Matrix-free Laser Desorption and Ionization Substrates for Mass Spectroscopy

项目摘要 这个多阶段的SBIR项目针对的是生命科学中的一个重要问题：提高分辨率和 使用廉价的纳米结构衬底的无基质激光器的质量谱(MS)吞吐量 解吸和电离(LDI)。MS的“软电离”技术，如基质辅助激光二极管阵列(MALDI)， 已经成为从蛋白质组学和基因组学到疾病应用的最重要的工具之一 研究、药物发现以及越来越多的临床诊断学。然而，在以下方面存在明显的限制 MALDI，包括样品前处理时间、低分子量来自基质的干扰、缺乏 由于分析物在基质中的分布不均匀而导致的重复性，并且可能最重要的是， 对于许多关键用途，如检测疾病标志物，灵敏度不足。虽然是最近的 纳米结构表面(如半导体)表面辅助激光二极管阵列(SALDI)的研究进展 纳米仿生器)使样品在没有基质的情况下成为可能，但很少有商用Saldi产品能做到 没有完全满足市场需求，很大程度上是由于成本过高、制造困难和保质期短。 因此，用于无基质LDI的可靠、低成本的衬底可以实现高效、可重复和 对于MS来说，需要不同分子的无干扰电离。 InRedox建议通过开发一种新的低成本但高效的衬底来满足这一需求 基于纳米结构陶瓷的局域化位置的表面辅助激光二极管成像 增强激光吸附和分析物电离。第一阶段的主要目标是展示 通过制造这种衬底的原型并确认它们 可能大大超过传统MALDI和Saldi的性能和成本指标 底物。如果项目目标实现，并且提议的无基质LDI基板成功 开发出来的产品将节省时间、降低检测下限、提高分辨率并改进 数据的重复性和一致性，对细胞生物学领域产生了重大影响， 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、环境检测等相关领域。

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.