Modulation-frequency encoded multi-color fluorescent DNA analysis in an optofluidic chip

C. Dongre, J. van Weerd, G.A.J. Besselink, R. Osellame, R. Martínez Vázquez, G. Cerullo, R. van Weeghel, H.H. van den Vlekkert, Hugo Hoekstra, Markus Pollnau

    Research output: Chapter in Book/Report/Conference proceedingConference contributionAcademic

    28 Citations (Scopus)
    142 Downloads (Pure)


    By capillary electrophoresis (CE) in miniaturized lab-on-a-chip devices, integrated DNA sequencing and genetic diagnostics have become feasible. We introduce a principle of parallel optical processing to significantly enhance analysis capabilities. In a commercial microfluidic chip, a plug of DNA molecules was injected and the DNA molecules were CE-separated with a high relative sizing accuracy of >99%. Through an optical waveguide inscribed by femtosecond-laser writing a laser was launched perpendicularly into the microfluidic channel. A photomultiplier collected the fluorescence signals from a small detection window with a limit of detection of ~8 DNA molecules. In our approach, different sets of exclusively end-labeled DNA fragments are unambiguously identified by simultaneously launching several continuous-wave lasers, each modulated with a different frequency, detection of the frequency-encoded signals at different fluorescence wavelengths by a single ultrasensitive, albeit color-blind photomultiplier, and Fourier-domain frequency decoding. As a proof of principle, fragments from independent human genomic segments, associated with genetic predispositions to breast cancer and anemia, are simultaneously analyzed in a single flow experiment. This novel method of modulation-frequency-encoded fluorescence excitation opens new opportunities in genetic diagnostics. It enables the identification of end-labeled DNA samples of different genetic origin during their electrophoretic separation, opening perspectives for intrinsic size calibration, malign / healthy sample comparison, and exploitation of multiplex ligation-dependent probe amplification.
    Original languageEnglish
    Title of host publicationInternational Laser Physics Workshop 2011
    Place of PublicationMoscow
    PublisherRAS - General Physics Institute
    Number of pages1
    Publication statusPublished - Jul 2011
    Event20th International Laser Physics Workshop, LPHYS 2011 - Hotel Hollywood, Sarajevo, Bosnia and Herzegovina
    Duration: 11 Jul 201115 Jul 2011
    Conference number: 20


    Conference20th International Laser Physics Workshop, LPHYS 2011
    Abbreviated titleLPHYS
    Country/TerritoryBosnia and Herzegovina
    Other11-15 July 2011
    Internet address



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