System and method for capturing dose information

Abstract

To provide a pen case.SOLUTION: Provided is a pen case that includes: a clamping system that clamps over the plunger of the syringe receiving cavity; an actuator that moves the clamping system and the plunger; a processor adapted to receive dosage commands and send control information to a controller, the controller operating the actuator and the clamping system; and a transceiver for receiving dosage commands; wherein the transceiver transmits the dosage command to a processor, the processor including an RFID chip, receives the dosage command, and sends control information corresponding to the dosage command to the controller, and the controller controls a clamping system and actuator to clamp the plunger of the syringe and move the plunger to withdraw a dose corresponding to the dose command.SELECTED DRAWING: Figure 12

Description

Technical Field

[0001] The present invention relates to systems and methods for obtaining the volume of a drug delivered by a syringe or other drug delivery device. In particular, the present invention relates to systems and methods for utilizing magnetic position sensing, such as Hall effect sensing and magnetoresistive (MR) sensing, and microelectromechanical systems (MEMS) flow sensing, along with various drug delivery devices and components, to obtain drug administration delivery information.

[0002] This application claims the benefit of U.S. Patent Application No. 14 / 485,749, filed on September 14, 2014, entitled "SYSTEM AND METHOD FOR CAPTURING DOSE INFORMATION", the entire contents of which are incorporated herein by reference.

Background Art

[0003] Diabetes is a group of diseases characterized by high levels of blood glucose resulting from defects in insulin production, insulin action, or both. In the United States, there are 25.8 million people (or 8.3% of the population) with diabetes. The total number of diabetes patients has increased by 13.5% from the period of 2005 - 2007. Diabetes can lead to serious complications and premature death, but there are well-known products available to people with diabetes to help control the disease and reduce the risk of complications. Chronic hyperglycemia leads to serious and sometimes irreversible complications, including kidney failure, peripheral neuropathy, retinopathy, and vascular complications.

[0004] Treatment options for diabetes patients include specialized diets, oral medications, and / or insulin therapy. The main objective regarding diabetes treatment is to control the patient's blood glucose (sugar) level in order to increase the chance of a life without complications.

[0005] An ideal diabetes therapy would involve continuous monitoring of blood glucose levels, insulin dosing, dietary intake such as carbohydrate estimation, activity tracking, stress levels, and acquisition of data on other factors. By continuously monitoring, healthcare providers can maximize the effectiveness of the treatment regimen for each patient. Unfortunately, traditional diabetes treatments, including multiple daily injections (MDI), insulin pens, patch pumps, and insulin pumps, do not adequately record information on the drug dosage delivered to the patient and do not provide feedback to the physician. Thus, the traditional feedback loop between the physician and the patient is infrequent and is primarily based on qualitative assessments between the physician and the patient. Accordingly, there is a need to add informatics such as dosing delivery acquisition and provide enhanced feedback to healthcare providers and to enhance drug delivery devices and methods for improving diabetes therapy.

[0006] To properly diagnose and treat diabetes mellitus (DM), patients and / or healthcare providers (HCPs) need to evaluate short-term daily records regarding (1) insulin dosing, (2) oral medications, (3) blood glucose monitoring (BGM), and (4) carbohydrate intake. These data are obtained from different sources such as settings for insulin pens, transient readings from BGM meters, and estimated carbohydrate values in meals all determined by the patient and transcribed into a logbook or diary. This method of recording data is extremely cumbersome and prone to errors and omissions. Even in the best-case scenario, the insights that can be gained are limited if handwritten data is not transcribed into software that can reconstruct the data, evaluate trends, and support therapeutic modifications when the historical record is complete. As a result, most patients do not properly maintain their logbooks, which reduces the ability of both the patient and the physician to accurately diagnose the illness, which can ultimately result in non-compliance with therapy and a decline in blood glucose control. Therefore, a system is needed that can automatically acquire, store, transfer, and enable optimal evaluation of all the data necessary for proper diagnosis and treatment of diabetes.

[0007] Patent Document 1 describes a monitor that can be attached to a patch pen, which is capable of sensing the time of each delivery event and transmitting it wirelessly. A flag, such as a magnet, is placed on a movable linkage within the patch pen, and a sensor within the monitor attachment detects the proximity of the magnet at the end of the linkage travel, i.e., at the end of the delivery cycle.

Prior Art Documents

Patent Documents

[0008]

Patent Document 1

Patent Document 2

[0009] According to embodiments of the present invention, the disadvantages described above are overcome or minimized, and the above advantages and other advantages are realized. Exemplary embodiments of the present invention provide a device for obtaining administered dose information. The device includes a drug delivery device, a dose information acquisition device adapted to be attached to the drug delivery device, and a sensor element adapted to be attached to the drug delivery device. The sensor element preferably includes at least one of a magnet, preferably a permanent magnet (although non - permanent magnets may also be used), and at least one iron - based element, and is attached to the drug delivery device above the administration delivery mechanism of the drug delivery device. The dose information acquisition device includes a magnetic position sensor adapted to detect the position of the sensor element.

[0010] Accordingly, embodiments of the present invention provide a device for sensing a delivered dosage by magnetic position sensing. Magnetic position sensing is achieved by a Hall effect sensor, a magnetoresistive sensor, or any other suitable device. Various embodiments are capable of sensing linear translation, rotational movement, flow, or drug levels in an insulin vial or reservoir. As described herein, magnetic position sensing determines a linear or rotational movement of a mechanical linkage or mechanization that correlates with the dosage to be delivered within an insulin pen or other pharmaceutical delivery device. In other embodiments, magnetic position sensing is utilized to determine the level of fluid in a container, such as by the linear translation or change in position of a magnet floating on top of the upper surface of insulin. Flow sensing, particularly MEMS flow sensors, includes Coriolis sensors, capacitance sensors, and thermal sensors such as Time of Flight (ToF) sensors used to determine the volume of a pharmaceutical delivered from a pen, syringe, or other pharmaceutical delivery device. Capacitance sensing is preferably used to measure and determine the level of a liquid, such as insulin, in a container, such as an insulin vial.

[0011] The above and other exemplary features and advantages of specific exemplary embodiments of the present invention will become more apparent from the following description of the specific exemplary embodiments when used in conjunction with the accompanying drawings.

Brief Description of the Drawings

[0012]

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DETAILED DESCRIPTION OF THE INVENTION

[0013] Throughout the figures, it will be understood that like reference numerals represent like elements, features, and structures.

[0014] In the example provided below, insulin delivery is described. However, it should be understood that insulin delivery is merely exemplary and any drug delivery is contemplated to be within the scope of the present invention. Informatics is defined herein as an interdisciplinary field primarily related to the analysis, collection, classification, manipulation, storage, retrieval, transfer, and dissemination of information.

[0015] Exemplary embodiments of the present invention obtain the amount or volume of a drug being delivered by any of a syringe, an insulin pen, or other drug delivery device. In some major technical fields, magnetic position sensing including Hall effect sensing, magnetoresistive (MR) sensing including anisotropic MR, MEMS flow sensing including thermal time-of-flight (ToF) sensing, micro-Coriolis pressure sensing, and capacitive pressure sensing are applied to various devices and device components to enable dose acquisition. MEMS capacitive pressure sensing uses Bernoulli's principle and / or the empirical Darcy-Weisbach equation to detect changes in pressure by varying the diameter of a conduit in a flow sensing element, and the pressure is measured using two capacitive MEMS pressure sensors respectively positioned in sections of conduits having different diameters. It should be understood that in the exemplary embodiments described herein, any type of MEMS flow sensing can be utilized in place of magnetic position sensing. Embodiments of the present invention are not limited to Hall effect sensing and MEMS flow sensing, but rather it should be understood that any suitable sensing technology is within the scope of the present invention.

[0016] Conventional Hall sensors are highly sensitive only to a magnetic field perpendicular to the chip surface, i.e., they are one-dimensional or 1D. Also, 3D Hall sensors advantageously respond to a magnetic field parallel to the chip surface. The sensor chip has separate sensors for each of three magnetic axes and uses a simple two-pole magnet as a magnetic field source to convert magnetic field data into absolute position information. For linear sensing applications, the 3D Hall sensor will be used in 2D mode. One advantage of this system for linear sensing is that it allows for a greater separation between the magnet source and the sensor than a standard 1D Hall sensor.

[0017] A basic anisotropic magnetoresistive (AMR) sensor uses a single-saturation-mode Wheatstone bridge, is typically made of permalloy (Ni-Fe alloy), and generates an output voltage with respect to the direction of the magnetic flux passing over the sensor surface. Thus, it operates in saturation mode, avoids interference from stray magnetic fields, and the magnetic field it senses is across the chip surface, in contrast to the perpendicular magnetic field of a Hall sensor. The AMR sensor generates an analog output voltage that varies with the direction of the magnetic flux passing over the chip surface. The minimum magnetic field required to put the AMR sensor into saturation mode is typically 50 to 80 gauss. A single-element AMR sensor has an operating range of ±45° when the voltage-versus-angle output is linear.

[0018] Embodiments of the present invention preferably meet the following functional capabilities. First, embodiments of the present invention preferably electronically acquire the amount of the injected formulation and the time of the injection event. Second, they preferably provide means for associating the acquired injection event data with the type of the injected formulation. Pharmaceutical identification techniques can be incorporated into embodiments of the present invention, which are described in Patent Document 2, Patent Document 3, and Patent Document 4, the entire contents of each of which are hereby incorporated by reference in their entirety. Third, they are preferably compatible with existing commonly prescribed diabetes pens and other devices utilized with respect to MDI or infusion therapy. Fourth, they transmit the acquired data in a common digital format compatible with a smartphone or similar device to be utilized in patient software such as a patient meaning engine. The patient meaning engine receives data, which includes, but is not limited to, any combination of a patient's blood glucose level, calorie intake, exercise, drug dosage, and other relevant data. One function of the engine is to track trends in the data, provide feedback to the user, and enhance the effectiveness of patient self-care through an improved understanding of the patient's illness and therapy in the patient's daily life. The meaning engine provides feedback to the patient to facilitate self-therapy and enable improved decision-making, for example, during dosing events such as mealtime dosing. This feedback and additional insights provided by the meaning engine provide sufficient value to the patient during dosing events and influence behavior modification. Also, the meaning engine can provide information or alerts to healthcare providers so that deviations from healthy trends are identified and actions are taken proactively. Using the meaning engine as defined herein eliminates or reduces bad medical treatment regimens that rely on fail-first, as opposed to facilitating the efficient use of a physician's time and identifying the shortest path to cost-effective results.Fifth, they preferably transmit the acquired data to the patient mining engine within one minute of sensing the delivered dosage. Sixth, they acquire data from all predetermined forms of T1 and T2 insulin, as well as from oral dosing regimens. Seventh, their accuracy preferably meets the injection standard ISO11608. One example of utilizing the mining engine is titrating new pharmaceuticals for a patient. The patient starts using a new pharmaceutical, such as long-acting insulin, by adjusting the dosage weekly, every few days, or as needed, based on analyzing the delivered insulin dosage and blood glucose readings over a period of time. The adjustments and data are sent to the patient's physician, closing the loop between the physician and the patient daily or as needed, while saving the physician's time and processing the titration process quickly for the patient. Of course, insulin is used herein as an example, and any suitable pharmaceutical can be similarly titrated by monitoring relevant factors such as the drug dosage and blood glucose levels.

[0019] Embodiments of the present invention further preferably meet the following additional criteria. They are implemented with the patient and can be used anytime, anywhere. They preferably do not increase the number of items typically carried by a diabetic patient. They are compatible with other elements in an informatics-enabled outcome (IEO) system, such as a blood glucose monitor (BGM) and an oral medication compliance device. That is, data transfer between devices in the system utilizes a common communication platform.

[0020] Embodiments of the present invention are preferably easy for a patient to use. That is, the device or system functionality preferably does not require a high level of user expertise or significant training. Embodiments of the present invention improve patient safety and preferably never compromise patient safety.

[0021] Exemplary embodiments of the present invention make it informatically possible for a drug delivery device to positively acquire administration delivery information. The following devices and device components, typically associated with administration delivery, are suitable for informatics use. A vial or pharmaceutical reservoir attachment is capable of sensing the movement of a syringe plunger. Also, a vial or pharmaceutical reservoir attachment is capable of sensing the level of the pharmaceutical in the vial or reservoir and determining the remaining volume, and thus the administered dose. A pen cap is capable of sensing the movement of the plunger in an insulin pen by means of magnetic sensing means. The magnetic sensor is preferably incorporated into a disposable insulin pen to determine the plunger position. A sleeve with an integrated flow sensor can be installed between the insulin pen and the pen needle. A cartridge for a reusable pen includes a sensor and is capable of determining the plunger position within the cartridge. A cartridge filler is utilized and it is possible to attach a sensing element to the cartridge. A flow sensor can be provided in a mechanism attached to the end of an insulin pen that exchanges the cannula into and out of a reusable cannula hub. A pen case is provided with a magnetic position sensor and is capable of determining the position of the plunger in the insulin pen when the pen is returned to the pen case. A patch pump configured to deliver a preset number of insulin units per activation (button press) can be configured to sense the button press by a sensor. Similar to the insulin "Insupad", an infusion patch can be modified to direct flow through a flow sensor from different infusions. Also, similar to the device provided by Patton Medical, an infusion port can be modified in the same manner. An insulin vial or fluid reservoir can be modified to incorporate an internal floating magnet and an external sleeve with an integrated magnetic sensor. Any all-in-one type device is provided with a suitable sensor as described herein and is capable of acquiring dose information.As used herein, an "all-in-one" device should be understood to be a device that includes, for example, a method for delivering BGM and insulin dosing, or a combination device such as a BGM and a bolus calculator. An attachment for a syringe, in which at least one sensor element is connected to a syringe plunger and at least one sensor, is attached to a syringe barrel.

[0022] A first embodiment of the present invention is shown in FIG. 1, which shows an attachment 102 for an insulin vial and a modified insulin syringe. The reusable attachment 102 engages the insulin vial and preferably remains attached until the insulin is depleted. The vial attachment 102 includes at least one linear Hall effect sensor 104 with an analog output, a flexible printed circuit board assembly (PCBA) 106, a battery 108, a power management system 110, a Bluetooth Low Energy (BLE) wireless transceiver 112, and a real-time clock (RTC) 114. During the manufacturing process of the syringe 116, an RFID chip 118 is installed in the syringe 116 and a permanent magnet 120 is overmolded into the stopper or plunger. In an alternative embodiment, rather than a magnet, an iron-based target such as an iron disk or slug is used to further significantly reduce the cost of disposal.

[0023] When an iron-based target is utilized, the Hall effect sensor 104 is preferably reverse-biased by integrating a magnet with the Hall sensor 104 such that an iron-based object within range will be sensed by the Hall sensor 104.

[0024] The vial attachment 102 reads the RFID chip in the syringe 116 and determines the inner diameter (ID) of the syringe barrel. The Hall effect sensor 104 measures the linear movement of the plunger, and the dosage is calculated from the ID and the plunger travel. The dosage is time-stamped and wirelessly transferred to a smartphone and / or the "cloud" or the Internet. Alternatively, a phone application (APP) for the smartphone is provided, and the phone camera captures an image of the syringe just before injection. The syringe diameter is recognized either by a barcode or QR code (registered trademark) printed on the outside of the syringe barrel, or by comparative measurement, or by any other optical method that is part of the smartphone, and the distance between the plunger and the nozzle just before injection can be determined by the same method. As in previous embodiments, these two values are then used to calculate the dosage. Also, a number of the features described herein can be combined to provide additional embodiments. For example, the smartphone APP can be combined with a vial attachment that measures the movement of the plunger by sensing the position of an embedded magnet, replacing the need for the RFID chip.

[0025] Figure 2A illustrates the flux density curve sensed by the Hall effect sensor described above when the magnet passes close to the sensor. Figure 2B illustrates the substantially linear analog output voltage response of the Hall effect sensor used in an embodiment of the present invention. The Hall effect sensor preferably converts the linear output voltage into a digital signal for output to a processor, for example, or for further processing.

[0026] Figure 3 is a cross-sectional view of a syringe and vial with an informatically usable vial attachment according to an exemplary embodiment of the present invention. A plurality of Hall effect sensors can be used depending on the total stroke intended to be sensed, but for short strokes, only one Hall effect sensor is required.

[0027] The second embodiment of the present invention is shown in FIG. 4. The magnetic strip 202 is overmolded into the syringe plunger. The strip 202 has a number of magnetic poles 204 that repeatedly alternate from N pole to S pole over the length of the strip. As in the first embodiment, the vial attachment includes the components necessary to read the RFID chip, sense the position of the plunger, and wirelessly communicate the volume of insulin being injected. In this embodiment, high resolution (position accuracy) is achieved using the same basic principle as that used in an optical encoder. That is, a set of stacked magnets forms a series of N and S poles that are sensed in a manner similar to the black and white (or opacity and light transmissibility) optical pattern on an optical encoder. The position sensor can be a single integrated circuit incorporating a plurality of Hall effect sensors, which are arranged to detect the motion of the magnetic strip with a high resolution output that can interface directly with a microcontroller. Such a high resolution magnetic position sensor is available, for example, from Austria Micro Systems, ams AG. In combination with the multipole strip, a single high resolution magnetic position sensor can sense the pole pairs passing through the face of the sensor to accommodate any length stroke with a single sensor. A high resolution single chip sensor with multiple Hall effect sensors is advantageously compact and can be used for both linear motion sensing and off-axis rotational motion sensing. These devices provide a resolution down to 15 microns (μm). For reference, for a 1 ml syringe with a 0.478 cm inner diameter, a 56 μm displacement of the plunger is equal to 0.1 unit or 0.001 ml.

[0028] A third embodiment of the present invention is shown in FIG. 5, which illustrates a disposable or reusable insulin injection pen 500. Any suitable flow sensor, preferably including a microelectromechanical systems (MEMS) flow sensor, can be utilized to provide an informatics-capable insulin pen. One type is a MEMS micro-Coriolis mass flowmeter, which utilizes a vibrating tube to accurately measure the force of mass flow within the tube. A second type is a thermal sensor, such as a MEMS time-of-flight thermal flow sensor. In addition, a pair of MEMS capacitive pressure sensors on either side of a constriction can be used. The pen attachment 502 includes a reusable portion 504 and a disposable portion 506. The reusable portion 504 is a pen cap or sleeve that is attached to the delivery end of the insulin pen and is used until the insulin in the pen is depleted. The disposable portion 506 is a small cylinder-shaped plastic-molded component that has a MEMS flow sensor integrated into a fluid channel through which insulin flows. The disposable MEMS cylinder is attached to the end of the pen, and the pen needle is attached to the MEMS cylinder. A removable or retractable end cap is used to protect and expose the MEMS cylinder, enabling the patient to replace the pen needle during use. The dosage is preferably obtained at the exact time of delivery, the data is time-stamped, and wirelessly transferred to a smartphone and / or the "cloud" or the Internet.

[0029] MEMS sensors are typically pre-packaged by the manufacturer. Conventional MEMS sensors, such as those described above, necessarily contain not only certain MEMS components that are very small, but also associated electronics and circuitry. However, in embodiments of the present invention, the small MEMS components are preferably separated from the associated circuitry. In this way, the small MEMS components can be disposable, and the associated circuitry can be reusable. In the embodiment shown in FIG. 5, for example, the small MEMS component will be positioned within a disposable flow sensor 506, while the associated circuitry will be positioned within a reusable pen cap 504. This arrangement has significant cost advantages with respect to manufacturing. As an example, a conventional MEMS sensor package can cost on the order of $10, while a small MEMS component can cost on the order of less than $1. Thus, it is advantageous to separate the small MEMS components from the associated circuitry so that the expensive parts can be reused and the inexpensive parts can be disposable. Alternatively, a magnet is attached to or incorporated within the plunger of an insulin cartridge adapted to be inserted into an insulin pen. In one exemplary embodiment, a Hall effect sensor is incorporated within the pen cap and detects the position of the plunger when the pen cap is placed back on top of the pen after injection. The relative movement of the cartridge plunger before and after injection corresponds to the dosage, which is recorded, logged, and preferably transmitted to a remote device, such as a cloud-based storage, for further processing and feedback. In another exemplary embodiment, the Hall effect sensor and associated circuitry are positioned within the pen case, and the relative movement of the cartridge plunger is measured each time the insulin pen is placed back into the pen case. This embodiment has the advantage of using the large amount of available space within the pen case for the Hall effect sensor and associated electronics.The position of the cartridge plunger within the pen case can be measured, for example, using an AMS5410 3D Hall sensor. Multiple sensors, at 40 mm per sensor range, can be used to triangulate the exact displacement of the cartridge plunger relative to the pen injector or cartridge.

[0030] In real time, i.e., while the dose is being injected into the patient's tissue, all system elements need to communicate during dose delivery in order for the systems described herein to be able to acquire dose delivery. The pen needle acquires the dose in real time when a reusable sleeve is attached and provides the following functions. The functions are: (1) receiving sensed data correlated to the volume of the dose, (2) calculating the dose, (3) timestamping the dose, (4) providing power for the sensors and these functions, and, (5) also, wirelessly communicating the dose and timestamp to somewhere within the IEO dose acquisition system, such as the patient's record in the cloud, either simultaneously or later. A replaceable pen cap that covers the needle tip of the insulin pen and senses plunger movement senses the movement of the plunger at the exact time of delivery. Since all system elements communicate during delivery, a pen cap that covers the knob end of the insulin pen and senses knob movement and travel can preferably acquire real-time delivery of the dose.

[0031] To reduce the cost of a disposable MEMS sleeve, the components within the sleeve, namely the MEMS chip and electrical contacts for power and data connection to an informatics-enabled pen sleeve, are minimized. The device includes a plastic sleeve into which the MEMS chip and electrical contacts are assembled and which are snap-fit, overmolded, or clamped by retaining components and septum that are pierced when engaged by a pen needle. These two concepts provide additional benefits compared to the embodiments described above. The reason is that they acquire the time of actual delivery compared to the time of plunger movement for filling the syringe, or the displacement of the plunger of an insulin pen, somewhat after the dose has been delivered, for example, when a smart pen cap is placed and returned onto the pen.

[0032] Also, the embodiments described above are applicable to infusion ports such as the Patton Medical infusion port. Embodiments for use with an infusion port can be fully disposable or a combination of disposable components and reusable components. Any of the MEMS sensors described above can be inserted into the fluid path within the infusion port, and the components and intelligence provided within the informatics-enabled sleeve described above are incorporated into the infusion port within the outer perimeter of the port, i.e., the area surrounding the septum into which the syringe will engage. Preferred embodiments regarding the infusion port are of a disposable / reusable design, in which the disposable portion includes components including an adhesive, a portion of the housing to which the adhesive is attached, as well as an MEMS sensor and an electrical connection from the sensor to the reusable portion enabled for informatics, which includes a fluid path and comprises all of the components described above within the informatics-enabled sleeve. Also, as discussed above, pharmaceutical identification techniques can be incorporated to verify that a particular pharmaceutical is being administered.

[0033] Another embodiment of the present invention is illustrated in FIG. 6, which shows an informatics-capable attachment 602 for either a reusable pen 600 or a disposable pen 600. This embodiment engages the adjustable end of the pen. More specifically, the rotary turn knob 604 on the informatics-capable sleeve 602 engages an adjustment knob (not shown) on the pen, and the sleeve portion 602 of the informatics-capable attachment slides over and engages the outer diameter of the pen barrel. In one alternative of this embodiment, an overmolded metal spline axially positioned around the diameter of the knob is used for proximity sensing, similar to the ring counter configuration, which utilizes proximity sensors to count the gear teeth, or in this case the splines, as they pass in front of the sensor. In another alternative of this embodiment shown in FIG. 7, a multipole annular magnetic ring 702 is used in combination with a Hall effect sensor 704. The rotational motion and direction of the cap are determined by a rotational Hall effect sensor or an MR sensor. Determining the direction requires two sensor devices such as the Allegro A1233, or four sensor chips such as the ams AS5304 / 5306. AMR sensors require integration with a single Hall effect sensor to provide direction and 360-degree sensing. It should be understood that an optical encoder could be used in place of the rotating magnet system.

[0034] Figure 8 is an exemplary embodiment of the SMART fixed-dose pen, in which the intelligence in the system is reduced, i.e., the dose is preset and each dose is the same, so only the actuation / delivery time needs to be acquired, and thus the Hall effect sensing arrangement described above is not required. Figure 9 is another explanatory view of either an adjustable dosing pen or a fixed-dose pen. Figures 10 and 11 illustrate embodiments of a mechanical patch pen that can be used with informatics. As used herein, the term "patch pen" represents a body-worn device that provides insulin delivery at a fixed dose each time the user manually actuates the device, which is mainly utilized for meal-time insulin delivery. Preferably, a magnetic flag or a metal flag is incorporated into the mechanization or linkage within the mechanical patch pen. The informatics-enabled attachment can be integrated into the patch pen (in which case it is disposable), or can be in the form of a separate element that engages the patch pen (in which case it is reusable). In one embodiment, an electrified "pump engine", i.e., a fluid driver used to transfer insulin from a reservoir to an infusion site, delivers 2.0 units per cycle. The electrified pump engine is described in more detail in Patent Document 5 filed on April 7, 2014, the entire content of which is incorporated herein by reference. This pump engine is modified to eliminate the motor and provide mechanization, which enables the pump engine to be driven by the user strongly pressing or depressing one or more buttons located outside the pump, and this pump engine includes a magnetic flag or a metal flag positioned on the linkage within the patch pen, which is sensed by the informatics-enabled attachment each time 2.0 units of insulin are manually delivered by the user. Any of the magnetic sensing solutions, optical sensing, or any suitable sensing technology described above can be utilized for sensing.Additionally, the same pump engine with similar manually-driven mechanization can be utilized to effect delivery within an insulin (or other pharmaceutical) pen, and each actuation provides a fixed dosage and records the amount and time of each administration.

[0035] The pen case provides a clean and sealed container in which the user can store their injection delivery devices and consumables such as insulin vials, insulin pens or syringes, pen needles, lancets, and alcohol swabs. The pen case can be either rigid (i.e., having a hard outer shell with a design similar to a jewelry box) or flexible (i.e., a flexible pouch similar to a pencil case). Figure 12 illustrates a rigid pen case 1200 that can be used with informatics according to another embodiment of the present invention. An informatics-enabled pen case stores the patient's syringe or insulin pen when the device is not in use. The nests or cavities in the pen case are used to align or position the pen each time the user places the pen into the case. Each time the pen case is closed, a hall effect sensor in the pen case determines the relative position of the plunger, thereby determining the dose to be delivered to the patient. For reusable pens, the insulin cartridge includes a magnetic or metal flag, such as a washer-shaped element having a pressure-sensitive adhesive (PSA) on one side, which is pressed onto the exposed surface of the stopper in the cartridge, and, optionally, some other means such as an RFID chip or a barcode, and needs to be modified to convey the ID of the insulin cartridge as well as the type and concentration of the pharmaceutical. The magnetic or metal element is preferably incorporated into the stopper / plunger during manufacture. In operation, each time the pen is placed into the case, the sensor in the pen case scans to detect the position of the stopper, compares the current position with the previous position, and determines the dose delivered. The data is time-stamped, stored in the case, and periodically transferred to a smartphone and / or the cloud.One advantage of the pen case is the volume of space available for configuring informatics-usable components therein, which can reduce costs and improve the performance of the solution by incorporating low-cost, high-performance components such as off-the-shelf (OTS) batteries, rigid PCBs, large-footprint antennas, RFID readers, large user interfaces (UIs) (which accept input from touchscreens, keypads, or audible commands and provide patient-related data, alerts, and warnings on a display), etc. To enable the use of a flexible pen case, two magnets are incorporated into the syringe or insulin pen, one fixed and the other on the movable plunger. Each time the pen is placed into the flexible case, the linear and relative distances between the two magnets are sensed, enabling the dose to be calculated. Also, this concept is applicable to reusable pens stored in the pen case and to informatics-usable cartridges utilized in informatics-usable pens, as described above. It will be understood that any suitable sensing technology may be utilized, and in particular, magnetic induction sensing is one suitable alternative for sensing within the pen case. A magnetic induction displacement sensor operates by using an induction sensor coil and detects changes in the magnetic field when the magnet moves. It is used in head-on sensing with a range of up to 60 mm, depending on the magnet size, and is used to detect the position of the magnet incorporated into the plunger piston of the insulin pen or within the syringe after being placed into the pen case.

[0036] FIG. 13 illustrates an informatics-enabled pen case that further enables drawing a dose into a syringe. This embodiment of the pen case includes a clamping system 1301 for aligning the syringe, i.e., for accurately positioning the syringe over two axes, a nest or cradle for aligning the insulin vial, and a second clamping system for gripping and controlling the movement of the syringe plunger. In operation, the user places the syringe into the nest adjacent the insulin vial in the pen case, closes the case, and enters the dose to be delivered into the UI. Two separate clamping components within the case grip the syringe. The first clamp system grips the syringe and advances the syringe into the insulin vial to engage the syringe needle. The second clamp system moves the plunger to draw the correct dose of insulin. The syringe is retracted from the vial either automatically or by the patient. The same components can be utilized to create positive pressure within the insulin vial. An orientation sensor or gyro sensor can be used to confirm the proper orientation of the pen case for air purging or insulin drawing and can accordingly prompt the user to orient the pen case. An exemplary smart pen case is described in Patent Document 6, the entire content of which is incorporated herein by reference.

[0037] Similar to all embodiments described in this specification, each injection is preferably recorded and timestamped in an electronic logbook and periodically transferred to a peripheral monitoring device, such as a laptop computer, a mobile phone, or other user interface, for patient review. Alternatively, the data can be communicated to and from the cloud and from the cloud to the patient's healthcare provider via a computer network. By incorporating auxiliary devices, such as a vital sign monitor, a fitness monitor or activity tracker, and a continuous glucose monitor (CGM), into the system, the functionality of the informatics-enabled insulin pen case can be further extended.

[0038] Another embodiment takes the form of an "all-in-one" or combination device. One example of a commercially available all-in-one device is Dario by LabStyle Innovations. Dario integrates a blood glucose meter, a lancet, a strip dispenser, and a phone application for either IOS or Android into a compact device. Similar to the pen case embodiment described above, the all-in-one device has a size and volume sufficient to incorporate the informatics-useable components described above, enabling an insulin pen or syringe that is informatics-useable to be attached, i.e., by providing a nest or holster for the pen or syringe, enabling it to be physically and electrically engaged to the all-in-one housing. In this case, the connection provides for the holding of the pen or syringe and the transfer of data. Such a device is described, for example, in Patent Document 7, the entire content of which is incorporated herein by reference. Alternatively, wireless communication solutions such as low-energy Bluetooth (BLE) or near-field communication (NFC) can be utilized to communicate directly with a smartphone. Examples of smartphone devices that communicate with other on-body devices in a personal area network are described in Patent Document 8, the entire content of which is incorporated herein by reference.

[0039] Another embodiment is an informatics-enabled insulin cartridge used in connection with a reusable pen that is informatics-enabled. The insulin cartridge is modified to include a magnetic or metal flag, such as a washer-shaped element having a pressure-sensitive adhesive (PSA) on one side, that is pressed onto the exposed surface of a stopper within the cartridge, and an RFID chip, or some other means such as a barcode, that conveys the ID of the insulin cartridge, as well as the specific pharmaceutical type and concentration. The cartridge will function in connection with an informatics-enabled attachment for the reusable pen. Alternatively, magnetic field strength can be used to distinguish between different cartridges, eliminating the need for RFID chips on disposable devices and RFID readers in the informatics system. The cartridge is preferably modified manually or automatically by the patient during the manufacturing process, following the filling process, or as part of a cartridge filling process designed for home use.

[0040] Figure 14 illustrates an informatics-enabled syringe sleeve according to an exemplary embodiment of the present invention. The syringe sleeve 1400 includes a plurality of magnetic position sensors 1402. The syringe 1404 has an embedded RFID chip 1406 and a magnet 1408, and the magnet 1408 is sensed by the Hall effect sensors 1402 to determine the dosage. Of course, any suitable sensing method, such as those discussed herein, may be used in place of magnetic position sensing, as will be understood by those skilled in the art.

[0041] In another embodiment, an external electrode is attached to the insulin reservoir and a variable capacitance value is sensed based on the fluid level of the reservoir. The electrode is preferably printed onto any insulin reservoir during manufacture and may also be manufactured as a strip to be attached to the insulin reservoir. Alternatively, as shown in FIG. 15, an informatics-usable sleeve 1500 is provided with an electrode 1502, which is provided on the inner diameter and will contact the reservoir when attached to a pen, syringe, vial, or patch pump. The electrode 1502 may be printed onto the sleeve or manufactured in any other suitable manner. The electrode 1502 preferably extends to dimensions corresponding to the volume of insulin in the vial. In this embodiment, the sleeve 1500 and the strip 1502 are advantageously reusable. In another embodiment of an informatics-usable insulin vial, the electrodes of the capacitance sensor are incorporated into a vial attachment such that when the vial attachment is engaged with the vial, the electrode strip makes intimate axial contact with the vial.

[0042] FIG. 16 illustrates an informatically usable vial sleeve 1600 according to an exemplary embodiment of the present invention. As shown, a floating magnetic ring 1602 is provided inside a drug vial 1604. The outer diameter of the ring magnet is slightly smaller than the inner diameter of the vial, and the ring is adapted to move freely within the vial according to the fluid level in the vial. The ring magnet 1602 is preferably installed into the pharmaceutical vial before the container is sealed. Also, a typical insulin vial can be modified to accommodate a rigid magnetic ring, or a flexible magnetic ring can be encapsulated within a coil and inserted into the vial through a standard vial neck, allowing the coil to be wound back after insertion to a diameter smaller than the inner diameter of the vial. In the case of an insulin vial, the ring magnet is preferably coated with an insulin-compatible material such as a polymer, which is compatible with insulin and has a thickness and overall buoyancy sufficient to allow the ring to float. As shown, the level of the ring is sensed by a linear magnetic position sensor such as a Hall effect sensor.

[0043] FIG. 17 illustrates another informationally usable vial sleeve 1700 according to an exemplary embodiment of the present invention. In this embodiment, floating magnetic beads 1702 are utilized to sense the level of fluid in a pharmaceutical vial such as insulin vial 1704. A smart vial sleeve 1700 is provided and attached to the drug vial 1704. The vial sleeve 1700 senses a layer of magnetic beads floating on the surface of the insulin. The beads are of a sufficient diameter such that they cannot be drawn into the dosage. That is, the beads 1702 are larger in diameter than the needle or cannula or syringe used to withdraw insulin from the vial. Advantageously, the user can add the magnetic beads 1702 to any drug vial after manufacture, enabling the smart vial sleeve 1700. In one embodiment, the magnetic beads are added to the insulin vial during the filling process at the time of manufacture. In another embodiment, the filled insulin vial is shipped with a syringe filled with magnetic beads, the syringe preferably having a large cannula for injecting the beads into the vial. The cannula of the syringe, or other device used to withdraw insulin from the syringe, is smaller than the beads, preventing the beads from being drawn into the injection device. The number of magnetic beads used is preferably sufficient to substantially cover most of the surface of the liquid drug inside the vial. The vial sleeve attachment utilizes a linear magnetic position sensor, such as a Hall effect sensor, an MR or AMR sensor, to detect the level of fluid remaining in the vial according to the position of the floating magnetic beads in the vial.

[0044] Figures 18A and 18B illustrate a linear magnetic positioning assembly 1800 externally attached to a syringe 1802 according to an exemplary embodiment of the present invention. The syringe attachment 1800 is conveniently attached to the syringe 1802 such that a standard syringe can be utilized without modification. The first attachment includes at least one magnet 1804 attached to the syringe 1802, and the second attachment includes a linear magnetic position sensor 1806, such as a Hall effect sensor, an MR sensor, or an AMR sensor, that detects the position of the magnet 1804. The first attachment 1804 is connected to the syringe plunger, and the second attachment 1806 is connected to the syringe barrel such that the movement of the plunger is tracked and the delivered dosage is determined. The smart syringe attachment 1800 preferably recognizes the "home" position of the plunger, i.e., the position where the plunger is fully advanced and fluid delivery is not possible. In practice, the syringe plunger can be retracted and advanced many times during a single dosage delivery cycle. To distinguish the movement associated with dosage delivery from other plunger movements, such as those used to inject air into a vial, for example, the smart attachment 1800 analyzes the complete cycle of plunger movement each time the syringe is used and, when the plunger finally advances to the home position, identifies the delivered dosage from the final movement and from other elements sensed in the dosage delivery cycle.

[0045] FIG. 19A illustrates a smart injection port 1900 according to an exemplary embodiment of the present invention. The exemplary smart injection port preferably includes a lower housing 1902 and an upper housing 1904. The lower housing includes an adhesive surface 1906 to facilitate attachment of the smart injection port to the patient's skin 1908. A septum 1910 is disposed between the upper housing 1902 and the lower housing 1904. The septum 1910 provides access to a cannula 1912 that is inserted into the patient's skin 1908. The septum 1910 can be pierced by an injection syringe or the like and insulin can be injected into the patient through the cannula 1912 without the need for needle pricks for each injection. The smart injection port 1900 includes a MEMS flow sensor 1914 disposed in a flow path between the septum 1910 and the cannula 1912. The MEMS flow sensor 1914 is electrically connected to associated electronics located within an area 1916 of the injection port 1900. The associated electronics include a power source, a processor, and a wireless transceiver for transmitting flow measurements to a remote device. The housing 1902 is preferably disposable and also includes the MEMS flow sensor 1914. The housing 1904 is preferably reusable and includes the associated electronics within the area 1916. The MEMS flow sensor is preferably a thermal time-of-flight type sensor, although any suitable MEMS flow sensor can be used.

[0046] FIG. 19B illustrates a conventional single-package MEMS flow sensor 1920. In a single-package MEMS flow sensor, the actual MEMS sensor 1922 is combined with associated electronics 1924. The MEMS sensor 1922 includes at least one heater, at least one sensor, and a flow channel through which a fluid such as insulin flows. The associated electronics 1924 are electrically connected to the MEMS sensor 1922 within the single package and include an integrated circuit, a processor, a power source, and a wireless transceiver chip, among others.

[0047] Figures 19C and 19D illustrate an improved MEMS flow sensor 1930, which includes only relatively low-cost disposable parts that should be replaced each time of use due to contact with, for example, insulin. As shown in Figure 19C, the MEMS flow sensor 1930 includes an input side portion 1932 with an input flow tube 1934 through which a liquid such as insulin flows to a MEMS sensor element 1936 (shown in Figure 19D). The MEMS flow sensor 1930 further includes an output side portion 1938 with an output flow tube 1940 through which a liquid such as insulin flows from the MEMS sensor element 1936 to a downstream element. As shown in Figure 19D, the MEMS flow sensor 1930 includes electrical contacts 1942 for connecting the MEMS sensor element 1936 to associated electronics as described above. The associated electronics include, for example, an integrated circuit, a processor, a power source, and a wireless transceiver chip. Since the associated electronics are packaged separately, they are incorporated into the reusable elements in an exemplary drug delivery device, thus making it possible to significantly reduce the overall cost.

[0048] Figure 20 illustrates a system according to an exemplary embodiment of the present invention. System 2000 includes various components for acquiring data, as well as at least one computing element for receiving data and performing calculations on the data. As illustrated, the exemplary system preferably includes a carbohydrate input element 2002, an oral medication input element 2004, and a blood glucose monitor (BGM) 2006 and / or a continuous glucose monitor (CGM) 2008. The system preferably includes a wellness data input element 2010. Finally, the system preferably includes one of various embodiments of a dosage acquisition device 2016 as described herein. By way of example, a smart pen 2016 is illustrated. Together, these devices input important relevant data required to monitor patients having diseases such as diabetes with respect to improved diabetes management. The exemplary carbohydrate input device 2002 can be an app that operates on, for example, the user's mobile phone 2011, which causes the patient to input the foods and drinks consumed. Similarly, the same or a related app can serve as the oral medication input element 2004, enabling the user to track the oral medications ingested. In addition, the oral medication input element 2004 is automated to warn the user to take the drug and is capable of verifying data related to the ingested oral medication and automatically transmitting it to a secure hub 2012. The BGM 2006 and / or CGM 2008 preferably communicate blood glucose readings directly to a data hub device 2012. Wellness data can be input by a separate device 2010 or by an app related to or the same as those described above. The dosage delivery information device 2016 according to the exemplary embodiment described herein preferably delivers dosage information, such as insulin injected into the patient, in real-time or near real-time. All of the data is received locally by a smart device such as the mobile phone 2011 that operates one or more of the apps discussed above.The carbohydrate input element 2002, the oral medicine input element 2004, the wellness data input element 2010, the mobile phone 2011, and the data hub 2012 are shown as separate elements, but it should be understood that all or any combination of them can be combined into a single mobile phone or similar computing device. Data is analyzed and calculations are performed locally by the smart device and / or smartphone 2011, the data hub 2012 is used to securely transmit, i.e., encrypt, the data to a remote server such as a cloud storage server, and calculations are performed on all of the received data to provide feedback to the user, send all or a portion of the data to a remote health management access point 2020 such as cloud storage, where the information can be accessed by healthcare stakeholders such as the patient's physician, caregiver, pharmacist, and family. Conversely, alerts, reminders, and interventions can be securely provided through the data hub 2012 by a network of users such as HCPs.

[0049] Embodiments of the present invention include several features. The first is dose acquisition, which measures the volume and timestamp of the delivered insulin. This information is preferably acquired in a manner that is transparent to the patient. The second is data transfer, which occurs at different interfaces, such as between a dose acquisition device and a user interface (UI), or between a patient and a healthcare provider. Additional functionality includes data transfer to a patient, a healthcare provider such as a PCP, an endocrinologist, or a nursing instructor, or another risk-bearing entity such as a family member or a diabetes support network. BGM data / CGM data can be incorporated, measured, and timestamped. Lifestyle data such as diet and exercise can be acquired and considered. Embodiments of the present invention are preferably compatible with fitness monitors and nutrition apps. Embodiments of the present invention preferably include additional intelligence that provides useful alerts, warnings, recommendations, interventions, intelligent decisions, such as trend analysis, prediction, and therapeutic modification. Finally, embodiments of the present invention are capable of incorporating or considering oral medications. Preferably, embodiments of the present invention are compatible with oral medication compliance devices such as smart pill containers.

[0050] Recent advances in infusion pump therapy have reduced the growth rate of the multiple daily injection (MDI) segment, but the overwhelming majority of diabetic patients receiving insulin therapy continue to receive delivery by MDI, primarily by disposable insulin pens.

[0051] The cost of incorporating components required for an informatics-usable disposable syringe or insulin pen can be reduced. The informatics-usable part of the device, such as within a replacement cap on the insulin pen, can be reused, or the number of uses of the disposable device can be increased such that additional costs per use, such as the replacement of a needle cannula to a "universal" needle hub, are acceptable. Such hubs are described, for example, in Patent Document 9, the entire content of which is incorporated herein by reference. An increase in the size of the device is another consideration. Adding accessories to the insulin pen, modifying the pen cap, and creating a larger and less attractive outer casing are not desirable as the modified device needs to be carried in a handbag or pack. Another matter is to create a universal solution that can be utilized with currently most commercially available insulin pens.

[0052] A preferred embodiment that meets the above criteria is an informatics-usable insulin pen case that can utilize several different methods to obtain the delivered dose, such as, for example, measuring the weight of the insulin pen each time the pen is placed in the case and the case is closed. The case provides sufficient space to incorporate the necessary electronics and, in some cases, by having more space than required, the design can be adjusted to utilize inexpensive electronics such as a rigid PCBA, a commercially available disposable battery, low-power data transmission, and a large-footprint antenna option for ease of assembly.

[0053] In addition to dose acquisition, an informatics-enabled drug delivery device can perform additional functions. For example, an informatics-enabled insulin pen with a smart cap can identify a specific pen needle for use with the insulin pen. Further, an informatics-enabled insulin pen can advantageously reduce or prevent unintended use. FIG. 21 illustrates a first exemplary system 2100, which includes an insulin pen 2102, a smart pen cap 2104, a package of disposable pen needles 2106, and a smartphone 2108 that runs an application. Using the smartphone's camera, a pen needle package barcode 2112 (or any suitable identification) is read by the mobile phone. The mobile phone 2108 then communicates with a cloud-based database 2110 to verify the pen needle package, unit size, lot number, and other factors identified by the barcode by the manufacturer. The mobile phone 2108 can confirm barcode validity in real-time or near real-time, or alternatively, periodically poll the cloud-based database to download a complete list of valid barcodes and associated information so that communication with cloud-based storage is not required when the barcode is scanned. In this embodiment, the barcode 2112 is printed statically on all pen needle packages and will therefore be reused.

[0054] In another embodiment illustrated in FIG. 22, system 2200 includes a penny needle package 2106 having a unique barcode 2202 (or any suitable unique identifier) imprinted thereon. The mobile phone 2108 is used to scan the unique identifier 2202 and communicate with a cloud-based database 2110 to verify that the unique identifier 2202 is in fact unique and remains valid. Such a system can advantageously be used to prevent the use of unauthorized penny needles, to assist in their recovery if necessary. In any of the exemplary systems described above, a down-counter is preferably set for the number of disposable penny needles in the identified package, and after the counter reaches zero (indicating that the package should be exhausted), certain functions are restricted. For example, the smart cap will stop logging the administered doses once the needle package is exhausted and until a new package is approved.

[0055] In another exemplary system 2300, a smart sleeve 2302 is provided within each package of disposable pen needles 2106. The smart sleeve 2302 is connected to the pen needle and contains an RFID chip. The RFID chip can be read by either the smart cap 2104 or the mobile phone 2108 to verify the pen needle package. Advantageously, the smart sleeve 2302 is read by the smart cap 2104 each time the cap is placed on the insulin pen 2102. When the smart cap 2104 reads the RFID chip, the chip information is preferably transmitted to the smartphone 2108, and the smartphone 2108 communicates with the cloud-based database 2110 as discussed in the example described above. The RFID chip preferably includes lot information, manufacturing date, and any other appropriate information and does not require a printed space on the pen needle package. Similar to the example provided above, when the disposable pen needle provided within the package 2106 is expected to be exhausted, a downcounter is preferably provided to limit higher levels of functionality. The smart sleeve 2302 preferably forms an interface between the insulin pen 2102 and the pen needle using the existing threaded interface on the pen and pen needle. That is, the sleeve includes an inward-facing thread that mates with the insulin pen 2104 and an outward-facing thread that mates with the disposable pen needle. In one version, the smart sleeve includes a septum and a cannula and forms part of the flow channel between the insulin cartridge and the pen needle. In this version, the smart sleeve preferably includes a flow sensor such as the MEMS flow sensor discussed above. In another version, the pen sleeve simply contains identification information such as an RFID chip and identifies the lot number, number of units, and other information of the disposable pen needle package.In this version, the smart sleeve still includes internal threads and external threads for mating with the pen and pen needle respectively, but the sleeve forms a hollow cylinder, and the pen needle mates with the smart sleeve, while the cannula facing inward of each pen needle still pierces the septum of the insulin pen, and the smart sleeve is configured not to form part of the fluid path between the insulin cartridge and the pen needle.

[0056] In another exemplary system 2400, the smart cap 2104 is provided with an array of emitters 2402 and an array of sensors 2404. A portion of the emitters 2402 and sensors 2404 senses the location of the plunger in the pen needle before and after injection and verifies the dosage delivered to the user. At least one other emitter and sensor are positioned adjacent to the pen needle 2406, and when the smart cap 2104 is attached to the pen 2102, the smart cap is able to identify the pen needle based on signals received by the sensors. The smart cap 2104 communicates with the mobile phone 2108, and the mobile phone 2108 communicates with the cloud-based storage 2110 as discussed above. In this embodiment, the dedicated disposable pen needle is preferably marked, and the emitters and sensors are configured to identify a unique signal for identifying the pen needle as being genuine. The signal can be optical, magnetic, or any other suitable signal means.

[0057] In yet another exemplary system, all of the above features are combined. That is, the disposable pen needle package 2106 is imprinted with a uniqueness barcode 2202 (or any suitable marking), the package of the pen needle 2106 is provided with a smart sleeve 2302, and the disposable pen needle is manufactured with a uniqueness signature such as an optical, magnetic, or any other suitable signature signal. The smart cap 2104 triggers a down-counter in the smart sleeve 2302 or the smartphone 2108 and senses the uniqueness signature of the genuine pen needle. If the pen needle is not recognized, some or all of the functions may be restricted as discussed above. The down-counter is used to restrict higher levels of features when the package of the pen needle is expected to be exhausted.

[0058] Further embodiments will now be described that include a rotary dosage adjustment knob or dial. As shown in FIGS. 25 and 26, an embodiment 2500 of the invention preferably uses a press-fit feature to hold and translate a rotary knob used to turn an insulin dosage dial prior to injection and is attached to a commercially available insulin pen. Another means of attachment can be a disposable plastic ring with customized internal and external features, where the internal features will mate with a particular commercially sold insulin pen and the external features will be common across all rings and will also mate with a rotary device. The body portion of device 2500 is attached to the insulin pen body portion and maintains sensor 2502 in a stationary state relative to the rotary pen body portion. The inner sleeve translates axially when rotary knob 2504 rotates, while outer sleeve 2506 remains stationary and provides a grip portion for the user. The outer sleeve is preferably held stationary on the insulin pen body portion using a locking collar tightened by a partial turn detent nut, a sliding "push-on" connector, or any other suitable single motion actuator for locking the collar.

[0059] The 360-degree dial 2504 of the rotary device holds a ring magnet 2508 with a total of 36 poles (alternating N and S poles, each measured 2 mm wide at the central diameter). Of course, the number of poles of the ring magnet can be changed without departing from the scope and spirit of the present invention, and the number 36 is considered a preferred embodiment. The device holds an off-axis Hall effect encoder, such as the AS5304 sensor manufactured by ams ag, at a position observing the ring magnet. When the dosage is turned on the dial, the device translates axially (telescopically) with the extension of the rotary knob. The magnet is preferably positioned 1.5 mm above the sensor and is oriented such that the central diameter of the ring magnet aligns with the Hall element of the sensor chip. When the dial 2504 is rotated, it directly translates the internal dosage selection knob and rotates the ring magnet 2508 relative to the sensor 2502. The software records all motions of the device dial. The device 2500 incorporates a button feature for converting the injection force during injection delivery into a non-spinning push button or actuator at the top of the insulin pen. The button uses the magnetic field measurement built into the sensor to recognize the start and end of administration. This is preferably achieved by using the force from the administration to offset the opposing plastic springs and move the magnet closer to the sensor. As the magnet moves closer, the analog voltage reading of the magnetic field passes a predetermined threshold set in the software. The LED incorporated in the rotary device is preferably lit to indicate to the user that the magnetic switch has been activated and rotation is being recorded.

[0060] All rotational data, both clockwise and counterclockwise, are preferably stored and processed to accurately record the dosage delivered from the insulin pen. Also, time and date information are preferably stored with each dosage entry. The dosage readings are calibrated from the angular rotation of the dial. The sensor, along with a ring magnet with 36 poles, allows for 2880 counts per revolution, which corresponds to 20 insulin units. This produces a resolution of 0.007 insulin units, with an average error of less than 0.5 insulin units being seen during laboratory tests.

[0061] According to this embodiment, the rotation of the insulin dial is sensed to accurately track the intended dosage. To convert the rotation tracking into dosage monitoring, the analog voltage supplied by the sensor indicates the magnetic field strength. A threshold is set in the software to recognize when the thumb force reaches the level at which pen injection administration will begin. A plastic spring, or another form of spring, is used to hold the ring magnet at a position more than 1 mm from the sensor when no force is exerted on the pen injector actuator. When force is exerted, the spring is depressed and the magnet moves closer to the sensor. When the magnetic field is increased, the device can differentiate the dosage injection movement from the dialing movement. Without a way to differentiate between dialing and dosing, effectiveness would be composed of false detections, where the user is allowed to dial back and forth without injecting. This embodiment uses an off-axis stationary sensor and a multipole ring magnet embedded in the rotating dial. Most insulin pens have dosage adjustment in 1.0 unit increments, and a small percentage of commercial injection pens have 0.5 unit increments. The resolution and accuracy provided by an exemplary embodiment of the present invention advantageously exceed the accuracy of the pen, thus enabling accurate measurement of the intended dosage delivered by the patient. Alternatively, clockwise (CW) and counterclockwise (CCW) rotational movements can be summed to determine the dosage. This embodiment eliminates the need to add excessive height to the OTS pen injector, allowing the user to more easily operate the combination pen and device. As shown in FIG. 27, the device preferably contains a PCB, a battery, and a ring magnet along and around the pen injector body, conforming to a natural hand grip.

[0062] An exemplary linear dosage measurement device according to an embodiment of the present invention will now be described in connection with FIG. 28. In one version, an array of anisotropic magnetoresistance (AMR) sensors, and a single neodymium magnet are incorporated. In another version, a single linear Hall encoder measures the displacement of a strip magnet with 28 poles that alternately reverse the N and S poles, with each pole measuring approximately 2 mm. In both versions, the syringe is inserted into and constrained within the body 2802 of the linear device 2800, and the syringe plunger 2804 is held within a "follower" 2806, which is an element of the linear device 2800 that converts the movement of the syringe plunger into a sensor within the linear device. The body 2802 of the linear device has a cavity or nest 2810 for receiving the syringe 2808. The cavity can be sized to receive only the diameter of one syringe, or the cavity can be flexibly adaptable to receive the diameters of multiple syringes, in which case the syringe diameter can be identified through one of (1) scanning a barcode on the outer surface of the syringe, or (2) using an optical element in a smartphone to measure the barrel, or (3) incorporating an RFID chip into the syringe, for example by overmolding. The linear device 2800 can read the RFID through means of near field communication (NFC) or other means.

[0063] The first version uses a neodymium magnet 2812 that travels over 55 mm and converts the position of the plunger 2804 within the syringe 2808. The sensor array is installed on a line parallel to the magnet path with a 10 mm offset and observes the magnetic field emitted from the magnet. The array preferably has six AMR sensors (Honeywell HMC1501) arranged at 10 mm intervals. As the magnetic field increases due to magnet proximity, a voltage is induced and recorded. The system is calibrated to fuse all sensor data and output the linear position of the magnet. The insulin dosage is calibrated from the linear position of the magnet and the cross-sectional area of the syringe it is tracking. In one example, a 1 mL syringe is used with a 55 mm travel, which is converted to 18.18 insulin units per mm.

[0064] The neodymium magnet is acquired within the device using a slide 2806, which is connected to and replaces the thumb actuator 2814 of the syringe plunger 2804. When the plunger 2804 moves linearly and draws fluid into the syringe, the magnet 2812 also moves directly in axial translation. The body of the syringe 2808 is held in place by clipping it into the device 2800, and the finger hold 2816 is held to prevent axial translation. The sensor array and the magnet are separated by a 10 mm gap, which provides a spatial margin for syringes of 1 mL or less with all important parts set on the same plane. A rear cover 2818 is connected to the body 2802 of the device using fasteners 2820, etc.

[0065] The linear hall encoder version has a form factor similar to the AMR approach. It positions the hall sensor within the body 2802 of the device 2800, providing a separation of less than 0.8 mm from the strip magnet. The strip magnet has a length of 55 mm and is adhered to the slide 2806, which is connected to the thumb actuator 2814 of the syringe plunger 2804 and replaces it. Also, when fluid is drawn into or injected from the syringe 2808, this slide 2806 will translate directly axially with the plunger 2804.

[0066] The linear hall encoder uses a home position to determine when the syringe plunger 2804 reaches the 0 mL position. To achieve this, the end of the strip magnet is placed 1 - 2 mm before the total travel of the slide 2806 ends. This causes a drop in 2 of the 4 hall element sensings, which triggers a magnetic intensity error. By knowing the travel required to re - establish the sensing of the first pole pair, the zero position can be calibrated. Alternatively, the zero position can be determined by placing an iron - based material at the zero position and changing the magnetic field in a unique way. This enables the linear hall encoder to record absolute measurements, which increases performance and eliminates offsets that can be introduced by sequential errors. Preferably, an LED is used to inform the user that the device recognizes motion away from the home position and records the position of the plunger. When a multi - color LED is used, one color can be used to indicate that the drug is being withdrawn, and different colors can indicate injection when the device 2800 tracks both directions of travel.

[0067] The preparation for movement is preferably recognized by an accelerometer and / or software, which rationalizes all movements of the delivery cycle, such as the final plunger movement before the syringe returns to the home position when the dose has been delivered, and determines the actual dose delivered to the patient.

[0068] The continuous flow tracking device 2900 illustrated in FIG. 29 will now be described. The continuous flow tracking device 2900 uses a MEMS thermal time-of-flight (TToF) liquid flow sensor to record the flow through the cannula adapter 2902. This adapter can be mounted on top of a commercially available insulin pen or incorporated into the design of the insulin pen, enabling the attachment of a traditional insulin pen needle 2904.

[0069] The adapter is prepared by the same process used with a traditional pen needle using less than 5 insulin units. A switch that triggers the sensor "on" is incorporated into the pen cap 2906. In one embodiment, the switch is operated in relation to an accelerometer to measure the movement of the device / pen and also to enter the low power mode from the sleep mode after the device has been placed at the side for a certain period of time. The flow rate is recorded by using a sinusoidal heat wave generated on one thermistor and measuring the amplitude and phase shift seen on the downstream thermistor. The flow rate is integrated with respect to time to calculate the dose volume.

[0070] Most of the device 2900 is constructed to be a durable assembly, which can be reused with many insulin pens and flow adapters over a period of one to two years. Preferably, only the pen needle 2904 needs to be disposed of after each use, and the flow channel adapter 2902 will be disposed of when each insulin pen is discarded. The flow channel adapter 2902 has male and female ends, which are identical to the male connection feature at the end of the insulin pen and the female connection hub on the pen needle 2904.

[0071] The flow sensing device 2900 can be used to promote compliance or conformance to procedures, i.e., it follows the guidance described in the Forum for Injection Technique (FIT), which was developed to establish and promote best practices in injection techniques for all stakeholders in diabetes treatment. The flow sensing device 2900 preferably utilizes a real-time clock (RTC) and a rolling event finder and stores only administration event data on a durable thermal time-of-flight (TToF) type device. The event finder will have "administration start" and "administration end" timestamps. The LED can be used and lit when the dose is being delivered and measured, and the LED can remain on for a specific number of seconds after the "administration end" event is sensed. Alternatively, a piezoelectric vibration device can be incorporated into the system to provide tactile feedback to the patient. Also, the flow sensing device 2900 includes an accelerometer (not shown) to distinguish random movement of the pen from the dosing event. Thus, the flow sensing device 2900 can be used to determine whether the patient is holding the insulin pen against their tissue for the recommended duration after the dose has been delivered, i.e., the device can advantageously measure compliance to the procedure. Non-compliance can be logged in the patient's electronic logbook, which can be evaluated by a healthcare provider (HCP).

[0072] For example, in cases of extreme incompatibility, such as when the patient removes the pen from the tissue before the full dose is delivered, a surge in the flow will be detected by the flow sensor. An alarm can be incorporated into the device to warn the patient of an incomplete dose. Both the intended dose and the portion of the dose delivered into the tissue are preferably recorded in the patient's logbook, along with any corrective doses, enabling the HCP to identify this shortcoming in the patient's self-therapy. In extreme cases of incompatibility, such as when the patient is receiving continuously lower doses than intended, the HCP can be directly notified and can intervene to provide guidance.

[0073] Also, the TToF sensor can advantageously detect reverse flow, which can be caused by cannula occlusion or excessive resistance in the flow as a result of the patient accidentally injecting into the intradermal space. In both cases, an alert is sent to the patient to prompt confirmation of whether proper and full dose delivery has occurred. This feature is also useful for subcutaneous or intravenous drug infusions in either outpatient or clinical settings.

[0074] Those skilled in the art will understand that modifications to the electronic circuitry and software can be made to improve the device and provide additional benefits, such as incorporating a Bluetooth Low Energy (BLE) chip with Near Field Communication (NFC) capabilities. Such additions would enable the system to identify, for example, a Pen Needle (PN) containing an NFC tag.

[0075] Another dosage measurement device 3200 that uses time-of-flight thermal to measure dosage will now be described in connection with FIGS. 32-42. As shown in FIG. 32, device 3200 works with a standard insulin pen 3202. The disposable portion 3204 of the dosage sensor is connected to the insulin pen 3202, where a standard pen needle 3206 would normally be connected. The durable portion 3208 of the dosage sensor fits over the disposable portion 3204. The pen needle 3206 is screwed onto the distal end of the disposable portion 3204. Finally, the cap 3210 fits over the durable portion 3208. The durable portion 3208 of the dosage sensor preferably includes electronics, and in particular wireless communication components, to communicate wirelessly with a smartphone 3212 or any other suitable remote device and exchange data.

[0076] The disposable portion 3204 of the dosage sensing described above utilizes an anisotropic (z-axis) thermal film and transmits thermal signals related to a time-of-flight flow sensor that is part of a dosage acquisition system used with a standard insulin pen. Here, the disposable portion 3204 will be described in more detail in connection with FIGS. 33-35. The disposable portion 3204 includes a z-axis film 3212, a plastic manifold 3214 used to create a uniform laminar flow near the sensor, an inlet cannula 3216 that pierces the septum of the standard insulin pen, and a rubber septum 3218 at the discharge end that receives the standard insulin pen needle. At the inlet end, a threaded or snap-fit portion 3220 is adapted to connect to the standard insulin pen 3202. As shown in FIG. 35, when assembled, the surface of the z-axis film 3212 protrudes into the flow channel, ensuring that the shear and velocity gradients across the surface of the film are in a steady state and that there is a minimum fluid stagnation zone.

[0077] The durability portion 3208 is illustrated in the exploded view of FIG. 36. The durability portion 3208 includes a battery 3222, a circuit board 3224 that includes a wireless communication component (not shown), a MEMS-based time-of-flight thermal sensor element 3226, a plastic housing 3228, and additional components 3230a, 3230b for engaging the sensor 3226 with the disposable portion 3204 and for locking or clamping the durability portion 3208 onto the insulin pen 3202.

[0078] The dosage sensor described above calculates the insulin volume by analyzing data received from the sensing element. The time delay associated with the thermal pulse traveling from the input heating element to the sensing element downstream is preferably used to determine the phase shift. The magnitude and phase shift of the measurements at the sensing element are preferably used to determine the insulin flow. Additional details regarding the time-of-flight thermal sensor element are shown and described in connection with FIG. 37. The sensing element 3226 is composed of a MEMS chip adhered to the circuit board. The MEMS chip is a ceramic or glass substrate with conductive traces for a heater 3230 and two symmetrically offset temperature sensing elements 3232. The central heating element 3230 is heated via an electric current, and the two outer elements 3232 are used to measure the thermal signal generated by this heater. The circuit board provides structural support and makes electrical connections to the MEMS sensor chip. The two sensing elements 3232 are preferably symmetrically offset from the heating element 3230. Modifying the offset distance allows for the selection of a specific flow rate range that exhibits a large phase resolution and produces better accuracy. In addition, multiple sensing element pairs are provided at different offset distances, such as 100 μm and 200 μm, and can be used to extend the dosage measurement accuracy to a larger flow rate range as needed.

[0079] Figures 38 to 40 show the interaction between the disposable portion 3204, the durable portion 3208, the insulin pen 3202, and the pen needle 3206. The disposable portion 3204 is assembled onto the insulin pen 3202, punctures the rubber septum on the insulin pen, and creates a flow path. Then, the durable portion 3208 is assembled onto the disposable portion 3202, and the time-of-flight thermal flow sensor in the durable portion 3202 is pressed against the surface of the z-axis film 3212 in the disposable portion 3202, such that the two components are in close contact with no gap between them. This mating condition shown at 3234 can be created via secondary steps such as pressing the button 3236. The sensor 3226 can alternatively be mounted on a spring-loaded arm or cam such that it is automatically done for the user. The components in the durable portion 3208 are designed in accordance with allowing the stacking of tolerances between the sensor 3226 and the disposable portion 3208. Figure 38 shows the sensor 3226 pressed against the surface of the z-axis film 3212. Figures 39 to 40 show cross-sections through the flow sensor with the two components mated.

[0080] Figure 41 shows a close-up of the cross-section of the z-axis film 3212. The film 3212 is a composite of thermally conductive particles, flakes, or fibers embedded in a matrix of low thermal conductivity. The components of the film allow for a relatively high thermal conductivity in a direction perpendicular to the plane of the film, and a much lower thermal conductivity in a direction along the plane of the film. Figure 42 illustrates the intended heat flow path during sensor operation. The heater 3230 sends a pulse of heat through the film 3212 into the fluid 3234, where it is carried downstream by the fluid flow. The heat is then conducted through the film in the opposite direction to the thermal sensor 3232. The ideal z-axis film will have a relatively high thermal resistance in the plane (XY) while having a minimum thermal resistance in the Z direction.

[0081] The devices described above preferably have the following characteristics. The z-axis film 3212 should be as thin as possible. The volume fraction of the thermally conductive particles should be as high as possible while allowing the separation between the particles to minimize the in-plane conductivity. The thermally conductive particles should be evenly spaced at a pitch much smaller than the spacing between the heater and the sensor. The particle thermal conductivity should be as high as possible. The ambient matrix thermal conductivity should be as low as possible. The ideal particles can have a cylindrical shape with a small diameter and length that span the thickness of the film. The particles should preferably extend beyond the surface of the non-conductive matrix material to minimize the thermal resistance. The film should be elastic or slightly flexible, conform to the surface of the MEMS sensor, be able to eliminate the air gap, and minimize the thermal resistance at the interface without cracking, breaking, or leaking. The pressure from the fluid channel ensures that the film is firmly pressed against the surface of the MEMS chip during operation, minimizing the thermal contact resistance. The z-axis film sheet preferably adheres to ABS or other common thermoplastic resins. An airtight seal is required between the film and the plastic manifold. The z-axis film ideally has a light tack such that it slightly penetrates the surface of the MEMS chip but can be completely peeled off without leaving residues or broken pieces on the surface of the MEMS chip. The z-axis film should be stable even when exposed to insulin for up to 5 days and must not release harmful substances into the fluid stream. A biocompatible coating or surface treatment can be applied to the base of the z-axis film to improve insulin and biocompatibility.Examples of currently manufactured z-axis films, and examples of z-axis films suitable for use, in some cases, with embodiments of the present invention, include Adhesives Research (EL-9032), 3M (9882), Btech (TP-1), Shin Etsu (Type AF), and Shin Etsu (Type MAF).

[0082] Embodiments of the present invention have several potential advantages. First, embodiments of the present invention enable an MEMS sensor to be moved from the disposable portion to the durable portion of a dosing sensing system, thereby reducing the cost of the system and, in some cases, allowing for the use of a higher accuracy sensor as the sensor cost is spread over many uses. Further, embodiments of the present invention isolate the sensor from insulin contact and allow all electrical connections to the sensor to be permanent.

[0083] One variation of the embodiments described above combines the manifold with a pen needle. The advantage of this configuration is that it eliminates the disposable portion of the sensor. The disadvantage of this configuration is that it increases insulin waste due to the need to prepare the sensor channel with each injection.

[0084] In another embodiment of combining the manifold and the pin needle, 3D printing can be utilized to facilitate both the pin needle body portion and the incorporated Z-axis film “window”. Nevertheless, 3D printing can advantageously be utilized to fabricate the Z-axis film with respect to a stand-alone manifold. There are several 3D printing techniques that can be utilized. One example is FDM (Fused Deposition Modeling), also known as FFF (Fused Filament Fabrication). Here, a thermally conductive polymer filament is used to print columns with an approximate diameter of 100 microns of thermal conductivity into the Z-axis film. The required diameter depends on the separation between the heater 3230 and the sensing element 3232 and its width in FIG. 42. The matrix of the film is printed using a low thermal conductivity polymer (unfilled) material. In one embodiment of the 3D printed Z-axis film, the structure is built on a very thin (within 25 microns) flexible polymer film, which will be the side that contacts the MEMS flow sensor. The advantage of this is to ensure a liquid-tight Z-axis film and provide a flexible substrate for a low thermal resistance attachment to the MEMS flow sensor, while the disadvantage is that it has a small thermal conductivity penalty in the Z direction.

[0085] In yet another embodiment, the z-axis material can be configured as a tube such that the film forms a complete flow path and no secondary manifold is required. For example, the z-axis tube can be overmolded into the body portion of the pin needle and reshaped, if required, into, for example, a square cross-section or a rectangular cross-section to provide a flat surface and be more easily fitted with the heater and sensor traces. The disadvantage of this configuration is that it becomes more difficult to make good contact between the sensor and the z-axis film tube.

[0086] In addition to being used with an insulin pen, the dosage sensor described above can be used with other flow sources such as an infusion pump, a syringe, or a gravity-fed infusion line.

[0087] Although only some embodiments of the present invention have been described, the present invention is not limited to the described embodiments. Instead, it will be understood by those skilled in the art that changes can be made to these embodiments without departing from the principles and spirit of the present invention.

Claims

1. An informatics-enabled pen case adapted to receive an insulin pen, comprising: a syringe receiving cavity; a clamping system adjacent to the syringe receiving cavity and adapted to clamp over a plunger of the syringe receiving cavity; an actuator adapted to move the clamping system and the plunger when the clamping system is clamped over the plunger; a processor adapted to receive a dosage command from a transceiver and to send control information to a controller, the controller being adapted to operate the actuator and the clamping system; a transceiver adapted to receive a dosage command from a user interface; wherein the transceiver transmits the received dosage command to the processor; wherein the processor includes an RFID chip, receives the dosage command, and sends control information corresponding to the dosage command to the controller; wherein the controller receives the control information, controls the clamping system and the actuator, clamps the plunger of the syringe, moves the plunger, and withdraws a dosage corresponding to the dosage command. An informatics-enabled pen case characterized thereby.

2. The informatics-enabled pen case according to claim 1, wherein the user interface includes an application operating on a smartphone.

3. An informatics-enabled drug delivery device and device case, comprising: a drug delivery device adapted to receive a removable reservoir filled with a drug, the reservoir including a plunger adapted to move axially within the reservoir to cause the drug to exit the reservoir, the plunger including a target element attached to the plunger and moving axially with the plunger. A device case including a cavity and a target element sensor, wherein the cavity corresponds to the drug delivery device and is shaped to receive the drug delivery device at a predetermined location, and the target element sensor is adapted to sense the location of the target element. The device case comprises The device case further includes a processor adapted to receive signals from the target element sensor, a real-time clock, a memory for storing the target element location sensed by the target element sensor, and a wireless transceiver. The processor is adapted to determine a dosage and an administration time based on the target element sensor signal and the real-time clock, and is also adapted to send the determined dosage and administration time to the wireless transceiver. The wireless transceiver is adapted to transmit the determined dosage and administration time to a remote device. A drug delivery device and a device case characterized by this.

4. The drug delivery device according to claim 3, wherein the drug delivery device is an insulin pen. The drug delivery device and the device case.

5. An informatically usable drug delivery device, A drug delivery device adapted to receive a removable reservoir filled with a drug, the reservoir including a plunger, the plunger being adapted to move axially within the reservoir and cause the drug to exit the reservoir, the plunger including a target element, the target element being attached to the plunger and moving axially with the plunger. A drug delivery device, A device cap adapted to receive the drug delivery device and surround the delivery end of the drug delivery device, the device cap including a target element sensor adapted to sense the location of the target element. A device cap comprises The device cap further includes a processor adapted to receive signals from the target element sensor, a real-time clock, a memory for storing the target element location sensed by the target element sensor, and a wireless transceiver, the processor being adapted to determine a dosage and an administration time based on the target element sensor signal and the real-time clock, and also being adapted to send the determined dosage and administration time to the wireless transceiver, the wireless transceiver being adapted to transmit the determined dosage and administration time to a remote device, a drug delivery device characterized by this.

6. The drug delivery device is an insulin pen, and the device cap is a smart pen cap. The drug delivery device and device case according to claim 5, characterized by this.

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