Dr. Stuart Farquharson has employed his talents for invention and enterpreneurship in detecting trace chemicals. As President of Real-Time Analyzers, a Connecticut company which is funded in part by NASA's Small Business program, he has turned his interest to the problem of looking for minute DNA quantities using miniaturized lab techniques.

When Farquharson talks about small samples, his typical unit of measurement is a multiple of nanoliters, or about one-millionth of a teaspoon. The goal is for a total instrument package that might evolve into a lab about the size of a credit card.

Astrobiology Magazine had the opportunity to talk with Stu Farquharson about how to measure biosignatures using his proposed lab-on-a-chip. Farquharson graduated from the University of Texas in 1981 with a Ph.D. in Physical Chemistry. He has published over 50 papers and holds 5 patents in the field of chemical analysis. Astrobiology Magazine (AM): What is the basic idea behind an astrobiology-related 'lab on a chip'? Stu Farquharson (SF): The idea is to measure biosignatures of present or past life in extraterrestrial settings. The lab-on-a-chip will provide the means to extract these signatures from soil or water samples. AM: Would the measurement be elemental, chemical or biological analysis? SF: The signatures of life we are analyzing for are biochemicals, such as the amino or nucleic acids, as well as peptides and nucleotides. These biochemicals could be fragments of proteins or DNA representing the remnants of life, as might be found in martian soil, or building blocks of life representing formative life, as might be found in Europa's ice covered ocean. AM: How will your lab-on-a-chip perform these measurements? SF: In the case of measurements on Mars, a drop of water would be added to a collected soil sample, an actuator would then draw approximately 100 nanoliters of this solution into our lab-on-a-chip.

Then it would first pass through a filter to remove particulate matter, then pass through a capillary containing a material to separate the amino acids from other organics, if they are present, and then deliver the pristine amino acids to our surface-enhanced Raman-active sol-gel, where it would be measured by a Raman spectrometer.

The sol-gels serve two purposes, they immobilize the silver nanoparticles that enhance Raman scattering, and they are functionalized to separate the amino acids as they pass through, to simplify and enhance identification.

AM: Several labs are developing Raman spectrometers for future Mars missions, how is surface-enhanced Raman spectroscopy different? SF: Those missions will use Raman spectroscopy to measure mineral types, and Raman spectroscopy is appropriate as a non-contact, optical technique, since it measures the energies of various molecular vibrations making it very powerful in identifying chemicals.

However, the inelastic collision between a photon and a molecule that produces a Raman photon is a very inefficient process, and only one Raman photon is produced for every one billion photons directed at the molecule of interest. This is sufficient to measure pure substances, such as minerals, but not part-per-billion concentrations of biochemicals in soil.

To overcome this limitation we are using surface-enhanced Raman spectroscopy, which employs metal nanoparticles capable of supporting surface plasmons that interact with nearby molecules to increase the Raman scattering efficiency by approximately one million times. AM: Are there any constraints to sample size or operating environments? SF: There isn't much of a constraint to sample size, 1 microliter should be plenty for analysis. However, the chip needs to be warm enough for water to flow. Since our chip will be incorporated into an overall robotic science laboratory, it will use existing soil collection systems and the Raman system proposed for Mars missions.

Fortunately, the operating requirements for these components will be addressed by others. Similarly, probes sent into Europa's oceans will likely provide sufficient heat to ensure sample flow within our chip. AM: Do you have an environment that you imagine might benchmark the testing? SF: I am aware of tests conducted in Chile's Atacama Desert, as a source of Mars-like soil, as well as planned tests in Lake Vostok, Antarctica to represent Europa. As we further develop our analyzer and method, these are certainly appropriate places to benchmark performance.

However, the recent evidence obtained by Opportunity that the Martian soil may be acidic suggests that this must also be considered. Since this does change the charge on the amino acids, pH dependence has been included in our studies.

We also plan to test the space-worthiness of our analyzer. This will include temperature cycling, high g-forces, micro-gravity, and radiation resistance through pre- and post-launch measurements. AM: As you may be aware, capillary electrophoresis has successfully been used to detect amino acids in the subsurface soil of the Atacama Desert, and this technology is also being developed for Mars Missions. How is your technology different? SF: The work being done by Professor Richard Mathies and his team is extraordinary. The primary difference between their technology and ours is sensitivity and selectivity.

They have achieved parts-per-trillion detection, while we have only achieved sub parts-per-million detection. The sensitivity of our surface-enhanced Raman active sol-gels continually improves, and sub part-per-billion detection is achievable.

The capillary electrophoresis measurement attaches a fluorescent molecule to the amino acids, so that they can be detected. Since it is uncertain as to what biochemicals may be present in extraterrestrial settings, the detection of a fluorescent signal may not necessarily identify the biochemical, amino acid or otherwise.

We are building a spectral library of biochemicals, including many amino acids beyond the 20 used by life on earth. This will allow us to identify any of a number of biochemicals that signify life.

Even if the measured spectrum does not match one in our library, Raman spectroscopy has the ability to identify unknown chemicals based on the energies of the vibrational bands measured.

But just like an analytical lab, the more techniques used to characterize an unknown chemical, the greater the confidence there will be that the identification is correct.

We believe capillary electrophoresis, surface-enhanced Raman spectroscopy, mass spectrometry, and any other techniques should be used if cost-effective. In that regard, our device will only weigh two to three hundred grams, or less than a pound, and require 10-20 milliwatts to deliver each 100 nL of sample. AM: What are the plans for future development? SF: We are only in the first phase of this small business innovative research program, and we have considerable work ahead of us. We have measured the 20 basic amino acids, the 5 nucleic acids, and we have used the sol-gels to separate some test mixtures of these chemicals.

We still have to build our spectral library, and most importantly, improve sensitivity. In addition, we still have to develop the lab-on-a-chip.

Credit card prototypes using sol-gel filled capillary columns, have been made, but using one hundred micron channels and incorporating valves is still ahead. Fortunately, JPL has this capability and we plan to enlist their help.

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