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Published September 2015 | Supplemental Material
Journal Article Open

Label-Free Single Exosome Detection Using Frequency-Locked Microtoroid Optical Resonators

Su, Judith

Abstract

Recently exosomes have attracted interest due to their potential as cancer biomarkers. We report the real-time, label-free sensing of single exosomes in serum using microtoroid optical resonators. We use this approach to assay the progression of tumors implanted in mice by specifically detecting low concentrations of tumor-derived exosomes. Our approach measures the adsorption of individual exosomes onto a functionalized silica microtoroid by tracking changes in resonant frequency of the microtoroid. When exosomes land on the microtoroid, they perturb its refractive index in the evanescent field and thus shift its resonance frequency. Through digital frequency locking, we are able to rapidly track these shifts with accuracies of better than 10 attometers (one part in 10^(11)). Samples taken from tumor-implanted mice from later weeks generated larger frequency shifts than those from earlier weeks. Analysis of these shifts shows a distribution of unitary steps, with the maximum step having a height of ∼1.2 fm, corresponding to an exosome size of 44 ± 4.8 nm. Our results demonstrate the development of a minimally invasive tumor "biopsy" that eliminates the need to find and access a tumor.

Additional Information

© 2015 American Chemical Society. Received: March 23, 2015. Publication Date (Web): June 29, 2015. We thank Andrew Raubitschek and Desiree Crow at the COH for the exosome samples and Scott Fraser (Caltech/USC) for discussions. This research was supported in part by the Caltech−UCLA Joint Center for Translational Medicine and a National Research Service Award (T32GM07616) from the National Institute of General Medical Sciences. The authors declare no competing financial interest.

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