Highly Specific Plasmonic Biosensors for UltrasensitiveMicroRNA Detection in Plasma from Pancreatic Cancer Patients

摘要

MicroRNAs (miRs) are small noncoding RNAs that regulate mRNA stability and/or translation. Because of their release into the circulation and their remarkable stability, miR levels in plasma and other biological fluids can serve as diagnostic and prognostic disease biomarkers. However, quantifying miRs in the circulation is challenging due to issues with sensitivity and specificity. This Letter describes for the first time the design and characterization of a regenerative, solid-state localized surface plasmon resonance (LSPR) sensor based on highly sensitive nanostructures (gold nanoprisms) that obviates the need for labels or amplification of the miRs. Our direct hybridization approach has enabled the detection of subfemtomolar concentration of miR-X (X = 21 and 10b) in human plasma in pancreatic cancer patients. Our LSPR-based measurements showed that the miR levels measured directly in patient plasma were at least 2-fold higher than following RNA extraction and quantification by reverse transcriptase-polymerase chain reaction. Through LSPR-based measurements we have shown nearly 4-fold higherconcentrations of miR-10b than miR-21 in plasma of pancreatic cancerpatients. We propose that our highly sensitive and selective detectionapproach for assaying miRs in plasma can be applied to many cancertypes and disease states and should allow a rational approach fortesting the utility of miRs as markers for early disease diagnosisand prognosis, which could allow for the design of effective individualizedtherapeutic approaches.