Solid hemoglobin-polymer biophotonic phantoms and their use
Inventors
Jang, Hyounguk • Wang, Jianting • Chen, Yu • Pfefer, Thomas Joshua
Assignees
University of Maryland Baltimore • University of Maryland College Park • US Department of Health and Human Services
Publication Number
US-10024785-B2
Publication Date
2018-07-17
Expiration Date
2036-06-20
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Abstract
Novel biophotonic phantoms are provided herein that can accurately mimic the optical properties of living tissue. The disclosed biophotonic phantoms comprise hemoglobin (Hb) in a native conformation that is distributed in a solid polymer matrix. Methods of producing the disclosed biophotonic phantoms are also provided. The biophotonic phantoms can be used, for example, to calibrate or test an optical imaging system, such as a near infrared spectroscopy imaging system.
Core Innovation
The invention provides novel biophotonic phantoms that can accurately mimic the optical properties of living tissue by incorporating hemoglobin (Hb) in its native conformation homogeneously distributed within a solid polymer matrix of cured polydimethylsiloxane (PDMS). These phantoms maintain stable attenuation and absorption coefficients across visible and near-infrared wavelengths for periods of at least two months, enabling realistic spectral characteristics of oxygenated, partially oxygenated, and deoxygenated forms of Hb.
The problem being addressed is the lack of solid, stable biophotonic phantoms containing biologically relevant Hb that faithfully represent tissue optical properties over time. Prior phantoms typically use dyes or liquid/gel formulations that either lack the spectral realism of Hb absorption or suffer from instability, evaporation, and denaturation issues, making them unsuitable for consistent calibration and testing of optical imaging and detection systems.
The invention also includes methods of producing such phantoms by mixing uncured PDMS with Hb in its native conformation using sonication under controlled temperature conditions to prevent denaturation, followed by curing with a cross-linking agent to form a shaped solid matrix. The phantoms can be customized with additives to simulate specific tissue types, incorporate inclusions with varying Hb concentration for calibration targets, and be encased in low oxygen permeability shells to maintain oxygenation states.
Claims Coverage
The patent contains several independent claims covering the composition of the biophotonic phantom, methods of its manufacture, and its use in calibration and testing of optical detection systems. The main inventive features are summarized below.
Biophotonic phantom composition with native hemoglobin in PDMS
The phantom comprises a solid matrix of cured polydimethylsiloxane containing hemoglobin that is maintained in a native conformation and distributed (preferably homogeneously) throughout the matrix, with stable optical attenuation and absorption properties across visible and near infrared spectra for at least two months.
Phantom customization and structural features
The phantom can include oxygenated, partially oxygenated, or deoxygenated hemoglobin; be shaped to simulate morphology and optical properties of human organs, tissues, body parts, or animals; include additives to mimic specific tissue types; be encased in a shell of PDMS without hemoglobin to inhibit oxygenation changes; and contain embedded filaments or inclusions with differing Hb concentrations as targets for calibrating or testing optical detection systems.
Method of manufacturing the biophotonic phantom
The method involves mixing hemoglobin in native conformation with uncured PDMS via sonication over 8 to 12 hours with intervals for heat dissipation at temperatures between 0-10°C to prevent Hb denaturation or oxidation, followed by removal of dissolved gases in a vacuum chamber, mixing in a curing agent at specific ratios, molding into desired shape, and curing at room temperature for 24 to 48 hours. Optionally, a desaturation agent can be added to produce deoxygenated Hb, and the phantom can be encased in a hemoglobin-free PDMS shell.
Use of the biophotonic phantom for calibration and testing
The phantom is used to calibrate or test optical detection systems by directing visible or near-infrared light at the phantom and detecting optical and/or acoustic signals produced in response, enabling performance assessment including Hb concentration and saturation measurements.
The patent claims cover the novel composition of a stable, solid Hb-PDMS biophotonic phantom with tunable Hb oxygenation states and customizable optical properties, the method of making the phantom with controlled sonication and curing processes, structural modifications to enhance functionality, and the phantom's application for calibrating and testing optical detection systems.
Stated Advantages
The phantoms have biologically relevant optical characteristics with stable attenuation and absorption coefficients that remain consistent for months, enabling standardized assessment of optical detection systems.
The solid polymer matrix provides mechanical robustness and ease of molding into complex shapes that realistically simulate organs or tissues, surpassing the fragility and instability of liquid and gel phantoms.
The ability to homogeneously distribute native hemoglobin allows the phantoms to reproduce the realistic spectral absorption features of hemoglobin in various oxygenation states, which prior dye-based phantoms cannot achieve.
Encasing in low oxygen permeability shells inhibits changes in hemoglobin oxygenation levels over time, enhancing long-term stability.
The process avoids thermal denaturation or oxidation of hemoglobin through controlled sonication and room temperature curing, preserving hemoglobin integrity.
Customizable optical properties via additives and inclusions enable simulation of different tissue types and inclusion of calibration targets for comprehensive device performance testing.
Phantoms provide practical and convenient standardized tools for device development, evaluation, quality assurance, benchmarking, and education related to biophotonic imaging systems.
Documented Applications
Calibration and testing of optical imaging systems such as near infrared spectroscopy (NIRS) and hyperspectral reflectance imaging (HRI) systems.
Standardized assessment and comparison of biophotonic diagnostic devices that rely on measuring hemoglobin concentration and oxygenation, including clinical oximeters for cerebral and muscle tissue.
Performance evaluation of optical devices measuring blood oxygen saturation, hemoglobin concentration, low contrast detectability, spatial resolution, penetration depth, and spectral measurement accuracy.
Testing of optical imaging platforms including functional Near-Infrared Spectroscopy (fNIRS), Diffuse Reflectance Spectroscopy (DRS), Fluorescence Spectroscopy, Raman Spectroscopy, Narrow Band Imaging, Spatial Frequency Domain Imaging (SFDI), Optical Coherence Tomography (OCT), Confocal Microscopy, Nonlinear Microscopy, Optical Tomography, and photoacoustic imaging systems.
Use in multi-modal diagnostic device development, manufacturing quality assurance, clinical trial standardization, system recalibration, and education for user training.
Simulation of biologically relevant tissues including brain, skin, mucosa, breast tissue, adipose, liver, esophagus, cervix, and muscle for imaging system evaluation.
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