Abstract: Methods for improved imaging of internal tissue structures, such as lesions in the peritoneum, are disclosed employing color-weighted Polarization Enhanced Light (mPEL) imaging. A target tissue can be Illuminated with light of defined polarization at a plurality of wavelengths or wavelength bands. Scattered light from the tissue is collected and its polarization states analyzed and detected either via a polarization sensitive camera or a combination or polarizing filters and a standard camera. Light detected at distinct polarization states and colors is weighted by a factor and combined to yield an image that results in optimized visualization of lesions and/or discrimination of malignant from benign lesions. The factors may be identified based on a combination of Monte Carlo simulations and regression analysis to yield enhanced sensitivity to the tissue scattering power. Alternatively, the factors may be identified through machine learning based optimization algorithms to optimize tissue classification.

Abstract: Methods and apparatus for improved imaging of internal tissue structures, such as lesions in the peritoneum, are disclosed employing Differentially Polarized Light (DPL) imaging. The optical system can include a laparoscope having at least one optical illumination waveguide for directing illuminating radiation and an optical collection waveguide having an aperture for collecting and transmitting radiation backscattered from a tissue region to a detector. The system further can include a polarizer for polarizing the illuminating radiation and a second analyzing polarizer disposed in the optical return path, whereby backscattered radiation of differing polarizations can be passed to the detector. End cap assemblies are also disclosed that that can be fitted to conventional laparoscopes, e.g., by a threaded connection or the like, to facilitate DPL imaging by polarizing the illuminating light of the laparoscope. For example, the end cap can include a polarizing film within a stainless steel housing.

Abstract: Methods and corresponding apparatus and systems for assessing cellular metabolic activity are disclosed. In one aspect, a cell can be illuminated with optical radiation in order to cause multi-photon excitation of at least one endogenous metabolic cofactor in that cell and cause the excited metabolic cofactor to emit fluorescent radiation. A detector can be used to detect the fluorescent radiation emitted by the excited endogenous metabolic cofactor. A computer processor can analyze the fluorescent radiation to derive the following parameters: (1) using a computer processor to analyze the intensity of the fluorescent radiation, (2) a fluorescence lifetime of at least one of the excited metabolic cofactor, (3) a parameter indicative of mitochondrial clustering in said cell. These parameters can be used to assess at least one metabolic process of the cell.

Abstract: Methods and corresponding apparatus and systems for assessing cellular metabolic activity are disclosed. In one aspect, a cell can be illuminated with optical radiation in order to cause multi-photon excitation of at least one endogenous metabolic cofactor in that cell and cause the excited metabolic cofactor to emit fluorescent radiation. A detector can be used to detect the fluorescent radiation emitted by the excited endogenous metabolic cofactor. A computer processor can analyze the fluorescent radiation to derive the following parameters: (1) using a computer processor to analyze the intensity of the fluorescent radiation, (2) a fluorescence lifetime of at least one of the excited metabolic cofactor, (3) a parameter indicative of mitochondrial clustering in the cell. These parameters can be used to assess at least one metabolic process of the cell.

Abstract: In one aspect, the present invention generally provides methods for characterizing mineralization of a material, e.g., a biomaterial, by illuminating the material with radiation and analyzing radiation scattered from the material in response to the illumination. For example, in some embodiments, a material can be illuminated with polarized radiation at a plurality of wavelengths and the elastically scattered radiation corresponding to two or more of those wavelengths can be collected at two polarizations: one parallel and the other perpendicular to the illumination polarization. A differential intensity of the scattered radiation at the two polarizations can be analyzed as a function of wavelength to obtain information regarding the morphology of mineral deposits in the sample. Further, the total scattered radiation can be analyzed to derive information regarding the level of mineralization.

Abstract: Methods and corresponding apparatus and systems for assessing cellular metabolic activity are disclosed. In one aspect, a cell can be illuminated with optical radiation in order to cause multi-photon excitation of at least one endogenous metabolic cofactor in that cell and cause the excited metabolic cofactor to emit fluorescent radiation. A detector can be used to detect the fluorescent radiation emitted by the excited endogenous metabolic cofactor. A computer processor can analyze the fluorescent radiation to derive the following parameters: (1) using a computer processor to analyze the intensity of the fluorescent radiation, (2) a fluorescence lifetime of at least one of the excited metabolic cofactor, (3) a parameter indicative of mitochondrial clustering in said cell. These parameters can be used to assess at least one metabolic process of the cell.

Abstract: A method of manufacturing a biopolymer sensor including providing a biopolymer, processing the biopolymer to yield a biopolymer matrix solution, adding a biological material in the biopolymer matrix, providing a substrate, casting the matrix solution on the substrate, and drying the biopolymer matrix solution to form a solidified biopolymer sensor on the substrate. A biopolymer sensor is also provided that includes a solidified biopolymer film with an embedded biological material.

Abstract: A method of manufacturing a biopolymer sensor including providing a biopolymer, processing the biopolymer to yield a biopolymer matrix solution, adding a biological material in the biopolymer matrix, providing a substrate, casting the matrix solution on the substrate, and drying the biopolymer matrix solution to form a solidified biopolymer sensor on the substrate. A biopolymer sensor is also provided that includes a solidified biopolymer film with an embedded biological material.

Abstract: A method of manufacturing a biopolymer sensor including providing a biopolymer, processing the biopolymer to yield a biopolymer matrix solution, adding a biological material in the biopolymer matrix, providing a substrate, casting the matrix solution on the substrate, and drying the biopolymer matrix solution to form a solidified biopolymer sensor on the substrate. A biopolymer sensor is also provided that includes a solidified biopolymer film with an embedded biological material.

Abstract: The present invention utilizes a plurality of spectroscopic systems and methods to measure characteristics of tissue useful in the diagnosis of disease. In a preferred embodiment, a combination of fluorescence, reflectance and light scattered spectra can be measured and processed to provide biochemical, architectural and morphological state of tissue. The methods and systems can be used particularly in the early detection of carcinoma within tissue in vivo and in vitro.

Abstract: A method of manufacturing a nanopatterned biophotonic structure includes forming a customized nanopattern mask on a substrate using E-beam lithography, providing a biopolymer matrix solution, depositing the biopolymer matrix solution on the substrate, and drying the biopolymer matrix solution to form a solidified biopolymer film. A surface of the film is formed with the nanopattern mask, or a nanopattern is machined directly on a surface of the film using E-beam lithograpy such that the biopolymer film exhibits a spectral signature corresponding to the E-beam lithograpy nanopattern. The resulting bio-compatible nanopatterned biophotonic structures may be made from silk, may be biodegradable, and may be bio-sensing devices. The biophotonic structures may employ nanopatterned masks based on non-periodic photonic lattices, and the biophotonic structures may be designed with specific spectral signatures for use in probing biological substances, including displaying optical activity in the form of opalescence.

Abstract: The present invention provides methods and systems for performing in-vivo flow cytometry to obtain desired information regarding one or more cell types of interest flowing through a subject's circulatory system. In one embodiment of the invention, a portion of the subject's circulating blood is illuminated with radiation having multiple wavelength components, and the backscattered radiation generated in response to the excitation radiation is detected at a plurality of scattering angles and analyzed to derive the desired information.

Abstract: The present invention is generally directed to imaging methods and apparatus that employ angular and/or wavelength distribution of light backscattered from multiple portions of a sample in response to illumination by electromagnetic radiation to generate one, two or three dimensional images of the sample. In many embodiments, confocal imaging can be employed to detect the backscattered radiation, e.g., to measure spectral signals of layered samples (such as biological samples) through optical sectioning. The methods of the invention can be applied to a variety of samples including, without limitation, biological and non-biological samples, organic and inorganic samples, to obtain information, e.g., regarding morphological, compositional, and/or structural variations among different portions of the sample. By way of example, in some applications the methods of invention can be employed to obtain light scattering signals from cells or tissues buried under the skin.

Abstract: In one aspect, the present invention generally provides methods for characterizing mineralization of a material, e.g., a biomaterial, by illuminating the material with radiation and analyzing radiation scattered from the material in response to the illumination. For example, in some embodiments, a material can be illuminated with polarized radiation at a plurality of wavelengths and the elastically scattered radiation corresponding to two or more of those wavelengths can be collected at two polarizations: one parallel and the other perpendicular to the illumination polarization. A differential intensity of the scattered radiation at the two polarizations can be analyzed as a function of wavelength to obtain information regarding the morphology of mineral deposits in the sample. Further, the total scattered radiation can be analyzed to derive information regarding the level of mineralization.

Abstract: Methods and computer program products for analyzing tissue are provided. The tissue is exposed to light at the appropriate wavelengths for inducing fluorescence. Images of the fluorescing tissue are taken at two or more depths within the tissue. The PSD function is determined for each image at a different depth within the tissue. A characteristic of each PSD function determined is compared, and it is determined whether or not the tissue exhibits a pre-cancerous characteristic.

Abstract: The present invention generally provides methods for assessing the potential of tumor formation and/or metastasis using a combination (e.g., a ratio) of the number of circulating tumor cells and the number of circulating cells exhibiting autofluorescence within a selected wavelength region (e.g., red autofluorescence). In one aspect, it is directed to a method for providing likelihood of occurrence of a primary and/or a metastatic cancerous tumor in an animal, which comprises inoculating the animal with a plurality of cancer cells, determining a ratio of a number of cancer cells relative to a number of circulating indicator cells (e.g., immature leukocytes) that exhibit autofluorescence in the inoculated animal's blood and correlating the ratio to a likelihood that the animal will develop at least one primary and/or metastatic cancerous tumor, e.g., by way of assigning a probability for tumor development and/or metastasis based on the measured ratio. The method can also be utilized in human studies using, e.

Abstract: A method of manufacturing a nanopatterned biopolymer optical device includes providing a biopolymer, processing the biopolymer to yield a biopolymer matrix solution, providing a substrate with a nanopatterned surface, casting the biopolymer matrix solution on the nanopatterned surface of the substrate, and drying the biopolymer matrix solution to form a solidified biopolymer film on the substrate, where the solidified biopolymer film is formed with a surface having a nanopattern thereon. In another embodiment, the method also includes annealing the solidified biopolymer film. A nanopatterned biopolymer optical device includes a solidified biopolymer film with a surface having a nanopattern is also provided.

Abstract: A method of manufacturing a biopolymer optofluidic device including providing a biopolymer, processing the biopolymer to yield a biopolymer matrix solution, providing a substrate, casting the biopolymer matrix solution on the substrate, embedding a channel mold in the biopolymer matrix solution, drying the biopolymer matrix solution to solidify biopolymer optofluidic device, and extracting the embedded channel mold to provide a fluidic channel in the solidified biopolymer optofluidic device. In accordance with another aspect, an optofluidic device is provided that is made of a biopolymer and that has a channel therein for conveying fluid.

Abstract: A method of manufacturing a biopolymer optical device includes providing a polymer, providing a substrate, casting the polymer on the substrate, and enzymatically polymerizing an organic compound to generate a conducting polymer between the provided polymer and the substrate. The polymer may be a biopolymer such as silk and may be modified using organic compounds such as tyrosines to provide a molecular-level interface between the provided bulk biopolymer of the biopolymer optical device and a substrate or other conducting layer via a tyrosine-enzyme polymerization. The enzymatically polymerizing may include catalyzing the organic compound with peroxidase enzyme reactions. The result is a carbon-carbon conjugated backbone that provides polymeric “wires” for use in polymer and biopolymer optical devices. An all organic biopolymer electroactive material is thereby provided that provides optical functions and features.

Abstract: A method of manufacturing a biopolymer sensor including providing a biopolymer, processing the biopolymer to yield a biopolymer matrix solution, adding a biological material in the biopolymer matrix, providing a substrate, casting the matrix solution on the substrate, and drying the biopolymer matrix solution to form a solidified biopolymer sensor on the substrate. A biopolymer sensor is also provided that includes a solidified biopolymer film with an embedded biological material.