Enhanced LSPR sensitivity for OpenSPR detection of therapeutic antibodies and polymer antibody conjugates

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Therapeutic antibodies represent a growing class of drug that are particularly important for cancer immunotherapies. Due to biological transport barriers, many treatments fail due to the lack of antibodies reaching the disease site. Furthermore, large doses of antibodies are commonly administered, which may lead to toxic side effects. Therefore, we are developing an injectable local release system to increase antibody concentrations at the disease site, while decreasing side effects and cost. To accomplish these goals, we need methods to rapidly detect and assess the activity of therapeutic antibodies released from our delivery systems. Nicoya Lifesciences has developed the first commercial instrument, OpenSPR, based on localized surface plasmon resonance (LSPR) biosensing. Compared to other techniques, OpenSPR has a high signal to noise ratios that is amenable to cost effective high throughput analysis. Currently, OpenSPR lacks the sensitivity to detect pico to femtomole amounts of antibodies, which is required for biologically relevant release studies. To this end, we will develop procedures and materials to enhance the LSPR detection of antibodies in the OpenSPR instrument. Because LSPR measures shifts in light absorption due to refractive index changes upon antibody binding to the gold OpenSPR surface, LSPR enhancement will be accomplished by: (1) modifying antibodies with chromophores that absorb visible light; and (2) adding antibody binding peptides modified with chromophores that absorb visible light. The combination of Nicoya's LSPR technology and the Wylie lab's expertise in therapeutic antibodies will result in the development of new LSPR protocols and materials to rapidly analyze dilute antibody solutions.****