Ilko K. Ilev

Mid–infrared laser applications in medicine and biology

The mid–infrared (mid–IR) should be a fruitful area for medical research and instrumentation since this is the region where the most identifiable molecular molecules absorb and radiate. Due to the unique specificity of a biological molecules spectrum in the mid–IR, semiconductor lasers in the mid–IR have a unique advantage over ultraviolet and visible or near–IR lasers. Small room–temperature laser diodes can be used in small hand–held, portable, and hopefully inexpensive, medical devices for rapid measurement, possibly in patient–operated home–care devices. Since the mid–IR radiation can be connected with otherwise invisible chemical processes, it becomes possible to watch the biochemical processes of life reveal themselves. Until recently, work in this region had been handicapped by lack of sources, detectors and optical materials, but this is changing, as this conference shows, and important new directions lie ahead.

ALL-FIBER-OPTIC SENSOR FOR LIQUID LEVEL MEASUREMENT

An experimental realization of a simple all-fiber-optic sensor for liquid level measurement is demonstrated. It is an intensity-modulated on–off switching sensor whose operating principle is based on the frustrated-total-internal-reflection effect caused by the refractive-index change of the surrounding medium. The basic optical element in the scheme is a sensing single fiber which serves simultaneously to transmit both the forward laser emission to the investigated medium and the useful signal backreflected from the fiber tip that is the sensing element. In order to achieve a maximum sensor sensitivity, we use a specially shaped fiber tip in two profile variants: angled and retroreflecting. The experimental investigations of the sensor properties and the results obtained at the pure-water level measurement confirm the sensor potential in liquid level determination with a high accuracy, exceeding 10 μm.

Dual-confocal fiber-optic method for absolute measurement of refractive index and thickness of optically transparent media

We present a novel noncontact optical method for absolute measurement of refractive index and thickness of optically transparent media. The method is based on a simple dual-confocal fiber-optic sensor design. It includes two independent confocal channels consisting of two identical apertureless fiber-optic-type confocal microscopes constructed by use of a single 2x2 fiber coupler. A geometrical-ray model is used to obtain the analytical dependence between the samples refractive index and its thickness. The measurement method provides high accuracy in spatially locating the specific imaging points that correspond to the backreflected intensity peaks of the confocal responses. Thus, a simultaneous measurement of the sample refractive index and thickness is achieved.

Retina-simulating phantom for optical coherence tomography

Abstract. Optical coherence tomography (OCT) is a rapidly growing imaging modality, particularly in the field of ophthalmology. Accurate early diagnosis of diseases requires consistent and validated imaging performance. In contrast to more well-established medical imaging modalities, no standardized test methods currently exist for OCT quality assurance. We developed a retinal phantom which mimics the thickness and near-infrared optical properties of each anatomical retinal layer as well as the surface topography of the foveal pit. The fabrication process involves layer-by-layer spin coating of nanoparticle-embedded silicone films followed by laser micro-etching to modify the surface topography. The thickness of each layer and dimensions of the foveal pit are measured with high precision. The phantom is embedded into a commercially available, water-filled model eye to simulate ocular dispersion and emmetropic refraction, and for ease of use with clinical OCT systems. The phantom was imaged with research and clinical OCT systems to assess image quality and software accuracy. Our results indicate that this phantom may serve as a useful tool to evaluate and standardize OCT performance.

Light Supports Neurite Outgrowth of Human Neural Progenitor Cells In Vitro : The Role of P2Y Receptors

The purpose of this study was to compare the effects of growth factors and 810-nm-wavelength light on the differentiation of normal human neural progenitor cells (NHNPCs) in vitro. Although growth factors are routinely used to study neural stem and progenitor cells in vitro, to date, light has not been used as a replacement for growth factors. This study demonstrates that NHNPCs are not only capable of being sustained by light in the absence of growth factors, but that they are also able to differentiate normally as assessed by neurite formation. The NHNPCs had an up-regulation in the expression of endogenous fibroblast growth factor-2, brain derived neurotrophic factor, and nerve growth factor in response to the light. Suramin, a nonselective P2 receptor antagonist, significantly decreased neurite outgrowth, and P2Y2 and P2Y11 receptors were found to be expressed by the NHNPCs by immunolabeling. Based on these findings, the mechanism by which light supports the NHNPC differentiation is hypothesized to be due to increases in adenosine triphosphate acting via P2Y receptors.

Highly efficient wideband continuum generation in a single-mode optical fiber by powerful broadband laser pumping

By pumping a single-mode optical fiber with a powerful broadband nonselective dye laser, we obtain a high-efficiency wideband continuum (530-930 nm) with nonlinear conversion efficiency exceeding 90%. Experimental conditions for a coherent regime of broadband stimulated Raman scattering are created, which in combination with the broadband self-phase modulation and the four-photon parametric processes leads to a spectral broadening and to the continuum formation. The influence of the pump laser spectral linewidth on the nonlinear conversion efficiency is analyzed and investigated by comparative experiments at narrow-band and broadband laser excitations.

Excitation of primary afferent neurons by near-infrared light in vitro

Near-infrared light therapy is an emerging neurostimulation technology, but its cellular mechanism of action remains unresolved. Using standard intracellular recording techniques, we observed that 5–10 ms pulses of 1889 nm light depolarized the membrane potential for hundreds of milliseconds in more than 85% of dorsal root ganglion and nodose ganglion neurons tested. The laser-evoked depolarizations (LEDs) exhibited complex, multiphasic kinetics comprising fast and slow components. There was no discernable difference in the LEDs in intact ganglion neurons and in acutely isolated neurons. Thus, the LED sensor seems to reside within the neuronal membrane. The near-uniform distribution of responsive neurons increased membrane conductance, and the negative reversal potential value (−41±2.9 mV) suggests that LED is unrelated to the activation of heat-sensitive transient receptor potential cation channel subfamily V member 1 channels. The long duration of LEDs favors an involvement of second messengers.

Grazing-incidence-based hollow taper for infrared laser-to-fiber coupling

Based on grazing incidence, a simple uncoated hollow glass taper as an alternative technique for efficient infrared laser-to-fiber coupling is presented. Because of the mutual action of the direct parallel laser excitation, the mode-coupling process, and mode filtering, the hollow taper serves as a mode converter that transforms the highly multimode intensity distribution of the input laser emission into a high-quality smooth profile at the taper output. When an uncoated Pyrex-glass hollow taper is used for direct launching, without any intermediate focusing elements, of a powerful infrared Er:YAG laser emission (λ=2.94 μm), we obtain high laser-to-taper (81%), taper-to-fiber (96%), and total laser-to-fiber (78%) coupling efficiencies.

Fiber-optic Fourier-domain common-path OCT

We experimentally and theoretically investigated the performance of a fiber-optic based Fourier-domain common-path optical coherence tomography (OCT). The fiber-optic common-path OCT operated at the 840-nm center wavelength. The resolution of the system was 8.8 \mum (in air) and the working depth using a bare fiber probe was approximately 1.5 mm. The signal-to-noise ratio (SNR) of the system was analyzed. OCT images obtained by the system were also presented.

Simple fiber-optic confocal microscopy with nanoscale depth resolution beyond the diffraction barrier

A novel fiber-optic confocal approach for ultrahigh depth-resolution (<or=2 nm) microscopy beyond the diffraction barrier in the subwavelength nanometric range below 200 nm is presented. The key idea is based on a simple fiber-optic confocal microscope approach that is compatible with a differential confocal microscope technique. To improve the dynamic range of the resolving laser power and to achieve a high resolution in the nanometric range, we have designed a simple apertureless reflection confocal microscope with a highly sensitive single-mode-fiber confocal output. The fiber-optic design is an effective alternative to conventional pinhole-based confocal systems and offers a number of advantages in terms of spatial resolution, flexibility, miniaturization, and scanning potential. Furthermore, the design is compatible with the differential confocal pinhole microscope based on the use of the sharp diffraction-free slope of the axial confocal response curve rather than the area around the maximum of that curve. Combining the advantages of ultrahigh-resolution fiber-optic confocal microscopy, we can work beyond the diffraction barrier in the subwavelength (below 200 nm) nanometric range exploiting confocal nanobioimaging of single cell and intracellular analytes.