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（NMR）光谱是有史以来最强大的分析技术之一 发明。例如，通过NMR方法授予的6项诺贝尔奖所认可的 独自发展。但是，常规NMR系统中的灵敏度和检测量是 不足以对PICOLITER样品量（例如单哺乳动物细胞）的代谢分析。同样 时间，急需非侵入性，无标签，化学特异性的技术 单细胞水平和/或可以集成到连字符的微流体测定中。 拟议的研究旨在开发一个新的NMR光谱和成像平台 单细胞（PICOLITERS）。该平台基于最近开发的传感器（逻辑位） 在量子计算机中）以检测环境参数，即所谓的“量子传感器”。具体来说， 钻石中的荧光自旋Qubt用于生成和检测核磁化。假设 该提案的基础是，使用非电感性钻石量子传感器可能会导致改进 在敏感性，频谱分辨率，空间分辨率和微流体整合以外 可在小体积NMR光谱中使用。 Pi的实验室最近证明了 将钻石量子传感器嵌入微流体芯片中，并检测到二维NMR光谱 液体分析物的PICOLITER量。但是，传感器光谱分辨率和 需要敏感性才能用单细胞空间量化物理浓度下的分子组成 解决。这就是该提议的目标。 这是一个高风险建议，发展工作的结果尚不清楚。但是建议 研究计划旨在涵盖以下四个目标： 1。钻石NMR光谱仪的分数光谱分辨率将提高到优于10 零件十亿。这将涉及构建一个在3特斯拉运营并开发的设备 针对此较高磁场优化的钻石量子传感协议。 2。钻石NMR光谱仪的敏感性将提高到10毫米的敏感性 （1秒集成后3个信噪比为3）。这涉及钻石的严格优化 传感器和开发方法通过光学超极化增强核自旋极化。 3。将使用一个代谢物复合物混合物的分子组成在溶液中使用 优化的钻石NMR光谱仪。 4。将进行原则证明实验，以验证钻石NMR的成像能力。 NMR显微镜将被构造并用于表征丙酮酸转化为乳酸的转化 乳腺癌细胞中的酸。 如果成功，picoliter NMR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。