Picosecond InfraRed Laser (PIRL) Technology: The Fundamental Limit to Minimally Invasive Surgery with Complete Biodiagnostics for Surgical Guidance

皮秒红光激光（PIRL）手术刀实现了微创手术的基本单细胞限制-没有疤痕组织形成，切除组织的完整分子特征保持完美完整。这种独特工具的基本物理学涉及水振动的选择性激发和与平移运动的直接耦合，以比周围组织的能量损失和相关的附带损伤或被切除组织的分子组成的热改性更快地驱动消融过程。人们可以获得组织分子指纹的即时快照，以确切地知道正在切割的组织。如果切除了错误的组织，手术就很难达到微创。PIRL提供分子水平的信息，用于识别癌症边界，疾病状态，并完全避免对健康组织的损害。发现愈合发生，没有可见的瘢痕组织形成。瘢痕组织不仅是不希望的美容，而且限制了所有外科手术的功效。这一特点为完全恢复功能和降低相关的保健费用提供了前景。拟议的研究将开发下一代PIRL手术系统，该系统将以与手术室中最高速度的手术工具相当的速度提供单细胞准确性。还将开发所有光纤光束传输系统，这些系统将能够进入身体的不同部位，进入伤口尺寸仅为200微米（单根头发的尺寸），用于以绝对最小的创伤去除癌症，活检，疾病组织。在基础科学方面，该研究计划将通过利用PIRL消融过程固有的完整分子特征和高收集效率来提高空间成像质谱（MS）的灵敏度，以推动单细胞分辨率，直接映射导致细胞功能和疾病状态发作的生化途径。该目标还将提供用于手术指导的组织特异性分子信息，并且鉴于MS的灵敏度，代表了在尽可能早的阶段检测疾病的生物诊断的最终限制。

The fundamental single cell limit to minimally invasive surgery has been achieved with the Picosecond InfraRed Laser (PIRL) scalpel - without scar tissue formation and with complete molecular signatures of excised tissue remaining perfectly intact. The basic physics of this unique tool involve the selective excitation of water vibrations and direct coupling to translational motions to drive ablation processes faster than energy loss to surrounding tissue and associated collateral damage or thermal modification of the molecular composition of the tissue being excised. One obtains an instant snapshot of the molecular fingerprints of the tissue to know exactly what tissue is being cut. If the wrong tissue is removed, the surgery is hardly minimally invasive. PIRL provides molecular level information for identifying cancer borders, disease states, and completely avoids damage to healthy tissue. Healing is found to occur with no visible scar tissue formation. Scar tissue is not only cosmetically undesirable but also limits the efficacy for all surgical procedures. This feature holds the prospect for full recovery of function and with the associated reduced health care costs. The proposed research will develop the next generation of PIRL surgical systems that will provide single cell accuracy at speeds comparable to the highest speed surgical tools in the OR. All fiber beam delivery systems will also be developed that will enable access to different parts of the body with entry wound sizes of only 200 microns (dimensions of a single hair) for removing cancers, biopsies, disease tissue with absolutely minimal trauma. On the basic science front, this research program will increase the sensitivity of spatial imaging mass spectrometry (MS) by exploiting the intact molecular signatures and high collection efficiency inherent to the PIRL ablation process to push towards single cell resolution to directly map biochemical pathways leading to cell functions and onset of disease states. This objective will additionally provide the tissue specific molecular information for surgical guidance and given the sensitivity of MS, represent the ultimate limit to biodiagnostics for the detection of diseases at the earliest possible stage.