Matrix-free Laser Desorption and Ionization Substrates for Mass Spectroscopy

项目总结

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.