This technology provides a novel method for determining antibody chain pairing by utilizing advanced mass spectrometry techniques. It addresses the limitations of traditional approaches by offering precise and comprehensive analysis, enhancing the identification of antibodies. This method is immediately relevant to the pharmaceutical and biotechnology industries.

The biopharmaceutical industry often faces challenges in accurately determining antibody chain pairing because of the complex structure of antibodies. This difficulty leads to inefficiencies in developing therapeutic antibodies and other biologics. The conventional methods lack precision and often result in incomplete information, causing delays and additional costs in research and development.

Researchers at Pacific Northwest National Laboratory have developed a pioneering method that overcomes these barriers by utilizing advanced mass spectrometry techniques, such as electron capture dissociation (ECD) and ultraviolet photodissociation (UVPD). The use of a unique combination of these techniques provides effective cleavage of intermolecular disulfide bonds linking the heavy and light chains of an antibody critical for accurate antibody chain pairing, and comprehensive sequence coverage of the heavy and light chains, including complementarity determining regions. This novel approach has the potential for de novo structure characterization workflows to reduce reliance on single-cell B cell sequencing and hybridoma-based methods in therapeutic antibody discovery.

This technology leverages engineered methodologies to enhance the efficiency and accuracy of antibody characterization. This results in detailed and reliable information about light and heavy chain pairing and significantly addresses inefficiencies faced by the industry. The impact of this technology is notable, offering potential cost reductions and streamlined processes in antibody development.

APPLICABILITY
This technology can be widely used in pharmaceutical and biotechnological industries, especially for companies involved in the research and development of therapeutic antibodies. Key potential users include biopharmaceutical research laboratories, drug development companies, and diagnostic tool manufacturers.

In addition to biomedical applications, this mass spectrometry approach can be applied to other complex, multi-chain and disulfide-bonded proteins, including enzymes and redox-active systems that are important in biotechnology, bioenergy, and environmental research. The ability to directly resolve intact protein connectivity and sequence supports efforts to understand and engineer biological pathways relevant to biocatalysis, microbial metabolism, and environmentally responsive processes.