Volume 1, Issue 6
From Crime Scene Clues To Life On Mars
UC Berkeley chemist Richard Mathies designs high-tech tools for two very different kinds of detectives. On Earth, his group is developing instruments that will be used by forensic scientists to help solve crimes using DNA analysis. A similar system could also aid astrobiologists in hunting for life on Mars without ever stepping foot on the red planet.
Richard Mathies, whose work is funded with both public and private grants, leads a multi-disciplinary research group consisting of physical chemists, biophysical chemists, mechanical engineers, bioengineers, and chemical engineers. He is also the director of the Center for Analytical Biotechnology in the College of Chemistry.
Mathies is the inventor of capillary electrophoresis arrays and energy transfer fluorescent dye labels, common technologies in today's DNA sequencers. Now he's combining those innovations with a microscale plumbing system to build an entire genetics laboratory on a chip.
The chip is the key component in the Mars Organic Analyzer, an instrument that will probe the Red Planet's soil for amino acids, the building blocks of organic life. The Mars Organic Analyzer may travel to the Red Planet as early as 2009 aboard either NASA's Mars Science Laboratory, the European Space Agency's ExoMars mission, or possibly both. Funded by NASA, the system was developed in collaboration with the Jet Propulsion Laboratory at the California Institute of Technology and UC San Diego's Scripps Institution of Oceanography.
"Up until now, chemistry has been done on microliter or milliliter scales," Mathies says. "But there's actually more than enough molecules in a few nanoliters, or billionths of a liter, to do most of today's chemical assays."
Still, the big hurdle in designing a lab-on-a-chip has not been integrating the chemical analyzers in such a small device, but rather controlling the flow of the tiny sample through the system. To that end, Mathies and graduate student Alison Skelley built a multi-layer plastic chip containing a complex system of etched channels. Fabricated with the same processes used to manufacture computer chips, the four-inch diameter device is outfitted with myriad plastic membranes and valves that control the flow of the sample.
"It's essentially a microfluidic microprocessor that runs very complex 'programs,'" Mathies says. "By activating the various pneumatic lines, you can react the samples, process them, mix them, and present them to analyzers all on this one chip."
The valves and pumps on this lab-on-a-chip are moved up and down using a pressure or vacuum source. (courtesy the researcher
On Mars, the chip will run a program that seeks out a specific characteristic of amino acids that Mathies says would be "strong proof of extraterrestrial life."
"The question we asked was if you were sitting on Mars right now, what experiment would you run to determine if a little bit of dirt contains evidence of life?" he says. "The challenge is to come up with a methodology that's not totally Earth-centric without it being so general that you don't learn anything."
The experiment they developed is based on the fact that amino acids are optically active molecules. They can exist as mirror-images, designated either "left-handed" or "right-handed" depending on their stereoisomeric structure. When amino acids are accidentally created in space without any basis in life, they're an equal mix of left and right-handed. So if a sample taken on Mars shows a "chiral excess" of one optical isomer versus the other, the amino acids are biological in origin.
Inside the Mars Organic Analyzer, the capillaries on the chip are filled with one of two kinds of chemical "gloves" that mate with either left- or right-handed amino acids. If a mix of amino acids moves down a capillary filled with left-handed mitts, the left-handed amino acids flow through the system more slowly because they'll slip inside the left-handed chemical gloves along the way. Meanwhile, the right-handed amino acids won't fit inside the gloves at all. The speed and mobility of the amino acids can then be analyzed to determine whether there's a prevalence of one optical isomer over the other. Such a prevalence, Mathies says, would provide evidence of life.
Recently, Mathies and his collaborators successfully demonstrated the system in the arid Panoche Valley near Fresno, California. The next field-test will take place in Chile's Atacama Desert, the driest, most Mars-like environment on our planet.
"If an instrument can't detect life there, it has no business going to Mars," says Mathies, who is also affiliated with the California Institute for Quantitative Biomedical Research (QB3).
While the researchers perfect their system for the rigors of space travel and robotic deployment, Mathies is applying a similar approach to solve a terrestrial problem. He's the recipient of a large National Institute of Justice grant to develop a compact, high-throughput genetic identification system. The goal is to build a machine, based on his lab-on-a-chip, that would allow forensic investigators to quickly analyze DNA evidence from crime scenes and known felons at very low cost.
"Forensic laboratories have hundreds of thousands of DNA samples that have never been analyzed or compared because it's too expensive and slow to run the tests," Mathies says. "With our integrated and automated system, you could place a sample in the machine and very rapidly and cheaply amplify and analyze the markers in our DNA that distinguish us as individuals."
That capability is especially important now, he adds, given the passage in the recent election of California Proposition 69. The proposition mandates that DNA samples be collected "from all felons, and from others arrested for or charged with specified crimes."
Eventually, Mathies says, a portable version of the machine could enable DNA tests right at the crime scene. This on-location testing would eliminate questions of whether a sample was tainted or mislabeled during handling, processing, or analysis, and provide crime scene investigators with immediate information on possible suspects.
"These lab-on-a-chip technologies motivated by such things as Mars exploration and forensic identification have larger applications in all areas of chemical and biochemical analysis, from genetic sequencing to pathogen detection," Mathies says. "This technology will lead to a real paradigm shift in chemistry."