CN112739395A

CN112739395A - Implantable drug delivery device with infusate measurement capability

Info

Publication number: CN112739395A
Application number: CN201980047955.3A
Authority: CN
Inventors: P·布尔克; S·奥图尔; J·科莱拉
Original assignee: Floonyx Medical Co
Current assignee: Floonyx Medical Co; Flowonix Medical Inc
Priority date: 2018-07-19
Filing date: 2019-07-16
Publication date: 2021-04-30
Also published as: WO2020018533A1; EP3823694A1; JP2021531109A

Abstract

An implantable drug delivery device and method includes a bellows sensor for detecting displacement of a bellows within an infusion reservoir. Sensor data from the bellows sensor may enable indirect measurement of the flow condition of the implantable drug delivery device or a connected catheter. A processor within the implantable drug delivery device may use the sensor data to determine whether the infusate delivered to the patient over time exceeds normal or acceptable parameters and take action in response.

Description

Implantable drug delivery device with infusate measurement capability

RELATED APPLICATIONS

The present application is a continuation-in-part application, serial No. 15/098,663, entitled "Implantable Drug Delivery Device with Flow measurement Capabilities" filed on 14/4/2016, which claims priority benefits of U.S. provisional application No. 62/148,457, entitled "Implantable Drug Delivery Device with Flow measurement Capabilities" filed on 16/4/2015, the entire contents of all applications being incorporated herein by reference.

Technical Field

The present invention generally relates to implantable infusion devices for delivering drugs or other fluids to a patient.

Background

There are various implantable devices for delivering infusions, such as drugs, to a patient. One such device is an implantable valve accumulator pump system. This system includes an electronically controlled metering assembly located between a drug reservoir and an outlet conduit. The metering assembly may comprise two normally closed solenoid valves positioned on the inlet side and the outlet side of the fixed-volume accumulator. The inlet valve opens to allow a fixed volume of infusate from the reservoir into the accumulator. The inlet valve is then closed and the outlet valve is opened to dispense a fixed volume of infusate from the reservoir to the outlet conduit through which the infusate is delivered to the patient. The valves may be electronically controlled by an electronic module, which may optionally be programmed with an external programmer to provide programmable drug delivery rates. Since the devices are typically implanted in the patient and are not readily accessible when operated, it may be difficult to detect when a fault condition or other deviation from normal operating conditions exists with the devices.

Disclosure of Invention

The systems, methods, and devices of the various embodiments provide an indirect measurement of the flow rate of an implantable drug delivery device by monitoring the volume of a bellows that provides a reservoir for an infusate. Various embodiments may enable monitoring of flow rate conditions of an implantable drug delivery device by measuring changes in shape or displacement of a bellows over time. Various embodiments include implantable drug delivery devices having a bellows sensor configured to measure changes in the shape or displacement of a bellows over time. The bellows sensor may be an electrical based sensor (such as a strain gauge or a capacitive displacement sensor), a light based sensor, a pressure sensor, or an acoustic wave based sensor.

Drawings

The accompanying drawings, which are incorporated herein and constitute part of this specification, illustrate exemplary embodiments of the invention and, together with the general description given above and the detailed description given below, serve to explain the features of the invention.

Fig. 1 is a schematic view of an implantable drug delivery system.

Fig. 2A-2D schematically show a fixed volume reservoir of a dosing assembly and a sequence of steps performed by the dosing assembly of an implantable drug delivery system.

Fig. 3 is a schematic view of an embodiment implantable drug delivery device including a strain gauge sensing device configured to measure changes in position or deflection of a diaphragm of the accumulator.

Fig. 4 is a schematic view of an embodiment implantable drug delivery device including a capacitive displacement sensor configured to measure a change in position or deflection of a diaphragm of an accumulator.

Fig. 5 is a schematic diagram of an embodiment implantable drug delivery device including a light-based sensor configured to measure a change in position or deflection of a diaphragm of the reservoir.

Fig. 6 is a schematic view of an embodiment implantable drug delivery device including a pressure sensor configured to measure a change in position or deflection of a diaphragm of the reservoir.

Fig. 7a is a schematic view of an embodiment implantable drug delivery device incorporating an acoustic wave based sensor configured to measure changes in position or deflection of a diaphragm of a reservoir.

Fig. 8 is a process flow diagram illustrating a method of operating an implantable drug delivery device according to an embodiment.

Fig. 9-15 are schematic diagrams of various embodiments of implantable drug delivery devices including different bellows sensors and/or detectors configured to measure one or more parameters associated with the volume of infusate and/or displacement of the bellows.

Fig. 16 is a process flow diagram illustrating an embodiment method for determining whether an infusion volume within a bellows of an implantable drug delivery device varies, in accordance with some embodiments.

FIG. 17 is a process flow diagram illustrating an embodiment method for an example abnormal infused volume rate program.

Fig. 18 is a process flow diagram illustrating an embodiment method for determining initial parameters associated with a bellows of an implantable drug delivery device.

Fig. 19 is a process flow diagram illustrating an embodiment method for taking action based on a change in a flow related parameter associated with an infusion within a bellows of an implantable drug delivery device.

Fig. 20 is a schematic view of another implantable drug delivery system according to an embodiment.

Detailed Description

Various embodiments will be described in detail with reference to the accompanying drawings. Wherever appropriate, the same reference numbers will be used throughout the drawings to refer to the same or like parts. References to specific examples and embodiments are for illustrative purposes and are not intended to limit the scope of the invention or the claims.

The words "exemplary" and/or "such as" are used herein to mean "serving as an example, instance, or illustration. Any embodiment described herein as "exemplary" or "e.g.," is not necessarily to be construed as preferred or advantageous over other embodiments.

The systems, methods, and devices of the various embodiments enable monitoring of the dosage of infusate to a patient by monitoring the displacement of a bellows that provides a reservoir for the infusate. An embodiment drug delivery system may include a bellows sensor configured to measure a change in displacement or shape of a bellows. The bellows sensor may be, for example, an electrical based sensor (such as a strain gauge or a capacitive displacement sensor), a light based sensor, a pressure sensor, or an acoustic wave based sensor. The bellows sensor may be used to provide an indirect measurement of the flow rate of the implantable drug delivery device by monitoring the change in volume of the bellows over time. Various embodiments may enable determining whether the flow rate of the implantable drug delivery device is within normal operating conditions by measuring the change in shape or displacement of the bellows over time.

Fig. 1 illustrates an embodiment of an implantable valve accumulator pump system 100 for delivering infusate (e.g., medication). The system 100 may typically include four assemblies. The first main assembly is a rechargeable, constant pressure drug reservoir 10 in series with a bacteria/air filter 24. In one embodiment, the reservoir 10 comprises a sealed housing 14 containing a bellows 16. The bellows 16 divides the housing 14 into two portions, a chamber 18 and a second region 20. The chamber 18 is for containing a medicament or other medicinal fluid. The second region 20 is typically filled with a two-phase fluid, e.g.

The two-phase fluid has a significant vapor pressure at body temperature. Thus, as the fluid within the second region 20 evaporates, the vapor compresses the bellows 16, thereby pressurizing the drug in the chamber 18. The chamber 18 may be refilled with infusate by refilling the septum 12.

The two-phase fluid helps maintain the chamber 18 at a constant pressure. When the chamber 18 is refilled, the two-phase fluid is pressurized, thereby condensing a portion of the vapor within the second region 20 to the liquid phase. When the chamber 18 is emptied, this liquid evaporates, maintaining the pressure on the bellows 16. Since the infusate in the chamber 18 is under positive pressure, the infusate is pushed out of the chamber through the bacterial filter 24 and towards the metering assembly.

The second main assembly is an electronically controlled metering assembly which may include two normally closed

solenoid valves

26, 28 positioned on the inlet and outlet sides of a fixed-volume accumulator 30. The valves are electronically controlled by an electronics module 32, which may be programmed by an external programmer 34. The metering assembly may be designed such that the inlet valve 26 and the outlet valve 28 are never opened simultaneously.

The third main assembly is an outlet conduit 36 for drug infusion in a localized area. The delivery of the fluid occurs at an infusion site that has a pressure less than the accumulator pressure. This pressure differential forces the infusate out through the catheter 36.

The drug reservoir 10 and the electronically controlled metering assembly may be contained within a biocompatible housing, also containing a power source (e.g. a battery) that may be implanted in the body of a human or animal patient. The outlet conduit 36 may be integral with the housing or may be a separate component attached to the housing. An access port 31 in communication with conduit 36 may be provided downstream of the metering assembly. The access port 31 may be used, for example, to manually provide bolus doses of a drug to a patient.

A fourth component of the system shown in fig. 1 is an external programmer 34 for communicating and programming a desired medication regimen. In one embodiment, external programmer 34 may be a handheld unit with a touch screen. External programmer 34 may provide a wireless data transmission link to a wireless communication transceiver within implanted electronic module 32 and may be enabled to exchange information with electronic module 32, including but not limited to battery status, diagnostic information, calibration information, and the like. In various embodiments described in further detail below, the electronics module 32 may communicate information regarding the flow rate of the infusate from the implantable system 100 to the external programmer 34. In one embodiment, external programmer 34 may send instructions to electronic module 32 to detect the flow rate of infusate from the implantable system, according to embodiments described below. In one embodiment, electronics module 32 may contain a coil configured to send and receive electromagnetic signals to/from external programmer 34.

Fig. 2A-2D schematically illustrate the structure and operation of a fixed-volume accumulator 30 of an electronically controlled metering assembly according to one embodiment. The accumulator 30 may include a housing 50 that defines a sealed gas chamber 52 with a cover 51. The cover 51 may be secured to the housing 50 using any suitable means, such as laser welding. A suitable gas may be sealed within the gas chamber 52 under positive pressure. The sealed gas chamber 52 may contain an inert gas such as argon, helium or nitrogen, air or a mixture of different gases. Alternatively, the sealed gas chamber 52 may contain a two-phase fluid. The bottom surface of the housing 50 may define a first (e.g., upper) surface 53 of the diaphragm chamber 57. One or more fluid passages 55 within the housing 50 may connect the gas chamber 52 with the diaphragm chamber 57.

A panel 56 (which may also be referred to as a spacer) may be fixed to the bottom surface of the case 50. The upper surface of the faceplate 56 may define a second (e.g., lower) surface 60 of the diaphragm chamber 57. The diaphragm 40 may be located between the housing 50 and the face plate 56 and within a diaphragm chamber 57 defined therebetween. In an embodiment, the edge of the diaphragm 40 may be sandwiched between the housing 50 and the face plate 56, and the assembly may be sealed, such as by laser welding. The membrane 40 may provide a barrier that separates the gas side (e.g., above the membrane 40) from the fluid side (e.g., below the membrane 40) in the accumulator 30. The face plate 56 may include a fluid inlet port 58 providing fluid communication between the inlet valve 26 and the diaphragm chamber 57 and a fluid outlet port 59 providing fluid communication between the outlet valve 28 and the diaphragm chamber 28.

In an embodiment, the diaphragm 40 may comprise a thin disk-shaped sheet. The diaphragm 40 may comprise a metal, such as titanium. The diameter and thickness of the diaphragm 40 may be selected to provide a low spring rate over a desired range of deflection. The membrane 40 may act as a compliant, flexible wall separating fluid (e.g., liquid infusate) from its environment behind. In the embodiment illustrated in fig. 2A-2B, deflection of the diaphragm 40 (illustrated as upward and downward movement) is limited by the first surface 53 and the second surface 60 of the diaphragm chamber 57, which act as mechanical stops for the diaphragm 40. In the embodiment illustrated in fig. 2A-2B, each of these

surfaces

53, 60 is formed with a dimple profile that acts as a contour stop for the diaphragm 40. The dimensions of the profile may be selected to match the overall profile of the diaphragm 40 when the dimensions are deflected or offset by a predetermined fixed volume. This predetermined fixed volume corresponds to the volume metered by the accumulator 30. In other embodiments, one of the

surfaces

53, 60 may have a generally flat profile that corresponds to the profile of the diaphragm in a flat, undeflected state, while the other surface may correspond to the profile of the diaphragm in a deflected state.

In some embodiments, the second (e.g., lower) surface 60 of the diaphragm chamber 57 may include one or more channels formed in the surface 60 to maximize the flush of fluid and minimize the dead volume within the chamber 57. For example, the surface 60 may be formed with an annular groove that intersects a groove connecting the inlet port 58 and the outlet port 59, as described in U.S. patent No. 8,273,058 to Burke et al, which is incorporated herein by reference for details of the diaphragm housing.

Fig. 2A illustrates accumulator 30 in a state where both inlet valve 26 and outlet valve 28 are closed and diaphragm 40 is deflected downward (in the orientation presented in fig. 2A) due to the bias caused by the gas pressure in gas chamber 52 and the gas side of diaphragm chamber 57. During this portion of the pumping cycle, there is no liquid infusate in the diaphragm chamber 57.

Fig. 2B shows accumulator 30 after inlet valve 26 is opened and outlet valve 28 remains closed. The pressure of the liquid infusate from the reservoir 10 (see fig. 1) is sufficient to overcome the bias of the pressurized gas against the backside of the diaphragm 40, thereby separating the diaphragm 40 from the second (lower) surface 60 of the diaphragm chamber 57. Infusate begins to flow into the diaphragm chamber 57 through the inlet port 58 as indicated by the arrows in fig. 2B. As the infusate fills diaphragm chamber 57, the bias caused by the fluid pressure in chamber 57 deflects diaphragm 40 upward (in the orientation presented in fig. 2B) toward first (upper) surface 53 of diaphragm chamber 57.

Fig. 2C shows the reservoir 30 filled with infusate to its fixed or desired volume. The diaphragm 40 is biased against a first (upper) surface 53 of the diaphragm chamber 57, which acts as a mechanical stop for the diaphragm 40. When the accumulator 30 is filled with infusate, the inlet valve 26 is closed, as shown in fig. 2C.

Fig. 2D shows the accumulator 30 after the outlet valve 28 is opened and the inlet valve 26 remains closed. Infusate begins to flow out of diaphragm chamber 57 through outlet port 59 and catheter 30 (see fig. 1), as indicated by the arrows in fig. 2D. As the infusate empties the accumulator, the diaphragm 40 separates from the first (upper) surface 53 of the diaphragm chamber 57. The bias caused by the gas pressure in the gas chamber 52 and in the gas side of the diaphragm chamber 57 deflects the diaphragm 40 downward (in the orientation presented in fig. 2D) toward the second (lower) surface 60 of the diaphragm chamber 57. When the chamber 57 is completely emptied of infusate, the diaphragm 40 is biased against a second (lower) surface 60 of the diaphragm chamber 57, which acts as a mechanical stop for the diaphragm 40. The outlet valve 28 is then closed and the accumulator 30 is again in the condition shown in fig. 2A. The pumping cycle illustrated in fig. 2A-2D may then be repeated. Accordingly, the accumulator 30 stores and expels predetermined volume spikes of infusate at a frequency defined by the cycling rate of the inlet valve 26 and the outlet valve 28 of the accumulator 30. The nominal flow rate of infusate from the system 100 may be controlled by controlling the circulation rate of the inlet valve 26 and the outlet valve 28 of the accumulator 30.

In operation, the programmed flow rate of infusate from the system may not be representative of the actual rate of infusate delivered to the patient for a number of reasons. For example, there may be an occlusion or blockage of infusate flow in a conduit or elsewhere in the device, a valve failure, a leak in the device, or another fault condition. Any one or combination of these conditions may result in a situation where more or less than the desired amount of infusate is delivered to the patient over a given period of time. This may result in reduced efficacy of the treatment regimen and may potentially be dangerous to the patient. Further, the amount of infusate delivered to a patient from a catheter (e.g., using a conventional fluid flow meter) typically cannot be measured directly, as infusate is typically delivered to narrow and sensitive areas within the patient where the use of a conventional flow meter is impractical.

Various embodiments include methods and systems for indirectly measuring a flow rate of an implantable drug delivery device by measuring movement of a membrane in a fixed volume reservoir. Embodiments include various systems and methods for measuring changes in position or deflection of a diaphragm over time to determine a flow rate of infusate from a reservoir. For example, referring to the fixed volume reservoir 30 illustrated in fig. 2A-2D, the amount of time it takes for the diaphragm 40 to move from the position shown in fig. 2C (i.e., the diaphragm is biased against the first (upper) surface 53 of the diaphragm chamber 57) to the position shown in fig. 2A (e.g., the diaphragm is biased against the second (lower) surface 60 of the diaphragm chamber 57) is directly related to the flow rate of a known volume of infusate dispensed from the reservoir during a pumping cycle. This time may vary based on the amount of flow restriction in the conduit or elsewhere in the system. In some cases, such as when there is a blockage or leak in the flow path of the device, the diaphragm chamber 57 may not completely fill or drain during each pumping cycle (e.g., such that the diaphragm does not deflect completely to the position shown in fig. 2A and/or 2C during the pumping cycle). This can be detected by measuring the change in position or deflection of the diaphragm over time.

Various embodiments may include an implantable drug delivery device including a diaphragm sensor for detecting changes in position or deflection of a diaphragm of a fixed volume reservoir. An electronics module coupled to the diaphragm sensor may monitor changes in the detected position or deflection of the diaphragm over time to determine whether the flow rate of the device meets at least one predetermined criterion. The electronics module may be configured such that, in response to determining that the flow rate does not meet the predetermined criteria, the electronics module may take appropriate action, such as sending a wireless signal to a user of the device and/or medical personnel providing notification, adjusting the circulation rate of the fixed-volume reservoir to bring the flow rate within the predetermined criteria, and/or turning off the device to prevent further infusion of the drug.

The diaphragm sensor may be any suitable diaphragm sensor configured to detect a change in position or bias of the diaphragm 40. Fig. 3 illustrates a first embodiment of an implantable drug delivery device 300 that includes an electrical-based diaphragm sensor 302 configured to measure a change in position or deflection of the diaphragm 40 of the accumulator 30 over time. In this embodiment, the electrical based diaphragm sensor 302 may comprise at least one strain gauge 301. At least one strain gauge 301 may be located on a surface 303 of the septum 40 that is exposed to gas from the sealed gas chamber 52 and opposite the surface of the septum 40 that is exposed to infusate (surface 303 may alternatively be referred to as the "back side" of the septum 40). Alternatively or additionally, one or more strain gauges may be located on the "front side" of the septum (i.e., the surface exposed to infusate in the septum chamber 57).

The at least one strain gauge 301 may comprise any suitable type of diaphragm sensor device for converting mechanical strain into a proportional electrical signal. For example, the at least one strain gauge 301 may comprise a bonded foil strain gauge, a bonded semiconductor strain gauge (e.g., a piezoresistor), a thin film strain gauge (e.g., a strain gauge formed by vapor depositing or sputtering insulator and strain gauge materials onto the surface of the diaphragm), and/or a diffused or implanted semiconductor strain gauge. At least one strain gauge may be calibrated to measure strain corresponding to displacement (i.e., deflection) of diaphragm 40 between flat rest state positions to a maximum upward and/or downward deflection position of diaphragm 40 within accumulator 30 (i.e., the position of the diaphragm shown in fig. 2A and 2C).

In the device 300 illustrated in fig. 3, the electronic module 32 may include a controller 92. In one embodiment, the controller 92 may include a processor 43 coupled to a memory 44. The processor 43 may be any type of programmable processor, such as a microprocessor or microcontroller, which may be configured with processor-executable instructions to perform the operations of the embodiments described herein. Processor-executable software instructions may be stored in memory 44, from which they may be accessed and loaded into processor 43. The processor 43 may contain internal memory sufficient to store the application software. The memory 44 may be volatile, non-volatile memory, such as flash memory, or a combination of both.

In one embodiment, the controller 92 may be coupled to the strain gauge monitoring circuitry 45 of the diaphragm sensor 302. The strain gauge monitoring circuitry 45 may measure a change in an electrical characteristic (e.g., resistance) of at least one strain gauge 301 corresponding to the strain experienced by the strain gauge 301. The strain gauge monitoring circuit 45 may comprise, for example, a four-specification Wheatstone bridge circuit (Wheatstone bridge circuit). The electronics module 32 may also contain a clock generator that generates timing signals so that each of the measured strain values may be associated with a particular measurement time. Controller 92 may compare the measured strain from monitoring circuitry 45 to predetermined strain values corresponding to different deflection positions of diaphragm 40 within accumulator 30. The predetermined strain values may be stored in the memory 44, for example, in the form of a look-up table. The controller 92 may use the measured strain values from the monitoring circuitry 45 and known predetermined values corresponding to different deflection positions of the diaphragm 40 to determine the change in position or deflection of the diaphragm 40 over time (i.e., the amount of upward and/or downward deflection of the diaphragm 40, as oriented in the figures). As discussed above, the change in position or deflection of the diaphragm over time may be directly related to the rate at which infusate is pumped from the reservoir. The controller 92 may be configured to determine whether the detected change in position or deflection of the septum over time is within normal operating parameters (i.e., the detected change in position or deflection of the septum over time corresponds to a clinically acceptable flow rate of the infusate). In some embodiments, the controller 92 may not convert the measured strain values to deflection values, but instead may be configured to determine whether a change in the measured strain values detected over a period of time is within normal operating parameters (i.e., a change in the detected measured strain values over time corresponds to a clinically acceptable flow rate of the infusate).

The controller 92 may be configured to provide a notification to the user, such as by sending a message to the external device 34, upon determining that the detected diaphragm motion is outside of normal operating parameters (i.e., not within such parameters). The external device 34 may be a programmer as described above, or alternatively, another external device may be configured to communicate with the implantable device 300 over a wireless data transmission link.

In various embodiments, the external device 34 may include a processor 47 coupled to a memory 46 and an indicator 48. The software instructions may be stored in the memory 46 before they are accessed and loaded into the processor 47. The processor 47 may be configured to activate the indicator 48 to provide a notification (e.g., an alarm) to the user when the external device 34 receives a message from the controller 92 of the implantable device 300 indicating that the detected septum movement and/or the flow rate of the infusate is not within the predetermined parameter range. The indicator 48 may be, for example, a display, a speaker for audio or sound messages, and/or a vibrator for generating tactile feedback. The processor 47 of the external device 34 may also be configured to notify remotely located medical personnel, such as over a wireless communication network, in response to receiving a message from the controller 92 of the implantable device 300.

In some embodiments, the controller 92 of the implantable device 300 may be configured to detect movement of the septum on a predetermined and/or periodic basis (e.g., hourly, every 12 hours, etc.). The predetermined time and/or frequency at which the controller 92 detects movement of the diaphragm may vary based on instructions received from the external device 34. Alternatively or additionally, the controller 92 of the implantable device 300 may detect movement of the septum "on demand" in response to a request or command from the external device 34. In some embodiments, the controller 92 of the implantable device 300 may be configured to continuously or frequently detect movement of the diaphragm 40 for the duration of the treatment regimen.

In some embodiments, the controller 92 of the implantable device 300 may forward the plurality of raw measurements from the strain gauge monitoring circuit 45 to the external device 34. The processor 47 of the external device 34 may use the raw measurements to determine changes in septum position or deflection over time and/or the flow rate of infusate from the device 300. The processor 47 of the external device 34 may compare the one or more calculated values to one or more stored thresholds to determine whether the flow rate is within clinically acceptable parameters. In other embodiments, the controller 92 of the implantable device 300 may determine an infusate flow rate value based on the detected change in diaphragm position or deflection over time, and may forward the determined infusate flow rate to the external device 34. The external device 34 may display the flow rate value on the indicator 48.

Fig. 4 illustrates a second embodiment of an implantable drug delivery device 400 that includes an electrical-based diaphragm sensor 402 configured to measure the change in position or deflection of the diaphragm 40 of the accumulator 30 over time. In this embodiment, the electrical based diaphragm sensor 402 may comprise at least one capacitive displacement sensor 401. The capacitive displacement sensor is a non-contact device configured to measure the capacitance between the probe 401 (e.g., the electrode surface) and a target conductive surface (e.g., the surface 303 of the diaphragm 40). The area of the probe 401 and the target surface 303 and the dielectric constant of the material (e.g., gas) between the probe 401 and the target surface 303 may be considered constant, in which case the capacitance between the probe 401 and the target surface 303 is proportionally related to the distance between the probe 401 and the target surface 303. Because of this proportional relationship, as the target surface 303 moves relative to the probe 402, the diaphragm sensor 402 can measure changes in capacitance, and the processor can use the measured changes to calculate a distance measurement, such as a relative change in separation distance.

In the embodiment illustrated in FIG. 4, the probe 401 is located near the first (upper) surface 53 of the diaphragm chamber 57 and is configured to measure the displacement of the diaphragm 40 from the first (upper) surface 53 of the chamber 57. Alternatively or additionally, the at least one probe 401 may be located near the second (lower) surface 60 of the diaphragm chamber 57 and may be configured to measure displacement of the diaphragm 40 from the second (lower) surface 60. In other embodiments, the probe 401 may be located on the diaphragm 40 and configured to measure the distance between the diaphragm 40 and the at least one

surface

53, 60 of the diaphragm chamber 57 as the diaphragm moves (i.e., deflects).

The implantable drug delivery device 400 of the embodiment illustrated in fig. 4 may be similar to the device 300 described above with reference to fig. 3, and may include an electronics module 32 having a controller 92 including a processor 43 and a memory 44 as described above. The controller 92 may be coupled to a capacitance monitoring circuit 450 connected to the probe 401 and configured to measure the capacitance between the probe 401 and the surface 303 of the diaphragm 40 as the diaphragm 40 moves within the chamber 57. The controller 92 may be configured to determine a change in position or deflection of the diaphragm 40 over time based on the measured change in capacitance. As discussed above, the change in position or deflection of the diaphragm over time may be directly related to the rate at which infusate is pumped from the reservoir. The controller 92 may be configured to determine whether the detected change in position or deflection of the septum over a period of time is within normal operating parameters (i.e., the detected change in position or deflection of the septum over time corresponds to a clinically acceptable flow rate of infusate). In some embodiments, the controller 92 may not convert the capacitance measurements to distance values, but instead may be configured to determine whether the detected change in capacitance over a period of time is within normal operating parameters (i.e., the detected change in capacitance over time corresponds to a clinically acceptable flow rate of the infusate).

When it is determined that the detected diaphragm motion (or change in capacitance) is not within the normal operating parameters, the controller 92 may be configured to provide a notification to the user, such as by sending a message to the external device 34. The operation of the apparatus 400 of the embodiment shown in fig. 4 may be substantially similar to the apparatus 300 as described above.

In addition to mechanical strain gauges and/or capacitive displacement diaphragm sensors as described above, other electrical-based diaphragm sensors may be used to detect changes in the position or deflection of the diaphragm 40 over time. For example, an electrical based diaphragm sensor according to various embodiments may include an eddy current diaphragm sensor and/or an inductive displacement diaphragm sensor.

Fig. 5 illustrates a third embodiment of an implantable drug delivery device 500 that includes a light-based diaphragm sensor 502 configured to measure the change in position or deflection of the diaphragm 40 of the accumulator 30 over time. Various devices for measuring distance using optical signals are known. The light-based distance measurement device may include a light source 501 (e.g., a laser, an LED, etc.) that transmits a beam of radiation 507 (e.g., visible, UV, and/or IR radiation) that reflects off of a target. The reflected beam 509 is received by an optical diaphragm sensor 503 (e.g., a photodiode sensor, a charge-coupled device (CCD) sensor, a CMOS based photosensor, etc.). The distance to the reflective target may be determined using one or more known techniques (e.g., triangulation, time-of-flight, phase shift, interferometry, chromatic confocal methods, etc.). In the embodiment illustrated in fig. 5, as the diaphragm 40 deflects within the accumulator 30, the light beam reflects off the surface 303 of the diaphragm 40 and the light-based diaphragm sensor 502 detects changes in the position or deflection of the diaphragm 40 over time.

In the embodiment illustrated in fig. 5, the light source 501 may be located outside the housing 50 of the accumulator 30 and direct the beam 507 through a transparent window 508 disposed in the cap 51 of the housing 50. The beam 507 may be directed through the sealed gas chamber 52 and channel 55 into the diaphragm chamber 57 where the beam 507 reflects off the surface 303 of the diaphragm 40. The membrane 40 may have a mirror surface 303 to enhance the reflection of the beam. The reflected beam 509 may travel through the passage 55, the gas chamber 52, and the window 508, and be detected by the optical sensor 503 located outside the housing 50 of the accumulator 30. Various other configurations of light-based diaphragm sensors for measuring diaphragm displacement in fixed volume accumulators may be used. For example, light source 501 and/or light sensor 503 may be located within housing 50 (e.g., within sealed gas chamber 52), or may be located within diaphragm chamber 57 (e.g., within surface 53 or 60).

The embodiment implantable drug delivery device 500 shown in fig. 5 may be similar to the

devices

300 and 400 described above and may contain an electronic module 32 having a controller 92 including a processor 43 and a memory 44 as described above. The electronics module 32 may also contain a light sensor control circuit 550 coupled to the light source 501 and the light sensor 503 to control the operation of the source 501 and the light sensor 503 and to generate an electronic signal representative of the reflected optical radiation received at the light sensor 503. The controller 92 may be coupled to the light sensor control circuitry 550 and may determine changes in the position or deflection of the diaphragm 40 over time based on the electronic signal representative of the reflected optical radiation received at the light sensor 503. The controller 92 may use any of the methods described above, including but not limited to triangulation, time-of-flight, phase shift, interferometry, and chromatic confocal techniques, to determine the change in position or deflection of the diaphragm 40 over time. As discussed above, the change in position or deflection of the diaphragm over time may be directly related to the rate at which infusate is pumped from the reservoir. The controller 92 may be configured to determine whether the detected change in position or deflection of the septum over time is within normal operating parameters (i.e., the detected change in position or deflection of the septum over time corresponds to a clinically acceptable flow rate of the infusate). In some embodiments, the controller 92 may not convert the measurements from the light sensor to distance values, but instead may be configured to determine whether the detected change in the measured light characteristic (e.g., time of flight, phase shift, interference, etc.) over a period of time is within normal operating parameters (i.e., the detected change in the measured light characteristic over time corresponds to a clinically acceptable flow rate of the infusate).

When it is determined that the detected diaphragm movement is not within the normal operating parameter range, the controller 92 may be configured to provide a notification to the user, for example, by sending a message to the external device 34. The operation of the apparatus 500 may be substantially similar to the operation of the

apparatuses

300 and 400 as described above.

Fig. 6 illustrates a fourth embodiment of an implantable drug delivery device 600 that includes a pressure sensor 602 configured to measure changes in pressure that correlate to changes in the position or deflection of the diaphragm 40 of the reservoir 30 over time. Pressure sensor 602 may contain a pressure transducer 601 that may be located within or in fluid communication with sealed gas chamber 52 of accumulator 30. Pressure transducer 602 may be calibrated to detect small changes in fluid pressure within chamber 52 as diaphragm 40 deflects within diaphragm chamber 57 and may output an electronic signal indicative of the detected pressure.

The embodiment implantable drug delivery device 600 shown in fig. 6 may be similar to the

devices

300, 400, and 500 described above, and may contain an electronic module 32 having a controller 92 that includes a processor 43 and a memory 44 as described above. Controller 92 may be coupled to pressure sensor 602 and may be configured to compare the pressure measured by pressure sensor 602 to predetermined pressure values corresponding to different deflection positions of diaphragm 40 within accumulator 30. The predetermined pressure value may be stored in the memory 44, for example, in the form of a look-up table. The controller 92 may use the measured pressure values and known predetermined pressure values corresponding to different deflection positions of the diaphragm 40 to determine the change in position or deflection of the diaphragm 40 over time (i.e., the amount of upward and/or downward deflection of the diaphragm 40). As discussed above, the change in position or deflection of the diaphragm over time may be directly related to the rate at which infusate is pumped from the reservoir. The controller 92 may be configured to determine whether the detected change in position or deflection of the septum over time is within normal operating parameters (i.e., the detected change in position or deflection of the septum over time corresponds to a clinically acceptable flow rate of the infusate). In some embodiments, the controller 92 may not convert the pressure measurements to distance or deflection values, but instead may be configured to determine whether the detected change in pressure over a period of time is within normal operating parameters (i.e., the detected change in pressure over time corresponds to a clinically acceptable flow rate of the infusate).

When it is determined that the detected diaphragm movement is not within the normal operating parameter range, the controller 92 may be configured to provide a notification to the user, for example, by sending a message to the external device 34. The operation of the apparatus 600 may be substantially similar to the operation of the

apparatuses

300, 400, and 500 as described above.

Fig. 7 illustrates a fifth embodiment of an implantable drug delivery device 700 that includes a sonic-based diaphragm sensor 702 configured to measure the change in position or deflection of the diaphragm 40 of the accumulator 30 over time. The displacement of the diaphragm 40 may be measured using acoustic signals using various techniques. For example, the source of sonic energy 701 (e.g., a sonic transducer) may generate an acoustic signal (e.g., in the audible, ultrasonic, or infrasonic range) within the sealed gas chamber 52 as shown in fig. 7 or alternatively within the diaphragm chamber 57 (above or below the diaphragm 40). As the diaphragm deflects within the diaphragm chamber 57, the fluid volumes above and below the diaphragm both change. This change in volume may change one or more characteristics of the acoustic signal, such as the harmonic frequencies of the signal, in a manner that may be detected by the acoustic wave sensing device 703. The source of acoustic energy 701 and the acoustic wave sensing device 703 are shown as separate devices in fig. 7, even though it should be understood that a single component (e.g., a transducer) may be used to transmit the acoustic wave energy pulse and receive the reflected pulse (e.g., echo).

The embodiment implantable drug delivery device 700 shown in fig. 7 may be similar to the

devices

300, 400, 500, and 600 described above, and may include an electronics module 32 having a controller 92 including a processor 43 and a memory 44 as described above. The electronics module 32 may also contain an acoustic wave sensor control circuit 750 coupled to the acoustic wave source 701 and the sensing device 703 to control the operation of the source 701 and the sensing device 703 and to generate an electronic signal representative of the acoustic wave signal received at the sensing device 703. Controller 92 may be coupled to acoustic wave sensor control circuitry 750 and may determine changes in the position or deflection of diaphragm 40 over time based on an electronic signal representative of the acoustic wave signal received at sensing device 703. As discussed above, the change in position or deflection of the diaphragm over time may be directly related to the rate at which infusate is pumped from the reservoir. The controller 92 may be configured to determine whether the detected change in position or deflection of the septum over time is within normal operating parameters (i.e., the detected change in position or deflection of the septum over time corresponds to a clinically acceptable flow rate of the infusate). In some embodiments, the controller 92 may not convert the changes in the received acoustic signal to a distance value, but instead may be configured to determine whether the detected changes in the received acoustic signal over a period of time are within normal operating parameters (i.e., the detected changes in the acoustic signal over time correspond to a clinically acceptable flow rate of the infusate).

When it is determined that the detected diaphragm movement is not within the normal operating parameter range, the controller 92 may be configured to provide a notification to the user, for example, by sending a message to the external device 34. The operation of the apparatus 700 may be substantially similar to the operation of the

apparatuses

300, 400, 500, and 600 as described above.

Various acoustic wave based diaphragm sensors may be used to detect changes in the position or deflection of the diaphragm 40 over time. For example, acoustic wave-based diaphragm sensors according to various embodiments may use Doppler (Doppler), pulse echo, and/or sonar techniques to measure the displacement of the diaphragm 40 over time.

Fig. 8 illustrates an embodiment method 800 for monitoring a flow rate of an infusate from an implantable drug delivery device by measuring movement of a septum in a reservoir of the implantable drug delivery device. The electronics module 32 as described above may detect the displacement (i.e., the amount of deflection) of the diaphragm over time.

In block 802, the electronics module 32 may begin flow rate measurements. In one embodiment, the electronics module 32 may initiate flow rate measurements at predetermined times or may initiate measurements in response to commands received from an external device 34 (e.g., an external programmer).

In block 804, the electronic module 32 may be at a first time T₁Detecting diaphragm P₁The position or deflection of. For example, when the accumulator 30 is in a filled state (as shown in fig. 2C), the electronics module 32 may detect the position (i.e., deflection) of the diaphragm with the diaphragm 40 in a maximum (e.g., upward) deflected position. Initial time T₁May correspond to the time at which outlet valve 28 of reservoir 30 is opened and infusate begins to drain from the reservoir (see fig. 2D). Thus, in some embodiments, the electronic module 32 may position the diaphragm at the P position₁Is synchronized with the opening of the outlet valve 28. Alternatively, in some embodiments, the electronics module 32 may detect the position P of the diaphragm 40 at any arbitrary time during the fill/empty cycle of the accumulator 30₁。

The electronics module 32 may detect the position or deflection of the diaphragm using diaphragm sensor data from a diaphragm sensor device configured to determine the position (i.e., the amount of deflection) of the diaphragm within the accumulator, such as any of the

diaphragm sensors

302, 402, 502, 602, and/or 702 described above with reference to fig. 3-7.

In block 806, the electronic module 32 may be at a first time T₂Detecting diaphragm P₂The position or deflection of. A second time T₂May be greater than the first time T₁A known or measured time period (i.e., Δ T) later. The time period can be less than about 5 seconds, such as less than about 1 second, including less than about half a second, less than about one-quarter second, less than about one-hundredth second, less than about one millisecond, and the like. The electronics module 32 may use the diaphragm sensor data from the diaphragm sensor device to detect the diaphragm P₂Is configured to determine a position (i.e., an amount of deflection) of a diaphragm within the accumulator, such as any of the

diaphragm sensors

302, 402, 502, 602, and/or 702 described above with reference to fig. 3-7.

The electronics module 32 may determine a change in the position or deflection of the diaphragm (i.e., P) over a measurement period Δ T₁And P₂Or the difference between Δ P). As discussed above, the change in position or deflection of the diaphragm over time may be directly related to the rate at which infusate is pumped from the reservoir. In some embodiments, the electronics module 32 may determine how much the diaphragm moves (i.e., deflects) within a predetermined time period Δ Τ. In other embodiments, the electronics module 32 may regularly or continuously monitor the position or deflection of the diaphragm until the diaphragm moves (i.e., deflects) a predetermined amount (i.e., Δ Ρ), and may then determine the amount of time (i.e., Δ Τ) that elapses during the predetermined change in the position of the diaphragm. For example, the electronics module 32 may be configured to determine the initial upward deflected position P of the diaphragm₁(with the accumulator 30 in a filled state, as shown in FIG. 2C) to a second position P₂(with diaphragm 40 fully deflected downward, as shown in figure 2A).

In determination block 808, the processor 43 of the electronics module 32 may determine whether the change in the position or deflection of the diaphragm detected over the measurement period (i.e., Δ P/Δ T) satisfies one or more threshold criteria. The at least one threshold criterion may be related to a flow rate of the infusate during normal operation of the implantable drug delivery device. In other words, the change in position or deflection of the diaphragm detected over the measurement period (i.e., Δ P/Δ T) may be compared to a stored value corresponding to an expected change in position or deflection of the diaphragm over the same period of time for a normally operating device. The detected Δ P/Δ T may satisfy one or more threshold criteria when the detected Δ P/Δ T deviates from the expected Δ P/Δ T by less than a predetermined amount (e.g., 0-10%). For example, if the detected Δ Ρ/Δ Τ is less than a first stored threshold value, this may indicate that there is a blockage or blockage in the flow path of the implantable drug delivery device and that the flow rate of the device is abnormal. In another example, if the detected Δ P/Δ T is greater than a second stored threshold (which may be equal to or greater than the first threshold), this may indicate that a leak or other problem exists in the device.

In some embodiments, processor 43 of the electronics module may optionally determine the flow rate of accumulator 30 based on a change in the position or deflection of the diaphragm (i.e., Δ P/Δ T) detected over a measurement period. For a fixed volume reservoir, a constant volume of infusate is dispensed each time the diaphragm 40 moves from the fully upwardly deflected position shown in fig. 2C to the fully downwardly deflected position shown in fig. 2A. Thus, the change in position or deflection of the diaphragm Δ Ρ may be equal to the volume, which may be expressed in mL of infusate, for example. Thus, the detected ap/at may be expressed as a flow rate (e.g., milliliters/second) that may be compared to one or more threshold criteria, including one or more predetermined flow rate values corresponding to normal and/or abnormal flow rates of the implantable drug delivery device.

In response to determining that the change in position or deflection of the diaphragm detected over the measurement period (i.e., Δ P/Δ T) does not satisfy one or more threshold conditions (i.e., determination block 808 ═ no), in block 810, the processor 43 of the electronics module 32 may determine that the flow rate of the infusate is abnormal. In some embodiments, the determination of an abnormal flow rate may be the result of an implantable drug delivery device becoming clogged or leaking. In block 814, the processor 43 of the electronics module 32 may provide a notification of the abnormal flow rate. For example, processor 43 may send a message to external device 34, such as an external programmer, over a wireless interface indicating that the implantable drug delivery device has an abnormal flow rate. Processor 43 may optionally take other remedial action in response to the determination of an abnormal flow rate, such as adjusting the circulation rate of the accumulator and/or shutting down the system.

In response to determining that the change in position or deflection of the diaphragm detected over the measurement period (i.e., Δ P/Δ T) satisfies one or more threshold conditions (i.e., determining block 808 ═ yes), the processor 43 of the electronics module 32 may determine that the flow rate of the infusate is normal in block 810.

In an alternative embodiment, the processor 43 within the implantable drug delivery device may be configured with processor-executable instructions to perform the operations of

blocks

804 and 806 and to communicate the detected septum position and time values to the external device 34. In this embodiment, processor 47 of external programmer 34 may receive the detected values from the implantable drug delivery device and determine whether the flow rate of the infusate is normal or abnormal based on determining whether the detected change in position or deflection of the septum (i.e., Δ Ρ/Δ Τ) over the measurement time period satisfies one or more threshold conditions.

As previously discussed, the efficacy of a treatment regimen performed by the implantable drug delivery device 300 may be affected by various obstacles (e.g., obstructions, blockages, etc.) within the flow path of the implantable drug delivery device 300. However, other factors may additionally or alternatively affect the treatment regime performed by implantable drug delivery device 300.

For example, the function or efficiency of one or more of the components of implantable drug delivery device 300 (e.g., filter 24, bellows 16, reservoir 30, access port 31, electronics 32, and conduit 36) may change over time. However, changes in function or efficiency may not be sufficient to immediately affect the flow rate and/or efficacy of the treatment regimen as perceived by the patient. Accordingly, it may be beneficial to monitor parameters associated with the function of one or more of the components of the implantable drug delivery device 300, either directly or indirectly.

In addition, the treatment regimen may comprise a predetermined dosage administration schedule as defined by the clinician. The amount of infusate prescribed for use during the treatment regimen may be the same as the amount of infusate used during the treatment regimen. In some embodiments and treatments, the treatment regimen may allow a predetermined number of patient priming doses. Thus, the amount of infusate administered during a treatment regimen may vary depending on whether the patient chooses to use one or more of the allowable number of patient priming doses during the treatment regimen. This may result in a difference in the length of time that the overall treatment protocol may be performed before refilling the implantable drug delivery device 300. Therefore, to more accurately predict when an infusate may need to be replenished, it may be beneficial to measure information associated with the amount of infusate administered during a treatment regimen, either directly or indirectly.

In various embodiments, the methods and systems for directly or indirectly measuring or determining the amount of infusate and/or the flow rate of infusate provided to a patient may be performed by measuring various parameters associated with the drug reservoir 10. As shown in fig. 9-15, various embodiments may include an implantable drug delivery device 300 including a bellows sensor for detecting various parameters associated with a drug reservoir. For example, the bellows sensor may measure one or more parameters associated with the bellows 16 and/or the second region 20 of the drug reservoir 10 that are related to the volume of infusate within the drug reservoir. In some embodiments, the bellows sensor may be configured to detect one or more of a position or displacement, a pressure, or a level/amount of the two-phase liquid in the second region 20 of the drug reservoir 10 or an infusate within the bellows 16. While various bellows sensors are described with reference to fig. 9-15, one or more bellows sensors may be any suitable sensor configured to provide information associated with one or more parameters corresponding to or associated with infusate volume, bellows 16, second region 20, and/or biphasic liquid in order to determine the amount of infusate and/or flow rate of the infusate provided to the patient. Additionally, although a single bellows sensor is illustrated in fig. 9-15, any number and combination of different bellows sensors may be utilized to detect one or more parameters associated with the bellows 16 and/or the second region 20 of the drug reservoir 10.

Referring to fig. 9, the implantable drug delivery device 300 may include an electrical based bellows sensor 92 configured to communicate information associated with the position or expanded/compressed state of the bellows 16. The bellows sensor 92 may comprise one or more electrically based bellows sensors. While the bellows sensor 92 is shown in fig. 9 as being disposed on an outer surface of the bellows 16 within the second region 20, the bellows sensor 92 may alternatively or additionally be disposed on another portion of the outer surface of the bellows 16 or on one or more inner surfaces of the bellows 16. In some embodiments, the bellows sensor 92 may be an integral part of the bellows 16, while in other embodiments, the bellows sensor 92 may be a separate device coupled to the inner or outer surface.

In some embodiments, bellows sensor 92 may be configured to convert the mechanical properties of bellows 16 into an electrical signal that is transmitted to electrical signal detector 91. The bellows sensor 92 may be configured or calibrated to provide information corresponding to or indicative of the displacement and/or expansion of the bellows 16. For example, the bellows sensor 92 may be configured to emit different electrical signals in response to the bellows 16 being in different displacement and/or expansion/compression states. For example, the bellows sensor 92 may generate a range electrical signal (e.g., an analog or digital signal) that corresponds to or indicates a range of displacement and/or expansion/compression of the bellows 16 between full (i.e., containing a maximum amount of infusate) and empty (i.e., containing a minimum amount of infusate). As another example, when bellows 16 is substantially empty, bellows sensor 92 may emit a first electrical signal; when the bellows 16 is filled with the maximum amount of infusate (e.g., immediately following refilling), the bellows sensor may emit a second electrical signal; when a minimum amount of infusate remains within the bellows 16 (e.g., after administration of a final dose of the treatment regimen), the bellows sensor may emit a third electrical signal; and the bellows sensor may emit a fourth electrical signal when the amount of infusate within the bellows 16 is less than a maximum amount of infusate retained within the bellows 16 and greater than a minimum amount.

The electrical signal detector 91 may be configured to detect an electrical signal emitted by the bellows sensor 92. The electrical signal detector 91 may be coupled to the electronics module 32. The electrical signal detector 91 may be integral with the electronics module 32, or the electrical signal detector 91 may be separate and/or spaced apart from the electronics module 32.

In some embodiments, the electrical signal detector 91 may be configured to send the detected electrical signal emitted by the bellows sensor 92 to the electronics module 32. In some embodiments, the electrical signal detector 91 may be configured to monitor or analyze the electrical signal from the bellows sensor 92 and send information to the electronics module 32 in response to determining that the change or rate of change of the electrical signal from the bellows sensor 92 exceeds a predetermined threshold. In some embodiments, electrical signal detector 91 or bellows sensor 92 may include a processor configured to determine whether a change or rate of change of the electrical signal from bellows sensor 92 exceeds a predetermined threshold. In some embodiments, electrical signal detector 91 or bellows sensor 92 may be configured to compare the change or rate of change of the electrical signal from bellows sensor 92 to a plurality of predetermined thresholds. For example, a first threshold may be associated with a prescribed flow rate of infusate to the patient (e.g., according to a dosage regimen configured by a physician), a second predetermined threshold may be associated with scheduling a refill of implantable drug delivery device 300 (e.g., a threshold indicating an amount of infusate usage that exceeds an amount assumed when a refill date was initially scheduled), and a third predetermined threshold may indicate a problem with implantable drug delivery device 300, and a fourth predetermined threshold may correspond to an unsafe flow rate of infusate (e.g., triggering a warning or alarm).

In some embodiments, the bellows sensor 92 may include one or more strain gauges that generate an electrical signal by changing an electrical characteristic (e.g., resistance) in response to a change in shape caused by expansion or contraction of the bellows 16. Strain gauge bellows sensor 92 may be configured and attached to or formed within bellows 16 such that the amount of change in electrical characteristics due to expansion and contraction of the bellows corresponds to the amount of infusate within bellows 16 and/or the gas-liquid ratio of the two-phase liquid within second region 20. Non-limiting examples of strain gauges that may be used in bellows sensor 92 include bonded foil strain gauges, bonded semiconductor strain gauges (e.g., piezoresistors), thin film strain gauges (e.g., strain gauges formed by vapor depositing or sputtering insulator and strain gauge materials onto the surface of a bellows or diaphragm), diffused or implanted semiconductor strain gauges, and combinations thereof.

Referring to fig. 10, the implantable drug delivery device 300 may include a bellows sensor 93 configured to communicate information associated with a position, orientation, expansion/compression state, and/or pressure associated with the bellows 16 to the electronics module 32. The bellows sensor 93 may be any sensor configured to detect a position, angle, and/or displacement associated with the bellows 16 and/or one or more blades of the bellows 16. For example, the bellows sensor 93 may include one or more or a combination of a flexure sensor, a gyroscope, a tilt sensor, a piezoelectric sensor, a linear, angular, and/or multi-axis position sensor. Additionally or alternatively, the bellows sensor 93 may be configured to measure information associated with the level of infusate within the bellows 16.

As illustrated in fig. 10, the bellows sensor 93 may be disposed within one or more blades of the bellows 16 and/or disposed on another outer surface of the bellows 16. Since implantable drug delivery device 300 may be operated in any orientation (e.g., the patient may stand, lie down, etc.), electronic module 32 may combine the orientation information with one or more other parameters for various determinations. For example, the orientation information may be used in conjunction with detected information associated with a position, expansion/compression state, and/or pressure associated with the bellows 16 and/or the level of infusate. Additionally or alternatively, the orientation information may be used in conjunction with the detected information to determine the flow rate at which infusate is pumped from the reservoir, as described in fig. 1-8.

Referring to fig. 11, the implantable drug delivery device 300 may include an optical-based or light-based bellows sensor that includes a light emitter 93 and a light detector 94. The light emitter 93 may be configured to emit one or more types of light (e.g., visible light, infrared light, laser light, ultraviolet light, etc.) onto the surface of the bellows 16. In some embodiments, the surface of the bellows 16 that directs the light emission may contain a reflective material to enhance or alter the reflection of the light generated by the light emitter 93 to the light detector 94. Light generated by the light emitter 93 may reflect off the surface of the bellows 16 and be detected and/or measured by the light detector 94. Based on the characteristics of the light (e.g., intensity, interference pattern, retardation, polarity, etc.) detected/measured by the light detector 94, the position and/or expansion/compression state of the bellows 16 may be determined.

Although fig. 11 shows light emitter 93 positioned to illuminate the bottom surface of bellows 16, one or more pairs of light emitter 93 and light detector 94 may be arranged to optically measure one or more other surfaces (e.g., top, sides, blades, etc.) of bellows 16.

Referring to fig. 12, the implantable drug delivery device 300 may contain a light-based bellows sensor featuring a light emitter/detector 95 and an extension 96. The light emitter/detector 95 may be configured to emit and detect one or more types of light (e.g., visible light, infrared light, laser light, ultraviolet light, etc.) through the second region 20 and onto the surface of the extension 92, which may be an appendage extending from the surface of the bellows 16. The extension 96 may be made of a material having reflective properties or comprise a reflective material disposed on a surface of the extension 96. Light emitted by the light emitter/detector 95 may be reflected off the surface of the extension 96 and detected or measured by the light emitter/detector 95. Based on the characteristics of the light detected or measured by the light emitter/detector 95, the position and/or expansion/compression state of the bellows 16 may be determined.

Although fig. 12 shows one light emitter/detector 95 disposed outside of the second region 20, one or more light emitter/detectors 95 may be disposed relative to any extension from any surface (e.g., top, side, blade, etc.) of the bellows 16.

Referring to fig. 13, the implantable drug delivery device 300 may include a bellows sensor 97 configured to detect the presence of vapor and/or liquid within the two-phase liquid within the second region 20. For example, as previously discussed, the ratio of the amount of the two-phase liquid in the vapor state to the amount of the two-phase liquid in the liquid state may indicate the amount of pressure required to pressurize the bellows 16 to perform the treatment protocol. For example, as the amount of infusate within the bellows 16 decreases, the amount of pressure provided by the two-phase liquid to the outer surface of the bellows 16 may increase to maintain stagnation. Thus, the bellows sensor 97 can detect the amount of the two-phase liquid in the vapor state and/or the amount of the two-phase liquid in the liquid state in order to determine the amount of infusate remaining within the bellows 16.

Referring to fig. 14, the implantable drug delivery device 300 may include a flow meter 98 configured to detect the flow of infusate as it travels between the drug reservoir 10 and the accumulator 30. Although the flow meter 98 is shown in fig. 14 as being disposed between the housing 14 and the filter 24, one or more flow meters 98 may be disposed between the filter 24 and the valve 26 and configured to measure the amount of infusate and/or the rate at which infusate flows between the drug reservoir 10 and the reservoir 30. The flow meter 98 may provide information to the electronics module 32 related to the amount of infusate and/or the rate at which infusate flows between the drug reservoir 10 and the reservoir 30.

Referring to fig. 15, an implantable drug delivery device 300 may include a coil 99 and an inductive bellows sensor 101 wound around the outer surface of the bellows 16. In some embodiments, the coil 99 may be disposed within the blades of the bellows 16, as illustrated in fig. 15. In other embodiments, the inductive bellows sensor 101 may be disposed in any location that enables measurement of at least a portion of the magnetic field generated by the coil 99. In some embodiments, the magnetic field measurements detected by the inductive bellows sensor 101 and/or the magnetic field changes associated with the coil 99 may be used to determine the amount of infusate within the bellows 16. For example, when the amount of infusate within the bellows 16 decreases (e.g., when the infusate is administered during a treatment protocol), the loops of the coil 99 may move closer together as the blades of the bellows 16 compress, which may cause a change in the magnetic field generated by the coil 99. Likewise, when the bellows 16 is refilled with infusate and the blades of the bellows 16 expand, the loops of the coil 99 may move further away from each other, thereby changing the magnetic field in an opposite manner.

Fig. 16 is a process flow diagram illustrating an embodiment method 1600 for determining whether a change in volume of an infusate within a bellows (e.g., 16) of an implantable drug delivery device is normal. Referring to fig. 1-16, method 1600 may be implemented by one or more processors of an implantable drug delivery device, a patient programmer, or a combination thereof. For example, method 1600 may be implemented by processor 43 of electronic module 32 and/or processor 47 of external programmer 34.

In block 1602, the processor may initiate an infusion volume change rate measurement procedure. The infusate volume change rate measurement routine may be configured to directly or indirectly determine the volume change rate of the infusate within the bellows. In addition, the infusate volume change rate measurement procedure may use the determined volume change rate of the infusate within the bellows to determine a number of factors, such as the efficacy of a treatment regimen or a change or rate of change in the function of the implantable drug delivery device or components thereof (e.g., to detect wear or failure of a component).

The infusion volume rate of change measurement program may be initiated by the processor in various ways. In some embodiments, the infusion volume rate of change measurement procedure may be initiated by the processor in response to communication between the external programmer 34 and the electronics module 32 of the implantable drug delivery device 300. For example, the processor 47 of the external programmer 34 may generate and send a message to the electronic module 32 containing instructions for initiating an infusion volume rate measurement procedure. In response to communication with external programmer 34, instructions for initiating the infusate volume change rate measurement program may be initiated by external programmer 34 or by electronics module 32.

In some embodiments, the infusate volume change rate measurement procedure may be triggered by a predetermined event or operation, such as filling or refilling the bellows 16 with infusate, receiving a treatment protocol, receiving an indication of one or more parameters for modifying the currently implemented treatment protocol, determining a flow rate anomaly, and so forth.

Additionally or alternatively, the volume rate measurement procedure may be initiated by the processor at periodic intervals during the treatment protocol. The number of infusate volume change rate measurements and/or the time interval between infusate volume change rate measurements performed during a treatment protocol may be predetermined or dynamically determined by the processor for a current treatment protocol, a predetermined number of sequential treatment protocols, and/or the expected lifetime of the implantable drug delivery device. For example, information associated with the number of times volume change rate measurements are performed and/or the time interval between volume change rate measurements may be included in one or more of information associated with a current therapy regime or information associated with operation of the implantable drug delivery device provided at manufacture, before implantation, and/or after implantation. The information associated with the number of times volume change rate measurements are performed and/or the time interval between volume change rate measurements may be a predefined number of times or interval, or information that may allow the processor to determine the number of times volume change rate measurements are performed and/or the time interval between volume change rate measurements.

The time interval between the number of executions and/or the volume change rate measurements may change over time. The volume change rate measurements may be performed more or less frequently by the processor over time intervals associated with one treatment protocol, multiple sequential treatment protocols, and/or the lifetime of the implantable drug delivery device. In some embodiments, volume change rate measurements may be performed more frequently by the processor immediately following filling or refilling of the bellows in order to determine the initial maximum volume of infusate for the current treatment protocol. Alternatively, the volume change rate measurement may be performed less frequently by the processor after filling or refilling of the bellows 16.

In some embodiments, the processor may perform volume rate measurements more frequently at the end of the current treatment protocol. For example, to prevent interruption of the delivery of infusate to the patient, it may be desirable to monitor the volume of infusate more closely so that measurements may be taken to prevent the implantable drug delivery device from emptying the bellows of the infusate before refilling the bellows 16 with more infusate. In some embodiments, in response to determining that the current volume of infusate is less than the predetermined threshold but greater than the minimum infusate volume level, the processor may increase the rate at which volume rate measurements are performed to more finely monitor the consumption of the infusate. In response to determining that the current volume of infusate is less than the predetermined threshold, the processor may send an alert to the patient and/or clinician. An alarm associated with the level of infusate may be provided as an indication or reminder that the infusate needs to be refilled within a predetermined amount of time.

In block 1604, the processor may be at a first time (T)₁) Determining a first variable (B) of the bellows₁). First variable B₁May be associated with the volume of infusate within the bellows 16 and may be detected or determined using the output of one or more bellows sensors and/or detectors associated with the bellows 16. For example, the electrical signal detector 91, the bellows sensor 93, the light detector 94, the light emitter/detector 95, the bellows sensor 97, the flow meter 98, and/or the inductive bellows sensor 101 may be electrically coupled to the processor such that the processor receives output signals corresponding to measured parameters associated with the infusate and/or the bellows 16. In some embodiments, the output of one or more bellows sensors and/or detectors associated with bellows 16 may correspond to an infusion within bellows 16Volume value of the object. In other embodiments, the processor may use the first variable B₁The volume of infusate within the bellows 16 is calculated.

The processor may store the determined first variable B of the bellows₁. Additionally, the processor may compare the first time T to₁The associated information is stored in a memory. In some embodiments, the first time T₁May be a time stamp or other value associated with a discrete time instance corresponding to when the parameter of the bellows 16 was measured. In other embodiments, the processor may be responsive to receiving a first variable B for determining the bellows corresponding to the bellows 16₁The measured parameter to start a timer.

In block 1606, the processor may be at a second time (T)₂) Determining a second variable (B) of the bellows₂). Second variable B₂May be associated with the volume of infusate within the bellows 16 and may be detected or determined by the processor using the output of one or more bellows sensors and/or detectors associated with the bellows 16. For example, the electrical signal detector 91, the bellows sensor 93, the light detector 94, the light emitter/detector 95, the bellows sensor 97, the flow meter 98, and/or the inductive bellows sensor 101 may be configured to generate an output to the processor corresponding to the measured parameter of the bellows 16. In some embodiments, the output of one or more bellows sensors and/or detectors associated with the bellows 16 may correspond to a volume value of infusate within the bellows 16. In other embodiments, the processor may use the second variable B₂The volume of infusate within the bellows 16 is calculated.

The processor may store the determined second variable B of the bellows₂. In addition, the processor may compare the second time T with a second time T₂The associated information is stored in a memory. In some embodiments, the second time T₂May be a time stamp or other value associated with a discrete time instance corresponding to when the parameter of the bellows 16 was measured. In other embodiments, the processor may be responsive to the received pairSecond variable B for determining the bellows, corresponding to the bellows 16₂The output of the measured parameter to stop the timer started.

In determination block 1608, the processor may determine that at a first time T₁And a second time T₂In the time period between, a first variable B of the bellows₁Second variable B of bellows₂Whether the variation in between meets the threshold criteria. The processor may perform any of a variety of calculations to determine the rate of change of volume of infusate within the bellows 16 based on the two measured parameters. In an exemplary embodiment, the following equation may be used to determine the time T at the first time T₁And a second time T₂In the time period between, a first variable B of the bellows₁Second variable B of bellows₂The rate of change therebetween:

after determining the rate of change Δ B/Δ T, the processor may compare the resulting value to a threshold criterion. In some embodiments, the threshold criteria may be predetermined, while in other embodiments, the threshold criteria may be dynamically determined by the processor based on parameters associated with one or more of a current treatment regimen, a predetermined number of sequential treatment regimens, and/or an expected life of the implantable drug delivery device. The threshold criteria may be static for a single treatment protocol, or the threshold criteria may be dynamically determined by the processor in response to determining that the infusate volume may be abnormal. The threshold criteria may be a single value or a range of values.

In block 1610, in response to determining that the rate of change Δ B/Δ T satisfies the threshold criteria (i.e., determining block 1608 — yes), the processor may determine that the infusion volume rate of change is normal.

In block 1610, in response to determining that the rate of change Δ B/Δ T does not meet the threshold criteria (i.e., determining block 1608 ═ no), the processor may determine that the infusion volume rate of change is abnormal. In some embodiments, determining an abnormal rate of change of infusate volume may indicate that the determined volume of infusate in the bellows does not match the expected amount or volume of remaining infusate. The difference between the determined volume and the expected volume of the infusate may be caused by a variety of factors, such as the patient intentionally exceeding a prescribed dose, additional doses administered to the patient, a change in the function of one or more elements in the implantable drug delivery device, and the like.

In some embodiments, in response to determining that infusate within the bellows exceeds the threshold criteria, the processor may determine that the infusate within the bellows does not meet the threshold criteria. For example, when the processor determines that infusate within the bellows is less than a threshold level (i.e., too much infusate has been expelled from the bellows), a condition may be detected in which the flow path between the bellows and the conduit is unobstructed (e.g., the valve is open). As another example, when the processor determines that infusate within the bellows is greater than a threshold criteria (i.e., too little infusate has been administered to the patient at a prescribed flow rate), a condition may be detected in which the flow path between the bellows and the catheter is obstructed (e.g., due to catheter occlusion). In some embodiments, the threshold criteria may be a rate of volume change within the bellows, in which case an unobstructed flow path may be detected when the rate of volume change exceeds the threshold criteria, and an obstructed flow path may be detected when the processor determines that the rate of volume change is less than the threshold criteria. For ease of reference, such a determination by the processor may be referred to as determining whether the measurement satisfies a threshold criterion.

In block 1614, in response to determining that the infusate volume rate is abnormal, the processor may initiate an abnormal infusate volume change rate routine. The abnormal infusate volume rate routine executed by the processor may include various operations configured to modify the current infusate volume change rate measurement routine, notify the patient and/or clinician that an abnormal operating condition is detected, determine a potential cause of triggering the abnormal operating condition, and/or abort operation of the implantable drug delivery device.

In some embodiments, a plurality of predetermined operations may be stored in the memory, and in response to determining a potential cause of the anomaly and/or the level of the anomaly, the processor may retrieve and execute the stored operations corresponding to the determined potential cause. In other embodiments, the operation of the infusate volume rate anomaly may be dynamically selected to create a unique anomalous infusate volume rate program based on current measurements.

FIG. 17 is a process flow diagram of a non-limiting example of an abnormal infusion volume change rate program 1614. Referring to fig. 1-17, method 1614 may be implemented by one or more processors (e.g., processor 43 and/or processor 47) of an implantable drug delivery device (e.g., implantable drug delivery device 100), a patient programmer (e.g., external programmer 34), or a combination thereof.

In block 1702, the processor may determine at a third time (T) in response to determining in block 1612 that the rate of change of the volume of infusate is abnormal₃) Determining a third variable (B) of the bellows₃). Third variable B₃May be associated with the volume of infusate within the bellows 16 and may be detected or determined using the output of one or more bellows sensors and/or detectors associated with the bellows 16. The processor may store the determined third variable B₃And a third time T₃Associated information.

In some embodiments, determining a third variable B of the bellows may be performed₃To confirm the validity of the anomaly determination. Various factors may inadvertently affect discrete time instances (e.g., T) by the bellows sensor and/or detector without affecting the actual infusate volume within the bellows 16₁Or T₂) The measured parameters of the bellows 16. For example, depending on the current state of the pumping cycle and/or the circulation rate of the accumulator, the infusate may be displaced within the bellows 16 such that any measurements associated with the height level and/or surface of the infusate within the bellows 16 may be inaccurate.

In optional block 1704, the processor may be at a fourth time (T)₄) Determining a fourth variable (B) of the bellows₄). Fourth variable B₄May be correlated to the volume of infusate within the bellows 16, and mayDetected or determined by a processor using the output of one or more bellows sensors and/or detectors associated with bellows 16. The processor may store the determined fourth variable B₄And a fourth time T₄Associated information.

At determination block 1706, the processor may determine a first variable B of the bellows over a period of time₁Second variable B of bellows₂Third variable B of corrugated pipe₃And fourth variation B of bellows₄Whether a change between at least two of the threshold criteria is met. The processor may perform any of a variety of calculations to determine the rate of change of volume of infusate within the bellows 16 based on the two or more measured parameters.

The processor may determine an amount of change between two or more of the determined variables of the bellows based on the measured parameters. For example, the processor may determine a third variable B of the bellows₃And fourth variation B of bellows₄(ΔB₃₄) First variable B of corrugated pipe₁And third variable B of bellows₃(ΔB₁₃) First variable B of corrugated pipe₁And fourth variation B of bellows₄(ΔB₁₄) Second variable B of bellows₂And third variable B of bellows₃(ΔB₂₃) And a second variable B of the bellows₂And fourth variation B of bellows₄(ΔB₂₄) A change in magnitude between one or more of the plurality of sensors. The processor may determine an amount of change between time intervals corresponding to the determined amount of change between the variables of the bellows.

After determining the one or more rates of change Δ B/Δ T, the processor may compare the resulting values to threshold criteria. In some embodiments, the threshold criteria may be a predetermined value, while in other embodiments, the threshold criteria may be dynamically determined by the processor based on parameters associated with one or more of a current treatment regimen, a predetermined number of sequential treatment regimens, and/or an expected life of the implantable drug delivery device. The threshold criteria may be static for a single treatment protocol, or the threshold criteria may be dynamically determined in response to determining that the infusate volume may be abnormal. The threshold criteria may be a single value or a range of values.

In some embodiments, the threshold criteria may be another determined rate of change during the current treatment regimen. For example, when the processor determines a third variable B of the bellows₃Fourth variable B of bellows₄Amount of change therebetween (Δ B)₃₄) The threshold criterion chosen may then be the first variable B of the bellows₁Second variable B of bellows₂Amount of change therebetween (Δ B)₁₂) To determine if the infusate is decreasing at a uniform rate.

Alternatively or additionally, the threshold criteria may be one or more rates of change determined during different treatment regimens. The threshold criteria may include the amount of change between variables of the bellows determined during one or more previous treatment protocols. In some embodiments, the selected threshold criteria may correspond to substantially similar time frames within the current and previous treatment protocols, or to substantially similar infusate volume levels during the current and previous treatment protocols. In some embodiments, the selected threshold criteria may correspond to any time frame within one or more of the prior treatment protocols. For example, if an abnormality is determined, the processor may determine whether a change in function of one or more elements of the implantable drug delivery device has occurred based on threshold criteria selected from one or more previous treatment protocols.

In block 1708, in response to determining that the rate of change Δ B/Δ T satisfies the threshold criteria (i.e., determining block 1706 — yes), the processor may determine that the rate of infused volume of the subject is normal and terminate the procedure. In some embodiments, the processor may determine that the determination of the rate of abnormal infusion volume change in block 1612 is a false positive based on whether the rate of change Δ B/Δ T satisfies a threshold criterion.

In block 1710, the processor may determine the infusate flow rate in response to determining that the rate of change Δ B/Δ T does not meet the threshold criteria (i.e., determining block 1706 — no). The processor may use various techniques to determine infusate flow rate, including the methods described herein. For example, the processor may use the output of a bellows sensor and/or a detector associated with the accumulator to determine the infusate flow rate. The processor may also use the output of a flow rate sensor associated with the flow of fluid within the implantable drug delivery device or catheter to determine the infusate flow rate.

In determination block 1712, the processor may determine whether the infusate flow rate meets a threshold criterion. The threshold criteria may be a predetermined value or may be dynamically determined by the processor using various parameters during the current treatment regimen. In some embodiments, the threshold criteria may be based on infusate flow rates determined in one or more previous treatment protocols.

In response to determining that the infusion flow rate satisfies the threshold criteria (i.e., determination block 1712 — yes), the processor may initiate a first abnormal infusion flow rate program, which may include various operations configured to identify one or more elements of the implantable drug delivery device that may result in an abnormal flow rate, and modify the flow rate or abort operation of the implantable drug delivery device. The first abnormal infusion flow rate program may further comprise various operations for notifying the patient and/or clinician. In some embodiments, the threshold standard value or range of values may be indicative of a change in operation of one or more elements of the implantable drug delivery device that result in an abnormal flow rate.

In response to determining that the infusate flow rate does not meet the threshold criteria (i.e., no at decision block 1712), the processor may initiate a second abnormal infusate flow rate routine that is different from the first abnormal infusate flow rate routine. The second abnormal infusate flow rate program may include various operations configured to modify the current infusate volumetric rate measurement program, modify the current treatment protocol, and/or determine the potential cause of triggering the abnormal flow rate. The second abnormal infusate flow rate routine may not suspend operation of the implantable drug delivery device. Thus, after the second abnormal infusate flow rate routine is executed, the processor may continue to perform normal operations including repeating the infusate volume change rate measurement routine of method 1600 at the appropriate time.

The first and second abnormal infusate flow rate programs may be predetermined and uniform for the lifetime of the implantable drug delivery device. Alternatively, the first and second abnormal infusate flow rate programs may be dynamically determined and/or modified by the processor. In some embodiments, a plurality of predetermined operations of the first abnormal infusate flow rate program or the second abnormal infusate flow rate program may be stored in the memory, and in response to determining a potential cause of the abnormal flow rate, the processor may retrieve and execute the stored operations corresponding to the determined potential cause. In some embodiments, the operation may be dynamically selected by the processor based on the current measurements and parameters of the current treatment protocol to create a unique abnormal infusate flow rate program.

Fig. 18 is a process flow diagram of an embodiment method 1800 for determining initial parameters associated with a bellows of an implantable drug delivery device. Referring to fig. 1-18, method 1800 may be implemented by one or more processors (e.g., processor 43 and/or processor 47) of an implantable drug delivery device (e.g., implantable drug delivery device 100), a patient programmer (e.g., external programmer 34), or a combination thereof.

In block 1802, the processor may determine an empty bellows parameter (B)_{Air conditioner}). When the bellows 16 is empty or substantially free of any infusate, the processor may determine an empty bellows parameter B based on one or more outputs received from one or more bellows sensors and/or detectors associated with the bellows 16_{Air conditioner}. The empty bellows parameter B may be determined at initialization of the implantable drug delivery device and/or whenever the bellows is empty or substantially free of any infusate_{Air conditioner}And (4) determining.

In block 1804, the processor may determine a bellows parameter B for the void_{Air conditioner}Stored in the memory of the implantable drug delivery device and/or in the patient programmer. In some embodiments, the empty bellows parameter B_{Air conditioner}Can be used to determine current and/or future treatment regimens and hereinAny of the exception procedures described.

In optional block 1806, the processor may determine a treatment protocol parameter. The treatment protocol parameters may be predefined by the clinician. Alternatively, the processor may receive information associated with a treatment protocol and use the information to determine corresponding treatment protocol parameters. Although block 1806 is shown after block 1804, the treatment protocol parameters may be determined at any point before, during, or after initialization of method 1800.

In block 1808, the processor may receive an infusate fill indication. In some embodiments, an infusate fill indication may be generated by fill detector 41. In some embodiments, the processor may receive an infusate fill indication in a message from the patient programmer.

In block 1810, the processor may determine an initial infusate parameter. After storing the full dose of infusate in the bellows, initial infusate parameters may be determined based on the output of one or more of the bellows sensors and/or detectors associated with the bellows.

In block 1812, the processor may store the initial infusate parameter as the maximum infusate value (I)_{Maximum of}). The processor may use the maximum infusate value I_{Maximum of}Determining a current and/or future treatment regimen and any of the abnormal procedures described herein. For example, the maximum infusate value I may be determined by the processor after each refill of infusate_{Maximum of}. Maximum infusate value I determined if during the lifetime of the implantable drug delivery device_{Maximum of}The implantable drug delivery device may be configured to deliver a drug to a patient in need thereof.

In block 1814, the processor may initiate a treatment protocol. The processor may instruct one or more elements of the implantable drug delivery device to begin administration of the infusate in accordance with the parameters of the treatment protocol.

Fig. 19 is a flow diagram of an embodiment method 1900 for determining whether a parameter change associated with an infusion in a bellows of an implantable drug delivery device is normal. Referring to fig. 1-19, method 1900 may be implemented by one or more processors of an implantable drug delivery device, a patient programmer, or a combination thereof. For example, method 1900 may be implemented by processor 43 of electronic module 32 and/or processor 47 of external programmer 34.

In block 1902, the processor may initiate a treatment protocol, such as by instructing one or more elements of the implantable drug delivery device to begin administration of an infusate according to a parameter of the treatment protocol.

In block 1904, the processor may determine a current parameter (I) associated with an infusion in a bellows of an implantable drug delivery device_{At present}). The current parameter I may be determined based on one or more outputs generated by one or more bellows sensors and/or detectors associated with the infusate and/or bellows_{At present}. For example, the electrical signal detector 91, the bellows sensor 93, the light detector 94, the light emitter/detector 95, the bellows sensor 97, the flow meter 98, and/or the inductive bellows sensor 101 may be configured to generate an output to the processor corresponding to a measured parameter associated with the infusate and/or the bellows.

The processor may determine the current parameter I using one or more of the measured parameters determined from the output of one or more bellows sensors and/or detectors associated with the infusate and/or bellows to determine the current parameter I_{At present}. For example, the processor may use the output of one or more of the measured parameters to determine a current volume of infusate, a current amount of infusate, a current weight associated with the infusate, and a current height of the infusate within the bellows. When the processor uses multiple outputs to determine the current parameter I_{At present}Where desired, the processor may use multiple outputs from the same bellows sensor and/or detector or one or more outputs from different bellows sensors and/or detectors. In some embodiments, the processor may store the determined current parameter I_{At present}For additional purposes during the current treatment protocol and/or for future treatment protocols and for related implantable drugsAny determination of a function, state, or condition of an object delivery device.

In determination block 1906, the processor may determine a current parameter I associated with the infusion_{At present}Whether equal or substantially equal to the expected parameter (I) associated with the infusion_{Anticipation of}). Expected parameter I_{Anticipation of}May correspond to the amount or volume of infusate expected to remain within the bellows. The expected parameter I may be dynamically determined or selected from predetermined values based on one or more parameters associated with a current treatment protocol, parameters associated with a previous treatment protocol, parameters associated with a future treatment protocol, and parameters associated with the patient_{Anticipation of}. For example, some of the parameters associated with a treatment protocol may include a number of doses that may be administered using the maximum amount of infusate filled in the bellows, a dose administration time interval, information associated with the time at which the last dose of infusate was administered during the current treatment protocol, a number of doses previously administered during the current treatment protocol, an amount of infusate consumed during the current treatment protocol. The processor may further consider information associated with one or more previously performed treatment protocols.

Expected parameter I_{Anticipation of}May vary with the treatment regimen being performed by the implantable drug delivery device. Parameter I is expected whenever a dose is administered_{Anticipation of}May be varied such that the expected parameter reflects a reduction in infusate consumed by a previous dose. In some embodiments, the dose of infusate may be administered at predetermined time intervals defined in the treatment regimen parameters and/or the dose may be administered in response to receiving a request from the patient. Each dose administered by the implantable drug delivery device may be uniform throughout the treatment regimen. Alternatively, the implantable drug delivery device may administer infusions at different doses.

In some embodiments, the different doses of infusate may be based on one or more treatment regimen parameters, additional inputs or requirements received from the patient, and/or parameters associated with the physical state of the patient. For example, if the implantable drug delivery device is configured to deliver insulin to a patient, the dose of insulin used to produce a therapeutic effect may vary based on the parameters of the last dose administration, the hydration level of the patient, the type and/or amount of food consumed by the patient, and the like.

In decision block 1806, the desired parameter I is determined_{Anticipation of}The processor may then compare the determined current parameter I_{At present}. In response to determining the determined current parameter I_{At present}Equal or substantially equal to the expected parameter I_{Anticipation of}(i.e., determination block 1906 — yes), the processor may determine the determined current parameter I in determination block 1908_{At present}Whether less than or equal to a desired refill value (I) associated with the infusion_Refilling). For example, the desired refill value may be greater than the minimum infusate value to provide the patient and/or clinician with the time required to access and refill the infusate in the bellows so that discontinuation of dose administration may be avoided.

In response to determining the determined current parameter I_{At present}Greater than the desired refill value I_Refilling(i.e., no in decision block 1908), the processor may determine the next current parameter in block 1904.

In response to determining the determined current parameter I_{At present}Less than or equal to the desired refill value I_Refilling(i.e., determine block 1908 — yes "), the processor may initiate a refill procedure in block 1910 and then determine the next current parameter again in block 1904. The refill procedure may include one or more operations configured to alter or notify the patient, clinician, and/or infusate provider of an impending refill time for the infusate. In some embodiments, the processor may generate a notification message that is transmitted to external programmer 34 such that the notification may be displayed on external programmer 34, or external programmer 34 may further transmit the notification message to an applicable device associated with the patient, clinician, and/or infusion provider. Additionally or alternatively, may be implantableThe drug delivery device may include a tactile feedback device that the processor may activate to generate an output to the tactile feedback device to alert the patient using vibrations generated by the tactile feedback device. The refilling procedure may be performed at predetermined time intervals until refilling is detected. In some embodiments, when the current parameter I is determined_{At present}The frequency of the refilling procedure may increase as the minimum volume of infusion approaches.

In response to determining the determined current parameter I_{At present}Is not equal or substantially not equal to the expected parameter I_{Anticipation of}(i.e., no in decision block 1906), the processor may determine the determined current parameter I in decision block 1912_{At present}Whether greater than or equal to a first threshold. The first threshold may be indicative of a substantial failure of the implantable drug delivery device to administer infusate at a rate exceeding a prescribed dose, which may cause harm to the patient.

Additionally or alternatively, in response to determining the determined current parameter I_{At present}Is not equal or substantially not equal to the expected parameter I_{Anticipation of}(i.e., no at decision block 1906), the processor may initiate an abnormal infusate volume routine. For example, in response to determining the determined current parameter I_{At present}Is not equal or substantially not equal to the expected parameter I_{Anticipation of}The processor may generate and send a message to the external device through the wireless communication interface of the implantable drug delivery device. The message may contain the current parameter I_{At present}Is not equal or substantially not equal to the expected parameter I_{Anticipation of}And/or the message may contain the determined current parameter I_{At present}. In some embodiments, the external device may be associated with a clinician and responsive to receiving the current parameter I determined_{At present}Associated information, the clinician can verify whether a volume difference exists. In some embodiments, the clinician (or an external device associated with the clinician) may determine the current parameter I determined_{At present}Compared to the specified flow rate times the elapsed time since the last refill event,to determine whether the implantable drug delivery device needs to be refilled without making a physical volume measurement by inserting the needle through the skin into the pump reservoir.

In response to determining the current parameter I_{At present}Greater than or equal to the first threshold (i.e., determination block 1912 — yes), in block 1914 the processor may initiate a "shut down" procedure, wherein the processor may shut down one or more flow control devices (e.g., valves) within the flow path of the implantable drug delivery device to prevent undesired administration of infusate to the patient.

Fig. 20 is a schematic view of another example of an implantable drug delivery system configured to perform a shutdown procedure. In particular, one or more flow control devices (e.g., valves) 71, 72, 73, 74, 75 may be disposed within the flow path between the bellows 16 and the conduit 36. During the shut down procedure, the processor may close one or more of the flow control devices 71, 72, 73, 74 and/or 75 to shut down. In some embodiments, a closed flow control device may prevent infusate from reaching the catheter.

Referring to FIG. 19, in response to determining the current parameter I_{At present}Less than the first threshold (i.e., no in decision block 1912), the processor may determine the current parameter I in decision block 1916_{At present}Whether greater than or equal to a second threshold. In some embodiments, the second threshold may indicate infusate usage I_{At present}Exceeding the expected parameter I_{Anticipation of}The amount of (a) is not significantly large to require immediate shut down of the implantable drug delivery device. In some embodiments, the second threshold may indicate that the dose administered to the patient in each treatment operation (e.g., a single bolus delivery) exceeds the amount expected under the current dosage regimen by an amount that is not dangerous for a certain period of time. It is acceptable that some variations in applied dose may occur from time to time, as long as the total or total number of such events is limited. For example, in some embodiments where some treatment protocols are implemented, the patient may be able to initiate an increased dose, such as by pressing a button on the patient programmer device.

In response to determining the current parameter I_{At present}Less than a second threshold (i.e., true)No) in block 1916, the processor may determine information related to or useful for evaluating the total dose administered to the patient priming dose in block 1918. In this logical branch, the rate of infusion administered deviates from the expected dose rate (high or low), but at a safe level. Deviations from the intended dose rate may be due to problems arising in various components or elements of the implantable drug delivery device. For example, a restriction of the flow path within an implantable drug delivery device or catheter may reduce the amount of infusate administered over time. As another example, changes in various components over time due to wear may increase the amount of infusate administered over time. Thus, to enable a clinician to monitor patient treatment using the implantable drug delivery device, in block 1918, the processor may determine and record information related to the total observed dose for subsequent reporting to an external device (e.g., a patent programmer or clinician programmer device). In some embodiments, such reporting may occur during a routine inspection of the implantable drug delivery device during which a series of operational information is reported. In some embodiments, such information may be transmitted to an external device when (or shortly after) such information is generated in optional block 1920. In block 1904, the processor may continue to measure the next infusate change rate.

In response to determining the current parameter I_{At present}Greater than or equal to the second threshold (i.e., yes to decision block 1916), the processor may determine whether the count of the number of times an abnormal dose measurement was detected is equal to a third threshold in decision block 1922. The third threshold may be the number of occurrences of an increased dose, which, if allowed to persist, is indicative of a potential health problem for the patient.

In response to determining that the count of the number of times an abnormal dose measurement is detected is less than the third threshold (i.e., determining that block 1922 is no), the processor may increment the count in block 1924 and return to measuring the next infusate change rate in block 1904.

In response to determining that the count of the number of times the processor detects an abnormal dose measurement is equal to the threshold number (i.e., determining that block ═ yes), in block 1928, the processor may initiate an abnormal operating procedure. The abnormal operation procedure may involve various operations for protecting the patient and/or notifying the clinician, and may be performed in a single abnormal operation procedure or multiple different abnormal operation procedures.

For example, the first abnormal operation procedure may modify various parameters associated with operation and/or operational monitoring of the implantable drug delivery device. In some embodiments, the processor may be configured to modify the current parameter I when one or more bellows sensors and/or detectors measure the current parameter I_{At present}Time phase correlated program. For example, the processor may reduce the current parameter I_{At present}The time between measurements of (a). The processor may also modify one or more of the first threshold criteria and the second threshold criteria consistent with the anomaly determination. In some embodiments, the abnormal operation procedure may further comprise incrementing a count threshold (i.e., a third threshold).

As another example, the second abnormal operation procedure may provide notification to the patient and/or clinician of an abnormal state of the implantable drug delivery device. Such notification may include sending a notification to an external programmer (e.g., a patient programmer and/or a clinician programmer). In some embodiments, the implantable drug delivery device may include a tactile feedback device (e.g., an oscillator), and the second abnormal operation procedure may include the processor activating the tactile feedback device to generate a vibration that is perceptible to the patient.

As another example, the third abnormal operating procedure may include operations that the processor may execute to determine a potential cause of an abnormal delivery of infusate to the patient. The third exception routine may be executed sequentially or concurrently with any other exception routine. In some embodiments, the processor may determine whether one or more of the elements of the implantable drug delivery device are potential causes of an abnormal operating state. Depending on the configuration of the implantable drug delivery system and the particular element or elements identified as affecting the operation of the implantable drug delivery device, the processor may initiate a program to correct or reconfigure the identified element or elements.

Referring to fig. 20, when the element is identified as a bellows, the processor may control the flow control devices 71 and/or 72 such that the flow control devices 71 and/or 72 may be used to regulate and meter the amount of infusate between the bellows 16 and the accumulator 30. For example, in response to identifying the bellows as the cause of an abnormal infusate dose, the processor implementing the third example abnormal operation procedure may close the flow control device 71 to prevent infusate from flowing between the bellows and the accumulator. Assuming that the first valve 26 is in the open position in anticipation of receiving infusate from the bellows, the processor may determine the amount of infusate that reaches the accumulator before closing the flow control device 71. The processor may then open the flow control device 71 to allow any additional infusion to flow to the accumulator in order to achieve a full dose. The processor may then open and close the flow control device 71 at a frequency that will allow a substantially similar amount of infusate to flow according to the current treatment protocol as if the bellows were operating normally. If both flow control devices 71 and 72 are implemented, the processor may further meter the flow of infusate between the flow control devices 71 and 72 such that both flow control devices 71 and 72 are not open at the same time.

As part of the abnormal operating sequence, a similar sequence may be implemented for the inlet valve 26 and the outlet valve 28, provided that the volume of infusate is still able to flow through each valve. For example, the processor may control the flow control device 73 in a similar manner that the inlet valve 26 is configured to operate, and the processor may control the flow control device 74 in a similar manner that the outlet valve 26 operates.

Alternatively, if the accumulator 30 and/or conduit 36 are identified, the processor implementing the abnormal operating procedure may control one or more of the flow control devices 71, 72, 73, 74, and 75 to prevent undesired damage to any of the other unaffected elements due to the infusate and/or operational modification of the accumulator 30 and/or conduit 36.

The above method descriptions and process flow diagrams are provided merely as illustrative examples and are not intended to require or imply that the blocks of the various aspects must all be performed in the order presented. Those skilled in the art will appreciate that the order of blocks in the above aspects may be performed in any order. The terms "thereafter," "then," "next," and the like are not intended to limit the order of the blocks; these words are used only to guide the reader through the description of the method. Further, references to diaphragm "up/upward" and "down/downward" movement are only used to refer to movement of the diaphragm in the orientation illustrated in the figures and are not intended to limit the scope of the claims with respect to a particular orientation of the device or diaphragm relative to the earth. Furthermore, any reference to an element in the singular (e.g., using the article "a/an" or "the") should not be construed as limiting the element to the singular.

The various illustrative logical blocks, modules, circuits, and algorithm blocks described in connection with the aspects disclosed herein may be implemented as electronic hardware, computer software, or combinations of both. To clearly illustrate this interchangeability of hardware and software, various illustrative components, blocks, modules, circuits, and blocks have been described above generally in terms of their functionality. Whether such functionality is implemented as hardware or software depends upon the particular application and design constraints imposed on the overall system. Skilled artisans may implement the described functionality in varying ways for each particular application, but such implementation decisions should not be interpreted as causing a departure from the scope of the present invention.

The previous description of the disclosed embodiments is provided to enable any person skilled in the art to make or use the present invention. Various modifications to these embodiments will be readily apparent to those skilled in the art, and the generic principles defined herein may be applied to other embodiments without departing from the spirit or scope of the invention. Thus, the present invention is not intended to be limited to the embodiments shown, but is to be accorded the widest scope consistent with the principles and novel features disclosed herein.

Claims

1. A method for determining whether a parameter change associated with an infusion within an implantable drug delivery device is normal, the method comprising:

measuring, by a processor, a current parameter associated with the infusate within a bellows of the implantable drug delivery device;

determining, by the processor, whether the measured current parameter is equal to or substantially equal to an expected parameter associated with an infusate expected to remain within the bellows;

determining, by the processor, whether the measured current parameter is greater than or equal to a first threshold in response to determining that the measured current parameter is not equal to or substantially not equal to the expected parameter;

in response to determining that the measured current parameter is greater than or equal to the first threshold, initiating, by the processor, a shutdown procedure, wherein the shutdown procedure comprises:

automatically closing, by the processor, one or more flow control devices within a fluid path of the implantable drug delivery device such that administration of the infusate to the patient is prevented.

2. The method of claim 1, wherein the shutdown procedure further comprises sending, by the processor, a notification over a wireless communication interface to an external device indicating that the implantable drug delivery device is operating in an abnormal state.

3. The method of claim 1, wherein the first threshold is indicative of a substantial failure of the implantable drug delivery device to administer infusate at a rate exceeding a prescribed dose.

4. The method of claim 1, wherein measuring the current parameter associated with the infusate is based on one or more outputs generated by one or more sensors associated with the infusate or the bellows.

5. The method of claim 1, wherein the current parameter associated with the infusate is selected from a volume of the infusate, an amount of the infusate, or a rate of change of the volume or the amount of the infusate within the bellows.

6. The method of claim 1, wherein the expected parameter comprises a desired amount or volume of infusate within the bellows.

7. The method of claim 1, wherein the expected parameter is based on at least one of:

parameters associated with a current treatment protocol, parameters associated with a previous treatment protocol, parameters associated with a future treatment protocol, parameters associated with the patient.

8. The method of claim 7, wherein the parameters associated with the current treatment protocol include at least one of:

a plurality of doses that can be administered using the maximum amount of infusate filled in the bellows, a dose administration time interval, information associated with the time at which the last dose of infusate was administered during the current treatment protocol, a plurality of doses previously administered during the current treatment protocol, or an amount of infusate consumed during the current treatment protocol.

9. The method of claim 7, wherein the expected parameters associated with the infusion that is expected to remain within the bellows are dynamically determined when the current treatment protocol is executed by the implantable drug device.

10. The method of claim 1, further comprising:

determining, by the processor, whether the current parameter is greater than a desired refill value associated with the infusate in response to determining that the measured current parameter is equal to or substantially equal to the expected parameter; and

in response to determining that the current parameter is not greater than the desired refill value:

initiating, by the processor, a refill procedure; and

determining, by the processor, a next current parameter associated with the infusate within the bellows.

11. The method of claim 10, wherein the refill procedure comprises one or more operations configured to notify the patient, clinician, or infusate provider of an impending refill time for the infusate.

12. The method of claim 10, further comprising:

determining, by the processor, a next current parameter associated with the infusate within the bellows in response to determining that the current parameter is greater than the desired refill value.

13. The method of claim 1, further comprising:

determining, by the processor, whether the current parameter is greater than or equal to a second threshold in response to determining that the measured current parameter is not greater than or equal to the first threshold,

wherein the second threshold is indicative of a current infusate usage that exceeds the expected infusate usage by an amount that is not dangerous for a period of time.

14. The method of claim 13, further comprising:

in response to determining that the measured current parameter is not greater than or equal to the second threshold, determining and recording, by the processor, information related to the observed total dose for subsequent reporting to an external device.

15. The method of claim 13, further comprising, in response to determining that the current parameter is greater than or equal to a second threshold:

determining, by the processor, whether a count of a number of detected abnormal dose measurements is less than a third threshold; and

initiating, by the processor, an abnormal operating procedure in response to determining that the count of the number of detected abnormal dose measurements is not less than the third threshold.

16. The method of claim 15, further comprising:

incrementing the count in response to determining that the count of the number of detected abnormal dose measurements is less than the third threshold.

17. The method of claim 1, wherein automatically closing one or more flow control devices comprises metering a flow of infusate between a first flow control device and a second flow control device such that at least one of the first flow control device and the second flow control device is closed.

18. The method of claim 1, wherein the shut-down procedure further comprises determining a volume of infusate reaching a reservoir of the device before the flow control device is closed.

19. The method of claim 1, further comprising:

receiving, by the processor, an indication that the bellows is filled with infusate;

in response to receiving the indication that the bellows is filled with an infusate, determining, by the processor, an initial parameter associated with the infusate, wherein the initial parameter is determined based on output from one or more sensors associated with the bellows;

determining, by the processor, a parameter associated with a treatment protocol based on the determined initial parameter; and

initiating, by the processor, the determined treatment protocol.

20. An implantable drug delivery device, comprising:

a bellows configured as a reservoir of infusate;

an accumulator coupled to the bellows and including a diaphragm chamber and a diaphragm that deflects within the diaphragm chamber to dispense the infusate to a patient;

at least one bellows sensor; and

a processor coupled to the at least one bellows sensor and configured with processor-executable instructions to perform operations comprising:

obtaining a first sensor output from a bellows sensor having a parameter related to a volume of infusate within a bellows of the implantable drug delivery device;

measuring a current parameter associated with the infusate within the bellows using an output from the at least one bellows sensor;

determining whether the measured current parameter is equal to or substantially equal to an expected parameter associated with an infusate expected to remain within the bellows;

in response to determining that the measured current parameter is not equal to or substantially not equal to the expected parameter, determining whether the measured current parameter is greater than or equal to a first threshold; and

initiating a shutdown procedure in response to determining that the measured current parameter is greater than or equal to the first threshold, wherein

The shutdown procedure includes:

automatically closing one or more flow control devices within a fluid path of the implantable drug delivery device such that administration of the infusate to the patient is prevented.