New optical methods for targeted laser processing of biomaterials

新颖的光子方法具有很大的前景，可以精确地靶向软物质，而不会对周围健康的“旁观者”细胞造成附带损害。然而，激光能量的传递方法缺乏精细的空间控制和与之相关的控制光物质相互作用区的热控制。脉冲的曝光时间和辐照度决定了激光与组织的相互作用机制。虽然高能脉冲是可交付的，但激光仍然具有有限的时域能力。这一方面极大地限制了调节生物物质中能量沉积速率的能力。微秒短脉冲辐照技术的进展为空间受限的激光干扰带来了希望。在像视网膜组织这样的复杂结构中，对于我们理解光子能量限制至关重要的模型存在显著的差距。应用有针对性和准确的能量剂量的挑战部分是由于组织的复杂多层结构及其异质的化学、光学、结构和机械性能。与激光能量的精确相互作用需要在组织的真实生物物理特性范围内进行控制，以获得总体功效和局部光剂量敏感测量的预测结果。我们提出的研究将开发新的时域方法，优化激光生物材料加工，以精确破坏目标细胞。具体来说，我们探索了新的光能沉积方法，以调节激光能量输送到视网膜样目标的速率。我们将描述诸如光破坏的能量阈值，空化形成的动力学以及关于热耗散的关键考虑因素等特性。目的是巩固我们对与局部能量限制有关的激光时间动力学的理解，并优化激光输送。我们的具体目标是：1 .确定提供最小光能的激光脉冲剖面，以在感兴趣的区域产生所需的反应，同时限制相邻的非目标相互作用；II .建立一种新的仿生聚合物视网膜模型，对这种选择性光处理方法进行系统研究；开发一种精确剂量测量的新概念，为激光能量开始时产生的O2和碳氧化物提供关键的、新的分子尺度信息。我们的剂量学概念将使生物相关应用中最大限度地提高光处理效率所需的精确传感成为可能。此外，生物物理模型的发展将允许对自然视网膜中遇到的条件进行广泛的经验和计算模拟，从而详细说明我们对生物现实和特殊环境中结果的了解。综上所述，该项目旨在为软物质中有效的激光限制开发创新的光学方法，将为最终的未来目标开辟一条道路：在不牺牲健康细胞的情况下实现分子精密激光治疗。

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.