Single-molecule nucleic acid interactions monitored on a label-free microcavity biosensor platform

Abstract

Biosensing relies on the detection of molecules and their specific interactions. It is therefore highly desirable to develop transducers exhibiting ultimate detection limits. Microcavities are an exemplary candidate technology for demonstrating such a capability in the optical domain and in a label-free fashion. Additional sensitivity gains, achievable by exploiting plasmon resonances, promise biosensing down to the single-molecule level. Here, we introduce a biosensing platform using optical microcavity-based sensors that exhibits single-molecule sensitivity and is selective to specific single binding events. Whispering gallery modes in glass microspheres are used to leverage plasmonic enhancements in gold nanorods for the specific detection of nucleic acid hybridization, down to single 8-mer oligonucleotides. Detection of single intercalating small molecules confirms the observation of single-molecule hybridization. Matched and mismatched strands are discriminated by their interaction kinetics. Our platform allows us to monitor specific molecular interactions transiently, hence mitigating the need for high binding affinity and avoiding permanent binding of target molecules to the receptors. Sensor lifetime is therefore increased, allowing interaction kinetics to be statistically analysed.

Template-Guided Self-Assembly of Discrete Optoplasmonic Molecules and Extended Optoplasmonic Arrays

“…While this can be accomplished -in principle -by directly attaching noble metal nanoparticles to a dielectric resonator [49][50][51][52][53], this approach is very limited in scope as it does not provide control over the location and, in the case of anisotropic nanoparticles, orientation of the noble metal nanoparticles. Geometric control over the positioning of nanoparticles is crucial, in particular, for a successful integration of the optoplasmonic structures into an on-chip platform.…”

On-Chip Tuning of the Resonant Wavelength in a High-Q Microresonator Integrated with a Microheater

“…Owing to their excellent capability to efficiently confine light in the periphery via total internal reflection, [1] whispering-gallery-mode (WGM) optical microresonators have been playing increasingly important roles in applications such as microlasers, [2,3] nonlinear optics, [4] chemical and biological sensing, [5,6] cavity quantum electrodynamics (c-QED), [7] and so on. In most of these applications, precise control of the resonant wavelength of WGM is highly desirable.…”

Whispering Gallery Microcavity Nanosensor with In-Line Interferometer

“…The application of whispering gallery mode (WGM) microcavities for Nano detection and biosensing is a field of research seeing ongoing attention [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15]. This method exploits the high quality-factor (Q) of the optical cavity for ultra-sensitive monitoring of shifts in the resonant wavelength.…”