SBIR Phase I: NIMS: A Matrix-Free Mass Spectrometry Imaging Platform for High Sensitivity, Spatial Resolution and Throughput

这项小企业创新研究（SBIR）第一阶段项目提出了一种基于质谱的新型成像平台的开发，以满足在低质量范围内具有高空间分辨率和灵敏度的技术需求。质谱成像（MSI）是一个快速发展的领域，因为它不需要标记样品，提供特定位置的化学信息，并且在图像的每个像素处检测到数千种化合物，具有很高的信息含量。然而，由于低质量范围的空间分辨率和灵敏度有限，MSI尚未实现广泛的适用性。第一阶段的总体目标是克服当前MSI的局限性，并通过利用纳米结构表面来扩大其适用性，纳米结构表面利用了与当前基于表面的质量分析技术完全不同的解吸/电离机制。我们第一阶段的目标是开发两个基于这种纳米结构表面的原型。首先，我们将开发一个基于质量的成像原型，具有高空间分辨率和高低质量灵敏度，可用于组织成像。其次，我们将生产一个原型，使基于质量成像的高通量筛选酶活性文库的新方法成为可能，预计通量超过10,000次/天。该项目更广泛的影响/商业潜力是，基于质量的成像可以用于当前MSI技术难以或不可能的应用，包括基质辅助激光解吸/电离（MALDI）和二次离子质谱（SIMS）技术。在低质量范围内进行MSI的能力将产生特别大的影响，因为许多重要的分子类别都在这个范围内，包括生物燃料、治疗化合物、疾病相关代谢物、环境毒素、食品污染物和工业化合物。该平台在社会和商业上具有重要意义的大规模成像应用包括：1)用于药物发现、药物定位/代谢、疾病标志物发现、环境研究的动物/植物组织成像；2)用于生物燃料生产和环境修复的生物膜成像。提出的基于msi的高通量筛选平台具有重大潜力，可以发现用于生物燃料生产工业过程的新酶以及治疗性酶抑制剂。此外，该提案中使用的纳米结构表面具有较低的进入门槛和对客户的高价值，因为最终用户可以利用所提议平台的新功能，同时使用与目前用于基质辅助激光/解吸电离（MALDI）相同的市售激光解吸/电离质谱仪。

This Small Business Innovation Research (SBIR) Phase I project proposes the development of a new imaging platform based on mass spectrometry that addresses the need for a technology with high spatial resolution and sensitivity in the low-mass range. Mass spectrometry imaging (MSI) is a rapidly growing area because it does not require a labeled sample, offers location-specific chemical information, and has high information content with potentially thousands of compounds detected at each pixel in the image. However, broad-based applicability of MSI has not been realized due to limited spatial resolution and sensitivity in the low-mass range. The overall Phase I goal is to overcome the current MSI limitations and expand the applicability by utilizing nanostructured surfaces that take advantage of an entirely different desorption/ionization mechanism than current surface-based mass analysis technologies. Our Phase I objective is to develop two prototypes based on this nanostructured surface. First, we will develop a prototype for mass-based imaging with high spatial resolution and high low-mass sensitivity that can be used for tissue imaging. Second, we will produce a prototype that enables a new approach to high-throughput screening of enzymatic activity libraries based on mass imaging, with a projected throughput of more than 10,000 assays/day.The broader impact/commercial potential of this project is that mass-based imaging can be used in applications that are difficult or impossible with the current MSI technologies, which includes the matrix-assisted laser desorption/ionization (MALDI) and secondary-ion mass spectrometry (SIMS) technologies. The ability to perform MSI in the low-mass range will have particularly high impact because many important classes of molecules fall within this range including biofuels, therapeutic compounds, disease-relevant metabolites, environmental toxins, food contaminants, and industrial compounds. Societal and commercially important mass-based imaging applications of the proposed platform include 1) animal/plant tissue imaging for drug discovery, drug localization/metabolism, disease marker discovery, environmental studies and 2) biofilm imaging for biofuel production and environmental remediation. The proposed MSI-based high-throughput screening platform has significant potential for discovery of new enzymes for biofuel production industrial processes as well as therapeutic enzyme inhibitors. In addition, the nanostructured surfaces used in this proposal have a low barrier of entry and high value to the customer because the end user can take advantage of the new capabilities enabled by the proposed platform, while using the same commercially available laser desorption/ionization mass spectrometer that they currently use for matrix-assisted laser/desorption ionization (MALDI).