Optical fibers sensors for detection of SARS-CoV-2 infection

In this chapter, the main techniques that use light to monitor and detect viruses and biomolecules will be presented, including Surface-Enhanced Raman Spectroscopy (SERS), Localized-Surface Plasmon Resonance (SPR), luminescence, and others. It will also be discussed the devices used to build biosensors and, in addition, the chemical modifications in waveguides to improve and innovate such technologies. Besides, it will also address how optical devices and materials are being explored in the detection and diagnosis of the new coronavirus, as some aspects related to the biological structure of SARS-CoV-2 and its detection. © The Author(s), under exclusive license to Springer Nature Switzerland AG 2023. All rights reserved.

Solid-Phase Optical Sensing Techniques for Sensitive Virus Detection.

Viral infections can pose a major threat to public health by causing serious illness, leading to pandemics, and burdening healthcare systems. The global spread of such infections causes disruptions to every aspect of life including business, education, and social life. Fast and accurate diagnosis of viral infections has significant implications for saving lives, preventing the spread of the diseases, and minimizing social and economic damages. Polymerase chain reaction (PCR)-based techniques are commonly used to detect viruses in the clinic. However, PCR has several drawbacks, as highlighted during the recent COVID-19 pandemic, such as long processing times and the requirement for sophisticated laboratory instruments. Therefore, there is an urgent need for fast and accurate techniques for virus detection. For this purpose, a variety of biosensor systems are being developed to provide rapid, sensitive, and high-throughput viral diagnostic platforms, enabling quick diagnosis and efficient control of the virus's spread. Optical devices, in particular, are of great interest due to their advantages such as high sensitivity and direct readout. The current review discusses solid-phase optical sensing techniques for virus detection, including fluorescence-based sensors, surface plasmon resonance (SPR), surface-enhanced Raman scattering (SERS), optical resonators, and interferometry-based platforms. Then, we focus on an interferometric biosensor developed by our group, the single-particle interferometric reflectance imaging sensor (SP-IRIS), which has the capability to visualize single nanoparticles, to demonstrate its application for digital virus detection.

Emerging trends in point-of-care biosensing strategies for molecular architectures and antibodies of SARS-CoV-2.

COVID-19, a highly contagious viral infection caused by the occurrence of severe acute respiratory syndrome coronavirus (SARS-CoV-2), has turned out to be a viral pandemic then ravaged many countries worldwide. In the recent years, point-of-care (POC) biosensors combined with state-of-the-art bioreceptors, and transducing systems enabled the development of novel diagnostic tools for rapid and reliable detection of biomarkers associated with SARS-CoV-2. The present review thoroughly summarises and discusses various biosensing strategies developed for probing SARS-CoV-2 molecular architectures (viral genome, S Protein, M protein, E protein, N protein and non-structural proteins) and antibodies as a potential diagnostic tool for COVID-19. This review discusses the various structural components of SARS-CoV-2, their binding regions and the bioreceptors used for recognizing the structural components. The various types of clinical specimens investigated for rapid and POC detection of SARS-CoV-2 is also highlighted. The importance of nanotechnology and artificial intelligence (AI) approaches in improving the biosensor performance for real-time and reagent-free monitoring the biomarkers of SARS-CoV-2 is also summarized. This review also encompasses existing practical challenges and prospects for developing new POC biosensors for clinical monitoring of COVID-19.

Overview of Optical Biosensors for Early Cancer Detection: Fundamentals, Applications and Future Perspectives.

Conventional cancer detection and treatment methodologies are based on surgical, chemical and radiational processes, which are expensive, time consuming and painful. Therefore, great interest has been directed toward developing sensitive, inexpensive and rapid techniques for early cancer detection. Optical biosensors have advantages in terms of high sensitivity and being label free with a compact size. In this review paper, the state of the art of optical biosensors for early cancer detection is presented in detail. The basic idea, sensitivity analysis, advantages and limitations of the optical biosensors are discussed. This includes optical biosensors based on plasmonic waveguides, photonic crystal fibers, slot waveguides and metamaterials. Further, the traditional optical methods, such as the colorimetric technique, optical coherence tomography, surface-enhanced Raman spectroscopy and reflectometric interference spectroscopy, are addressed.

Emerging nanophotonic biosensor technologies for virus detection

Highly infectious viral diseases are a serious threat to mankind as they can spread rapidly among the community, possibly even leading to the loss of many lives. Early diagnosis of a viral disease not only increases the chance of quick recovery, but also helps prevent the spread of infections. There is thus an urgent need for accurate, ultrasensitive, rapid, and affordable diagnostic techniques to test large volumes of the population to track and thereby control the spread of viral diseases, as evidenced during the COVID-19 and other viral pandemics. This review paper critically and comprehensively reviews various emerging nanophotonic biosensor mechanisms and biosensor technologies for virus detection, with a particular focus on detection of the SARS-CoV-2 (COVID-19) virus. The photonic biosensing mechanisms and technologies that we have focused on include: (a) plasmonic field enhancement via localized surface plasmon resonances, (b) surface enhanced Raman scattering, (c) nano-Fourier transform infrared (nano-FTIR) near-field spectroscopy, (d) fiber Bragg gratings, and (e) microresonators (whispering gallery modes), with a particular emphasis on the emerging impact of nanomaterials and two-dimensional materials in these photonic sensing technologies. This review also discusses several quantitative issues related to optical sensing with these biosensing and transduction techniques, notably quantitative factors that affect the limit of detection (LoD), sensitivity, specificity, and response times of the above optical biosensing diagnostic technologies for virus detection. We also review and analyze future prospects of cost-effective, lab-on-a-chip virus sensing solutions that promise ultrahigh sensitivities, rapid detection speeds, and mass manufacturability.

Recent Advances of Representative Optical Biosensors for Rapid and Sensitive Diagnostics of SARS-CoV-2.

The outbreak of Corona Virus Disease 2019 (COVID-19) has again emphasized the significance of developing rapid and highly sensitive testing tools for quickly identifying infected patients. Although the current reverse transcription polymerase chain reaction (RT-PCR) diagnostic techniques can satisfy the required sensitivity and specificity, the inherent disadvantages with time-consuming, sophisticated equipment and professional operators limit its application scopes. Compared with traditional detection techniques, optical biosensors based on nanomaterials/nanostructures have received much interest in the detection of SARS-CoV-2 due to the high sensitivity, high accuracy, and fast response. In this review, the research progress on optical biosensors in SARS-CoV-2 diagnosis, including fluorescence biosensors, colorimetric biosensors, Surface Enhancement Raman Scattering (SERS) biosensors, and Surface Plasmon Resonance (SPR) biosensors, was comprehensively summarized. Further, promising strategies to improve optical biosensors are also explained. Optical biosensors can not only realize the rapid detection of SARS-CoV-2 but also be applied to judge the infectiousness of the virus and guide the choice of SARS-CoV-2 vaccines, showing enormous potential to become point-of-care detection tools for the timely control of the pandemic.

Detection of SARS-CoV-2 Using a Miniaturized Spectrometer Chip: A Comparative Study Against Benchtop Spectrometer and Its Potential Application to Handheld Detection

A global pandemic of SARS-CoV-2 was caused around the world. The virus is highly contagious and rapidly spreads. Early detection of the virus is crucial to prevent its spread and control outbreaks. Owing to the drawbacks of waiting time and high cost involved in polymerase chain reaction (PCR) testing, low-cost and accurate detection setups with the possibility of being realized as portable systems are desirable. In this study, we examined the feasibility of using a small spectrometer in conjunction with optical biosensors as a measurement system. According to the experimental results related to different concentrations of SARS-CoV-2 ranging from 106 to 102 copies/mL, the surface-mounted device (SMD) size spectrometer and benchtop fiber-optic spectrometer showed good agreement, demonstrating the possibility of using tiny spectrometers to detect the virus at different concentrations using optical biosensors. © 2022 ACM.

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)

A Framework for Biosensors Assisted by Multiphoton Effects and Machine Learning.

The ability to interpret information through automatic sensors is one of the most important pillars of modern technology. In particular, the potential of biosensors has been used to evaluate biological information of living organisms, and to detect danger or predict urgent situations in a battlefield, as in the invasion of SARS-CoV-2 in this era. This work is devoted to describing a panoramic overview of optical biosensors that can be improved by the assistance of nonlinear optics and machine learning methods. Optical biosensors have demonstrated their effectiveness in detecting a diverse range of viruses. Specifically, the SARS-CoV-2 virus has generated disturbance all over the world, and biosensors have emerged as a key for providing an analysis based on physical and chemical phenomena. In this perspective, we highlight how multiphoton interactions can be responsible for an enhancement in sensibility exhibited by biosensors. The nonlinear optical effects open up a series of options to expand the applications of optical biosensors. Nonlinearities together with computer tools are suitable for the identification of complex low-dimensional agents. Machine learning methods can approximate functions to reveal patterns in the detection of dynamic objects in the human body and determine viruses, harmful entities, or strange kinetics in cells.

High throughput optical modulation biosensing for highly sensitive and rapid detection of biomarkers.

Rapid, highly sensitive, and high-throughput detection of biomarkers at low concentrations is invaluable for early diagnosis of various diseases. In many highly sensitive immunoassays, magnetic beads are used to capture fluorescently labeled target molecules. The target molecules are then quantified by detecting the fluorescent signal from individual beads, which is time consuming and requires a complicated and expensive detection system. Here, we demonstrate a high-throughput optical modulation biosensing (ht-OMB) system, which uses a small permanent magnet to aggregate the beads into a small detection volume and eliminates background noise by steering a laser beam in and out of the cluster of beads. Shortening the aggregation, acquisition, and well-to-well scanning transition times enables reading a 96-well plate within 10 min. Using the ht-OMB system to detect human Interleukin-8, we demonstrated a limit of detection of 0.14 ng/L and a 4-log dynamic range. Testing 94 RNA extracts from 36 confirmed RT-qPCR SARS-CoV-2-positive patients (Ct≤40) and 58 confirmed RT-qPCR SARS-CoV-2-negative individuals resulted in 100% sensitivity and 100% specificity.

Optimization of Silicon Nitride Waveguide Platform for On-Chip Virus Detection.

This work presents a rigorous and generic sensitivity analysis of silicon nitride on silicon dioxide strip waveguide for virus detection. In general, by functionalizing the waveguide surface with a specific antibodies layer, we make the optical sensor sensitive only to a particular virus. Unlike conventional virus detection methods such as polymerase chain reaction (PCR), integrated refractive index (RI) optical sensors offer cheap and mass-scale fabrication of compact devices for fast and straightforward detection with high sensitivity and selectivity. Our numerical analysis includes a wide range of wavelengths from visible to mid-infrared. We determined the strip waveguide's single-mode dimensions and the optimum dimensions that maximize the sensitivity to the virus layer attached to its surface at each wavelength using finite difference eigenmode (FDE) solver. We also compared the strip waveguide with the widely used slot waveguide. Our theoretical study shows that silicon nitride strip waveguide working at lower wavelengths is the optimum choice for virus detection as it maximizes both the waveguide sensitivity (Swg) and the figure of merit (FOM) of the sensor. The optimized waveguides are well suited for a range of viruses with different sizes and refractive indices. Balanced Mach-Zehnder interferometer (MZI) sensors were designed using FDE solver and photonic circuit simulator at different wavelengths. The designed sensors show high FOM at λ = 450 nm ranging from 500 RIU-1 up to 1231 RIU-1 with LMZI = 500 µm. Different MZI configurations were also studied and compared. Finally, edge coupling from the fiber to the sensor was designed, showing insertion loss (IL) at λ = 450 nm of 4.1 dB for the design with FOM = 500 RIU-1. The obtained coupling efficiencies are higher than recently proposed fiber couplers.

Optical Biosensors for Diagnostics of Infectious Viral Disease: A Recent Update.

The design and development of biosensors, analytical devices used to detect various analytes in different matrices, has emerged. Biosensors indicate a biorecognition element with a physicochemical analyzer or detector, i.e., a transducer. In the present scenario, various types of biosensors have been deployed in healthcare and clinical research, for instance, biosensors for blood glucose monitoring. Pathogenic microbes are contributing mediators of numerous infectious diseases that are becoming extremely serious worldwide. The recent outbreak of COVID-19 is one of the most recent examples of such communal and deadly diseases. In efforts to work towards the efficacious treatment of pathogenic viral contagions, a fast and precise detection method is of the utmost importance in biomedical and healthcare sectors for early diagnostics and timely countermeasures. Among various available sensor systems, optical biosensors offer easy-to-use, fast, portable, handy, multiplexed, direct, real-time, and inexpensive diagnosis with the added advantages of specificity and sensitivity. Many progressive concepts and extremely multidisciplinary approaches, including microelectronics, microelectromechanical systems (MEMSs), nanotechnologies, molecular biology, and biotechnology with chemistry, are used to operate optical biosensors. A portable and handheld optical biosensing device would provide fast and reliable results for the identification and quantitation of pathogenic virus particles in each sample. In the modern day, the integration of intelligent nanomaterials in the developed devices provides much more sensitive and highly advanced sensors that may produce the results in no time and eventually help clinicians and doctors enormously. This review accentuates the existing challenges engaged in converting laboratory research to real-world device applications and optical diagnostics methods for virus infections. The review's background and progress are expected to be insightful to the researchers in the sensor field and facilitate the design and fabrication of optical sensors for life-threatening viruses with broader applicability to any desired pathogens.

High-Order Multimode Waveguide Interferometer for Optical Biosensing Applications.

A generalization of the concept of multimode interference sensors is presented here for the first time, to the best of our knowledge. The existing bimodal and trimodal sensors correspond to particular cases of those interference sensors. A thorough study of the properties of the multimode waveguide section provided a deeper insight into the behavior of this class of sensors, which allowed us to establish new criteria for designing more sensitive structures. Other challenges of using high-order modes within the sensing area of the device reside in the excitation of these modes and the interpretation of the output signal. To overcome these, we developed a novel structure to excite any desired high-order mode along with the fundamental mode within the sensing section, while maintaining a fine control over the power distribution between them. A new strategy to detect and interpret the output signal is also presented in detail. Finally, we designed a high-order sensor for which numerical simulations showed a theoretical limit of detection of 1.9×10-7 RIU, making this device the most sensitive multimode interference sensor reported so far.

Evaluation of kinetics and thermodynamics of interaction between immobilized SARS-CoV-2 nucleoprotein and specific antibodies by total internal reflection ellipsometry.

During the pandemic, different methods for SARS-CoV-2 detection and COVID-19 diagnostics were developed, including antibody and antigen tests. For a better understanding of the interaction mechanism between SARS-CoV-2 virus proteins and specific antibodies, total internal reflection ellipsometry based evaluation of the interaction between SARS-CoV-2 nucleoprotein (SCoV2-rN) and anti-SCoV2-rN antibodies was performed. Results show that the appropriate mathematical model, which takes into account the formation of an intermediate complex, can be applied for the evaluation of SCoV2-rN/anti-SCoV2-rN complex formation kinetics. The calculated steric factor indicated that SCoV2-rN/anti-SCoV2-rN complex formation has very strict steric requirements. Estimated Gibbs free energy (ΔGAssoc) for SCoV-rN and anti-SCoV-rN binding was determined as -34 kJ/mol. The reported findings are useful for the design of new analytical systems for the determination of anti-SCoV2-rN antibodies and for the development of new anti-SARS-CoV-2 medications.

Recent advances in nanomaterials based biosensors for point of care (PoC) diagnosis of Covid-19 - A minireview.

Early diagnosis and ultrahigh sample throughput screening are the need of the hour to control the geological spread of the COVID-19 pandemic. Traditional laboratory tests such as enzyme-linked immunosorbent assay (ELISA), reverse transcription polymerase chain reaction (RT-PCR) and computed tomography are implemented for the detection of COVID-19. However, they are limited by the laborious sample collection and processing procedures, longer wait time for test results and skilled technicians to operate sophisticated facilities. In this context, the point of care (PoC) diagnostic platform has proven to be the prospective approach in addressing the abovementioned challenges. This review emphasizes the mechanism of viral infection spread detailing the host-virus interaction, pathophysiology, and the recent advances in the development of affordable PoC diagnostic platforms for rapid and accurate diagnosis of COVID-19. First, the well-established optical and electrochemical biosensors are discussed. Subsequently, the recent advances in the development of PoC biosensors, including lateral flow immunoassays and other emerging techniques, are highlighted. Finally, a focus on integrating nanotechnology with wearables and smartphones to develop smart nanobiosensors is outlined, which could promote COVID-19 diagnosis accessible to both individuals and the mass population at patient care.

Optical Biosensors for Virus Detection: Prospects for SARS-CoV-2/COVID-19.

The recent pandemic of the novel coronavirus disease 2019 (COVID-19) has caused huge worldwide disruption due to the lack of available testing locations and equipment. The use of optical techniques for viral detection has flourished in the past 15 years, providing more reliable, inexpensive, and accurate detection methods. In the current minireview, optical phenomena including fluorescence, surface plasmons, surface-enhanced Raman scattering (SERS), and colorimetry are discussed in the context of detecting virus pathogens. The sensitivity of a viral detection method can be dramatically improved by using materials that exhibit surface plasmons or SERS, but often this requires advanced instrumentation for detection. Although fluorescence and colorimetry lack high sensitivity, they show promise as point-of-care diagnostics because of their relatively less complicated instrumentation, ease of use, lower costs, and the fact that they do not require nucleic acid amplification. The advantages and disadvantages of each optical detection method are presented, and prospects for applying optical biosensors in COVID-19 detection are discussed.

How Nanophotonic Label-Free Biosensors Can Contribute to Rapid and Massive Diagnostics of Respiratory Virus Infections: COVID-19 Case.

The global sanitary crisis caused by the emergence of the respiratory virus SARS-CoV-2 and the COVID-19 outbreak has revealed the urgent need for rapid, accurate, and affordable diagnostic tests to broadly and massively monitor the population in order to properly manage and control the spread of the pandemic. Current diagnostic techniques essentially rely on polymerase chain reaction (PCR) tests, which provide the required sensitivity and specificity. However, its relatively long time-to-result, including sample transport to a specialized laboratory, delays massive detection. Rapid lateral flow tests (both antigen and serological tests) are a remarkable alternative for rapid point-of-care diagnostics, but they exhibit critical limitations as they do not always achieve the required sensitivity for reliable diagnostics and surveillance. Next-generation diagnostic tools capable of overcoming all the above limitations are in demand, and optical biosensors are an excellent option to surpass such critical issues. Label-free nanophotonic biosensors offer high sensitivity and operational robustness with an enormous potential for integration in compact autonomous devices to be delivered out-of-the-lab at the point-of-care (POC). Taking the current COVID-19 pandemic as a critical case scenario, we provide an overview of the diagnostic techniques for respiratory viruses and analyze how nanophotonic biosensors can contribute to improving such diagnostics. We review the ongoing published work using this biosensor technology for intact virus detection, nucleic acid detection or serological tests, and the key factors for bringing nanophotonic POC biosensors to accurate and effective COVID-19 diagnosis on the short term.