Ultrasound imaging of biomarker sensitive hydrogels
Inventors
Avula, Mahender nath • Christensen, Douglas A. • Farhoudi, Navid • Kanarowski, Stan • Koerner, Julia • Magda, Jules John • Marrouche, Rami Sami • Reiche, Christopher F. • Solzbacher, Florian • Sorenson, Michael David
Assignees
Sentiomed Inc • University of Utah • University of Utah Research Foundation Inc
Publication Number
US-11445997-B2
Publication Date
2022-09-20
Expiration Date
2037-09-01
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Abstract
Systems and methods for accurately measuring changes in biomarker sensitive hydrogel volume and shape due to exposure to various biomarkers include a system for identifying one or more dimensional changes in a biomarker sensitive hydrogel positioned within an in vivo environment. The system includes a biomarker sensitive hydrogel positioned within an in vivo environment and configured to dimensionally change in response to interaction with predefined biomarkers. The system additionally includes an ultrasound transducer for locating and identifying one or more characteristics of the biomarker sensitive hydrogel and a computer system in electrical communication with the ultrasound transducer. The computer system is configured to receive characteristics of the biomarker sensitive hydrogel from the ultrasound transducer and determine dimensional changes of the biomarker sensitive hydrogel based on the received characteristics.
Core Innovation
The invention provides systems and methods for accurately measuring changes in the volume and shape of biomarker sensitive hydrogels due to exposure to various biomarkers by using ultrasound imaging technology. The system includes a biomarker sensitive hydrogel positioned within an in vivo environment, which is configured to undergo dimensional changes in response to specific biomarkers. An ultrasound transducer is employed to locate the hydrogel and to identify its acoustic resonance characteristics, and a computer system receives data from the transducer to determine any dimensional changes of the hydrogel based on this information.
Traditional medical imaging methods, especially ultrasound, are limited as they are typically unable to report on the presence, absence, or concentration of biomarkers within the body. This is because current imaging techniques generally visualize sonically reflective structures but lack the ability to provide direct information about specific biomarker concentrations, particularly in real time and non-invasively. The core problem addressed by this invention is the need for an effective way to visually track hydrogel response to biomarkers in vivo using available imaging technology.
Implementations of the invention overcome these shortcomings by providing hydrogels embedded or associated with ultrasound-visible markers or contrast agents. These may include microbubbles, metals, microwires, nanoparticles, or specially arranged features within the hydrogel to enhance ultrasound detectability. The computer system can analyze changes in hydrogel characteristics—such as shifts in acoustic resonance frequency, marker spacing, or contrast density—between imaging time points or in comparison with a non-responsive control hydrogel, thereby allowing for accurate, noninvasive determination of biomarker concentrations within the in vivo environment.
Claims Coverage
The claims feature multiple inventive aspects centering on systems and methods for detecting changes in biomarker sensitive hydrogels using ultrasound and for determining biomarker concentrations from such changes.
System for identifying changes in biomarker sensitive hydrogels using ultrasound resonance
A system comprising a biomarker sensitive hydrogel configured to be positioned within an in vivo environment and unconstrained to resonate, an ultrasound transducer configured to locate the hydrogel and identify shifts in its acoustic resonance frequency, and a computer system configured to receive acoustic resonance frequency data from the transducer and determine changes in the hydrogel based on this data.
Comparison to a control hydrogel for differential measurement
A system wherein a control hydrogel, which does not dimensionally change in response to interaction with biomarkers, is also positioned in the in vivo environment. The ultrasound transducer identifies characteristics of both hydrogels, and the computer system determines changes based on differences between the biomarker sensitive hydrogel and the control hydrogel.
Biomarker sensitive hydrogel with markers or contrast agents for measurement
Biomarker sensitive hydrogels and control hydrogels each comprise one or more markers or contrast agents, including metals, microspheres, microbubbles, microwires, nanowires, or sonically reflective nanoparticles. Markers can be arranged as barber pole stripes or foci within or along the hydrogel to enhance ultrasound measurement of dimensional changes, such as changes in marker density or inter-marker distance over time.
Hydrogel resonator sheet structured for ultrasonic frequency band absorption
A system wherein the biomarker sensitive hydrogel is configured as a hydrogel resonator sheet that absorbs a subset of ultrasonic frequency bands, formed as an array of acoustic resonators that change physically in response to specific biomarkers. The system measures shifts in the frequency position of the absorption maxima to detect swelling or shrinking of the resonator array, allowing determination of biomarker concentration.
Computer-implemented method for determining biomarker changes by acoustic properties
A computer-implemented method of receiving, at a first time, characteristics (including resonance frequency or acoustic absorption) of a biomarker sensitive hydrogel from an ultrasound receiver, determining these acoustic features, receiving updated characteristics at a later time, and calculating biomarker concentration based on changes in resonance frequency or acoustic absorption.
In summary, the inventive features span ultrasound-resonant biomarker sensitive hydrogels, their combination with markers or control hydrogels, specialized hydrogel array resonator sheets, and computer-based analytical methods for determining biomarker concentrations from acoustic resonance data.
Stated Advantages
Enables noninvasive, real-time, visual readout of hydrogel swelling and thereby biomarker concentration using existing, comparably cheap medical ultrasound technology.
Allows use and readout of long-term, biocompatible, and immunologically inert hydrogel implants for monitoring biomarker concentrations at in vivo sites.
Provides deeper reach into tissue compared to optical sensing techniques, enabling detection of biomarker concentrations in deep tissue areas.
Hydrogel visibility is enhanced with ultrasound markers or contrast agents, allowing detection and measurement of dimensional changes via standard ultrasound imaging devices.
Enables site-specific measurement using hydrogel resonator sheets or sleeves that can be applied to ultrasound transducers or implants.
Documented Applications
Use in vivo to monitor and determine concentrations of biomarkers such as thrombin, clotting factors, interleukins, cytokines, chemokines, C-reactive protein, glucose, insulin, anesthesia drugs, and restricted drugs within the bloodstream.
Monitoring for blood-based infections by detecting bacterial or viral antigens, including peptidoglycan and viral capsid proteins, for noninvasive infection surveillance in patients.
Application in organs such as the bladder (organ failure, infection, eating disorders, preeclampsia), vagina (monitoring pH, hormones, pregnancy biomarkers), liver, kidney, or in deep tissue sites for biomarker concentration measurement.
Implantation in animal in vivo environments for analogous biomarker monitoring.
Deployment within environmental locations such as water lines to detect pollutants, toxic metals, carcinogens, microbial contamination, or additives using analyte-sensitive hydrogels and ultrasound.
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