System and single-channel biosensor for and method of determining analyte value
Inventors
Rice, Brad • Gamsey, Soya • McMillan, William A.
Assignees
Publication Number
US-11331018-B2
Publication Date
2022-05-17
Expiration Date
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Abstract
Some embodiments described herein relate to a sensor that includes an analyte-sensing dye and a reference dye. The analyte-sensing dye can be configured to emit an analyte-dependent optical signal in the presence of an analyte. Similarly stated, the intensity and/or duration of the analyte-dependent optical signal can be modulated by a quantity and/or concentration of the analyte in the environment of the sensor. The reference dye can be configured to emit an analyte-independent optical signal. The analyte-dependent optical signal and the analyte-independent optical signal have an analyte-dependent spectrum and an analyte-independent spectrum, respectfully. The analyte-dependent optical spectrum and the analyte-independent spectrum can be the same, substantially the same, and/or overlapping. The analyte-dependent optical signal can have a duration of lifetime that is shorter than a duration or lifetime of the analyte-independent optical signal.
Core Innovation
Some embodiments relate to a sensor that includes an analyte-sensing dye and a reference dye, wherein the analyte-sensing dye is configured to emit an analyte-dependent optical signal in the presence of an analyte and the reference dye is configured to emit an analyte-independent optical signal. The analyte-sensing dye and the reference dye can each be configured to be excited by a common illumination signal, and the analyte-dependent optical spectrum and the analyte-independent spectrum can be the same, substantially the same, and/or overlapping. The analyte-dependent optical signal can have a duration or lifetime that is shorter than a duration or lifetime of the analyte-independent optical signal.
Some embodiments relate to a reader configured to excite the sensor and detect optical signals emitted from the sensor and to a method that includes illuminating a sensor, detecting an analyte-dependent optical signal and an analyte-independent optical signal, and determining a quantity of analyte based on a ratio of a short-lifetime intensity (SLI) of the analyte-dependent signal to a long-lifetime intensity (LLI) of the analyte-independent signal. The intensity ratio (SLI/LLI) can be used to normalize the analyte value for dynamic and tissue optics variations between the sensor and the surface of the skin where the reader is located, thereby providing a highly quantitative analyte measurement with reduced sensitivity to variables other than the analyte.
The background describes a need for implantable sensors that continuously and accurately determine quantities or concentrations of analytes in vivo, preferably in a non-invasive manner with minimal user maintenance and long sensor longevity. It also identifies challenges with intensity-based systems, including accuracy degradation due to dynamic tissue optics between an implanted sensor and a surface reader, motivating a need for single-channel luminescent sensors.
Claims Coverage
Two independent claims are identified (a system claim and a method claim) with 9 main inventive features extracted from the claims.
Sensor comprising analyte-sensing dye and reference dye with overlapping spectra
A sensor including an analyte-sensing dye configured to emit an analyte-dependent optical signal in the presence of an analyte and a reference dye configured to emit an analyte-independent optical signal, wherein the analyte-dependent spectrum and the analyte-independent spectrum overlap and the second duration exceeds the first duration.
Different lifetimes for analyte-dependent and analyte-independent signals
The analyte-dependent optical signal has a first duration and the analyte-independent optical signal has a second duration, where the second duration exceeds the first duration (the second duration being at least an order of magnitude greater than the first duration in some claims).
Light source configured to excite both dyes simultaneously
A reader including a light source configured to emit an illumination signal configured to excite the analyte-sensing dye and the reference dye, the analyte-sensing dye and the reference dye configured to emit their respective signals in response to being excited by the illumination signal.
Detector configured to detect both analyte-dependent and analyte-independent signals
A detector configured to detect the analyte-dependent optical signal and the analyte-independent optical signal, wherein the detector can be a single detector configured to detect each of the analyte-dependent optical signal and the analyte-independent optical signal.
Amplifier with variable gain processing time-separated signals
An amplifier having variable gain, configured to process a signal received during a first time period associated with the analyte-dependent optical signal with a first gain to produce a first processed signal, and to process a signal received during a second time period associated with the analyte-independent signal with a second gain different from the first gain to produce a second processed signal, the second time period being after the first time period.
Processor determining analyte quantity from ratio of processed signals
A processor configured to determine at least one of a concentration or a quantity of the analyte based on a ratio of the first processed signal and the second processed signal.
Sensor implantable in tissue with external reader
The sensor is configured to be implanted in tissue of a body and the reader is configured to be disposed outside the body, the sensor and the reader not being physically coupled.
Spectral overlap enabling single illumination and detection channels
The illumination signal has a spectrum configured to simultaneously excite both dyes and the emission spectra overlap so that a single illumination source and a single detection channel can be used to excite and detect both dyes.
Method of time-separated detection and gain-adjusted processing
A method comprising illuminating a sensor to simultaneously excite analyte-dependent and analyte-independent dyes with overlapping spectra and different durations, detecting the analyte-dependent signal during a first time period and processing it with an amplifier at a first gain, detecting the analyte-independent signal during a second time period after the first and processing it with the amplifier at a higher second gain, and determining an analyte quantity or concentration based on the ratio of the processed signals.
The independent system and method claims disclose a single-channel sensor architecture using an analyte-sensing dye and a reference dye with overlapping spectra but different lifetimes, a reader with a single illumination source and detector, an amplifier with time-dependent variable gain, and a processor that determines analyte concentration from the ratio of time-separated processed signals.
Stated Advantages
Enables use of a single illumination source and a single detector channel because the excitation and emission spectra of the analyte-sensing dye and reference dye are the same, substantially the same, or overlapping.
Reduces sensitivity to dynamic and tissue optics variations (e.g., motion artifacts, reader position, tissue depth, pressure, oxygenation, temperature) by normalizing analyte measurement using a short-lifetime to long-lifetime intensity ratio, providing a highly quantitative analyte measurement.
Avoids the requirement of a second light source, second detector, and/or second detection step that would be needed if dyes had different excitation or emission spectra.
Documented Applications
Monitoring analyte levels in vivo using an implantable single-channel luminescent sensor and a reader device for determining analyte concentration, including implantation a few millimeters under the skin with a reader on the surface of the skin.
Blood glucose monitoring for diabetic patients, wherein blood glucose measurements can be used to determine insulin dose amounts and self-monitoring of blood glucose levels by diabetic patients.
Continuous and/or implantable measurement of physiological, metabolic, or fatigue status and measuring concentrations of biothreat or therapeutic agents in vivo and providing early detection of disease prior to onset of symptoms.
Determining analyte concentration within blood or interstitial fluid of tissue for analytes including, for example, oxygen, glucose, lactate, carbon dioxide, H+, and OH− as explicitly listed in the specification.
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