Electro-opto-fluidics: Nanopore-gated devices for multimodal analysis of single biomolecules.

摘要

Biological and solid-state nanopore sensors have proven their capability of high-throughput electrical single molecule sensing and potential in DNA/RNA sequencing. On the other hand, optofluidics, the combination of integrated optics and microfluidics, has drawn extensive attention over the past decade. The combination of nanopore technology and optofluidics is bound to bring impressive features and superiority. In this work, we innovatively integrated the solid-state nanopore into an optofluidic device, anti-resonant reflecting optical waveguides (ARROWs), to form an electro-opto-fluidic sensing platform, and demonstrate for the first time correlated electro-optical detection of single biological nanoparticles.;In order to successfully fabricate the solid-state nanopore in the semiconductor based ARROWs, we developed different fabrication methods, which are either based on standard semiconductor processes, or require the help of a focused ion beam milling. Solid-state nanopores fabricated with these methods were thoroughly characterized, analyzed, and compared using cross section analysis, energy dispersive X-ray analysis, and finite element simulation. We demonstrated that the fabrication dependent geometric shape of the pore determines the electrical blockade signal.;Afterwards, our nanopore-optofluidic device was used for the correlated electro-optical detection of single synthesized nanoparticles, single viruses, and single DNA molecules. The nanopore functions as a smart gate for sequential introduction of single nanoparticles for optical analysis. We proved that the electrical signals and the optical signals of individual nanoparticles can be clearly detected and cross correlated with a fidelity of up to 100%. On top of that, the electrical signal and the optical signal were used together to distinguish and identify different particles which could not be differentiated using either one of the signals. Moreover, information about the flow velocity, the particle-nanopore interaction, and the particle's fine structure could be extracted by analyzing electrical and optical signals. Furthermore, the combined analysis of optical signal intensity distribution and the simulated particle locations in the flow assisted us to find out the optical mode location.;Both the results and the theoretical analysis show that our novel electro-opto-fluidic platform is promising for further scientific research and clinical applications.