Noise-reduced optical detection of miRNA-155 by porous silicon through Morlet wavelet phase analysis

Porous silicon (pSi) reflectance-based optical biosensors are highly promising platforms for miRNA detection. However, reliable detection of very small effective optical thickness changes associated with miRNA binding remains challenging using conventional Reflective Interferometric Fourier Transform Spectroscopy (RIFTS). In this work, a reflectometric pSi thin-film biosensor was developed for miRNA-155 detection, and complex Morlet wavelet phase analysis (MWPA) was applied, for the first time in miRNA sensing, to suppress spectral noise in the reflectance spectra of the pSi thin film. Using MWPA, small optical thickness changes were detected with high confidence in phosphate-buffered saline (PBS), yielding an ultralow LOD of approximately 0.13 pM. In contrast, detectable changes were observed in only 28% of the data when RIFTS was used, and the LOD was estimated at approximately 0.72 pM from data with poor reliability. High selectivity against mismatched miRNA-148 was also achieved. These results demonstrate the superiority of MWPA over RIFTS for the analysis of reflectance spectra from pSi nanostructures optimized for miRNA detection, providing a reliable and sensitive platform for label-free optical biosensing of miRNA.