Single particle studies on an integrated nanopore-optofluidic chip

We discuss development and demonstrate applications of a novel integrated sensor which draws on recent advances in optofluidics and nanopore technologies. We first show detection and analysis of viral particles on an integrated optofluidic chip using fluorescence correlation spectroscopy. The resulting sensitivity of single viral particles and simultaneous extraction of the diffusion coefficient, flow velocity, and concentration are promising for a virus sensor for medical and research applications. We then discuss a novel nano/microfabrication process which allows integration of a solid state nanopore into an optofluidic chip. We demonstrate detection and analysis capabilities of single nanoparticle electrical signatures (current blockades and enhancements) of the integrated solid state nanopore on such examples as: nanoparticle Coulter counting, size differentiation; protein detection, and controllable ribosome introduction into the optofluidic chip. We perform theoretical analysis of the observed blockade depth dependencies on particle size, number of particles residing in the pore, magnitude of the applied bias, and resistance of the optofluidic channel in two different configurations. We observe excellent predictive power of the developed theoretical model for practically all dependencies, except blockade amplitude when size of the particle is very close to the size of the nanopore. We also study theoretically experimentally observed exponential dependence of the frequency of ribosome capture events on the applied bias, extracting activation energy and minimal voltage required for controlled single ribosome introduction into the optofluidic channel through the nanopore. We later discuss an experimental demonstration of simultaneous electrical (integrated solid state nanopore) and optical (optofluidic chip) detection and analysis of single fluorescently labeled nanoparticles. We successfully apply fluorescence correlation spectroscopy to the resulting signals and confirm fluorescent nanoparticle translocation, and electrical and optical detection on the single particle level.;The results of this work are promising for a new type of sensitive detector combining advantages of two ultrasensitive technologies: integrated optofluidics and solid state nanopores.