High Mass MALDI TOF Employing a Novel High-Tc Superconducting Ion Detector

Qualitative and quantitative analysis of antibodies and related macromolecular immune complexes is a prerequisite for determining their identity, binding partners, stoichiometries, and affinities. Native mass spectrometry (MS) is an analytical technique capable of measuring the mass of such complexes. As any binding event leads to a corresponding increase in mass, native MS offers an accurate readout of ligand binding and can readily distinguish different binding stoichiometries and different ligands by their unique masses. Two soft ionization techniques are typically used to generate ions for mass analysis: electrospray ionization (ESI) and matrix- assisted laser desorption ionization (MALDI). Native MS using ESI for analysis of complex samples encounter significant challenges in interpreting highly complicated spectra because of intrinsic protein heterogeneity. MALDI is a robust ionization technique which produces mostly singly charged ions thus minimizing spectral complexity. However, its application in native MS is hampered by low sensitivity of currently available ion detectors for high m/z ions. The goal of this project is to develop and evaluate a system for fast analysis of antibodies and related macromolecular immune complexes based on time-of-flight (TOF) mass spectrometer with MALDI ionization. High m/z ion detection will be realized using a novel high-temperature superconducting nanowire detector. To cool down the detector to the required temperature an inexpensive commercially available compact cryocooler, which operates without any consumables, will be used.