Giant Enhancement of Raman Scattering by a Hollow-Core Microstructured Optical Fiber Allows Single Exosome Probing

Abstract

Microstructured optical fibers (MOFs) provide solutions for breaking through the bottlenecks in areas of high-power transmission and high-efficiency optical waveguides. Other than transporting light waves, MOFs can synergistically combine microfluidics and optics in a single fiber with an unprecedented light path length not readily achievable by planar optofluidic configurations. Here, we demonstrate that hollow-core anti-resonant optical fibers (HcARFs) can significantly enhance Raman scattering by over three orders of magnitude (EF ≈ 5000) compared with a planar setup, due to the joint mechanisms of strong light−matter interaction in the fiber core and the cumulative effect of the fiber. The giant enhancement enables us to develop the first optical fiber sensor to achieve single cancer exosome detection via a sandwich-structured strategy. This enables a multiplexed analysis of surface proteins of exosome samples, potentially allowing an accurate identification of the cellular origin of exosomes for cancer diagnosis. Our findings could expand the applications of HcARF in many exciting areas beyond the waveguide.

Miniaturized Laser Probe for Exosome-Based Cancer Liquid Biopsy

“…Conventional approaches, such as Western blot analysis and ELISA, often require a large quantity of samples and are time-consuming. More frontier technologies, such as surface plasmon resonance (SPR), 4−6 surface-enhanced Raman scattering, 7,8 electrochemical methods, 9−11 optical sensing, and imaging flow cytometry (IFC), 12−16 allow the detection of vesicle quantity down to a very low level. For example, using an optical fiber platform, single exosome detection in the nanoliter sample was achieved.…”

“…For example, using an optical fiber platform, single exosome detection in the nanoliter sample was achieved. 8 Aiming at cancer diagnosis, exosome subpopulations of ovarian cancer patients' plasma samples were analyzed with a 3D nanopatterned microfluidic device. 16 These creative strategies greatly accelerate exosome analysis.…”