This PDF file contains the front matter associated with SPIE Proceedings Volume 6433, including the Title Page, Copyright information, Table of Contents, and the Conference Committee listing.

The application of autofluorescence in non-invasive medical diagnostics could have great potential. Two major drawbacks inherent to this approach are low signal levels compared to those from exogenous fluorescent probes and complexity caused by the multiplicity of fluorescent biomolecules in tissue. Here we present a new optical system that is based on single channel detection via an optical fiber and can measure the fluorescence emission spectrum and fluorescence lifetime simultaneously for excitation wavelengths of 355 and 435nm. Single channel measurements integrate the signal normally available in an imaging setup and therefore have a better signal-tonoise ratio. Resolving both the fluorescence emission spectrum and fluorescence lifetime provides the opportunity to discriminate multiple fluorophores. This instrument is intended for NAD(P)H and flavin measurements for the dynamic monitoring of cellular metabolism and optical measurements of cancerous tissue. Initial results from a study of live cells and a clinical study of human skin lesions are presented.

An innovative fiber optic pressure microsensor has been developed that is based upon on Luna Innovations' patented extrinsic Fabry-Perot interferometric (EFPI) technique. The basic physics governing the operation of these sensors makes them relatively tolerant or immune to the effects of high-temperature, high-EMI, and highly-corrosive environments. Luna's pressure microsensor is extremely small, with an outer diameter of only 200 microns and a length of less than 1mm. The pressure microsensor has a high sensitivity that allows for sub-mmHg resolution over a dynamic range of 0-300 mmHg. The combination of these features makes this pressure microsensor ideal for medical applications where small size, high sensitivity and accuracy, EMI immunity, biocompatibility, and survivability (e.g. sterilizable - steam, ethylene oxide) are important. One example medical application of the pressure microsensor has been to adapt the microsensor for measurement of intramuscular pressure in vivo during active and passive muscle activation. Clinically it is difficult to study the in vivo mechanical properties of individual skeletal muscles for a variety of reasons. Initial experiments have demonstrated a correlation between intramuscular pressure and force. Such measurements can be a useful diagnostic tool for clinicians assessing muscular deficits in patients.

With the debut of antibiotic drug therapy, and as a result of its ease of use and general success in treating infection, drugs have become the treatment of choice for most bacterial infections. However, the advent of multiple, very aggressive drug-resistant bacteria, an increasing population which cannot tolerate drugs, and the high cost of drug therapy suggest that a new modality for treating infections is needed. The complex interplay of clonal spread, persistence, transfer of resistance elements and cell-to-cell interaction all contribute to the difficulty in developing drugs to treat new antibiotic-resistant bacterial strains. A dynamic non-drug system, using extant pulsed ultraviolet lightwave technology to kill infection, is being developed to destroy pathogens. This paper theorizes that the shock effect of pulsed xenon's high energy ultraviolet pulses at wavelengths between 250-270nm separates the bacteria's DNA bands, and, subsequently, destroys them. Preliminary laboratory tests have demonstrated the ability of the technology to destroy Staphylococcus aureus, Pseudomonas aeruginosa Escherichia coli, Helicobacter pylori, Acinetobacter baumannii, Klebsiella punemonia, Bacillus subtillis, and Aspergillus fumigates at penetration depths of greater than 3mm in fluids with 100% effectiveness in less than five seconds of exposure to pulsed xenon lightwaves. Micro Invasive Technology, Inc is developing .pulsed xenon therapeutic catheters and endoscopic instruments for internal antimicrobial eradication and topographical devices for prophylactic wound, burn and surgical entrance/exit site sterilization. Pulsed Xenon light sources have a broad optical spectrum (190-1200nm), and can generate light pulses with sufficient energy for combined imaging and therapeutic intervention by multiplexing a fiber optic pathway into the body. In addition, Pulsed Xenon has proven ability to activate photo reactive dyes; share endoscopic lightguides with lasers while, simultaneously, capturing high quality visual and activated video images.

The beam spatial structure of mid-infrared laser radiation delivered by hollow glass waveguides was investigated. As laser sources flash-lamp pumped Er:YAG, Tm:YAG, and diode-pumped Tm:YAG, Tm:YAP laser systems generating radiation in a free-running regime were designed and constructed. The base of transfer systems was cyclic olefin polymer-coated silver hollow glass waveguide having 700 &mgr;m inner diameter and length up to 1.3 m. The changes of beam spatial structures through the delivery system are presented. For Er:YAG laser system the waveguide was investigated both straight and bent cases and also output laser beam stability was observed. The energy transmission characteristics were measured for all systems.

We demonstrate, for the first time to our knowledge, a hollow core photonic crystal fiber (HCPCF) surface-enhanced Raman probe. The probe consists of a HCPCF (also known as a holey fiber) with a layer of Au nanoparticles coated on the inner surface of the air holes serving as the substrate of surface enhanced Raman scattering (SERS). The sample being tested enters the air holes by the capillary effect. The excitation light is coupled into the fiber core from one end (measuring-tip) while the sample entrance is at the other end (probing-tip) of the fiber. The SERS signal scattered by the sample propagates through the fiber core back to the measuring-tip; then is coupled out of the fiber into the Raman spectrometer. The advantages of such probes include, the confinement of light inside the HCPCF provides a higher light efficiency; and the nanoparticles coated inside the air holes offers a larger interaction area for SERS. Both experimental results and theoretical analysis are presented and discussed.

With the rapid development and widely used of fiber grating, the demand of high quality photosensitive fiber has increase greatly. Based on the plasma chemical vapor deposition (PCVD) process, the Ge/F co-doped photosensitive fiber was developed. Through analyze the fiber's photosensitivity, study the fiber's photosensitivity influenced by the doping process. The data indicate that the high F doped (5%) Ge/F photosensitive fiber's grating has the 80% reflectivity, much lower than the low F doped(1%) Ge/F photosensitive fiber's 94%. The F doped content can influence the fiber's photosensitivity distinctly.

Silica optical fibers are being increasingly used for delivering laser power in various medical applications. Damage to the optical fiber caused by the high laser power level and tight bend of the fiber in these applications poses a serious concern. In this study, we examined the damage of step index multimode fibers transmitting Ho:YAG laser power up to 100 W at wavelength of 2140 nm when bent to a diameter down to 5 mm. The performance of different types of fibers was compared and other relevant issues were discussed.

Effect of simultaneous delivery of ErYAG and HoYAG lasers was tested by using a hollow optical fiber and a taper coupler. The lasers are irradiated to hard tissue at the same time, and vaporization characteristic, and fragmentation efficiency are discussed.

The aim of the present study focuses on experimentally demonstrating the efficacy of using angularly-variable fiber geometry to achieve the desired tissue-layer selection and probing depths with the further objective of enhancing the sensitivity and specificity of spectral diagnosis in stratified architectures that resemble human cervical epithelia. The morphological and biochemical features of epithelial tissue vary in accordance with tissue depths; consequently, the accuracy of spectroscopic diagnosis of epithelial dysplasia may be enhanced by probing the optical properties of this tissue. When correlated to cellular dysplasia, layer-specific changes in tissue optical properties may be deciphered by reflectance spectroscopy coupled with angularly-variable fiber geometry. This study addresses the utility of using such angularly-variable fiber geometry for resolving spatially-specific spectral signatures of tissue pathology. This is accomplished by interpreting and analyzing the reflectance spectra of increasingly dysplastic epithelial tissue in two-layer epithelial phantoms. Spectral sensitivity to tissue abnormalities in the epithelial layer is significantly improved as the obliquity of the collection fibers increases from 0 to 40 degrees. Conversely, conventionally orthogonal fibers are found to be more sensitive to changes in stromal tissue properties.

Previous studies of the hyphenation of gas chromatographic separation and spectrophotometric detection in the ultraviolet wavelength range between 168 and 330 nm showed a high potential for applications where the analysis of complex samples is required. Within this paper the development of a state-of-the-art detection system for compounds in the vapour phase is described, offering an improved behaviour compared to previous systems: Dependent on the requirements of established detection systems hyphenated with gas chromatography, the main components of the system have to be designed for optimum performance and reliability of the spectrophotometric detector: A deuterium lamp as a broadband light source has been selected for improved stability in the measurements. A new-type absorption cell based on fiber-optics has been developed considering the dynamic necessary to compete with existing techniques. In addition, the influence of the volume of the cell on the chromatogram needs to be analyzed. Tests for determining the performance of the absorption cell in terms of chemical and thermal influences have been carried out. A new spectrophotometer with adequate spectral resolution in the wavelength range, offering improved stability and dynamic for an efficient use in this application was developed. Furthermore, the influence of each component on the performance, reliability and stability of the sensor system will be discussed. An overview and outlook over the potential applications in the environmental, scientific and medical field will be given.

Polystyrene (PS) as a low index dielectric material in silver-coated hollow glass waveguides (HGW) has been studied as an alternative to the more conventional Ag/AgI HGWs. Polystyrene was chosen because it has been well characterized and it is easily dissolved in toluene. The waveguides were made using an electroless, wet chemistry technique. The absorbance spectrum for polystyrene indicates it will transmit from 1 to 3 &mgr;m and thus, it is useful at the Er:YAG laser wavelength of 2.94 &mgr;m. For multilayer HGWs, cadmium sulfide is the high index dielectric material.

In thin-layer chromatography, fiber-bundle arrays have been introduced for spectral absorption measurements in the UV-region. Using all-silica fiber bundles, the exciting light will be detected after re-emission on the plate with a fiberoptic spectrometer. In addition, fluorescence light can be detected which will be masked by the re-emitted light. Therefore, it is helpful to separate the absorption and fluorescence on the TLC-plate. A modified three-array assembly has been developed: using one array for detection, the two others are used for excitation with broadband band deuterium-light and with UV-LEDs adjusted to the substances under test. As an example, the quantification of glucosamine in nutritional supplements or spinach leaf extract will be described. Using simply heating of the amino-plate for derivation, the reaction product of Glucosamine can be detected sensitively either by light absorption or by fluorescence, using the new fiber-optic assembly. In addition, the properties of the new 3-row fiber-optic array and the commercially available UV-LEDs will be shown, in the interesting wavelength region for excitation of fluorescence, from 260 nm to 360 nm. The squint angle having an influence on coupling efficiency and spatial resolution will be measured with the inverse farfield method. Some properties of UV-LEDs for analytical applications will be described and discussed, too.

Concentrations of DNA and proteins are traditionally detected at 260/280nm using laboratory spectrophotometers. Recently, AlGaN/GaN ultraviolet Light Emitting Diodes (LED) became available in the 250 nm to 350 nm wavelength region. An inexpensive fiber optic detection system based on these UV LEDs and photodiodes has been developed. It allows concentration measurements of such popular biochemistry samples. Measurement stability and noise will be discussed. The performance of the system in comparison to a standard spectrophotometer will be evaluated. In particular, the effect of decreasing the spectral resolution from usually used 2-3 nm to 10-20 nm Full Width Half Maximum (FWHM) is simulated and experimentally confirmed.

Infrared remote spectroscopy systems based on hollow optical-fiber probes are proposed and experimental results are shown. A hollow fiber probe with silver inner coating is used to deliver incoherent light to a target and a separate, another hollow fiber is used to collect reflected light. By using the probe, reflectance spectra of a tooth, skin, etc were successfully measured even for surfaces giving reflectance lower than 0.5%. This remote FT-IR spectroscopy is useful for endoscopic measurement of infrared reflectometry of inside body because of high flexibility and durability, non-toxicity, and low transmission losses of the hollow-fiber-based probes.

A coating material characterized by wide-range thermal stability, water repellence, and physiological inertness. is newly employed as a dielectric layer in the dielectric-coated silver hollow optical fiber. This material, whose trade name is OC-300, is a semi-inorganic polymer based on the structural unit R₂SiO, where R is an organic group. A smooth hardened film is formed at room-temperature on the silver layer by using a liquid-phase coating technique. The transmission properties of the OC-300 coated silver hollow fiber are evaluated for infrared laser light. Sterilization experiments by using an autoclave shows that the hollow fiber showed strong durability and promising application in medical filed as well as in other harsh environment.

Scanning fiber endoscope (SFE) technology has shown promise as a minimally invasive optical imaging tool. To date, it is capable of capturing full-color 500-line images, at 15 Hz frame rate in vivo, as a 1.6 mm diameter endoscope. The SFE uses a singlemode optical fiber actuated at mechanical resonance to scan a light spot over tissue while backscattered or fluorescent light at each pixel is detected in time series using several multimode optical fibers. We are extending the capability of the SFE from a RGB reflectance imaging device to a diagnostic tool by imaging laser induced fluorescence (LIF) in tissue, allowing for correlation of endogenous fluorescence to tissue state. Design of the SFE for diagnostic imaging is guided by a comparison of single point spectra acquired from an inflammatory bowel disease (IBD) model to tissue histology evaluated by a pathologist. LIF spectra were acquired by illuminating tissue with a 405 nm light source and detecting intrinsic fluorescence with a multimode optical fiber. The IBD model used in this study was mdr1a-/- mice, where IBD was modulated by infection with Helicobacter bilis. IBD lesions in the mouse model ranged from mild to marked hyperplasia and dysplasia, from the distal colon to the cecum. A principle components analysis (PCA) was conducted on single point spectra of control and IBD tissue. PCA allowed for differentiation between healthy and dysplastic tissue, indicating that emission wavelengths from 620 - 650 nm were best able to differentiate diseased tissue and inflammation from normal healthy tissue.

Multiphoton autofluorescence imaging became an important technique for minimal invasive examination of cells in biological tissue. Rigid and flexible endoscopes based on gradient index lenses (GRIN-lenses) extend this minimalinvasive technique to deep lying cell layers, inner body and specimens, difficult to access. In the rigid endoscope, a GRIN-lens overcomes the limited depth range, given by the working distance of the microscope objective. The focus of the conventional laser scanning tomography is reproduced tens of millimeters in the specimen under study by the GRIN-lens (diameter 1.8 and 3 &mgr;m). We will present images of fluorescent beads, proteins cells and skin tissue, as well as first in vivo measurements on human skin. The autofluorescence signal stems from the endogenous fluorophore elastin and SHG from collagen. The flexible endoscope dispenses completely the need of a microscope next to the specimen of interest. The excitation laser pulses is delivered via a well-characterized photonic crystal fiber and subsequently focused by a newly designed GRIN-lens system. The fluorescence, also transferred by a fiber is detected by a PMT detector. We will show the excellent imaging qualities of a newly developed GRIN-lens system with high-resolution images of proteins, cells and plant tissue and give an out-look on multiphoton endoscopy.

Two types of hollow fiber-optic probes are developed to measure the in vivo Raman spectra of small animals. One is the minimized probe which is end-sealed with the micro-ball lens. The measured spectra reflect the information of the sample's sub-surface. This probe is used for the measurement of the esophagus and the stomach via an endoscope. The other probe is a confocal Raman probe which consists of a single fiber and a lens system. It is integrated into the handheld microscope. A simple and small multimodal probe is realized because the hollow optical fiber requires no optical filters. The performance of each probe is examined and the effectiveness of these probes for in vivo Raman spectroscopy is shown by animal tests.

A new family of Tellurium based glasses from the Ge-Te-I ternary system has been investigated for use in bio-sensing applications. A systematic series of compositions have been synthesized in order to explore the ternary phase diagram in an attempt to optimize the glass composition for the fiber drawing process. The characteristic temperatures Tg, the glass transition temperature, and T_x, the onset crystallization temperature, were measured in order to obtain &Dgr;T, the difference between T_g and T_x, which must be maximized for optimum fiber drawing ability. The resulting glass transition temperature range lies between 139^oC and 174^oC, with &Dgr;T values between 64^oC and 124^oC. The mechanical properties of a selected number of glass compositions were also investigated, including hardness and Young's Modulus. The Ge-Te-I glasses have an effective transmission window between 2-27 microns, encompassing the region of interest for the identification of biologically relevant species such as carbon dioxide. Furthermore, the fibering potential of the Ge-Te-I glasses makes them an interesting candidate for use in fiber evanescent wave spectroscopy (FEWS) and other bio-sensing applications.