried out based on a heterogeneous sandwich procedure. The PSA capture antibody was immobilized on the gold electrode via glutaraldehyde crosslink. After reaction with the antigen in human serum, Si NPs colabeled with detection antibody and alkaline phosphatase (ALP) was sandwiched to form the immunocomplex on the gold electrode. ALP carried by Si NPs convert nonelectroactive substrate into the reducing agent and the latter, in turn, reduce metal ions to form electroactive metallic product on the electrode. Linear sweep voltammetry (LSV) was used to quantify the amount of the deposited silver and give the analytical signal for PSA. The parameters including the concentration of the ALP used to functionalize the Si NPs and the enzyme catalytic reaction time have been studied in detail and optimized. Under the optimum conditions of immunoreaction and electrochemical detection, the electrochemical immunosensor was able to realize a reliable determination of PSA in the range of 1–35 ng/mL with a detection limit of 0.76 ng/mL. For six human serum samples, the results performed with the electrochemical immunosensor were in good agreement with those obtained by chemiluminescent microparticle immunoassay (CMIA), indicating that the electrochemical immunosensor could satisfy the need of practical sample detection.     

Selective Electrochemical Detection of Explosives with Nanomaterial Based Electrodes

Explosive detection technologies play a critical role in maintaining national security, remain an active research field with many devices and analytical/electroanalytical techniques. Analytical chemistry needs for homeland defense against terrorism make it clear that real-time and on-site detection of explosives and chemical warfare agents (CWAs) are in urgent demand. Thus, current detection techniques for explosives have to be improved in terms of sensitivity and selectivity, opening the way to electrochemical devices suitable to obtain the targeted analytical information in a simpler, cheaper and faster way. For the electrochemical determination of energetic substances, a large number of sensor electrodes have been presented in literature using different modification materials, especially displaying higher selectivity with molecularly imprinted polymers (MIPs). MIPs have already been utilized for the detection of hazardous materials due to their mechanical strength, flexibility, long-time storage and low cost. The sensitivity of MIP-based electrosensors can be enhanced by coupling with nanomaterials such as graphene oxide (GOx), carbon nanotubes (CNTs), or nanoparticles (NPs). Specific characteristics of involved nanomaterials, their modification, detection mechanism, and other analytical aspects are discussed in detail. Non-MIP electrosensors are generally functionalized with materials capable of charge transfer, H-bonding or electrostatic interactions with analytes for pre-concentration and electrocatalysis on their surface, whereas nanobio-electrosensors use analyte-selective aptamers having specific sequences of DNA, peptides or proteins to change the potential or current. This review intends to provide a combination of information related to MIPs and nanomaterial-based electrochemical sensors, limited to the most significant and illustrative work recently published.     

Targeting Chemical and Biological Warfare Agents at the Molecular Level

After the September 11 tragedies of 2001, scientists and law‐enforcement agencies have shown increasing concern that terrorist organizations and their “rogue” foreign government‐backers may resort to the use of chemical and/or biological agents against U.S. military or civilian targets. In addition to the right mix of policies, including security measures, intelligence gathering and training for medical personnel on how to recognize symptoms of biochemical warfare agents, the major success in combating terrorism lies in how best to respond to an attack using reliable analytical sensors. The public and regulatory agencies expect sensing methodologies and devices for homeland security to be very reliable. Quality data can only be generated by using analytical sensors that are validated and proven to be under strict design criteria, development and manufacturing controls. Electrochemical devices are ideally suited for obtaining the desired analytical information in a faster, simpler, and cheaper manner compared to traditional (lab‐based) assays and hence for meeting the requirements of decentralized biodefense applications. This articler presents a review of the major trends in monitoring technologies for chemical and biological warfare (CBW) agents. It focuses on research and development of sensors (particularly electrochemical ones), discusses how advances in molecular recognition might be used to design new multimission networked sensors (MULNETS) for homeland security. Decision flow‐charts for choosing particular analytical techniques for CBW agents are presented. Finally, the paths to designing sensors to meet the needs of today's measurement criteria are analyzed.     

Electrochemical Sensing of Explosives

This article reviews recent advances in electrochemical sensing and detection of explosive substances. Escalating threats of terrorist activities and growing environmental concerns have generated major demands for innovative field‐deployable tools for detecting explosives in a fast, sensitive, reliable and simple manner. Field detection of explosive substances requires that a powerful analytical performance be coupled to miniaturized low‐cost instrumentation. Electrochemical devices offer attractive opportunities for addressing the growing explosive sensing needs. The advantages of electrochemical systems include high sensitivity and selectivity, speed, a wide linear range, compatibility with modern microfabrication techniques, minimal space and power requirements, and low‐cost instrumentation. The inherent electroactivity of nitroaromatic, nitramine and nitroester compounds makes them ideal candidates for electrochemical detection. Recent activity in various laboratories has led to the development of disposable sensor strips, novel electrode materials, submersible remote sensors, and electrochemical detectors for microchip (‘Lab‐on‐Chip’) devices for on‐site electrochemical detection of explosive substances. The attractive behavior of these electrochemical monitoring systems makes them very promising for addressing major security and environmental problems.     

Review: Carbon nanotube based electrochemical sensors for biomolecules

Carbon nanotubes (CNTs) have been incorporated in electrochemical sensors to decrease overpotential and improve sensitivity. In this review, we focus on recent literature that describes how CNT-based electrochemical sensors are being developed to detect neurotransmitters, proteins, small molecules such as glucose, and DNA. Different types of electrochemical methods are used in these sensors including direct electrochemical detection with amperometry or voltammetry, indirect detection of an oxidation product using enzyme sensors, and detection of conductivity changes using CNT-field effect transistors (FETs). Future challenges for the field include miniaturizing sensors, developing methods to use only a specific nanotube allotrope, and simplifying manufacturing.     

Paper-based electrochemiluminescent 3D immunodevice for lab-on-paper, specific, and sensitive point-of-care testing

Recent research on microfluidic paper-based analytical devices (μPADs) has shown that paper has great potential for the fabrication of low-cost diagnostic devices for healthcare and environmental monitoring applications. Herein, electrochemiluminescence (ECL) was introduced for the first time into μPADs that were based on screen-printed paper-electrodes. To further perform high-specificity, high-performance, and high-sensitivity ECL on μPADs for point-of-care testing (POCT), ECL immunoassay capabilities were introduced into a wax-patterned 3D paper-based ECL device, which was characterized by SEM, contact-angle measurement, and electrochemical impedance spectroscopy. With the aid of a home-made device-holder, the ECL reaction was triggered at room temperature. By using a typical tris(bipyridine)ruthenium-tri-n-propylamine ECL system, this paper-based ECL 3D immunodevice was applied to the diagnosis of carcinoembryonic antigens in real clinical serum samples. This contribution further expands the number of sensitive and specific detection modes of μPADs.     

Distance versus Capillary Flow Dynamics-Based Detection Methods on a Microfluidic Paper-Based Analytical Device (μPAD)

In recent years, there has been high interest in paper-based microfluidic sensors or microfluidic paper-based analytical devices (μPADs) towards low-cost, portable, and easy-to-use sensing for chemical and biological targets. μPAD allows spontaneous liquid flow without any external or internal pumping, as well as an innate filtration capability. Although both optical (colorimetric and fluorescent) and electrochemical detection have been demonstrated on μPADs, several limitations still remain, such as the need for additional equipment, vulnerability to ambient lighting perturbation, and inferior sensitivity. Herein, alternative detection methods on μPADs are reviewed to resolve these issues, including relatively well studied distance-based measurements and the newer capillary flow dynamics-based method. Detection principles, assay performance, strengths, and weaknesses are explained for these methods, along with their potential future applications towards point-of-care medical diagnostics and other field-based applications.