Label-free detection of MiRNA biomarkers using broadband multi-resonant infrared metasurfaces for early breast cancer diagnosis

Breast cancer is the most prevalent cancer globally. Early detection is crucial and can be achieved by detecting cancer biomarkers in blood, such as circulating miRNAs (microRNAs). In this study, we present a label-free detection method based on broadband multi-resonant infrared metasurface for surface-enhanced infrared absorption (SEIRA) spectroscopy to detect miRNAs. The SEIRA resonances were optimized to match the miRNA biomarker fingerprint regions in the range of 800 to 2000 cm(-1) and 2800 to 3500 cm(-1), resulting in a simulated resonance enhancement of up to 10(3) times. Nine patient samples (six cancerous and three non-cancerous) were measured using SEIRA multi-well sensor chips. A novel analysis method, SEIRA-AR, was also developed to benchmark the results against industry standards, such as quantitative reverse transcription polymerase chain reaction (RT-qPCR) and next-generation sequencing (NGS). Our results showed an excellent linear correlation with a Pearson's r value of up to 0.99 and an R Squared value of up to 0.98. This study represents the first use of a SEIRA sensor for biomarker detection on clinical breast cancer samples and introduces an analysis method that produces results comparable to industry standards. Our findings pave the way for routine cancer diagnosis in the future. Additionally, the method discussed can be generalized to other biosensing activities involving two-step binding processes with complementary molecule-capturing agents.

Automated summary

In this study, a label-free detection method based on broadband multi-resonant infrared metasurface for surface-enhanced infrared absorption (SEIRA) spectroscopy was used to detect miRNAs as biomarkers for breast cancer. The SEIRA resonances were optimized and showed a simulated resonance enhancement of up to 10(3) times. Testing on nine patient samples demonstrated good linear correlation with industry standards and introduced a novel analysis method. The findings pave the way for routine cancer diagnosis and have the potential for application in other biosensing activities.