Revolutionary Point-of-Care Wearable Diagnostics for Early Disease Detection and Biomarker Discovery through Intelligent Technologies.

Early-stage disease detection, particularly in Point-Of-Care (POC) wearable formats, assumes pivotal role in advancing healthcare services and precision-medicine. Public benefits of early detection extend beyond cost-effectively promoting healthcare outcomes, to also include reducing the risk of comorbid diseases. Technological advancements enabling POC biomarker recognition empower discovery of new markers for various health conditions. Integration of POC wearables for biomarker detection with intelligent frameworks represents ground-breaking innovations enabling automation of operations, conducting advanced large-scale data analysis, generating predictive models, and facilitating remote and guided clinical decision-making. These advancements substantially alleviate socioeconomic burdens, creating a paradigm shift in diagnostics, and revolutionizing medical assessments and technology development. This review explores critical topics and recent progress in development of 1) POC systems and wearable solutions for early disease detection and physiological monitoring, as well as 2) discussing current trends in adoption of smart technologies within clinical settings and in developing biological assays, and ultimately 3) exploring utilities of POC systems and smart platforms for biomarker discovery. Additionally, the review explores technology translation from research labs to broader applications. It also addresses associated risks, biases, and challenges of widespread Artificial Intelligence (AI) integration in diagnostics systems, while systematically outlining potential prospects, current challenges, and opportunities.

Recent Progress and Challenges on the Microfluidic Assay of Pathogenic Bacteria Using Biosensor Technology.

Microfluidic technology is one of the new technologies that has been able to take advantage of the specific properties of micro and nanoliters, and by reducing the costs and duration of tests, it has been widely used in research and treatment in biology and medicine. Different materials are often processed into miniaturized chips containing channels and chambers within the microscale range. This review (containing 117 references) demonstrates the significance and application of nanofluidic biosensing of various pathogenic bacteria. The microfluidic application devices integrated with bioreceptors and advanced nanomaterials, including hyperbranched nano-polymers, carbon-based nanomaterials, hydrogels, and noble metal, was also investigated. In the present review, microfluid methods for the sensitive and selective recognition of photogenic bacteria in various biological matrices are surveyed. Further, the advantages and limitations of recognition methods on the performance and efficiency of microfluidic-based biosensing of photogenic bacteria are critically investigated. Finally, the future perspectives, research opportunities, potential, and prospects on the diagnosis of disease related to pathogenic bacteria based on microfluidic analysis of photogenic bacteria are provided.

A Low-Cost Handheld Impedimetric Biosensing System for Rapid Diagnostics of SARS-CoV-2 Infections.

Current laboratory diagnostic approaches for virus detection give reliable results, but they require a lengthy procedure, trained personnel, and expensive equipment and reagents; hence, they are not a suitable choice for home monitoring purposes. This paper addresses this challenge by developing a portable impedimetric biosensing system for the identification of COVID-19 patients. This sensing system has two main parts: a throwaway two-working electrode (2-WE) strip and a novel read-out circuit, specifically designed for simultaneous signal acquisition from both working electrodes. Highly reliable electrochemical signal tracking from multiplex immunosensors provides a potential for flexible and portable multi-biomarker detection. The electrodes' surfaces were functionalized with SARS-CoV-2 Nucleocapsid Antibody enabling the selective detection of Nucleocapsid protein (N-protein) along with self-validation in the clinical nasopharyngeal swab specimens. The proposed programmable highly sensitive impedance read-out system allows for a wide dynamic detection range, which makes the sensor capable of detecting N-protein concentrations between 0.116 and 10,000 pg/mL. This lightweight and economical read-out arrangement is an ideal prospect for being mass-produced, especially during urgent pandemic situations. Also, such an impedimetric sensing platform has the potential to be redesigned for targeting not only other infectious diseases but also other critical disorders.

Oral Cells-On-Chip: Design, Modeling and Experimental Results.

Recent advances in periodontal studies have attracted the attention of researchers to the relation between oral cells and gum diseases, which is a real threat to overall human health. Among various microfabrication technologies, Complementary Metal Oxide Semiconductors (CMOSs) enable the development of low-cost integrated sensors and circuits for rapid and accurate assessment of living cells that can be employed for the early detection and control of periodontal diseases. This paper presents a CMOS capacitive sensing platform that can be considered as an alternative for the analysis of salivatory cells such as oral neutrophils. This platform consists of two sensing electrodes connected to a read-out capacitive circuitry designed and fabricated on the same chip using Austria Mikro Systeme (AMS) 0.35 µm CMOS process. A graphical user interface (GUI) was also developed to interact with the capacitive read-out system and the computer to monitor the capacitance changes due to the presence of saliva cells on top of the chip. Thanks to the wide input dynamic range (IDR) of more than 400 femto farad (fF) and high resolution of 416 atto farad (aF), the experimental and simulation results demonstrate the functionality and applicability of the proposed sensor for monitoring cells in a small volume of 1 µL saliva samples. As per these results, the hydrophilic adhesion of oral cells on the chip varies the capacitance of interdigitated electrodes (IDEs). These capacitance changes then give an assessment of the oral cells existing in the sample. In this paper, the simulation and experimental results set a new stage for emerging sensing platforms for testing oral samples.

Laser-Induced Graphene-Functionalized Field-Effect Transistor-Based Biosensing: A Potent Candidate for COVID-19 Detection.

Speedy and on-time detection of coronavirus disease 2019 (COVID-19) is of high importance to control the pandemic effectively and stop its disastrous consequences. A widely available, reliable, label-free, and rapid test that can recognize tiny amounts of specific biomarkers might be the solution. Nanobiosensors are one of the most attractive candidates for this purpose. Integration of graphene with biosensing devices shifts the performance of these systems to an incomparable level. Between the various arrangements using this wonder material, field-effect transistors (FETs) display a precise detection even in complex samples. The emergence of pioneering biosensors for detecting a wide range of diseases especially COVID-19 created the incentive to prepare a review of the recent graphene-FET biosensing platforms. However, the graphene fabrication and transfer to the surface of the device is an imperative factor for researchers to take into account. Therefore, we also reviewed the common methods of manufacturing graphene for biosensing applications and discuss their advantages and disadvantages. One of the most recent synthesizing techniques - laser-induced graphene (LIG) - is attracting attention owing to its extraordinary benefits which are thoroughly explained in this article. Finally, a conclusion highlighting the current challenges is presented.

Electronic Sensing Platform (ESP) Based on Open-Gate Junction Field-Effect Transistor (OG-JFET) for Life Science Applications: Design, Modeling and Experimental Results.

This paper presents a new field-effect sensor called open-gate junction gate field-effect transistor (OG-JFET) for biosensing applications. The OG-JFET consists of a p-type channel on top of an n-type layer in which the p-type serves as the sensing conductive layer between two ohmic contacted sources and drain electrodes. The structure is novel as it is based on a junction field-effect transistor with a subtle difference in that the top gate (n-type contact) has been removed to open the space for introducing the biomaterial and solution. The channel can be controlled through a back gate, enabling the sensor's operation without a bulky electrode inside the solution. In this research, in order to demonstrate the sensor's functionality for chemical and biosensing, we tested OG-JFET with varying pH solutions, cell adhesion (human oral neutrophils), human exhalation, and DNA molecules. Moreover, the sensor was simulated with COMSOL Multiphysics to gain insight into the sensor operation and its ion-sensitive capability. The complete simulation procedures and the physics of pH modeling is presented here, being numerically solved in COMSOL Multiphysics software. The outcome of the current study puts forward OG-JFET as a new platform for biosensing applications.

Recent Advances of Field-Effect Transistor Technology for Infectious Diseases.

Field-effect transistor (FET) biosensors have been intensively researched toward label-free biomolecule sensing for different disease screening applications. High sensitivity, incredible miniaturization capability, promising extremely low minimum limit of detection (LoD) at the molecular level, integration with complementary metal oxide semiconductor (CMOS) technology and last but not least label-free operation were amongst the predominant motives for highlighting these sensors in the biosensor community. Although there are various diseases targeted by FET sensors for detection, infectious diseases are still the most demanding sector that needs higher precision in detection and integration for the realization of the diagnosis at the point of care (PoC). The COVID-19 pandemic, nevertheless, was an example of the escalated situation in terms of worldwide desperate need for fast, specific and reliable home test PoC devices for the timely screening of huge numbers of people to restrict the disease from further spread. This need spawned a wave of innovative approaches for early detection of COVID-19 antibodies in human swab or blood amongst which the FET biosensing gained much more attention due to their extraordinary LoD down to femtomolar (fM) with the comparatively faster response time. As the FET sensors are promising novel PoC devices with application in early diagnosis of various diseases and especially infectious diseases, in this research, we have reviewed the recent progress on developing FET sensors for infectious diseases diagnosis accompanied with a thorough discussion on the structure of Chem/BioFET sensors and the readout circuitry for output signal processing. This approach would help engineers and biologists to gain enough knowledge to initiate their design for accelerated innovations in response to the need for more efficient management of infectious diseases like COVID-19.

Portable Sensing Devices for Detection of COVID-19: A Review.

The coronavirus pandemic is the most challenging incident that people have faced in recent years. Despite the time-consuming and expensive conventional methods, point-of-care diagnostics have a crucial role in deterrence, timely detection, and intensive care of the disease's progress. Hence, this detrimental health emergency persuaded researchers to accelerate the development of highly-scalable diagnostic devices to control the propagation of the virus even in the least developed countries. The strategies exploited for detecting COVID-19 stem from the already designed systems for studying other maladies, particularly viral infections. The present report reviews not only the novel advances in portable diagnostic devices for recognizing COVID-19, but also the previously existing biosensors for detecting other viruses. It discusses their adaptability for identifying surface proteins, whole viruses, viral genomes, host antibodies, and other biomarkers in biological samples. The prominence of different types of biosensors such as electrochemical, optical, and electrical for detecting low viral loads have been underlined. Thus, it is anticipated that this review will assist scientists who have embarked on a competition to come up with more efficient and marketable in-situ test kits for identifying the infection even in its incubation time without sample pretreatment. Finally, a conclusion is provided to highlight the importance of such an approach for monitoring people to combat the spread of such contagious diseases.

Biosensing based on field-effect transistors (FET): Recent progress and challenges.

The use of field-Effect-Transistor (FET) type biosensing arrangements has been highlighted by researchers in the field of early biomarker detection and drug screening. Their non-metalized gate dielectrics that are exposed to an electrolyte solution cover the semiconductor material and actively transduce the biological changes on the surface. The efficiency of these novel devices in detecting different biomolecular analytes in a real-time, highly precise, specific, and label-free manner has been validated by numerous research studies. Considerable progress has been attained in designing FET devices, especially for biomedical diagnosis and cell-based assays in the past few decades. The exceptional electronic properties, compactness, and scalability of these novel tools are very desirable for designing rapid, label-free, and mass detection of biomolecules. With the incorporation of nanotechnology, the performance of biosensors based on FET boosts significantly, particularly, employment of nanomaterials such as graphene, metal nanoparticles, single and multi-walled carbon nanotubes, nanorods, and nanowires. Besides, their commercial availability, and high-quality production on a large-scale, turn them to be one of the most preferred sensing and screening platforms. This review presents the basic structural setup and working principle of different types of FET devices. We also focused on the latest progression regarding the use of FET biosensors for the recognition of viruses such as, recently emerged COVID-19, Influenza, Hepatitis B Virus, protein biomarkers, nucleic acids, bacteria, cells, and various ions. Additionally, an outline of the development of FET sensors for investigations related to drug development and the cellular investigation is also presented. Some technical strategies for enhancing the sensitivity and selectivity of detection in these devices are addressed as well. However, there are still certain challenges which are remained unaddressed concerning the performance and clinical use of transistor-based point-of-care (POC) instruments; accordingly, expectations about their future improvement for biosensing and cellular studies are argued at the end of this review.

Bio-assay of the non-amidated progastrin-derived peptide (G17-Gly) using the tailor-made recombinant antibody fragment and phage display method: a biomedical analysis.

In this research, four novel and sensitive immunosensors for electrochemical determination of G17-Gly were designed based on signal amplification and tailor-made recombinant antibody technology. Anti-G17-Gly antibody fragments (i.e. scFv and VL specific to the N- and C-terminal of G17-Gly) were immobilized onto a polymeric nanocomposite comprising poly cetyl trimethyl ammonium bromide (P(CTAB)) as the conductive matrix, chitosan (CS) as a biocompatible agent and gold nanoparticles (AuNPs) as the signal amplification element. The high surface area provided by AuNPs and the small size of scFv/VL establish the basis for immobilizing a high amount of the anti-G17-Gly on the surface of the electrode for detecting G17-Gly in human plasma samples. Under optimal conditions, the designed immunosensors provide an excellent analytical capability for detecting and determining G17-Gly in human plasma samples with a linear range from 0.5 mM to 0.05 pM and a LLOQ of 0.05 pM. The sensitivity order of the immunosensors was Ag/2-mercaptoethanol/phage displaying scFv/P(CTAB-CS)-AuNP/GE, Ag/2-mercaptoethanol/phage displaying VL/P(CTAB-CS)-AuNP/GE, Ag/BSA/scFv/P(CTAB-CS)-AuNP/GE, and Ag/BSA/VL/P(CTAB-CS)-AuNP/GE. The aforementioned characteristics demonstrate that the proposed immune-devices can be used in biological and clinical diagnosis as reliable tools for identifying different oncobiomarkers.