CN108355194B - Apparatus for dispensing a fluid - Google Patents

Abstract

The present invention relates to an apparatus for dispensing a fluid, the apparatus comprising: a housing sized for attachment to a patient's body; a reservoir for holding a therapeutic fluid enclosed in the housing; a pump downstream of the reservoir and fluidly communicable with the reservoir, the pump enclosed in the housing; and a dispensing assembly downstream of the pump and capable of fluid communication with the pump; wherein the dispensing assembly has a sensor for repeatedly determining a parameter measuring the volume of therapeutic agent exiting the dispensing assembly or determining a function of the volume of therapeutic agent exiting the dispensing assembly.

Description

Apparatus for dispensing a fluid

Divisional application

The present application is a divisional application of the chinese patent application No. 201410309548.4. The Chinese invention application No. 201410309548.4 is a divisional application of the Chinese invention application No. 200780007306.8 (International application No. PCT/US2007/003587) and the application date is 2/9 of 2007, and the invention name is "peripheral system". The application date of the Chinese application No. 200780007306.8 is 2, 9 and 2007, and the invention name is 'peripheral system'.

Technical Field

The present application relates generally to an adhesive and peripheral system for medical devices and methods, and more particularly to an apparatus for dispensing fluids.

Background

Many potentially valuable drugs or compounds, including biological products, are not orally effective due to malabsorption, liver metabolism, or other pharmacokinetic factors. Additionally, some therapeutic compounds, although they can be absorbed orally, sometimes require administration so often that it is difficult for the patient to maintain the intended schedule. In these cases, parenteral delivery is often employed or can be employed.

Effective parenteral routes of drug delivery, as well as other fluid and compound delivery, such as subcutaneous injection, intramuscular injection, and Intravenous (IV) administration, include puncturing the skin with a needle or stylet. Insulin is an example of a therapeutic fluid that tens of millions of diabetic patients self-inject. Users of parenteral drug delivery would benefit from a wearable device that automatically delivers the desired drug/compound over a period of time.

To this end, efforts have been made to design portable devices for the controlled release of therapeutics. Such devices are known to have a reservoir, such as a cartridge, syringe or pouch, and to be electronically controlled. These devices disadvantageously have a number of disadvantages, including failure rate. Reducing the size, weight and cost of these devices is also a current challenge.

Disclosure of Invention

In one embodiment of the invention, an apparatus for dispensing a therapeutic fluid comprises: a housing sized for attachment to a patient's body; a reservoir for holding a therapeutic fluid enclosed in the housing; a pump downstream of the reservoir and fluidly communicable with the reservoir, the pump enclosed in the housing; and a dispensing assembly downstream of the pump and capable of fluid communication with the pump; wherein the dispensing assembly has a sensor for repeatedly determining a parameter measuring the volume of therapeutic agent exiting the dispensing assembly or determining a function of the volume of therapeutic agent exiting the dispensing assembly.

In another embodiment of the present invention, an apparatus for dispensing a fluid comprises: a patch-sized housing; a pump disposed in the housing, the pump having a pump outlet; a dispensing assembly also disposed in the housing, the dispensing assembly including a dispensing chamber having a dispensing inlet and a dispensing outlet, wherein the dispensing inlet is coupled to the pump outlet, the dispensing assembly having a sensor for repeatedly determining a parameter that measures a volume of fluid exiting the dispensing chamber or a function of the volume of fluid exiting the dispensing chamber; and a finite flow resistance coupled to the outlet of the dispensing chamber, wherein the finite flow resistance is a passive flow resistance comprising a tortuous path, wherein the housing comprises a disposable portion having an integral fluid path comprising the tortuous path.

In one embodiment of the present invention, a transponder system is provided for controlling a medical device. Such a system may include a repeater and a user interface. The transponder may comprise circuitry (i) for receiving signals from at least one wearable medical device over a given range, (ii) for transmitting signals to the wearable medical device over the given range, (iii) for transmitting the received signals to a user interface located remotely from the patient over a larger range beyond the given range, and (iv) for receiving signals from the user interface over the larger range. The user interface may include circuitry (i) for receiving signals from the transponder, and (ii) for transmitting signals to the transponder. The medical device may be a wearable or an implantable device.

In some embodiments, circuitry of the user interface may also be provided for directly receiving signals from and transmitting signals directly to the wearable device. Moreover, the circuitry of the transponder may be adapted to receive signals from a plurality of medical devices.

In some embodiments, the repeater may include one or more of the following components: a memory for recording received data, a processor for analyzing the received data with respect to the presence of a fault condition, and an alarm for notifying a user of the presence of a fault condition. The fault condition may include the occurrence of an event wherein the transponder is separated from the wearable medical device by a distance greater than a given range.

In one embodiment of the invention, the transponder is adapted to control a patch-sized pump worn on a subject to deliver fluid to the subject. In this embodiment, the transponder may have circuitry (i) for receiving a signal from the pump over a given range, the received signal containing data relating to the volume of fluid delivered by the pump and relating to an alarm condition, and (ii) for transmitting the received signal over a larger range beyond the given range to an interface for monitoring the volume of fluid delivered and the alarm condition. The circuitry of such a transponder may also be provided for receiving control signals from the interface over a larger range, the control signals containing control information for controlling the pump, and for transmitting the control signals to the pump over a given range.

Such a transponder may have the characteristics of the transponder described above in relation to the transponder system. In addition to or instead of having an alarm for the occurrence of an event in which the transponder is separated from the wearable medical device by a distance greater than a given range, the transponder may also include an alarm for detecting a flow blockage or air bubbles in the pump.

In another embodiment of the present invention, an adhesive patch system is provided for attaching an object to a human body. Such an adhesive patch system may include two sets of adhesive components. In a first kit of three or more components, each component comprising an adhesive material on at least one side for attachment to the body upon application of pressure, the components are arranged around a central area. Similarly, in a second set of three or more members, each member comprising an adhesive material on at least one side for adhering to the body upon application of pressure, the members are arranged around a central area. The first set of members is spaced to allow the second set of members to attach to the body in the space provided between the first set of members, and the second set of members is spaced to allow the first set of members to detach from the body without detaching the members of the second set.

In one embodiment of the adhesive patch system, at least one of the components is perforated to allow easy tearing off of the component. Tearing the member away may reduce irritation of the underlying skin. Furthermore, the central region is adapted to secure a wearable medical device. The adhesive patch may be semicircular. The adhesive patch may include a release liner. The components of the adhesive patch system may be bonded to the central region with fibers. The members of the first set may have a first color and the members of the second set may have a second color different from the first color.

Such an adhesive patch system may be used to attach an object to a human body by a method comprising the steps of: providing a first kit of three or more components (each of which, as noted above, includes an adhesive material on at least one side to adhere to the body when pressure is applied, the components being disposed about a central region); attaching a first set of parts to the body so as to leave a space between each part for holding the object to the body; providing a second set of three or more components (each component of which includes an adhesive material on at least one side so as to adhere to the body when pressure is applied, the components being arranged around a central area); attaching a second set of parts to the body in the spaces between the first set of parts, thereby holding the object to the body with the second set of parts; and removing the first set of components from the body after attaching the second set of components to the body.

The attached object may be a pump that pumps the therapeutic fluid through the skin to the body. The cannula of such a pump may be passed through the skin to allow fluid to be delivered from the pump through the skin. In a preferred embodiment of the method, the sleeve does not move and remains threaded through the skin when the second set of components is attached to the body and when the first set of components is removed from the body.

Similarly, the attached object may be a probe for measuring a parameter in the body through the skin. Such a probe may be passed through the skin. In a preferred embodiment of the method, the probe does not move and remains through the skin when the second set of parts is attached to the body and when the first set of parts is removed from the body.

The objects being joined in such an adhesive patch system may be provided with air channels to allow air to flow under the objects towards the body when the objects are attached to the body.

An alternative bonding system for attaching an object to a human body comprises a central component adapted to secure a wearable object and having an adhesive material on at least one side for attachment to the body upon application of pressure, the alternative bonding system further comprising a plurality of peripheral components, each component comprising an adhesive material on at least one side for attachment to the body upon application of pressure, wherein a fibrous connector is provided for connecting each peripheral component to the central component. In a preferred embodiment, the fibrous connector is resilient.

In one embodiment of the present invention, a method for filling a reservoir with a therapeutic liquid is provided. Such a method may include providing a filling station having a substantially rigid filling station base for holding the reservoir at an incline, and a substantially rigid filling station cover coupled to the filling station base. The fill station cover portion has a fill aperture for receiving fluid from a syringe. The fill station cover and fill station base define a volume to prevent overfilling of the reservoir. The method further includes placing a reservoir in the filling station, closing the filling station cap on the reservoir, applying a syringe containing a therapeutic liquid to the filling aperture, and injecting the therapeutic liquid from the syringe into the reservoir through the filling aperture. In a preferred embodiment, any air in the reservoir after the injection step is removed. A window may be provided in the filling station cover to view the amount of liquid in the reservoir. The amount of liquid can be estimated by comparing the liquid level viewed through the window to the fluid level indicia.

In one embodiment of the invention, a base station is provided for a patch-sized infusion device, wherein the infusion device includes a disposable portion and a reusable portion, and the disposable portion and reusable portion are connectable to one another via an attachment mechanism associated with the reusable portion. The base station comprises a receiver for holding a reusable part of the infusion device, the receiver comprising means for cooperating with an attachment mechanism of the reusable part. The base station may also include a charger for charging the battery in the reusable part. The base station may also include a communication interface between the stand-alone computer and the reusable part to upload information to, and download information from, the reusable part.

These aspects of the invention are not intended to be exclusive and other features, aspects and advantages of the invention will be readily apparent to those of ordinary skill in the art when read in conjunction with the appended claims and accompanying drawings.

Drawings

The foregoing features of the invention will be more readily understood by reference to the following detailed description, taken with reference to the accompanying drawings, in which:

FIG. 1 depicts a patient with a patch and a wireless handheld user interface assembly;

FIG. 2A is a diagrammatic view of a fluid delivery device with feedback control;

FIG. 2B is a diagrammatic view of a fluid delivery device having a feedback control and reservoir;

FIG. 3 is a diagrammatic view of a fluid delivery device having a non-pressurized reservoir;

4A-4C are diagrammatic cross-sectional views of various embodiments of flow restrictors;

FIG. 5 shows a resilient dispensing assembly in series with a flow restrictor;

FIG. 6 shows a dispensing assembly with a metering chamber and a sensor;

FIG. 7 shows a dispensing assembly having a metering chamber with a dispensing spring and a sensor;

FIG. 8 shows a cross-sectional view of a dispensing assembly with an alternative acoustic path;

FIG. 9 shows a schematic view of a dispensing assembly;

FIG. 10 shows a diaphragm spring for a resiliently variable volume dispensing chamber;

FIG. 11A shows the dynamic profile of an exemplary base fluid delivery;

FIG. 11B shows a kinetic profile of exemplary bolus fluid delivery;

FIG. 11C shows kinetic data representative of normal fluid delivery;

11D-11F illustrate dynamic data representing various fault conditions;

FIG. 12 shows a flow chart of a sensing and reaction process of an embodiment of a fluid delivery device;

FIG. 13 shows a block diagram of a flow line with a pressure generating assembly;

FIG. 14 shows a block diagram of a flow line with a valve pump;

15A-15D show diagrammatic views of a pumping mechanism;

FIG. 16 shows a diagrammatic view of a pumping mechanism;

FIG. 17 diagrammatically shows a cross-sectional view of an embodiment including a shape-memory actuator that can have multiple pumping modes;

FIG. 18 diagrammatically shows a cross-sectional view of an embodiment that includes two shape-memory actuators and can have multiple pumping modes;

FIG. 19 diagrammatically shows a cross-sectional view of an embodiment including a shape-memory actuator of different length;

20A-20B schematically illustrate an embodiment for attaching a shape memory actuator;

21A-21B diagrammatically illustrate an embodiment for attaching a shape memory actuator to a pumping mechanism;

figures 22 and 23 show a pumping mechanism employing fingers;

FIG. 24 shows a pumping mechanism employing a rotating lobe;

FIG. 25 shows a pumping mechanism employing a plunger and plunger barrel;

FIG. 26 shows a view of the shape memory actuator in an expanded state;

FIG. 27 shows a view of the shape memory actuator in a contracted state;

FIG. 28 shows a view of a pumping assembly employing a plunger and plunger barrel and a shape memory motor with a lever;

FIG. 29 shows a view of a pumping assembly and shape memory motor employing a plunger and plunger barrel;

FIG. 30 shows a view of a pumping device employing a plunger and plunger barrel and a shape memory motor with wires in the plunger shaft;

FIG. 31 shows a flow line embodiment with a combination pump and reservoir;

FIG. 32 schematically illustrates a cross-sectional view of the valve pump in a resting position;

FIG. 33 diagrammatically shows a cross-sectional view of the valve pump of FIG. 32 in an intermediate position;

FIG. 34 is a cross-sectional view of the valve pump of FIG. 32, shown schematically in an actuated position;

FIG. 35 diagrammatically shows a cross-sectional view of a pumping diaphragm for a valve pump;

FIG. 36 shows a perspective view of a diaphragm spring for pumping the diaphragm;

FIG. 37 diagrammatically shows a cross-sectional view of a valve pump and shape memory wire actuator employing a lever;

FIG. 38 diagrammatically shows a cross-sectional view of an embodiment including a valve pump employing resilient cylindrical flexure;

FIG. 39 diagrammatically shows a cross-sectional view of an embodiment including a valve pump flexure having a resilient member and a rigid support;

FIG. 40 schematically illustrates a cross-sectional view of a valve pump in a resting state with a diaphragm spring upstream of a flexible diaphragm;

FIG. 41 schematically illustrates a cross-sectional view of the valve pump of FIG. 40 in an intermediate state;

FIG. 42 is a sectional view of the valve pump of FIG. 40 shown schematically in an actuated state;

FIG. 43 is a diagrammatic sectional view of a valve pump having a diaphragm spring upstream of a flexible diaphragm circumferentially attached to a force application member;

FIG. 44 is a schematic cross-sectional view of a valve pump with a diaphragm spring upstream of a flexible diaphragm, including a rigid ball for transmitting force;

FIG. 45 diagrammatically shows a cross-sectional view of an embodiment of a valve pump including a resilient pump blade;

FIG. 46 diagrammatically shows a cross-sectional view of an embodiment including an alternative form of resilient pump vane for a valve pump;

FIG. 47 schematically illustrates a cross-sectional view of an embodiment including a valve pump having a plurality of force applying members;

FIG. 48 diagrammatically shows a pumping mechanism including a bellcrank actuated valve pump and a bias valve in a dwell or fill mode;

fig. 49 diagrammatically shows the pumping mechanism of fig. 48 in an actuated state.

FIG. 50 schematically illustrates a cross-sectional view of a biasing valve having a raised valve seat and in a closed position, in accordance with an embodiment of the invention;

FIG. 51 schematically illustrates a cross-sectional view of the deflector valve of FIG. 50 in an open position;

FIG. 52 schematically illustrates a cross-sectional view of a biasing valve without a raised valve seat and in an open position, in accordance with an embodiment of the invention;

FIG. 53 schematically illustrates a cross-sectional view of the bias valve of FIG. 52 in a closed position; '

FIG. 54 schematically illustrates forces acting on a poppet valve near the valve outlet in accordance with an embodiment of the present invention;

FIG. 55 diagrammatically shows in a detailed view forces acting on a poppet valve near the valve inlet in accordance with an embodiment of the invention;

FIG. 56 schematically illustrates a deflector valve with adjustable cracking pressure in accordance with an embodiment of the invention;

FIGS. 57 and 58 show diagrammatic views of flow lines utilizing a non-pressurized reservoir;

FIGS. 59A-59E show diagrammatic views of fluid flow in a fluid delivery device;

FIGS. 60A-60D show exploded diagrammatic views of fluid flow in a fluid delivery device;

61A-61C illustrate diagrammatic views of fluid flow in a fluid delivery device;

fig. 62A and 62B show schematic diagrams of individual devices;

FIGS. 63A-63C illustrate cross-sectional schematics of device embodiments;

FIGS. 64A-64D illustrate cross-sectional schematics of device embodiments;

65A-65B show cross-sectional schematics of an embodiment of an infusion device connected to a flow line;

66A-66D show cross-sectional schematics of a sequence for inserting a reservoir into a device;

67A-67F show diagrammatic views of embodiments of fluid delivery devices;

FIG. 68 is a diagrammatic view of one embodiment of a portable pump embodiment of the device connected to a patient;

69A-69B show a diagrammatic view of the underside of the housing of the device;

FIGS. 70-70D are diagrams depicting various components that may be used in embodiments of a fluid delivery device;

FIG. 71 schematically shows components that may be assembled to form a fluid delivery device according to a device embodiment;

FIG. 72 shows a side view of a fluid delivery device with an acoustic volume measurement member;

FIG. 73 shows a printed circuit board for acoustic volume measurement;

FIG. 74 shows a diagrammatic view of a device embodiment;

FIG. 75 shows a diagrammatic sectional view of an embodiment of a fluid delivery device;

FIG. 76 shows an exploded pictorial view of an embodiment of a fluid delivery device;

FIG. 77 shows an exploded view of components that may be assembled to form one embodiment of a fluid delivery device;

FIG. 78 shows an exploded view of an embodiment of a fluid delivery device;

FIG. 79 illustrates a top view of a base of an embodiment of a fluid delivery device;

FIG. 80 illustrates the underside of the top of one embodiment of a fluid delivery device;

FIGS. 81A-81C illustrate a sequence for illustrating the process of clamping the reservoir 20 between the top and base;

fig. 82 shows an exploded top view of the device;

FIG. 83 illustrates an exploded view of the bottom of one embodiment of the device showing the fluid path assembly, bottom housing and septum and adhesive;

FIG. 84 illustrates a bottom view of the base showing a bottom view of the fluid path assembly;

FIGS. 85A-85D illustrate exploded, partially exploded, and non-exploded views of device embodiments;

FIG. 86A shows a diagrammatic view of an infusion and sensor assembly with an infusion device and an attached analyte sensor;

FIG. 86B shows an exploded view of the infusion and sensor assembly of FIG. 86A with an introduction needle;

FIGS. 87A-87E illustrate a sequence in which an embodiment of an infusion and sensor assembly is inserted into a device;

88A-88B illustrate one embodiment of an inserter device in sequence with a fluid delivery and sensor assembly;

88C-88D illustrate partial cross-sectional views of the inserter of FIGS. 88A-88B;

FIG. 89A illustrates a front view of one embodiment of an inserter device for inserting infusion and sensor assemblies;

FIG. 89B shows a rear view of the interposer device of FIG. 89A;

FIG. 90 shows a perspective view of one embodiment of a cartridge for an infusion and sensor assembly;

91A-91C illustrate front and side perspective views of an inserter device for insertion of an infusion and sensor set;

92A-92F diagrammatically illustrate a timing sequence for operating one embodiment of an inserter mechanism;

FIG. 92G shows the inserter mechanism with catch and compression spring lever in the closed position;

FIG. 92H shows the inserter mechanism with detents and a compression spring lever in an open position;

FIGS. 93A-93C illustrate a time sequence for inserting a cannula into a base of a fluid delivery device;

94A-94C illustrate a timing sequence for inserting a sleeve into a base while consistently connecting the sleeve to a flowline;

fig. 95 shows a top view of an adhesive patch for holding a fluid delivery device;

fig. 96 schematically illustrates a cross-sectional view of the fluid delivery device under the adhesive patch;

FIG. 97 shows a perspective view of two overlapping adhesive patches for holding a fluid delivery device;

FIG. 98 shows a top view of two semicircular adhesive patch sections;

FIG. 99 shows a perspective view of two semicircular adhesive patch portions holding a fluid delivery device;

fig. 100 shows a perspective view of a semicircular adhesive patch portion removed by a patient;

FIG. 101 illustrates a perspective view of a fluid delivery device attached to a patient using a plurality of adhesive members and a tether;

FIG. 102A shows a fixture for assembling a device;

FIG. 102B shows a base portion of a fluid delivery device having a keyhole for insertion of a clamp;

FIG. 102C shows a cross-sectional view of a fluid delivery device assembled using a clamp;

FIG. 103A shows a perspective view of a cam guide for assembling a fluid delivery device;

figure 103B shows a top view of the cam guide of figure 103A;

FIG. 103C shows a perspective view of a clamp pin used to assemble the fluid delivery device;

FIG. 103D illustrates an embodiment of a fluid delivery device assembled using a clamp pin and cam guide;

FIG. 104 illustrates a cross-sectional view of a collapsible reservoir, according to one embodiment;

fig. 105 shows a perspective view of the reservoir of fig. 104;

106A-106C illustrate a series of steps for securing a septum to an end cap to form a reservoir, according to one embodiment;

fig. 107 shows a reservoir filling station according to an embodiment;

fig. 108A-108B illustrate an embodiment of a reservoir filling station in open (108A) and closed (108B) positions;

FIG. 109A shows a block diagram of one embodiment of a data acquisition and control scheme for an embodiment of a fluid delivery system;

FIG. 109B illustrates a block diagram of one embodiment of a data acquisition and control scheme for an embodiment of a fluid delivery system

FIG. 110A shows a flow chart describing the operation of a fluid delivery device according to one embodiment;

FIG. 110B shows a flow chart describing the operation of a fluid delivery device according to one embodiment;

FIG. 111 shows a block diagram of a user interface and a fluid delivery member in wireless communication with each other;

FIG. 112 illustrates a data flow diagram that shows the use of an intermediate transceiver in accordance with one embodiment;

FIG. 113 shows a block diagram of an intermediate transceiver, according to one embodiment;

FIG. 114 shows a dataflow diagram for a generic patient interface, according to one embodiment;

fig. 115 shows a non-disposable part of a fluid delivery device and a battery charger in a decoupled state according to an embodiment;

FIG. 116 illustrates a non-disposable portion of the fluid delivery device of FIG. 115 and a battery charger in a docked state according to one embodiment; and is

FIG. 117 is a flow chart depicting a process for measuring the volume of liquid delivered during a pump stroke in accordance with an embodiment of the invention.

It should be understood that the above figures, and the elements depicted therein, are not necessarily drawn to scale consistently or in any proportion.

Detailed Description

And (4) defining. As used in this specification and the appended claims, the following terms shall have the meanings indicated, unless the context requires otherwise:

"user input" of a device includes any mechanism by which a user or other operator of the device can control the function of the device. The user input may include mechanical means (e.g., switches, knobs), a wireless interface (e.g., RF, infrared) for communicating with a remote control, an acoustic interface (e.g., with voice recognition), a computer network interface (e.g., a USB port), and other types of interfaces.

The "button" associated with the user input, such as the so-called "bolus button" discussed below, may be any type of user input capable of performing the desired function and is not limited to a push button.

An "alarm" includes any mechanism that can be used to alert a 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., vibrating element), a wireless signal (e.g., wireless transmission to a remote control or caretaker), or other mechanism. Alarms may be generated using multiple mechanisms, including a backup mechanism (e.g., two different audio alarms) or a complementary mechanism (e.g., an audio alarm, a tactile alarm, and a wireless alarm), simultaneously, or sequentially.

By "fluid" is meant a substance, such as a liquid, capable of flowing through a flow line.

"impedance" means the obstruction of a device or flow line to the flow of fluid therethrough.

"wetting" describes a member that makes direct contact with a fluid during normal fluid transfer operations. Because the fluid is not limited to a liquid, the "wetted" member does not necessarily become wetted.

"patient" includes a person or animal that receives fluid from or otherwise receives fluid delivery devices as part of a medical procedure.

By "cannula" is meant a disposable device capable of infusing fluid to a patient. A cannula as used herein can refer to a conventional cannula or needle.

By "analyte sensor" is meant any sensor capable of determining the presence of an analyte in a patient. Embodiments of analyte sensors include, but are not limited to, sensors capable of determining the presence of any viral, parasitic, bacterial, or chemical analyte. The term analyte includes glucose. The analyte sensor may be in communication with other components in the fluid delivery device (e.g., a controller in the non-disposable portion) and/or with a remote controller.

By "dispensing assembly sensor" is meant a mechanism for determining the volume of fluid present in the dispensing chamber.

By "sharp object" is meant any object capable of piercing or puncturing the skin of an animal, particularly the skin of a human. The sharp object may comprise a cannula, a cannula insertion device, an analyte sensor or an analyte sensor insertion device. For example, multiple sharps may be provided separately in the cartridge or may be provided together.

"disposable" refers to a component, device, portion, or the like that is intended to be used for a fixed period of time, and then discarded and replaced.

"non-disposable" refers to reusable portions that are intended to have an unlimited period of use.

By "patch size" is meant a size small enough to be secured to the skin of a patient and worn as a medical device during delivery of the substance contained in the device using, for example, an adhesive or tape. Medical devices that are small enough to be useful as implants fall within this definition.

By "a limited flow resistance that is normally present" is meant a limited flow resistance that is present during the normal course of fluid delivery, i.e. when no error condition (e.g. clogging) is present.

A "passive" impedance is an impedance that is not actively controlled during a pumping cycle.

By "acoustic volume measurement" is meant a quantitative measurement of the volume of interest using, for example, the acoustic techniques described in U.S. patent nos. 5,349,852 and 5,641,892, and the techniques described herein.

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

Embodiments of the devices, pumping mechanisms, systems, and methods described herein relate to fluid delivery including pumping and fluid volume measurement and actuation and control of fluid delivery. Embodiments of the device include portable or non-portable devices for fluid delivery. Some embodiments of the device include a disposable base and a non-disposable top. The device includes embodiments in which the infusion device is inserted through the base and directly into the patient. These device embodiments are patch pump devices (patch pump devices). The patch pump may be attached to the patient using an adhesive, tape, or other suitable means. The adhesive may have a protective peelable strip that can be removed prior to use to expose the adhesive.

However, in other embodiments, the fluid delivery device is a portable device in which the tubing line is connected to a flow line. Typically, the line is connected to the patient by a cannula.

In some embodiments in which a disposable base and a non-disposable top are used, the base includes wetted components, while the portion included in the non-disposable top is typically a non-wetted component.

Various embodiments of the pumping mechanism include an upstream inlet valve, a pumping actuation member, a downstream outlet valve, and a movable member. In some embodiments, the pumping actuation component and the downstream valve function are implemented using the same device. The pumping mechanism pumps fluid from the reservoir to the outlet through the flow line. The pumping mechanism is typically used with a non-pressurized reservoir, however, the scope of the present invention is not so limited.

In one embodiment of the fluid delivery system, the device includes an analyte sensor housing. The analyte sensor is introduced into the patient through an analyte sensor housing at the base of the device. In these embodiments, the infusion set is also introduced through the tube cover of the base of the set. In these embodiments, the device is worn by the user as a patch pump.

The system generally includes a controller, which may include a wireless transceiver. Thus, the device may be fully or partially controlled by a wireless controller device. The controller device may receive information from the analyte sensor and/or the fluid delivery device via wireless communication. The patient or a third party can control the function of the fluid delivery means using the controller means.

In one embodiment of the fluid delivery device, the device is an insulin pump and the analyte sensor is a blood glucose sensor. The controller, which receives information relating to the volume of insulin delivered (or the number of pump strokes during a certain time period) and blood glucose data, assists the user in programming the actuation schedule of the pump mechanism.

Exemplary dispensing assemblies and volume sensing devices are described herein. The dispensing assembly includes at least one microphone and a loudspeaker. The assembly determines the volume change in the dispensing chamber to determine the volume of fluid pumped. The volume sensing data is used to determine the state of the fluid delivery device. Thus, various controls may rely on the volume sensing data.

In an embodiment of the invention, the user configures the fluid delivery device via the user interface such that the fluid delivery device delivers the fluid in an appropriate manner. In one embodiment, the user interface is a stand-alone handheld user interface component that can communicate wirelessly with the patch. The patch may be disposable, or partially disposable.

As noted above, an exemplary use of the device embodiments is for the delivery of insulin to a diabetic patient, but other uses include the delivery of any fluid. The fluid includes an analgesic for pain patients, chemotherapy for cancer patients, and enzymes for metabolic disorder patients. Various therapeutic fluids may include small molecules, natural products, peptides, proteins, nucleic acids, carbohydrates, nanoparticle suspensions, and related pharmaceutically acceptable carrier molecules. The therapeutically active molecule may be modified to improve stability in the delivery device (e.g., by pegylation (pegylation) of a peptide or protein). While the illustrative embodiments herein describe drug delivery applications, embodiments may be used in other applications, including liquid dispensing of reagents for high-throughput analytical measurements (e.g., microtechnical applications and capillary chromatography). For purposes of the following description, the terms "therapeutic agent" or "fluid" are used interchangeably, however, in other embodiments, any fluid as described above can be used. Thus, the devices and descriptions included herein are not limited to therapeutic use.

Typical embodiments include a reservoir for holding a supply of fluid. In the case of insulin, the reservoir may conveniently be sized to hold a supply of insulin sufficient for delivery over one or more days. For example, the reservoir may contain about 1 to 2ml of insulin. For about 90% of potential users, a 2ml insulin reservoir may correspond to about 3 days of supply. In other embodiments, the reservoir can be of any size or shape and can be adapted to hold any number of insulin or other fluids. In some embodiments, the size and shape of the reservoir is related to the type of fluid the reservoir is adapted to contain. The fluid reservoir may have an eccentric or irregular shape and/or may be keyed to prevent incorrect installation or use.

Some embodiments of the fluid delivery device are adapted for use by a diabetic patient, and therefore, in these embodiments, the device delivers insulin for replenishing or replacing the beta cells of the patient's islets. Embodiments suitable for insulin delivery attempt to mimic pancreatic action by providing basal levels of fluid delivery as well as bolus levels of delivery. The basal level, bolus level and timing can be set by the patient or another party by using a wireless handheld user interface. Additionally, basal and/or bolus levels can be triggered or adjusted in response to the output of an integral or external analyte sensor (e.g., a glucose monitoring device or a blood glucose sensor). In some embodiments, the bolus can be triggered by the patient or a third party using a defined button or other input device located on the fluid delivery device. In further embodiments, the bolus or basal level can be programmed or administered through a user interface located on the fluid delivery device.

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, according to an exemplary embodiment of the present invention. The user interface component 14 generally includes a device (e.g., an LCD display, speaker, or vibration alarm) for inputting information (e.g., a touch screen or keypad) and for communicating information to a user. The fluid delivery device is generally small and light enough to remain comfortably attached to the patient for several days.

In fig. 1, fluid delivery device 10 is shown worn on an arm of patient 12. In other embodiments, the fluid delivery device 10 may be worn at other locations on the patient where the patient's body can advantageously utilize the particular fluid being delivered. For example, fluid may be advantageously delivered to the abdominal region, lumbar region, legs, or other portions of a patient.

Referring now to fig. 2A, a schematic representation of fluid delivery device 10 is shown having a feedback loop 360 from dispensing assembly 120 to pumping assembly 16. Pumping assembly 16 pumps fluid to dispensing assembly 120; the fluid then exits through the outlet assembly 17, which includes the flow restrictor 340 and an output. The output generally comprises a cannula and leads to the patient. The dispensing assembly 120 may comprise a resilient variable volume dispensing chamber and at least one microphone and loudspeaker for measuring a parameter related to flow through the output over time. Feedback loop 360 allows the operation of pumping assembly 16 to be adjusted based on repeated measurements made by the sensors. The flow restrictor 340 creates a high impedance between the distribution assembly 120 and the output of the flow line 5010. The flow restrictor 340 may be, for example, a portion of a narrow bore tube or a microcatheter.

Referring now to fig. 2B, in one embodiment, pumping assembly 16 pumps fluid from reservoir 20 to dispensing assembly 120.

Referring now to FIG. 3, a block diagram of another embodiment employing principles of fluid mechanics is shown. Flow line 310 couples reservoir 20, pumping assembly 16, dispensing assembly 120, and outlet assembly 17. The outlet assembly 17 may include a high impedance occluder 340 and an infusion set 5010, such as a cannula. The output of the occluder 340 is sent to an infusion set 5010 for delivery to the patient. The flow restrictor 340 has a higher flow resistance than the portion of the flow line 310 upstream of the dispensing assembly 120. Thus, pumping assembly 16 is able to pump fluid into dispensing assembly 120 faster than if the fluid were able to exit outlet assembly 17. The dispensing assembly 120 may include a variable volume dispensing chamber 122 having a resilient wall. In the embodiments given below, the elastic wall is a membrane. Examples of septum materials include silicone, nitril, and any other material having the desired elasticity and properties for functioning as described herein. Additionally, other structures may be used for the same purpose. When a fluid supply is received due to the action of pumping assembly 16, the diaphragm elasticity will allow chamber 122 to first expand and then provide the delivery pressure required to drive the fluid contents of dispensing assembly 120 through restrictor 340 to the patient. When equipped with appropriate sensors (examples of which are described below), dispensing assembly 120 may measure fluid flow through variable volume dispensing chamber 122 and may provide feedback through feedback loop 360 to control the timing and/or rate at which pumping assembly 16 pumps or partially fills dispensing chamber 122, thereby delivering a desired dose to a patient at a desired rate.

Referring again to fig. 3, additionally, the flow restrictor 340 prevents fluid flow from exceeding a specified flow rate. Further, because pressurized fluid delivery is accomplished by the interaction of pumping assembly 16, dispensing assembly 120, and restrictor 340, non-pressurized reservoir 20 can be employed.

Still referring to fig. 3, the feedback loop 360 may include a controller 501. Controller 501 may include a processor and control circuitry for actuating pumping assembly 16 to pump fluid to dispensing assembly 120. The controller 501 canA sensor integral with dispensing assembly 120 repeatedly receives a parameter related to fluid flow and uses that parameter to control pumping assembly 16 to achieve a desired flow through the output. For example, the controller 501 can adjust the timing or degree of actuation of the pumping assembly 16 to achieve a desired basal or bolus flow rate and/or deliver a desired basal or bolus cumulative dose. In determining the timing or extent of pumping, the controller 501 may use the output of a sensor (not shown) to estimate the rate of fluid flow, the cumulative flow rate, or both (and many other quantities), and then determine the appropriate compensation behavior based on the estimation. In various embodiments, pumping may be pulsed, which may be at 10^-9Delivery is at any rate between liters per pulse to microliters per pulse. Basal or bolus dosing can be achieved by delivering multiple pulses. (examples of basal and bolus doses are shown and described below).

The use of a partially collapsible, non-pressurized reservoir 20 may advantageously prevent the accumulation of air in the reservoir when the fluid in the reservoir is depleted. The reservoir 20 may be connected to the flow line 310 by a septum (not shown). The accumulation of air in the vented reservoir can prevent fluid from flowing out of the reservoir 20, particularly when the system is tilted such that an air pocket is interposed between the fluid contained in the reservoir and the septum of the reservoir 20. During normal operation of the wearable device, for example, it is desirable that the system be tilted. Fig. 104-106C depict various embodiments and views of one embodiment of a reservoir. Additionally, further description of the reservoir is included below.

Referring now to fig. 4A-4C, various embodiments of a flow restrictor 340 are shown. Referring now to fig. 4A, the flow restrictor is a molded runner 340, which may be a molded recess (not shown) in the base. In one embodiment, mold runner 340 is approximately 0.009 inches in cross-section. In this embodiment, the flow restrictor 340 is molded into the device. Referring now to FIG. 4B, a microcatheter 340 is shown as an alternative embodiment of the flow restrictor. In one embodiment, the microtube has an inner diameter of approximately 0.009 inches. Both the molded runners and microtubes use long paths with small inner diameters or cross sections to impart flow resistance. Referring now to FIG. 4C, a precision orifice plate is shown as a flow restrictor 340. In one embodiment, the precision orifice plate is a plate with laser drilled holes. In alternative embodiments, any flow resistance device or method known in the art may be used. Unlike prior art fluid delivery systems having active downstream valves, which may generally be considered to create infinite flow resistance in a functional sense, the flow restrictor 340 creates a finite flow resistance. Unlike prior art systems, which may sometimes be impeded by clogging, the impedance of the present invention is also present under normal conditions. Due to the limited flow resistance, in embodiments including the dispensing chamber 122, fluid may leak through the outlet even when the dispensing chamber 122 expands.

Fig. 5-8 schematically illustrate cross-sectional views of exemplary embodiments of the dispensing assembly 120. It is to be understood that fluid transport for other purposes, such as industrial processes, is within the scope of the present invention and that the description given in specific terms is by way of example only. As shown in fig. 5, the dispensing assembly 120 may include a variable volume dispensing chamber 122 and a sensor 550. The variable volume dispensing chamber 122 includes a resilient dispensing diaphragm 125 that allows the chamber 122 to expand and contract in response to fluid flow into and out of the dispensing assembly 120. In certain embodiments of the present invention, the variable volume dispensing chamber 122 may be detachable from other elements of the dispensing assembly 120, as will be discussed further herein. The concept of a resilient dispensing membrane 125 that allows the chamber 122 to expand and contract is illustrated with double-headed arrows. The metering chamber 122 is considered to comprise a portion of the line 110 characterized by fluid flow, designated by arrow 112 in fig. 5. Neither the location nor the nature of the termination of fluid flow 112 or line 110 limits the scope of the invention as specifically claimed in the appended claims. The flow restrictor 340 causes the fluid to exit the dispensing chamber 122 more slowly than if the fluid entered the chamber 122 when pumped into the chamber 122 by the pumping assembly 16. As a result, when a fluid supply enters, the dispensing chamber 122 expands and is pressurized. The dispensing diaphragm 125, which deforms due to the expansion of the dispensing chamber 122, provides the force required to deliver the metered volume through the flow restrictor 340 to the outlet assembly 17. As discussed above, the sensor 550 repeatedly measures a parameter that can be related to the volume of the resilient dispensing chamber 122, such as displacement, or a thermodynamic variable or capacity. The volumetric measurements produced by sensor 550 may be used to control the timing and rate at which the pumping assembly pumps fluid to dispensing chamber 122 through a feedback loop so that an appropriate flow of fluid is delivered to outlet assembly 17 and subsequent lines, and thus, for example, to a patient. The sensor 550 may employ, for example, acoustic volume sensing (described in more detail below) or other methods (optical or capacitive, as other examples) for determining a volume or volume-related parameter. Acoustic volume measurement techniques are the subject of U.S. patent nos. 5,575,310 and 5,755,683 to DEKA Products Limited partnershirp and co-pending provisional U.S. patent application entitled "volume measurement method for flow control" filed on 4/5 2006, serial No.60/789,243, all of which are incorporated herein by reference. With this embodiment fluid volume sensing in the nanoliter range is enabled, thus facilitating highly accurate and precise monitoring and delivery. Other alternative techniques for measuring fluid flow may also be used; for example, Doppler (Doppler) based methods; using Hall effect sensors in combination with leaf or flapper valves; using a strain beam (e.g., in relation to a flexible member on a fluid chamber for sensing deflection of the flexible member); capacitive sensing using a plate; or thermal time of flight method.

Referring now to fig. 6 to 9, embodiments are shown in which the sensor utilizes Acoustic Volume Sensing (AVS) technology. The first discussion refers to the embodiment depicted in fig. 6 and 7. The dispensing assembly 120 has a sensor that includes a reference chamber 127 and a variable volume measurement chamber 121 connected to a fixed volume chamber 129 by a port 128. Although the present invention may be practiced with a reference chamber 127 as shown in fig. 6 and 7, in certain other embodiments of the present invention, no reference space is provided. It should be understood that space 129 is referred to herein as "fixed" as that term, but that its actual volume may vary slightly on the acoustic excitation timescale, such as when the region referred to as fixed space 129 is driven with a loudspeaker diaphragm. Fluid flows from pumping assembly 16 through resilient dispensing chamber 122 to input 123 and out outlet passage 124. Due to the high downstream impedance, the distribution diaphragm 125 expands into the variable volume chamber 121 as fluid enters the distribution chamber 122. The electronic assembly, which may be arranged on the printed circuit board 126, has a microphone 1202, a sensing microphone 1203 and a reference microphone 1201 for measuring acoustic parameters related to the gas (typically air) in the variable volume chamber 121, the chamber volume being defined by the position of the dispensing diaphragm 125. Sound waves induced by the microphone 134 travel through the fixed volume chamber 129 to the variable volume chamber 121 via the port 128; the sound wave also travels to the reference chamber 127. As the dispensing diaphragm 125 moves with fluid flow through the flow line, the volume of air in the variable volume chamber 121 changes, causing a related change in its acoustic properties, which can be detected using the microphone 1203 and microphone. For the same acoustic stimulus, the reference microphone 1201 may detect the acoustic properties of the fixed reference space 127. These reference measurements may be used, for example, to eliminate inaccuracies and to reject inaccuracies of common patterns in acoustic excitation and other errors. The volume of fluid displaced 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 remains constant, the absolute volume of the dispensing chamber 122 can also be estimated.

The embodiment shown in fig. 6 utilizes an inherently resilient dispensing diaphragm 125, while the embodiment shown in fig. 7 utilizes a resilient dispensing spring 130, which resilient dispensing spring 130, when combined with dispensing diaphragm 125, increases the resiliency of dispensing chamber 122 and may allow for the use of a more compliant (i.e., less resilient) dispensing diaphragm 125 than would be required in the embodiment shown in fig. 5. The dispensing spring 130 is generally positioned adjacent to the dispensing diaphragm 125 on a side of the diaphragm 125 opposite the dispensing chamber 122.

Alternatively, to reduce background noise from the microphone, the loudspeaker 1202 and the sensing microphone 1203 may be connected to the variable volume chamber 121 via separate ports. As diagrammatically shown in fig. 8, the microphone 1202 generates pressure waves in a fixed microphone volume 6000 that is acoustically coupled to the variable volume chamber 121 via a microphone port 6020. Pressure waves travel from the loudspeaker 1202, through the loudspeaker port 6020 to the variable volume chamber 121 and then through the microphone port 6010 before being recorded by the sensing microphone 1203. The microphone port 6020 may include a line section 6040 having a flared aperture 6030. The flared aperture 6030 serves to create a uniform length of acoustic wave travel therealong for all axial paths of the line portion 6040. For example, the line segment 6040 may have a cylindrical geometry, such as a right cylinder or a right circular cylinder. A similar flared aperture may also adjoin the line portion to define the microphone port 6010. Unlike the AVS sensor of fig. 6 and 7, in the embodiment of fig. 8, the pressure wave traveling from the loudspeaker 1202 does not have a direct path to the sensing microphone 1203. Thus, pressure waves from the loudspeaker 1202 are prevented from directly impinging the sensing microphone 1203 without first passing through the variable volume 121. The microphone receives a reduced background signal and a better signal/noise ratio is achieved. Additionally, an upper shelf 6050 may be included in any of the embodiments of fig. 6-8 to advantageously reduce the volume of the reference chamber 127.

In embodiments which will be described further, the sensor and metering chamber portions of the dispensing assembly may be conveniently separated so that the dispensing chamber is removable and disposable. In this case, the dispensing chamber is located in the disposable portion of the patch, while the sensor is located in the reusable portion. The dispensing chamber may be bounded by a resilient fluid dispensing membrane (as shown at 122 and 124 in fig. 6). Alternatively, as in FIG. 7, the dispensing chamber 122 may be bounded by a compliant membrane 125. In this case, the dispensing spring 130 can be used to impart elasticity on the dispensing chamber 122. When the sensor 550 and the dispensing chamber 122 are brought together, the dispensing spring 130 covers the compliant dispensing diaphragm 125. The dispensing spring 130 and the dispensing diaphragm 125 may alternatively be employed as a single part defining the dispensing chamber 122.

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 measurement chamber 121 shares a compliant wall (shown here as a compliant membrane 125) with the dispensing chamber 122. The port 128 acoustically couples the measurement chamber 121 to the fixed volume chamber 129, forming an acoustic abutment region generally designated by the reference numeral 1290. A compressible fluid (typically air or another gas) fills acoustic abutment region 1290 and is excited by drive component 1214, which drive component 1214 is itself driven by actuator 1216. The driver component 1214 may be a diaphragm of a speaker, such as a hearing assistance speaker, in which the actuator 1216 is, for example, a voice coil solenoid or a piezoelectric element. It is also within the scope of the present invention that drive component 1214 may also be coextensive (coextensive) with actuator 1216, for example, when drive component 1214 may itself be a piezoelectric element. The drive component 1214 may be contained in a driver module 1212, which may contain a reference space 1220 on the side of the drive component 1214 remote from the fixed space 129. However, reference space 1220 is not generally employed in the practice of the present invention.

The reference microphone 1208 is shown in acoustic communication with the fixed space 129 when the signal microphone 1209 is acoustically coupled to the measurement chamber 121. The volume of measurement region 121 may be determined by an electronic signal provided by one or more microphones 1208, 1209 based on pressure changes (or, equivalently, acoustic signals) measured at their respective locations in acoustic border region 1290. The phase measurement may be performed by comparing the phase of the response at one or more microphones with the phase of the acoustic excitation or with the phase of the response at the location of another microphone. The volume of the measurement region 121 and hence the volume of the dispensing chamber 122 is determined based on phase and/or amplitude measurements as discussed below by a processor 1210, which obtains power from a power source 1211, representatively shown as a battery.

In order to accurately deliver minute amounts of therapeutic agents, it is desirable to deliver small but very accurately metered amounts in each pump stroke. However, if a minute volume of fluid is pumped through line 110 during each pump stroke, the metering process requires extremely high resolution. Thus, according to an embodiment of the present invention, changes in volume are measured by sensor 550 with a resolution of at least 10 nanoliters. A 0.01% resolution measurement of the empty volume of the measurement region 121 may be achieved in some embodiments of the present invention. According to other embodiments of the present invention, sensor 550 provides a resolution of better than 13 nanoliters. In other embodiments, however, the sensor 550 provides a resolution of better than 15 nanoliters, and in other embodiments, a resolution of better than 20 nanoliters. In such a case, the total volume of acoustic border region 1290 can be less than 130 μ l, and, in other embodiments, less than 10 μ l.

According to various embodiments of the invention, prior modeling of the volumetric response of the dispensing chamber 122 and subsequently the variable volume chamber 121 (also referred to herein as the "metering space") based on the dispensing chamber being filled by the pumped volume of fluid entering the input 123 may be used. While other models are within the scope of the invention, one model that can be employed expresses the volume of fluid in the dispensing chamber 122 responsive to the pumped influent fluid and having an outlet with a fixed flow resistance as the baseline volume V_BAnd is displaced by the peak value V_DThe sum of the characterised exponentially decaying volumes, whereby the metering chamber volume during a measurement is characterised as a function of time t, as follows:

in order to fit a parametrization modeling the exponential decay (or other functional model) to a series of acoustic measurements, the response of the system, for example as depicted in fig. 6 to 9, is derived as follows. To model the response, the port 128 is characterized by a length l and a diameter d. The pressure and volume of the ideal insulating gas can pass through the PV^γK is associated, where K is a constant defined by the initial state of the system.

The ideal adiabatic gas law can be expressed in terms of mean pressure P and volume V, and small time-varying perturbations P (t) V (t) above those pressures:

(P+p(t))(V+v(t))^γ＝K

the equation differential was obtained:

alternatively, the simplification yields:

if the acoustic pressure level is much less than the ambient pressure, the equation can be further simplified as:

applying the ideal gas law, P ═ ρ RT, and replacing it with pressure gives the following results:

can be based on the speed of sound

It is written as:

furthermore, the acoustic impedance with respect to a volume is defined as:

according to one set of models, the acoustic port is modeled assuming that substantially all of the fluid in the port moves as a rigid cylinder that reciprocates along the axial direction. Assuming all of the fluid in the channel (port 128) is traveling at the same rate, the channel is assumed to have a constant cross-section, and the "end effects" caused by the fluid entering and exiting the channel are ignored.

Suppose that

Laminar friction in the form of frictional forces acting on the fluid substance in the channel can be written as:

a second order differential equation can then be written for the fluid dynamics in the channel:

alternatively, depending on the volumetric flow rate:

the acoustic impedance of the channel can then be written as:

using the volume and port dynamics defined above, an acoustic volume sensor system can be described by the following system of equations (where index k represents the speaker and r represents the resonator):

according to the same convention,

and is

In addition, the first and second substrates are,

if p is₂Greater than p₁The volume tends to accelerate in the positive direction.

Reduce the number of equations (let p₀As input) and substitute

Using these equations gives a simple expression

Or

v₀p₀+V₁p₁＝-V₂p₂

These equations can also be expressed in the form of transfer functions. "Cross-speaker" transfer function, p₁/p₀Comprises the following steps:

or

Wherein:

and is

Similarly, the "cross-system" transfer function based on measurements of either end of the port 128 is p₂/p₀Given by:

volume estimation using cross system phase

Similarly, using the same principles, it is easy to derive the transfer function, with the pressure in the fixed volume chamber 129 being indicative of the pressure in the fixed volume chamber 129, with the pressure in the variable volume chamber 121 to which the fixed volume chamber 129 is coupled via the port 128. In particular, the transfer function is:

in either of the foregoing cases, the system resonance frequency may be expressed as a variable volume V₂Function of (c):

since all other parameters are known, the variable volume V can be calculated, for example, based on the resonance frequency₂But derive itV₂May be advantageous and is further described in the present application. One parameter that is not constant in this equation is the speed of sound, a, which may be calculated or otherwise derived or measured based on the relevant temperature.

As noted, various strategies may be employed to interrogate the system to derive the volume V₂. According to some embodiments of the invention, the system is excited at a single frequency by the drive assembly 1214 while monitoring the response of one or more transducers ( microphones 1208 and 1209, FIG. 9). The response is captured as a complex signal, maintaining the amplitude and phase of the pressure change. Advantageously, the single interrogation frequency approaches the resonance of the system in the middle stroke, since thereby a maximum phase change of the accompanying volume in the entire range for emptying the chamber is achieved.

The response of the signal microphone 1208 may be corrected to eliminate common mode effects due to the frequency-dependent characteristics of the excitation microphone 1202 (shown in fig. 6) or the drive component 1214 (shown in fig. 9). The correction signal obtained as a complex ratio (complex ratio) of the microphone signals may be expressed as m_iWhere the index i represents successive time samples of the signal.

Similar to a second-order mechanical Helmholtz resonator (Helmholtz resonator), expressed in the form of a transfer function, the signal can be expressed as:

here, normalization variables have been introduced to keep the relevant parameters within the computationally useful dynamic range of order units. The final expression is expressed by dividing the real and imaginary parts by the common denominator. Taking the ratio of the real part μ to the imaginary part v, (i.e., the phase cotangent),

the error can be defined as:

where N and D represent the numerator and denominator of the model, respectively.

If the error is minimized with respect to each model parameter, a best fit is achieved. Any method may be used to fit the model parameters. In one embodiment of the invention, a gradient descent method is used to find the minimum:

for each particular application of the invention, the interval of each successive time domain sample is obtained and the number of intervals sampled for fitting the time domain model parameters is advantageously optimized. Sampling at periods from τ/3 to 3 τ has been found to be effective when the fluid is flowing at a slow but relatively constant rate, as in basal insulin delivery. In the other extreme, when delivering a relatively large bolus of fluid, on the time scale of the exponential decay time constant, the fluid may only be present in the dispensing space 122 for a short period of time. In this case, the sampling is performed over a shorter period of the characteristic decay time.

According to a preferred embodiment of the present invention, the volume of fluid dispensed through the dispense space 122 is determined from a fit to a volume-time model based on cross-system phase measurements taken at a single excitation frequency. Also, during the initial portion of the pump stroke, with reference to the flow chart shown in FIG. 117, a preliminary measurement is taken in conjunction with the measurement protocol to calibrate system operation, as now described. The metering process, generally designated by the numeral 1170, advantageously conserves computer resources and reduces power consumption, thereby extending the time of use between charging or replacing the power source 1211 (shown in fig. 9) while providing the measurement accuracy required to deliver fluid in a manner having the resolution described above per stroke through frequency calibration.

The processor 1210 initiates a self-calibration phase 1172 of the AVS system prior to each pump stroke or at its start 1171, or both. No measurement is made until the electronic transients due to the actuation of the pump have decayed significantly. In step 1173, microphone and speaker gains are set and drive components 1214 are actuated at a succession of frequencies, typically employing five frequencies that resonate generally close to the adjacent acoustic region 1290 (or referred to herein as an "acoustic chamber"). Frequencies in the range of 6-8kHz are typically employed, but it is within the scope of the invention to use any frequency. At the beginning of each successive frequency actuation, data acquisition is delayed for a period of approximately 5ms until the acoustic transient has substantially attenuated.

For a duration of approximately 64 acoustic cycles, data is acquired as follows: the temperature readings provided by the temperature sensor 132 (shown in fig. 70B) are sampled in step 1174, and the real and imaginary parts, denoted by p and iota, of the ratio of the signal microphone 1209 relative to the output signal of the reference microphone 1208 are sampled, respectively. For the purposes of describing an AVS system, the complex ratio of signals, or other functional combination of microphone signals relative to the reference, may be referred to herein as a "signal".

Based on measurements at each frequency taken over a period of approximately 200ms at each frequency, a set of mean and variance is derived for each of the real and imaginary parts of the signal at each frequency and for the temperature readings. Analysis of these values in step 1175 allows a determination to be made as to whether the error is within a specified range. The anomalous transfer function may advantageously indicate system failure including, but not limited to, failure in microphones or other sensors, speakers, transducers, electronics, mechanical components, fluid inlets, poor acoustic sealing, excessive ambient noise, and excessive shock and vibration. Additionally, the functional dependence of the phase angle of the signal as a function of frequency is determined in step 1176. The phase angle of the signal, i.e. the arctangent of its ratio of the imaginary part to the real part, may be used as a phase measurement, however any phase measurement may be used within the scope of the invention. The functional dependence may be derived by a polynomial fit of phase versus frequency or otherwise. In step 1177, a slope of phase versus frequency is determined at the volume measurement frequency based on the polynomial fit, or otherwise, and a volume measurement is taken. Additionally, and importantly, the abnormal slope of phase versus frequency indicates the presence of a bubble in the fluid contained in dispense chamber 122.

For the subsequent portion of each pump stroke, the drive member 1214 is actuated substantially at a single frequency, thereby acoustically exciting at that frequencyAcoustically adjoining the gas in region 1290. Signal data, typically based on the complex ratio of the output signal of the signal microphone 1209 relative to the reference microphone 1208, is collected and averaged over a prescribed sampling interval of approximately 64 cycles. Real and imaginary parts of the signal and temperature data are recorded for each sampling interval. Based on the sampled and collected data, a time domain model is fitted. In various embodiments of the present invention, as described above, a gradient descent method is employed to fit model parameters, i.e., the baseline volume V of the variable volume chamber 121, during each pump stroke_BPeak displacement V_DAnd the error in the decay time τ, thereby providing the volume of fluid delivered through the dispensing chamber 122.

Referring now to fig. 10, the dispensing spring 130 may have a spiral or fan shape complementary to the diaphragm and may have a plurality of spiral grooves 131. The embodiment of the spring as shown is capable of exerting a substantially uniform force on the diaphragm. This substantially uniform force helps the diaphragm to maintain a substantially concave shape as it expands. The recess 131 allows air to pass freely through the spring so most of the air is not trapped between the spring and the diaphragm.

Referring now to fig. 11A and 11B, a kinetic measurement of the volume of dispensing chamber 122 (shown in fig. 5) and an example of the calculated cumulative volume expelled from dispensing chamber 122 are shown for a typical basal delivery pulse (fig. 11A) and for a typical bolus delivery (fig. 11B). As can be seen from fig. 11A, actuating pumping assembly 16 causes dispensing chamber 122 to expand from about 0 to about 1.5 μ Ι in about 2 seconds, as measured by acoustic volume sensor 550. Note that the resilient dispensing chamber 122 contracts over a period of about 30 seconds and expels its fluid from the chamber 122 through a high impedance output, with an exponential decay kinetics defined by a half-life (t) of about 6 seconds_1/2) And (5) characterizing. The cumulative volume output from dispensing chamber 122 is calculated from the measurements taken with sensor 550 and is also noted to grow exponentially to about 1.5 μ l. It can be seen that the high impedance output introduces a delay between actuating the pump assembly and delivering the majority of the displaced fluid. The elastic force exerted by the dispensing chamber 122 can be taken into account andt of the output impedance level selection system_1/2And (4) characteristics. In various embodiments, the time constant may be changed to save power and eliminate drift problems. The time constant may be, for example, t _1/22 seconds or t _1/c2 seconds.

Fig. 11B shows the kinetic profile of bolus fluid delivery using the fluid delivery device 10. About 29 pump actuations (i.e., pulses) in rapid succession each move fluid from the fluid source into the resilient dispensing chamber 122, thus causing a corresponding change in the parameter measured by the acoustic volume measuring sensor 550. It can be noted that the volume of the dispensing chamber 122 expands to about 1.5 μ l on the first pump pulse, a value similar to that observed in fig. 11A. At additional pulsed pumping at pulse intervals shorter than the period required to achieve full discharge of dispensing assembly 120, dispensing chamber 122 expands further in volume; the swelling reached a maximum of about 6. mu.l. After about 85 seconds the pump pulsation ceases and the volume of chamber 122 is found to decrease with exponentially decaying dynamics, thereby completely discharging the fluid it contains for about 30 seconds after the pumping ceases. T for this final discharge_1/2Substantially the same as that used for the basic conveyance shown in fig. 11A. Note that the calculated cumulative output volume rises during pumping with a substantially linear dynamic behavior and reaches a plateau when pumping is stopped.

In the described system, the fault condition is detected by volume measurement and not by pressure measurement, and therefore, the fault can be determined within a few seconds. Fig. 11C-11F illustrate the sensor 550 of fig. 5-7 detecting various types of fault conditions. All of the descriptions with respect to fig. 11C-11F are described with reference to fig. 5-7.

Fig. 11C shows the dynamic profile of sensor 550 output versus time with respect to pumping pulses in a normal operating state. In contrast, FIG. 11D shows the expected result of a blockage occurring downstream of the dispensing assembly 120; sensor 550 quickly detects an increased (or no decrease) volume of fluid in dispensing chamber 122.

The low volume state is shown in fig. 11E-11F. In FIG. 11E, a substantially maximum sensor signal is reached, followed by too fast an attenuation; this condition may indicate an internal leak in pump 16, flow line 310, or dispense assembly 120. The kinetic profile of fig. 11F has a low peak volume signal and may represent a pump failure, an empty reservoir 20, or a blockage upstream of the dispensing chamber 122. Delayed expansion of the dispensing chamber 122 in response to pump actuation may also indicate a problem in the flow line 310. Sensor 550 may also be capable of detecting bubbles in the fluid. An alarm can be actuated in response to detection of a fault condition.

Fig. 12 shows a flow chart depicting a cycle of acoustic volume sensing and compensation (corresponding to control loop 360 of fig. 2A-3). The sensor may measure the amount of fluid dispensed from the device 10 based on the magnitude of the cyclical change in the variable volume chamber 121 induced by the pumping cycle. For example, the sensor 550 may repeatedly acquire the acoustic spectra of the resonant variable volume chamber 121 and the reference space chamber 127 (step 2611) and maintain a parameter for each pumping pulse that is updated to incorporate the volume reduction of the gas in the variable volume chamber 121. Accordingly, the updated parameters indicate the net amount of fluid that has entered the dispensing chamber 122. When there is a sufficient delay between pulses, the fluid entering the dispensing chamber 122 is approximately equal to the volume that has been dispensed by the device 10. Alternatively, the sensor 550 can repeatedly measure the increase in volume of gas in the variable volume chamber 121 to determine the amount dispensed by the device (if there is a sufficient delay between pulses). The acoustic spectrum is compared to the model spectra in the lookup table, which may correspond to any or all of the distribution chambers 122 having bubbles, no bubbles, or bubbles of varying size (step 2621). The look-up table may contain data obtained experimentally, determined using a model, or determined from working experience. The lookup table may have data representing normal conditions containing varying bubbles and/or representing multiple degrees of expansion with respect to dispensing chamber 122. If the sum of the spectrum and the update fits the normal flow model (step 2631), another acoustic spectrum is acquired and the loop is repeated at step 2611. If the sum of the spectra and/or updates does not fit the normal flow model, then it is determined that there is low or occluded flow (step 2641). By utilizing an updated sum of the undershoots of the predicted or set value, or both, the constant over-range volume of the variable volume chamber 121 may indicate a low or blocked flow. If a low or blocked flow condition is detected, an alarm will be triggered (step 2671). The alarm may include an audible signal, a vibration, or both. If no low or occluded flow condition is found, the device determines whether the spectrum fits a model corresponding to a condition having bubbles in the distribution chamber 122 (step 2661). If it is determined that air bubbles are present, a reaction is initiated that may include an alarm and/or a compensation action that may include temporarily increasing the pumping rate (step 2651) and the cycle begins again at step 2611. If it is determined that no air bubbles are present, an alarm is triggered to signal an undetermined fault condition (step 2671). Embodiments of the present invention may also utilize bubble detection using AVS technology as disclosed in co-pending U.S. patent application Ser. No.60/789,243, which is incorporated herein by reference.

The pumping assembly 16 of fig. 2A-3 urges fluid from the reservoir 20 to the dispensing assembly 120. When using a dispensing assembly according to fig. 6-7, it is not necessary to use a high precision pump, since the feedback provided by the dispensing assembly 120 to the pumping assembly 16 allows the pumping assembly 16 to be adjusted based on an accurate measurement of the volume delivered. Each pumping pulse may have a volume low enough to allow for accurate compensation based on feedback. Many different pumping assembly 16 schemes can be employed. Various possible embodiments of pumping assembly 16 are described below.

Fig. 13 and 14 diagrammatically illustrate alternative embodiments of some components in a fluid delivery device according to embodiments of the invention. Fig. 13 shows a flowline 310 with a pumping assembly 16 having a pumping element 2100 between an upstream check valve 21 and a downstream check valve 22. The pumping element 2100 may use an actuator to deform a portion of the flowline to create pressure in the flowline 310. Upstream check valve 21 inhibits retrograde flow from pumping element 2100 toward a fluid source (not shown), while downstream check valve 22 inhibits retrograde flow from volume sensing chamber 120 to pumping element 2100. As a result, the fluid is driven in the direction of the outlet assembly 17, which in one embodiment comprises a high impedance channel.

In an alternative embodiment shown in fig. 14, the function of the pumping element, i.e. the pressure generation in the flow line 310 and the upstream non-return valve 21, is performed by a combined valve pump 2200. Thus, the pumping assembly 16 in the embodiment of fig. 14 is formed of two components, i.e., a combination valve pump 2200 and downstream check valve 22, rather than the three components used in the embodiment of fig. 13. Other embodiments of pumping assembly 16 may be used. The combination of valve and pumping functions in the valve pump 2200 may be accomplished by a variety of mechanisms, some of which are described below with reference to fig. 15A-16 and 22-56.

In many of the embodiments described below, the poppet valve for the inlet valve 21, the poppet valve for the outlet valve 22, and the pumping actuation member 54 are all in direct or indirect (e.g., as in fig. 50-56) communication with the flow line 310, such that each of these elements is capable of developing or reacting to various fluid pressures. As noted above, the upstream and downstream valves (which may also be referred to herein as inlet and outlet valves) are one-way valves. In other types of one-way valves, the valve may be a volcano valve (volcano), a flapper valve, a check valve, or a duckbill valve, or other types of valves that output a bias flow toward the device. An example of a volcano valve is disclosed in U.S. application No.5,178,182 issued to Dean l.kamen on 12.1.1993, which is incorporated herein by reference.

In the embodiment shown in fig. 15A-15D, the pumping assembly comprises an inlet valve 21 and an outlet valve 22, wherein each valve comprises a fluid inlet, a fluid outlet, and a movable member (for each valve, the movable member is a portion of the membrane 2356). The pumping assembly also includes a pumping element 2100. The pumping elements are located downstream of the inlet valve 21 and upstream of the outlet valve 22. In the following description, the outlet valve starts from a closed position, i.e. fluid does not flow through the outlet valve. However, when the fluid provides sufficient pressure, the valve is opened by applying pressure on the diaphragm and poppet 9221 of the outlet valve, such that the fluid pressure opens the outlet valve and fluid is then able to flow through the outlet valve 22. The embodiment of fig. 15A-15D may be considered a combination valve pump (e.g., item 2200 in fig. 14) in the sense that a single mechanical action both blocks the pump inlet and thereby forces flow through the pump outlet.

This pumping device has the advantage of separating the moving portion and the wetting wire member to opposite sides of the flexible barrier membrane 2356. As a result, the moving portion may be located in the reusable member and the wetted portion (flowline 310) may be located in the disposable member.

In a preferred embodiment of the pumping mechanism, the fluid source is a non-pressurized reservoir. When the movable part of the inlet valve is in the open position and there is a negative pressure in the pumping chamber, there is a pressure difference drawing fluid from the reservoir towards the inlet valve. The negative pressure may be formed by the elasticity of a diaphragm in the pumping chamber. In an alternative embodiment, a spring that may be built into the diaphragm may be used to assist the recoil of the diaphragm in the pumping chamber. The non-pressurized reservoir may be collapsible such that when fluid is drawn from the reservoir, a corresponding collapse in the reservoir reduces its volume. As a result, a negative pressure or air is prevented from being formed in the reservoir.

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 towards the outlet valve. The pressure created by the pumping motion opens the outlet valve and allows fluid to flow through the fluid outlet of the outlet valve.

The movable member may be any member capable of functioning as described above. In some embodiments, the movable component is a flexible diaphragm or an elastic pumping membrane. In other embodiments, the moveable component is a spherical rigid structure or another object capable of preventing fluid from flowing out of the opening in the fluid path.

In practice, the pumping mechanism may be primed prior to use. Thus, the pumping mechanism cycles through multiple strokes, expelling air from the flow line until most or all of the air in the flow line is expelled. Many of the pumping mechanisms disclosed herein have the ability to "self prime" because of the small volume of fluid that is present outside the pumping chamber but between the valves. When the pump actuates air in the pump chamber, it substantially builds up sufficient pressure to pass through the outlet valve. The subsequent return stroke can thus create sufficient negative pressure to cause 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 build sufficient pressure to escape from the outlet valve. As a result, the pump may stop operating.

Fig. 15A-15D, 16, and 22-56 illustrate various embodiments of pumping mechanisms. Referring now to fig. 15A-15D, one embodiment of a pumping mechanism is shown to illustrate various steps in the pumping process: 1. fluid passes through inlet valve 21 (as shown in fig. 15B); 2. inlet valve closed (as shown in fig. 15C); and 3. pumping actuation member 54 urges fluid downstream and through the fluid outlet when fluid pressure opens outlet valve 22 (as shown in fig. 15D).

The pumping mechanism of fig. 15A-15D includes a movable member, which in this embodiment is a portion of flexible membrane 2356. The inlet and outlet valves include poppet valves 9221, 9222 that act as valve plugs. Each of the poppet valves 9221, 9222 and the pump actuation member 54 includes a spring 8002, 8004, 8006. The pump plate 8000 is attached to the pump actuation member 54 and the inlet poppet 9221 and serves as a termination point for its respective spring 8004, 8002.

The term "poppet valve" is used to refer to a member that applies pressure against a movable member (i.e., a diaphragm) to affect the position of the diaphragm. Some specific examples of spring-loaded poppet valves that utilize mechanically advantageous structures and principles are described below (in conjunction with fig. 50-56), although other designs may be used. However, mechanisms other than poppet valves can be used to perform the same function. In fig. 15B-15D, the inlet valve 21 includes a fluid inlet and a fluid outlet, a portion of the membrane 2356, and a poppet 9221. The outlet valve 22 includes a fluid inlet, a fluid outlet, a portion of a diaphragm, and a poppet 9222.

In the embodiment illustrated in fig. 15A-15D, the fluid path 310 is defined by a structure (item 9310 in fig. 15A) that may be rigid or have some flexibility (preferably a lower flexibility 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 chambers are located in the fluid path 310.

Referring now to fig. 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 actuation member 54 has a pumping chamber 2350 where fluid flows after exiting the inlet valve. The pumping actuation member 54 exerts a pressure on the membrane 2356, creating a positive pressure in the flow line.

As shown in fig. 15B-15D (and similarly for the valve seat 4070 for the outlet valve shown in fig. 50-56), the valve seat 9121 in the inlet valve 21 is preferably spaced from the diaphragm 2356 when the diaphragm is not actuated by the inlet valve poppet 9221.

The flow line 310 is partially defined by a membrane 2356. In this embodiment, the membrane 2356 separates some portions of the pumping mechanism from the fluid. Thus, the flow line 310 is wetted and the pumping actuator 54 and valve poppets 9221, 9222 are not wetted. However, alternative embodiments of the pumping assembly need not include a membrane 2356 in contact with the flowline 310. Instead, different movable parts may be used for the valves and/or the pumps. In further embodiments, only portions of the flowline 310 are separated from the pumping mechanism, thus locally wetting the pumping assembly.

The inlet poppet 9221 includes an end 8018 that represents the surface area of the inlet poppet that contacts the diaphragm portion of the flow line 310. Pumping actuation member 54 includes an end 8012 that contacts a diaphragm portion of flow line 310. Likewise, the outlet poppet 22 includes an end 8022 that contacts the diaphragm portion of the flow line 310. The ends 8018, 8022 of the valve poppet exert pressure on their respective areas of the membrane 2356, blocking or opening respective portions of the flow path 310. The end 8012 of the pressure actuated component also exerts a pressure on a corresponding area of the diaphragm, thereby inducing a flow through the flow line 310.

Pumping actuation member 54 is surrounded by plunger biasing spring 8004. The plunger biasing spring 8004 has termination points at the pump plate 8000 and at 8014, and a support structure that also holds the pumping actuation components.

The inlet poppet 21 is surrounded by an inlet poppet spring 8002, but in an alternative embodiment the inlet poppet itself is resilient and therefore provides the function of a spring. The inlet poppet spring 8002 has a terminus at the pump plate 8000 and near the end 8018 of the inlet poppet 9221.

The outlet poppet 9222 is surrounded by a passive outlet poppet spring 8006. The outlet poppet spring 8006 has a lip 8020 located at the terminus of the outlet poppet plate 8024 and near the end of the outlet poppet 9222.

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

In a preferred embodiment, the fluid pumping device further comprises 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 varied by means of a heater, or more conveniently by applying an electric current. Fig. 15B-15D illustrate an embodiment having one shape-memory actuator 278, however, in other embodiments (described below) there may be more than one shape-memory actuator 278. In one embodiment, the shape memory actuator is a shape memory wire constructed using a nickel/titanium alloy, such as NITINOL^TMOr

However, in other embodiments, any device capable of generating a force, such as a solenoid, may be used. In certain embodiments, 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 may be made of any alloy that can contract with heat (and expansion may be assisted by a mechanism that exerts a force on the alloy to stretch the alloy to an initial length, i.e., a spring, although such a mechanism is not required) to actuate the pumping mechanism as in the embodiments described herein. In some embodiments, the shape memory actuator278 may be from 0.001 inches in diameter to any diameter desired and may be any length desired. Generally, the larger the diameter, the higher the available retraction force. However, the current required for heating the wire will generally increase with diameter. Thus, the diameter, length, and composition of the shape memory alloy 278 may affect the current required to actuate the pumping mechanism. Regardless of the length of the shape memory actuator 278, the actuation force is substantially constant. An increase in actuation force can be created by increasing the diameter of the shape memory actuator 278.

The shape memory actuator 278 is connected to the pump plate 8000 through a connector 8008. Connector 8008 is described in more detail below. The shape memory actuator 278 is connected to the fluid pumping device by a destination connector 8010. Depending on the device or system in which the pumping mechanism is used, the end connection location will vary. The end connector 8010 is described in more detail below.

Fig. 15B-15D illustrate the flowline 310 and pumping mechanism that has been primed as discussed above. Referring now to fig. 15B, the inlet valve 21 is open and the pumping actuation member 54 is not pressing against the membrane 2356. The outlet valve 22 is in the closed position. The shape memory actuator 278 is in the expanded position. In this configuration, fluid is drawn from a reservoir (not shown) to the inlet valve 21 fluid inlet. (although shown as a bump in the diaphragm in the region of the inlet valve, pumping fluid during this step may cause the diaphragm to sag, or the diaphragm does not deform). When the inlet poppet is in the open position, fluid can flow from the fluid inlet to the fluid outlet and into the pumping chamber 2350. At this point, the outlet poppet end 8022 is pressed tightly against the membrane 2356 and seals the outlet valve 22.

Referring now to FIG. 15C, current has been applied to the shape memory actuator 278, and the shape memory actuator has contracted from the starting length toward the desired final length. The contraction of the shape memory actuator 278 pulls the pump plate 8000 towards the flow line 310. The inlet poppet 9221 and the pumping actuation member 54 are both connected to the pumping plate 8000. The movement of the plate 8000 pulls the inlet poppet 9221 and pumping actuation member 54 toward the membrane 2356. As shown in fig. 15C, the inlet poppet end 8018 is pressed firmly against the diaphragm 2356, sealing the diaphragm to the valve seat 9121 and closing the inlet valve 21. (movement of the inlet poppet can actuate a small amount of fluid in the inlet valve chamber, i.e., item 9321 in FIG. 15A, to flow through the fluid inlet or fluid outlet of the inlet valve 21.)

Simultaneously, the pumping actuation member 54 begins its path toward the pumping chamber 2350. During this process, as the inlet poppet spring 8002 is compressed (at which point the inlet poppet end 8018 is firmly pressed against the flow line 310), the pump plate 8000 and pumping actuation member 54 continue to travel toward the flow line 310. The inlet poppet spring 8002 allows the pump plate 8000 to continue to move with the pump actuation member 54 toward the flow line 310, even when the inlet poppet 9221 is no longer able to travel.

Referring now to fig. 15D, the pumping actuation member 54 presses against the region of the membrane 2356 above the pumping chamber 2350 and fluid is pumped, thereby increasing the pressure of the fluid in the pumping chamber 2350. The outlet poppet end 8022 remains firmly pressed (aided by the outlet poppet spring 8006) against the diaphragm 2356, thereby sealing the fluid inlet and fluid outlet of the outlet valve 22 until the pressure of the fluid flowing out of the pumping chamber 2350 forces the outlet valve 22 to open. When sufficient pressure is reached, the fluid exits through the fluid outlet of the outlet valve 22, thus overcoming the pressure exerted by the outlet valve 22 on the diaphragm 2356. When flow stops, the passive spring 8006 forces the outlet valve 22 to close.

During the power stroke, the pump actuation member spring 8004 is loaded. Eventually, the pump actuation member spring 8004 will pull the pump actuation member 54 away from the membrane 2356. As a result, during the relaxation stroke, the spring 8004 returns the pump actuation member 54 and the pumping plate 8000 to the relaxed position of fig. 15C; charging inlet poppet spring 8002 may also provide energy for the return stroke. As the pumping plate 8000 approaches its relaxed position, it engages the end cap of the inlet poppet 9221 to lift the inlet poppet and pull it off of the seat, thereby opening the inlet valve 21. The pump actuation member spring 8004 is also unloaded during the return stroke.

When a threshold distance is reached where the inlet poppet spring 8002 is at the same level as the pump plate 8000, the pump plate 8000 will be unloaded with the pump actuation member spring 8004. The resilient membrane 2356 in the pumping chamber 2350 will return to its starting position. This creates a negative pressure and when the inlet valve is opened, fluid will flow through the fluid inlet of the inlet valve to the fluid outlet and toward the pumping chamber 2350. Thus, the pumping mechanism will now be in the state shown in fig. 15B.

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

What is referred to herein as a diaphragm includes the diaphragm 2356, which may be made of any resilient material capable of producing the necessary characteristics to function as described herein. Additionally, the septum material may comprise a biocompatible material so as not to impede operation of the pump or reduce the therapeutic value of the fluid. A variety of biocompatible elastomeric materials may be suitable, including nitrile and silicone. However, different therapeutic fluid compositions may require different elastomeric materials to be selected.

The pumping mechanism described above can also be described in terms of stroke length as well as the various embodiments described herein. One way to determine the stroke length is to use the total change in length of the shape memory actuator during one cycle of contraction and expansion of the shape memory actuator. This difference will determine the total distance the pump rod travels and thus the total amount of fluid flowing out of the inlet chamber 2354 and to the pumping chamber 2350, the outlet chamber 2352, and finally out of the outlet chamber 2352. Another way to determine the stroke length is the travel distance of the pump plate 8000. For a partial stroke, the pump plate 8000 will not reach its maximum travel distance. In one embodiment, a very small stroke or micro-stroke is continuously activated to pump a microliter volume of fluid from the reservoir to the outlet in a continuous or regular manner. For example, the micro-stroke may displace less than 20%, 10%, or 1% of the volume of the pumping chamber 2350.

Figure 16 illustrates a variation of the embodiment of the pumping mechanism illustrated in figure 15B. In fig. 16, two different shape memory actuators are used — the longer one and the shorter one. Fig. 16 illustrates an embodiment of the pumping mechanism shown in fig. 15B in which the shape memory wire 278 is tensioned around the pulley 286 and split into longer and shorter strands. The common junction point serving as the negative terminal may be located at the position where the longer and shorter strands split. A circuit implemented with either or both of the two alternative paths allows for adjustment of the pumping force and/or stroke length. In an alternative embodiment, a sheet of material, such as Kevlar material, extends around the pulley from the common junction to the force plate 8000, while two separate shape memory wires extend from the common junction to their respective supports. By using two wires having different lengths, these embodiments provide a pumping mode and an exhaust mode as described below.

With respect to varying the stroke using shape memory actuator variables, for a given length of shape memory actuator, the stroke depends on the number of variables: 1. total time of energization/heating; 2. a total voltage; and 3. diameter of the shape memory actuator. Some of the variations are shown in fig. 17-19. However, in some embodiments, the stroke can be varied while maintaining the length, energization time and voltage. These embodiments include shape memory actuators (see fig. 19) and switches (see fig. 17) on a shape memory wire. As discussed above, the desired stroke length can also be obtained by modifying any one or more of the variables.

Additionally, the timing of heating or energizing the shape memory actuation can be varied to control the stroke. The shape memory actuator may be considered to be a pulse at a time when it is heated. Factors such as pulse frequency, pulse duration, and stroke length may affect the amount of fluid delivered over a period of time.

Fig. 17-19 additionally depict an embodiment of a pumping assembly having a fluid pumping mode and an exhaust mode. When actuated, the exhaust mode applies an enhanced application of force and/or a compression stroke that increases displacement through the force application member. The exhaust mode may be activated based on the likelihood of air being present in the pumping assembly or knowledge of the relevant conditions. For example, the venting mode may be activated when the line is attached to the reservoir, when an air bubble is detected by a sensor or sensing device, or when insufficient flow is detected by a sensor or sensing device. Alternatively, the two modes may be used to select between displacing smaller and larger volumes of fluid for a given pumping pulse.

Referring now to FIG. 17, a pumping assembly that is actuated using a shape memory actuator 278 and has multiple modes of operation is diagrammatically illustrated. 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 negative electrical lead 2960 and the positive electrical lead 2961, causing the alloy shape memory actuator 278 to resistively heat and thereby cause a phase change and a power stroke. In one embodiment, during priming of the pumping mechanism or when a bubble 2950 is suspected of being present in the pumping chamber 2350, the venting mode is actuated and current flows along a path extending the length between the negative electrical lead 2960 and the positive electrical lead 2965; the result is a compression stroke with a higher force and displacement of the force application member 2320 should be sufficient to displace air 2950 from the pumping chamber 2350 to the pump outlet 2370. In alternative embodiments, the positive and negative leads may be reversed.

Referring now to FIG. 18, an alternative pumping assembly having a plurality of shape memory actuators 278 of the same length is diagrammatically shown. Additional actuators may be used, for example, to increase the actuation pressure on the pumping chamber 2350 to eliminate blockages or air bubbles in the flow line, pumping chamber, or other areas of the pumping mechanism. The additional actuator may also provide redundancy to any pumping device. A single shape memory actuator may be capable of generating sufficient force to eliminate air bubbles from the pumping chamber. Additionally, in the embodiment shown in fig. 18, an additional return spring may be necessary depending on the length of the second shape memory actuator.

The pumping mechanism (item 16 in fig. 13-14) is typically filled with air when the reservoir is first attached to a flow line having a pumping assembly. Air can also enter the pumping mechanism during normal operation for various reasons. Because air is more easily compressed than fluid, if there is a large amount of air in the flow line, applying a compression stroke having a length sufficient to displace the fluid may not be sufficient to generate sufficient pressure to overcome the cracking pressure of the pumping mechanism check valve. Accordingly, the pumping mechanism may cease to operate. However, it may be desirable to force air through the line during priming or when there is a small amount of air harmlessly in the pumping assembly. Thus, the embodiment shown in fig. 18 can be used to generate additional force in this situation.

Figure 19 diagrammatically shows an alternative pumping assembly 16 having a plurality of shape memory actuators. The first, shorter shape memory actuator 2975 has a first electrical lead 2976 and a second electrical lead 2977. The shorter actuator 2975 can generate a compression stroke sufficient to displace fluid in the pumping chamber 2350; shorter shape memory alloy actuators 2975 are used during normal fluid pumping mode operation. When venting mode is indicated or a larger volume of fluid being pumped is desired, a second, longer shape memory alloy actuator 2970 may be used by sending an electrical current along the length of the actuator disposed between the first electrical lead 2973 and the second electrical lead 2972. The longer shape memory alloy actuator 2970 may also be used as a backup actuator for fluid pumping mode operation by forming a shorter electrical circuit that includes an electrical path between the first electrical lead 2972 and the second electrical lead 2971. Shorter shape memory actuators 2975 can also be used to vary the stroke volume to provide better control at reduced fluid volume rates. The multi-modal actuator of fig. 17-19 is not limited to use with the pump components shown, but can be used with any of the various embodiments of pumping mechanisms described herein, including those using fluid pumping devices as described below as well as those employing valve pumps as described below. Thus, the desired stroke length can be formed by energizing/heating a length shape memory actuator that provides the desired stroke length.

Referring now to fig. 20A and 20B, each illustrates one embodiment for attaching a shape memory actuator. These various embodiments can be used in any of the mechanisms or devices described herein in which the shape memory actuator 278 is employed. Referring to fig. 20A and 20B, the shape memory actuator 278 is fed into a grommet 280. Grommet 280 is then attached to component 284. Although only two embodiments of this mode of attachment are shown, various other modes are used in other embodiments. Other modes of attaching the cable loop to a portion or any fixed location can be used.

21A and 21B, two exemplary embodiments of shape memory actuators 278 attached for use with pumping mechanism 16 are shown. In each of these embodiments, the shape memory actuator 278 is designed to rotate about the pulley 286. Referring to fig. 21A, shape memory actuator 278 is attached by grommet 280 to piece 288, preferably made of KEVLAR material. One end of the shape memory actuator 278 is shown attached to the component 284 by a set screw arrangement 289. Referring now to fig. 21B, one end of the shape memory actuator is shown attached to component 284 by grommet 280.

Various embodiments of a pumping mechanism are shown herein. The pumping mechanism may include an inlet valve, a pumping actuation member, and an outlet valve. As discussed above, different types of one-way valves may be used in alternative embodiments. While the schematics shown in fig. 15A-15D illustrate one embodiment, the following figures illustrate alternative embodiments.

Referring now to fig. 22 and 23, a side view and cross-section of one portion of the pumping mechanism is shown. In this embodiment, the pumping actuation member is a pumping elongate finger 32. When a force is applied to the fingers 32, the fingers 32 depress the movable member and reduce the internal volume of the flow line.

The portion of the pumping mechanism in fig. 22 and 23 shows only the pumping chamber. When combined with a one-way valve ( items 21 and 22 in fig. 13), a deforming force is applied to the movable member 23, forcing fluid towards the outlet assembly (not shown). As shown in fig. 22 and 23, the fingers 32 are pointed to focus the force, but in other embodiments the fingers 32 may be flat or any other suitable shape. The spring 31 serves to bias the fingers 32 relative to the resilient member 23 towards a retracted position, so that the fingers 32 return to a retracted, non-depressed position in the absence of an applied force. As shown in fig. 23, a motor can be used to apply force to the fingers 23. However, in other embodiments, a shape memory actuator is used. Various types of motors are suitable, including electric motors and piezoelectric motors.

Referring to fig. 22 and 23, by preventing the displaceable member 23 from unseating in response to the application of force by the fingers 32, the backstop 33 limits the potential travel of the fingers 32, supports the displaceable member 23, and ensures that the volume of the flow line or pumping chamber is reduced. As shown in fig. 22, the backstop 33 may advantageously have a shape complementary to the elastic member 23. In various embodiments, the pumping assembly 16 may include a lever or crank that is driven by the motor on one end and compresses the resilient member 23 at the other end.

Referring now to fig. 24, another embodiment of a pumping actuation member is shown with respect to one portion of a pumping assembly. A motor or shape memory actuator (not shown) applies a rotational force to a set of coupled projections 42. These projections 42 act as pumping actuation members and in turn apply a force to the movable member 23. Accordingly, intermittent pulses of force are applied to the movable member 23. The backstop 33, as shown, is able to travel within the housing 44 and is biased upwardly by the spring 46 towards the resilient member 23.

Referring now to FIG. 25, an embodiment of a force application assembly having a pumping actuation member (here a plunger) 54 in a plunger barrel 52 is shown. The motor causes the plunger 54 to be alternately withdrawn and inserted into the plunger barrel. When the plunger 54 is retracted, the negative pressure draws fluid from a reservoir (not shown) into the channel 51 and the lumen 56. When the plunger 54 is inserted, the increased pressure in conjunction with the one-way valve (not shown) drives the fluid toward the dispensing assembly (not shown). Lumen 56 is connected to passage 51 via connecting passage 58 and the volume of plunger barrel lumen 56 decreases with the insertion action of plunger 54, thereby actuating fluid through flow line 310.

Fig. 26 and 27 show another embodiment in which the pumping actuation member is a plunger 54. The force application assembly and linear actuator including shape memory actuation 278 drive the plunger 54. In fig. 26, the shape memory wire 278 is in a low temperature, expanded state and attached to the first support 241 and the plunger attachment end cap 244. The end cap 244 is in turn attached to a biasing spring 243, which is in turn attached to the second support 242. When the wire 278 is in the expanded state, the biasing 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 the concurrent heating. When retracted, a force is applied to end cap 244, causing an insertion movement of plunger 54 and a corresponding pumping action. In the contracted state, the biasing spring 243 is in a high potential energy state. When the application of the electric field is stopped, the Nitinol wire 278 cools and expands again to allow the biasing spring 243 to return the plunger 54 to its retracted state. As shown in fig. 21A-21B, the shape memory actuator 278 may be wrapped around one or more pulleys.

Fig. 28-30 illustrate various embodiments in which pumping is accomplished by using a shape memory actuator 278 to compress the pumping actuation member 54 that forms the movable member of the pumping chamber. The pumping chamber is delimited by one- way valves 21, 22. Fig. 28 shows an embodiment of a pumping mechanism comprising a plunger 54 in which the pumping actuation component is a plunger barrel 52. The mechanism also includes a lever 273, a fulcrum 274, and a shape memory actuator 278. The shape memory actuator 278 is held in a housing 298 and is attached at one end to a conductive support 279 and at the other end to the positive terminal 275 of the lever 273. The lever 273 is in turn attached at its center to the fulcrum 274 and at a second end to the plunger 54. Application of an electrical current causes current to flow through the terminals 275, the shape memory actuator 278, and the conductive support 279, thereby causing the shape memory actuator 278 to contract, causing the lever 273 to pivot about the fulcrum 274 and effective retraction of the plunger 54. De-energizing allows the shape memory actuator 278 to cool, allowing it to expand. The return spring 276 acts via a lever 273 to return the plunger 54 to an inserted position in the plunger barrel 52. The return spring 276 is retained in a housing 277. O-ring 281 prevents fluid leakage from the plunger 54-plunger barrel 52 assembly. Insertion and retraction of the plunger 54 causes fluid to flow through the flow line in a direction determined by the orientation of the two check valves (first check valve 21 and second check valve 22). Any suitable backflow prevention device may be used including one-way valves, check valves, duckbill valves, flapper valves and volcano valves.

Fig. 29 illustrates another embodiment of a pumping mechanism having a plunger 54, a plunger barrel 52, and a force application assembly including a shape memory actuator 278. However, unlike the embodiment shown in fig. 28, this embodiment does not include a lever. The shape memory actuator 278 is held in a housing 298 and is attached at one end to a conductive support 279 and at the other end to the plunger end cap 244 through contacts 275. A plunger end cap 244 is attached to the plunger 54. Upon application of sufficient current through the contacts 275, the shape memory actuator 278 contracts. This retraction causes a pull on plunger end cap 244 to effect insertion of plunger 54 into plunger barrel 52. De-energizing allows the shape memory actuator 278 to cool, thereby allowing it to expand. When the wire expands, the return spring 276 acts to return the plunger 54 to a retracted position in the plunger barrel 52. The return spring 276 is retained in a housing 277. O-ring 281 prevents fluid leakage from the plunger 54-plunger barrel 52 assembly. Insertion and retraction of the plunger 54 causes fluid to flow through the flow line in a direction determined by the orientation of the first check valve 21 and the second check valve 22.

Referring now to fig. 30, an embodiment of a pumping device using a plunger 54 and a plunger barrel 52 is shown. In this embodiment, a shape memory actuator 278 in the form of a wire located within a shaft in the plunger 54 is used to exert a force on the plunger. The shape memory actuator 278 extends from the plunger end cap 272, through the shaft in the plunger 54, and through the passage 58 to the support base 299. O- rings 281 and 282 seal plunger 54, plunger barrel 52 and passage 58. Application of current to the first lead 258 and the second lead 257 causes the shape-memory actuator 278 to heat, which causes the shape-memory actuator 278 to contract. The contraction of the shape memory actuator 278 causes a downward force to be exerted on the plunger end cap 272 sufficient to overcome the upward biasing force of the return spring 276, thereby driving the plunger 54 into the interior cavity 290 of the plunger barrel 52. Expansion of the shape memory actuator 278 allows the return spring 276 to return the plunger 54 to the retracted position. Insertion and retraction of the plunger 54 causes fluid to flow through the flow line in a direction determined by the orientation of the first check valve 21 and the second check valve 22.

Fig. 31 shows an alternative embodiment of the pumping mechanism. The pumping actuation means is an assembly 101 that combines the functions of a reservoir and a pumping mechanism. Under the command of the controller 501, the motor 25 drives the plunger 102 to build pressure in the reservoir 104, thereby forcing fluid through the first one-way valve 106. The fluid then enters the resilient dispensing chamber 122 of the volume sensing assembly 120 with the sensor 550 and flows to 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 controller 501 ensures that the desired fluid flow to the patient. The first one-way valve 106 serves to prevent reverse fluid flow due to the elastic force of the dispensing chamber 122 of the volume sensing assembly 120 when the chamber is filled and expanded. Second one-way valve 107 is used to prevent reverse flow of fluid from outlet assembly 17 or patient 12 into dispensing chamber 122. In this embodiment, the sensor 550 is capable of immediately detecting the volume in the dispensing chamber 122.

Fig. 32-34 diagrammatically show cross-sectional views of a combination valve pump 2200. FIG. 32 shows a valve pump 2200 with the collection chamber 2345 and pumping chamber 2350 in a resting position prior to actuation; FIG. 33 shows the valve pump 2200 in an actuated state during a compression stroke; and figure 34 shows the pump in an actuated state at the end of the compression stroke. Pump inlet 2310 is in fluid communication with an upstream fluid source, such as a reservoir, and is connected to a first end of a channel 2360. The channel 2360 is connected at a second end to a collection chamber 2345 that is in fluid communication with a membrane aperture 2390 disposed in the resilient pumping membrane 2340. The collection chamber 2345 is bounded on a first side by a resilient pumping membrane 2340 and on a second side by a resilient pumping diaphragm 2330. Pumping diaphragm 2330 may be made of latex or silicone, among various materials. The downstream side of the diaphragm aperture 2390 opens into the pumping chamber 2350. During priming of the pump and between actuation cycles, fluid travels from a fluid source, e.g., a reservoir, through the pump inlet 2310, the channel 2360, the collection chamber 2345, and the membrane aperture 2390, and then to the pumping chamber 2350. The one-way valve 22 prevents fluid from exiting the pumping chamber 2350 via the pump outlet 2370 until and unless sufficient fluid pressure is applied to the one-way valve 22 such that the one-way valve 22 opens. In fig. 32, the pumping actuation member 2320 is shown in a resting position and the resilient pumping diaphragm 2330 is shown in a relaxed configuration with minimal surface area, thereby maximizing the volume of the collection chamber 2345. Although in this embodiment, the pumping actuation member is shown as a ball, in other embodiments, the pumping actuation member may be any actuation member that is capable of actuating and applies sufficient force to resilient pumping diaphragm 2330 to actuate the pumping mechanism.

As can be seen from fig. 33, when the pumping actuation member 2320 is actuated during a compression stroke, the pumping actuation member 2320 begins to travel towards the membrane aperture 2390 of the resilient pumping membrane 2340 and expands the resilient pumping membrane 2330, causing a reverse flow of fluid that has collected in the collection chamber 2345. Later on in the force application stroke, as shown in fig. 34, pumping actuation member 2320 will send resilient pumping diaphragm 2330 to diaphragm orifice 2390 in a sealed manner. To assist in sealing, the pumping actuation member 2320 may have a shape that is complementary to the shape of the diaphragm aperture 2390. For example, pumping actuation member 2320 may be spherical or conical and diaphragm aperture 2390 may be a cylindrical through hole. During this phase of the force application stroke, reverse flow from the pumping chamber 2350 will be inhibited. Continued travel of the pumping actuation member 2320 will deform the resilient pumping membrane 2340 and increase the pressure in the pumping chamber 2350, while continuing to seal the membrane aperture 2390 to prevent backflow from the pumping chamber 2350. When the pressure in the pumping chamber 2350 applies sufficient fluid pressure to the one-way valve 22, fluid will flow from the pumping chamber 2350 through the pump outlet 2370. During the return stroke, the pumping actuation member 2320, resilient pumping diaphragm 2330 and resilient pumping membrane 2340 return to the relaxed position shown in fig. 32. During the return stroke, the internal pressure of the pumping chamber 2350 and the collection chamber 2345 will drop, which will cause the valve pump 2200 to be refilled by inducing fluid to flow from the fluid source through the pump inlet 2310 and the passage 2360.

Referring now to fig. 35, a diagrammatic cross-sectional view of one embodiment of an elastic pumping membrane 2340 is illustrated. The diaphragm body 2515 may be constructed of an elastomeric material such as silicone. A diaphragm spring 2510 may also be included to impart elasticity to the flexible or already elastic body 2515. The diaphragm spring 2510 may be embedded in the resilient pumping membrane 2340 or disposed adjacent to the resilient pumping membrane 2340. An example of one embodiment of a diaphragm spring 2510 is shown in fig. 36. A combination of a diaphragm body 2515 comprising a compliant material and a diaphragm spring 2510 comprising an elastomeric material may be used; the result is that the pumping membrane 2340 will exhibit a high degree of sealing and also be highly resilient when it contacts the resilient pumping diaphragm 2330 which is deformed by the pumping actuation member (not shown, see fig. 32-34). The valve seat 2517 may be positioned around the diaphragm aperture 2390. Valve seat 2517 may serve as a receptacle for the deformed portion of resilient pumping diaphragm 2330. Force application member 2320 may deform pumping diaphragm 2330, causing diaphragm 2330 to deform and contact valve seat 2517 in a sealing manner. If sufficient force is applied, the valve seat may elastically deform to ensure a complete seal to prevent backflow of fluid. The ratio of the cross-sectional height to the cross-sectional width of the valve seat 2517 can generally be selected differently to match the flow environment.

Referring now to FIG. 36, an example of a diaphragm spring 2510 for use in the pumping membrane 2340 of FIG. 35 is shown. Outer annulus 2520 and inner annulus 2540 are connected by at least three resilient arms 2530. The center of inner annulus 2540 has a spring hole 2550 that can be aligned with a membrane hole 2390 of pumping membrane 2340 as shown in fig. 35.

Referring now to FIG. 37, a schematic diagram is shown illustrating a cross-sectional view of the valve pump 2200 previously illustrated in FIGS. 32-34, in combination with a force application assembly including a pump actuation member 2320, an actuator and a lever 273. When energized by an actuator, such as shape memory actuator 278, the lever 273 pivots about the fulcrum 274 to initiate a compression stroke. The hammer 2630 protrudes from the lever 273. During the compression stroke, the hammer 2630 contacts the rounded pumping actuation member 2320, causing the pumping actuation member to travel in the void of the support structure 2660 and urge the pumping actuation member 2320 against the resilient pumping diaphragm 2330 until the pumping actuation member 2320 is sealingly retained to the diaphragm aperture 2390 located in the resilient pumping diaphragm 2340. As the lever 273 continues to travel, the pumping actuation member 2320 causes the pumping membrane 2340 to deform. When sufficient fluid pressure is applied to the check valve 22, the check valve 22 opens. This allows fluid to flow from the pumping chamber 2350 through the pump outlet 2370. When the shape memory actuator 278 cools, the elasticity of the pumping membrane 2340 and the elasticity of the pumping diaphragm 2330 will cause the lever 273 to return to the starting position determined by the lever stop 2650 and the lever stop 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 force-applying member 2320 may alternatively be a piston, a protrusion of the lever 273, or other suitable form.

Fig. 38 schematically illustrates a cross-sectional view of an embodiment of a valve pump using resilient cylindrical flexures 2670. In one embodiment, the resilient cylindrical flexure is made of rubber, but in other embodiments it can be made of any resilient material. Cylindrical flexure 2670 has a central passageway 2675 and a plurality of resilient radial tabs 2672 sealingly disposed against housing 2673. Fluid entering pump inlet 2310 passes through channel 2360 and is collected in the area upstream of check valve 22: a collection chamber 2345, a central passageway 2675 of a cylindrical flexure 2670, and a pumping chamber 2350. The pumping chamber is coupled in fluid communication with the collection chamber 2345 through a central passageway 2675. During the compression stroke of the pumping mechanism, the pumping actuation member 2320 applies a force to the resilient pumping diaphragm 2330, deforming it until the resilient pumping diaphragm 2330 is sealingly held to the valve seat 2680 of the cylindrical flexure 2670; thereby preventing reverse flow from the collection chamber 2345 to the pump inlet 2310. Continued travel of the pumping actuation member 2320 causes deformation of the cylindrical flexures 2670; the pressure in the pumping chamber 2350 increases until sufficient to open the one-way valve 22. Fluid can then flow through the pump outlet 2370.

The pumping actuation member 2320 is shown as spherical in fig. 38. However, in other embodiments, the pumping actuation member 2320 may be any shape capable of functioning as described above.

Referring now to fig. 39, an alternative embodiment of a cylindrical flexure 2670 (shown in fig. 38) employing a resilient portion 2680 and a rigid cylindrical support 2690 is shown. Similar to the cylindrical flexure 2680 of fig. 38, the resilient portion of the cylindrical flexure 2670 includes a valve seat 2680 that seals the central passage 2675 when force is applied by the pumping actuation component 2320. Accordingly, the resilient portion 2680 of the cylindrical flexure 2670 deforms to transmit pressure to the pumping chamber 2350.

40-44 diagrammatically illustrate cross-sectional views of an alternative embodiment of the valve pump in various actuation states. The valve pump 2200 of fig. 40-44 has a resilient diaphragm spring 6100 and a resilient sealing diaphragm 6120 that together function similarly to the resilient pumping diaphragm 2340 of the valve pump 2200 of fig. 32-34. Fig. 40 shows the valve pump 2200 in a rest state. In the rest state, fluid may flow from the inlet 2360 to the upper portion 2346 of the collection chamber 2345, through the aperture 6110 in the diaphragm spring 6100 and into the lower portion 2347 of the collection chamber 2345. The fluid may then continue through the one or more openings 6130 in the sealing membrane 6120 and into the pumping chamber 2350. At low pressure, further fluid flow is prevented by the one-way valve 22. Both spring diaphragm 6100 and sealing diaphragm 6120 can be constructed of resilient, biocompatible materials. The spring diaphragm 6100 may have a higher elasticity than the seal diaphragm 6120. For example, spring diaphragm 6100 may be a flexible bio-inert plastic disc and sealing diaphragm 6120 may be silicone or fluorosilicone elastomer.

Fig. 41 and 42 show the valve pump 2200 in two intermediate, partially actuated states. The pumping actuation member 2320 deforms the pumping diaphragm 2330 and forces it through the collection chamber 2345 and against the spring diaphragm 6100, which in turn deforms and is forced against the sealing diaphragm 6120. At this point in the compression stroke, blow back through the aperture 6110 of the spring diaphragm 6100, or through the opening 6130 in the sealing diaphragm 6120, or both, is inhibited. The offset of the sealing diaphragm opening 6130 relative to the spring aperture 6100 allows a seal to be formed between the spring diaphragm 6100 and the sealing diaphragm 6120. In some embodiments, this seal may be supplemented by a backup seal between fill chamber elastomeric pumping diaphragm 2330 and spring diaphragm 6100 (e.g., the embodiment of fig. 43-44 lacks such a backup seal). A circumferential ridge (not shown) around the spring membrane holes 6110 may act as a valve seat to enhance the seal.

Referring now to fig. 42, continued travel of pumping actuation member 2320 causes further deformation of pumping diaphragm 2330, spring diaphragm 6100, and sealing diaphragm 6120. As a result, fluid in the pumping chamber 2350 is compressed until fluid pressure forces the one-way valve 22 to open; further compression causes fluid to flow out through outlet 2370.

An alternative embodiment of the valve pump 2200 of fig. 40-42 is schematically illustrated in fig. 43. In this embodiment, pumping actuation member 2320 passes through resilient pumping diaphragm 2330. The pumping diaphragm 2330 is sealingly attached to the perimeter of the pumping actuation member 2320 at a midpoint along the length of the pumping actuation member 2320. When actuated, the diaphragm spring aperture 6110 is only sealed by the sealing diaphragm 6120 to prevent backflow; resilient pumping diaphragm 2330 will not contact aperture 6110. An alternative embodiment of the device shown in fig. 40 is shown in fig. 44.

Referring now to FIG. 45, a cross-sectional view of an alternative embodiment of a combination valve pump 2200 is shown. Shape-memory actuator 278 actuates a compression stroke to cause resilient pump blade 2710 to lift (lever) about fulcrum 274, which causes resilient pumping diaphragm 2330 to deform. The resilient pump blade 2710 and resilient pumping diaphragm 2330 apply pressure to fluid in a stepped pumping chamber 2720 having a shallow region 2730 and a deeper region 2740. Early in the compression stroke, pump blade 2710 causes resilient pumping diaphragm 2330 to block passage 2360 connecting pump inlet 2310 to stepped pumping chamber 2720. As the compression stroke continues, a force is applied to the fluid in the stepped pumping chamber 2720 until the fluid pressure in the stepped pumping chamber 2720 is high enough to open the one-way valve 22. The fluid then exits the pump outlet 2370. The pump blade 2710 may be constructed in whole or in part from a resilient material such as rubber. In some embodiments, the elastic material comprises a non-elastic spline (spline). Alternatively, in some embodiments, the elasticity is applied by the elastic region 2750, and thus, the elastic region 2750 is the only elastic portion of the pump blade 2710 in these embodiments. In these embodiments, the resilient region 2750 contacts the bottom of the stepped pumping chamber 2720. The elasticity of the pumping blade 2710 allows the compression stroke to continue after the pumping blade 2710 contacts the base 2780 of the shallow region 2730. A return spring (not shown) returns the pump blade 2710 to the starting position during the return stroke.

Referring now to FIG. 46, a cross-sectional view of an alternative embodiment of a pumping mechanism is shown. This embodiment includes a resilient pump blade 2710. The resilient pump blade 2710 includes a resilient region 2830 that provides resilience to the pump blade 2710. The resilient region 2830 bonds the pumping actuation member 2820 to the pump blade 2810. When used with a valve pump (not shown), the resilient pump blade 2710 of fig. 42 will block the inlet passage (not shown, shown as 2360 in fig. 45) and then bend at the flexible region 2830 to allow the force application member 2820 to apply further pressure to the fluid in the stepped pumping chamber (not shown, shown as 2720 in fig. 45). The force application member 2820 may be constructed entirely of a resilient material such as rubber. However, in an alternative embodiment, only the area contacting the bottom of the pumping chamber (not shown) is made of an elastic material. The resilient pump blade 2710 will return to its relaxed configuration during the return stroke.

Referring now to FIG. 47, a cross-sectional view of another embodiment of a pumping mechanism is shown. The pumping mechanism is shown with the lever in an intermediate stage of actuation, in which the inlet valve 2941 is closed. The pumping mechanism includes a flow line 2930, a movable member 2330, which in this embodiment is a diaphragm, an inlet valve 2941 poppet 2940, a pumping actuation member 2942, a pumping chamber 2350, and an outlet valve 22. The inlet valve 2941 and the pumping actuation member 2942 are each actuated by a shape memory actuator 278 surrounded by a return spring 276 and connected to the lever 273. The lever 273 actuates the inlet valve 2941 and the pumping actuation member 2942. The lever 273 includes an elongated spring member 2910 attached to the lever 273 that is hinged to the fulcrum 274 and terminates in a valve actuator ram 2946. The spring member 2910 may be curved. The spring member 2910 biases the position of the valve actuating hammer 2946 away from the lever 273 and toward the inlet valve 2941. The lever 273 has a pump actuating hammer body 2948 that is not attached to the spring member 2910 and is positioned adjacent the pump actuating member 2942.

The current causes the shape memory actuator 278 to contract and the lever 273 to pivot about the fulcrum 274. The pivoting places the valve actuator ram 2946 in a position that forces the inlet valve 2941 closed. As the shape memory actuator 278 continues to contract, the lever 273 continues to pivot and the pump actuating ram 2948 presses the pump actuating member 2942 toward the pumping chamber 2350, even when the elongated spring member 2910 is further compressed. When sufficient pressure is achieved, the fluid pressure opens the outlet valve 22 and fluid flows out through the valve.

During the relaxation stroke, the return spring 276 unloads and returns the lever 273 to the starting position, releasing the pumping actuation member 2942. The inlet valve 2941 is opened. The elasticity of the pumping chamber 2350 causes the pumping chamber 2350 to refill.

Reference is now made to fig. 48 and 49, which schematically show cross-sections of embodiments in which the pumping mechanism employs a bell crank 7200 and incorporates a valve pump 2200 with a bias flow valve. Bell crank 7200 converts the force generated by linear shape memory actuator 278 to a lateral pumping force. Fig. 48 shows the mechanism in a rest or refill mode, and fig. 49 shows the mechanism in an actuated state. Contraction of actuator 278 causes bell crank 7200 to rotate about shaft 7210 and press against force application member 2320. This drives the resilient diaphragm 7220 to seal against the resilient pumping membrane 2340 and urge fluid from the pumping chamber 2350 toward the dispensing chamber 122. The return spring 276 cooperates with the return spring support 7221 to release the pumping force, causing the pumping chamber 2350 to expand and draw fluid from the reservoir 20. Still referring to fig. 48 and 49, there is also shown a bias valve 4000 having a valve spring 4010, a poppet or plunger 4020.

In some embodiments of the pumping mechanism described above, one or more aspects of the following valve operational description are relevant. Referring now to FIG. 50, an example of a bias valve 4000 that is closed is shown. The valve spring 4010 exerts a force on the poppet valve 4020 to sealingly press the valve diaphragm 4060 against the valve seat 4070 surrounding the terminal aperture of the valve outlet 4040. The valve seat 4070 may include a circumferential raised portion to improve sealing. As explained below with reference to fig. 54-55, the back pressure created by the action of the resilient dispensing component should be insufficient to cause reverse flow through the bias valve 4000. As shown in figure 51, when the pumping assembly is actuated, sufficient pressure should be generated to disengage the diaphragm 4060 and poppet 4020 from the valve seat 4070, thereby allowing fluid to flow from the valve inlet 4030, through the inlet chamber 4050 and to the valve outlet 4040. Fig. 52-53 illustrate an alternative valve having a valve seat 4070 without a circumferential raised portion.

Referring now to fig. 54 and 55, an illustration of how an exemplary bias valve distinguishes between forward flow and reverse flow is shown. Figure 54 diagrammatically represents the valve in the closed position. The back pressure in the outlet 4040 applies a force to a smaller area of the flexible valve diaphragm 4060 adjacent the valve seat 4070 and is therefore unable to move the poppet valve 4020 out. Referring now to fig. 55, the valve is shown schematically during actuation of the pumping actuation member. The pressure of the pumped fluid exerts a force on the area of the diaphragm 4060 that is larger than the area adjacent to the valve seat. As a result, the inlet pressure has a greater mechanical advantage to unseat the poppet valve 4020 and forward flow ensues in response to the action of the pumping actuation member. Thus, the critical pressure required to displace the poppet valve 4020 is lower in the inlet than in the outlet. Accordingly, the spring-biased force and the size of the force application areas associated with the fluid inlet and the fluid outlet may be selected such that the flow is substantially in the forward direction.

Referring now to FIG. 56, there is shown a cross-sectional view of an adjustable bias valve 4130 that operates on a similar principle to the bias valve of FIG. 50, but allows for adjustment of the pressure necessary to open the valve, i.e., the "cracking pressure" (which may be from 0.2 to 20 pounds per square inch or "psi" in some embodiments). The cracking pressure is adjusted by rotating spring tensioning screw 4090, which changes the volume of recess 4080 to compress or decompress valve spring 4010, thereby changing the biasing force of spring 4010. Valve spring 4010 biases plunger 4100 toward valve diaphragm 4060 to urge it to a valve seat. Plunger 4100 performs a force application function similar to that of a fixed force poppet valve of a bias flow valve (shown in fig. 50-53 as 4020 and 4000, respectively). Compressing the valve spring 4010 will increase its biasing force, thereby increasing the cracking pressure. Conversely, decompressing spring 4010 will decrease its biasing force and associated cracking pressure. Valve spring 4010 is positioned coaxially about the axis of plunger 4100 and exerts its biasing force on plunger 4100. In some embodiments, the shaft of the plunger 4100 may be shorter than the length of the valve spring 4010 and the recess 4080 to allow it to freely displace in response to increased fluid pressure in the fluid inlet 4030. The plunger 4100 can have any size necessary to function as desired. As in the embodiment of fig. 50-53, the wetting section can be located in disposable section 2610 and the force applying member (e.g., plunger and spring) can be located in reusable section 2620. The principle of operation is also similar; the greater mechanical advantage in the fluid inlet 4030 relative to the outlet 4040 is more favorable for forward flow rather than reverse flow. Alternatively, the plunger 4100 may be replaced by a poppet valve (shown as 4020 in fig. 50-55). In some embodiments, it may be desirable to eliminate the raised valve seat; in these embodiments, the plunger may be spherical or another shape capable of concentrating the force.

The bias flow valve 4000 substantially alleviates or prevents reverse flow from the dispensing chamber 122 into the pumping chamber 2350. As in fig. 50-56, valve spring 4010 biases poppet or plunger 4040 to press diaphragm 7220 toward valve seat 4070 in a manner that provides a mechanical advantage to forward flow through wire 310. By functioning as a pumping diaphragm 2330 and a valve diaphragm, diaphragm 7220 allows flow line 310, pumping chamber 2350, and pumping membrane 2340 to be located in one component (e.g., disposable portion 2610) and the remainder of the pumping mechanism to be located in a second, removable component (e.g., reusable portion 2620). Economy and convenience can be achieved by placing more durable and expensive components in reusable portion 2620.

The pumping mechanisms described in the various embodiments above can be used in a variety of devices to pump fluids. The pumping mechanisms described in fig. 59A-59E, 60A-60D, and 60A-60C will be described as integrated into a fluid pumping device as one exemplary embodiment.

Referring to fig. 57 and 58, an alternative for fluidic schematic is shown. They are two schematic diagrams in which reservoir 20 and pumping assembly 16 are coupled to dispensing assembly 120. In the embodiment shown in fig. 57, the reservoir and pumping assembly are coupled in series to the dispensing assembly 120. In the embodiment illustrated in fig. 58, a shunt line 150 is coupled from the output of pumping assembly 16 and returns to reservoir 20. Because most of the fluid output of pumping assembly 16 is returned to reservoir 20 via diverter line 150, pumping assembly 16 can include a variety of pumping mechanisms 16 that may not function as required by the embodiment shown in fig. 57. Thus, in some embodiments in which a large volume pumping mechanism is employed, the diversion line 150 can impart small volume functionality to the large volume pumping mechanism. The check valves 21 and 22 are oriented in the same direction and are included to prevent unwanted backflow.

Referring now to fig. 59A-59E, fluid schematic diagrams of one embodiment of a fluid pumping device are shown. In this embodiment, the fluid is located in a reservoir 20 connected to a flow line 310. Flow line 310 communicates with pumping mechanism 16, separated by membrane 2356. Fluid is pumped through the occluder 340 to an infusion set or cannula 5010 for delivery to the patient. It should be understood that the infusion device or cannula 5010 is not part of the device itself, but is attached to the patient for delivery of fluid. System embodiments are described in more detail below and include an infusion device or cannula 5010.

Referring now to FIG. 59B, an alternative embodiment of the diagrammatical illustration of FIG. 59A is shown. In the embodiment shown in fig. 59A, fluid is pumped through the flow restrictor 340 and then through the sleeve 5010. However, in fig. 59B, the fluid is not pumped through the flow restrictor; instead, the fluid is pumped through the sleeve 5010, which has the same impedance.

In fig. 59A and 59B, in one embodiment, the volume of fluid pumped to the patient is roughly calculated using the pump stroke. The stroke length will provide a rough estimate of the volume pumped to the patient.

Referring now to fig. 59C, a fluid schematic diagram of one embodiment of a fluid pumping device is shown. In this embodiment, the fluid is located in a reservoir 20 connected to a flow line 310 by a septum 6270. Flow line 310 communicates with pumping mechanism 16, separated by membrane 2356. Fluid is pumped into the variable volume delivery chamber 122 and then through the flow restrictor 340 to the cannula 5010 for delivery to the patient.

The volume of fluid delivered is determined using a dispensing assembly 120 that includes an Acoustic Volume Sensing (AVS) assembly 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 in the pumping mechanism 16 (described in detail above). The AVS component is described in more detail above.

Referring now to fig. 59D, an alternative embodiment to that shown in fig. 59C is shown in which there is no flow restrictor between the variable volume delivery chamber 122 and the sleeve 5010. Referring now to fig. 59E, an alternative embodiment to that shown in fig. 59C is shown with an alternative pumping mechanism 16.

Referring now to fig. 59A-59E, the reservoir 20 can be any fluid source including, but not limited to, a syringe, a collapsible reservoir pouch, a glass vial or any other container capable of safely containing a fluid to be delivered. Septum 6270 is a connection point between flow line 310 and reservoir 20. Various embodiments of the septum 6270 and the reservoir 20 are described in more detail below.

The fluid delivery device embodiments shown in fig. 59A-59E can be used to deliver any type of fluid. Alternatively, this embodiment can be used as one, two or three separate mating parts. Referring now to fig. 60A-60D, the same embodiment described with respect to fig. 59A-59D is shown separated into multiple mating portions. Portion X includes the movable portion and portion Y includes flow line 310 and membrane 2356. In some embodiments of this design, portion Y is a disposable portion and portion X is a non-disposable portion. The portion X does not directly contact the fluid, only the portion Y is the portion with the wetted area. In the above embodiments, the reservoir 20 can be of any size and is either integrated into the disposable component or is a separate disposable component. In either embodiment, the reservoir 20 can be refilled. In embodiments in which the reservoir 20 is integrated into the disposable portion Y, the reservoir 20 can be manufactured to be filled with fluid, or the reservoir 20 can be filled by the patient or user through the septum 6270 using a syringe. In embodiments in which the reservoir 20 is a separate mating component, the reservoir 20 can be manufactured to be filled with fluid, or the patient or user can fill the reservoir 20 with a syringe (not shown) through the septum 6270 as part of a reservoir loading means (not shown, described in more detail below) or manually fill the reservoir 20 with a syringe through the septum 6270. Further details regarding the process of filling reservoir 20 are described below.

While various embodiments have been described with respect to fig. 59A-59E and 60A-60D, the pumping mechanism may be any of the pumping mechanisms described herein as embodiments or alternative embodiments having similar functions and features. For example, referring now to fig. 61A, an embodiment similar to that shown in fig. 59A is shown with a representative module including pumping mechanism 16. This is to illustrate that any of the pumping mechanisms 16 described herein or functioning similarly can be used in the fluid pumping device. Similarly, fig. 61B and 61C are representations of systems including the embodiments of fig. 59B and 59C, respectively.

The overview of the fluid pumping device described above can be implemented in a device that can be used by a patient. There are a number of embodiments. The device may be a stand-alone device or integrated into another device. The device may be of any size or shape. The device may be portable or non-portable. The term "portable" means that the patient is able to carry the device in the body-worn pocket area or otherwise. The term "non-portable" means that the device is located in a healthcare facility or at home, except that the patient cannot bring the device to almost any location where they can move. The remainder of the description will focus on the portable device as an exemplary embodiment.

With respect to portable devices, the device can be worn by a patient or carried by a patient. In embodiments in which the device is worn by the patient, it will be referred to as a "patch pump" for the purposes of this description. When the device is carried by a patient, it will be referred to as a "portable pump" for the purposes of this description.

The following description can be applied to various embodiments with respect to either the patch pump embodiment or the portable pump embodiment. In various embodiments, the device includes a housing, a pumping mechanism, a flow line, a movable component, a reservoir, a power source, and a microprocessor. In various embodiments, a dispensing assembly, such as a volume sensing device including an AVS assembly in some embodiments, is included in the device. Also, embodiments can also include a flow restrictor, but this is not depicted in the figures below, as the flow lines are shown as being uniform to simplify the illustration. For purposes of this description, when including a dispensing component, exemplary embodiments will include an AVS component. While the AVS assembly is the preferred embodiment, in other embodiments, other types of volume sensing devices can be used. However, in some embodiments, rather than using a volume sensing device, the reservoir itself will determine the volume of fluid delivered, or be adapted for the pump stroke to roughly determine the volume delivered. It will be appreciated that the schematic devices shown herein are intended to illustrate some of the variations in the devices described. The embodiments represented by these schematics may each also include a sensor housing, a vibration motor, an antenna, a radio, or other components described with respect to fig. 70-70D. Thus, these depictions are not intended to limit the components but to illustrate how the various components can be interrelated in the device.

Referring now to fig. 62A, a diagrammatic view of the individual device 10 is shown. The housing 10 can have any shape or size and be adapted to the intended use. For example, when the device is used as a patch, the device will be compact enough to be worn by itself. When the device is used as a portable pump, the device will be compact enough to be used accordingly. In some embodiments, the housing is made of plastic, and in some embodiments, the plastic is any injection molding fluid compatible plastic, such as polycarbonate. In other embodiments, the housing is made of a combination of aluminum or titanium and plastic or any other material that is lightweight and durable in some embodiments. Additional materials may include, but are not limited to, rubber, steel, titanium, and alloys thereof. As shown in fig. 62A, the device 10 can have any size or shape desired.

Fig. 62A to 69B are schematic diagrams showing a representative embodiment. The exact design depends on many factors including, but not limited to, device size, power limitations, and intended use. Thus, fig. 62A-69B are intended to depict various features and possible combinations of devices, however, one of ordinary skill in the art can readily design and implement actual devices. Device embodiments are described and illustrated below as examples. However, these embodiments are not intended to be limiting, but rather are intended to be exemplary.

Referring now to fig. 62B, with respect to the patch device, in some embodiments, the housing 10 includes an insertion region window 342. The viewing window allows a site on the patient where an infusion set or cannula (not shown) is inserted and viewed. The boot 5030 region of the device 10 is shown here. The viewing window 342 is made of any material that can be transparent, including but not limited to plastic. Although the window 342 is shown in a particular position on a specifically shaped device, the window 342 can be integrated in any position desired in any housing embodiment.

Referring now to fig. 63A, device 10 is shown. The reservoir 20 is shown connected to a flow line 310, which is then connected to the pumping mechanism 16. The dispensing assembly 120 is shown connected to a flow line 310. The pumping mechanism 16 and dispense assembly 120 are separated from the flowline 310 by a membrane 2356. A boot 5030 is located downstream of the volume measurement device. The shape memory actuator 278 is shown connected to the pumping mechanism 16. A microprocessor on a printed circuit board 13 and a power supply or battery 15 are included. A flow resistance as described above can also be achieved between the dispensing assembly 120 and the tube housing 5030.

Referring now to FIG. 63B, a similar device 10 as shown in FIG. 63A is shown except that in this embodiment, the dispensing assembly is not included. In this embodiment, the volume of fluid delivered will depend on the pump strokes (number and length), the reservoir 20 (volume and time), both, or any other method previously described with respect to monitoring the volume of fluid delivered.

Referring now to FIG. 63C, a similar device 10 as shown in FIG. 63B is shown, except that the device 10 includes a dispensing chamber 122 and a sensor housing 5022.

Referring now to fig. 64A, one 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 parts: a top X and a base Y. The top portion X contains the pumping mechanism 16, the dispensing assembly 120 (which is optional but shown as an exemplary embodiment), the power supply 15 and microprocessor, and the printed circuit board 13. They are non-wetting elements, i.e. they do not directly contact the fluid. Base Y contains flow line 310 and membrane 2356. When the reservoir 20 is built into the device, the reservoir is also contained on the base Y. However, in embodiments where the reservoir 20 is a separate mating component, the reservoir 20 is connected to the flow line when fully assembled (see fig. 66A-66D and the description referencing them) and is not built into the device.

The patch pump device also includes a cannula housing 5030. This is the region where the cannula line 5031 is located. A portion of the flow line 310, the cannula line 5031, allows the cannula (or other infusion device) to receive and deliver fluid to a patient (not shown).

Referring now 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 septum (not shown) that connects the cannula wire 5031 to the cannula 5010.

Referring now to fig. 65B, in other embodiments, an insertion set (including cannula and tubing, not shown in fig. 65B, shown as items 5033 and 5010 in fig. 64B) is used; thus, the tubing line 5033 inserted into the kit will connect to the cannula line 5030 on one end and to the cannula (not shown) on the opposite end of the tubing line.

Referring again to fig. 64A, in use, a reservoir 20 (either molded into base Y or separate and attached to base Y as described above) with fluid therein is connected to flow line 310. The microprocessor on the printed circuit board 13 sends a signal to actuate the pumping mechanism 16 and initiate a stroke by applying a current to the shape memory actuator 278. Fluid flows in flow line 310 from the reservoir 20 to the dispensing assembly 120 or AVS assembly. Here, the exact volume of fluid in the AVS chamber is determined and fluid is forced out of the AVS chamber to the cannula line 5031 and the cannula shield 5030.

Referring now to fig. 64B, the device shown in fig. 64A is shown connected to an insertion set, i.e., tubing 5033 and cannula 5010. In fig. 64C, the base Y of the device is shown attached to the body of the patient 12 using an adhesive patch or pad 3100. It should be noted that in this embodiment, element 3100 can be a pad or a patch. However, as described in more detail below, item 3100 is referred to as a patch, and item 3220 is referred to as a pad. The object 3100 is used for purposes of simplicity only; however, in some embodiments, a pad is used, so item 3220 would be appropriate in those situations.

A cannula 5010, which is inserted through the cannula housing 5030 so as to fit to the cannula line 5031 with a cannula septum 5060, is inserted into the patient 12. However, as shown and described above with respect to fig. 64B, the base Y can be fluidly attached to the patient by an insertion set comprising a tubing 5033 and a cannula 5010. In fig. 64B and 64C, the base Y can be attached to the patient either before or after insertion of the cannula 5010. Referring again to fig. 64C, the cannula 5010, once inserted into the patient 12, will receive fluid directly from the device without the infusion set line (shown in fig. 64B). The base Y is attached to the patient 12 with an adhesive patch 3100 either before or after insertion of the cannula 5010. Referring now to fig. 64D, after the cannula 5010 has been inserted into the patient 12, the top portion X of the device 10 is in turn attached to the base portion Y of the device 10.

As described below, the adhesive patch can have many embodiments, and in some cases, the patch is placed on top of the device. Thus, the patch shown in these embodiments is only one embodiment. As described above, the pads, if used, will be placed in the same positions as the patches in FIGS. 64A-64D.

Referring now to fig. 66A-66D, in this embodiment, the reservoir 20 is shown as a separate component. As shown in fig. 66A, 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 top reservoir cavity 2640. At this time, the reservoir 20 is not attached to the device. Referring now to fig. 66C, when the top portion X is placed over the base portion Y, the reservoir 20 is sandwiched in the base reservoir cavity 2645. As shown in fig. 66D, the force created by attaching the top portion to the base Y pushes the septum needle 6272 into the septum 6270 of the reservoir 20, which septum 6270 connects the reservoir 20 to the flow line 310 of the base Y.

Referring now to fig. 67A-67F, an alternative embodiment to the embodiment shown in fig. 64A, 64C, and 66A-66D is shown. In these alternative embodiments, the base Y includes a sensor housing 5022 in addition to the boot 5030. Referring now to fig. 69A-69B, the sensor housing 5022 and the vial shield 5030 each include an outlet to the underside of the base Y, shown in fig. 69A as 5022 and 5030, respectively. FIG. 69B depicts the embodiment shown in FIG. 69A, wherein a sharp object protrudes 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 type of analyte sensor desired.

Referring now to fig. 67B, the base Y is shown positioned on the body of the patient 12. The sensor 5020 is shown as having been inserted into the patient 12 through the base Y sensor housing 5022. Referring now to fig. 67C, in some embodiments, the cannula 5010 and the sensor 5020 are simultaneously inserted through their respective housings (5030 and 5022) and into the patient 12. Referring now to fig. 67D, the base Y is shown attached to the patient with both the cannula 5010 and the sensor 5020 attached to the patient 12 through the base Y.

Referring now to fig. 67E, the base Y is shown attached to the patient 12 and the cannula 5010 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 into the patient 12 in another location. Thus, the sensor 5020 is not required to be inserted through the base Y, however, the embodiments described below relating to monitoring blood glucose and pumping insulin through the cannula can be implemented in this manner. Additionally, other embodiments related to administration of fluids in response to or related to analyte levels can be practiced in this manner.

Referring now to FIG. 67F, the device 10 with the sensor 5020 and cannula 5010 through the base Y is shown with the top X thereon. Again, in the embodiment shown in fig. 66A-66D, once the top X is placed on the base Y, the reservoir 20 is fluidly connected to the flow line 310.

Referring now to fig. 68, one embodiment of a portable pump embodiment of the device 10 is shown. In this device 10, an insertion set comprising the cannula 5010 and the tubing 5033 must connect the flow lines in the device 10 to the patient 12. Thus, the cannula 5010 is not directly connected to the patient 12 by the portable pump device 10 in this embodiment. Additionally, while this embodiment is capable of functioning as described below with respect to analyte sensors and fluid pumps, the sensor 5020 would be located external to the portable pump device 10 similar to the embodiment of the sensor 5020 shown in figure 67F.

Referring now to fig. 70-70D, the patch pump and portable pump embodiments described each additionally contain various components of the dispensing assembly (in applicable embodiments), and for embodiments that include an AVS assembly, the various components of the dispensing assembly include at least one microphone, a temperature sensor, at least one speaker, a variable volume dispensing chamber, a variable volume chamber, a port, and a reference chamber. In some embodiments, the device contains one or more of the following devices: a vibrator motor (and, in those embodiments, a motor driver), an antenna, a radio, a skin temperature sensor, a bolus button, and, in some embodiments, one or more additional buttons. In some embodiments, the antenna is a quarter-wave tracking antenna. In other embodiments the antenna may be a half-wavelength or quarter-wavelength tracking, dipole, monopole or loop antenna. The radio is, in some embodiments, a 2.4GHz radio, but in other embodiments the radio is a 400MHz radio. In further embodiments, the radio can be any frequency radio. Thus, in some embodiments, the device includes a radio that is strong enough to communicate with a receiver within a few feet of the device. In some embodiments, the device comprises a second radio. In some embodiments, the second radio may be a special long-range radio, such as a 433 or 900MHz radio, or, in some embodiments, have any frequency in the ISM band or other bands, not shown in fig. 70-70D, the device containing a screen and/or a user interface in some embodiments.

The following description of these components and their various embodiments can be applied to both device types, and in turn can be applied to the various embodiments described with respect to each device type. Referring now to FIG. 67F, for illustrative purposes only, the cannula 5010 and the sensor 5020 have been inserted into the device 10. Also, with reference to fig. 70-70D, various components (some of which are not necessarily included in all embodiments) are shown as being generally representative of the electrical connections of those components. Fig. 70-70D thus represent various elements that may be included in the device. These elements can be mixed and matched according to size requirements, power limitations, usage and preferences, and other variables. FIG. 70 illustrates the relationship of FIGS. 70A-70D.

The device contains at least one microprocessor 271. The microprocessor can be any speed microprocessor capable of handling at least the various electrical connections necessary to enable the device to function. In some embodiments, the device contains more than one microprocessor, as shown in fig. 70A-70B, the device is shown with two microprocessors 271.

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

In some embodiments, the device includes a radio 370 connected to the main PCB 13. The radio 370 communicates with the remote controller 3470 using an antenna 3580. Communication between the device 10 and the remote controller 3470 is thus wireless.

In some embodiments, the device contains a vibration motor 3210. The vibration motor 3210 is connected to a motor driver 3211 on the motor driver 3211 of the main PCB 13.

Some embodiments include a bolus button 3213. Bolus button 3213 functions by the user applying a force to button structure 3213, which may be made of rubber or any other suitable material. This force actuates a bolus button actuation of bolus button switch 3214 attached to main PCB 13. Switch 3214 actuates a single bolus, which will indicate that a particular predetermined volume of fluid is to be delivered to the patient. After the user presses bolus button 3213, in some embodiments, device 10 will generate an alert (e.g., actuate vibration motor 3210 and/or send a signal to a remote controller) to signal the user that button 3213 is pressed. The user then needs to confirm that the bolus should be delivered, for example, by depressing button 3213. In further embodiments, remote controller 3470 queries the user to confirm that a bolus should be delivered.

Similar challenge/response sequences may be used in various embodiments to test and report patient responsiveness. For example, the device may be configured to test patient responsiveness by generating an alarm (e.g., an audible and/or tactile alarm) and waiting for a patient response (e.g., actuating button 3213). Such testing may be performed at different times (e.g., every five minutes) or when a condition such as an abnormal analyte level monitored via an analyte sensor or an abnormal body temperature monitored via a temperature sensor is detected. The reusable portion may send an alert to a remote controller or caretaker if the patient does not provide an appropriate response within a predetermined time. Such testing and reporting may be particularly valuable for patients who may become unconscious or incapacitated due to device failure or other reasons.

NITINOL circuitry (reference shape memory actuator, in some embodiments, NITINOL strand) 278 on the main PCB 13 provides current to the NITINOL connector. As shown in fig. 67F and 70A, the device can include two NITINOL connectors 278 (and two NITINOL strands). However, as described above, in some embodiments, the device includes a NITINOL connector (and a NITINOL strand).

In some embodiments, the device includes a temperature sensor 3216 shown in fig. 70B. A temperature sensor 3216 is located on the underside of the base Y and senses the skin temperature of the patient. The skin temperature sensor 3216 is connected to a signal conditioner represented by 3217. As shown in fig. 70B, the signal conditioner 3217 is shown as a block, however the device includes multiple signal conditioners, each filtering a different signal, as desired. Next, the AVS temperature sensor 132, AVS microphone 133, and analyte sensor 5020 are all connected to a signal conditioner represented in one block as 3217.

The AVS speaker 134 is connected to a speaker driver 135 on the main PCB 13. The AVS speaker 134 is a hearing assistance speaker in one embodiment. However, in other embodiments, speaker 134 (speaker with voice coil, magnet with electromagnetic coil) is a piezoelectric speaker (shown in FIG. 50, representing one embodiment of the device).

Still referring to fig. 70-70D, in some embodiments, the antenna 3580 has a dedicated PCB 3581 that is then connected to the main PCB 13. Also, in some embodiments, the AVS microphones 133 each have a dedicated PCB 1332, 1333 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.

Referring to fig. 67F, device 10 is shown as an exemplary embodiment for illustrative purposes. However, the layout of the various parts can vary, and many embodiments are shown below. However, further alternative embodiments are not shown, but can be determined based on size, power and use.

According to an alternative embodiment, disposable portion 2610 may include reservoir 20 and optionally an accumulator. The reservoir 20 may be integral with or otherwise coupled to the disposable portion. The battery may be the primary or sole power source for the device or may be a backup power source and may be used to provide power to the electronics on the reusable and/or disposable portions. Both the reservoir 20 and the batteries typically require periodic replacement, so including both components in the disposable portion 2610 can provide the user with this added convenience of simultaneous replacement. Additionally, by replacing the battery each time the reservoir is replaced, the user may be less likely to drain the battery.

Disposable portion 2610 can additionally or alternatively include a processor that can be used, for example, to continue operation of certain devices in the event of a failure (e.g., failure of a master controller in the reusable portion), to generate an alarm in the event of a failure, or to provide status information to the reusable portion. With respect to the status information, the processor can keep track of the operational history and various characteristics of the disposable portion and retain the status information for access by the user, the fluid delivery device 10, and/or the user interface 14 during installation of the disposable portion 2610. For example, the processor can store state relating to a shelf life, maximum exposure or operating temperature, manufacturer, safety dispensing limits for treatment, and the like. If the device determines that any of these status indicators are not acceptable, the device can deny power to the pumping and dispensing assemblies and indicate to the user that the disposable portion is not available. The processor may be powered by a battery in the reusable part or the disposable part.

More generally, the device may be configured to obtain status information via a bar code reader, or via RFID technology, from any disposable portion (including, for example, disposable portion 2610 and any disposable components used therein, such as a fluid reservoir, a battery, or a sharpened cartridge or respective sharpened member), for example, from a processor disposed in the disposable portion. If the device detects a problem with the disposable portion (e.g., an invalid model number for the reusable portion or fluid expiration), the device may take remedial action, such as, for example, preventing or terminating device operation and generating an appropriate alarm.

Additional components may be included in some embodiments. For example, a backup failure detection and notification mechanism can be employed. The device may employ an audible alarm. The microphone 1202 of the sensor 550 may be for an audible alarm, or another speaker may include a microphone and be for an audible alarm. The device vibration mechanism 3210 can also be used as an alarm. Both alarms can be activated if a system fault is detected that requires immediate attention. Additionally, a rechargeable battery or a super capacitor may be employed as a backup to the primary battery. If neither battery is operational, the controller can activate one or more alarms to provide at least one notification of a battery failure.

The alarm can also be used to indicate to the user that the device is functioning properly. For example, a user may program the device with respect to bolus delivery over a particular period of time. The user may desire to know that the programmed delivery is proceeding correctly. The processor can use a vibration motor or audio sounds to signal successful programmed delivery. Thus, some mechanism can be employed in some embodiments of the device to provide positive or negative feedback to the patient or user.

The microphone may also be used to detect any abnormal vibration or lack of normal vibration and trigger an alarm condition. In various embodiments, a microphone of the acoustic volume sensing system may be used to perform such monitoring, or a separate microphone may be included for such monitoring. A periodic check can also be performed to determine that the device is operating by checking for expected pump vibrations with the microphone. An alarm can be activated if the microphone detects an incorrect vibration, or if the correct vibration is not detected.

Referring now to fig. 71, the various components of the device 10 are schematically illustrated. In one embodiment of the device 10, the top portion X mates with the base portion Y and the reservoir 20 is sandwiched between the top portion X and the base portion Y. The clamping force allows reservoir septum 6272 to mate with base Y. In some embodiments, the infusion device 5010 and the analyte sensor 5020 are both inserted through the base Y and into a patient (not shown).

In many embodiments, the base Y and reservoir 20 are disposable portions and the top X is a non-disposable portion. The infusion set 5010 and analyte sensor are also disposable.

As previously discussed, the patch pump device may be wholly or partially disposable. Fig. 72 illustrates an embodiment of the fluid delivery device 10 having disposable and non-disposable portions. In this embodiment, the disposable part Y contains components in direct contact with the fluid, including the collapsible reservoir 20, the pumping assembly (not shown), the variable-volume dispensing chamber 122 (the portion of the dispensing assembly 120 on the top X) and the flow restrictor (not shown), as well as a fluid path (not shown) and a one-way valve (not shown) connecting the reservoir to the pumping mechanism to the variable-volume dispensing chamber 122. Additionally, disposable portion Y includes a reservoir cavity 2645.

Reusable portion X includes the elements of dispensing assembly 120 except for variable volume dispensing chamber 122 located on disposable portion Y. In some embodiments, the distribution component 120 is an AVS component. The AVS components are described in detail above. Referring now to fig. 73, the integrated acoustic volume measurement sensor is shown on a PCB.

Referring now to fig. 74, the device 10 shown in fig. 49 is shown. The base disposable portion Y includes a reservoir cavity 2645. The top non-disposable portion X includes the battery 15 and the dispensing assembly 120. A microphone 133 is shown, as well as a diaphragm spring 130. In some embodiments, the dispensing component 120 includes more than one microphone. Although each microphone is referred to as 133 throughout this description, this does not imply that the microphones are always the same. In some embodiments, the microphones are identical, and in other embodiments, the microphones are different.

In fig. 74, the top non-disposable portion X further includes the main PCB 13, the vibration motor 3210, and the pumping actuation member 54. The top, non-disposable portion X includes an AVS component or dispensing component 120. In fig. 74, a microphone 133 is shown. The top, non-disposable part X also includes a battery 15 that can be used to power the electronics on the non-disposable part and/or disposable part. In some embodiments, the battery 15 is rechargeable. Recharging can be performed by the method described below. Disposable part Y comprises a wetting member with a flow line (not shown) and a pumping assembly. In fig. 74, only the pumping plunger 54 is visible. This embodiment of the device 10 can also include many of the elements described above, including but not limited to flow resistance, flexible diaphragms, tube shields, and sensor housings. Any pumping mechanism can be used.

Referring now to fig. 75, device 10 is shown in another view in which more elements may be seen. In figure 75, device 10 is shown with a base disposable portion Y comprising coiled micro-tube flow restrictor 340 and flow line 310 connecting inlet 21 and outlet 22 valves. Pumping actuation member 54 is also shown. The top X includes the main PCB 13, the vibration motor 3210, the two microphones 133, the speaker 134, the reference chamber 127, and the fixed volume chamber 129. A battery 15 is also shown. Because selecting a very small diameter for the flow restrictor 340 may cause the flowline 310 to become plugged (e.g., due to protein polymerization in the therapeutic fluid), it may be desirable to use a longer length flowline with a larger diameter. However, in order to package a tubing having a longer length in a patch-sized housing, it may be necessary to bend the tubing to form a curved path, such as coiled or serpentine.

Referring now to fig. 76, an exploded view of the device 10 shown in fig. 72, 74 and 75 is shown. The top, non-disposable portion X is shown separated from the base disposable portion Y. In practice, a reservoir (not shown) will be placed between the top X and base Y portions. Once the top X and base Y are assembled to form the device 10, the reservoir will be connected to the flow line 310.

Referring now to fig. 77, an exploded view of another embodiment of the device 10 is shown including a disposable base Y and a non-disposable top X portion. Also included is a reservoir 20, an adhesive 3100 to hold the infusion device 5010 with the sensor 5020, and a bridge 5040 device. The device 10 includes a more rounded footprint and dome shape. The battery 15 and the main PCB 13 are shown on the top X. Base Y includes a reservoir cavity 2645. Adhesive 3100 is shown in a two-piece embodiment. The bridge 5040 is used to insert the infusion set 5010 and sensor 5020 through the base Y. The reservoir 20 is shown as 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 capacity. In this embodiment of device 10, the non-wetting member is located in the top non-disposable portion X and the wetting member is located in the base disposable portion Y.

When assembled, the device 10 may be attached together with an adhesive central region (not shown). Alternatively, the devices 10 may be mechanically locked together using any of the many embodiments for locking described herein. While some embodiments are described herein below, many others are apparent, and when the device shape is changed, in many cases the lock will also change.

Referring now to fig. 78, an exploded view of another embodiment of the device 10 is shown. The top non-disposable portion X is substantially dome shaped, however, the protrusion Xl is shown as accommodating a mechanism in the top X. Thus, the device shape can vary and can include polyps and bulges, dimples and other textural features to suit various designs of the device.

A reservoir 20, an infusion device 5010, and a sensor 5020 are shown. The infusion set 5010 and sensor 5020 can be inserted through the base Y and into a patient (not shown). The base Y is shown with an adhesive 3100 or a pad 3220 underneath. In practice, the adhesive 3100 or the pad 3220 can be first adhered to the skin and the base Y. Next, the infusion device 5010 and sensor 5020 are inserted into the patient through the base Y (not shown, shown as 5020 and 5010 in FIG. 79). The reservoir 20 is then placed in the reservoir cavity 2645 by first placing the reservoir 20 in the top portion X and then sandwiched between the top portion X and the base portion Y, or, alternatively, placing the reservoir 20 in the reservoir cavity 2645 and then sandwiched between the top portion X and the base portion Y. Either method may be used. The end result is that the reservoir 20 is connected to a flow line (not shown) located in the base Y by a septum (shown inverted) and a septum needle (not shown, see 6272) on the reservoir 20. The top X is then secured to the base Y by using an adhesive, or in this embodiment, mechanically clamping the top X and base Y together using the lock 654.

The base Y includes those members that are wetted. The base Y is disposable. The top X comprises a non-wetting member. The top X is non-disposable. Referring now to fig. 79, the base Y includes the variable volume dispensing chamber 122, the inlet valve 21, and the outlet valve 22 and pumping chamber 2350. As shown in this figure, those elements are shown as a membrane covering the area that functions as a chamber or valve. Thus, the base Y comprises a membrane that securely holds the wetted area and, therefore, the non-wetted area such as in the top (not shown). As shown in fig. 79, the sensor 5020 and the infusion set 5010 have been inserted into their respective housings and through the base Y to the patient (not shown). Base Y is shown with reservoir cavity 2645 but requires a connection to the reservoir (not shown) so that a flow line from the reservoir to the chamber and to the infusion device is connected.

Referring now to fig. 80, the top X of the device is shown. The top X includes those non-wetting components including, as shown, a temperature sensor 3216, a diaphragm spring 130, an inlet valve poppet 21 and an outlet valve poppet 22, and a pumping actuation member 54. The top portion Y also includes a recess 2640 to accommodate a reservoir (not shown).

Referring now to fig. 81A-81C, a sequence is shown for illustrating the process of clamping the reservoir 20 between the top X and the base Y. As shown in fig. 81A, the top X is shown with the reservoir 20 outside the top X. The reservoir includes a septum 6270. The top X includes a reservoir recess 2640. Next, as shown in fig. 81B, the top portion is prepared to be clamped together with the base portion Y. Referring now to fig. 81C, the reservoir 20 is placed in the base Y with the septum side down. The septum would connect with a cannulated septum needle (not shown) in base Y and connect the reservoir to a flow line (not shown). In an alternative embodiment, the reservoir may include a needle with a cannula instead of a septum, and the fluid path may include a reservoir interface with a septum instead of a needle with a cannula.

Referring now to FIG. 82, a top portion X is shown with one embodiment of pumping mechanism 16 exploded. The pumping mechanism 16 is fitted into a pumping mechanism housing 18 in the top portion X. Base Y is also shown, as well as a portion of latch 654 that clamps top X and base Y together.

Referring now to fig. 83, the base Y is shown with the fluid path assembly 166 as a membrane 2356 exploded from the base Y. This illustrates that in some embodiments of the device, the fluid path assembly 166 is a separate component inserted into the base Y and clamped with the membrane 2356. Also shown in this figure, the adhesive or pad 3100/3220 in some embodiments includes apertures for the infusion set and sensors (not shown). Referring now to fig. 84, a bottom view of the base Y is shown. The bottom of the fluid path assembly 166.

Referring now to fig. 85A and 85B, another embodiment of a device is shown. In this embodiment, the top portion X, which is also non-disposable, includes a bolus button 654. Reservoir 20 is shown in an exploded view, however, in one embodiment, reservoir 20 is built into base Y. In another embodiment, the reservoir 20 is removable and placed in the reservoir cavity 2645 using a process similar to that described above with respect to another embodiment of the device.

The base Y is disposable and comprises the wetted portion of the device 10. A sensor 5020, a cannula 5010, a variable volume dispensing chamber 122, an inlet valve region 21, an outlet valve region 22, and a pumping chamber 2350. The volume dispensing chamber, the inlet valve region 21, the outlet valve region 22, and the pumping chamber 2354 are all covered by a membrane material, which may be in the form of a single membrane or different membranes.

The device 10 is clamped together using a lock mechanism 654 on the top X and base Y. Referring now to fig. 85C-85D, device 10 is shown with locking mechanism 654 in an open position (fig. 85C) and a clamped or closed position (fig. 85D). A bolus button 3213 as described in greater detail above can also be seen.

A cover (not shown) may be provided for use in any of the device embodiments to replace the reservoir and top when the reservoir is removed and the base is connected to the patient. The lid will be free of electrical components and therefore can be used in a wet state. However, in some cases, the reservoir can be removed without using any lid.

Cannula and inserter

Fig. 86A diagrammatically shows a representative embodiment of an infusion and sensor assembly 5040 that includes an infusion set, which can be a cannula or needle 5010, and an analyte sensor that includes a sensor probe 5025 and a sensor base 5023. The bridge 5070 securely joins the infusion cannula 5010 and the analyte sensor base 5023. The infusion device 5010 is bounded on an upper side by a septum 5060 that allows fluid to flow from a fluid source and be delivered to a patient through the infusion device 5010. The sensor base 5023 is the portion of the analyte sensor that is not inserted into the patient. In one embodiment, the base 5023 contains electrical contacts for electrochemical analysis of blood glucose. The probes 5025 protrude from the base 5023 of the analyte sensor 5020.

Referring now to fig. 86B, in this embodiment, the infusion device 5010 is a cannula that is introduced into the patient using an introducer needle 5240. When inserted into the patient, the introducer needle 5240 is positioned within the cannula 5010. After inserting cannula 5010 into the patient, introducer needle 5240 is removed and septum 5060 is sealed from the fluid source, which in some embodiments of the devices described herein is a flow line. In some embodiments, the sensor probe 5025 is associated with an introducer needle 5072, which facilitates skin penetration for insertion of the sensor probe 5025. When the sensor probe 5025 is inserted into the patient, the sensor introduction needle 5072 at least partially surrounds the sensor probe 5025 in some embodiments.

In other embodiments, the infusion device 5010 is a needle and does not require an introducer needle 5240. In these embodiments, the infusion device 5010 is inserted into the patient and the septum 5060 seals against the fluid source.

In fig. 86A and 86B, when the infusion device 5010 and the sensor probe 5025 are both properly aligned, a force is applied to the bridge 5070. This forces the infusion device 5010 and sensor probe 5025 into the patient. Once in the patient, the release member 5052 is actuated through the aperture, thereby separating the infusion device 5010 and the septum 5060, and separating the sensor base 5023 from the bridge 5070. Referring to fig. 86B, introducer needles 5240 and 5072 are used which typically remain attached to bridge 5070 after insertion.

The bridge can be made of any desired material including plastic. The cannula can be any cannula in the art. The spacer 5060 can be made of rubber or plastic and of any design that can produce the desired function. In embodiments where the infusion device is a needle, any needle may be used. In embodiments in which an introducer needle is used, any needle, needle device, or introducer device may be used.

Infusion and sensor assemblies require the application of force to be inserted into the patient. Moreover, the infusion and sensor assembly requires that the infusion device and sensor be released from the infusion and sensor assembly. Thus, both the force and the release can be actuated manually, i.e. by the person performing these functions, or the insertion means can be used to actuate the assembly correctly. Referring now to fig. 87A-87E, an example of an inserter 5011 that can be manually operated is shown. The infusion device 5010 and the sensor 5023 are held by the bridge 5070. The inserter 5011 includes a cover 5012 for both the infusion device 5010 and the sensor 5023. As shown in FIGS. 87B-87E, using an inserter 5011, an infusion device 5010 and a sensor 5023 are both inserted into the device 10. Although fig. 87A shows the sharps exposed, in some embodiments, the cap 5012 completely encapsulates the sharps prior to the insertion process.

Interposer 5011 can be manually operated, but can also be incorporated into another interposer device, enabling mechanical advantage to be applied. Referring now to fig. 88A-88B, one embodiment of an interposer device 5013 is used in an apparatus similar to the interposer 5012 shown in fig. 87A-87E. The mechanism of the interposer device 5013 is shown in fig. 88C-88D. The actuating lever 5014 releases a spring (as shown in fig. 88C-88D) or provides another mechanical advantage that allows the inserter 5012 to be inserted into a device (not shown). The interposer 5012 will thus release the infusion device 5010 and the sensor 5023 and then the interposer 5012 can be removed from the interposer device 5013 and the interposer device 5013 refilled or the interposer device 5013 and the interposer 5012 can be discarded.

Various interposer devices are described herein. However, in other embodiments, a different insertion device is used, or the infusion device and sensor are introduced manually.

Features for securing the infusion and sensor assembly 5040 to the automatic inserter may be included. For example, the release member, shown as 5052 in fig. 86A-86B, may receive a pin of an automatic insertion device. Referring to fig. 89A and 89B, a representative embodiment of an automatic inserter 5100 is shown. As shown in the front view of fig. 89A, inserter 5100 includes a pin 5130 that travels within a pin slot 5140 inserted into cartridge recess 5120. In practice, the infusate and sensor assembly (not shown, shown as 5040 in fig. 86A and 86B) is pressed into the cartridge recess 5120, causing the pin 5130 to be inserted into a hole (shown as 5052 in fig. 86A and 86B) in the infusate and sensor assembly. As shown in the back view of fig. 89B, the compression spring rod 5145 is used to prepare inserter 5100 for release. Inserter 5100 is then held to the skin or to the tube housing and sensor housing on an alignment base (not shown) and released by depressing trigger 5110. When released, the pins 5130 travel in their slots 5140, thereby forcing the infusion set and sensor (neither shown) into the patient. Inserter foot 5160 limits the downward travel of the infusion and sensor assembly. The inserter may also automatically retract the introducer needle (not shown, see fig. 86B) from the infusion and sensor assembly.

The infusion and sensor assemblies may be preloaded in inserter 5100 prior to dispensing to the end user. As shown in fig. 90, in other embodiments, a cartridge 5080 may be used to protect a user and to protect sharps held in the assembly shown as 5040 in fig. 86A and 86B. Referring to fig. 90 and 86A-86B and 89A, in the cartridge embodiment 5080, the infusion and sensor assembly 5040 is embedded in a cartridge 5080. A cartridge 5080 is mounted in the cartridge recess 5120. The pin 5130 may protrude through the hole 5052 and into a recess 5090 in the cartridge 5080. When the inserter 5100 is actuated, the pin travels in the groove 5090 to insert a sharp object as the cartridge 5080 travels toward the patient. The cartridge 5080 may be constructed of a rigid material.

Referring now to fig. 91A-91C, various views of an embodiment of an inserter mechanism for use with an inserter are shown, such as the one shown as 5100 in fig. 89A and 89B. Fig. 91A shows a perspective view, fig. 91B shows a front view, and fig. 91C shows a side view of one embodiment of an inserter mechanism. The inserter 5100 has a pressure spring rod 5145, which is connected to a hammer pressure spring slider 5330 via a pressure spring link 5350, and serves to move the pressure spring slider 5330 to a load position. A power spring 5390 connects the hammer compression spring slide 5330 to the trigger 5110 and, when compressed, provides the downward force necessary to insert an infusion device or infusion and sensor assembly (not shown). The trigger hammer body 5340 is arranged below the hammer body pressure spring sliding block 5330 and between the pair of pressure spring connecting rods 5350; the trigger hammer 5340 transmits kinetic energy released from the power spring 5390 when the trigger 5110 is depressed. The energized trigger ram 5340 impacts a cartridge bolt 5380 located below. The cartridge bolts 5380 are coupled to a cartridge housing 5370 that houses a cartridge, one of which is shown, for example, in fig. 90. A cartridge bolt 5380 is also placed on top of the return spring 5360 to return the cartridge housing 5350 to the retracted position.

Fig. 92A-92F diagrammatically show a time sequence for cocking (cock) and releasing an inserter 5100 of the type described with reference to fig. 91A-91C. Fig. 92A shows inserter 5100 in a resting position. Lowering the pressure spring lever (not shown, see fig. 91A, 5145) causes the hammer pressure spring slide 5330 to lower and engage the trigger hammer 5340. Fig. 92B shows the hammer compression spring slide 5330 in a lowered position in which it engages the trigger hammer 5340. Raising the compression spring rod causes the ram compression spring slide 5330 and ram 5340 to be raised, thus compressing the power spring 5390; the resulting positions are shown in fig. 92C. After ensuring proper positioning of the inserter 5100 relative to the base (not shown) and/or the patient's skin, the trigger is depressed, thereby sending the trigger ram 5340 downward; fig. 92D shows the trigger ram 5340 in transit. As shown in fig. 92E, the trigger hammer 5340 impacts the cartridge bolt 5380 causing it to travel downward, insert one or more needles held in the cartridge housing (not shown), and compress the return spring 5360. FIG. 92F shows the return spring 5360 in the process of urging the cartridge bolt 5380 upward; this causes the cartridge housing and the cartridge (not shown) contained therein, as well as any associated introduction needle used, to retract.

Referring now to fig. 93A-93C, one embodiment of a time sequence for inserting and securing an infusion device (i.e., cannula or needle 5010) into base Y is shown. Fig. 93A shows a base Y with a locking feature 5210 located above the boot 5030. When the infusion device or cannula 5010 is inserted, the base Y is typically positioned against the skin of the patient 5220. Fig. 93B shows the cannula 5010 being forced through the cannula housing 5030 in the base Y. In this figure, an introducer needle 5240 is used, which extends through a septum (not shown) and is coaxially positioned within the cannula 5010; the sharp point of the introduction needle 5240 emerges from the tip (not shown) of the cannula 5010 in order to pierce the patient 5220. During insertion of the sleeve 5010, the resilient locking feature 5210 is pushed to one side. Fig. 93C shows the cannula 5010 fully inserted through the boot 5030 of the base Y with the cannula tip fully inserted into the patient 5220. The introducer needle 5240 has been removed and the septum 5060 has been self-sealing relative to a fluid source or flowline (not shown). The resilient locking feature 5210 engages the sleeve 5010, thereby preventing the sleeve 5010 from moving relative to the base Y. Although fig. 93A-93C illustrate the cannula 5010, the infusion and sensor assembly shown in fig. 86B can be inserted using the locking feature 5210 and method shown and described in fig. 93A-93C.

Referring now to fig. 92G-92H, an inserted cartridge bolt locking mechanism for use with an inserter, such as the one shown in fig. 91A-92F, is shown as 5100. The cartridge bolt locking mechanism can act as an interlock to prevent accidental release when the mechanism is cocked. The locking mechanism includes a detent 5420, which detent 5420 prevents downward movement of the cartridge bolt 5380 when engaged in the detent recess 5410. As shown in fig. 92G, when the pressure spring lever 5145 is in the closed position, the pressure spring lever 5145 contacts the stopper lever 5440, thereby rotating the stopper 5420 and preventing the stopper 5420 from being inserted into the stopper recess 5410. A detent spring 5430, which is disposed between the detent 5420 and the detent spring support 5450, is in a compressed position. The cartridge bolt 5380 and the trigger ram 5340 are free to move. As shown in fig. 92H, when the pressure spring lever 5145 is rotated into the downward position, the catch lever 5440 is released, thereby allowing the catch spring 5430 to force the catch 5420 to be inserted into the recess (here the catch 5420 is shown in the recess, but the recess is shown as 5410 in fig. 92G); thereby preventing downward movement of the cartridge bolt 5380. The return of the compression spring lever 5145 in turn returns the detent 5420 to the unlocked position. The cartridge bolt 5380 is then free to move downward during firing.

Referring now to fig. 94A-94C, one embodiment of a process of mating a cannula 5010, which is a conventional cannula requiring an introducer needle (as shown in fig. 86B), to base Y and into fluid communication with flowline 310 is shown. Fig. 94A shows a cross-sectional view of cannula 5010 with two septa (introducer needle septum 5062 and flow line septum 5270). The introducer needle septum 5062 seals the passageway 5280 of the hollow needle (not shown, shown as 5290 in fig. 94B) of the guide cannula 5010. The cannula introducer needle 5240 is shown positioned over the introducer needle septum 5062 and just prior to insertion of the introducer needle 5240.

Referring now to fig. 94B, introduction needle 5240 is shown inserted through introduction needle septum 5062. The user fits the cannula 5010 into the base Y, which has the rigid hollow needle 5290 facing upward. During insertion of cannula 5010 into base Y, introducer needle 5240 pierces flowline septum 5270 to establish fluid communication between flowline 310 and passageway 5280. If base Y is held against the patient (not shown) during insertion of cannula 5010 into base Y, fluid communication is established between flowline 310 and passageway 5280 at about the same time that the patient's skin is punctured. Referring now to fig. 94C, cannula 5010 is shown fully inserted into base Y with the introducer needle removed and in fluid communication with flowline 310.

In an alternative embodiment, the insertion of the infusion means and/or sensor is assisted by a vibrating motor cooperating with the fluid delivery means. The vibration motor may be activated simultaneously with the insertion of the infusion device and/or the sensor.

Binder

Referring now to fig. 95, a top perspective view of one embodiment of an adhesive patch 3100 for securing an object, such as the fluid delivery device 10, to the skin of a patient (not shown) is shown. While the adhesive patch 3100 is shown in the present shape, other shapes can be used. Any adhesive patch 3100 capable of securely holding the fluid delivery device may be used.

The fluid delivery device 10 is held securely under the central region 3130 of the adhesive patch 3100, which is attached to the patient's skin by the adhesive member 3111.

The adhesive features 3111 fan out in a radial pattern from the central region 3130 and are spaced apart from one another by intervening regions 3121. The radial arrangement of the adhesive members 3111 allows for attachment of the device 10 to a patient in a secure manner. In some embodiments, central region 3130 covers the entire device 10, however, in other embodiments, central region 3130 covers a portion of device 10. The central region 3130 may also include interlocking attachment features (not shown) that may be supported by complementary interlocking features (not shown) of the device 10. In alternative embodiments, the device 10 is securely attached on top of the central region 3130 (e.g., by an adhesive or interlocking features).

The adhesive patch 3100 is generally flat and is constructed from a polymer sheet or fabric. The adhesive patch 3100 may be supplied with adhesive adhered on one side and protected by a release liner, e.g. a sheet of releasable plastic, to which the adhesive will be more loosely adhered than the patch 3100. The pad may be a single continuous piece or may be divided into a plurality of areas that may be separately removed.

In an exemplary embodiment, the liner for the central region 3130 may be removed without removing the liner for the adhesive part 3111. To use the adhesive patch 3100, the user removes the pad of the central region 3130 and presses the device 10 against the newly exposed adhesive of the central region to attach the device 10 to the central region 3130. The user then places the device on the skin again, removes the liner from the adhesive part 3111, attaches the adhesive part to the skin, and repeats the attachment process with additional parts. The user may attach all of the adhesive parts 3111 or only some of the parts and save additional adhesive parts 3111 for use on another day. Because the adhesive typically used to attach to the skin remains securely attached for only a few days, using a set of adhesive parts 3111 on different days (e.g., every 3 to 5 days) will extend the time the device 10 remains securely attached to the skin and reduce the time, cost, and discomfort often involved in reapplying the device. Different patches may have indicia, such as different colors or numbers, to indicate the appropriate time to attach the various adhesive members 3111. The adhesive means 3111 may comprise perforations making it more frangible with respect to the central region 3130, so that the adhesive means used may be removed after use. Additional embodiments for extending the duration of time that the device 10 remains attached are discussed above with reference to fig. 79-83.

Fig. 96 schematically shows a cross-sectional view of the fluid delivery device 10 with the inserted cannula 5010 held securely underneath the adhesive patch 3100. The pad 3220 may be included between the device 10 and the patient's skin 3250 and allow air to flow to the skin. Air flow to the skin may be increased by including a passage 3230 in the pad 3220. The passage 3230 may also be formed by using a plurality of shims spaced apart or by constructing the shims 3220 from a highly porous material. Accordingly, the pad 3220 can have any shape and size, and in some embodiments, the pad 3220 is comprised of a plurality of separate pieces. The pad 3220 may be attached to the underside of the device 10 during manufacture, or may be attached to the device 10 by a user. Alternatively, the pad 3220 may be loosely placed on the skin by the user prior to use of the adhesive patch 3100. The pad 3220 may comprise a compliant material, such as a porous polymer foam.

Fig. 97 illustrates an embodiment of the invention using a first adhesive patch 3100 and a further adhesive patch 3300 to secure a device (not shown) to a patient. First, the device (not shown) is positioned for use and secured to the patient's skin (not shown) with the adhesive patch 3100 using the sheet-adhesive member 3111. The central region 3130 may be located on top of the device (as shown) or fixed underneath it. After a period of time, which may be longer or shorter, the second adhesive patch 3300 is positioned so that its central area is on top of the first adhesive patch 3100, and the adhesive parts 3320 of the second adhesive patch are secured to the patient's skin in the intervening areas between the adhesive parts 3111 of the first adhesive patch. A frangible region may be provided to remove loose or unwanted adhesive components 3111 associated with the earlier placed patch 3100.

Referring now to fig. 98 and 99, an embodiment is shown in which the adhesive patch 3100 has been 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 adhesive features 3111 radially arranged around the central void 3430. The two adhesive patches 3410 and 3420 each span approximately 180 ° of a semicircle, but other configurations can be used, such as: three patches each deployed at 120 or four patches each deployed at 90. In some embodiments, the adhesive can include more than four patches. The configuration described with respect to these embodiments follows the formula 360/n, where n is the number of patches. However, in other embodiments, the formulas shown and described herein are not applicable depending on the shape of the device. In further embodiments, the patches may also cover a range of more than 360 ° and thus overlap.

As shown in the perspective view of fig. 99, the central region 3130 has the form of a thin strip for attachment location along the periphery of the device 10, due to the presence of a central void (not shown, shown in fig. 98). Together, the two patches 3410 and 3420 securely attach 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 when the passageway 3230 is provided.

Fig. 100 shows a perspective view of an embodiment that includes the use of multiple patches of adhesive to extend the time that the device 10 remains attached to a patient (not shown) prior to removal. One of the plurality of partial adhesive pads 3420 is removed while the device 10 is held in place (either 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 alternative adhesive patch may be the same as the removed pad 3420 or may have an adhesive member 3111 that is positioned in an alternative configuration to allow adhesion to new skin between the areas previously covered by the adhesive patch 3420. The remaining adhesive patches 3410 may then be replaced in a similar manner. Indicia such as a color code may be used to indicate the elapsed time of the adhesive patch. The patches may also have a color change mechanism to indicate that their useful life has expired. Decorative patterns such as images and designs may be included on the patch.

Fig. 101 diagrammatically shows an embodiment in which a plurality of adhesive members 3111 are attached to the patient 12 and are also connected to the annular central region 3130 via a tether 3730. The tether 3730 may be a fiber or cord and may be elastic to reduce movement of the device 10 in response to movement of the patient 12. The use of the tether 3730 also increases the options available for the skin location of the adhesive member 3111.

The adhesive used in the embodiment illustrated in fig. 95-101 can be any effective and safe adhesive that can be applied to the skin of a patient. However, in one embodiment, the adhesive used is 3M product number 9915, a light and dark lace (value lace) medical non-woven tape.

Clamping and locking

Fig. 102A-102C schematically illustrate a mechanism for clamping or locking together the top and base of a fluid delivery device. Referring first to fig. 102A, a front view of the clip 6410 is shown. FIG. 102B shows a base Y with keyholes 6440 for two clamps; corresponding keyholes may also be included in the top (not shown). Referring now to fig. 102C, the top X and base Y may be aligned and a clip 6410 may be inserted through a keyhole (not shown, shown as 6440 in fig. 102B). Rotating the clamp 6410 at 90 ° causes the mast 6430 to move into the locked position. Depressing cam lever 6400 engages cam 6415, which is hinged to clamp pin 6420, to push against top X. As a result, the top X and the base Y are held between the cam 6415 and the post 6430 with a clamping force. Raising cam lever 6400 releases the clamping force and clamp 6410 can be rotated 90 ° and retracted to allow separation of top X and base Y. In some embodiments, the lever may serve as a protective cover for the top X.

An alternative embodiment for clamping portions of the device together is shown in fig. 103A-103D. Fig. 103A shows a perspective view of the cam guide 6500 and fig. 103B shows a top view. Cam guide 6500 has a key hole 6440 and a sloped surface 6510. Fig. 103C shows a cam follower 6520 having a central pin 6540 with a head 6560 attached at a first end and a rod 6550 attached to an opposite end. As shown in the cross-sectional view of fig. 103D, a cam follower (not shown, shown in fig. 103C) may be inserted into a keyhole (not shown, shown in fig. 103C) in top X, base Y, and cam guide 6500. Movement of the lever 6530 attached to the central pin 6540 causes the cam follower (not shown, shown in fig. 103C) to rotate, which causes the rod 6550 to ride along the sloped surface (not shown, shown as 6510 in fig. 103C) and thereby convert the rotational force into a force that firmly clamps the base Y and top X between the cam follower tip 6560 and the rod 6550.

Liquid storage device

An exemplary embodiment of a collapsible reservoir for retaining fluid is shown in fig. 104-106C. The collapsible reservoir has at least one portion or wall that is concave when fluid is withdrawn, thereby maintaining ambient pressure in its interior. In most embodiments, a sealable port (e.g., septum) is included in the reservoir. The port allows the reservoir to be filled with fluid using a syringe and also serves to connect to a flow line without leakage. Alternatively, an adapter may be used to connect the reservoir to the flow line. Alternatively, as shown above with reference to fig. 71, the needle may be associated with the reservoir and the septum may be associated with the terminal end of the flow line. The reservoir may be constructed of a plastic material known to be compatible with the fluid contained in the reservoir, even for very short durations. In some embodiments, the reservoir is fully collapsible, i.e., the reservoir does not include any rigid body surfaces.

Referring now to fig. 104, a cross-sectional view of the reservoir 20 is shown. A cavity 2645 is formed between the rigid reservoir body 6200 and the flexible reservoir diaphragm 6330 for holding a volume of fluid. Flexible diaphragm 6330 is sealingly attached around the perimeter of cavity 2645 to contain the fluid in cavity 2645. The flexible membrane 6330 imparts collapsible properties to the reservoir 20; it deforms inward when fluid is pumped from cavity 2645.

The septum 6270 sits in a neck 6240 extending from the body 6200. Septum 6270 serves as an interface between cavity 2645 and the flow lines. In some devices, the flow line terminates in a needle (not shown). In these embodiments, the needle can be inserted through septum 6270 to access the needle chamber 6280 portion of cavity 2645. The septum 6270 position can be maintained by positioning the septum 6270 between the endcap 6250 and a flange (not shown) formed at the junction of the interior wall 6281 of the needle chamber 6280 and the endcap bore 6282. A friction fit may be utilized to retain the endcap 6250 in the endcap bore 6282. When the endcap 6250 is inserted, its position is limited by the wall 6261 of the endcap bore 6282. The portion of the endcap 6250 closest to the septum 6270 may have a central aperture to allow a needle to be inserted through the endcap 6250 and into the septum 6270. Alternatively, the endcap 6250 can be pierced by a needle.

Fig. 105 shows a perspective view of the interior of the collapsible reservoir 20. The rim 6230 allows for attachment of a flexible reservoir diaphragm that may be attached by welding, clamping, adhering, or other suitable method to form a fluid seal. A guard structure 6290 may be included to allow fluid to flow to or from cavity 2645, but prevent the needle from entering the cavity, thereby preventing it from potentially piercing the reservoir septum.

Fig. 106A-106C illustrate an alternative embodiment of the reservoir, wherein an endcap 6250 sealingly attaches a septum 6270 to a wall 6320 of the reservoir. The wall 6320 may be constructed, for example, from a flexible sheet, such as PVC, silicone, polyethylene, or from ACLAR film. In some embodiments, the wall 6320 may be constructed of a thermoformable polyethylene sheet formed using an ACLAR film. The flexible sheet is compatible with the fluid. The wall may be attached to a rigid housing or may be part of a flexible plastic bag formed, for example, by folding and welding the ends of a plastic sheet. Fig. 106A shows an endcap 6250 sealed to a wall 6320 via a circular flap 6350. Spacers 6270 may be inserted into a turret 6340 protruding from the endcap 6250. The turret 6340 may be constructed of a material that is capable of deforming at high temperatures but is rigid at room temperature, such as low density polyethylene. Referring now to fig. 106B, a hot press 6310 or another device or process for melting is used to melt or bend the turret 6340 over the spacers 6270. Referring now to fig. 106C, a septum 6270 is shown secured to an endcap 6250.

Some fluids are sensitive to the storage state. For example, insulin is somewhat stable in glass vials in which it is typically stored during transportation, but may be unstable when exposed to certain plastics for extended periods of time. In some embodiments, the reservoir 20 is constructed of such plastic. In this case, the reservoir 20 may be filled with fluid just prior to use so that there is contact between the fluid and the plastic over a short period of time.

Reservoir filling station

Referring now to fig. 107, a reservoir filling station 7000 for filling the reservoir 20 with fluid is shown. Fluid may be withdrawn from its original container using syringe 7040 and introduced into reservoir 20 using filling station 7000. Filling station 7000 can include a substantially rigid filling station base 7010 hinged to a substantially rigid filling station cover 7020 via a hinge 7030. Accordingly, station 7000 can be opened and closed to receive and hold reservoir 20. A needle 7050 attached to the syringe 7040 may then be inserted through a filling aperture 7060 in the cap 7020 and through the reservoir septum 6270. Because the fill station cover 7020 is rigid, it limits the travel of the syringe 7040 and thus controls the depth of penetration of the needle 7050 into the reservoir 20 to prevent puncturing of the underside of the reservoir 20. The legs 7070, when supported on a surface, hold the station 7000 in an inclined position. Because the station 7000 is tilted, air will tend to rise toward the septum 6270 as fluid is injected from the syringe 7040 into the reservoir 20. After the injector 7040 injects the desired amount of fluid into the reservoir 20, the injector 7040 may be used to remove any remaining air in the reservoir 20. Because the filling station base 7010 and the cover 7020 are rigid, the flexible reservoir 20 generally cannot expand beyond a fixed volume and prevent overfilling of the reservoir 20. The base 7010 and the cover 7020 may be locked together with fasteners or a heavy lid may be used to further prevent over-inflation and overfilling of the reservoir.

Referring now to fig. 108A and 108B, an alternative embodiment of a reservoir filling station 7000 is shown. In this embodiment, a reservoir (not shown) is placed in the space between the cover 7020 and the base 7010. A hinge 7030 attaches the cover 7020 and the base 7010. As shown in fig. 108B, the reservoir (not shown) is located inside and a syringe (not shown) needle (not shown) is inserted into the fill aperture 7060. The fill aperture 7060 is directly connected to a septum (not shown) of the reservoir. Window 7021 represents the flow line in terms of the volume of fluid that has been injected into the reservoir.

The fluid delivery system typically includes a fluid delivery device and an external user interface, but in some embodiments, a full or partial internal user interface is included in the device. The device can be any device described herein or variations thereof.

FIG. 109A illustrates a flow chart of a data acquisition and control scheme for an exemplary embodiment of a fluid delivery system. The patient or healthcare professional utilizes an external user interface 14, which external user interface 14 is typically a base station or a hand-held unit housed separately from the fluid delivery device 10. In some embodiments, the user interface 14 is integrated with a computer, portable wireless telephone, personal digital assistant, or other consumer device. The user interface components may be in continuous or intermittent data communication with the fluid delivery device 10 via radio frequency transmission (e.g., via LF, RF, or a standard wireless protocol such as "bluetooth"), but can also be connected via a data cable, optical connection, or other suitable data connection. The external user interface 14 communicates with the processor 1504 to input control parameters, such as weight, fluid dosage ranges, or other data, and to receive status and functional updates, such as the presence of any error conditions due to a blocked flow, a leak, an empty reservoir, a poor battery condition, a need for maintenance, an expiration, a total amount of fluid delivered or remaining, or an unauthorized disposable component. The interface 14 may communicate the error signal to the patient monitor or medical professional by telephone, email, pager, instant message, or other suitable communication medium. The reservoir actuator assembly 1519 includes an actuator 1518 and a reservoir 1520. The distribution component 120 communicates data related to flow through the flow line to the processor 1504. The processor 1504 uses the flow data to adjust the actuation of the actuator 1518 to increase or decrease the flow from the reservoir pump assembly 1519 to approximately the desired dose and timing. Optionally, the feedback controller 1506 of the processor 1504 can receive data related to the operation of the reservoir pump assembly 1519 to detect a condition, such as an open or short circuit fault, or an actuator temperature.

FIG. 109B shows an alternative embodiment of the flowchart in FIG. 102A. In this embodiment, the absence of a dispensing assembly/sensor eliminates feedback based on fluid volume.

Referring now to fig. 110A, a flow diagram of one embodiment of the overall operation of a fluid delivery device in a fluid delivery system is shown. The user starts the system using a switch or from an external user interface (step 2800). The system is initialized by loading default values, running system tests (step 2810) and obtaining variable parameters such as desired basal and bolus doses. The variable parameters may be selected by the user using the user interface, i.e., using an input device such as a touch screen on the user interface, or by loading the saved parameters from memory (step 2820). Actuator timing is calculated based on the predicted or calibrated performance of the fluid delivery device (step 2830). The dispensing assembly is activated at the beginning of the actuation of the fluid delivery device (step 2840). Dispensing assembly data collection 2835 continues by actuation and delivery. During operation, the dispensing assembly provides data that allows for the determination of the cumulative volume of fluid that has flowed through the dispensing chamber over one or more time periods, as well as the flow rate. The fluid delivery device is actuated to cause fluid to flow through the flow line and into the dispensing chamber (step 2840). The drug flows from the dispensing chamber to the patient at a rate determined by the outlet impedance and, in some embodiments, the force applied by the diaphragm spring and the force applied by the pumping assembly (step 2860). If there is a user stop interruption, a low flow condition, a determination that the reservoir is empty based on expected cumulative flow or detection with an additional reservoir volume sensor, or any other alert operation with any part of the system, or any other alert operation specified by the user, the system will stop and notify the user (step 2870). If there is no user stop signal, a determination that the reservoir is empty, or another warning indicator, a check is made to determine if the actuator timing needs to be adjusted due to a deviation between the actual and desired flow rates or due to the user changing the desired flow rate (step 2880). If no adjustment is needed, the process returns to step 2840. If an adjustment is required, the process returns to step 2830. Referring now to fig. 110B, a flow diagram of another embodiment of the overall operation of the fluid delivery device in a fluid delivery system is shown. In this embodiment, the decision to adjust the actuation timing is made based on a change in user input or another feedback. In this embodiment, a dispensing assembly having a sensor for determining volume is not included; adjustments are therefore made based on alternative feedback mechanisms.

Wireless communication

Referring now to fig. 111, a layout of an embodiment using coils for inductive charging and wireless communication in a fluid delivery system is shown. As previously mentioned, the user interface assembly 14 may be embodied in the form of a handheld user interface assembly 14 that is in wireless communication with the fluid delivery device 10. A secondary coil (i.e., solenoid) 3560 may be employed in the fluid delivery device 10 as a wireless transceiver antenna in conjunction with a wireless controller 3580. Secondary coil 3560 may also function as a secondary transformer for at least partially charging device battery 3150 in conjunction with battery charging circuit 3540. In this embodiment, the user interface assembly 14 contains a primary coil 3490 for inductively coupling energy to a secondary coil 3560. When the user interface assembly 14 is proximate to the fluid delivery device 10, the primary coil 3490 energizes the secondary coil 3560. The energized secondary coil 3560 powers a battery charging circuit 3540 to charge a battery 3150 in the fluid delivery device 10. In some embodiments, primary coil 3490 also functions as an antenna to transmit and receive information from fluid delivery device 10 in conjunction with wireless controller 3470.

Referring now to fig. 112, some embodiments include long-range wireless communication (e.g., 20-200 feet or more) hardware in the fluid delivery device 10. Thus, the fluid delivery device 10 may be remotely monitored.

Still referring to fig. 112, an intermediate transceiver 6600, typically carried by the patient, can provide the advantages of telecommunications without increasing the size, weight, and power consumption of the fluid delivery device 10. As shown in the dataflow diagram representation of fig. 112, the wearable fluid delivery device 10 uses short-range hardware and associated software to transmit data to and receive data from the intermediate transceiver 6600. For example, the device 10 may be equipped to transmit data over a distance of approximately 3-10 feet. The intermediate transceiver 6600 can then receive the data and transfer the data to the user interface component 14 using remote hardware and software. The intermediate transceiver 6600 may also accept control signals from the user interface component 14 and relay these signals to the device 10. Alternatively, the user interface assembly 14 may also be capable of communicating directly with the fluid delivery device 10 located in the field. Such direct communication may be configured to occur only when the intermediate transceiver 6600 is not detected or alternatively whenever the user interface assembly 14 and the fluid delivery device are within range of each other.

Many types of data may be transmitted in this manner, including but not limited to:

data relating to pump actuation timing and volume measurements, as well as other data from the dispensing assembly, may be transmitted to the intermediate transceiver 6600 and in turn to the user interface assembly 14;

the alarm signal may be transmitted to the fluid delivery device 10 and may be transmitted from the fluid delivery device 10;

signals may be transmitted from the user interface 14 to the intermediate transceiver 6600 and from the intermediate transceiver 6600 to the fluid delivery device 10 to confirm data receipt;

an intermediate transceiver 6600 may be used to transmit control signals from the user interface assembly 14 to the fluid delivery device 10 for changing operating parameters of the device 10.

Referring now to fig. 113, a plan view of a particular embodiment of an intermediate transceiver 6600 is shown. Short-range transceiver 6610 communicates with nearby fluid delivery devices. The short-range transceiver and the intermediate transceiver 6600 of the device may communicate using one or more of a number of protocols and transmission frequencies known for short-range communications (e.g., radio frequency transmissions). Data received by the intermediate transceiver 6600 is fed to a microprocessor 6630, which may store the data in a memory 6620 (e.g., a flash memory chip), and retrieve the data as needed. Microprocessor 6630 is also connected to a remote transceiver 6640 that is in data communication with the user interface. For example, the intermediate transceiver 6600 and user interface components may operate in accordance with the bluetooth standard, which is a spread spectrum protocol that uses a radio frequency of about 2.45MHz and may operate over distances of up to about 30 feet. The Zigbee standard is an alternative standard operating in the ISM band of about 2.4GHz, 915MHz and 868 MHz. However, any wireless communication may be used.

Optionally, microprocessor 6630 analyzes the received data to detect a fault condition or maintenance need associated with the device. Some examples of fault conditions include, but are not limited to:

lack of received data for a period exceeding a set limit;

lack of data reception confirmation signals from the device or user interface component;

an overflow or near-overflow condition of the device reservoir 6620;

low power;

too high, too low, or incorrectly timed volume measurements are received from the fluid delivery device 10.

Based on the fault analysis, the microprocessor 6630 may trigger an alarm 6650 (e.g., a bell or buzzer). Microprocessor 6630 may also communicate an 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. Upon receiving the alarm signal, the user interface component may then relay the alarm signal over a longer distance to a medical professional or patient monitor (e.g., by pager or telephone or other communication method).

The power supply 6670 can be rechargeable and can store sufficient energy to operate continuously for a period of time, for example, at least 10 hours. However, the operating time will vary based on the application and device. The fluid delivery device may be reduced in size so that it can be easily carried in a pocket, purse, briefcase, backpack, or the like. One embodiment of the device comprises means for withstanding a conventional shock or flooding. Additional features may be included in some embodiments, including but not limited to decorative features or any of a wide range of consumer electronics capabilities, such as being able to play video games, send and receive instant messages, watch digital video, listen to music, and the like. A third party control may be included to cancel or restrict the use of such functionality during some or all of the day. Alternatively, the device may be as small and simple as possible and only used to repeat close-range signals over longer distances. For example, memory and analysis capabilities may be omitted.

Referring now to FIG. 114, a dataflow diagram for an embodiment of a system is shown. The intermediate transceiver 6600 is shown as serving as a universal patient interface that communicates with multiple devices in close proximity and relays information from those devices over long distances to one or more user interfaces associated with those devices. Examples of devices include wearable, implantable or internal medical devices, including fluid delivery systems, glucose sensors, knee joints with integrated strain sensors, tool electronic probes in pill form, defibrillators, pacemakers, and other wearable therapy delivery devices. Because different types of devices, and devices from different manufacturers, may utilize different close range communication standards and frequencies, the intermediate transceiver 6600 may include hardware (e.g., multiple antennas and circuitry) and software that support multiple protocols.

Storage battery charger

Reference is now made to fig. 115 and 116. One embodiment 7100 of an apparatus for recharging a battery is shown. In fig. 115, the top, non-disposable portion of the fluid delivery device 2620 is shown disconnected from the base, disposable portion of the fluid delivery device. The battery charger 7100 is used to charge a battery (not shown) in the top section 2620. In fig. 116, the top 2620 is shown positioned on the battery charger 7100. Latch 6530 is shown closed, connecting top 2620 to battery charger 7100. Thus, the latch 6530 for connecting the top 2620 to a base (not shown) also serves to connect the top 2620 to the battery charger 7100. The docking may form a direct power connection or may transfer power using inductive coupling. Also, in some embodiments of the system, the patient employs a plurality of non-disposable portions 2620 that rotate; that is, one non-disposable portion 2620 is charged while a second non-disposable portion (not shown) is used.

Various embodiments described herein include different types and configurations of elements, such as, for example, pump configurations, pump actuators, volume sensors, flow restrictors, reservoirs (and reservoir interfaces), sharps inserters, housings, locking mechanisms, user interfaces, on-board peripherals (e.g., controllers, processors, power supplies, network interfaces, sensors), and other peripherals (e.g., handheld remote controllers, base stations, repeaters, filling stations). It should be noted that alternative embodiments may incorporate various combinations of these elements. Thus, for example, the pump structures described with reference to one embodiment (e.g., the pumps shown and described with reference to fig. 15A-15D) may be used with any of a variety of configurations of pump actuators (e.g., a single shape memory actuator having a single mode of operation, a single shape memory actuator having multiple modes of operation, multiple shape memory actuators of the same size or of different sizes), and may be used with devices having various combinations of other elements (or the absence of other elements) and/or any of a variety of flow restrictors.

Further, while various embodiments are described herein with reference to a non-pressurized reservoir, it should be noted that a pressurized reservoir may be used in certain embodiments or under certain conditions (e.g., during priming and/or venting). In particular, pressurizing the reservoir may facilitate filling of the pump chamber, for example following retraction of the pump actuation member 54 shown and described with reference to fig. 15A-15D.

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

It should be noted that the section headings are included for convenience and are not intended to limit the scope of the invention.

In various embodiments, the methods disclosed herein, including those operations for controlling and measuring fluid flow and for establishing communication between related components, may be implemented as a computer program product for use with a suitable controller or other computer system (referred to generally herein as a "computer system"). Such an implementation may comprise a sequence of computer instructions fixed either on a tangible medium, such as a computer readable medium (e.g., a diskette, CD-ROM, EPROM, EEPROM, or fixed disk) or transmittable to a computer system, via a modem or other interface device, such as a communications adapter connected to a network over a medium. The medium may be either a tangible medium (e.g., optical or analog communications lines) or a medium implemented with wireless techniques (e.g., microwave, infrared or other transmission techniques). The sequences of computer instructions may implement the desired functionality previously described herein with respect to the described system. Those skilled in the art will appreciate that such computer instructions can be programmed in a number of programming languages for use with many computer architectures or operating systems.

Further, such instructions may be stored in any memory device, such as semiconductor, magnetic, optical, or other memory devices, and may be transmitted using any communications technology (e.g., optical, infrared, acoustic, radio, microwave, or other transmission technology). It is expected that such a computer program product will be distributed as a removable medium with accompanying printed or electronic literature (e.g., shrink wrapped software), preloaded with a computer system (e.g., on system ROM, EPROM, EEPROM, or fixed disk), or distributed from a server or electronic bulletin board over the network (e.g., the internet or world wide web). Of course, some embodiments of the invention may be implemented as a combination of software (e.g., a computer program product) and hardware. Further embodiments of the invention are implemented wholly in hardware or substantially in software (e.g. a computer program product).

It should be noted that the dimensions, sizes and numbers listed herein are exemplary and the invention is in no way limited thereto. In an exemplary embodiment of the invention, the patch-sized fluid delivery device may be approximately 6.35cm (2.5 inches) in length, approximately 3.8cm (1.5 inches) in width, and approximately 1.9cm (0.75 inches) in height, although again, these dimensions are merely exemplary and can vary widely for different embodiment dimensions.

While the principles of the invention have been described herein, it is to be understood by those skilled in the art that this description is made only by way of example and not as a limitation as to the scope of the invention. In addition to the exemplary embodiments shown and described herein, other implementations are also contemplated as falling within the scope of the present invention. Modifications and substitutions by one of ordinary skill in the art are considered to be within the scope of the present invention.

Claims (23)

1. An apparatus for dispensing a therapeutic fluid, the apparatus comprising:

a housing sized for attachment to a patient's body;

a reservoir for holding a therapeutic fluid enclosed in the housing;

a pump downstream of the reservoir and fluidly communicable with the reservoir, the pump enclosed in the housing; and

a dispensing assembly downstream of the pump and capable of fluid communication with the pump;

wherein the dispensing assembly has a sensor for repeatedly determining a parameter measuring the volume of therapeutic agent exiting the dispensing assembly or determining a function of the volume of therapeutic agent exiting the dispensing assembly.

2. The apparatus of claim 1, further comprising a control loop coupled to the sensor and the pump for adjusting the pump firing during normal flow conditions based on the measured parameter.

3. The apparatus of claim 2, wherein adjusting the pump firing comprises controlling at least one of a time of pump firing, a rate of pump firing, and a degree of pump firing.

4. The apparatus of claim 2, wherein the control loop further comprises a controller.

5. Apparatus according to claim 4, wherein the controller is arranged to estimate at least one of a flow rate of the fluid and an accumulated flow present in a dispensing chamber of the dispensing assembly based on the determined parameter.

6. Apparatus according to claim 5, wherein the controller is arranged to determine a compensation behaviour based on the estimate.

7. The apparatus of claim 1, wherein the sensor is one of an optical sensor and a capacitive sensor.

8. The apparatus of claim 1, wherein the sensor is an acoustic volume sensor.

9. The device according to claim 8, wherein the acoustic volume sensor comprises a loudspeaker arranged for acoustic volume sensing and generation of an audible alarm.

10. The apparatus of claim 8, wherein the acoustic volume sensor comprises a microphone arranged for acoustic volume sensing and monitoring operation of the pump.

11. The apparatus of claim 8, further comprising electronic components including a microphone and at least one of a sensing microphone and a reference microphone.

12. The device of claim 11, wherein the electronic component is disposed on a printed circuit board.

13. The apparatus of claim 8, further comprising:

a drive component for acoustically exciting a gas in an acoustically contiguous region to produce an acoustic reaction therein, the region comprising a sub-region of a dispensing chamber coupled to the dispensing assembly such that a change in volume of the dispensing chamber causes a change in volume of the sub-region; and

a processor.

14. The apparatus of claim 13, wherein the sensor comprises: a first acoustic transducer mounted at a first location in the acoustically contiguous region for generating an electrical signal based on the acoustic reaction; and a second acoustic transducer installed at a second position in the acoustic adjacent region for generating an electric signal constituting a reference, and

the processor is coupled to the first and second acoustic transducers and arranged to perform a flow determination step for determining a quantity related to a change in volume of the sub-region based on the acoustic reaction.

15. Apparatus according to claim 14, wherein the drive means is arranged to excite the gas at only a single frequency, and the electrical signal generated by the first acoustic transducer has a phase relationship with respect to the reference; and

the processor is arranged to perform the flow determining step by determining a quantity related to a change in the volume of the sub-region based on the temporal evolution of the phase relationship.

16. The apparatus of claim 13, wherein the sensor is configured to sense a blockage downstream of the dispensing assembly.

17. An apparatus for dispensing a fluid, the apparatus comprising:

a patch-sized housing;

a pump disposed in the housing, the pump having a pump outlet;

a dispensing assembly also disposed in the housing, the dispensing assembly including a dispensing chamber having a dispensing inlet and a dispensing outlet, wherein the dispensing inlet is coupled to the pump outlet, the dispensing assembly having a sensor for repeatedly determining a parameter that measures a volume of fluid exiting the dispensing chamber or a function of the volume of fluid exiting the dispensing chamber; and

a limited flow resistance coupled to the dispensing outlet of the dispensing chamber,

wherein the finite flow resistance is a passive flow resistance characterized in that the passive flow resistance comprises a tortuous path, wherein the housing comprises a disposable portion having an integral fluid path comprising the tortuous path.

18. The apparatus of claim 17, wherein the curved path comprises a coiled tubing.

19. The apparatus of claim 18, wherein the coiled tubing comprises at least two bends.

20. The apparatus of claim 17, wherein the curved path has a serpentine shape.

21. The apparatus of claim 17, wherein the housing has a maximum dimension, and the length of the path is greater than the maximum dimension.

22. The apparatus of claim 17, wherein the path comprises an effective diameter selected to provide a predetermined resistance based on at least one of a viscosity and a density of the fluid.

23. The apparatus of claim 17, wherein the length and inner diameter of the path are selected to provide a predetermined resistance based on at least one of a viscosity and a density of the fluid.

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