TECHNICAL AREA

The present disclosure relates to the use of microwires in medical devices to provide information relating to the status, changes, and operation of the medical device. One or more microwires can be located on or within the medical device such that an electronics module can interrogate and receive signals from the microwire(s) that reflect

information directly related to the medical device. Interrogation can be through wireless or wired connections. The electronics module can be an integral part of the medical device or can be a separate device that can be reused with a plurality of medical devices.

BACKGROUND

There are a vast number of medicament delivery devices on the market that are capable of performing any number of operations that benefit a user or patient. For example, there exist a variety of devices that automatically, semi-automatically or manually deliver one or more doses of medicament through injection (needle and needleless), inhalation, infusion, atomization, drops, patches, and implants. In each case there are a number of important device attributes that are beneficial to know and monitor, for example, temperature, pressure, position and motion of select mechanical components (linear and rotational), force, and of course, changes in specific parameters of the device. The ability to monitor one or more these device attributes with one or more sensors would greatly benefit patient safety, drug administration compliance, anti counterfeiting, device failure analysis, and future device design, just to name a few benefits.

Known medical devices are constructed with drug delivery setting mechanisms that include a variety of inneracting mechanical components to achieve desired functions, such as setting a dose, dose cancellation, and ultimately delivering the set dose. In some cases, these devices are designed for non-medically trained individuals to self- administer medicaments. Users of such devices include diabetics., where medication management and compliance, i.e. the degree to which a patient follows medical instructions and protocols, is often of extreme importance. To evaluate and determine compliance of a self-medicating user, it is desirable to obtain as much information about each injection as possible, for example, the determination of the actual dose of the medication injected, the temperature of the device and/or the medicament in the device, the amount of the set dose, whether a dose setting correction was needed, the rate of dose injection, whether the injection was halted, the time of day when the injection was performed, and the time required to complete the injection. Collection and evaluation of such data can be especially important if the user is physical impaired, for example, having reduced eyesight or severe arthritis.

Passive wireless sensors are known and include Radio Frequency Identification (RFID) and magnetic element markers used in electronic article surveillance (EAS) systems or other authentication systems. The markers or tags associated with these known sensors are passive and, in some forms, can transmit their information wirelessly to a detector even when embedded within a structural component. Another known sensor relies on magnetostriction, which is a known property of certain metals, specifically those containing ferromagnetic materials. This property causes the metals to change its properties during the process of magnetization. Recently, these materials have been manufactured as very fine wires having dimensions similar to a human hair, with diameters on the order of 12 pm. These fine wires, known as "microwires", can be formed as metallic bodies in an amorphous and/or nanocrystalline state and can include an optional outer coating, such as glass. Such micro wires can be produced by the known Taylor-Ulitovsky technique by simultaneously drawing and quenching a molten master alloy, for example, an iron, molybdenum, bismuth, and copper containing alloy.

Microwires have found use in temperature sensors to wirelessly determine the temperature of an object and to control the object’s temperature during heating/cooling cycles in a manufacturing process. However, the use of microwire technology in medical devices to monitor and report device attributes is not known.

With the need to monitor, collect and evaluate medical device attributes, especially in drug delivery devices, it is desirable to provide medical devices, such as medication delivery systems, that are economical to manufacture and that can monitor, record, and report various device attributes and that can work wirelessly and with other devices. As such, it an object of the present disclosure to provide medical devices that include one or more microwire sensors to allow the above-mentioned device attributes to be monitored, measured, recorded and transmitted so that the collected data can be evaluated by patients, health care professionals, and device manufactures. Incorporation of the microwires into existing medical device designs would add only a minimum manufacturing cost to the already existing devices. The disclosure presented below achieves the above-mentioned goals by combining medical devices with microwires and/or electronic modules.

BRIEF DESCRIPTION The present disclosure is applicable to a number of medical devices, including, but not limited to, devices that automatically, semi-automatically or manually deliver one or more doses of medicament through injection (needle and needleless), inhalation, infusion, atomization, drops, patches, and implants. Incorporating one or more microwires into these medical devices that can communicate with an electronics module, allows a number of device attributes to be monitored, measured, recorded, and transmitted. The electronics module can be incorporated into the medical device, or be removably attached to the medical device, or be a completely stand-alone component.

In one non-limiting embodiment of the present disclosure there is a medical device having a medicament container, a medicament delivery mechanism operatively associated with the medicament container, a microwire attached to a component of the medicament delivery mechanism or to the medicament container, and an electronics module operatively associated with the microwire. The electronics module can be removably attached to the medical device and reusable, also can comprises a user interface. The electronics module is configured to interrogate the microwire and to receive a signal from the microwire, where the received signals are processed and transformed to generate reportable information about the microwire itself that includes temperature, pressure, position and motion of select mechanical components (linear and rotational), force, fluid flow, stress, or strain. The electronics module can also be configured to communicate with a remote device having a user interface. The microwire preferably is in the shape of a wire having an outer diameter in the range from about 5 pm to about 60 pm and a length of from about 1 mm to about 40 mm and can be affixed to an outer surface of a mechanical component in the medicament delivery mechanism. Alternatively, or in addition, the microwire is integrally incorporated into a mechanical component in the medicament delivery mechanism.

The electronics module would wirelessly interrogate the microwire(s) and receive a signal from the microwire(s), where those signal(s) would be indicative of the properties of the microwire or the changes in the properties of the microwire. The microprocessor in the electronics module would process and transform those signals into reportable information about the microwire, such as, temperature, pressure, position and motion of select mechanical components (linear and rotational), force, fluid flow, stress, and strain. It is to be noted that signals relating to motion or changes in position of the microwire, and hence the component to which the microwire is associated, can be captured only when the electronics module is activated or in an energized

sending/receiving state while the monitored component is moving, such as during dose setting or dose delivery operations. This information could then be reported in real time to a display that is part of the electronics module or is part of another reporting device, such as a dedicated remote device, a cell phone or a desktop computer. Alternatively, the electronics module could record and store the information until the information was transmitted to another device automatically or be manually interrogated by a user using a separate remote device. The information acquired as a result of the microwire and electronics module communication can provide historical information regarding both the manufacture, shipping, storing and ultimate use of the medical device.

As mentioned, one or more microwires could be used on or within the medical device, depending on the attributes that are being monitored. As these microwires are very small dimensionally, for example having outer diameters in the range from about 5 pm to about 60 pm and lengths of from about 1 mm to about 40 mm, the microwire can be conveniently added to one or more previously designed or existing components of a medical device through affixation to an outer surface using an adhesive or other bonding method to render the microwire spatially fixed to or on the component. It is also possible to embed a microwire in a component of the medical device during the manufacturing process, for example, using a co-extrusion and co-molding techniques. In both situations, because the microwires are so small, the addition of a microwire to a particular component of the medical device does not require a fundamental change of the design or the component or to the overall functioning of the medical device.

The microwire can be advantageously formed as metallic bodies in an amorphous, nanocrystalline, or mixed state. Such metallic bodies are preferably in the form of very thin and elongated wires or strips that can be produced in a variety of manners. One particularly suitable form of the microwire comprises an inner metallic core and an optional outer glass coating. Such microwires are produced such they are magnetically susceptible. Continuous lengths of micro wires can be produced inexpensively where the selected metal alloy is converted to a molten state and contained in a glass tube. The softened bottom of the glass tube is grasped and drawn into continuous microwire.

Rapid reduction of alloy cross-section, together with use of secondary cooling means, causes the alloy to become amorphous, nanocrystalline or a mixture of both during the drawing process. The microwire magnetic properties and resultant hysteresis loops can be controlled by varying the alloy composition and the glass-to-metal diameter ratio. The re-magnetization properties of the microwire can also be important, where extremely short re-magnetization peaks allow discrimination of a microwire response from background noise such as that caused by field interaction with other external objects. Different alloy compositions achieved through chemical modification of the starting compositions used to form the microwire will alter the properties of the resultant microwire. One preferred chemical modification of Fe-based and/or Co-based alloys is the adjustment of the atomic percentage of chromium therein. Chromium in amorphous iron-based alloys has a sizeable effect on magnetic properties. Other chemical changes to Fe-based and Co-based alloys can also be utilized to alter the magnetic characteristics of amorphous microwire elements. For example, Co can be substituted for Fe in certain alloys. One preferred composition is one with a nominal composition of Fe ₇₆ Mo ₅ Bis Cui. In order to most effectively make use of the micro wire containing devices of the present invention, it is preferable to use an electronics module comprising a detector correlated with the microwire. Such a detector generally has a device for generating an alternating magnetic field of sufficient magnitude to interrogate the microwire to create re- magnetization responses of the microwire, and a device for detecting such responses. In practice, the detector can have a magnetic field generator coil and a field receiving coil both coupled with a signal processing unit. Alternatively, there could be a single coil performing both functions. In use, the detector generates the requisite alternating magnetic field, and the field receiving coil detects the re -magnetization responses of the microwire, issuing output signals to the signal processing unit. The signal processing unit, preferably in the form of a digital microprocessor, employs a decoding algorithm which allows determination of the one or more device parameters being observed or monitored, such as object temperature. In preferred forms, the decoding algorithm comprises one or more look-up tables correlating the re-magnetization responses of the sensor elements with the object attribute being monitored. One possible electronics module of the present invention includes a detector device used to detect an attribute of a medical device. Such a module can broadly include an alternating magnetic field transmitter unit in the form of a frequency generator coupled with a field generator coil, such that the transmitter unit is operable to create an alternating magnetic field for interrogating one or more microwires located in the medical device. The electronics module further includes a field receiving coil operably coupled with a digital signal processing unit and a display. The electronics module can also be equipped with communication ports and may be operably coupled with a frequency generator that may be equipped with an optional input to permit remote control of the frequency generator.

The signal processing unit may operate using a decoding algorithm having the capability to decode the magnetic field perturbation information received upon interrogation of the microwire(s). Preferably the decoding algorithm is in the form of one or more look-up tables for the different microwires located on or in the medical device. These look-up tables can be stored within memory associated with the electronics module. Those skilled in the art will appreciate that a wide variety of corresponding algorithms tables can be provided. The electronic module would have the means to interrogate the microwires contained in the medical device and also include a means for determining the response to that interrogation. The electronics module could also comprise a power supply and an application-specific integrated circuit (ASIC) to generate and receive signals to and from the one or more microwires located in the medical device. The ASIC may be adapted to collect information regarding the operation of the injection device and to transform the information collected into a format recognizable to a user or healthcare provider. A processor within the electronics module could use the received signals from the interrogated microwire to calculate a dose setting or dose delivered. This calculated result could be transmitted to a display accessible by the user and it could be stored in memory for transmission to another device via wired or wireless connection. The processor could also include a clock function to allow it to monitor the time/date of injection, the rate of change of the magnetic properties of the microwire, i.e., the speed of injection, and whether the injection was halted and for how long. It is also possible that the electronics module could determine the temperature of device and hence provide an approximate temperature of the medicament at the time of injection or during non-use of the device. Temperature profiles of the injection device can be related to the effectiveness of medicaments, e.g., degree of degradation or reduced potency of the medicament.

The use of micro wires in medical devices can provide information concerning the following attributes: a. the position of specific device components within the medical device based on determining the position or physical state of micro wires attached to or relative to other device components;

b. the linear and rotational movement of one or more component parts, for example, an axial movement of a piston rod in an injection device, rotational movement of a drive shaft in an infusion pump;

c. the force exerted on or by a device component, for example, pressure exerted by a piston rod on a sliding piston within a medicament container;

d. the current temperature, and changes in temperature, of a medical device, including the temperature, and changes in temperature, of a medicament container within the medical device;

e. the mechanical stress and/or strain experienced by particular components in a

medical device during use, such as physical hard stops, springs, flexible arms, and releasable connectors, dose counters, and/or during the manufacturing or assembly procedure, such as forces applied to components by automated assembly machines and storage and transportation containers;

f. the identification of a specific type of medicament within the medical device; g. whether the medical device or the container of medicament is counterfeit; h. providing anti-tampering features and prevention against counterfeit medical device components and/or medicament containers;

i. the flow of fluids through cannula or other conduits within the medical device, for example, to compare a set dose of fluid versus actual dose delivered to a user; j. capturing the position of the medical device against a user’s body through the use of force and/or temperature measurements obtained by interrogating one or more microwires position on or within device components;

k. measuring, collecting and determining performance of selected mechanical

components with the medical device;

l. collection of process control information, e.g., stress forces, during the

manufacturing and assembly of medical devices;

m. measuring volume or mass fluid flow through a needle by placing microwire within a needle hub; and

n. providing information to a user concerning needle hub removal from or positioning on the medical device to ensure proper attachment or prevent re-use of the needle hub.

The information obtained from interrogating the one or more microwires can be obtained through wireless communication from the electronics module to a portable or remote device 300 (see Fig. 4) that can be dedicated to the electronics module. The portable device can be a smartphone or tablet or other portable device such as a laptop or handheld personal data assistant (PDA) Such as a personal diabetes manager (PDM) which has a processing device, memory, display, user interface and communications interface. The electronics module 200 can also enable a user to manipulate or configure or simply view different desired characteristics of the interrogated microwire 100, such as sensing volume or mass flow rates or pressure to determine leakage or occlusion or incomplete drug delivery, or constituent, diluent, temperature to determine drug degradation or expiry or incorrect drug. The microwire can be configured to detect one or more of a drug identification, concentration, agglomeration, degradation and/or other drug or delivery characteristics thereby enabling a user of the medical device to stop or prevent medication errors that occur primarily through self or automated injection or other self-administrating drug delivery device.

The combination of the one or microwires with the electronics module can monitor such parameters as temperature, contamination, drug manufacturer, compromised drugs (e.g., due to light exposure, improper handling, contaminated or faulty containers, tampering, temperature exposure, or expiry from actual drug deterioration which is more accurate than projected expiry based on date of preparation), time of

injection/infusion(s), drug, dose, diluent, concentration, or agglomeration. The electronics module can also provide convenient and wireless access to stored data, such as, but not limited to, use by date, medication storage device information (e.g., catalog information and/or lot number), patient information (e.g., one or more of height, weight, gender, ethnicity, allergies, conditions), patient's electronic medication administration record (eMAR) downloaded from hospital information technology (IT) system, drug use conditions, dates of preparation or device access, and/or drug information (e.g., lot number, manufacturer), as well as actions/alerts such as, but limited to, visual or audible cues if the drug should not be administered, documentation (e.g., information automatically provided to the patient’s medical record or the doctors office), potential display of information about contents and delivery instructions and a locking mechanism if drug should not be delivered for any reason.

The portable device 300 can be used wirelessly to program the electronics module with customized medicament delivery instructions, data logging and data integration procedures to provide a user with convenient access to accurate information on the electronics module 200 and/or the portable device 300 display or screen to see current dose amount, time of dose and dose information relative to previously stored, historical medicament administration events. The combination of a micro wires and an electronics module can also provide sensing capabilities in or with respect to infusion devices to allow for early detection of site failures, medication errors and compliance. This allows for real-time detection and feedback loops for infusion site failures (e.g., leakage, occlusions, medicament instability) and ensures improved safety (e.g., via early detections of drug and/or delivery parameters as described herein that can prevent adverse drug interactions), both of which have previously been unmet needs for users of conventional self-administered drug delivery devices.

Illustrative embodiments of the present invention can be implemented, at least in part, in digital electronic circuitry, analog electronic circuitry, or in computer hardware, firmware, software, or in combinations of them. The one or more microwires communicating with the electronics module and its respective components, namely, a signal processing unit 201, a frequency generator 202, a field generator coil 203 and a field receiving coil 204 can be implemented through application of one or more computer program products, i.e., a computer program tangibly embodied in an information carrier, e.g., in a machine -read able storage device or in a propagated signal, for execution by, or to control the operation of data processing apparatus, e.g., a programmable processor, a computer, or multiple computers. A computer program can be written in any form of programming language, including compiled or interpreted languages, and it can be deployed in any form, including as a stand-alone program or as a module, component, subroutine, or other unit suitable for use in a computing environment. A computer program can be deployed to be executed on one computer or on multiple computers at one site or distributed across multiple sites and interconnected by a communication network.

Portions of the present disclosure can also be embodied as computer-readable codes on a computer-readable recording medium. The computer readable recording medium is any data storage device that can store data which can thereafter be read by a computer system. Examples of the computer-readable recording medium include, but are not limited to, read-only memory (ROM), random-access memory (RAM), CD-ROMs, magnetic tapes, floppy disks, and optical data storage devices. The computer readable recording medium can also be distributed over network-coupled computer systems so that the computer-read able code is stored and executed in a distributed fashion. Also, functional programs, codes, and code segments for accomplishing the present disclosure can be easily construed as within the scope of the invention by programmers skilled in the art to which the present disclosure pertains. Method steps, processes or operations associated with the one or more microwires, electronics module and/or portable devices operating in conjunction with a signal processing unit 201 (processor) or controller associated with the microwire itself, or the medical device, or a user portable device 300 (e.g., a handheld user device such as a smartphone, laptop, PDM and the like), can be performed by one or more

programmable processors executing a computer program to perform functions of the invention by operating on input data and generating an output. Method steps can also be performed by, and an apparatus according to illustrative embodiments of the present invention, can be implemented as, special purpose logic circuitry, e.g., an FPGA (field programmable gate array) or an ASIC (application-specific integrated circuit).

Processors suitable for the execution of one or more computer programs associated with the present disclosure include, by way of example, both general and special purpose microprocessors, and any one or more processors of any kind of digital computer.

Generally, a processor will receive instructions and data from a read-only memory or a random access memory or both. The essential elements of a computer are a processor for executing instructions and one or more memory devices for storing instructions and data. Generally, a computer will also include, or be operatively coupled to receive data from or transfer data to, or both, one or more mass storage devices for storing data, e.g., magnetic, magneto -optical disks, or optical disks. Information carriers suitable for embodying computer program instructions and data include all forms of non-volatile memory, including by way of example, semiconductor memory devices, e.g., EPROM, EEPROM, and flash memory devices; magnetic disks, e.g., internal hard disks or removable disks; magneto optical disks; and CD-ROM and DVD-ROM disks. The processor and the memory can be supplemented by or incorporated in special purpose logic circuitry. The following list of medical devices, although not exhaustive, can benefit by the inclusion of one or more micro wires:

a. injection devices, including reusable and disposable designs, needle or needleless, manually driven by a user or triggered to automatically perform medicament delivery;

b. pumps that deliver medicament continuously or through intermittent bolus

amounts;

c. inhalers, both dry powder and pressurized liquid atomizers;

d. osmotic delivery devices;

e. wearable patches; and

f implanted biosensors and drug delivery devices.

As described in more detailed below, one possible medical device to benefit from the use of microwire sensors is a self-injection pen-shaped device, such as those used to dispense insulin or fertility drugs, which historically have been strictly mechanical devices. There is growing interest in incorporating electronic functionality in these self- injection pens to monitor, track and accurately measure the volume of the drug dispensed. It is also of interest to incorporate wireless transmission of the injected dose to the cloud to assist physicians in monitoring injection parameters. Solutions should be low cost, especially for the disposable pen market, must be accurate and should not require substantial modification of the existing pen mechanics.

One possible pen-type injection device that can incorporate one or more micro wires is one that is capable of variable, user settable, multiple doses from a single container of medicament, where the container is preferably a cartridge. Examples of such devices are described in U.S. 8,512,296, U.S. Pub. No. 2018/0001031 and U.S. Serial

No. 15/649,287, filed July 13, 2017, the contents of each of these patent applications are fully incorporated by reference in this application. The injection device can be reusable meaning that the container of medicament is replaceable through partial disassembly and resetting of the injection device, for example by replacing an empty cartridge with a full cartridge and retracting a piston rod back into a dose setting mechanism. In a reusable device, a cartridge holder is removed from the proximal end of the dose setting mechanism and the old empty cartridge is replaced by a new full cartridge and the cartridge holder is reattached to the dose setting mechanism. In a disposable injection device, the cartridge holder is permanently attached to the dose setting mechanism and once the cartridge of medicament is empty, the entire injection device is disposed of.

One or more microwires and an associated electronics module can be utilized with the above described existing mechanical injection pen design for the purpose of measuring and communicating the dispensed dose. This disclosure describes in detail just one possible application of the use of a micro wire that is integrated into an injection pen to measure the position or change in position that is caused by mechanical motion of the piston rod that moves linearly in a proximal direction to expel drug from the container. An electronics module, removably attached to the pen or which is separate and remote from the pen, wirelessly communicates with the microwire to collect linear motion information that is then processed into a set dose and a delivered dose of medicament. This measured motion of the microwire is directly proportional to the relative movement of two component parts in the injection device, which in turn can be directly correlated to a dose of medicament set by the user and/or a dose of medicament delivered during the injection procedure.

The determination of dosage utilizing microwire technology, as described in the present disclosure, is applicable to a wide variety of injection device designs, provided that at least one component of the dose setting and delivery mechanism moves during dose delivery. This change in position of the microwire that is caused by linear or rotational movement can be directly proportional to an amount of medicament that would be expelled from the container of medicament if the injection procedure was fully carried out. One possible dose delivery component that moves linearly is described in more detail below. That component is a piston rod that translates proximally relative to the outer housing during dose delivery. Preferably, a microwire is fixedly attached to the piston rod either through adhesion to an outside surface or incorporated in the piston through co-molding. As mentioned, an electronic module may constitute a separate measuring device that collects, computes and records data derived from interrogating one or more microwires that is attached or imbedded into one or components of the medical device. Preferably the separate electronics module is attachable, removable and reusable relative to the medical device of the present disclosure. By having a separate and reusable electronics module allows the medical device, for example an injection device, to be manufactured economically in a "ready state", meaning ready for attachment of the electronics module. Further details of the separate electronics module is disclosed below.

Alternatively, the electronics module can be integral, i.e., not a separate, removable part of the medical device.

The microwire(s) can be glued, press-fit, clamped, screwed, or otherwise physically attached to one or more selected components of the medical device, thus the microwire is attached as a separate standalone item during assembly of the device. Alternatively, the microwires could be made integral to selected components of the medical device by co-molding the microwire when the selected component is manufactured in the first instance. Such a manufacturing process is sometimes referred to a "two-shot" molding process. Co-molding allows for economically efficient manufacturing, especially when the medical device, such as an injection device or an inhaler, is intended as a disposable device, meaning that the container of medicament is sealed within the device and once all of the medicament has been expelled, usually through repeated injections or inhalations of the same or different doses, the medical device is then discarded. In other words, in such a disposable device there is no mechanism or means to remove an empty container of medicament or to reset the device to insert a new filled container of medicament. These and other aspects of, and advantages with, the present disclosures will become apparent from the following detailed description of the present disclosure and from the accompanying drawings.

BRIEF DESCRIPTION OF DRAWINGS

In the following detailed description of the present disclosure, reference will be made to the accompanying drawings, of which

Fig. 1 is a perspective illustration of one possible complete medicament delivery device that can incorporate one or more micro wires, where the cap of device is removed allowing attachment of a pen needle to the cartridge holder and showing an exploded view of the device;

Fig. 2 illustrates one possible example of applying a microwire to a rotating component part of the dose setting mechanism of the device of Fig. 1 ;

Fig. 3 illustrates another possible example of applying a microwire to the piston rod of the device of Fig. 1; Fig. 4 illustrates one possible embodiment of an electronics module;

Fig. 5 illustrates one possible embodiment of a reusable electronics module; and Fig. 6 and Fig. 7 illustrate the device of Fig. 1 having the electronics module of Fig. 5 releasably attached to the injection device of Fig. 1 where the display shows a zero dose setting and where the display shows that a dose of 30 IU has been set, respectively.

DETAILED DESCRIPTION

In the present application, the term "distal part/end" refers to the part/end of the device, or the parts/ends of the components or members thereof, which in accordance with the use of the device, is located the furthest away from a delivery/injection site of a patient. Correspondingly, the term "proximal part/end" refers to the part/end of the device, or the parts/ends of the members thereof, which in accordance with the use of the device is located closest to the delivery/injection site of the patient. One example of a medical device that can have one or more micro wires is a pen-type injector device 10, as shown in Fig. 1. The complete injection device 10 is illustrated as well as an exploded view of the device, which is presented in the zero dose state as indicated by indicia 40 showing a zero through the window 3 a of housing 3. The device 10 with cap 1 removed exposes the cartridge holder 2 and the proximal needle connector 7 that is configured for a pen needle 4 that is typically attached to the needle connector 7 through a snap fit, thread, Luer-Lok, or other secure attachment with hub 5 such that a double ended needle cannula 6 can achieve a fluid communication with medicament contained in cartridge 8 positioned within cartridge holder 2. The cartridge 8 is sealed at the proximal end by septum 8a and with a sliding piston 9 (or piston disc, bung, stopper) at the opposite distal end.

The pen-type injection device of Fig. 1 has a sleeve 35 that translates in a longitudinal direction during dose setting, dose correction and dose delivery. A dose is set with dose setting mechanism 30 through rotation of dose knob 31, which causes sleeve 35 to move linearly in the distal direction. A dose is delivered by pushing on the end of the dose knob in the opposite or proximal direction. This in turn causes sleeve 35 to move linearly back into the dose setting mechanism in the proximal direction.

The linear movement of the dose selector 35 is a result the outer surface that has one or more longitudinal grooves that are always engaged with longitudinal splines located on the inner surface of housing 3. This engagement prevents relative rotation between the dose selector and the housing, but allows the dose selector to move axially relative to the housing. The outer surface of the dose selector also has connecting cut-outs that permanently engage and lock with snap fits on the dose knob 31 such that the dose knob is axially fixed to the dose selector 35. These permanent snap fits allow the dose knob to rotate relative to the dose selector during both dose setting and dose cancellation.

The particular design of device 10 allows for setting of one or more of the

predetermined fixed doses through the interaction of snap element 33 with dose selector 35. Fig. 2 shows snap element 33 with microwire 52 fixed to an outer surface. As mentioned the microwire could also be imbedded into the snap element during the manufacture of the snap element, for example by co-molding. The rotation of the dose knob and snap element, along with the microwire, occurs during dose setting and is relative to housing 3. This rotational movement or the change in position due to the rotational movement could be sensed by an electronics module, like the one illustrated in Fig. 4, and is indicative of an amount of medicament set for injection. During the initiation of the dose delivery procedure the dose knob 31 is pressed in the proximal direction causing it and the dose selector to move axially relative to the snap element. This initial movement disengages a splined connection and causes engagement of a different spline connection which prevents the doe knob from rotating relative to the housing 3 during dose delivery. The initial movement of the dose selector proximally does not cause movement of the piston rod 42.

Part of the dose setting mechanism of most pen-type injectors, including device 10, is a piston rod 42 as illustrated in Fig. 1. In those device designs where the piston rod does not rotate during dose delivery, a microwire 51 may be applied to or incorporated within the outer surface of the piston rod as illustrated in Fig. 3. Such piston rods usually have a non-circular cross-section and have two flat surfaces that are designed to prevent the piston rod from rotating, but allowing it to move linearly in the proximal direction. A preferred method to measure the translation of the piston rod is to apply or otherwise add the microwire 51 along the length of the existing piston rod design.

Using existing piston rod designs, the microwire 51 can be applied to or made integral with the flat sides, for example by co-molding. As the piston rod moves proximally during dose delivery, the microwire changes position and this change could be sensed by the electronics module.

Returning to the specifics of the dose setting mechanism 30 of device 10, a nut 36 and a clutch 32 are permanently splined to each other during assembly of the dose setting mechanism through a splined connection. The splined connection ensures that clutch 32 and nut 36 are always rotationally fixed to each other during both dose setting and dose delivery. This splined connection also allows the clutch and the nut to move axially relative to each other. The sliding connection is necessary to compensate for the difference in the pitch of the thread between nut and the outer surface of the piston rod and the pitch of the thread between dose sleeve and body. The thread between driver and piston guide has basically the same pitch as the thread between piston rod and nut.

The proximal end of nut 36 has internal threads 70 that match threads 60 of piston rod 42. The distal end of clutch 32 is configured as a dose button 72 and is permanently attached to distal end of the dose knob 31 through engagement of connectors, which may also include snap locks, an adhesive and/or a sonic weld. This connection ensures that the clutch is both rotationally and axially fixed to the dose knob during both dose setting and dose delivery. In addition to threads 60 on the outer surface of the piston rod 42 and the above mentioned two longitudinal flats, the terminal proximal end has a connector 62, shown as a snap fit, that connects with a disc or foot 42a. The disc could also include a microwire so that contact and force could be sensed between the foot and the sliding piston 9 within the medicament container. At the distal end of piston rod 42 is a last dose feature of the dose setting mechanism, illustrated as an enlarged section 63. This enlarge section 63 is designed to stop the rotation of nut 36 about threads 60 when the amount of medicament remaining in the cartridge 8 is less than the next highest predetermined dose setting. In other words, if the user tries to set one of the

predetermined fixed dose settings that exceeds the amount of medicament remaining in the cartridge, then the enlarged section 63 will act as a hard stop preventing the nut from further rotation along threads 60 as the user attempts to reach the desired predetermined fixed dose setting. A microwire could also be used with the stop to detect when the stop is reached by sensing a stress in the microwire. Such a microwire could also detect an overturning situation where the stop is exceeded by the user applying too much force.

The piston rod 42 is held in a non-rotational state relative to housing 3 during both dose setting and dose delivery because it is arranged within the non-circular pass through hole in the center of piston guide 43 (see Fig. 3). The piston guide is both rotationally and axially fixed to housing 3. This fixation can be achieved when the piston guide is a separate component from the housing 3 as illustrated in the figures or the piston guide could be made integral with the housing. Piston guide 43 also engages the proximal end of a rotational biasing member, shown as torsion spring 90, the function of which will be explained below. This connection of the rotational biasing member to the piston guide anchors one end in a rotational fixed position relative to the housing.

The distal end of the rotational biasing member, for example torsion spring 90, is connected to the driver 41. Driver 41 is connected and rotationally fixed with the inner surface of dose sleeve 38 through a sp lined connection on the distal outer surface of the driver. On the proximal end of driver 41 on the outer surface is threads 67 that are engaged with matching threads on the inner distal surface of the piston guide 43. The thread between driver and piston guide has a significantly different pitch than the thread between dose sleeve and housing. The nut and the driver rotate together both during dose setting and dose cancellation and, as such, they perform essentially the same axial movement. However, this movement is independent from each other, i.e., the nut is turned by the clutch and performs an axial movement due to the thread to the piston rod, while the driver is rotated by the dose sleeve and performs an axial movement due to the thread to the piston guide. The driver is rotating during injection also, and so it actively moves in the proximal direction during injection. But, the nut does not rotate during injection and as such does not perform an active axial movement. The nut is only moving in proximal direction during injection because it is being pushed axially by the driver. The rotating driver pushing the non-rotating nut causes the injection because the piston rod is pushed forward due to the threaded engagement with the nut. If, for example, the thread of the nut had a higher pitch than the thread of the driver, the nut could not freely move in the distal direction during dose setting because it would be hindered by the slower moving driver. As such, this would cause drug to be expelled during dose setting. Alternatively, if the thread of the nut had a significantly lower pitch than the thread of the driver, the driver would move away from the nut during dose setting and the driver would not push the nut at the beginning of the injection already, but would do so only after the gap is closed. Accordingly, it is preferred that the pitch of the thread on the driver is equal or a slightly higher than the pitch of the thread on the nut. And, the thread between the dose sleeve and the housing has a higher pitch than that of the nut and piston rod. This is desirable because it yields a mechanical advantage that makes the dose delivery process easier for the user. For example, when pushing the knob a distance of 15 mm, the piston rod only moves by 4.1 mm. This results in a gearing ratio of about 3.6: 1. A lower gearing ratio would result increase the force the user needs to complete the injection. Because the torsion spring is attached to the driver 41 and the driver is rotationally fixed to the dose sleeve 38, then rotation of the dose sleeve in a first direction during dose setting will wind the torsion spring such that it exerts a counter rotational force on the dose sleeve in an opposite second direction. This counter rotational force biases the dose sleeve to rotate in a dose canceling direction.

The fluid volume dispensed by an injection pen is determined by the linear translation of a threaded piston rod that in turn pushes a slidable piston (bung or stopper) within the drug cartridge. In a number of pen-type injection devices, the user is able to manually adjust the desired dose setting by manipulation (e.g., turning a dose setting knob) of a mechanical component of the injection pen. In the case where the pen design has a dose setting knob, the knob (or a button associated with the knob) is then pushed to translate the piston rod axially in a distal direction within the pen to displace the drug from the cartridge. Measurement of the microwire 51 movement or a change in position as a result of the movement as the piston rod translates during dose delivery can be correlated to calculate the volume of fluid dispensed.

The electronics module either built into the pen, or as an attachable and reusable separate device, must be able to interrogate the microwires present in the device and determine the specific response from the microwires, whether it is position, motion, force or temperature. The electronic circuit (see Fig. 4) in the electronics module should include a means for wireless communication using a low power protocol such as Bluetooth. The electronics can take many forms. Although the one or more microwires are fixedly attached to select components of the injection device, the electronics module can be attached to the outside housing of the injection device, or even in some cases, can be located remotely from the injection device. One possible attachable electronics module 50 is illustrated in Fig. 5, which is preferably designed to be reusable. This electronics module could be releasably attached to the injection device outer surface of housing 3 through clips and could include a display 50e to present relevant information to the user, such as, for example, the time when the last injection took place, and the dose amount of that last injection. Fig. 11 and Fig. 12 illustrate the electronics module 50 releasably attached to an injection device where the display shows a zero-dose setting (Fig. 11) and where the display shows that a dose of 30 IU has been set (Fig. 12), respectively. Clearly, other pertinent information could be displayed by the electronics module, such as battery charge level, temperature, alarm status, medicament identification information, connectivity status, etc. The electronics module 50 device could also have one or more input features, such as buttons or touch screen features, for the user to press to activate the various features of the electronics module.

Alternatively, the electronics module may be incorporated into the cap of the device or a truncated cap. In such an embodiment the cap would detect the position of the piston rod before and after an injection. It could also determine temperature of the device and/or medicament in the device.

In addition to using linear motion to determine dose delivery, an alternative design may include a micro wire on or in nut 36 to measure rotation relative to the piston rod. As the nut 36 rotates relative to the piston rod, the nut climbs up the piston rod in the distal direction. Determining the movement of micro wire attached to the nut 36 can be used to determine the dose setting. Since the nut rotates only during dose setting, and not during the injection process, this rotary design does not directly measure the piston translation and therefore is not a direct measure of the expelled medicament. However, this design could be used in conjunction with one of the above designs to directly measure the actual dose of medicament delivered.

The function of the complete injection device 10 and the dose setting mechanism 30 according to this disclosure will now be described. Injection device 10 is provided to a user with or without the cartridge 8 of medicament positioned within the cartridge holder 2. If the injection device 10 is configured as a reusable device, then cartridge holder 2 is connected to housing 3 of the dose setting mechanism 30 in a releasable and reusable manner. This allows the user to replace the cartridge with a new full cartridge when all the medicament is expelled or injected from the cartridge. If the device is configured as a disposable injection device, then the cartridge of medicament is not replaceable because the connection between the cartridge holder 2 and the housing 3 is permanent. Only through breaking or deformation of this connection can the cartridge be removed from the injection device. Such a disposable device is designed to be thrown out once the medicament has been expelled from the cartridge. The user first removes the cap 1 from the device and installs an appropriate pen needle 4 to the cartridge holder 2 using connector 7. If the device is not pre-primed during the device assembly, or does not have an automatic or forced priming feature, then the user will need to manually prime the device as follows. The dose knob 31 is rotated such that a first dose stop is reached, which corresponds to a predetermined small fixed dose of medicament.

The injection device 10 of this disclosure can also have a so-called forced or automatic priming feature. Prior to using the dose setting mechanism, i.e., before a user could dial one of the predetermined fixed dose setting, a sliding lock would necessarily need to pushed in the proximal direction such that is moves distally relative to the dose knob. This axial movement forms an irreversible locking relationship between the dose knob and the distal end of the clutch. This locking relationship also causes the dose knob and clutch to be rotationally fixed to each other. Before the sliding lock is engaged with the clutch, the clutch can be rotated, which also causes rotation of the nut, to cause the piston rod 42 to move axially relative to the housing. The clutch is rotated until a visual observation and/or tactile notification indicates that the foot 42a located on the piston rod 42 is in firm abutment with distal facing surface of the sliding piston 9. This abutment between the foot and the sliding piston will ensure that an accurate dialed dose will be delivered out of the needle cannula. As mentioned, a microwire associate with either the foot or with the sliding piston can be used to ensure that the priming step is complete. The rotation of the clutch is preferably performed during the assembly of the injection device and likewise after ensuring abutment of the foot with the sliding piston 9, the manufacturing process would cause the sliding lock to be pushed to the final, locked position.

Returning to the priming procedure, once the priming stop is reached, the user may need to cancel the priming procedure and can do so by using the dose canceling procedure. This cancellation procedure also applies to any dose setting. Dose cancellation is accomplished by turning the dose knob in the opposite direction and will generate a notification that can be the same or different as the dose setting notification and/or dose delivery notification. Because the snap element 33 is rotationally fixed to the dose sleeve 38, and the dose sleeve is threaded engaged to the inner surface of housing 3, rotation of the dose knob during dose setting and dose cancellation causes relative rotation between the dose sleeve and the housing. The threaded connection between the housing and the dose sleeve causes the dose sleeve, snap element, clutch, and dose knob to translate axially as the dose knob is rotated. During dose cancellation, these components rotate and translate axially in the opposite or proximal direction.

Rotation of the dose knob also causes rotation of nut 36 about threads 60 on the outer surface of piston rod 42, which does not rotate and remains axially fixed relative to the housing 3 because of relative pitch differences in the threaded parts as explained above. The rotation of the nut relative to the stationary piston rod, which is supported by its contact with the sliding piston, causes the nut to translate or climb up the piston rod in the distal direction. A reverse rotation during dose cancellation causes the nut to translate in the reverse direction relative to piston rod. The distance traveled by the nut to achieve the desired dose setting is directly proportional to an amount of medicament that would be expelled if the dose delivery procedure were initiated and completed. Because the pitch of the threaded connection between the dose sleeve and the housing is greater than pitch of the threads on the nut, the dose sleeve, snap element, clutch and dose knob will travel a greater axial distance than the nut as it climbs up or down the piston rod. The difference in axial movement would normally bind the dose setting mechanism, but does not do so because the difference in pitch is compensated for by the sliding splined connection between the nut and the clutch, thus allowing the clutch to travel axially a greater distance longitudinally than the nut. During injection, the clutch pushes on the snap element and as such on the dose sleeve. This axial force causes the dose sleeve to turn due to the thread to the body. The dose sleeve will only start to turn when it is pushed, if the pitch of the thread is high enough. If the pitch is too low the pushing will not cause rotation because the low pitch thread becomes what is called a "self-locking thread".

Rotation of the dose knob also causes rotation of the driver because of the splined rotationally fixed connection to the dose sleeve. Since the torsion spring 90 is fixed at one end to the driver and at the other end to the piston guide, which in turn is fixed axially and rotationally to the housing, the torsion spring is wound up increasing in tension during dose setting. As mentioned, the torque of the tension spring exerts a counter rotational force on the dose sleeve. Preferably during assembly of the dose setting mechanism, the torsion spring is pre -tensioned so that even at the zero dose condition the torsion spring exerts a counter rotational force on the dose sleeve. The counter rotation force provides a first fail-safe feature of the dose setting mechanism. This first fail-safe mechanism prevents a user from setting a dose that is not one of the finite set of predetermined dose settings. In other words, if a user is rotating the dose knob such that it is between two dose stops, or between the zero dose hard stop and a first dose stop or a priming stop, and the user releases the dose knob, the counter rotational force of the torsion spring will return the protrusion to the last engaged dose stop or to the zero dose hard stop. Additionally, during a dose cancellation procedure the counter rotational force will assist the user in rotating the dose knob back down to the next lower fixed dose setting or possibly all the way back to the zero dose setting. Microwires could be incorporated with these various stops to determine contact or an overturning of and/or damage to the stop. During dose setting, the dose knob 31 translates out and away from the distal end of housing 3. As the dose sleeve 38 rotates and translates, the progress of the dose setting (or dose cancellation) is observed in window 3 a of housing 3 as the printed indicia 40 on the dose sleeve moves past the open window. When a desired predetermined dose setting is reached the indicia for that dose will appear in the window. At this point the injection device 10 is ready for a priming procedure or, if already primed, the delivery of the medicament to an injection site. In either the case, the user will push on the dose knob in the proximal direction until the zero dose hard stop is reached and a zero dose indicia is observed in the window. During a priming step the user will observe whether medicament is expelled out of the cannula 6 of pen needle 4. If no medicament is expelled this means the piston foot 42a is not in abutment with the distal surface of sliding piston 9. The priming step is then repeated until medicament is observed exiting the cannula. The dose setting mechanism of the present disclosure can also have a maximum dose hard stop feature that prevents a user from setting a dose greater than the highest predetermined dose setting.

Once the dose setting mechanism is primed, the user then selects and sets a desired fixed dose by repeating the same steps used for priming except that the dose knob will be rotated past the priming stop until the appropriate dose stop is and the desired dose value appears in the window 3a. In some cases, it is preferred to have no indicia show in the window when dialing between predetermined dose settings, while in other cases it is desirable to show an indicia in the window that is indicative of a non-settable dose position between the fixed dose settings.

Once one of the predetermined dose settings has been dialed on the dose setting mechanism, the user can then exert an axial force in the proximal direction to initiate the dose delivery procedure. The axial force exerted by the user overcomes the distally directed force exerted by the second biasing member 91 causing the dose knob 31 , clutch 32 and dose selector 35 to move axially in the proximal direction relative to the snap element 33 and housing 3. This initial movement rotationally fixes the clutch and dose knob to the housing through the splined connection between the floating spline 34 and splines inside dose selector 35. The splined connection between the dose selector and floating spline 34 remains engaged during dose setting and during dose delivery even though the dose selector 35 moves axially with the dose knob 31 and relative to the floating spline 34.

As the user maintains the axial force on both the dose knob 31 and the dose button 72 during the continuation of the dose delivery procedure, the clutch 32 will abut the distal end of the snap element causing it to move axially in the proximal direction. The clutch pushes on the snap element. The snap element is fixed to the dose sleeve, so the clutch pushes on the dose sleeve. As the dose sleeve has a thread with a sufficiently high pitch relative to the body, the axial force on the dose sleeve will cause the dose sleeve and as such the snap element to turn relative to the body, and by turning relative to the body it moves in the proximal direction. The dose selector slides into the housing but does not rotate relative to the housing 3 due to the splined engagement with the housing. The rotation of the dose sleeve 38 also causes rotation of the driver 41 into the threaded connection with piston guide 43, which drives the piston rod proximally and results in a concurrent de -tensioning of torsion spring 90. The driver does not directly drive the piston rod. As the driver rotates, the driver moves in the proximal direction and pushes the nut forwards. As the nut doesn’t turn, the driver pushes the nut and the piston rod forward. The nut 36 does not rotate during dose delivery because of the rotationally fixed relationship with clutch 32 that is rotationally fixed to the housing through rotationally fixed relationship of the dose knob, floating spline and the housing. The nut therefore can only move axially carrying the piston rod 42 with it because the piston rod is prevented from rotating by the non-circular opening 64 engaged with the flats 203 on the piston rod. The piston rod is moved axially the same distance that the nut originally translated relative to the piston rod during dose setting. This axial movement without rotation is caused by the rotational and axial movement of the proximal end of the driver in abutment with a flange 36a on nut 36. Axial movement of the piston rod causes the sliding piston 9 to also move axially relative to the inside walls of the stationary cartridge 8 forcing an amount of medicament out of the needle cannula 6 that is equivalent to the predetermined fixed dose that was set during the dose setting procedure.

If the user stops or halts the dose delivery procedure by removing the axial force on the dose knob a fail-safe mechanism is activated. Removal of the axial force causes the compression spring 91 to bias the dose knob in the distal direction. If the user halts the dose delivery between two predetermined fixed dose settings, then the dose knob and the axially fixed dose selector will both be prevented from moving proximally because of a projecting rib inside the dose selector that will stop the axially movement of dose selector and dose knob. Without this projecting rib, the dose selector would move distally such that the dose knob would re-engage with the snap element, thus placing the dose knob, clutch and nut back into rotational engagement with the snap element. The torque exerted on the snap element through the driver would then counter rotate the nut, thus reducing the set dose by an unknown amount. This counter rotation would continue until the next lowest predetermined fixed dose setting is reached, where the

corresponding dose stop would stop the counter rotation. Therefore, a resumption of the halted dose delivery procedure will continue without any unknown decrease in the set dose, thus allowing the originally set predetermined dose to be delivered. A halted dose delivery could be determined using a microwire described above because the electronics module would sense a rate change of movement or time lag during dose setting.

Likewise, a halted dose delivery could be determined and recorded by using a clock function of the electronics module that would sense no movement of the microwire over a period of time for the injection corresponding to the halted injection. The above-presented description and figures are intended by way of example only and are not intended to limit the present invention in any way except as set forth in the following claims. It is particularly noted that persons skilled in the art can readily combine the various technical aspects of the various elements of the various exemplary embodiments that have been described above in numerous other ways, all of which are considered to be within the scope of the invention.

While the invention herein disclosed has been described by means of specific embodiments and applications thereof, numerous modifications and variations can be made thereto by those skilled in the art.