Single-fiber probes for combined sensing and imaging in biological tissue: recent developments and prospects.

Single-fiber-based sensing and imaging probes enable the co-located and simultaneous observation and measurement (i.e., 'sense' and 'see') of intricate biological processes within deep anatomical structures. This innovation opens new opportunities for investigating complex physiological phenomena and potentially allows more accurate diagnosis and monitoring of disease. This prospective review starts with presenting recent studies of single-fiber-based probes for concurrent and co-located fluorescence-based sensing and imaging. Notwithstanding the successful initial demonstration of integrated sensing and imaging within single-fiber-based miniaturized devices, the realization of these devices with enhanced sensing sensitivity and imaging resolution poses notable challenges. These challenges, in turn, present opportunities for future research, including the design and fabrication of complex lens systems and fiber architectures, the integration of novel materials and other sensing and imaging techniques.

Development of a glass-based imaging phantom to model the optical properties of human tissue.

The fabrication of a stable, reproducible optical imaging phantom is critical to the assessment and optimization of optical imaging systems. We demonstrate the use of an alternative material, glass, for the development of tissue-mimicking phantoms. The glass matrix was doped with nickel ions to approximate the absorption of hemoglobin. Scattering levels representative of human tissue were induced in the glass matrix through controlled crystallization at elevated temperatures. We show that this type of glass is a viable material for creating tissue-mimicking optical phantoms by providing controlled levels of scattering and absorption with excellent optical homogeneity, long-term stability and reproducibility.

Controlled formation of gold nanoparticles with tunable plasmonic properties in tellurite glass.

Silicate glasses with metallic nanoparticles (NPs) have been of intense interest in art, science and technology as the plasmonic properties of these NPs equip glass with light modulation capability. The so-called striking technique has enabled precise control of the in situ formation of metallic NPs in silicate glasses for applications from coloured glasses to photonic devices. Since tellurite glasses exhibit the unique combination of comparably easy fabrication, low phonon energy, wide transmission window and high solubility of luminescent rare earth ions, there has been a significant amount of work over the past two decades to adapt the striking technique to form gold or silver NPs in tellurite glasses. Despite this effort, the striking technique has remained insufficient for tellurite glasses to form metal NPs suitable for photonic applications. Here, we first uncover the challenges of the traditional striking technique to create gold NPs in tellurite glass. Then, we demonstrate precise control of the size and concentration of gold NPs in tellurite glass by developing new approaches to both steps of the striking technique: a controlled gold crucible corrosion technique to incorporate gold ions in tellurite glass and a glass powder reheating technique to subsequently transform the gold ions to gold NPs. Using the Mie theory, the size, size distribution and concentration of the gold NPs formed in tellurite glass are determined from the plasmonic properties of the NPs. This fundamental research provides guidance for designing and manipulating the plasmonic properties in tellurite glass for photonics research and applications.

Mitigating stimulated Brillouin scattering in multimode fibers with focused output via wavefront shaping.

The key challenge for high-power delivery through optical fibers is overcoming nonlinear optical effects. To keep a smooth output beam, most techniques for mitigating optical nonlinearities are restricted to single-mode fibers. Moving out of the single-mode paradigm, we show experimentally that wavefront-shaping of coherent input light to a highly multimode fiber can increase the power threshold for stimulated Brillouin scattering (SBS) by an order of magnitude, whilst simultaneously controlling the output beam profile. The SBS suppression results from an effective broadening of the Brillouin spectrum under multimode excitation, without broadening of transmitted light. Strongest suppression is achieved with selective mode excitation that gives the broadest Brillouin spectrum. Our method is efficient, robust, and applicable to continuous waves and pulses. This work points toward a promising route for mitigating detrimental nonlinear effects in optical fibers, enabling further power scaling of high-power fiber systems for applications to directed energy, remote sensing, and gravitational-wave detection.

Edge chipping damage in lithium silicate glass-ceramics induced by conventional and ultrasonic vibration-assisted diamond machining.

OBJECTIVES: Diamond machining of lithium silicate glass-ceramics (LS) induces extensive edge chipping damage, detrimentally affecting LS restoration functionality and long-term performance. This study approached novel ultrasonic vibration-assisted machining of pre-crystallized and crystallized LS materials to investigate induced edge chipping damage in comparison with conventional machining. METHODS: The vibration-assisted diamond machining was conducted using a five-axis ultrasonic high-speed grinding/machining machine at different vibration amplitudes while conventional machining was performed using the same machine without vibration assistance. LS microstructural characterization and phase development were performed using scanning electron microscopy (SEM) and x-ray diffraction (XRD) techniques. Machining-induced edge chipping depths, areas and morphology were also characterized using the SEM and Java-based imaging software. RESULTS: All machining-induced edge chipping damages resulted from brittle fractures. The damage scales, however, depended on the material microstructures; mechanical properties associated with the fracture toughness, critical strain energy release rates, brittleness indices, and machinability indices; and ultrasonic vibration amplitudes. Pre-crystallized LS with more glass matrix and lithium metasilicate crystals yielded respective 1.8 and 1.6 times greater damage depths and specific damage areas than crystallized LS with less glass matrix and tri-crystal phases in conventional machining. Ultrasonic machining at optimized amplitudes diminished such damages by over 50 % in pre-crystallized LS and up to 13 % in crystallized LS. SIGNIFICANCE: This research highlights that ultrasonic vibration assistance at optimized conditions may advance current dental CAD/CAM machining techniques by significant suppression of edge chipping damage in pre-crystallized LS.

Multimodal Raman spectroscopy and optical coherence tomography for biomedical analysis.

Optical techniques hold great potential to detect and monitor disease states as they are a fast, non-invasive toolkit. Raman spectroscopy (RS) in particular is a powerful label-free method capable of quantifying the biomolecular content of tissues. Still, spontaneous Raman scattering lacks information about tissue morphology due to its inability to rapidly assess a large field of view. Optical Coherence Tomography (OCT) is an interferometric optical method capable of fast, depth-resolved imaging of tissue morphology, but lacks detailed molecular contrast. In many cases, pairing label-free techniques into multimodal systems allows for a more diverse field of applications. Integrating RS and OCT into a single instrument allows for both structural imaging and biochemical interrogation of tissues and therefore offers a more comprehensive means for clinical diagnosis. This review summarizes the efforts made to date toward combining spontaneous RS-OCT instrumentation for biomedical analysis, including insights into primary design considerations and data interpretation.

Tailored Multi-Color Dispersive Wave Formation in Quasi-Phase-Matched Exposed Core Fibers.

Widely wavelength-tunable femtosecond light sources in a compact, robust footprint play a central role in many prolific research fields and technologies, including medical diagnostics, biophotonics, and metrology. Fiber lasers are on the verge in the development of such sources, yet widespan spectral tunability of femtosecond pulses remains a pivotal challenge. Dispersive wave generation, also known as Cherenkov radiation, offers untapped potentials to serve these demands. In this work, the concept of quasi-phase matching for multi-order dispersive wave formation with record-high spectral fidelity and femtosecond durations is exploited in selected, partially conventionally unreachable spectral regions. Versatile patterned sputtering is utilized to realize height-modulated high-index nano-films on exposed fiber cores to alter fiber dispersion to an unprecedented degree through spatially localized, induced resonances. Nonlinear optical experiments and simulations, as well as phase-mismatching considerations based on an effective dispersion, confirm the conversion process and reveal unique emission features, such as almost power-independent wavelength stability and femtosecond duration. This resonance-empowered approach is applicable to both fiber and on-chip photonic systems and paves the way to instrumentalize dispersive wave generation as a unique tool for efficient, coherent femtosecond multi-frequency conversion for applications in areas such as bioanalytics, life science, quantum technology, or metrology.

Real-time Raman analysis of the hydrolysis of formaldehyde oligomers for enhanced collagen fixation.

Formaldehyde (FA) is widely applied as a fixative for proteins such as collagen. Current studies have confirmed that the reversible oligomer-to-monomer equilibrium of FA in aqueous solution and the proportion of FA monomer is a significant factor affecting tissue fixation. Since the hydrolysis of FA oligomers is a dynamic process affected jointly by different factors, its real time monitoring has proved to be challenging. In this work, by utilizing the well-established Raman technique as an analytical platform, we identified the factors affecting the hydrolysis of FA oligomers by rationally examining the νs (OCO) and νas (OCO) modes with varying conditions, such as time, pH, temperature, and FA concentration. The optimized conditions of the highest hydrolysis rate of oligomers into monomers for fixation on collagen and tissues have been found to be relatively low FA concentration (≤5%) in phosphate-buffered saline at pH 9.0 in room temperature. In order to compare the fixation quality of the optimized conditions to that of the conventional conditions used by current medical practices (4% FA concentration in tap water under room temperature), Raman spectroscopy and chemical derivatization methods with o-phthalaldehyde and fluorescent probe FAP-1 have been investigated, and our results revealed that the FA molecules under our optimized conditions have reacted with at least 15% more amino groups within collagen compared to those under the conventional conditions mentioned above. This study provides direct evidence of the FA equilibrium in solution by Raman spectroscopy, which could be applied for the optimal use of FA in medicine, even at an industrial scale.

Controlled delivery of quantum dots using microelectrophoresis technique: Intracellular behavior and preservation of cell viability.

The use of synthetic nanomaterials as contrast agents, sensors, and drug delivery vehicles in biological research primarily requires effective approaches for intracellular delivery. Recently, the well-accepted microelectrophoresis technique has been reported to exhibit the ability to deliver nanomaterials, quantum dots (QDs) as an example, into live cells, but information about cell viability and intracellular fate of delivered nanomaterials is yet to be provided. Here we show that cell viability following microelectrophoresis of QDs is strongly correlated with the amount of delivered QDs, which can be finely controlled by tuning the ejection duration to maintain long-term cell survival. We reveal that microelectrophoretic delivered QDs distribute homogeneously and present pure Brownian diffusion inside the cytoplasm without endosomal entrapment, having great potential for the study of dynamic intracellular events. We validate that microelectrophoresis is a powerful technique for the effective intracellular delivery of QDs and potentially various functional nanomaterials in biological research.

Microfluidic Raman Sensing Using a Single Ring Negative Curvature Hollow Core Fiber.

A compact microfluidic Raman detection system based on a single-ring negative-curvature hollow-core fiber is presented. The system can be used for in-line qualitative and quantitative analysis of biochemicals. Both efficient light coupling and continuous liquid injection into the hollow-core fiber were achieved by creating a small gap between a solid-core fiber and the hollow-core fiber, which were fixed within a low-cost ceramic ferrule. A coupling efficiency of over 50% from free-space excitation laser to the hollow core fiber was obtained through a 350 µm-long solid-core fiber. For proof-of-concept demonstration of bioprocessing monitoring, a series of ethanol and glucose aqueous solutions at different concentrations were used. The limit of detection achieved for the ethanol solutions with our system was ~0.04 vol.% (0.32 g/L). Such an all-fiber microfluidic device is robust, provides Raman measurements with high repeatability and reusability, and is particularly suitable for the in-line monitoring of bioprocesses.

Whispering gallery mode excitation using exposed-core fiber.

Whispering gallery modes (WGMs) in micro-resonators are of interest due to their high Q-factors. Ultra-thin fiber tapers are widely deployed to couple light into micro-resonators but achieving stable and practical coupling for out-of-lab use remains challenging. Here, a new WGM coupling scheme using an exposed-core silica fiber (ECF) is proposed, which overcomes the challenge of using fragile fiber tapers. Microspheres are deposited onto the exposed channel for excitation via the evanescent field of the fiber's guided modes. The outer jacket of the ECF partially encapsulates the microspheres, protecting them from external physical disturbance. By varying the mode launching conditions in this few-mode ECF, in combination with a Fano resonance effect, we demonstrate a high degree of tunability in the reflection spectrum. Furthermore, we show multi-particle WGM excitation, which could be controlled to occur either simultaneously or separately through controlling the ECF mode launching conditions. This work can bring value towards applications such as optical switches and modulators, multiplexed/distributed biosensing, and multi-point lasing, integrated in a single optical fiber device that avoids fiber post-processing.

In Situ Temperature-Compensated DNA Hybridization Detection Using a Dual-Channel Optical Fiber Sensor.

A multifunction, high-sensitivity, and temperature-compensated optical fiber DNA hybridization sensor combining surface plasmon resonance (SPR) and Mach-Zehnder interference (MZI) has been designed and implemented. We demonstrate, for the first time to our knowledge, the dual-parameter measurement of temperature and refractive index (RI) by simultaneously using SPR and MZI in a simple single-mode fiber (SMF)-no-core fiber (NCF)-SMF structure. The experimental results show RI sensitivities of 930 and 1899 nm/RIU and temperature sensitivities of 0.4 and -1.4 nm/°C for the MZI and SPR, respectively. We demonstrate a sensitivity matrix used to simultaneously detect both parameters, solving the problem of temperature interference of RI variation-based biosensors. In addition, the sensor can also distinguish biological binding events by detecting the localized RI changes at the fiber's surface. We realize label-free sensing of DNA hybridization detection by immobilizing probe DNA (pDNA) onto the fiber as the probe to capture complementary DNA (cDNA). The experimental results show that the sensor can qualitatively detect cDNA after temperature compensation, and the limit of detection (LOD) of the sensor reaches 80 nM. The proposed sensor has advantages of high sensitivity, real time, low cost, temperature compensation, and low detection limit and is suitable for in situ monitoring, high-precision sensing of DNA molecules, and other related fields, such as gene diagnosis, kinship judgment, environmental monitoring, and so on.

Preferential coupling of diamond NV centres in step-index fibres.

Diamonds containing the negatively charged nitrogen-vacancy centre are a promising system for room-temperature magnetometry. The combination of nano- and micro-diamond particles with optical fibres provides an option for deploying nitrogen-vacancy magnetometers in harsh and challenging environments. Here we numerically explore the coupling efficiency from nitrogen-vacancy centres within a diamond doped at the core/clad interface across a range of commercially available fibre types so as to inform the design process for a diamond in fibre magnetometers. We determine coupling efficiencies from nitrogen-vacancy centres to the guided modes of a step-index fibre and predict the optically detected magnetic resonance (ODMR) generated by a ensemble of four nitrogen-vacancy centres in this hybrid fibre system. Our results show that the coupling efficiency is enhanced with a high refractive index difference between the fibre core and cladding and depends on the radial position of the nitrogen-vacancy centres in the fibre core. Our ODMR simulations show that due to the preferential coupling of the nitrogen-vacancy emission to the fibre guided modes, certain magnetometry features such as ODMR contrast can be enhanced and lead to improved sensitivity in such diamond-fibre systems, relative to conventional diamond only ensemble geometries.

Cytoplasmic delivery of quantum dots via microelectrophoresis technique.

Nanoparticles with specific properties and functions have been developed for various biomedical research applications, such as in vivo and in vitro sensors, imaging agents and delivery vehicles of therapeutics. The development of an effective delivery method of nanoparticles into the intracellular environment is challenging and success in this endeavor would be beneficial to many biological studies. Here, the well-established microelectrophoresis technique was applied for the first time to deliver nanoparticles into living cells. An optimal protocol was explored to prepare semiconductive quantum dots suspensions having high monodispersity with average hydrodynamic diameter of 13.2-35.0 nm. Micropipettes were fabricated to have inner tip diameters of approximately 200 nm that are larger than quantum dots for ejection but less than 500 nm to minimize damage to the cell membrane. We demonstrated the successful delivery of quantum dots via small electrical currents (-0.2 nA) through micropipettes into the cytoplasm of living human embryonic kidney cells (roughly 20-30 µm in length) using microelectrophoresis technique. This method is promising as a simple and general strategy for delivering a variety of nanoparticles into the cellular environment.

A Fibre-Optic Platform for Sensing Nitrate Using Conducting Polymers.

Monitoring nitrate ions is essential in agriculture, food industry, health sector and aquatic ecosystem. We show that a conducting polymer, poly(3,4-ethylenedioxythiophene) (PEDOT), can be used for nitrate sensing through a process in which nitrate ion uptake leads to oxidation of PEDOT and change of its optical properties. In this study, a new platform is developed in which a single-mode fibre coated at the tip with PEDOT is used for nitrate sensing. A crucial step towards this goal is introduction of carbonate exposure to chemically reduced PEDOT to a baseline value. The proposed platform exhibits the change in optical behaviour of the PEDOT layer at the tip of the fibre as it undergoes chemical oxidation and reduction (redox). The change in optical properties due to redox switching varies with the intensity of light back reflected by the fibre coated with PEDOT. The proposed platform during oxidation demonstrates linear response for the uptake of nitrate ions in concentrations ranging between 0.2 and 40 parts per million (ppm), with a regression coefficient R2=0.97 and a detection limit of 6.7 ppm. The procedure for redox switching is repeatable as the back reflection light intensity reaches ±1.5% of the initial value after reduction.

Scalable Functionalization of Optical Fibers Using Atomically Thin Semiconductors.

Atomically thin transition metal dichalcogenides are highly promising for integrated optoelectronic and photonic systems due to their exciton-driven linear and nonlinear interactions with light. Integrating them into optical fibers yields novel opportunities in optical communication, remote sensing, and all-fiber optoelectronics. However, the scalable and reproducible deposition of high-quality monolayers on optical fibers is a challenge. Here, the chemical vapor deposition of monolayer MoS2 and WS2 crystals on the core of microstructured exposed-core optical fibers and their interaction with the fibers' guided modes are reported. Two distinct application possibilities of 2D-functionalized waveguides to exemplify their potential are demonstrated. First, the excitonic 2D material photoluminescence is simultaneously excited and collected with the fiber modes, opening a novel route to remote sensing. Then it is shown that third-harmonic generation is modified by the highly localized nonlinear polarization of the monolayers, yielding a new avenue to tailor nonlinear optical processes in fibers. It is anticipated that the results may lead to significant advances in optical-fiber-based technologies.

Development of innovative tools for investigation of nutrient-gut interaction.

The gastrointestinal tract is the key interface between the ingesta and the human body. There is wide recognition that the gastrointestinal response to nutrients or bioactive compounds, particularly the secretion of numerous hormones, is critical to the regulation of appetite, body weight and blood glucose. This concept has led to an increasing focus on "gut-based" strategies for the management of metabolic disorders, including type 2 diabetes and obesity. Understanding the underlying mechanisms and downstream effects of nutrient-gut interactions is fundamental to effective translation of this knowledge to clinical practice. To this end, an array of research tools and platforms have been developed to better understand the mechanisms of gut hormone secretion from enteroendocrine cells. This review discusses the evolution of in vitro and in vivo models and the integration of innovative techniques that will ultimately enable the development of novel therapies for metabolic diseases.

Single-peak fiber Bragg gratings in suspended-core optical fibers.

Femtosecond laser inscribed fiber Bragg gratings in pure-silica suspended-core optical fibers have previously been demonstrated as a promising platform for high temperature sensing. However, the density of gratings that could be written on a single fiber was limited by undesired reflections associated with higher order modes in these high numerical aperture fibers. This resulted in a complex, broadband reflection spectrum with limited multiplexing capability. In this work we utilize modifications to the fine structure of the suspended core optical fibers to fine tune the relative confinement loss of the optical fiber modes, thus reducing the contribution from such higher order modes. The effects of these changes on mode propagation are modeled, giving a range of fibers with different confinement loss properties which can be tailored to the specific length scale of a desired application. We achieve single-peak reflections from individual fiber Bragg gratings, significantly improving performance for multipoint sensing and demonstrate this technique by writing 20 gratings onto a single fiber.

All-fiber all-optical quantitative polymerase chain reaction (qPCR).

Quantitative polymerase chain reaction (qPCR), the real-time amplification and measurement of a targeted DNA molecule, has revolutionized the biological sciences and is routinely applied in areas such as medical diagnostics, forensics, and agriculture. Despite widescale use of qPCR technology in the lab, the availability of low-cost and high-speed portable systems remains one of the barriers to routine in-field implementation. Here we propose and demonstrate a potential solution using a photonics-based qPCR system. By using an all-optical approach, we achieve ultra-fast temperature response with real-time temperature feedback using nanoliter scale reaction volumes. The system uses a microcavity to act as a nanoliter scale reaction vessel with a laser-driven and optically monitored temperature cycling system for ultrafast thermal cycling and incorporates an all-fiber fluorescence excitation/detection system to achieve real-time, high sensitivity fluorescence monitoring of the qPCR process. Further, we demonstrate the potential of the system to operate as a label-free qPCR system through direct optical measurement of the sample refractive index. Due to advantages in portability and fabrication simplicity, we anticipate that this platform technology will offer a new strategy for fundamental techniques in biochemistry applications, such as point-of-care and remote diagnostics.

Ultra-simplified Single-Step Fabrication of Microstructured Optical Fiber.

Manufacturing optical fibers with a microstructured cross-section relies on the production of a fiber preform in a multiple-stage procedure, and drawing of the preform to fiber. These processes encompass the use of several dedicated and sophisticated equipment, including a fiber drawing tower. Here we demonstrate the use of a commercial table-top low-cost filament extruder to produce optical fibers with complex microstructure in a single step - from the pellets of the optical material directly to the final fiber. The process does not include the use of an optical fiber drawing tower and is time, electrical power, and floor space efficient. Different fiber geometries (hexagonal-lattice solid core, suspended core and hollow core) were successfully fabricated and their geometries evaluated. Air guidance in a wavelength range where the fiber material is opaque was shown in the hollow core fiber.