Synchronous optical and electrical detection of biomolecules traversing through solid-state nanopores

We present a novel method for integrating two single-molecule measurement modalities, namely, total internal reflection microscopy and electrical detection of biomolecules using nanopores. Demonstrated here is the electrical measurement of nanopore based biosensing performed simultaneously and in-sync with optical detection of analytes. This method makes it possible, for the first time, to visualize DNA and DNA-protein complexes translocating through a nanopore with high temporal resolution (1000 frames/s) and good signal to background. This paper describes a detailed experimental design of custom optics and data acquisition hardware to achieve simultaneous high resolution electrical and optical measurements on labeled biomolecules as they traverse through a approximately 4 nm synthetic pore. In conclusion, we discuss new directions and measurements, which this technique opens up.