Random Lasing for Bimodal Imaging and Detection of Tumor.

The interaction of light with biological tissues is an intriguing area of research that has led to the development of numerous techniques and technologies. The randomness inherent in biological tissues can trap light through multiple scattering events and provide optical feedback to generate random lasing emission. The emerging random lasing signals carry sensitive information about the scattering dynamics of the medium, which can help in identifying abnormalities in tissues, while simultaneously functioning as an illumination source for imaging. The early detection and imaging of tumor regions are crucial for the successful treatment of cancer, which is one of the major causes of mortality worldwide. In this paper, a bimodal spectroscopic and imaging system, capable of identifying and imaging tumor polyps as small as 1 mm2, is proposed and illustrated using a phantom sample for the early diagnosis of tumor growth. The far-field imaging capabilities of the developed system can enable non-contact in vivo inspections. The integration of random lasing principles with sensing and imaging modalities has the potential to provide an efficient, minimally invasive, and cost-effective means of early detection and treatment of various diseases, including cancer.

Lasing from Micro- and Nano-Scale Photonic Disordered Structures for Biomedical Applications.

A disordered photonic medium is one in which scatterers are distributed randomly. Light entering such media experiences multiple scattering events, resulting in a "random walk"-like propagation. Micro- and nano-scale structured disordered photonic media offer platforms for enhanced light-matter interaction, and in the presence of an appropriate gain medium, coherence-tunable, quasi-monochromatic lasing emission known as random lasing can be obtained. This paper discusses the fundamental physics of light propagation in micro- and nano-scale disordered structures leading to the random lasing phenomenon and related aspects. It then provides a state-of-the-art review of this topic, with special attention to recent advancements of such random lasers and their potential biomedical imaging and biosensing applications.

Raman spectroscopy for viral diagnostics.

Raman spectroscopy offers the potential for fingerprinting biological molecules at ultra-low concentration and therefore has potential for the detection of viruses. Here we review various Raman techniques employed for the investigation of viruses. Different Raman techniques are discussed including conventional Raman spectroscopy, surface-enhanced Raman spectroscopy, Raman tweezer, tip-enhanced Raman Spectroscopy, and coherent anti-Stokes Raman scattering. Surface-enhanced Raman scattering can play an essential role in viral detection by multiplexing nanotechnology, microfluidics, and machine learning for ensuring spectral reproducibility and efficient workflow in sample processing and detection. The application of these techniques to diagnose the SARS-CoV-2 virus is also reviewed. Supplementary Information: The online version contains supplementary material available at 10.1007/s12551-023-01059-4.

Plasmonic random laser enabled artefact-free wide-field fluorescence bioimaging: uncovering finer cellular features.

Narrow bandwidth, high brightness, and spectral tunability are the unique properties of lasers that make them extremely desirable for fluorescence imaging applications. However, due to the high spatial coherence, conventional lasers are often incompatible for wide-field fluorescence imaging. The presence of parasitic artefacts under coherent illumination causes uneven excitation of fluorophores, which has a critical impact on the reliability, resolution, and efficiency of fluorescence imaging. Here, we demonstrate artefact-free wide-field fluorescence imaging with a bright and low threshold silver nanorod based plasmonic random laser, offering the capability to image finer cellular features with sub-micrometer resolution even in highly diffusive biological samples. A spatial resolution of 454 nm and up to 23% enhancement in the image contrast in comparison to conventional laser illumination are attained. Based on the results presented in this paper, random lasers, with their laser-like properties and spatial incoherence are envisioned to be the next-generation sources for developing highly efficient wide-field fluorescence imaging systems having high spatial and temporal resolution for real-time, in vivo bioimaging.

Surface roughness mapping of large area curved aerospace components through spectral correlation of speckle images.

Measurement of surface roughness over a large area is a very challenging task due to the limitations with the existing techniques. Surface roughness measurement techniques including stylus and microscopy are limited by point-by-point data acquisition and a small field of view (FOV). In effect, any solution that would subdue these limitations would be characterized by its full-field nature, large FOV, and the ability to acquire and process data at high speeds. To meet these requirements, large area speckle imaging has been used to obtain areal surface roughness parameters through the processing of spectrally correlated speckle images. An automated optical system is developed for surface roughness evaluation of components with large and curved surface areas. In order to extract areal surface roughness parameters from the captured set of images, processing algorithms are developed. The methodology is first validated using a comparator plate containing areas having an average surface roughness (Ra) ranging between 0.2 µm and 0.6 µm. Further, statistical significance tests are conducted to determine the main factors affecting system performance. The measurement results are compared and validated using a 3D optical microscope. The results obtained from the blind tests performed on aerospace component surfaces as large as 450mm×210mm are also presented.

(Cu2O-Au) - Graphene - Au layered structures as efficient near Infra - Red SERS substrates.

Near Infra-Red Surface Enhanced Raman Spectroscopy (NIR SERS) has gained huge attention in recent years as the conventional visible SERS suffers from overwhelming fluorescence background from the fluorophore resulting in the masking of Raman signals. In this paper, we propose a novel multi-layered SERS substrate- (Cu2O - Au) - Graphene - Au - for efficient NIR SERS applications. The proposed structure has a monolayer of Cu2O - Au core-shell particles on a Au substrate with 1 nm thick graphene spacer layer. Mie simulations are used to optimize the aspect ratios of core-shell particles to shift their plasmon resonances to NIR region using MieLab software. Further, Finite Difference Time Domain (FDTD) simulations using Lumerical software are used for the design of the multiparticle layered SERS substrate as MieLab software works only for single particle systems. Designed structure is shown to provide high field enhancement factor of the order of 108 at an excitation of 1064 nm thus ensuring the possibility of using the proposed structure as efficient NIR SERS substrate which could probably be used for various NIR sensing applications.

Au nano-urchins enabled localized surface plasmon resonance sensing of beta amyloid fibrillation.

Early stage detection of neurodegenerative diseases such as Alzheimer's disease (AD) is of utmost importance, as it has become one of the leading causes of death of millions of people. The gradual intellectual decline in AD patients is an outcome of fibrillation of amyloid beta 1-42 (Aß1-42) peptides in the brain. In this paper, we present localized surface plasmon resonance (LSPR) based sensing of Aß1-42 fibrillation using Au nano-urchins. Strongly localized field confinement at the spiky nanostructures of nano-urchin surfaces enables them to detect very low concentrations of Aß1-42. In addition, the LSPR peak of Au nano-urchins, which is very sensitive to ambient conditions, shows significant responses at different fibrillation stages of Aß1-42. Reduction in LSPR peak intensity with an increase in the fibrillation is chosen as the sensing parameter here. This paper in this context provides LSPR based highly sensitive, label-free and real-time sensing of Aß1-42 fibrillation that is highly advantageous compared to the existing techniques which require binding additives or fluorescent biomarkers.

Spectral phase-based automatic calibration scheme for swept source-based optical coherence tomography systems.

The automatic calibration in Fourier-domain optical coherence tomography (FD-OCT) systems allows for high resolution imaging with precise depth ranging functionality in many complex imaging scenarios, such as microsurgery. However, the accuracy and speed of the existing automatic schemes are limited due to the functional approximations and iterative operations used in their procedures. In this paper, we present a new real-time automatic calibration scheme for swept source-based optical coherence tomography (SS-OCT) systems. The proposed automatic calibration can be performed during scanning operation and does not require an auxiliary interferometer for calibration signal generation and an additional channel for its acquisition. The proposed method makes use of the spectral component corresponding to the sample surface reflection as the calibration signal. The spectral phase function representing the non-linear sweeping characteristic of the frequency-swept laser source is determined from the calibration signal. The phase linearization with improved accuracy is achieved by normalization and rescaling of the obtained phase function. The fractional-time indices corresponding to the equidistantly spaced phase intervals are estimated directly from the resampling function and are used to resample the OCT signals. The proposed approach allows for precise calibration irrespective of the path length variation induced by the non-planar topography of the sample or galvo scanning. The conceived idea was illustrated using an in-house-developed SS-OCT system by considering the specular reflection from a mirror and other test samples. It was shown that the proposed method provides high-performance calibration in terms of axial resolution and sensitivity without increasing computational and hardware complexity.

A simple and non-contact optical imaging probe for evaluation of corneal diseases.

Non-contact imaging techniques are preferred in ophthalmology. Corneal disease is one of the leading causes of blindness worldwide, and a possible way of detection is by analyzing the shape and optical quality of the cornea. Here, a simple and cost-effective, non-contact optical probe system is proposed and illustrated. The probe possesses high spatial resolutions and is non-dependent on coupling medium, which are significant for a clinician and patient friendly investigation. These parameters are crucial, when considering an imaging system for the objective diagnosis and management of corneal diseases. The imaging of the cornea is performed on ex vivo porcine samples and subsequently on small laboratory animals, in vivo. The clinical significance of the proposed study is validated by performing imaging of the New Zealand white rabbit's cornea infected with Pseudomonas.

Narrow band wavelength selective filter using grating assisted single ring resonator.

This paper illustrates a filter configuration which uses a single ring resonator of larger radius connected to a grating resonator at its drop port to achieve single wavelength selectivity and switching property with spectral features suitable for on-chip wavelength selection applications. The proposed configuration is expected to find applications in silicon photonics devices such as, on-chip external cavity lasers and multi analytic label-free biosensors. The grating resonator has been designed for a high Q-factor, high transmittivity, and minimum loss so that the wavelength selectivity of the device is improved. The proof-of-concept device has been demonstrated on a Silicon-on-Insulator (SOI) platform through electron beam lithography and Reactive Ion Etching (RIE) process. The transmission spectrum shows narrow band single wavelength selection and switching property with a high Free Spectral Range (FSR) ~60 nm and side band rejection ratio >15 dB.

Note: A gel based imaging technique of the iridocorneal angle for evaluation of angle-closure glaucoma.

Noninvasive medical imaging techniques have high potential in the field of ocular imaging research. Angle closure glaucoma is a major disease causing blindness and a possible way of detection is the examination of the anterior chamber angle in eyes. Here, a simple optical method for the evaluation of angle-closure glaucoma is proposed and illustrated. The light propagation from the region associated with the iridocorneal angle to the exterior of eye is considered analytically. The design of the gel assisted probe prototype is carried out and the imaging of iridocorneal angle is performed on an eye model.

Design, fabrication, and characterization of thermoplastic microlenses for fiber-optic probe imaging.

Microlens-ended fibers could find great usefulness in future biomedical applications, particularly in endoscopic imaging applications. In this context, this paper focuses on microlens-attached specialty optical fibers such as imaging fiber that can be used for probe imaging applications. Stand-alone self-aligned polymer microlenses have been fabricated by microcompression molding. The fabrication parameters have been optimized for different materials, such as poly(methyl methacrylate) (PMMA), polycarbonate (PC Lexan 123R), Zeonor 1060R (ZNR), and Topas COC. A comparison study of the focusing and spatial resolution of the fabricated lenses is performed prior to employing them for fiber-optic fluorescence imaging applications.

Sub-60 nm periodic grating feature patterning by immersion based 364 nm laser interference.

In this paper, we report a methodology to fabricate high resolution periodic grating features using high index prism based interferometer and i-line laser source. Features with sub-60 nm half pitch size were fabricated on i-line resist in an immersion medium using a prism of high index 1.939.

Hollow-core photonic crystal fiber based multifunctional optical system for trapping, position sensing, and detection of fluorescent particles.

We demonstrate a novel multifunctional optical system that is capable of trapping, imaging, position sensing, and fluorescence detection of micrometer-sized fluorescent test particles using hollow-core photonic crystal fiber (HC-PCF). This multifunctional optical system for trapping, position sensing, and fluorescent detection is designed such that a near-IR laser light is used to create an optical trap across a liquid-filled HC-PCF, and a 473 nm laser is employed as a source for fluorescence excitation. This proposed system and the obtained results are expected to significantly enable an efficient integrated trapping platform employing HC-PCF for diagnostic biomedical applications.

Characteristics of stand-alone microlenses in fiber-based fluorescence imaging applications.

Microlens-ended fibers, which have found tremendous interest in the recent past, find potential biomedical applications, in particular, in endoscopic imaging. The work presented in this paper focuses on the stand-alone microlenses along with custom-fabricated specialty optical fiber, such as imaging fiber, for probe imaging applications. Stand-alone self-aligned microlenses have been fabricated employing microcompression molding and then attached at the end facet of imaging fiber. A detailed characterization of the fabricated microlens is carried and it demonstrates appropriate focusing ability, high fluorescence collection efficiency and imaging ability for biomedical applications. The surface roughness of the microlens is found to be 25 nm with a minimum spot size of 38 µm. The probe imaging system is found to be able to image the fluorescence microspheres of 10 µm size. The collection efficiency of the fiber probe with lens found to be enhanced by three times approximately.

Large-area maskless surface plasmon interference for one- and two-dimensional periodic nanoscale feature patterning.

A promising maskless surface-plasmon-interference nanoscale lithographic technique is proposed and demonstrated experimentally in this paper. One-dimensional (grating-type) and two-dimensional (pillar-type) nanocale features were patterned on the photoresist layer using a 364 nm illumination wavelength source with a single exposure, by employing a custom-made prism layer configuration. Large-area patterns of grating lines and pillars with feature size approximately 90 nm were realized experimentally using this configuration.

Broadband tunable bandpass filters using phase shifted vertical side wall grating in a submicrometer silicon-on-insulator waveguide.

We propose the silicon-on-insulator (SOI) based, phase shifted vertical side wall grating as a resonant transmission filter suitable for dense wavelength division multiplexing (DWDM) communication channels with 100 GHz channel spacing. The gratings are designed and numerically simulated to obtain a minimum loss in the resonant cavity by adjusting the grating parameters so that a high transmittivity can be achieved for the resonant transmission. The resonant grating, which is designed to operate in the DWDM International Telecommunication Union (ITU) grid C band of optical communication, has a high free spectral range of 51.7 nm and a narrow band resonant transmission. The wavelength selectivity of the filter is improved through a coupled cavity configuration by applying two phase shifts to the gratings. The observed channel band width and channel isolation of the resonant transmission filter are good and in agreement with the ITU specifications.

Compact SOI nanowire refractive index sensor using phase shifted Bragg grating.

The phase shifted vertical side wall gratings are designed and numerically simulated on a submicron SOI waveguide to obtain the performance characteristics needed for an integrated refractive index sensor. The gratings are designed to obtain narrow band width, high transmittivity and sharp line shape in the resonant transmission so that the sensor sensitivity can be improved. The proposed sensor is easy to fabricate and will provide a linear response over a wide wavelength range with a compact structure dimension which is suitable for label free biosensing applications. The detection limit of the sensor is investigated through both wavelength shift and intensity measurement method and the performance parameter is compared with other silicon based structures like Mach-Zehnder interferometer, ring resonator and surface corrugated Bragg grating.

C-band external-cavity wavelength-tunable laser based on a liquid-crystal deflector.

A novel C-band external-cavity wavelength-tunable laser is proposed. The laser consists of a semiconductor gain chip, a collimating lens, a fixed etalon, a liquid-crystal deflector and a diffraction grating in a Littrow configuration. The lasing wavelength of this tunable external-cavity laser can be tuned to 19 wavelength channels of 100 GHz spacing. All channels are within 2.5 GHz of the ITU grids with a side-mode suppression ratio of approximately 35 dB over the whole range.

All fiber based multispeckle modality endoscopic system for imaging medical cavities.

Disease detection in body cavities, such as the detection of abnormal growths in the colon path, has been illustrated here using an image fiber guided catheter based multispeckle modality endoscopic system. An all fiber-optic approach for the illumination and imaging of the inner cavity walls is adopted here. An endoscope probe to carry the illumination fibers as well as the imaging lens-image fiber unit is designed and custom fabricated in order to operate the probe in its various direction sensitive configurations. This is facilitated by the selection of suitable optical elements such as beam combiner and biprism at the probe proximal end. Experimental investigations were carried out using the endoscope system employing phantom model of colon as the test specimen that has normal and abnormal (representing growth) regions and the obtained results indicated the system effectiveness in identifying the abnormal growths at an early stage.