CovalX: High-Mass MALDI
MALDI’s ability to nondestructively ionize biological materials makes it valuable in proteomics applications, including protein identification and sequencing determination. Nevertheless, MALDI comes with limitations when analyzing large molecules, including dissociating weak covalent bonds and a low efficiency in detecting masses above 30–50 kDa. CovalX was founded more than four years ago in Zurich, Switzerland, to address these obstacles. Formed as a result of high-mass MALDI research conducted at the Swiss Federal Institute of Technology Zurich, CovalX now provides high-mass MALDI MS detectors, reagents and software to the academic and pharmaceutical markets for use with commercial MALDI-TOF instruments.
One hurdle the company faced was introducing its offerings to the pharmaceutical market. According to Dr. Ryan Wenzel, chief scientific officer and co-founder of CovalX, “Initially, [company sales] were almost exclusively for research but we quickly developed some applications to focus on the pharmaceutical market.” Dr. Wenzel explained that CovalX systems used for immunology, and more specifically, the characterization of antibody-antigen reactions, gave the company’s detectors a foothold in the production of antibody and antibody-like drugs. CovalX further penetrated the pharmaceutical market as high-mass MALDI detectors increasingly were used for the measurement of biopharmaceutical aggregation in antibody and antibody-like drugs. “Now more than 50% [of our sales] are for pharmaceutical applications,” he said. Other pharmaceutical applications driving company sales include the screening of small molecule interactions and the study of intact protein interactions.
The company’s HM2 line of high-mass detectors includes the HM2 and the HM2 TUVO, both of which detect macromolecular ions up to 1.2 Mda. The HM2 TUVO, unlike the positive-ion HM2 detector, can detect both positive and negative ions, which is useful for polymer detection. According to Dr. Wenzel, this type of polymer detection is still a niche application that the company is hoping to expand on. The company’s kits and reagents are used to stabilize non-covalent bonds before analysis, which stops the dissociation that can occur with high-mass MALDI detection. CovalX’s software is designed to import and manage files from commercial MALDI MS systems.
Dr. Wenzel explained that the high-mass capability of CovalX’s detectors makes the company unique in the MS market. “Some people might think that we’re competing with existing MALDI mass spec companies, but we actually work alongside them. I wouldn’t say we were competing with them, because we have agreements with [Shimadzu, Bruker and Applied Biosystems].” According to Mr. Wenzel, the company’s competition is outside of the MS space, and includes analytical ultracentrifugation for aggregation applications and surface plasmon resonance for the analysis of protein interaction points. “These are completely different technologies that have their pros and cons. They don’t have the benefits of the MALDI, including high speed and low sample volume.” Other benefits of high-mass MALDI include high-mass accuracy and tolerance toward sample heterogeneity.