This PDF file contains the front matter associated with SPIE Proceedings Volume 10488 including the Title Page, Copyright information, Table of Contents, Introduction, and Conference Committee listing.

Silicon microring resonators are widely used as optical biosensors because of their high sensitivity and promise of low-cost mass-manufacturing. Usually, they only measure the adsorbed molecular mass via the refractive index change they detect. Here, we propose and demonstrate a silicon microring biosensor that can measure molecular thickness and density as well as electrochemical activity simultaneously, thereby enabling quantification of the conformation of sur-face-immobilized biological and molecular layers in real time. Insight into the molecular conformation is obtained by recording the resonance shift from two geometrically distinct ring-resonators connected to a single access waveguide. The resonant cavities both support a single TE polarized optical mode but have different widths (480 and 580 nm); thus the penetration depth of their evanescent fields is very different providing different depth-resolution of the interaction with the adlayer on the sensor surface. By combining the optical shift from these two measurements, we demonstrate unambiguous quantification of the thickness and the refractive index of a molecular layer assembled on the waveguide. The precision of the technique is 0.05 nm and 0.005 RIU in the molecular layer thickness and refractive index, respectively. We demonstrate the cascaded electrophotonic ring resonator system using two exemplar systems, namely a) physisorption of a bovine serum albumin monolayer and b) an electroactive DNA oligonucleotide hairpin, where we uniquely show the ability to monitor electrochemical activity and conformational change with the same device. This novel sensor geometry provides a new approach for monitoring the conformation and conformational changes in an inexpensive and miniaturized platform that is amenable to multiplexed, high-throughput measurements.

For deep imaging depth and least invasiveness, people commonly use 1100-1300 nm femtosecond laser sources to perform label-free in vivo microscopy. The modalities include reflectance confocal, two & three photon fluorescence, and second & third harmonic generation microscopy. However, most of the laser sources are typically based on bulky oscillators, which are sensitive to environment conditions and less stable for routine clinical use. In contrast, fiber-based lasers have simpler cavity design and potentially compact size for movable use. In this presentation, we demonstrate a fiber-based 1150 nm femtosecond laser source, with 6.5 nJ pulse energy, 86 fs pulse-width, and 11.25 MHz pulse repetition rate. It was achieved by a Bismuth Borate (BIBO) or Magnesium-doped periodically poled Lithium Niobate (MgO:PPLN) mediated frequency doubling of the 2300 nm solitons, generated from an excitation of 1550 nm Er:fiber femtosecond laser pulses on a large mode area photonic crystal fiber. Combined with a laser scanned microscope and a home-build data acquisition card, we achieve a pulse-per-pixel harmonic generation microscopy in vivo at a 30 Hz frame rate. In the future, this solution is potential to be used for label-free clinical virtual optical biopsy.

Stainless pipe is used as the supporting tube for the infrared hollow fiber to obtain high durability and strong mechanical strength. In order to reduce roughness of inner surface of stainless tubes which causes the additional transmission loss, an acrylic-silicon resin material is used as a buffer layer to the inner wall of stainless tube for a low-loss characteristic. For the dielectric inner-coating layer, cyclic olefin polymer (COP) is used to lower the transmission loss. The COP layer is formed by using liquid-phase coating method. The hollow fiber with optimized COP inner film thickness for CO₂ laser light were fabricated and reasonable transmission loss was demonstrated.

Electrosurgery, i.e. the application of radiofrequency current for tissue ablation, is a frequently used treatment for many cardiac arrhythmias. Electrophysiological and anatomic mapping, as well as careful radiofrequency power control typically guide the radiofrequency ablation procedure. Despite its widespread application, accurate monitoring of the lesion formation with sufficient spatio-temporal resolution remains challenging with the existing imaging techniques. We present a novel integrated catheter for simultaneous radiofrequency ablation and optoacoustic monitoring of the lesion formation in real time and 3D. The design combines the delivery of both electric current and optoacoustic excitation beam in a single catheter consisting of copper-coated multimode light-guides and its manufacturing is described in detail. The electrical current causes coagulation and desiccation while the excitation light is locally absorbed, generating OA responses from the entire treated volume. The combined ablation-monitoring capabilities were verified using ex-vivo bovine tissue. The formed ablation lesions showed a homogenous coagulation while the ablation was monitored in realtime with a volumetric frame rate of 10 Hz over 150 seconds.

Flexible fiber-optic based imaging probes have significantly broadened the clinical application scope of optical coherence tomography (OCT), enabling high-resolution imaging of several regions in human body. The movement of flexible catheter causes the asymmetries of fiber geometry and stress, resulting in the presence of fiber birefringence. Scanning and flexing of the OCT probes results in variations in the polarization states of light from the sample arm. When the polarization states of light from the sample are misaligned with those of the reference arm, the interference fringes would fade out, leading to intensity variations and SNR degradation in OCT images. From the statistical view, we characterized the intensity fluctuation and average signal-to-noise ratio (SNR) loss induced by the fringe fading of the sample arm polarization randomization. By taking advantage of an interesting observation, that the output polarization states of round-trip sample arm SMF are not uniformly distributed on the Poincare sphere, an optimum polarization state of reference arm can be found for the Michelson-type OCT configuration. From our analysis, we also suggested that the light source with low degree of polarization such as super-continuum source, or light source with long fiber, should be carefully managed to achieve the optimal SNR. We demonstrated our optimal polarization management, using two additional polarizers, could statistically provide 3.5 dB increase in system sensitivity.

Terahertz gas sensing system based on time-domain spectroscopy (THz-TDS) using a hollow-optical fiber gas cell is proposed. A hollow optical fiber functions as a long-path and low-volume gas cell and loading a dielectric layer on the inside of the fiber reduces the transmission loss and the dielectric layer also protects the metal layer of the fiber from deterioration. In the fabrication process, a polyethylene tube with a thin wall is drawn from a thick preform and a metal layer is formed on the outside of the tube. By using a 34-cm long fiber gas cell, NH3 gas with a concentration of 8.5 % is detected with a good SN ratio. However, the absorption peaks of NH3 and water vapor appeared at around 1.2 THz are not separated. To improve the frequency resolution in Fourier transformation, the time scan width that is decided by the scanning length of linear stage giving a time delay in the probing THz beam is enlarged. As a result, the absorption peaks at around 1.2 THz are successfully separated. In addition, by introducing a longer fiber gas cell of 60-cm length, the measurement sensitivity is improved and an absorption spectrum of NH3 gas with a concentration of 0.5 % is successfully detected.

In this work, Pd/Pt material based fiber Bragg grating (FBG) sensors has been proposed for detection of hydrogen sulfide gas. Here, characteristics of FBG parameters were numerically calculated and simulated. The variation in reflectivity based on refractive index has been shown. The reflectivity of FBG can be varied when refractive index is changed. The proposed sensor works on very low concentration i.e., 0% to 1%, which has the capability to detect in the early stage.

Stress-induced hyperglycemia is very common for patients in intensive care units, which can become fatal if left uncontrolled. Blood glucose concentrations for patients at the intensive care units should therefore be monitored at all times. To be successful in monitoring the glucose concentrations of patients, the sensor needs to be fast, accurate and able to measure in real time. In addition, the pH level should be monitored, as a diagnostic parameter by itself, or to improve the reliability of the glucose measurement. To address this challenge, a fiber optic sensor for dual parameter measurement of glucose concentration and pH level for use in point-of-care testing has been developed. The sensor utilizes two stimuli responsive hydrogels to create two interferometers combined on one single mode fiber. The sensor is created by splicing a short section of thin-core fiber (SM450) coated with a pH-sensitive polymer, which constitutes a Mach-Zehnder type interferometer. The glucose is measured with a low finesse Fabry-Perot cavity made by polymerizing a glucose sensitive hydrogel hemisphere at the end face of the fiber. A versatile Fourier transform based, low pass filter was developed, which enable evaluation of the two signals independently. Our results show the feasibility of measuring glucose concentration and pH level by using a single fiber. This dual parameter and single point fiber optic biosensor is expected to be of great interest for in vivo measurements in medical applications where pH and glucose, as specific markers are monitored in real time, during or after surgery.

Label-free fiber optical biosensor has a promising prospect in “point-of-care” (POC) test for disease diagnosis. A sensitive label-free fiber-optic based immunosensor for quantitative Cardiac Troponin I (cTn-I) testing has been proposed by using a phase-shifted Bragg grating directly inscribed in microfiber. The fine notch signal in the grating spectrum remarkably enhances the ability of the sensor in detecting an extremely small amount of immune binding events, which is essential for AMI diagnosis at very early stage. A cTn-I concentration of 6 pg/mL is enough to arouse the response of the sensor with high specificity. According to the log-linear range of the concentration between 0.1-10 ng/mL, measurements with shorter detection time are analyzed to demonstrate the potential of the sensor in the fast screen of the high-risk patients. The proposed sensing probe is compact and feasible, easy to handle, fabricate and network, making itself a competitive candidate in POC diagnosis of AMI.

For non-invasive blood glucose measurement, a measurement system based on mid-infrared ATR spectroscopy equipped with a combination of a QCL as a light source and a hollow-optical fiber as a beam delivery medium is developed. Firstly the measurement sensitivity of the system is evaluated by using glucose solutions and the result shows a significant correlation between optical absorbance and solution concentration. It is also confirmed that the system has a sensitivity that is enough for blood glucose measurement. Then optical absorption of human lips in the mid-infrared wavelength region is measured using a QCL with a wavenumber of 1080 cm^-1 where human tissue exhibits strong absorption of glucose and its metabolites. As a result, the measured absorption follows the change of blood glucose well with a time delay of around 10 minutes and correlation factor between the absorbance and the blood glucose level is 0.42.

Percutaneous coronary interventions are widely performed minimally invasive procedures used to treat narrowing (stenosis) of arteries in the heart. Differential blood pressure measurements across a stenosis are invaluable to estimate the prognostic benefit of performing angioplasty and stenting via calculation of the fractional flow reserve. Achieving stable measurements from within pressure microcatheters and guidewires that are compatible with stenosed vessels, and which can be fabricated with low cost manufacturing methods, remains an important challenge. We have developed all-optical pressure and temperature sensors with a single optical fibre and sensing element. This approach provides simultaneous temperature and pressure measurements in a highly miniaturised device, with a simple construction method using low cost materials. Polymeric structures including membranes and domes are applied to the distal ends of single mode optical fibres. Temperature and pressure changes induce time-varying displacements of these structures, which are monitored using phase-resolved low-coherence interferometry. Phase measurements are acquired at 250 Hz with a sensitivity of approximately 0.2 rad/°C for temperature measurements between 20 and 45°C, and approximately 0.08 rad/mmHg for pressure between 760 and 1060 mmHg. In vivo studies in arteries and hearts of sheep and swine indicate that the sensors have sufficient sensitivity and speed for measurement of physiological pressure waveforms in clinical settings. We will discuss the integration of these sensors within medical devices, and the potential for providing additional physiological parameters with the same devices.

Time-resolved spectroscopy in the presence of noise is challenging. We have developed a new 512 pixel line sensor with 16 single-photon-avalanche (SPAD) detectors per pixel and ultrafast in-pixel time-correlated single photon counting (TCSPC) histogramming for such applications. SPADs are near shot noise limited detectors but we are still faced with the problem of high dark count rate (DCR) SPADs. The noisiest SPADs can be switched off to optimise signal-to-noiseratios (SNR) at the expense of longer acquisition/exposure times than would be possible if more SPADs were exploited. Here we present detailed noise characterization of our array. We build a DCR map for the sensor and demonstrate the effect of switching off the noisiest SPADs in each pixel. 24% percent of SPADs in the array are measured to have DCR in excess of 1kHz, while the best SPAD selection per pixel reduces DCR to 53+/-7Hz across the entire array. We demonstrate that selection of the lowest DCR SPAD in each pixel leads to the emergence of sparse spatial sampling noise in the sensor.

We report on the employment of a biodegradable phosphate-based optical fiber as a pH sensing probe in physiological environment. The phosphate-based optical fiber preform was fabricated by the rod-in-tube technique. The fiber biodegradability was first tested in-vitro and then its biodegradability and toxicity were tested in-vivo. Optical probes for pH sensing were prepared by the immobilization of a fluorescent dye on the fiber tip by a sol-gel method. The fluorescence response of the pH-sensor was measured as a ratio of the emission intensities at the excitation wavelengths of 405 and 450 nm.

One approach to overcome the poor efficiency of the Raman scattering as a sensing platform is to use microstructured optical fibers. In this type of fibers with a longitudinal holey structure, light interacts with the target sample, which is confined in the core, giving rise to a light intensity increase of the obtained Raman spectra due to the large interaction distances and the guidance of the scattered light. In this work, we present an ad-hoc fabricated liquid-core microstructured polymer optical fiber (LC-mPOF) as a bio-sensing platform for Raman Spectroscopy. Arising from an initial simulation stage, we create the desired preform using the drilling technique and afterwards the LC-mPOF is drawn in our fiber drawing tower. The guiding mechanism of the light through the solution has a major importance, being a key factor to obtain appreciable enhancements in Raman scattering. In this case, in order to optimize the Raman scattering signal of dissolved glucose (target molecule), we have filled the core with an aqueous solution of the target molecule, enabling in this way the modified total internal reflection mechanism. Experimental Raman measurements are performed and results are discussed.

We present a near-infrared tunable vertical cavity surface emitting laser (VCSEL) based upon a unique electrothermally tunable microelectromechanical systems (MEMS) topside mirror designed for tissue imaging and sensing. At room temperature, the laser is tunable from 769-782nm with single mode CW output and a peak output power of 1.3mW. We show that the tunable VCSEL is suitable for use in frequency domain diffuse optical spectroscopy by measuring the optical properties of a tissue-simulating phantom over the tunable range. These results indicate that tunable VCSELs may be an attractive choice to enable high spectral resolution optical sensing in a wearable format.

A highly sensitive fiber-optic Fabry-Perot photoacoustic transducer is proposed in this work. The transducer will consist of separate transmit and receive fibers. The receiver will be composed of a Fabry-Perot Ultrasound sensor with a selfwritten waveguide with all-optical ultrasound detection with high sensitivity. In previous work, we have shown an increase in resonator Q-factor from 1900 to 3200 for a simulated Fabry-Perot ultrasound detector of 45 μm thickness upon including a waveguide to limit lateral power losses. Subsequently, we demonstrated a prototype device with 30nm gold mirrors and a cavity composed of the photosensitive polymer Benzocyclobutene. This 80 µm thick device showed an improvement in its Q-factor from 2500 to 5200 after a selfaligned waveguide was written into the cavity using UV exposure. Current work uses a significantly faster fabrication technique using a combination of UV-cured epoxies for the cavity medium, and the waveguide within it. This reduces the fabrication time from several hours to a few minutes, and significantly lowers the cost of fabrication. We use a dip-coating technique to deposit the polymer layer. Future work will include the use of Dielectric Bragg mirrors in place of gold to achieve better reflectivity, thereby further improving the Q-factor of the device. The complete transducer presents an ideal solution for intravascular imaging in cases where tissue differentiation is desirable, an important feature in interventional procedures where arterial perforation is a risk. The final design proposed comprises the transducer within a guidewire to guide interventions for Chronic Total Occlusions, a disease state for which there are currently no invasive imaging options.

Retinal photocoagulation techniques are widely used to treat various retinal diseases such as retinal detachment, diabetic retinopathy and ischemic retinal vein occlusion. The degree of coagulation, which plays important role for optimal surgical outcomes, depends on the tissue temperature achieved and the exposure time. The temperature distribution is affected by indeterminate characteristics, such as the pigmentation of the retinal tissue and the radiative transfer by its structure, in addition to the laser radiation condition. Therefore, an accurate measurement of the tissue temperature offers crucial information that could prevent excessive burning and collateral damage. There have been many researches on temperature monitoring methods using various sensors or imaging systems such as fiber optic sensor, ultrasound imaging, MRI, photoacoustic imaging, and optical coherence tomography (OCT). Among them, the OCT is a promising technique for retina imaging because it is a non-invasive system providing depth resolved images with microscale resolution. One of the OCT technique, speckle variance optical coherence tomography (svOCT), is known to detect moving molecules or coagulation in tissues sensitively by calculating changes of speckle pattern with time. In this paper, we proposed temperature monitoring of retinal tissues by svOCT imaging during photocoagulation since photocoagulation of retinal tissues is closely related to its temperature distribution. An ex-vivo bovine retina was continuously radiated by 10 mW green laser after removal of cornea, lens, and vitreous humor. SvOCT images of the retina was acquired every 1 minutes and analyzed with temperature data measured by thermometer. The results showed that speckle variance signal increases as temperature increases. Based on our result, we expect that svOCT will be an effective method for temperature monitoring to improve and automate laser treatments in ophthalmology.

Current methods for guiding cancer biopsies rely almost exclusively on images derived from X-ray, ultrasound, or magnetic resonance, which essentially characterize suspected lesions based only on tissue density. This paper presents a sensor integrated biopsy device for in situ tissue analysis that will enable biopsy teams to measure local tissue chemistry in real time during biopsy procedures, adding a valuable new set of parameters to augment and extend conventional image guidance. A first demonstrator integrating three chemical and biochemical sensors was tested in a mice strain that is a spontaneous breast cancer model. In all cases, the multisensory probe was able to discriminate between healthy tissue, the edge of the tumor, and total insertion inside the cancer tissue, recording real-time information about tissue metabolism.

Spectroscopic analysis of different biofluids and bodyfluid-like media has been realized by using tapered flat silver halide fiber elements as infrared biosensors. Optical stability and biocompatibility testing of the sensor elements have been performed with in-vitro samples under representative physiological conditions. After improving the reproducibility of manufacturing the sensor elements, the incoupling of radiation and the general handling including their chemical composition characterization, the fiber sensors were further optimized for the experiments. Stability tests in physiological solutions as well as porcine blood have shown that best results for biospectroscopic applications are available for the mid-IR fingerprint region, with the most stable behaviour as analyzed by the single-beam spectra. Despite several contrary reports, the silver halide material tested is toxic to cell lines chosen from the DIN standard specification for biocompatibility testing. Spectral changes as well as the results based on the DIN standard showed that pretreatment of the fibers is unavoidable to prevent direct contact of cells or human tissue and the silver halide material. Further applications of tapered flat silver halide fibers for the quantification of analytes in bodyfluids have also been tested by ensheathing the fiber-optic sensor element with a dialysis membrane. With the successfully produced prototype, results of diffusion rates and performance of a membrane-ensheathed fiber probe have been obtained. An invitro monitoring fiber sensor was developed aiming at the implantation of a microdialysis system for the analytical quantification of biomolecules such as glucose, lactate and others.

An endoscopic fluorescence imaging system based on fiber speckle illumination is proposed. In this system, a multimode fiber for transmission of excitation laser light and collection of fluorescence is inserted into a conventional flexible endoscope. Since the excitation laser light has random speckle structure, one can detect fluorescence signal corresponding to the irradiation pattern if the sample contains fluorophores. The irradiation pattern can be captured by the endoscope camera when the excitation wavelength is within the sensitivity range of the camera. By performing multiple measurements while changing the irradiation pattern, a fluorescence image is reconstructed by solving a norm minimization problem. The principle of our method was experimentally demonstrated. A 2048 pixels image of quantum dots coated on a frosted glass was successfully reconstructed by 32 measurements. We also confirmed that our method can be applied on biological tissues.

High-purity chalcogenide glasses and fiber draw processes enable the production of state-of-the-art mid-infrared fibers for 1.5 to 10 micron transmission. Multimode and single-mode mid-infrared fibers are produced with low-loss (<0.2 dB/m), high tensile strength (>25 kpsi), and high power laser handling capability (>11.8 MW/cm²). Chalcogenide fibers support the development of cutting-edge devices for mid-infrared medical applications. Connectorized cables transmit laser power to a sample or mid-infrared radiation to a detector. Broadband antireflection microstructures are thermally stamped on the chalcogenide fiber tip to reduce the surface reflection from 17% to <5%. Also custom fiber-optic probe bundles are made with multiple fiber legs (source, sample, signal) for reflection and backscatter spectroscopy measurement. For example, a 7 x 1 fiber probe bundle is presented. Additionally imaging fiber bundle is made to perform remote thermal and spectral imaging. Square preforms are drawn, stacked, squared and fused multiple times to produce a 64 x 64 imaging fiber bundle with fiber pixel size of 34 microns and the numerical aperture of 0.3. The 2- meter long imaging fiber bundle is small (2.2 mm x 2.2 mm), flexible (bend radius >10 mm) and transmits over the spectral range of 1.5 to 6.5 micron.

Breast cancer is the most frequently diagnosed cancer among women in the Western world. Currently, no imaging technique assesses tumor heat generation and vasculature changes during radiotherapy in viable tumor and as adjuvant therapy. Thermography is a non-ionizing, non-invasive, portable and low-cost imaging modality. The purpose of this study was to investigate the use of thermography in cancer treatment monitoring for feedback purposes. Six stage-IV breast cancer patients with viable breast tumor and 8 patients (9 breasts) who underwent tumor resection were monitored by a thermal camera prior to radiotherapy sessions over several weeks of radiation treatment. The thermal changes over the treated breast were calculated and analyzed for comparison with healthy surrounded breast tissue or contralateral breast. A model of a breast with a tumor was created. The COMSOL FEM software was used to carry out the analysis. The effects of tumor metabolism and breast tissue perfusion on the temperature difference were analyzed. All patients with active tumors exhibited drops in maximal temperature of the tumor during radiation therapy. The patients who underwent radiotherapy as adjuvant treatment exhibited a rise in maximal temperature over the treated breast in correlation with skin erythema during radiation. This difference between the groups was statistically significant (P=0.001). The simulated human breast cancer models analysis showed that tumor aggressiveness reduction causes decrease in the tumor temperature. Inflammation causes vasodilatation and increases tissue perfusion, resulted in an increase in breast tissue temperature. A correlation was demonstrated between the clinical outcome and the simulation. We report a method for monitoring cancer response to radiation therapy, which measures the physiological response along with clinical response. These anticipatory efficacy evaluations of radiotherapy during treatment may further promote changes in treatment regimen, either radiation associated or combination as in chemo-radiation protocols. The probable treatment delivery changes may incorporate the total dose delivery, fraction dose and intensity as well as adding chemotherapy for non-responding tumors during radiotherapy. All the above possibilities will contribute to the advances of individualized, personalized cancer treatment for optimal treatment effectiveness.

Er:YAG lasers (3μm) allow efficient bone ablation caused by the strong absorption in water. Unfortunately, there are only a few and comparable expensive fiber materials for this wavelength available which are suitable for high laser power. The bone ablation efficiency of the Tm:YAG laser is minor (2μm) but inexpensive silica fibers can be used. The aim of this study was to investigate the bone ablation, using novel diode pumped high power Er:YAG (laser power 40W) and Tm:YAG laser system (60W) and adaptive fiber delivery systems. Expected advantage of these lasers is the longer lifetime of the fibers because of the high repetition rate and low pulse energy compared to the flash lamp pumped laser systems. The bare fiber output ends of a sapphire fiber (Er:YAG laser) and of a silica fiber (Tm:YAG laser) were attached under water and a water filled container including the fixed sample (bovine bone slices) was moved by a computer controlled translation stage. In a second set-up we provided a focusing unit and appropriate water spray unit. The generated cut kerfs were analyzed by light microcopy and laser scanning microscopy. The results show that with the diode pumped Er:YAG laser and sapphire fiber a particular high efficient bone ablation (> 0.16mm²/J) is possible both with bare fiber under water and focusing unit with water spray. The higher power of the Tm:YAG laser also results in high ablation rates but causes enlarged thermal damages. In conclusion, this study demonstrates that efficient bone ablation is possible with both diode pumped laser systems. In terms of efficiency the Er:YAG laser is outstanding. The Tm:YAG laser also allows fast bone ablation, provided that the thermal impact is limited by effective cooling and high movement velocity of the laser spot, for example by using an automatic scanner.

We present a multifunctional endoscope capable of imaging, fluid delivery and fluid sampling in the alveolar space. The endoscope consists of an imaging fibre bundle fabricated from cost effective OM1 PCVD graded index preforms made for the telecommunications market. These low-cost fibres could potentially make our endoscope disposable after a single use. The performance of our low-cost imaging fibre bundle is shown to be comparable to the current commercial state-of-the-art. The imaging fibre bundle is packaged alongside two channels for the delivery and extraction of fluids. The fluid delivery channels can be used to deliver fluorescent smart probes for the detection of pathogens and to perform a targeted alveolar lavage without the removal of the imaging fibre as is currently standard procedure. Our endoscope is fully biocompatible and with an overall outer diameter of 1.4 mm allowing it to fit into the standard working channel of a bronchoscope. We demonstrate the use of our endoscope in ex-vivo human lungs. We show alveolar tissue and bacterial imaging over two wavelength bands 520 nm – 600 nm and 650 nm – 750 nm both commonly used for bacterial smart probe detection.

Plasmon-enhanced spectroscopies such as surface-enhanced Raman spectroscopy (SERS) concern the detection of enhanced optical responses of molecules in close proximity to plasmonic structures, which results in a strong increase in sensitivity. Recent advancements in nanofabrication methods have paved the way for a controlled design of tailor-made nanostructures with fine-tuning of their optical and surface properties. Among these, silver nanocubes (AgNCs) represent a convenient choice in SERS owing to intense electromagnetic fields localized at their extremities, which are further intensified in the gap regions between closely spaced nanoparticles. The integration of AgNCs assemblies within an optofluidic platform may confer potential for superior optical investigation due to a molecular enrichment on the plasmonic structures to collect an enhanced photonic response. We developed a novel sensing platform based on an optofluidic system involving assembled silver nanocubes of 50 nm in size for ultrasensitive SERS detection of biomolecules in wet conditions. The proposed system offers the perspective of advanced biochemical and biological characterizations of molecules as well as of effective detection of body fluid components and other molecules of biomedical interest in their own environment.

The under laid gas and oil pipelines on the seafloor are prone to various disturbances like seismic movements of the sea bed, oceanic currents, tsunamis. These factors tend to damage such pipelines connecting different locations of the world dependent on these pipelines for their day-to-day use of oil and natural gas. If damaged, the oil spills in the water bodies cause grave loss to marine life along with serious economic issues. It is not feasible to monitor the undersea pipelines manually because of the huge seafloor depth. For timely detection of such damage, a new technique using optical Fiber Bragg grating (FBG) sensors and its installation has been given in this work. The idea of an FBG sensor for detecting damage in pipeline structure based on the acoustic emission has been worked out. The numerical calculation has been done based on the fundamental of strain measurement and the output has been simulated using MATLAB.

Photoacoustic imaging system using a bundle of hollow-optical fibers to detect hidden dental caries is proposed. Firstly, we fabricated a hidden caries model with a brown pigment simulating a common color of caries lesion. It was found that high frequency ultrasonic waves are generated from hidden carious part when radiating Nd:YAG laser light with a 532 nm wavelength to occlusal surface of model tooth. We calculated by Fourier transform and found that the waveform from the carious part provides frequency components of approximately from 0.5 to 1.2 MHz. Then a photoacoustic imaging system using a bundle of hollow optical fiber was fabricated for clinical applications. From intensity map of frequency components in 0.5-1.2 MHz, photoacoustic images of hidden caries in the simulated samples were successfully obtained.

Hollow core fibers (HCFs) have found extensive use for biological sensing applications, with areas such as Raman spectroscopy being of key interest for deployment of these fibers due to their low Raman background and broad transmission spectral windows. However, fabrication of these fibers is currently based on capillary stacking of hollow tubes, a complex, time-consuming and therefore costly process that limits their potential for use in practical devices. Glass billet extrusion, an alternative to the capillary stacking process, presents a potential pathway to reducing the high fabrication cost of HCFs. Extrusion is a process in which a glass billet is heated to its softening point and is then forced through a metallic die containing the inverse of the desired structure. This is a one-step, automated process that requires no manual stacking to obtain the desired glass preform. Initial work using extrusion for HCF fabrication has resulted in fibers with large variations in the uniformity of the core walls, leading to increases in the optical loss of these fibers over the theoretical predictions. Here we present work on improvements to the extrusion process of these fibers, aiming to both reduce the loss of the fibers. Several iterations of the die exit geometry are shown to affect the geometry and uniformity of the preform structure, which translates into changes in the final fiber geometry and therefore the transmission properties of the HCFs. The fabrication methods used here show strong potential for improved guidance properties in future generations of HCFs.

Breast lesions diagnosis and characterization need additional cost-effective techniques to avoid unnecessary invasive procedures, such as core needle biopsies, in the case of benign tumors. Endogenous fluorescence is an effective method to highlight in situ metabolic and/or structural changes between cancerous and non-cancerous lesions. In this context, we developed an original set-up, consisting of a 405 nm laser diode transmitting light through a 25 Gauge (0.45 mm x 50mm) 14° sharp fibered needle to excite intranodular fluorophores around the needle tip and providing real-time labelfree fluorescence spectral analysis of lesions from 450 nm to 650 nm. The objective was to help radiologists to classify suspicious masses in vivo and in real-time within the lesion. We reported the results of spectral differences between 14 invasive lobular carcinomas and 6 intraductal papilloma enrolled in a clinical study.

The treatment using photodynamic therapy (PDT) among cancer treatment methods shows remedial value in various cancers. The optical fiber probe infiltrates into affected parts of the tissues that are difficult to access, such as pancreatic cancer, carcinoma of extrahepatic bile duct, prostate cancer, and bladder cancer by using endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic ultrasonography (EUS) with various types of diffusing tips.

In this study, we developed cylindrical diffusing optical fiber probe (CDOFP) for PDT, manufactured ball-shaped end which is easily infiltrated into tissues with diffusing length ranging from 10mm to 40mm through precision laser processing, and conducted beam profile characterization of manufactured CDOFP. Also, chemical reaction between photo-sensitizer and laser in PDT is important, and hence the thermal effect in tissues as per diffusing length of probe was also studied as it was used in a recent study.

Hollow glass waveguides (HGWs) have been extensively investigated for the transmission of broadband, high-power radiation, particularly in the mid-infrared. One area of particular interest is the deposition of dielectric thin films within the hollow core of the HGW in order to reduce the losses at desired wavelengths. By implementing a thin film multilayer structure with high index mismatch between adjacent films, it is possible to dramatically improve the losses of the waveguides due to the thin film interference effect. Existing multilayer film research has utilized heavy metal halides, which although provide considerable index contrast, are toxic and unsuitable for clinical applications in which they are often used. Polymer dielectric thin films provide desirable optical properties for HGWs but are hindered by solvent compatibility in the deposition procedure. This work demonstrates implementation of a polymer multilayer dielectric thin film stack within a HGW, using ChemoursTM Teflon AF (n = 1.29) as the low-index material and polystyrene (n = 1.59) as the high-index material. These two polymers were deposited using liquid phase techniques within a HGW; the absorption spectra of waveguide as each layer was deposited on was analyzed in the mid-IR with an FTIR, and straight and bending losses were measured on a CO₂ laser. Appreciable losses were realized with the addition of the second polymer film and the interference bands red-shifted with the second layer, suggesting the successful creation of the multilayer structure.

An optical fibre sensor for monitoring low dose radiation is presented. The sensor is based on a scintillation material embedded within the optical fibre core, which emits visible light when exposed to low level ionising radiation. The incident level of ionising radiation can be determined by analysing the optical emission. An optical fibre sensor is developed, based on radioluminescence whereby radiation sensitive scintillation material, terbium doped gadolinium oxysulphide (Gd₂O₂S:Tb), is embedded in a cavity of 700μm of a 1mm plastic optical fibre. The sensor is designed for in-vivo monitoring of the radiation dose during radio-active seed implantation for low dose rate (LDR) brachytherapy, in prostate cancer treatment, providing radiation oncologists with real-time information of the radiation dose to the target area and/or nearby organs at risk (OARs). The radiation from the brachytherapy seeds causes emission of visible light from the scintillation material through the process of radioluminescence, which penetrates the fibre, propagating along the optical fibre for remote detection using a multi-pixel photon counter. The sensor demonstrates a high sensitivity to 0.397mCi of Iodine125, the radioactive source most commonly used in brachytherapy for treating prostate cancer.

In recent works it has been demonstrated the suitability of using resonant nanopillars (R-NPs) as biochemical. In this work it has been shown the capability of the R-NPs to behave as label-free multiplexed biological sensors. Each R-NP is formed by silicon oxide (SiO2) and silicon nitride (Si3N4) Bragg reflectors and a central cavity of SiO₂, and they are grouped into eight arrays called BICELLs, which are distributed on a single chip of quartz substrate for multiplexing measurements. For the biological sensing assessment it was developed an immunoassay on the eight single BICELLs. The biofunctionalization process was performed by a silanization protocol based on 3-aminopropyltrymethoxysilane (APTMS) and glutaradheyde (GA) as a linker between APTMS and the IgG which acted as biorreceptor for the anti-IgG recognition. In this work, there were compared two forms of immobilization: on one hand by incubating the R-NPs under static drop of 50 μg/mL and on the second hand by introducing the sensing chip in a flow cell with a continuous flow of the same concentration of IgG. The eight arrays of R-NPs or BICELLs were independently optically interrogated by a bundle of fiber connected to a spectrometer. The multiplexing analysis showed reproducibility among the BICELLs, suggesting the potentially of using R-NPs for multiplexed biosensors. Performance in the immobilization process apparently does not have a signification effect. However the election of one method or another should be a commitment between time and resources.

Purpose: Optical stimulation methods in development aim to provide high spatial selectivity of target tissue, overcoming a critical limitation of contemporary neural prostheses. The purpose of this study is to determine if tapered fibers are capable of delivering the minimum necessary power density 1W/mm2 within a 0.050mm spot size to induce focused infrared neural stimulation (INS). Materials: A numerical simulation program based on equations derived from Snell’s law was developed in MATLAB to predict the energy emitted from a tapered fiber coupled to a Capella laser (λ=1863nm, Lockheed Martin Aculight). Energy predictions were compared to emittance from a tapered fiber (core diameter = 200µm, tapered output face = 50µm, NA=0.22) to determine its accuracy. Energy measurements were made at 17.8, 41.6, 65.4, 89.3, and 113.1µJ output energy and at distances between 0-2 mm from the fiber-tip with a Coherent FieldMax Energy meter coupled to a detector with a 2.1 mm aperture. Results: Mean difference between the predicted and measured energy ranged from 4.3±1.9µJ (17.8µJ) to 16.3±11.3 µJ (113.1µJ). Minimum required power density within a 0.05 mm spot size was predicted to be achieved at 0 mm for all energies, at 2 mm for 41.6µJ, and at distances ≥ 1.0 mm for 17.8 µJ. Conclusion: A numerical simulation program was developed that accurately predicts within minimal error the emittance from a tapered fiber. The predicted results indicate feasibility of tapered optical fibers to provide a more efficient and selective means of delivering the minimum power density necessary to achieve INS.

Refractive index measurement is important for evaluation of liquid materials, optical components, and bio sensing. One promising approach for such measurement is use of optical fiber sensors such as surface plasmonic resonance or multi-mode interference (MMI), which measure the change of optical spectrum resulting from the refractive index change. However, the precision of refractive index measurement is limited by the performance of optical spectrum analyzer. If such the refractive index measurement can be performed in radio frequency (RF) region in place of optical region, the measurement precision will be further improved by the frequency-standard-based RF measurement. To this end, we focus on the disturbance-to-RF conversion in a fiber optical frequency comb (OFC) cavity. Since frequency spacing f_rep of OFC depends on an optical cavity length nL, f_rep sensitively reflects the external disturbance interacted with nL. Although we previously demonstrated the precise strain measurement based on the f_rep measurement, the measurable physical quantity is limited to strain or temperature, which directly interacts with the fiber cavity itself. If a functional fiber sensor can be installed into the fiber OFC cavity, the measurable physical quantity will be largely expanded. In this paper, we introduce a MMI fiber sensor into a ring-type fiber OFC cavity for refractive index measurement. We confirmed the refractive-index-dependent f_rep shift.

We present a balanced detection method for spectral domain optical coherence tomography (SD-OCT) using a fiberoptic phase shifter. SD-OCT systems typically use a single line scan camera to detect the spectrogram, and noninterfered signals are not excluded from the recorded signal. That limits dynamic range and reduces image quality. Balanced detection methods are used to overcome these problems in swept-source OCT system. Detection using two line scan cameras or multi line camera was proposed to perform the balanced detection in SD-OCT systems. Time delayed replica generated by long optical fiber have been made for that purpose. To induce a phase shift in interference signal, we used a phase shifting interferometry based on an optically tunable phase shifter. The proposed phase shifter can control refractive index variations using the optical power of the pumping beam incident on the rare-earth doped optical fiber. Phase shifts on the optical power represent non-linear behavior and require optimized tuning for proper phase shift. We measured the spectrogram and analyzed the phase change characteristics. By subtracting the phase-shifted replica from the original interference signal, the amplitude of the interference signal is doubled and sensitivity is improved. We prove balanced detection performance based on a phase shifting interferometer.

We developed SRS-sensor 13C/12C isotops measurements detecting Helicobacter Pylori for medical diagnostics of human health. Measuring of absolute 13С/12С isotope amount ratios allows to explore the topical problems of the modern world, alcoholic beverages and tobacco, medical diagnostics of human health. SRS method is used to measure the ratio of carbon isotopes in the exhaled carbon dioxide, which is used to diagnose the human infection of Helicobacter pylori and the influence of the Helicobacter pylori bacterium on the occurrence of gastritis, gastric and duodenal ulcers. A method for the analysis of human infection with Helicobacter pylori was developed on the basis of measurements of the ratio of 13C / 12C carbon isotopes in human exhaled air with a high level of measurement accuracy. The article reviews the work in the field of provision comparability of absolute 13С/12С isotope amount ratios in the environment and food. The analysis of the technical and metrological characteristics of traditional and perspective instruments for measuring isotope ratios is presented. The provision of comparability of absolute 13С/12С isotope amount ratios is carried by gravimetrically prepared reference standards. The key features and emerging issues are discussed.