A growing number of women develop breast cancer and require surgery. Many lumpectomies lead to follow-up procedures after the initial surgery. Advanced scanning technologies have reduced the number of second and third surgeries, but only by about 50%. This paper assesses the potential of using multispectral images of intrinsic fluorescence to detect breast cancer. Images and spectra of intrinsic fluorescence from fresh ex vivo human specimens are related to pathological analysis, and predict high sensitivity and specificity. A design for a hand-held surgical scanning tool is presented.
The enhanced uptake of glucose by cancer cells via aerobic glycolysis occurs when the lactic acid pathway is favored over the citric acid cycle. The lactic acid cycle in cancer cells influences the cytosolic concentration of metabolic fluorophores including NADH (the reduced form of nicotinamide adenine dinucleotide) and flavin adenine dinucleotide (FAD). In particular, the literature has shown that breast cancer influences the relative magnitude of fluorescence from NADH and FAD. A multispectral imaging system has been developed for rapid non-destructive imaging of intrinsic fluorescence in tissue. This paper compares in vivo data to fresh ex vivo data gathered as a function of time in mouse models. The data indicate that, if measured within 30 min of excision, a cancer diagnosis in fresh ex vivo tissue correlates with a cancer diagnosis in in vivo tissue. These results justify a plan to evaluate fresh ex vivo human tissue to quantify the sensitivity and specificity of the multispectral system.
The physical and optical properties of coatings deposited using physical vapor deposition techniques exhibit changes during post deposition annealing. Optical properties including the index of refraction and spectral transmission vary when coatings are annealed. Physical and mechanical properties such as thickness, density, and stress are also impacted by annealing. In this paper, we study the source of these changes by examining the impact of 150-500°C annealing on Nb2O5 films deposited using thermal evaporation and reactive magnetron sputtering. Models based on the Lorentz-Lorenz equation and potential energy considerations explain the data, and rationalize conflicts between previously reported results.
The impact of post-deposition annealing on the optical and physical properties of sputtered and evaporated metal-oxide coatings was examined. Models based on the Lorentz-Lorenz equation and potential energy considerations are used to explain the data.
Raman spectroscopy can be used extensively, from handheld substance identification systems to in-vivo cancer detection. The ability to quickly and non-invasively identify compounds based on intrinsic vibrational signatures has seen Raman applications skyrocket in recent years - many using fiber optic probes. This paper describes the modeling, deposition, lithographic patterning, and testing of filters directly deposited onto the distal tip of a fiber bundle. These spectrally sharp bandpass and long pass filters allow for the detection of Raman scattering down to about 200 cm-1 . Blocking of laser radiation above OD6 is enabled by coating both the distal and proximal tips.
Many free space optical systems can be fiberized, enabling advantages in function, size and weight. Implementations include fiber-based lasers, interferometers, polarimeters, spectrometers, endoscopic probes, and pigtailed detectors. Interference filters can be integrated into a fiberized system by depositing the filters on fiber tips. Omega has deposited a variety of interference stacks on fiber tips. One can think of fiber tips as miniaturized substrates – the ultimate small part configuration. This article reviews optical fibers and fiber tips, coating fiber tips, testing the coated tips, as well as the performance and applications of the coated tips.
Raman spectroscopy is used in many areas including pharmaceuticals, geology, chemical engineering, semiconductors, and the life sciences. More recently, Raman fiber sensors have been developed for minimally invasive applications in clinical histopathology. This paper describes the modeling, fabrication, and testing of filters directly deposited onto the excitation and collection fiber tips of a Raman probe. The narrow spectral width of laser rejection filters on the collection fibers should allow for the detection of low wavenumber Raman scattering within the “fingerprint” region. Deep blocking of the laser radiation is enabled by coating both ends of the collection fibers.
Multi-channel microscopy and multi-channel flow cytometry generate high bit data streams. Multiple channels (both spectral and spatial) are important in diagnosing diseased tissue and identifying individual cells. Omega Optical has developed techniques for mapping multiple channels into the time domain for detection by a single high gain, high bandwidth detector. This approach is based on pulsed laser excitation and a serial array of optical fibers coated with spectral reflectors such that up to 15 wavelength bins are sequentially detected by a single-element detector within 2.5 μs. Our multichannel microscopy system uses firmware running on dedicated DSP and FPGA chips to synchronize the laser, scanning mirrors, and sampling clock. The signals are digitized by an NI board into 14 bits at 60MHz – allowing for 232 by 174 pixel fields in up to 15 channels with 10x over sampling. Our multi-channel imaging cytometry design adds channels for forward scattering and back scattering to the fluorescence spectral channels. All channels are detected within the 2.5 μs – which is compatible with fast cytometry. Going forward, we plan to digitize at 16 bits with an A-toD chip attached to a custom board. Processing these digital signals in custom firmware would allow an on-board graphics processing unit to display imaging flow cytometry data over configurable scanning line lengths. The scatter channels can be used to trigger data buffering when a cell is present in the beam. This approach enables a low cost mechanically robust imaging cytometer.
Novel optoelectronic instrumentation has been developed for the multispectral imaging of autofluorescence emitted by metabolic fluorophores. The images resolve individual cells while spectra are collected for each pixel in the images. These datacubes are generated at a rate of 10 per second-fast enough for surgical guidance. The data is processed in real time to provide a single color-coded image to the surgeon. To date, the system has been applied to fresh, ex vivo, human surgical specimens and has distinguished breast cancer from benign tissue. The approach is applicable to in vivo measurements of surgical margins and needle-based optical biopsies. Ongoing work demonstrates that the system has great potential for translation to a hand-held probe with high sensitivity and specificity.
Compact optical systems can be fabricated by integrating coatings on fiber tips. Examples include fiber lasers, fiber interferometers, fiber Raman probes, fiber based spectrometers, and anti-reflected endoscopes. These interference filters are applied to exposed tips – either connectorized or cleaved. Coatings can also be immersed within glass by depositing on one tip and connecting to another uncoated tip. This paper addresses a fiber spectrometer for multispectral imaging - useful in several fields including biomedical scanning, flow cytometry, and remote sensing. Our spectrometer integrates serial arrays of reflecting fiber tips, delay lines between these elements, and a single element detector.
Rapid multispectral confocal imaging is performed with a single shot-limited detector. This approach uses fiber delay lines to map spectral bands into the time domain, and has been integrated with fiber bundles for endoscopic applications.
Ultra-narrow band pass filters are used to maximize LIDAR range and sensitivity. Alternate designs and measured fabrication results are presented for sub-nanometer band pass filters down to quarter nanometer bandwidths with 95% transmission. Thermal and angle sensitivity have been minimized. The filters are fabricated using dual source, plasma assisted magnetron sputtering. Single and multi-cavity designs are presented.
A new approach for generating high-speed multispectral images has been previously reported by our team. The central concept is that spectra can be acquired for each pixel in a confocal spatial laser scan by using a fast spectrometer based on optical fiber delay lines. This method merges fast spectroscopy with standard spatial scanning to create image datacubes in real time. The datacubes can be analyzed to define regions of interest (ROIs) containing diseased tissue. Firmware and software have been developed for selectively scanning these ROIs with increased optical power. This enables real time image-guided laser treatment with a spatial resolution of a few microns.
Interference filters have improved over the years. Sharp spectral edges (> 1 db/nm) reach high optical density (OD > 8) in a few nm. In-situ optical monitoring to within 0.1 % error enables these levels of performance. Due to limitations related to f-number and resolution bandwidth, post-deposition testing in typical spectrophotometers cannot reveal the quality of today’s filters. Laser based measurements at selected wavelengths prove that blocking above OD8 to OD9 is manufacturable with high yield. This paper compares modeled spectra and laser based measurements.
A new approach for generating high-speed multispectral images has been developed. The central concept is that spectra can be acquired for each pixel in a confocal spatial scan by using a fast spectrometer based on optical fiber delay lines. This concept merges fast spectroscopy with standard spatial scanning to create datacubes in real time. The spectrometer is based on a serial array of reflecting spectral elements, delay lines between these elements, and a single element detector. The spatial, spectral, and temporal resolution of the instrument is described, and illustrated by multispectral images of laser-induced autofluorescence in biological tissues.
Interference filters have improved over the years. Sharp spectral edges (>1db/nm) reach high optical density (OD>8) in a few nm. In-situ optical monitoring to within 0.1% error enables these levels of performance. Due to limitations related to f-number and resolution bandwidth, post-deposition testing in typical spectrophotometers cannot reveal the quality of today's filters. Laser based measurements at selected wavelengths prove that blocking above OD8 to OD9 is manufacturable with high yield. This paper compares modeled spectra and laser based measurements.
This project centered on creating a solar cell prototype enabling significant reductions in module cost and increases in module efficiency. Low cost was addressed by using plentiful organic materials that only comprise 16% of the total module cost, and by leveraging building integrated PV concepts that reduce the cost of key module components to zero. High efficiency was addressed by implementing multiband organic PV, low cost spectral splitting, and possibly integrating photovoltaic and photothermal mechanisms. This research has contributed to the design of multiband organic PV, and the sealing of organic PV cells. If one assumes that the aggregate multiband efficiency can reach 12%, projected cost would be $0.97/W. If the sealing technology enables 10 to 20 year lifetimes, the LCOE will match that of domestic coal. The final report describes progress towards these goals.
Spectral data for each pixel in a confocal spatial scan are acquired by mapping spectral slices into the time domain with an array of visible fiber Bragg gratings. Multispectral images of biomedical tissue can be generated in real time.