Nuclear magnetic resonance microscope based on diamond quantum sensors

基于金刚石量子传感器的核磁共振显微镜

• 批准号: 10002721
• 负责人: Victor Marcel Acosta
• 金额: $ 211.55万
• 依托单位: UNIVERSITY OF NEW MEXICO
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-30 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10002721
• 关键词: Acute; Analytical Biochemistry; Awards and Prizes; Biological; Biological Assay; Breast Cancer Cell; Cells; Cellular biology; Chemicals; Complex Mixtures; Detection; Development; Diamond; Goals; Image; Label; Lactic acid; Lead; Liquid substance; Mammalian Cell; Metabolic; Methods; Microfluidic Microchips; Microfluidics; Microscope; Molecular; NMR Spectroscopy; Nobel Prize; Noise; Nuclear; Nuclear Magnetic Resonance; Optics; Outcome; Physiological; Protocols documentation; Pyruvate; Research; Resolution; Sampling; Signal Transduction; System; Techniques; Time; base; experimental study; high risk; imaging capabilities; improved; metabolomics; method development; quantum; quantum computer; qubit; sensor; small molecule; tool; two-dimensional

Project Summary Nuclear magnetic resonance (NMR) spectroscopy is among the most powerful analytical techniques ever invented. This has been recognized by, for example, the 6 Nobel Prizes awarded for NMR methods development alone. However, the sensitivity and detection volumes in conventional NMR systems are insufficient for metabolic analysis of picoliter sample volumes such as single mammalian cells. At the same time, there is an acute need for non-invasive, label-free, chemically-specific techniques that operate at the single-cell level and/or can be integrated into hyphenated microfluidic assays. The proposed research seeks to develop a new platform for NMR spectroscopy and imaging at the scale of single cells (picoliters). The platform is based on recently-developed sensors which use qubits (the logical bits in quantum computers) to detect environmental parameters, so-called “quantum sensors”. Specifically, fluorescent spin qubits in diamond are used to generate and detect nuclear magnetization. The hypothesis underlying this proposal is that the use of non-inductive diamond quantum sensors could lead to improvements in sensitivity, spectral resolution, spatial resolution, and microfluidic integration beyond what is currently available in small-volume NMR spectroscopy. The PI’s lab has recently demonstrated a proof of concept by embedding a diamond quantum sensor in a microfluidic chip and detecting two-dimensional NMR spectra of picoliter volumes of fluid analytes. However ​substantial improvements in sensor spectral resolution and sensitivity are required to quantify molecular composition at physiological concentrations with single-cell spatial resolution. That is the goal of this proposal. This is a high risk proposal and the outcomes of development efforts are unknown. However the proposed research plan seeks to cover the following four objectives: 1. The fractional spectral resolution of diamond NMR spectrometers will be improved to better than 10 parts per billion. This will involve constructing an apparatus that operates at 3 tesla and developing diamond quantum sensing protocols optimized for this higher field. 2. The sensitivity of diamond NMR spectrometers will be improved to better than 10 millimolar (signal-to-noise ratio of 3 after 1 second integration). This involves rigorous optimization of the diamond sensor and developing methods to enhance nuclear spin polarization via optical hyperpolarization. 3. The molecular composition of complex mixtures of metabolites in solution will be quantified using an optimized diamond NMR spectrometer. 4. A proof-of-principle experiment will be conducted to validate the imaging capabilities of diamond NMR. An NMR microscope will be constructed and used to characterize the conversion of pyruvate to lactic acid in breast cancer cells. If successful, the demonstration of ​picoliter NMR metabolomics may have a substantial impact on analytical biochemistry and single-cell biology.

项目概要 核磁共振 (NMR) 光谱是迄今为止最强大的分析技术之一 例如，核磁共振方法获得了 6 项诺贝尔奖，这一点得到了认可。 然而，传统 NMR 系统的灵敏度和检测量是有限的。 同时不足以进行皮升样品体积（例如单个哺乳动物细胞）的代谢分析。 时间，迫切需要非侵入性、无标记、化学特异性技术 单细胞水平和/或可以整合到连字符的微流体测定中。 拟议的研究旨在开发一个新的核磁共振波谱和成像平台 该平台基于最近开发的使用量子位（逻辑位）的传感器。 在量子计算机中）来检测环境参数，即所谓的“量子传感器”。 金刚石中的荧光自旋量子位用于产生和检测核磁化强度。 该提案的基础是使用非感应金刚石量子传感器可以带来改进 在灵敏度、光谱分辨率、空间分辨率和微流体集成方面超出了目前的水平 PI 实验室最近展示了一个概念验证。 将金刚石量子传感器嵌入微流控芯片中并检测二维核磁共振谱 然而，传感器光谱分辨率和体积的显着提高。 使用单细胞空间定量生理浓度的分子组成需要灵敏度 这就是该决议的目标。 这是一个高风险的提案，开发工作的结果未知。 研究计划旨在涵盖以下四个目标： 1、金刚石核磁共振波谱仪的分数谱分辨率将提高到优于10 这将涉及建造一个以 3 特斯拉运行的设备并进行开发。 针对这一更高领域进行了优化的金刚石量子传感协议。 2、金刚石核磁共振波谱仪的灵敏度将提高到优于10毫摩尔 （1 秒积分后信噪比为 3）这涉及到钻石的严格优化。 传感器并开发通过光学超极化增强核自旋极化的方法。 3. 溶液中代谢物复杂混合物的分子组成将使用 优化的金刚石核磁共振波谱仪。 4. 将进行原理验证实验来验证金刚石核磁共振的成像能力。 将建造核磁共振显微镜并用于表征丙酮酸向乳酸的转化 乳腺癌细胞中的酸。 如果成功，皮升核磁共振代谢组学的演示可能会对分析产生重大影响 生物化学和单细胞生物学。