February 8, 2005, Nashville, TN and Menlo Park, CA--A portable micro-optical, microfluidic device that can quickly detect the presence of infectious diseases, including HIV/AIDS and measles, as well as biological agents such as ricin and anthrax, is the object of a university and industry research project. Vanderbilt University's Institute for Integrative Biosystems Research and Education (VIIBRE) and Pria Diagnostics LLC, a privately held California company that specializes in miniaturized medical diagnostics, agreed to collaborate on the device's development at the end of last year.
VIIBRE has spent the last three years developing the ability to measure the metabolism of small groups of cells and studying how they respond to drugs, toxins and pollutants. To do so, the interdisciplinary team has developed two basic technologies: special electrodes that can measure the concentrations of the chemicals that cells consume and excrete in extremely small volumes and the use of fluids flowing through microscopic channels to move and manipulate small numbers of cells reliably. In the process, the group has applied for more than a dozen patents.
Meanwhile, Pria has developed a micro-optical fluorescence-spectroscopy system and used it as the basis for a inexpensive male fertility detector that can be used in the home to measure sperm motility with an accuracy comparable to laboratory analyses.
"Today the treatment for AIDS is very expensive and there is always a question about when to start and stop anti-retroviral therapy," says Pria's chief technology officer Jason Pyle. "We are developing a device that we hope will allow medical professionals and HIV patients to manage their disease in a way that is similar to how diabetes patients can monitor their condition since the introduction of home blood glucose detectors."
The collaboration's goal is to produce its first portable HIV monitor within two years. In addition to such "point-of-care" devices, the two groups are joining forces to develop high-throughput screening systems that can determine the biological activity of large numbers of compounds with extreme rapidity and so could have a major impact on the drug discovery process.
Fifteen years ago, a number of start-up companies were created to make the goal of creating a commercially viable "lab on a chip." But putting microscopic arrays of channels, pumps and valves to move around minute amounts of liquid on silicon chips proved to be considerably more difficult than most of the inventors had expected; the products that these companies have created thus far have been too expensive for the point-of-care diagnostics market.
For its home fertility tester, Pria kept costs down by keeping its system as simple as possible. Instead of trying to squeeze everything onto a single chip, Pria designers started with a desktop diagnostic system and shrank it down into a device about the size of a coffee cup. One of the cost-saving aspects of the design was to keep the fluid-handling components separate from the microelectronics. The resulting device is considerably larger than comparable lab-on-a-chip systems, but it is also much less expensive.
One of the key VIIBRE capabilities, which was developed by a research team headed by Assistant Professor of Chemistry David Cliffel, is the development of a sensor suite capable of simultaneously measuring the concentrations of the key chemicals that cells consume and excrete¿oxygen, glucose and lactic acid¿with enough sensitivity to monitor the health of a few thousand cells confined in a small volume.
Under the leadership of Franz Baudenbacher, assistant professor of biomedical engineering and physics, Vanderbilt researchers have further miniaturized this sensor technology to record rapid changes in the metabolism and signaling of individual cells. To handle such small numbers of cells, they have adapted a method for molding microchannels and valves into a material similar to that used in soft contact lenses. This has given them the capability to capture, manipulate, grow and study single living cells in extraordinarily small containers--volumes that are barely larger than the cells themselves.
Most sensors that have been developed to identify toxic agents are single-purpose. That is, they can identify the presence of a single toxin, or a limited number of closely related toxins. The ability to monitor the health of small groups of cells, however, makes it possible to detect the presence of unknown poisons as long as they affect cell metabolism. Furthermore, by examining the impact that an unknown agent has on different cell types--such as heart, lung, nerve, skin, and so on--this approach also can rapidly provide critical insights into its mode of action.