Optical Biosensors for the Diagnosis of COVID-19 and Other Viruses-A Review.

The sudden outbreak of the COVID-19 pandemic led to a huge concern globally because of the astounding increase in mortality rates worldwide. The medical imaging computed tomography technique, whole-genome sequencing, and electron microscopy are the methods generally used for the screening and identification of the SARS-CoV-2 virus. The main aim of this review is to emphasize the capabilities of various optical techniques to facilitate not only the timely and effective diagnosis of the virus but also to apply its potential toward therapy in the field of virology. This review paper categorizes the potential optical biosensors into the three main categories, spectroscopic-, nanomaterial-, and interferometry-based approaches, used for detecting various types of viruses, including SARS-CoV-2. Various classifications of spectroscopic techniques such as Raman spectroscopy, near-infrared spectroscopy, and fluorescence spectroscopy are discussed in the first part. The second aspect highlights advances related to nanomaterial-based optical biosensors, while the third part describes various optical interferometric biosensors used for the detection of viruses. The tremendous progress made by lab-on-a-chip technology in conjunction with smartphones for improving the point-of-care and portability features of the optical biosensors is also discussed. Finally, the review discusses the emergence of artificial intelligence and its applications in the field of bio-photonics and medical imaging for the diagnosis of COVID-19. The review concludes by providing insights into the future perspectives of optical techniques in the effective diagnosis of viruses.

Dual-wavelength absorption technique for dryness measurement of wet steam.

This paper presents a dual-wavelength absorption-based approach for measuring and validating the steam dryness fraction of wet steam. A thermally insulated steam cell with a temperature-controlled measurement window (up to 200°C) is designed and fabricated to minimize condensation during water vapor measurements at different operating pressures (1-10 bars). Water vapor's measurement sensitivity and accuracy are limited due to other absorbing and non-absorbing species in wet steam. The measurement accuracy is significantly improved with the proposed dual-wavelength absorption technique (DWAT) measurement method. The influence of modifying factors-namely, pressure and temperature-on water vapor absorbance is minimized by a non-dimensional correction factor. The dryness is measured with the help of the water vapor concentration and wet steam mass present in the steam cell. The DWAT dryness measurement approach is validated using a four-stage separating and throttling calorimeter combined with a condensation rig. The accuracy of the dryness measurement system using this optical method is determined to be ±1% for the range of dryness and operating pressure (1-10 bars) of wet steam.

Laser-Induced Breakdown Spectroscopy Combined with Temporal Plasma Analysis of C2 Molecular Emission for Carbon Analysis in Coal.

A benchtop laser-induced breakdown spectroscopy is demonstrated to determine the elemental carbon content present in raw coal used for combustion in power plants. The spectral intensities of molecular CN and C2 emission are measured together with the atomic carbon (C) and other inorganic elements (Si, Fe, Mg, Al, Ca, Na, and K) in the laser-induced breakdown spectroscopy spectrum of coal. The emission persistence time of C2 molecule emission is measured from the coal plasma generated by a nanosecond laser ablation with a wavelength of 266 nm in the Ar atmosphere. The emission persistence time of molecular C2 emission along with the spectral intensities of major ash elements (Fe, Si, Al, and Ca) and carbon emissions (atomic C, molecular CN, and C2) shows a better relationship with the carbon wt% of different coal samples. The calibration model to measure elemental carbon (wt%) is developed by combining the spectral characteristics (spectral intensity) and the temporal characteristics (emission persistence time of C2 molecule emission). The temporal characteristic studies combined with the spectroscopic data in the partial least square regression model have resulted in an improvement in the root mean square error of validation, and the relative standard deviation is reduced from 10.8% to 4.1% and from 11.3% to 6.0%, respectively.

Advances in Mid-Infrared Spectroscopy-Based Sensing Techniques for Exhaled Breath Diagnostics.

Human exhaled breath consists of more than 3000 volatile organic compounds, many of which are relevant biomarkers for various diseases. Although gas chromatography has been the gold standard for volatile organic compound (VOC) detection in exhaled breath, recent developments in mid-infrared (MIR) laser spectroscopy have led to the promise of compact point-of-care (POC) optical instruments enabling even single breath diagnostics. In this review, we discuss the evolution of MIR sensing technologies with a special focus on photoacoustic spectroscopy, and its application in exhaled breath biomarker detection. While mid-infrared point-of-care instrumentation promises high sensitivity and inherent molecular selectivity, the lack of standardization of the various techniques has to be overcome for translating these techniques into more widespread real-time clinical use.

Off-Resonance Photoacoustic Spectroscopy Technique for Multi-Gas Sensing in Biogas Plants.

An off-resonance broadband photoacoustic spectroscopy (PAS) technique with a supercontinuum laser (SCL) in the near-infrared range is demonstrated for biogas measurements with different biomass matrices. The PAS sensor system has been calibrated with known concentrations of methane (CH4), carbon dioxide (CO2), water vapor (H2O vapor), and hydrogen sulfide (H2S). A laboratory-scale bioreactor was set up to monitor CH4 and CO2 generation using the SCL-PA sensor system. The obtained results show the suitability of the PAS sensor to be employed in a fully operational large scale biogas plant for online monitoring. The periodic variations in concentration for CH4, CO2, and H2O vapor were monitored in a large scale cattle dung based biogas plant in real-time, and the operating ranges were measured to be around 50-65%, 34-48%, and 0-1%, respectively. The SCL-PA sensor was also employed at two different Sewage Treatment Plants in Chennai, Tamilnadu, India, where along with CH4 (60-63%), CO2 (34-38%), and H2O vapor (0.8-1%), trace concentration levels of H2S were found to be around 0.04-1%.

Off-resonant photoacoustic spectroscopy for analysis of multicomponent gas mixtures at high concentrations using broadband vibrational overtones of individual gas species.

The broadband photoacoustic spectroscopy (PAS) technique is proposed and demonstrated for measurement of CH4, CO2, and H2O vapor in the 1.6 to 2.0 µm wavelength region. The wide spectrum of a supercontinuum light source is used to cover broadband absorption bands of multiple gas species. This sensor works in the off-resonant frequency of the designed photoacoustic cell and exhibits a wide concentration measurement range of parts per billion by volume (ppb-v) to 100%. The PAS sensor is further tested in real time by measuring the concentration of CO2, CH4, and H2O vapor in biogas plants.

KTN-based high-speed axial and lateral scanning technique for an optical coherence tomography system and application to dental imaging.

A high-speed 840 nm based polarization-sensitive time domain optical coherence tomography (PSOCT) technique is proposed and demonstrated based on the quadratic electro-optic property of potassium tantalate niobate (KTN) crystals. A longitudinal (axial) scanning depth of ≈10 µm is obtained for an applied AC voltage of 600 V, at 1000 Hz and temperature maintained around 40°C. The OCT system with the KTN-based electro-optic delay line combined with a linear actuation is extended to image an early dental demineralization. For enhanced contrast by the elimination of the strong surface reflection from the sample and high-speed imaging, the quadratic electro-optically tunable PSOCT technique is proposed and demonstrated. Further, a lateral scanning range of 490 µm is also demonstrated by controlling the KTN temperature at 35°C for an applied voltage of 600 V on the tooth sample. This KTN-based quadratic electro-optic delay line combined with lateral scan approach provides an automated high-speed two-dimensional scanning of samples of interest.

Glucose sensing in oral mucosa simulating phantom using differential absorption based frequency domain low-coherence interferometry.

The superluminescent diode based differential absorption frequency domain low-coherence interferometry (FD-DALCI) technique is proposed and demonstrated for sensing physiological concentrations of glucose (0-250 mg/dl) in oral mucosa simulating phantoms (intralipid of concentrations 0.25-0.50%) with wavelengths at 1589 and 1310 nm. The proposed technique allows simultaneous measurements of refractive index based spectral shift and estimation of physiological concentration of glucose in intralipid with scattering characteristics using the differential absorption approach. The sensitivity of the glucose concentration obtained by spectral shift measurement was ≈0.016 nm/(mg/dl), irrespective of the intralipid concentration. The resolution of the glucose level was estimated to be ≈15 mg/dl in 0.25% intralipid and ≈19 mg/dl in 0.5% intralipid using the FD-DALCI technique.

Development of an electro-optically tuned optical coherence tomography system for imaging dental lesions.

A conventional optical coherence tomography (OCT) system was set up in-house to image early dental caries, identify gap formation in the bonding interface for restoration and secondary caries. Two-dimensional images of tooth samples was obtained and dental defect were identified. A novel electro-optic tuning system is proposed in order to improve scanning speed and to perform noiseless imaging. Preliminary studies were conducted with two crystals namely, LiNbO3 (Lithium Niobate) and KTP (Potassium Titanyl Phosphate) using a SLED source for OCT system and the simulated and experimental results were found to be qualitatively similar. The tuning range for LiNbO3 and KTP was found to be in the order of few micrometers whereas KTN (Potassium Tantalate Niobate) using the quadratic electro-optic effect is expected to show scanning range of tens of micrometers. KTN based hybrid scanning for dental caries imaging is also planned.

Development of UV-ionization based trace differential mobility sensor for acetone and hexane.

Clinical studies in recent times confirm feasibility of using trace concentrations of volatile organic compounds (VOC) in human exhale air as potential bio-markers for a variety of disease states. A Differential Mobility Sensor (DMS) with dual ultra-violet (UV) photo-ionization source is proposed and demonstrated for measurement of trace amounts of VOC gases in human exhale air. Experimental work performed with the DMS using high frequency asymmetrical waveform field for detection of trace concentrations of acetone and hexane with a few carrier gases including air, CO2 and O2 is discussed. The detection limit as estimated for Signal to Noise Ratio (SNR) of 3 is of the order of sub ppm levels for acetone and hexane. Experimental studies clearly demonstrate selective sensing of a gas in a mixture of gases by applying appropriate compensation field. Preliminary study on sensing of acetone in human breath shows good a correlation with blood glucose measurements.

Gas sensors based on superluminescent diodes for combustion monitoring.

Application of fiber-coupled superluminescent diodes with a wideband optical source for the detection of various gases is reported. Superluminescent diodes with two different wavelengths around 760 and 1530 nm are used for O(2) and NH(3) gas sensing, respectively. The technique allows multiple-gas sensing for combustion monitoring.

Tuning of a Ti3+:sapphire laser by an electro-optic beam deflection method.

A wavelength-switching method for tuning a self-injection-seeded Ti3+:sapphire laser that uses an electro-optic beam deflection technique is reported. A LiNbO3 prism was employed in a tuning arm of the dual-cavity Ti3+:sapphire laser, and wavelength tuning of approximately 94 pm was attained by altering the deflection angle with the application of an electric field of 10 kV/cm to the prism. The spectral characteristics of the output laser were mainly determined by the diffraction grating in the dual-cavity laser, and the electro-optic prism just behaved as a light-beam deflector for the wavelength tuning purpose. This configuration can allow a simple tuning approach where fast and stable electronic wavelength switching is required in a narrow tuning range, on an order between a few tens of picometers to nanometers, without involving any mechanical movement.

Feasibility of nonlinear Raman lidar based on stimulated Raman gain spectroscopy without a tunable laser.

A novel technique of lidar for atmospheric gas detection by use of stimulated Raman gain spectroscopy without any tunable laser is proposed. Detection sensitivity and detectable range are estimated on the basis of the lidar equation for CO2, CH4, and H2 in the atmosphere. The feasibility study clearly shows that the technique has a potential for application to lidar and that, in addition, the construction of the system is simpler than those of traditional differential absorption lidars.

Multiwavelength distributed-feedback dye laser array and its application to spectroscopy.

A multiwavelength, multistripe tunable laser array is proposed, and its application to absorption spectroscopy is demonstrated. Laser waveguides doped with Rhodamine 6 G dye were integrated on a plastic chip, and simultaneous output at different wavelengths was obtained by use of a distributed-feedback technique. A very low threshold of 3 muJ was attained, and spectrally narrowed output (<0.1 nm) was obtained. A scheme for digital spectroscopy is also proposed based on this laser array, and absorption spectroscopy of sodium atoms without wavelength scanning is demonstrated by use of a sodium-vapor cell.