Lab on a Chip for Oral Cancer Shows Promise
Finding out whether that unusual sore in your mouth is cancerous
should become a lot faster and easier in the years ahead. Scientists
supported by the National Institute of Dental and Craniofacial
Research (NIDCR), part of the National Institutes of Health, have
engineered the first fully automated, all-in-one test, or lab on
a chip, that can be programmed to probe cells brushed from the
mouth for a common sign of oral cancer.
About half the size of a toaster, the portable device yields results
in just under 10 minutes, or well within the duration of a routine
visit to a dentist or doctor. Currently, patients must undergo
an often painful tissue biopsy and usually wait three days to a
week for the lab results. “What’s exciting is the speed and efficiency
that this test will bring to the diagnostic process,” said John
McDevitt, Ph.D., a scientist at the University of Texas at Austin
and the senior author on the paper, published in the August issue
of the journal Lab on a Chip. “No longer will patients need to
endure referrals, long waits for test results, and scheduling follow
up consultations. Patients will get immediate results and feedback
from their dentist or doctor on how best to proceed.”
McDevitt said his group’s proof of principle study showed that
their test could accurately measure levels of epidermal growth
factor receptor, or EGFR, on three distinct types of oral cancer
cells. This protein, which is normally displayed on the surface
of our cells, tends to be overproduced in oral tumor cells and
serves as a measurable marker of oral cancer.
His group’s next step is to program the device to read not just
EGFR levels but those of other proteins and genes that, when altered,
are indicative of a developing oral tumor. This work already is
well under way, and the group anticipates evaluating their test
in the clinic with patients in the foreseeable future. “It could
take several months to more than a year before we make the transition,” said
McDevitt. “But the diagnostic platform has been built, and it’s
just a matter of fine tuning the components that already are in
place.”
According to McDevitt, the lab on a chip evolved from a conversation
that he had a few years ago with Dr. Spencer Redding of the University
of Texas Health Sciences Center in San Antonio about the difficulties
of diagnosing oral cancer. Redding explained that dentists routinely
face the dilemma of whether or not to refer patients to an oral
surgeon for biopsies of suspicious sores, particularly possible
recurrences of a previously diagnosed oral cancer. On the one hand,
early detection is a key to fighting cancer and saving lives and,
on the other, if the pathology report comes back negative, dentists
risk upsetting their patients.
McDevitt was uniquely qualified to consider the problem. He studied
in his laboratory functional molecular assemblies, or manipulating
individual molecules to assemble miniaturized electronic or sensor
components. This area of research has contributed greatly toward
developing nano scale devices and popularizing the new discipline
of nanotechnology.
The McDevitt laboratory already had an excellent track record
of assembling novel, easy-to-use sensing devices that involve microfluidics,
the science of precisely controlling micro or nano volumes of fluid.
Among their accomplishments were a novel, miniaturized sensor to
detect anthrax spores for the Nation’s biodefense efforts and thereafter
a test for HIV infection and immune function in resource poor African
nations. The laboratory also was working in the mouth, having received
an NIDCR research grant to develop similar tests that use saliva,
rather than blood, as a diagnostic fluid.
Combining these areas of research expertise, the McDevitt laboratory
developed a test for oral cancer that begins with brushing cells
from a suspicious lesion, suspending them in fluid, and loading
roughly a drop of the mixture into their device. When activated,
the device conveys the fluid down a tiny, microfluidic channel
to a chamber with a porous membrane. “The cells stick to the membrane
floor like starfish in a net,” said Shannon Weigum, a member of
the McDevitt laboratory and lead author on the paper. “The floor
has little exit holes that drain the fluid out of the chamber and
allow us to pump in a cocktail of, in this case, antibodies that
are tagged with a fluorescent dye and that are programmed to seek
out and attach to the EGFR displayed on the cells.”
“The chamber creates a nice, miniaturized platform with a digital
camera interface to display the fluorescent tags for analysis on
a computer screen,” she continued. “We can then read the level
of fluorescence and determine how much EGFR is present on the cell
surface. It automates a process that is done now by a pathologist.
Think of the test as pathology on a chip.”
In their initial experiments, the all-in-one test detected significantly
higher levels of EGFR in three known oral cancer cell lines compared
to normal cells, which would have been expected. This indicated
that the lab on a chip had excellent specificity for its protein
target. The scientists also found that their results correlated
well with those using flow cytometry, the current gold-standard
analytical technique to quantify protein expression.
The scientists reported that their lab-on-a-chip protocol took
about nine minutes to complete, from sample collection to digital
display. For flow cytometry, the protocol took two hours and five
minutes. “We are doing our immune function test in eight minutes,
and that includes the software manipulation and collecting the
sample,” said McDevitt. “I feel comfortable saying that, with further
manipulations, the oral cancer test ultimately will be completed
somewhere between five and ten minutes. We have developed tests
that can be performed in thirty seconds, but there is some loss
in accuracy when you do things in an ultra fast manner.”
The Food and Drug Administration approved the EGFR-targeted monoclonal
antibody called cetuximab in March 2006 to treat oral squamous
cell carcinoma, the most common type of oral cancer. This marked
the first new drug approved for this cancer in 45 years. But challenges
remain to identify patients who might benefit from this therapy.
With further development and clinical validation, the oral cancer
lab on a chip could one day fill this diagnostic niche.
The National Institute of Dental and Craniofacial Research (NIDCR)
is the Nation’s leading funder of research on oral, dental, and
craniofacial health.
The National Institutes of Health (NIH) — The Nation's
Medical Research Agency — includes 27 Institutes and
Centers and is a component of the U.S. Department of Health and
Human Services. It is the primary federal agency for conducting
and supporting basic, clinical and translational medical research,
and it investigates the causes, treatments, and cures for both
common and rare diseases. For more information about NIH and
its programs, visit www.nih.gov.
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