Automated Ultradilute Measurements of Self-Association for the Identification of Antibodies with Favorable...

One of the key challenges in antibody engineering is the development of analytical screening methods to assess colloidal stability, ensuring that biologics are suitable for high-concentration formulation and administration. Charge-stabilized self-interaction nanoparticle spectroscopy (CS-SINS), a modified version of the conventional affinity-capture self-interaction nanoparticle spectroscopy (AC-SINS), has been adapted as a robust colloidal stability assessment for predicting high-concentration solution behavior. This method enables critical early-stage developability decisions by identifying colloidal stability issues before significant resources are invested, substantially reducing downstream attrition rates and accelerating candidate selection timelines. This study demonstrates that the assay seamlessly integrates into existing discovery workflows and can be performed in parallel with typical early-stage assays due to its minimal sample requirements, providing valuable data to predict high-concentration behavior without compromising other characterization efforts. It has been shown that routine dynamic light scattering (DLS) measurements, in addition to the shift in the plasmon resonance wavelength, can improve the reliability of the HTP method described here. Taken together, it is anticipated that the cross-validation using DLS measurements and automated analysis programs will facilitate the reliable selection of candidate antibody therapeutics of various modalities.