This PDF file contains the front matter associated with SPIE Proceedings Volume 9317, including the Title Page, Copyright information, Table of Contents, Introduction (if any), and Conference Committee listing.

Raman spectroscopy represents a label-free vibrational spectroscopic technique for studying the biochemical and biomolecular compositions of human body. Raman probe is a key component to facilitate the in vivo diagnosis by using Raman spectroscopy. We investigated a compact Raman needle probe design to be integrated into a device that can also take biopsies of solid tissues for cytological assessment, enabling concurrent Raman spectroscopic interrogation and fine needle aspiration biopsy with a single needle penetration. We described the fabrication of the Raman needle probe and its assembly with the biopsy device. Example Raman spectra of various solid tissues are given.

In this study, a photoacoustic detector integrated with Fourier-transform infrared spectroscopy was used to measure biomarkers in gas samples independently. Simulated exhaled breath samples were created by mixing varying concentrations of acetone, ammonia and ethane. The results of these measurements demonstrate the potential of photoacoustic spectroscopy to detect biomarkers from human breath.

Tumor necrosis factor (TNF)-alpha is a pleiotropic cytokine up-regulated in inflammatory bowel disease, rheumatoid arthritis and psoriasis. The introduction of anti-TNF drugs such as infliximab has revolutionized the treatment of these diseases. Recently, therapeutic drug monitoring (TDM) of infliximab has been introduced in clinical decision making to increase cost-efficiency. Nowadays, TDM is performed using radio-immunoassays, homogeneous mobility shift assays or ELISA. Unfortunately, these assays do not allow for in situ treatment optimization, because of the required sample transportation to centralized laboratories and the subsequent assay execution time. In this perspective, we evaluated the potential of fiber optic-surface plasmon resonance (FO-SPR). To achieve this goal, a panel of 55 monoclonal anti-infliximab antibodies (MA-IFX) was developed and characterized in-house, leading to the identification of nine different clusters. Based on this high diversity, 22 antibody pairs were selected and tested for their reactivity towards IFX, using one MA-IFX as capture and one MA-IFX for detection, in a sandwich type ELISA and FO-SPR. This study showed that the reactivity towards IFX of each antibody pair in ELISA is highly similar to its reactivity on FO-SPR, indicating that antibody pairs are easily transferable between both platforms. Given the fact that FO-SPR shows the potential for miniaturization and fast assay time, it can be considered a highly promising platform for on-site infliximab monitoring.

In this study, we demonstrate an automated data acquisition/analysis platform for both long-term motion tracking and functional brain imaging in freely moving mice. Our system utilizes a fiber-bundle based fluorescence microscope for 24 hours imaging of cellular activities within the brain while also monitoring corresponding animal behaviors using a NIR camera. Synchronized software and automation of analysis allow quantification of all animal behaviors and their brain activities over extended periods of time. Our platform can be used for interrogation of the brain activities in different behavioral states and is also well-suited for longitudinal studies of cellular activities in freely moving animals.

In-vivo measurement of the concentrations of biological compounds using fluorescence is one of the challenging biophotonic fields. These measurements are useful in diagnostic and treatment monitoring applications that use fluorescent probes which may bond to specific proteins and drugs. In some cases the relative concentration of two compounds is a sufficient biological indicator. For instance, it has been shown that the ratio between Amyloid-Beta and tau protein in the Cerebrospinal fluid (CSF) may predict the development of Alzheimer’s disease (AD) several years before current diagnosis. We have previously suggested a system that could measure the concentration ratio of these two proteins in-vivo without the need to collect CSF samples. This system uses a miniature needle with an optical fiber which is coupled to a laser source and a detector. The fiber excites fluorescent probes which were injected and bond to the proteins in the CSF, and collects the fluorescence emission. Using the fluorescence intensity ratio, the concentration ratio between the proteins is estimated, and AD may be diagnosed. In this work we present the results of an in-vivo trial performed on mice. Miniature tubes containing two fluorescent probes in several concentration ratios were inserted into the mice in two locations: subcutaneously, and deeper in the abdomen. The fluorescent probes were excited and the fluorescence intensity was measured. The concentration ratios were extracted from the fluorescence intensities using a simple calibration curve. The extracted ratios are compared to the true ratios and the system’s accuracy is estimated.

Optical key parameter of fiber optic flow cells for absorbance measurements are transmission and numerical aperture. In this work we introduce an experimental setup to determine the far field intensity profile of flow cells at different wavelengths in the UV and visible part of the light spectrum. Comparison to spectral transmission will be shown, too.

Ongoing efforts on the purification of chalcogenide glasses and fiber draw processes enable the production of commercial-grade mid-infrared (MIR) fibers for 1.5-10 μm transmission. Results show multimode and single-mode MIR fibers with low-loss (<0.1dB/m) and high tensile strength (>20kpsi). High-power laser transmission has been achieved in single-mode fiber (>5 MW/cm² CW).

In this work we report on a fiber grating fabrication platform suitable for parallel fabrication of Bragg grating arrays over arbitrary lengths of multicore optical fiber. Our system exploits UV transparent coatings and has precision fiber translation that allows for quasi-continuous grating fabrication. Our system is capable of both uniform and chirped fiber grating array spectra that can meet the demands of medical sensors including high speed, accuracy, robustness and small form factor.

Diagnostic value of minimally invasive medical devices can be improved by putting electronic functionality at the tip. At the same time the device should remain slim, flexible and affordable. We show transfer of high power and data over a catheter by a single optical fiber and LED. We find that simultaneous photovoltaic power conversion and data communication can be achieved via Photo-Induced Electro Luminescence (PEL), but only in case the LED has a high bidirectional conversion efficiency (η<0.3). This eliminates the necessity of using thin electrical wires with fragile interconnects that compromise bandwidth as well as RF and MRI compatibility.

An effort to demonstrate long term transmission stability in a high –OH synthetic fused silica step index multimode optical fiber optimized for Deep-UV operation, designated as FDP, was successfully completed at Polymicro Technologies. The development achieved significant improvement in long term stability for the 214 and 265nm absorption bands typically associated with solarization effects in fused silica. The improvements were applied to fiber core sizes from 67 to 100µm, a common size range for bundle applications used in medical and spectroscopy. Results of UV degradation measurements for the fiber with minimum 70 hour exposures are presented along with a description of the test protocols.

We are presenting a novel photoplethysmographic (PPG) optical sensor and device with ambient optical, electrical and electromagnetic noises cancellation, thus allowing only the useful optical signals to be received by the health monitoring device. We are also presenting a new processing technique for canceling the ambient noises contributed by optical, electrical and electromagnetic artifacts in the measured PPG signals. Such a device and method allow the enhancement of the performance of the PPG sensors compared to conventional apparatus and methods. The presented sensor and methodology have been integrated into a prototype standalone device for noninvasive, continuous, wearable, remote and mobile monitoring of blood pressure and other human vital signs, such as heart rate, oxygen saturation, respiration rate, etc This small device allows the user to read, store, process and transmit all the measurements made using the PPG optical sensor and the electronic unit to a remote location.

Hollow Glass Waveguides (HGWs) present a viable option for the low-loss transmission of radiation over a broad range spanning from visible to far-infrared wavelengths. Cyclic Olefin Copolymer (COC), a commercially available polymer known as TOPAS®, is chosen for this study due to its exceptionally low absorption losses throughout the spectrum, particularly in the visible and near-infrared (NIR) regions. While silver-coated HGWs are capable of transmitting visible and NIR radiation with low losses, theory predicts that the addition of a uniform dielectric thin film of quarter wavelength thickness will reduce these losses for both straight and bent configurations, while additionally providing a potentially more desirable modal output for laser applications. In this paper, the procedures for the deposition of the silver and subsequent COC films are outlined. Spectroscopy is used to obtain the thickness of the polymer film. The theoretical attenuation losses of the silver and Ag/COC HGWs are explored and experimental values are obtained using various visible and IR lasers. Moreover, the modal output of the silver and Ag/COC HGWs is qualitatively compared. The possibility of use of these Ag/COC HGWs at mid- and far-IR wavelengths is discussed.

An extremely rugged hollow fiber is fabricated by liquid-phase coating technique. A silica glass capillary is used as the substrate and 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. The additional transmission loss caused by the roughness of the protective film is decreased by limiting the length of the protective film. The whole length of 0.7-mm-bore hollow fiber was 1.2 m and the length of the rugged part which formed the protective film was only 30 cm. Transmission properties of the rugged polymer-coated silver hollow fibers for the Er:YAG laser and red pilot beam delivery have been improved. The loss for the 0.7-μm-bore size, 1.2-m-length rugged polymer-coated silver hollow fiber was 1 dB and 6.9 dB under straight condition, and 1.9 dB and 9.4 dB under the condition of a 270 degree bend with a 15-mm bending radius at the wavelength of 2.94 μm and 650 nm, respectively.

Polarimetric optical fiber-based stress and pressure sensors have proven to be a robust tool for measuring and detecting changes in the Young’s modulus (E) of materials in response to external stimuli, including the real-time monitoring of the structural integrity of bridges and buildings. These sensors typically work by using a pair of polarizers before and after the sensing region of the fiber, and often require precise alignment to achieve high sensitivity. The ability to perform similar measurements in natural and in engineered biomaterials could provide significant insights and enable research advancement and preventative healthcare. However, in order for this approach to be successful, it is necessary to reduce the complexity of the system by removing free-space components and the need for alignment. As the first step in this path, we have developed a new route for performing these measurements. By generalizing and expanding established theoretical analyses for these types of sensors, we have developed a predictive theoretical model. Additionally, by replacing the conventional free space components and polarization filters with a polarimeter, we have constructed a sensor system with higher sensitivity and which is semi-portable. In initial experiments, a series of polydimethylsiloxane (PDMS) samples with several base:curing agent ratios ranging from 5:1 up to 30:1 were prepared to simulate tissues with different stiffnesses. By simultaneously producing stress-strain curves using a load frame and monitoring the polarization change of light traveling through the samples, we verified the accuracy of our theoretical model.

The demand for highly sensitive and reliable sensors to assess the refractive index of liquid get many applications in chemical and biomedical areas. Indeed, the physical parameters such as concentration, pressure and density, etc., can be found using the refractive index of liquid. In contrast to the conventional refractometer for measurement, optical fiber sensor has several advantages like remote sensing, small in size, low cost, immune to EMI etc., In this paper we have discussed determination of refractive index of sugar solution using optical fiber. An intensity modulated low cost plastic fiber optic refractive index sensor has been designed for the study. The sensor is based on principle of change in angle of reflected light caused by refractive index change of the medium surrounding the fiber. The experimental results obtained for the sugar solution of different refractive indices prove that the fiber optic sensor is cable of measuring the refractive indices as well as the concentrations.

Temperature controlled laser bonding of the cornea is analyzed in this paper using optical coherence tomography imaging, histological section evaluations and tensile strength measurements. The heat generated to obtain the bonding causes changes to the tissue structure, which appear as a bowl shaped lesion around the heated spot. Optical coherence tomography is established as an appropriate modality for the assessment of these lesions, using the other methods for validation. A quantitative analysis of the lesions attributes is produced, using a dedicated image processing algorithm. By means of this method we observed that the depth of the lesion is the most effective measure in estimating the extent of the tissue reaction to heat. A comparison of the measured lesion depth, produced by different heating profiles, is presented. This comparison shows a linear dependence on both the temperature and the exposure time, within the boundaries of the experiment. The bond strength was evaluated for several set temperatures (with 20 seconds heating time in each case) displaying an optimal value at 70°C. Yet if an incision was successfully bonded, it held a higher burst pressure for a higher temperature value. These findings demonstrate the plausibility of an integrated laser tissue bonding apparatus with an optical coherence tomography probe, which will provide, for the first time, a real time feedback of the tissue structural change, and indicate the bonding progress and end point.

Hand tremor reduction is important to achieve stable micro manipulation of the tool tip. A micro-scissors can be used for cutting delicate tissues safely. Here, we implement an OCT distance sensor guided SMART micro-scissors which could incise micro-surgical targets precisely and horizontally. Compared to freehand incision, it demonstrates enhanced incision performance on dry phantoms with great tremor suppression.

We have designed, fabricated, and characterized a fiberoptic probe composed of terbium-based phosphors for ionizing radiation dosimetry. Fiber optic probes consisting of ~1 mm layer of TbF3 covering the tip embedded in tissue-mimicking phantoms were irradiated with electron beams produced by a medical linear accelerator. Optical spectra of irradiated tips were taken using a fiber spectrometer. The luminescence signal from the phosphors was spectrally separated from the Čerenkov radiation generated in the fiber. In order to obtain the percent depth dose curve, the resultant decomposed spectra corresponding to the emission from the phosphors were considered as a measure of the absorbed dose. The measured depth dose curves using our fiber probes are in agreement with measurements performed by an electron diode, indicating the feasibility of using such fiber probes for ionizing radiation dosimetry.

Multimode UV-fibers with high-OH synthetic silica core and F-doped silica cladding have been available for over 40 years. At the beginning, the spectral UV-range above 250 nm wavelength was commonly used, because the generation of UV-absorbing defect centers prevented reliable light transfer below 250 nm; even light from a low-power broadband deuterium-lamp was sufficient to damage these UV-fibers of the 1^st generation. However, even then, applications in the field of spectroscopy, laser light delivery, sensors and process control were discussed and improvements of fiber quality in this very interesting UVC range required by researchers and industrial end-users. Starting in 1993 with hydrogen-loaded fibers, further modification in preform and fiber manufacturing including additional fiber treatments lead to currently available hydrogen-free UV-fiber (4^th generation) with significantly improved stability in the UVC, enabling routine use of optical fibers in this field. In addition to the UV-fiber improvements, some selected UV fiber-optic applications using broadband deuterium-lamps will be discussed. Finally, there is still room for further improvements, especially in combination with newly available pulsed UV light sources, which are low-cost, small sized and highly reliable.

The paper reports - with simulations and experiments - on the development of low-cost Surface Plasmon Resonance fiber probes for bio-sensing. The simulations analyze the impact of non-uniform metal layer depositions, a situation that would typically occur in a simplified fabrication process, whereas the experimental section discusses some preliminary results of the characterization of large-core fiber probes used as refractometers of aqueous solutions.

This paper presents a handheld micro-injector system using common-path swept source optical coherence tomography (CP-SSOCT) as a distal sensor with highly accurate injection-depth-locking. To achieve real-time, highly precise, and intuitive freehand control, the system used graphics processing unit (GPU) to process the oversampled OCT signal with high throughput and a smart customized motion monitoring control algorithm. A performance evaluation was conducted with 60-insertions and fluorescein dye injection tests to show how accurately the system can guide the needle and lock to the target depth. The evaluation tests show our system can guide the injection needle into the desired depth with 4.12μm average deviation error while injecting 50nƖ of fluorescein dye.

A Raman imaging system which combined a hollow fiber bundle and a direct imaging technique was constructed for high-speed endoscopic Raman imaging. The hollow fiber bundle is fabricated by depositing a silver thin film on the inner surface of pre-drawn glass capillary bundle. It performs as a fiber optic probe which transmits a Raman image with high signal-to-noise ratio because the propagating light is confined into the air core inducing little light scattering. The field of view on the sample is uniformly irradiated by the excitation laser light via the probe. The back-scattered image is collected by the probe and captured directly by an image sensor. A pair of thin film tunable filters is used to select target Raman band. This imaging system enables flexible and high-speed Raman imaging of biological tissues.

The paper presents our recent results towards the development of a miniaturized all-fiber probe for laser induced thermal ablation of tumor cells, which combines the optimal delivery of a near-infrared high power ablating beam, a low power visible aiming beam and fast Bragg grating (FBG) temperature sensors. Specific combiner and probe end-cap based on dual cladding fibers have been developed to allow the simultaneous handling of the laser beams and of the signal that feeds the temperature sensor. Moreover, a very fast FBG interrogation system has been implemented to track abrupt temperature variations during medical treatment.

Endoscopic submucosal dissection using carbon dioxide laser is a promising treatment of early digestive cancer because it can avoid the risk of perforation. Although a hollow optical fiber transmitting mid-infrared light has been used, it was observed that the irradiation effect was influenced by bending a gastrointestinal gastrointestinal endoscope due to the change in transmittance by the bending loss. Therefore, we quantitatively evaluated the change in the irradiation effect by bending the hollow optical fiber in the gastrointestinal endoscope and proposed a correction method to stabilize the irradiation effect. First, the relationship between the irradiated laser energy density and the incision depth for porcine stomach was measured by bending the head of the gastrointestinal endoscope. Next, the relationship between the bending angle of the head of the gastrointestinal endoscope and the temperature rise of the hollow optical fiber in the head of the gastrointestinal endoscope was measured during the laser irradiation. As a result, the laser energy density and the incision depth decreased as the bending angle increased, and linear correlation between the laser energy density and the incision depth was observed. It was found that the bending angle can be estimated by the ratio of the setting laser power to time derivative of the temporal profile of the temperature of the hollow optical fiber. In conclusion, it is suggested that the correction of the laser energy density and stabilization of the incision capability is possible by measuring the temporal profile of the temperature of the hollow optical fiber.

Typical L-type photonic crystal (PC) microcavities have a dynamic range of approximately 3-4 orders of magnitude in biosensing. We experimentally demonstrated that multiplexing of PC sensors with different geometry can achieve a wide dynamic range covering 6 orders of magnitude with potential for 8 or more orders with suitable optimization.

Refractive index variation in rare-earth doped specialty fiber can be possible through resonantly enhanced optical nonlinearity with the assistance of an optical pumping. The quantity of the variation under low-power optical pumping is enough to induce phase shift of 2π. By using this nonlinear effect in the specialty fiber, optical imaging system can perform phase shift-based optical imaging without mechanically controlled phase stepping. The pump-induced refractive index from the specialty fiber in reference arm of interferometer can produce optical delay depending on applied optical pumping power. At low optical power under few hundred mW, optical delay corresponding to 2π can be yielded in the reference arm efficiently. Contrast to the conventional mechanical phase stepping method, optically actuated phase stepping with the specialty optical fiber can avoid drawback of mechanical hysteresis and requirement of high voltage controllable electronics. The feasibility of the proposed method on optical imaging is suggested with demonstrating full range imaging in optical coherence tomography. Extended imaging range under optical phase stepping was successfully presented. The proposed method could be applied for detailed control of phase shift-based interferometry.