New optical methods for targeted laser processing of biomaterials

新的光子方法具有很好的前景，可以精确定位软物质，而不会对周围健康的“旁观者”细胞造成附带损害。然而，输送激光能量的方法缺乏精细的空间控制和控制光-物质相互作用区的相关热。 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。虽然高能脉冲是可以传输的，但激光的时域能力仍然有限。这一方面极大地限制了调节生物体内能量沉积速率的能力。微秒短脉冲辐照的进展为更多空间受限的激光分裂提供了希望。在复杂的结构中，如视网膜组织，对于我们理解光子能量限制至关重要的模型中存在着显著的差距。应用定向和准确的能量剂量的挑战在一定程度上是由于组织的复杂的多层结构及其不同的化学、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属性内进行控制，以实现局部光剂量敏感测量的总体疗效和预测结果。我们提议的研究将开发新的时域方法，优化激光生物材料处理，仅对目标细胞进行精确破坏。 具体地说，我们探索了新的光学能量沉积方法，以调节激光向视网膜样目标传递能量的速度。我们将描述一些特性，如光破坏的能量阈值、空化形成的动力学，以及有关热耗散的关键考虑因素。其目的是巩固我们对与局部能量限制相关的激光时间动力学的理解，并优化激光传输。我们的具体目标是：i确定提供最小光能以在感兴趣区域产生所需反应的激光脉冲轮廓，同时限制相邻的非靶相互作用；ii创建新的仿生聚合物视网膜模型，用于系统研究这种选择性光处理方法；iii开发精确剂量测量的新概念，提供关于激光能量开始时产生的O2和二氧化碳的关键的新的分子尺度信息。我们的剂量学概念将实现在生物相关应用中最大限度地提高光处理效率所需的极其精确的检测。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，从而阐述我们对生物现实和特殊环境中结果的知识。 综上所述，该项目旨在开发创新的光学方法，在软物质中有效地进行激光限制，将开辟一条通往未来最终目标的道路：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.