QII-TAQS: Quantum Metrological Platform for Single-Molecule Bio-Sensing

量子系统使人类已知的一些最精确的测量成为可能。例如，现代原子钟测量时间的精度超过宇宙年龄的一秒。最近，出现了一类新的室温固态量子系统，它们利用类似的量子测量概念，但测量磁场而不是时间。原则上，这些基于金刚石晶体缺陷的量子传感器可以检测单个分子中核自旋产生的微小磁场。这样的测量可以在具有原子分辨率的单个分子水平上为复杂的分子生物学过程提供重要的见解。虽然强大，但目前的量子技术缺乏在单分子体系中探测生物系统的灵敏度和生物物理工具。为了克服这些限制，该项目依赖于一种新颖的跨学科方法，结合了物理学，计算机科学，材料科学和生物物理学的研究。在这样一个新的制度下探测生物系统的能力将对基础生物学研究产生深远的影响。与此同时，该项目中开发的概念将为基于量子传感的新一代生物医学设备铺平道路，这些设备可以显着简化样品制备并以当今成本的一小部分实现高通量筛选。与此同时，该研究项目还将通过开发新的课程材料，建立访问量子传感跨学科方面的会议，以及创建研讨会，使来自世界各地的科学家能够在量子技术方面获得实践培训，从而为培训量子工程的新员工做出贡献。这种跨学科的合作努力为小集合和单个生物分子的核磁共振（NMR）光谱学开发了量子传感能力。基于金刚石中的氮空位（NV）中心的传感使得能够检测单个蛋白质和基本NMR光谱中的核自旋。然而，这些实验无法提供生物信息，需要数天的数据采集，并且仅限于变性蛋白质。由于量子传感方法的局限性，缺乏单分子技术以及金刚石材料工程的不完善，完整蛋白质的应用仍然是一个开放的挑战。该项目研究基本机制和克服这些限制的系统工程。具体目标包括：（1）单分子NMR基本极限的理论探索，（2）单分子NMR的量子共振协议的研究，（3）金刚石表面及其功能化的光谱研究，以及（4）量子传感设备的单分子平台的工程设计。目标1采用理论方法研究单分子NMR在退相干下多参数传感的限制。目标2通过结合经典信号处理和实验量子控制来开发和基准测试单分子NMR协议。目标3依靠材料科学技术和量子传感来理解浅NV中心退相干的起源。目标4结合了单分子生物物理学和基于金刚石的NMR光谱学的方法，用于开发生物量子传感器接口。该项目将在量子信息，工程和生物学的交叉点推进对量子传感的理解。这将导致新的计算协议和单分子NMR传感设备的开发和表征。该项目由Quantum Leap Big Idea Program、数学和物理科学理事会化学部以及国际科学与工程办公室共同资助。该奖项反映了NSF的法定使命，并通过使用基金会的智力价值和更广泛的影响审查标准进行评估，被认为值得支持。

Quantum systems enable some of the most accurate measurements known to man. For example, modern atomic clocks measure time with an accuracy exceeding one second over the age of the universe. Recently, a new class of room temperature, solid state, quantum systems emerged that utilize similar quantum measurement concepts, but measure magnetic fields rather than time. In principle, these quantum sensors based on crystallographic defects in diamond could enable the detection of tiny magnetic fields created by nuclear spins in an individual molecule. Such a measurement could provide important insights into complex molecular biological processes at the level of individual molecules with atomic resolution. Although powerful, current quantum technologies lack the sensitivity and biophysical tools to probe biological systems in a single-molecule regime. To overcome these limitations, this project relies on a novel, interdisciplinary approach that combines research in physics, computer science, materials science, and biophysics. The ability to probe biological systems in such a new regime would be of far reaching consequences to fundamental biological research. At the same time the concepts developed in this project will pave the way to a new generation of biomedical devices based on quantum sensing that could significantly simplify sample preparation and enable high throughput screening at a fraction of today's cost. In parallel, this research project will also contribute to training a new workforce in quantum engineering through the development of new course materials, the establishment of conferences that access the interdisciplinary aspects of quantum sensing, and the creation of workshops that enable scientists from all over the world to get hands-on training in the quantum technologies. This collaborative, interdisciplinary effort develops quantum sensing capabilities for nuclear magnetic resonance (NMR) spectroscopy of small ensembles and individual biomolecules. Sensing based on nitrogen vacancy (NV) centers in diamond enabled the detection of nuclear spins in single proteins and basic NMR spectra. However, these experiments are unable to provide biological information, require days of data acquisition, and are limited to denatured proteins. Applications to intact proteins remain an open challenge due to limitations in quantum sensing methodology, a lack of single-molecule techniques, and imperfections in diamond material engineering. This project investigates fundamental mechanisms and the engineering of systems that overcome these limitations. Specific objectives include: (1) Theoretical exploration of the fundamental limits in single-molecule NMR, (2) Investigation of quantum metrological protocols for single-molecule NMR, (3) Spectroscopic study of diamond surfaces and their functionalization, and (4) Engineering of a single-molecule platform for quantum sensing devices. Goal 1 employs theoretical methods to investigate the limits of single-molecule NMR in the context of multi-parameter sensing under decoherence. Goal 2 develops and benchmarks single-molecule NMR protocols by combining classical signal processing and experimental quantum control. Goal 3 relies on materials science techniques and quantum sensing to understand the origin of decoherence in shallow NV centers. Goal 4 combines methods from single-molecule biophysics and diamond-based NMR spectroscopy for the development of a bio quantum sensor interface. The project will advance understanding of quantum sensing at the intersection of quantum information, engineering, and biology. This will lead to the development and characterization of new computational protocols and devices for single-molecule NMR sensing. This project is jointly funded by Quantum Leap Big Idea Program, the Division of Chemistry in the Mathematical and Physical Sciences Directorate, and the Office of International Science and Engineering.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.