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dc.contributor.advisorGu, Li-Quneng
dc.contributor.authorWang, Yong, 1980-eng
dc.date.issued2012eng
dc.date.submitted2012 Springeng
dc.descriptionTitle from PDF of title page (University of Missouri--Columbia, viewed on May 15, 2013).eng
dc.descriptionThe entire thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file; a non-technical public abstract appears in the public.pdf file.eng
dc.descriptionDissertation advisor: Dr. Li-Qun (Andrew) Gueng
dc.descriptionIncludes bibliographical references.eng
dc.descriptionVita.eng
dc.descriptionPh. D. University of Missouri--Columbia 2012.eng
dc.description"May 2012"eng
dc.description.abstractMicroRNAs (miRNAs) are a class of short (~14-27 nucleotides) noncoding RNAs that regulate gene expression at the post-transcriptional level. Aberrant expression of miRNAs has been found in all types of tumors. Reverse transcription real-time polymerase chain reaction (qRT-PCR) and microarrays have been developed for detecting microRNA; however, these methods need labeling and amplification, and suffer from cross-hybridization, low selectivity and lack of valid internal controls. The development of nanopore sensors for microRNA detection is a new effort. One of the superior properties of nanopore is that the ion current in a nanometer-scaled pore structure is very sensitive to the presence, location and conformation of single target molecules occupying the ion pathway. Here we show that a nanopore sensor based on the alpha-hemolysin protein can selectively detect microRNAs at the single molecular level in the plasma samples of lung cancer patients without labeling and amplification of microRNAs. First, we uncovered a signature current pattern that can be used to electrically track the double-stranded DNA (dsDNA) unzipping process. With the signature signals, we can also distinguish the release of dsDNA without unzipping. Second, based on the electrical signatures we identified, we have designed a nanopore-based microRNA sensor for the direct and label-free detection of target microRNA in a fluctuating background, such as plasma RNA extracts from clinical samples. This sensor can quantify picomolar levels of cancer-associated microRNAs and can distinguish single-nucleotide differences between microRNA family members. This nanopore method can be a useful tool for quantitative studies of microRNAs, which are important for non-invasive screening and the early diagnosis of diseases such as cancer.eng
dc.description.bibrefIncludes bibliographical references.eng
dc.format.extentx, 105 pageseng
dc.identifier.oclc872568848eng
dc.identifier.urihttps://doi.org/10.32469/10355/35199eng
dc.identifier.urihttps://hdl.handle.net/10355/35199
dc.languageEnglisheng
dc.publisherUniversity of Missouri--Columbiaeng
dc.relation.ispartofcommunityUniversity of Missouri--Columbia. Graduate School. Theses and Dissertationseng
dc.rightsOpenAccess.eng
dc.rights.licenseThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 License.
dc.sourceSubmitted by University of Missouri--Columbia Graduate School.eng
dc.subjectnanopore sensoreng
dc.subjectmicroRNA detectioneng
dc.subjectdiagnostic medicineeng
dc.titleCharacterization [of] nucleic acids unwinding and exploring its application in miRNA detection in the nanoporeeng
dc.typeThesiseng
thesis.degree.disciplineBiological engineering (MU)eng
thesis.degree.grantorUniversity of Missouri--Columbiaeng
thesis.degree.levelDoctoraleng
thesis.degree.namePh. D.eng


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