This PDF file contains the front matter associated with SPIE Proceedings Volume 8576, including the Title Page, Copyright Information, Table of Contents, and the Conference Committee listing.

A rugged hollow fiber is fabricated by liquid-phase coating techniques. A silica glass capillary is used as the substrate and a vitreous film is firstly coated on the inner surface of the capillary to protect the glass tube from moisture. This protective coating keeps the thin-wall glass tube away from damage due to the following silver plating process. On the protective coating, a silver film is deposited by the conventional mirror plating technique. Subsequently, a polymer film is coated on the silver film to reduce transmission loss by employing interference effect of the polymer film. Fabrication processes and transmission properties of the rugged polymer-coated silver hollow fiber were discussed. The loss for the 700-μm-bore size, 1-m-length hollow fiber was 2 dB under straight configuration, and 3.5 dB under the configuration of a 270 degree bending with a 15-mm bending radius at the wavelength of 2.94 μm.

We demonstrate a digital phase conjugation technique for generating a sharp focus point at the end of a multimode optical fiber. A sharp focus is experimentally obtained at the distal end of a 200μm core multimode fiber. By recording the digital holograms for different excitation conditions, the sharp focus can be digitally scanned over a 175μm diameter regular grid. The demonstrated technique is used for high resolution scanning lensless imaging based on multimode fibers, of stained biological samples that can enable diagnosis from the investigation of cellular phenotype.

The most common optical method to validate intracellular gene delivery in cancer is to detect tagged fluorescence signals from the cells. However, fluorescent detection is usually performed in vitro due to the limitation of standard microscopes. Herein, we propose a highly sensitive dual-modality fiber-optic imager (DFOI), which enables in vivo fluorescence imaging. Our system uses a coherent fiber bundle based imager capable of simultaneously performing both confocal reflectance and fluorescent microscopy. Non-viral vectors targeting human cervical cancer cells (HeLa) were used to evaluate the performance. Preliminary results demonstrated the DFOI is promising for in vivo evaluation of intracellular gene delivery.

In the brain-cell microenvironment, diffusion plays an important role: apart from delivering glucose and oxygen from the vascular system to brain cells, it also moves informational substances between cells. The brain is an extremely complex structure of interwoven, intercommunicating cells, but recent theoretical and experimental works showed that the classical laws of diffusion, cast in the framework of porous media theory, can deliver an accurate quantitative description of the way molecules are transported through this tissue. The mathematical modeling and the numerical simulations are successfully applied in the investigation of diffusion processes in tissues, replacing the costly laboratory investigations. Nevertheless, modeling must rely on highly accurate information regarding the main parameters (tortuosity, volume fraction) which characterize the tissue, obtained by structural and functional imaging. The usual techniques to measure the diffusion mechanism in brain tissue are the radiotracer method, the real time iontophoretic method and integrative optical imaging using fluorescence microscopy. A promising technique for obtaining the values for characteristic parameters of the transport equation is the direct optical investigation using optical fibers. The analysis of these parameters also reveals how the local geometry of the brain changes with time or under pathological conditions. This paper presents a set of computations concerning the mass transport inside the brain tissue, for different types of cells. By measuring the time evolution of the concentration profile of an injected substance and using suitable fitting procedures, the main parameters characterizing the tissue can be determined. This type of analysis could be an important tool in understanding the functional mechanisms of effective drug delivery in complex structures such as the brain tissue. It also offers possibilities to realize optical imaging methods for in vitro and in vivo measurements using optical fibers. The model also may help in radiotracer biomarker models for the understanding of the mechanism of action of new chemical entities.

Optical fibers with different types of polymer coatings were exposed to three sterilization conditions: multiple autoclaving, treatment with ethylene oxide and treatment with gamma rays. Effects of different sterilization techniques on key optical and mechanical properties of the fibers are reported. The primary attention is given to behavior of the coatings in harsh sterilization environments. The following four coating/buffer types were investigated: (i) dual acrylate, (ii) polyimide, (iii) silicone/PEEK and (iv) fluoroacrylate hard cladding/ETFE.

In this paper we present a study of laser damage to large core multimode glass optical fibers by high peak laser power of up to 175 kW. Fibers samples prepared with polymer coatings having different refractive indices were tested in a two-point bend tester while transmitting laser light. The peak power used in the experiment clearly differentiated the performance among the samples. A polymer coating having lower refractive index significantly improves the fiber resistance to bending while transmitting laser. This observation provides important insight into the damage mechanism for this particular failure mode.

In this work we present the delivery of high energy Er:YAG laser pulses operating at 2.94 μm through a hollow-core negative curvature fibre (HC-NCF) and a hollow-core photonic crystal fibre (HC-PCF) and their use for the ablation of biological tissue. In HC-NCF fibres, which have been developed recently, the laser radiation is confined in a hollow core and by an anti-resonant or reflection principle (also known as ARROW). Both fibres are made of fused silica which has high mechanical and chemical durability, is bio-inert and results in a fibre with the flexibility that lends itself to easy handling and minimally invasive procedures. The HC-NCF structure consists of only one ring of capillaries around a realtively large core, followed by a protecting outer layer, hence the preform is relatively easy to build compared to traditional HC-PCF. The measured attenuation at 2.94 μm is 0.06 dB/m for the HC-NCF and 1.2 dB/m for the HC-PCF. Both fibres have a single mode output beam profile which can be advantageous for surgical applications as the beam profile is maintained during fibre movement. We demonstrate delivery of high energy pulses through both fibres, well above the thresholds needed for the ablation of biological tissue in non-contact and contact mode. Delivered energy densities reached > 750 J/cm^-2 after 10 m of HC-NCF and > 3400 J/cm² through a 44 cm HC-PCF.

We propose a dual-channel fiber scanning probe for simultaneous measurement of swept source optical coherence tomography (SS OCT) and fluorescence spectroscopy (FS) signals. For the purpose, SS OCT and FS system were combined by adopting the specially fabricated double cladding fiber (DCF) and wavelength division multiplexer (WDM) coupler, and DCF fiber was directly connected to sample arm of DCF coupler for fiber-based probe. Moreover, for sample scanning, the fiber was driven by piezoelectric bender. Since DCF has dual-channel configuration consists of core and inner cladding, both OCT and FS signals propagate through the two channels at the same time. Therefore, the suggested system enables multifunctional imaging that would make it possible to determine a more specific diagnosis. To demonstrate the feasibility of the probe, a photosensitizer injected in-vivo mice were imaged with scanning speed of 16 Hz and scanning range of 2 mm.

Raman spectroscopy is a vibrational analytic technique sensitive to the changes in biomolecular composition and conformations occurring in tissue. With our most recent development of depth-resolved near-infrared (NIR) Raman endoscopy integrated with on-line diagnostic algorithms, in vivo real-time epithelial diagnostics has been realized under multimodal wide-field imaging (i.e., white- light reflectance (WLR), narrow-band imaging (NBI), autofluorescence imaging (AFI)) modalities. A selection of 43 patients who previously underwent Raman endoscopy (n=146 spectra) was used to render a robust model based on partial least squares - discriminant analysis (PLS-DA) for diagnosis of dysplasia in Barrett’s esophagus. The Raman endoscopy technique was validated prospectively on 2 new esophageal patients for in vivo tissue diagnosis. The Raman endoscopic technique could identify esophageal high-grade dysplasia in vivo with an accuracy of 85.9% (sensitivity: 91.3% (21/23): specificity 83.3% (40/48)) on spectrum basis. This study realizes for the first time depth-resolved Raman endoscopy for real-time in vivo diagnosis of dysplasia in Barrett’s epithelium at the biomolecular level.

In this work the inner surface of a microstructured optical fiber, where a Bragg grating was previously inscribed, has been functionalized using peptide nucleic acid probe targeting a DNA sequence of the cystic fibrosis disease. The solution of DNA molecules, matched with the PNA probes, has been infiltrated inside the fiber capillaries and hybridization has been realized according to the Watson - Crick Model. In order to achieve signal amplification, oligonucleotide-functionalized gold nanoparticles were then infiltrated and used to form a sandwich-like system. Experimental measurements show a clear wavelength shift of the reflected high order mode for a 100 nM DNA solution. Several experiments have been carried out on the same fiber using the identical concentration, showing the same modulation and proving a good reproducibility of the results, suggesting the possibility of the reuse of the sensor. Measurements have been also made using a 100 nM mis-matched DNA solution, containing a single nucleotide polymorphism, demonstrating the high selectivity of the sensor.

The present work demonstrates the integration of hollow core photonic crystal fibers (HC-PCF), microfluidics, and statistical analysis for monitoring biomolecules using Raman spectroscopy. HC-PCF as a signal enhancer has been proven by many researchers. However, there have been challenges in using HC-PCF for practical applications due to limitations such as coupling, stability, evaporation, clogging, consistent filling, and reusing the same fiber. This limited the potential of HC-PCF to detect low concentrations of liquid samples, which is why HC-PCF still hasn’t transcended the lab barriers. The current device is based on an H-design lay-out which uses the pressure difference between the two ends of the fiber for filling and flushing the liquid samples. This mitigated several issues related to device performance by allowing us to fill the fiber with liquid samples consistently, rapidly and reproducibly. The resulting Raman signals were significantly more stable as various concentrations of ethanol in water were sequentially introduced into the fiber. The scheme also allowed us to overcome the barrier of predicting low concentrations by applying Partial Least Square (PLS) technique which was done for the first time using HC-PCF. Thus, the present scheme paves path for the inclusion of HC-PCF in the main stream point-of-care technology.

This paper describes a new infusion catheter, based on our fiberoptic microneedle device (FMD), designed with the objective of photothermally augmenting the volumetric dispersal of infused therapeutics. We hypothesize that concurrent delivery of laser energy, causing mild localized photothermal heating (4-5 °C), will increase the spatial dispersal of infused chemotherapy over a long infusion period. Agarose brain phantoms, which mimic the brain’s mechanical and fluid conduction properties, were constructed from 0.6 wt% Agarose in aqueous solution. FMDs were fabricated by adhering a multimode fiberoptic to a silica capillary tube, such that their flat-polished tips co-terminated. Continuous wave 1064 nm light was delivered simultaneously with FD&C Blue #2 (5%) dye into phantoms. Preliminary experiments, where co-delivery was tested against fluid delivery alone (through symmetrical infusions into in vivo rodent models), were also conducted. In the Agarose phantoms, volumetric dispersal was demonstrated to increase by more than 3-fold over a four-hour infusion time frame for co-delivery relative to infusion-only controls. Both forward and backward (reflux) infusions were also observed to increase slightly. Increased volumetric dispersal was demonstrated with co-delivery in an in vivo rodent model. Photothermal augmentation of infusion was demonstrated to influence the directionality and increase the volume of dye dispersal in Agarose brain phantoms. With further development, FMDs may enable a greater distribution of chemotherapeutic agents during CED therapy of brain tumors.

During freehand performance of vitreoretinal microsurgery the surgeon must perform precise and stable maneuvers that achieve surgical objectives and avoid surgical risk. Here, we present an improved smart handheld microsurgical tool which is based on a ball lens fiber optic sensor that utilizes common path swept source optical coherence tomography. Improvements include incorporation of a ball lens single mode fiber optic probe that increases the working angle of the tool to greater than 45 degrees; and increases the magnitude of the distance sensing signal through water. Also presented is a cutting function with an improved ergonomic design.

Medical treatments benefit from increased sharpness of radiation emission or detection. Noncircular core silica/silica optical fibers have benefits of better control of irradiation of diseased tissue and more uniform irradiations. Description of tested fiber structures and others available are presented Data will be presented on mechanical reliability of such fibers, primarily, medium-to-long term static fatigue experiments as well as shorter term strength experiments. Spectral behavior will also be presented. The loss of radial symmetry provides for more uniform output across the core face. These fibers have mechanical properties remarkably as good as standard circular core fibers, with high dynamic strengths and very good Static Fatigue Parameters.

In the past, the spectral stability of multimode UV-fibers has been mainly characterized using deuterium lamps with a broadband spectrum in the DUV. In meantime, new UV light-sources with higher powers are available. For example, improved pulsed Nd:YAG lasers with higher harmonics or high-power broadband plasma lamps are interesting candidates for new systems and applications. Because of better beam quality, multimode all-silica fibers with core diameter smaller than 100 μm can be recommended. A new step-index fiber with a large cladding-to-core ratio will be introduced. Using the new light-sources, the degradation during UV-light delivery will be described in detail, comparing the hydrogen-loaded and non-loaded version of this fiber. These results of UV-induced damage will be compared to a commercially available improved 100 μm UV-fiber damaged with deuterium lamp.

A scanning fiber endoscope (SFE) and the cancer biomarker 5-aminolevulinic acid (5-ALA) were used to fluorescently detect and destroy superficial cancerous lesions, while experimenting with different dosimetry levels for concurrent or sequential imaging and laser therapy. The 1.6-mm diameter SFE was used to fluorescently image a confluent monolayer of A549 human lung cancer cells from culture, previously administered with 5 mM solution of 5-ALA for 4 hours. Twenty hours after therapy, cell cultures were stained to distinguish between living and dead cells using a laser scanning confocal microscope. To determine relative dosimetry for photodynamic therapy (PDT), 405-nm laser illumination was varied from 1 to 5 minutes with power varying from 5 to 18 mW, chosen to compare equal amounts of energy delivered to the cell culture. The SFE produced 500-line images of fluorescence at 15 Hz using the red detection channel centered at 635 nm. The results show that PDT of A549 cancer cell monolayers using 405nm light for imaging and 5-ALAinduced PpIX therapy was possible using the same SFE system. Increased duration and power of laser illumination produced an increased area of cell death upon live/dead staining. The ultrathin and flexible SFE was able to direct PDT using wide-field fluorescence imaging of a monolayer of cultured cancer cells after uptaking 5-ALA. The correlation between light intensity and duration of PDT was measured. Increased length of exposure and decreased light intensity yields larger areas of cell death than decreased length of exposure with increased light intensity.

Skin perfusion and oxygenation is easily disrupted by imposed pressure. Fiber optics probes, particularly those spectroscopy or Doppler based, may relay misleading information about tissue microcirculation dynamics depending on external forces on the sensor. Such forces could be caused by something as simple as tape used to secure the fiber probe to the test subject, or as in our studies by the full weight of a patient with spinal cord injury (SCI) sitting on the probe. We are conducting a study on patients with SCI conducting pressure relief maneuvers in their wheelchairs. This study aims to provide experimental evidence of the optimal timing between pressure relief maneuvers. We have devised a wireless pressure-controlling device; a pressure sensor positioned on a compression aluminum plate reads the imposed pressure in real time and sends the information to a feedback system controlling two position actuators. The actuators move accordingly to maintain a preset value of pressure onto the sample. This apparatus was used to monitor the effect of increasing values of pressure on spectroscopic fiber probes built to monitor tissue oxygenation and Doppler probes used to assess tissue perfusion.

Metal coated Hollow Glass Waveguides (HGWs) incorporating single dielectric thin films have been widely used for the low-loss transmission of infrared radiation in applications ranging from surgery to spectroscopy. While the incorporation of single dielectric film designs have traditionally been used in metal/dielectric coated HGWs, recent research has focused on the development of alternating low/high refractive index multilayer dielectric thin film stacks for further transmission loss reduction. Continuing advances in the deposition of optically functional cadmium sulfide and lead sulfide thin films in HGWs have allowed for the simultaneous increase in film quality and greater film thickness control necessary for the implication of such multilayer stack designs for enhanced reflectivity at infrared wavelengths. This study focuses on the theoretical and practical considerations in the development of such multilayer stack coated waveguides and presents novel results including film growth kinetics of multilayer stack thin film materials, IR spectroscopic analysis, and IR laser attenuation measurements. The effects of incorporating progressive alternating cadmium sulfide and lead sulfide dielectric thin films on the optical properties of next generation dielectric thin film stack coated HGWs in the near and mid infrared regions are thoroughly presented. The implications of incorporating such dielectric multilayer stack coatings based on metal sulfide thin films on the future of IR transmitting hollow waveguides for use in applications ranging from spectroscopy, to high laser power delivery are briefly discussed.

An optical fiber ultrasound probe for all-optical photoacoustic endoscopy imaging is developed. The probe has a Fabry Perot interferometer consisting of a polymer film attached at the end surface of a single-mode optical fiber. The interferometer detects acoustically-induced pressure change in the optical thickness and transforms the change into output optical power. Experimental results show that the probe functions well as a photoacoustic probe and the SNR is comparable to that of a PVDF hydrophone. Results for B-mode imaging of blood vessel phantom taken by using the fiber probe are also shown.

Low-loss hollow waveguides with multiple dielectric layer are designed and fabricated for use in cavity ring-down spectroscopy. The waveguides are composed of four glass strips with dielectric multilayer that are deposited on the surface in advance. Experimental results show that the waveguides with double dielectric layers have lower losses at a target wavelength in the infrared than those with a single dielectric layer.

An infrared spectroscopy system based on a hollow-optical fiber probe for measurement of blood glucose concentration is developed. The probe consists of a flexible hollow-optical fiber and an ATR prism attached at the distal end of the fiber. This flexible probe enables measurement of oral mucosa and ear lobes that have blood capillaries near the skin surface. Experimental results show that absorption peaks of blood glucose are detected by the system.

Whispering gallery mode resonators (WGMR), as silica microspheres, have been recently proposed as an efficient tool for the realisation of optical biosensors. In this work we present a functionalization procedure based on the DNA-aptamer sequence immobilization on WGMR, able to recognize specifically thrombin or VEGF protein, preserving a high Q factor. The protein binding was numerically modelled and optically characterized in terms of specificity in buffer solution or in 10% diluted human serum. The aptasensor was also chemically regenerated and tested again, demonstrating the reusability of our system.

The remarkable progress made towards mid-IR spectral in vitro mapping of tissue and cancer detection is reviewed, with emphasis on diagnosis of skin cancer. The status quo of chalcogenide glass mid-IR fiberoptics and photonics for meeting opportunities for remote mid-IR sensing in general, and in in vivo cancer detection in particular, is assessed. Raman spectroscopy is a sister technique to mid-IR spectroscopy. The current success of Raman spectroscopy in medical diagnosis is appraised, with particular emphasis on Raman spectral imaging of tissue towards skin cancer diagnosis in vivo, based on a silica-glass fiberoptic sensor-head. The challenges to be met in chalcogenide glass science and technology towards facilitating analogous fiberoptic diagnostics based on mid-IR spectroscopy are addressed.

A measurement method of glucose concentration based on fiber-optic surface plasmon resonance (FO-SPR) is proposed to achieve online, real-time detection of human blood glucose concentration. The end-reflection structure of FO-SPR sensor was simulated and the impact of different parameters on sensor performance was analyzed. Then the FO-SPR sensor was manufactured according to the optimized parameters. A glucose concentration measurement system with SPR sensor was set up. Glucose solutions with different concentrations were measured and the experiment results showed that the correlation coefficient of fitting curve between the glucose concentration and resonance wavelength was above 0.95 at the human blood glucose range of 0~200mg/dL. The measurement repeatability was also proved to be able to meet the requirements of blood glucose concentration detection in clinics.

OCT is playing an important role in interventional operations and some other therapies recent years. In many interventional operations the temperature of the tissue is also one of the main factors that will influence the operation result. Therefore monitoring the temperature of the operational tissue real time is critical for the operation and therapy. In this paper an endoscopic OCT probe for interventional operation with real time temperature monitoring function is presented. It consists of a micro OCT probe and a fluorescence thermometer. These two parts are installed in a base with a transparent shell of 3.0mm diameter and share one light source. Principles and structures of each part and the whole system are stated in detail. The experimental results indicate that the interventional operations OCT system can be used for rotated scanning imaging to obtain more tissue information and at the same time the temperature of the operational tissue can be monitored precisely.

The objective of this experiment is to evaluate the utility and limitations of optical coherence tomography (OCT) for real-time, high-resolution structural analysis. We monitored the degradation of the rat’s articular cartilage inducing osteoarthritis (OA) and the change of the rat’s articular cartilage recovery by treatment medication, using our developed common-path Fourier-domain (CP-FD) OCT. Also, we have done a comparative analysis the rat’s articular cartilage and OA grade. To observe the progression of OA, we induced OA by injecting the monosodium iodoacetate (MIA) into the right knee joint. After the injection of MIA, we sacrificed the rats at intervals of 3 days and obtained OCT and histological images. OCT and histological images showed the OA progress of similar pattern. These results illustrated the potential for non-invasive diagnosis about the grade of OA using CP-FD OCT.