title: Mach-Zehnder interferometer (MZI) point-of-care system for rapid multiplexed detection of microRNAs in human urine specimens.
abstract: MicroRNAs have been identified as promising biomarkers for human diseases. The development of a point-of-care (POC) test for the disease-associated miRNAs would be especially beneficial, since miRNAs are unexpectedly well preserved in various human specimens, including urine. Here, we present the Mach-Zehnder interferometer-miRNA detection system capable of detecting multiple miRNAs in clinical urine samples rapidly and simultaneously in a label-free and real-time manner. Through measurement of the light phase change, the MZI sensor provides an optical platform for fast profiling of small molecules with improved accuracy. We demonstrate that this system could specifically detect target miRNAs (miR-21, and let-7a), and even identify the single nucleotide polymorphism of the let-7 family of miRNAs from synthetic and cell line samples. The clinical applicability of this system is confirmed by simultaneously detecting two types of miRNAs in urine samples of bladder cancer patients in a single reaction, with a detection time of 15 min. The POC system can be expanded to detect a number of miRNAs of different species and should be useful for a variety of clinical applications requiring at or near the site of patient care.
authors.affiliation: Institute of Microelectronics, A⁎STAR (Agency for Science, Technology and Research), 11 Science Park Road, Singapore Science Park II, 117685, Singapore.
authors.forename: Qing
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Institute of Microelectronics, A⁎STAR (Agency for Science, Technology and Research), 11 Science Park Road, Singapore Science Park II, 117685, Singapore.
authors.forename: Yong
authors.initials: Y
authors.lastname: Shin
authors.affiliation: Institute of Microelectronics, A⁎STAR (Agency for Science, Technology and Research), 11 Science Park Road, Singapore Science Park II, 117685, Singapore.
authors.forename: Jack Sheng
authors.initials: JS
authors.lastname: Kee
authors.affiliation: Institute of Microelectronics, A⁎STAR (Agency for Science, Technology and Research), 11 Science Park Road, Singapore Science Park II, 117685, Singapore.
authors.forename: Kyung Woo
authors.initials: KW
authors.lastname: Kim
authors.affiliation: Institute of Microelectronics, A⁎STAR (Agency for Science, Technology and Research), 11 Science Park Road, Singapore Science Park II, 117685, Singapore.
authors.forename: Siti Rafeah
authors.initials: SR
authors.lastname: Mohamed Rafei
authors.affiliation: Institute of Microelectronics, A⁎STAR (Agency for Science, Technology and Research), 11 Science Park Road, Singapore Science Park II, 117685, Singapore.
authors.forename: Agampodi Promoda
authors.initials: AP
authors.lastname: Perera
authors.affiliation: Institute of Microelectronics, A⁎STAR (Agency for Science, Technology and Research), 11 Science Park Road, Singapore Science Park II, 117685, Singapore.
authors.forename: Xiaoguang
authors.initials: X
authors.lastname: Tu
authors.affiliation: Institute of Microelectronics, A⁎STAR (Agency for Science, Technology and Research), 11 Science Park Road, Singapore Science Park II, 117685, Singapore.
authors.forename: Guo-Qiang
authors.initials: GQ
authors.lastname: Lo
authors.affiliation: Service d'Urologie et Chirurgie de la Transplantation, Hôpital Edouard Herriot, 5 Place d'Arsonval, 69437 Lyon Cedex 03, France.
authors.forename: Estelle
authors.initials: E
authors.lastname: Ricci
authors.affiliation: Service d'Urologie et Chirurgie de la Transplantation, Hôpital Edouard Herriot, 5 Place d'Arsonval, 69437 Lyon Cedex 03, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Colombel
authors.affiliation: Department of Urology, National University Health System, Singapore.
authors.forename: Edmund
authors.initials: E
authors.lastname: Chiong
authors.affiliation: Institute of Molecular and Cell Biology, A*STAR (Agency for Science, Technology and Research), 61 Biopolis Drive, 138673, Singapore.
authors.forename: Jean Paul
authors.initials: JP
authors.lastname: Thiery
authors.affiliation: Institute of Microelectronics, A⁎STAR (Agency for Science, Technology and Research), 11 Science Park Road, Singapore Science Park II, 117685, Singapore. Electronic address: parkmk@ime.a-star.edu.sg.
authors.forename: Mi Kyoung
authors.initials: MK
authors.lastname: Park
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics / Q000652:urine; D045424:Complex Mixtures / Q000652:urine; D003199:Computer Systems; D004252:DNA Mutational Analysis / Q000295:instrumentation; D004867:Equipment Design; D019544:Equipment Failure Analysis; D006801:Humans; D007368:Interferometry / Q000295:instrumentation*; D035683:MicroRNAs / Q000235:genetics* / Q000652:urine*; D046228:Microarray Analysis / Q000295:instrumentation; D019095:Point-of-Care Systems; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D017423:Sequence Analysis, RNA / Q000295:instrumentation*; D001749:Urinary Bladder Neoplasms / Q000175:diagnosis / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; D045424:Complex Mixtures; D035683:MicroRNAs; C487931:mirnlet7 microRNA, human