March 15, 2004
Optical glucose sensor developed at UCSC holds
promise for diabetics and intensive care patients
By Tim Stephens
UCSC researchers have developed a novel optical glucose sensor that
could be used to provide continuous monitoring of glucose levels in
diabetics and hospitalized patients.
Bakthan Singaram, professor of chemistry and biochemistry, has been
working on the glucose sensor for four years. Photo:
Recently published studies showed that the sensor detects glucose
under physiological conditions, giving a reversible fluorescent signal
that changes intensity in response to changes in the concentration of
Bakthan Singaram, professor of chemistry and biochemistry, has been
working on the glucose sensor for the past four years, along with visiting
scientist Rich Wessling and several graduate students. The team's latest
results were published in December in the international journal Angewandte
"We are very excited about the prospects for our optical glucose
sensor to be used in a viable device for continuous glucose monitoring,"
Diabetes is a chronic disease that affects the body's ability to produce
or respond to insulin, the hormone that allows glucose to enter the
body's cells and be stored or used for energy. Many diabetics require
insulin injections, and all must carefully monitor and manage their
blood glucose levels. For millions of diabetics, this means drawing
blood several times a day, usually from finger pricks. But glucose levels
can fluctuate widely throughout the day, making it difficult to know
when to do the blood tests for optimal control of glucose levels.
A device that can provide continuous monitoring of blood glucose levels
has been eagerly sought by many research groups for more than a decade,
with limited success. Singaram started working to develop a glucose
sensor at the suggestion of Paul Levin, founder of Palco Labs, a Santa
Cruz company that makes products for diabetics. Palco funded the first
two years of research on the optical glucose sensor, but was eventually
unable to continue its support.
"The support from Palco Labs carried us through the early stages
when we were stumbling around and trying to figure out how to do this,"
Singaram's group is now collaborating with a local company, Glumetrics
LLC, which is developing a line of products based on the optical glucose
Glumetrics was founded by Singaram's colleague Todd Wipke, a professor
of chemistry and biochemistry at UCSC, but not a member of Singaram's
"I thought it was a good project and wanted to see if I could
put together a group of investors and a management team to take it on
and develop the applications," said Wipke, who chairs the Board
of Directors of Glumetrics.
The optical glucose sensor consists of a fluorescent chemical complex
immobilized in a "thin-film hydrogel." The hydrogel, a biocompatible
polymer similar to that used to make soft contact lenses, is permeable
to glucose. The sensing system has two components: a fluorescent dye
and a "quencher" that is responsive to glucose.
In the absence of glucose, the quencher binds to the dye and prevents
fluorescence, while the interaction of glucose with the quencher leads
to dissociation of the complex and an increase in fluorescence.
Singaram's team tested the sensor by mounting it in a flow cell and
circulating a solution with varying concentrations of glucose through
the cell. The results showed that the system functions as a continuous
glucose monitor capable of operating under physiological conditions.
The sensor shows outstanding glucose response over the full range of
glucose levels that might occur in a diabetic, Singaram said.
"This is the first system to show reversible optical sensing of
glucose with a thin-film hydrogel. We tested the sensor under conditions
that are as close as possible to the physiological conditions under
which a continuous glucose monitor would have to operate," he said.
In addition to Singaram and Wessling, the authors of the recent paper
include Jeff Suri, now a postdoctoral researcher at Scripps Research
Institute, and graduate students David Cordes and Frank Cappuccio.
The researchers have also applied the hydrogel to the end of an optical
fiber, enabling the signal from the glucose sensor to be transmitted
through the optical fiber.
The application of this technology that is closest to yielding a marketable
product is a catheter device, called GluCath, for monitoring blood glucose
levels in hospitalized patients, Wipke said. Glucose levels must be
regularly monitored in patients in intensive care units and others being
fed intravenously with glucose drips. Research has shown that tight
control of blood glucose levels can significantly reduce mortality of
ICU patients, but the only way to do this currently is by taking frequent
blood samples for analysis, which is painful for the patient and expensive
for the hospital.
"The GluCath catheter is inserted into a blood vessel and gives
a continuous reading, and it can sound an alarm if the glucose level
goes too high or too low. GluCath should reduce pain, reduce costs,
and reduce deaths," Wipke said.
An implantable glucose monitor for diabetics is the next product in
the pipeline, he said. Other companies have used different technologies
to develop continuous glucose monitors for diabetics, but currently
there is nothing on the market that is effective enough to be used in
place of the standard blood tests.
"Every conceivable method of detection has been explored, with
very limited success, even after years of intensive research and development,"
In Singaram's sensing system, glucose modulates the fluorescent signal
by binding reversibly to a boronic acid component attached to the quencher
Singaram's team designed the fluorescent dye (an anionic pyranine sulfonamide
monomer) and the quencher (benzyl viologen with a boronic acid functional
group attached). The fluorescence is stimulated by light from an LED
and can be easily measured because it occurs at a distinct wavelength
from the LED light.
"This technology satisfies all of the requirements for a working
optical glucose sensor--it operates in the physiological pH range in
blood or water, it can be stimulated by LED light, the response time
is very fast, and the compounds are stable and don't degrade over time,"
One of the biggest challenges for an implantable device is the body's
tendency to encapsulate any foreign substance. Encapsulation could affect
the ability of glucose to reach the sensor. If this problem can be overcome,
however, an implantable glucose monitor would provide the crucial "missing
link" in the development of an artificial pancreas.
Insulin pumps are already available that diabetics can use to deliver
their insulin doses instead of giving themselves injections. In concept,
at least, an artificial pancreas is simply a continuous glucose monitor
connected to an insulin pump that is programmed to deliver appropriate
doses of insulin to maintain healthy blood glucose levels.
"That is the holy grail that many people have been pursuing. It
won't cure diabetes, but it would make management of the disease a lot
easier," Singaram said.
Singaram's research on the glucose sensor is funded by UC's BioStar
Discovery Grant program in collaboration with Glumetrics.
"It is a great example of successful technology transfer from
the university to a company that can commercialize on this," Wipke
said. "The collaboration has enabled the research to flourish and
supported graduate student education at the university, and it has enabled
the start of a new company in the Santa Cruz area."
Glumetrics is based at the UC Monterey Bay Education, Science, and
Technology (MBEST) Center in Marina, where UCSC is helping to establish
a community of high-technology businesses through strategic partnerships
with the education and research institutions in the Monterey Bay Area.
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