| A CIPI team is developing an instrument
to prevent the collateral damage that frequently destroys healthy
retinal tissue during treatment of the leading cause of blindness.
| Biophotonics: New light on
medical applications
Photons are subatomic particles of light. Like atoms,
they have energy and momentum; unlike atoms, however,
they have no mass or electric charge.
Photonics is the technology of light: how to produce
it, detect it, manipulate it, amplify it, and analyze
it. Photons have properties such as colour, polarization,
and directionality that offer us invaluable opportunities
for probing and energizing materials with extraordinary
finesse. The technical world is just beginning to tap
into this complexity.
Biophotonics – the application of photonic science
and technology to life sciences – is rapidly emerging
as a new field. Already it ranges from medical applications
such as optical diagnostics, light-based therapies,
and minimally invasive patient monitoring to advanced
tools for biology, biotechnology, environmental monitoring,
and detecting pathogens for such applications as fighting
bioterrorism.
Researchers in the Canadian Institute for Photonic
Innovations (CIPI) are focusing much of their efforts
on biotechnology, engineering, and life sciences applications
that complement other significant Canadian photonics
organizations, such as Photonics Research Ontario, the
Canadian Light Source in Saskatchewan, and the Advanced
Laser Light Source in Quebec.
In addition to the Two-Photon Excitation Photodynamic
Therapy project described here, CIPI researchers at
universities and institutions throughout Canada are
collaborating with researchers in other biological or
biomedical sciences, as well as with interested pharmaceutical
and technological companies on several other major biophotonics
projects. These include:
- Projects with the potential to provide breakthrough
technologies for analyzing single molecules within
a cell – relevant to many biotechnology applications,
including drug discovery.
- Micro-imaging projects with specific applications
for neuroscience and projects that will exploit the
properties of light to image genetic micro arrays
and molecular pathology tissues.
CIPI's biophotonics work involves collaborations not
only within the Canadian science community, but with
photonics researchers around the world. For example,
CIPI researchers have established linkages with the
National Science Foundation's new Center for Biophotonics
Science and Technology at the University of California
at Davis, the Laser Laboratorium in Goettingen, Germany,
the Israel Institute of Technology, and Cornell University.
International industrial linkages include collaboration
with Hamburg, Germany's Evotech, which will support
development of single-cell handling systems; the American
firm Hysitron, for collaboration on probes of atomic
forces; the American firm Rasiris, which will provide
new light-sensitive test drugs for CIPI's two-photon
photodynamic therapy project; and anticipated support
from the U.S. National Institutes of Health for the
clinical-trials phase of the two-photon photodynamic
therapy project.
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Age-related macular degeneration – the leading cause of blindness
in most developed countries – occurs when tissue and blood
vessels in the centre of the retina grow too rapidly.
The current treatment of choice is photodynamic therapy (PDT).
Patients are given a light-sensitive drug that is taken up only
by the damaged tissue. Therapists then selectively irradiate the
area with light that energizes the drug to destroy the unhealthy
tissue.
Although this treatment halts the disease's progress, explains
CIPI team leader Dr. David Cramb, it seldom allows for recovery
of lost sight. "The inability to restore sight," says
Dr. Cramb, "may be due to collateral damage to surrounding
healthy tissue." But such damage could be minimized, even eliminated,
he says, if therapists could focus the treatment more precisely.
By "more precisely," the University of Calgary professor
is talking about focusing on areas as minute as an individual cell.
"To treat only the unhealthy tissue," he explains, "we
need to use light that will pass harmlessly through all the healthy
tissue, but will enter the cells that have been identified by the
light-sensitive drug. That would enable us to eliminate the collateral
damage, creating a better chance for sight to be recovered."
A process of advanced photonics – two-photon absorption –
provides the basis for a new version of photodynamic therapy. If
two photons must be simultaneously absorbed to excite the drug,
then sensitivity to the light intensity is greatly increased. Only
at the focal point of a highly focused laser beam will the drug
be energized sufficiently to destroy the damaged cell, leaving all
healthy surrounding tissue untouched.
By adapting ultrafast laser technology to current ophthalmoscopes,
Dr. Cramb's multidisciplinary team, working out of six universities
(McGill, Waterloo, Sherbrooke, McMaster, Toronto, and Dr. Cramb's
own labs at the University of Calgary), are bringing their collective
expertise to create ways of delivering light with sufficient control
and precision to deliver two-photon PDT. The goal is to build a
prototype "point and shoot" instrument that ophthalmologists
can use in their offices.
How soon before the project moves "from bench top to bedside"?
Within the next four years, the team expects to meet such challenges
as developing lasers less expensive than those used in the prototype;
enabling the light-sensitive drugs to handle the new two-photon
technology; circumventing a patient's eye movements during retina
scans; and making the optical system adaptive to correct for optical
aberrations in the lens or cornea of the patient's eye.
The team expects to complete work on the prototype point-and-shoot
version within two years. Working with collaborators in the biological
and medical sciences, as well as the pharmaceutical industry, within
four years they expect that animal tests will have yielded the data
needed to conduct clinical trials with humans and to support commercialization
of the technology.
As for commercialization, Dr. Cramb reports that several companies
well known for ophthalmology instruments are already interested.
Right now, the titanium sapphire laser that the CIPI team is working
with costs approximately $150,000. Dr. Cramb foresees reducing
that cost to approximately $20,000 – a price that would enable
physicians to equip their offices with an instrument for on-site
treatment.
www.cipi.ulaval.ca
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