Photonics enabled intelligence system to identify SARS-CoV 2 mutations.

The COVID-19, MERS-CoV, and SARS-CoV are hazardous epidemics that have resulted in many deaths which caused a worldwide debate. Despite control efforts, SARS-CoV-2 continues to spread, and the fast spread of this highly infectious illness has posed a grave threat to global health. The effect of the SARS-CoV-2 mutation, on the other hand, has been characterized by worrying variations that modify viral characteristics in response to the changing resistance profile of the human population. The repeated transmission of virus mutation indicates that epidemics are likely to occur. Therefore, an early identification system of ongoing mutations of SARS-CoV-2 will provide essential insights for planning and avoiding future outbreaks. This article discussed the following highlights: First, comparing the omicron mutation with other variants; second, analysis and evaluation of the spread rate of the SARS-CoV 2 variations in the countries; third, identification of mutation areas in spike protein; and fourth, it discussed the photonics approaches enabled with artificial intelligence. Therefore, our goal is to identify the SARS-CoV 2 virus directly without the need for sample preparation or molecular amplification procedures. Furthermore, by connecting through the optical network, the COVID-19 test becomes a component of the Internet of healthcare things to improve precision, service efficiency, and flexibility and provide greater availability for the evaluation of the general population. KEY POINTS: • A proposed framework of photonics based on AI for identifying and sorting SARS-CoV 2 mutations. • Comparative scatter rates Omicron variant and other SARS-CoV 2 variations per country. • Evaluating mutation areas in spike protein and AI enabled by photonic technologies for SARS-CoV 2 virus detection.

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.

Label-Free Digital Detection of Intact Virions by Enhanced Scattering Microscopy.

Several applications in health diagnostics, food, safety, and environmental monitoring require rapid, simple, selective, and quantitatively accurate viral load monitoring. Here, we introduce the first label-free biosensing method that rapidly detects and quantifies intact virus in human saliva with single-virion resolution. Using pseudotype SARS-CoV-2 as a representative target, we immobilize aptamers with the ability to differentiate active from inactive virions on a photonic crystal, where the virions are captured through affinity with the spike protein displayed on the outer surface. Once captured, the intrinsic scattering of the virions is amplified and detected through interferometric imaging. Our approach analyzes the motion trajectory of each captured virion, enabling highly selective recognition against nontarget virions, while providing a limit of detection of 1 × 103 copies/mL at room temperature. The approach offers an alternative to enzymatic amplification assays for point-of-collection diagnostics.

Engineering Polysaccharide-Based Hydrogel Photonic Constructs: From Multiscale Detection to the Biofabrication of Living Optical Fibers.

Solid-state optics has been the pillar of modern digital age. Integrating soft hydrogel materials with micro/nanooptics could expand the horizons of photonics for bioengineering. Here, wet-spun multilayer hydrogel fibers are engineered through ionic-crosslinked natural polysaccharides that serve as multifunctional platforms. The resulting flexible hydrogel structure and reversible crosslinking provide tunable design properties such as adjustable refractive index and fusion splicing. Modulation of the optical readout via physical stimuli, including shape, compression, and multiple optical inputs/outputs is demonstrated. The unique permeability of the hydrogels is also combined with plasmonic nanoparticles for molecular detection of SARS-CoV-2 in fiber-coupled biomedical swabs. A tricoaxial 3D printing nozzle is then employed for the continuous fabrication of living optical fibers. Light interaction with living cells enables the quantification and digitalization of complex biological phenomena such as 3D cancer progression and drug susceptibility. These fibers pave the way for advances in biomaterial-based photonics and biosensing platforms.

Monitoring Serum Spike Protein with Disposable Photonic Biosensors Following SARS-CoV-2 Vaccination.

While mRNA vaccines have been well-studied in vitro and in animals prior to their use in the human population during the Covid-19 pandemic, their exact mechanisms of inducing immunity are still being elucidated. The large-scale collection of data necessary to fully understand these mechanisms, and their variability across heterogeneous populations, requires rapid diagnostic tests that accurately measure the various biomarkers involved in the immune response following vaccination. Recently, our lab developed a novel "Disposable Photonics" platform for rapid, label-free, scalable diagnostics that utilizes photonic ring resonator sensor chips combined with plastic micropillar cards able to provide passive microfluidic flow. Here, we demonstrate the utility of this system in confirming the presence of SARS-CoV-2 spike protein in the serum of recently vaccinated subjects, as well as tracking a post-vaccination rise in anti-SARS-CoV-2 antibodies. A maximum concentration in SARS-CoV-2 spike protein was detected one day after vaccination and was reduced below detectable levels within 10 days. This highlights the applicability of our rapid photonic sensor platform for acquiring the data necessary to understand vaccine mechanisms on a large scale, as well as individual patient responses to SARS-CoV-2 mRNA vaccines.

Label-free detection of virus-like particles employing rotationally symmetric nanowire array based whispering gallery and quasi-whispering gallery resonant modes onto a silicon platform.

In spite of tremendous advancements in modern diagnostics, there is a dire need for reliable, label-free detection of highly contagious pathogens like viruses. In view of the limitations of existing diagnostic techniques, the present theoretical study proposes a novel scheme of detecting virus-like particles employing whispering gallery and quasi-whispering gallery resonant modes of a composite optical system. Whereas whispering gallery mode (WGM) resonators are conventionally realized using micro-disk, -ring, -toroid or spherical structures, the present study utilizes a rotationally symmetric array of silicon nanowires which offers higher sensitivity compared to the conventional WGM resonator while detecting virus-like particles. Notwithstanding the relatively low quality factor of the system, the underlying multiple-scattering mediated photon entrapment, coupled with peripheral total-internal reflection, results in high fidelity of the system against low signal-to-noise ratio. Finite difference time domain based numerical analysis has been performed to correlate resonant modes of the array with spatial location of the virus. The correlation has been subsequently utilized for statistical analysis of simulated test cases. Assuming detection to be limited by resolution of the measurement system, results of the analysis suggest that for only about 5% of the simulate test cases the resonant wavelength shift lies within the minimum detection range of 0.001-0.01 nm. For a single virus of 160 nm diameter, more than 8 nm shift of the resonant mode and nearly 100% change of quality factor are attained with the proposed nanowire array based photonic structure.

Engineering Hydrogel-Based Biomedical Photonics: Design, Fabrication, and Applications.

Light guiding and manipulation in photonics have become ubiquitous in events ranging from everyday communications to complex robotics and nanomedicine. The speed and sensitivity of light-matter interactions offer unprecedented advantages in biomedical optics, data transmission, photomedicine, and detection of multi-scale phenomena. Recently, hydrogels have emerged as a promising candidate for interfacing photonics and bioengineering by combining their light-guiding properties with live tissue compatibility in optical, chemical, physiological, and mechanical dimensions. Herein, the latest progress over hydrogel photonics and its applications in guidance and manipulation of light is reviewed. Physics of guiding light through hydrogels and living tissues, and existing technical challenges in translating these tools into biomedical settings are discussed. A comprehensive and thorough overview of materials, fabrication protocols, and design architectures used in hydrogel photonics is provided. Finally, recent examples of applying structures such as hydrogel optical fibers, living photonic constructs, and their use as light-driven hydrogel robots, photomedicine tools, and organ-on-a-chip models are described. By providing a critical and selective evaluation of the field's status, this work sets a foundation for the next generation of hydrogel photonic research.

Disposable photonics for cost-effective clinical bioassays: application to COVID-19 antibody testing.

Decades of research have shown that biosensors using photonic circuits fabricated using CMOS processes can be highly sensitive, selective, and quantitative. Unfortunately, the cost of these sensors combined with the complexity of sample handling systems has limited the use of such sensors in clinical diagnostics. We present a new "disposable photonics" sensor platform in which rice-sized (1 × 4 mm) silicon nitride ring resonator sensor chips are paired with plastic micropillar fluidic cards for sample handling and optical detection. We demonstrate the utility of the platform in the context of detecting human antibodies to SARS-CoV-2, both in convalescent COVID-19 patients and for subjects undergoing vaccination. Given its ability to provide quantitative data on human samples in a simple, low-cost single-use format, we anticipate that this platform will find broad utility in clinical diagnostics for a broad range of assays.

Detection of SARS-CoV-2 DNA Targets Using Femtoliter Optofluidic Waveguides.

Chip-scale SARS-CoV-2 testing was demonstrated using silicon nitride (Si3N4) nanoslot fluidic waveguides to detect a tagged oligonucleotide with a coronavirus DNA sequence. The slot waveguides were fabricated using complementary metal-oxide-semiconductor (CMOS) fabrication processes, including multiscale lithography and selective reactive ion etching (RIE), forming femtoliter fluidic channels. Finite difference method (FDM) simulation was used to calculate the optical field distribution of the waveguide mode when the waveguide sensor was excited by transverse electric (TE) and transverse magnetic (TM) polarized light. For the TE polarization, a strong optical field was created in the slot region and its field intensity was 14× stronger than the evanescent sensing field from the TM polarization. The nanoscale confinement of the optical sensing field significantly enhanced the light-analyte interaction and improved the optical sensitivity. The sensitivity enhancement was experimentally demonstrated by measuring the polarization-dependent fluorescence emission from the tagged oligonucleotide. The photonic chips consisting of femtoliter Si3N4 waveguides provide a low-cost and high throughput platform for real-time virus identification, which is critical for point-of-care (PoC) diagnostic applications.

Ultrafast Surface Plasmon Resonance Imaging Sensor via the High-Precision Four-Parameter-Based Spectral Curve Readjusting Method.

A variety of surface plasmon resonance (SPR) sensing devices have been extensively used in biochemical detection for their characteristics of label-free, highly sensitive, and faster detecting. Among them, the spectrum-based SPR sensing devices have offered us great advantages in high-throughput sensing due to their large dynamic range and the possibility of detection resolution similar to that offered by angle interrogation. This paper demonstrates a spectrum-based SPR imaging sensing system with fast wavelength scanning capability achieved by an acousto-optic tunable filter (AOTF) and a low-cost and speckle-free halogen lamp implemented as the SPR excitation source. Especially, we developed a novel four-parameter-based spectral curve readjusting (4-PSCR) method for data processing, which offered us a faster and more accurate spectral data curve fitting process than the traditional polynomial fitting method. With the configuration, we have also conducted an SPR high-throughput detection of the novel coronavirus (COVID-19) spike protein, proving its application possibility in the screening of COVID-19 with high accuracy. We believe that the higher sensitivity and accuracy of the system have made it readily used in biochemical imaging and detecting applications.

Label-free optical antibody testing kit based on a self-assembled whispering-gallery-mode microsphere.

The appearance of antibodies in blood is a critical signal to suggest the infection. A rapid and accurate detection method for the antibody is significant to the disease diagnosis, especially for the epidemic. To this end, a highly sensitive whispering-gallery-mode (WGM) optical testing kit is designed and fabricated for detecting the specific immunoglobulin antibodies. The key component of the kit is a silica self-assembled microsphere decorated with the nucleocapsid proteins (N-proteins) of the SARS-CoV-2 virus. After the N-protein antibody immunoglobulin G (N-IgG) and immunoglobulin M (N-IgM) solutions being injected into the kit, the WGM red-shifts due to the antigen-antibody reaction. The wavelength displacement rates are proportional to the concentrations of these two antibodies from 1 to 100 µg/mL. A good specificity of the kit is demonstrated by the nonspecific human immunoglobulin G (H-IgG) and immunoglobulin M (H-IgM).

Light and corona: guided-wave readout for coronavirus spike protein-host-receptor binding.

We show that waveguide sensors can enable a quantitative characterization of coronavirus spike glycoprotein-host-receptor binding-the process whereby coronaviruses enter human cells, causing disease. We demonstrate that such sensors can help quantify and eventually understand kinetic and thermodynamic properties of viruses that control their affinity to targeted cells, which is known to significantly vary in the course of virus evolution, e.g., from SARS-CoV to SARS-CoV-2, making the development of virus-specific drugs and vaccine difficult. With the binding rate constants and thermodynamic parameters as suggested by the latest SARS-CoV-2 research, optical sensors of SARS-CoV-2 spike protein-receptor binding may be within sight.