Oxygen sensors
Inventors
Gamsey, Soya • Wisniewski, Natalie • Helton, Kristen • McMillan, William A.
Assignees
Publication Number
US-12048535-B2
Publication Date
2024-07-30
Expiration Date
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Abstract
Oxygen sensing luminescent dyes, polymers and sensors comprising these sensors and methods of using these sensors and systems are provided.
Core Innovation
Oxygen sensing luminescent dyes, polymers comprising said dyes, and sensors comprising the polymers of the present invention are provided. In one embodiment, the present invention relates to a compound of Formula 1 and, in another aspect, to a polymer comprising as a monomer repeat unit, the residue of the compound of Formula 1. The polymers provided herein can be luminescent biocompatible hydrogels. The present disclosure includes luminescent sensors comprising the polymers for detecting an analyte, e.g., oxygen, in vivo or in vitro.
Diagnosis, treatment and management of some medical conditions require monitoring of oxygen concentration in the afflicted organ or tissue, and current monitoring methods are expensive, cumbersome, time consuming, and do not provide accurate, continuous tissue oxygenation information. There is a need for a better long-term oxygen tissue monitoring system that operates non-invasively with minimal user maintenance and sensor longevity of days to months. Luminescent oxygen sensors exploit oxygen quenching of molecular luminescence and require highly stable dyes with excitation and emission spectra in the near-infrared optical window of the skin to enable implantation deep into tissue. The patent notes that commercially available NIR dyes can be prone to photobleaching and that some palladium porphyrins require excitation wavelengths largely absorbed by skin.
The sensors described can be tissue-integrating or comprise a tissue-integrating scaffold and produce a detectable signal in the presence of the analyte, and further wherein the sensors provide detection of the analyte when placed into the tissue of a subject. The sensors can be in the form of a powder, fabric (e.g., wound dressing), sutures, needle, rod, disk or any other suitable form. In addition to direct oxygen sensing, the sensors can include an oxidase such as glucose oxidase so that the luminescent dyes measure oxygen consumption by the oxidase to provide detection of additional analytes. The tissue-integrating sensors described can provide long-term detection of the analyte(s).
Claims Coverage
One independent claim is identified (claim 1). Three main inventive features are extracted from the independent claim.
Method of detecting an analyte by placing a tissue-integrating sensor under the skin
placing a tissue-integrating sensor under the skin of a mammalian subject
Sensor comprising a polymer with residues of a luminescent dye and HEMA
the sensor comprises a polymer comprising one or more residues of a luminescent dye and one or more residues of 2-hydroxyethyl methacrylate (HEMA)
Luminescent dye defined by the specified formula
wherein the luminescent dye is a compound having the formula
The independent claim covers a method of analyte detection that places a tissue-integrating sensor under the skin, where the sensor is a polymer comprising residues of a specified luminescent dye and residues of HEMA; the luminescent dye is defined by the formula recited in the claim.
Stated Advantages
Excitation and emission wavelengths in the optical window of the skin (approximately 550 nm to 1000 nm) allowing detection of analytes deep within a tissue or an organ.
High signal-to-noise ratio and large Stokes shifts and emission.
Photostability, e.g., the dyes and/or polymers do not undergo rapid photobleaching.
Devices that generate a stable signal over a long period of time (e.g., greater than a week, greater than a month, greater than 6 months).
Tissue integration through tissue and/or capillary in-growth enabling long-term accurate analyte measurements.
Implantation via syringe injection or trocar injection without the need for surgery and sensors that do not include sensor electronics in the body.
Small dimensions that increase patient comfort and acceptance by the body.
Documented Applications
Monitoring oxygen concentration in tissues in vivo, including ensuring that blood and oxygen flow are adequately restored and maintained during and after revascularization procedures for Peripheral Arterial Disease (PAD).
Wound healing monitoring, including use as an oxygen-sensing wound dressing or powder used directly in the wound to constantly and non-invasively assess oxygenation during healing.
Use in skin closure, hernia repair, flap transfer surgeries, reconstructive surgery, and other plastic surgery applications where monitoring of oxygenation of skin or underlying tissue is beneficial.
Measurement for microcirculatory dysfunction and peripheral artery disease, including monitoring tissue oxygen directly in revascularization procedures or upon administration of drug.
Oncology applications to determine the degree of hypoxia in a tissue or an organ and to monitor tumor growth in animal models (e.g., mouse or rat) for oncology pharmaceutical and diagnostic research, including cancer therapy dosing or monitoring of tumor metabolism.
Monitoring the state of pulmonary function, for example in COPD and asthma disease states.
Exercise or training optimization applications, for example soldier and athlete performance or personal exercise programs.
An oxygen-sensing tattoo embodiment.
Neuroscience monitoring applications where continuous monitoring of oxygen is required, for example subarachnoid hemorrhage monitoring.
Multi-analyte sensing and enzymatic sensor embodiments where an oxidase (e.g., glucose oxidase) is included so that oxygen consumption by the oxidase enables detection of other analytes such as glucose.
Form factors for sensors explicitly described include powder, fabric (wound dressing), sutures, needle, rod, disk and injectable or implantable meshes.
Interested in licensing this patent?