fountain pen used to rapidly write protein arrays
(Nanowerk News) 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
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
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
"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
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."