New optical methods for targeted laser processing of biomaterials

新的光子方法有很大的希望精确地靶向软物质，而不会对周围健康的“旁观者”细胞造成附带损害。然而，用于输送激光能量的方法缺乏精细的空间控制和管理光-物质相互作用区的热的相关控制。 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。虽然高能量脉冲是可输送的，但激光器仍然具有有限的时域能力。这个方面极大地限制了调节生物物质中能量沉积速率的能力。微秒级短脉冲辐照技术的发展有望实现更大空间限制的激光破坏。在复杂的结构，如视网膜组织，显着的差距存在于模型中的光子能量约束的理解至关重要。施加靶向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不均匀的化学、光学、结构和机械特性。与激光能量的精确相互作用需要在组织的真实的生物物理特性内进行控制，以获得总体疗效和来自局部光剂量的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，优化激光生物材料处理，仅对靶细胞进行精确破坏。 具体来说，我们探索新的光学能量沉积方法，调制激光能量传递到视网膜样目标的速率。我们将描述的属性，如光致破裂的能量阈值，空化形成的动力学，以及关于热耗散的关键考虑因素。我们的目标是巩固我们的理解激光的时间动力学相关的本地能量约束和优化激光传输。我们的具体目标是：I确定激光脉冲轮廓，该激光脉冲轮廓提供最小的光能以在感兴趣的区域中产生期望的反应，同时限制相邻的非目标相互作用; II创建新的仿生聚合物视网膜模型，用于系统地研究这种选择性光处理方法;和III开发用于精确剂量测量的新概念，新的分子尺度上的信息O2和碳氧化物产生的激光能量的开始。我们的剂量学概念，将使极其准确的传感需要最大限度地提高生物相关应用中的光处理效率。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的结果的知识。 总之，该项目旨在开发创新的光学方法，以有效地将激光限制在软物质中，将为实现最终的未来目标开辟一条道路：实现分子精密激光治疗，而不牺牲健康细胞。

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.