blog: how MedImmune and UCB Pharma created more sensitive and efficient antibody screening assays
Biopharmaceuticals are a highly-effective drug class, based on naturally occurring proteins and produced using biological sources. They are much larger than the chemically-synthesised small molecules that still represent the majority of medicines. However, biologics have revolutionised medicine. They bind to specific targets that are known to be involved in the disease, and they are often the only medicines capable of effectively treating complex diseases, (for example, EPO and Insulin). There is a drive for high throughput antibody screening to further this research and produce more effective drug candidates.
Are you deciding between flow cytometry and ELISA for your biopharmaceuticalscreen?
It doesn’t have to be either!
ELISA or flow cytometry can represent a bottleneck in the biopharmaceutical screening process as they require lengthy, multi-step preparation stages, large cell numbers and use precious sample material inefficiently. Both assay types transition easily to a high throughput, high sensitivity, mix-and-read format made possible with mirrorball®.
mirrorball, an innovative high sensitivity microplate cytometerhas been a significant, technical driving force enabling automated high throughput antibody assays to be performed, reducing costs at the same time. It uses TTP Labtech’s laser scanning technology to offer many benefits that include:
- streamlined no-wash assay format
- capable of walk-away 24/7 operation
- preservation of cell morphology
- investigation of multiple targets in one well (mirrorball has 3 lasers and 6 detection channels)
- more stringent results by screening out non-specific and non-selective hits
- assay miniaturisation using high density microplates (screening assays can be performed in 96-, 384-, and 1536-well plates)
- observation of results in an imaging format
Its application areas include antibody discovery, hybridoma screening, phage and yeast display libraries, B-cell cloning, fragment screening, cytokine measurement and peptide binding.
Having the right tools for the job
Evidence of the use of TTP Labtech’s mirrorball® in antibody discovery comes from two recent scientific papers
Tickle et al from UCB Pharma (Slough, UK) describe the successful design, construction and commissioning of a bespoke automated screening platform that incorporates mirrorball and how it can be used for screening antibodies against two specific targets . This automated platform can combine high throughput B cell culture screening with the identification and isolation of single, antigen-specific IgG-secreting B cells through a proprietary technique called ‘fluorescent foci’. More than 1 billion immune B cells can now be screened to provide a useful starting point from which to identify the rare therapeutic antibody.
In a second paper England et al from MedImmune (Cambridge, UK) have evaluated a selection of typical cell- and bead- based assays that demonstrate how the multilaser capability of the mirrorball can be exploited to develop highly sensitive multiplex assays . This allows for identifying antibody cross-reactivity and selectivity but without the loss of throughput. In this study the multiplexing of 2 antibody–cell binding assays (using different dyes) and 3 cytokine quantitation bead assays (using the same dye at different intensities) was developed. The results demonstrated an improvement in sensitivity and efficiency of biologics screening.
mirrorball represents one of the most versatile instruments available for a complete solution to biopharmaceutical screening.
 Tickle, S. et al., A Fully Automated Primary Screening System for the Discovery of Therapeutic Antibodies Directly from B Cells. J Biomol Screen (2015) 20:492-497
 England, E. et al., Application of the Mirrorball High-Sensitivity Cytometer to Multiplexed Assays for Antibody Drug Discovery. J Biomol Screen (2015) 20: 536-544