Carterra LSA for the University of Oxford - Enabling High-Throughput SPR and Antibody Characterisation

Lead Research Organisation: University of Oxford
Department Name: Biochemistry

Abstract

Understanding the interactions that occur between molecules is a central goal in nearly every branch of biomedical research. By understanding how molecules interact, research groups can then use a whole range of approaches to innovate ways of changing these interactions; in many cases this will open up avenues to develop interventions or treatments that can improve human health or prevent disease.

Critical to understanding molecular interactions is gaining knowledge about where molecules bind to each other and how quickly they can interact, also known as binding "kinetics". A number of biophysical research instruments are available that enable scientists to accurately measure the binding and kinetics of such molecules. However, a limitation of these machines is their throughput, i.e. only a small number of interactions can be measured at any one time and typically these experiments can take a number of days. Conversely, other fields have greatly advanced their throughput in recent years, building on other exciting advances that enable resarchers to study larger and bigger systems relevant to human health. Consequently, the throughput to measure molecular interactions has become a bottleneck or rate-limiting for many types of research that now wish to study 100s of molecules at once, as opposed to just a few.

Recently, a new machine has become available on the market called a "Carterra LSA High-Throughput SPR" platform. The Carterra LSA has rapidly become the clear frontrunner technology worldwide for high-throughput antibody characterisation, used by global pharmaceutical companies and leading US-based academic institutions. The abilities of this machine provide a clear step-change in scientific ambition. For example, the LSA was the primary tool used by Eli Lilly and AbCellera in the discovery of Bamlanivimab, the first COVID-19 therapeutic and fastest biologic ever to reach clinical trials during the pandemic. There is currently, however, no Carterra LSA permanently available in any UK-based academic institution. Access to such a platform is now of strategic importance and critical for the international competitiveness of UK research. This application thus seeks to acquire and enable ease of access to this machine at the University of Oxford. Specific areas of high demand for platform access at the University of Oxford will include:

i) vaccine antibody research;
ii) development of antibody-based drugs;
iii) development of novel antibody-based diagnostics;
iv) molecular drug screening for protein-protein interactions; and
v) T cell binding and kinetics, relevant to numerous infectious diseases, autoimmune diseases and cancer.

All of these areas fall within MRC-relevant research, and will greatly benefit from the unique opportunities of high-throughput screening that will be enabled via access to the LSA.

Technical Summary

The Carterra LSA high-throughput (HT) surface plasmon resonance (SPR) platform has rapidly become the clear frontrunner technology worldwide for HT antibody characterisation, used by global pharmaceutical companies and leading US-based academic institutions. The LSA is the only fully integrated HT monoclonal antibody (mAb) screening and characterisation platform on the market that combines flow printing microfluidics with SPR detection, thereby enabling epitope discovery in parallel with kinetic/affinity measurements and delivering state-of-the-art mAb discovery programmes. Its greatly expanded throughput, as compared to other label-free methods commonly used to monitor biomolecular reactions, will also energise other applications where SPR-based analyses are critical, including small molecule drug discovery and peptide-MHC/TCR interactions. Ease of access to such a platform is now of strategic importance and critical for the international competitiveness of UK research. Specific areas of high demand for platform access at the University of Oxford will include:

i) vaccine antibody research (serology and mAb analysis to guide rational design);
ii) development of antibody-based prophylactic and therapeutic interventions;
iii) development of novel antibody-based diagnostics;
iv) molecular drug screening for protein-protein complexes; and
v) HT measurement of TCR/peptide-MHC binding affinities and kinetics.

All of these areas fall within MRC-relevant research, and will greatly benefit from the unique opportunities of HT SPR screening that will be enabled via access to the LSA at Oxford.