Breakthrough sub-cellular 3D chemical composition research platform for live cells, based on the new invention of nanoscale - confocal photothermal IR micro-spectroscopy (n-CPIR)

基于纳米级新发明——共焦光热红外显微光谱（n-CPIR）的突破性活细胞亚细胞3D化学成分研究平台

基本信息

批准号：
9466345
负责人：
Ji-Xin Cheng
金额：
$ 22.5万
依托单位：
ANASYS INSTRUMENTS CORPORATION
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-09-30 至 2018-03-31
项目状态：
已结题

项目摘要

Abstract This proposal will lead to a Breakthrough sub‐cellular 3D chemical composition research platform for live cells, based on the new invention of sub‐micron confocal photothermal IR micro‐spectroscopy (CPIR). Label‐free sub‐micron chemical imaging and spectroscopy has long been sought for visualization of biomolecules and materials in complex living systems. Many diseases first manifest themselves at the cellular, or subcellular level. IR micro‐spectroscopy is a powerful technique but its use in life sciences in general and cellular analysis in particular has been limited due to the following 2 key limitations: a) Spatial resolution limited by diffraction to ~ 10 µm. b) Inability for in‐vivo imaging due to strong IR absorption by water. This proposal eliminates both of the above limitations and is based on a recently published patent‐ pending breakthroughby the PI, Prof. Ji‐Xin Cheng of Boston University and is licensed exclusively by Anasys Instruments for commercialization. Prof. Cheng is one of the world's leading vibrational spectroscopy researchers and is the co‐inventor of the CARS (Coherent Anti‐Stokes Raman Scattering) microscope, which is a major innovation in the field of Raman Spectroscopy. Anasys pioneered the field of AFM (Atomic force microscope) based photothermal nanoscale IR Spectroscopy where an AFM probe detects the photothermal signal induced by IR absorption. The goal of this proposal is to create a high speed confocal optical microscopy platform capable of 300 nm IR Spectroscopy in fluid. This platform can be used in sub‐cellular chemical composition research of live cells which has many applications in the life sciences. The proposed CPIR platform is highly innovative because it would enable real‐time imaging of lipid metabolites in single live tumor cells based on fingerprint IR bands. Compared to the widely studied genetic aspect of cancer and the well‐known Warburg effect, appreciation of the role of lipids in cancer development is still emerging. Aberrant expressions of lipogenic genes have been found in brain, mammary, prostate and many other cancer. Even with these discoveries, lipid metabolism has not been used as a prognostic factor for cancer aggressiveness due to lack of differential detection and quantitation technology. Our proposal aims to fill this gap by quantifying the amount and composition of lipid droplets, an important aspect of lipogenesis in tumor cells. Though we focus on lipid metabolites here, our spectroscopic imaging platform is generally applicable to monitor the intracellular dynamics of other metabolites, anti‐cancer drugs, and nutrition molecules such as fatty acids and amino acids, thus having a far‐reaching impact on cancer research.

抽象的该提案将带来突破性的亚细胞 3D 化学成分研究平台细胞，基于亚微米共焦光热红外显微光谱（CPIR）的新发明。无标记亚微米化学成像和光谱学长期以来一直被认为可以用于可视化复杂生命系统中的生物分子和材料首先表现在身体上。细胞或亚细胞水平的红外显微光谱是一种强大的技术，但它在生命科学中的应用由于以下两个关键限制，一般分析和特别是细胞分析受到限制： a) 空间分辨率受衍射限制为 ~ 10 µm。 b) 由于水对红外线的强烈吸收而无法进行体内成像。该提案消除了上述两个限制，并且基于最近发布的专利- 正在等待 PI 波士顿大学 Ji‐Xin Cheng 教授的突破，并获得程教授是Anasys Instruments 商业化领域的世界领先者之一。光谱研究人员，是 CARS（相干反斯托克斯拉曼散射）的共同发明者显微镜，这是 Anasys 开创的拉曼光谱领域的一项重大创新。基于 AFM（原子力显微镜）的光热纳米级红外光谱，其中 AFM 探头检测由红外吸收引起的光热信号。该提案的目标是创建一个高速共焦光学显微镜平台，能够进行 300 该平台可用于流体中的亚细胞化学成分研究。活细胞在生命科学中有许多应用。拟议的 CPIR 平台具有高度创新性，因为它可以实现脂质的实时成像。基于指纹红外谱带的单个活肿瘤细胞中的代谢物与广泛研究的比较。癌症的遗传方面和众所周知的瓦尔堡效应，对脂质在癌症中的作用的认识。在大脑中发现脂肪生成基因的异常表达，乳腺癌、前列腺癌和许多其他癌症。即使有了这些发现，脂质代谢仍然没有发生变化。由于缺乏差异检测和缺乏而被用作癌症侵袭性的预后因素我们的建议旨在通过量化的数量和成分来填补这一空白。脂滴是肿瘤细胞脂肪生成的一个重要方面，尽管我们关注的是脂质代谢物。在这里，我们的光谱成像平台通常适用于监测细胞内的动态其他代谢物、抗癌药物以及脂肪酸、氨基酸等营养分子，从而对癌症研究产生深远影响。