Photonics probing of DNA mass density spatial structure for cancer diagnostics

用于癌症诊断的 DNA 质量密度空间结构的光子学探测

基本信息

批准号：
10196725
负责人：
Prabhakar Pradhan
金额：
$ 39.74万
依托单位：
MISSISSIPPI STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-04-02 至 2024-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10196725
关键词：
Affect Americas Biological Biological Markers Biological Sciences Biophysics Breast Cancer Detection Cancer Diagnostics Cancerous Cell Culture Techniques Cell Nucleus Cells Cellular Structures Communities Computer software Confocal Microscopy Coupled Coupling Cytoskeleton DNA DNA Binding DNA Probes DNA Sequence Alteration DNA Structure Data Detection Development Dimensions Disease Disease Progression Dyes Fluorescence Microscopy Fluorescent Dyes Gene Rearrangement Goals Heterogeneity Human Image Institutes Journals Lasers Lead Length Light Liver Malignant Neoplasms Measurement Measures Methods Molecular Morphology Mutation Normal Cell Nuclear Nuclear Structure Optics Organelles Outcome Physics Physiological Process Property Prostate Publishing Refractive Errors Refractive Indices Research Research Design Research Personnel Resolution Sampling Scanning Series Skin Slice Societies Spectrum Analysis Stains Statistical Data Interpretation Structure System Techniques Thinness Tissue Sample Tissues Tumor Cell Biology Tumorigenicity Validation Variant Work base cancer biomarkers cancer cell carcinogenesis cell type cellular imaging condensed matter physics confocal imaging density indexing microscopic imaging molecular mass nano nanoscale neglect news novel optical lattices photonics physical state skeletal submicron success tool user-friendly

项目摘要

Abstract Cancer is known to be associated with genetic mutations. Evidences suggest that these genetic changes lead to increased structural disorder in biological cell nuclei. This disorder is believed to result from alteration and rearrangement of DNA molecular mass density at the beginning. In the case of progressive carcinogenesis, such changes occur at length scales ranging from nano- (<100nm) to submicron (>100nm) scales. Consequently, it has been recognized that measurement and quantification of these structural changes could, therefore, be a potential cancer biomarker. Accordingly, some recent studies based on partial wave spectroscopy and other nano-optical techniques have quantified the nanoscale structural properties in cells. However, these techniques are still in the early stages and require complicated new experimental setup, thus limiting access to these studies to only a handful of research groups in the biomedical and biological sciences. Meanwhile, the use of existing optical techniques, e.g., confocal microscopy, to conduct such studies is still unexplored. In view of that, we have developed a novel method, by combining confocal microscopy imaging and a technique borrowed from mesoscopic physics, termed as inverse participation ratio (IPR) technique, or simply the “IPR technique”, to measure and quantify the degree of structural disorder in cell nuclei. Components of the cellular matrix are highly heterogeneous, including multifractality of dimensions, e.g., cellular structures formed at different scales. Thus, to interrogate cellular heterogeneity and to obtain quantitative data about structural or DNA molecular morphological disorder (from the norm), it is generally necessary to establish a number of parameters. However, with the present IPR approach it is possible to selectively quantify structural changes in the nuclear DNA, by using DAPI stained confocal micrographs, and represent it in just one single parameter, namely the <IPR> value. The <IPR> value provides a measure of the degree of structural disorder, i.e., “disorder strength”, of the sample. Our preliminary results show an underlying relationship between structural disorder in nuclear DNA and carcinogenesis. Therefore, in this proposal, we will measure and quantify the submicron-scale structural disorder in the nuclear DNA of different normal and cancerous cells, obtained from cell cultures and tissues, via IPR analysis of the confocal micrographs. By coupling the IPR technique to the widely used confocal microscopy, we aim to (i) develop an automated quantification technique to measure the degree of structural disorder of selective molecular density in an organelle, in particular nuclear DNA, from DAPI stained confocal micrographs of the cells, and (ii) calibrate the degree of structural disorder in normal and cancer cells in liver, skin, and skeletal cell cultures and tissues nuclear structure. The success of this project will lead to a new direction in cancer detection, as well as cell characterization based on quantified structural changes in nuclear DNA.

抽象的已知癌症与基因突变有关。有证据表明这些基因变化导致癌症。生物细胞核结构紊乱增加，这种紊乱被认为是由改变和改变造成的。在进行性致癌的情况下，DNA分子质量密度在开始时发生重排。经过测试，变化发生在从纳米（<100nm）到亚微米（>100nm）尺度的长度范围内。因此，人们已经认识到，对这些结构性变化的测量和量化可能是一种因此，最近一些基于部分波光谱和其他的研究。纳米光学技术已经量化了细胞中的纳米级结构特性。仍处于早期阶段，需要复杂的新实验装置，从而限制了对这些研究的访问同时，只有少数生物医学和生物科学研究小组利用现有的技术。有鉴于此，我们尚未探索用于进行此类研究的光学技术，例如共焦显微镜。通过结合共焦显微镜成像和借鉴的技术，开发了一种新方法介观物理，称为逆参与比（IPR）技术，或简称为“IPR技术”，测量和量化细胞核的结构紊乱程度。异质的，包括维度的多重分形，例如，在不同尺度上形成的细胞结构。询问细胞异质性并获得有关结构或 DNA 分子的定量数据形态紊乱（来自规范），一般需要建立一些参数。利用目前的 IPR 方法，可以选择性地量化核 DNA 的结构变化，方法是使用 DAPI 染色共焦显微照片，并仅用一个参数（即 <IPR> 值）表示它。 <IPR>值提供了样品结构无序程度的测量，即“无序强度”。我们的初步结果表明核 DNA 结构紊乱与因此，在本提案中，我们将测量和量化亚微米级的结构紊乱。通过 IPR 从细胞培养物和组织中获得不同正常细胞和癌细胞的核 DNA 通过将 IPR 技术与广泛使用的共焦显微镜相结合，我们对共焦显微照片进行了分析。目标是（i）开发一种自动量化技术来测量选择性结构紊乱的程度细胞器（特别是核 DNA）中的分子密度，来自 DAPI 染色的共聚焦显微照片 (ii) 校准肝脏、皮肤和骨骼细胞中正常细胞和癌细胞的结构紊乱程度该项目的成功将为癌症检测带来新的方向，以及基于核 DNA 定量结构变化的细胞表征。

项目成果

期刊论文数量（2）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Photonics probing of pup brain tissue and molecular-specific nuclear nanostructure alterations due to fetal alcoholism via light scattering/localization approaches.

DOI：
10.1117/1.jbo.27.7.076002
发表时间：
2022-07
期刊：
JOURNAL OF BIOMEDICAL OPTICS
影响因子：
3.5
作者：
Adhikari, Prakash;Shukla, Pradeep;Alharthi, Fatemah;Bhandari, Shiva;Meena, Avtar;Rao, Radhakrishna;Pradhan, Prabhakar
通讯作者：
Pradhan, Prabhakar