Plasmoelectronic-Based Ultrasensitive Assay of Tumor Suppressor microRNAs Directly in Patient Plasma: Design of Highly Specific Early Cancer Diagnostic Technology.

It is becoming understood that microRNAs hold great promise for non-invasive liquid biopsies for screening for different types of cancer, but current state-of-the-art RT-PCR and microarray techniques have sensitivity limitations that currently restrict their use. Herein, we report a new transduction mechanism involving delocalization of photoexcited conduction electrons wavefunction of gold triangular nanoprism (Au TNP) in the presence of -ssDNA/microRNA duplexes. This plasmoelectronic effect reduces the electron density of Au TNPs and substantially affects their localized surface plasmon resonance (LSPR) properties that together allow us to achieve a sensitivity for microRNA assay as low as 140 zeptomolar concentrations for our nanoplasmonic sensors. We show that the position of a single base-pair mismatch in the -ssDNA/microRNA duplex dramatically alters the LSPR properties and detection sensitivity. The unprecedentedly high sensitivity of nanoplasmonic sensors has allowed us to assay four different microRNAs (microRNA-10b, -182, -143 and -145) from bladder cancer patient plasma (50 microL/sample). For the first time, we demonstrate the utility of a label-free, nanoplasmonic sensor in quantification of tumor suppressor microRNAs - the level of tumor suppressor microRNAs goes down in cancer patient as compared to normal healthy individuals - in metastatic and non-metastatic bladder cancer patient plasma. Our statistical analysis of patient samples unequivocally suggests that the tumor suppressor microRNAs are more specific biomarkers (p-value of <0.0001) than oncogenic microRNAs for differentiation between metastatic and non-metastatic bladder cancer, and non-metastatic cancer from healthy individuals. This work demonstrating the electron wavefunctions delocalization dependent ultrasensitive LSPR properties of noble metal nanoparticles has a great potential for fabrication of miniaturized and extremely powerful sensors to investigate microRNA properties in other cancers (for example breast, lung, and pancreatic) through liquid biopsy.