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In the first-generation lab-on-a-chip device, invented at ORNL 10 years ago, researchers separated chemicals inside channels etched into glass while under the influence of an electric field. In ORNL's latest lab-on-a-chip device, separation occurs on the surface of a silicon chip under the influence of laser light.
The invention, the "Photo-Molecular Comb," has been
licensed exclusively to Protein Discovery, Inc., and should be
commercially available in 2005 for select researchers working
in drug discovery.
The inventor of the Photo-Molecular Comb is Thomas Thundat, leader of the Nanoscale Science and Devices Group in ORNL's Life Sciences Division. For his invention Thundat was selected as ORNL's Inventor of the Year in 2003 and honored by the Battelle Memorial Institute in 2004. He was recognized "for the development of a new paradigm for achieving biomolecular transport and separation using optical manipulation of surface charge." "The Photo-Molecular Comb can be used to rapidly concentrate, separate, and analyze molecules," Thundat says. "The device has the advantages of high resolution, low cost, small size, and low power requirements." A 9-volt battery can power the device, which includes a laser diode. When light from the laser diode shines on one type of semiconductor coated with a gel and put under a positive electric potential, negatively charged electrons from the chip rush toward the spot on the gel surface where the light falls. With a different coating on the semiconductor and negative electric potential, positively charged holes go to the spot of illumination. Negatively charged molecules, such as DNA, placed in the gel are attracted to the holes, while positively charged proteins are attracted to the electrons. The Photo-Molecular Comb consists of a gel sandwiched between a silicon semiconductor chip and a piece of conducting glass. In one application, proteins scattered throughout the gel are attracted to the concentrated electrons so they accumulate where the light is parked. The "photo-accumulated" proteins can be visualized by scanning the laser light in a parallel-line, or raster, pattern to create a photocurrent map of the surface. "We are reducing the diameter of the light spot from 30 microns to 3 microns," Thundat says. "Then we can further concentrate molecules of one type for analysis. Also, we can see how much two different molecules, such as a disease protein and potential drug, interact at the illuminated spot by measuring changes in the photocurrent level." The device can also separate proteins in a gel containing a sieving medium. When the light is scanned, the proteins follow the light, like hair following a comb. The smaller proteins flow farther and faster than the larger, heavier proteins in the sieving medium, resulting in separation. Protein Discovery expects that its first tier of customers will be academic and government laboratory research teams. The next tier, according to Witkowski, will be pharmaceutical firms involved in drug discovery. The third tier will be diagnostics organizations working in clinical proteomics to discover unique protein fingerprints for disease states. Protein Discovery has received its first round of venture capital funding from MB Venture Partners, has assembled an outstanding scientific advisory board, and has hired a new vice president of research and development. He is Dean Hafeman, a co-founder of Molecular Devices Corporation in California. Contributors to the development of the device are Tom Ferrell of Thundat's group and Gil Brown of ORNL's Chemical Sciences Division. Several molecular biologists employed by Protein Discovery collaborate with Thundat under a cooperative research and development agreement, funded by the National Cancer Institute, the National Science Foundation, and the company's equity capital. Among biomedical lab-on-achip devices, the Photo-Molecular Comb may prove to be a microscopic invention with enormous financial potential.
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