文献名： Sequence-Specific Detection of MicroRNAs Related to Clear Cell Renal Cell Carcinoma at fM Concentration by an Electroosmotically Driven Nanopore-Based Device

 

作者： Yuqian Zhang† , Ankit Rana† , Yiwen Stratton‡, Maria F. Czyzyk-Krzeska‡§, and Leyla Esfandiari*†∥

† Department of Electrical Engineering and Computing Systems, University of Cincinnati, Cincinnati, Ohio 45221, United States

‡ Department of Cancer Biology, University of Cincinnati, Cincinnati, Ohio 45267, United States

§ Department of Veterans Affairs, VA Research Service, Cincinnati, Ohio 45220, United States

∥ Department of Biomedical Chemical and Environmental Engineering, University of Cincinnati, Cincinnati, Ohio 45221, United States

 

 

摘要：MicroRNAs (miRs) are small noncoding RNAs that play a critical role in gene regulation. Recently, traces of cancer-related miRs have been identified in body fluids, which make them remarkable noninvasive biomarkers. In this study, a new nanopore-based detection scheme utilizing a borosilicate micropipette and an assay of complementary γ-peptide nucleic acid (γ-PNA) probes conjugated to polystyrene beads have been reported for the detection of miR-204 and miR-210 related to the clear cell Renal Cell Carcinoma (ccRCC). Electroosmotic flow (EOF) is induced as the driving force to transport PNA-beads harboring target miRs to the tip of the pore (sensing zone), which results in pore blockades with unique and easily distinguishable serrated shape electrical signals. The concentration detection limit is investigated to be 1 and 10 fM for miR-204 and miR-210, respectively. The EOF transport mechanism enables highly sensitive detection of molecules with low surface charge density with 97.6% detection accuracy compared to the conventional electrophoretically driven methods. Furthermore, resistive-pulse experiments are conducted to study the correlation of the particles’ surface charge density with their translocation time and verify the detection principle.