Matrix-free Laser Desorption and Ionization Substrates for Mass Spectroscopy

用于质谱的无基质激光解吸和电离基质

• 批准号: 9409728
• 负责人: DMITRI ROUTKEVITCH
• 金额: $ 23.25万
• 依托单位: INREDOX, LLC
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-15 至 2019-09-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9409728
• 关键词: Address; Adsorption; Agriculture; Aluminum Oxide; Biological Assay; Biological Sciences; Biology; Biotechnology; Blood; Caliber; Cancer Patient; Cells; Cellular biology; Ceramics; Clinical; Collaborations; Complement; Complex; Complex Mixtures; Crystallization; Data; Deposition; Detection; Development; Disease; Disease Marker; Drug Industry; Engineering; Ensure; Environmental Monitoring; Evaluation; Forensic Medicine; Generic Drugs; Genetic; Genomics; Geometry; Government; Growth; Health; Industrialization; Ions; Lasers; Length; Letters; Life; Mass Spectrum Analysis; Metals; Modernization; Molecular Biology; Molecular Weight; Nanostructures; Neurobiology; Non-Small-Cell Lung Carcinoma; Panthera leo; Peptides; Performance; Persons; Phase; Plasma; Preparation; Protein Analysis; Proteins; Proteomics; Protocols documentation; Reproducibility; Research; Resolution; Role; Sampling; Semiconductors; Serum; Site; Small Business Innovation Research Grant; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Surface; Technology; Testing; Time; Titania; Toxicology; United States National Institutes of Health; Urine; Validation; base; clinical diagnostics; cost; design; drug development; drug discovery; improved; ionization; ionization technique; metal oxide; nanocomposite; nanoparticle; nanopore; nanoscale; nanostructured; novel; personalized cancer therapy; personalized medicine; protein complex; prototype; small molecule; targeted treatment; tool

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.

项目概要 这个多阶段 SBIR 项目针对生命科学中的一个重要问题：提高分辨率和 使用廉价的纳米结构基底实现无基质激光的质谱 (MS) 通量 MS 的“软电离”技术，例如基质辅助 LDI (MALDI)， 已成为从蛋白质组学、基因组学到疾病应用的最重要工具之一 然而，这些研究、药物发现以及越来越多的临床诊断都存在很大的局限性。 MALDI，包括样品制备时间、基质的低分子量干扰、缺乏 由于基质内分析物分布不均匀而导致的重现性，也许最重要的是， 许多关键用途的灵敏度不足，例如疾病标记物的检测。 纳米结构表面（例如半导体表面）表面辅助 LDI（SALDI）的发展 纳米柱）使得在没有基质的情况下放大样品成为可能，但很少有商业 SALDI 产品具有 未能完全满足市场需求，很大程度上是由于成本极高、制造困难、保质期短。 因此，可靠、低成本的无基质 LDI 基材可以实现高效、可重复和 MS 需要对不同分子进行无干扰电离。 InRedox 建议通过开发一种高度新颖的低成本但有效的基质来满足这一需求 基于纳米结构陶瓷局部位点的表面辅助 LDI，其中包含以下材料： 增强激光吸附和分析电离 第一阶段的主要目标是演示。 通过制造此类基板的原型并确认它们来验证所提出方法的可行性 可以显着超过传统 MALDI 和 SALDI 的性能和成本指标 如果项目目标实现并且所提出的无基质 LDI 基板成功。 开发出来的产品将节省时间、降低检测限、提高分辨率并改善 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。