New optical methods for targeted laser processing of biomaterials

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Novel photonic approaches hold great promise to precisely target soft matter without resulting in collateral damage to surrounding healthy "bystander" cells. However, methods for delivery of laser energy lack fine spatial control and the associated control of heat governing the light-matter interaction zone. Exposure time and irradiance of pulses dictate laser interaction mechanisms with tissue. While high energy pulses are deliverable, lasers still have limited time-domain capabilities. This facet greatly restricts the ability to modulate the rate of energy deposited in biomatter. Advances in short pulse irradiation of =microsecond hold promise for more spatially confined laser disruptions. In complex architectures such as retinal tissues, significant gaps exist in models crucial for our understanding of photonic energy confinement. The challenge of applying a targeted and accurate energy dose is in part due to the complex multilayer structure of tissues and their heterogeneous chemical, optical, structural and mechanical properties. Precise interaction with laser energy necessitates control within the real biophysical properties of tissues for overall efficacy and predictive outcomes from sensitive measures of local light dose. Our proposed research will develop new time domain approaches that optimize laser-biomaterials processing for precise disruption to only targeted cells. Specifically, we explore new optical energy deposition methods that modulate the rate of laser energy delivery to retina-like targets. We will characterize properties such as energy threshold for photodisruptions, dynamics of cavitation formation, and key considerations regarding thermal dissipation. The objective is to solidify our understanding of laser temporal dynamics related to local energy confinement and to optimize laser delivery. Our Specific Aims are to: I Determine laser pulse profiles that deliver minimal light energy to produce the desired reaction in the region of interest while limiting adjacent, non-target interactions; II Create a new biomimetic polymer retina model for systematic investigations of this selective photoprocessing method; and III Develop a novel concept for accurate dose measures that provides critical, new molecular-scale information on O2 and carbon oxides produced at onset of laser energy. Our dosimetry concept, will enable critically accurate sensing needed to maximize photoprocessing efficacy in bio-relevant applications. Further, development of the biophysical model will allow a wide range of empirical and computational simulations of conditions encountered in the natural retina thereby elaborating our knowledge of outcomes in bio-realistic and idiosyncratic environments. Taken together, this project to develop innovative optical methods for effective laser light confinement in soft matter, will spearhead a path towards the ultimate future goal: Achieving molecular precision laser treatment with no sacrifice to healthy cells.