Our traditional methods for functional screening of anti-IDs involved labeling each anti-ID for capture and detection. For 18 different anti-IDs this is a laborious process resulting in a large number of labeled reagent enumeration to screen every potential pairing. To this end, 324 different combinations would need to be tested per assay format, at a single concentration, if a traditional approach was used. Therefore, an indirect format (Figure ) was used to perform an initial screen of anti-IDs to examine the effects of matrix (pooled human serum) and soluble antigen interference on the ability of the anti-IDs to bind to the therapeutic antibody. A standardized plate map was also selected to allow for development of automation procedure and for the future use of this workflow in screening anti-IDs in other projects. In addition, a scoring system was established to rank order the anti-IDs based on the effect of 1) soluble antigen interference in buffer, 2) matrix interference (blank serum), 3) soluble antigen in matrix versus buffer, and 4) soluble antigen in matrix versus blank matrix (Figure ). This was performed at three levels of each anti-ID (1x, 10x, 100x) in the presence of soluble antigen that was calculated to be at least 10x greater than the lowest expected levels of soluble antigen in patients. Additionally, this format was tested in the presence of 40x of the soluble antigen for super saturating conditions of soluble antigen. The composite scores from each experiment were tabulated and are shown in Figure . Complete data and scoring are in Supplementary Tables 1, 2, 3. The top five anti-IDs with the highest composite score and the least interference from matrix and/or soluble antigen were then selected for progression to a more rigorous labeled-anti-ID sandwich assay format.