Nanotechnology offers unique opportunities to
advance the life sciences by facilitating the
delivery, manipulation and observation of
biological materials with unprecedented
resolution.
The ability to pattern nanoscale arrays of
biological material assists studies of genomics,
proteomics and cell adhesion, and may be applied
to achieve increased sensitivity in drug screening
and disease detection, even when sample volumes
are severely limited.
Unfortunately, most tools capable of patterning
with such tiny resolution were developed for the
silicon microelectronics industry and cannot be
used for soft and relatively sensitive
biomaterials such as DNA and proteins.
Now a team of researchers at Northwestern University has
demonstrated the ability to rapidly write
nanoscale protein arrays using a tool they call
the nanofountain probe (NFP).
"The NFP works much like a fountain pen, only
on a much smaller scale, and in this case, the ink
is the protein solution," said Horacio Espinosa,
head of the research team and professor of
mechanical engineering in the McCormick School of
Engineering and Applied Science at
Northwestern.
The results, which will be published online the
week of Oct. 13 in the Proceedings of the National
Academy of Sciences (PNAS), include demonstrations
of sub-100-nanometer protein dots and
sub-200-nanometer line arrays written using the
NFP at rates as high as 80 microns/second.
Each nanofountain probe chip has a set of ink
reservoirs that hold the solution to be patterned.
Like a fountain pen, the ink is transported to
sharp writing probes through a series of
microchannels and deposited on the substrate in
liquid form.
"This is important for a number of reasons,"
said Owen Loh, a graduate student at Northwestern
who co-authored the paper with fellow student
Andrea Ho. "By maintaining the sensitive proteins
in a liquid buffer, their biological function is
less likely to be affected. This also means we can
write for extended periods over large areas
without replenishing the ink."
Earlier demonstrations of the NFP by the
Northwestern team included directly writing
organic and inorganic materials on a number of
different substrates. These included suspensions
of gold nanoparticles, thiols and DNA patterned on
metallic- and silicon-based substrates.
In the case of protein deposition, the team
found that by applying an electrical field between
the nanofountain probe and substrate, they could
control the transport of protein to the substrate.
Without the use of electric fields, protein
deposition was relatively slow and sporadic.
However, with proper electrical bias, protein dot
and line arrays could be deposited at extremely
high rates.
"The use of electric fields allows an
additional degree of control," Espinosa said. "We
were able to create dot and line arrays with a
combination of speed and resolution not possible
using other techniques."
Positively charged proteins can be maintained
inside the fountain probe by applying a negative
potential to the NFP reservoirs with respect to a
substrate. Reversing the applied potential then
allows protein molecules to be deposited at a
desired site.
To maximize the patterning resolution and
efficiency, the team relied on computational
models of the deposition process. "By modeling the
ink flow within the probe tip, we were able to get
a sense of what conditions would yield optimal
patterns," says Jee Rim, a postdoctoral researcher
at Northwestern.
Espinosa collaborated closely with Neelesh
Patankar, associate professor of mechanical
engineering at Northwestern, and Punit Kohli,
assistant professor of chemistry and biochemistry
at Southern Illinois University, Carbondale.
"We are very excited by these results," said
Espinosa. "This technique is very broadly
applicable, and we are pursuing it on a number of
fronts." These include single-cell biological
studies and direct-write fabrication of
large-scale arrays of nanoelectrical and
nanoelectromechanical devices.
"The fact that we can batch fabricate large
arrays of these fountain probes means we can
directly write large numbers of features in
parallel," added Espinosa. "The demonstration of
rapid protein deposition rates further supports
our efforts in producing a large-scale
nanomanufacturing tool."
Posted October 14th,
2008
