Monitoring DNA hybridization using optical microcavities

Article (PDF Available)inOptics Letters 38(22):4690-3 · November 2013with39 Reads
DOI: 10.1364/OL.38.004690 · Source: PubMed
Abstract
The development of DNA analysis methods is rapidly expanding as interest in characterizing subtle variations increases in biomedicine. A promising approach is based on evanescent field sensors that monitor the hybridization process in real time. However, one challenge is discriminating between nonspecific and specific attachment. Here, we demonstrate a hybridization sensor based on an integrated toroidal optical microcavity. The surface is functionalized with ssDNA using an epoxide method, and the evanescent wave of the microresonator excites a fluorescent label on the complementary ssDNA during hybridization. Based on a temporal analysis, the different binding regimes can be identified.

Figures

Figure
Figure
Figure
    • "Dielectric microresonators such as spheres, toroids, disks, etc. have been considered as optical telecommunication devices (multiplexers , switches, and filters)123. More recently, they have also been used for mechanical4567891011121314151617181920, chemical [21] , and biologi- cal222324 sensing. In most applications, solid resonators were used although liquid droplets have also been shown to be effective [25,26]. "
    [Show abstract] [Hide abstract] ABSTRACT: An approach to high-speed tracking of optical mode shifts of microresonators for wide-bandwidth sensing applications is presented. In the typical microresonator sensor, the whispering gallery optical modes (WGM) are excited by tangentially coupling tunable laser light into the resonator cavity, such as a microsphere. The light coupling is achieved by overlapping the evanescent field of the cavity with that of a prism or the tapered section of a single-mode optical fiber. The transmission spectrum through the fiber is observed to detect WGM shifts as the laser is tuned across a narrow wavelength range. High data rate transient-sensing applications require the tuning of the diode laser at high repetition rates and tracking of the WGM shifts. At high repetition rates, the thermal inertia prevents appropriate tuning of the laser, thus leading to smaller tuning ranges and waveform distortions. In the present paper, the laser is tuned using a harmonic (rather than ramp or triangular) waveform, and its output is calibrated at various input frequencies and amplitudes using a Fabry–Perot interferometer to account for the tuning range variations. The WGM shifts are tracked by performing a modified cross-correlation method on the transmission spectra. Force sensor experiments were performed using ramp and harmonic waveform tuning of the diode laser with rates up to 10 kHz. Results show that the harmonic tuning of the laser eliminates the high-speed transient thermal effects. The thermal model developed to predict the laser tuning agrees well the experiments.
    Full-text · Article · Jul 2015
    • "For nucleic acid detection by receptor-ligand type interactions between singlestranded DNA strands, epoxy groups have been conjugated to glass microtoroids via silane chemistry so that covalent bonds can be formed to amine-modified oligonucleotides. With this protocol, detection of complementary DNA strands has been achieved down to the nanomolar concentration range [279]. In another nucleic acid biosensing approach, biotinylated oligonucleotides are attached via streptavidin to a glass microsphere coated with a biotin–dextran layer, resulting in ∼10 13 oligonucleotide receptors∕cm 2 for direct detection of hybridization, or detection of strand displacement reactions via a catalytic DNA network [281]. "
    [Show abstract] [Hide abstract] ABSTRACT: We present a comprehensive overview of sensor technology exploiting optical whispering gallery mode (WGM) resonances. After a short introduction, we begin by detailing the fundamental principles and theory of WGMs in optical microcavities and the transduction mechanisms frequently employed for sensing purposes. Key recent theoretical contributions to the modelling and analysis of WGM systems are highlighted. Subsequently we review the state of the art of WGM sensors, by outlining efforts made to-date to improve current detection limits. Proposals in this vein are numerous and range, for example, from plasmonic enhancements and active cavities, through to hybrid optomechanical sensors which are already working in the shot noise limited regime. In parallel to furthering WGM sensitivity, efforts to improve the time resolution are beginning to emerge. We therefore summarise the techniques being pursued in this vein. Ultimately, WGM sensors aim for real-world applications, such as measurements of force and temperature, or alternatively gas and bio-sensing. Each such application is thus reviewed in turn and important achievements discussed. Finally, we adopt a more forward-looking perspective and discuss the outlook of WGM sensors within both a physical and biological context, and consider how they may yet push the detection envelope further.
    Full-text · Article · Jun 2015
    • "For nucleic acid detection by receptor-ligand type interactions between singlestranded DNA strands, epoxy groups have been conjugated to glass microtoroids via silane chemistry so that covalent bonds can be formed to amine-modified oligonucleotides. With this protocol, detection of complementary DNA strands has been achieved down to the nanomolar concentration range [279]. In another nucleic acid biosensing approach, biotinylated oligonucleotides are attached via streptavidin to a glass microsphere coated with a biotin–dextran layer, resulting in ∼10 13 oligonucleotide receptors∕cm 2 for direct detection of hybridization, or detection of strand displacement reactions via a catalytic DNA network [281]. "
    [Show abstract] [Hide abstract] ABSTRACT: Optical resonator-based biosensors are emerging as one of the most sensitive microsystem biodetection technology that boasts all of the capabilities for a next-generation lab-on-chip device: label-free detection down to single molecules, multiplexed sensing capability, operation in aqueous environment as well as cost-effective integration on microchips. A scholarly introduction to the emerging field of whispering gallery mode resonator-based biosensors is given and their current applications are reviewed.
    Article · Jan 2014
Show more

Recommended publications

Discover more