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.

Surface Functionalised Optical Fibre for Detection of Hydrogen Sulphide.

Dysregulated production of hydrogen sulphide in the human body has been associated with various diseases including cancer, underlining the importance of accurate detection of this molecule. Here, we report the detection of hydrogen sulphide using fluorescence-emission enhancement of two 1,8-naphthalimide fluorescent probes with an azide moiety in position 4. One probe, serving as a control, featured a methoxyethyl moiety through the imide to evaluate its effectiveness for hydrogen sulphide detection, while the other probe was modified with (3-aminopropyl)triethoxysilane (APTES) to enable direct covalent attachment to an optical fibre tip. We coated the optical fibre tip relatively homogeneously with the APTES-azide fluorophore, as confirmed via x-ray photoelectron spectroscopy (XPS). The absorption and fluorescence responses of the control fluorophore free in PBS were analysed using UV-Vis and fluorescence spectrophotometry, while the fluorescence emission of the APTES-azide fluorophore-coated optical fibres was examined using a simple, low-cost optical fibre-based setup. Both fluorescent probes exhibited a significant increase (more than double the initial value) in fluorescence emission upon the addition of HS- when excited with 405 nm. However, the fluorescence enhancement of the coated optical fibres demonstrated a much faster response time of 2 min (time for the fluorescence intensity to reach 90% of its maximum value) compared to the control fluorophore in solution (30 min). Additionally, the temporal evolution of fluorescence intensity of the fluorophore coated on the optical fibre was studied at two pH values (7.4 and 6.4), demonstrating a reasonable overlap and confirming the compound pH insensitivity within this range. The promising results from this study indicate the potential for developing an optical fibre-based sensing system for HS- detection using the synthesised fluorophore, which could have significant applications in health monitoring and disease detection.

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.

Label-free DNA quantification using isothermal amplification on an exposed core optical fiber microfluidic platform.

Isothermal amplification technology has triggered a surge in research due to its compatibility with small and portable equipment, simplicity, and high efficiency, especially in light of the COVID-19 pandemic where reliable widescale testing is critical to outbreak management. In this paper, a label-free isothermal deoxyribonucleic acid (DNA) amplification method based on refractive index (RI) quantification is proposed and demonstrated for the first time by combining optical fiber sensing, microfluidics, and isothermal amplification. A highly RI-sensitive Mach-Zehnder (MZ) interference is formed by splicing a short length of an exposed-core fiber between two lengths of a single-mode fiber while the microfluidic liquid channel on the exposed side of the ECF is filled with target DNA and the amplification solution. Real-time quantitative measurement of the target DNA is then realized by monitoring the change in RI of the solution during the isothermal DNA amplification process. The experimental results show that the platform successfully realizes real-time label-free monitoring of isothermal amplification of 0.16 aM DNA samples. This method is a breakthrough for applications in the fields of DNA detection and quantification where simple operation, rapid detection, portability, small size, high selectivity, and high sensitivity are required.

In-situ detection scheme for EGFR gene with temperature and pH compensation using a triple-channel optical fiber biosensor.

An advanced multi-parameter optical fiber sensing technology for EGFR gene detection based on DNA hybridization technology is demonstrated in this paper. For traditional DNA hybridization detection methods, temperature and pH compensation can not be realized or need multiple sensor probes. However, the multi-parameter detection technology we proposed can simultaneously detect complementary DNA, temperature and pH based on a single optical fiber probe. In this scheme, three optical signals including dual surface plasmon resonance signal (SPR) and Mach-Zehnder interference signal (MZI) are excited by binding the probe DNA sequence and pH-sensitive material with the optical fiber sensor. The paper proposes the first research to achieve simultaneous excitation of dual SPR signal and Mach-Zehnder interference signal in a single fiber and used for three-parameter detection. Three optical signals have different sensitivities to the three variables. From a mathematical point of view, the unique solutions of exon-20 concentration, temperature and pH can be obtained by analyzing the three optical signals. The experimental results show that the exon-20 sensitivity of the sensor can reach 0.07 nm nM-1, and the limit of detection is 3.27 nM. The designed sensor gives a fast response, high sensitivity, and low detection limit, which is important for the field of DNA hybridization research and for solving the problems of biosensor susceptibility to temperature and pH.

Multimode optical fiber specklegram smart bed sensor array.

SIGNIFICANCE: Monitoring the movement and vital signs of patients in hospitals and other healthcare environments is a significant burden on healthcare staff. Early warning systems using smart bed sensors hold promise to relieve this burden and improve patient outcomes. We propose a scalable and cost-effective optical fiber sensor array that can be embedded into a mattress to detect movement, both sensitively and spatially. AIM: Proof-of-concept demonstration that a multimode optical fiber (MMF) specklegram sensor array can be used to detect and image movement on a bed. APPROACH: Seven MMFs are attached to the upper surface of a mattress such that they cross in a 3 × 4 array. The specklegram output is monitored using a single laser and single camera and movement on the fibers is monitored by calculating a rolling zero-normalized cross-correlation. A 3 × 4 image is formed by comparing the signal at each crossing point between two fibers. RESULTS: The MMF sensor array can detect and image movement on a bed, including getting on and off the bed, rolling on the bed, and breathing. CONCLUSIONS: The sensor array shows a high sensitivity to movement, which can be used for monitoring physiological parameters and patient movement for potential applications in healthcare settings.

Temperature compensated fiber optic magnetic sensor based on the combination interference principle.

In this paper, a highly sensitive temperature compensated fiber optic magnetic field sensor by Sagnac and Mach-Zehnder combination interference (SMZI) is proposed and verified. The sensing structure relies on microstructured exposed core fiber (ECF) filled with ethanol and magnetic fluid (MF). The refractive index of MF and ethanol is affected by the magnetic field and temperature (MFT). SMZI is based on the multimode and birefringence characteristics of ECF. The measurement principle is that the spectra of Sagnac interference and Mach-Zehnder interference have respective sensitivities to the MFT. The magnetic sensitivity can reach 1.17 nm/mT, and the temperature sensitivity is up to -1.93 nm/°C. At the same time, the sensor has good repeatability and low detection limits of 0.41 mT and 0.25°C, respectively. It not only solves the cross-influence of temperature but also makes the spectral analysis more intuitive. The sensor has a broad development prospect in the application of MFT detection.

Machine learning for sensing with a multimode exposed core fiber specklegram sensor.

Fiber specklegram sensors (FSSs) traditionally use statistical methods to analyze specklegrams obtained from fibers for sensing purposes, but can suffer from limitations such as vulnerability to noise and lack of dynamic range. In this paper we demonstrate that deep learning improves the analysis of specklegrams for sensing, which we show here for both air temperature and water immersion length measurements. Two deep neural networks (DNNs); a convolutional neural network and a multi-layer perceptron network, are used and compared to a traditional correlation technique on data obtained from a multimode fiber exposed-core fiber. The ability for the DNNs to be trained against a random noise source such as specklegram translations is also demonstrated.

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.

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.

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.

Multimode exposed core fiber specklegram sensor.

The inception of photonic crystal fibers (PCFs) allowed for unprecedented tailoring of waveguide properties for specialty sensing probes. Exposed core microstructured fibers (ECFs) represent a natural evolution of the PCF design for practical liquid and gas sensing. Until now, to the best of our knowledge, only single-mode or few-modes ECFs have been explored. In this Letter, we demonstrate a highly multimode ECF with a lateral access that extends throughout the whole length of the fiber. The ECF is operated as a fiber specklegram sensor for assessing properties of fluids and interrogated using a simple and low-cost setup. The probe exhibits a refractive index resolution and sensitivity of at least 4.6×10-4 refractive index units (RIUs) and -10.97RIU-1, respectively. A maximum temperature resolution up to 0.017°C with a -0.20∘C-1 temperature sensitivity over the 23°C-28°C range and a liquid level sensing resolution up to 0.12 mm with -0.015mm-1 sensitivity over the 0.0-50.0 mm bathed the length range in water.

Quantum noise limited nanoparticle detection with exposed-core fiber.

Label-free biosensors are important tools for clinical diagnostics and for studying biology at the single molecule level. The development of optical label-free sensors has allowed extreme sensitivity but can expose the biological sample to photodamage. Moreover, the fragility and complexity of these sensors can be prohibitive to applications. To overcome these problems, we develop a quantum noise limited exposed-core fiber sensor providing robust platform for label-free biosensing with a natural path toward microfluidic integration. We demonstrate the detection of single nanoparticles down to 25 nm in radius with optical intensities beneath known biophysical damage thresholds.

Tunable multi-wavelength third-harmonic generation using exposed-core microstructured optical fiber.

We demonstrate that exposed-core microstructured optical fibers offer multiple degrees of freedom for tailoring third-harmonic generation through the core diameter, input polarization, and nanofilm deposition. Varying these parameters allows control of the phase-matching position between an infrared pump wavelength and the generated visible wavelengths. In this Letter, we show how increasing the core diameter over previous experiments (2.57 µm compared to 1.85 µm) allows the generation of multiple wavelengths, which can be further controlled by rotating the input pump polarization and the deposition of dielectric nanofilms. This can lead to highly tailorable light sources for applications such as spectroscopy or nonlinear microscopy.

Soft-glass imaging microstructured optical fibers.

We demonstrate the fabrication of multi-core (imaging) microstructured optical fiber via soft-glass preform extrusion through a 3D printed titanium die. The combination of extrusion through 3D printed dies and structured element (capillary) stacking allows for unprecedented control of the optical fiber geometry. We have exploited this to demonstrate a 100 pixel rectangular array imaging microstructured fiber. Due to the high refractive index of the glass used (n = 1.62), such a fiber can theoretically have a pixel pitch as small as 1.8 µm. This opens opportunities for ultra-small, high-resolution imaging fibers fabricated from diverse glass types.

Nanofilm-induced spectral tuning of third harmonic generation.

Intermodal third-harmonic generation using waveguides is an effective frequency conversion process due to the combination of long interaction lengths and strong modal confinement. Here we introduce the concept of tuning the third harmonic phase-matching condition via the use of dielectric nanofilms located on an open waveguide core. We experimentally demonstrate that tantalum oxide nanofilms coated onto the core of an exposed core fiber allow tuning the third harmonic wavelength over 30 nm, as confirmed by qualitative simulations. Due to its generic character, the presented tuning scheme can be applied to any form of exposed core waveguide and will find applications in fields including microscopy, biosensing, and quantum optics.

Third harmonic generation in exposed-core microstructured optical fibers.

Inter-modal phase-matched third harmonic generation has been demonstrated in an exposed-core microstructured optical fiber. Our fiber, with a partially open core having a diameter of just 1.85 µm, shows efficient multi-peak third-harmonic generation between 500 nm and 530 nm, with a maximum visible-wavelength output of 0.96 µW. Mode images and simulations show strong agreement, confirming the phase-matching process and polarization dependence. We anticipate this work will lead to tailorable and tunable visible light sources by exploiting the open access to the optical fiber core, such as depositing thin-film coatings in order to shift the phase matching conditions.

Quantification of the fluorescence sensing performance of microstructured optical fibers compared to multi-mode fiber tips.

Microstructured optical fibers, particularly those with a suspended-core geometry, have frequently been argued as efficient evanescent-field fluorescence-based sensors. However, to date there has not been a systematic comparison between such fibers and the more common geometry of a multi-mode fiber tip sensor. In this paper we make a direct comparison between these two fiber sensor geometries both theoretically and experimentally. Our results confirm that suspended-core fibers provide a significant advantage in terms of total collected fluorescence signal compared to multi-mode fibers using an equivalent experimental configuration.