High-Throughput Pharmacologic Activity Profiling of Antibodies

Drug discovery demands high-throughput binding measurements across diverse compound classes, protein targets, and biological matrices. Yet most label-free biosensors require purified samples and measure one compound at a time. The MACS Matchmaker, based on focal molography, breaks both limits: up to 64 simultaneous interactions per chip, label-free, in undiluted plasma, serum, or cell lysate.

Application 1: 8-plex Fc receptor profiling panel

FcγRI, FcγRIIa, FcγRIIb, FcγRIIIa, FcγRIIIb, FcεRI, FcεRII, and the neonatal Fc receptor (FcRn) co-immobilized via DNA-directed immobilization (DDI) on a single chip. Antibody candidates injected as analytes give a full effector function profile from a single experiment, directly in development buffer. The profile discriminates IgG subclasses (IgG1, IgG2, IgG4) and engineered Fc variants (LALA, GASDALIE, YTE).

Application 2: serum protein binding

Three FDA-approved anti-CD20 antibodies (rituximab, obinutuzumab, ofatumumab) profiled in human serum within a 1-hour single-cycle kinetic run. Apparent dissociation constants (K_D) cluster around 1 µM in full human serum. A partially humanized reference antibody shows a distinctly different serum-interaction profile (~4× higher K_D). The MACS Matchmaker delivers the answer in plasma, in parallel, in one hour, a question SPR cannot answer.

Application 3: on-DNA DEL hit validation

Conventional DNA-encoded library (DEL) hit validation requires off-DNA synthesis, the hit made again without its DNA tag, before biophysical testing. That route has a 70 to 90 percent false-positive rate and takes weeks to months. Focal molography enables direct on-DNA affinity measurement of intact DEL hits via DDI. It ranks k_on, k_off, and K_D per compound with the same library prep used for screening. Lower false positives, hours instead of weeks, and LC-MS identifies which binds.

Presented at PEGS Boston 2026, Booth 615 (Poster A073). Authors: Lukas Heuberger, Alexander Geiger, Andreas Frutiger, Simona Notova, Volker Gatterdam, lino Biotech AG (a Miltenyi Biotec Company).