Detecting DNA with nanomachines

DNA is small. Despite being the code that spells out how to make each of the billions upon billions of proteins that make up who you are, each base, or letter of DNA, is 2 nano meters wide, and 0.3 nanometers long. Even stretched out, 800,000 letters of DNA can fit around a single strand of hair. One difference in a million separates you from smelly Bob, and only a few changes in key places would give you cancer. So how would you read something so small, yet so important? Well, how about with tiny diving board?

In 2000, a significant work [1] from J. Fritz and the team at the IBM Zurich Research Laboratory presented a method that have been commonly used to create CPUs to sense biomolecules, including DNA, RNA, and proteins. They used semiconductor fabrication technology to create silicon cantilevers, which are tiny diving boards measuring 1 x 500 x 100 microns to create a platform where the materials would be detected. These cantilevers are still much larger than biomolecules, but they are small enough that they would be affected by them.

So to detect a specific sequence of DNA, they put complementary sequences stacked vertically on the cantilever. When a sample is placed on the device, the DNA from the sample would pair up and bind with those on the platform. The surface that was already crowded would now be even more packed, and the stress that is only on only one side of the cantilever causes it to bend, which can then be detected with high accuracy by a laser.

To test out their device, they created two such cantilevers, one with a 12 letter DNA sequence and the other with a 16 letter sequence and then they put two samples with the complementary sequence one after the other on the device. Of course, we cannot perfectly predict the reactions between the things in the sample and the DNA molecules on the platform, but with two such platforms, any difference would be significant. If the things in the samples bound to one platform stronger than the other, we can assume it was caused by the very specific DNA pairing. Sure enough, the laser signal showed the cantilever wobble and then stabilize with one cantilever bent lower after the first sample was added, and then wobble and stabilize with the other cantilever bent lower after the second sample was added. Even DNA sequences that differed by only one base pair caused a noticeable difference. Other than just attaching DNA sequences to the platform, they also tried proteins -- to see whether it interacted with another protein, and antibodies -- which can be made to bind to just about anything.

Microarrays and high throughput sequencing also offer scientists information on the microscopic world, yet both require probes and a complex procedure to perform the experiment. These micro cantilevers offer an unique advantage in its simplicity. Since the publication of the paper, people have proposed microfluidic devices that pump samples into a chamber with many cantilevers for detection, incredibly complex, but completely automated and miniaturized to fit just about anywhere.

We now know a lot about DNA, proteins, and other tiny molecules that makes a big difference in a living organism, but so far we haven't been able to detect these molecules cheaply and reliably to help with medical diagnosis. The devices that we do have are large and clunky. Soon, however, we will have laboratories on a chip that will be able to put all this knowledge to good use for everyone. And it is all thanks to a very tiny diving board.

[1] Fritz, J. et al., “Translating Biomolecular Recognition into Nanomechanics,” Science 288, 316, 2000.