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.

Grant Number: 1R43GM153742-01
NIH Institute/Center: NIH
Principal Investigator: VADYM BERKOUT