Tweaking Samples for High-Speed Chemistry

A new way to print, and modify, nanoscale molecular samples could mean faster drug discovery and scientific experimentation. Combinatorial chemistry—exposing a huge array of slightly different molecules to samples in parallel—is an extremely fast way to screen drug molecules, or to test the way certain molecules affect biological cells.

Researchers at the International Institute for Nanotechnology at Northwestern University, in Chicago, led by director Chad Mirkin, have devised a way to rapidly prepare the smallest type of combinatorial chemistry array. They tested the approach by exposing stem cells to different-sized samples of fibronectin, a protein that plays an important role in cell adhesion, growth, and differentiation. The researchers used a nanoprinting technique previously developed by Mirkin’s group, called polymer pen lithography, that delivers samples to a substrate in parallel via the tips of millions of pyramid-shaped “pens.”

The innovation was to tilt the array slightly as these molecules were deposited, so that the pyramids closest to the surface make more contact and leave more material, while those farthest away leave less. Mirkin and colleagues found that, by tilting an array just 0.01 degrees, they could create 25 million fibronectin deposits of different size and structure.

When they applied stem cells to the array, they found that the size of the fibronectin molecules controlled the differentiation of these cells. “In the experiment, we only adjusted the size,” says Mirkin, whose group published their results in Proceedings of the National Academy of Science earlier this month

It may eventually be possible to change other features of samples, such as composition or shape, using the same technique. These are common features explored by drug companies, Mirkin says.

“The technique they developed is extremely powerful with the generation of a large number of features in parallel,” says Bing Yan, director of the High-Throughput Analytical Chemistry Facility at St Jude’s Children’s Research Hospital in Memphis, Tennessee, who was not involved with the research. “The number alone is very impressive.”

Along with drug testing, Yan says the approach could be used to test the reactivity of catalysts and the properties of new materials.