Instrument development for vibrational circular dichroism imaging

振动圆二色性成像仪器的开发

基本信息

批准号：
10650769
负责人：
Rohit Bhargava
金额：
$ 33.27万
依托单位：
UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
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：
2021-07-01 至 2025-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10650769
关键词：
Address Algorithms Amyloid Basic Science Biogenesis Biological Biological Process Biomedical Research Chemicals Circular Dichroism Spectroscopy Complex Computer software Custom DNA Data Data Analyses Dependence Deposition Development Device or Instrument Development Disease Drug Design Electronics Feasibility Studies Fingerprint Fourier Transform Frequencies Goals Handedness Health Heart Hour Human Image Imaging Device Imaging technology Intervention Knowledge Lasers Life Light Maps Measurable Measurement Measures Medical Microscope Microscopic Microscopy Modeling Modernization Molecular Molecular Profiling Molecular Structure Morphologic artifacts Noise Nucleic Acids Optics Peptides Performance Pharmaceutical Preparations Process Publishing Reporting Research Sampling Scanning Science Signal Transduction Site Spectroscopy, Fourier Transform Infrared Spectrum Analysis Speed System Techniques Technology Testing Theoretical model Time Tissue Sample Validation Vibrational Circular Dichroism Work analytical method biological research clinical diagnostics data management data visualization design enantiomer experience instrument instrumentation microscopic imaging new technology novel prototype quantum sugar technology development technology research and development temporal measurement theories timeline tool transmission process

项目摘要

Abstract Molecular chirality is at the heart of many chemical processes that determine life and drives significant research in development and disease. All life has chiral asymmetry with naturally occurring molecules and long-range assemblies being of distinct handedness. Many exogenous molecules, for example those useful as drugs, also have a distinct enantiomeric dependence for their efficacy in benefiting human health. Thus, measurement of molecular chirality is of critical importance across the medical sciences. Vibrational Circular Dichroism (VCD) spectroscopy has emerged as a powerful platform for quantifying chirality and molecular structure. However, imaging has not been demonstrated due to technological challenges. VCD measurements are largely of homogeneous materials, neat or in solution and probed with sensitive Fourier transform infrared (FT-IR) spectrometers. Microscopy would require ~105 reduction of the typical sensing volume and increase in speed that would make imaging feasible. Instead of utilizing FT-IR spectroscopy, we built a custom quantum cascade laser (QCL) microscope to demonstrate feasibility of a point scanning VCD instrument capable of acquiring spectra rapidly across all fingerprint region wavelengths in both transflection and transmission configurations. Moreover, for the first time, we also demonstrate the VCD imaging performance of our instrument for site-specific chirality mapping of biological tissue samples. However, the feasibility data also point to several technological and conceptual challenges that this project seeks to address in developing a practical prototype. The prototype to be developed here, termed vibrational circular dichroism imaging microscope or VIM, aims to record chirality from microscopically heterogeneous biomedical samples. We propose a design for VIM using a laser scanning approach to minimize artifacts and maximize signal. Starting from a de novo design, we will use commercial and custom optics, custom electronics for control and data management, and in-house software to develop the prototype. Next, we model the VCD image formation process and develop the analytical methods for VIM. The theoretical model developed here builds on our models of IR microscopy and will guide prototype development while ultimately provide greater accuracy, precision and assurance to data recorded. Finally, we validate the performance and broad utility of VIM using well-characterized samples. Together, the work will develop new VCD imaging technology that opens capability to measure and research a wide variety of biological problems.

抽象的分子手性是许多化学过程的核心，这些化学过程决定生命并推动大量研究在发育和疾病中。所有生命都有手性不对称性，天然存在分子和远程组件是独特的惯用性。许多外源分子，例如那些用作药物的分子对于它们在受益于人类健康方面的功效，具有独特的对映体依赖性。因此，测量分子手性在整个医学科学中至关重要。振动圆二色性（VCD）光谱已成为量化手性和分子结构的强大平台。然而，由于技术挑战，尚未证明成像。 VCD测量很大均匀的材料，整洁或溶液中，并用敏感的傅立叶变换红外（FT-IR）探测光谱仪。显微镜需要〜105典型的感应体积减少并增加速度那将使成像可行。我们建立了一个定制的量子级联，而不是利用FT-IR光谱法激光（QCL）显微镜证明了能够获取的点扫描VCD仪器的可行性光谱在转移和传输构型中迅速在所有指纹区域波长中。此外，我们还第一次演示了我们的仪器的VCD成像性能生物组织样品的手性图。但是，可行性数据也指出了几种技术以及该项目在开发实际原型时试图解决的概念挑战。原型在此要开发的，称为振动圆二色性成像显微镜或VIM，旨在记录手性来自显微镜异质生物医学样品。我们建议使用激光扫描为VIM设计设计最小化伪影并最大化信号的方法。从从头设计开始，我们将使用商业和自定义光学器件，用于控制和数据管理的自定义电子设备以及内部软件以开发原型。接下来，我们对VCD图像形成过程进行建模，并为VIM开发分析方法。这这里开发的理论模型以我们的IR显微镜模型为基础，并将指导原型开发尽管最终为记录的数据提供了更高的准确性，精度和保证。最后，我们验证了使用良好的样品使用VIM的性能和广泛的效用。一起工作将开发新的 VCD成像技术开放了衡量和研究各种生物学问题的能力。