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 发明的。这已经得到了认可，例如，6项诺贝尔奖授予NMR方法 独自发展。然而，常规NMR系统中的灵敏度和检测体积是有限的。 不足以进行皮升样品体积如单个哺乳动物细胞的代谢分析。在同一 与此同时，迫切需要非侵入性的，无标记的，化学特异性的技术， 单细胞水平和/或可以整合到联用微流体测定中。 拟议的研究旨在开发一个新的平台，用于核磁共振光谱和成像， 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）检测环境参数，即所谓的“量子传感器”。具体地说， 金刚石中的荧光自旋量子位用于产生和检测核磁化。的假设 这一提议的基础是，使用非感应金刚石量子传感器可能会导致改进 在灵敏度、光谱分辨率、空间分辨率和微流体集成方面， 可用于小体积NMR光谱。PI的实验室最近展示了一个概念证明， 将金刚石量子传感器嵌入微流控芯片中， 皮升体积的流体分析物。然而，传感器光谱分辨率和 需要灵敏度来用单细胞空间分析在生理浓度下定量分子组成 分辨率这就是本提案的目标。 这是一个高风险提案，开发工作的结果未知。然而，拟议的 研究计划的目标包括以下四个方面： 1.金刚石核磁共振谱仪的分数光谱分辨率将提高到优于10 十亿分之几这将涉及建造一个在3特斯拉下工作的装置， 钻石量子传感协议优化了这一更高的领域。 2.金刚石核磁共振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 通过光学超极化增强核自旋极化的传感器和开发方法。 3.溶液中代谢物复杂混合物的分子组成将使用 优化的金刚石核磁共振光谱仪。 4.将进行原理验证实验，以验证金刚石NMR的成像能力。 核磁共振显微镜将被构建并用于表征丙酮酸转化为乳酸 乳腺癌细胞中的酸性物质。 如果成功，皮升NMR代谢组学的演示可能对分析产生重大影响。 生物化学和单细胞生物学。