Ultra-sensitive detection of microRNA in intraocular fluid using optical fiber sensing technology for central nervous system lymphoma diagnosis

MicroRNA (miRNA) in aqueous humor holds significant promise as a non-invasive biomarker of primary central nervous system lymphoma (PCNSL), enabling early diagnosis and prognosis. However, current methods for miRNA detection often suffer from limitations affecting sensitivity, specificity, and clinical applicability. This study introduces a novel black phosphorus (BP)-enhanced fiber-optic surface plasmon resonance sensor integrated with a clustered regularly interspaced short palindromic repeats (CRISPR)-Cas13a system for ultrasensitive and single-base-specific detection of PCNSL-associated miRNA in aqueous humor. The BP nano-interface significantly enhances the surface plasmon resonance signal, while the CRISPR-Cas13a technology enables highly specific detection of miRNA, down to single nucleotide mismatches. This system achieves a detection limit as low as 21 aM without the need for amplification and demonstrates robust performance in analyzing clinical samples. With its unparalleled sensitivity, specificity, label-free operation, and potential for portability, this biosensing platform offers transformative capabilities for early PCNSL diagnosis, prognosis, and treatment monitoring.