Scientists at Northwestern University have developed a new detection technology on the nanometer scale that could lead to the next generation of proteomic arrays and new methods for diagnosing infectious diseases.

Once optimized, the new nanotechnology holds promise for biological detectors that can yield more information more accurately in a shorter period of time. Such devices ultimately could be used in the doctor’s office to rapidly screen for a wide range of pathogenic diseases or in the field to detect biological weapons such as anthrax and smallpox.

A report on the protein nanoarrays was published online Feb. 7 by the journal Science at the Science Express Web site (

Genetic and proteomic screening with so-called gene-chips and proteomic arrays are allowing researchers to peer into the genetic code of individuals and develop leads for important therapeutic agents in the pharmaceutical industry. Current technology uses arrays of either proteins or DNA on the micrometer level as screening tools for analyzing DNA, protein-protein interactions and cell biology and for drug testing. Miniaturizing these arrays could dramatically improve their capabilities.

The researchers utilize a process invented at Northwestern called Dip-Pen Nanolithography to make arrays of proteins with features more than 1,000 times smaller than those used in conventional arrays. This leads to nanoarrays with more than 1 million times the density of current commercial microarrays.

Led by Chad A. Mirkin, director of Northwestern’s Institute for Nanotechnology, the research team combined expertise with Professor Milan Mrksich of the University of Chicago and his group and also showed that the novel arrays could be used to study important biological processes, such as cell adhesion. This involves discovering and then writing a pattern of proteins that attracts a particular molecule.

“Our technology opens up many new possibilities for detection and understanding the interactions of biomolecules with each other and synthetic agents,” said Mirkin. “We have developed a simple way of recognizing complex materials. Once the pattern of protein dots that matches a particular biomolecule or structure is known, we can build a detector for that biomolecule. This means that instead of testing for anthrax DNA, which requires a lot of processing, we might be able to test for the anthrax spore itself.”

“Creating patterns on a sub-micrometer level is important,” added Mirkin, also George B. Rathmann Professor of Chemistry. “More detailed questions can be asked and answered when working on the nanometer scale. This is a fundamental advance in biorecognition.”

Mirkin’s method of Dip-Pen Nanolithography allowed the researchers to use an atomic force microscope tip as a nano-pen to write out a tiny protein array on a gold surface. With an array of protein “dots” as small as 100 nanometers in diameter, the gold surface in between the dots was processed to prevent it from absorbing target proteins and disturbing the readings. (A nanometer is one-billionth of a meter.) When an array on a chip was exposed to protein targets in solution, the protein on the substrate (16-mercaptohexadecanoic acid or MHA) bound its complementary proteins (lysozyme and rabbit immunoglobin). The atomic force microscope then read the chip and recorded a match where a change in height was detected.


Other authors on the paper are Ki-Bum Lee (lead author) and So-Jung Park, both of Northwestern. The research was supported by the Air Force Office of Scientific Research, the Defense Advanced Research Projects Agency (DARPA), the National Science Foundation and the National Institutes of Health.