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Nanofluidics Get More Complex

A new three-dimensional device sorts and separates nanoparticles by size.

Researchers at the National Institute of Standards and Technology (NIST), in Gaithersburg, MD, have made one of the most sophisticated nanofluidics device to date. They make it using a one-step process, as opposed to by using the multilayer lithography techniques employed to fabricate integrated circuits.

Baby steps: A photomicrograph shows nanoparticles at the 100-nanometer “step” of the nanofluidic chamber. The nanoparticles are fluorescently tagged.

So far, nanofluidic devices have been mainly used to analyze DNA and proteins. Because the new device could separate particles of different sizes from a mixture, it could also be useful in the preparation of nanoparticles for gene therapy, drug delivery, and toxicity analysis.

Nanofluidics technology, which is still at a nascent stage, deals with the manipulation and control of a few molecules or minute quantities of fluids. Nanofluidic devices are made by etching tiny channels on silicon or glass wafers, typically using photolithography. These devices have relatively simple structures, with the branched channels having the same depths.

The new device, presented online in the journal Nanotechnology, is a chamber with 30 different depths. Its side profile looks like a staircase, with a depth ranging from 10 nanometers at the shallowest end to 620 nanometers at the other end.

The researchers place nanoparticles in the deep end. They use an electric field to push the particles toward the shallow end. The particles can only move to the next step if they are smaller than the depth of the step. As a result, nanoparticles of different widths get separated along different steps.

The device could be useful for sorting and measuring nanoparticles that are employed for drug delivery and gene therapy, says NIST’s Samuel Stavis, a coauthor of the paper. Moreover, since the properties of nanoparticles can depend on their size, the device could be useful for testing the potential toxicity of different particles. “If you want to do experiments where you’re investigating the dependence of a nanoparticle’s function on its size, it would be nice to have a tool to take a mixture of nanoparticles, separate them, sort them, and deliver them,” Stavis says.

Han Cao, founder and chief scientific officer of BioNanomatrix, a startup based in Philadelphia that uses nanofluidics for DNA analysis, says that the significant aspect of the new work is that the researchers have used a one-step lithography process.

In the one-step process, a mask is used that lets different levels of light fall on the photoresist (in conventional photolithography, the mask either allows light through or blocks it). Different amounts of photoresist are then washed away, etching the substrate to varying degrees.

Stavis says that the technique could be used to make much more complicated devices. The researchers should also be able to fabricate structures with smooth curves, he says. Such devices could provide new lab-on-a-chip tools for DNA analysis, biotechnology, and medicine.