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Profusa, Inc.Profusa, Inc. is a pioneering digital health company based in the San Francisco Bay Area, dedicated to making the body’s chemistry easily accessible to improve health and wellness. Profusa develops tissue-integrating biosensors for continuous, real-time monitoring of body chemistries, empowering individuals and clinicians with actionable, medical-grade data to transform personal health management and disease prevention. Their unique bioengineering approach overcomes the foreign body response, enabling long-term, in-body monitoring through tiny, flexible biosensors that become one with the body. Profusa’s technology platform supports both consumer and medical applications, with a vision to revolutionize personalized medicine and digital health. The company is supported by significant grant funding from agencies such as DARPA and NIH, and collaborates with leading academic, hospital, and industry partners worldwide.
Profusa, Inc. is a pioneering digital health company based in the San Francisco Bay Area, dedicated to making the body’s chemistry easily accessible to improve health and wellness. Profusa develops tissue-integrating biosensors for continuous, real-time monitoring of body chemistries, empowering individuals and clinicians with actionable, medical-grade data to transform personal health management and disease prevention. Their unique bioengineering approach overcomes the foreign body response, enabling long-term, in-body monitoring through tiny, flexible biosensors that become one with the body. Profusa’s technology platform supports both consumer and medical applications, with a vision to revolutionize personalized medicine and digital health. The company is supported by significant grant funding from agencies such as DARPA and NIH, and collaborates with leading academic, hospital, and industry partners worldwide.
Publication Number
US-9375494-B2
Publication Date
2016-06-28
Expiration Date
Abstract
Oxygen sensing luminescent dyes, polymers and sensors comprising these sensors and methods of using these sensors and systems are provided.
Core Innovation
Disclosed herein are luminescent dyes, polymers comprising said dyes, and sensors comprising the polymers of the present invention. The invention includes a compound of Formula 1 and polymers comprising as a monomer repeat unit the residue of the compound of Formula 1, wherein the polymers can be luminescent biocompatible hydrogels and the sensors can be in the form of a powder, fabric, sutures, needle, rod, disk or other suitable form. The luminescent sensors provided herein can be tissue-integrating or comprise a tissue-integrating scaffold, produce a detectable signal in the presence of an analyte (e.g., oxygen), and provide detection of the analyte when placed into the tissue of a subject.
The background identifies a need for improved stable, near-IR luminescent compounds and sensors for direct, rapid and accurate measurement of oxygen levels in tissue, particularly in vivo, because current monitoring methods are expensive, cumbersome, time consuming, and do not provide accurate, continuous tissue oxygenation information. The patent states that monitoring non-invasively through the skin requires dyes with excitation and emission wavelengths in the optical window of the skin (approximately 550 nm to 1000 nm) and that commercially available NIR dyes can be prone to photobleaching, while some porphyrins require excitation wavelengths largely absorbed by the skin. The disclosure further notes that currently available sensors are rigid, differ from the mechanical properties of tissue, are bulky, and can induce biological events culminating in a fibrous capsule, creating a need for long-term, minimally invasive, tissue-compatible oxygen sensing.
The sensors described can optionally include an oxidase (for example glucose oxidase) to detect analytes other than oxygen by measuring oxygen consumption, and can provide long-term detection of analytes when implanted; the dyes and polymers are described as having excitation and emission wavelengths in the optical window of the skin, high signal-to-noise ratio, large Stokes shifts and emission, and photostability. The disclosure also describes tissue-integrating scaffold architectures that promote capillary in-growth to enable accurate analyte measurements over long term and sensors that can be implanted through syringe or trocar injection without implantable electronics in the body.
Claims Coverage
Independent claim 1 is identified and recites three main inventive features.
Polymer comprising residues of a luminescent dye
A sensor for detecting an analyte comprising a polymer, wherein said polymer comprises one or more residues of a luminescent dye.
Photostable porphyrin dye with NIR excitation and emission
Wherein the luminescent dye is a photostable porphyrin dye and has excitation and emission spectra in the NIR optical window of a mammalian skin.
Luminescent dye defined by the recited formula
Wherein the luminescent dye is a compound having the Formula as recited in the claim.
Claim 1 covers a sensor whose polymer contains residues of a luminescent dye, where the dye is a photostable porphyrin with excitation and emission in the NIR optical window of mammalian skin, and where the dye is the compound defined by the recited Formula.
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.
Large Stokes shifts and emission.
Photostability, e.g., the dyes and/or polymers do not undergo rapid photobleaching.
Sensors generate stable signal over a long period of time (e.g., greater than a week, greater than a month, greater than 6 months).
Sensors that integrate into the subject's tissue (e.g., through tissue and/or capillary in-growth) and provide accurate analyte measurements over long term.
Sensors that can be implanted through syringe injection or trocar injection so that no surgery is required to place the sensing media in the body.
Sensors that do not include sensor electronics in the body.
Devices of small dimensions which result in increased patient comfort and better acceptance by the body.
Documented Applications
Monitoring oxygen concentration in tissues in vivo or in vitro, including long-term or continuous collection of data.
Oxygen-sensing wound dressing to monitor wound healing.
Powder sensor used directly in the wound as a sensor for wound-healing monitoring.
Injectable implant, mesh or sutures to monitor oxygenation for wound healing, skin closure, hernia repair, flap transfer surgeries, reconstructive surgery, and other plastic surgery applications.
Measurement for microcirculatory dysfunction and peripheral artery disease and monitoring tissue oxygen in revascularization procedures or upon administration of drug.
Oncology applications to determine the degree of hypoxia in a tissue or organ and to monitor tumor growth in animal models used in oncology research and discovery.
Monitoring the state of pulmonary function, for example in COPD and asthma disease states.
Exercise or training optimization, e.g., soldier and athlete performance or personal exercise programs.
An oxygen-sensing tattoo.
Neuroscience monitoring applications where continuous monitoring of oxygen (for example in subarachnoid hemorrhage monitoring) is desired.
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