The practical utility of technologies for early detection of human exposure to a variety of toxic agents has been
limited in many cases by the absence of instruments suitable for first responders and at field hospitals. Microarrays
provide multiplexed assay of a large number of human biomarkers, including cytokines and chemokines, indicators
of immune system health. Assay of saliva is less invasive and provides quick indication of exposure especially of the
respiratory system. Our pilot clinical study has uncovered an early cytokine response in human saliva. As a model
for respiratory exposure, a cohort of 16 adult volunteers was challenged with FluMistTM vaccinations, an FDA
approved, attenuated live influenza virus. Blood and saliva cytokine levels were monitored immediately prior to and
up to 7 days afterwards. Bead assay found little change in blood cytokine levels while several of those in saliva
were frequently elevated above two standard deviations on trial days one and three. We have developed a prototype
portable saliva monitoring system consisting of microarray cytokine capture plate, luminescent reporter, and whole
plate imaging. Assay is with a commercial 96-well plate spotted with up to 16 distinct biomarkers per well and read
by chemiluminescence. A battery-powered, 16-bit, cooled-CCD camera and laptop PC provide imaging and data
reduction. Detection limits of common inflammatory cytokines were measured at about 1-5 pg/ml which is within
the clinically significant range for saliva of exposed individuals, as verified for samples from the small clinical trial.
An expanded study of cytokine response in saliva of therapeutic radiation oncology patients is being launched.
Photodynamic therapy (PDT) is a promising cancer treatment. PDT uses the affinity of photosensitizers to be selectively retained in malignant tumors. When tumors, pretreated with the photosensitizer, are irradiated with visible light, a photochemical reaction occurs and tumor cells are destroyed. Oxygen molecules in the metastable singlet delta state O2(1) are believed to be the species that destroys cancerous cells during PDT. Monitoring singlet oxygen produced by PDT may lead to more precise and effective PDT treatments. Our approach uses a pulsed diode laser-based monitor with optical fibers and a fast data acquisition system to monitor singlet oxygen during PDT. We present results of in vitro singlet oxygen detection in solutions and in a rat prostate cancer cell line as well as PDT mechanism modeling.
A novel instrument for real-time in vivo measurement of blood composition is presented. Two optical technologies are combined in this instrument: spectral domain low coherence interferometry (SD-LCI) and retinal tracking. Retinal tracking is used to stabilize the LCI beam on vessels. SD-LCI is used to get depth-reflectivity profiles within the vessels. Multiple signals are rapidly acquired, averaged and processed. Differences in the slopes of the depth reflectivity profiles for different subjects correspond to the difference in the scattering coefficient, which is proportional to the concentration of red blood cells per cubic mm of blood (hematocrit). Preliminary measurements on several healthy volunteers show a good correlation with the normal range of the hematocrit.
Mid infrared Quantum Cascade (QCL) and Interband Cascade Lasers (ICL) coupled with cavity-enhanced techniques, have proven to be sensitive optical diagnostic tools for both atmospheric sensing as well as breath analysis. In this work, a TE-cooled, pulsed QCL and a cw ICL are coupled to high finesse cavities, for trace gas measurements of nitric oxide, carbon dioxide, carbon monoxide and ethane. QCL's operating at 5.26 μm and 4.6 μm were used to record ICOS spectra for NO, CO2, and CO. ICOS spectra of C2H6 were recorded at 3.35 μm using an ICL. Ringdown decay times on the order to 2-3 μs are routinely obtained for a 50 cm cavity resulting in effective pathlengths on the order of 1000 meters. The sample cell is compact with a volume of only 60ml. Details of the QCL and ICL cavity enhanced spectrometers are presented along with the detection results for trace gas species. Here we report a detection limit of 0.7 ppbv in 4 s for NO in simulated breath samples as well as human breath samples. A preliminary detection limit of 250 pptv in 4 s for CO is obtained and 35 ppb in 0.4 s for C2H6.
Monitoring singlet molecular oxygen (1O2) produced by photodynamic therapy (PDT) can lead more precise and effective cancer treatment. Physical Sciences Inc. (PSI) has developed a singlet oxygen monitor based on a pulsed diode laser technology. In this paper, we present results of singlet oxygen detection in the solution phase and in a rat prostate cancer cell line, as well as PDT mechanism modeling. We describe an improved detection approach for singlet oxygen monitoring that employs a fiber-coupled optical set-up and fast data acquisition system.
Recent advances in current-pumped, bandgap-engineered semiconductor lasers have dramatically impacted laser-based sensor concepts for in-situ trace species measurement and standoff sensing applications. These devices allow a common technology platform to access strong fundamental vibrational absorption transitions of many gases, liquids, and solids in the mid-wave and long-wave IR, as well as far-IR, or THz. The THz wavelength region is particularly interesting for applications related to structure penetrating detection of hidden materials and biomolecular spectroscopy. This presentation will briefly review the important properties of these lasers as they apply to sensor design and present highlights of recent sensor development activity for trace gas analysis in environmental and biomedical applications, remote sensing LIDAR systems, and detection of hidden explosives.
In this paper we present results from experiments to develop a real-time, optical monitor for singlet molecular oxygen produced during photodynamic therapy. Using a pulsed diode laser and a sensitive photomultiplier tube, we have obtained signals from singlet oxygen during and following pulsed laser excitation. Several photosensitizers were used, and we obtained strong signals even in the presence of protein laden environments. Values obtained for the lifetimes of the singlet oxygen state and the photosensitizer triplet state are compared to literature values.
Laser lithotripsy is now an accepted modality for the intracorporeal fragmentation of urinary tract and, to a lesser extent, biliary tract calculi. However, under conditions where constant direct vision is not possible or compromised, the risk of inadvertent laser damage to healthy soft tissue cannot be discounted. This is especially true at the higher laser pulse energies required to fragment the more recalcitrant stones. A series of in vitro and in vivo investigations are described which demonstrate a method and apparatus for the automatic feedback control of laser lithotriptors. In preliminary experiments, the control device, incorporated into a commercial flashlamp-pumped dye laser, is shown to significantly improve the margin of safety against laser tissue damage while still allowing effective stone fragmentation. The practical implications of our findings for the clinical possibility of `blind' laser lithotripsy are discussed.