The dream of personalized medicine - in which diagnostics, risk predictions and treatment decisions are based on a patient's genetic profile - may be on the verge of being expanded beyond the wealthiest of nations with state-of-the-art clinics.
A team of researchers with the U.S. Department of Energy's Lawrence Berkeley National Laboratory (Berkeley Lab) has invented a technique in which DNA or RNA assays - the key to genetic profiling and disease detection - can be read and evaluated without the need of elaborate chemical labeling or sophisticated instrumentation. Based on electrostatic repulsion - in which objects with the same electrical charge repel one another - the technique is relatively simple and inexpensive to implement, and can be carried out in a matter of minutes.
"One of the most amazing things about our electrostatic detection method is that it requires nothing more than the naked eye to read out results that currently require chemical labeling and confocal laser scanners," said Jay Groves, a chemist with joint appointments at Berkeley Lab's Physical Biosciences Division and the Chemistry Department of the University of California (UC) at Berkeley, who led this research. "We believe this technique could revolutionize the use of DNA microarrays for both research and diagnostics."
Groves, who is also a Howard Hughes Medical Institute (HHMI) investigator, and members of his research group Nathan Clack and Khalid Salaita, have published a paper on their technique in the journal Nature Biotechnology, which is now available online. The paper is entitled "Electrostatic readout of DNA microarrays with charged microspheres."
In their paper, Groves, Clack, and Salaita describe how dispersing a fluid containing thousands of electrically-charged microscopic beads or spheres made of silica (glass) across the surface of a DNA microarray and then observing the Brownian motion of the spheres provides measurements of the electrical charges of the DNA molecules. These measurements can in turn be used to interrogate millions of DNA sequences at a time. What's more, these measurements can be observed and recorded with a simple hand-held imaging device - even a cell phone camera will do.
"The assumption has been that no detection technique could be more sensitive than fluorescent labeling, but this is completely untrue, as our results have plainly demonstrated," said Groves. "We've shown that changes in surface charge density as a result of specific DNA hybridization can be detected and quantified with 50-picometer sensitivity, single base-pair mismatch selectivity, and in the presence of complex backgrounds. Furthermore, our electrostatic detection technique should render DNA and RNA microarrays sufficiently cost effective for broad world-health applications, as well as research."
Your susceptibility to a given disease and how your body will respond to drugs or other interventions is unique to your genetic makeup. Under a personalized medicine plan, treatment effectiveness is maximized and risks are minimized by tailoring disease treatments specifically to you. This requires the precise diagnostic tests and targeted therapies that can stem from assays using a DNA microarray - a thumbnail-sized substrate containing thousands of microscopic spots of oligonucleotides (stretches of DNA about 20 base pairs in length) laid out in a grid.
Often referred to as "gene chips," DNA microarray assays and their RNA counterparts have become one of the most powerful tools for gene-expression profiling, the identification of mutations, and the detection of multiple pathogens in patients afflicted either by multiple diseases or drug-resistant strains of diseases. Aside from their potential future role in personalized medicine, the widespread use of DNA microarray assay devices could have an immediate and profound impact on the treatment of diseases today. For example, according to a report two years ago from the Global Health Diagnostics Forum, 400,000 lives could be saved each year from death by tuberculosis through the use of DNA microarray assays rather than the standard TB diagnostic test, which is known to miss nearly half of all cases.
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