Biophotonics is an emerging field in modern biomedical technology that has opened up new horizons for transfer of state-of-the-art techniques from the areas of lasers, fiber optics and biomedical optics to the life sciences and medicine. This field continues to vastly expand with advanced developments across the entire spectrum of biomedical applications ranging from fundamental “bench” laboratory studies to clinical patient “bedside” diagnostics and therapeutics. However, in order to translate these technologies to clinical device applications, the scientific and industrial community, and FDA are facing the requirement for a thorough evaluation and review of laser radiation safety and efficacy concerns. In many cases, however, the review process is complicated due the lack of effective means and standard test methods to precisely analyze safety and effectiveness of some of the newly developed biophotonics techniques and devices. There is, therefore, an immediate public health need for new test protocols, guidance documents and standard test methods to precisely evaluate fundamental characteristics, performance quality and safety of these technologies and devices. Here, we will overview our recent developments of novel test methodologies for safety and efficacy evaluation of some emerging biophotonics technologies and medical devices. These methodologies are based on integrating the advanced features of state-of-the-art optical sensor technologies and approaches such as high-resolution fiber-optic sensing, confocal and optical coherence tomography imaging, and infrared spectroscopy. The presentation will also illustrate some methodologies developed and implemented for testing intraocular lens implants, biochemical contaminations of medical devices, ultrahigh-resolution nanoscopy, and femtosecond laser therapeutics.
Some of the most commonly performed surgical operations in the world, including laser-assisted in-situ keratomileusis (LASIK), lens replacement (e.g. cataract surgery), and keratoplasty (cornea transplant), now employ therapeutic infrared femtosecond lasers (FSLs) for their extreme precision, low energy delivered into tissue and advanced ablation characteristics. Although the widely exploited applications of FSLs in medical therapeutics offer significant benefits, FSLs must generate very high intensities in order to achieve optical breakdown, the predominant tissue ablative mechanism, which can also stimulate nonlinear optical effects such as harmonic generation, an effect that generates coherent visible and UV light in the case of second- (SHG) and third-harmonic generation (THG), respectively. In order to improve the understanding of HG in corneal tissue, the effect of FSL polarization and pulse energy were investigated. FSL stimulated SHG intensity in corneal tissue was measured as the laser polarization was rotated 360 degrees. Further, the pulse energy at the SHG wavelength were measured for single FSL pulses as the pulse energy at the fundamental wavelength was varied through a range of clinically relevant values. The results of this study revealed SHG intensity oscillated with laser polarization, having a variation greater than 20%. This relationship seems to due to the intrinsic anisotropy of collagen fibril hyperpolarizability, not related to tissue birefringence. SHG pulse energy measurements showed an increase in SHG pulse energy with increasing FSL pulse energy, however conversion efficiency decreased. This may be related to the dynamic relationship between optical breakdown leading to tissue destruction and HG evolution.
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.
A first accurate measurement of the complex refractive index in an intralipid emulsion is demonstrated, and thereby the average scatterer particle size using standard Mie scattering calculations is extracted. Our method is based on measurement and modeling of the reflectance of a divergent laser beam from the sample surface. In the absence of any definitive reference data for the complex refractive index or particle size in highly turbid intralipid emulsions, we base our claim of accuracy on the fact that our work offers several critically important advantages over previously reported attempts. First, our measurements are in situ in the sense that they do not require any sample dilution, thus eliminating dilution errors. Second, our theoretical model does not employ any fitting parameters other than the two quantities we seek to determine, i.e., the real and imaginary parts of the refractive index, thus eliminating ambiguities arising from multiple extraneous fitting parameters. Third, we fit the entire reflectance-versus-incident-angle data curve instead of focusing on only the critical angle region, which is just a small subset of the data. Finally, despite our use of highly scattering opaque samples, our experiment uniquely satisfies a key assumption behind the Mie scattering formalism, namely, no multiple scattering occurs. Further proof of our method’s validity is given by the fact that our measured particle size finds good agreement with the value obtained by dynamic light scattering.
The use of femtosecond lasers (FSL) in ophthalmic procedures, such as LASIK, lens replacement (cataract surgery), as well as several other treatments, is growing rapidly. The treatment effect is based on photo ablation of ocular tissues by a series of ultra-short laser pulses. However, the laser beam characteristics change dynamically due to interactions with birefringent corneal tissue, which may affect the outcome of the laser treatment. To better understand the effect the cornea has on the laser characteristics, we developed a system for measuring retardation and validated it with precise, standard phase retarders. Then we measured the phase retardation of FSLs through bovine corneas and found that there is a considerable, location dependent, variation in retardation values. This information can potentially help optimize FSL parameters to make their application in ophthalmic procedures safer and more effective.
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