Precise detection of trace level protein using MIP-MoS2 nanocomposite functionalized PCF based interferometer.

Fiber optic interferometry combined with recognizing elements has attracted intensive attention for the development of different biosensors due to its superior characteristic features. However, the immobilization of sensing elements alone is not capable of low-concentration detection due to weak interaction with the evanescent field of the sensing transducer. The utilization of different 2D materials with high absorption potential and specific surface area can enhance the intensity of the evanescent field and hence the sensitivity of the sensor. Here, a biosensor has been fabricated using an inline hetero fiber structure of photonic crystal fiber (PCF) and single-mode fiber (SMF) functionalized with a nanocomposite of molybodenum di-sulfide (MoS2) and molecular imprinting polymer (MIP) to detect trace levels of bovine serum albumin (BSA). The sensor showed a wide dynamic detection range with a high sensitivity of 2.34 × 107 pm/µg L-1. It shows working potential over a wide pH range with a subfemtomolar detection limit. The compact size, easy fabrication, stable structure, long detection range, and high sensitivity of this sensor would open a new path for the development of different biosensors for online and remote sensing applications.

TEX13B is essential for metabolic reprogramming during germ cell differentiation.

STUDY QUESTION: What is the functional significance of Tex13b in male germ cell development and differentiation? SUMMARY ANSWER: Tex13b regulates male germ cell differentiation by metabolic reprogramming during spermatogenesis. WHAT IS KNOWN ALREADY: Studies in mice and humans suggest that TEX13B is a transcription factor and is exclusively expressed in germ cells. STUDY DESIGN, SIZE, DURATION: We sequenced the coding regions of TEX13B in 628 infertile men and 427 ethnically matched fertile control men. Further, to identify the molecular function of Tex13b, we created a Tex13b knockout and conditional overexpression system in GC-1spg (hereafter, GC-1) cells. PARTICIPANTS/MATERIALS, SETTING, METHODS: Our recent exome sequencing study identified novel candidate genes for male infertility. TEX13B was found to be one of the potential candidates, hence we explored the role of TEX13B in male infertility within a large infertile case-control cohort. We performed functional analyses of Tex13b in a GC-1 cell line using CRISPR-Cas9. We differentially labelled the cell proteins by stable isotope labelling of amino acids in cell culture (SILAC) and performed mass spectrometry-based whole-cell proteomics to identify the differential protein regulation in knockout cells compared to wild-type cells. We found that Tex13b knockout leads to downregulation of the OXPHOS complexes and upregulation of glycolysis genes, which was further validated by western blotting. These results were further confirmed by respirometry analysis in Tex13b knockout cells. Further, we also performed a conditional overexpression of TEX13B in GC-1 cells and studied the expression of OXPHOS complex proteins by western blotting. MAIN RESULTS AND THE ROLE OF CHANCE: We identified a rare variant, rs775429506 (p.Gly237Glu), exclusively in two non-obstructive-azoospermia (NOA) men, that may genetically predispose these men for infertility. Further, we demonstrated that Tex13b functions in the transcription regulation of OXPHOS complexes. LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: We examined the function of Tex13b in GC-1 in vitro by knocking out and conditional overexpression, for understanding the function of Tex13b in germ cells. Unfortunately, this could not be replicated in either an animal model or in patient-derived tissue due to the non-availability of an animal model or patient's testis biopsies. WIDER IMPLICATIONS OF THE FINDINGS: This study identified that Tex13b plays an important role in male germ cell development and differentiation. The findings of this study would be useful for screening infertile males with spermatogenic failure and counselling them before the implementation of assisted reproduction technique(s). STUDY FUNDING/COMPETING INTEREST(S): Funding was provided by the Council of Scientific and Industrial Research (CSIR) under the network project (BSC0101 and MLP0113) and SERB, the Department of Science and Technology, Government of India (J C Bose Fellowship: JCB/2019/000027). The authors do not have any competing interest.

Ultra-wide range non-contact surface profilometry based on reconfigurable fiber interferometry.

Surface characterization is essential for a technical evaluation of device performance and to assess surface dynamics in fabrication units. In this regard, a number of surface profiling techniques have been developed that accurately map sample topography but have significantly limited detection range. Here, we demonstrate a cascaded non-contact fiber interferometer-based approach for real-time high-precision surface profiling with ultrawide detection range (nm to mm). This compact interferometers' system operates by wavelength interrogation that provides a scope to study several types of surfaces and has a tunable cavity configuration for varying the sensitivity and range of the detectable features' size. The proposed system enables nanoscale profiling over 10-1000 nm with resolution of 10 nm and microscale mapping over 1-1000 µm with resolution of 0.2 µm. The technique is utilized to map the features of nanostructured surfaces and estimate the surface roughness of standardized industrial samples.

Humanoid shaped optical fiber plasmon biosensor functionalized with graphene oxide/multi-walled carbon nanotubes for histamine detection.

Histamine is a biologically active molecule that serves as a reliable predictor of the quality of fish. In this work, authors have developed a novel humanoid-shaped tapered optical fiber (HTOF) biosensor based on the localized surface plasmon resonance (LSPR) phenomenon to detect varying histamine concentrations. In this experiment, a novel and distinctive tapering structure has been developed using a combiner manufacturing system and contemporary processing technologies. Graphene oxide (GO)/multi-walled carbon nanotubes (MWCNTs) are immobilized on the HTOF probe surface to increase the biocompatibility of biosensor. In this instance, GO/MWCNTs are deployed first, then gold nanoparticles (AuNPs). Consequently, the GO/MWCNTs help to give abundant space for the immobilization of nanoparticles (AuNPs in this case) as well as increase surface area for the attachment of biomolecules to the fiber surface. By immobilizing AuNPs on the surface of the probe, the evanescent field can stimulate the AuNPs and excite the LSPR phenomena for sensing the histamine. The surface of the sensing probe is functionalized with diamine oxidase enzyme in order to enhance the histamine sensor's particular selectivity. The proposed sensor is demonstrated experimentally to have a sensitivity of 5.5 nm/mM and a detection limit of 59.45 µM in the linear detection range of 0-1000 µM. In addition, the probe's reusability, reproducibility, stability, and selectivity are tested; the results of these indices show that the probe has a high application potential for detecting histamine levels in marine products.

Fast, selective, and sensitive detection of 2,4-dichlorophenol by an imprinted polymer functionalized core-offset U-shaped fiber sensor.

Pollution monitoring in waterways and oceans is often performed in a laboratory on samples previously taken from the environment. The integration of molecular imprinting polymer nanoparticles (MIP-NPs) with a novel, to the best of our knowledge, fiber optic interferometer allowed a fast and selective detection of water pollutant 2,4-Dichlorophenol (2,4-DCP). The proposed sensor with an increased surface-to-volume ratio of MIP-NPs provided an enhanced sensitivity of 17.1 nm/µM and a wide operating range of 0.1-100 µM. It showed a highly repeatable performance and potential to measure up to nM concentrations. This integrated technique is suitable for the development of compact, stable, precise, and sensitive biosensors for online monitoring and remote chemical sensing applications.

Numerical Investigation on High-Performance Cu-Based Surface Plasmon Resonance Sensor for Biosensing Application.

This numerical research presents a simple hybrid structure comprised of TiO2-Cu-BaTiO3 for a modified Kretschmann configuration that exhibits high sensitivity and high resolution for biosensing applications through an angular interrogation method. Recently, copper (Cu) emerged as an exceptional choice as a plasmonic metal for developing surface plasmon sensors (SPR) with high resolution as it yields finer, thinner SPR curves than Ag and Au. As copper is prone to oxidation, especially in ambient conditions, the proposed structure involves the utilization of barium titanate (BaTiO3) film as a protection layer that not only preserves Cu film from oxidizing but enhances the performance of the sensor to a great extent. Numerical results also show that the utilization of a thin adhesive layer of titanium dioxide (TiO2) between the prism base and Cu film not only induces strong interaction between them but also enhances the performance of the sensor. Such a configuration, upon suitable optimization of the thickness of each layer, is found to enhance sensitivity as high as 552°/RIU with a figure of merit (FOM) of 136.97 RIU-1. This suggested biosensor design with enhanced sensitivity is expected to enable long-term detection with greater accuracy and sensitivity even when using Cu as a plasmonic metal.

Numerical simulation on the performance analysis of a graphene-coated optical fiber plasmonic sensor at anti-crossing.

A graphene-based surface plasmon resonance sensor using D-shaped fiber in anti-crossing has been designed. Silver as a plasmon active metal is followed by graphene, which helps in preventing oxidation and shows better adsorption efficiency to biomolecules. A wavelength interrogation technique based on the finite element method has been used to evaluate performance parameters. Design parameters such as thickness of silver, residual cladding, and GeO2 dopant concentration have been optimized. The wavelength sensitivity is found to be 6800 nm/RIU and resolution of 8.05×10-5 RIU. We believe that usage of graphene on silver may open a new window for study of online biomolecular interaction.

Nano-displacement sensor based on photonic crystal fiber modal interferometer.

A stable nano-displacement sensor based on large mode area photonic crystal fiber (PCF) modal interferometer is presented. The compact setup requires simple splicing of a small piece of PCF with a single mode fiber (SMF). The excitation and recombination of modes is carried out in a single splice. The use of a reflecting target creates an extra cavity that discretizes the interference pattern of the mode interferometer, boosting the displacement resolution to nanometer level. The proposed modal interferometric based displacement sensor is highly stable and shows sensitivity of 32 pm/nm.

Fabry-Perot based strain insensitive photonic crystal fiber modal interferometer for inline sensing of refractive index and temperature.

We report a highly stable, compact, strain insensitive inline microcavity-based solid-core photonic crystal fiber (SCPCF) modal interferometer for the determination of the refractive index (RI) of an analyte and its temperature. The interferometer is fabricated by splicing one end of SCPCF with single-mode fiber (SMF) and the other end with hollow-core PCF. This is followed by cleaving the part of the solid glass portion possibly present after the microcavity. The formation of the cavities at the end faces of the SCPCF results in reduction of the period of the interference pattern that helps in achieving distinctiveness in the measurement. Three sensor heads have been fabricated, and each has a different length of the collapsed region formed by splicing SMF with SCPCF. The response of the sensors is found to be sensitive to the length of this collapsed region between SMF and SCPCF with a sensitivity of 53 nm/RI unit (RIU) and resolution of 1.8×10(-4) RIU. The temperature response of the sensor is found to be linear, having a temperature sensitivity of 12 pm/°C. In addition to these findings, the effect of strain on the proposed structure is analyzed in both wavelength and intensity interrogation.

Tamm-plasmon and surface-plasmon hybrid-mode based refractometry in photonic bandgap structures.

The transverse magnetic (TM) polarized hybrid modes formed as a consequence of coupling between Tamm plasmon polariton (TM-TPP) mode and surface plasmon polariton (SPP) mode exhibit interesting dispersive features for realizing a highly sensitive and accurate surface plasmon resonance (SPR) sensor. We found that the TM-TPP modes, formed at the interface of distributed Bragg reflector and metal, are strongly dispersive as compared to SPP modes at optical frequencies. This causes an appreciably narrow interaction bandwidth between TM-TPP and SPP modes, which leads to highly accurate sensing. In addition, appropriate tailoring of dispersion characteristics of TM-TPP as well as SPP modes could ensure high sensitivity of a novel SPR platform. By suitably designing the Au/TiO2/SiO2-based geometry, we propose a TM-TPP/SPP hybrid-mode sensor and achieve a sensitivity ≥900 nm/RIU with high detection accuracy (≥30 µm⁻¹) for analyte refractive indices varying between 1.330 and 1.345 in 600-700 nm wavelength range. The possibility to achieve desired dispersive behavior in any spectral band makes the sensing configuration an extremely attractive candidate to design sensors depending on the availability of optical sources.

Advancements in optical fiber-based wearable sensors for smart health monitoring.

Healthcare system is undergoing a significant transformation from a traditional hospital-centered to an individual-centered one, as a result of escalating chronic diseases, ageing populations, and ever-increasing healthcare costs,. Wearable sensors have become widely used in health monitoring systems since the COVID-19 pandemic. They enable continuous measurement of important health indicators like body temperature, wrist pulse, respiration rate, and non-invasive bio fluids like saliva and perspiration. Over the last few decades, the development has mostly concentrated on electrochemical and electrical wearable sensors. However, due to the drawbacks of such sensors, such as electronic waste, electromagnetic interference, non-electrical security, and poor performance, researchers are exhibiting a strong interest in optical principle-based systems. Fiber-based optical wearables are among the most promising healthcare systems because of advancements in high-sensitivity, durable, multiplexed sensing, and simple integration with flexible materials to improve wearability and simplicity. We present an overview of recent developments in optical fiber-based wearable sensors, focusing on two mechanisms: wavelength interrogation and intensity modulation for the detection of body temperature, pulse rate, respiration rate, body movements, and biomedical noninvasive fluids, with a thorough examination of their benefits and drawbacks. This review also focuses on improving working performance and application techniques for healthcare systems, including the integration of nanomaterials and the usage of the Internet of Things (IoT) with signal processing. Finally, the review concludes with a discussion of the future possibilities and problems for optical fiber-based wearables.

Label-Free Biochemical Sensing Using Processed Optical Fiber Interferometry: A Review.

Over the last 20 years, optical fiber-based devices have been exploited extensively in the field of biochemical sensing, with applications in many specific areas such as the food processing industry, environmental monitoring, health diagnosis, bioengineering, disease diagnosis, and the drug industry due to their compact, label-free, and highly sensitive detection. The selective and accurate detection of biochemicals is an essential part of biosensing devices, which is to be done through effective functionalization of highly specific recognition agents, such as enzymes, DNA, receptors, etc., over the transducing surface. Among many optical fiber-based sensing technologies, optical fiber interferometry-based biosensors are one of the broadly used methods with the advantages of biocompatibility, compact size, high sensitivity, high-resolution sensing, lower detection limits, operating wavelength tunability, etc. This Review provides a comprehensive review of the fundamentals as well as the current advances in developing optical fiber interferometry-based biochemical sensors. In the beginning, a generic biosensor and its several components are introduced, followed by the fundamentals and state-of-art technology behind developing a variety of interferometry-based fiber optic sensors. These include the Mach-Zehnder interferometer, the Michelson interferometer, the Fabry-Perot interferometer, the Sagnac interferometer, and biolayer interferometry (BLI). Further, several technical reports are comprehensively reviewed and compared in a tabulated form for better comparison along with their advantages and disadvantages. Further, the limitations and possible solutions for these sensors are discussed to transform these in-lab devices into commercial industry applications. At the end, in conclusion, comments on the prospects of field development toward the commercialization of sensor technology are also provided. The Review targets a broad range of audiences including beginners and also motivates the experts helping to solve the real issues for developing an industry-oriented sensing device.

Cardiac Troponin I Detection Using Gold/Cerium-Oxide Nanoparticles Assisted Hetro-Core Fiber Structure.

The article describes the development of a hetro-core optical fiber sensor structure based on localized surface plasmon resonance (LSPR) for the detection of cardiac troponin I (cTnI) solution. This was accomplished by fabricating a single-mode fiber - multimode fiber - single-mode fiber (SMS) structure. Then, fiber structure is immobilized with gold nanoparticles (AuNPs) and cerium oxide nanoparticles (CeO2-NPs) to improve its sensing capabilities. An UV-Vis spectrophotometer and a high-resolution transmission electron microscope (HR-TEM) are used to determine the morphology of synthesized nanoparticles. Scanning electron microscopy (SEM) is used to examine the state of immobilized NPs on the surface of sensing region. The developed sensor probe has a linear range of 0 to 1000 ng/mL cTnI, a sensitivity of 3 pm/(ng/mL), and a limit of detection (LoD) of 108.15 ng/mL. In real time, the proposed sensor will be used in a practice to detect acute myocardial infarction (AMI).

On the performance of 2D materials based plexcitonic sensor: numerical analysis.

In this paper, we propose the implementation of few layers of 2D materials in plexcitonic sensor for sensitivity enhancement. The positioning of the graphene layer implantation in such structure affects the sensitivity. The presence of graphene in contact with analyte offers ∼14% increase in the sensitivity of a bare plexcitonic sensor. Also, the performance of the sensor with the application of other 2D materials such as black phosphorus and MoS2has been studied. It is found that among graphene and black phosphorous, though MoS2offers highest sensitivity yet, low operating range limits its appropriateness. We believe that this study will provide a new insight in the applicability of 2D materials for sensing application.

Multipoint monitoring of amplitude, frequency, and phase of vibrations using concatenated modal interferometers.

Concatenated modal interferometers-based multipoint monitoring system for detection of amplitude, frequency, and phase of mechanical vibrations is proposed and demonstrated. The sensor probes are fabricated using identical photonic crystal fiber (PCF) sections and integrated along a single fiber channel to act as a compact and efficient sensing system. Each identical probe acts as a modal interferometer to generate a stable interference spectrum over the source spectrum. In the presence of an external dynamic field about each probe, the probes respond independently, producing a resultant signal superposition of each interferometer response signal. By analyzing the resultant signals using computational techniques, the vibration parameters applied to each interferometer are realized. The sensing system has an operation range of 1 Hz-1 kHz with a sensitivity of 51.5 pm/V. Such a sensing system would find wide applications at industrial, infrastructural, and medical fronts for monitoring various dynamic physical phenomena.

Mitochondrial Genetic Heterogeneity in Leber's Hereditary Optic Neuropathy: Original Study with Meta-Analysis.

Leber's hereditary optic neuropathy (LHON) is a mitochondrial disorder that causes loss of central vision. Three primary variants (m.3460G>A, m.11778G>A, and m.14484T>C) and about 16 secondary variants are responsible for LHON in the majority of the cases. We investigated the complete mitochondrial DNA (mtDNA) sequences of 189 LHON patients and found a total of 54 disease-linked pathogenic variants. The primary variants m.11778G>A and m.14484T>C were accountable for only 14.81% and 2.64% cases, respectively. Patients with these two variants also possessed additional disease-associated variants. Among 156 patients who lacked the three primary variants, 16.02% harboured other LHON-associated variants either alone or in combination with other disease-associated variants. Furthermore, we observed that none of the haplogroups were explicitly associated with LHON. We performed a meta-analysis of m.4216T>C and m.13708G>A and found a significant association of these two variants with the LHON phenotype. Based on this study, we recommend the use of complete mtDNA sequencing to diagnose LHON, as we found disease-associated variants throughout the mitochondrial genome.

Water Pollutants p-Cresol Detection Based on Au-ZnO Nanoparticles Modified Tapered Optical Fiber.

In this work, a localized plasmon-based sensor is developed for para-cresol (p-cresol) - a water pollutant detection. A nonadiabatic [Formula: see text] of tapered optical fiber (TOF) has been experimentally fabricated and computationally analyzed using beam propagation method. For optimization of sensor's performance, two probes are proposed, where probe 1 is immobilized with gold nanoparticles (AuNPs) and probe 2 is immobilized with the AuNPs along with zinc oxide nanoparticles (ZnO-NPs). The synthesized metal nanomaterials were characterized by ultraviolet-visible spectrophotometer (UV-vis spectrophotometer) and transmission electron microscope (HR-TEM). The nanomaterials coating on the surface of the sensing probe were characterized by a scanning electron microscope (SEM). Thereafter, to increase the specificity of the sensor, the probes are functionalized with tyrosinase enzyme. Different solutions of p-cresol in the concentration range of [Formula: see text] - [Formula: see text] are prepared in an artificial urine solution for sensing purposes. Different analytes such as uric acid, ß -cyclodextrin, L-alanine, and glycine are prepared for selectivity measurement. The linearity range, sensitivity, and limit of detection (LOD) of probe 1 are [Formula: see text] - [Formula: see text], 7.2 nm/mM (accuracy 0.977), and [Formula: see text], respectively; and for probe 2 are [Formula: see text] - [Formula: see text], 5.6 nm/mM (accuracy 0.981), and [Formula: see text], respectively. Thus, the overall performance of probe 2 is quite better due to the inclusion of ZnO-NPs that increase the biocompatibility of sensor probe. The proposed sensor structure has potential applications in the food industry and clinical medicine.

Contribution of nuclear and mitochondrial gene mutations in mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome.

BACKGROUND: Mitochondrial disorders are clinically complex and have highly variable phenotypes among all inherited disorders. Mutations in mitochon drial DNA (mtDNA) and nuclear genome or both have been reported in mitochondrial diseases suggesting common pathophysiological pathways. Considering the clinical heterogeneity of mitochondrial encephalopathy, lactic acidosis and stroke-like episodes (MELAS) phenotype including focal neurological deficits, it is important to look beyond mitochondrial gene mutation. METHODS: The clinical, histopathological, biochemical analysis for OXPHOS enzyme activity, and electron microscopic, and neuroimaging analysis was performed to diagnose 11 patients with MELAS syndrome with a multisystem presentation. In addition, whole exome sequencing (WES) and whole mitochondrial genome sequencing were performed to identify nuclear and mitochondrial mutations. RESULTS: Analysis of whole mtDNA sequence identified classical pathogenic mutation m.3243A > G in seven out of 11 patients. Exome sequencing identified pathogenic mutation in several nuclear genes associated with mitochondrial encephalopathy, sensorineural hearing loss, diabetes, epilepsy, seizure and cardiomyopathy (POLG, DGUOK, SUCLG2, TRNT1, LOXHD1, KCNQ1, KCNQ2, NEUROD1, MYH7) that may contribute to classical mitochondrial disease phenotype alone or in combination with m.3243A > G mutation. CONCLUSION: Individuals with MELAS exhibit clinical phenotypes with varying degree of severity affecting multiple systems including auditory, visual, cardiovascular, endocrine, and nervous system. This is the first report to show that nuclear genetic factors influence the clinical outcomes/manifestations of MELAS subjects alone or in combination with m.3243A > G mutation.

Embedded optical micro/nano-fibers for stable devices.

We present a technique to embed silica micro and nanofibers in low-index material (Teflon) using an inexpensive and straightforward fabrication process based on spin coating. The optical properties of the silica micro/nano-fibers have been investigated when they are bare or completely or partially embedded. Optical degradation occurs in bare fibers with diameters smaller than twice the wavelength of the guided light, thus making protection through embedding necessary. Our results also show that completely embedded fibers do not degrade over a long time, while partially embedded fibers can preserve the large evanescent waves without undergoing considerable degradation, which would be further reduced or even become negligible with functional overlayers. The results represent a step forward toward the development of durable and stable devices based on optical micro/nano fibers.

Etched multicore fiber sensor using copper oxide and gold nanoparticles decorated graphene oxide structure for cancer cells detection.

A compact, portable, label-free, and ultra-sensitive sensor is proposed to detect cancerous cells based on Multi-Core Fiber (MCF) comprising of seven cores arranged in a hexagonal shape spliced with Single-Mode Fiber (SMF). Here, cytosensing based on fiber optic Localized Surface Plasmon Resonance (LSPR) is used for the efficient detection of different types of cancer cells. The proposed sensor structure is etched in a controlled manner to increase the evanescent wave (EWs) and coupling of modes between the cores of MCF. The etched MCF based LSPR probe has high refractive index sensitivity (RIS). To further increase the sensitivity, the sensor structure is immobilized with different nanomaterials (NMs) such as optimized size of gold nanoparticles (AuNPs), graphene oxide (GO), and copper oxide nanoflowers (CuO-NFs). AuNPs increase the sensitivity using LSPR, whereas, GO and CuO-NFs helps to increase the biocompatibility of sensor. The developed probe is further coated with 2-deoxy-D-glucose (2-DG) over NMs that are specific for the detection of cancer cells. In this work, various cancerous cell lines i.e. HepG2, Hepa 1-6, MCF-7, A549, and normal cell lines i.e. NCF and LO2 are detected using the developed sensing probe. Various analysis of proposed sensor such as selectivity, reusability, anti-interference ability, and involvement of GLUT receptor in detection has also been performed. The proposed etched sensor is ultra-sensitive for detection of HepG2, Hepa1 6, A549, MCF-7, LO2, and NCF cell lines with a limit of detection (LoD) of 3, 2, 2, 2, 4, 10 cells/mL, respectively in the linear range of 1 × 102-1 × 106 cells/mL.