Patent Description:
Embodiments of the subject matter described herein relate generally to drug delivery systems and, more specifically, to systems for controlling the operation of an insulin infusion device that delivers insulin to the body of a patient.

Infusion pump devices and systems are relatively well known in the medical arts, for use in delivering or dispensing an agent, such as insulin or another prescribed medication, to a patient. A typical infusion pump includes a pump drive system which typically includes a small motor and drive train components that convert rotational motor motion to a translational displacement of a plunger (or stopper) in a fluid reservoir that delivers medication from the reservoir to the body of a patient via a fluid path created between the reservoir and the body of a patient. Use of infusion pump therapy has been increasing, especially for delivering insulin for diabetics.

Control schemes have been developed to allow insulin infusion pumps to monitor and regulate a patient's blood glucose level in a substantially continuous and autonomous manner. Managing a diabetic's blood glucose level is complicated by variations in a patient's daily activities (e.g., exercise, carbohydrate consumption, and the like) in addition to variations in the patient's individual insulin response and potentially other factors. Some control schemes may attempt to proactively account for daily activities to minimize glucose excursions. At the same time, patients may manually initiate delivery of insulin prior to or contemporaneously with consuming a meal (e.g., a meal bolus or correction bolus) to prevent spikes or swings in the patient's blood glucose level that could otherwise result from the impending consumption of carbohydrates and the response time of the control scheme. That said, a manually-initiated bolus could introduce a risk of a postprandial glucose excursion if preceding insulin deliveries are not accounted for.

An insulin infusion pump can be operated in an automatic mode wherein basal insulin is delivered at a rate that is automatically adjusted for the user. While controlling the delivery of basal insulin in this manner, the pump can also control the delivery of correction boluses to account for rising glucose trends, a sudden spike in detected blood glucose, etc. Ideally, the amount of a correction bolus should be accurately calculated and administered to maintain the user's blood glucose within the desired range. In particular, an automatically generated and delivered correction bolus should safely manage the user's blood glucose level and keep it above a defined threshold level. Accordingly, there is a need to improve the handling of correction boluses that are delivered during an automatic mode of an insulin infusion pump.

<CIT> discloses an infusion device with a basal insulin delivery and a correction bolus according to the state of the art.

The invention is defined by claims <NUM> and <NUM>. Dependent claims define further embodiments.

A method of controlling operation of an insulin infusion device is described but not claimed. The insulin infusion device includes a fluid reservoir for insulin to be delivered from the insulin infusion device to a body of a user, and has at least one processor device to perform the method. The method involves the steps of: controlling the insulin infusion device to operate in an automatic basal insulin delivery mode; obtaining a blood glucose measurement that indicates a current blood glucose level of the user; and initiating a correction bolus procedure when: (<NUM>) the blood glucose measurement exceeds a correction bolus threshold value; and (<NUM>) a maximum allowable basal insulin infusion rate (Umax) has been reached during operation in the automatic basal insulin delivery mode. The correction bolus procedure involves the steps of: calculating an initial correction bolus amount for the user; scaling the initial correction bolus amount to obtain a final correction bolus amount for the user, such that a predicted future blood glucose level of the user resulting from simulated delivery of the final correction bolus amount exceeds a low blood glucose threshold level; and delivering the final correction bolus amount to the body of the user during operation in the automatic basal insulin delivery mode.

An insulin infusion device is also described but not claimed. The insulin infusion device includes: a fluid reservoir for insulin to be delivered from the insulin infusion device to a user; at least one processor device; and at least one memory element associated with the at least one processor device. The at least one memory element stores processor-executable instructions configurable to be executed by the at least one processor device to perform the method summarized in the preceding paragraph.

Also described but not claimed here is a tangible and non-transitory electronic storage medium having processor-executable instructions configurable to be executed by at least one processor device to perform the method summarized above.

Exemplary embodiments of the subject matter described herein are implemented in conjunction with medical devices, such as portable electronic medical devices. Although many different applications are possible, the following description focuses on embodiments that incorporate a fluid infusion device (or infusion pump) as part of an infusion system deployment. That said, the subject matter may be implemented in an equivalent manner in the context of other medical devices, such as continuous glucose monitoring (CGM) devices, injection pens (e.g., smart injection pens), and the like. For the sake of brevity, conventional techniques related to infusion system operation, insulin pump and/or infusion set operation, and other functional aspects of the systems (and the individual operating components of the systems) may not be described in detail here. Examples of infusion pumps may be of the type described in, but not limited to, <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; and <CIT>. That said, the subject matter described herein can be utilized more generally in the context of overall diabetes management or other physiological conditions independent of or without the use of an infusion device or other medical device (e.g., when oral medication is utilized), and the subject matter described herein is not limited to any particular type of medication.

Generally, a fluid infusion device includes a motor or other actuation arrangement that is operable to linearly displace a plunger (or stopper) of a fluid reservoir provided within the fluid infusion device to deliver a dosage of fluid, such as insulin, to the body of a user. Dosage commands that govern operation of the motor may be generated in an automated manner in accordance with the delivery control scheme associated with a particular operating mode, and the dosage commands may be generated in a manner that is influenced by a current (or most recent) measurement of a physiological condition in the body of the user. For example, in a closed-loop or automatic operating mode, dosage commands may be generated based on a difference between a current (or most recent) measurement of the interstitial fluid glucose level in the body of the user and a target (or reference) glucose value. In this regard, the rate of infusion may vary as the difference between a current measurement value and the target measurement value fluctuates. For purposes of explanation, the subject matter is described herein in the context of the infused fluid being insulin for regulating a glucose level of a user (or patient); however, it should be appreciated that many other fluids may be administered through infusion, and the subject matter described herein is not necessarily limited to use with insulin.

Exemplary embodiments of the subject matter described herein generally relate to proactively adjusting correction bolus amounts that are administered during automated operation of an insulin infusion device. As described in greater detail below, in exemplary embodiments, one or more mathematical models for the patient's physiological response are utilized to predict or forecast future glucose levels for a patient based on the patient's current and/or recent glucose measurements, preceding insulin deliveries, manually-input carbohydrate amounts, meal boluses, and a calculated correction bolus amount. When the patient's predicted future glucose level using the initial correction bolus amount is below a threshold value within a specified time window, the initial correction bolus amount is reduced to an amount that results in the patient's predicted future glucose level being maintained above that threshold value. According to the invention, the initial correction bolus value is progressively or iteratively scaled down to reduce the bolus amount as needed. In certain exemplary embodiments, the scaling methodology attempts to maximize the correction bolus dosage within the search space defined by the initial correction bolus amount while maintaining a predicted future glucose level for the patient that satisfies the designated hypoglycemic threshold during the time period of interest.

By virtue of the physiological model for the patient's predicted future glucose level accounting for the preceding automated or autonomous insulin deliveries along with the patient's current glucose level and the current trend in the patient's glucose level, the adjusted correction bolus amount reduces the risk of a post-bolus hypoglycemic event. For example, in some embodiments, closed-loop control information may be automatically adjusted in advance of an anticipated event likely to influence the patient's glucose levels or insulin response. In this regard, prospective closed-loop control adjustments account for the relatively slow action of long-acting subcutaneously administered insulin by adjusting insulin delivery in advance of an event to increase or decrease the amount of yet to be metabolized insulin on board prior to start of the event. Thus, the adjusted bolus amount accounts for prospective closed-loop insulin deliveries in a manner that reduces the risk of a post-bolus glucose excursion.

Turning now to <FIG>, one exemplary embodiment of an infusion system <NUM> includes, without limitation, a fluid infusion device (or infusion pump) <NUM>, a sensing arrangement <NUM>, a command control device (CCD) <NUM>, and a computer <NUM>. The components of an infusion system <NUM> may be realized using different platforms, designs, and configurations, and the embodiment shown in <FIG> is not exhaustive or limiting. In practice, the infusion device <NUM> and the sensing arrangement <NUM> are secured at desired locations on the body of a user (or patient), as illustrated in <FIG>. In this regard, the locations at which the infusion device <NUM> and the sensing arrangement <NUM> are secured to the body of the user in <FIG> are provided only as a representative, non-limiting, example. The elements of the infusion system <NUM> may be similar to those described in <CIT>.

In the illustrated embodiment of <FIG>, the infusion device <NUM> is designed as a portable medical device suitable for infusing a fluid, a liquid, a gel, or other medicament into the body of a user. In exemplary embodiments, the infused fluid is insulin, although many other fluids may be administered through infusion such as, but not limited to, HIV drugs, drugs to treat pulmonary hypertension, iron chelation drugs, pain medications, anti-cancer treatments, medications, vitamins, hormones, or the like. In some embodiments, the fluid may include a nutritional supplement, a dye, a tracing medium, a saline medium, a hydration medium, or the like.

The sensing arrangement <NUM> generally represents the components of the infusion system <NUM> configured to sense, detect, measure or otherwise quantify a condition of the user, and may include a sensor, a monitor, or the like, for providing data indicative of the condition that is sensed, detected, measured or otherwise monitored by the sensing arrangement. In this regard, the sensing arrangement <NUM> may include electronics and enzymes reactive to a biological condition, such as a blood glucose level, or the like, of the user, and provide data indicative of the blood glucose level to the infusion device <NUM>, the CCD <NUM> and/or the computer <NUM>. For example, the infusion device <NUM>, the CCD <NUM> and/or the computer <NUM> may include a display for presenting information or data to the user based on the sensor data received from the sensing arrangement <NUM>, such as, for example, a current glucose level of the user, a graph or chart of the user's glucose level versus time, device status indicators, alert messages, or the like. In other embodiments, the infusion device <NUM>, the CCD <NUM> and/or the computer <NUM> may include electronics and software that are configured to analyze sensor data and operate the infusion device <NUM> to deliver fluid to the body of the user based on the sensor data and/or preprogrammed delivery routines. Thus, in exemplary embodiments, one or more of the infusion device <NUM>, the sensing arrangement <NUM>, the CCD <NUM>, and/or the computer <NUM> includes a transmitter, a receiver, and/or other transceiver electronics that allow for communication with other components of the infusion system <NUM>, so that the sensing arrangement <NUM> may transmit sensor data or monitor data to one or more of the infusion device <NUM>, the CCD <NUM> and/or the computer <NUM>.

Still referring to <FIG>, in various embodiments, the sensing arrangement <NUM> may be secured to the body of the user or embedded in the body of the user at a location that is remote from the location at which the infusion device <NUM> is secured to the body of the user. In various other embodiments, the sensing arrangement <NUM> may be incorporated within the infusion device <NUM>. In other embodiments, the sensing arrangement <NUM> may be separate and apart from the infusion device <NUM>, and may be, for example, part of the CCD <NUM>. In such embodiments, the sensing arrangement <NUM> may be configured to receive a biological sample, analyte, or the like, to measure a condition of the user.

In some embodiments, the CCD <NUM> and/or the computer <NUM> may include electronics and other components configured to perform processing, delivery routine storage, and to control the infusion device <NUM> in a manner that is influenced by sensor data measured by and/or received from the sensing arrangement <NUM>. By including control functions in the CCD <NUM> and/or the computer <NUM>, the infusion device <NUM> may be made with more simplified electronics. However, in other embodiments, the infusion device <NUM> may include all control functions, and may operate without the CCD <NUM> and/or the computer <NUM>. In various embodiments, the CCD <NUM> may be a portable electronic device. In addition, in various embodiments, the infusion device <NUM> and/or the sensing arrangement <NUM> may be configured to transmit data to the CCD <NUM> and/or the computer <NUM> for display or processing of the data by the CCD <NUM> and/or the computer <NUM>.

In some embodiments, the CCD <NUM> and/or the computer <NUM> may provide information to the user that facilitates the user's subsequent use of the infusion device <NUM>. For example, the CCD <NUM> may provide information to the user to allow the user to determine the rate or dose of medication to be administered into the user's body. In other embodiments, the CCD <NUM> may provide information to the infusion device <NUM> to autonomously control the rate or dose of medication administered into the body of the user. In some embodiments, the sensing arrangement <NUM> may be integrated into the CCD <NUM>. Such embodiments may allow the user to monitor a condition by providing, for example, a sample of his or her blood to the sensing arrangement <NUM> to assess his or her condition. In some embodiments, the sensing arrangement <NUM> and the CCD <NUM> may be used for determining glucose levels in the blood and/or body fluids of the user without the use of, or necessity of, a wire or cable connection between the infusion device <NUM> and the sensing arrangement <NUM> and/or the CCD <NUM>.

In some embodiments, the sensing arrangement <NUM> and/or the infusion device <NUM> are cooperatively configured to utilize a closed-loop system for delivering fluid to the user. Examples of sensing devices and/or infusion pumps utilizing closed-loop systems may be found at, but are not limited to, the following <CIT>, <CIT>,<CIT>, <CIT>,<CIT>, <CIT>, and <CIT> or <CIT>. In such embodiments, the sensing arrangement <NUM> is configured to sense or measure a condition of the user, such as, blood glucose level or the like. The infusion device <NUM> is configured to deliver fluid in response to the condition sensed by the sensing arrangement <NUM>. In turn, the sensing arrangement <NUM> continues to sense or otherwise quantify a current condition of the user, thereby allowing the infusion device <NUM> to deliver fluid continuously in response to the condition currently (or most recently) sensed by the sensing arrangement <NUM> indefinitely. In some embodiments, the sensing arrangement <NUM> and/or the infusion device <NUM> may be configured to utilize the closed-loop system only for a portion of the day, for example only when the user is asleep or awake.

<FIG> depict one exemplary embodiment of a fluid infusion device <NUM> (or alternatively, infusion pump) suitable for use in an infusion system, such as, for example, as infusion device <NUM> in the infusion system <NUM> of <FIG>. The fluid infusion device <NUM> is a portable medical device designed to be carried or worn by a patient (or user), and the fluid infusion device <NUM> may leverage any number of conventional features, components, elements, and characteristics of existing fluid infusion devices, such as, for example, some of the features, components, elements, and/or characteristics described in <CIT> and <CIT>. It should be appreciated that <FIG> depict some aspects of the infusion device <NUM> in a simplified manner; in practice, the infusion device <NUM> could include additional elements, features, or components that are not shown or described in detail herein.

As best illustrated in <FIG>, the illustrated embodiment of the fluid infusion device <NUM> includes a housing <NUM> adapted to receive a fluid-containing reservoir <NUM>. An opening <NUM> in the housing <NUM> accommodates a fitting <NUM> (or cap) for the reservoir <NUM>, with the fitting <NUM> being configured to mate or otherwise interface with tubing <NUM> of an infusion set <NUM> that provides a fluid path to/from the body of the user. In this manner, fluid communication from the interior of the reservoir <NUM> to the user is established via the tubing <NUM>. The illustrated fluid infusion device <NUM> includes a human-machine interface (HMI) <NUM> (or user interface) that includes elements <NUM>, <NUM> that can be manipulated by the user to administer a bolus of fluid (e.g., insulin), to change therapy settings, to change user preferences, to select display features, and the like. The infusion device also includes a display element <NUM>, such as a liquid crystal display (LCD) or another suitable display element, that can be used to present various types of information or data to the user, such as, without limitation: the current glucose level of the patient; the time; a graph or chart of the patient's glucose level versus time; device status indicators; etc..

The housing <NUM> is formed from a substantially rigid material having a hollow interior <NUM> adapted to allow an electronics assembly <NUM>, a sliding member (or slide) <NUM>, a drive system <NUM>, a sensor assembly <NUM>, and a drive system capping member <NUM> to be disposed therein in addition to the reservoir <NUM>, with the contents of the housing <NUM> being enclosed by a housing capping member <NUM>. The opening <NUM>, the slide <NUM>, and the drive system <NUM> are coaxially aligned in an axial direction (indicated by arrow <NUM>), whereby the drive system <NUM> facilitates linear displacement of the slide <NUM> in the axial direction <NUM> to dispense fluid from the reservoir <NUM> (after the reservoir <NUM> has been inserted into opening <NUM>), with the sensor assembly <NUM> being configured to measure axial forces (e.g., forces aligned with the axial direction <NUM>) exerted on the sensor assembly <NUM> responsive to operating the drive system <NUM> to displace the slide <NUM>. In various embodiments, the sensor assembly <NUM> may be utilized to detect one or more of the following: an occlusion in a fluid path that slows, prevents, or otherwise degrades fluid delivery from the reservoir <NUM> to a user's body; when the reservoir <NUM> is empty; when the slide <NUM> is properly seated with the reservoir <NUM>; when a fluid dose has been delivered; when the infusion device <NUM> is subjected to shock or vibration; when the infusion device <NUM> requires maintenance.

Depending on the embodiment, the fluid-containing reservoir <NUM> may be realized as a syringe, a vial, a cartridge, a bag, or the like. In certain embodiments, the infused fluid is insulin, although many other fluids may be administered through infusion such as, but not limited to, HIV drugs, drugs to treat pulmonary hypertension, iron chelation drugs, pain medications, anti-cancer treatments, medications, vitamins, hormones, or the like. As best illustrated in <FIG>, the reservoir <NUM> typically includes a reservoir barrel <NUM> that contains the fluid and is concentrically and/or coaxially aligned with the slide <NUM> (e.g., in the axial direction <NUM>) when the reservoir <NUM> is inserted into the infusion device <NUM>. The end of the reservoir <NUM> proximate the opening <NUM> may include or otherwise mate with the fitting <NUM>, which secures the reservoir <NUM> in the housing <NUM> and prevents displacement of the reservoir <NUM> in the axial direction <NUM> with respect to the housing <NUM> after the reservoir <NUM> is inserted into the housing <NUM>. As described above, the fitting <NUM> extends from (or through) the opening <NUM> of the housing <NUM> and mates with tubing <NUM> to establish fluid communication from the interior of the reservoir <NUM> (e.g., reservoir barrel <NUM>) to the user via the tubing <NUM> and infusion set <NUM>. The opposing end of the reservoir <NUM> proximate the slide <NUM> includes a plunger <NUM> (or stopper) positioned to push fluid from inside the barrel <NUM> of the reservoir <NUM> along a fluid path through tubing <NUM> to a user. The slide <NUM> is configured to mechanically couple or otherwise engage with the plunger <NUM>, thereby becoming seated with the plunger <NUM> and/or reservoir <NUM>. Fluid is forced from the reservoir <NUM> via tubing <NUM> as the drive system <NUM> is operated to displace the slide <NUM> in the axial direction <NUM> toward the opening <NUM> in the housing <NUM>.

In the illustrated embodiment of <FIG>, the drive system <NUM> includes a motor assembly <NUM> and a drive screw <NUM>. The motor assembly <NUM> includes a motor that is coupled to drive train components of the drive system <NUM> that are configured to convert rotational motor motion to a translational displacement of the slide <NUM> in the axial direction <NUM>, and thereby engaging and displacing the plunger <NUM> of the reservoir <NUM> in the axial direction <NUM>. In some embodiments, the motor assembly <NUM> may also be powered to translate the slide <NUM> in the opposing direction (e.g., the direction opposite direction <NUM>) to retract and/or detach from the reservoir <NUM> to allow the reservoir <NUM> to be replaced. In exemplary embodiments, the motor assembly <NUM> includes a brushless DC (BLDC) motor having one or more permanent magnets mounted, affixed, or otherwise disposed on its rotor. However, the subject matter described herein is not necessarily limited to use with BLDC motors, and in alternative embodiments, the motor may be realized as a solenoid motor, an AC motor, a stepper motor, a piezoelectric caterpillar drive, a shape memory actuator drive, an electrochemical gas cell, a thermally driven gas cell, a bimetallic actuator, or the like. The drive train components may comprise one or more lead screws, cams, ratchets, jacks, pulleys, pawls, clamps, gears, nuts, slides, bearings, levers, beams, stoppers, plungers, sliders, brackets, guides, bearings, supports, bellows, caps, diaphragms, bags, heaters, or the like. In this regard, although the illustrated embodiment of the infusion pump utilizes a coaxially aligned drive train, the motor could be arranged in an offset or otherwise non-coaxial manner, relative to the longitudinal axis of the reservoir <NUM>.

As best shown in <FIG>, the drive screw <NUM> mates with threads <NUM> internal to the slide <NUM>. When the motor assembly <NUM> is powered and operated, the drive screw <NUM> rotates, and the slide <NUM> is forced to translate in the axial direction <NUM>. In an exemplary embodiment, the infusion device <NUM> includes a sleeve <NUM> to prevent the slide <NUM> from rotating when the drive screw <NUM> of the drive system <NUM> rotates. Thus, rotation of the drive screw <NUM> causes the slide <NUM> to extend or retract relative to the drive motor assembly <NUM>. When the fluid infusion device is assembled and operational, the slide <NUM> contacts the plunger <NUM> to engage the reservoir <NUM> and control delivery of fluid from the infusion device <NUM>. In an exemplary embodiment, the shoulder portion <NUM> of the slide <NUM> contacts or otherwise engages the plunger <NUM> to displace the plunger <NUM> in the axial direction <NUM>. In alternative embodiments, the slide <NUM> may include a threaded tip <NUM> capable of being detachably engaged with internal threads <NUM> on the plunger <NUM> of the reservoir <NUM>, as described in detail in <CIT> and<CIT>.

As illustrated in <FIG>, the electronics assembly <NUM> includes control electronics <NUM> coupled to the display element <NUM>, with the housing <NUM> including a transparent window portion <NUM> that is aligned with the display element <NUM> to allow the display <NUM> to be viewed by the user when the electronics assembly <NUM> is disposed within the interior <NUM> of the housing <NUM>. The control electronics <NUM> generally represent the hardware, firmware, processing logic and/or software (or combinations thereof) configured to control operation of the motor assembly <NUM> and/or drive system <NUM>, as described in greater detail below in the context of <FIG>. Whether such functionality is implemented as hardware, firmware, a state machine, or software depends upon the particular application and design constraints imposed on the embodiment. Those familiar with the concepts described here may implement such functionality in a suitable manner for each particular application, but such implementation decisions should not be interpreted as being restrictive or limiting. In an exemplary embodiment, the control electronics <NUM> includes one or more programmable controllers that may be programmed to control operation of the infusion device <NUM>.

The motor assembly <NUM> includes one or more electrical leads <NUM> adapted to be electrically coupled to the electronics assembly <NUM> to establish communication between the control electronics <NUM> and the motor assembly <NUM>. In response to command signals from the control electronics <NUM> that operate a motor driver (e.g., a power converter) to regulate the amount of power supplied to the motor from a power supply, the motor actuates the drive train components of the drive system <NUM> to displace the slide <NUM> in the axial direction <NUM> to force fluid from the reservoir <NUM> along a fluid path (including tubing <NUM> and an infusion set), thereby administering doses of the fluid contained in the reservoir <NUM> into the user's body. Preferably, the power supply is realized one or more batteries contained within the housing <NUM>. Alternatively, the power supply may be a solar panel, capacitor, AC or DC power supplied through a power cord, or the like. In some embodiments, the control electronics <NUM> may operate the motor of the motor assembly <NUM> and/or drive system <NUM> in a stepwise manner, typically on an intermittent basis; to administer discrete precise doses of the fluid to the user according to programmed delivery profiles.

Referring to <FIG>, as described above, the user interface <NUM> includes HMI elements, such as buttons <NUM> and a directional pad <NUM>, that are formed on a graphic keypad overlay <NUM> that overlies a keypad assembly <NUM>, which includes features corresponding to the buttons <NUM>, directional pad <NUM> or other user interface items indicated by the graphic keypad overlay <NUM>. When assembled, the keypad assembly <NUM> is coupled to the control electronics <NUM>, thereby allowing the HMI elements <NUM>, <NUM> to be manipulated by the user to interact with the control electronics <NUM> and control operation of the infusion device <NUM>, for example, to administer a bolus of insulin, to change therapy settings, to change user preferences, to select display features, to set or disable alarms and reminders, and the like. In this regard, the control electronics <NUM> maintains and/or provides information to the display <NUM> regarding program parameters, delivery profiles, pump operation, alarms, warnings, statuses, or the like, which may be adjusted using the HMI elements <NUM>, <NUM>. In various embodiments, the HMI elements <NUM>, <NUM> may be realized as physical objects (e.g., buttons, knobs, joysticks, and the like) or virtual objects (e.g., using touch-sensing and/or proximity-sensing technologies). For example, in some embodiments, the display <NUM> may be realized as a touch screen or touch-sensitive display, and in such embodiments, the features and/or functionality of the HMI elements <NUM>, <NUM> may be integrated into the display <NUM> and the HMI <NUM> may not be present. In some embodiments, the electronics assembly <NUM> may also include alert generating elements coupled to the control electronics <NUM> and suitably configured to generate one or more types of feedback, such as, without limitation: audible feedback; visual feedback; haptic (physical) feedback; or the like.

Referring to <FIG>, in accordance with one or more embodiments, the sensor assembly <NUM> includes a back plate structure <NUM> and a loading element <NUM>. The loading element <NUM> is disposed between the capping member <NUM> and a beam structure <NUM> that includes one or more beams having sensing elements disposed thereon that are influenced by compressive force applied to the sensor assembly <NUM> that deflects the one or more beams, as described in greater detail in <CIT>. In exemplary embodiments, the back plate structure <NUM> is affixed, adhered, mounted, or otherwise mechanically coupled to the bottom surface <NUM> of the drive system <NUM> such that the back plate structure <NUM> resides between the bottom surface <NUM> of the drive system <NUM> and the housing cap <NUM>. The drive system capping member <NUM> is contoured to accommodate and conform to the bottom of the sensor assembly <NUM> and the drive system <NUM>. The drive system capping member <NUM> may be affixed to the interior of the housing <NUM> to prevent displacement of the sensor assembly <NUM> in the direction opposite the direction of force provided by the drive system <NUM> (e.g., the direction opposite direction <NUM>). Thus, the sensor assembly <NUM> is positioned between the motor assembly <NUM> and secured by the capping member <NUM>, which prevents displacement of the sensor assembly <NUM> in a downward direction opposite the direction of the arrow that represents the axial direction <NUM>, such that the sensor assembly <NUM> is subjected to a reactionary compressive force when the drive system <NUM> and/or motor assembly <NUM> is operated to displace the slide <NUM> in the axial direction <NUM> in opposition to the fluid pressure in the reservoir <NUM>. Under normal operating conditions, the compressive force applied to the sensor assembly <NUM> is correlated with the fluid pressure in the reservoir <NUM>. As shown, electrical leads <NUM> are adapted to electrically couple the sensing elements of the sensor assembly <NUM> to the electronics assembly <NUM> to establish communication to the control electronics <NUM>, wherein the control electronics <NUM> are configured to measure, receive, or otherwise obtain electrical signals from the sensing elements of the sensor assembly <NUM> that are indicative of the force applied by the drive system <NUM> in the axial direction <NUM>.

<FIG> depicts an exemplary embodiment of an infusion system <NUM> suitable for use with an infusion device <NUM>, such as any one of the infusion devices <NUM>, <NUM> described above. The infusion system <NUM> is capable of controlling or otherwise regulating a physiological condition in the body <NUM> of a patient to a desired (or target) value or otherwise maintain the condition within a range of acceptable values in an automated or autonomous manner. In one or more exemplary embodiments, the condition being regulated is sensed, detected, measured or otherwise quantified by a sensing arrangement <NUM> (e.g., a blood glucose sensing arrangement <NUM>) communicatively coupled to the infusion device <NUM>. However, it should be noted that in alternative embodiments, the condition being regulated by the infusion system <NUM> may be correlative to the measured values obtained by the sensing arrangement <NUM>. That said, for clarity and purposes of explanation, the subject matter may be described herein in the context of the sensing arrangement <NUM> being realized as a glucose sensing arrangement that senses, detects, measures or otherwise quantifies the patient's glucose level, which is being regulated in the body <NUM> of the patient by the infusion system <NUM>.

In exemplary embodiments, the sensing arrangement <NUM> includes one or more interstitial glucose sensing elements that generate or otherwise output electrical signals (alternatively referred to herein as measurement signals) having a signal characteristic that is correlative to, influenced by, or otherwise indicative of the relative interstitial fluid glucose level in the body <NUM> of the patient. The output electrical signals are filtered or otherwise processed to obtain a measurement value indicative of the patient's interstitial fluid glucose level. In exemplary embodiments, a blood glucose meter <NUM>, such as a finger stick device, is utilized to directly sense, detect, measure or otherwise quantify the blood glucose in the body <NUM> of the patient. In this regard, the blood glucose meter <NUM> outputs or otherwise provides a measured blood glucose value that may be utilized as a reference measurement for calibrating the sensing arrangement <NUM> and converting a measurement value indicative of the patient's interstitial fluid glucose level into a corresponding calibrated blood glucose value. For purposes of explanation, the calibrated blood glucose value calculated based on the electrical signals output by the sensing element(s) of the sensing arrangement <NUM> may alternatively be referred to herein as the sensor glucose value, the sensed glucose value, or variants thereof.

In exemplary embodiments, the infusion system <NUM> also includes one or more additional sensing arrangements <NUM>, <NUM> configured to sense, detect, measure or otherwise quantify a characteristic of the body <NUM> of the patient that is indicative of a condition in the body <NUM> of the patient. In this regard, in addition to the glucose sensing arrangement <NUM>, one or more auxiliary sensing arrangements <NUM> may be worn, carried, or otherwise associated with the body <NUM> of the patient to measure characteristics or conditions of the patient (or the patient's activity) that may influence the patient's glucose levels or insulin sensitivity. For example, a heart rate sensing arrangement <NUM> could be worn on or otherwise associated with the patient's body <NUM> to sense, detect, measure or otherwise quantify the patient's heart rate, which, in turn, may be indicative of exercise (and the intensity thereof) that is likely to influence the patient's glucose levels or insulin response in the body <NUM>. In yet another embodiment, another invasive, interstitial, or subcutaneous sensing arrangement <NUM> may be inserted into the body <NUM> of the patient to obtain measurements of another physiological condition that may be indicative of exercise (and the intensity thereof), such as, for example, a lactate sensor, a ketone sensor, or the like. Depending on the embodiment, the auxiliary sensing arrangement(s) <NUM> could be realized as a standalone component worn by the patient, or alternatively, the auxiliary sensing arrangement(s) <NUM> may be integrated with the infusion device <NUM> or the glucose sensing arrangement <NUM>.

The illustrated infusion system <NUM> also includes an acceleration sensing arrangement <NUM> (or accelerometer) that may be worn on or otherwise associated with the patient's body <NUM> to sense, detect, measure or otherwise quantify an acceleration of the patient's body <NUM>, which, in turn, may be indicative of exercise or some other condition in the body <NUM> that is likely to influence the patient's insulin response. While the acceleration sensing arrangement <NUM> is depicted as being integrated into the infusion device <NUM> in <FIG>, in alternative embodiments, the acceleration sensing arrangement <NUM> may be integrated with another sensing arrangement <NUM>, <NUM> on the body <NUM> of the patient, or the acceleration sensing arrangement <NUM> may be realized as a separate standalone component that is worn by the patient.

In the illustrated embodiment, the pump control system <NUM> generally represents the electronics and other components of the infusion device <NUM> that control operation of the fluid infusion device <NUM> according to a desired infusion delivery program in a manner that is influenced by the sensed glucose value indicating the current glucose level in the body <NUM> of the patient. For example, to support a closed-loop operating mode, the pump control system <NUM> maintains, receives, or otherwise obtains a target or commanded glucose value, and automatically generates or otherwise determines dosage commands for operating an actuation arrangement, such as a motor <NUM>, to displace the plunger <NUM> and deliver insulin to the body <NUM> of the patient based on the difference between the sensed glucose value and the target glucose value. In other operating modes, the pump control system <NUM> may generate or otherwise determine dosage commands configured to maintain the sensed glucose value below an upper glucose limit, above a lower glucose limit, or otherwise within a desired range of glucose values. In practice, the infusion device <NUM> may store or otherwise maintain the target value, upper and/or lower glucose limit(s), insulin delivery limit(s), and/or other glucose threshold value(s) in a data storage element accessible to the pump control system <NUM>. As described in greater detail, in one or more exemplary embodiments, the pump control system <NUM> automatically adjusts or adapts one or more parameters or other control information used to generate commands for operating the motor <NUM> in a manner that accounts for a likely change in the patient's glucose level or insulin response resulting from a meal, exercise, or other activity.

Still referring to <FIG>, the target glucose value and other threshold glucose values utilized by the pump control system <NUM> may be received from an external component (e.g., CCD <NUM> and/or computing device <NUM>) or be input by a patient via a user interface element <NUM> associated with the infusion device <NUM>. In practice, the one or more user interface element(s) <NUM> associated with the infusion device <NUM> typically include at least one input user interface element, such as, for example, a button, a keypad, a keyboard, a knob, a joystick, a mouse, a touch panel, a touchscreen, a microphone or another audio input device, and/or the like. Additionally, the one or more user interface element(s) <NUM> include at least one output user interface element, such as, for example, a display element (e.g., a light-emitting diode or the like), a display device (e.g., a liquid crystal display or the like), a speaker or another audio output device, a haptic feedback device, or the like, for providing notifications or other information to the patient. It should be noted that although <FIG> depicts the user interface element(s) <NUM> as being separate from the infusion device <NUM>, in practice, one or more of the user interface element(s) <NUM> may be integrated with the infusion device <NUM>. Furthermore, in some embodiments, one or more user interface element(s) <NUM> are integrated with the sensing arrangement <NUM> in addition to and/or in alternative to the user interface element(s) <NUM> integrated with the infusion device <NUM>. The user interface element(s) <NUM> may be manipulated by the patient to operate the infusion device <NUM> to deliver correction boluses, adjust target and/or threshold values, modify the delivery control scheme or operating mode, and the like, as desired.

Still referring to <FIG>, in the illustrated embodiment, the infusion device <NUM> includes a motor control module <NUM> coupled to a motor <NUM> (e.g., motor assembly <NUM>) that is operable to displace a plunger <NUM> (e.g., plunger <NUM>) in a reservoir (e.g., reservoir <NUM>) and provide a desired amount of fluid to the body <NUM> of a patient. In this regard, displacement of the plunger <NUM> results in the delivery of a fluid, such as insulin, that is capable of influencing the patient's physiological condition to the body <NUM> of the patient via a fluid delivery path (e.g., via tubing <NUM> of an infusion set <NUM>). A motor driver module <NUM> is coupled between an energy source <NUM> and the motor <NUM>. The motor control module <NUM> is coupled to the motor driver module <NUM>, and the motor control module <NUM> generates or otherwise provides command signals that operate the motor driver module <NUM> to provide current (or power) from the energy source <NUM> to the motor <NUM> to displace the plunger <NUM> in response to receiving, from a pump control system <NUM>, a dosage command indicative of the desired amount of fluid to be delivered.

In exemplary embodiments, the energy source <NUM> is realized as a battery housed within the infusion device <NUM> (e.g., within housing <NUM>) that provides direct current (DC) power. In this regard, the motor driver module <NUM> generally represents the combination of circuitry, hardware and/or other electrical components configured to convert or otherwise transfer DC power provided by the energy source <NUM> into alternating electrical signals applied to respective phases of the stator windings of the motor <NUM> that result in current flowing through the stator windings that generates a stator magnetic field and causes the rotor of the motor <NUM> to rotate. The motor control module <NUM> is configured to receive or otherwise obtain a commanded dosage from the pump control system <NUM>, convert the commanded dosage to a commanded translational displacement of the plunger <NUM>, and command, signal, or otherwise operate the motor driver module <NUM> to cause the rotor of the motor <NUM> to rotate by an amount that produces the commanded translational displacement of the plunger <NUM>. For example, the motor control module <NUM> may determine an amount of rotation of the rotor required to produce translational displacement of the plunger <NUM> that achieves the commanded dosage received from the pump control system <NUM>. Based on the current rotational position (or orientation) of the rotor with respect to the stator that is indicated by the output of the rotor sensing arrangement <NUM>, the motor control module <NUM> determines the appropriate sequence of alternating electrical signals to be applied to the respective phases of the stator windings that should rotate the rotor by the determined amount of rotation from its current position (or orientation). In embodiments where the motor <NUM> is realized as a BLDC motor, the alternating electrical signals commutate the respective phases of the stator windings at the appropriate orientation of the rotor magnetic poles with respect to the stator and in the appropriate order to provide a rotating stator magnetic field that rotates the rotor in the desired direction. Thereafter, the motor control module <NUM> operates the motor driver module <NUM> to apply the determined alternating electrical signals (e.g., the command signals) to the stator windings of the motor <NUM> to achieve the desired delivery of fluid to the patient.

When the motor control module <NUM> is operating the motor driver module <NUM>, current flows from the energy source <NUM> through the stator windings of the motor <NUM> to produce a stator magnetic field that interacts with the rotor magnetic field. In some embodiments, after the motor control module <NUM> operates the motor driver module <NUM> and/or motor <NUM> to achieve the commanded dosage, the motor control module <NUM> ceases operating the motor driver module <NUM> and/or motor <NUM> until a subsequent dosage command is received. In this regard, the motor driver module <NUM> and the motor <NUM> enter an idle state during which the motor driver module <NUM> effectively disconnects or isolates the stator windings of the motor <NUM> from the energy source <NUM>. In other words, current does not flow from the energy source <NUM> through the stator windings of the motor <NUM> when the motor <NUM> is idle, and thus, the motor <NUM> does not consume power from the energy source <NUM> in the idle state, thereby improving efficiency.

Depending on the embodiment, the motor control module <NUM> may be implemented or realized with a general purpose processor, a microprocessor, a controller, a microcontroller, a state machine, a content addressable memory, an application specific integrated circuit, a field programmable gate array, any suitable programmable logic device, discrete gate or transistor logic, discrete hardware components, or any combination thereof, designed to perform the functions described herein. In exemplary embodiments, the motor control module <NUM> includes or otherwise accesses a data storage element or memory, including any sort of random access memory (RAM), read only memory (ROM), flash memory, registers, hard disks, removable disks, magnetic or optical mass storage, or any other short or long term storage media or other non-transitory computer-readable medium, which is capable of storing programming instructions for execution by the motor control module <NUM>. The computer-executable programming instructions, when read and executed by the motor control module <NUM>, cause the motor control module <NUM> to perform or otherwise support the tasks, operations, functions, and processes described herein.

It should be appreciated that <FIG> is a simplified representation of the infusion device <NUM> for purposes of explanation and is not intended to limit the subject matter described herein in any way. In this regard, depending on the embodiment, some features and/or functionality of the sensing arrangement <NUM> may implemented by or otherwise integrated into the pump control system <NUM>, or vice versa. Similarly, in practice, the features and/or functionality of the motor control module <NUM> may implemented by or otherwise integrated into the pump control system <NUM>, or vice versa. Furthermore, the features and/or functionality of the pump control system <NUM> may be implemented by control electronics <NUM> located in the fluid infusion device <NUM>, while in alternative embodiments, the pump control system <NUM> may be implemented by a remote computing device that is physically distinct and/or separate from the infusion device <NUM>, such as, for example, the CCD <NUM> or the computing device <NUM>.

<FIG> depicts an exemplary embodiment of a pump control system <NUM> suitable for use as the pump control system <NUM> in <FIG> in accordance with one or more embodiments. The illustrated pump control system <NUM> includes, without limitation, a pump control module <NUM>, a communications interface <NUM>, and a data storage element (or memory) <NUM>. The pump control module <NUM> is coupled to the communications interface <NUM> and the memory <NUM>, and the pump control module <NUM> is suitably configured to support the operations, tasks, and/or processes described herein. In various embodiments, the pump control module <NUM> is also coupled to one or more user interface elements (e.g., user interface <NUM>, <NUM>) for receiving user inputs (e.g., target glucose values or other glucose thresholds) and providing notifications, alerts, or other therapy information to the patient.

The communications interface <NUM> generally represents the hardware, circuitry, logic, firmware and/or other components of the pump control system <NUM> that are coupled to the pump control module <NUM> and configured to support communications between the pump control system <NUM> and the various sensing arrangements <NUM>, <NUM>, <NUM>. In this regard, the communications interface <NUM> may include or otherwise be coupled to one or more transceiver modules capable of supporting wireless communications between the pump control system <NUM>, <NUM> and the sensing arrangement <NUM>, <NUM>, <NUM>. For example, the communications interface <NUM> may be utilized to receive sensor measurement values or other measurement data from each sensing arrangement <NUM>, <NUM>, <NUM> in an infusion system <NUM>. In other embodiments, the communications interface <NUM> may be configured to support wired communications to/from the sensing arrangement(s) <NUM>, <NUM>, <NUM>. In various embodiments, the communications interface <NUM> may also support communications with another electronic device (e.g., CCD <NUM> and/or computer <NUM>) in an infusion system (e.g., to upload sensor measurement values to a server or other computing device, receive control information from a server or other computing device, and the like).

The pump control module <NUM> generally represents the hardware, circuitry, logic, firmware and/or other component of the pump control system <NUM> that is coupled to the communications interface <NUM> and configured to determine dosage commands for operating the motor <NUM> to deliver fluid to the body <NUM> based on measurement data received from the sensing arrangements <NUM>, <NUM>, <NUM> and perform various additional tasks, operations, functions and/or operations described herein. For example, in exemplary embodiments, pump control module <NUM> implements or otherwise executes a command generation application <NUM> that supports one or more autonomous operating modes and calculates or otherwise determines dosage commands for operating the motor <NUM> of the infusion device <NUM> in an autonomous operating mode based at least in part on a current measurement value for a condition in the body <NUM> of the patient. For example, in a closed-loop operating mode, the command generation application <NUM> may determine a dosage command for operating the motor <NUM> to deliver insulin to the body <NUM> of the patient based at least in part on the current glucose measurement value most recently received from the sensing arrangement <NUM> to regulate the patient's blood glucose level to a target reference glucose value. Additionally, the command generation application <NUM> may generate dosage commands for boluses that are manually-initiated or otherwise instructed by a patient via a user interface element.

In exemplary embodiments, the pump control module <NUM> also implements or otherwise executes a personalization application <NUM> that is cooperatively configured to interact with the command generation application <NUM> to support adjusting dosage commands or control information dictating the manner in which dosage commands are generated in a personalized, patient-specific manner. In this regard, in some embodiments, based on correlations between current or recent measurement data and the current operational context relative to historical data associated with the patient, the personalization application <NUM> may adjust or otherwise modify values for one or more parameters utilized by the command generation application <NUM> when determining dosage commands, for example, by modifying a parameter value at a register or location in memory <NUM> referenced by the command generation application <NUM>. In yet other embodiments, the personalization application <NUM> may predict meals or other events or activities that are likely to be engaged in by the patient and output or otherwise provide an indication of the predicted patient behavior for confirmation or modification by the patient, which, in turn, may then be utilized to adjust the manner in which dosage commands are generated to regulate glucose in a manner that accounts for the patient's behavior in a personalized manner.

Still referring to <FIG>, depending on the embodiment, the pump control module <NUM> may be implemented or realized with at least one general purpose processor device, a microprocessor, a controller, a microcontroller, a state machine, a content addressable memory, an application specific integrated circuit, a field programmable gate array, any suitable programmable logic device, discrete gate or transistor logic, discrete hardware components, or any combination thereof, designed to perform the functions described herein. In this regard, the steps of a method or algorithm described in connection with the embodiments disclosed herein may be embodied directly in hardware, in firmware, in a software module executed by the pump control module <NUM>, or in any practical combination thereof. In exemplary embodiments, the pump control module <NUM> includes or otherwise accesses the data storage element or memory <NUM>, which may be realized using any sort of non-transitory computer-readable medium capable of storing programming instructions for execution by the pump control module <NUM>. The computer-executable programming instructions, when read and executed by the pump control module <NUM>, cause the pump control module <NUM> to implement or otherwise generate the applications <NUM>, <NUM> and perform tasks, operations, functions, and processes described herein.

It should be understood that <FIG> is a simplified representation of a pump control system <NUM> for purposes of explanation and is not intended to limit the subject matter described herein in any way. For example, in some embodiments, the features and/or functionality of the motor control module <NUM> may be implemented by or otherwise integrated into the pump control system <NUM> and/or the pump control module <NUM>, for example, by the command generation application <NUM> converting the dosage command into a corresponding motor command, in which case, the separate motor control module <NUM> may be absent from an embodiment of the infusion device <NUM>.

<FIG> depicts an exemplary closed-loop control system <NUM> that may be implemented by a pump control system <NUM>, <NUM> to provide a closed-loop operating mode that autonomously regulates a condition in the body of a patient to a reference (or target) value. It should be appreciated that <FIG> is a simplified representation of the control system <NUM> for purposes of explanation and is not intended to limit the subject matter described herein in any way.

In exemplary embodiments, the control system <NUM> receives or otherwise obtains a target glucose value at input <NUM>. In some embodiments, the target glucose value may be stored or otherwise maintained by the infusion device <NUM> (e.g., in memory <NUM>), however, in some alternative embodiments, the target value may be received from an external component (e.g., CCD <NUM> and/or computer <NUM>). In one or more embodiments, the target glucose value may be calculated or otherwise determined prior to entering the closed-loop operating mode based on one or more patient-specific control parameters. For example, the target blood glucose value may be calculated based at least in part on a patient-specific reference basal rate and a patient-specific daily insulin requirement, which are determined based on historical delivery information over a preceding interval of time (e.g., the amount of insulin delivered over the preceding <NUM> hours). The control system <NUM> also receives or otherwise obtains a current glucose measurement value (e.g., the most recently obtained sensor glucose value) from the sensing arrangement <NUM> at input <NUM>. The illustrated control system <NUM> implements or otherwise provides proportional-integral-derivative (PID) control to determine or otherwise generate delivery commands for operating the motor <NUM> based at least in part on the difference between the target glucose value and the current glucose measurement value. In this regard, the PID control attempts to minimize the difference between the measured value and the target value, and thereby regulates the measured value to the desired value. PID control parameters are applied to the difference between the target glucose level at input <NUM> and the measured glucose level at input <NUM> to generate or otherwise determine a dosage (or delivery) command provided at output <NUM>. Based on that delivery command, the motor control module <NUM> operates the motor <NUM> to deliver insulin to the body of the patient to influence the patient's glucose level, and thereby reduce the difference between a subsequently measured glucose level and the target glucose level.

The illustrated control system <NUM> includes or otherwise implements a summation block <NUM> configured to determine a difference between the target value obtained at input <NUM> and the measured value obtained from the sensing arrangement <NUM> at input <NUM>, for example, by subtracting the target value from the measured value. The output of the summation block <NUM> represents the difference between the measured and target values, which is then provided to each of a proportional term path, an integral term path, and a derivative term path. The proportional term path includes a gain block <NUM> that multiplies the difference by a proportional gain coefficient, KP, to obtain the proportional term. The integral term path includes an integration block <NUM> that integrates the difference and a gain block <NUM> that multiplies the integrated difference by an integral gain coefficient, KI, to obtain the integral term. The derivative term path includes a derivative block <NUM> that determines the derivative of the difference and a gain block <NUM> that multiplies the derivative of the difference by a derivative gain coefficient, KD, to obtain the derivative term. The proportional term, the integral term, and the derivative term are then added or otherwise combined to obtain a delivery command that is utilized to operate the motor at output <NUM>. Various implementation details pertaining to closed-loop PID control and determining gain coefficients are described in greater detail in <CIT>.

In one or more exemplary embodiments, the PID gain coefficients are patient-specific and dynamically calculated or otherwise determined prior to entering the closed-loop operating mode based on historical insulin delivery information (e.g., amounts and/or timings of previous dosages, historical correction bolus information, or the like), historical sensor measurement values, historical reference blood glucose measurement values, user-reported or user-input events (e.g., meals, exercise, and the like), and the like. In this regard, one or more patient-specific control parameters (e.g., an insulin sensitivity factor, a daily insulin requirement, an insulin limit, a reference basal rate, a reference fasting glucose, an active insulin action duration, pharmodynamical time constants, or the like) may be utilized to compensate, correct, or otherwise adjust the PID gain coefficients to account for various operating conditions experienced and/or exhibited by the infusion device <NUM>. The PID gain coefficients may be maintained by the memory <NUM> accessible to the pump control module <NUM>. In this regard, the memory <NUM> may include a plurality of registers associated with the control parameters for the PID control. For example, a first parameter register may store the target glucose value and be accessed by or otherwise coupled to the summation block <NUM> at input <NUM>, and similarly, a second parameter register accessed by the proportional gain block <NUM> may store the proportional gain coefficient, a third parameter register accessed by the integration gain block <NUM> may store the integration gain coefficient, and a fourth parameter register accessed by the derivative gain block <NUM> may store the derivative gain coefficient.

In one or more exemplary embodiments, one or more parameters of the closed-loop control system <NUM> are automatically adjusted or adapted in a personalized manner to account for potential changes in the patient's glucose level or insulin sensitivity resulting from meals, exercise, or other events or activities. For example, in one or more embodiments, the target glucose value may be decreased in advance of a predicted meal event to achieve an increase in the insulin infusion rate to effectively pre-bolus a meal, and thereby reduce the likelihood of postprandial hyperglycemia. Additionally or alternatively, the time constant or gain coefficient associated with one or more paths of the closed-loop control system <NUM> may be adjusted to tune the responsiveness to deviations between the measured glucose value and the target glucose value. For example, based on the particular type of meal being consumed or the particular time of day during which the meal is consumed, the time constant associated with the derivative block <NUM> or derivative term path may be adjusted to make the closed-loop control more or less aggressive in response to an increase in the patient's glucose level based on the patient's historical glycemic response to the particular type of meal.

<FIG> depicts an exemplary embodiment of a patient monitoring system <NUM>. The patient monitoring system <NUM> includes a medical device <NUM> that is communicatively coupled to a sensing element <NUM> that is inserted into the body of a patient or otherwise worn by the patient to obtain measurement data indicative of a physiological condition in the body of the patient, such as a sensed glucose level. The medical device <NUM> is communicatively coupled to a client device <NUM> via a communications network <NUM>, with the client device <NUM> being communicatively coupled to a remote device <NUM> via another communications network <NUM>. In this regard, the client device <NUM> may function as an intermediary for uploading or otherwise providing measurement data from the medical device <NUM> to the remote device <NUM>. It should be appreciated that <FIG> depicts a simplified representation of a patient monitoring system <NUM> for purposes of explanation and is not intended to limit the subject matter described herein in any way.

In exemplary embodiments, the client device <NUM> is realized as a mobile phone, a smartphone, a tablet computer, or other similar mobile electronic device; however, in other embodiments, the client device <NUM> may be realized as any sort of electronic device capable of communicating with the medical device <NUM> via network <NUM>, such as a laptop or notebook computer, a desktop computer, or the like. In exemplary embodiments, the network <NUM> is realized as a Bluetooth network, a ZigBee network, or another suitable personal area network. That said, in other embodiments, the network <NUM> could be realized as a wireless ad hoc network, a wireless local area network (WLAN), or local area network (LAN). The client device <NUM> includes or is coupled to a display device, such as a monitor, screen, or another conventional electronic display, capable of graphically presenting data and/or information pertaining to the physiological condition of the patient. The client device <NUM> also includes or is otherwise associated with a user input device, such as a keyboard, a mouse, a touchscreen, or the like, capable of receiving input data and/or other information from the user of the client device <NUM>.

In exemplary embodiments, a user, such as the patient, the patient's doctor or another healthcare provider, or the like, manipulates the client device <NUM> to execute a client application <NUM> that supports communicating with the medical device <NUM> via the network <NUM>. In this regard, the client application <NUM> supports establishing a communications session with the medical device <NUM> on the network <NUM> and receiving data and/or information from the medical device <NUM> via the communications session. The medical device <NUM> may similarly execute or otherwise implement a corresponding application or process that supports establishing the communications session with the client application <NUM>. The client application <NUM> generally represents a software module or another feature that is generated or otherwise implemented by the client device <NUM> to support the processes described herein. Accordingly, the client device <NUM> generally includes a processing system and a data storage element (or memory) capable of storing programming instructions for execution by the processing system, that, when read and executed, cause processing system to create, generate, or otherwise facilitate the client application <NUM> and perform or otherwise support the processes, tasks, operations, and/or functions described herein. Depending on the embodiment, the processing system may be implemented using any suitable processing system and/or device, such as, for example, one or more processor devices, central processing units (CPUs), controllers, microprocessors, microcontrollers, processing cores and/or other hardware computing resources configured to support the operation of the processing system described herein. Similarly, the data storage element or memory may be realized as a random-access memory (RAM), read only memory (ROM), flash memory, magnetic or optical mass storage, or any other suitable non-transitory short or long-term data storage or other computer-readable media, and/or any suitable combination thereof.

In one or more embodiments, the client device <NUM> and the medical device <NUM> establish an association (or pairing) with one another over the network <NUM> to support subsequently establishing a point-to-point or peer-to-peer communications session between the medical device <NUM> and the client device <NUM> via the network <NUM>. For example, in accordance with one embodiment, the network <NUM> is realized as a Bluetooth network, wherein the medical device <NUM> and the client device <NUM> are paired with one another (e.g., by obtaining and storing network identification information for one another) by performing a discovery procedure or another suitable pairing procedure. The pairing information obtained during the discovery procedure allows either of the medical device <NUM> or the client device <NUM> to initiate the establishment of a secure communications session via the network <NUM>.

In one or more exemplary embodiments, the client application <NUM> is also configured to store or otherwise maintain an address and/or other identification information for the remote device <NUM> on the second network <NUM>. In this regard, the second network <NUM> may be physically and/or logically distinct from the network <NUM>, such as, for example, the Internet, a cellular network, a wide area network (WAN), or the like. The remote device <NUM> generally represents a server or other computing device configured to receive and analyze or otherwise monitor measurement data, event log data, and potentially other information obtained for the patient associated with the medical device <NUM>. In exemplary embodiments, the remote device <NUM> is coupled to a database <NUM> configured to store or otherwise maintain data associated with individual patients. In practice, the remote device <NUM> may reside at a location that is physically distinct and/or separate from the medical device <NUM> and the client device <NUM>, such as, for example, at a facility that is owned and/or operated by or otherwise affiliated with a manufacturer of the medical device <NUM>. For purposes of explanation, but without limitation, the remote device <NUM> may alternatively be referred to herein as a server.

Still referring to <FIG>, the sensing element <NUM> generally represents the component of the patient monitoring system <NUM> that is configured to generate, produce, or otherwise output one or more electrical signals indicative of a physiological condition that is sensed, measured, or otherwise quantified by the sensing element <NUM>. In this regard, the physiological condition of a patient influences a characteristic of the electrical signal output by the sensing element <NUM>, such that the characteristic of the output signal corresponds to or is otherwise correlative to the physiological condition that the sensing element <NUM> is sensitive to. In exemplary embodiments, the sensing element <NUM> is realized as an interstitial glucose sensing element inserted at a location on the body of the patient that generates an output electrical signal having a current (or voltage) associated therewith that is correlative to the interstitial fluid glucose level that is sensed or otherwise measured in the body of the patient by the sensing element <NUM>.

The medical device <NUM> generally represents the component of the patient monitoring system <NUM> that is communicatively coupled to the output of the sensing element <NUM> to receive or otherwise obtain the measurement data samples from the sensing element <NUM> (e.g., the measured glucose and characteristic impedance values), store or otherwise maintain the measurement data samples, and upload or otherwise transmit the measurement data to the remote device <NUM> or server via the client device <NUM>. In one or more embodiments, the medical device <NUM> is realized as an infusion device <NUM>, <NUM>, <NUM> configured to deliver a fluid, such as insulin, to the body of the patient. That said, in other embodiments, the medical device <NUM> could be a standalone sensing or monitoring device separate and independent from an infusion device (e.g., sensing arrangement <NUM>, <NUM>). It should be noted that although <FIG> depicts the medical device <NUM> and the sensing element <NUM> as separate components, in practice, the medical device <NUM> and the sensing element <NUM> may be integrated or otherwise combined to provide a unitary device that can be worn by the patient.

In exemplary embodiments, the medical device <NUM> includes a control module <NUM>, a data storage element <NUM> (or memory), and a communications interface <NUM>. The control module <NUM> generally represents the hardware, circuitry, logic, firmware and/or other component(s) of the medical device <NUM> that is coupled to the sensing element <NUM> to receive the electrical signals output by the sensing element <NUM> and perform or otherwise support various additional tasks, operations, functions and/or processes described herein. Depending on the embodiment, the control module <NUM> may be implemented or realized with a general purpose processor device, a microprocessor device, a controller, a microcontroller, a state machine, a content addressable memory, an application specific integrated circuit, a field programmable gate array, any suitable programmable logic device, discrete gate or transistor logic, discrete hardware components, or any combination thereof, designed to perform the functions described herein. In some embodiments, the control module <NUM> includes an analog-to-digital converter (ADC) or another similar sampling arrangement that samples or otherwise converts an output electrical signal received from the sensing element <NUM> into corresponding digital measurement data value. In other embodiments, the sensing element <NUM> may incorporate an ADC and output a digital measurement value.

The communications interface <NUM> generally represents the hardware, circuitry, logic, firmware and/or other components of the medical device <NUM> that are coupled to the control module <NUM> for outputting data and/or information from/to the medical device <NUM> to/from the client device <NUM>. For example, the communications interface <NUM> may include or otherwise be coupled to one or more transceiver modules capable of supporting wireless communications between the medical device <NUM> and the client device <NUM>. In exemplary embodiments, the communications interface <NUM> is realized as a Bluetooth transceiver or adapter configured to support Bluetooth Low Energy (BLE) communications.

In exemplary embodiments, the remote device <NUM> receives, from the client device <NUM>, measurement data values associated with a particular patient (e.g., sensor glucose measurements, acceleration measurements, and the like) that were obtained using the sensing element <NUM>, and the remote device <NUM> stores or otherwise maintains the historical measurement data in the database <NUM> in association with the patient (e.g., using one or more unique patient identifiers). Additionally, the remote device <NUM> may also receive, from or via the client device <NUM>, meal data or other event log data that may be input or otherwise provided by the patient (e.g., via client application <NUM>) and store or otherwise maintain historical meal data and other historical event or activity data associated with the patient in the database <NUM>. In this regard, the meal data include, for example, a time or timestamp associated with a particular meal event, a meal type or other information indicative of the content or nutritional characteristics of the meal, and an indication of the size associated with the meal. In exemplary embodiments, the remote device <NUM> also receives historical fluid delivery data corresponding to basal or bolus dosages of fluid delivered to the patient by an infusion device <NUM>, <NUM>, <NUM>. For example, the client application <NUM> may communicate with an infusion device <NUM>, <NUM>, <NUM> to obtain insulin delivery dosage amounts and corresponding timestamps from the infusion device <NUM>, <NUM>, <NUM>, and then upload the insulin delivery data to the remote device <NUM> for storage in association with the particular patient. The remote device <NUM> may also receive geolocation data and potentially other contextual data associated with a device <NUM>, <NUM> from the client device <NUM> and/or client application <NUM>, and store or otherwise maintain the historical operational context data in association with the particular patient. In this regard, one or more of the devices <NUM>, <NUM> may include a global positioning system (GPS) receiver or similar modules, components or circuitry capable of outputting or otherwise providing data characterizing the geographic location of the respective device <NUM>, <NUM> in real-time.

The historical patient data may be analyzed by one or more of the remote device <NUM>, the client device <NUM>, and/or the medical device <NUM> to alter or adjust operation of an infusion device <NUM>, <NUM>, <NUM> to influence fluid delivery in a personalized manner. For example, the patient's historical meal data and corresponding measurement data or other contextual data may be analyzed to predict a future time when the next meal is likely to be consumed by the patient, the likelihood of a future meal event within a specific time period, the likely size or amount of carbohydrates associated with a future meal, the likely type or nutritional content of the future meal, and/or the like. Moreover, the patient's historical measurement data for postprandial periods following historical meal events may be analyzed to model or otherwise characterize the patient's glycemic response to the predicted size and type of meal for the current context (e.g., time of day, day of week, geolocation, etc.). One or more aspects of the infusion device <NUM>, <NUM>, <NUM> that control or regulate insulin delivery may then be modified or adjusted to proactively account for the patient's likely meal activity and glycemic response.

In one or more exemplary embodiments, the remote device <NUM> utilizes machine learning to determine which combination of historical sensor glucose measurement data, historical delivery data, historical auxiliary measurement data (e.g., historical acceleration measurement data, historical heart rate measurement data, and/or the like), historical event log data, historical geolocation data, and other historical or contextual data are correlated to or predictive of the occurrence of a particular event, activity, or metric for a particular patient, and then determines a corresponding equation, function, or model for calculating the value of the parameter of interest based on that set of input variables. Thus, the model is capable of characterizing or mapping a particular combination of one or more of the current (or recent) sensor glucose measurement data, auxiliary measurement data, delivery data, geographic location, patient behavior or activities, and the like to a value representative of the current probability or likelihood of a particular event or activity or a current value for a parameter of interest. It should be noted that since each patient's physiological response may vary from the rest of the population, the subset of input variables that are predictive of or correlative for a particular patient may vary from other patients. Additionally, the relative weightings applied to the respective variables of that predictive subset may also vary from other patients who may have common predictive subsets, based on differing correlations between a particular input variable and the historical data for that particular patient. It should be noted that any number of different machine learning techniques may be utilized by the remote device <NUM> to determine what input variables are predictive for a current patient of interest, such as, for example, artificial neural networks, genetic programming, support vector machines, Bayesian networks, probabilistic machine learning models, or other Bayesian techniques, fuzzy logic, heuristically derived combinations, or the like.

An insulin infusion device of the type described above can be suitably configured to calculate an upper limit on the insulin delivery rate that can be used during an automatic basal insulin delivery mode. In such an automatic mode, the infusion device automatically delivers insulin (at a rate that is less than or equal to the calculated upper limit). This upper limit, Umax, can be dynamically adjusted to better suit the needs of the user. For example, an exemplary embodiment of the infusion device adapts Umax once a day, e.g., at midnight. In addition to the basal insulin that is automatically provided by the infusion device, the user (or a caregiver) can also issue additional insulin boluses by announcing (entering) a carbohydrate value for a meal and/or by entering a blood glucose meter reading.

If the insulin infusion device is already delivering insulin at the Umax rate (the upper limit) while in the automatic basal insulin mode, then it can be assumed that the patient needs additional insulin to better regulate blood glucose levels. To this end, the infusion device can respond to such a condition by considering whether a correction bolus is needed. In certain embodiments, when the automated insulin delivery rate exceeds a specified rate for at least a designated period of time, then the infusion device reacts by initiating an automated correction bolus procedure to calculate and possibly deliver a correction bolus. If the calculated correction bolus is above a baseline threshold amount and is determined to be safe to administer, then the infusion device issues the correction bolus as a supplement to the basal insulin that is already being delivered. As one non-limiting example, if the automatic basal insulin rate has been above a specified percentage of Umax (e.g., <NUM>%, <NUM>%, etc.) for at least one hour, then the insulin infusion device will proceed with the automated correction bolus procedure. As another non-limiting example, if the automatic basal insulin rate reaches Umax at any time, then the automated correction bolus procedure will be triggered. These and other triggering conditions and mechanisms can be employed in an exemplary embodiment of the insulin infusion device.

In accordance with the embodiments presented here, the initial (potential) correction bolus is calculated as follows: <MAT> In this expression:.

The initial correction bolus can be scaled by a multiplier that has a value between <NUM> and <NUM> to reduce the bolus amount as needed. More specifically, the infusion device intelligently scales the initial correction bolus amount (or withholds the bolus) to prevent the risk of hypoglycemia following delivery of the correction bolus.

In accordance with certain embodiments, the insulin infusion device performs a correction bolus check during the automatic mode under the following conditions: a BG value (e.g., a BG meter reading or a glucose sensor reading) is entered into the device or is otherwise obtained by the device; the BG value is greater than a threshold value, such as <NUM>/dL or <NUM>/dL; and the calculated correction bolus value is greater than zero after deducting active insulin and applying safe correction bolus logic. If all of these conditions are met, then the infusion device provides a message recommending a correction bolus to the user. The user may decide to either accept the correction bolus or reject it.

As mentioned above, the baseline initial correction bolus value can be scaled, based on a safe correction bolus methodology utilized by the infusion device. The safe correction bolus methodology incorporates a prediction model to estimate whether the correction bolus is likely to lower the user's BG level below a stated low glucose threshold (such as <NUM>/dL) in the near future (such as within the next two to four hours). If the BG level is predicted to go below the low glucose threshold value, then the initial correction bolus value is incrementally reduced until the predicted level remains above the threshold value.

The improved methodology described here delivers correction boluses automatically without any user input or acknowledgement. The core computation of the automatic correction bolus is based on Equation <NUM> set forth above. However, the correction target is lowered from a default, standard, or typical value to a reduced value, such as <NUM>/dL. Moreover, correction boluses do not require BG meter readings; they can be computed based on readings from a patient-worn continuous glucose sensor. That said, if a valid BG meter value is available, then that value will be preferred.

A meal detection algorithm is also utilized in the exemplary embodiment of the insulin infusion device. In this regard, <FIG> is a diagram that illustrates a scenario where an automatic correction bolus can be delivered. The vertical axis indicates BG measurements, and the horizontal axis represents time. <FIG> includes a plot <NUM> of BG values, and an indication of the lowered correction target of <NUM>/dL. For this particular implementation, the BG values are actual (measured) values, although predicted values could also be used in certain applications. <FIG> also depicts a zone <NUM> that identifies low BG thresholds that are used for comparison against predicted BG values in the manner described in more detail below. The BG limits for this particular example are <NUM>/dL and <NUM>/dL. In practice, different default and reduced BG limits (which may be fixed or dynamically adjustable) may be employed as desired for the given implementation.

The meal detection algorithm calculates the rate of change (slope) defined by previous sensor glucose readings (e.g., the last three to seven readings) to detect a postprandial rise based on the direction, magnitude, and duration of the slopes. The four circled points of the plot <NUM> depict an instance of such a rise in measured BG values. If a meal is detected in this manner by the algorithm, then the low prediction threshold used in the safe correction bolus algorithm will be temporarily lowered from <NUM>/dL to <NUM>/dL. The timing of this reduction is depicted in <FIG>, where the plot <NUM> indicates the value of the low prediction threshold (also referred to herein as the low BG threshold level) over time. As the plot <NUM> indicates, the low prediction threshold remains at its default value of <NUM>/dL unless the measured BG values exhibit a rising trend that is typically associated with consumption of a meal. If a meal is detected, the low prediction threshold is adjusted downward to <NUM>/dL. As a result of this low glucose threshold reduction, the safe correction bolus algorithm deducts less from a calculated correction bolus (if there is a detected pattern of sustained rising rate of change of sensed glucose values at the time of the correction bolus). That said, the final correction bolus amount will not exceed the initially calculated value (as computed by Equation <NUM>).

For this particular embodiment, the automatic correction bolus algorithm computes a possible correction bolus amount with each new BG measurement that is obtained, and delivers the calculated correction bolus if the following conditions are met: (<NUM>) the automatic basal insulin delivery is currently at the maximum allowable rate of Umax, (<NUM>) the intended correction bolus amount is greater than <NUM>% of the Umax level; and (<NUM>) the automatic delivery mode is neither operating in the Safe Basal mode nor the Temporary Glucose Target mode.

In general, automatic correction boluses will be relatively small and will occur during periods of positive rates of glucose change when BG values are rising above <NUM>/dL. For example, assume that the previous BG value was <NUM>/dL, the user's BG is rising rapidly at a rate of <NUM>/dL/min, the automatic basal delivery is at Umax, and there is no insulin on board from a prior bolus. If a new BG value of <NUM>/dL is received (for example, sensor glucose values are received every five minutes in the exemplary system described here), an automatic correction bolus would be delivered based on the <NUM>/dL difference between the current BG value of <NUM>/dL and the correction target value of <NUM>/dL. Note that for this example, the first automatic correction bolus must exceed Umax by at least <NUM>% for it to be delivered. Accordingly, it is not obvious at what level of glucose the first correction bolus will be implemented.

Continuing this example, if glucose continues to rise at the same rate and the next BG value of <NUM>/dL is received five minutes later, then another correction bolus would be calculated based on the <NUM>/dL difference between the current BG value and the correction target, and the infusion device would deduct the active insulin from the prior correction bolus. Therefore, the new correction bolus would effectively only account for the <NUM>/dL difference between the current BG value and the previous BG value instead of the <NUM>/dL difference between the current BG value and the correction target. If the user's BG then stabilized at <NUM>/dL and a new BG value is received, then the insulin on board deduction from the previous two corrections would counter the correction calculation based on the <NUM>/dL difference between the BG and the correction target, so no additional correction would be given.

The benefits of automating the correction bolus will help to provide more effective therapy while reducing the burden on the user to manage their diabetes. There are multiple safeguards in place to prevent over-delivery of insulin by the automatic correction bolus feature. These safeguards include the following, without limitation:.

The correction bolus target is fixed at <NUM>/dL, which provides a margin against hypoglycemia.

Safety of each correction bolus is checked by predicting BG two hours in the future with the help of a mathematical model. If hypoglycemia is predicted, the safeguard can reduce the size of the correction bolus (up to zero) until no hypoglycemia is predicted.

In certain embodiments, automatic correction boluses are suppressed when the total amount of correction bolus commands in a <NUM>-minute moving window exceeds <NUM>% of the total daily dose. Correction boluses resume when the total amount of correction bolus commands within the <NUM>-minute window does not exceed <NUM>% of total daily dose.

In certain embodiments, sensor glucose values that may be used for correction boluses are limited to <NUM>/dL when a new sensor is less than <NUM> hours old and the calibration factor is greater than <NUM>/dL/nA.

In certain embodiments, automatic correction boluses are suppressed when a sensor glucose spike is detected that is greater than <NUM>/dL/<NUM> minutes (if a sensor glucose measurement is available) or <NUM>/dL/<NUM> minutes (based on the current ISIG and calibration factor when a sensor glucose measurement is not available), and the associated ISIG spike is greater than <NUM> nA/<NUM> minutes. Correction boluses may resume following a blood glucose entry with successful calibration factor.

Automatic correction bolus is delivered after deducting insulin on board. The duration of active insulin on board can be adjusted by the user (minimum two hours, maximum eight hours).

The insulin sensitivity factor, ISF, used in the automatic correction bolus calculation is adapted to the user's physiology based on total daily dose instead of an adjustable user setting. Accordingly, the user may not use the ISF setting to adjust the size of automatic correction boluses.

A prolonged high alert occurs if measured sensor glucose stays above <NUM>/dL for three hours.

The continuous glucose sensor is calibrated at least once every <NUM> hours by an independent fingerstick (or other blood sample) BG measurement.

All BG meter measurements that are entered into the insulin infusion device (either manually or through a linked meter) and confirmed by the user are used for a sensor integrity check and to calibrate the continuous glucose sensor.

<FIG> is a flow diagram that illustrates an exemplary embodiment of an insulin infusion device control process <NUM>. The process <NUM> is suitable for controlling the operation of an infusion device of the type described above with reference to <FIG>, namely, an infusion device having a fluid reservoir for insulin to be delivered from the device to the body of a user, and having at least one processor device that executes computer-readable instructions to carry out the process <NUM>. The various tasks performed in connection with a process described herein may be performed by software, hardware, firmware, or any combination thereof. For illustrative purposes, a description of a process may refer to elements mentioned above in connection with <FIG>. It should be appreciated that a described process may include any number of additional or alternative tasks, the tasks shown in the figures need not be performed in the illustrated order, and an illustrated process may be incorporated into a more comprehensive procedure or process having additional functionality not described in detail herein. Moreover, one or more of the tasks shown for an illustrated process could be omitted from an embodiment of the process as long as the intended overall functionality remains intact.

The process <NUM> represents one iteration that is performed for a current sampling point or period of time, which corresponds to the most recent sampling period. This example assumes that the insulin infusion device is already being controlled to operate in an automatic basal insulin delivery mode (task <NUM>) that delivers basal insulin to the body of the user. This example also assumes that the process <NUM> receives relevant data in accordance with a predetermined schedule (e.g., a sampling period of five minutes). Accordingly, the process <NUM> receives, obtains, or accesses information that may have an influence on the manner in which the infusion device delivers insulin to the user. For example, the process <NUM> obtains a current or most recent BG measurement that indicates a current BG level of the user (task <NUM>). As mentioned above, the BG measurement can be obtained from a BG meter (typically a fingerstick measurement) or a continuous glucose sensor that is coupled to the body of the user.

For this particular embodiment, the correction bolus procedure is initiated when two conditions are satisfied: (<NUM>) the current BG measurement exceeds a correction bolus threshold value; and (<NUM>) a maximum allowable basal insulin infusion rate (Umax) has been reached during operation in the automatic basal insulin delivery mode. To this end, the process <NUM> checks whether the obtained BG measurement is greater than the correction bolus threshold value, LIMIT<NUM>, (query task <NUM>) and whether the current basal insulin infusion rate equals Umax (query task <NUM>). For this non-limiting example, the correction bolus threshold value (LIMIT<NUM>) is <NUM>/dL and Umax will typically fall within the range of about <NUM> to about <NUM> Units/hour (the actual value checked at query task <NUM> is patient-specific). If either of these conditions are not met, then the process <NUM> exits without considering an automatic correction bolus. If both of these conditions are satisfied, however, then the process <NUM> continues by initiating and performing the correction bolus procedure to calculate an automatic correction bolus amount (task <NUM>). The manner in which the automatic correction bolus (ACB) amount is calculated will be described in more detail below with reference to <FIG>. In certain implementations, an initial or proposed ACB amount is calculated and scaled or adjusted as needed to arrive at a final ACB amount.

The illustrated embodiment of the process <NUM> performs an additional check before delivering a correction bolus. More specifically, the process <NUM> checks whether the computed final ACB amount exceeds a bolus delivery threshold amount, LIMIT<NUM> (query task <NUM>). If the final ACB amount does not exceed the bolus delivery threshold amount (the "No" branch of query task <NUM>), then the insulin infusion device is controlled such that the calculated final ACB amount is not delivered to the user (task <NUM>). If the final ACB amount exceeds the bolus delivery threshold amount (the "Yes" branch of query task <NUM>), then the insulin infusion device is controlled to deliver the calculated final ACB amount to the user (task <NUM>). In other words, the final ACB amount is delivered only when it exceeds the bolus delivery threshold amount, which may be defined as a percentage of Umax, e.g., ten percent of the current value of Umax. The bolus delivery threshold amount is utilized in the exemplary embodiment to avoid delivery of small insulin boluses, which may have little effect and/or be unnecessary. Whether or not the final ACB amount is delivered, the process <NUM> continues by delivering basal insulin at the rate of Umax for at least the next cycle or sampling period (task <NUM>). As depicted in <FIG>, the process <NUM> leads back to task <NUM> to repeat itself for the next iteration.

<FIG> is a flow diagram that illustrates an exemplary embodiment of an ACB calculation process <NUM>, which can be performed during task <NUM> of the process <NUM> (see <FIG>). The process <NUM> is one suitable methodology for calculating the final ACB amount to be considered for delivery to the user. Alternative embodiments, however, may utilize different methodologies or approaches to determine a recommended ACB amount.

The exemplary embodiment of the process <NUM> calculates an initial correction bolus amount for the user (task <NUM>). In this regard, the initial correction bolus can be calculated in accordance with Equation <NUM>. The exemplary embodiment described here includes an optional feature that automatically detects a BG trend that is indicative of meal consumption and, in response to such detection, adjusts the methodology by which the final ACB amount is calculated. In this regard, <FIG> includes a query task <NUM> that checks whether the user's BG measurements are indicative of meal consumption. In practice, the process <NUM> analyzes the current BG measurement and at least one historical BG measurement to check whether those measurements reflect a BG trend that is indicative of meal consumption by the user. As explained above, if the BG measurements under analysis exhibit a sharp rise over time, a slope that exceeds a threshold value, or the like, then the process <NUM> will indicate that a meal has been detected for purposes of query task <NUM> (the "Yes" branch); if not, then the process <NUM> continues via the "No" branch of query task <NUM>.

If query task <NUM> detects conditions indicative of meal consumption, then the process <NUM> continues by reducing a default value of a low BG threshold level to obtain a reduced value (task <NUM>). The resulting low BG threshold value, which is labeled LIMIT<NUM> in <FIG>, is utilized as a comparison value in the manner described in more detail below with reference to query task <NUM>. If query task <NUM> determines that the user's BG trend does not reflect the recent consumption of a meal (the "No" branch of query task <NUM>), then the process <NUM> continues with the default, unadjusted, value of the low BG threshold level (task <NUM>). Accordingly, the default low BG threshold level is utilized to calculate the final ACB amount unless the process <NUM> detects conditions that indicate meal consumption - if so, the default low BG threshold level is lowered. As mentioned above, for the exemplary embodiment described here, the default low BG threshold value is <NUM>/dL and the reduced low BG threshold value is <NUM>/dL. It should be appreciated that these thresholds may vary from one embodiment to another, and that the thresholds may be fixed values, automatically adjustable values, or manually adjustable values if so desired.

After settling on the value to be used for the low BG threshold level (LIMIT<NUM>), the process <NUM> continues by computing a predicted future BG level (PBG) of the user, which results from simulated delivery of the calculated correction bolus amount (task <NUM>). In accordance with the exemplary embodiment presented here, the process <NUM> calculates a set of predicted or forecasted glucose measurement values for the patient corresponding to a time period into the future and simulates delivery of the initial correction bolus amount (obtained at task <NUM>). The resulting PBG can be calculated as a function of the current BG measurement value, the current BG measurement derivative or trend, historical insulin delivery, the amount of carbohydrates associated with a detected or announced meal, and the amount of insulin for the correction bolus to be administered. Additionally, the PBG may account for estimated future insulin deliveries that may be automatically or autonomously delivered by the control scheme implemented by the insulin infusion device.

In exemplary embodiments, future glucose values are predicted using a mathematical model of the patient that characterizes the glucose response to insulin delivery by a set of differential equations. Meal information could also be incorporated into the predictions, but the described methodology is more conservative if the influence of carbohydrates on blood glucose is ignored. These equations may be based on a mass balance between estimated glucose utilization as result of insulin delivery. The mathematical model may also include specific parameters that enable it to predict the blood glucose at fasting.

The process <NUM> uses the PBG for purposes of scaling the initial correction bolus amount (if needed) to obtain a final correction bolus amount for the user. The goal of the scaling is to reduce the initial correction bolus amount such that the PBG resulting from simulated delivery of the final correction bolus amount exceeds the low BG threshold level. According to the invention, the initial correction bolus amount is reduced in a stepwise (iterative) manner to obtain the final correction bolus amount. Thus, the final correction bolus amount can be equal to or less than the initial correction bolus amount.

<FIG> depicts an exemplary embodiment that iteratively reduces the initial correction bolus amount in a stepwise manner such that the scaling maximizes the final correction bolus amount without causing the PBG to fall below the low BG threshold level In this regard, a query task <NUM> of the process <NUM> compares the PBG against the low BG threshold level (which may be its default value or the reduced value, as explained above). If the PBG is not lower than the low BG threshold level (the "No" branch of query task <NUM>), then the calculated correction bolus amount is used as the final ACB for delivery (task <NUM>). For the first iteration of the methodology, the calculated correction bolus amount is equal to the initial correction bolus amount calculated at task <NUM>. For subsequent iterations of the methodology, the calculated correction bolus amount will be less than the initial amount.

If the PBG is lower than the low BG threshold value (the "Yes" branch of query task <NUM>), then the process <NUM> checks whether the calculated correction bolus amount has reached a minimum value (query task <NUM>). The minimum value may be any defined amount of insulin, a percentage of the initially calculated correction bolus amount, or the like. For example, the minimum bolus value considered at query task <NUM> may be zero Units of insulin. If the calculated correction bolus amount for the current iteration of the methodology has reached the minimum value (the "Yes" branch of query task <NUM>), then the process <NUM> exits without delivering a correction bolus to the user (task <NUM>), or sets the final ACB amount to be equal to the minimum value, e.g., zero Units.

If the calculated correction bolus amount for the current iteration of the methodology has not reached the minimum value (the "No" branch of query task <NUM>), then the correction bolus amount is reduced or scaled down, preferably in a stepwise manner (task <NUM>). The type and amount of scaling/reduction may vary from one implementation to another, and different techniques can be used. The embodiment described here employs a simple scaling factor (multiplier) to progressively reduce the initial correction bolus amount as needed. More specifically, the first comparison at query task <NUM> considers the unsealed initial correction bolus amount (i.e., <NUM>% of the initial correction bolus amount), the second iteration of query task <NUM> considers <NUM>% of the initial correction bolus amount, the third iteration of query task <NUM> considers <NUM>% of the initial correction bolus amount, the fourth iteration of query task <NUM> considers <NUM>% of the initial correction bolus amount, and the fifth iteration of query task <NUM> considers <NUM>% of the initial correction bolus amount (i.e., no correction bolus). Ultimately, the scaling step multiplies the initial correction bolus amount by a scaling factor between <NUM> and <NUM>, inclusive, to obtain the final correction bolus amount.

In other embodiments, a golden ratio-based search or a Fibonacci search is utilized to progressively or iteratively reduce the search space defined by the initial correction bolus amount using intermediate values within the search space that progressively converge toward an adjusted bolus amount that is selected to be administered in lieu of the initial correction bolus amount. In this regard, in exemplary embodiments, the search attempts to maximize the final correction bolus dosage within the search space defined by the initial correction bolus amount while maintaining a predicted future glucose level for the patient that satisfies a postprandial hypoglycemic threshold during a predefined postprandial analysis time period. The bolus search process identifies or otherwise determines an initial adjusted bolus amount to be used to probe or test for use in lieu of the initial correction bolus amount that was originally determined (e.g., at task <NUM>). In this regard, the bolus search process identifies the initial adjusted bolus amount within a search space defined by a bolus of zero as a lower limit and an upper limit equal to the initial correction bolus amount (bcorr).

In exemplary embodiments, the golden ratio is utilized to identify the initial adjusted bolus amount as a fraction of the initial correction bolus amount corresponding to the golden ratio by multiplying the initial correction bolus amount by <NUM>. That said, the subject matter described herein is not intended to be limited to any particular manner for dividing the search space. The bolus search process also utilizes the initial adjusted bolus amount to define or otherwise determine search spaces for subsequent analysis. For example, an upper search space may be defined relative to the initial adjusted bolus amount as being bounded by the initial adjusted bolus amount as its lower limit and the initial correction bolus amount as its upper limit (e.g., [<NUM>bcorr, bcorr]), while a lower search space may be bounded by the initial adjusted bolus amount as its upper limit and a bolus dosage of zero as its lower limit (e.g., [<NUM>,<NUM>bcorr]). This methodology can be used during each iteration of the described methodology to progressively adjust the correction bolus amount and arrive at the final ACB amount.

After reducing the calculated correction bolus amount (at task <NUM>), the process <NUM> returns to task <NUM> to compute another PBG, based on simulated delivery of the reduced correction bolus amount. Thereafter, the process <NUM> continues in the manner described above. The stepwise scaling of the initial correction bolus amount results in a "maximized" correction bolus that should not result in a BG level that goes below the applicable low BG threshold level for the user. Assuming that a nonzero final correction bolus amount is eventually obtained at task <NUM>, the ACB calculation process <NUM> exits and leads to task <NUM> of the insulin infusion device control process <NUM> (see <FIG> and the relevant description of tasks <NUM> and <NUM>).

For the sake of brevity, conventional techniques related to glucose sensing and/or monitoring, bolusing, closed-loop glucose control, and other functional aspects of the subject matter may not be described in detail herein. In addition, certain terminology may also be used in the herein for the purpose of reference only, and thus is not intended to be limiting. For example, terms such as "first", "second", and other such numerical terms referring to structures do not imply a sequence or order unless clearly indicated by the context. The foregoing description may also refer to elements or nodes or features being "connected" or "coupled" together. As used herein, unless expressly stated otherwise, "coupled" means that one element/node/feature is directly or indirectly joined to (or directly or indirectly communicates with) another element/node/feature, and not necessarily mechanically.

Claim 1:
An insulin infusion device (<NUM>, <NUM>, <NUM>) comprising:
a fluid reservoir (<NUM>) for insulin to be delivered from the insulin infusion device;
at least one processor device; and
at least one memory element (<NUM>) associated with the at least one processor device, the at least one memory element storing processor-executable instructions configurable to be executed by the at least one processor device to perform a method of controlling delivery of insulin from the insulin reservoir, the method comprising:
controlling (<NUM>) the insulin infusion device to operate in an automatic basal insulin delivery mode;
obtaining (<NUM>) a blood glucose measurement that indicates a current blood glucose level of a user; and
initiating (<NUM>) a correction bolus procedure when: (<NUM>) the blood glucose measurement exceeds a correction bolus threshold value (<NUM>); and (<NUM>) a maximum allowable basal insulin infusion rate (Umax) has been reached during operation in the automatic basal insulin delivery mode (<NUM>), the correction bolus procedure comprising:
calculating (<NUM>) an initial correction bolus amount for the user;
iteratively scaling down the initial correction bolus amount to obtain a final correction bolus amount for the user, such that a predicted future blood glucose level of the user resulting from simulated delivery of the final correction bolus amount exceeds a low blood glucose threshold level; and
delivering (<NUM>) the final correction bolus amount to the body of the user during operation in the automatic basal insulin delivery mode.