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.

抽象的该建议将导致实时的突破性亚细胞3D化学组成研究平台细胞，基于亚微米共聚焦光热IR微光谱（CPIR）的新发明。长期以来，已经感觉到无标签的亚微米化学成像和光谱法以可视化复杂生活系统中的生物分子和材料。许多疾病首先在细胞或亚细胞水平。红外微光谱是一种强大的技术，但在生命科学中的使用由于以下2个关键局限性，尤其是一般和细胞分析受到限制： a）衍射限制为〜10 µm的空间分辨率。 b）由于水吸收强大的IR吸收，无法进行体内成像。该提案消除了以上两种限制，并基于最近发表的专利 - 在Breakthy By Pi，Boston University的Ji-Xin Cheng教授之前，仅由 Anasys商业化工具。郑教授是世界上领先的振动之一光谱研究人员是汽车的共同发入者（连贯的反stokes拉曼散射）显微镜，这是拉曼光谱领域的主要创新。阿纳西斯开创了场地基于AFM（原子力显微镜）的光热纳米级红外光谱法探针检测通过IR吸收得出的光热信号。该提案的目的是创建一个能够300的高速共聚焦光学显微镜平台流体中的NM红外光谱。该平台可用于用于的亚细胞化学组成研究在生命科学中具有许多应用的活细胞。提出的CPIR平台具有高度创新性，因为它可以实时成像脂质基于指纹IR带中的单个活肿瘤细胞中的代谢产物。与所研究的广泛研究癌症的通用方面和著名的沃伯格效应，对脂质在癌症中的作用的欣赏发展仍在出现。在大脑中发现了脂肪生成基因的异常表达，乳腺，前列腺和许多其他癌症。即使有这些发现，脂质代谢也不是由于缺乏差异检测和定量技术。我们的建议旨在通过量化的数量和组成来填补这一空白脂质液滴，肿瘤细胞中脂肪生成的重要方面。尽管我们专注于脂质代谢物在这里，我们的光谱成像平台通常适用于监视细胞内动力学其他代谢产物，抗癌药和营养分子，例如脂肪酸和氨基酸，因此对癌症研究产生深远影响。