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Plasmoelectronic-Based Ultrasensitive Assay of Tumor Suppressor microRNAs Directly in Patient Plasma: Design of Highly Specific Early Cancer Diagnostic Technology Thakshila Liyanage, Adrianna N Masterson, Hector H. Oyem, Hristos Kaimakliotis, Hang Nguyen, and Rajesh Sardar Anal. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.analchem.8b03768 • Publication Date (Web): 04 Jan 2019 Downloaded from http://pubs.acs.org on January 7, 2019
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Analytical Chemistry
Plasmoelectronic-Based Ultrasensitive Assay of Tumor Suppressor microRNAs Directly in Patient Plasma: Design of Highly Specific Early Cancer Diagnostic Technology Thakshila Liyanage,1 Adrianna N. Masterson,1 Hector H. Oyem,2 Hristos Kaimakliotis,3 Hang Nguyen,1 and Rajesh Sardar*,1,4 1Department
of Chemistry and Chemical Biology, Indiana University-Purdue University
Indianapolis, 402 N. Blackford Street, Indianapolis, Indiana 46202, United States 2School
of Chemistry, Newcastle University, NE1 7RU, United Kingdom
3Department
of Urology, Indiana University School of Medicine, 535 N. Barnhill Dr.
Indianapolis, Indiana 46202, United States 4Integrated Nanosystems Development Institute, Indiana University-Purdue University
Indianapolis, 402 N. Blackford Street, Indianapolis, Indiana 46202, United States
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ABSTRACT: 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 increases the electronic dimension 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 L/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
