Matrix-free Laser Desorption and Ionization Substrates for Mass Spectroscopy

项目摘要 这个多阶段SBIR项目针对生命科学中的一个重要问题：提高分辨率， 使用廉价的纳米结构基底进行无基质激光的质谱（MS）的吞吐量 解吸和电离（LDI）。用于MS的“软电离”技术，例如基质辅助LDI（MALDI）， 已经成为从蛋白质组学和基因组学到疾病的应用中最重要的工具之一 研究、药物发现以及越来越多的临床诊断。然而，在这方面存在重大局限性。 MALDI，包括样品制备时间、来自基质的低分子量干扰、缺乏 由于分析物在基质内的不均匀分布，以及，也许最重要的是， 对于许多关键用途，如检测疾病标志物，灵敏度不足。虽然最近 从纳米结构表面（如半导体）的表面辅助激光直接淀积（SALDI）的发展 纳米柱）使得在没有基质的情况下将样品电离成为可能，但是很少有商业SALDI产品具有 不能完全满足市场需求，主要是由于成本高、制造困难和保质期短。 因此，用于无基质LDI的可靠、低成本的基底可以实现高效、可再现和可重构的制备。 需要用于MS不同分子的无干扰电离。 InRedox提出通过开发一种新型低成本但高效的底物来解决这一需求， 基于来自纳米结构陶瓷的局部化位点的表面辅助LDI， 增强激光吸收和分析物电离。第一阶段的主要目标是证明 所提出的方法的可行性，通过制造这种基板的原型，并确认它们 可以大大超过传统的MALDI和SALDI的性能和成本指标 印刷受体.如果项目目标得以实现，并且拟议的无基质LDI基板成功 开发，由此产生的产品将节省时间，降低检测限，提高分辨率和改善 数据的可重复性和一致性，对细胞生物学领域产生重大影响， 蛋白质组学、仿制药、疾病研究、临床诊断、个性化治疗、药物发现和 毒理学以及生物技术、农业、法医学、环境测试等相关领域。

Project Summary This multi-phase SBIR project targets an important problem in life science: increasing resolution and throughput of mass spectroscopy (MS) using inexpensive nanostructures substrates for matrix-free laser desorption and ionization (LDI). ‘Soft ionization’ techniques for MS, such matrix-assisted LDI (MALDI), have become among the most important tools in applications from proteomics and genomics to disease studies, drug discovery and, increasingly, clinical diagnostics. However, there are significant limitations in MALDI, including sample preparation time, low molecular weight interferences from the matrix, lack of reproducibility due to non-uniform distribution of analyte within the matrix, and, perhaps most importantly, insufficient sensitivity for many key uses, such as detection of disease markers. Although recent developments on surface-assisted LDI (SALDI) from nanostructured surfaces (such as semiconductor nanoposts) made it possible to lionize samples without a matrix, few commercial SALDI products have not fully met the market needs, largely due to extreme cost, manufacturing difficulties, and short shelf life. Therefore, reliable, low cost substrates for matrix-free LDI that can enable efficient, reproducible and interference-free ionization of different molecules for MS are needed. InRedox proposes to address this need by developing a novel low-cost yet highly effective substrate for surface-assisted LDI based on localized sites from nanostructured ceramics incorporating materials that enhance laser adsorption and analyte ionization. The main objective of the Phase I is to demonstrate feasibility of the proposed approach by fabricating prototypes of such substrates and confirming that they could significantly exceeds the performance and cost metrics of conventional MALDI and SALDI substrates. If the project aims are achieved and proposed matrix-free LDI substrates are successfully developed, the resulting products will save time, reduce detection limits, increase resolution and improve reproducibility and consistency of data, making a significant impact on the fields of cell biology, proteomics, generics, disease studies, clinical diagnostics, personalized therapy, drug discovery and toxicology, as well as in related fields of biotechnology, agriculture, forensics, environmental testing etc.