(5ab) Analytical Ultracentrifugation of Colloidal Nanomaterials for Disease Detection and Drug Delivery Applications

Few methods exist to monitor important parameters such as aggregation, molecular surface coverage, and molecular surface conformation of biomedical nanodevices. Seemingly minor changes in the formulation such as reversible aggregates, surface coverage of the functional molecules, and molecule conformation can incite life threatening side effects or reduce the effectiveness of the device in the most benign case. Examining the device in its native suspending liquid simplifies sample preparation and helps ensure that reversible aggregation can be detected before the devices are used. Analytical ultracentrifugation (AUC) is an established technique that has been used extensively to study molecular conformation and reversible interactions between biomolecules such as proteins. The high sensitivity of AUC to protein shape and state of aggregation make it ideal to investigate the subtle changes that can make the nanodevices unsafe. The flexibility to use different matrix fluids makes AUC ideal for performing systematic studies on factors that initiate aggregation and alter the apparent size of the device. Sedimentation velocity AUC was performed on model nanodevices consisting of 10 nm gold particles derivatized with thiol terminated thymidine homooligomers to demonstrate how systematic changes in molecular surface coverage and conformation could be reliably detected.