Tracking single particle dynamics via combined optical and electrical sensing

Nanopores and nanochannels have been widely used as a useful platform for electrical detections of single-particles to study the fast translocation dynamics.  The sensing mechanism involves measurements of temporal blockage of the ionic current through a fluidic channel, which is called resistive pulses, by an individual particle passing through it.  In recent years, there has been increasing number of research efforts in this field reporting miscellaneous features in the electrical signatures of single-molecule or -particle translocations, e.g. ionic current blockage, enhancement, or even composites of these two aspects.  Although systematic and statistical analysis of numerous electrical signals gives comprehensible explanations on the underlying physics in many cases, electrical detections alone can never ensure whether a resistive pulse is associated with envisaged translocation of individual analyte particles.  Here we report a single-particle tracking by combined electrical and optical sensing using a fluidic microsystem lithographed on a glass substrate.  This breakthrough approach offers the missing function of the electrical method for identifying the presence and absence of analyte in a nanopore or nanochannel at the moment when a resistive pulse is detected.  We demonstrate that our technique enables unambiguous sorting of resistive pulses to translocation-derived and non-translocation-derived, particle-particle collisions and temporal blocking, and even discriminates single-particle and two-particle-cluster translocations.  We also find that the combined optical/electrical sensing reveals an important role of particle history in the pre-translocation regime in determining its electrophoretic dynamics in a microchannel by allowing detections of single-particle motions at extensive spatial and dynamic ranges.

Scientific Reports 3 doi: 10.1038/srep01855 (2013).