Instrument development for vibrational circular dichroism imaging

振动圆二色性成像仪器的开发

• 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
• 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

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.

摘要 分子手性是许多决定生命的化学过程的核心，并推动了重要的研究 发展和疾病。所有的生命都具有手性不对称性， 有明显的偏手性。许多外源分子，例如可用作药物的那些，也 对有益于人体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是至关重要的。振动圆二色性（VCD） 光谱学已经成为量化手性和分子结构的有力平台。然而，在这方面， 由于技术上的挑战，成像还没有得到证实。VCD测量主要是 均质材料，纯的或在溶液中，并用灵敏的傅里叶变换红外（FT-IR）探测 光谱仪显微镜将需要典型的感测体积减少约105并且速度增加 这将使成像成为可能。我们没有使用FT-IR光谱，而是建立了一个定制的量子级联， 激光（QCL）显微镜，以证明点扫描VCD仪器的可行性， 在透射反射和透射配置中，光谱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的VCD成像性能， 生物组织样品的手性映射。然而，可行性数据也指出了一些技术问题。 和概念上的挑战，这个项目试图解决在开发一个实际的原型。原型 在这里开发的，称为振动圆二色成像显微镜或Vim，旨在记录手性 从微观上异质的生物医学样本中。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 样机其次，我们建立VCD影像形成过程的模型，并发展Vim的分析方法。的 这里开发的理论模型建立在我们的红外显微镜模型上，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，我们验证了 Vim的性能和广泛的实用性使用良好的表征样品。在一起，这项工作将发展新的 VCD成像技术，开启了测量和研究各种生物问题的能力。