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.

项目摘要 这个多相SBIR项目针对生命科学中的一个重要问题：增加解决方案和 使用廉价的纳米结构底物的质谱（MS）吞吐量，无基质激光器 解吸和电离（LDI）。 MS的“软电离”技术，此类矩阵辅助LDI（MALDI）， 已成为从蛋白质组学和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。但是，在 MALDI，包括样本准备时间，矩阵的低分子量访谈，缺乏 由于矩阵中分析物的不均匀分布而引起的可重复性，也许最重要的是 对许多关键用途的敏感性不足，例如检测疾病标志物。虽然最近 来自纳米结构表面的表面辅助LDI（SALDI）的发展（例如半导体 纳米管）使得不含基质的样品使样品成为可能，很少有商业Saldi产品具有 由于极高的成本，制造业困难和短暂的保质期，因此无法完全满足市场需求。 因此，可靠的无基质LDI的可靠，低成本基板，可以使高效，可重现和 需要对MS的不同分子的无干扰电离。 通过开发一种新型的低成本但高效的底物来满足这种需求的建议 表面辅助LDI基于来自纳米结构陶瓷的局部位点编码材料的局部位点 增强激光吸附和分析物电离。第一阶段的主要目的是证明 通过制造此类基材的原型并确认拟议方法的可行性 常规MALDI和SALDI的性能和成本指标可能会大大超过 基材。如果实现了项目目标并提出了无基质LDI底物是成功的 开发的产品将节省时间，减少检测限，增加分辨率并改善 可重复性和数据的一致性，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，个性化疗法，药物发现和 毒理学以及生物技术，农业，法医，环境测试等的相关领域等。