Since the pioneering studies on single ion-channel recordings in 1976, single molecule
methods have evolved into powerful tools capable of probing biological systems with unprecedented
detail.
In this work, we build on the versatility of a type of nanofluidic devices, called nanopipettes,
to explore novel modes of single molecule detection and manipulation with the aim of improving
spatial and temporal control of biomolecules.
In particular, a novel nanopore configuration is presented, where biomolecules were
individually confined into a zeptoliter volume bridging two adjacent nanopores at the tip
of a nanopipette. As a result of this confinement, the transport of biomolecules such as
DNA and proteins was slow down by nearly three orders of magnitude, leading to an
improved sensitivity and superior signal-to-noise performances compared to conventional
nanopore sensing. Active ways of controlling the transport of biomolecule by combining
the advantages of nanopore single-molecule sensing and Field-Effect Transistors are also
presented. These hybrid platforms were fabricated in a simple two step process which
integrates a gold electrode at the apex of a nanopipette. We show that these devices were
effective in modulating the charge density of the nanopore and in actively switching "on"
and "off" the transport of DNA through the nanopore.
Finally, a nanoscale dielectrophoretic nanotweezer device has been developed for high
resolution manipulation and interrogation of individual entities. Two closely spaced carbon
nanoelectrodes were embedded at the apex of a nanopipette. Voltage and frequency applied
to the electrodes generated a highly localized force capable of trapping and manipulating a
broad range of biomolecules. These dielectrophoretic nanotweezers were suitable for probing
complex biological environments and a new technique for minimally invasive single-cell
nanobiopsy was established. Such study provides encouraging results on how nanopipettebased
platforms can be integrated as a future tool for routinely interrogating molecules at the
nanoscale.