The field of biomedical photonics
has recently experienced an explosive growth due to the non-invasive or
minimally invasive nature and the cost-effectiveness of biophotonic modalities
in environmental sensing, medical diagnostics and therapy. This lecture
discusses the development and application of advanced biomedical photonics,
molecular spectroscopy, biosensors and biochips for environmental and
biomedical diagnostics.
The first research area involves the development of metallic nanoprobes
that can produce the surface-enhanced Raman scattering (SERS) effect for
ultrasensitive biochemical analysis. The intensity of the normally weak
Raman scattering process is increased by factors as large as 106-1013
for compounds adsorbed onto a SERS substrate, allowing for trace-level
detection. Our nanoparticle-based SERS technology has enabled sensitive
detection of a variety of compounds of environmental and medical interest.
The SERS nanoprobe technology has also been incorporated in several fiberoptic
probe designs for remote analysis. The development of a SERS gene probe
technology based on the solid surface-based technology has also been reported.
In one study, the selective detection of HIV and cancer gene was demonstrated.
An important area in chemical and biological sensing is the sensitive
detection and selective identification of toxic chemical compounds (carcinogens,
pollutants, etc.) or living systems (bioaerosols, bacteria, viruses or
related components) at ultra-trace levels in complex samples. Combining
the exquisite specificity of biological recognition probes and the excellent
sensitivity of laser-based optical detection, biosensors are capable of
detecting and differentiating bio/chemical constituents of complex systems
in order to provide unambiguous identification and accurate quantitation,
and open new horizons for chemical and biological sensing.
Recently, we have developed a novel integrated Multi-functional Biochip
(MFB) which allows simultaneous detection of several disease end-points
using different bioreceptors such as DNA, antibodies, enzymes, cellular
probes) on a single biochip system. An important element in the development
of the MFB involves the design and development of an integrated circuit
(IC) electro-optic system for the microchip detection elements using the
complementary metal oxide silicon (CMOS) technology. The biochip has recently
been developed to detect the gene fragments of Tuberculosis and the HIV
gene system as well as the p53 and FHIT proteins. The biochip could be
used to diagnose genetic susceptibility and diseases, or to monitor exposure
to biological pathogens and to bioactive environmental samples.
For in vivo medical diagnostics, the optical diagnostic procedure based
on laser-induced fluorescence (LIF) was developed for direct in-vivo cancer
diagnosis without requiring biopsy. LIF measurements were conducted during
routine gastrointestinal endoscopy examinations of patients. The fiberoptic
probe was inserted into the biopsy channel of an endoscope and lightly
touched the surface of the tissue being monitored. The system was programmed
to measure the fluorescence of the target tissue for each laser pulse.
The LIF measurement was completed in approximately 0.6 second for each
tissue site. The results of this LIF approach were compared with histopathology
results of the biopsy samples and indicated excellent agreement (98%)
in the classification of normal tissue and malignant tumors of gastro-intestinal
cancer in clinical studies involving over 100 patients.
Acknowledgements. This work was sponsored by the National
Institutes of Health (RO1 CA88787-01) and by the US Department of Energy
(DOE) Office of Biological and Environmental Research, under contract
DEAC05-00OR22725 with UT-Batelle, LLC.
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