WO2011084713A1 - Détecteur de glucose et dispositif de commande pourvu d'une sortie sélectionnable par un utilisateur - Google Patents

Détecteur de glucose et dispositif de commande pourvu d'une sortie sélectionnable par un utilisateur Download PDF

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Publication number
WO2011084713A1
WO2011084713A1 PCT/US2010/061163 US2010061163W WO2011084713A1 WO 2011084713 A1 WO2011084713 A1 WO 2011084713A1 US 2010061163 W US2010061163 W US 2010061163W WO 2011084713 A1 WO2011084713 A1 WO 2011084713A1
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WIPO (PCT)
Prior art keywords
glucose
blood
activity
plasma
concentration
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PCT/US2010/061163
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English (en)
Inventor
Anthony P. Furnary
Soya Gamsey
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Glumetrics, Inc.
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Application filed by Glumetrics, Inc. filed Critical Glumetrics, Inc.
Publication of WO2011084713A1 publication Critical patent/WO2011084713A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/145—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
    • A61B5/14532—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue for measuring glucose, e.g. by tissue impedance measurement
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/145—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
    • A61B5/1455—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue using optical sensors, e.g. spectral photometrical oximeters

Definitions

  • Preferred embodiments of the present invention relate to detection of glucose in blood or interstitial fluid. More particularly, the disclosed device allows a user to select from among different glucose sensor output options, including conventional blood glucose concentration (mg/dl) and the level of glucose activity (mmoles glucose/kg water). Description of the Related Art
  • Glucose concentrations are typically measured either using milligrams of glucose per deciliter of fluid or in SI Units which measure millimoles of glucose per liter of fluid.
  • the fluid used as the reference is generally either whole blood or plasma.
  • the American Diabetic Association bases its criteria for the diagnosis and treatment of diabetes on the glucose concentration in plasma.
  • the World Health Organization uses glucose concentration in whole blood in all of its diagnostic and treatment criteria.
  • An example of a treatment protocol based on blood glucose might call for the administration of a set quantity of carbohydrate for a blood glucose level below 60, the administration of 3 units of regular insulin for blood glucose measured between 151 and 200, the administration of 5 units for a reading of 201 to 250, and so on.
  • a blood glucose monitoring system with user selectable output.
  • the monitoring system comprises: (a) a glucose sensor configured to reside in a blood vessel and provide a signal related to the level of glucose activity; (b) a data processing unit programmed to convert the level of glucose activity to a blood glucose concentration and/or a plasma glucose concentration; (c) a toggle system operable by the user and coupled to the data processing unit for selecting a desired output from among the level of glucose activity, the blood glucose concentration, and the plasma glucose concentration; and (d) an output device configured to allow the user to receive the output.
  • the toggle system comprises a knob, button, switch, touchpad, computer interface, or other means of relaying commands to the data processing device.
  • the user can elect to receive blood or plasma glucose concentrations in the form of conventional mg/dL units.
  • the user can elect to receive blood or plasma glucose concentrations in the form of SI Units (mmol/L).
  • the output device is selected from the group consisting of a graphic display, printer, network data connection, or other means of transmitting information to the user.
  • the hematocrit level is input into the processor.
  • a blood glucose monitor with user selectable output is disclosed in accordance with another aspect of the invention.
  • the monitor comprises: (a) a data processing unit programmed to convert a measured level of glucose activity to a blood glucose concentration and/or a plasma glucose concentration; (b) a toggle system operable by the user and coupled to the data processing unit for selecting a desired output from among the level of glucose activity, the blood glucose concentration, and the plasma glucose concentration; and (c) an output device configured to allow the user to receive the output.
  • FIG. 1 is a block diagram showing the components of a controller in accordance with one preferred embodiment of the glycemic control system.
  • FIG. 2 shows aspects of the optical signal path in accordance with one embodiment of the present system. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
  • Glucose activity as used herein reflects a measurement of the amount of free, bioavailable glucose. It represents the amount of glucose present per kilogram of water in the blood. It is measured in millimoles per kilogram of water. This provides a means of quantifying glucose that is not affected by the presence of red blood cells, protein concentration, lipid concentration, or oxygenation. Because protein-bound glucose is not part of the measured glucose activity level, the result represents an accurate quantification of the freely circulating glucose that is actually available for use by the body. Therefore, glucose activity measurements can provide a more physiologically relevant index a patient's glycemic status than either plasma or blood glucose concentrations.
  • Glucose activity also offers a number of advantages for use in glycemic control systems wherein a sensor capable of measuring glucose activity is operably coupled to a device capable of administering a glucose activity modulator such as insulin. Because the beta cells of the pancreas bind and respond to glucose activity (and not total blood glucose concentration, etc.) in regulating insulin secretion, a measurement of glucose activity represents the closest approximation to the body's own mechanism for glycemic control. Indeed, glucose activity can be measured as disclosed herein through implanted sensors configured to reversibly bind free glucose and elicit a detectable signal related to the amount of glucose binding. This allows for near-instantaneous monitoring and feedback in a manner approximating physiologic glucose control.
  • the invention disclosed herein comprises a toggle system on a controller that enables a user to select whether to receive information on a patient's glucose levels in the form of glucose activity (e.g., mmol/kg water), blood glucose concentration (e.g., mg/dL blood), or plasma glucose (e.g., mg/dL plasma).
  • the toggle system can comprise a button, switch, knob, touchpad, computer interface, or any other control device that can be operably coupled with a controller comprising a data processing unit capable of performing mathematical calculations.
  • the controller can be integral with the data processing unit.
  • the interface between the controller and the data processing unit can be by means of a direct electrical and/or mechanical connection.
  • the controller can interface with the data processing unit remotely via wired, wireless, network or other type of connection.
  • Preferred embodiments would be capable of converting glucose activity to blood and/or plasma glucose concentrations.
  • the user may elect to receive this data in mg/dL system or in SI units (mmol/L), such that the displayed or output blood or plasma glucose concentration is in the selected units. If the user wishes to receive said data in the form of SI units, it will be necessary for the data processing device to perform a simple additional calculation, wherein the mg/dL output is multiplied by 0.0555. Once the necessary calculations are complete, many embodiments of the processing device can then relay the data to a user using an operably coupled data output device.
  • the glucose sensors of the present invention can be utilized under a variety of conditions.
  • the particular configuration of a sensor may depend on the use for which it is intended and the conditions under which it will operate.
  • One embodiment includes a sensor configured for implantation into a patient or user.
  • implantation of the sensor may be made in the arterial or venous systems for direct testing of glucose activity in blood.
  • a glucose activity sensor may be implanted in the interstitial tissue for determining the glucose activity in interstitial fluid.
  • the site and depth of implantation may affect the particular shape, components, and configuration of the sensor.
  • glucose activity can be directly measured using an optical detector system designed to detect and quantify glucose activity.
  • glucose activity is measured using a sensor comprising a light sensitive chemical indicator system disposed within the light path of an optical fiber, which is sized and configured to be deployed within a blood vessel or within the interstitial space.
  • the chemical indicator system is configured to interact with free, unbound glucose dissolved within the aqueous compartment of the plasma.
  • Examples of such chemical indicator systems and sensor configurations for intravascular or interstitial glucose monitoring include the optical sensors disclosed in U.S. Patent Nos. 5,137,033, 5,512,246, 5,503,770, 6,627,177, 7,417,164 and 7,470,420, and U.S. Patent Publ. Nos. 2008/0188722, 2008/0188725, 2008/0187655, 2008/0305009, 2009/0018426, 2009/0018418, and co-pending U.S. Patent Appl. Nos. 11/296,898, 12/187,248, 12/172,059, 12/274,617 and 12/424,902; each of which is incorporated herein in its entirety by reference thereto.
  • the chemical indicator system comprises a fluorophore (or fluorescent dye) capable of absorbing light at an excitation wavelength and generating a detectable fluorescent signal at an emission wavelength.
  • the chemical indicator system also comprises a glucose binding moiety capable of reversibly binding glucose and interacting with the fluorophore in a manner related to the amount of glucose binding.
  • the fluorophore is operably coupled to the glucose binding moiety, such that the detectable fluorescent signal generated by the fluorophore is modulated by the interaction between the fluorophore and the glucose binding moiety.
  • the intensity of the emission wavelength is modulated.
  • the operable coupling between the fluorophore and glucose binding moiety may be a direct covalent coupling, an indirect covalent coupling (e.g., via a linker), or a non-covalent association (e.g., an electrostatic attraction).
  • Various embodiments may include more than one fluorophore and more than one glucose binding moiety.
  • some fluorophores that may be useful in such a chemical indicator system may be capable of absorbing light at more than one excitation wavelength and generating detectable signals at more than one emission wavelength.
  • the above described chemical indicator system also comprises a polymer matrix that is permeable to glucose, wherein the fluorophore and the glucose binding moiety are immobilized therein and capable of sufficient molecular interaction to facilitate glucose-dependent modulation of the detectable fluorescent signal.
  • the fluorophore and glucose binding moiety may be covalently or non- covalently associated with the polymer matrix.
  • the chemical indicator system comprises HPTS-triCys-MA (fluorophore) and 3,3'- oBBV (glucose binding moiety) immobilized within a glucose permeable polymer matrix and disposed within a cavity in the distal end region of an optical fiber.
  • the opening to the cavity is preferably covered by a semipermeable membrane which is permeable to free dissolved glucose, but not macromolecular or cell associated glucose.
  • the preferred HTPS-tri-Cys-MA fluorophore and the benzylboronic acid substituted viologen (3,3'-oBBV) are described in US Patent No.
  • the charge is altered, and the glucose binding moiety (sometimes referred to hereinafter as the "quencher") dissociates from the fluorophore, thereby allowing fluorescent emission in response to the excitation light.
  • the intensity of the fluorescent emission signal in this preferred embodiment of the glucose activity sensor is therefore proportional to the concentration of free, bioavailable glucose.
  • an indicator system may comprise an analyte binding protein operably coupled to a fluorophore, such as the indicator systems and glucose binding proteins disclosed in U.S. Patent Nos. 6,197,534, 6,227,627, 6,521,447, 6,855,556, 7,064,103, 7,316,909, 7,326,538, 7,345,160, and 7,496,392, U.S. Patent Application Publication Nos.
  • the glucose activity sensor is adapted to facilitate ratiometric correction of glucose activity measurements for optical artifacts of the system as disclosed in co-pending US Publication No 2008-0188725 Al and US Application No. 12/612,602, and for pH as disclosed in co-pending US Publication No. 2008-0188722 Al, which are hereby incorporated by reference herein in their entireties.
  • the glucose activity sensor described above is further incorporated into a system whereby optical information (fluorescent emission signal) about a patient's glucose activity can be converted to an electrical (analog or digital) signal and communicated to a user programmable (or pre-programmed) controller.
  • the controller may comprise an integral visual and/or audio output device, such as a conventional computer monitor/display, alarm, speaker, and/or an integral or operably coupled printer.
  • the controller comprises a visual display that indicates the present glucose activity level (mmoles glucose/kg water), the trend (steady, rising or falling), and the relative rate of change.
  • the controller comprises one or more data processing units or devices, as well as storage device(s), computer and/or network connectivity interfaces (e.g., USB ports, etc.).
  • Controller electronics are well known.
  • the controller may comprise electronics and receiver/display unit configurations such as those described in US Patent Appl. No. 2009/0188054 Al, the entire disclosure of which is incorporated herein by reference.
  • the controller may also be in communication with other devices, including e.g., data processing device(s), storage devices, and/or networks.
  • the patient's glucose activity level can be transmitted to a data network for viewing via a computer or other network interface device.
  • Embodiments that transmit information in this manner are disclosed in U.S. Patent Numbers 6,024,699, 6,168,563, 6,645,142, 6,976,958 and 7,156,809, the disclosures of which are incorporated herein in their entirety by reference thereto.
  • information about the patient's glucose activity level can be transmitted through voice synthesizer or earcon.
  • An example of a system that transmits information to the user via auditory output is disclosed in U.S. Patent Number 7,440,786 the disclosure of which are incorporated herein in their entirety by reference thereto.
  • the controller can be configured to alert the user if the measured glucose activity level rises above or falls below a certain threshold.
  • Examples of such devices that are capable of alerting the user of abnormal glucose levels are described in U.S. Patent Numbers 5,497,772 and 5,791,344, and US Patent Publication No. 2009/0177054A1; the disclosures of which are incorporated herein in their entirety by reference thereto.
  • Such an alarm function may also desirably be initiated based on rates of glucose activity change, e.g., if the glucose activity is dropping rapidly, then an alarm may alert medical personnel that rapid intervention (infusion of glucose) may avert a critical condition before a programmed threshold is reached and thereby facilitate glycemic control.
  • the glucose activity level and/or rate of change thereof is communicated from the controller to a blood glucose modulating unit (e.g., an insulin and glucose infusion pump).
  • the controller Besides receiving information from the sensor, the controller preferably also controls the light interrogation of the sensor chemistry, e.g., by actuating LED's to provide the excitation light and/or reference light.
  • LED's e.g., by actuating LED's to provide the excitation light and/or reference light.
  • other light sources e.g., laser light
  • the frequency of light interrogation can be controlled based on the blood glucose activity. For example, where the glucose activity level is steady, interrogation rate may be relatively slow/infrequent, thereby conserving energy (battery life in portable controllers) and minimizing any photo-bleaching effect on the indicator chemistry.
  • the glucose activity level is increasing or decreasing the interrogation rate may be increased. This is especially desirable, where glucose activity is dropping and establishing real-time or near real-time glucose monitoring may have greater clinical relevance.
  • the controller enables a number of functions to be described herein; primarily, however, its fundamental purpose is to "interrogate” (illuminate) the sensor chemistry and to respond to the resultant fluorescent signals which are proportional to the glucose concentration present, and to convert the signal into a glucose value for display and trending.
  • it also measures the temperature of the sensor tip and uses the temperature to correct for the glucose concentration as a function of sensed temperature.
  • the glucose concentration is also corrected by an indirect measurement of pH which is derived from the same signals fluorescent signals as used for the glucose concentration measurement (algorithmically as described for example in 2008- 0188722 Al).
  • the controller connects to the optical sensor and makes the measurements of signal intensity and temperature to produce a glucose value based on the modulation of the fluorescent chemistry.
  • it includes a User Interface which is comprised of a LCD and simple keypad, which enables the user to input various parameters e.g., alarm limits, values for the in-vivo adjustment, set the display mode, confirmation of pre-patient insertion calibration of the sensor, etc.
  • a User Interface which is comprised of a LCD and simple keypad, which enables the user to input various parameters e.g., alarm limits, values for the in-vivo adjustment, set the display mode, confirmation of pre-patient insertion calibration of the sensor, etc.
  • it will also produce error codes and advise the user via the LCD and built-in alarm buzzer when errant conditions or situations are detected.
  • the controller may communicate to an external PC via an IrDA port, for the purpose of programming specific parameters prior to any use, and also for downloading data after use to the PC for further display, printing and report generation.
  • the major functional blocks of the controller are itemized in Table 1, although it is to be understood that these are illustrative of one preferred embodiment of a controller useful in the systems described herein. Any of the specific functional blocks may be substituted with art-recognized equivalents or alternatives. Likewise, in some embodiments of the controller, not all of these functional blocks be included.
  • the microcontroller 1 is at the core of the controller. It and all other circuitry is powered by the Power Supply circuit 14, which obtains its input power from 4 x AA NiMH batteries 13. Microcontroller 1 monitors the Power Supply voltage via Battery Monitor Circuit 12. [0036] Microcontroller 1 controls all of the elements of the system including the User Interface devices (Keypad 9, LCD 5 and the Audible alarm 6) and provides all control for the Optical Subassembly 7.
  • the Optical Subassembly 7 includes LEDs 7a for illuminating the Sensor 17 and detectors 7b for receiving the fluorescent and reference signals. The Optical Subassembly communicates with the Sensor 17 and the Microcontroller 1.
  • the Optical Subassembly 7 is comprised of two LEDs 7a of two different wavelengths, and two photodiode detectors 7b.
  • the LEDs may be controlled by signals from Microcontroller 1 and an interface circuit (not shown), and via embedded software, can be set to pulse periodically and sequentially e.g., 1/min, 5/min, etc. and at any pulse width between 1 ms to 100 ms.
  • the amplitude of the LED drive current is also adjustable by the Microcontroller 1 up to about 50 ma from virtually 0 ma.
  • the two photodiode detectors 7b receive the "green” and or “blue” signals; green being the result of the fluorescent response of the chemistry and blue being the "reflected" or reference signal. It should be noted that other sensor embodiments could utilize other referencing signals, and that "blue” is just an illustration for the current design embodiment.
  • the photodiode detectors 7b are configured in a fairly typical, but highly optimized "transimpedance amplifier” configuration which converts the sensed photodiode current to a voltage. Signal currents are typically in the low picoampere range, from perhaps a few picoamps to a few hundred picoamps.
  • the detected pulses - from each detector - are then amplified and the signals digitized via dual A/D convertors within the Dual Detector Circuit.
  • the A/D convertors enable the digital voltages to be read and stored by the Microcontroller 1.
  • variable parameters at which the LEDs are excited can be adjusted in response to conditions of the patient. For example, the rate could be adjusted to be more frequent at lower glucose levels, and/or when the glucose values are changing rapidly to provide a higher density of information which could be relevant for clinical decision making. Likewise, at higher glucose levels, the excitation values (pulse rate, pulse width) might be reduced in order to reduce the power consumption and extend the overall use time if needed.
  • Thermocouple Measurement circuitry 8 measures the sensor temperature via thermocouple embedded within the sensor itself. Likewise, the heater temperature of the separate Calibration Chamber heater is controlled by Heater Controller 4.
  • the User Interface 5 is preferably a graphical LCD (e.g., configured as 240 x 160 pixels) which provides all of the controller's information including the calculated (and pH/temperature corrected) glucose value, trend information, rate of change, alarms and alerts, and in conjunction with Keypad 9 enables the User to input and adjust parameters.
  • a graphical LCD e.g., configured as 240 x 160 pixels
  • an aspect of the optical signal path is the actual transmission of the optical signals from the monitor Optical Subassembly 7 to the sensor (the efferent path) and from the Sensor 17 to the Optical Subassembly 7 (the afferent path).
  • the optical signal transmission is accomplished with the use of a bundled fiber optic cable, which contains a mix of fibers for the efferent and afferent signals.
  • the orientation of the fibers is such that specific fibers are mapped for the efferent blue signals and likewise a number of fibers mapped for the afferent green and blue signals.
  • This particular fiber mapping is an example of one mapping format; other mappings may be used to match new sensor designs which require more or less light or different wavelengths of light for enhanced functionality.
  • the controller is operably coupled to the glucose activity sensor.
  • the controller device can be physically attached to, or an integral part of, a glucose activity sensor.
  • the controller can be operably coupled to the glucose activity sensor via a network or wireless connection.
  • data concerning the patient's glucose activity level can automatically be input into the controller, e.g., via the operably coupled sensor, or manually input into the controller, e.g., data regarding hematocrit and other blood chemistry measurements.
  • the controller comprises a toggle system that allows a user to select the desired output (e.g., glucose activity, blood and/or plasma glucose concentration).
  • the toggle system can comprise a button, switch, knob, touchpad, computer interface, or any other selection actuator that can be operably coupled to the controller.
  • the control system can direct the data processing unit to perform calculations capable of converting glucose activity data to the desired measurement format. The calculations can be performed using established formulae depending on whether the conversion is to plasma or blood glucose concentration.
  • the toggle system can direct the data processing unit to perform a mathematical calculation to convert the glucose activity to [BG].
  • This calculation requires that the device determine the percentage of blood composed of water. Because blood consists almost entirely of red blood cells and plasma, the water components of these two elements must be determined separately in order to calculate the total volume of water. The percentage of blood composed of red blood cells (hematocrit or HCT) is measured. Since red blood cells are 71% water, the HCT is multiplied by 0.71 to determine the percentage of the HCT composed of water. This sum is then adjusted to take into account the fact that the mass of water at body temperature is 0.99kg/liter. As a result the HCT portion of the blood is 70.29% water.
  • the patient's HCT can be directly input by the user into the controller.
  • the HCT can be input automatically by direct data input from any operably coupled means of accessing, storing, or measuring HCT; in one embodiment, the sensor may further comprise a means for estimating HCT (e.g., optical density).
  • the controller may comprise the necessary algorithms and program instructions to convert direct measurements of glucose activity, along with HCT input, into conventional [BG] values, and further comprise a user selectable toggle system to allow toggling between the measured glucose activity and the calculated [BG] values.
  • the data processing unit can calculate plasma glucose concentration [PG] from glucose activity by determining the percentage of water present in the plasma.
  • the mass of water at body temperature is 0.99kg/liter.
  • Plasma is made up of approximately 93% water. Therefore the conversion factor for plasma is 0.93 divided by 0.99 which yields 0.939394. Therefore, [PG] can be calculated by equation (2):
  • the data processing unit can convert glucose activity to [PG] using equation (2). These results can then be made available to the user using a data output device (e.g., display, printer, etc.).
  • a data output device e.g., display, printer, etc.

Abstract

Les modes de réalisation préférés de la présente invention ont pour objet la détection du glucose dans le sang ou le fluide interstitiel. Plus particulièrement, le dispositif selon la présente invention permet à un utilisateur de choisir parmi différentes options de sortie du détecteur de glucose, comprenant les concentrations de glucose dans le sang ou le plasma classiques (mg/dL) et le niveau de l'activité du glucose (mmoles glucose/kg d'eau).
PCT/US2010/061163 2009-12-17 2010-12-17 Détecteur de glucose et dispositif de commande pourvu d'une sortie sélectionnable par un utilisateur WO2011084713A1 (fr)

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Cited By (18)

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US9839378B2 (en) 2007-02-06 2017-12-12 Medtronic Minimed, Inc. Optical systems and methods for ratiometric measurement of blood glucose concentration
US8983565B2 (en) 2007-02-06 2015-03-17 Medtronic Minimed, Inc. Optical determination of pH and glucose
US8838195B2 (en) 2007-02-06 2014-09-16 Medtronic Minimed, Inc. Optical systems and methods for ratiometric measurement of blood glucose concentration
US8979790B2 (en) 2007-11-21 2015-03-17 Medtronic Minimed, Inc. Use of an equilibrium sensor to monitor glucose concentration
US10258743B2 (en) 2012-05-21 2019-04-16 Common Sensing Inc. Dose measurement system and method
US10684156B2 (en) 2012-05-21 2020-06-16 Common Sensing Inc. Dose measurement system and method
US10190901B2 (en) 2012-05-21 2019-01-29 Common Sensing Inc. Dose measurement system and method
US11566931B2 (en) 2012-05-21 2023-01-31 Bigfoot Biomedical, Inc. Dose measurement system and method
US10821234B2 (en) 2012-05-21 2020-11-03 Common Sensing Inc. Dose measurement system and method
CN106537126A (zh) * 2014-08-01 2017-03-22 普通感应股份有限公司 利用温度感测来优化的液体测量系统、装置和方法
EP3175226A4 (fr) * 2014-08-01 2018-04-11 Common Sensing Inc. Systèmes, appareil et procédés de mesures de liquide optimisés avec détection de température
CN106537126B (zh) * 2014-08-01 2020-11-27 普通感应股份有限公司 利用温度感测来优化的液体测量系统、装置和方法
US11183278B2 (en) 2014-08-01 2021-11-23 Bigfoot Biomedical, Inc. Liquid measurement systems, apparatus, and methods optimized with temperature sensing
US10255991B2 (en) 2014-08-01 2019-04-09 Common Sensing Inc. Liquid measurement systems, apparatus, and methods optimized with temperature sensing
US11670407B2 (en) 2014-08-01 2023-06-06 Bigfoot Biomedical, Inc Liquid measurement systems, apparatus, and methods optimized with temperature sensing
US10695501B2 (en) 2016-07-15 2020-06-30 Common Sensing Inc. Dose measurement systems and methods
US11389595B2 (en) 2016-07-15 2022-07-19 Bigfoot Biomedical, Inc. Dose measurement systems and methods
US11690959B2 (en) 2016-07-15 2023-07-04 Bigfoot Biomedical, Inc. Dose measurement systems and methods

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