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A digitally magnified image shows DNA density by varying brightness. There are anywhere from 200 to 300 silica microspheres in each dot.  (Source: Lawrence Berkeley National Laboratory)
Detecting specific genes and pathogens in DNA and RNA is typically quite expensive and time consuming. But that's about to change.

Analyzing DNA and RNA -- examining it for things like certain genes, mutations and pathogens -- has become somewhat more commonplace in the past few years. One problem is that it requires equipment and expertise that few of even the best medical centers posses. A group at the Department of Energy's Lawrence Berkeley Laboratory may change that with their new DNA microarray analysis technique.

One area of great interest to medical researchers is personalized medicine. Each person's body reacts differently to diseases, infections, and viruses and the same can be said for medicines and other treatments. But knowing a person’s genetic makeup by analyzing their DNA can give treatment specialists insight on what drug or treatment may work best for a certain individual.

Unfortunately, though the technology exists and works, as mentioned previously, it presently lies in the hands of a few advanced institutions worldwide. Fluorescence detection is the most utilized method of DNA analytics, but it takes specialized equipment and high power devices to implement. Not to mention time for an analysis to take place.

The Berkeley team's method uses none of these things, instead relying on a relatively simple approach based on electrostatics. It requires no chemicals markers, no high energy excitation, and best of all, no microscopes. They boast that the imaging can be done with nothing more complex than a cell phone camera if necessary.

They start off with a standard hybridized DNA microarray, set on a positively charged base. DNA hybridization is a fairly standard technique in which complementary single strands of DNA combine to form a double-stranded hybrid. Some DNA will not find complementary strands and will remain single. Then, after the array is placed in a well chamber, a solution of negatively-charged silica microspheres is disbursed over the surface of the microarray using gravitational sedimentation. As the base is positively charged and the microspheres are negatively charged, the silica spheres will adhere to it in most places.

The trick is that DNA, hybridized or not, is also negatively charged, with hybridized segments more so than single strands. This negative charge causes the silica beads to be repelled and hover above the spots that contain the DNA. The beads hover at a state of equilibrium based on the repulsion of the negatively charged DNA samples and the force of gravity. This causes a slightly frosted look in areas where samples are present, with hybridized samples standing out more due to the distance of the beads from the surface. Images of the areas can be analyzed for known genes, mutations or pathogens based on their charge-density and Brownian motion.

While the technique is much less expensive and complex than fluorescence detection, the group says they still have room for improvement and intend to move in that direction. They will be further testing their method on higher density arrays and experimenting with the absolute limit of resolution available to the method. Ultimately, it could be used to examine millions of strands of DNA simultaneously.

This kind of technology could serve to put genetic profiling for medical purposes like personalized medicine into the hands of doctors in hospitals worldwide. Rather than relying on a standard treatment, ushering in an era of personalized medicine may save hundreds of thousands of lives, or more, world-wide where these blanket treatments are sometimes ineffective. This type of analytics is looking very promising for the future of medicine, and groups like Berkeley's are making it more and more possible every day.



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RE: Interesting, but....
By geddarkstorm on 7/2/2008 1:12:40 PM , Rating: 2
There's a major flaw with this system though--sensitivity. Since hybridized or not, the DNA/RNA will repel the silicon beads, you end up having to subjectively score whether an intensity means you had hybridization or not, or more DNA/RNA bound to the chip there, or the beads didn't distribute right there, or what not. Man, the error rate on this will be huge if they don't think of something. There's already enough subjective trouble with fluorescent detection in microarrays as it is.


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