Chemically induced dimerization (CID) techniques, wherein two pro-teins dimerize solely within the presence of a small molecule ligand, supply versatile instruments for small molecule sensing and actuation. Nonetheless, solely a handful of CID techniques exist and creating one with the specified sensi-tivity and specificity for any given ligand is an unsolved downside. Right here, we developed a combinatorial binders-enabled number of CID (COMBINES-CID) technique broadly relevant to completely different ligands. We demonstrated a proof-of-principle by producing nanobody-based heterodimerization techniques induced by cannabidiol with excessive ligand selectivity. We utilized the CID system to a delicate sandwich ELISA-like assay of cannabidiol in physique fluids with a detection restrict of ~0.25 ng/mL. COMBINES-CID offers an environment friendly, cost-effective answer for increasing the biosensor toolkit for small molecule detection.