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.

项目摘要 核磁共振光谱学是有史以来最强大的分析技术之一。 是虚构的。例如，这一点已经被授予核磁共振方法的6个诺贝尔奖所认可 单单是发展。然而，常规核磁共振系统的灵敏度和检测体积是 不足以进行皮升样本量的代谢分析，例如单个哺乳动物细胞。同时 随着时间的推移，迫切需要非侵入性的、无标记的、具有化学特异性的技术，这些技术在 单细胞水平和/或可以集成到联用微流控分析中。 拟议的研究旨在开发一个新的核磁共振波谱和成像平台，其规模为 单细胞(皮升)。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”。具体来说， 钻石中的荧光自旋量子位被用来产生和检测核磁化。假说 这一提议的基础是无感钻石量子传感器的使用可能会带来改进 在灵敏度、光谱分辨率、空间分辨率和微流控集成方面超越了当前 在小体积核磁共振波谱中可用。PI的实验室最近展示了一种概念证明 在微流控芯片中嵌入金刚石量子传感器并检测其二维核磁共振谱 皮升体积的流体分析物。然而，​在传感器光谱分辨率和 用单细胞空间法定量生理浓度下的分子组成需要灵敏度 决议。这就是这项提案的目标。 这是一个高风险的提议，发展努力的结果是未知的。然而，建议的 研究计划力求涵盖以下四个目标： 1.钻石核磁共振谱仪的分数光谱分辨率将提高到10 十亿分之几。这将包括建造一台以3特斯拉速度运行的设备，并开发 钻石量子传感协议针对这一更高的领域进行了优化。 2.钻石核磁共振谱仪的灵敏度将提高到10毫米以下 (1秒积分后的信噪比为3)。这涉及到对钻石的严格优化 通过光学超极化增强核自旋极化的传感器和开发方法。 3.溶液中代谢物的复杂混合物的分子组成将使用 优化的钻石核磁共振波谱仪。 4.进行原则性验证实验，验证钻石核磁共振的成像能力。 将建造一个核磁共振显微镜，并用来表征丙酮酸转化为乳酸的过程 乳腺癌细胞中的酸性物质。 如果成功，​核磁共振代谢组学的证明可能会对分析产生重大影响 生物化学和单细胞生物学。