Early stage cancer is hard to detect, mostly because traditional diagnostic imaging cannot detect tumors smaller than a certain size. One Houston innovator is looking to change that.

Wei-Chuan Shih, professor of electrical and computer engineering at the University of Houston's Cullen College of Engineering, recently published his findings in IEEE Sensors journal. According to a news release from UH, the cells around cancer tumors are small — ~30-150nm in diameter — and complex, and the precise detection of these exosome-carried biomarkers with molecular specificity has been elusive, until now.

"This work demonstrates, for the first time, that the strong synergy of arrayed radiative coupling and substrate undercut can enable high-performance biosensing in the visible light spectrum where high-quality, low-cost silicon detectors are readily available for point-of-care application," says Shih in the release. "The result is a remarkable sensitivity improvement, with a refractive index sensitivity increase from 207 nm/RIU to 578 nm/RIU."

Wei-Chuan Shih is a professor of electrical and computer engineering at the University of Houston's Cullen College of Engineering. Photo via UH.edu

What Shih has done is essentially restored the electric field around nanodisks, providing accessibility to an otherwise buried enhanced electric field. Nanodisks are antibody-functionalized artificial nanostructures which help capture exosomes with molecular specificity.

"We report radiatively coupled arrayed gold nanodisks on invisible substrate (AGNIS) as a label-free (no need for fluorescent labels), cost-effective, and high-performance platform for molecularly specific exosome biosensing. The AGNIS substrate has been fabricated by wafer-scale nanosphere lithography without the need for costly lithography," says Shih in the release.

This process speeds up screening of the surface proteins of exosomes for diagnostics and biomarker discovery. Current exosome profiling — which relies primarily on DNA sequencing technology, fluorescent techniques such as flow cytometry, or enzyme-linked immunosorbent assay (ELISA) — is labor-intensive and costly. Shih's goal is to amplify the signal by developing the label-free technique, lowering the cost and making diagnosis easier and equitable.

"By decorating the gold nanodisks surface with different antibodies (e.g., CD9, CD63, and CD81), label-free exosome profiling has shown increased expression of all three surface proteins in cancer-derived exosomes," said Shih. "The sensitivity for detecting exosomes is within 112-600 (exosomes/μL), which would be sufficient in many clinical applications."