January 08, 2007
Chip Measures Protein Binding Energies In Parallel

To accelerate the pace of biological research we need automation and miniaturization to drive down costs. The development of miniature silicon devices that can measure biological systems with a high degree of parallelism is going to drive down costs by orders of magnitude just as happened in the computer industry. The trend toward labs on a chip continues to accelerate. In a recent example of this trend Stanford microfluidics researcher Stephen Quake and collaborator Sebastian Maerkl have developed a silicon chip that can measure the affinity of transcript factor proteins (which regulate gene expression) for sections of DNA with simultaneous measurements of 2400 pairs of proteins and DNA fragments.

To understand complex biological systems and predict their behavior under particular circumstances, it is essential to characterize molecular interactions in a quantitative way, Quake said. Binding energy-the energy with which one protein bind to another or to DNA-is one important quantitative measurement researchers would like to know. But these interactions are highly transient and often involve extremely low binding affinities, so they are difficult to measure on a large scale. To overcome this hurdle, Quake and Maerkl set out to develop a microlaboratory that could trap a type of protein known as a transcription factor. Once the transcription factor was trapped, the scientists hoped to measure the binding energy of the transcription factor bound to specific DNA sequences.

But simply measuring the binding energy between a transcription factor and a single DNA sequence is not enough, Quake said. He said it would be more meaningful to know the energy involved in a transcription factor binding to many different DNA sequences. This would give researchers a more complete picture of the “DNA binding energy landscape” of each transcription factor.

To determine the binding energy landscape, Quake and Maerkl's microlaboratory needed to conduct thousands of binding-energy experiments at once. The apparatus they created, which they called mechanically induced trapping of molecular interactions (MITOMI), consists of 2,400 individual reaction chambers, each controlled by two valves and including a button membrane. Each of the chambers is less than a nanoliter in volume. That's one-billionth of a liter—enough to hold a snippet of human hair only as long as the hair's diameter. The MITOMI apparatus fits over a 2,400-unit DNA microarray, or gene chip, onto which the researchers can dab minute amounts of DNA sequences. Each spot of DNA is then enclosed in its own reaction chamber.

Quake wants to use this approach to map all the protein-protein binding energies of a single organism. The ability to use semiconductor industry manufacturing processes to cheaply mass produce silicon chips will make this possible.

The ability to conduct many measurements cheaply and in parallel will eventually enable the use of simulations to carry out much biological research. The measurements of biological phenomena made by silicon chips will serve as useful data to feed into computer simulations.

According to Quake, MITOMI brings scientists closer to an important goal. “To test theories of systems biology, we should now be able to predict biology without making any measurements on the organism itself,” he said.

Technologies from the computer industry are accelerating the rate of advance of biomedical science. This trend is why I expect the defeat of almost all diseases in the lifetimes of some people who are already alive. Technologies to achieve full body rejuvenation will even stop the process of aging.

Share |      Randall Parker, 2007 January 08 06:26 PM  Biotech Advance Rates

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