Fluid delivery system and method

Abstract

To provide a method for dispensing liquid.SOLUTION: A method of dispensing fluid includes three processes. A first one of these processes includes a step of pumping fluid into a resilient variable-volume dispensing chamber. The dispensing chamber is in series with a normally present finite fluid impedance and an output. The impedance is sufficient so as to cause expansion of the dispensing chamber as it receives pumped fluid even while some fluid flows through the output. Another one of these processes includes a step of repeatedly measuring a parameter related to volume of the dispensing chamber over time. A third one of these processes includes a step of controlling the pumping of fluid based on repeated measurements of the parameter to produce a desired fluid flow through the output. A corresponding system for dispensing fluid implements these processes.SELECTED DRAWING: Figure 1

Description

Technical Field

[0001] This application generally relates to pumping fluid delivery systems and methods using a boosting assembly.

Background Art

[0002] Many potentially beneficial drugs or compounds, including biologic agents, are not orally effective due to low absorption rates, hepatic metabolism, or other pharmacokinetic factors. Further, some therapeutic compounds can be absorbed orally, but sometimes require frequent administration, and maintaining a desired schedule can be difficult for patients. In such cases, parenteral delivery is often employed or can be employed.

[0003] Drug delivery, including percutaneous puncture of the skin by a needle or stylet, is an effective parenteral route for other fluids and compounds such as subcutaneous injection, intramuscular injection, and intravenous (IV) administration. Insulin is an example of a therapeutic fluid self-injected by millions of diabetic patients. Users of drugs delivered parenterally would benefit from a wearable device that automatically delivers the required drug / compound over a period of time.

[0004] To achieve this goal, efforts have been made to design portable devices for the controlled release of therapeutic agents. Such devices are known to have a reservoir such as a cartridge, syringe, or bag and be electronically controlled. These devices suffer from several drawbacks including a failure rate. Also, reducing the size, weight, and cost of these devices remains an ongoing challenge.

Summary of the Invention

Means for Solving the Problems

[0005] In one embodiment, the present invention provides a method for dispensing a fluid. In this embodiment, the method includes three processes. The first of these processes includes pumping a fluid into an elastically variable volume dispensing chamber. The dispensing chamber is in series with a normally present finite fluid impedance and a discharge port. The impedance is sufficient to cause an expansion of the dispensing chamber while receiving the pumped fluid even while a portion of the fluid flows through the discharge port. Another of these processes includes repeatedly measuring over time a parameter related to the volume of the dispensing chamber. The third of these processes includes controlling the pumping of the fluid based on the repeated measurements of the parameter to produce a desired fluid flow through the discharge port.

[0006] In related embodiments, the step of repeatedly measuring the parameter includes acoustically exciting a gas within an acoustically continuous region to produce an acoustic response therein. The region includes a sub-region connected to the dispensing chamber such that a change in the volume of the dispensing chamber causes a change in the volume of the sub-region. This embodiment also includes characterizing the acoustic response. In further related embodiments, the step of acoustically exciting the gas is performed at only a single frequency. Also, the step of characterizing the acoustic response includes determining a phase relationship between the acoustic response measured at a first position within the acoustically continuous region and a reference value at the single frequency. The method of this embodiment further includes calculating a change in the volume of the sub-region based on the time evolution of the phase relationship.

[0007] Alternatively or additionally, the impedance is a passive impedance. The passive impedance may optionally include a conduit. The conduit may have any of several forms. It may include a coiled tube. The coiled tube may include at least two turning points. Alternatively or additionally, the conduit has a meandering shape.

[0008] Alternatively or additionally, the conduit has a length and an inner diameter selected to provide a predetermined impedance based on at least one of the viscosity and density of the fluid. Optionally, the inner diameter is of sufficient size to prevent blockage due to the flow of the therapeutic agent through the conduit. Optionally, the conduit has a length greater than 2 cm.

[0009] In a further embodiment, the method includes providing an infusion line connectable to an upstream fluid source. The infusion line is in fluid communication downstream with a pumping chamber. The pumping chamber has a pump outlet. The method also includes operating a pressurizing assembly to restrict backflow of fluid into the inlet while pressurizing the pumping chamber and biasing flow toward the pump outlet.

[0010] In a related embodiment, operating the pressurizing assembly includes utilizing movement of the pressurizing assembly between work strokes to restrict backflow and pressurize the pumping chamber in a single mechanical action. In a further related embodiment, backflow is restricted by a given mobility of the pressurizing assembly and the pumping chamber is pressurized by a greater mobility.

[0011] In a further related embodiment, operating the pressurizing assembly includes restricting backflow of fluid to the fluid source by closing the infusion line. Alternatively or additionally, the method also includes using a passive valve interposed to prevent reverse flow of fluid from the dispensing chamber into the pumping chamber.

[0012] In another related embodiment, a portion of the pumped fluid may be returned to the fluid source (e.g., an unpressurized fluid reservoir) without flowing into the dispensing chamber, for example, by providing a shunt line returning from the pump outlet to the fluid source.

[0013] In another related embodiment, the three processes described above are performed by components within a housing of patch size. The housing has a maximum dimension and the conduit has a length exceeding the maximum dimension.

[0014] Optionally, the conduit includes a length and an inner diameter selected to provide a predetermined impedance based on at least one of the viscosity and density of the fluid. Also optionally, the dispensing chamber has an inlet, and the conduit has an inner diameter smaller than the inner diameter of the dispensing chamber inlet.

[0015] In another embodiment, the present invention provides an apparatus for dispensing a fluid. In this embodiment, the apparatus includes a housing of patch size, a pump enclosed within the housing, and a dispensing assembly downstream of the pump in fluid communication with the pump. The dispensing assembly has an elastic dispensing chamber and a sensor for quantitatively measuring a parameter related to the volume of the dispensing chamber or the derivative of the volume with respect to time. The pump pulsates to discharge fluid to expand the elastic dispensing chamber every cycle, and the chamber repeatedly delivers fluid to the outlet. The apparatus also includes a control loop connected to the sensor and the pump for controlling the operation of the pump during normal flow conditions so as to achieve the delivery of a fluid having a desired cumulative volume. The loop includes a control device for determining the cumulative volume of the fluid delivered through the outlet based on the measured parameter.

[0016] Further related embodiments also include an acoustic energy source that acoustically excites a gas within an acoustically continuous region to produce an acoustic response therein. The region includes a sub-region connected to the dispensing chamber, such that a change in the volume of the dispensing chamber causes a change in the volume of the sub-region. Further, this embodiment includes a processor, and the sensor includes a first acoustic transducer placed at a first position within the acoustically continuous region for generating an electrical signal based on the acoustic response. The processor is connected to the first acoustic transducer and a reference value, and implements a flow rate determination process for determining an amount related to the volume change of the sub-region based on the acoustic response.

[0017] Optionally, the acoustic energy source excites the gas with only a single frequency, the electrical signal generated by the first acoustic transducer has a phase relationship with respect to a reference value, and further, the flow rate determination process determines an amount related to the volume change of the sub-region based on the temporal evolution of the phase relationship.

[0018] Optionally, in addition, the device of the present embodiment further includes a finite fluid impedance connected to the outlet. The impedance is sufficient to allow such an expansion of the elastic dispensing chamber. Also optionally, the impedance is a passive impedance. The passive impedance may optionally include a conduit. In the case of the above-described method, the conduit may have any of several forms. It may include a coiled tube. The coiled tube may include at least two turning points. Alternatively or additionally, the conduit has a meandering shape.

[0019] Alternatively or additionally, the conduit has a length and an inner diameter selected to provide a predetermined impedance based on at least one of the viscosity and density of the fluid. Optionally, the inner diameter is of sufficient size to prevent blockage due to the flow of the therapeutic agent flowing through the conduit. Optionally, the conduit has a length greater than 2 cm.

[0020] In a further related embodiment, the housing has a maximum dimension and the conduit has a length exceeding the maximum dimension. Optionally, the dispensing chamber has an inlet and the conduit has an inner diameter smaller than the inner diameter of the dispensing chamber inlet.

[0021] Optionally, the present invention provides a system for pumping fluid through a line. In this embodiment, the system includes a pumping chamber having a connectable inlet for providing fluid communication with a fluid source and a pump outlet. The system also includes a force application assembly adapted to provide a compression stroke to the pumping chamber. In this embodiment, the compression stroke restricts the backflow of fluid from the pumping chamber to the inlet while urging the fluid from the pumping chamber to the pump outlet.

[0022] Optionally, the boosting assembly is connected to the inlet valve actuator and the pump actuator such that when the compression stroke causes fluid to be urged from the pumping chamber to the pump discharge port by the pump actuator, the inlet valve connected between the inlet and the fluid source is actuated to close the valve.

[0023] Optionally, the boosting assembly includes a plate connected to a valve actuator, a pump actuator, and a motor for the coordinated operation of the valve actuator and the pump actuator. Optionally, the motor includes a shape memory actuator. Also optionally, the motor includes at least one pulley for bending the shape memory actuator and fitting it within a reusable portion. Optionally, the boosting assembly includes a motor.

[0024] Additionally or alternatively, a shunt line is provided that is in fluid communication with the pump discharge port and a fluid source (e.g., an unpressurized fluid reservoir) to return a portion of the fluid discharged by the pump to the fluid source.

[0025] In another embodiment, the present invention provides an apparatus for dispensing fluid, the apparatus including a housing of patch size. The housing encloses a pressurized fluid source in series with a downstream flow resistance distortion conduit.

[0026] In a further related embodiment, the apparatus further includes a sensor for measuring a parameter related to the fluid flow rate in the conduit and a control loop for adjusting the fluid flow rate based on the measured parameter.

[0027] Optionally, the source includes a pump operably connected to provide pressurized fluid to a downstream flow resistance distortion conduit. Also optionally, the apparatus includes a sensor for measuring a parameter related to the fluid flow rate in the conduit and a control loop for adjusting the operation of the pump based on the measured parameter.

[0028] Optionally, the present invention provides a system for pumping fluid through a line. In this embodiment, the system includes a pumping chamber having a connectable inlet for providing fluid communication with a fluid source, and a pump outlet. The system also includes a biasing assembly adapted to provide a compression stroke to the pumping chamber. In this embodiment, the compression stroke restricts backflow of fluid from the pumping chamber to the inlet while urging fluid from the pumping chamber to the pump outlet.

[0029] Optionally, the biasing assembly is connected to an inlet valve actuator and a pump actuator such that when the compression stroke urges fluid from the pumping chamber to the pump outlet by the pump actuator, it actuates an inlet valve connected between the inlet and the fluid source and closes the valve.

[0030] Optionally, the biasing assembly includes a valve actuator, a pump actuator, and a plate connected to the valve actuator, the pump actuator, and a motor for the coordinated operation of the valve actuator and the pump actuator. Optionally, the motor includes a shape memory actuator. Optionally, the motor includes at least one pulley for bending the shape memory actuator and fitting it within a reusable portion. Optionally, the biasing assembly includes a motor.

[0031] Additionally or alternatively, a shunt line fluidly communicating the pump outlet with a fluid source (e.g., an unpressurized fluid reservoir) may be provided to return a portion of the fluid discharged by the pump to the fluid source.

[0032] In a further related embodiment, the source further includes an unpressurized reservoir operatively connected to provide fluid to the pump.

[0033] As in the above-described embodiments, the flow-inhibiting tortuous conduit may be implemented in various ways. For example, it may be coiled and may include at least two turning points. Alternatively or additionally, the flow-inhibiting tortuous conduit has a meandering shape. Optionally, the housing includes a disposable portion having an integral fluid path with the flow-inhibiting tortuous conduit. Also optionally, the conduit is disposed within the housing. Optionally, the conduit has a length and an inner diameter selected to provide a predetermined impedance based on at least one of the viscosity and density of the fluid. Optionally, the inner diameter is large enough to prevent blockage due to the flow of the therapeutic agent through the conduit. Optionally, the conduit has a length greater than 2 cm. Optionally, the housing has a maximum dimension and the conduit has a length greater than the maximum dimension.

[0034] In further related embodiments, the device additionally includes a dispensing chamber in fluid communication with the source and the conduit. The dispensing chamber includes an inlet for receiving fluid from the source and an outlet through which the fluid is provided to the conduit. Optionally, the conduit has an inner diameter smaller than the inner diameter of the dispensing chamber inlet.

[0035] Alternatively or additionally, the dispensing chamber is an elastically variable volume dispensing chamber. Optionally, the conduit has an effective diameter smaller than the effective diameter of the inlet.

[0036] Optionally, the present invention provides a system for pumping fluid through a line. In this embodiment, the system includes a pumping chamber having a connectable inlet for providing fluid communication with a fluid source and a pump outlet. The system also includes a biasing assembly adapted to provide a compression stroke to the pumping chamber. In this embodiment, the compression stroke restricts backflow of fluid from the pumping chamber to the inlet while urging fluid from the pumping chamber to the pump outlet.

[0037] Optionally, the boosting assembly, by being connected to the inlet valve actuator and the pump actuator, closes the inlet valve connected between the inlet and the fluid source when the compression stroke biases fluid from the pumping chamber to the pump discharge port by the pump actuator.

[0038] Optionally, the boosting assembly includes a plate connected to a valve actuator, a pump actuator, and a motor for the coordinated operation of the valve actuator and the pump actuator. Optionally, the motor includes a shape memory actuator. Also optionally, the motor includes at least one pulley for bending the shape memory actuator and fitting it within a reusable portion. Optionally, the boosting assembly includes a motor.

[0039] Additionally or alternatively, a shunt line fluidly communicating the pump discharge port with a fluid source (e.g., a non-pressurized fluid reservoir) may be provided to return a portion of the fluid discharged by the pump to the fluid source.

[0040] In another embodiment, the present invention provides an apparatus for dispensing fluid. The apparatus includes a housing of patch size and a pump disposed within the housing. The pump has a pump discharge port. The apparatus further includes a dispensing chamber disposed within the housing as well. The dispensing chamber has a dispensing inlet and a dispensing outlet. The dispensing inlet is connected to the pump discharge port. The apparatus also includes a distortion conduit connected to the dispensing outlet to provide a flow impedance.

[0041] Optionally, the apparatus includes a sensor for measuring a parameter related to the fluid flow rate in the conduit and a control loop for adjusting the fluid flow rate based on the measured parameter. Also optionally, the apparatus further includes a non-pressurized reservoir disposed within and operably connected to the housing to provide fluid to the pump inlet.

[0042] As in the foregoing embodiments, the tortuous conduit may be implemented in various ways. For example, it may be coiled. It may include at least two turning points. Alternatively or additionally, the tortuous conduit has a meandering shape. Optionally, the conduit is arranged with the housing. Optionally, the housing includes a disposable portion having an integrated fluid path with the tortuous conduit. Optionally, the conduit has a length exceeding 2 cm. Optionally, the housing has a maximum dimension and the conduit has a length exceeding the maximum dimension. Optionally, the conduit has a length and an inner diameter selected to provide a predetermined impedance based on at least one of the viscosity and density of the fluid. Optionally, the conduit has a length and an inner diameter selected to provide a predetermined impedance based on at least one of the viscosity and density of the fluid. Optionally, the inner diameter is large enough to prevent blockage due to the flow of the therapeutic agent through the conduit.

[0043] Optionally, the dispensing chamber is an elastically variable volume dispensing chamber. Also optionally, the dispensing chamber has an inlet and the conduit has an inner diameter smaller than the inner diameter of the dispensing chamber inlet.

[0044] In another embodiment, the present invention provides a method for measuring the fluid flow rate delivered through a line. The method of this embodiment includes acoustically exciting a gas within an acoustically continuous region at only a single frequency during a change in the volume of a sub-region of the acoustically continuous region caused by fluid flow in a band connected to the volume of the sub-region, to produce an acoustic response. Further, the method includes determining the phase relationship between the acoustic response measured at a first position within the acoustically continuous region and a reference value at a single frequency, calculating the change in volume of the sub-region based on the temporal evolution of the phase relationship, and inferring a measured value of the fluid flow rate through the line based on the change in volume of the gas within the sub-region.

[0045] Optionally, the method further includes measuring a reference value at a second position within the acoustically continuous region. Also optionally, the band is connected to the volume of the sub-region via a membrane.

[0046] In further related embodiments, the step of acoustically exciting the gas includes the step of driving a transducer. Optionally, the step of acoustically exciting the gas includes the step of driving a speaker. This embodiment optionally includes the step of calibrating a phase relationship as a function of the volume of the sub-region. Optionally, the acoustically continuous region has a volume of less than 200 microliters. In a further embodiment, the acoustically continuous region has a volume of less than 130 microliters. In another further embodiment, the acoustically continuous region has a volume of less than 10 microliters.

[0047] Optionally, the step of calculating a volume change includes the step of determining such a change having a resolution better than 20 nanoliters. In a further embodiment, the step of calculating a volume change includes the step of determining such a change having a resolution better than 15 nanoliters. In a further embodiment, the step of calculating a volume change includes the step of determining such a change having a resolution better than 13 nanoliters. In another further embodiment, the step of calculating a volume change includes the step of determining such a change having a resolution of at least 1 / 10000 of the volume of the acoustically continuous region.

[0048] Optionally, the single frequency is the resonance frequency of the sub-region or close thereto.

[0049] In further related embodiments, the method further includes the step of performing a calibration step by acoustically exciting the region at a series of frequencies and determining a transfer function that characterizes the phase relationship between the acoustic response measured at a first position within the acoustically continuous region and the respective reference values of the series of frequencies as a function of frequency.

[0050] Optionally, the method further includes measuring a respective reference value of a series of frequencies at a second position within an acoustically continuous region. Alternatively or additionally, the method further includes detecting the presence of bubbles based on a transfer function. Optionally, the method further includes entering an alarm state based on detecting the presence of bubbles. Optionally, the step of calculating the volume change is performed repeatedly during the measurement phase, and the measurement phase is performed alternately with the calibration phase. In a further related embodiment, the fluid is delivered per cycle, and the calibration and measurement phases cooperate with the cycle.

[0051] In another embodiment, the present invention provides a system for measuring the fluid flow rate delivered through a line. In this embodiment, the system acoustically excites the gas within the acoustically continuous region at only a single frequency during a change in the volume of the sub-region of the acoustically continuous region caused by fluid flow in a band coupled to the volume of the sub-region, to produce an acoustic response, and includes an acoustic energy source for this purpose. The system also includes a first acoustic transducer placed at a first position within the acoustically continuous region for generating an electrical signal based on the acoustic response. The electrical signal of the first acoustic transducer has a phase relationship with respect to the reference value. The system also includes a processor coupled to the first acoustic transducer and the reference value, for implementing a flow rate determination process for determining an amount related to the volume change of the sub-region based on the temporal evolution of the phase relationship, and inferring a measured value of the fluid flow rate flowing through the line based on the volume change of the gas within the sub-region.

[0052] Optionally, the system further includes a second acoustic transducer placed at a second position within the acoustically continuous region for generating an electrical signal constituting the reference value. Optionally, the system also has a power consumption of less than 500 joules per day.

[0053] In a further related embodiment, a fluid delivery system is provided that utilizes a system for measuring the fluid flow rate delivered through a line, in accordance with the above-described embodiments. The fluid delivery system of this embodiment causes the flow of fluid delivered through the line and additionally includes a pump coupled to a processor.

[0054] Optionally, the present invention provides a system for pumping fluid through a line. In this embodiment, the system includes a pumping chamber having a connectable inlet for providing fluid communication with a fluid source and a pump outlet. The system also includes a force - applying assembly adapted to provide a compression stroke to the pumping chamber. In this embodiment, the compression stroke restricts the back - flow of fluid from the pumping chamber to the inlet while urging the fluid from the pumping chamber to the pump outlet.

[0055] Optionally, the force - applying assembly is coupled to an inlet valve actuator and a pump actuator such that when the compression stroke urges fluid from the pumping chamber to the pump outlet by the pump actuator, it actuates an inlet valve connected between the inlet and the fluid source and closes the valve.

[0056] Optionally, the force - applying assembly includes a plate coupled to a valve actuator, a pump actuator, and a motor for the coordinated operation of the valve actuator and the pump actuator. Optionally, the motor includes a shape - memory actuator. Also optionally, the motor includes at least one pulley for bending the shape - memory actuator and fitting it within a reusable portion. Optionally, the force - applying assembly includes the motor.

[0057] Power consumption by the processor does not substantially exceed power consumption by the pump. Optionally, the system further includes a membrane connecting a band to the volume of a sub - region. Also optionally, the acoustic energy source includes an acoustic transducer coupled to an electrical signal. Optionally, the transducer is a speaker.

[0058] In further related embodiments, the processor implements a calibration process to calibrate the phase relationship as a function of the volume of the sub-region. Optionally, the acoustically continuous region has a volume of less than 200 microliters. In further embodiments, the acoustically continuous region has a volume of less than 130 microliters. In another further embodiment, the acoustically continuous region has a volume of less than 10 microliters.

[0059] Alternatively or additionally, the flow rate determination process determines a quantity related to a volume change corresponding to a resolution better than 20 nanoliters. In further embodiments, the flow rate determination process determines a quantity related to a volume change corresponding to a resolution better than 15 nanoliters. In further embodiments, the flow rate determination process determines a quantity related to a volume change corresponding to a resolution better than 13 nanoliters. In another further embodiment, the flow rate determination process determines a quantity related to a volume change corresponding to a resolution of at least 1 / 10,000 of the volume of the acoustically continuous region.

[0060] Optionally, the single frequency is the resonance frequency of the sub-region or close thereto. In further embodiments, the acoustic source includes an acoustic radiation transducer coupled to the processor. Further, the processor implements a calibration process to acoustically excite the region with a series of frequencies at the acoustic source, and as part of such a process, the processor determines a transfer function that characterizes the phase relationship between the electrical signal of the first transducer and each reference value of the series of frequencies as a function of frequency.

[0061] In further embodiments, the processor implements a bubble detection process to detect the presence of bubbles based on the transfer function. Optionally, the bubble detection process places the system in an alarm state based on the step of detecting the presence of bubbles.

[0062] In further embodiments, the flow rate determination process is performed repeatedly during the measurement phase, and the measurement phase is performed alternately with the calibration phase. Optionally, the fluid is delivered every cycle, and the calibration and measurement phases are coordinated with the cycle.

[0063] These aspects of the invention are not meant to be exclusive, and other features, aspects, and advantages of the invention will be readily apparent to those skilled in the art by a careful reading in connection with the appended claims and the accompanying drawings. For example, the present invention provides the following items. (Item 1) (a) Pumping fluid into an elastically variable volume dispensing chamber, the dispensing chamber being in series with a normally present finite fluid impedance and a discharge port, the impedance being sufficient to cause expansion of the dispensing chamber while receiving the pumped fluid even while a portion of the fluid flows through the discharge port; (b) Repeatedly measuring over time a parameter related to the volume of the dispensing chamber; (c) Controlling the pumping of the fluid based on the repeated measurements of the parameter to cause a desired fluid flow through the discharge port A method of dispensing fluid, comprising: (Item 2) The step of repeatedly measuring the parameter comprises: Acoustically exciting a gas within an acoustically continuous region to produce an acoustic response within the region, the region including a sub-region connected to the dispensing chamber such that a change in the volume of the dispensing chamber causes a change in the volume of the sub-region; Characterizing the acoustic response; The method according to Item 1, comprising: (Item 3) The step of acoustically exciting the gas is performed at only a single frequency, and the step of characterizing the acoustic response includes determining a phase relationship between the acoustic response when measured at a first location in the acoustically continuous region and a reference value of the single frequency, and the method further includes calculating a change in the volume of the sub-region based on the temporal evolution of the phase relationship. The method according to Item 2. (Item 4) The method according to item 1, wherein the impedance is a passive impedance. (Item 5) The method according to item 4, wherein the passive impedance includes a conduit. (Item 6) The method according to item 5, wherein the conduit includes a coiled tube. (Item 7) The method according to item 6, wherein the coiled tube includes at least two turning points. (Item 8) The method according to item 5, wherein the conduit has a serpentine shape. (Item 9) The method according to item 5, wherein the conduit has a length and an inner diameter selected to provide a predetermined impedance based on at least one of the viscosity and density of the fluid. (Item 10) The method according to item 9, wherein the inner diameter is large enough to prevent blockage due to the flow of the therapeutic agent flowing through the conduit. (Item 11) The method according to item 10, wherein the conduit has a length exceeding 2 cm. (Item 12) The method according to item 5, wherein processes (a), (b), and (c) are performed by components within a housing of a patch size, the housing has a maximum dimension, and the conduit has a length exceeding the maximum dimension. (Item 13) The method according to item 5, wherein the conduit includes a length selected to provide a predetermined impedance based on at least one of the viscosity and density of the fluid. (Item 14) The method according to item 5, wherein the dispensing chamber has an inlet, and the conduit has an inner diameter smaller than the inner diameter of the dispensing chamber inlet. (Item 15) The step of pumping the fluid is providing an injection line connectable to an upstream fluid source, the injection line being in fluid communication downstream with a pumping chamber, the pumping chamber having a pump discharge port, and the step Actuating the boosting assembly to pressurize the pumping chamber while restricting backflow of fluid into the injection port and biasing flow toward the pump discharge port, and The method of claim 1, comprising: (Item 16) The step of actuating the boosting assembly includes restricting backflow using movement of the boosting assembly during a working stroke and pressurizing the pumping chamber in a single mechanical action, the method of claim 15. (Item 17) Restricting backflow according to a given mobility of the boosting assembly and pressurizing the pumping chamber according to a greater mobility, the method of claim 16. (Item 18) The step of actuating the boosting assembly includes restricting backflow to the fluid source by closing the injection line, the method of claim 15. (Item 19) Further comprising preventing reverse flow of fluid from the dispensing chamber to the pumping chamber using a passive valve disposed between the dispensing chamber and the pumping chamber, the method of claim 15. (Item 20) The step of pumping fluid further includes enabling a portion of the fluid to return to the fluid source without flowing into the dispensing chamber, the method of claim 1. (Item 21) A housing of patch size, and A pump contained within the housing, and A dispensing assembly downstream of the pump in fluid communication with the pump, the dispensing assembly having an elastic dispensing chamber and a sensor for quantitatively measuring a parameter of the volume of the dispensing chamber or the derivative of the volume with respect to time, the pump pulsatingly discharging fluid to expand the elastic dispensing chamber each cycle, the chamber repeatedly delivering fluid to an outlet. A control loop coupled to the sensor and the pump for controlling the operation of the pump during normal flow conditions based on the measured parameters so as to achieve delivery of a fluid having a desired cumulative volume, the control loop including a control device for determining the cumulative volume of the fluid delivered through the outlet based on the measured parameters An apparatus for dispensing a fluid, comprising (Item 22) An acoustic energy source for acoustically exciting a gas within an acoustically continuous region and generating an acoustic response within the region, the region including a sub-region coupled to the dispensing chamber such that a change in volume of the dispensing chamber causes a change in volume of the sub-region A processor Further comprising The sensor is placed at a first position within the acoustically continuous region and includes a first acoustic transducer for generating an electrical signal based on the acoustic response The processor is coupled to the first acoustic transducer and a reference value and implements a flow rate determination process for determining an amount related to a change in volume of the sub-region based on the acoustic response, the apparatus according to item 21 (Item 23) The acoustic energy source excites the gas at only a single frequency, the electrical signal generated by the first acoustic transducer has a phase relationship with the reference value, and the flow rate determination process determines an amount related to a change in volume of the sub-region based on a temporal evolution of the phase relationship, the apparatus according to item 22 (Item 24) A finite fluid impedance coupled to the outlet, the apparatus according to item 21, further comprising a finite fluid impedance sufficient to allow such expansion of the elastic dispensing chamber (Item 25) The impedance is a passive impedance, the apparatus according to item 24 (Item 26) The passive impedance includes a conduit, the apparatus according to item 25 (Item 27) The catheter is the device according to item 26, including a coiled tube. (Item 28) The coiled tube is the device according to item 27, including at least two conversion points. (Item 29) The catheter is the device according to item 26, having a meandering shape. (Item 30) The catheter is the device according to item 26, having a length and an inner diameter selected to provide a predetermined impedance based on at least one of the viscosity and density of the fluid. (Item 31) The inner diameter is of sufficient size to prevent blockage due to the flow of the therapeutic agent flowing through the catheter, which is the device according to item 30. (Item 32) The catheter is the device according to item 31, having a length exceeding 2 cm. (Item 33) The housing has a maximum dimension, and the catheter is the device according to item 26, having a length exceeding the maximum dimension. (Item 34) The dispensing chamber has an injection port, and the catheter is the device according to item 26, having an inner diameter smaller than the inner diameter of the dispensing chamber injection port. (Item 35) The pump has a pumping chamber having a connectable injection port for providing fluid communication with a fluid source and a pump discharge port, and a biasing assembly adapted to provide a compression stroke to the pumping chamber and includes, by the compression stroke, biasing the fluid from the pumping chamber to the pump discharge port while restricting the backflow of the fluid from the pumping chamber to the injection port, which is the device according to item 21. (Item 36) The apparatus of claim 35, wherein said boosting assembly is coupled to an inlet valve actuator and a pump actuator such that when said pump actuator urges fluid from said pumping chamber to said pump discharge port, said compression stroke actuates an inlet valve coupled between said inlet and said fluid source and closes said valve. (Claim 37) The apparatus of claim 36, wherein said boosting assembly includes a plate coupled to said valve actuator, said pump actuator, and a motor for coordinated operation of said valve actuator and said pump actuator. (Claim 38) The apparatus of claim 37, wherein said motor includes a shape memory actuator. (Claim 39) The apparatus of claim 38, wherein said motor includes at least one pulley for bending said shape memory actuator for insertion within a reusable portion. (Claim 40) The apparatus of claim 21, further comprising a shunt line in fluid communication with said pump discharge port and said fluid source and capable of returning a portion of said fluid discharged by said pump to said fluid source. (Claim 41) The apparatus of claim 40, wherein said fluid source includes an unpressurized fluid reservoir. (Claim 42) An apparatus for dispensing fluid, comprising a housing of patch size enclosing a pressurized fluid source in series with a downstream flow resistance distortive conduit. (Claim 43) A sensor for measuring a parameter related to the flow rate of fluid to said conduit, a control loop for adjusting the flow rate of said fluid based on said measured parameter and further comprising the apparatus of claim 42. (Claim 44) The apparatus of claim 42, wherein said source includes a pump operatively coupled to provide pressurized fluid to said downstream flow resistance distortive conduit. (Claim 45) The pump is A pumping chamber having an inlet connectable to provide fluid communication with a fluid source and a pump outlet, A boosting assembly adapted to provide a compression stroke to the pumping chamber, and The apparatus according to item 44, comprising, wherein the compression stroke biases fluid from the pumping chamber to the pump outlet while restricting backflow of fluid from the pumping chamber to the inlet. (Item 46) The apparatus according to item 45, wherein the boosting assembly is coupled to an inlet valve actuator and a pump actuator, and when the pump actuator biases fluid from the pumping chamber to the pump outlet, the compression stroke actuates an inlet valve connected between the inlet and the fluid source and closes the valve. (Item 47) The apparatus according to item 46, wherein the boosting assembly includes a plate coupled to the valve actuator, the pump actuator, and a motor for coordinated operation of the valve actuator and the pump actuator. (Item 48) The apparatus according to item 47, wherein the motor includes a shape memory actuator. (Item 49) The apparatus according to item 48, wherein the motor includes at least one pulley for bending the shape memory actuator for insertion into a reusable part. (Item 50) The apparatus according to item 44, further comprising a shunt line in fluid communication with the pump outlet and the fluid source and capable of returning a portion of the fluid discharged by the pump to the fluid source. (Item 51) The apparatus according to item 50, wherein the fluid source includes an unpressurized fluid reservoir. (Item 52) A sensor for measuring a parameter related to the fluid flow rate to the conduit, and A control loop for adjusting the fluid flow rate based on the measured parameter. The device according to item 44, further comprising (Item 53) The device according to item 44, wherein the source includes a pump operably connected to provide pressurized fluid to the downstream flow-inhibiting and distorting conduit. (Item 54) The device according to item 42, wherein the flow-inhibiting and distorting conduit includes a coiled tube. (Item 55) The device according to item 54, wherein the coiled tube includes at least two turning points. (Item 56) The device according to item 42, wherein the conduit has a meandering shape. (Item 57) The device according to item 42, wherein the housing includes a disposable portion having an integrated fluid path with the flow-inhibiting and distorting conduit. (Item 58) The device according to item 42, wherein the conduit is disposed within the housing. (Item 59) The device according to item 42, wherein the conduit has a length and an inner diameter selected to provide a predetermined impedance based on at least one of the viscosity and density of the fluid. (Item 60) The device according to item 42, wherein the inner diameter is large enough to prevent blockage due to the flow of the therapeutic agent through the conduit. (Item 61) The device according to item 42, wherein the conduit has a length exceeding 2 cm. (Item 62) The device according to item 42, wherein the housing has a maximum dimension, and the conduit has a length exceeding the maximum dimension. (Item 63) The device according to item 42, further comprising a dispensing chamber having an inlet in fluid communication with the source to receive fluid from the source and an outlet through which the fluid is provided to the conduit. (Item 64) The device according to item 63, wherein the conduit has an inner diameter smaller than the inner diameter of the dispensing chamber inlet. (Item 65) The device according to item 63, wherein the dispensing chamber is an elastic variable volume dispensing chamber. (Item 66) The device according to item 63, wherein the conduit has an effective diameter smaller than the effective diameter of the injection port. (Item 67) A housing with a patch size, A pump disposed within the housing and having a pump discharge port, A dispensing chamber disposed within the housing in the same manner and having a dispensing inlet and a dispensing outlet, wherein the dispensing inlet is connected to the pump discharge port, A distorted conduit connected to the dispensing outlet and providing a flow impedance And a device for dispensing a fluid. (Item 68) A sensor for measuring a parameter related to the fluid flow rate in the conduit, A control loop for adjusting the fluid flow rate based on the measured parameter, The device according to item 67, further comprising. (Item 69) The device according to item 67, further comprising a non-pressurized reservoir disposed within the housing and operably connected to provide fluid to the inlet of the pump. (Item 70) The device according to item 67, wherein the distorted conduit includes a coiled tube. (Item 71) The device according to item 70, wherein the coiled tube includes at least two turning points. (Item 72) The device according to item 67, wherein the distorted conduit has a meandering shape. (Item 73) The device according to item 67, wherein the housing includes a disposable portion having an integrated fluid path including the distorted conduit. (Item 74) The device according to item 67, wherein the conduit is disposed within the housing. (Item 75) The device according to item 67, wherein the conduit has a length exceeding 2 cm. (Item 76) The apparatus according to item 67, wherein the housing has a maximum dimension and the conduit has a length exceeding the maximum dimension. (Item 77) The apparatus according to item 67, wherein the conduit includes an effective diameter selected to provide a predetermined impedance based on at least one of the viscosity and density of the fluid. (Item 78) The apparatus according to item 67, wherein the conduit has a length and an inner diameter selected to provide a predetermined impedance based on at least one of the viscosity and density of the fluid. (Item 79) The apparatus according to item 67, wherein the dispensing chamber is an elastically variable volume dispensing chamber. (Item 80) The apparatus according to item 67, wherein the dispensing chamber has an inlet and the conduit has an inner diameter smaller than the inner diameter of the dispensing chamber inlet. (Item 81) The pump has a pumping chamber having a connectable inlet for providing fluid communication with a fluid source and a pump outlet, and a biasing assembly adapted to provide a compression stroke to the pumping chamber and includes, wherein the compression stroke restricts backflow of fluid from the pumping chamber to the inlet while urging fluid from the pumping chamber to the pump outlet, the apparatus according to item 67. (Item 82) The apparatus according to item 81, wherein when the biasing assembly is connected to an inlet valve actuator and a pump actuator such that the pump actuator urges fluid from the pumping chamber to the pump outlet, the compression stroke actuates an inlet valve connected between the inlet and the fluid source and closes the valve. (Item 83) The booster assembly includes a plate coupled to the valve actuator, the pump actuator, and a motor for the coordinated operation of the valve actuator and the pump actuator, the apparatus according to item 82. (Item 84) The motor includes a shape memory actuator, the apparatus according to item 83. (Item 85) The motor includes at least one pulley for bending the shape memory actuator for embedding within a reusable portion, the apparatus according to item 84. (Item 86) The apparatus according to item 67 further includes a shunt line in fluid communication with the discharge port of the pump and a fluid source and returning a portion of the fluid discharged by the pump to the fluid source. (Item 87) The fluid source includes a non-pressurized fluid reservoir, the apparatus according to item 86. (Item 88) During a change in volume of a sub-region of an acoustically continuous region caused by fluid flow in a band coupled to the volume of the sub-region, acoustically exciting a gas within the acoustically continuous region at only a single frequency to produce an acoustic response, and determining a phase relationship between the acoustic response measured at a first position within the acoustically continuous region and a reference value of the single frequency, and calculating a change in volume of the sub-region based on a temporal evolution of the phase relationship, and estimating a measured value of a fluid flow rate flowing through the line based on the change in volume of the gas within the sub-region A method for measuring a fluid flow rate delivered through a line, including. (Item 89) The method according to item 88 further includes measuring a reference value at a second position within the acoustically continuous region. (Item 90) The band is coupled to the volume of the sub-region via a membrane, the method according to item 88. (Item 91) The method according to item 88, wherein the step of acoustically exciting the gas includes driving a transducer. (Item 92) The method according to item 88, wherein the step of acoustically exciting the gas includes driving a speaker. (Item 93) The method according to item 88, further comprising the step of calibrating the phase relationship as a function of the volume of the sub-region. (Item 94) The method according to item 88, wherein the acoustically continuous region has a volume of less than 200 microliters. (Item 95) The method according to item 88, wherein the acoustically continuous region has a volume of less than 130 microliters. (Item 96) The method according to item 88, wherein the acoustically continuous region has a volume of less than 10 microliters. (Item 97) The method according to item 88, wherein the step of calculating the volume change includes determining such a change having a resolution better than 20 nanoliters. (Item 98) The method according to item 88, wherein the step of calculating the volume change includes determining such a change having a resolution better than 15 nanoliters. (Item 99) The method according to item 88, wherein the step of calculating the volume change includes determining such a change having a resolution better than 13 nanoliters. (Item 100) The method according to item 88, wherein the step of calculating the volume change includes determining such a change having a resolution of at least 1 / 10000 of the volume of the acoustically continuous region. (Item 101) The method according to item 88, wherein the single frequency is the resonance frequency of the sub-region or close thereto. (Item 102) The method according to item 88, further comprising the step of performing a calibration step by acoustically exciting the region at a series of frequencies, and determining a transfer function characterizing the phase relationship between the acoustic response measured at a first position within the acoustically continuous region and each reference value of the series of frequencies as a function of the frequency. (Item 103) The method according to item 102, further comprising the step of measuring each reference value of the series of frequencies at a second position within the acoustically continuous region. (Item 104) The method according to item 102, further comprising the step of detecting the presence of bubbles based on the transfer function. (Item 105) The method according to item 104, further comprising the step of entering an alarm state based on the step of detecting the presence of the bubbles. (Item 106) The method according to item 102, wherein the step of calculating the volume change is performed repeatedly during the measurement step, and the measurement step is performed alternately with the calibration step. (Item 107) The method according to item 106, wherein the fluid is delivered every cycle, and the calibration and measurement steps cooperate with the cycle. (Item 108) During the volume change of the sub-region of the acoustically continuous region caused by fluid flow in a band connected to the volume of the sub-region, an acoustic energy source for acoustically exciting the gas within the region acoustically continuous with only a single frequency to produce an acoustic response, A first acoustic transducer placed at a first position within the acoustically continuous region and for generating an electrical signal based on the acoustic response, wherein the electrical signal of the first acoustic transducer has a phase relationship with a reference value, the first acoustic transducer; A processor coupled to the first acoustic transducer and the reference value, which determines an amount related to the volume change of the sub-region based on the temporal evolution of the phase relationship, and implements a flow rate determination process for estimating a measured value of the fluid flow rate flowing through the line based on the volume change of the gas in the sub-region. And a processor A system for measuring the fluid flow rate delivered through a line, including (Item 109) The system according to item 108, further including a second acoustic transducer placed at a second position within the acoustically continuous region for generating an electrical signal constituting the reference value. (Item 110) The system according to item 108, wherein the system has a power consumption of less than 500 joules per day. (Item 111) A fluid delivery system that utilizes the system for measuring the fluid flow rate delivered through a line according to item 108 to cause the fluid to flow through the line, Further including a pump coupled to the processor, The system in which the power consumption by the processor does not substantially exceed the power consumption by the pump. (Item 112) The pump Has a pumping chamber having a connectable inlet for providing fluid communication with a fluid source and a pump outlet, A boosting assembly adapted to provide a compression stroke to the pumping chamber And includes, wherein the compression stroke restricts the backflow of fluid from the pumping chamber to the inlet while urging the fluid from the pumping chamber to the pump outlet. The system according to item 111. (Item 113) The system of item 112, wherein the boosting assembly is connected to an inlet valve actuator and a pump actuator, such that when the pump actuator urges fluid from the pumping chamber to the pump outlet, the compression stroke actuates an inlet valve connected between the inlet and the fluid source and closes the valve. (Item 114) The system of item 113, wherein the boosting assembly includes a plate connected to the valve actuator, the pump actuator, and a motor for the coordinated operation of the valve actuator and the pump actuator. (Item 115) The system of item 114, wherein the motor includes a shape memory actuator. (Item 116) The system of item 115, wherein the motor includes at least one pulley for bending the shape memory actuator for embedding within a reusable portion. (Item 117) The system of item 108, further including a membrane connecting the band to the volume of the sub-region. (Item 118) The system of item 108, wherein the acoustic energy source includes an acoustic transducer connected to an electrical signal. (Item 119) The system of item 108, wherein the transducer is a speaker. (Item 120) The system of item 108, wherein the processor implements a calibration process for calibrating the phase relationship as a function of the volume of the sub-region. (Item 121) The system of item 108, wherein the acoustically continuous region has a volume of less than 200 microliters. (Item 122) The system of item 108, wherein the acoustically continuous region has a volume of 130 microliters or less. (Item 123) The acoustically continuous region is the system according to item 108, having a volume of less than 10 microliters. (Item 124) The flow rate determination process is the system according to item 108, which determines an amount related to a volume change corresponding to a resolution better than 20 nanoliters. (Item 125) The flow rate determination process is the system according to item 108, which determines an amount related to a volume change corresponding to a resolution better than 15 nanoliters. (Item 126) The flow rate determination process is the system according to item 108, which determines an amount related to a volume change corresponding to a resolution better than 13 nanoliters. (Item 127) The flow rate determination process is the system according to item 108, which determines an amount related to a volume change corresponding to a resolution of at least 1 / 10000 of the volume of the acoustically continuous region. (Item 128) The single frequency is the resonance frequency of the sub-region or close thereto, which is the system according to item 108. (Item 129) The acoustic source includes an acoustic radiation transducer connected to the processor. The processor implements a calibration process to acoustically excite the region with a series of frequencies by the acoustic source. As part of such a process, the processor determines a transfer function that characterizes the phase relationship between the electrical signal of the first transducer and the respective reference values of the series of frequencies as a function of the frequency, which is the system according to item 108. (Item 130) The processor implements a bubble detection process to detect the presence of bubbles based on the transfer function, which is the system according to item 129. (Item 131) The bubble detection process is the system according to item 130, which places the system in an alarm state based on the step of detecting the presence of the bubbles. (Item 132) The above flow rate determination process is repeatedly performed during the above measurement stage, and the above measurement stage is performed alternately with the above calibration stage, the system according to item 131. (Item 133) The above fluid is delivered every cycle, and the above calibration and measurement stages cooperate with the above cycle, the system according to item 132.

Brief Description of the Drawings

[0064] The above features of the present invention will be more easily understood by referring to the following detailed description in relation to the accompanying drawings.

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DETAILED DESCRIPTION OF THE INVENTION

[0065] Note that the elements depicted in the accompanying figures and this specification are not necessarily drawn to a consistent scale or any scale.

[0066] (Definitions) As used in this description and the accompanying claims, the following terms shall have the indicated meanings unless otherwise required by the context.

[0067] The "user input section" of a device includes any mechanism by which a user or other operator of the device can control the functions of the device. The user input section may include a mechanical arrangement (e.g., switches, push buttons), a communication wireless interface with a remote control device (e.g., RF, infrared), an acoustic interface (e.g., with voice recognition), a computer network interface (e.g., USB port), and other types of interfaces.

[0068] As used in the context of user input parts such as the so-called "Bolus button" discussed below, the "button" may be any type of user input part capable of performing a desired function, and is not limited to a push button.

[0069] "Alarm" includes any mechanism capable of generating a warning to the user or a third party. The alarm may include an audible alarm (e.g., speaker, buzzer, voice generator), a visual alarm (e.g., LED, LCD screen), a tactile alarm (e.g., vibration element), a wireless signal (e.g., wireless transmission to a remote control device or caregiver), or other mechanisms. The alarm may be generated using multiple mechanisms simultaneously, in parallel, or in sequence, including redundant mechanisms (e.g., two different audible alarms) or complementary mechanisms (e.g., audible alarm, tactile alarm, and wireless alarm).

[0070] "Fluid" is meant to mean a substance such as a liquid that can flow through a flow line.

[0071] "Impedance" is meant to mean the opposition of the device or flow line to the flow of fluid flowing therethrough.

[0072] "Wetted surface" represents a component that comes into direct contact with the fluid during normal fluid delivery operations. Since the fluid is not limited to a liquid, the "wetted" component does not necessarily get wet.

[0073] "Patient" includes a person or animal who receives fluid from a fluid delivery device, whether as part of a treatment or otherwise.

[0074] "Cannula" is meant to mean a disposable device capable of injecting fluid into a patient. The cannula as used herein may refer to a conventional cannula or a needle.

[0075] "Specimen sensor" shall mean any sensor capable of determining the presence of a specimen within a patient. Embodiments of the specimen sensor include, but are not limited to, sensors capable of determining the presence of any viral, parasitic, bacterial, or chemical specimen. The term "specimen" includes glucose. The specimen sensor may communicate with other components within the fluid delivery device (e.g., a control device within a non-disposable portion) and / or a remote control device.

[0076] "Dispensing assembly sensor" shall mean a mechanism for determining the fluid volume present within the dispensing chamber.

[0077] "Sharp" shall mean anything capable of piercing or protruding into the skin of an animal, particularly the skin of a human. The sharp may include a cannula, a cannula insertion device, a specimen sensor, or a specimen sensor insertion device. The sharp may be provided individually or, for example, together within a cartridge.

[0078] "Disposable" shall indicate a part, device, portion, or other that is intended to be used for a fixed period and then discarded and replaced.

[0079] "Non-disposable" shall indicate a reusable part that is intended to have an indefinite period of use.

[0080] "Patch size" shall mean small enough to be fixed to a patient's skin by an adhesive or strap, etc., and worn as a medical device during the administration of the substance contained within the device. A medical device small enough to function as an implant is within the scope of this definition.

[0081] "Normal existing finite fluid impedance" shall mean the finite fluid impedance that exists when a predetermined process of fluid delivery, i.e., a failure state (e.g., occlusion) does not exist.

[0082] The "passive" impedance is not actively controlled during the pumping cycle.

[0083] "Acoustic volume measurement" shall mean the quantitative measurement of relevant volumes using, for example, the acoustic techniques as described in U.S. Pat. Nos. 5,349,852 and 5,641,892 and the techniques described herein.

[0084] A "temperature sensor" includes any mechanism for measuring temperature and communicating temperature information to a control device. The device may include one or more temperature sensors for measuring, for example, skin temperature, AVS temperature, ambient temperature, and fluid temperature.

[0085] Embodiments of the devices, pumping mechanisms, systems, and methods described herein relate to fluid delivery and include pumping and volume measurement of fluids, as well as their operation and control. Embodiments of the devices include portable or non-portable devices for fluid delivery. Some embodiments of the devices include a disposable base and a non-disposable upper portion. The devices include embodiments where an infusion device is inserted directly into a patient through the base. These device embodiments are patch pump devices. The patch pump may be adhered to a patient using an adhesive, strap, or other suitable arrangement. The adhesive may have a protective peelable strip that can be removed prior to use to expose the adhesive.

[0086] However, in other embodiments, the fluid delivery device is a portable device where a tube is connected to a fluid line. The tube is typically connected to a patient through a cannula.

[0087] In some embodiments where a disposable base and a non-disposable upper portion are implemented, the base includes wetted components, and the components included in the non-disposable upper portion are typically non-wetted components.

[0088] Various embodiments of the pumping mechanism include an upstream inlet valve, a pumping actuating member, a downstream outlet valve, and a movable member. In some embodiments, the pumping actuating member and the downstream valve function are implemented using the same device. The pumping mechanism pumps fluid from a reservoir, through a fluid line, to an outlet. The pumping mechanism is typically employed with an unpressurized reservoir, however, the scope of the present invention is not limited thereto.

[0089] In one embodiment of the fluid delivery system, the device includes a sample sensor housing. The sample sensor is introduced into the patient through the sample sensor housing at the base of the device. In these embodiments, the infusion device is also introduced through a cannula housing on the base of the device. In these embodiments, the device is worn by the user as a patch pump.

[0090] The system typically includes a control device that may include a wireless transceiver. Thus, the device may be controlled exclusively or in part through the wireless control device. The control device may receive information through wireless communication from the sample sensor and / or the fluid delivery device. A patient or third party may use the control device to control the functions of the fluid delivery device.

[0091] In one embodiment of the fluid delivery device, the device is an insulin pump and the sample sensor is a blood glucose sensor. A control device that receives information related to both the volume of insulin delivered (or the number of pump strokes over time) and the blood glucose data assists the user in programming an operating schedule for the pump mechanism.

[0092] Exemplary dispensing assemblies and volume sensing devices are described herein. The dispensing assembly includes at least one microphone and a speaker. The assembly measures a change in volume within the dispensing chamber and determines the volume of fluid being pumped. The volume sensing data is used to determine the state of the fluid delivery device. Thus, various control units may rely on the volume sensing data.

[0093] In embodiments of the present invention, a user configures a fluid delivery device via a user interface in order to cause the fluid delivery device to deliver fluid in an appropriate manner. In one embodiment, the user interface is present on a separate portable user interface assembly that can communicate wirelessly with the patch. The patch may be disposable or partially disposable.

[0094] An exemplary use of an embodiment of the present device is the delivery of insulin to a diabetic patient, but as noted above, other uses include the delivery of any fluid. Fluids include analgesics to a pain sufferer, chemotherapeutic agents to a cancer patient, and enzymes to a patient with a metabolic disorder. The various therapeutic fluids may include small molecules, natural products, peptides, proteins, nucleic acids, carbohydrates, nanoparticle suspensions, and associated pharmaceutically acceptable carrier molecules. Molecules with therapeutic effects may be modified to improve their stability within the delivery device (e.g., by pegylation of a peptide or protein). The exemplary embodiments herein describe drug delivery applications, but the present embodiments may be used for other applications, including liquid dispensing of reagents for lab-on-a-chip applications and high-throughput analytical measurements such as capillary chromatography. For the purposes of the following description, the terms "therapeutic agent" or "fluid" are used interchangeably, but as noted above, in other embodiments, any fluid may be used. Thus, the devices and descriptions included herein are not limited to the use of therapeutic agents.

[0095] Exemplary embodiments include a reservoir for holding a supply of fluid. In the case of insulin, the reservoir may be sized conveniently to hold sufficient insulin for delivery over one or more days. For example, the reservoir may hold about 1-2 ml of insulin. A 2 ml insulin reservoir may correspond to a supply for about 3 days for approximately 90% of potential users. In other embodiments, the reservoir can be of any size or shape and can be further adapted to hold any amount of insulin or other fluid. In some embodiments, the size and shape of the reservoir are related to the type of fluid the reservoir is adapted to hold. The fluid reservoir may be shaped eccentrically or irregularly and / or may be sealed with a wedge plug to prevent improper installation or use.

[0096] Some embodiments of fluid delivery devices are adapted for use by diabetic patients and, thus, in these embodiments, the device delivers insulin that complements or replaces the action of the patient's pancreatic beta cells. Embodiments adapted for insulin delivery attempt to mimic the action of the pancreas by providing both a basal level of fluid delivery as well as a bolus level of delivery. The basal level, bolus level, and timing are settable by the patient or another party by using a wireless handheld user interface. Further, the basal and / or bolus levels are initiable or adjustable in response to the output of an integrated or external analyte sensor, such as a glucose monitoring device or a blood glucose sensor. In some embodiments, the bolus is initiable by the patient or a third party using a designated button or other input means located on the fluid delivery device. In still other embodiments, the bolus or basal is programmable or manageable through a user interface located on the fluid delivery device.

[0097] FIG. 1 shows a patient 12 wearing a fluid delivery device 10 and holding a wireless user interface assembly 14 for monitoring and adjusting the operation of the fluid delivery device 10. The user interface assembly 14 typically includes a device for inputting information (such as a touch screen or keypad) and a device for communicating information to the user (such as an LCD display, speaker, or vibration alarm). The fluid delivery device is typically small and lightweight enough to remain comfortably adhered to the patient for several days.

[0098] The fluid delivery device 10 is shown worn on the arm of the patient 12 in FIG. 1. In other embodiments, the fluid delivery device 10 may be worn at other locations on the patient where the particular fluid being delivered can be advantageously utilized by the patient's body. For example, the fluid may be advantageously delivered to the patient's abdomen, renal region, lower extremities, or elsewhere.

[0099] Next, referring to FIG. 2A, a schematic of the fluid delivery device 10 having a feedback loop 360 from the dispensing assembly 120 to the pumping assembly 16 is shown. The pumping assembly 16 pumps fluid to the dispensing assembly 120. The fluid then flows out to an outlet assembly 17 that includes a flow restrictor 340 and an output. The output typically includes a cannula and leads to the patient. The dispensing assembly 120 may include an elastically variable volume dispensing chamber, at least one microphone, and a speaker for measuring parameters regarding the flow rate through the output over time. The feedback loop 360 enables adjustment of the operation of the pumping assembly 16 based on repeated measurements made by sensors. The flow restrictor 340 creates a high impedance between the dispensing assembly 120 and the output of the flow line 5010. The flow restrictor 340 can be, for example, a section of a small diameter tube or a microtube. Next, referring to FIG. 2B, in one embodiment, the pumping assembly 16 pumps fluid from a reservoir 20 to the dispensing assembly 120.

[0100] Next, referring to FIG. 3, a block diagram of a further embodiment employing fluid principles is shown. Flow line 310 connects reservoir 20, pumping assembly 16, dispensing assembly 120, and outlet assembly 17. Outlet assembly 17 may include a high impedance flow restrictor 340 and an injection device 5010 (e.g., a cannula). The output of flow restrictor 340 is sent to injection device 5010 for delivery to the patient. Flow restrictor 340 has a higher flow impedance than a portion of flow line 310 upstream of dispensing assembly 120. Thus, pumping assembly 16 can pump fluid into dispensing assembly 120 faster than the fluid can flow out of outlet assembly 17. Dispensing assembly 120 may include a variable volume dispensing chamber 122 having an elastic wall. In the embodiments presented below, the elastic wall is a membrane. Examples of membrane materials include silicone, nitrile, and any other material having the desired elasticity and properties to function as described herein. Additionally, other structures can serve the same purpose. As a result of the action of pumping assembly 16, upon receiving a certain fluid charge, the elasticity of the membrane can first expand chamber 122 and then provide the delivery pressure necessary to pass the fluid content of dispensing assembly 120 from flow restrictor 340 to the patient. When an appropriate sensor (examples are described below) is placed, dispensing assembly 120 may measure the flow rate of the fluid flowing through variable volume dispensing chamber 122 and further provide feedback through feedback loop 360 to control the timing and / or speed at which pumping assembly 16 pumps or partially fills dispensing chamber 122, thereby delivering a desired dosage to the patient at a desired rate.

[0101] Again, referring to FIG. 3, further, flow restrictor 340 prevents fluid flow rates in excess of a specified flow rate. Additionally, since pressurized fluid delivery is achieved through the interaction of pumping assembly 16, dispensing assembly 120, and flow restrictor 340, it is also possible to employ a non-pressurized reservoir 20.

[0102] Referring further to FIG. 3, feedback loop 360 may include a control device 501. The control device 501 may include a processor and a control circuit for operating the pumping assembly 16 to pump fluid to the dispensing assembly 120. The control device 501 may be integral with the dispensing assembly 120, repeatedly receive parameters regarding fluid flow rate from a sensor, and use this parameter to control the pumping assembly 16 to achieve a desired flow rate of the output flowing therethrough. For example, the control device 501 can adjust the timing or operating range of the pumping assembly 16 to achieve a desired basal or bolus flow rate and / or deliver a desired basal or bolus cumulative dose. When determining the timing or range of pumping, the control device 501 may use the output of a sensor (not shown) to estimate, inter alia, the fluid flow rate, the cumulative fluid flow rate, or both, and then determine an appropriate compensatory action based on the estimate. In various embodiments, pumping can occur in pulses deliverable between 10 -9 liters per pulse and microliters per pulse. A steady or bolus amount may be achieved by delivering multiple pulses (examples of basal and bolus amounts are presented and described below).

[0103] The use of the partially collapsible non-pressurized reservoir 20 can advantageously prevent the accumulation of air in the reservoir as the fluid in the reservoir is consumed. The reservoir 20 may be connected to the fluid line 310 through a diaphragm (not shown). In particular, when the system is tilted such that a cavity region is interposed between the fluid contained in the reservoir and the diaphragm of the reservoir 20, air accumulation in the vented reservoir can prevent fluid release from the reservoir 20. Tilting of the system is expected during normal operation as a wearable device. FIGS. 104-106C depict diagrams of various embodiments and one embodiment of the reservoir. Further description of the reservoir is included below.

[0104] Next, referring to FIGS. 4A - 4C, various embodiments of the flow restrictor 340 are shown. Next, referring to FIG. 4A, the flow restrictor may be a shaped flow channel 340 or a shaping groove (not shown) within the base. In one embodiment, the cross - section of the shaped flow channel 340 is about 0.009 inches. In this embodiment, the flow restrictor 340 is formed in the instrument. Next, referring to FIG. 4B, a capillary tube 340 is shown as an alternative embodiment of the flow restrictor. In one embodiment, the capillary tube has an inner diameter of about 0.009 inches. Both the shaped flow channel and the capillary tube use a long path with a small inner diameter or cross - section to impart flow impedance. Next, referring to FIG. 4C, a precision hole is shown as the flow restrictor 340. In one embodiment, the precision hole is a plate with laser - drilled holes. In alternative embodiments, any flow impedance device or method well - known in the art may be used.

[0105] Generally, in a functional sense, in contrast to prior - art fluid delivery systems having active downstream valves that may be considered to generate infinite fluid impedance, the flow restrictor 340 generates a finite fluid impedance. Also, in contrast to prior - art systems, the impedance is usually present rather than being sometimes obstructed by occlusion. As a result of the finite nature of the fluid impedance, in embodiments including the dispensing chamber 122, fluid can leak out of the outlet even when the dispensing chamber 122 is expanding.

[0106] Figures 5 - 8 schematically show cross - sectional views of an exemplary embodiment of the dispensing assembly 120. It should be understood that the delivery of fluids for other purposes such as industrial processes etc. is within the scope of the present invention and the explanations of specific terms are merely examples. As shown in Figure 5, the dispensing assembly 120 may include a variable - volume dispensing chamber 122 and a sensor 550. The variable - volume dispensing chamber 122 includes an elastic dispensing diaphragm 125 and expands and contracts the chamber 122 in response to the flow rate of the fluid flowing into and out of the dispensing assembly 120. In certain embodiments of the present invention, the variable - volume dispensing chamber 122 may be further detachable from other elements of the dispensing assembly 120 as described herein. The concept of the elastic dispensing diaphragm 125 that expands and contracts the chamber 122 is illustrated by the double - headed arrow. The measurement chamber 122 is considered to include a portion of line 110 characterized by the flow of fluid, designated by arrow 112 in Figure 5. Neither the end position nor the nature of the fluid flow 112 or line 110 need limit the scope of the present invention as claimed in the specific claims appended hereto. The flow restrictor 340 allows the fluid to be discharged from the dispensing chamber 122 more slowly than it flows into the chamber 122 when pumped into the chamber 122 by the pumping assembly 16. As a result, when a certain fluid charge flows in, the dispensing chamber 122 expands and is pressurized. The dispensing diaphragm 125 deformed by the expansion of the dispensing chamber 122 provides the force required to deliver the measured volume through the flow restrictor 340 to the outlet assembly 17. As described above, the sensor 550 repeatedly measures parameters such as displacement, or thermodynamic variables or capacitances related to the volume of the elastic dispensing chamber 122. Using the volume measurements generated by the sensor 550, the pumping assembly may control, through a feedback loop, the timing and speed at which the appropriate flow rate of the fluid is delivered to the outlet assembly 17 and subsequent lines, and further therefrom, for example, to a patient, by pumping the fluid into the dispensing chamber 122.Sensor 550 may employ, for example, an acoustic volume sensor (detailed below), or other methods (in other embodiments, optical, or capacitance), to determine volume or volume-related parameters. Acoustic volume measurement techniques are the subject of U.S. Patents Nos. 5,575,310 and 5,755,683 to DEKA Products Limited Partnership, and co-pending provisional U.S. patent application No. 60 / 789,243, "METHOD OF VOLUME MEASUREMENT FOR FLOW CONTROL," filed Apr. 5, 2006 (all of which are incorporated herein by reference). Fluid volume sensors in the nanoliter range are possible with this embodiment, and thus contribute to highly accurate and precise monitoring and delivery. Also, other alternative techniques for measuring fluid flow may be used. For example, Doppler methods, use of Hall effect sensors in combination with vanes or flapper valves, use of dual beams (e.g., associated with a flexible member over a fluid chamber for sensing distortion of the flexible member), use of capacitance sensors with plates, or thermal time-of-flight methods.

[0107] Next, referring to FIGS. 6 to 9, an embodiment utilizing Acoustic Volume Sensing (AVS) technology as a sensor is shown. The first discussion refers to the embodiments depicted in FIGS. 6 and 7. The dispensing assembly 120 has a sensor. It includes a reference chamber 127 and a variable volume measurement chamber 121 connected to a fixed volume chamber 129 by a port 128. The present invention can be practiced by the reference chamber 127, but in certain other embodiments of the present invention as shown in FIGS. 6 and 7, a reference volume is not provided. The volume 129 is herein termed "fixed" for terminology purposes, but it should be understood that the actual volume can vary slightly on the time scale of acoustic excitation, such as when the region called the fixed volume 129 is driven by a speaker diaphragm. Fluid flows from the pumping assembly 16 into the inlet 123, through the elastic dispensing chamber 122, and out of the outlet channel 124. Due to the high downstream impedance, when fluid flows into the dispensing chamber 122, the dispensing diaphragm 125 expands into the variable volume chamber 121. An electronic assembly that can be arranged on the printed circuit board 126 has a loudspeaker 1202, a sensing microphone 1203, and a reference microphone 1201 for measuring acoustic parameters related to the gas (typically air) within the variable volume chamber 121, the volume of which is defined by the position of the dispensing diaphragm 125. Sound waves induced by the loudspeaker 134 move from the fixed volume chamber 129 into the variable volume chamber 121 through the port 128. Also, the sound waves move into the reference chamber 127. When the dispensing diaphragm 125 moves with the flow of the fluid flowing through the flow line, the volume of air within the variable volume chamber 121 changes, causing a related change in its acoustic characteristics (which can be detected by the loudspeaker and the microphone 1203). For the same acoustic simulation, the reference microphone 1201 may detect the acoustic characteristics of the fixed reference volume 127. These reference measurements can be used to remove inaccuracies and prevent common mode inaccuracies, for example, in acoustic simulations and other errors. The displacement volume of the fluid may be determined by comparing the measured volume of the variable volume chamber 121 with the initial volume of the variable volume chamber 121.Since the total volume of the dispensing chamber 122 and the variable volume chamber 121 is constant, the absolute volume of the dispensing chamber 122 can also be estimated.

[0108] The embodiment shown in FIG. 6 utilizes an essentially elastic dispensing diaphragm 125, and the embodiment shown in FIG. 7, when coupled to the dispensing diaphragm 125, increases the elasticity of the dispensing chamber 122 and enables the use of a dispensing diaphragm 125 that is more flexible (i.e., less elastic) than that required in the embodiment shown in FIG. 5. The dispensing spring 130 is typically positioned adjacent to the dispensing diaphragm 125 on the side of the dispensing diaphragm 125 facing the dispensing chamber 122.

[0109] Alternatively, to reduce background noise from the microphone, the loudspeaker 1202 and the sensing microphone 1203 may be coupled to the variable volume chamber 121 via separate ports. As schematically shown in FIG. 8, the loudspeaker 1202 generates a pressure wave within a fixed loudspeaker volume 6000 that is acoustically coupled to the variable volume chamber 121 via a loudspeaker port 6020. Before being recorded by the sensing microphone 1203, the pressure wave travels from the loudspeaker 1202, through the loudspeaker port 6020, to the variable volume chamber 121, and then to the microphone port 6010. The loudspeaker port 6020 may include a tube portion 6040 with a protruding opening 6030. The protruding opening 6030 serves to create a uniform length along which sound waves travel along the entire axial path of the tube portion 6040. For example, the tube portion 6040 can have a cylindrical shape such as a straight circular cylinder or a straight circular cylindrical body. Also, a similar protruding opening may be joined to the tube portion to define the microphone port 6010. In contrast to the AVS sensors of FIGS. 6 and 7, in the embodiment of FIG. 8, the force wave traveling from the compression loudspeaker 1202 does not have a direct path to the sensing microphone 1203. Thus, the pressure wave from the loudspeaker 1202 is prevented from directly affecting the sensing microphone 1203 without first passing through the variable volume chamber 121. Thus, a low background signal is received by the microphone and an excellent signal-to-noise ratio is achieved. Further, the upper shelf 6050 may be included in any of the embodiments of FIGS. 6-8, advantageously reducing the volume of the reference chamber 127.

[0110] In further described embodiments, it may be expedient to make the dispensing chamber detachable and disposable by separating the sensor from the metering chamber portion of the dispensing assembly. In this case, the dispensing chamber is in the disposable section of the patch and the sensor is in the reusable section. The dispensing chamber may be actuated by an elastomeric fluid dispensing diaphragm (as shown as 122 and 124 in FIG. 6). Alternatively, as shown in FIG. 7, the dispensing chamber 122 may be actuated by a flexible diaphragm 125. In this case, a dispensing spring 130 can be used to impart elasticity to the dispensing chamber 122. When the sensor 550 is joined to the dispensing chamber 122, the dispensing spring 130 covers the flexible dispensing diaphragm 125. The dispensing spring 130 and the dispensing diaphragm 125 may alternatively be employed as a single component that defines the dispensing chamber 122.

[0111] As shown in FIG. 9, an alternative embodiment of the dispensing assembly is shown. In the embodiment of the dispensing assembly 120 depicted in FIG. 9, the variable volume metering chamber 121 shares a flexible wall (here shown as the flexible diaphragm 125) with the dispensing chamber 122. The port 128 acoustically couples the metering chamber 121 to a fixed volume chamber 129, forming an acoustically continuous region generally designated by the numeral 1290. A compressible fluid (typically air or another gas) fills the acoustically continuous region 1290 and is excited by a drive member 1214 (which itself is driven by an actuator 1216). The drive member 1214 may be the diaphragm of a speaker such as a hearing aid speaker, and the actuator 1216 may be, for example, a voice coil solenoid or a piezoelectric element. Within the scope of the present invention, the drive member 1214 may also have the same extent as the actuator 1216, for example, the drive member 1214 itself may be a piezoelectric element. The drive member 1214 may be included within a drive device module 1212 that may contain a reference volume 1220 on the drive member 1214 side distal to the fixed volume 129. However, the reference volume 1220 is typically not employed in the practice of the present invention.

[0112] The reference microphone 1208 is shown to acoustically communicate with the fixed volume 129, and the signal microphone 1209 is acoustically coupled to the measurement chamber 121. The volume of the measurement region 121 may be determined from the electrical signals provided by one or more microphones 1208, 1209 based on the pressure fluctuations (or, equivalently, acoustic signals) measured at respective positions within the acoustically continuous region 1290. Phase measurements may be made by comparing the response phase at one or more microphones relative to the phase of the acoustic excitation or relative to the response phase at another microphone position. The volume of the measurement region 121, and implicitly the dispensing chamber 122, is determined by the processor 1210 (typically powered by power supply 1211 shown as a battery) based on phase and / or amplitude measurements as discussed below.

[0113] For the purpose of precise delivery of a small amount of therapeutic agent, it is desirable to deliver a small but very accurately measured amount per pump stroke. However, if a small amount of fluid is pumped through line 110 between each pump stroke, a very high resolution is required for the measurement process. As a result, in accordance with embodiments of the present invention, volume changes are measured by a sensor 550 having a resolution of at least 10 nanoliters. Measurement of the dead volume of the measurement region 121 with a resolution of 0.01% may be achieved in some embodiments of the present invention. According to other embodiments of the present invention, the sensor 550 provides a resolution higher than 13 nanoliters. In yet other embodiments, the sensor 550 provides a resolution higher than 15 nanoliters, and in further embodiments, a resolution higher than 20 nanoliters is provided. In such cases, the total volume of the acoustically continuous region 1290 may be less than 130 μl, and in yet other embodiments, less than 10 μl.

[0114] According to various embodiments of the present invention, based on the filling of the dispensing chamber by the pumped fluid volume flowing through the inlet portion 123, an empirical model of the volume response of the dispensing chamber 122 and, as a result, the variable volume chamber 121 (also referred to herein as the "measurement volume") may be used. Other models are within the scope of the present invention, but one of the models that may be employed is a basic volume V depending on the inflow of the pumped fluid and the output of the fixed flow impedance. B and a peak displacement V D as the sum of an exponentially decaying volume characterized by, the fluid volume in the dispensing chamber 122 is represented by, and the measurement chamber volume during measurement is characterized as a function of time t as follows.

[0115]

Equation

[0116] The ideal gas law can be expressed as follows using the mean pressure P and volume V, and in addition to those pressures p(t), a small time-dependent perturbation v(t).

[0117]

Equation

[0118]

Equation

[0119]

Number

[0120]

Number

[0121]

Number

[0122]

Number

[0123]

Number

[0124] The laminar flow friction of this form

[0125]

Number

[0126]

Number

[0127]

Number

[0128]

Number

[0129]

Number

[0130]

Number

[0131]

Number

[0132]

Number

[0133]

Number

[0134]

Number

[0135]

Number

[0136]

Number

[0137]

Number

[0138]

Number

[0139]

Number

[0140]

Number

[0141]

Number

[0142] Similarly, the "inter-system" transfer function p2 / p0 based on the measured values on one side of port 128 is obtained by the following equation.

[0143]

Number

[0144]

Number

[0145] [Number] Since all other parameters are well-known, the variable volume V2 can be calculated, for example, based on the resonance frequency. However, other methods of determining V2 may also be advantageous and will be further explained in the course of this application. One of the parameters that is not a constant in this formula is the speed of sound, which can be calculated based on knowledge of the appropriate temperature, or otherwise determined, or measured.

[0146] As described above, various measures may be adopted and the system may be interrogated to obtain the volume V2. According to an embodiment of the present invention, the system is excited at a single frequency by the drive member 1214 while monitoring the response of one or more transducers (microphones 1208 and 1209 in FIG. 9). The response is captured as a complex signal and retains both the amplitude and phase of the pressure fluctuations. Since the maximum phase change of the volume over the range from chamber full to empty is thereby achieved, it is advantageous for a single interrogation frequency to be positioned close to the resonance of the system at the intermediate stroke.

[0147] The response of the signal microphone 1208 may be corrected to prevent the common mode effect due to the frequency-dependent characteristics of the excitation loudspeaker 1202 (shown in FIG. 6) or the drive member 1214 (shown in FIG. 9). The correction signal, which is obtained as the complex ratio of the microphone signals, can be represented as m i and can be expressed as such, where the index i indicates the continuous time samples of the signal.

[0148] Similarly, when expressed in the form of a transfer function for a secondary mechanical Helmholtz resonator, the signal can be represented as follows.

[0149] [Number] Here, a normalization variable is introduced to maintain relevant parameters within a computationally useful dynamic range of the order of 1. The final equation is expressed using the real and imaginary parts over a common denominator. Applying the ratio of the real part μ to the imaginary part v (i.e., the cotangent of the phase), it is obtained as follows.

[0150]

Number

[0151]

Number

[0152] When the error is minimized with respect to each model parameter, the best fit is achieved. Any method may be employed to fit the model parameters. In one embodiment of the present invention, the gradient descent method is employed, and the minimum value is obtained as follows.

[0153]

Number

[0154]

Number

[0155] According to a preferred embodiment of the present invention, the fluid volume dispensed through the dispensing volume chamber 122 is determined based on a fit to a volume-versus-time model based on system cross-phase measurements performed at a monotonic excitation frequency. Referring to the process diagram shown in FIG. 117, a preliminary measurement is made during the initial part of the pump stroke and also to calibrate the system operation, as described next in connection with the measurement protocol. The measurement process generally indicated by the numeral 1170 advantageously conserves computer resources, minimizes power consumption, thereby extending the useful time during loading or replacement of the power supply 1211 (shown in FIG. 9), while providing the measurement accuracy required for delivery of fluid having the resolution per stroke described above through frequent calibration.

[0156] Prior to each pump stroke, or at the start of 1171, or both, the processor 1210 starts the self-calibration phase 1172 of the AVS system. The measurement is held until the electronic transient current due to pump startup has substantially decayed. In step 1173, the microphone and speaker amplification factors are set and the drive member 1214 is actuated at a series of frequencies, typically five frequencies that are approximately close to the resonance of the adjacent acoustic region 1290 (alternatively, herein referred to as the "acoustic chamber"). Frequencies in the range of 6-8 kHz are typically employed, although the use of any frequency is within the scope of the present invention. At the start of activation of each successive frequency, data collection is delayed for about 5 ms until the acoustic transient current has substantially decayed.

[0157] During approximately 64 acoustic cycles, data is collected as follows. The temperature measurement provided by the temperature sensor 132 (shown in FIG. 70B) is sampled in step 1174, and the real and imaginary parts (denoted by p and ι, respectively) of the output signal ratio of the signal microphone 1209 to the reference microphone 1208 are sampled. The complex ratio of the signals, or other functional combinations of the microphone signals with respect to the reference microphone, may be referred to herein as the "signal" for the purpose of describing the AVS system.

[0158] Based on the measurements at each frequency performed for approximately 200 ms per frequency, mean values and variance values of a set are determined for each of the real and imaginary parts of the signal and the temperature measurement value at each frequency. In step 1175, analysis of these values enables determination of whether there is an error within a specified boundary. An abnormal transfer function can advantageously indicate a system failure, including, but not limited to, failures in microphones or other sensors, speakers, transducers, electronic devices, mechanical components, fluid ingress, poor acoustic seals, excessive ambient noise, excessive shock and vibration. Further, the functional dependence of the signal phase angle as a function of frequency is determined in step 1176. The signal phase angle, i.e., the arctangent of the ratio of its imaginary part to its real part, can be used as a measurement of phase, however, any phase measurement may also be used within the scope of the present invention. The functional dependence may be determined by a polynomial fit of the phase to the frequency or otherwise. Based on the polynomial fit or otherwise, the slope of the phase versus frequency is determined at the volume measurement frequency, and the volume measurement is performed in step 1177. Additionally and significantly, an abnormal slope of the gradient versus frequency indicates bubbles in the fluid contained within the dispensing chamber 122.

[0159] For the subsequent portion of each pump stroke, the drive member 1214 is operated at a substantially single frequency, thereby acoustically exciting the gas within the acoustically continuous region 1290 at that frequency. Typically, the signal data based on the complex ratio of the output signal of the signal microphone 1209 to the reference microphone 1208 is collected and averaged over a specified sampling interval of approximately 64 cycles. The real and imaginary parts of the signal, as well as the temperature data, are recorded for each sampling interval. Based on the sampled and collected data, a fit is performed to the time model. In various embodiments of the present invention, as described above, at each pump stroke, the model parameters, i.e., the basic volume V of the variable volume chamber 121 B , peak displacement V DAnd in order to minimize the error in fitting the decay time τ, a gradient descent method is adopted, thereby providing a fluid volume delivered through the dispensing chamber 122.

[0160] Next, referring to FIG. 10, the dispensing spring 130 may have a spiral or fan shape that is complementary to the diaphragm and may have a plurality of helical grooves 131. The illustrated spring embodiment is capable of applying a substantially uniform force to the diaphragm. This substantially uniform force helps to maintain a substantially concave shape when the diaphragm expands. The grooves 131 allow air to pass freely through the spring, and thus air is hardly trapped between the spring and the diaphragm.

[0161] Next, referring to FIGS. 11A and 11B, examples of the volume dynamics measurements of the dispensing chamber 122 (shown in FIG. 5) and the calculated accumulated volume discharged from the dispensing chamber 122 are shown for a typical steady delivery pulse (FIG. 11A) and a typical bolus delivery (FIG. 11B). As can be seen from FIG. 11A, upon actuation of the pumping assembly 16, as measured by the acoustic volume sensor 550, the dispensing chamber 122 expands from approximately 0 to approximately 1.5 μl in approximately 2 seconds. Over a period of approximately 30 seconds with an exponential decay dynamics characterized by a half-life (t 1 / 2 ) of approximately 6 seconds, the elastic dispensing chamber 122 contracts and discharges its fluid from the chamber 122 through the high impedance output. The accumulated volume of the output from the dispensing chamber 122 is calculated from the measurements made by the sensor 550 and is also seen to increase exponentially to approximately 1.5 μl. It can be seen that the high impedance output introduces a delay between the actuation of the pump assembly and the delivery of most of the fluid being discharged. The t 1 / 2 characteristics of the system can be selected taking into account the elastic force imparted by the dispensing chamber 122 and the degree of output impedance. In various embodiments, the time constant may be varied to conserve power and eliminate drift problems. The time constant may be, for example, t 1 / 2 = 2 seconds, i.e., t1 / e It may also be 2 seconds.

[0162] FIG. 11B shows the dynamic profile of bolus delivery of fluid by the fluid delivery device 10. Approximately 29 high-speed continuous pump operations (i.e., pulses) each discharge fluid from the fluid source into the elastomeric dispensing chamber 122, thus causing a change corresponding to the parameter measured by the acoustic volume measurement sensor 550. The volume of the dispensing chamber 122 expands to approximately 1.5 μl by the first pump pulse and is found to be similar to the value observed in FIG. 11A. The volume of the dispensing chamber 122 is further expanded by additional pulsatile pumping at a pulse interval shorter than the time required to achieve complete discharge of the dispensing assembly 120. The expansion reaches up to approximately 6 μl. The cessation of the pump pulsation occurs after approximately 85 seconds, and the volume of the chamber 122 decreases with an exponential decay dynamic, resulting in complete discharge of its contents by approximately 30 seconds after pumping stops. The t 1 / 2 for this final discharge is approximately the same as that for the steady delivery shown in FIG. 11A. The calculated accumulated output volume is found to increase in a substantially linear dynamic during pumping and become stagnant upon cessation of pumping.

[0163] In the described system, the failure state is detected by volume measurement rather than by pressure measurement, and thus the failure can be determined within seconds. FIGS. 11C - 11F show various detected failure states by the sensor 550 of FIGS. 5 - 7. All descriptions for FIGS. 11C - 11F are explained with reference to FIGS. 5 - 7.

[0164] FIG. 11C shows the output dynamic profile over time of the pumping pulses of the sensor 550 under normal operating conditions. In contrast, FIG. 11D shows the expected result of an occlusion downstream of the dispensing assembly 120. The increase (or non - decrease) in the fluid volume within the dispensing chamber 122 is detected more rapidly by the sensor 550.

[0165] The low volume state is shown in FIGS. 11E - 11F. In FIG. 11E, the substantially maximum sensor signal is achieved, followed by an excessive rapid decay. This state may indicate an internal leak in pump 16, line 310, or dispensing assembly 120. The dynamic profile of FIG. 11F has a low peak volume signal and may be indicative of a pump failure, an empty reservoir 20, or an obstruction upstream of the dispensing chamber 122. Also, a delayed expansion of the dispensing chamber 122 relative to pump operation may indicate a problem with fluid line 310. Further, sensor 550 may be capable of detecting air bubbles in the fluid. An alarm may be activated in response to the detection of a failure condition.

[0166] FIG. 12 shows a process diagram depicting an acoustic volume sensing and compensation cycle (corresponding to control loop 360 of FIGS. 2A - 3). The sensor may measure the amount of fluid dispensed from device 10 based on the magnitude of the cyclic change within variable volume chamber 121 induced by the pumping cycle. For example, sensor 550 may repeatedly acquire the acoustic spectra of resonant variable volume 121 and reference volume chamber 127 (step 2611) and maintain parameters (updated for each pumping pulse and incorporating the reduction in the volume of gas within variable volume chamber 121).

[0167] Therefore, the updated parameter indicates the net amount of fluid flowing into the dispensing chamber 122. If there is sufficient delay between pulses, the fluid flowing into the dispensing chamber 122 is approximately equal to the volume dispensed by the device 10. Alternatively, the sensor 550 can repeatedly measure the increase in the volume of gas in the variable volume chamber 121 and determine the amount dispensed by the device (if there is sufficient delay between pulses). The acoustic spectrum is compared with the model spectrum in the reference table (step 2621), which can correspond to part or all of the dispensing chamber 122 with bubbles, without bubbles, or with bubbles of various sizes. The reference table may hold data obtained experimentally, determined using a model, or determined to act empirically. The reference table may include data representing various bubble-containing states and / or normal states for multiple extents of the dispensing chamber 122. If the spectrum and the updated total value conform to the normal flow model (step 2631), another acoustic spectrum is acquired in step 2611 and the cycle is repeated. If the spectrum and / or the updated total value do not conform to the normal flow model, the presence of low flow or blocked flow is determined (step 2641). Low flow or blocked flow can be indicated by a volume outside the sustainable range of the variable volume chamber 121, an updated total value below the predicted or set value, or both. When a low flow or blocked flow state is detected, an alarm is initiated (step 2671). The alarm may include an audible signal, vibration, or both. If no low flow or blocked flow state is found, the device determines whether the spectrum conforms to a model corresponding to the state of the bubbles in the dispensing chamber 122 (step 2661). If it is determined that bubbles are present, a response may be initiated that includes an alarm and / or a compensating action, which may include temporarily increasing the pumping rate (step 2651), and the cycle is resumed in step 2611. If it is determined that no bubbles are present, an alarm is initiated indicating an unknown failure state (step 2671). Also, embodiments of the present invention may utilize bubble detection using AVS technology as disclosed in co-pending U.S. Patent Application No. 60 / 789,243, which is incorporated herein by reference.

[0168] The pumping assemblies 16 of FIGS. 2A - 3 bias fluid from the reservoir 20 to the dispensing assembly 120. When a dispensing assembly according to FIGS. 6 - 7 is used, feedback provided from the dispensing assembly 120 to the pumping assembly 16 enables adjustment of the pumping assembly 16 based on an accurate measurement of the delivered volume, obviating the need to use a high-precision pump. The individual pumping pulses may be of sufficiently low volume to allow for precise compensation based on the feedback. Thus, it is possible to employ many different implementations of the pumping assembly 16. Various possible embodiments of the pumping assembly 16 are described below.

[0169] FIGS. 13 and 14 schematically illustrate alternative embodiments of some of the components within a fluid delivery device according to embodiments of the present invention. FIG. 13 shows a flow line 310 comprising a pumping assembly 16 having a pumping element 2100 positioned between an upstream one-way valve 21 and a downstream one-way valve 22. The pumping element 2100 may use an actuator to deform a portion of the flow line and generate pressure within the flow line 310. The upstream one-way valve 21 prevents backflow from the pumping element 2100 to a fluid source (not shown), and the downstream one-way valve 22 prevents backflow from the volume sensing chamber 120 to the pumping element 2100. As a result, the fluid is driven in the direction of the outlet assembly 17 and, in one embodiment, includes a high impedance path.

[0170] In the alternative embodiment shown in FIG. 14, the function of the pumping element, i.e., the function of generating pressure in the flow line 310, and the function of the upstream one-way valve 21 are performed by the combined valve pump 2200. Thus, the pumping assembly 16 of the embodiment of FIG. 14 consists of two components (i.e., the combined valve pump 2200 and the downstream one-way valve 22) instead of the three components used in the embodiment of FIG. 13. Other embodiments of the pumping assembly 16 may be used. The combination of the valve function and the pumping function within the valve pump 2200 may be achieved by various mechanisms, some of which will be described later with reference to FIGS. 15A - 16 and 22 - 56.

[0171] In many of the embodiments described later, the poppet of the inlet valve 21, the poppet of the outlet valve 22, and the pumping actuator member 54 all communicate directly or indirectly (e.g., as in FIGS. 50 - 56) with the fluid line 310 such that each of these elements can generate or react to various fluid pressures. As described above, the upstream and downstream valves (which may be referred to herein as the inlet and outlet valves) are one-way valves. The valve can be other types of one-way valves, i.e., among other types of valves that bias the flow towards the device output, a tuyere-like valve, a flap valve, a check valve, or a duckbill valve. An example of a tuyere-like valve is disclosed in U.S. Application No. 5,178,182, issued to Dean L. Kamen on January 12, 1993 (incorporated herein by reference).

[0172] In the embodiments shown in FIGS. 15A - 15D, the pumping assembly includes both an inlet valve 21 and an outlet valve 22, each including a fluid inlet, a fluid outlet, and a movable member (a part of the membrane 2356 for each valve). The pumping assembly also includes a pumping element 2100. The pumping element is located downstream from the inlet valve 21 and upstream from the outlet valve 22. In the following description, the outlet valve starts from a closed position, i.e., a position where fluid does not flow to the outlet valve. However, when the fluid exhibits sufficient pressure, pressure is applied to the membrane and the poppet 9221 of the outlet valve to open the valve, and thus the outlet valve is opened by the fluid pressure, and accordingly, the fluid can flow to the outlet valve 22. The embodiments of FIGS. 15A - 15D may be regarded as a combined valve pump (such as element 2200 in FIG. 14) in the sense that it closes the pump inlet and then biases the flow to the pump outlet by a single mechanical action.

[0173] This pumping arrangement has the advantage of separating the moving parts and the wetted - line components on opposite sides of the flexible barrier membrane 2356. As a result, the moving parts are located within a reusable component, and the wetted parts (fluid line 310) can be located within a disposable component.

[0174] In a preferred embodiment of the pumping mechanism, the fluid source is an unpressurized reservoir. When the movable member of the inlet valve is in the open position and there is a negative pressure in the pumping chamber, there is a pressure difference that draws fluid from the reservoir to the inlet valve. This negative pressure can be caused by the elasticity of the membrane in the pumping chamber. In an alternative embodiment, a spring (which can be built into the membrane) may be used to assist the rebound of the membrane in the pumping chamber. The unpressurized reservoir may be collapsible so that as fluid is taken in from it, its volume is decreased by a corresponding contraction within the reservoir. As a result, the accumulation of negative pressure or air within the reservoir is prevented.

[0175] In a preferred embodiment of the pumping mechanism, after the inlet valve is closed, pressure is applied to the pumping chamber to urge fluid from the pumping chamber to the outlet valve. The pressure generated by the pumping motion opens the outlet valve and allows the fluid to flow to the fluid outlet of the outlet valve.

[0176] The movable member can be any one that can function as described above. In some embodiments, the movable member is a flexible membrane or an elastic pumping diaphragm. In other embodiments, the movable member is a ball-shaped rigid structure or another object capable of preventing the outflow of fluid from the opening in the fluid passage.

[0177] In practice, the pumping mechanism may be primed before use. Thus, the pumping mechanism repeats several strokes to remove air from the fluid line until most or all of the air in the fluid line is removed. Many of the pumping mechanisms disclosed herein have the ability to "automatically prime" because the fluid volume contained outside the pumping chamber (except between the valves) is small. When the pump injects air into the pump chamber, generally, sufficient pressure is accumulated to blow through the outlet valve. Thus, subsequent return strokes can generate sufficient negative pressure on the pump to draw liquid from the reservoir. If the "dead" volume of the pump is too large, the air in the pumping chamber may not accumulate sufficient pressure to escape from the outlet valve. As a result, the pump may stall.

[0178] Figures 15A - 15D, 16, and 22 - 56 show some embodiments of the pumping mechanism. Next, referring to Figures 15A - 15D, an embodiment of the pumping mechanism is shown that illustrates some steps in the pumping process. 1. Fluid passes through the inlet valve 21 (as shown in Figure 15B). 2. The inlet valve is closed (as shown in Figure 15C). 3. The pumping actuator member 54 urges the fluid in the downstream direction, opens the outlet valve 22 by the fluid pressure, and allows it to flow to the fluid outlet (as shown in Figure 15D).

[0179] The pumping mechanisms of FIGS. 15A - 15D include a movable member, which in this embodiment is part of a flexible membrane 2356. The inlet valve and the outlet valve include poppets 9221, 9222 that function as valve occluders. The poppets 9221, 9222, and the pumping actuator member 54 each include springs 8002, 8004, 8006. The pump plate 8000 is attached to both the pumping actuator member 54 and the inlet poppet 9221 and acts as a termination for the respective springs 8004, 8002.

[0180] The term "poppet" is used to refer to a member that applies pressure to a movable member (i.e., the membrane) and affects the position of the membrane. Although other designs may be used, a specific example of a spring - loaded poppet valve that utilizes the structure and principle of mechanical advantage will be described later (in connection with FIGS. 50 - 56). However, it is also possible to use mechanisms other than poppets to perform the same function. In FIGS. 15B - 15D, the inlet valve 21 includes a fluid inlet, a fluid outlet, a part of the membrane 2356, and the poppet 9221. The outlet valve 22 includes a fluid inlet, a fluid outlet, a part of the membrane, and the poppet 9222.

[0181] In the embodiment shown in FIGS. 15A - 15D, the fluid path 310 is defined by a structure (element 9310 in FIG. 15A) that can have rigidity or a certain flexibility (preferably less flexible than the membrane 2356). As shown in FIG. 15A, the housing structure 9310 defines valve chambers 9321, 9322, and a pumping chamber 2350. All three of these chambers are within the fluid path 310.

[0182] Next, referring to FIGS. 15B - 15D, the inlet valve 21, the outlet valve 22, and the pump element 2100 each have a fluid inlet and a fluid outlet. The pumping actuator member 54 has a pumping chamber 2350 through which fluid flows after flowing out of the inlet valve. The pumping actuator member 54 applies pressure to the membrane 2356 to generate a positive pressure within the fluid line.

[0183] As shown in FIGS. 15B - 15D (and similarly for the valve seat 4070 of the discharge port valve shown in FIGS. 50 - 56), the valve seat 9121 in the inlet valve 21 preferably is spaced from the membrane when the membrane is not actuated by the poppet 9221 of the inlet valve.

[0184] The fluid line 310 is partially defined by the membrane 2356. In this embodiment, the membrane 2356 separates the components of the pumping mechanism from the fluid. Thus, the fluid line 310 is in contact with the fluid, and the pumping actuator 54 and the valve poppets 9221, 9222 are not in contact with the fluid. However, alternative embodiments of the pumping assembly need not include the membrane 2356 in contact with the fluid line 310. Instead, different movable members may be used for the valves and / or pumps. In still other embodiments, only the components of the fluid line 310 are separated from the pumping mechanism and thus the pumping assembly is partially in contact with the fluid.

[0185] The inlet poppet 9221 includes an end 8018 that represents the surface area of the inlet poppet in contact with the membrane portion of the fluid line 310. The pumping actuating member 54 includes an end 8012 in contact with the membrane portion of the fluid line 310. Similarly, the outlet poppet 22 includes an end 8022 in contact with the membrane portion of the fluid line 310. The ends 8018, 8022 of the valve poppet apply pressure to respective regions of the membrane 2356 to block or unblock respective portions of the flow path 310. Also, the end 8012 of the pressure - actuating member causes a flow through the fluid line 310 by applying pressure to respective regions of the membrane.

[0186] The pumping actuating member 54 is surrounded by a plunger bias spring 8004. The plunger bias spring 8004 has both the terminations of the pump plates 8000 and 8014 and a support structure that holds the pumping actuating member as well.

[0187] The injection port poppet 21 is surrounded by the injection port poppet spring 8002. However, in an alternative embodiment, the injection port poppet itself is elastic and performs the function of a spring. The injection port poppet spring 8002 has both the end of the pump plate 8000 and the vicinity end 8018 of the injection port poppet 9221.

[0188] The outlet poppet 9222 is surrounded by the passive outlet poppet spring 8006. The outlet poppet spring 8006 has both the end of the outlet poppet plate 8024 and the edge 8020 near the end of the outlet poppet 9222.

[0189] In each case, the springs 8002, 8004, 8006 terminate before their respective ends and do not interfere with the surface regions 8018, 8012, 8022 that contact the membrane 2356.

[0190] Also, in a preferred embodiment, the fluid pumping device also includes at least one shape memory actuator 278 (e.g., a conductive shape memory alloy wire) that changes shape with temperature. The temperature of the shape memory actuator may be changed by a heater or, more conveniently, by the application of an electric current. FIGS. 15B - 15D show an embodiment having one shape memory actuator 278. However, in other embodiments (described later), there may be two or more shape memory actuators 278. In one embodiment, the shape memory actuator is NITINOL TMOr a shape memory wire made of a nickel / titanium alloy such as FLEXINOL®. However, in other embodiments, any device capable of generating a force, such as a solenoid, can also be used. In one embodiment, the shape memory actuator 278 has a diameter of about 0.003 inches and a length of about 1.5 inches. However, in other embodiments, the shape memory actuator 278 is made of any alloy that can contract with heat (expansion may be assisted by a mechanism that applies a force to the alloy and stretches the alloy to its original length, i.e., a spring, but such a mechanism is not necessary) and may operate the pumping mechanism as described in the embodiments herein. In one embodiment, the diameter of the shape memory actuator 278 can be from 0.001 inches to any desired diameter, and the length can be any desired length. Generally, the larger the diameter, the greater the available contraction force. However, the current required to heat the wire generally increases with the diameter. Thus, the diameter, length, and composition of the shape memory alloy 278 can affect the current required to operate the pumping mechanism. Regardless of the length of the shape memory actuator 278, the operating force is substantially constant. An increase in the operating force can be imparted by increasing the diameter of the shape memory actuator 278.

[0191] The shape memory actuator 278 is connected to the pump plate 8000 through the connector 8008. The connector 8008 is detailed below. The shape memory actuator 278 is connected to the fluid pumping device via the terminal connector 8010. The terminal connection position varies depending on the device or system in which the pumping mechanism is used. The terminal connector 8010 is detailed below.

[0192] As described above, FIGS. 15B - 15D show a primed pumping mechanism and a fluid line 310. Next, referring to FIG. 15B, the inlet valve 21 is open, and the pumping actuator member 54 is not in pressure contact with the membrane 2356. The outlet valve 22 is in the closed position. The shape memory actuator 278 is in the extended position. In this configuration, fluid is drawn from a reservoir (not shown) into the inlet valve 21 fluid inlet. (Shown as a bulge within the membrane in the inlet valve region, but the step of drawing fluid in this step can cause a depression within the membrane, i.e., does not cause deformation of the membrane.) When the inlet poppet is in the open position, fluid can flow from the fluid inlet to the fluid outlet and further into the pumping chamber 2350. At this point, the outlet poppet end 8022 is firmly in pressure contact with the membrane 2356, sealing the outlet valve 22.

[0193] Next, referring to FIG. 15C, a current is applied to the shape memory actuator 278, and the shape memory actuator is contracting from its starting length to a desired end length. The step of the shape memory actuator 278 contracting draws the pump plate 8000 towards the fluid line 310. The inlet poppet 9221 and the pumping actuator member 54 are both connected to the pump plate 8000. The movement of the plate 8000 draws both the inlet poppet 9221 and the pumping actuator member 54 towards the membrane 2356. As shown in FIG. 15C, the inlet poppet end 8018 is firmly in pressure contact with the membrane 2356, sealing the membrane against the valve seat 9121 and closing the inlet valve 21. (The movement of the inlet poppet can bias a small amount of fluid within the inlet valve chamber (element 9321 in FIG. 15A) through either the fluid inlet or the fluid outlet of the inlet valve 21.) At the same time, the pumping actuator member 54 starts its path to the pumping chamber 2350. During this process, when the inlet poppet spring 8002 is compressed (at this point, the inlet poppet end 8018 is firmly pressed against the fluid line 310), the pump plate 8000 and the pumping actuator member 54 continue to move towards the fluid line 310. Even if the inlet poppet 9221 cannot move further due to the inlet poppet spring 8002, the pump plate 8000 can continue to move towards the fluid line 310 together with the pumping actuator member 54.

[0194] Next, referring to FIG. 15D, the pumping actuator member 54 presses against the region of the membrane 2356 on the pumping chamber 2350, and as the fluid is pumped, the pressure of the fluid in the pumping chamber 2350 increases. The outlet poppet end 8022 remains firmly pressed against the membrane 2356 (assisted by the outlet poppet spring 8006) until the outlet valve 22 is opened by the pressure from the fluid flowing from the pumping chamber 2350, sealing the fluid inlet and fluid outlet of the outlet valve 22. When sufficient pressure is reached, the fluid flows out through the fluid outlet of the outlet valve 22, thus overcoming the pressure applied to the membrane 2356 by the outlet valve 22. When the flow stops, the outlet valve 22 is closed by the passive spring 8006.

[0195] During the working stroke, the pumping actuator member spring 8004 is loaded. Finally, the pumping actuator member spring 8004 pulls the pumping actuator member 54 away from the membrane 2356. As a result, during the relaxation stroke, the spring 8004 returns the pumping actuator member 54, and the pump plate 8000 returns to the relaxation position in FIG. 15C. Also, the loaded inlet poppet spring 8002 may provide energy for the return stroke. As the pump plate 8000 approaches its relaxation position, it engages with the cap of the inlet poppet 9221, lifts the inlet poppet, and disengages it, thereby opening the inlet valve 21. Also, the pumping actuator member spring 8004 is unloaded during the return stroke.

[0196] When the injection port poppet spring 8002 reaches a threshold distance at the same level as the pump plate 8000, the pumping actuator spring 8004 is unloaded from the pump plate 8000. The membrane 2356 within the elastic pumping chamber 2350 returns to its starting position. As a result, a negative pressure is generated, and when the injection port valve opens, fluid flows from the fluid injection port of the injection port valve to the fluid outlet and further into the pumping chamber 2350. Therefore, the pumping mechanism assumes the state as shown in FIG. 15B.

[0197] The entire pump sequence described with respect to FIGS. 15B to 15D is repeated each time the pump is actuated by applying a current to the shape memory actuator 278.

[0198] The membranes referred to in this specification, including the membrane 2356, may be made of any elastic material capable of providing the necessary properties for functioning as described in this specification. Further, the membrane material may include a biocompatible material so as not to interfere with the pump operation or reduce the therapeutic value of the fluid. A plurality of biocompatible elastic materials, including nitrile and silicone, may be suitable. However, different therapeutic fluid compositions require the selection of different elastic materials.

[0199] The pumping mechanism described above and the various embodiments described herein can be explained from the perspective of the stroke length. One way to determine the stroke length is by the total change in the length of the shape memory actuator during one cycle of contraction and expansion of the shape memory actuator. This difference determines the total distance the pump rod has moved and thus the total amount of fluid that has been pumped from the inlet chamber 2354 to the pumping chamber 2350, then to the outlet chamber 2352, and finally out of the outlet chamber 2352. Another way to determine the stroke length is the distance the pump plate 8000 moves. For a partial stroke, the pump plate 8000 does not reach its maximum travel distance. In one embodiment, a small or micro stroke is continuously initiated to continuously or periodically pump fluid in a microliter volume from a reservoir to an outlet. For example, a micro stroke can displace the volume of the pumping chamber 2350 by 20%, 10%, or less than 1%.

[0200] FIG. 16 shows a variant of the embodiment diagram of the pumping mechanism shown in 15B. In FIG. 16, two different shape memory actuators (long and short) are used. FIG. 16 shows an embodiment of the pumping mechanism shown in FIG. 15B, where the shape memory wire 278 is stretched around the pulley 286 and splits into long and short fiber bundles. The common joint serving as the negative terminal may be located at the place where the long and short fiber bundles split. Completion of the circuit with either or both of the alternative paths allows for adjustment of the pumping force and / or the stroke length. In an alternative embodiment, a portion of a material such as a Kevlar material extends from the common joint around the pulley to the force application plate 8000, and the two separate shape memory wire portions extend from the common joint to their respective supports. These embodiments provide both a pumping mode and an air discharge mode by using two wires having different lengths, as will be described later.

[0201] Regarding a variable stroke that uses a shape memory actuator variable for a given length of a shape memory actuator, the stroke depends on several variables: 1) the total number of hours that electricity / heat is applied, 2) the total amount of voltage of the electricity, and 3) the diameter of the shape memory actuator. Some variable embodiments are shown in FIGS. 17-19. However, in some embodiments, while the stroke is variable, the length, current time, and voltage are maintained. These embodiments include multiple shape memory actuators (see FIG. 19) and multiple switches on a single shape memory wire (see FIG. 17). Also, as described above, the desired stroke length can be achieved by modifying any one or more of the variables.

[0202] Furthermore, it is possible to control the stroke by varying the timing of applying heat or current to the shape memory actuator. Each time the shape memory actuator is heated can be called a pulse. Factors such as pulse frequency, pulse width, and stroke length can affect the amount of fluid delivered over time.

[0203] FIGS. 17-19 further depict an embodiment of a pumping assembly that has both a fluid pumping mode and an air purging mode. When initiated, the air purging mode utilizes a compression stroke with an increased displacement amount and / or an applied force by an increased force member. The air purging mode may be initiated based on the possibility or recognition of air present within the pumping assembly. For example, the air purging mode may be initiated when a line is attached to a reservoir, when air bubbles are detected by a sensor or sensing device, or when an insufficient flow rate is detected by a sensor or sensing device. Alternatively, two modes may be used to select to discharge a smaller or larger fluid volume for a given pumping pulse.

[0204] Next, referring to FIG. 17, the schematic shows a pumping assembly that is actuated by a shape memory actuator 278 and has multiple operating modes. When the pumping chamber 2350 is filled with fluid, the pumping assembly operates in a fluid pumping mode. During the fluid pumping mode, current flows between the cathode conductor 2960 and the anode conductor 2961, resulting in resistive heating of the alloy shape memory actuator 278, and the resulting phase change and power stroke. In one embodiment, during the step of priming the pumping mechanism, or when the presence of air bubbles 2950 in the pumping chamber 2350 is suspected, an air purging mode is initiated and the current flows along a path of an extended length between the cathode conductor 2960 and the anode conductor 2965. As a result, a compression stroke with a greater force and displacement amount to the force applying member 2320 sufficient to discharge the air 2950 from the pumping chamber 2350 to the pump discharge port 2370 is obtained. In an alternative embodiment, the anode and cathode conductors may be reversed.

[0205] Next, referring to FIG. 18, the schematic shows an alternative pumping assembly having a plurality of shape memory actuators 278 of the same length. Additional actuators may be used to increase the operating pressure to the pumping chamber 2350, for example, to remove blockages or air bubbles in the fluid lines, pumping chambers, or other regions of the pumping mechanism. Also, the additional actuators may provide surrogate functionality to any pumping device. A single shape memory actuator may be capable of imparting sufficient force to remove air bubbles from the pumping chamber. Further, in the embodiment shown in FIG. 18, an additional return spring may be required depending on the length of the second shape memory actuator.

[0206] If the reservoir is initially attached to a fluid line having a pumping assembly, the pumping mechanism (element 16 of FIGS. 13-14) is typically filled with air. Also, air can enter the pumping mechanism during normal operation for various reasons. Since air is more compressible than the fluid, if there is a significant amount of air in the fluid line, applying a compression stroke of sufficient length to discharge the fluid may not be sufficient to generate enough pressure to overcome the cracking pressure of the check valve of the pumping mechanism. Therefore, the pumping mechanism can stall. However, during priming or when a small amount of air that does not have an impact is present in the pumping assembly, it may be desirable to urge the air through the line. Therefore, in this situation, it is possible to apply additional force using the embodiment shown in FIG. 18.

[0207] FIG. 19 schematically shows an alternative pumping assembly 16 having a plurality of shape memory actuators. The first shorter shape memory actuator 2975 has a first conductor 2976 and a second conductor 2977. The short actuator 2975 is capable of producing a compression stroke sufficient to discharge the fluid within the pumping chamber 2350. The shorter shape memory alloy actuator 2975 is used during normal fluid pumping mode operation. When the air evacuation mode is shown or when a greater pumping fluid volume is required, the second shorter shape memory alloy actuator 2970 may be used by sending a current along the actuator length disposed between the first conductor 2973 and the second conductor 2972. Also, the longer shape memory alloy actuator 2970 may be used as an auxiliary actuator for fluid pumping mode operation by creating a short circuit including an electrical path between the first conductor 2972 and the second conductor 2971. Also, the shorter shape memory actuator 2975 may be used to vary the stroke volume and provide better control with a low fluid volume amount. The multi-mode actuators of FIGS. 17 - 19 are not limited to use with the illustrated pump components and may be employed with any of the various embodiments of the pumping mechanisms described herein, including those using the fluid pumping devices described hereinafter and those employing the valve pumps described hereinafter. Accordingly, the desired stroke length can be initiated by applying electricity / heat to the shape memory actuator length that provides the desired stroke length.

[0208] Next, referring to FIGS. 20A and 20B, each shows an embodiment for attaching a shape memory actuator. These various embodiments are applicable to any mechanism or device described herein that employs a shape memory actuator 278. Referring to both FIGS. 20A and 20B, the shape memory actuator 278 is fed into grommet 280. The grommet 280 is then attached to component 284. Only two embodiments of this attachment method are shown, but various other methods are used in other embodiments. Other methods of attaching the grommet to a component or any fixed position are also applicable.

[0209] Next, referring to FIGS. 21A and 21B, two exemplary embodiments of the step of attaching a shape memory actuator 278 for use with a pumping mechanism 16 are shown. In each of these embodiments, the shape memory actuator 278 is designed to rotate around pulley 286. Referring to FIG. 21A, the shape memory actuator 278 is attached, preferably via a fragment 288 made of Kevlar material, to the grommet 280. One end of the shape memory actuator 278 is shown attached to the component 284 by a set of screws 289. Next, referring to FIG. 21B, one end of the shape memory actuator is shown attached to the component 284 by the grommet 280.

[0210] Various embodiments of the pumping mechanism are shown herein. The pumping mechanism may include an inlet valve, a pumping actuator member, and an outlet valve. As described above, different types of one-way valves may be used in alternative embodiments. The schematic diagrams shown in FIGS. 15A - 15D illustrate one embodiment, while the following figures illustrate alternative embodiments.

[0211] Next, referring to FIGS. 22 and 23, a side view and a cross-sectional view of a cross-section of the pumping mechanism portion are shown. In the present embodiment, the pumping actuating member is an elongated pumping finger portion 32. When a force is applied to the finger portion 32, the finger portion 32 presses against the movable member, reducing the internal volume of the fluid line. The pumping mechanism portions of FIGS. 22 and 23 show only the pumping chamber. When a one-way valve (elements 21 and 22 in FIG. 13) is coupled, application of a deformation force to the movable member 23 causes fluid to flow to an outlet assembly (not shown). As shown in FIGS. 22 and 23, the finger portion 32 is pointed to concentrate the force, but in other embodiments, the finger portion 32 may be flat or any other suitable shape. The spring 31 serves to return the finger portion 32 to the contracted non-pressing position when no force is applied by biasing the finger portion 32 to the contracted position relative to the elastic member 23. As shown in FIG. 23, it is possible to apply a force to the finger portion 23 using a motor. However, in other embodiments, a shape memory actuator is used. Various types of motors, including electric motors and piezoelectric motors, are suitable.

[0212] Referring to both FIGS. 22 and 23, the anti-reversal device 33 limits the potential movement of the finger portion 32, supports the movable member 23, and prevents the movable member 23 from moving from a fixed position in response to the application of force by the finger portion 32, thereby ensuring a reduction in the volume within the fluid line or pumping chamber. As can be seen from FIG. 22, the anti-reversal device 33 may advantageously have a complementary shape to the elastic member 23. In various embodiments, the pumping assembly 16 may include a lever or crank driven at one end by a motor and compressing the elastic member 23 at the other end.

[0213] Next, referring to FIG. 24, another embodiment of the pumping actuating member is shown in connection with a portion of the pumping assembly. A motor or a shape memory actuator (not shown) applies a rotational force to a group of interconnected protrusions 42. These protrusions 42 serve as the pumping actuating member and further apply a force to the movable member 23 in turn. Thus, an intermittent pulse of force is applied to the movable member 23. The anti-reversal device 33 is movable within the housing 44 and is biased upwardly by a spring 46 against the resilient member 23, as shown.

[0214] Next, referring to FIG. 25, an embodiment of a boosting assembly is shown that includes a pumping actuating member (here, a plunger) 54 within an outer cylinder 52. By a motor, the plunger 54 is alternately retracted and inserted into the outer cylinder. When the plunger 54 is retracted, a negative pressure draws fluid from a reservoir (not shown) into the channels 51 and the lumen 56. When the plunger 54 is inserted, the pressure increased in combination with a one-way valve (not shown) drives the fluid to a dispensing assembly (not shown). The lumen 56 is connected to the channel 51 via a connecting channel 58, and the volume of the outer cylinder lumen 56 decreases with the sudden drop action of the plunger 54, thereby biasing the fluid to the flow line 310.

[0215] Figures 26 and 27 show another embodiment where the pumping actuating member is the plunger 54. A boosting assembly and a linear actuator including a shape memory actuator 278 drive the plunger 54. In FIG. 26, the shape memory wire 278 is in a cooled-expanded state and is attached to the first support portion 241 and the plunger-attached cap 244. The cap 244 is further attached to a bias spring 243 which is in turn attached to the second support portion 242. When the wire 278 is in the expanded state, the bias spring 243 is in a relaxed state. FIG. 27 shows the shape memory actuator 278 in a contracted state due to the application of current to the wire 278 and simultaneous heating. In response to the contraction, a force is applied to the cap 244, causing the insertion movement of the plunger 54 and the corresponding pumping action. In the contracted state, the bias spring 243 is in a high energy potential state. In response to the cessation of the application of the magnetic field, the nitinol wire 278 cools and expands again, causing the bias spring 243 to return the plunger 54 to its contracted state. As shown in FIGS. 21A-21B, the shape memory actuator 278 may be wound around one or more pulleys.

[0216] Figures 28 to 30 show various embodiments in which pumping is achieved by a pumping actuator member 54 using a shape memory actuator 278 for compressing a movable member forming a pumping chamber. The pumping chamber is bounded by one-way valves 21, 22. FIG. 28 shows an embodiment including a pumping mechanism in which the pumping actuator member is a plunger 54 within an outer cylinder 52. The mechanism also includes a lever 273, a fulcrum 274, and a shape memory actuator 278. The shape memory actuator 278 is held within a housing 298, with one end attached to a conductive support 279 and the other end attached to the positive potential 275 of the lever 273. The lever 273 is further attached at its center to the fulcrum 274 and at a second end to the plunger 54. A current is applied, flowing through the terminals 275, the shape memory actuator 278, and the conductive support 279, thereby causing the shape memory actuator 278 to contract, pivoting the lever 273 around the fulcrum 274 and causing the retraction of the plunger 54. Stopping the current cools and expands the shape memory actuator 278. A return spring 276 acts via the lever 273 to return the plunger 54 to its inserted position within the outer cylinder 52. The return spring 276 is held within a housing 277. An O-ring 281 prevents fluid leakage from the plunger 54 / outer cylinder 52 assembly. Insertion and retraction of the plunger 54 causes fluid flowing in a flow line to flow in a direction determined by the orientation of two check valves (a first one-way valve 21 and a second one-way valve 22). Any suitable backflow prevention device may be used, including one-way valves, check valves, duckbill valves, flapper valves, and tuyere-like valves.

[0217] FIG. 29 shows another embodiment of a pumping mechanism having a plunger 54, an outer cylinder 52, and a boosting assembly including a shape memory actuator 278. However, this embodiment, unlike the embodiment shown in FIG. 28, does not include a lever. The shape memory actuator 278 is held within a housing 298 and has one end attached to a conductive support 279 and the other end attached to a plunger cap 244 by a contact 275. The plunger cap 244 is attached to the plunger 54. When sufficient current is applied through the contact 275, the shape memory actuator 278 contracts. This contraction draws the plunger cap 244, causing the plunger 54 to be inserted into the outer cylinder 52. Stopping the current cools the shape memory actuator 278, thereby expanding it. In response to the expansion of the wire, a return spring 276 acts to return the plunger 54 to its retracted position within the outer cylinder 52. The return spring 276 is held within a housing 277. An O-ring 281 prevents leakage of fluid from the plunger 54 / outer cylinder 52 assembly. Insertion and retraction of the plunger 54 causes fluid flowing in the flow line to flow in a direction determined by the orientation of the first check valve 21 and the second check valve 22.

[0218] Next, referring to FIG. 30, an embodiment of a pumping device using a plunger 54 and an outer cylinder 52 is shown. In this embodiment, a shape memory actuator 278 in the form of a wire positioned on a shaft within the plunger 54 is used to apply a force to the plunger. The shape memory actuator 278 extends from the plunger cap 272 to the shaft within the plunger 54 and further to the support base 299 from the channel 58. O-rings 281 and 282 seal the plunger 54, the outer cylinder 52, and the channel 58. By applying current to the first conductor 258 and the second conductor 257, the shape memory actuator 278 is heated and contraction of the shape memory actuator 278 occurs. The contraction of the shape memory actuator 278 generates a downward force sufficient to overcome the upward biasing force of the return spring 276 applied to the plunger cap 272, thereby driving the plunger 54 into the lumen 290 of the outer cylinder 52. By the expansion of the shape memory actuator 278, the return spring 276 returns the plunger 54 to the retracted position. The insertion and retraction of the plunger 54 causes fluid flowing in the flow line to flow in a direction determined by the orientation of the first one-way valve 21 and the second one-way valve 22.

[0219] An alternative embodiment of the pumping mechanism is shown in FIG. 31. The pumping actuating member is an assembly 101 that combines the functions of the reservoir and the pumping mechanism. Based on the commands of the control device 501, the motor 25 drives the plunger 102 to generate pressure within the reservoir 104, thereby urging fluid towards the first one-way valve 106. The fluid then flows from the elastic dispensing chamber 122 of the volume sensor assembly 120 having the sensor 550 into the outlet assembly 17. An optional second one-way valve 107 may be included. Feedback control between the sensor 550 and the motor 25 via the control device 501 ensures the desired flow rate of fluid to the patient. The first one-way valve 106 serves to prevent reverse flow of fluid due to the elastic force of the dispensing chamber 122 of the volume sensor assembly 120 when the chamber is filled and expanded. The second one-way valve 107 serves to prevent reverse flow of fluid from the outlet assembly 17 or the patient 12 into the dispensing chamber 122. In this embodiment, the sensor 550 can immediately detect the volume within the dispensing chamber 122.

[0220] Figures 32 to 34 schematically show cross-sectional views of the combined valve pump 2200. Figure 32 shows the valve pump 2200 having a collection chamber 2345 and a pumping chamber 2350 in a stationary position before operation. Figure 33 shows the valve pump 2200 in an operating state during the compression stroke. Figure 34 shows the pump in an operating state at the end of the compression stroke. The pump inlet 2310 is in fluid communication with an upstream fluid source such as a reservoir and is connected to the first end of the channel 2360. The channel 2360 is connected at a second end to the collection chamber 2345, which is in fluid communication with a diaphragm opening 2390 disposed within the elastic pumping diaphragm 2340. The collection chamber 2345 is bounded on a first side by the elastic pumping diaphragm 2340 and on a second side by the elastic pumping membrane 2330. The pumping membrane 2330 may consist of, among other things, latex or silicone rubber. The downstream side of the diaphragm opening 2390 opens into the pumping chamber 2350. During the step of priming the pump and during the operating cycle, fluid moves from a fluid source such as a reservoir, through the pump inlet 2310, the channel 2360, the collection chamber 2345, and the diaphragm opening 2390, and then reaches the pumping chamber 2350. The one-way valve 22 prevents fluid from flowing out of the pumping chamber 2350 through the pump outlet 2370 until sufficient fluid pressure is applied to the one-way valve 22 to open it and as long as it remains closed. In Figure 32, the pumping actuating member 2320 is shown in a stationary position and the elastic pumping membrane 2330 is shown in a relaxed configuration of minimum surface area, thereby maximizing the volume of the collection chamber 2345. In this embodiment, the pumping actuating member is shown as a ball, but in other embodiments, the pumping actuating member can be anything that operates to actuate the pumping mechanism and is capable of applying sufficient force to the elastic pumping membrane 2330.

[0221] As can be seen from FIG. 33, when the pumping actuator member 2320 operates during the compression stroke, the pumping actuator member 2320 starts to move towards the diaphragm opening 2390 of the elastic pumping diaphragm 2340, expands the elastic pumping membrane 2330, and causes a reverse flow of the fluid collected in the collection chamber 2345. In the latter half of the boosting stroke, as shown in FIG. 34, the pumping actuator member 2320 seals and houses the elastic pumping membrane 2330 with respect to the diaphragm opening 2390. To assist in the sealing, the pumping actuator member 2320 may have a complementary shape to the shape of the diaphragm opening 2390. For example, the pumping actuator member 2320 may be spherical or conical, and the diaphragm opening 2390 may be a cylindrical through-hole. In the main stage of the boosting stroke, the reverse flow from the pumping chamber 2350 is blocked. By the continuous movement of the pumping actuator member 2320, the elastic pumping diaphragm 2340 is deformed, increasing the pressure in the pumping chamber 2350 while continuously sealing the diaphragm opening 2390 against the reverse flow from the pumping chamber 2350. When the pressure in the pumping chamber 2350 provides sufficient fluid pressure to the one-way valve 22, the fluid flows from the pumping chamber 2350 to the pump discharge port 2370. During the return stroke, the pumping actuator member 2320, the elastic pumping membrane 2330, and the elastic pumping diaphragm 2340 return to the relaxed position shown in FIG. 32. During the return stroke, the internal pressures of the pumping chamber 2350 and the collection chamber 2345 decrease, but by inducing the flow of fluid from the fluid source, through the pump inlet 2310, and then through the channel 2360, it promotes the replenishment of the valve pump 2200.

[0222] Next, referring to FIG. 35, a schematic cross-sectional view of one embodiment of the elastic pumping diaphragm 2340 is shown. The diaphragm body 2515 may be made of an elastic material such as silicone rubber. Also, elasticity may be imparted to the flexible or already elastic body 2515 including the diaphragm spring 2510. The diaphragm spring 2510 may be incorporated within the elastic pumping diaphragm 2340 or may be disposed adjacent to the elastic pumping diaphragm 2340. An example of one embodiment of the diaphragm spring 2510 is shown in FIG. 36. A combination of a diaphragm body 2515 including a flexible material and a diaphragm spring 2510 including an elastic material may be used. As a result, when the pumping diaphragm 2340 is contracted together with the elastic pumping membrane 2330 deformed by a pumping operating member (not shown, see FIGS. 32 - 34), it exhibits a high degree of sealing and has a high degree of elasticity. The valve seat 2517 may be positioned around the diaphragm opening 2390. The valve seat 2517 may function as a receptacle for the deformed portion of the elastic pumping membrane 2330. The biasing member 2320 may deform the pumping membrane 2330, deforming and sealing it to contact the valve seat 2517. When sufficient force is applied, the valve seat is elastically deformed and can ensure complete sealing against backflow of the fluid. The ratio of the cross-sectional height to the cross-sectional width of the valve seat 2517 can generally be selected differently and adapted to the flow environment.

[0223] Next, referring to FIG. 36, an example of the diaphragm spring 2510 for use in the pumping diaphragm 2340 of FIG. 35 is shown. The outer annular portion 2520 and the inner annular portion 2540 are connected by at least three elastic arms 2530. The center of the inner annular portion 2540 has a spring opening 2550 and can be aligned with the diaphragm opening 2390 of the pumping diaphragm 2340 as shown in FIG. 35.

[0224] Next, referring to FIG. 37, a schematic view is shown that represents a cross-sectional view of the valve pump 2200 shown in FIGS. 32-34 in combination with an assist assembly including a pumping actuator member 2320, an actuator, and a lever 273. When excited by an actuator such as a shape memory actuator 278, the lever 273 pivots about a fulcrum 274 and initiates a compression stroke. The hammer 2630 rises from the lever 273. During the compression stroke, the hammer 2630 contacts the circular pumping actuator member 2320 and moves within the gap of the support structure 2660 of the pumping actuator member until the pumping actuator member 2320 is pushed against the elastic pumping diaphragm 2330 until it is held sealed against the diaphragm opening 2390 located within the elastic pumping diaphragm 2340. With the continued movement of the lever 273, the pumping actuator member 2320 causes deformation of the pumping diaphragm 2340. When sufficient fluid pressure is applied to the one-way valve 22, the one-way valve 22 opens. This allows fluid to flow from the pumping chamber 2350 to the pump discharge port 2370. In response to the cooling of the shape memory actuator 278, the elasticity of the pumping diaphragm 2340 and the elastic pumping diaphragm 2330 return the lever 273 to the starting position determined by the lever stop 2650 and the lever detent 2640. Alternatively, a return spring (not shown) may be used to return the lever 273 to the starting position. Although shown as a sphere, the assist member 2320 may alternatively be a piston, a protrusion of the lever 273, or other suitable form.

[0225] Figure 38 schematically shows a cross-sectional view of an embodiment of a valve pump using an elastic cylindrical bending portion 2670. In one embodiment, the elastic cylindrical bending portion is made of rubber, but in other embodiments, it can be made of any elastic material. The cylindrical bending portion 2670 has a central passage 2675 and a plurality of elastic radial fins 2672 arranged in sealing contact with the housing 2673. The fluid flowing into the pump inlet 2310 passes through the channel 2360 and collects in the upstream region of the one-way valve 22 (collection chamber 2345, central passage 2675 of the cylindrical bending portion 2670, and pumping chamber 2350). The pumping chamber is connected through the central passage 2675 to be in fluid communication with the collection chamber 2345. During the compression stroke of the pumping mechanism, the pumping actuating member 2320 applies a force to and deforms the elastic pumping membrane 2330 until the elastic pumping membrane 2330 is held in sealing contact with the valve seat 2680 of the cylindrical bending portion 2670. Thereby, the backflow from the collection chamber 2345 to the pump inlet 2310 is blocked. By the continuous movement of the pumping actuating member 2320, deformation of the cylindrical bending portion 2670 occurs. The pressure in the pumping chamber 2350 increases until sufficient time to open the one-way valve 22. Then, the fluid can flow to the pump outlet 2370.

[0226] The pumping actuating member 2320 is shown as a ball shape in Figure 38. However, in other embodiments, the pumping actuating member 2320 can be of any shape that can function as described above.

[0227] Next, referring to Figure 39, an alternative embodiment of the cylindrical bending portion 2670 (shown in Figure 38) employing an elastic portion 2680 and a rigid cylindrical support portion 2690 is shown. Similar to the cylindrical bending portion 2680 of Figure 38, the elastic portion of the cylindrical bending portion 2670 includes a valve seat 2680 that seals the central passage 2675 in response to the application of force by the pumping actuating member 2320. Thus, the elastic portion 2680 of the cylindrical bending portion 2670 deforms and transmits the pressure to the pumping chamber 2350.

[0228] Figures 40-44 schematically show cross-sectional views of alternative embodiments of the valve pump in various operating states. The valve pump 2200 of Figures 40-44 has an elastic diaphragm spring 6100 and an elastic sealing membrane 6120, and together performs a function similar to that of the elastic pumping diaphragm 2340 of the valve pump 2200 shown in Figures 32-34. Figure 40 shows the valve pump 2200 in a stationary state. In the stationary state, fluid can flow from the inlet 2360 to the upper part 2346 of the collection chamber 2345, and from the opening 6110 in the diaphragm spring 6100 to the lower part 2347 of the collection chamber 2345. Then, the fluid can proceed from one or more openings 6130 in the sealing membrane 6120 into the pumping chamber 2350. Under low pressure conditions, further fluid flow is blocked by the one-way valve 22. Both the spring diaphragm 6100 and the sealing membrane 6120 may be composed of an elastic biocompatible material. The spring diaphragm 6100 may have a greater elastic force than the sealing membrane 6120. For example, the spring diaphragm 6100 may be a circular piece of flexible biocompatible plastic, and the sealing membrane 6120 may be a sheet of silicone or fluorosilicone elastomer.

[0229] Figures 41 and 42 show two intermediate, partially actuated valve pumps 2200. The pumping actuator member 2320 deforms the pumping membrane 2330 and biases the spring diaphragm 6100 through the collection chamber 2345, thereby deforming and biasing it against the sealing membrane 6120. At this point in the compression stroke, backflow into the opening 6110 of the spring diaphragm 6100, or the opening 6130 within the sealing membrane 6120, or both, is inhibited. The offset arrangement of the sealing membrane opening 6130 relative to the spring opening 6100 creates a seal between the spring diaphragm 6100 and the sealing membrane 6120. In some embodiments, this seal may be complemented by an excess sealant between the filling chamber elastic pumping membrane 2330 and the spring diaphragm 6100 (e.g., in the embodiments of Figures 43 - 44, there is no such excess sealant). The outer peripheral portion (not shown) around the spring diaphragm opening 6110 may act as a valve seat to improve sealing.

[0230] Next, referring to Figure 42, continued movement of the pumping actuator member 2320 causes further deformation of the pumping membrane 2330, spring diaphragm 6100, and sealing membrane 6120. As a result, the fluid within the pumping chamber 2350 is compressed until the fluid pressure opens the one - way valve 22. With further compression, the fluid flows out through the discharge port 2370.

[0231] An alternative embodiment of the valve pump 2200 of Figures 40 - 42 is schematically shown in Figure 43. In this embodiment, the pumping actuator member 2320 traverses the elastic pumping membrane 2330. The pumping membrane 2330 is hermetically attached to the outer periphery of the pumping actuator member 2320 at an intermediate point along the length of the pumping actuator member 2320. During operation, the diaphragm spring opening 6110 is sealed against backflow only by the sealing membrane 6120. The elastic pumping membrane 2330 does not contact the opening 6110. An alternative embodiment of the device shown in Figure 40 is shown in Figure 44.

[0232] Next, referring to FIG. 45, a cross-sectional view of an alternative embodiment of the coupling valve pump 2200 is shown. The shape memory actuator 278 actuates a compression stroke, thereby moving the elastic pump vane 2710 as a lever about the fulcrum 274 and deforming the elastic pumping membrane 2330. The elastic pump vane 2710 and the elastic pumping membrane 2330 apply pressure to the fluid within the inclined pumping chamber 2720 having a shallow region 2730 and a deep region 2740. In the first half of the compression stroke, the pump vane 2710 closes the channel 2360 connecting the pump inlet 2310 and the inclined pumping chamber 2720 to the elastic pumping membrane 2330. As the compression stroke continues, force is applied to the fluid within the inclined pumping chamber 2720 until the fluid pressure within the inclined pumping chamber 2720 becomes sufficient to open the one-way valve 22. The fluid then exits from the pump outlet 2370. The pump vane 2710 may be wholly or partially constructed from an elastic material such as rubber. In some embodiments, the elastic material includes inelastic splines. Alternatively, in some embodiments, the elastic force is applied through the elastic region 2750, and thus the elastic region 2750 is the only elastic component of the pump vane 2710 in these embodiments. In these embodiments, the elastic region 2750 contacts the bottom of the inclined pumping chamber 2720. Due to the elasticity of the pump vane 2710, after the pumping vane 2710 contacts the base 2780 of the shallow region 2730, the compression stroke is continued. A return spring (not shown) returns the pump vane 2710 to its starting position during the return stroke.

[0233] Next, referring to FIG. 46, a cross-sectional view of an alternative embodiment of the pumping mechanism is shown. This embodiment includes an elastic pump vane 2710. The elastic pump vane 2710 includes an elastic region 2830 that provides an elastic force to the pump vane 2710. The elastic region 2830 joins the pumping actuating member 2820 to the pump vane 2810. When used with a valve pump (not shown), the elastic pump vane 2710 of FIG. 42 closes an inlet channel (not shown, shown as 2360 in FIG. 45), then bends in the flexible region 2830, causing the actuating member 2820 to apply additional pressure to the fluid within an inclined pumping chamber (not shown, shown as 2720 in FIG. 45). The actuating member 2820 may be entirely composed of an elastic material such as rubber. However, in an alternative embodiment, only the region contacting the bottom of the pumping chamber (not shown) is made of elastic material. The elastic pump vane 2710 returns to its relaxed structure during the return stroke.

[0234] Next, referring to FIG. 47, a cross-sectional view of another embodiment of the pumping mechanism is shown. The pumping mechanism is shown in an operating intermediate stage with the inlet valve 2941 closed. The pumping mechanism includes a fluid line 2930, a movable member 2330 which is a membrane in this embodiment, an inlet valve 2941, a poppet 2940, a pumping actuating member 2942, a pumping chamber 2350, and an outlet valve 22. The inlet valve 2941 and the pumping actuating member 2942 are each peripherally surrounded by a return spring 276 and actuated by a shape memory actuator 278 connected to a lever 273. The lever 273 actuates both the inlet valve 2941 and the pumping actuating member 2942. The lever 273 is pivotally attached to a fulcrum 274 and includes an elongated spring member 2910 attached to the lever 273 that terminates at a valve actuating striker 2946. The spring member 2910 may be curved. The spring member 2910 biases the position of the valve actuating striker 2946 away from the lever 273 and towards the inlet valve 2941. The lever 273 has a pump actuating striker 2948 that is not attached to the spring member 2910 and is positioned adjacent to the pumping actuating member 2942.

[0235] The current causes the shape memory actuator 278 to contract, and the lever 273 pivots around the fulcrum 274. By the pivoting step, the valve actuating striker 2946 is placed in a fixed position, closing the inlet valve 2941. As the shape memory actuator 278 continues to contract, the lever 273 also continues to pivot and further compresses the elongated spring member 2910. During this time, the pump actuating striker 2948 biases the pumping actuating member 2942 against the pumping chamber 2350. When sufficient pressure is reached, the outlet valve 22 is opened by the fluid pressure, and the fluid flows out of the valve.

[0236] During the relaxation stroke, the return spring 276 is unloaded, returning the lever 273 to the starting position, releasing the pumping actuating member 2942. The inlet valve 2941 opens. Due to the elasticity of the pumping chamber 2350, the pumping chamber 2350 is replenished.

[0237] Next, referring to FIGS. 48 and 49, a cross-section of an embodiment in which the pumping mechanism employs a bell crank 7200 and couples a valve pump 2200 with a flow bias valve is schematically shown. The bell crank 7200 converts the force generated by the linear shape memory actuator 278 into a lateral pumping force. FIG. 48 shows the mechanism in the stationary or replenishing mode, and FIG. 49 shows the mechanism in the operating state. The contraction of the actuator 278 rotates the bell crank 7200 around the shaft 7210, presses against the force applying member 2320, seals the elastic membrane 7220 against the elastic pumping diaphragm 2340, and biases the fluid from the pumping chamber 2350 to the dispensing chamber 122. The return spring 276 cooperates with the return spring support 7221 to release the pumping force, expand the pumping chamber 2350, and draw the fluid from the reservoir 20. Further referring to FIGS. 48 and 49, a flow bias valve 4000 having a valve spring 4010 and a poppet or plunger 4020 is also shown.

[0238] In some embodiments of the pumping mechanism described above, one or more aspects of the following valve operation descriptions are relevant. Next, referring to FIG. 50, an example of a closed fluid bias valve 4000 is shown. The valve spring 4010 applies a force to the poppet 4020, and seals and presses the valve membrane 4060 against the valve seat 4070 surrounding the terminal opening of the valve discharge port 4040. The valve seat 4070 may include a protruding portion in the circumferential direction to improve sealing. As will be described later with reference to FIGS. 54-55, the back pressure generated by the action of the elastic dispensing assembly should be insufficient to cause backflow into the fluid bias valve 4000. As shown in FIG. 51, when the pumping assembly is actuated, sufficient pressure is generated to dislodge the membrane 4060 and the poppet 4020 from the valve seat 4070, thereby allowing fluid to flow from the valve inlet 4030, through the inlet chamber 4050, to the valve discharge port 4040. FIGS. 52-53 show an alternative valve having a valve seat 4070 without a circumferential protrusion.

[0239] Next, referring to FIGS. 54 and 55, diagrams are shown of how an exemplary fluid bias valve selects between forward and reverse flow. FIG. 54 schematically represents the valve in the closed position. The back pressure in the discharge port 4040 applies a force to a relatively small area of the flexible valve membrane 4060 adjacent to the valve seat 4070, and thus the poppet 4020 cannot be removed. Next, referring to FIG. 55, this figure schematically represents the valve during the operation of the pumping actuator member. The pressure of the pumped fluid applies a force over a larger area of the membrane 4060 than the area adjacent to the valve seat. As a result, the inlet pressure has a greater mechanical advantage for dislodging the poppet 4020, and forward flow occurs in response to the action of the pumping actuator member. Thus, the critical pressure required to displace the poppet 4020 is lower at the inlet than at the discharge port. Therefore, the spring bias force and the applied area size associated with both the fluid inlet and the fluid outlet can be selected such that the flow is substantially in the forward direction.

[0240] Next, referring to FIG. 56, similar to the flow bias valve of FIG. 50, a cross-sectional view of an adjustable flow bias valve 4130 is shown that operates on the main structure but allows adjustment of the pressure required to open the valve, i.e., the "cracking pressure" (which can be, in some embodiments, 0.2 to 20 pounds per square inch or "psi"). The cracking pressure is adjusted by rotating the spring tension screw 4090, changing the volume of the recess 4080, compressing or restoring the valve spring 4010, thereby changing the bias force of the spring 4010. The valve spring 4010 biases the plunger 4100 against the valve diaphragm 4060 and biases it against the valve seat. The plunger 4100 serves as a force - applying function similar to the fixed - pressurized poppets (shown as 4020 and 4000 in FIGS. 50 - 53 respectively) of the flow bias valve. The step of compressing the valve spring 4010 reduces its bias force, thereby increasing the cracking pressure. Conversely, the step of restoring the spring 4010 reduces its bias force and the accompanying cracking pressure. The valve spring 4010 is positioned coaxially around the shaft of the plunger 4100 and applies its bias force to the plunger 4100. In some embodiments, the shaft of the plunger 4100 may be shorter than the lengths of both the valve spring 4010 and the recess 4080 and may be freely displaced in response to the increasing fluid pressure within the fluid inlet 4030. The plunger 4100 may be of any size necessary to function as desired. As in the embodiments of FIGS. 50 - 53, the wetted parts are present within the disposable portion 2610, and the force - applying components (e.g., the plunger and spring) may be present within the reusable portion 2620. Also, the main structure of the operation is similar. The greater mechanical advantage of the fluid inlet 4030 over the discharge port 4040 works advantageously for the forward flow as compared to the reverse flow. Alternatively, the plunger 4100 may be replaced with a poppet (shown as 4020 in FIGS. 50 - 55). In some embodiments, it may be desirable to eliminate the raised valve seat. In these embodiments, the plunger may be ball - shaped or another shape capable of concentrating the force.

[0241] The flow bias valve 4000 substantially reduces or prevents backflow from the dispensing chamber 122 to the pumping chamber 2350. As shown in FIGS. 50-56, the valve spring 4010 biases the poppet or plunger 4040 and presses the diaphragm 7220 against the valve seat 4070 to provide a mechanical advantage in the forward flow through line 310. By performing the functions of the pumping diaphragm 2330 and the valve diaphragm, the diaphragm 7220 can place line 310, the pumping chamber 2350, and the pumping diaphragm 2340 within one component (e.g., the disposable portion 2610) and the remainder of the pumping mechanism within a second removable component (e.g., the reusable portion 2620). By placing the more durable and expensive components in the reusable portion 2620, economy and convenience can be achieved.

[0242] The pumping mechanisms described in the various embodiments above can be used in various devices and are capable of pumping fluids. As an exemplary embodiment, the pumping mechanisms described in FIGS. 59A-59E, FIGS. 60A-60D, and FIGS. 60A-60C are described as being integrated into a fluid pumping device.

[0243] Referring to FIGS. 57 and 58, an alternative method of a fluid schematic is shown. These are two schematics in which the reservoir 20 and the pumping assembly 16 are connected to the dispensing assembly 120. In the embodiment shown in FIG. 57, the reservoir and the pumping assembly are connected in parallel to the dispensing assembly 120. In the embodiment shown in FIG. 58, the shunt line 150 is connected back from the output of the pumping assembly 16 to the reservoir 20. Since much of the fluid output of the pumping assembly 16 returns to the reservoir 20 via the shunt line 150, the pumping assembly 16 can be accommodated in various pumping mechanisms 16 that cannot function as desired in the embodiment shown in FIG. 57. Thus, in some embodiments where a large-volume pumping mechanism is employed, the shunt line 150 can provide a small-volume function for the large-volume pumping mechanism. The one-way valves 21 and 22 are oriented in the same direction and are included to prevent unwanted backflow.

[0244] Next, referring to FIG. 59A, a fluid schematic of an embodiment of a fluid pumping device is shown. In this embodiment, the fluid is located within a reservoir 20 connected to a fluid line 310. The fluid line 310 communicates with a pumping mechanism 16 separated by a membrane 2356. The fluid is pumped from a flow restrictor 340 to a delivery cannula 5010 for injection into the device or the patient. It should be understood that the injection device or cannula 5010, although not part of the device, is worn by the patient for fluid delivery. Embodiments of the system are described in detail below and these include the injection device or cannula 5010.

[0245] Next, referring to FIG. 59B, an alternative embodiment of the schematic shown in FIG. 59A is shown. In the embodiment shown in FIG. 59A, the fluid is pumped to the flow restrictor 340 and then to the cannula 5010. However, in FIG. 59B, the fluid is not pumped to the flow restrictor. Instead, the fluid has the same impedance and is pumped to the cannula 5010.

[0246] In both FIGS. 59A and 59B, a fixed volume of fluid is pumped to the patient, and in one embodiment, is approximated by the pump stroke. The stroke length provides an approximation of the volume pumped to the patient.

[0247] Next, referring to FIG. 59C, a schematic fluid diagram of one embodiment of the fluid pumping device is shown. In this embodiment, the fluid is located within a reservoir 20 connected to a fluid line 310 by a diaphragm 6270. The fluid line 310 communicates with a pumping mechanism 16 separated by a membrane 2356. The fluid is pumped to a variable volume delivery chamber 122 and then to a delivery cannula 5010 to the patient from a flow restrictor 340.

[0248] The volume of fluid delivered is determined using a dispensing assembly 120 that includes an acoustic volume sensor (AVS) assembly (such as described above), a variable volume delivery chamber 122, and a dispensing spring 130. Similar to the pumping mechanism, the membrane 2356 forms the variable volume dispensing chamber 122. The membrane is made of the same material (or in some embodiments, a different material) as the membrane 2356 within the pumping mechanism 16 (detailed above). The AVS assembly is detailed above.

[0249] Next, referring to FIG. 59D, which is an alternative embodiment to the embodiment shown in FIG. 59C, in this embodiment, there is no flow restrictor between the variable volume delivery chamber 122 and the cannula 5010. Next, referring to FIG. 59E, an alternative embodiment to the embodiment shown in FIG. 59C is shown with an alternative pumping mechanism 16.

[0250] Next, referring to FIGS. 59A - 59E, the reservoir 20 can be any fluid source and includes, but is not limited to, a syringe, a collapsible reservoir bag, a glass bottle, a glass vial, or any other container capable of safely holding the fluid to be delivered. The diaphragm 6270 is the connection point between the fluid line 310 and the reservoir 20. Various embodiments of the diaphragm 6270 and the reservoir 20 are detailed below.

[0251] The embodiments of the fluid delivery device shown in FIGS. 59A - 59E can be used for delivering any type of fluid. Further, this embodiment can be used as one, two, or three separate fitting components. Next, referring to FIGS. 60A - 60D, the same embodiment described with reference to FIGS. 59A - 59D is shown separated into fitting components. Component X includes movable components, and component Y includes fluid line 310 and membrane 2356. In some embodiments of this design, component Y is a disposable part, and component X is a non - disposable part. Component X does not come into direct contact with the fluid, and component Y is a component that only has a wetted area. In the above - described embodiment, reservoir 20 can be of any size and is integrated into either this disposable part or a separate disposable part. In any embodiment, reservoir 20 can be refillable. In an embodiment where reservoir 20 is integrated into the disposable component Y, reservoir 20 is manufactured to be filled with fluid or the patient or user fills reservoir 20 using a syringe through diaphragm 6270. In an embodiment where reservoir 20 is a separate fitting component, reservoir 20 is manufactured to be filled with fluid or the patient or user fills reservoir 20 using a syringe (not shown) through diaphragm 6270 as part of a reservoir filling device (not shown, described in detail below) or manually using a syringe through diaphragm 6270. Further details regarding the process of filling reservoir 20 will be described later.

[0252] Although various embodiments have been described with respect to FIGS. 59A - 59E and FIGS. 60A - 60D, the pumping mechanism can be any pumping mechanism described in the embodiments of this specification or alternative embodiments having similar functions and features. For example, referring to FIG. 61A, a similar embodiment as shown in FIG. 59A is shown having a typical block that includes pumping mechanism 16. This shows that any pumping mechanism 16 described herein and functioning similarly can be used in a fluid pumping device. Similarly, FIGS. 61B and 61C are depictions of systems that include the embodiments of FIGS. 59B and 59C respectively.

[0253] The schematic diagram of the fluid pumping device described above can be implemented within a device that can be used by a patient. There are several embodiments. The device can be a stand-alone device or integrated into another device. The device can be of any size or shape. The device can be either portable or non-portable. The term "portable" means that the patient can carry the device in a pocket, wear it on the body, or otherwise transport the device. The term "non-portable" means that the device is in a medical facility or at home, but the patient does not carry the device to almost all places where the patient moves. The remainder of this description focuses on a portable device as an exemplary embodiment.

[0254] Because it is a portable device, the device can be worn by the patient or carried by the patient. In an embodiment where the device is worn by the patient, it is referred to as a "patch pump" for the purposes of this description. When the patient carries the device, it is referred to as a "portable pump" for the purposes of this description.

[0255] The following description pertains to various embodiments for either a patch pump embodiment or a portable pump embodiment. In various embodiments, the apparatus includes a housing, a pumping mechanism, a fluid line, a movable member, a reservoir, a power source, and a microprocessor. In various embodiments, a dispensing assembly, for example, a volume sensing device (in some embodiments, including an AVS assembly), is included within the apparatus. Also, certain embodiments may include a fluid restrictor, which is not described in the following figures, and the fluid lines are shown homogeneously for simplicity of the figures. For the purposes of this description where a dispensing assembly is included, the exemplary embodiment includes an AVS assembly. The AVS assembly is a preferred embodiment, but in other embodiments, other types of volume sensing devices may be used. However, in some embodiments, a volume sensing device is not used, and conversely, the reservoir itself determines the volume of fluid delivered or estimates the volume amount delivered using the pump stroke. It should be understood that the schematic apparatus shown herein is intended to illustrate some variations within the apparatus. Also, the embodiments represented by these schematics may each include a sensor housing, a vibration motor, an antenna, a wireless communicator, or other components described with reference to FIGS. 70 - 70D. Accordingly, these depictions are not intended to limit the components, but rather to illustrate how the various components may be correlated within the apparatus.

[0256] Next, referring to FIG. 62A, a schematic diagram of the stand-alone device 10 is shown. The housing 10 can be of any shape or size and can accommodate the intended use. For example, if the device is used as a patch, the device is compact enough to be worn as such. If the device is used as a portable pump, the device is compact enough to be used as such. In some embodiments, the housing is made of plastic, and in some embodiments, the plastic is any injection-moldable fluid-compatible plastic such as polycarbonate. In other embodiments, the housing consists of a combination of aluminum or titanium and plastic or any other material, and in some embodiments, the materials are lightweight and durable. Additional materials can include, but are not limited to, rubber, steel, titanium, and their alloys. As shown in FIG. 62A, the device 10 can be of any desired size or shape.

[0257] FIGS. 62A-69B are schematic diagrams showing exemplary embodiments. The exact design depends on many factors including, but not limited to, the size of the device, power limitations, and intended use. Thus, FIGS. 62A-69B are intended to illustrate various features and possible combinations of the device, however, the actual device can be easily designed and implemented by one of ordinary skill in the art. By way of example, embodiments of the device are described and illustrated below. However, these are not intended to be limiting, but rather are intended to be exemplary.

[0258] Next, referring to FIG. 62B, for the patch device, in some embodiments, the housing 10 includes an insertion area confirmation window 342. This allows the area of the patient where the injection device or cannula (not shown) is to be inserted to be confirmed. Shown here is the cannula housing 5030 area of the device 10. The confirmation window 342 is made of any permeable material including, but not limited to, plastic. The confirmation window 342 is shown to be in a specific position on a specific shaped device, however, the confirmation window 342 can be integrated at any desired position within any housing embodiment.

[0259] Next, referring to FIG. 63A, the apparatus 10 is shown. The reservoir 20 is shown connected to the fluid line 310 (which is then connected to the pumping mechanism 16). The dispensing assembly 120 is shown connected to the fluid line 310. The pumping mechanism 16 and the dispensing assembly 120 are separated from the fluid line 310 by a membrane 2356. The cannula housing 5030 is downstream from the volume measuring device. The shape memory actuator 278 is shown connected to the pumping mechanism 16. A microprocessor on the printed circuit board 13, as well as a power supply or battery 15 are included. Also, a flow impedance as described above can be implemented between the dispensing assembly 120 and the cannula housing 5030.

[0260] Next, referring to FIG. 63B, in this embodiment, a similar apparatus 10 as shown in FIG. 63A is shown, except that the dispensing assembly is not included. In this embodiment, the volume of fluid delivered depends on either the pump stroke (number and length), the reservoir 20 (volume and time), or both, or any other method described above for monitoring the volume of fluid delivered.

[0261] Next, referring to FIG. 63C, a similar apparatus 10 as shown in FIG. 63B is shown, except that the apparatus 10 includes a dispensing chamber 122 and a sensor housing 5022.

[0262] Next, referring to FIG. 64A, an embodiment of the patch pump device 10 is shown. This embodiment is based on the embodiment of the device 10 shown in FIG. 63A. In this embodiment, the patch pump device 10 is divided into two sections (upper section X and base section Y). The upper section X includes a pumping mechanism 16, a dispensing assembly 120 (optional but shown as an exemplary embodiment), a power source 15, and a microprocessor and printed circuit board 13. These are non-wetted elements, i.e., they do not come into direct contact with the fluid. The base section Y includes a fluid line 310 and a membrane 2356. Also, if a reservoir 20 is incorporated into the device, the reservoir is also included in the base section Y. However, in embodiments where the reservoir 20 is a separate fitting, the reservoir 20 is connected to the fluid line when fully assembled (see FIGS. 66A - 66D and their description), but is not incorporated into the device.

[0263] Also, the patch pump device includes a cannula housing 5030. This is the area where the cannula line 5031 is located. The cannula line 5031, which is part of the fluid line 310, allows a cannula (or other injection device) to receive fluid and deliver that fluid to a patient (not shown).

[0264] Next, referring to FIG. 65A, in some embodiments, the cannula 5010 is inserted directly into the patient through the housing 5030. The cannula 5010 is connected to a diaphragm (not shown) that connects the cannula line 5031 to the cannula 5010. Next, referring to FIG. 65B, in other embodiments, an insertion set (including a cannula and a tube, not shown in FIG. 65B but shown as elements 5033 and 5010 in FIG. 64B) is used. Thus, the tube 5033 of the insertion set is connected to the cannula line 5030 at one end of the tube and to a cannula (not shown) at the other end.

[0265] Referring again to FIG. 64A, in use, the reservoir 20 (formed in the base Y or separately attached to the base Y as described above) containing fluid internally is connected to the fluid line 310. The microprocessor on the printed circuit board 13 transmits a signal to activate the pumping mechanism 16 and initiate the stroke through the current applied to the shape memory actuator 278. The fluid flows from the reservoir 20 through the fluid line 310 to the dispensing assembly 120 or the AVS assembly. Here, the exact fluid volume within the AVS chamber is determined and the fluid is biased from the AVS chamber to the cannula line 5031 and the cannula housing 5030.

[0266] Next, referring to FIG. 64B, the device shown in FIG. 64A is shown connected to an insertion set, a tube 5033, and a cannula 5010. In FIG. 64C, the base Y of the device is shown adhered to the body of the patient 12 using an adhesive patch or pad 3100. It should be noted that in this embodiment, the element 3100 can be either a pad or a patch. However, as detailed below, the element 3100 is referred to as a patch and the element 3220 is referred to as a pad. For simplicity purposes only, the element 3100 is used. However, in some embodiments, a pad is used and thus the element 3220 would be appropriate in those situations.

[0267] The cannula 5010, which is inserted through the cannula housing 5030 to fit into the cannula line 5031 by the cannula diaphragm 5060, is inserted into the patient 12. However, as illustrated and described above with respect to FIG. 2B, the base Y can be fluidly attached to the patient through an insertion set including the tube 5033 and the cannula 5010. In both FIGS. 64B and 64C, the base Y can be adhered to the patient before or after the insertion of the cannula 5010. Again, referring to FIG. 2C, when the cannula 5010 is inserted into the patient 12, it receives fluid directly from the device without using the infusion set tube (illustrated in FIG. 64B). The base Y can be adhered to the patient before or after the insertion of the cannula 5010 by the adhesive patch 3100. Next, referring to FIG. 64D, the upper part X of the device 10 is attached to the base Y of the device 10 after the cannula 5010 is inserted into the patient 12.

[0268] As described below, the adhesive patch can have many embodiments, and in some cases, the patch is placed on the upper part of the device. Therefore, the patches shown in these embodiments are only one embodiment. As described above, the pad (when used) is placed at the same position as the patches in FIGS. 64A - 64D.

[0269] Next, referring to FIGS. 66A - 66D, in this embodiment, the reservoir 20 is shown as a separate component. As shown in FIG. 66A, the base Y includes a reservoir cavity 2645 with a septum needle 6272. As shown in FIG. 66B, the reservoir 20 is first placed in the upper reservoir cavity 2640. At this point, the reservoir 20 is not attached to the device. Next, referring to FIG. 66C, when the upper part X is placed on the base Y, the reservoir 20 is clamped into the base reservoir cavity 2645. As shown in FIG. 66D, the force generated by the attachment of the upper part and the base Y presses the septum needle 6272 into the septum 6270 of the reservoir 20, connecting the reservoir 20 to the fluid line 310 of the base Y.

[0270] Next, referring to FIGS. 67A - F, alternative embodiments of the embodiments shown in FIGS. 64A, 64C, and 66A - 66D are shown. In these alternative embodiments, in addition to the cannula housing 5030, the base Y includes a sensor housing 5022. Next, referring to FIGS. 69A - 69B, both the sensor housing 5022 and the cannula housing 5030 include outlets to the bottom surface of the base Y, shown as 5022 and 5030 respectively in FIG. 69A. FIG. 69B shows the embodiment shown in FIG. 69A with a sharp portion protruding through the housing. The sensor housing houses a sensor. In some embodiments, the sensor is an analyte sensor. The analyte sensed includes blood glucose, but in other embodiments, the analyte sensor can be any desired type of analyte sensor.

[0271] Next, referring to FIG. 67B, the base Y is shown on the body of patient 12. The sensor 5020 is shown inserted into patient 12 through the base Y sensor housing 5022. Next, referring to FIG. 67C, in some embodiments, the cannula 5010 and the sensor 5020 are inserted into patient 12 simultaneously through their respective housings (5030 and 5022). Next, referring to FIG. 67D, the base Y is shown attached to a patient having both a cannula 5010 and a sensor 5020 attached to patient 12 through the base Y.

[0272] Next, referring to FIG. 67E, the base Y is attached to patient 12 and the cannula 5010 is shown inserted through the cannula housing 5030. In this embodiment, the sensor housing 5022 is shown without a sensor. However, the sensor 5020 is shown inserted at another location on patient 12. Thus, the sensor 5020 need not be inserted through the base Y, but embodiments described hereinafter regarding the step of monitoring blood glucose and the step of pumping insulin through the cannula can be implemented in this method. Further, other embodiments regarding the step of administering a fluid in response to or in relation to an analyte level can be administered in this method.

[0273] Next, referring to FIG. 67F, an apparatus 10 having both a sensor 5020 and a cannula 5010 through a base Y is shown together with an upper portion X placed thereon. Again, in the embodiments shown in FIGS. 66A - 66D, when the upper portion X is placed on the base Y, the reservoir 20 is in fluid communication with the fluid line 310.

[0274] Next, referring to FIG. 68, an embodiment of a portable pump embodiment of the apparatus 10 is shown. In the apparatus 10, an insertion set including a cannula 5010 and a tube 5033 is required to connect the fluid lines within the apparatus 10 to the patient 12. Thus, in this embodiment, the cannula 5010 is not directly connected from the portable pump apparatus 10 to the patient 12. Further, this embodiment is capable of functioning as described hereinafter with respect to the specimen sensor and the fluid pump, but the sensor 5020 is located outside the portable pump apparatus 10 similar to the embodiment of the sensor 5020 shown in FIG. 5F.

[0275] Next, referring to FIGS. 70-70D, both the described patch pump and portable pump embodiments further include various components of an embodiment including a dispensing assembly (in the applicable embodiment) and an AVS assembly, the various components including at least one microphone, a temperature sensor, at least one speaker, a variable volume dispensing chamber, a variable volume chamber, ports, and a reference chamber. In some embodiments, the device includes one or more of the following. A vibration motor (in those embodiments, further a motor drive), an antenna, a wireless communicator, a skin temperature sensor, a bolus button, and in some embodiments, one or more additional buttons. In some embodiments, the antenna is a quarter wavelength tracking antenna. In other embodiments, the antenna may be a half wavelength or quarter wavelength tracking, dipole, monopole, or loop antenna. The wireless communicator is, in some embodiments, 2.4 GHz, but in other embodiments, is a frequency of 400 MHz. In still other embodiments, the wireless communicator can be any frequency. Thus, in some embodiments, the device includes a wireless communicator of sufficient strength to communicate with a receiver within a few feet of the device. In some embodiments, the device includes a second wireless communicator. In some embodiments, the second wireless communicator may be a specific long distance frequency, such as 433 or 900 MHz, or in some embodiments, any frequency within the ISM band or other band. Although not shown in FIGS. 70-70D, the device includes a screen and / or user interface in some embodiments.

[0276] The following description of these components and their various embodiments applies to both the type of device and the various embodiments described with respect to each type of device. Next, referring to FIG. 67F, for illustrative purposes only, both the cannula 5010 and the sensor 5020 are inserted into the device 10. Also, referring to FIGS. 70 - 70D, various components (some of which are not necessarily included in all embodiments) are shown in schematic diagrams representing the electrical connections of those components. Thus, FIGS. 70 - 70D represent the various elements that can be included in the present device. These can be mixed and adapted according to size requirements, power limitations, uses, and preferences, as well as other variables. FIG. 70 shows the relationship of FIGS. 70A - 70D.

[0277] The present device includes at least one microprocessor 271. This can be a microprocessor of any speed that can handle at least the various electrical connections necessary for the functions of the present device. In some embodiments, the present device includes two or more microprocessors, and as can be seen from FIGS. 70A - 70B, the present device is shown to have two microprocessors 271.

[0278] The microprocessor 271 (or, in some embodiments, multiple microprocessors) is connected to the main printed circuit board (hereinafter, "PCB" refers to "printed circuit board") 13. In some embodiments, a power source, which is the battery 15, is connected to the main PCB 13. In one embodiment, the battery 15 is a rechargeable lithium polymer battery. In other embodiments, the battery can be any type of replaceable or rechargeable battery.

[0279] In some embodiments, the present device includes a wireless communication device 370 connected to the main PCB 13. The wireless communication device 370 uses the antenna 3580 to communicate with the remote control device 3470. Thus, the communication between the device 10 and the remote control device 3470 is wireless.

[0280] In some embodiments, the device includes a vibration motor 3210. The vibration motor 3210 is connected to a motor driver 3211 on the main PCB 13 motor driver device 3211.

[0281] Some embodiments include a bolus button 3213. The bolus button 3213 functions when the user applies force to the button form 3213 (which can be made of rubber or any other suitable material). That force causes the bolus button actuation to operate (attached to the bolus button switch 3214 on the main PCB 13). The switch 3214 actuates a single - shot bolus indicating a specific predetermined fluid volume to be delivered to the patient. In some embodiments after the user presses the bolus button 3213, the device 10 emits an alarm (e.g., activates the vibration motor 3210 and / or sends a signal to a remote control device), signaling to the user that the button 3213 has been pressed. Then the user needs to confirm, for example, by pressing the button 3213, whether the bolus should be delivered. In yet other embodiments, the remote control device 3470 queries the user to confirm whether the bolus should be delivered.

[0282] In various embodiments, a similar query / response sequence may be used to test and report patient responsiveness. For example, the device may be configured to test patient responsiveness by emitting an alarm (e.g., an audible and / or tactile alarm) and waiting for a response from the patient (e.g., actuation of the button 3213). Such tests may be performed at various times (e.g., every 5 minutes), or based on the detection of conditions such as abnormal analyte levels monitored via an analyte sensor, or abnormal body temperature monitored via a temperature sensor. If the patient does not provide an appropriate response within a predetermined time, the reusable portion may send an alarm to the remote control device or caregiver. Such tests and reports can be particularly beneficial for patients who may become unconscious or unresponsive due to device malfunction or otherwise.

[0283] The NITINOL circuit (see shape memory actuator, in some embodiments, a NITINOL fiber bundle) 278 on the main PCB 13 provides current to the NITINOL connectors. As shown in FIGS. 67F and 70A, the device can include two NITINOL connectors 278 (and two NITINOL fiber bundles). However, as described above, in some embodiments, the device includes one NITINOL connector (and one NITINOL fiber bundle).

[0284] In some embodiments, the device includes a temperature sensor 3216 as shown in FIG. 70B. The temperature sensor 3216 is located on the bottom surface of the base Y and senses the skin temperature of the patient. The skin temperature sensor 3216 is connected to a signal converter represented by 3217. As shown in FIG. 70B, the signal converter 3217 is represented as one block, however, the device can include multiple signal converters that filter different signals respectively as needed. Subsequently, the AVS temperature sensor 132, the AVS microphone 133, and the analyte sensor 5020 are all connected to the signal converter represented as one block by 3217.

[0285] The AVS speaker 134 is connected to a speaker driver 135 on the main PCB 13. The AVS speaker 134 is, in one embodiment, a hearing aid speaker. However, in other embodiments, the speaker 134 (a speaker including a voice coil and a magnet having an electromagnetic coil) is a piezoelectric speaker (illustrated in FIG. 50, representing one embodiment of the device).

[0286] Referring further to FIGS. 70 - 70D, in some embodiments, the antenna 3580 has a dedicated PCB 3581 (which is then connected to the main PCB 13). Also, in some embodiments, the AVS microphone 133 has dedicated PCBs 1332, 1333 that are each connected to the main PCB 13. The various PCBs may be connected to the main PCB 13 using conventional methods, such as flexible circuits or wires.

[0287] Referring to FIG. 67F, for purposes of explanation, apparatus 10 is shown as an exemplary embodiment. However, the layout of the various components is changeable, and many of the embodiments are described below. However, additional alternative embodiments are not shown but are determinable based on size, power, and application.

[0288] According to an alternative embodiment, the disposable portion 2610 may include a reservoir 20 and optionally a battery. The reservoir 20 may be integrated into or otherwise connected to the disposable portion. The battery may be the main or sole power source of the device or an auxiliary power source and may further be used to provide power to the electronics on the reusable and / or disposable portions. Both the reservoir 20 and the battery are typically required to be replaced periodically, and thus including both of these components in the disposable portion 2610 may provide the user with the convenience of simultaneous replacement. Further, by replacing the battery each time the reservoir is replaced, the user may reduce the likelihood of running out of battery.

[0289] The disposable part 2610 can additionally or alternatively include a processor that can be used, for example, to continue a particular device operation in the event of a failure (e.g., a failure of the main control device within the reusable part), to issue an alarm in the event of a failure, or to provide status information to the reusable part. Regarding the status information, the processor can record the operating history and various characteristics of the disposable part and hold the status information of the user interface 14 including during access by the user, the fluid delivery device 10, and / or the installation of the disposable part 2610. For example, the processor can store statuses regarding the expiration date, maximum exposure or operating temperature, manufacturer, safety dispensing limits of the therapeutic agent, etc. If any of these status indicators are determined by the device to be unacceptable, the device can refuse to supply power to the pumping assembly and the dispensing assembly and can indicate to the user that the disposable part is unusable. The processor may be powered by a battery within the reusable part or the disposable part.

[0290] More specifically, the device can be configured to obtain status information from any disposable part (e.g., including the disposable part 2610 and any disposable component used with it such as a fluid reservoir, battery, or sharp part cartridge, or individual sharp part components) from, for example, a processor disposed in the disposable part, via a barcode reader, or via RFID technology. If the device detects a problem with the disposable part (e.g., an invalid model number for use with the reusable part, expiration of the fluid's shelf life), then the device can take corrective measures such as, for example, preventing or terminating the operation of the device and issuing an appropriate alarm.

[0291] Additional components may be included in some embodiments. For example, it is possible to employ redundant fault detection and warning mechanisms. The device may employ an audible alarm. The loudspeaker 1202 of the sensor 550 may be used for the audible alarm, or an additional speaker may be included in the loudspeaker and used for the audible alarm. Also, the device vibration mechanism 3210 can also be used as an alarm. When a system fault requiring emergency treatment is detected, both alarms can be activated. Further, a secondary battery or a supercapacitor may be employed as an auxiliary to the primary battery. If any of the batteries fails, the control device can cause at least one warning of the battery failure by activating one or more alarms.

[0292] Also, the alarm can also be used to indicate to the user that the device is operating properly. For example, the user may program the device for a bolus delivery over a certain period. The user may desire to confirm whether the programmed delivery is occurring properly. The processor can use the vibration motor or an audible sound to indicate that the programmed delivery is satisfactory. Thus, several mechanisms can be employed in some embodiments of the device for providing to the patient or user, regardless of positive or negative feedback.

[0293] Also, a microphone may be used to detect any abnormal vibrations or the absence of normal vibrations and initiate an alarm state. In various embodiments, the microphone of the acoustic volume sensing system may be used for such monitoring, or a separate microphone may be included for such monitoring. Also, it is possible to perform periodic inspections to determine that the device is operating by checking the expected pump vibrations using a microphone. If inappropriate vibrations are detected, or if no appropriate vibrations are detected by the microphone, an alarm can be initiated.

[0294] Next, referring to FIG. 71, various components of the apparatus 10 are shown schematically. In one embodiment of the apparatus 10, the upper X portion mates with the base Y, and the reservoir 20 is sandwiched between the upper X and the base Y. By the clamping force, the reservoir diaphragm 6272 is mated with the base Y. In some embodiments, both the injection device 5010 and the specimen sensor 5020 are inserted through the base Y into a patient (not shown).

[0295] In many embodiments, the base Y and the reservoir 20 are disposable parts, and the upper X is a non - disposable part. Also, both the injection device 5010 and the specimen sensor are disposable.

[0296] As described above, the patch pump device may be wholly or partially disposable. FIG. 72 shows an embodiment of the fluid delivery device 10 having disposable and non - disposable parts. In this embodiment, the disposable part Y includes components that come into direct contact with the fluid, such as the collapsible reservoir 20, a pumping assembly (not shown), the variable - volume dispensing chamber 122 (part of the dispensing assembly 120, located in the upper X), and a flow restrictor (not shown), and a one - way valve (not shown), and a fluid path (not shown) connecting the reservoir to the variable - volume dispensing chamber 122 from the pumping mechanism. Further, the disposable part Y includes the reservoir cavity 2645.

[0297] The reusable part X includes the elements of the dispensing assembly 120 except for the variable - volume dispensing chamber 122 located in the disposable part Y. In some embodiments, the dispensing assembly 120 is an AVS assembly. The AVS assembly is detailed above. Next, referring to FIG. 73, an integrated acoustic volumetric measurement sensor is shown on a PCB.

[0298] Next, referring to FIG. 74, the apparatus 10 shown in FIG. 49 is shown. The disposable portion Y of the base includes a reservoir cavity 2645. The non-disposable upper portion X includes a battery 15 and a dispensing assembly 120. The microphone 133 is shown together with a diaphragm spring 130. In some embodiments, the dispensing assembly 120 includes more than one microphone. Throughout this description, each microphone is referred to as 133, but this does not imply that the microphones are always equivalent. In some embodiments, the microphones are identical, while in other embodiments, the microphones are different.

[0299] Also, in FIG. 74, the non-disposable upper portion X includes a main PCB 13, a vibration motor 3210, and a pumping actuating member 54. The non-disposable upper portion X includes an AVS assembly or a dispensing assembly 120. In FIG. 74, the microphone 133 is shown. Also, the non-disposable upper portion X includes a battery 15 that can be used to provide power to the non-disposable and / or disposable portion electronic devices. In some embodiments, this battery 15 is rechargeable. The charging step can be accomplished by the method described later. The disposable portion Y includes fluid lines (not shown) and wetted components such as a pumping assembly. In FIG. 74, only the pumping plunger 54 can be confirmed. Also, embodiments of the apparatus 10 can include many of the above-described elements including, but not limited to, fluid impedance, a flexible membrane, a cannula housing, and a sensor housing. Any pumping mechanism can be used.

[0300] Next, referring to FIG. 75, the apparatus 10 is shown from another perspective where more elements are visible. In FIG. 75, the apparatus 10 is shown as a disposable portion Y of the base that includes a coiled, small-diameter tube flow restrictor 340 and a fluid line 310 connected to the inlet 21 and outlet 22 valves. Also shown is the pumping actuator member 54. The upper portion X includes the main PCB 13, the vibration motor 3210, two microphones 133, a speaker 134, a reference chamber 127, and a fixed volume chamber 129. Also shown is the battery 15. When selecting a smaller diameter for the flow restrictor 340, it may be desirable to use a larger diameter, longer tube as there is a possibility of blockage of line 310 (e.g., due to protein aggregation in the treatment fluid). However, in order to package a longer tube within the patch size housing, it may be necessary to bend the tube in the form of a meandering path, such as a coiled or serpentine shape.

[0301] Next, referring to FIG. 76, an exploded view of the apparatus 10 shown in FIGS. 72, 74, and 75 is shown. The non-disposable upper portion X is shown separated from the disposable base portion Y. In practice, a reservoir (not shown) is placed between the upper X and base Y portions. When the upper X and base Y are assembled and the apparatus 10 is formed, the reservoir is connected to the fluid line 310.

[0302] Next, referring to FIG. 77, an exploded view of another embodiment of the apparatus 10 is shown, which includes a disposable base Y and a non-disposable upper X component. Also included are a reservoir 20, an adhesive 3100, and a bridge 5040 instrument that holds an injection device 5010 and a sensor 5020. The present apparatus 10 includes a more circular footprint and a dome shape. A battery 15 and a main PCB 13 are shown located on the upper X. The base Y includes a reservoir cavity 2645. The adhesive 3100 is shown in two fragmentary embodiments. The bridge 5040 is used to insert the injection device 5010 and the sensor 5020 through the base Y. The reservoir 20 is shown having an irregular shape, however, in other embodiments, the reservoir 20 can have any shape and can vary in size depending on the desired fluid volume. In this embodiment of the apparatus 10, the non-wetted components are within the non-disposable upper X, and the wetted components are within the disposable portion Y of the base.

[0303] Upon assembly, the apparatus 10 may be adhesively bonded together using a central region of the adhesive (not shown). Alternatively, the apparatus 10 may be mechanically latched together using any of the many embodiments described herein for latching. Some embodiments are described later herein, but many others are obvious and, depending on the shape variations of the apparatus, often the latch also varies.

[0304] Next, referring to FIG. 78, an exploded view of another embodiment of the apparatus 10 is shown. The non-disposable upper portion X is most often dome-shaped, however, a protrusion X1 is shown to house the mechanism within the upper X. Thus, the apparatus shape can be variable and includes polyp and protrusions, indentations, as well as other tissue-like characteristics to accommodate various designs of the apparatus.

[0305] A reservoir 20, an injection device 5010, and a sensor 5020 are shown. The injection device 5010 and the sensor 5020 are insertable into a patient (not shown) through a base Y. The base Y is shown having an adhesive 3100 or a pad 3220 at the lower part. In practice, the adhesive 3100 or the pad 3220 can be first adhered to the skin and the base Y. Next, the injection device 5010 and the sensor 5020 are inserted into the patient (not shown, shown as 5020 and 5010 in FIG. 79) through the base Y. Then, the reservoir 20 is first placed on the upper part X and then placed in the reservoir cavity 2645 by sandwiching the upper part X and the base Y, or the reservoir 20 is placed in the reservoir cavity 2645 by first placing the reservoir 20 in the reservoir cavity 2645 and then sandwiching the upper part X and the base Y. Either method can be used. As a final result, the reservoir 20 is connected to a fluid line (not shown) located at the base Y through a diaphragm (shown upside down) on the reservoir 20 and a diaphragm needle (not shown, see 6272). Then, the upper part X is fixed to the base X using an adhesive or, in this embodiment, mechanically using a latch 654 to grip both the upper part X and the base Y.

[0306] The base Y includes components that come into contact with the liquid. The base Y is disposable. The upper part X includes non-liquid-contact components. The upper part X is non-disposable. Next, referring to FIG. 79, the base Y includes a variable-volume dispensing chamber 122, an inlet valve 21, an outlet valve 22, and a pumping chamber 2350. As shown in this figure, those elements are shown as membranes covering the areas that act as chambers or valves. Thus, the base Y includes a membrane that firmly maintains the liquid-contact area and thus maintains a non-liquid-contact area such as in the upper part (not shown). As shown in FIG. 79, the sensor 5020 and the injection device 5010 are inserted into the patient (not shown) through their respective housings and through the base Y. The base Y is shown together with the reservoir cavity 2645, but the reservoir (not shown) needs to be connected such that a fluid line from the reservoir to the chamber and then to the injection device is connected.

[0307] Next, referring to FIG. 80, the upper part X of the present device is shown. The upper part X includes non-wetted components such as a temperature sensor 3216, a diaphragm spring 130, an inlet valve poppet 21, an outlet valve poppet 22, and a pumping actuator member 54, as shown. Also, the upper part Y includes a raised portion 2640 for accommodating a reservoir (not shown).

[0308] Next, referring to FIGS. 81A to 81C, an order for illustrating the process of clamping the reservoir 20 between the upper part X and the base Y is shown. As seen in FIG. 81A, the upper part X and the reservoir 20 outside the upper part X are shown. The reservoir includes a diaphragm 6270. The upper part X includes a reservoir raised portion 2640. Next, as shown in FIG. 81B, the upper part is prepared to be clamped with the base Y. Next, referring to FIG. 81C, with the diaphragm side down, the reservoir 20 is placed inside the base Y. The diaphragm is connected to a diaphragm needle (not shown) into which a cannula inside the base Y is inserted, and connects the reservoir to a fluid line (not shown). In an alternative embodiment, the reservoir may include a needle into which a cannula is inserted instead of a diaphragm, and the fluid path may include a reservoir interface with a diaphragm instead of a needle into which a cannula is inserted.

[0309] Next, referring to FIG. 82, the upper part X is shown together with an embodiment of a disassembled pumping mechanism 16. The pumping mechanism 16 fits into a pumping mechanism housing 18 inside the upper part X. Also, the base Y is shown together with one part of a latch 654 that clamps both the upper part X and the base Y.

[0310] Next, referring to FIG. 83, the base Y is shown together with a fluid path assembly 166, and the membrane 2356 is disassembled from the base Y. This illustrates that in some embodiments of the present device, the fluid path assembly 166 is a separate component that is inserted into the base Y and clamped by the membrane 2356. Also, as shown in this figure, an adhesive or pad 3100 / 3220 includes openings for an injection device and a sensor (not shown) in some embodiments. Next, referring to FIG. 84, a bottom view of the base Y is shown. It is the bottom of the fluid path assembly 166.

[0311] Next, referring to FIGS. 85A and 85B, another embodiment of the device is shown. In this embodiment, the upper part X is also non-disposable and includes a bolus button 654. The reservoir 20 is shown in an exploded view, however, in one embodiment, the reservoir 20 is built into the base Y. In another embodiment, the reservoir 20 is removable and is placed within the reservoir cavity 2645 using a similar process as described above for another embodiment of the device.

[0312] The base Y is disposable and includes the fluid contact components of the device 10. The sensor 5020, the cannula 5010, the variable volume dispensing chamber 122, the inlet valve region 21, the outlet valve region 22, and the pumping chamber 2350. The volume dispensing chamber, the inlet valve region 21, the outlet valve region 22, and the pumping chamber 2354 may all be covered by a membrane material, which may be in the form of a single membrane or individual membranes.

[0313] The device 10 is held together by a latching mechanism 654 on the upper part X and the base Y. Next, referring to FIGS. 85C - 85D, the device 10 is the latching mechanism 654 shown in the open position (FIG. 85C) and the clamped or closed position (FIG. 85D). As detailed above, the bolus button 3213 is also shown.

[0314] A cover (not shown) may be provided for use in any embodiment of the device to replace the reservoir and the upper part in the event that the reservoir is removed when the base is connected to the patient. The cover does not include electrical components and thus can be used even in a fluid contact state. However, in some examples, the reservoir can also be removed without using any cover.

[0315] (Cannula and Insertion Device) FIG. 86A schematically shows an exemplary embodiment of an injection and sensor assembly 5040 that includes both an injection device, which can be a cannula or needle 5010, and a specimen sensor that includes a sensor probe 5025 and a sensor base 5023. A bridge 5070 rigidly joins the injection cannula 5010 and the specimen sensor base 5023. The injection device 5010 is bounded above by a diaphragm 5060 that causes fluid to flow from a source and be administered to a patient through the injection device 5010. The sensor base 5023 is a section of the specimen sensor that is not inserted into the patient. In one embodiment, the base 5023 has an electrical contact for the electrochemical analysis of blood glucose. The probe 5025 protrudes from the base 5023 of the specimen sensor 5020.

[0316] Next, referring to FIG. 86B, in this embodiment, the injection device 5010 is a cannula that is introduced into the patient using a patient introduction needle 5240. The introduction needle 5240 is inside the cannula 5010 when inserted into the patient. After the cannula 5010 is inserted into the patient, the introduction needle 5240 is removed and the diaphragm 5060 is sealed against a fluid source (which is a fluid line in some embodiments of the devices described herein). In some embodiments, the sensor probe 5025 is associated with an introduction needle 5072 that aids in skin puncture for insertion of the sensor probe 5025. The sensor introduction needle 5072 at least partially surrounds the sensor probe 5025 in some embodiments while the sensor probe 5025 is inserted into the patient.

[0317] In other embodiments, the injection device 5010 is a needle and does not require an introduction needle 5240. In these embodiments, the injection device 5010 is inserted into the patient and the diaphragm 5060 is sealed against a fluid source.

[0318] In both FIGS. 86A and 86B, a force is applied to the bridge 5070 in response to both the properly aligned injection device 5010 and the sensor probe 5025. This presses both the injection device 5010 and the sensor probe 5025 into the patient. Once inside the patient, the release device 5052 operates through the hole to separate the injection device 5010 and the diaphragm 5060 further from the bridge 5070 to the sensor base 5023. Referring to FIG. 86B, when the introduction needles 5240 and 5072 are used, typically they remain attached to the bridge 5070 after insertion.

[0319] The bridge can be made of any desired material, including plastic. The cannula can be any cannula in the art. The diaphragm 5060 is made of rubber or plastic and can have any design capable of providing the desired function. In embodiments where the injection device is a needle, any needle may be used. In embodiments where an introduction needle is used, any needle, needle device, or introduction device can be used.

[0320] The injection and sensor assembly requires an applied force for insertion into the patient. Similarly, the injection and sensor assembly requires that the injection device and the sensor be released from the injection and sensor assembly. Thus, both the force and the release can be manually actuated. That is, a person may perform these functions or use an insertion device to properly operate the assembly. Next, referring to FIGS. 87A - 87E, an example of a manually operable insertion device 5011 is shown. The injection device 5010 and the sensor 5023 are held by the bridge 5070. The insertion device 5011 includes a cover 5012 for both the injection device 5010 and the sensor 5023. As shown in FIGS. 87B - 87E, using the insertion device 5011, both the injection device 5010 and the sensor 5023 are inserted through the device 10. FIG. 87A shows the disassembled sharp part, but in some embodiments, the cover 5012 completely encloses the sharp part prior to the insertion process.

[0321] The insertion device 5011 can be operated manually, but can also be incorporated within another insertion device such that mechanical advantages are applied. Next, referring to FIGS. 88A - 88B, one embodiment of the insertion device 5013 is used with an instrument similar to the insertion device 5012 shown in FIGS. 87A - 87E. The mechanism of the insertion device 5013 is shown in FIGS. 88C - 88D. The actuating lever 5014 releases the spring (as shown in FIGS. 88C - 88D) or provides another mechanical advantage for inserting the insertion device 5012 through a device (not shown). Thus, the insertion device 5012 releases the injection device 5010 and the sensor 5023, and then the insertion device 5012 can be removed from the insertion device 5013 and the insertion device 5013 can be refilled or the insertion device 5013 and the insertion device 5012 can be discarded.

[0322] Various insertion devices are described herein. However, in other embodiments, different insertion devices are used or the injection device and sensor are introduced manually.

[0323] Features for fixing the injection and sensor assembly 5040 to the automatic insertion device may be included. For example, the release device shown as 5052 in FIGS. 86A - 86B may receive the pins of the automatic insertion device. Referring to both FIGS. 89A and 89B, a typical embodiment of the automatic insertion device 5100 is shown. As shown in the front view of FIG. 89A, the insertion device 5100 includes a pin 5130 that moves within a pin slot 5140 in an insertion cartridge recess 5120. In practice, the injection and sensor assembly (not shown, shown as 5040 in FIGS. 86A and 86B) is pushed into the cartridge recess 5120, and the pin 5130 is inserted into a hole in the injection and sensor assembly (shown as 5052 in FIGS. 86A and 86B). As shown in the rear view of FIG. 89B, a cocking lever 5145 is used to prepare the insertion device 5100 for firing. Then, the insertion device 5100 is either held against the skin or aligned with the cannula housing and sensor housing on a base (not shown), and fired by depressing a trigger 5110. Upon firing, the pin 5130 moves within the slot 5140, thereby press - fitting the injection device and sensor (both not shown) into the patient. The insertion device base 5160 limits the downward movement of the injection and sensor assembly. Also, the insertion device may automatically retract an introducer needle (not shown, see FIG. 86B) from the injection and sensor assembly.

[0324] The injection and sensor assembly may be pre-mounted on the insertion device 5100 before being distributed to the end user. As shown in FIG. 90, in other embodiments, a cartridge 5080 may be used to protect the user and further protect the sharp portion held within the assembly shown as 5040 in FIGS. 56A and 56B. Referring to FIGS. 90, 86A-86B, and 89A, in the cartridge embodiment 5080, the injection and sensor assembly 5040 is incorporated within the cartridge 5080. The cartridge 5080 is mounted within a cartridge recess 5120. A pin 5130 may project from a hole 5052 into a groove 5090 within the cartridge 5080. In response to the operation of the insertion device 5100, the pin moves within the groove 5090 as 5080 moves towards the patient for inserting the sharp portion. The cartridge 5080 may be composed of a rigid material.

[0325] Next, referring to FIGS. 91A-91C, there are shown several views of an embodiment of an insertion device mechanism for an insertion device, such as that shown in FIGS. 89A and 89B as 5100. FIG. 91A shows a perspective view of an embodiment of the insertion device mechanism, FIG. 91B shows a front view, and FIG. 91C shows a side view. The insertion device 5100 has a cocking lever 5145 that is connected to a sear cocking slide 5330 via a cocking connection portion 5350 and is used to move the cocking slide 5330 to a loading position. A power spring 5390 connects the sear cocking slide 5330 to a trigger 5110 and provides a downward force necessary for the insertion of an injection device or an injection and sensor assembly (not shown) when compressed. A trigger sear 5340 is disposed under the sear cocking slide 5330 and between a pair of cocking connection portions 5350. The trigger sear 5340 transmits the kinetic energy released from the power spring 5390 in response to the depression of the trigger 5110. The actuated trigger sear 5340 imparts an impact to a cartridge bolt 5380 positioned below. The cartridge bolt 5380 is coupled, for example, to a cartridge housing 5370 that holds a cartridge as shown in FIG. 90. Also, the cartridge bolt 5380 is disposed on top of a return spring 5360 for returning the cartridge housing 5350 to a retracted position.

[0326] Figures 92A - 92F schematically show the time sequence for cocking and firing the hammer of an insertion device 5100 of the type described with reference to Figures 91A - 91C. Figure 92A shows the insertion device 5100 in the rest position. By lowering a cocking lever (not shown, see 5145 in Figure 91A), the hammer cocking slide 5330 is lowered and engaged with the trigger hammer 5340. Figure 92B shows the hammer cocking slide 5330 in the lowered position engaged with the trigger hammer 5340. By raising the cocking lever, the hammer cocking slide 5330 and the hammer 5340 are raised, thus compressing the power spring 5390, and the resulting position is shown in Figure 92C. After ensuring the proper position of the insertion device 5100 against the base (not shown) and / or the patient's skin, the trigger is depressed, thereby sending the trigger hammer 5340 downward. Figure 92D shows the trigger hammer 5340 in transit. As shown in Figure 92E, the trigger hammer 5340 impacts the cartridge bolt 5380, moves it downward, inserts a needle or needles held within a cartridge housing (not shown), and compresses the return spring 5360. Figure 92F shows the return spring 5360 biasing the cartridge bolt 5380 back. This causes the contraction of the cartridge housing and the cartridge (not shown) contained therein, as well as any associated introduction needle used.

[0327] Next, referring to FIGS. 93A-93C, an embodiment of the time sequence for inserting and securing an injection device (i.e., cannula or needle 5010) to base Y is shown. FIG. 93A shows base Y with a locking feature 5210 located at the top of cannula housing 5030. Base Y is typically positioned against the skin of patient 5220 when inserting the injection device or cannula 5010. FIG. 93B shows cannula 5010 being press-fitted into base Y through cannula housing 5030. In this figure, an introducer needle 5240 that traverses a septum (not shown) and is coaxially positioned with cannula 5010 is used. The tip of the sharp portion of introducer needle 5240 emerges from the tip (not shown) of cannula 5010 to assist in piercing patient 5220. Elastic locking feature 5210 is pushed aside during the insertion of cannula 5010. FIG. 93C shows cannula 5010 fully inserted through cannula housing 5030 of base Y with the tip of the cannula fully inserted into patient 5220. Introducer needle 5240 is removed and septum 5060 is self-sealing against a fluid source or fluid line (not shown). Elastic locking feature 5210 engages cannula 5010, thereby preventing cannula 5010 from moving in conjunction with base Y. FIGS. 93A-93C show cannula 5010, but the injection and sensor assembly shown in FIG. 86B can also be inserted using the locking features 5210 and method illustrated and described in FIGS. 93A-93C.

[0328] Next, referring to FIGS. 92G - 92H, an insertion cartridge bolt locking mechanism for use with an insertion device, such as that shown in FIGS. 91A - 92F as 5100, is shown. The cartridge bolt locking mechanism functions as an interconnection device and is capable of preventing accidental firing while the mechanism is holding the hammer back. The locking mechanism includes a detent 5420 that prevents downward movement of the cartridge bolt 5380 when engaged with a detent recess 5410. As shown in FIG. 92G, when the cocking lever 5145 is in the closed position, the cocking lever 5145 rotates the detent 5420 and contacts a detent lever 5440 that prevents the detent 5420 from inserting into the detent recess 5410. A detent spring 5430 disposed between the detent 5420 and a detent spring support 5450 is in a compressed position. The cartridge bolt 5380 and the trigger hammer 5340 are free to move. As shown in FIG. 92H, when the cocking lever 5145 rotates downward, the detent lever 5440 is released, thereby forcing the detent 5420 into a recess (where the detent 5420 is shown inside the recess, and the recess is shown as 5410 in FIG. 92G) by the detent spring 5430. Downward movement of the cartridge bolt 5380 is thereby prevented. Then, when the cocking lever 5145 is returned, the detent 5420 is returned to the unlocked position. Then, the cartridge bolt 5380 is free to move downward in the trigger process.

[0329] Next, referring to FIGS. 94A - 94C, an embodiment of the process of fitting a cannula 5010 that is a conventional cannula (as shown in FIG. 86B) that requires an introducer needle with respect to a base Y and establishes fluid communication with a fluid line 310 is shown. FIG. 94A shows a cross - sectional view of the cannula 5010 having two diaphragms (an introducer needle diaphragm 5062 and a fluid line diaphragm 5270). The introducer needle diaphragm 5062 seals a passage 5280 that leads to a hollow needle (not shown, shown as 5290 in FIG. 94B) of the cannula 5010. The cannula introducer needle 5240 is shown positioned on the introducer needle diaphragm 5062 immediately prior to insertion of the introducer needle 5240.

[0330] Next, referring to FIG. 94B, the introduction needle 5240 is shown penetrating the introduction needle diaphragm 5062. The user inserts the cannula 5010 into the base Y (which has a rigid hollow needle 5290 facing upward). When inserting the cannula 5010 into the base Y, the introduction needle 5240 pierces the fluid line diaphragm 5270 and establishes fluid communication between the fluid line 310 and the passage 5280. When inserting the cannula 5010 into the base Y and holding the base Y against the patient (not shown), the fluid communication between the fluid line 310 and the passage 5280 is established almost simultaneously as it penetrates the patient's skin. Next, referring to FIG. 94C, the cannula 5010 is shown fully inserted into the base Y with the introduction needle removed and fluid communication with the fluid line 310 established.

[0331] In an alternative embodiment, the insertion of the infusion device and / or sensor is assisted by a vibration motor that is linked to the fluid delivery device. The vibration motor may be activated simultaneously with the insertion of the infusion device and / or sensor.

[0332] (Adhesive) Next, referring to FIG. 95, an upper perspective view of one embodiment of the adhesive patch 3100 for fixing the fluid delivery device 10 etc. to the skin of a patient (not shown) is shown. The adhesive patch 3100 is shown in a presented shape, but other shapes can also be used. Any adhesive patch 3100 capable of holding the fluid delivery device can be used.

[0333] The fluid delivery device 10 is held beneath the central region 3130 of the adhesive patch 3100, which is attached to the patient's skin by the adhesive members 3111. These adhesive members 3111 radiate out from the central region 3130 and are spaced apart from each other by intervening in the region 3121. The radial arrangement of the adhesive members 3111 enables secure attachment of the device 10 to the patient. In some embodiments, the central region 3130 covers the entire device 10, however, in other embodiments, the central region 3130 covers a portion of the device 10. Also, the central region 3130 may include an interlocking adhesion feature (not shown) that can be held by complementary interconnect features (not shown) of the device 10. In an alternative embodiment, the device 10 is secured to the upper portion of the central region 3130 (e.g., by an adhesive or interconnect features).

[0334] The adhesive patch 3100 is typically flat and is made of a polymer sheet or fiber. The adhesive patch 3100 may be supplied with an adhesive attached to one side and protected by a release liner such as a peelable plastic sheet that adheres less tightly than the patch 3100. The release liner may be a single continuous piece or may be divided into regions that can be removed separately.

[0335] In an exemplary embodiment, the backing of the central region 3130 may be a removable type that does not remove the backing of the adhesive member 3111. To use the adhesive patch 3100, the user removes the backing of the central region 3130, presses the device 10 against the adhesive of the newly exposed central region, and adheres the device 10 to the central region 3130. The user then places the device on the skin, removes the backing from the adhesive member 3111, attaches the adhesive member to the skin, and repeats the attachment process with additional members. The user may attach all or only a portion of the adhesive member 3111 and reserve the additional adhesive member 3111 for application on another day. Typically, since the adhesion period of the adhesive used for skin adhesion is only a few days, by applying the set of adhesive members 3111 on different days (e.g., every 3 to 5 days), the time that the device 10 remains adhered to the skin is extended, reducing the time, cost, and discomfort often associated with reapplication of the device. The variable tab may have indicators such as different colors or numbers indicating the appropriate time to apply the various adhesive members 3111. The adhesive member 3111 may include perforations and provide vulnerability to the central region 3130 so that the used adhesive member can be removed after use. Additional embodiments for extending the period that the device 10 remains adhered are discussed above with reference to FIGS. 79 - 83.

[0336] FIG. 96 schematically shows a cross-sectional view of the fluid delivery device 10 with the cannula 5010 inserted and held under the adhesive patch 3100. The pad 3220 may be included between the device 10 and the patient's skin 3250 to allow air to flow across the skin. The air flow rate to the skin may be increased by including a passage 3230 within the pad 3220. Also, the passage 3230 may be formed by using multiple spaced pads or by constructing the pad 3220 from a highly porous material. Thus, the pad 3220 can be of any shape and size, and in some embodiments, the pad 3220 consists of several separate pieces. The pad 3220 may be adhered to the bottom surface of the device 10 during manufacture or by the user to the device 10. Alternatively, the pad 3220 may be loosely placed on the skin by the user prior to application of the adhesive patch 3100. The pad 3220 may include a flexible material such as a porous polymer foam.

[0337] FIG. 97 shows an embodiment of the invention for securing a device (not shown) to a patient using a first adhesive patch 3100 and an additional adhesive patch 3300. Initially, the device (not shown) is positioned for use and secured to the patient's skin (not shown) with the adhesive patch 3100 using the tab-like adhesive member 3111. The central region 3130 may be positioned at the top (as shown) or secured under the device. After a period of time, a second, elongated or short, adhesive patch 3300 is positioned such that its central region is placed over the first adhesive patch 3100 and the adhesive member 3320 of the second adhesive patch is secured to the patient's skin within the intervening region between the adhesive members 3111 of the first adhesive patch. A frangible region may be provided to assist in removing loose or undesirable adhesive members 3111 associated with the previously placed patch 3100.

[0338] Next, referring to both FIGS. 98 and 99, an embodiment is shown in which the adhesive patch 3100 is divided into at least two smaller adhesive patches. In these embodiments, the adhesive patch 3100 is divided into two adhesive patches (3410 and 3420), each having an adhesive member 3111 arranged radially around a central gap 3430. The two adhesive patches (3410 and 3420) each extend over a semi-circle of approximately 180°, although other configurations such as three patches each extending over 120° or four patches each extending over 90° may also be used. In some embodiments, the adhesive may include more than four patches. The configurations described for these embodiments follow the formula 360° / n, where n is the number of patches. However, in other embodiments, depending on the shape of the device, the formula shown and the description herein do not apply. In still other embodiments, the patches may also cover more than 360° and thus may overlap.

[0339] As shown in the perspective view of FIG. 99, due to the presence of a central void (not shown, shown in FIG. 98), the central region 3130 is in the shape of a strip for adhering and positioning along the periphery of the device 10. The two patches (3410 and 3420) together secure the device 10 to the skin (not shown). As in the embodiment described with reference to FIG. 95, air may flow between the adhesive members 3111 and under the device 10 (particularly if a passage 3230 is provided).

[0340] Figure 100 shows a perspective view of an embodiment that includes the step of using a plurality of adhesive patches to extend the time that device 10 remains adhered to a patient (not shown) prior to removal. Even if one of the plurality of partial adhesive pads 3420 is removed, device 10 remains held in place (by the remaining adhesive patches 3410 and / or by the user). The removed adhesive patch 3420 is then replaced with a new replacement adhesive patch (not shown). The replacement adhesive patch may be of the same quality as the removed pad 3420, or may have an adhesive member 3111 positioned in an alternative configuration that adheres to the fresh skin between areas previously covered by the adhesive patch 3420. The remaining adhesive patches 3410 may then be replaced in a similar manner. Indicators such as color identification may be used to indicate the duration of use of the adhesive patch. Also, the patch may have a color change mechanism that indicates the expiration of its service life. Decorative patterns such as images and designs may be included on the patch.

[0341] Figure 101 schematically shows an embodiment in which a plurality of adhesive members 3111 are attached to patient 12 and also connected via a tether 3730 to a ring-shaped central region 3130. The tether 3730 may be a fiber or a cord and may be elastic to reduce the movement of device 10 in response to the movement of patient 12. Also, the use of the tether 3730 increases the options available for the skin position of the adhesive members 3111.

[0342] The adhesive used in the embodiments described in FIGS. 95 - 101 can be any effective and safe adhesive for use on a patient's skin. However, in one embodiment, the adhesive used is the useful span lace medical non-woven tape of 3M product number 9915.

[0343] (Clamps and Latches) Figures 102A - 102C schematically show one mechanism for gripping or latching both the upper and base portions of a fluid delivery device. First, referring to Figure 102A, an elevation view of clamp 6410 is shown. Figure 102B shows base Y with keyholes 6440 for two clamps. Corresponding keyholes may also be included in the upper portion (not shown). Next, referring to Figure 102C, upper portion X and base Y are aligned and clamp 6410 may be inserted into a keyhole (not shown, shown as 6440 in Figure 102B). By rotating clamp 6410 by 90°, stud bar 6430 is moved to the locking position. By pushing down cam lever 6400, cam 6415 screwed to clamp pin 6420 is engaged to push upper portion X. As a result, upper portion X and base Y are held by the gripping force between cam 6415 and stud bar 6430. By pushing up cam lever 6400, the gripping force is released and clamp 6410 may be rotated 90°, pulled back, and upper portion X and base Y may be disassembled. In some embodiments, the lever may act as a protective cover for upper portion X.

[0344] Alternative embodiments for gripping portions of the device together are shown in Figures 103A - 103D. Figure 103A shows a perspective view of cam guide 6500 and Figure 103B shows a top view. Cam guide 6500 has keyholes 6440 and inclined surfaces 6510. Figure 103C shows cam follower 6520 having a central pin 6540 with a head 6560 attached to one end and a bar 6550 attached to the other end. As shown in the cross - sectional view of Figure 103D, the cam follower (not shown, shown in Figure 103C) may be inserted into upper portion X, base Y, and the keyhole of cam guide 6500 (not shown, shown in Figure 103C). The movement of lever 6530 attached to central pin 6540 causes rotation of the cam follower (not shown, shown in Figure 103C), moving bar 6550 along the inclined surface (not shown, shown as 6510 in Figure 103C), thereby converting the rotational force into a force that firmly grips base Y and upper portion X between cam follower head 6560 and bar 6550.

[0345] (Reservoir) Exemplary embodiments of a foldable reservoir for holding fluid are shown in FIGS. 104 - 106C. The foldable reservoir has at least one compartment or wall that collapses and folds as fluid is drawn in, thereby maintaining the ambient pressure inside it.

[0346] In most embodiments, a sealed port (e.g., a septum) is included within the reservoir. The port allows the reservoir to be filled with fluid by a syringe and enables a leak - free fluid line. Alternatively, an adapter may be used to connect the reservoir to a fluid line. Alternatively, as described above with reference to FIG. 71, a needle may be associated with the reservoir and a septum may be associated with the end of the fluid line. The reservoir may be made of a known plastic material that is compatible with the fluid contained within the reservoir for even short periods of time. In some embodiments, the reservoir is entirely foldable, i.e., the reservoir does not include a rigid surface.

[0347] Next, referring to FIG. 104, a cross - sectional view of the reservoir 20 is shown. A cavity 2645 for holding a fluid volume is formed between a rigid reservoir body 6200 and a flexible reservoir membrane 6330. The flexible membrane 6330 is sealed around the cavity 2645 and holds the fluid within the cavity 2645. The flexible membrane 6330 provides foldability to the reservoir 20. When fluid is pumped out of the cavity 2645, it deforms inwards.

[0348] The septum 6270 is seated on a neck 6240 extending from the body 6200. The septum 6270 serves as an interface between the cavity 2645 and the fluid line. In some devices, the fluid line terminates within a needle (not shown). In these embodiments, the needle may be inserted through the septum 6270 to access the needle chamber 6280 portion of the cavity 2645. The position of the septum 6270 can be maintained between the cap 6250 and a protrusion (not shown) formed at the junction of the inner wall 6281 of the needle chamber 6280 and the cap opening 6282. The cap 6250 may be held by a friction fit within the cap opening 6282. Insertion of the cap 6250 restricts its position by the wall 6261 of the cap opening 6282. A portion of the cap 6250 closest to the septum 6270 may have a central opening to allow insertion of a needle that penetrates through the cap 6250 and into the septum 6270. Alternatively, the cap 6250 may be punctured by the needle.

[0349] FIG. 105 shows a perspective view of the interior of the collapsible reservoir 20. The edge 6230 allows attachment of a flexible reservoir membrane that can be attached by welding, clamping, adhesion, or other suitable methods to create a fluid seal. The protective structure 6290 may be included to allow fluid to flow into or out of the cavity 2645, but prevents a needle from entering the cavity, thereby also preventing the possibility of puncturing the reservoir membrane.

[0350] Figures 106A - 106C show alternative embodiments of a reservoir in which a cap 6250 seals and adheres a diaphragm 6270 to a wall 6320 of the reservoir. The wall 6320 can be made of a flexible sheet such as, for example, PVC, silicone, polyethylene, or from an ACLAR film. In some embodiments, the wall 6320 may consist of a thermoformable polyethylene laminate formed from an ACLAR film. The flexible sheet is compatible with the fluid. The wall may be attached to a portion of a flexible plastic pouch such that it can be formed by bending and welding the ends of a rigid housing or a plastic sheet. Figure 106A shows a cap 6250 sealed to the wall 6320 via a circular fin 6350. The diaphragm 6270 may be inserted into a turret 6340 protruding from the cap 6250. The turret 6340 may be made of a material such as, for example, low density polyethylene, which deforms at high temperatures but is rigid at room temperature. Next, referring to Figure 106B, a heating press 6310, or another instrument, or a melting process is used to melt or bend the turret 6340 on the diaphragm 6270. Next, referring to Figure 106C, the diaphragm 6270 is shown fixed to the cap 6250.

[0351] Certain fluids are sensitive to storage conditions. For example, insulin is somewhat stable within a glass vial (typically when shipped), but can become unstable when in contact with certain plastics for extended periods of time. In some embodiments, the reservoir 20 is made of such a plastic. In this case, the reservoir 20 may be filled with the fluid immediately prior to use such that the fluid and the plastic are in contact for a short period of time.

[0352] (Reservoir filling station) Next, referring to FIG. 107, a reservoir filling station 7000 for filling reservoir 20 with fluid is shown. The fluid may be drawn from its original container with syringe 7040 and introduced into reservoir 20 using filling station 7000. Filling station 7000 may include a substantially rigid filling station base 7010 screwed to a substantially rigid filling station cover 7020 via hinge 7030. Thus, the stand 7000 can be opened and closed to receive and hold reservoir 20. Then, a needle 7050 attached to syringe 7040 may penetrate a filling opening 7060 in cover 7020 and reservoir septum 6270. Since filling station cover 7020 is rigid, movement of syringe 7040 is restricted, thus controlling the penetration depth of needle 7050 into reservoir 20 and preventing penetration of the bottom surface of reservoir 20. Legs 7070 hold stand 7000 in an inclined position when supported on a surface. Since stand 7000 is inclined, when fluid is injected from syringe 7040 into reservoir 20, air tends to rise upward to septum 6270. After syringe 7040 has injected a desired amount of fluid into reservoir 20, syringe 7040 may be used to remove residual air within reservoir 20. Since filling station base 7010 and cover 7020 are rigid, flexible reservoir 20 generally cannot expand beyond a fixed volume, preventing overfilling of reservoir 20. Base 7010 and cover 7020 may be latched together with a fastener or a heavy cover may be used to further prevent overexpansion and overfilling of the reservoir.

[0353] Next, referring to FIGS. 108A and 108B, an alternative embodiment of the reservoir filling station 7000 is shown. In this embodiment, a reservoir (not shown) is placed within the space between a cover 7020 and a base 7010. A hinge 7030 is attached to the cover 7020 and the base 7010. As shown in FIG. 108B, the reservoir (not shown) is on the inside and a syringe (not shown) needle (not shown) is inserted into a filling opening 7060. The filling opening 7060 is directly connected to a septum (not shown) of the reservoir. A viewing window 7021 indicates a fluid line based on the volume of fluid injected into the reservoir.

[0354] A fluid delivery system typically includes a fluid delivery device and an external user interface, although in some embodiments, a complete or partial internal user interface is included within the device. The device can be any of the devices described herein or variations thereof.

[0355] FIG. 109A shows a process diagram of a data acquisition and control scheme for an exemplary fluid delivery system embodiment. A patient or caregiver typically utilizes an external user interface 14, which is a base station or portable device stored separately from the fluid delivery device 10. In some embodiments, the user interface 14 is integrated with a computer, mobile phone, portable terminal, or other consumer device. The user interface assembly may communicate continuously or intermittently with the fluid delivery device 10 via wireless communication (e.g., a standard wireless protocol such as LF, RF, or "Bluetooth"), but may also be connected via a data cable, optical connection, or other suitable data connection. The external user interface 14 communicates with a processor 1504, inputs control parameters such as weight, fluid dosage range, or other data, and receives updates on status and functionality such as occluded flow, leakage, empty reservoir, battery malfunction, need for maintenance, expiration of the expiration date, total fluid delivery, or the presence of error conditions arising from remaining or unauthorized disposable components. The interface 14 may transmit an error signal to the patient's monitor or medical professional through a telephone, email, pager, instant message, or other suitable communication medium. The reservoir actuator assembly 1519 includes an actuator 1518 and a reservoir 1520. The dispensing assembly 120 transmits data regarding the flow from the flow line to the processor 1504. The processor 1504 uses the flow data to increase or decrease the flow rate from the reservoir pump assembly 1519 and adjusts the operation of the actuator 1518 to approximate the desired dosage and timing. Optionally, the feedback control device 1506 of the processor 1504 may receive data related to the operation of the reservoir pump assembly 1519 for detecting conditions such as open or short circuit faults, or actuator temperature.

[0356] FIG. 109B shows an alternative embodiment of the process diagram in FIG. 102A. In this embodiment, the lack of a dispensing assembly / sensor eliminates the fluid volume-based feedback.

[0357] Next, referring to FIG. 110A, a process diagram of one embodiment of the overall operation of a fluid delivery device within a fluid delivery system is shown. The user starts the system 2800 (step 2800) using a switch or in the form of an external user interface. The system reads default values, starts a system test (step 2810), and initializes by determining variable parameters such as desired steady state and bolus amounts. The variable parameters may be selected by the user using an input device such as a touch screen on the user interface, or by reading stored parameters from memory using the user interface (step 2820). Actuator timing is calculated based on the predicted or calibrated performance of the fluid delivery device (step 2830). The dispensing assembly is started at the start of startup of the fluid delivery device (step 2840). Dispensing assembly data collection 2835 continues throughout operation. During operation, the dispensing assembly provides data, enabling measurement of the accumulated fluid volume that has flowed through the dispensing chamber over one hour or more and the flow rate. The fluid delivery device starts and causes fluid to flow from the fluid line into the dispensing chamber (step 2840). In some embodiments, due to the outlet impedance, the force applied by a diaphragm spring, and the force applied by the pumping assembly, the drug flows from the dispensing chamber to the patient at a rate established thereby (step 2860). Based on detection by a user interruption, low flow state, predicted accumulated flow, or additional reservoir volume sensor, if it is determined that the reservoir is empty, or if there is any other alarm operation due to a part of the system or user specification, the system stops and the user is notified (step 2870). In the absence of a user stop signal, confirmation of an empty reservoir, or another alarm indication, an inspection is performed to determine whether adjustment of the actuator timing is required due to a deviation between the actual flow rate and the desired flow rate, or due to a change in the desired flow rate by the user (step 2880). If no adjustment is required, the process returns to step 2840. If adjustment is required, instead, the process returns to step 2830.

[0358] Next, referring to FIG. 110B, a process diagram of another embodiment of the overall operation of a fluid delivery device within a fluid delivery system is shown. In this embodiment, the determination of the actuation timing adjustment is made based on user input variables or other feedback. In this embodiment, a dispensing assembly with a sensor for measuring volume is not included. Thus, the adjustment is made based on an alternative feedback mechanism.

[0359] (Wireless communication) Next, referring to FIG. 111, a layout of an embodiment using coils for inductive charging and wireless communication within a fluid delivery system is shown. As described above, the user interface assembly 14 can be embodied as a portable user interface assembly 14 that wirelessly communicates with the fluid delivery device 10. A secondary coil (i.e., solenoid) 3560 may be employed within the fluid delivery device 10 as a wireless transceiver antenna that interfaces with a wireless control device 3580. Also, the secondary coil 3560 may at least partially serve as a secondary transformer for charging the device battery 3150 that interfaces with a battery charging circuit 3540. In this embodiment, the user interface assembly 14 includes a primary coil 3490 for inductively coupling energy to the secondary coil 3560. When the user interface assembly 14 is in proximity to the fluid delivery device 10, the primary coil 3490 excites the secondary coil 3560. The excited secondary coil 3560 supplies power to a battery charging circuit 3540 for charging the battery 3150 within the fluid delivery device 10. Also, in some embodiments, the primary coil 3490 functions as an antenna and interfaces with a wireless control device 3470 to transmit information to and receive information from the fluid delivery device 10.

[0360] Next, referring to FIG. 112, some embodiments include long-range wireless communication (e.g., 20 - 200 feet or more) hardware within the fluid delivery device 10. Thus, the fluid delivery device 10 can be monitored remotely.

[0361] Referring further to FIG. 112, typically, an intermediate transceiver 6600 mediated by a patient can provide the advantages of long-range communication without increasing the size, weight, and power consumption of the fluid delivery device 10. As shown in the data flow diagram of FIG. 112, the wearable fluid delivery device 10 uses short-range hardware and associated software to transmit data to, or receive data from, the intermediate transceiver 6600. For example, the device 10 can be equipped to transmit data over a distance of about 3 to 10 feet. The intermediate transceiver 6600 then receives this data and can relay it to the user interface assembly 14 using long-range hardware and software. Also, the intermediate transceiver 6600 can receive control signals from the user interface assembly 14 and relay these signals to the device 10. Optionally, the user interface assembly 14 can also communicate directly with the fluid delivery device 10 if within range. This direct communication can be configured to occur only if the intermediate transceiver 6600 is not detected, or alternatively, always when the user interface assembly 14 and the fluid delivery device are within range of each other.

[0362] Many types of data may be transmitted in ways including, but not limited to, the following. Data regarding pump actuation timing and volume measurements, as well as other data from the dispensing assembly, may be transmitted to the intermediate transceiver 6600 and thereby to the user interface assembly 14. Alarm signals may be transmitted to and from the fluid delivery device 10. Signals for confirming data reception may be transmitted from the user interface 14 to the intermediate transceiver 6600 and then from the intermediate transceiver 6600 to the fluid delivery device 10. Control signals for changing the operating parameters of the device 10 may be transmitted from the user interface assembly 14 to the fluid delivery device 10 using the intermediate transceiver 6600.

[0363] Next, referring to FIG. 113, a plan view of a particular embodiment of the intermediate transceiver 6600 is shown. The short-range transceiver 6610 communicates with nearby fluid delivery devices. The short-range transceivers of the device and the intermediate transceiver 6600 may communicate using one or more of many protocols and transmission frequencies known to be useful for short-range communication such as, for example, wireless communication. Data received by the intermediate transceiver 6600 is stored in a memory 6620 (e.g., a flash memory chip) and communicated to a microprocessor 6630 that can read the data as needed. Also, the microprocessor 6630 is connected to a long-range transceiver 6640 that communicates data with a user interface. For example, the intermediate transceiver 6600 and the user interface assembly may operate using the Bluetooth standard, which is a spread-spectrum protocol that uses a radio frequency of approximately 2.45 MHz, and may operate over a distance of up to approximately 30 feet. The Zigbee standard is an alternative standard that operates in the ISM bands of approximately 2.4 GHz, 915 MHz, and 868 MHz. However, any wireless communication may be used.

[0364] Optionally, the microprocessor 6630 analyzes the received data and detects the presence of malfunctions or the need for maintenance associated with the device. Some examples of fault conditions include, but are not limited to, the following. Absence of received data within a time period exceeding a set limit. Absence of a data reception confirmation signal from the device or the user interface assembly. Overflow or near overflow of the in-device memory 6620. Low power. Excessively high, low, or inappropriately timed volume measurements received from the fluid delivery device 10.

[0365] Based on this failure analysis, the microprocessor 6630 may activate an alarm 6650 (e.g., a bell or buzzer). Also, the microprocessor 6630 may communicate the alarm state to a remote device. The remote device may be, for example, a user interface assembly using a long-range transceiver 6640, a fluid delivery device 10 using a short-range transceiver, or both a user interface assembly and a fluid delivery device. In response to receiving the alarm signal, the user interface assembly may relay the alarm signal to a medical professional or patient monitor over a long distance (e.g., by pager or telephone, or other communication means).

[0366] The power supply 6670 may be rechargeable and store sufficient energy to operate continuously for a certain period of time, e.g., at least 10 hours. However, the operating time will vary based on the application and device. The size of the fluid delivery device may be reduced to be easily portable and fit into a pocket, handbag, briefcase, backpack, etc. One embodiment of the device includes means for resistance to daily shocks or spills. Some embodiments may include additional features, including but not limited to decorative features, or the ability to play video games, send and receive instant messages, view digital videos, play music, etc., of a wide range of household electronic devices. The use of such functions may be excluded or restricted for several hours a day or throughout the day, including third-party control devices. Alternatively, the device may be as small and simple as possible and only serve to repeat short-range signals over a long distance. For example, the memory and analysis functions may be omitted.

[0367] Next, referring to FIG. 114, a data flow diagram for an embodiment of the present system is shown. The intermediate transceiver 6600 is shown to operate as a general-purpose patient interface that performs short-range communication with a plurality of devices and relays information from those devices over a long distance to one or more user interfaces associated with those devices. Examples of devices include wearable, implantable, or internal medical devices such as fluid delivery systems, glucose sensors, knee joints with integrated strain sensors, tablet-form device-mounted enteric probes, defibrillators, pacemakers, and other wearable therapeutic delivery devices. Since different types of devices and devices from different manufacturers may utilize different short-range communication standards and frequencies, the intermediate transceiver 6600 may include hardware (e.g., a plurality of antennas and circuits), as well as software that supports a plurality of protocols.

[0368] (Battery charger) Next, referring to FIGS. 115 and 116, an embodiment of an instrument for charging the battery 7100 is shown. In FIG. 15, the non-disposable upper portion of the fluid delivery device 2620 is shown cut away from the disposable base portion of the fluid delivery device. The charger 7100 is used to charge the battery (not shown) of the upper portion 2620. In FIG. 116, the upper portion 2620 is shown on the charger 7100. The latch 6530 is shown closed, connecting the upper portion 2620 to the charger 7100. Thus, the latch 6530, which is used to connect the upper portion 2620 to the base (not shown), is also used to connect the upper portion 2620 to the charger 7100. A direct power connection may be established by docking, or power may be transmitted by inductive coupling. Also, in some embodiments of the present system, the patient alternates between using a plurality of non-disposable portions 2620. That is, while one non-disposable portion 2620 is being charged, a second non-disposable portion (not shown) is being used.

[0369] The various embodiments described herein include elements of different types and configurations, such as, for example, pump structures, pump actuators, volume sensors, flow restrictors, reservoirs (and reservoir interfaces), sharp tip insertion devices, housings, latching mechanisms, user interfaces, placement peripheral devices (e.g., control devices, processors, power supplies, network interfaces, sensors), and other peripheral devices (e.g., portable remote control devices, base stations, repeaters, filling stations), etc. It should be noted that alternative embodiments may incorporate various combinations of such elements. Thus, for example, the pump structure described with reference to one embodiment (e.g., the pump illustrated and described with reference to FIGS. 15A - 15D) may be used with any of various configured pump actuators (e.g., a single shape memory actuator with a single operating mode, a single shape memory actuator with multiple operating modes, multiple shape memory actuators of the same size or different sizes), and further may be used within a device having various combinations of other elements (or the absence of other elements) and / or any of various flow restrictors.

[0370] Furthermore, while the various embodiments are described herein with reference to non - pressurized reservoirs, it should be noted that pressurized reservoirs may be used in certain embodiments or under certain conditions (e.g., during priming and / or air removal). In particular, a pressurized reservoir may, for example, facilitate filling of the pump chamber after contraction of the pumping actuator member 54 illustrated and described with reference to FIGS. 15A - 15D.

[0371] Furthermore, while the various embodiments are described herein with reference to a pump motor disposed in a reusable portion of the housing, it should be noted that the pump and / or pump motor may alternatively be positioned in a disposable portion, for example, together with various components that contact the fluid. Similar to some of the other motors described herein, a motor disposed in a disposable portion may include one or more shape memory actuators.

[0372] Note that the title is included for convenience and is not intended to limit the scope of the present invention.

[0373] In various embodiments, the methods disclosed herein, including methods for controlling and measuring fluid flow rates and for establishing communication between connected components, may be implemented as a computer program product for use with a suitable control device or other computer system (generally referred to herein as a "computer system"). Such an implementation may include a series of computer instructions fixed on a tangible medium such as a computer-readable medium (e.g., a diskette, CD-ROM, ROM, EPROM, EEPROM, or fixed disk), or transmitted to the computer system via another interface device such as a modem or a communication adapter connected to a network via a medium. The medium may be a tangible medium (e.g., an optical or analog communication line), or a medium implemented with wireless technology (e.g., microwave, infrared, or other transmission technologies). The series of computer instructions may embody the desired functionality described herein with respect to the system. Those skilled in the art should understand that such computer instructions can be written in several programming languages for use with many computer architectures or operating systems.

[0374] Furthermore, such instructions may be stored in any storage device, such as a semiconductor, magnetic, optical, or other memory device, and may be transmitted using any communication technology, such as optical, infrared, acoustic, wireless, microwave, or other transmission technologies. Such computer program products may be distributed as removable media with accompanying printed or electronic documentation (e.g., commercially available software), preloaded onto a computer system (e.g., on a system ROM, EPROM, EEPROM, or fixed disk), or distributed from a server or electronic bulletin board via a network (e.g., the Internet or World Wide Web). Of course, some embodiments of the present invention may be implemented as a combination of both software (e.g., a computer program product) and hardware. Still other embodiments of the present invention may be implemented entirely in hardware or substantially within software (e.g., a computer program product).

[0375] It should be noted that the dimensions, sizes, and quantities described herein are merely illustrative and the present invention is in no way limited thereto. In an exemplary embodiment of the present invention, the patch-sized fluid delivery device may be approximately 6.35 cm (~2.5 inches) in length, approximately 3.8 cm (~1.5 inches) in width, and approximately 1.9 cm (~0.75 inches) in height. Of course, these dimensions are merely illustrative and the dimensions can vary widely for different embodiments.

[0376] Although the principles of the present invention have been described herein, it will be understood by those skilled in the art that the description has been made by way of example only and is not intended to be limiting of the scope of the present invention. In addition to the exemplary embodiments illustrated and described herein, other embodiments are also intended to be within the scope of the present invention. Modifications and alternatives by those skilled in the art are considered to be within the scope of the present invention.

Claims

【Claim 1】 The invention described in the specification of this application.

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