This illustration shows how a DNA origami nanoplate with a central aperture can serve as a smart lid or “gatekeeper” for a solid-state nanopore sensor. |
The
latest advance in solid-state nanopore sensors—devices that are made
with standard tools of the semiconductor industry yet can offer
single-molecule sensitivity for label-free protein screenings—expands
their bag of tricks through bionanotechnology. Researchers at the
Technische Universität München have enhanced the capabilities of
solid-state nanopores by fitting them with cover plates made of DNA. The
results are published in Angewandte Chemie International Edition.
The
nanoscale cover plates, with central apertures tailored to various
“gatekeeper” functions, are formed by so-called DNA origami—the art of
programming strands of DNA to fold into custom-designed structures with
specified chemical properties. Over the past few years, Prof. Hendrik
Dietz’s research group at TUM has been refining control over DNA origami
techniques and demonstrating how structures made in this way can enable
scientific investigations in diverse fields. Meanwhile, Dr. Ulrich
Rant’s research group has been doing the same for solid-state nanopore
sensors, where the basic working principle is to urge biomolecules of
interest, one at a time, through a nanometer-scale hole in a thin slab
of semiconductor material. When biomolecules pass through or linger in
such a sensor, minute changes in electrical current flowing through the
nanopore translate into information about their identity and physical
properties. Now Dietz and Rant, who are both Fellows of the TUM
Institute for Advanced Study, have begun to explore what these two
technologies can accomplish together.
The
new device concept – purely hypothetical before this series of
experiments—begins with the placement of a DNA origami “nanoplate” over
the narrow end of a conically tapered solid-state nanopore. “Tuning” the
size of the central aperture in the DNA nanoplate should allow
filtering of molecules by size. A further refinement, placing
single-stranded DNA receptors in the aperture as “bait,” should allow
sequence-specific detection of “prey” molecules. Conceivable
applications include biomolecular interaction screens and detection of
DNA sequences. In principle, such a device could even serve as the basis
of a novel DNA sequencing system.
Step
by step, the researchers investigated each of these ideas. They were
able to confirm the self-assembly of custom-designed DNA origami
nanoplates, and then their placement—after being electrically guided
into position—over solid-state nanopores. They were able to demonstrate
both size-based filtering of biomolecules and bait/prey detection of
specific target molecules.
“We’re
especially excited about the selective potential of the bait/prey
approach to single-molecule sensing,” Dietz says, “because many
different chemical components beyond DNA could be attached to the
appropriate site on a DNA nanoplate.”
High-resolution
sensing applications such as DNA sequencing will face some additional
hurdles, however, as Rant explains: “By design, the nanopores and their
DNA origami gatekeepers allow small ions to pass through. For some
conceivable applications, that becomes an unwanted leakage current that
would have to be reduced, along with the magnitude of current
fluctuations.”
“Future
work will need to address fundamental questions, such as how the
transport of ions across the DNA origami nanoplates affects the
measurement accuracy, and how the nanoplates can be anchored more stably
on top of the solid-state nanopores.”
This
research was supported by the German Excellence Initiative through the
TUM Institute for Advanced Study, the Nano Initiative Munich, and the
Center for Integrated Protein Science Munich; by the Collaborative
Research Center SFB 863 of the German Research Foundation (DFG); and by a
European Research Council Starting Grant to Hendrik Dietz. Ruoshan Wei
was supported by the TUM Graduate School’s Faculty Graduate Center of
Physics.
DNA Origami Gatekeepers for Solid-State Nanopores
Source: Munich Technical University