Tailoring the protein adsorption properties of whispering gallery mode optical biosensors

Label-free biosensor technologies have the potential to revolutionize environmental monitoring, medical diagnostics, and food safety evaluation processes due to their unique combinations of high-sensitivity signal transducers and high-specificity recognition elements. This enables their ability to perform real-time detection of deleterious compounds at extremely low concentrations. However, to further improve the biosensors' performance in complex environments, such as wastewater, blood, and urine, it is necessary to minimize nonspecific binding, which in turn will increase their specificity, and decrease the rate of false positives. In the present work, we illustrate the potential of combining emerging high-sensitivity optical signal transducers, such as whispering gallery mode (WGM) microcavities, with covalently bound poly(ethylene glycol) (PEG) coatings of varying thickness, as an effective treatment for the prevention of nonspecific protein adsorption onto the biosensor surface. We monitor the sensitivity of the coated biosensor, and investigate the effect of PEG chain length on minimizing nonspecific adsorption via protein adsorption studies. Experimental results confirm not only that PEG-functionalization reduces nonspecific protein adsorption to the surface of the sensor by as much as a factor of 4 compared to an initialized control surface, but also that chain length significantly impacts the nonfouling character of the microcavity surface. Surprisingly, it is the short chain PEG surfaces that experience the best improvement in specificity, unlike many other systems where longer PEG chains are preferred. The combination of WGM microcavities with PEG coatings tuned specifically to the device will significantly improve the overall performance of biosensor platforms, and enable their wider application in complex, real-world monitoring scenarios.