Description of Research
Program
Our research program focuses on the development of new analytical techniques in infrared spectroscopy for use in clinical and environmental applications. A major component of our work is the design of methods for both qualitative and quantitative determinations of analytes in complex sampling environments. We are combining state-of-the-art methods in spectroscopy with advanced computer-based data analysis in the solution of these problems.
We
are developing environmental monitoring techniques based on the synergistic use
of a single-point passive Fourier transform infrared (FT-IR) spectrometer
coupled to an infrared line scanner imaging system. These passive remote
sensors are configured to collect naturally occurring infrared radiance from
the outdoor environment. The spectral
features of airborne compounds are superimposed on this ambient infrared
background emission as either absorption or emission bands. By use of
appropriate data processing methods, these analyte
signatures can be extracted and used to identify target chemicals, as well as
estimate their concentrations. The combined use of an imaging line scanner
system with a single-point spectrometer provides a unique capability for
identifying chemical plumes and then interrogating them in detail. When mounted
on an aircraft platform in a downward-looking configuration, these sensors
provide unique capabilities for wide-area air monitoring. In Figure 1, imaging
data collected from an overflight of an industrial
facility are displayed. A plume of methanol can be observed. In Figure 2, an
ethanol release is detected from the air with the downward-looking FT-IR
spectrometer. The ethanol detection is performed by use of signal processing
and pattern recognition methods applied directly to the interferogram
data collected by the spectrometer. Example applications for this technology
include regulatory monitoring of industrial stack emissions, chemical leak
detection, pollutant monitoring at hazardous waste sites, and emergency
response scenarios such as chemical plant accidents or terrorist incidents. In conjunction with our collaborators at the
United States Environmental Protection Agency, our work is focusing on new
design concepts for these sensors, as well as the development of signal
processing, pattern recognition, and image analysis methodology for use in data
interpretation.
In collaboration with Professor Mark Arnold, we are pursuing the development of infrared-based chemical sensors for use in clinical applications. Our current efforts are directed to the use of near-infrared spectroscopy for monitoring glucose in blood and for measuring protein and urea during hemodialysis treatments. The near-infrared spectral region is particularly suited to these measurements because of the presence of transmission windows in which the strong background absorbance of water is reduced. Within these windows, combination and overtone bands of glucose and other analytes can be observed on top of the spectral background associated with the aqueous biological matrix. Figure 3 plots the spectra of glucose and five potential interferents in the region of 4200-4800 cm-1. While the spectra have overlapping features, each compound has a unique signature. For the glucose measurement, a noninvasive sensor is being developed that transmits near-infrared light through the dermis, followed by the application of chemometric methods to the resulting spectra to extract glucose information from the complex spectral background. Research is underway to improve and simplify the required spectroscopic instrumentation, as well as to develop the signal processing and calibration protocols necessary for implementing a robust analysis. If successful, the noninvasive glucose sensor will allow the direct measurement of blood glucose levels without requiring the collection of a blood sample. This technology will greatly benefit diabetic patients who must monitor their glucose levels several times per day.
A third area
of interest lies in the application of FT-IR microscopic imaging to biomedical
applications. This emerging technique couples an FT-IR spectrometer, infrared
microscope, and multichannel focal plane array
detector for use in acquiring infrared images of biological 
samples
such as cells and tissue. By either transmitting infrared light through the
sample or reflecting light from it, a single image acquisition can produce up
to 16,384 infrared spectra. This corresponds to a 128×128 grid of discrete spatial
locations across the sample. Spatial resolutions can be achieved down to the
diffraction limit of less than 10 mm. Applications of interest for this technology include
the automated diagnosis of disease state from spectra of tissues collected
during biopsies and the correlation of spectral information in diseased tissue
with treatment outcomes. A major issue in working with this technique is how to
handle the tremendous volume of data acquired. We are pursuing a variety of
research strategies in signal processing, data compression, feature extraction,
numerical optimization, and pattern recognition in the design of tools for use
in processing and extracting information from these infrared images. Figure 4
presents an example of some of this work. FT-IR microscopic imaging data were
acquired from normal and carcinoma human breast cells, as well as a mixture of the
two. On the basis of the cell morphology, pixels corresponding to cells were
assigned to the normal or carcinoma data categories. Signal processing methods
were devised to remove baseline artifacts from the spectral data and an
artificial neural network classifier was developed to discriminate between the
two data classes. The output from the neural network was used to construct
classification images such as those displayed in the figure. An approach using
rejection thresholds was employed to reject pixels that were of indeterminate
classification. Excellent classification results were obtained, demonstrating
the power and potential practical utility of this imaging approach in medical
diagnostic applications.
The
research topics described above are indicative of the overall theme of our
research program. We wish to exploit the intrinsic selectivity of infrared
spectroscopy for chemical sensing applications. By taking advantage of new
technologies in instrumentation and the growing computational power on-board
our laboratory spectrometers, we hope to increase the applicability of infrared
spectroscopy to a variety of challenging measurement problems.