Smart microfluidics: Synergy of machine learning and microfluidics in the development of medical diagnostics for chronic and emerging infectious diseases

The COVID-19 pandemic, emerging/re-emerging infections as well as other non-communicable chronic diseases, highlight the necessity of smart microfluidic point-of-care diagnostic (POC) devices and systems in developing nations as risk factors for infections, severe disease manifestations and poor clinical outcomes are highly represented in these countries. These POC devices are also becoming vital as analytical procedures executable outside of conventional laboratory settings are seen as the future of healthcare delivery. Microfluidics have grown into a revolutionary system to miniaturize chemical and biological experimentation, including disease detection and diagnosis utilizing muPads/paper-based microfluidic devices, polymer-based microfluidic devices and 3-dimensional printed microfluidic devices. Through the development of droplet digital PCR, single-cell RNA sequencing, and next-generation sequencing, microfluidics in their analogous forms have been the leading contributor to the technical advancements in medicine. Microfluidics and machine-learning-based algorithms complement each other with the possibility of scientific exploration, induced by the framework's robustness, as preliminary studies have documented significant achievements in biomedicine, such as sorting, microencapsulation, and automated detection. Despite these milestones and potential applications, the complexity of microfluidic system design, fabrication, and operation has prevented widespread adoption. As previous studies focused on microfluidic devices that can handle molecular diagnostic procedures, researchers must integrate these components with other microsystem processes like data acquisition, data processing, power supply, fluid control, and sample pretreatment to overcome the barriers to smart microfluidic commercialization.Copyright © 2023 by Begell House, Inc.

An intelligent platform of services based on multimedia understanding and telehealth for supporting the management of SARS-CoV-2 multi-pathological patients

The combination of pervasive sensing and multimedia understanding with the advances in communications makes it possible to conceive platforms of services for providing telehealth solutions responding to the current needs of society. The recent outbreak has indeed posed several concerns on the management of patients at home, urging to devise complex pathways to address the Severe Acute Respiratory Syndrome (SARS) in combination with the usual diseases of an increasingly elder population. In this paper, we present TiAssisto, a project aiming to design, develop, and validate an innovative and intelligent platform of services, having as its main objective to assist both Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) multi-pathological patients and healthcare professionals. This is achieved by researching and validating new methods to improve their lives and reduce avoidable hospitalisations. TiAssisto features telehealth and telemedicine solutions to enable high-quality standards treatments based on Information and Communication Technologies (ICT), Artificial Intelligence (AI) and Machine Learning (ML). Three hundred patients are involved in our study: one half using our telehealth platform, while the other half participate as a control group for a correct validation. The developed AI models and the Decision Support System assist General Practitioners (GPs) and other healthcare professionals in order to help them in their diagnosis, by providing suggestions and pointing out possible presence or absence of signs that can be related to pathologies. Deep learning techniques are also used to detect the absence or presence of specific signs in lung ultrasound images. © 2022 IEEE.

CRISPR­based diagnostic approaches: Implications for rapid management of future pandemics (Review).

Sudden viral outbreaks have increased in the early part of the 21st century, such as those of severe acute respiratory syndrome coronavirus (SARS­CoV), Middle East respiratory syndrome corona virus, and SARS­CoV­2, owing to increased human access to wildlife habitats. Therefore, the likelihood of zoonotic transmission of human­associated viruses has increased. The emergence of severe acute respiratory syndrome coronavirus 2 in China and its spread worldwide within months have highlighted the need to be ready with advanced diagnostic and antiviral approaches to treat newly emerging diseases with minimal harm to human health. The gold­standard molecular diagnostic approaches currently used are time­consuming, require trained personnel and sophisticated equipment, and therefore cannot be used as point­of­care devices for widespread monitoring and surveillance. Clustered regularly interspaced short palindromic repeats (CRISPR)­associated (Cas) systems are widespread and have been reported in bacteria, archaea and bacteriophages. CRISPR­Cas systems are organized into CRISPR arrays and adjacent Cas proteins. The detection and in­depth biochemical characterization of class 2 type V and VI CRISPR­Cas systems and orthologous proteins such as Cas12 and Cas13 have led to the development of CRISPR­based diagnostic approaches, which have been used to detect viral diseases and distinguish between serotypes and subtypes. CRISPR­based diagnostic approaches detect human single nucleotide polymorphisms in samples from patients with cancer and are used as antiviral agents to detect and destroy viruses that contain RNA as a genome. CRISPR­based diagnostic approaches are likely to improve disease detection methods in the 21st century owing to their ease of development, low cost, reduced turnaround time, multiplexing and ease of deployment. The present review discusses the biochemical properties of Cas12 and Cas13 orthologs in viral disease detection and other applications. The present review expands the scope of CRISPR­based diagnostic approaches to detect diseases and fight viruses as antivirals.

Insight of smart biosensors for COVID-19: A review.

The review discusses the diagnostic application of biosensors as point-of-care devices in the COVID-19 pandemic. Biosensors are important analytical tools that can be used for the robust and effective detection of infectious diseases in real-time. In this current scenario, the utilization of smart, efficient biosensors for COVID-19 detection is increasing and we have included a few smart biosensors such as smart and intelligent based biosensors, plasmonic biosensors, field effect transistor (FET) biosensors, smart optical biosensors, surface enhanced Raman scattering (SERS) biosensor, screen printed electrode (SPE)-based biosensor, molecular imprinted polymer (MIP)-based biosensor, MXene-based biosensor and metal-organic frame smart sensor. Their significance as well as the benefits and drawbacks of each kind of smart sensor are mentioned in depth. Furthermore, we have compiled a list of various biosensors which have been developed across the globe for COVID-19 and have shown promise as commercial detection devices. Significant challenges in the development of effective diagnostic methods are discussed and recommendations have been made for better diagnostic outcomes to manage the ongoing pandemic effectively.

Electrochemical point-of-care devices for monitoring waterborne pathogens: Protozoa, bacteria, and viruses – An overview

Water is considered a natural resource of high importance to the society whose availability and quality are in great demand. The water that reaches homes may contain different species, among them microorganisms like bacteria, protozoa and viruses that can contaminate and compromise the health and safety of the population. Thus, frequent water analysis would allow the monitoring of potentially harmful and/or toxic species that can be found in water resources. The application of point-of-care devices (POCs) for monitoring water ensures faster on-site analysis. The use of electrochemistry as a detection technique for a specific analyte presents itself as a promising way, being able to serve different targets reporting fast, selective and reproducible responses. After the COVID-19 outbreak in the world, the necessity of the development of such devices that may monitor species quickly, even at low concentrations was evidenced. The conventional methods of water analysis are still the most widely employed, despite the existence of already well-established modes of detection of target species by electrochemical techniques allowing on-site detection with POCs. In the quest to elucidate such issues, this review aims to show some biosensors devices developed for the detection of bacteria, protozoa, and viruses, attempting to understand what would still be needed for the large-scale application of these devices in water monitoring, identifying the innovative features and shortcomings of POCs. © 2022 The Authors

Aspects of Point-of-Care Diagnostics for Personalized Health Wellness.

Advancements in analytical diagnostic systems for point-of-care (POC) application have gained considerable attention because of their rapid operation at the site required to manage severe diseases, even in a personalized manner. The POC diagnostic devices offer easy operation, fast analytical outcome, and affordable cost, which promote their advanced research and versatile adoptability. Keeping advantages in view, considerable efforts are being made to design and develop smart sensing components such as miniaturized transduction, interdigitated electrodes-based sensing chips, selective detection at low level, portable packaging, and sustainable durability to promote POC diagnostics according to the needs of patient care. Such effective diagnostics systems are in demand, which creates the challenge to make them more efficient in every aspect to generate a desired bio-informatic needed for better health access and management. Keeping advantages and scope in view, this mini review focuses on practical scenarios associated with miniaturized analytical diagnostic devices at POC application for targeted disease diagnostics smartly and efficiently. Moreover, advancements in technologies, such as smartphone-based operation, paper-based sensing assays, and lab-on-a-chip (LOC) which made POC more sensitive, informative, and suitable for major infectious disease diagnosis, are the main focus here. Besides, POC diagnostics based on automated patient sample integration with a sensing platform is continuously improving therapeutics interventions against specific infectious disease. This review also discussed challenges associated with state-of-the-art technology along with future research opportunities to design and develop next generation POC diagnostic systems needed to manage infectious diseases in a personalized manner.

COVID-19 diagnosis -A review of current methods.

A fast and accurate self-testing tool for COVID-19 diagnosis has become a prerequisite to comprehend the exact number of cases worldwide and to take medical and governmental actions accordingly. SARS-CoV-2 (formerly, 2019-nCoV) infection was first reported in Wuhan (China) in December 2019, and then it has rapidly spread around the world, causing ~14 million active cases with ~582,000 deaths as of July 2020. The diagnosis tools available so far have been based on a) viral gene detection, b) human antibody detection, and c) viral antigen detection, among which the viral gene detection by RT-PCR has been found as the most reliable technique. In this report, the current SARS-CoV-2 detection kits, exclusively the ones that were issued an "Emergency Use Authorization" from the U.S. Food and Drug Administration, were discussed. The key structural components of the virus were presented to provide the audience with an understanding of the scientific principles behind the testing tools. The methods that are still in the early research state were also reviewed in a subsection based on the reports available so far.

Molecular diagnosis of COVID-19 in different biologic matrix, their diagnostic validity and clinical relevance: A systematic review.

Due to COVID 19 outbreak many studies are being conducted for therapeutic strategies and vaccines but detection methods play an important role in the containment of the disease. Hence, this systematic review aims to evaluate the effectiveness of the molecular detection techniques in COVID-19. For framing the systematic review 6 literature databases (PubMed, EMBASE, OVID, Web of Science, Scopus and Google Scholar) were searched for relevant studies and articles were screened for relevant content till 25th April 2020. Observations from this systematic review reveal the utility of RT-PCR with serological testing as one such method cannot correlate with accurate results. Availability of point of care devices do not conform to sensitivity and specificity in comparison to the conventional methods due to lack of clinical investigations. Pivotal aim of molecular and serological research is the development of detection methods that can support the clinical decision making of patients suspected with SARS-CoV-2. However, none of the methods were 100% sensitive and specific; hence additional studies are required to overcome the challenges addressed here. We hope that the present article with its observations and suggestions will assist the researchers to realize this vision in future.

Point-of-Care Diagnostics of COVID-19: From Current Work to Future Perspectives.

Coronaviruses have received global concern since 2003, when an outbreak caused by SARS-CoV emerged in China. Later on, in 2012, the Middle-East respiratory syndrome spread in Saudi Arabia, caused by MERS-CoV. Currently, the global crisis is caused by the pandemic SARS-CoV-2, which belongs to the same lineage of SARS-CoV. In response to the urgent need of diagnostic tools, several lab-based and biosensing techniques have been proposed so far. Five main areas have been individuated and discussed in terms of their strengths and weaknesses. The cell-culture detection and the microneutralization tests are still considered highly reliable methods. The genetic screening, featuring the well-established Real-time polymerase chain reaction (RT-PCR), represents the gold standard for virus detection in nasopharyngeal swabs. On the other side, immunoassays were developed, either by screening/antigen recognition of IgM/IgG or by detecting the whole virus, in blood and sera. Next, proteomic mass-spectrometry (MS)-based methodologies have also been proposed for the analysis of swab samples. Finally, virus-biosensing devices were efficiently designed. Both electrochemical immunosensors and eye-based technologies have been described, showing detection times lower than 10 min after swab introduction. Alternative to swab-based techniques, lateral flow point-of-care immunoassays are already commercially available for the analysis of blood samples. Such biosensing devices hold the advantage of being portable for on-site testing in hospitals, airports, and hotspots, virtually without any sample treatment or complicated lab precautions.