Patent Description:
The present invention relates to calculating levels in a first medium using measurements from a second medium. More specifically, aspects of the present invention relate to using estimating the rate of change of the level in the second medium using a measurement of the level in the second medium and one or more diffusion barrier-delayed measurements of the level in the second medium. Even more specifically, aspects of the present invention relate to calculating a blood analyte level using a measurement of an interstitial fluid analyte level and one or more measurements of diffusion barrier-delayed measurements of the interstitial fluid analyte level to instantaneously estimate the rate of change of the interstitial fluid analyte level.

Analyte monitoring systems may be used to monitor analyte levels, such as analyte concentrations. One type of analyte monitoring system is a continuous glucose monitoring (CGM) system. A CGM system measures glucose levels throughout the day and can be very useful in the management of diabetes. Some analyte monitoring systems use measurements indicative of analyte levels in interstitial fluid ("ISF") to calculate ISF analyte levels and then convert the ISF analyte levels to blood analyte levels. The analyte monitoring systems may display the blood analyte levels to a user. Exemplary analyte monitoring systems are known from <CIT>; from <NPL>; and from <CIT>.

However, because ISF analyte levels lag behind blood analyte levels, accurate conversion of ISF analyte levels to blood analyte levels is difficult.

Aspects of the present invention relate to improving the accuracy of blood analyte levels displayed to a user.

One aspect of the invention may provide an analyte detection system comprising a sensor configured for at least partial placement in an analyte-containing medium. In some embodiments, the sensor may include a first transducer that exhibits one or more detectable properties based on an amount or concentration of an analyte in proximity to the first transducer. The sensor includes a first diffusion barrier arranged such that, when the sensor is placed in the medium, analyte contained in the medium diffuses through the first diffusion barrier before reaching the first transducer, wherein the first diffusion barrier is configured such that analyte contained in the medium diffuses through the first diffusion barrier at a first diffusion rate r<NUM>. The sensor further includes a second transducer that exhibits one or more detectable properties based on an amount or concentration of an analyte in proximity to the second transducer. In some embodiments, when the sensor is placed in the medium, diffusion of analyte contained in the medium to the first transducer is delayed relative to diffusion of analyte contained in the medium to the second transducer.

In any of the above embodiments, the first diffusion barrier may comprise an outer surface configured to be disposed adjacent the analyte-containing medium, an inner surface disposed opposite the outer surface and adjacent the first transducer, and a first thickness defined between the outer surface and the inner surface of the first diffusion barrier. In some embodiments, the second diffusion barrier may comprise an outer surface configured to be disposed adjacent the analyte-containing medium, an inner surface disposed opposite the outer surface and adjacent the second transducer, and a second thickness defined between the outer surface and the inner surface of the second diffusion barrier. In some embodiments, the second thickness may be greater than the first thickness such that when the sensor is placed in the medium, analyte diffusing from the medium will exhibit a greater lag time diffusing through the second diffusion barrier than through the first diffusion barrier.

In any of the above embodiments, the first diffusion barrier may be disposed over the first transducer, and the first diffusion barrier may be configured such that, when the sensor is placed in the medium, the first diffusion barrier at least partially inhibits diffusion of analyte to the second transducer.

In any of the above embodiments, the second diffusion barrier may be disposed over the second transducer, and the second diffusion barrier may be configured such that, when the sensor is placed in the medium, the second diffusion barrier at least partially inhibits diffusion of analyte to the second transducer, and the first diffusion barrier inhibits diffusion of analyte to a greater degree than the second diffusion barrier.

In any of the above embodiments, the sensor may include a third transducer that exhibits one or more detectable properties based on an amount or concentration of an analyte in proximity to the third transducer. In some embodiments, the sensor may further include a third diffusion barrier arranged such that, when the sensor is placed in the medium, analyte contained in the medium may diffuse through the third diffusion barrier before reaching the third transducer. In some embodiments, the third diffusion barrier may be configured such that analyte contained in the medium diffuses through the third diffusion barrier at a third diffusion rate r<NUM>, wherein r<NUM> is greater than r<NUM>.

In any of the above embodiments, the second transducer may be arranged such that, when the sensor is placed in the medium, analyte contained in the medium need not diffuse through a diffusion barrier before reaching the second transducer.

The ananalyte detection system according to the invention further includes a transceiver configured to receive first sensor data collected from the first transducer. The transceiver is also configured to receive second sensor data collected from the second transducer. The transceiver is further configured to calculate an interstitial fluid analyte level rate of change based on at least the first sensor data, the second sensor data, and r<NUM>.

In any of the above embodiments, the analyte-containing medium may be an interstitial fluid, and the analyte level rate of change may be an interstitial fluid analyte level rate of change.

In any of the above embodiments, the system may comprise a second diffusion barrier arranged such that when the sensor is placed in the interstitial fluid, analyte contained in the interstitial fluid may diffuse through the second diffusion barrier before reaching the first transducer. In some embodiments, the second transfusion barrier may be further configured such that analyte contained in the interstitial fluid diffuses through the second diffusion barrier at a second diffusion rate r<NUM>, r<NUM> being greater than r<NUM>. In embodiments, calculating the interstitial fluid analyte level rate of change may be further based on r<NUM>.

In a second third aspect, which may be combinable with features of any of the above embodiments, a method for detecting the rate of change of an analyte concentration in a medium is provided. The method includes using the transceiver of the above-mentioned system to receive from a sensor at least first sensor data corresponding to a first measurement of a detectable property exhibited by a first transducer and second sensor data corresponding to a second measurement of a detectable property exhibited by a second transducer. The first sensor data is indicative of an amount or concentration of an analyte in proximity to the first transducer after passing through a first diffusion barrier The method further includes using the transceiver to calculate the analyte level rate of change based on at least the first sensor data, the second sensor data, and a first diffusion rate r<NUM> of the analyte through the first diffusion barrier.

In any of the above embodiments of the second aspect, a detectable property exhibited by the second transducer may be indicative of an amount or concentration of the analyte in proximity to the second transducer after passing through a second diffusion barrier. In some embodiments, calculating the analyte level rate of change may be further based on a second diffusion rate r<NUM> of the analyte through the second diffusion barrier, r<NUM> being greater than r<NUM>.

In any of the above embodiments of the second aspect, the method may include calculating an interstitial fluid analyte level based on at least one of the first sensor data and the second sensor data. In some embodiments, the method may include calculating a blood analyte level based on the interstitial fluid analyte level and the analyte level rate of change.

In any of the above embodiments of the second aspect, the method may include detecting that a transceiver is positioned within a proximity of the sensor. In some embodiments, the method may include transmitting, in response to detecting that the transceiver is proximate the sensor, from the transceiver to the sensor power sufficient to perform the first measurement and the second measurement, the transmitted power being used to perform the first measurement and the second measurement. In some embodiments, the method may include removing the transceiver from the proximity of the sensor. In some embodiments, this removing step may occur after receiving from the sensor the first sensor data and the second sensor data, and before additional measurements are performed.

Further variations encompassed within the systems and methods are described in the detailed description of the invention below.

The accompanying drawings illustrate various, non-limiting examples.

In the drawings, like reference numbers indicate identical or functionally similar elements.

<FIG> is a schematic view of an analyte monitoring system embodying aspects of the present invention. In one non-limiting embodiment, the system includes a sensor <NUM> and an external transceiver <NUM>. In the embodiment shown in <FIG>, the sensor <NUM> is implanted in a living animal (e.g., a living human). The sensor <NUM> may be implanted, for example, in a living animal's arm, wrist, leg, abdomen, or other region of the living animal suitable for sensor implantation. For example, as shown in <FIG>, in one non-limiting embodiment, the sensor <NUM> may be implanted between the skin and subcutaneous tissues. In some embodiments, the sensor <NUM> may be an optical sensor. In some embodiments, the sensor <NUM> may be a chemical or biochemical sensor.

In some embodiments, as illustrated in <FIG> and <FIG>, the transceiver <NUM> may be an electronic device that communicates with the sensor <NUM> to power the sensor <NUM> and/or obtain analyte (e.g., glucose) readings from the sensor <NUM>. In some non-limiting embodiments, the transceiver <NUM> may be a handheld reader, a wristwatch, waistband, armband, keychain attachment, or it may be incorporated within or a component of a user device <NUM> (e.g., a smartphone, personal data assistant, handheld device, or laptop computer). In other non-limiting embodiments, the transceiver <NUM> may be held on a user's body by adhesive (e.g., as part of a biocompatible patch). In some embodiments, positioning (i.e., hovering or swiping/waiving/passing) the transceiver <NUM> within range over the sensor implant site (i.e., within proximity of the sensor <NUM>) may cause the transceiver <NUM> to automatically convey a measurement command to the sensor <NUM> and receive a reading from the sensor <NUM>.

In some embodiments, as shown in <FIG>, the transceiver <NUM> may include one or more of an antenna <NUM> and a processor <NUM>. The processor <NUM> may perform one or more of steps <NUM>, <NUM>, <NUM>, and <NUM> as illustrated in <FIG> and discussed below. In some embodiments, the transceiver may include a user interface <NUM>. In one non-limiting embodiment, the user interface <NUM> may include one or more of a liquid crystal display (LCD) and vibration motor, but, in other embodiments, different types of user interfaces may be used, or the transceiver <NUM> may not include a user interface.

In some embodiments, the antenna <NUM> may include an inductive element, such as, for example, a coil. In some embodiments, the antenna <NUM> may generate an electromagnetic wave or electrodynamic field (e.g., by using a coil) to induce a current in an inductive element of the sensor <NUM>, which may power the sensor <NUM> via an inductive element (e.g., inductive element <NUM> of <FIG>) disposed in the sensor <NUM> and configured to receive and/or transmit electromagnetic waves or electrodynamic fields from and/or to the transceiver antenna <NUM>. In some embodiments, the antenna <NUM> may additionally or alternatively convey data (e.g., commands) to the sensor <NUM>. For example, in a non-limiting embodiment, the antenna <NUM> may convey data by modulating the electromagnetic wave used to power the sensor <NUM> (e.g., by modulating the current flowing through a coil of the antenna <NUM>). The modulation in the electromagnetic wave generated by the transceiver <NUM> may be detected/extracted by the sensor <NUM>. Moreover, the antenna <NUM> may receive data (e.g., measurement information) from the sensor <NUM>. For example, in a non-limiting embodiment, the antenna <NUM> may receive data by detecting modulations in the electromagnetic wave generated by the sensor <NUM>, e.g., by detecting modulations in the current flowing through the coil of the antenna <NUM>.

The inductive element of the transceiver <NUM> and the inductive element (e.g., inductive element <NUM> illustrated in <FIG>) of the sensor <NUM> may be in any configuration that permits adequate field strength to be achieved when the two inductive elements are brought within adequate physical proximity.

In some embodiments, the processor <NUM> may calculate one or more analyte concentrations based on the analyte readings received from the sensor <NUM>. In some embodiments, the processor <NUM> may also generate one or more alerts and/or alarms based on the calculated analyte concentrations (e.g., if the calculated analyte concentration exceeds or falls below one or more thresholds). The calculated analyte concentrations, alerts, and/or alarms may be communicated (e.g., displayed) via the user interface <NUM>.

In some embodiments, the transceiver <NUM> may communicate (e.g., using a wireless communication standard, such as, for example and without limitation, Bluetooth) with a user device (e.g., a smartphone, personal data assistant, handheld device, or laptop computer). In other embodiments, the transceiver <NUM> may be incorporated within or a component of a user device. In some embodiments, the user device may receive calculated analyte concentrations, alerts, and/or alarms from the transceiver <NUM> and display them. Display by the user device may be in addition to, or in the alternative to, display by the user interface <NUM> of the transceiver <NUM>. For example, in some embodiments, as illustrated in <FIG>, the transceiver <NUM> may include a user interface <NUM>, but this is not required. In some alternative embodiments, the transceiver <NUM> may not have a user interface <NUM>, and calculated analyte concentrations, alerts, and/or alarms may instead be displayed by a user device. In other embodiments, the transceiver <NUM> may be incorporated within or a component of a user device, and the transceiver <NUM> and user device may share a user interface and/or display.

In some non-limiting embodiments, the transceiver <NUM> and sensor <NUM> may have some or all of the structure described in <CIT>and <CIT>.

<FIG> illustrate aspects of non-limiting examples of a sensor <NUM> that may be used in the analyte monitoring system illustrated in <FIG>. In some embodiments, the sensor <NUM> may be an optical sensor. In one non-limiting embodiment, sensor <NUM> includes a sensor housing <NUM> (i.e., body, shell, or capsule). In exemplary embodiments, sensor housing <NUM> may be formed from a suitable, optically transmissive polymeric material, such as, for example, acrylic polymers (e.g., polymethylmethacrylate (PMMA)).

The sensor <NUM> includes a first transducer <NUM> and a second transducer <NUM>. In some embodiments, the first transducer <NUM> may include one or more first indicator molecules <NUM>. In some non-limiting embodiments, the second transducer <NUM> may include one or more second indicator molecules <NUM>. In some embodiments, the first and second indicator molecules <NUM>, <NUM> may be fluorescent indicator molecules or absorption indicator molecules. In some non-limiting embodiments, the first and second indicator molecules <NUM>, <NUM> may be as described in <CIT> or <CIT>. In some non-limiting embodiments, one or more of the transducers <NUM>, <NUM> may include a polymer graft (e.g., matrix layer or hydrogel) coated or embedded on or in at least a portion of the exterior surface of the sensor housing <NUM>. In some non-limiting embodiments, first and second indicator molecules <NUM>, <NUM> may be distributed throughout the polymer graft. In some embodiments, the first and second transducers <NUM>, <NUM> may be embedded within the sensor housing <NUM>. In some embodiments, the first and second transducers <NUM>, <NUM> may cover the entire surface of sensor housing <NUM> or only one or more portions of the surface of housing <NUM>. In some non-limiting embodiments, the first indicator molecules <NUM> may be distributed throughout the entire first transducer <NUM> or only throughout one or more portions of the first transducer <NUM>. In some non-limiting embodiments, the second indicator molecules <NUM> may be distributed throughout the entire second transducer <NUM> or only throughout one or more portions of the second transducer <NUM>.

In some embodiments, as shown in <FIG>, the sensor <NUM> may include one or more light sources <NUM>, which may be, for example, a light emitting diode (LED) or other light source that emits light over a range of wavelengths that interact with the first and second indicator molecules <NUM>, <NUM>. In some embodiments, the second indicator molecules <NUM> may be chemically identical to first indicator molecules <NUM>, and/or may interact with and/or emit the same or similar wavelengths of light. In other embodiments, the second indicator molecules <NUM> may differ from the first indicator molecules <NUM>, and/or may interact with and/or emit different wavelengths of light.

In some embodiments, the sensor <NUM> may include one or more photodetectors <NUM>, <NUM> (e.g., photodiodes, phototransistors, photoresistors, or other photosensitive elements). In some embodiments, the one or more photodetectors of the sensor <NUM> may include one or more signal photodetectors <NUM> that may be sensitive to emission light (e.g., fluorescent light) emitted by the indicator molecules <NUM>, <NUM> such that a signal may be generated by the photodetectors <NUM> in response thereto that is indicative of the level of the indicator molecules <NUM>, <NUM> and, thus, the concentration of analyte of interest (e.g., glucose). In some embodiments, as shown in <FIG>, the one or more signal photodetectors <NUM> may include at least one first signal photodetector 226a configured to receive first emission light 331a emitted by the first indicator molecules <NUM> of the first transducer <NUM> and to output a signal indicative of an amount thereof. In some embodiments, as shown in <FIG>, the one or more signal photodetectors <NUM> may include at least one second signal photodetector 226b configured to receive second emission light 331b light emitted by the second indicator molecules <NUM> of the second transducer <NUM> and to output a signal indicative of an amount thereof.

In some embodiments, the one or more photodetectors of the sensor <NUM> may include one or more reference photodetectors <NUM> that may be sensitive to excitation light <NUM> (e.g., ultraviolet light) emitted by the one or more light sources <NUM> such that a signal may be generated by the photodetectors <NUM> in response thereto that is indicative of an amount of excitation light <NUM> reflected by the first and second transducers <NUM>, <NUM>. In some embodiments, as shown in <FIG>, the one or more reference photodetectors <NUM> may include at least one first reference photodetector 224a configured to receive excitation light <NUM> reflected by the first transducer <NUM> and to output a signal indicative of an amount thereof. In some embodiments, as shown in <FIG>, the one or more reference photodetectors <NUM> may include at least one second reference photodetector 224b configured to receive excitation light <NUM> reflected by the second transducer <NUM> and to output a signal indicative of an amount thereof.

As illustrated in <FIG>, some embodiments of sensor <NUM> include one or more optical filters 112a, 112b, 113a, 113b, such as high pass or band pass filters, and the sensor <NUM> may be configured such that light passes through an optical filter 112a, 112b, 113a, or 113b before reaching a photosensitive side of the one or more photodetectors 224a, 224b, 226a, 226b. In some non-limiting embodiments, the one or more optical filters 112a, 112b, 113a, 113b may cover a photosensitive side of the one or more photodetectors 224a, 224b, 226a, 226b, respectively.

In some embodiments, sensor <NUM> may be wholly self-contained. In other words, the sensor may be constructed in such a way that no electrical leads extend into or out of the sensor housing <NUM> to supply power to the sensor (e.g., for driving a light source <NUM>) or to convey signals from the sensor <NUM>. In some non-limiting embodiments, the sensor <NUM> may be powered by an external power source (e.g., external transceiver <NUM>). For example, the external power source may generate a magnetic field to induce a current in an inductive element <NUM> (e.g., a coil or other inductive element). In some embodiments, the sensor <NUM> may use the inductive element <NUM> to communicate information to an external sensor reader (e.g., transceiver <NUM>). In some embodiments, the external power source and data reader may be the same device (e.g., transceiver <NUM>). In some embodiments, an antenna <NUM> of transceiver <NUM> may be arranged as a coil that wraps around the sensor <NUM>. In other embodiments, the sensor may have a different configuration, such as, for example, those described in <CIT>, with particular reference to FIGS. 2A-2C, or those described in <CIT>.

In some embodiments, the sensor <NUM> may include a substrate <NUM>. In some non-limiting embodiments, the substrate <NUM> may be a semiconductor substrate and circuitry may be fabricated in the semiconductor substrate <NUM> (see <FIG>). In some embodiments, the circuitry may include analog and/or digital circuitry. In some embodiments, the circuitry may incorporate some or all of the structure described in <CIT>, with particular reference to FIG. Although in some embodiments the circuitry may be fabricated in the semiconductor substrate <NUM>, in alternative embodiments, a portion or all of the circuitry may be mounted or otherwise attached to the semiconductor substrate <NUM>. In other words, in alternative embodiments, a portion or all of the circuitry may include discrete circuit elements, an integrated circuit (e.g., an application specific integrated circuit (ASIC)) and/or other electronic components discrete and may be secured to the semiconductor substrate <NUM>, which may provide communication paths between the various secured components. In some alternative embodiments, the substrate <NUM> may be a printed circuit board.

In some embodiments, the one or more photodetectors <NUM>, <NUM> may be mounted on the semiconductor substrate <NUM>, but, in some embodiments, as shown in <FIG>, the one or more photodetectors <NUM>, <NUM> may be fabricated in the semiconductor substrate <NUM>. In some embodiments, the one or more light sources <NUM> may be mounted on the semiconductor substrate <NUM>. For example, in a non-limiting embodiment, the light source(s) <NUM> may be flip-chip mounted on the semiconductor substrate <NUM>. However, in some embodiments, the light source(s) <NUM> may be fabricated in the semiconductor substrate <NUM>.

According to one aspect of the invention, the sensor <NUM> may be configured to measure various biological analytes in the living body of an animal (including a human). For example, sensor <NUM> may be used to measure glucose, oxygen toxins, pharmaceuticals or other drugs, hormones, and other metabolic analytes in, for example, the human body. The specific composition of the transducers <NUM>, <NUM> and the indicator molecules <NUM>, <NUM> therein may vary depending on the particular analyte the sensor is to be used to detect and/or where the sensor is to be used to detect the analyte (i.e., in interstitial fluid). The transducers <NUM>, <NUM> may facilitate exposure of the indicator molecules <NUM>, <NUM> to the analyte. The optical characteristics of the indicator molecules (e.g., the level of fluorescence of fluorescent indicator molecules) may be a function of the concentration of the specific analyte to which the indicator molecules are exposed.

In some embodiments, one or more the light sources <NUM> may be positioned to emit excitation light <NUM> that travels within the sensor housing <NUM> and reaches the first and second indicator molecules <NUM>, <NUM> of the first and second transducers <NUM>, <NUM>, respectively. In some embodiments, the photodetectors 224a, 226a, which may be located beneath filters 112a, 113a, may be positioned to receive light from the first indicator molecules <NUM> of the first transducer <NUM>. In some embodiments, the photodetectors 224b, 226b, which may be located beneath filters 112b, 113b, may be positioned to receive light from the second indicator molecules <NUM> of the second transducer <NUM>.

In operation, as shown in <FIG>, the light source(s) <NUM> may emit excitation light <NUM> that travels within the sensor housing <NUM> and reaches the first and second indicator molecules <NUM>, <NUM> of the first and second transducers <NUM>, <NUM>. In a non-limiting embodiment, the excitation light <NUM> may cause the indicator molecules <NUM>, <NUM> distributed in transducers <NUM>, <NUM> to emit light (e.g., to fluoresce). In some embodiments, the transducers <NUM>, <NUM> may be permeable to the analyte (e.g., glucose) in the medium (e.g., blood or interstitial fluid) into which the sensor <NUM> is implanted. Accordingly, in some embodiments, the first and second indicator molecules <NUM>, <NUM> in the first and second transducers <NUM>, <NUM>, respectively, may interact with the analyte in the medium and, when irradiated by the excitation light <NUM>, may emit first and second emission light 331a, 331b, respectively, which may be indicative of the presence and/or concentration of the analyte in the medium. In some embodiments, the one or more of the first and second emission light 331a and 331b may be, for example and without limitation, fluorescent light.

In some embodiments, the photodetectors <NUM>, <NUM> may receive light. In some embodiments, the one or more photodetectors <NUM> may be covered by filters <NUM>, and the one or more photodetectors <NUM> may be covered by filters <NUM>. In some embodiments, the filters <NUM>, <NUM> may allow only a certain subset of wavelengths of light to pass through. In some embodiments, the filters <NUM>, <NUM> may be thin film (e.g., dichroic) filters deposited on glass, and the filters <NUM>, <NUM> may pass only a narrow band of wavelengths and otherwise reflect (or absorb) the remaining light. In some embodiments, the filters <NUM>, <NUM> may be identical (e.g., each filter <NUM>, <NUM> may allow signal light to pass) or different (e.g., filters <NUM> may allow signal light to pass, and filters <NUM> may allow reference light to pass). In some embodiments where the first and second indicator molecules <NUM>, <NUM> emit light at different wavelengths, the signal light filter 112a may be configured to pass light 331a emitted by the first indicator molecules <NUM> to the first signal photodetector 226a but to reflect (or absorb) the excitation light <NUM> and the light 331b emitted by the second indicator molecules <NUM>. Similarly, the signal light filter 112b may be configured to pass light 331b emitted by the second indicator molecules <NUM> to the second signal photodetector 226b but to reflect (or absorb) the excitation light <NUM> and the light 331a emitted by the first indicator molecules <NUM>. In this manner, the first and second signal photodetectors 226a and 226b disposed under the signal light filters 112a and 112b, respectively, may be selected to receive only a respective one of light 331a and 331b emitted by the first and second indicator molecules <NUM>, <NUM> of the first and second transducer <NUM>, <NUM>, respectively.

In some embodiments, the filters <NUM> may pass light at the same wavelength as the wavelength of the excitation light <NUM> emitted from the light source <NUM> (e.g., <NUM>). In some embodiments, first indicator molecules <NUM> and second indicator molecules <NUM> may be excited by light emitted at different wavelengths. In such embodiments, multiple (e.g., two) light sources <NUM> may be provided, wherein one light source <NUM> emits light at a wavelength capable of exciting indicator molecules <NUM>, and a second light source <NUM> emits light at a wavelength capable of exciting indicator molecules <NUM>.

Photodetectors 226a, 226b may be signal photodetectors that detect the amount of fluoresced light <NUM> that is emitted from the first and second indicator molecules <NUM>, <NUM> in the first and second transducers <NUM>, <NUM>. In some non-limiting embodiments, the signal filters 112a, 112b-which may in some embodiments cover photodetectors 224a, 224b-may pass light in the range of about <NUM> to <NUM>. Higher analyte levels may correspond to a greater amount of fluorescence of the molecules <NUM>, <NUM> in the transducers <NUM>, <NUM>, and therefore, a greater amount of photons striking the signal photodetectors <NUM>.

As illustrated in <FIG>, a diffusion barrier <NUM> is disposed on or over a portion of the sensor body <NUM>. In some embodiments, the diffusion barrier <NUM> may be formed as a membrane, graft, mesh, sputtered layer, or any other structural arrangement configured to permit at least partial diffusion of analyte therethrough. When the sensor <NUM> is implanted, for example in a medium such as interstitial fluid, analyte may diffuse through the diffusion barrier <NUM> before reaching the transducer <NUM>. The diffusion barrier <NUM> may have an associated diffusion rate r, which may represent the rate at which analyte may diffuse across the diffusion barrier <NUM>. The diffusion barrier <NUM> may further have an associated lag time τ, which may represent the time for analyte to diffuse across the diffusion barrier <NUM>. The lag time τ and diffusion rate r may be inversely related (e.g., τ may be equal to <NUM>/r). Values for both lag time τ and diffusion rate r may be determined or measured in advance through quality assurance or testing practices.

In some embodiments, such as that illustrated in <FIG>, only one transducer <NUM> is covered by a diffusion barrier <NUM>. In this manner, analyte in the medium will reach the transducer <NUM> at a delay (which may correspond to lag time τ) relative to when it reaches transducer <NUM>. Thus, signal received from the transducer <NUM> may be indicative of current analyte levels proximate the sensor <NUM>, and signal received from the transducer <NUM> may be indicative of analyte levels proximate the sensor <NUM> at a time period (which may correspond to lag time τ) prior to the time at which the measurement signal is received. By comparing the measurements from the transducers <NUM>, <NUM>, an analyte level rate of change proximate the sensor <NUM> may be calculated. In some embodiment, this rate of change may be calculated based on measurement data received from the first transducer <NUM>, measurement data received from the second transducer <NUM>, and the diffusion rate r and/or lag time τ of the diffusion barrier <NUM>.

In other exemplary embodiments, as illustrated in <FIG>, the first transducer <NUM> may be covered by a first diffusion barrier <NUM>, and the second transducer <NUM> may be covered by a second diffusion barrier <NUM>. The first and second diffusion barriers <NUM> and <NUM> may have different diffusion characteristics. For example, the first diffusion barrier <NUM> may have a first diffusion rate r<NUM> and a first lag time τ<NUM>, and the second diffusion barrier <NUM> may have a second diffusion rate r<NUM> and a second lag time τ<NUM>, each different than the respective values for the diffusion barrier <NUM>. Values for the diffusion rates and lag times may be determined or measured in advance through quality assurance or testing practices. Signal received from the first transducer <NUM> may be indicative of analyte levels proximate the sensor <NUM> at a time period (which may correspond to lag time τ<NUM>) prior to the time at which the measurement signal is received, and signal received from the second transducer <NUM> may be indicative of analyte levels proximate the sensor <NUM> at a time period (which may correspond to lag time τ<NUM>) prior to the time at which the measurement signal is received. By comparing the measurements from the first and second transducers <NUM>, <NUM>, an analyte level rate of change proximate the sensor <NUM> may be calculated. In some embodiment, this rate of change may be calculated based on measurement data received from the first transducer <NUM>, measurement data received from the second transducer <NUM>, the diffusion rate r<NUM> and/or lag time τ<NUM> of the diffusion barrier <NUM>, and the diffusion rate r<NUM> and/or lag time τ<NUM> of the diffusion barrier <NUM>.

A difference between the diffusion rates (and lag times) of the diffusion barriers <NUM>, <NUM> may be effected by varying any of a variety of characteristics of the respective diffusion barriers <NUM>, <NUM>. For example, as illustrated in <FIG>, the diffusion barriers <NUM>, <NUM> may have different thicknesses. In other embodiments, the diffusion barriers <NUM>, <NUM> may have different porosities or structural characteristics (e.g., channels) allowing passage of analyte. In still other embodiments, the diffusion barriers <NUM>, <NUM> may have different chemical compositions, such that one of the barriers may be more or less hydrophobic or hydrophilic than the other. Other arrangements for controlling the diffusion rates of the diffusion membranes may be used.

Although one diffusion barrier <NUM> is shown in <FIG> and <FIG> and two diffusion barriers <NUM> and <NUM> are shown in <FIG>, in some embodiments, the sensor <NUM> may include more than two diffusion barriers. For example, as shown in <FIG>, the sensor <NUM> may include first, second, and third diffusion barriers <NUM>, <NUM>, and <NUM>, each with differing diffusion characteristics. In other embodiments, the sensor <NUM> may have more than three diffusion barriers with differing diffusion characteristics.

Similarly, although two transducers <NUM> and <NUM> are shown in <FIG>, in some embodiments, the sensor <NUM> may include more than two transducers. For example, as shown in <FIG>, the sensor <NUM> may include first, second, third, and fourth transducers <NUM>, <NUM>, <NUM>, and <NUM>. In some embodiments, the sensor <NUM> may use the additional transducers with additional diffusion barriers to measure simultaneously analyte levels at additional lag times. In some embodiments, the transceiver <NUM> may use these additional measurements to obtain a more accurate estimate for the analyte level rate of change proximate the sensor body <NUM>. In some non-limiting embodiments, the transceiver <NUM> perform non-linear regression to calculate the analyte level rate of change using the differently delayed analyte levels.

As illustrated in <FIG> and <FIG>, the transducers <NUM>, <NUM> may be axially arranged along the length of the sensor body <NUM>, such that the transducer <NUM> is disposed along a first axial portion of the sensor body <NUM>, and the transducer <NUM> is disposed along a second axial portion of the sensor body <NUM>, the first axial portion being different than the first. The photodetectors <NUM>, <NUM> and optical filters <NUM>, <NUM> may also be axially arranged, such that the photodetectors <NUM>, <NUM> and optical filters <NUM>, <NUM> for measuring signal from the transducer <NUM> may be disposed along the first axial portion of the sensor body <NUM>, and the photodetectors <NUM>, <NUM> and optical filters <NUM>, <NUM> for measuring signal from the transducer <NUM> may be disposed along the second axial portion of the sensor body <NUM>.

<FIG> shows a cross-sectional view of another exemplary embodiment of a sensor <NUM>. In some embodiments, as illustrated in <FIG>, the transducers <NUM>, <NUM> may be circumferentially arranged along the perimeter of the sensor body <NUM>, such that the transducer <NUM> is disposed along a first perimeter portion of the sensor body <NUM>, and the transducer <NUM> is disposed along a second perimeter portion of the sensor body, the first perimeter portion being different than the first.

The embodiment illustrated in <FIG> features many of the same elements and function as discussed above with respect to <FIG> and <FIG>. Here, however, a divider member <NUM> may be disposed between the transducers <NUM> and <NUM>. The divider member <NUM> may be opaque to the wavelengths of light emitted by the transducers <NUM> and <NUM> and/or the light source <NUM>, thereby isolating the measurement signals received from the respective transducers <NUM>, <NUM>. In embodiments in which an opaque divider member <NUM> is provided, signal produced by the first and second transducers <NUM>, <NUM> may be naturally isolated. The first and second indicator molecules <NUM>, <NUM> of the first and second transducers <NUM>, <NUM>, respectively, may emit light at the same wavelength or at different wavelengths.

<FIG> illustrate exemplary arrangements for providing a diffusion barrier over one or more of the first and second transducers <NUM>, <NUM>. <FIG> illustrates a sensor <NUM> without a diffusion barrier <NUM>, and <FIG> shows the sensor <NUM> with the diffusion membrane <NUM>. In some non-limiting embodiments, the sensor <NUM> may have a sensor housing/shell <NUM> and transducers <NUM>, <NUM> embedded within and/or covering at least a portion of the housing <NUM>. In some embodiments, the first transducer <NUM> may include one or more first indicator molecules <NUM>, and the second transducer <NUM> may include one or more second indicator molecules <NUM>, as discussed above.

In some embodiments, the diffusion barrier <NUM> may be a polymer membrane that is deposited over the surface of sensor body <NUM>. The polymer membrane may then be partially or fully removed from a portion of the sensor body <NUM>, such as directly over transducer <NUM> to thereby reduce the diffusion lag time associated with transducer <NUM>. In other embodiments, the lag time may be selectively controlled by machining or processing the membrane after deposition on the sensor body. In still other embodiments, portions of the sensor body <NUM> may be wrapped in a removable material prior to applying the polymer membrane, thereby selectively preventing or inhibiting the membrane from being deposited over the transducer <NUM> and/or other portions of the sensor body <NUM>.

As illustrated in the exemplary embodiment of <FIG>, a mesh <NUM> may be provided over a portion <NUM> of the sensor body <NUM>. One or more of the transducers may be disposed within the sensor body portion <NUM>. The mesh <NUM> may itself act as a diffusion barrier. For example, mesh fibers (e.g., metallic or polymeric fibers) may be woven at selected densities in order to selectively control the diffusion characteristics at different positions along the mesh <NUM>. In other embodiments, a graft material (e.g., a polymeric graft) may be affixed to the mesh <NUM>, which may then be affixed at a selected portion of the sensor body <NUM> (see also <FIG>, depicting a polymeric graft affixed to a selected portion of a sensor body).

<FIG> illustrates an exemplary embodiment in which a material is selectively sputtered onto a portion <NUM> of a sensor body <NUM>, thereby forming a diffusion barrier <NUM>. As shown in <FIG>, the diffusion barrier <NUM> may cover transducer <NUM> but not transducer <NUM>. In other embodiments, the diffusion barrier <NUM> may cover both transducer <NUM> and <NUM>, but may be deposited to form a thicker or denser coating over transducer <NUM> relative to transducer <NUM>.

<FIG> depicts a diagram in which a sensor <NUM> is implanted within the interstitial fluid under a subject's skin and proximate to a capillary. In some embodiments, it may be desired to precisely estimate a concentration of analyte contained within the subject's blood. For example, the analyte monitoring system may be used to estimate a blood glucose level within a capillary as depicted in <FIG>. Analyte molecules (e.g., glucose) may diffuse from the capillary through the interstitial fluid toward the sensor <NUM>. After reaching the sensor <NUM>, the analyte molecules may diffuse through any diffusion barriers and into the transducers to interact with indicator molecules disposed therein. The sensor <NUM> is able to detect analyte concentration when the analyte molecules reach and interact with the indicator molecules contained in the transducers.

In human subjects with diabetes, meanwhile, blood analyte concentration may change significantly over time, which in turn causes the interstitial fluid analyte concentration (CISF) to change over time. Due to the lag time required for analyte to diffuse from the capillary through the interstitial fluid to the sensor transducers, measurement accuracy can be improved by calculating the interstitial fluid rate of change (RISF), and using the measured CISF in combination with the calculated RISF to estimate the current blood analyte level. By using at least two transducers associated with different lag times as described above, it is possible to determine the RISF with a single measurement (e.g., by performing a swipe measurement).

<FIG> is a flow chart illustrating an exemplary process <NUM> for measuring an analyte concentration. In some embodiments, the process <NUM> may include a step <NUM> in which a transceiver <NUM> may detect that it is positioned within a proximity of a sensor <NUM>. For example, the sensor may be subcutaneously implanted within an analyte-containing medium (e.g., interstitial fluid), and the transceiver <NUM> may be swiped, waved, or held within the sensor proximity. The proximity detection may be performed according to the systems and processes discussed in <CIT>.

In some embodiments, the process <NUM> may include a step <NUM> in which, in response to detecting that the transceiver is proximate the sensor, the transceiver <NUM> may transmit to the sensor power sufficient to perform at least a first measurement using a first transducer <NUM> of the sensor <NUM> and a second measurement using a second transducer <NUM> of the sensor <NUM>. Power may be transmitted via inductive elements as described above with respect to <FIG>. The transceiver <NUM> may also transmit one or more commands to the sensor <NUM>, the one or more commands instructing the sensor <NUM> to perform one or more measurements, such as the first and second measurements described above.

The method <NUM> includes a step <NUM> in which the sensor <NUM> performs a first measurement of a detectable property exhibited by a first transducer <NUM> and a second measurement of a detectable property exhibited by a second transducer <NUM>. The first and second transducers <NUM>, <NUM> may exhibit one or more detectable properties based on an amount or concentration of an analyte in proximity to the respective first and second transducers <NUM>, <NUM>. The first measurement is indicative of an amount or concentration of an analyte in proximity to the first transducer <NUM> after passing through a first diffusion barrier <NUM>. In some embodiments, the second measurement may be indicative of an amount or concentration of an analyte in proximity to the second transducer <NUM> after passing through a second diffusion barrier <NUM> (if present). In some embodiments, one or more of the first measurement and second measurement may be performed using the power transmitted in step <NUM>.

In some embodiments (e.g., embodiments in which the sensor <NUM> has more than two transducers associated with different time lags (see <FIG>)), the sensor <NUM> may perform one or more additional measurements of a detectable property of the one or more additional transducers. In some embodiments, the additional transducers (e.g., third and fourth transducers <NUM> and <NUM> of <FIG>) may exhibit one or more detectable properties based on an amount or concentration of an analyte in proximity to the one or more additional transducers. In some embodiments, a third measurement may be indicative of an amount or concentration of an analyte in proximity to the third transducer <NUM> after passing through a second diffusion barrier <NUM>. In some embodiments, the fourth measurement may be indicative of an amount or concentration of an analyte in proximity to a fourth transducer <NUM> after passing through a third diffusion barrier <NUM>. In some embodiments, the third and/or fourth measurements may be performed using the power transmitted in step <NUM>.

The method <NUM> includes a step <NUM> in which the sensor <NUM> conveys and the transceiver <NUM> receives first sensor data corresponding to the first measurement and second sensor data corresponding to the second measurement. In some embodiments, the step <NUM> includes the transceiver <NUM> receiving the first sensor data.

The method <NUM> includes a step <NUM> in which the transceiver <NUM> (or other device) calculates an analyte level rate of change, in particular an interstitial fluid analyte level rate of change RISF based on at least the first sensor data, the second sensor data, and a diffusion rate of the first diffusion barrier. In some embodiments, RISF may be calculated further based on a diffusion rate of the second diffusion barrier <NUM>. In embodiments with more than two diffusion barriers, these diffusion rates and additional sensor data may also be taken into account when calculating RISF in step <NUM>.

In some embodiments where two transducers are used, RISF may be calculated according to the following formula, in which CG1 represents the analyte measurement from the first transducer <NUM>, CG0 represents the analyte measurement from the second transducer <NUM>, τ<NUM> represents the delay associated with the first diffusion barrier <NUM>, and τ<NUM> represents the delay associated with the second diffusion barrier <NUM>, if present.

In some embodiments, the method <NUM> may include a step <NUM> in which the transceiver <NUM> (or other device) may calculate a blood analyte level based on the interstitial fluid analyte level (as measured by the first and/or second transducers) and RISF as calculated in step <NUM>. In some embodiments, blood analyte level CB may be calculated according to the following formula, in which p<NUM> represents the rate at which analyte in the interstitial fluid is consumed (e.g., by cells) and p<NUM> represents the rate at which glucose diffuses from the blood vessel to the interstitial fluid immediate proximate the sensor, and CG0 represents the analyte measurement from the second transducer (which may be associated with a shorter lag time).

In some embodiments, the method <NUM> may include a step <NUM> in which the transceiver <NUM> may be removed from the proximity of the sensor <NUM>. The transceiver <NUM> may be removed from the proximity of the sensor <NUM> at any time after the first sensor data and second sensor data are received. Further, the transceiver <NUM> may be removed before additional measurements are performed. In this manner, the transceiver <NUM> may be positioned (e.g., swiped) proximate to the sensor <NUM> for a brief time sufficient to perform a single measurement cycle and removed from the proximity of the sensor <NUM> immediately thereafter.

Claim 1:
An analyte detection system comprising:
a sensor (<NUM>) configured for at least partial placement in an analyte-containing medium, the sensor comprising:
a first transducer (<NUM>) that exhibits one or more detectable properties based on an amount or concentration of the analyte in proximity to the first transducer (<NUM>);
a first diffusion barrier (<NUM>) arranged such that, when the sensor (<NUM>) is placed in the medium, the analyte contained in the medium diffuses through the first diffusion barrier (<NUM>) before reaching the first transducer (<NUM>), wherein the first diffusion barrier (<NUM>) is configured such that the analyte contained in the medium diffuses through the first diffusion barrier (<NUM>) at a first diffusion rate r<NUM>; and
a second transducer (<NUM>) that exhibits one or more detectable properties based on an amount or concentration of the analyte in proximity to the second transducer (<NUM>); wherein, when the sensor (<NUM>) is placed in the medium, diffusion of the analyte contained in the medium to the first transducer (<NUM>) is delayed relative to diffusion of the analyte contained in the medium to the second transducer (<NUM>); $
said analyte detection system further comprising
a transceiver (<NUM>) configured to:
receive first sensor data collected from the first transducer (<NUM>); and
receive second sensor data collected from the second transducer (<NUM>);
characterized in that:
the transceiver (<NUM>) is further configured to calculate an analyte level rate of change based on at least the first sensor data, the second sensor data, and the first diffusion rate r<NUM>.