Label-free single molecule detection for basic science and translational medicine

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PROJECT SUMMARY. We have recently developed a label-free biological and chemical sensing system known as a frequency locked optical whispering evanescent resonator (FLOWER) that integrates microtoroid optical resonators with frequency locking feedback control, which aids the suppression of noise. FLOWER is currently capable of highly sensitive and rapid (under 30 seconds) label-free detection down to the single macromolecule level, as demonstrated by the detection of single human interleukin-2 (IL-2) molecules. To date, FLOWER has achieved a signal-to-noise ratio of 5 using an anti-IL-2 antibody layer immobilized on a microtoroid to specifically capture IL-2. In addition to its high sensitivity, FLOWER has an advantage over other nanoscale sensing platforms such as cantilevers or nanowires in that it possesses a relatively large capture area, increasing the probability of analyte detection. We propose (1) using FLOWER to target a large number of current biomedical problems which would benefit from a rapid, sensitive, and accurate means to identify key microscopic, nanoscopic, or molecular markers specific to the problem; (2) miniaturizing and multiplexing FLOWER and making it part of a self- contained, compact portable device to quickly establish the prognosis of various conditions; and (3) further increasing FLOWER’s sensitivity and selectivity, making it capable of detecting even smaller molecules with societal interest such as insulin or more capable of detecting the small signal changes mentioned in (1). As such, FLOWER may be used to understand the process of olfaction in synthetic optical noses or disease progression in Alzheimer’s. FLOWER is a new method that has not been applied to these questions before and, with proof of concept, has great potential to advance several fields. If successful, this project would allow for a robust, extremely sensitive, and portable device that could be given to an EMT or a solider in order for them to rapidly detect diseases or viruses and bacteria in drinking water or food. These devices could empower citizen scientists to monitor their drinking supply or breathing air. Furthermore, these devices could be easily translatable to other labs, enabling robust assays for drug library screening, cell signaling studies, and clinical assays. Eventually, we envision these devices to be prevalent in drug stores throughout the country, creating a convenient, inexpensive, routine, accessible, and non-invasive means to impact the diagnosis and treatment of many diseases, including Alzheimer’s, cancer, pain from multiple sclerosis, diabetes, addiction, and depression.