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决定生命并推动重大研究的化学过程的核心在发育和疾病方面。所有生命都具有天然存在的分子和长程手性不对称性组件具有明显的偏手性。许多外源分子，例如那些用作药物的分子，也其有益于人类健康的功效具有明显的对映体依赖性。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) 光谱学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，成像尚未得到证实。 VCD 测量主要是纯质或溶液中的均质材料，并用灵敏的傅里叶变换红外 (FT-IR) 进行探测光谱仪。显微镜需要将典型传感体积减少约 105 倍并提高速度这将使成像变得可行。我们没有使用 FT-IR 光谱，而是构建了定制的量子级联激光 (QCL) 显微镜展示了能够采集数据的点扫描 VCD 仪器的可行性在半透反射和透射配置中，光谱可快速跨越所有指纹区域波长。此外，我们还首次展示了我们的仪器针对特定地点的VCD成像性能生物组织样本的手性图谱。然而，可行性数据也指出了一些技术以及该项目在开发实用原型时寻求解决的概念挑战。原型机这里开发的称为振动圆二色性成像显微镜或 VIM，旨在记录手性来自微观异质生物医学样本。我们提出了一种使用激光扫描的 VIM 设计最小化伪影并最大化信号的方法。从头开始设计，我们将使用商业和定制光学器件、用于控制和数据管理的定制电子器件以及用于开发的内部软件原型。接下来，我们对 VCD 图像形成过程进行建模并开发 VIM 的分析方法。这这里开发的理论模型建立在我们的红外显微镜模型的基础上，并将指导原型开发同时最终为记录的数据提供更高的准确性、精确度和保证。最后，我们验证使用特征良好的样本来展示 VIM 的性能和广泛实用性。共同努力，这项工作将发展出新的 VCD 成像技术开启了测量和研究各种生物问题的能力。