Advanced laser physics and nonlinear optics: pushing the limits of ultrashort pulse laser sources and nonlinear imaging techniques

极短的(10^-13-10^-15 S)激光脉冲与物质相互作用可以产生各种光信号。这些次级信号中的每一个(或它们的个别属性，如颜色、强度、方向性、时间行为等)。可用于构建样品的高分辨率图像。多种信号可以直接由样品本身产生，也可以通过添加被称为标签的额外化学物质来产生。更重要的是，每个产生的信号都带有关于样品的结构、结构组织、化学成分或生化性质的特定信息。因此，这种基于激光的成像技术在与活细胞或组织一起使用时，在许多疾病的早期发展阶段就具有快速、敏感和可靠的诊断的巨大潜力。这可以显著提高医疗效率和结果。不幸的是，由于产生短脉冲激光的激光光源的高成本和低性能，这些诊断工具在实际临床环境中的渗透受到阻碍。此外，许多化学标签的毒性使其无法在人类身上使用。为了应对这些具有挑战性的因素，拟议的研究计划将开发(A)新的创新和具有成本效益的激光光源；(B)一种先进的激光成像技术，它不需要化学标签，并且可以同时提供关于样品的几种不同性质的信息。这些工具将由9名研究生(6名博士和3名硕士)在5年内开发。这些学生将接受激光、成像和光谱技术、光学材料、探测器、电子学和高精度机械、数据采集和分析方面的尖端培训。还将通过监督本科生论文和暑期项目以及合作研究活动，向本科生、研究生和研究生级别的高素质人员提供培训。拟议的研究计划产生的新知识将使基于激光的生物医学诊断技术更强大、更高效、更可靠、更具成本效益，从而更加成熟和具有临床应用吸引力。

Interaction of extremely short (10^-13 - 10^-15 s) pulses of laser light with matter can produce various optical signals. Each of these secondary signals (or their individual properties such as colour, intensity, directionality, temporal behaviour, etc.) can be used to construct a high resolution image of a sample. Multiple signals can be produced directly by the sample itself or by adding additional chemicals that are called labels. More importantly, each of the generated signals carries specific information about the sample's structure, its structural organization, chemical composition or biochemical properties. Therefore, such laser based imaging technologies when used with live cells or tissues have enormous potential for rapid, sensitive and reliable diagnostics of many diseases at their very early stages of development. This can significantly improve efficiency and outcomes of medical treatments. Unfortunately, penetration of these diagnostic tools into real clinical environment is hampered by the high cost and poor performance of laser sources that produce short pulses of laser light. In addition, toxicity of many chemical labels precludes their use with humans. To address these challenging factors the proposed research program will develop (a) new innovative and cost-effective laser sources; and (b) an advanced laser imaging technique that does not require chemical labels and can simultaneously provide information about several different properties of a sample. These instruments will be developed by 9 graduate students (6 PhDs and 3 MScs) over a 5 year period. The students will receive cutting-edge training in laser, imaging and spectroscopy technologies, optical materials, detector, electronics and high-precision mechanics, data acquisition and analysis. The training will be also offered to highly qualified personnel at the undergraduate, graduate and postgraduate levels through supervision of undergraduate thesis and summer projects and collaborative research activities. The new knowledge generated by the proposed research program will make laser-based biomedical diagnostic techniques more powerful, efficient, reliable, cost-effective, and therefore, more mature and attractive for clinical applications.