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

皮秒红外激光(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签名保持完好。这一独特工具的基本物理原理包括选择性地激发水的振动和直接耦合到平移运动，以比对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修改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，以准确地知道哪些组织正在被切割。如果切除了错误的组织，手术就很难达到最小的侵入性。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。愈合过程中没有明显的疤痕组织形成。疤痕组织不仅在美观上是不可取的，而且还限制了所有外科手术的疗效。这一特征具有完全恢复功能的前景，并伴随着相关的医疗保健成本的降低。这项拟议的研究将开发下一代PIRL手术系统，该系统将提供单细胞精度，其速度可与OR中最快的手术工具相媲美。还将开发所有光纤光束传输系统，使进入伤口大小仅为200微米(一根头发的尺寸)的身体不同部位能够以绝对最小的创伤移除癌症、活检和疾病组织。在基础科学方面，这项研究计划将提高空间成像质谱仪(MS)的灵敏度，利用PIRL消融过程固有的完整分子特征和高收集效率，推动单细胞分辨率，以直接绘制导致细胞功能和疾病状态发生的生化路径。这一目标还将为手术指导提供组织特异性的分子信息，并考虑到MS的敏感性，代表着生物诊断的极限，以便在尽可能早的阶段发现疾病。

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.