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

Abstract

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 higher concentrations of miR-10b than miR-21 in plasma of pancreatic cancer patients. We propose that our highly sensitive and selective detection approach for assaying miRs in plasma can be applied to many cancer types and disease states and should allow a rational approach for testing the utility of miRs as markers for early disease diagnosis and prognosis, which could allow for the design of effective individualized therapeutic approaches.

Achieving biosensing at attomolar concentrations of cardiac troponin T in human biofluids by developing a label-free nanoplasmonic analytical assay

“…14 In this context, ultrasensitive and novel biosensors can be developed by characterizing the LSPR response (extinction or absorption peak position and intensity) of nanoparticles as a function of the changes in their local dielectric environment. 6,[15][16][17] In this article, we report the first quantification of cardiac Troponin-T (cTnT) in diverse human biofluids (plasma, serum, and urine) utilizing a LSPR biosensor. Our chip-based LSPR cTnT biosensor provides a limit of detection (LOD) as low as 507 fg/L, which is 10 4 fold more sensitive than the commercial Elecys troponin T electrolumi-nescense immunoassay (ECLIA, 4 th generation, Roche Diagnostic) 18 and at least 50 fold lower than other label-free analytical techniques.…”

Contact Transfer Printing of Side Edge Prefunctionalized Nanoplasmonic Arrays for Flexible microRNA Biosensor

“…Results from a number of clinically relevant microRNAs, but different from our target miR‐21, such as miR‐16, miR‐122, miR‐126, miR‐141, and miR‐206 have been presented by other researchers 78. Additionally, miR‐15 and miR‐16 are structurally similar to our target miRNA‐21 in the 5′region 55, 79.…”

Emerging applications of label-free optical biosensors

“…[58], where the phase shift of p-polarized light interacting with surface plasmon was measured by creating an interference fringe image on the interface, which changed upon hybridization of DNA 30mers, yielding a LOD of 50 pg/ml ( Figure 5B). As for the second, localized SPR can instead be obtained with various types of patterning, like gold nanoprisms with 30-50 nm edges [68,59], which allowed miRNA quantitation with an impressive LOD as low as 0.25 fg/ml ( Figure 5C). …”