Classification of nucleic acid amplification on ISFET arrays using spectrogram-based neural networks.

The COVID-19 pandemic has highlighted a significant research gap in the field of molecular diagnostics. This has brought forth the need for AI-based edge solutions that can provide quick diagnostic results whilst maintaining data privacy, security and high standards of sensitivity and specificity. This paper presents a novel proof-of-concept method to detect nucleic acid amplification using ISFET sensors and deep learning. This enables the detection of DNA and RNA on a low-cost and portable lab-on-chip platform for identifying infectious diseases and cancer biomarkers. We show that by using spectrograms to transform the signal to the time-frequency domain, image processing techniques can be applied to achieve the reliable classification of the detected chemical signals. Transformation to spectrograms is beneficial as it makes the data compatible with 2D convolutional neural networks and helps gain significant performance improvement over neural networks trained on the time domain data. The trained network achieves an accuracy of 84% with a size of 30kB making it suitable for deployment on edge devices. This facilitates a new wave of intelligent lab-on-chip platforms that combine microfluidics, CMOS-based chemical sensing arrays and AI-based edge solutions for more intelligent and rapid molecular diagnostics.

Molecular imprinting-based sensors: Lab-on-chip integration and biomedical applications.

The innovative technology of a marketable lab-on-a-chip platform for point-of-care (POC) in vitro detection has recently attracted remarkable attention. The POC tests can significantly enhance the high standard of medicinal care. In the last decade, clinical diagnostic technology has been broadly advanced and successfully performed in several areas. It seems that lab-on-a-chip approaches play a significant role in these technologies. However, high-cost and time-consuming methods are increasing the challenge and the development of a cost-effective, rapid and efficient method for the detection of biomolecules is urgently needed. Recently, polymer-coated sensing platforms have been a promising area that can be employed in medical diagnosis, pharmaceutical bioassays, and environmental monitoring. The designed on-chip sensors are based on molecular imprinting polymers (MIPs) that use label-free detection technology. Molecular imprinting shines out as a potentially promising technique for creating artificial recognition material with molecular recognition sites. MIPs provide unique advantages such as excellent recognition specificity, high selectivity, and good reusability. This review article aims to define several methods using molecular imprinting for biomolecules and their incorporation with several lab-on-chip technologies to describe the most promising methods for the development of sensing systems based on molecularly imprinted polymers. The higher selectivity, more user-friendly operation is believed to provide MIP-based lab-on-a-chip devices with great potential academic and commercial value in on-site clinical diagnostics and other point-of-care assays.

Towards hospital-on-chip supported by 2D MXenes-based 5th generation intelligent biosensors.

Existing public health emergencies due to fatal/infectious diseases such as coronavirus disease (COVID-19) and monkeypox have raised the paradigm of 5th generation portable intelligent and multifunctional biosensors embedded on a single chip. The state-of-the-art 5th generation biosensors are concerned with integrating advanced functional materials with controllable physicochemical attributes and optimal machine processability. In this direction, 2D metal carbides and nitrides (MXenes), owing to their enhanced effective surface area, tunable physicochemical properties, and rich surface functionalities, have shown promising performances in biosensing flatlands. Moreover, their hybridization with diversified nanomaterials caters to their associated challenges for the commercialization of stability due to restacking and oxidation. MXenes and its hybrid biosensors have demonstrated intelligent and lab-on-chip prospects for determining diverse biomarkers/pathogens related to fatal and infectious diseases. Recently, on-site detection has been clubbed with solution-on-chip MXenes by interfacing biosensors with modern-age technologies, including 5G communication, internet-of-medical-things (IoMT), artificial intelligence (AI), and data clouding to progress toward hospital-on-chip (HOC) modules. This review comprehensively summarizes the state-of-the-art MXene fabrication, advancements in physicochemical properties to architect biosensors, and the progress of MXene-based lab-on-chip biosensors toward HOC solutions. Besides, it discusses sustainable aspects, practical challenges and alternative solutions associated with these modules to develop personalized and remote healthcare solutions for every individual in the world.

Miniaturized Real-Time PCR systems for SARS-CoV-2 detection at the Point-of-Care.

Over the past two years, SARS-CoV-2 (Severe Acute Respiratory Syndrome-Coronavirus 2) infection has spread globally causing multi-organ disease and severely impacting the healthcare systems of all countries. Accordingly, the development of easy-to-access diagnostic devices has become essential to limit the effect of the virus worldwide. Real-Time PCR is considered the gold standard to identify SARS-CoV-2 infection due to high sensitivity, affordability, and capacity to detect low viral loads at early disease stage. Advances in lab on a chip technology has led to the development of some Point-of-Care (POC) devices using Real-Time PCR and approved by the United States Food and Drug Administration. We provide an overview on recently developed POC tests for the rapid diagnosis of COVID-19 infection. Practical applications of miniaturized devices based on viral genome amplification as well as favorable features such as reduced sample processing time, ease of use by non-specialized personnel, and the potential of PCR-based POC technologies will be highlighted and reviewed.

A Miniaturized Silicon Lab-on-Chip for Integrated PCR and Hybridization Microarray for High Multiplexing Nucleic Acids Analysis.

A silicon lab-on-chip, for the detection of nucleic acids through the integrated PCR and hybridization microarray, was developed. The silicon lab-on-chip manufactured through bio-MEMS technology is composed of two PCR microreactors (each volume 11.2 µL) and a microarray-hybridization microchamber (volume 30 µL), fluidically connected by buried bypass. It contains heaters and temperature sensors for the management and control of the temperature cycles during the PCR amplification and hybridization processes. A post-silicon process based on (i) plasmo-O2 cleaning/activation, (ii) vapor phase epoxy silanization, (iii) microarray fabrication and (iv) a protein-based passivation step was developed and fully characterized. The ssDNA microarray (4 rows × 10 columns) composed of 400 spots (spot size-70 ± 12 µm; spot-to-spot distance-130 ± 13 µm) was manufactured by piezo-dispense technology. A DNA microarray probe density in the range of 1310 to 2070 probe µm-2 was observed, together with a limit of detection of about 19 target µm-2. The performances of the silicon lab-on-chip were validated by the detection of the beta-globin gene directly from human blood. Remarkable sensitivity, multiplexing analysis and specificity were demonstrated for the detection of beta-globin and mycobacterium tuberculosis sequences.

LAB-ON-PCB TECHNOLOGY FOR HANDHELD, SAMPLE-IN-ANSWER-OUT SARS-CoV-2 DIAGNOSTIC

Since the early reports of SARS-CoV-2 in Wuhan, China in the winter of 2019, the virus spread has resulted in the most socially-crippling pandemic of the last century. Here, we report the development of a rapid, molecular COVID-19 test utilizing for the first time a loop-mediated isothermal amplification (LAMP) assay on Lab-on-Printed Circuit Board (Lab-on-PCB) to exploit the established integration and up-scaling advantages the latter offers. © 2021 MicroTAS 2021 - 25th International Conference on Miniaturized Systems for Chemistry and Life Sciences. All rights reserved.

All-in-One Optofluidic Chip for Molecular Biosensing Assays.

Integrated biosensor platforms have become subjects of high interest for consolidated assay preparation and analysis to reduce sample-to-answer response times. By compactly combining as many biosensor processes and functions as possible into a single lab-on-chip device, all-in-one point-of-care devices can aid in the accessibility and speed of deployment due to their compact size and portability. Biomarker assay preparation and sensing are functionalities that are often carried out on separate devices, thus increasing opportunity of contamination, loss of sample volume, and other forms of error. Here, we demonstrate a complete lab-on-chip system combining sample preparation, on-chip optofluidic dye laser, and optical detection. We first show the integration of an on-chip distributed feedback dye laser for alignment-free optical excitation of particles moving through a fluidic channel. This capability is demonstrated by using Rhodamine 6G as the gain medium to excite single fluorescent microspheres at 575 nm. Next, we present an optofluidic PDMS platform combining a microvalve network (automaton) for sample preparation of nanoliter volumes, on-chip distributed feedback dye laser for target excitation, and optical detection. We conduct concurrent capture and fluorescence tagging of Zika virus nucleic acid on magnetic beads in 30 min. Target-carrying beads are then optically excited using the on-chip laser as they flow through an analysis channel, followed by highly specific fluorescence detection. This demonstration of a complete all-in-one biosensor is a tangible step in the development of a rapid, point-of-care device that can assist in limiting the severity of future outbreaks.

Point-of-Care Diagnostics for Farm Animal Diseases: From Biosensors to Integrated Lab-on-Chip Devices.

Zoonoses and animal diseases threaten human health and livestock biosecurity and productivity. Currently, laboratory confirmation of animal disease outbreaks requires centralized laboratories and trained personnel; it is expensive and time-consuming, and it often does not coincide with the onset or progress of diseases. Point-of-care (POC) diagnostics are rapid, simple, and cost-effective devices and tests, that can be directly applied on field for the detection of animal pathogens. The development of POC diagnostics for use in human medicine has displayed remarkable progress. Nevertheless, animal POC testing has not yet unfolded its full potential. POC devices and tests for animal diseases face many challenges, such as insufficient validation, simplicity, and portability. Emerging technologies and advanced materials are expected to overcome some of these challenges and could popularize animal POC testing. This review aims to: (i) present the main concepts and formats of POC devices and tests, such as lateral flow assays and lab-on-chip devices; (ii) summarize the mode of operation and recent advances in biosensor and POC devices for the detection of farm animal diseases; (iii) present some of the regulatory aspects of POC commercialization in the EU, USA, and Japan; and (iv) summarize the challenges and future perspectives of animal POC testing.

Plasmonic Biosensors: Review.

Biosensors have globally been considered as biomedical diagnostic tools required in abundant areas including the development of diseases, detection of viruses, diagnosing ecological pollution, food monitoring, and a wide range of other diagnostic and therapeutic biomedical research. Recently, the broadly emerging and promising technique of plasmonic resonance has proven to provide label-free and highly sensitive real-time analysis when used in biosensing applications. In this review, a thorough discussion regarding the most recent techniques used in the design, fabrication, and characterization of plasmonic biosensors is conducted in addition to a comparison between those techniques with regard to their advantages and possible drawbacks when applied in different fields.

Advancements of Lab on Chip in Reducing Human Intervention: A Study

The tremendous advancements in nanotechnology have given life to the technology called Lab-on-Chip (LoC). The Nanoscale impression on semiconductors and the metals are achieved by the Lithography processes. Many of the experiments and analysis which are to be done in the laboratory have been done on this miniaturized module. The LoC technology helps to perform many laboratory functions on a single few centimeters chip size. This helps achieve high-throughput screening and automation. LoC technology requires a very less sample in drops for the analysis of the sample provided and also helps in cost effectiveness and speed response. It has great control over the concentration of samples as well as interactions to reduce the huge chemical waste. LoC through mass production aids to the development of highly compact design of systems. This paper overviews the development in the field of LoC. © 2021 IEEE.

CRISPR-Powered Microfluidics in Diagnostics: A Review of Main Applications

In the past few years, the CRISPR (clustered regularly interspaced short palindromic repeats) applications in medicine and molecular biology have broadened. CRISPR has also been integrated with microfluidic-based biosensors to enhance the sensitivity and selectivity of medical diagnosis due to its great potentials. The CRISPR-powered microfluidics can help quantify DNAs and RNAs for different diseases such as cancer, and viral or bacterial diseases among others. Here in this review, we discussed the main applications of such tools along with their advantages and limitations.

State of Sweat: Emerging Wearable Systems for Real-Time, Noninvasive Sweat Sensing and Analytics.

Skin-interfaced wearable systems with integrated colorimetric assays, microfluidic channels, and electrochemical sensors offer powerful capabilities for noninvasive, real-time sweat analysis. This Perspective details recent progress in the development and translation of novel wearable sensors for personalized assessment of sweat dynamics and biomarkers, with precise sampling and real-time analysis. Sensor accuracy, system ruggedness, and large-scale deployment in remote environments represent key opportunity areas, enabling broad deployment in the context of field studies, clinical trials, and recent commercialization. On-body measurements in these contexts show good agreement compared to conventional laboratory-based sweat analysis approaches. These device demonstrations highlight the utility of biochemical sensing platforms for personalized assessment of performance, wellness, and health across a broad range of applications.

Applications of CMOS Devices for the Diagnosis and Control of Infectious Diseases.

Emerging infectious diseases such as coronavirus disease of 2019 (COVID-19), Ebola, influenza A, severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) in recent years have threatened the health and security of the global community as one of the greatest factors of mortality in the world. Accurate and immediate diagnosis of infectious agents and symptoms is a key to control the outbreak of these diseases. Rapid advances in complementary metal-oxide-semiconductor (CMOS) technology offers great advantages like high accuracy, high throughput and rapid measurements in biomedical research and disease diagnosis. These features as well as low cost, low power and scalability of CMOS technology can pave the way for the development of powerful devices such as point-of-care (PoC) systems, lab-on-chip (LoC) platforms and symptom screening devices for accurate and timely diagnosis of infectious diseases. This paper is an overview of different CMOS-based devices such as optical, electrochemical, magnetic and mechanical sensors developed by researchers to mitigate the problems associated with these diseases.

Scalable COVID-19 Detection Enabled by Lab-on-Chip Biosensors.

Introduction: The emergence of a novel coronavirus, SARS-CoV-2, has highlighted the need for rapid, accurate, and point-of-care diagnostic testing. As of now, there is not enough testing capacity in the world to meet the stated testing targets, which are expected to skyrocket globally for broader testing during reopening. Aim: This review focuses on the development of lab-on-chip biosensing platforms for diagnosis of COVID-19 infection. Results: We discuss advantages of utilizing lab-on-chip technologies in response to the current global pandemic, including their potential for low-cost, rapid sample-to-answer processing times, and ease of integration into a range of healthcare settings. We then highlight the development of magnetic, colorimetric, plasmonic, electrical, and lateral flow-based lab-on-chip technologies for the detection of SARS-CoV-2, in addition to other viruses. We focus on rapid, point-of-care technologies that can be deployed at scale, as such devices could be promising alternatives to the current gold standard of reverse transcription-polymerase chain reaction (RT-PCR) diagnostic testing. Conclusion: This review is intended to provide an overview of the current state-of-the-field and serve as a resource for innovative development of new lab-on-chip assays for COVID-19 detection.