Real-time monitoring of recombinant protein concentration in animal cell cultures using an optical biosensor

Measurement of the concentration of specific proteins in complex mixtures has traditionally relied on time-consuming and labour-intensive procedures such as ELISA. In this paper, we demonstrate that optical biosensors employing surface plasmon resonance technology may be employed to quantitate recombinant protein product in crude animal cell culture supernatant in real time by measuring the rate of ligand binding to an immobilised monospecific antibody. A model system-binding of recombinant human tissue inhibitor of metalloproteinases-1 (TIMP-1; a glycoprotein of approximately 30 kDa produced by NSO cells) to the monoclonal antibody MAC019-was employed to evaluate key assay parameters necessary for reliable determination of product concentration: dynamic range, sensitivity, speed and reproducibility. These have been compared to traditional ELISA protocols.