Download
a high-resolution image of the type of microfluidic cells that will be
used in the VIIBRE/Pria project (Credit: Vanderbilt University / Neil
Brake).
Download a high-resolution image of John Wikswo (Credit: Vanderbilt University / Daniel Dubois).
Download a high-resolution image of Jason Pyle (Credit: Pria).
NASHVILLE, Tenn. ñ A portable device similar to today‘s home pregnancy
tests 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 new joint university-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 development before the
holidays.
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 12
patents.
Meanwhile, Pria has developed a micro-optical fluorescence spectroscopy
system and used it as the basis for an inexpensive male fertility
detector that can be used in the home to measure sperm motility with an
accuracy comparable to laboratory analyses.
“I‘m thrilled at how well the VIIBRE and PRIA technologies mesh,” says
John P. Wikswo, professor of biomedical engineering, physiology and
physics at Vanderbilt and director of VIIBRE. “We are already making
rapid progress on prototyping portable instruments for clinical
diagnosis and biodefense.”
“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, Wikswo
and Pyle 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 “lab-on-a-chip” a reality. However, 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, and the products
that these companies have created thus far have been too expensive for
the point-of-care diagnostics market.
For their home fertility tester, Pria kept costs down by keeping their
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. “That‘s one of the
appealing features about Pria‘s approach,” says Wikswo. “They keep
their microfluidics and microelectronics as simple as possible.”
“Pria‘s first product focused on fertility,” says VIIBRE project
engineer David Schaffer. “With our capabilities, they can begin
applying their technology to a goldmine of different applications.”
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 ñ
oxygen, glucose and lactic acid ñ with enough sensitivity to monitor
the health of a few thousand cells confined in a small volume. (For
more details, see “New device can help defend against novel biological
agents” at http://exploration.vanderbilt.edu/news/news_microphys.htm.)
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 micro-channels
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 ñ 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 ñ such as heart, lung, nerve, skin, etc. ñ
this approach also can rapidly provide critical insights into its mode
of action.
“Pria has an outstanding understanding of the clinical and diagnostic
device market and the ability to rapidly prototype optical and
microfluidics devices,” says Wikswo, “but it is difficult for the
company to survey large numbers of possible applications. Yet, here at
the university, searching for new applications is one of the things
that we do best.”
The origin of the collaboration is an example of the power of
serendipity. It started when Schaffer, a VIIBRE student who stayed on
at the institute as a project engineer after he graduated, was browsing
the Web looking for a permanent job. Although looking for a local
position, he inadvertently opened a Web page with listings from
California. He came across an interesting opening at Pria, located in
Menlo Park, and decided to apply. Although Pria decided that he wasn‘t
the right person for the job, in their correspondence Pyle expressed
potential interest in collaborating with VIIBRE. Schaffer passed the
information along to Wikswo, who gave Pyle a call. That was in early
September. By mid-November a joint research agreement for $120,000 for
the first year was completed and signed.
For more news about Vanderbilt research, visit Exploration, Vanderbilt‘s online research magazine, at www.exploration.vanderbilt.edu.
Media contact: David F. Salisbury, (615) 343-6803
david.salisbury@vanderbilt.edu