Diamond NMR spectrometer for microfluidic metabolite profiling

用于微流体代谢物分析的金刚石核磁共振波谱仪

基本信息

批准号：
10385582
负责人：
Victor Marcel Acosta
金额：
$ 25.9万
依托单位：
ODMR TECHNOLOGIES, INC.
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：
2021-09-16 至 2023-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10385582
关键词：
Academia Amino Acids Analytical Biochemistry Analytical Chemistry Biological Assay Chemical Structure Chemicals Chromatography Collaborations Collection Communities Detection Devices Diamond Electron Nuclear Double Resonance Engineering Feedback Film Fluorescence Glucose Glutamine High Pressure Liquid Chromatography Industry Label Lasers Magnetic Resonance Mass Spectrum Analysis Measurement Methods Microfluidic Microchips Microfluidics NMR Spectroscopy Natural Products Nitrogen Nobel Prize Nuclear Nuclear Magnetic Resonance Optics Performance Pharmacodynamics Phase Photons Physiologic pulse Physiological Positioning Attribute Protocols documentation Raman Spectrum Analysis Research Resolution Sampling Science Side Signal Transduction Specificity Structure Techniques Technology Urea Work analytical method base cost design detector drug development feature detection improved instrument magnetic field metabolomics method development microwave electromagnetic radiation novel operation portability prototype quantum scale up sensor

项目摘要

Project Summary. Nuclear magnetic resonance (NMR) is among the most powerful analytical techniques ever invented, as recognized by 6 Nobel Prizes for methods development alone. Nonetheless, NMR is notoriously plagued by poor sensitivity. State-of-the-art NMR spectrometers feature detection thresholds of ~1 nanomole for µL sample volumes (~100 nanograms). This places NMR sensitivity many orders of magnitude behind other analytical chemistry techniques such as mass spectrometry, Raman spectroscopy, and fluorescence labeling. Improvements in NMR often focus on using larger magnets, but progress has plateaued; over the last 25 years, the fundamental signal strength has only increased ~2-fold. We seek to fundamentally change the NMR hardware by using diamond films doped with Nitrogen-Vacancy centers to detect nuclear magnetization non-inductively via pulsed optically detected magnetic resonance methods. The form factor of our NMR detector is easily integrated with hyphenation techniques so that samples can be separated into sub-components before analysis. Recently, we built a tabletop microfluidic diamond NMR apparatus with 40 pL detection volume and used it in proof-of-principle analytical chemistry applications including the first 2D NMR spectra acquired by a diamond NMR sensor. In Phase I, we will optimize sensor spectral resolution and sensitivity and validate its operation using metabolite mixtures. This work will place us in the position to deliver our devices to end-users in industry (Merck) and academia (UW) and incorporate feedback to scale up to market. If successful, our prototype could have a profound impact on analytic biochemistry research, by combining mass-spectrometry-level sensitivity with NMR-level accuracy. Specifically, we improve upon existing analytical methods by offering: 1. Greater performance. We offer 1000-fold better sensitivity (pmol instead of nmol) than current NMR spectrometers. This sensitivity approaches that of mass spectrometry but retains benefits of NMR such as non-destructive, absolute quantitation and structural identification. 2. Compatibility with hyphenated separation techniques. Our spectrometer is compact and easily integrated into microfluidic chips for online chromatography-based assays (HPLC) for sample-limited analyses (metabolomics, pharmacodynamics, natural products). 3. Lower cost. The small sample volume in our spectrometer leads to reduced engineering costs, leading to greater affordability compared to current NMR spectrometers.

项目摘要。核磁共振 (NMR) 是最强大的分析方法之一。迄今为止发明的技术，仅仅因为方法开发就获得了 6 项诺贝尔奖的认可。然而，最先进的 NMR 一直受到灵敏度较差的困扰。光谱仪的检测阈值为 µL 样品体积的 ~1 纳摩尔（~100 纳克），这使得 NMR 灵敏度比其他分析方法低许多数量级。化学技术，例如质谱、拉曼光谱和荧光核磁共振标记的改进通常集中在使用更大的磁铁上，但进展已经很明显了。在过去 25 年中，基本信号强度仅增加了约 2 倍。我们寻求通过使用掺杂金刚石薄膜从根本上改变核磁共振硬件氮空位中心通过脉冲光学非感应检测核磁化强度我们的 NMR 探测器的外形尺寸易于集成。使用连字符技术，以便在之前可以将样本分成子组件最近，我们建造了一台具有 40 pL 检测能力的台式微流控金刚石核磁共振仪。卷并将其用于原理验证分析化学应用，包括第一个 2D 由金刚石 NMR 传感器获取的 NMR 光谱在第一阶段，我们将优化传感器光谱。这项工作将提高分辨率和灵敏度，并使用代谢物混合物验证其操作。使我们能够向工业界（默克）和学术界的最终用户提供我们的设备（华盛顿大学）并结合反馈以扩大市场规模。如果成功，我们的原型可能会对分析生物化学研究产生深远的影响，通过具体来说，我们将质谱级灵敏度与核磁共振级精度相结合。通过提供以下功能来改进现有的分析方法： 1. 性能比我们高 1000 倍（pmol 而不是 nmol）。目前的核磁共振波谱仪的灵敏度接近质谱仪，但仍保持不变。 NMR 的优点，例如无损、绝对定量和结构鉴定。 2. 与联用分离技术的兼容性我们的光谱仪结构紧凑。轻松集成到微流控芯片中，用于基于色谱的在线分析 (HPLC) 有限样本分析（代谢组学、药效学、天然产物）。 3. 成本更低。我们的光谱仪中的样品量较小，因此可以减少工程量。成本，与当前的 NMR 波谱仪相比，具有更高的承受能力。

项目成果

期刊论文数量（1）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Nuclear quadrupole resonance spectroscopy with a femtotesla diamond magnetometer.

使用飞特斯拉金刚石磁力计的核四极共振光谱。

DOI：
10.1126/sciadv.adh3189
发表时间：
2023-02-24
期刊：
Science advances
影响因子：
13.6
作者：
Yaser Silani;J. Smits;I. Fescenko;M. Malone;A. Mcdowell;A. Jarmola;P. Kehayias;B. Richards
通讯作者：
B. Richards