SBIR Phase I: Quantitative Space-time Control for High Contrast Multiphoton Microscopy

SBIR 第一阶段：高对比度多光子显微镜的定量时空控制

• 批准号: 1248772
• 负责人: Daniel Kane
• 金额: $ 14.9万
• 依托单位: Mesa Photonics, LLC
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-01-01 至 2013-11-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1248772&HistoricalAwards=false
• 关键词: SBIR; Phase; Quantitative; Space; time

This Small Business Innovation Research Program (SBIR) Phase I project will develop improvements to multiphoton microscopy, especially two-photon excitation fluorescence (TPEF). This technology has radically changed the manner in which quantitative biological studies are performed. It is now the tool of choice in dynamic, high-resolution (sub-micrometer) studies because scattering is mitigated, penetration depths can reach 1 mm, and impact of the excitation wavelength is minimized (near-infrared wavelengths are significantly less harmful to living systems.) However, challenges that limit application of TPEF imaging are setup time, image optimization and consistency. By rapidly measuring pulse characteristics, in situ, within the imaged sample itself, using this information to perfectly adjust pulse characteristics at the imaged point, in situ, within the sample itself, sample setup times can be improved and images can be made to be brighter, higher contrast and have better consistency. This holds for both commercial imaging systems using pulse width ranges from 70-100 fs, as well as home-built systems using pulse widths of 50 fs or less. This project will develop a novel, drop-in device, useable on any multiphoton microscopy system that will enable completely automated sample setup for the biologist to produce higher quality TPEF images faster, with better consistency. The broader impact/commercial potential of this project is the development of instrumentation and control systems to facilitate the improved utility of ultrafast lasers for new and important applications by allowing the production of high-contrast femtosecond pulses. These pulses are transform-limited in space and time, which not only impacts imaging, but all commercial applications of femtosecond lasers. For example, plasma-mediated ablation utilizes amplified femtosecond pulses and is a powerful process that is incorporated in a broad range of industries includes microfluidic platforms, and cataract surgeries, such as femtosecond laser assisted cataract surgery as well as Laser-Assisted in Situ Keratomileusis (LASIK) procedures. Current technologies only facilitate pulse optimization prior to the focus and interaction region. In fact, present femtosecond laser eye-surgery is based on twenty-year old technology. As industries begin to re-tool to take advantage of the benefits of improved femtosecond lasers, new pulse enhancement tools, such as proposed here, will be imperative to their successful implementation.

这个小型企业创新研究计划 (SBIR) 第一阶段项目将开发多光子显微镜的改进，特别是双光子激发荧光 (TPEF)。这项技术从根本上改变了定量生物学研究的进行方式。它现在已成为动态高分辨率（亚微米）研究的首选工具，因为散射得到缓解，穿透深度可达 1 毫米，并且激发波长的影响最小化（近红外波长对生物的危害明显较小）系统。）然而，限制 TPEF 成像应用的挑战是设置时间、图像优化和一致性。通过在成像样品本身内原位快速测量脉冲特性，利用该信息完美调整样品本身内原位成像点的脉冲特性，可以缩短样品设置时间并使图像变得更亮，对比度更高，一致性更好。这适用于使用 70-100 fs 脉冲宽度范围的商业成像系统，以及使用 50 fs 或更小的脉冲宽度的自制系统。该项目将开发一种新颖的嵌入式设备，可用于任何多光子显微镜系统，使生物学家能够实现完全自动化的样品设置，从而更快地生成更高质量的 TPEF 图像，并具有更好的一致性。该项目更广泛的影响/商业潜力是仪器和控制系统的开发，通过允许产生高对比度飞秒脉冲，促进超快激光器在新的重要应用中的实用性的提高。这些脉冲在空间和时间上受到变换限制，这不仅影响成像，而且影响飞秒激光器的所有商业应用。例如，等离子体介导的消融利用放大的飞秒脉冲，是一种强大的过程，可广泛应用于微流体平台和白内障手术等行业，例如飞秒激光辅助白内障手术以及激光辅助原位角膜磨镶术。 LASIK）手术。当前的技术仅促进聚焦和交互区域之前的脉冲优化。事实上，目前的飞秒激光眼科手术是基于二十年前的技术。随着各行业开始重新调整工具以利用改进的飞秒激光器的优势，新的脉冲增强工具（例如此处提出的）对于其成功实施至关重要。