On-chip multivariant COVID 19 photonic sensor based on silicon nitride double-microring resonators

Coronavirus disease 2019 (COVID-19) is a newly emerging human infectious disease that continues to develop new variants. A crucial step in the quest to reduce the infection is the development of rapid and reliable virus detectors. Here, we report a chip scale photonic sensing device consisting of a silicon-nitride double microring resonator (MRR) for detecting SARS-CoV-2 in clinical samples. The sensor is implemented by surface activation of one of the MRRs, acting as a probe, with DNA primers for SARS-CoV-2 RNA, whereas the other MRR is used as a reference. The performance of the sensor is determined by applying different amounts of SARS-CoV-2 complementary RNA. As will be shown in the paper, our device detects the RNA fragments at concentrations of 10 cp/μL and with sensitivity of 750 nm/RIU. As such, it shows a promise toward the implementation of label-free, small form factor, CMOS compatible biosensor for SARS-CoV-2, which is also environment, temperature, and pressure independent. Our approach can also be used for detecting other SARS-CoV-2 genes, as well as other viruses and pathogens. © 2023 the author(s), published by De Gruyter, Berlin/Boston 2023.

A Novel Project-Oriented System on Chip (SoC) Design Course for Computer and Electrical Engineers

This paper describes a novel project-oriented system on chip (SoC) design course. The course is taught in the Computer Science and Engineering (CSE) Department at the University of Texas at Arlington and is offered as CSE 4356 System on Chip Design for computer engineering undergraduates, as CSE 5356 for computer engineering graduate students, and as EE 5315 for electrical engineering graduate students. It is taught as one course combining all numbers. All students are given the same lectures, course materials, assignments, and projects. Grading standards and expectations are the same for all students as well. The course in its current form was first offered in fall 2020 and was taught online due to COVID-19 restrictions. The course was offered again in fall 2021 in a traditional on-campus, in-person mode of delivery. Two seasoned educators, with more than eighty years of total teaching experience, combined to team teach the course. One also brought more than thirty years of industrial design experience to the course. SoC FPGA devices have been available for use by designers for more than 10 years and are widely used in applications that require both an embedded microcomputer and FPGA-based logic for real-time computationally-intense solutions. Such solutions require skills in C programming, HDL programming, bus topologies forming the bridge between FPGA fabric and the microprocessor space, Linux operating systems and virtualization, and kernel device driver development. The breadth of the skills that were conveyed to students necessitated a team teaching approach to leverage the diverse background of the instructors. With such a wide range of topics, one of the biggest challenges was developing a course that was approachable for a greatly varied population of students - a mix of Computer Engineering (CpE) and Electrical Engineering (EE) students at both the graduate and undergraduate level. Another, perhaps less obvious, challenge was the inherently application focus of the course, which presents challenges to many graduate students whose undergraduate degree lacked a robust hands-on design experience. Selection of an appropriate project was key to making the course effective and providing a fun learning experience for students. The projects were aligned to relevant industry applications, stressing complex modern intellectual property (IP) work flows, while still being approachable to students. The design of a universal asynchronous receiver transmitter (UART) IP module in 2020 and a serial peripheral interface (SPI) IP module in 2021 were chosen as the projects for the first two offerings of the course. The Terasic/Intel DE1-SoC development board and Intel Quartus Prime 18.1 design software were the technologies chosen for the course. The development board and basic test instruments were provided to each student in a take-home lab kit. The system on chip design course has proven to be a popular but challenging course for our undergraduate and graduate students in computer engineering and electrical engineering. The course has demonstrated that it is possible to successfully teach an advanced design-oriented course to students of varying majors, levels, educational backgrounds, and cultures. © American Society for Engineering Education, 2022.

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.

A Point-of-care Biosensor with Subwavelength Grating Waveguide-based Micro-ring Resonator for Detection of COVID-19

We present an on-chip optical biosensor for the detection of COVID-19. The subwavelength grating waveguide-based micro-ring resonator with high sensitivity and low limit of detection integrates with microfludic channel, which promises clinical utility in point-of-care diagnostic. © Optica Publishing Group 2022, © 2022 The Author(s)

AN INTEGRATED RT-LAMP AND CRISPR ASSAY FOR NUCLEIC ACID DETECTION IN A SINGLE MICROFLUIDIC CHIP

We will present a microfluidic assay to detect SARS-CoV-2 RNA from nasopharyngeal swab samples. Our method leverages isotachophoresis (ITP) to integrate sample preparation, RT-LAMP, and CRISPR-based nucleic acid detection in an automatable chip. For the first time, we use ITP to purify, pre-concentrate and isothermally amplify target nucleic acids into a ~1 µL reaction volume on-chip. The device then transitions LAMP amplicons into an on-chip zone containing Cas12-gRNA complexes and reporter molecules to measure target-activated CRISPR activity. We will use our method to automatically detect COVID-19 from nasopharyngeal swab samples. © 2021 MicroTAS 2021 - 25th International Conference on Miniaturized Systems for Chemistry and Life Sciences. All rights reserved.

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.

Securing Biochemical Samples Using Molecular Barcoding on Digital Microfluidic Biochips*

Microfluidic biochips are being adopted today in point-of-care diagnostics, e.g., COVID-19 testing;therefore, it is critical to ensure integrity of bio-sample before bioassays are run on-chip. A security technique called molecular barcoding was recently proposed to thwart sample-forgery attacks in DNA forensics. Molecular barcoding refers to addition of unique DNA molecules in bio-samples, and the sequence of the added DNA sample serves as a distinct 'barcode' for the sample. The existence of the added molecule can be validated using polymerase chain reaction (PCR) and gel electrophoresis. However, this security solution has several limitations: (1) the lack of robustness of the barcode molecules when they are added to other genomic DNA (e.g., samples collected for diagnostics);(2) the need for special bulk instrumentation for validation;(3) the need for human intervention during the overall process. To overcome the limitations, we design a set of robust molecular barcodes that can be validated using both traditional polymerase chain reaction and loop mediated isothermal amplification (LAMP). The validation using LAMP can be executed on a small-in-size and portable digital microfluidic biochip (DMFB). Our LAMP workflow includes a color-changing visual indicator for simple, rapid identification of the barcode existence in solutions. We first demonstrate the proposed security workflow using benchtop techniques. Next, we fabricate a printed circuit board (PCB)-based DMFB with heaters and demonstrate, for the first time, the LAMP assay on a DMFB. © 2021 IEEE.

Human Organoids and Organs-on-Chips for Addressing COVID-19 Challenges.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), poses an imminent threat to our lives. Although animal models and monolayer cell cultures are utilized for pathogenesis studies and the development of COVID-19 therapeutics, models that can more accurately reflect human-relevant responses to this novel virus are still lacking. Stem cell organoids and bioengineered organs-on-chips have emerged as two cutting-edge technologies used to construct biomimetic in vitro three-dimensional (3D) tissue or organ models. In this review, the key features of these two model systems that allow them to recapitulate organ physiology and function are introduced. The recent progress of these technologies for virology research is summarized and their utility in meeting the COVID-19 pandemic is highlighted. Future opportunities and challenges in the development of advanced human organ models and their potential to accelerate translational applications to provide vaccines and therapies for COVID-19 and other emerging epidemics are also discussed.

Beyond liquid biopsy: Toward non-invasive assays for distanced cancer diagnostics in pandemics.

Liquid biopsy technologies have seen a significant improvement in the last decade, offering the possibility of reliable analysis and diagnosis from several biological fluids. The use of these technologies can overcome the limits of standard clinical methods, related to invasiveness and poor patient compliance. Along with this there are now mature examples of lab-on-chips (LOC) which are available and could be an emerging and breakthrough technology for the present and near-future clinical demands that provide sample treatment, reagent addition and analysis in a sample-in/answer-out approach. The possibility of combining non-invasive liquid biopsy and LOC technologies could greatly assist in the current need for minimizing exposure and transmission risks. The recent and ongoing pandemic outbreak of SARS-CoV-2, indeed, has heavily influenced all aspects of life worldwide. Ordinary tasks have been forced to switch from "in presence" to "distanced", limiting the possibilities for a large number of activities in all fields of life outside of the home. Unfortunately, one of the settings in which physical distancing has assumed noteworthy consequences is the screening, diagnosis and follow-up of diseases. In this review, we analyse biological fluids that are easily collected without the intervention of specialized personnel and the possibility that they may be used -or not-for innovative diagnostic assays. We consider their advantages and limitations, mainly due to stability and storage and their integration into Point-of-Care diagnostics, demonstrating that technologies in some cases are mature enough to meet current clinical needs.

Advanced human-relevant in vitro pulmonary platforms for respiratory therapeutics.

Over the past years, advanced in vitro pulmonary platforms have witnessed exciting developments that are pushing beyond traditional preclinical cell culture methods. Here, we discuss ongoing efforts in bridging the gap between in vivo and in vitro interfaces and identify some of the bioengineering challenges that lie ahead in delivering new generations of human-relevant in vitro pulmonary platforms. Notably, in vitro strategies using foremost lung-on-chips and biocompatible "soft" membranes have focused on platforms that emphasize phenotypical endpoints recapitulating key physiological and cellular functions. We review some of the most recent in vitro studies underlining seminal therapeutic screens and translational applications and open our discussion to promising avenues of pulmonary therapeutic exploration focusing on liposomes. Undeniably, there still remains a recognized trade-off between the physiological and biological complexity of these in vitro lung models and their ability to deliver assays with throughput capabilities. The upcoming years are thus anticipated to see further developments in broadening the applicability of such in vitro systems and accelerating therapeutic exploration for drug discovery and translational medicine in treating respiratory disorders.