Oxidase-based sensors and methods of using
Inventors
BALACONIS, Mary K. • Nichols, Scott
Assignees
Publication Number
US-11534503-B2
Publication Date
2022-12-27
Expiration Date
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Abstract
Oxidase-based sensors and methods of using the sensors are provided.
Core Innovation
The invention is directed to oxidase-based sensors comprising one or more analyte sensing populations that include (a) one or more polymers formed from one or more monomers, one or more comonomers, and one or more crosslinkers, (b) one or more oxidases, and (c) one or more oxygen sensitive dyes. The one or more monomers can be selected from 2-hydroxyethyl methacrylate (HEMA) and hydroxypropyl methacrylate (HPMA), the one or more comonomers can be selected from HPMA and n-hexylacrylate (nHA), and the one or more crosslinkers can be ethylene glycol dimethacrylate (EGDMA). The sensors can additionally include an oxygen reference population comprising an oxygen reference dye and can include multiple sensing populations that detect the same analyte or different analytes or the same analyte at different oxygen concentrations.
The background identifies a need for reliable and accurate long-term in vivo measurement of analytes without drawing blood, noting that current approaches require regular blood withdrawal and impose financial cost, pain and discomfort. Prior implanted sensors are described as typically failing after a relatively short period due to electrical failure, degradation of the analyte recognition element, component degradation and delamination, uptake of sensing particles by macrophages, migration through tissue, foreign body response and encapsulation, which limit accurate sensing. Thus there remains a need for sensing technologies that provide long-term (e.g., weeks, months or years) and accurate readings by remaining in contact with interstitial fluid and remaining in close proximity to the vasculature so that the interstitial fluid surrounding the sensor is in constant rapid equilibrium with nearby capillaries.
Without being bound by a particular mechanism, the sensors are described as functioning when the analyte is enzymatically converted and oxygen is consumed by the enzyme, such that measurement of oxygen depletion by an oxygen-sensitive dye provides a signal related to analyte concentration; luminescence and phosphorescent lifetimes from the oxygen-sensitive dyes are thus proportional to the concentration of the analyte in the sensor. Measurements are collected non-invasively through luminescent near infrared signals with an optical reader located outside of the body. The disclosure describes embodiments for measuring analytes such as lactate, glucose and alcohol using corresponding oxidases including lactate oxidase, glucose oxidase and alcohol oxidase, and contemplates polymer variants including methacrylate/acrylate and methacrylamide/acrylamide chemistries.
Claims Coverage
The patent includes one independent claim (claim 1) with three main inventive features.
Polymer formed from specified monomers, comonomers, and crosslinker
One or more polymers formed from one or more monomers, one or more comonomers, and one or more crosslinkers, wherein the one or more monomers are selected from HEMA and HPMA, the one or more comonomers are selected from HPMA and n-hexylacrylate (nHA), the one or more crosslinkers is ethylene glycol dimethacrylate (EGDMA), and the one or more comonomers is different from the one or more monomers.
Incorporation of one or more oxidases
The analyte sensing population comprises one or more oxidases.
Inclusion of one or more oxygen sensitive dyes
The analyte sensing population comprises one or more oxygen sensitive dyes.
Claim 1 defines a sensor combining a polymer composition with specified monomer/comonomer/crosslinker selections, incorporation of one or more oxidases, and inclusion of one or more oxygen sensitive dyes; dependent claims further specify analytes (e.g., lactate, glucose, alcohol), an oxygen reference population, additional sensing populations, and positional ranges for reference populations.
Stated Advantages
Provide non-invasive, real-time, continuous analyte measurements in a user-friendly, cost-effective format.
Allow first responders to begin monitoring in the field, providing an early assessment by the time the patient reaches the emergency room.
Be beneficial in non-traditional clinical environments such as developing countries and military field operations.
Documented Applications
Blood glucose monitoring for diabetic patients to ensure correct insulin dosing and long-term glycemic control.
Lactate monitoring for assessment of health, disease state, acute conditions (e.g., sepsis and trauma), metabolic activity, and exercise physiology, including use by first responders and in critical care.
Monitoring trauma, sepsis, exercise physiology/performance optimization, skin grafts, wound healing, and shock.
Alcohol (ethanol) detection using alcohol oxidase-based sensors.
Implantation or placement subcutaneously, surrounding tissue of muscle, subcutaneous fat, dermis, in muscle, in skin, in the limbs, sternum, neck, ear, brain, or other locations for in vivo monitoring.
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