DNA immunization, in combination with our improved hybridoma platform, has been the gold standard for many years. This approach has served very well for a variety of targets, including challenging multi-transmembrane spanning targets. However, as the complexity of our projects increase, along with our client’s growing demands for antibody discovery campaigns against the most difficult targets, we have expanded our services by offering a B cell platform. This platform enables direct screening of primary B cells, as an alternative to the less efficient hybridoma technology. In this case study, we discuss several targets that we performed projects on. These targets each represent a different difficulty level, and we discuss the various success of the Beacon and Hybridoma platforms with generating antibodies.
Screening of primary B cell on Berkeley Lights Beacon® accelerates the antibody discovery process by weeks compared to standard hybridoma. The technology facilitates rapid and robust screening of thousands of single plasma cells at extremely high monoclonality for their specificity in one day. Target-binding candidates are identified on the day of organ-harvest, and sequencing of variable chains as well as generation of recombinant antibodies is carried out in 2–4 weeks. In addition to time, one of the Beacon’s strongest advantages is its ability to “find the needle in the haystack”.
Recovery of Antibodies Against Difficult Targets Using the Beacon® Instrument
In a comparative campaign between hybridoma and Beacon for the three targets introduced previously, we were able increase yields by a factor of ten (above figure). The more difficult the target, the more distinct the gain in antibodies obtained by the Beacon compared to hybridoma. This increased number of antibodies combined with an increased sequence variety distinctive for plasma cells allows us to increase the chances to find the antibody exhibiting the desired characteristics.