I grew up on a steady diet of Star Trek. The portrayal of the modern medical clinic aboard the Enterprise was of particular interest to me, with such wonders as instant inoculations and vaccines, and biosensors that could provide readouts following a mere touch to the skin. Of course, this was pure science fiction, but in some ways, we are moving toward these fanciful ideas.
An example of this march to the future can be found in the collaboration between Vanderbilt University’s Institute for Integrative Biosystems Research and Education (VIIBRE) and Pria Diagnostics, a privately held California company that specializes in miniaturized medical diagnostics. The agreement, announced late last year, aims to develop a portable device similar to today’s home pregnancy tests that could quickly detect the presence of infectious diseases, including HIV and measles, as well as biological agents such as ricin and anthrax.
VIIBRE has developed special electrodes that have been customized to measure the concentrations of the metabolites that cells consume and excrete in extremely small volumes. It has also developed microfluidic devices that enable the electrodes to move and manipulate small numbers of cells reliably. Meanwhile, Pria has developed a micro-optical fluorescence spectroscopy system and used it as the basis for a portable male fertility detector that measures sperm motility with accuracy comparable to laboratory analyses. The device includes an optical MEMS component together with an LED to read fluorescent chemicals that bind to a sample of sperm. The groups plan to work together to prototype portable instruments for clinical diagnosis and biodefense.
Treating AIDS patients is expensive, and healthcare professionals have the problem of deciding when to start and stop anti-retroviral therapy. According to CTO Jason Pyle, Pria is developing a device that it hopes will allow medical professionals and HIV patients to manage the disease in a way similar to how diabetes patients monitor their condition with home blood-glucose detectors. A goal of the collaboration is to produce the first portable HIV monitor within two years.
A key VIIBRE technology is an electrode-based sensor capable of simultaneously measuring the concentrations of key chemicals and metabolites that cells consume and excrete — oxygen, glucose, and lactic acid — with sufficient sensitivity to monitor the health of a few thousand cells. Called a four-channel microphysiometer, the device is a modification of Molecular Devices’ decade-old Cytosensor, which was designed to measure changes in acidity in a small chamber holding 100,000 to 1,000,000 cultured cells. The VIIBRE group added three additional sensors, allowing the device to simultaneously chart variations in the concentrations of oxygen, glucose, and lactic acid, in addition to pH, in real time. Described in an article last year in Analytical Chemistry (76, 519-27; 2004), the added capability is important because monitoring variations in these four parameters allow researchers to quickly assess the impact that exposure to different chemicals has on the metabolic activity and health of small groups of cells.
Vanderbilt researchers have recently further miniaturized the customized sensors to record rapid changes in the metabolism and signaling of individual cells. To handle such small numbers of cells, they adapted a method for molding microchannels and valves from a plastic similar to that used in soft contact lenses. This has given them the capability to capture, manipulate, grow, and study single living cells in volumes that are barely larger than the cells themselves.
While most sensors identify a single toxic agent or group of agents, the ability to monitor the health of small groups of cells makes it possible to detect the presence of unknown poisons as long as they affect cell metabolism. Furthermore, by examining the impact
an unknown agent has on different cell types the approach may provide insights into its mode of toxicity. The device may also find application as a high-throughput screening system to determine the biological activity of large numbers of compounds.
Clearly not science fiction, but devices that might have come in handy while exploring new worlds!
Robert M. Frederickson is a science writer based in Seattle. E-mail: rfreder@yahoo.com.