US20070066939A1 - Electrokinetic Infusion Pump System - Google Patents

Abstract

Various methods and devices are provided for delivering an infusion liquid using an electrokinetic infusion pump. The electrokinetic infusion pump can generally include an infusion housing having an infusion reservoir. The infusion reservoir has an infusion outlet and is capable of containing an infusion liquid. A plunger is movably coupled to the infusion housing and is adapted to be manually displaced relative to the infusion housing to load the infusion reservoir with infusion liquid. A movable partition can be disposed within the infusion housing and has a first surface in communication with an electrokinetic solution and a second surface, isolated from the first surface, in communication with the infusion reservoir. The electrokinetic infusion pump can further include an electrokinetic engine integrated within the plunger and adapted to selectively deliver electric potential across an electrokinetic porous media to cause the electrokinetic solution within the electrokinetic engine to displace the movable partition to effect delivery of at least a portion of the infusion liquid through the infusion outlet.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS
• This Application claims the benefit of priority to U.S. Provisional Application Serial No. 60/718,400, filed Sep. 19, 2005 entitled “Electrokinetic Pump Integrated within a Plunger of a Syringe Assembly;” No. 60/718,398, filed Sep. 19, 2005 entitled “Reduced Size Electrokinetic Pump Using an Indirect Pumping mechanism with Hydraulic Assembly;” No. 60/718,399, filed Sep. 19, 2005 entitled “Electrokinetic Syringe Pump with Manual Prime Capacity and Method of Use;” No. 60/718,364, filed Sep. 19, 2005 entitled “Syringe-Type Electrokinetic Infusion Pump for Delivery of Therapeutic Agents;” No. 60/718,578, filed Sep. 19, 2005 entitled “Syringe-Type Electrokinetic Infusion Pump and Method of Use;” No. 60/718,289, filed Sep. 19, 2005 entitled “Manual Prime Capability of an Electrokinetic Syringe Pump and Method of Use;” No. 60/718,572, filed Sep. 19, 2005 entitled “Electrokinetic Infusion Pump with Detachable Controller and Method of Use;” No. 60/718,397, filed Sep. 19, 2005 entitled “A Method for Detecting Occlusions in an Electrokinetic Pump using a Position Sensor;” No. 60/718,412, filed Sep. 19, 2005 entitled “A Magnetic Sensor Capable of Measuring a Position at an Increased Resolution;” and No. 60/718,577, filed Sep. 19, 2005 entitled “A Drug Delivery device Using a Magnetic Position Sensor for controlling a Dispense Rate of Volume;” all of which are hereby incorporated by reference in their entirety.
• This application is related to the following applications, all incorporated by reference herein in their entirety, and all filed concurrently herewith; “Infusion Pump with Closed Loop Control and Algorithm” (Attorney Docket No. 106731-3), “Malfunction Detection via Pressure Pulsation” (Attorney Docket No. 106731-6), “Infusion Pumps with a Position Sensor” (Attorney Docket No. 106731-18), “Systems and Methods for Detecting a Partition Position in an Infusion Pump” (Attorney Docket No. 106731-21), “Malfunction Detection with Derivative Calculation” (Attorney Docket No. 106731-22).
FIELD OF THE INVENTION
• The present invention relates to electrokinetic pumps useful for medical applications.
BACKGROUND OF THE INVENTION
• In many diagnostic and therapeutic medical applications (including drug delivery and analyte sampling/monitoring), precise transport of a drug, blood and/or other bio-fluid is important. However, with most conventional diagnostic and therapeutic medical systems, precise movement of large and small aqueous volumes of drugs and other bio-fluids is difficult to achieve. This difficulty arises because conventional systems employ mechanical components to effect fluid transport and delivery. Modification of such systems, to enable highly precise movement of small and large aqueous volumes of a solution containing biomaterials, would be impractical, as the complexity of such systems would make their manufacture expensive, time consuming and labor intensive. Further, such modification is likely to result in systems that are too large for many intended applications.
• Presently, electrokinetic (“EK”) or electro-osmotic manipulations of fluids represent the state-of-the art in controlled, high precision, small volume fluid transport and handling. Electro-osmosis involves the application of an electric potential to an electrolyte, in contact with a dielectric surface, to produce a net flow of the electrolyte.
• While electro-osmosis has found widespread and wide ranging applications in chemical analysis (e.g., high-speed liquid chromatography and other chemical separation procedures), its medical applications, such as for drug delivery and analyte sampling, have been limited, despite its advantages over conventional, mechanical approaches. Design challenges, including gas generation in the EK pump fluid, insufficient hydraulic pressure generation, and chemical degradation of the transported material caused by an applied electrical field, need to be overcome. When configured for non-medical use, these drawbacks do not pose major issues because the consequences are minimal, unlike in medical applications.
• One potentially useful medical application of such electro-osmosis technology is in the design and manufacture of infusion pumps for the delivery of agents such as drugs to a wearer of the pump.
• Accordingly, the present invention is directed to low-cost, high precision, reliable and compact EK pumps and systems adapted for medical applications, including, but not limited to, drug delivery and/or analyte sampling.
SUMMARY OF THE INVENTION
• The present invention generally provides methods and devices for delivering an infusion liquid using an electrokinetic infusion pump. In one embodiment, an electrokinetic infusion pump is provided which includes an infusion housing having an infusion reservoir. The infusion reservoir has an infusion outlet and is capable of containing an infusion liquid. A plunger is movably coupled to the infusion housing and is adapted to be manually displaced relative to the infusion housing to load the infusion reservoir with infusion liquid. A movable partition can be disposed within the infusion housing and has a first surface in communication with an electrokinetic solution and a second surface, isolated from the first surface, in communication with the infusion reservoir. The electrokinetic infusion pump further includes an electrokinetic engine integrated within the plunger and adapted to selectively apply electric potential across an electrokinetic porous media to cause the electrokinetic solution within the electrokinetic engine to displace the movable partition to effect delivery of at least a portion of the infusion liquid through the infusion outlet.
• In one exemplary embodiment, the movable partition can form part of a displacement piston that is adapted to be slidably disposed within the infusion housing to form, with an inner surface of the displacement piston, an adjustable receiving reservoir which is fluidly isolated from the infusion reservoir and capable of containing an electrokinetic solution. The adjustable receiving reservoir can be formed by a chamber extending within the displacement piston. The plunger can be in the form of a generally elongate member having a forward piston extending from a distal portion of an outer plunger housing.
• The electrokinetic infusion pump can also include other features, including a fixed supply reservoir effective to contain an electrokinetic solution and having a first electrode in communication therewith and a fixed receiving chamber being capable of receiving a volume of the electrokinetic solution from the fixed supply reservoir and having a second electrode in communication therewith. The electrokinetic porous media is disposed between the fixed supply reservoir and the fixed receiving chamber. The infusion pump can also include an inner channel formed in the forward piston and providing a fluid communication pathway between the adjustable receiving reservoir and a fixed receiving chamber. The forward piston can be adapted to slidably mate within the chamber extending within the displacement piston.
• The application of electric potential across the porous media can be effective to cause electrokinetic solution in the fixed supply chamber to flow through the porous media, into the fixed receiving chamber, through the inner channel of the forward piston and into the adjustable receiving chamber, causing a distally directed force to be placed on the displacement piston. This results in distal movement of the movable partition which will effect dispensing of at least a portion of the infusion liquid through the infusion outlet.
• In one exemplary embodiment, the diameter of the adjustable receiving chamber (D₁) can be less then the diameter of the fixed supply reservoir (D₂) to allow for a larger volume of infusion liquid to be displaced than the volume of electrokinetic solution that is displaced within the electrokinetic engine. In one embodiment, the ratio of (D₁/D₂)²defines an amplification factor and the amplification factor is greater than 1 and, for example, can be about 4.
• The electrokinetic infusion pump can also include a latch disposed on a portion of the plunger. The latch is selectively movable between a latched condition in which it is coupled to the displacement piston to allow movement of the displacement piston and the movable partition with movement of the plunger, and an unlatched condition in which it is uncoupled from the displacement piston to permit movement of the displacement piston and the movable partition independent of the plunger. The latched condition allows for loading of the infusion liquid into the infusion reservoir, and the unlatched condition allows for delivery of at least a portion of the infusion liquid through the infusion outlet when an electric potential is applied across the porous media to cause the electrokinetic solution within the electrokinetic engine to displace the movable partition.
• In one embodiment of the invention, the plunger can include a knob disposed on a proximal end thereof. The knob is adapted for grasping by a user to enable rotational and longitudinal movement of the plunger. In one exemplary embodiment, a surface of the outer plunger housing includes an axial groove formed along at least a portion of the length thereof and a perimeter groove extending transversely from a distal portion of the axial groove. The perimeter groove is angled towards a proximal end of the outer plunger housing. The infusion housing can include a surface feature slidably disposed within the axial and perimeter grooves of the outer plunger housing. The knob disposed on the plunger is adapted to move the plunger proximally to fill the infusion reservoir with infusion liquid, and the plunger is adapted to move proximally until the surface feature reaches the distal end of the axial groove. The knob is able to be rotated to cause the surface feature to travel along the perimeter groove to allow at least a portion of the infusion liquid to be delivered through the infusion outlet to prime the infusion pump. A first locking feature provided on the infusion housing can irreversibly engage a second locking features provided on the plunger to lock the plunger to the infusion housing.
• In another exemplary embodiment of the invention, an electrokinetic infusion pump is provided that includes a base capable of being attached to a patient, and an electrokinetic engine infusion module adapted to selectively apply an electric potential across an electrokinetic porous media. This causes an electrokinetic solution within the module to displace a movable partition disposed adjacent to a deformable infusion reservoir that is adapted to contain an infusion liquid to effect delivery of at least a portion of the infusion liquid through an infusion outlet. The module can be adapted to be detachably coupled to the base. The electrokinetic infusion pump further includes a controller configured to control the application of electric potential across the electrokinetic porous media and adapted to be detachably coupled to the base.
• The base can attach to a patient in a variety of way. For example, the base can be attachable to the patient using an adhesive, or the base can include a clip to enable attachment of the base to an article of clothing worn by a user. In one embodiment, the controller can be integrated with the electrokinetic engine infusion module, or the controller can be separate from the electrokinetic engine infusion module. The infusion pump can further include a battery disposed within the controller, or disposed within the electrokinetic engine infusion module. Further, the infusion outlet can include a needle or plastic cannula that extends through an opening in the base, or the infusion outlet can include a catheter extending from a portion of the infusion pump.
• In one embodiment, the electrokinetic porous media can separate a collapsible supply chamber containing an electrokinetic solution and an expandable receiving chamber within the electrokinetic engine such that electrokinetic solution is able to flow from the supply chamber through the porous media and into the expandable receiving chamber when a voltage is applied to the electrokinetic solution infusion module. The transfer of the electrokinetic solution from the collapsible supply chamber can be effective to expand the expandable receiving chamber such that the expandable receiving chamber applies a compressive force to the deformable infusion reservoir to effect delivery of the infusion liquid.
• Methods for delivering an infusion liquid using an electrokinetic infusion pump is also provided, and in one embodiment, the method can include priming the infusion liquid housed in an infusion reservoir of the electrokinetic pump to displace air in an infusion pump outlet and an infusion tubing. To dispense infusion liquid from the infusion pump, an electric potential, such as a voltage, can be applied across an electrokinetic porous media using a first and second electrode disposed on either side of the porous media. The electrical potential causes an electrokinetic solution to flow through the porous media from a first chamber containing the electrokinetic solution to a second chamber. As the second chamber fills with the electrokinetic solution, a movable partition is displaced and puts pressure on the infusion reservoir, causing infusion liquid to be delivered through the infusion outlet and into a user.
BRIEF DESCRIPTION OF THE DRAWINGS
• The invention will be more fully understood from the following detailed description taken in conjunction with the accompanying drawings, in which:
• FIGS. 1A and 1B are schematic illustrations of an electrokinetic infusion pump with closed loop control according to an embodiment of the present invention;
• FIG. 2 is an illustration of an electrokinetic infusion pump coupled with a vial containing infusion liquid;
• FIG. 3 is an illustration of a low profile electrokinetic infusion pump according to another exemplary embodiment of the present invention;
• FIG. 4 is an illustration of the electrokinetic infusion pump and pump controller ofFIG. 3 after the electrokinetic infusion pump has been filled with infusion liquid, connected to an infusion tube, and inserted into the pump controller;
• FIG. 5 is an illustration of an electrokinetic infusion pump according to another embodiment of the present invention, and includes an electrokinetic engine and an infusion module.
• FIG. 6 is a cross-sectional illustration of the electrokinetic infusion pump ofFIG. 5;
• FIG. 7 is an exploded view of the electrokinetic infusion pump ofFIG. 5;
• FIG. 8 is an illustration of an electrokinetic engine subassembly, as used in the electrokinetic infusion pump ofFIG. 5;
• FIG. 9 is an illustration of a piston/engine subassembly, as used in the electrokinetic infusion pump ofFIG. 5;
• FIG. 10 is a perspective view of an infusion housing, as used in the electrokinetic infusion pump ofFIG. 5;
• FIG. 11 is another perspective view of an infusion housing, as used in the electrokinetic infusion pump ofFIG. 5;
• FIG. 12 is a perspective view of an engine housing, as used in the electrokinetic infusion pump ofFIG. 5;
• FIG. 13 is another perspective view of an engine housing, as used in the electrokinetic infusion pump ofFIG. 5;
• FIG. 14 is a perspective view of a displacement piston, as used in the electrokinetic infusion pump ofFIG. 5;
• FIG. 15 is another perspective view of a displacement piston, as used in the electrokinetic infusion pump ofFIG. 5;
• FIGS. 16 through 29 are a series of drawings that illustrate operation of the electrokinetic infusion pump ofFIG. 5.
• FIG. 30 is an illustration of an electrokinetic infusion pump according to another embodiment of the present invention, and includes an electrokinetic engine and infusion module, and was used to generate basal and bolus delivery of infusion liquid;
• FIG. 31 is a graphical illustration of basal delivery shot size as a function of time using the electrokinetic infusion pump illustrated inFIG. 30;
• FIG. 32 is a graphical illustration of bolus delivery shot size as a function of time using the electrokinetic infusion pump illustrated inFIG. 30;
• FIG. 33 is an illustration of an electrokinetic infusion pump with closed loop control according to an additional embodiment of the present invention;
• FIG. 34 is an illustration of a magnetic linear position sensor as can be used in an electrokinetic infusion pump with closed loop control according to an embodiment of the present invention;
• FIGS. 35 and 36 illustrate portions of an electrokinetic infusion pump with closed loop control according to an embodiment of the present invention, including an electrokinetic engine, an infusion module, a magnetostrictive waveguide, and a position sensor control circuit;
• FIG. 37 is a block diagram of a circuit that can be used in an electrokinetic infusion pump with closed loop control according to an additional embodiment of the present invention;
• FIG. 38 is a block diagram of a sensor signal processing circuit that can be used in an electrokinetic infusion pump with closed loop control according to an additional embodiment of the present invention;
• FIG. 39 is an illustration of an electrokinetic infusion pump with closed loop control according to an embodiment of the present invention. The electrokinetic infusion pump with closed loop control illustrated inFIG. 39 includes an electrokinetic engine and infusion module, and was used to generate basal and bolus delivery of infusion liquid;
• FIG. 40 is a graph showing the performance of the electrokinetic infusion pump with closed loop control illustrated inFIG. 39 in both basal and bolus modes;
• FIG. 41 is a flow diagram illustrating a method of detecting occlusions in an electrokinetic infusion pump with closed loop control according to an additional embodiment of the present invention;
• FIG. 42 is a graph illustrating back pressure in an electrokinetic infusion pump with closed loop control according to an embodiment of the present invention;
• FIG. 43 is a graph illustrating the position of a moveable partition as a function of time when an occlusion occurs in an electrokinetic infusion pump with closed loop control according to an embodiment of the present invention;
• FIGS. 44A, 44B, and44C illustrate a low profile electrokinetic infusion pump according to an additional embodiment of the present invention. InFIG. 44A, the combined electrokinetic engine/infusion module is in an initial state, ready to draw infusion liquid from a vial. InFIG. 44B, the combined electrokinetic engine/infusion module illustrated inFIG. 44A is connected to a vial, and partially filled with infusion liquid. InFIG. 44C, the combined electrokinetic engine/infusion module illustrated inFIG. 44B is connected to an infusion line, and is dispensing infusion liquid;
• FIGS. 45A, 45B, and45C are illustrations of a low profile electrokinetic infusion pump according to an additional embodiment of the present invention. The low profile electrokinetic infusion pump illustrated inFIGS. 45A, 45B, and45C include a combined electrokinetic engine/infusion module, and a controller. InFIG. 45A, the combined electrokinetic engine/infusion module and controller are detached. InFIG. 45B, the combined electrokinetic engine/infusion module and controller are attached. InFIG. 45C, the combined electrokinetic engine/infusion module and controller are attached, and an infusion reservoir outlet is protruding from the combined electrokinetic engine/infusion module;
• FIGS. 46A and 46B are cross sectional illustrations the low profile electrokinetic infusion pump illustrated inFIGS. 45A, 45B, and45C;
• FIG. 47 is an illustration of the low profile electrokinetic infusion pump illustrated inFIGS. 45A, 45B,45C,46A, and46B with an alternative infusion reservoir outlet and mounting clip;
• FIG. 48 is an illustration of the low profile electrokinetic infusion pump illustrated inFIGS. 4A, 4B,4C,5A,5B and6 attached to a user by way of an adhesive. InFIG. 48, the low profile electrokinetic infusion pump is in wireless communication with a remote controller;
• FIG. 49 is an illustration of the low profile electrokinetic infusion pump illustrated inFIGS. 4A, 4B,4C,5A,5B,6, and7 attached to a user by way of a mounting clip and belt. InFIG. 49, the low profile electrokinetic infusion pump is in wireless communication with a remote controller, and an infusion line connects the user to the infusion reservoir outlet;
• FIG. 50 illustrates a perspective view of a mounting plate adapted to attach to a user and coupled to an electrokinetic infusion pump;
• FIG. 51 illustrates the mounting plate as shown inFIG. 50 with the electrokinetic infusion pump uncoupled therefrom;
• FIG. 52 illustrates another exemplary embodiment of a mounting plate adapted to attach to a user that includes a hole therethrough adapted to be positioned over an infusion tip disposed in the user;
• FIG. 53 is a perspective view of the mounting plate shown inFIG. 52;
• FIG. 54 illustrates another exemplary embodiment of a mounting plate and an electrokinetic infusion pump which are coupled together using a tubing;
• FIG. 55 is a cross-sectional view of an assembly adapted to allow a user to adjust the depth of a needle and cannula;
• FIG. 56 illustrates the assembly shown inFIG. 55 where the needle and the cannula are at a first position corresponding to a first depth;
• FIG. 57 illustrates the assembly shown inFIG. 55 where the needle and the cannula are at a second position corresponding to a second depth;
• FIG. 58 illustrates the assembly shown inFIG. 55 where the needle and the cannula are at a third position corresponding to a third depth;
• FIG. 59 illustrates a needle inserter assembly as used with the assembly shown inFIG. 55;
• FIG. 60A illustrates a cannula having a flange at a proximal end thereof;
• FIG. 60B illustrates a cannula having a flared proximal end;
• FIG. 60C illustrates a cannula having an extended flange at a proximal end thereof;
• FIG. 60D illustrates a cannula having a squared flange at a proximal end thereof;
• FIG. 61 illustrates a top septum and septum cap for use with the assembly shown inFIG. 55;
• FIG. 62 illustrates a bottom septum and septum cap for use with the assembly shown inFIG. 55;
• FIG. 63 is an illustration of an exemplary embodiment of an infusion pump that allows a user to modify the configuration and showing the infusion pump attached to a user in various stages of assembly;
• FIG. 64 is an illustration of an another exemplary embodiment of an infusion pump that allows a user to modify the configuration and showing the infusion pump attached to a user in various stages of assembly;
• FIG. 65 is an illustration of an another exemplary embodiment of an infusion pump that allows a user to modify the configuration and showing the infusion pump attached to a user in various stages of assembly; and
• FIG. 66 is an illustration of an another exemplary embodiment of an infusion pump that allows a user to modify the configuration and showing the infusion pump attached to a user in various stages of assembly.
DETAILED DESCRIPTION OF THE INVENTION
• Certain exemplary embodiments will now be described to provide an overall understanding of the principles of the structure, function, manufacture, and use of the devices and methods disclosed herein. One or more examples of these embodiments are illustrated in the accompanying drawings. Those skilled in the art will understand that the devices and methods specifically described herein and illustrated in the accompanying drawings are non-limiting exemplary embodiments and that the scope of the present invention is defined solely by the claims. The features illustrated or described in connection with one exemplary embodiment may be combined with the features of other embodiments. Such modifications and variations are intended to be included within the scope of the present invention.
• Various exemplary methods and devices are provided for electrokinetic pumping, which provides a driving force for displacing infusion liquid. Electrokinetic pumping (also known as electroosmotic flow) works by applying an electric potential across an electrokinetic porous media that is filled with electrokinetic solution. Ions in the electrokinetic solution form double layers in the pores of the electrokinetic porous media, countering charges on the surface of the electrokinetic porous media. Ions migrate in response to the electric potential, dragging the bulk electrokinetic solution with them. Electrokinetic pumping can be direct or indirect, depending upon the design. In direct pumping, infusion liquid is in direct contact with the electrokinetic porous media, and is in direct electrical contact with the electrical potential. In indirect pumping, infusion liquid is separated from the electrokinetic porous media and the electrokinetic solution by way of a moveable partition. Further details regarding electrokinetic pumps, including materials, designs, and methods of manufacturing, suitable for use in devices according to the present invention are included in U.S. patent application Ser. No. 10/322,083 filed on Dec. 17, 2002, which is hereby incorporated by reference.
• A variety of infusion liquids can be used in the electrokinetic infusion pumps illustrated inFIGS. 1-66, including insulin for diabetes; morphine and/or other analgesics for pain; barbiturates and ketamine for anesthesia; anti-infective and antiviral therapies for AIDS; antibiotic therapies for preventing infection; bone marrow for immunodeficiency disorders, blood-borne malignancies, and solid tumors; chemotherapy for cancer; and dobutamine for congestive heart failure. The electrokinetic infusion pumps illustrated inFIGS. 1-66 can also be used to deliver biopharmaceuticals. Biopharmaceuticals are difficult to administer orally due to poor stability in the gastrointestinal system and poor absorption. Biopharmaceuticals that can be delivered using the electrokinetic infusion pumps illustrated inFIGS. 1-62 include monoclonal antibodies and vaccines for cancer, BNP-32 (Natrecor) for congestive heart failure, and VEGF-121 for preeclampsia. A person skilled in the art will appreciate that any infusion liquid can be used with the infusion pumps described herein. The electrokinetic infusion pumps illustrated inFIGS. 1-62 can deliver infusion liquids to the patient in a number of ways, including subcutaneously, intravenously, or intraspinally. For example, the electrokinetic infusion pumps illustrated inFIGS. 1-66 can deliver insulin subcutaneously as a treatment for diabetes, or can deliver stem cells and/or sirolimus to the adventitial layer in the heart via a catheter as a treatment for cardiovascular disease.
• FIGS. 1A and 1B are schematic illustrations of an electrokinetic infusion pump withclosed loop control100 according to an embodiment of the present invention. The electrokinetic infusion pump withclosed loop control100 illustrated inFIGS. 1A and 1B includes anelectrokinetic infusion pump103, and aclosed loop controller105. The electrokinetic infusion pump withclosed loop control100 illustrated inFIG. 1A is in a first dispense position, while the electrokinetic infusion pump withclosed loop control100 illustrated inFIG. 1B is in a second dispense position.Electrokinetic infusion pump103 includes anelectrokinetic engine102 and aninfusion module104.Electrokinetic engine102 includes anelectrokinetic supply reservoir106, an electrokineticporous media108, an electrokineticsolution receiving chamber118, afirst electrode110, asecond electrode112, and anelectrokinetic solution114.Closed loop controller105 includes avoltage source115, and controls theelectrokinetic engine102.Infusion module104 includes aninfusion housing116, an electrokineticsolution receiving chamber118, amovable partition120, aninfusion reservoir122, aninfusion reservoir outlet123, and aninfusion liquid124. In operation, theelectrokinetic engine102 provides the driving force for displacing the infusion liquid124 from theinfusion module104.
• In one aspect, theelectrokinetic supply reservoir106, the electrokineticporous media108, and the electrokineticsolution receiving chamber118 can be filled during fabrication with anelectrokinetic solution114. Before use, the majority of theelectrokinetic solution114 is typically in theelectrokinetic supply reservoir106, with a small amount in the electrokineticporous media108 and the electrokineticsolution receiving chamber118. To displace theinfusion liquid124, a voltage is established across the electrokineticporous media108 by applying potential across thefirst electrode110 and thesecond electrode112. This causes electrokinetic pumping of theelectrokinetic solution114 from theelectrokinetic supply reservoir106, through the electrokineticporous media108, and into the electrokineticsolution receiving chamber118. As the electrokineticsolution receiving chamber118 receives theelectrokinetic solution114, pressure in the electrokineticsolution receiving chamber118 increases, forcing themoveable partition120 in the direction ofarrows127. As themoveable partition120 moves in the direction ofarrows127, it forces theinfusion liquid124 out of theinfusion reservoir outlet123. Theelectrokinetic engine102 continues to pump theelectrokinetic solution114 until themoveable partition120 reaches the end nearest theinfusion reservoir outlet123, displacing nearly all the infusion liquid124 from theinfusion reservoir122.
• Once again referring to the electrokinetic infusion pump withclosed loop control100 illustrated inFIGS. 1A and lB, the rate of displacement of the infusion liquid124 from theinfusion reservoir122 is directly proportional to the rate at which theelectrokinetic solution114 is pumped from theelectrokinetic supply reservoir106 to the electrokineticsolution receiving chamber118. The rate at which theelectrokinetic solution114 is pumped from theelectrokinetic supply reservoir106 to the electrokineticsolution receiving chamber118 is a function of the voltage and current applied across thefirst electrode110 and thesecond electrode112. It is also a function of the physical properties of the electrokineticporous media108 and the physical properties of theelectrokinetic solution114. As mentioned previously, further details regarding electrokinetic pumps, including materials, designs, and methods of manufacturing, suitable for use in devices according to the present invention are included in U.S. patent application Ser. No. 10/322,083 filed on Dec. 17, 2002, which has been incorporated by reference.
• InFIG. 1A, themovable partition120 is in afirst position119, while inFIG. 1B, themovable partition120 is in asecond position121. The position of themovable partition120 can be determined, and used by theclosed loop controller105 to control the voltage and current applied across thefirst electrode110 and thesecond electrode112. By controlling the voltage and current applied across thefirst electrode110 and thesecond electrode112, the rate at which theelectrokinetic solution114 is pumped from theelectrokinetic supply reservoir106 to the electrokineticsolution receiving chamber118 and the rate at which theinfusion liquid124 is pumped through theinfusion reservoir outlet123 can be controlled. The use of the position of themovable partition120 to control the voltage and current applied to thefirst electrode110 and thesecond electrode112 is referred to as closed loop control, and is a feature of an electrokinetic infusion pump according to one embodiment of the invention.
• The position of themovable partition120 can be determined using a variety of techniques. In one exemplary embodiment, themovable partition120 can include a magnet, and a magnetic sensor can be used to determine its position. In another exemplary embodiment, optical components can be used to determine the position of themovable partition120. Light emitters and photodetectors can be placed adjacent to theinfusion housing116, and the position of themovable partition120 can be determined by measuring variations in detected light. In still other embodiments, a linear variable differential transformer (LVDT) can be used. In embodiments where an LVDT is used, themoveable partition120 can include an armature made of magnetic material. An LVDT that is suitable for use in this invention can be purchased from RDP Electrosense Inc., of Pottstown, Pa.
• Depending upon the desired end use, electrokinetic infusion pumps can be completely integrated in a single assembly, or can be separated into a multitude of subassemblies that are connected by way of tubing. The electrokinetic infusion pumps100 illustrated inFIGS. 2 through 29 are integrated, while the electrokinetic infusion pump illustrated inFIG. 30 and39 are not integrated. Regardless of whether theelectrokinetic engine102 and theinfusion module104 are integrated, the position of themovable partition120 can be measured, and used to control the voltage and current applied across the electrokineticporous media108. In this way, theelectrokinetic solution114 and theinfusion liquid124 can be delivered consistently in either an integrated or separate configuration.
• Electrokinetic supply reservoirs106 as used in the electrokinetic infusion pumps100 illustrated inFIGS. 2-29,33, and35-38, and in low profile electrokinetic infusion pumps101 illustrated inFIGS. 44A-49, are collapsible, at least in part. This allows the size of theelectrokinetic supply reservoir106 to decrease as theelectrokinetic solution114 is removed, helping to minimize the power required in moving theelectrokinetic solution114 from theelectrokinetic supply reservoir106 to the electrokineticsolution receiving chamber118, and helping to prevent bubble formation that could cover thefirst electrode110, thesecond electrode112, or the electrokineticporous media108. Theelectrokinetic supply reservoir106 can be constructed using a collapsible sack, or can include a moveable piston with seals. Also, theinfusion housing116, as used in the electrokinetic infusion pumps100 illustrated inFIGS. 2 through 30, can be often rigid, at least in part. This feature favors displacement of themoveable partition120 as opposed to expansion of theinfusion housing116 as the electrokineticsolution receiving chamber118 receives theelectrokinetic solution114 pumped from theelectrokinetic supply reservoir106, and can provide more precise delivery ofinfusion liquid124.Moveable partition120 is designed to prevent migration of theelectrokinetic solution114 into theinfusion liquid124, while minimizing resistance to displacement as the electrokineticsolution receiving chamber118 receives theelectrokinetic solution114 pumped from theelectrokinetic supply reservoir106. In some embodiments, themoveable partition120 includes elastomeric seals that provide intimate yet movable contact betweenmoveable partition120 andinfusion housing116. In some embodiments, themoveable partition120 is piston-like, while in other embodiments themoveable partition120 is fabricated using membranes and/or bellows. As mentioned previously, closed loop control helps in maintaining consistent delivery of theelectrokinetic solution114 and theinfusion liquid124, in spite of variations in resistance caused by variations in the volume of theelectrokinetic supply reservoir106, by variations in the diameter of theinfusion housing116, and by variations in back pressure at the user's infusion site.
• FIG. 2 is an illustration of anelectrokinetic infusion pump100 coupled to avial134 containing theinfusion liquid124. Theelectrokinetic infusion pump100 illustrated inFIG. 2 has been partially filled withinfusion liquid124 and is connected to aneedle136. When fillingelectrokinetic infusion pump100 withinfusion liquid124, theelectrokinetic infusion pump100 and thevial134 are connected by way of theneedle136, and can be oriented as shown inFIG. 2. This assures introduction of theinfusion liquid124 into theelectrokinetic infusion pump100, as opposed togas125.Vial134 is typically sealed with arubber septum135.Rubber septum135 can be punctured by theneedle136, providing a conduit for theinfusion liquid124 to travel into theinfusion module104. When fillingelectrokinetic infusion pump100 using theneedle136 and thevial134, theelectrokinetic engine102 can be pulled out of theinfusion module104, drawing theinfusion liquid124 into theinfusion module104 in the same way one withdraws the plunger of a hypodermic syringe to draw liquid into the syringe. In another embodiment of this invention, a plunger can be sealingly adapted to said inner surface of theinfusion housing116. The plunger may include a handle capable of being manually withdrawn to prime theinfusion housing116 with theinfusion liquid124. The plunger may further include adisplacement piston146, a fixed receivingchamber154, and theelectrokinetic engine102.Displacement piston146 may be fixedly attached to aforward piston166, sometimes referred to as a forward portion. In turn, theforward piston166 may be fixedly attached to the fixed receivingchamber154. Fixed receivingchamber154 may be fixedly attached to theelectrokinetic engine102.
• FIG. 3 is an illustration of a low profileelectrokinetic infusion pump101 according to an additional embodiment of the present invention. Low profileelectrokinetic infusion pump101 includescontroller105 and combined electrokinetic engine/infusion module103. In the embodiments of low profileelectrokinetic infusion pump101 illustrated inFIGS. 1, 2,3A,3B,3C,4A,4B,4C,5A,5B,6,7, and8, combined electrokinetic engine/infusion module103 andcontroller105 can be handheld, or mounted to a user by way of clips, adhesives, or non-adhesive removable fasteners. Thecontroller105 can be directly or wirelessly connected to remote controllers that provide additional data processing and/or analyte monitoring capabilities. Thecontroller105 includesdisplay140,input keys142, andinsertion port156. After filling combined electrokinetic engine/infusion module103 with infusion liquid, combined electrokinetic engine/infusion module103 is inserted intoinsertion port156. Upon insertion intoinsertion port156, electrical contact is established betweencontroller105 and combined electrokinetic engine/infusion module103. An infusion set is connected to theinfusion reservoir outlet123 after combined electrokinetic engine/infusion module103 is inserted intoinsertion port156, or before it is inserted intoinsertion port156. Various means can be provided for priming of the infusion set, such as manual displacement ofmoveable partition120 towardsinfusion reservoir outlet123. After insertion, voltage and current are applied to the combined electrokinetic engine/infusion module103, and infusion liquid is dispensed. In one embodiment, the low profileelectrokinetic infusion pump101 can be worn on a user's belt providing an ambulatory infusion system.Display140 can be used to display a variety of information, including infusion rates, error messages, and logbook information. Thecontroller105 can be designed to communicate with other equipment, such as analyte measuring equipment and computers, either wirelessly or by direct connection.
• FIG. 4 is an illustration of theelectrokinetic infusion pump100 and thepump controller115 ofFIG. 3 after theelectrokinetic infusion pump100 has been filled with theinfusion liquid124, connected to theinfusion tube138, and inserted into thepump controller115. While theelectrokinetic infusion pump100 is in thepump controller115, an electrical contact is established between theelectrokinetic infusion pump100 and thepump controller115. This allows thepump controller115 to apply potential to theelectrokinetic infusion pump100, causing it to displace theinfusion liquid124. Theinfusion tube138 can be connected to a user subcutaneously to facilitate delivery of infusion liquid.Electrokinetic infusion pump100, thepump controller115, and theinfusion tube138 can be worn on a user's belt, providing an ambulatory infusion system. Thepump controller115 can include thedisplay140 and theinput keys142, allowing the user to communicate with thepump controller115. Thedisplay140 can be used to display a variety of information, including infusion rates, error messages, and logbook information. Thepump controller115 can be designed to communicate with other equipment, such as analyte measuring equipment and computers, either wirelessly or by direct connection. Theinfusion tube138 can be made using a wide variety of materials, but is typically made from flexible tubing, as commonly found in intravenous and subcutaneous infusion lines. Such lines are typically terminated with luer or other interlocking fittings.
• FIG. 5 is an illustration of anelectrokinetic infusion pump100 according to an embodiment of the present invention. Theelectrokinetic infusion pump100, as shown inFIG. 5, includes aninfusion housing116,infusion reservoir outlet123, apositioning knob170, and analignment tab176. Theinfusion housing116 is typically made from injection molded plastic, or machined plastic or metal. In one example,infusion housing116 is injection molded polypropylene, and is about 0.5 inches in diameter and about 2 inches long with a wall thickness of about 0.040 inches. Theinfusion reservoir outlet123 provides a conduit for infusion liquid to leaveelectrokinetic infusion pump100, and is designed in a way that allows rapid and removable connection toinfusion tube138, illustrated inFIG. 4. Theinfusion reservoir outlet123 can include an appropriate connector mechanism, such as male or female luer fittings to facilitate ease of connection toinfusion tube138. Thepositioning knob170 and thealignment tab176 allow precise positioning ofelectrokinetic infusion pump100 components, as discussed below. Thepositioning knob170 can be made out of any rigid material, but is typically injection molded from materials such as acrylic, polypropylene, and polycarbonate. Thealignment tab176 can be a separate component, but is typically an integral part ofinfusion housing116. Thealignment tab176 can be formed by injection molding or by machining, and it is generally finger-shaped such that it can provide deflection while in contact with positioning grooves, as discussed below. Theinfusion housing116 can be opaque, or it can be clear, thus allowing the amount of infusion liquid inelectrokinetic infusion pump100 to be determined visually.
• FIG. 6 is a cross-sectional illustration of theelectrokinetic infusion pump100 ofFIG. 5. As illustrated inFIG. 6, theelectrokinetic infusion pump100 is an integrated design, and includes theelectrokinetic engine102 and theinfusion module104. For purposes of clarity, the electrokinetic infusion pumps100 that are illustrated inFIGS. 6 through 29 are drawn without infusion liquid and electrokinetic solution, even though infusion liquid and electrokinetic solution is present in operation. It is envisioned thatelectrokinetic infusion pump100 could be provided to the user with theinfusion liquid124 preloaded. Alternatively, theelectrokinetic infusion pump100 can be provided without theinfusion liquid124, and the user can fillelectrokinetic infusion pump100 with theinfusion liquid124, such as by the technique illustrated inFIG. 2. Fillingelectrokinetic infusion pump100 is discussed in greater detail in reference toFIGS. 16 through 29. Whetherelectrokinetic infusion pump100 is provided to the user with or without infusion liquid, it will be pre-filled with electrokinetic solution.
• Referring again toFIG. 6, theelectrokinetic engine102 includes theengine housing163, thepositioning knob170, fixedsupply reservoir162,collapsible supply reservoir160, fixed receivingchamber154, connectingchannel156,electrokinetic seal168,first electrode110, electrokineticporous media108,second electrode112, andconnector172. Theengine housing163 has both aforward portion166 andrear portion164. Theaxial groove174 is located on the outside ofrear portion164 ofengine housing163. Theengine housing163 can be made using rigid materials, such as metals or plastics. Theengine housing163 is typically formed from injection molded plastics, such as polycarbonate, acrylic, acrylonitrile butadiene styrene, polypropylene, and polyethylene. Althoughengine housing163 is illustrated as a single piece, it can be molded in sections, then assembled using a variety of methods, including ultrasonic welding, adhesives, or mechanical press fit. The fixedsupply reservoir162 and the fixed receivingchamber154 are disposed insideengine housing163, and their inner surfaces may include portions offirst electrode110 andsecond electrode112. Fixedsupply reservoir162 and fixed receivingchamber154 are typically not flexible, and retain their shape during use.Collapsible supply reservoir160, on the other hand, is typically flexible, and collapses during use.Collapsible supply reservoir160 is typically molded using thermoplastic rubbers or reaction injection molding compounds. It can also be thermoformed using thin sheets of plastic. The connectingchannel156 is typically tubular in shape, and provides a conduit for electrokinetic solution to flow from fixed receivingchamber154 toadjustable receiving chamber158. The connectingchannel156 is typically about 0.039 inches in diameter by about 0.8 inches in length, and is formed by a variety of methods including injection molding and machining.
• Thefirst electrode110 and thesecond electrode112 can be made using a variety of techniques, as is described in previously mentioned U.S. patent application Ser. No. 10/322,083 filed on Dec. 17, 2002, which is incorporated by reference herein. In some embodiments of the present invention, thefirst electrode110 and thesecond electrode112 can be made from materials that do not produce gas bubbles when conducting electrical current, such as silver/silver chloride, oxides such as iridium oxide and zinc oxide, or combinations of metals and oxides. In other embodiments, a combination of electrode material and electrokinetic solution can be selected as to minimize gas bubble formation when conducting electrical current. For example, platinum electrodes can be used with an electrokinetic solution that contains quinone ions. When current is passed through platinum electrodes and electrokinetic solution that contains quinone ions, quinone is converted to hydroquinone without generating gas. It is desirable that the electrodes are conductive on at least the inside and outside surfaces to allow connection with theconnector172.
• Again referring toFIG. 6, theinfusion module104 includes theinfusion housing116, thealignment tab176, themovable partition120, theinfusion reservoir122, and theinfusion reservoir outlet123. Thealignment tab176 is movably disposed in theaxial groove174 of theelectrokinetic engine102 so as to guide movement of theelectrokinetic engine102 when it travels in an axial direction. In one embodiment, themovable partition120 forms a distal portion of thedisplacement piston146, which can also include afirst infusion seal148 and asecond infusion seal150 on an outer surface thereof, and anadjustable receiving chamber158 extending axially therein. Afirst latch pocket152 can also be formed on an outer surface of thedisplacement piston146. Together with thelatch151, thefirst latch pocket152 provides a means for removably latchingelectrokinetic engine102 todisplacement piston146.
• During operation,latch151 is unlatched from theelectrokinetic engine102, enabling thedisplacement piston146 to be free to move towardsinfusion reservoir outlet123, and during such movement, thefirst infusion seal148 andsecond infusion seal150 maintain a seal between theinfusion housing116 and thedisplacement piston146. Although two infusion seals are illustrated inFIGS. 6, 7,9, and14 through30, a single infusion seal can alternatively be used.
• Thefirst infusion seal148 and thesecond infusion seal150 can be made from a variety of materials, including buna, viton, and neoprene elastomers. Thefirst infusion seal148 andsecond infusion seal150 are typically ring shaped, and they can have a variety of cross-sectional shapes, including square, rectangular, and circular. Thefirst infusion seal148 and thesecond infusion seal150 typically have an inside diameter of about 0.350 inches, and a cross sectional diameter of about 0.080 inches.
• One skilled in the art will appreciate that theinfusion reservoir122 can vary in size, depending upon a variety of factors, including the particular pump application and the position of thedisplacement piston146. When thedisplacement piston146 is in the completely forward position nearest theinfusion reservoir outlet123, the volume of theinfusion reservoir122 is nearly zero.
• As further illustrated inFIG. 6, theengine housing163 has both aforward portion166 andrear portion164. Theforward portion166 mates within a channel formed inside of thedisplacement piston146 forming theadjustable receiving chamber158. Theelectrokinetic seal168 forms a seal between the inner surface of theadjustable receiving chamber158 and theforward portion166 of theengine housing163.
• Theelectrokinetic seal168 can be made from a variety of materials, as discussed previously with respect to thefirst infusion seal148 and thesecond infusion seal150. Theelectrokinetic seal168 typically has an inside diameter of about 0.110 inches, and a cross sectional diameter of about 0.085 inches. When thedisplacement piston146 is in the completely retracted position, farthest from theinfusion reservoir outlet123, theadjustable receiving chamber158 is at its minimum volume. When thedisplacement piston146 is in the completely forward position, closest to theinfusion reservoir outlet123, theadjustable receiving chamber158 is at its maximum volume.
• FIG. 7 is an exploded view of theelectrokinetic infusion pump100 ofFIG. 5, illustrating theinfusion housing116, thedisplacement piston146, theengine housing163, andinternal engine components165. Thedisplacement piston146 can include thefirst infusion seal148, thesecond infusion seal150, and thefirst latch pocket152. Theengine housing163 can include arear portion164, aforward portion166, asecond latch pocket178, afirst connector opening180, asecond connector opening182, and anelectrokinetic seal168.Internal engine components165 can include thefirst electrode110, thesecond electrode112, the electrokineticporous media108, thecollapsible supply reservoir160, theconnector172 and thepositioning knob170.Latch151 is also illustrated inFIG. 7.
• Thepositioning knob170 can perform several functions. First, it provides a handle that allows a user to grip and move theelectrokinetic engine102 and thedisplacement piston146, as further described below. Thepositioning knob170 can also provide a means to compressinternal engine components165. For example, during assembly, thefirst electrode110, thesecond electrode112, the electrokineticporous media108, thecollapsible supply reservoir160, and theconnector172 can be press fit into theengine housing163 using thepositioning knob170. Once assembled, thepositioning knob170 remains in place as a result of being press fit.
• Theconnector172 provides means for making electrical contact between thefirst electrode110, thesecond electrode112, and theelectrokinetic pump controller115, which is illustrated inFIGS. 3 and 4. Theconnector172 can be fabricated using a variety of materials and processes. In one embodiment, theconnector172 is die cut polyester, about 0.003 inches thick, with screen printed conductive carbon traces. In another embodiment, theconnector172 is die cut polyimide, about 0.003 inches thick, with gold traces that are formed using lithography. In either embodiment, theconnector172 is sandwiched between thefirst electrode110 and thesecond electrode112, and theengine housing163 during assembly, establishing electrical contact with thefirst electrode110 and thesecond electrode112. As illustrated inFIG. 4, when theelectrokinetic infusion pump100 is inserted into theelectrokinetic pump controller115, electrical contact is established with theconnector172 by way offirst connector opening180 andsecond connector opening182. Thefirst connector opening180 and the second connector opening182 are typically holes in theengine housing163, allowing contact with theconnector172, and can have diameters of approximately 0.060 inches.
• FIG. 8 is an illustration of anelectrokinetic engine subassembly184, as used in theelectrokinetic infusion pump100 ofFIG. 5.FIG. 8 illustrates the assembly of internal engine components, including thefirst electrode110, thesecond electrode112, the electrokineticporous media108, thecollapsible supply reservoir160, theconnector172, and thepositioning knob170. Theengine subassembly184 can be fitted into theengine housing163, as illustrated inFIG. 6, by a variety of techniques that are effective to form a leak proof seal between these components. Effective sealing is important to ensure that that the only path for flow of electrokinetic solution is through the electrokineticporous media108. For this reason a tight, and leak-proof assembly is required. Suitable joinder techniques includes press fitting, the use of adhesives, or heat sealing.
• FIG. 9 is an illustration of a piston/engine subassembly186, as used in theelectrokinetic infusion pump100 ofFIG. 5. InFIG. 9, thedisplacement piston146 is attached to theengine housing163, and fastened using thelatch151. Also visible in this view are thefirst infusion seal148, thesecond infusion seal150, thefirst connector opening180, and thesecond connector opening182. As will be discussed in respect toFIGS. 16 through 29, thedisplacement piston146 is initially attached to theengine housing163 using thelatch151. This allows thedisplacement piston146 and theengine housing163 to be moved back and forth as a unit, such as to load theinfusion liquid124. During operation, thelatch151 is disengaged, allowing thedisplacement piston146 and theengine housing163 to move independently, such as to dispenseinfusion liquid124.
• FIG. 10 is a perspective view of theinfusion housing116, as used in theelectrokinetic infusion pump100 ofFIG. 5. As illustrated inFIG. 10, theinfusion reservoir outlet123 and thealignment tab176 form part of theinfusion housing116.
• FIG. 11 is another perspective view of theinfusion housing116, as used in theelectrokinetic infusion pump100 ofFIG. 5. InFIG. 11, thealignment tab176 can be seen to include analignment pin188. Thealignment pin188 rides in theaxial groove174 and theperimeter groove192, as described below with reference toFIG. 13. Thealignment pin188 can have a variety of shapes, such as cylindrical or spherical, and it can be about 0.030 inches in diameter by about 0.040 inches high, and is either cylindrical or spherical in shape.
• FIG. 12 is a perspective view of theengine housing163, as used in theelectrokinetic infusion pump100 ofFIG. 5. InFIG. 12, thefirst connector opening180 and the second connector opening182 can be seen, as well as thesecond latch pocket178 andelectrokinetic seal groove190. Thelatch151, as seen inFIG. 9, is attached to theengine housing163 using thesecond latch pocket178, and can be attached permanently, for example, using adhesives, or it can be removable. Theelectrokinetic seal groove190 can provide a pocket for placement of theelectrokinetic seal168, as seen inFIG. 7. Theelectrokinetic seal groove190 can have a variety of shapes and configurations that are appropriate to seat theelectrokinetic seal168, but is typically rectangular in cross section and about 0.085 inches wide by about 0.049 inches deep.
• FIG. 13 is another perspective view ofengine housing163, as used in theelectrokinetic infusion pump100 ofFIG. 5. Theengine housing163 can include anaxial groove start175, anaxial groove174, anaxial groove stop177, aperimeter groove192, and a perimeter groove stop194 formed on the outside surface of therear portion164 of theengine housing163. As shown inFIG. 13, theelectrokinetic seal168 is disposed at the end of theforward portion166 of theengine housing163. Referring toFIGS. 6, 7,11, and13, theaxial groove start175, theaxial groove174, theaxial groove stop177, theperimeter groove192, and the perimeter groove stop194 can provide a guide when positioningelectrokinetic engine102. Thealignment pin188 is movably disposed in theaxial groove start175, theaxial groove174, theaxial groove stop177, theperimeter groove192, and theperimeter groove stop194, and can provide precise positioning of theelectrokinetic engine102 relative to theinfusion housing116. The axial groove start175 can limit movement of thealignment pin188 in the forward direction, towards theinfusion reservoir outlet123, and the axial groove stop177 can limit movement of thealignment pin188 in the backward direction, away from theinfusion reservoir outlet123. Theaxial groove174 can also limit rotational motion about the axis of theinfusion housing116 while positioning theelectrokinetic engine102 in either the forward or backward direction, towards or away from theinfusion reservoir outlet123. Theperimeter groove192 and the perimeter groove stop194 can be used to provide a consistent displacement of theinfusion liquid124 while priming theelectrokinetic infusion pump100, which is discussed in more detail below relative toFIGS. 20 through 23. Theaxial groove start175, theaxial groove174, theaxial groove stop177, theperimeter groove192, and the perimeter groove stop194 can have a variety of sizes, but in one embodiment, are typically about 0.031 inches wide and about 0.040 inches deep and can be formed from a variety of techniques, including by machining or injection molding.
• FIG. 14 is a perspective view of thedisplacement piston146, as used in theelectrokinetic infusion pump100 ofFIG. 5. Thedisplacement piston146 can include afirst latch pocket152, anadjustable receiving chamber158, a firstinfusion seal groove196, and a secondinfusion seal groove198. As mentioned above, although two infusion seals are illustrated inFIGS. 6, 7,9, and14 through30, a single infusion seal can be used in some embodiments. Thedisplacement piston146 can be made from a variety of materials, although it is preferably made of a plastic such as polyethylene, polypropylene, polycarbonate, acrylic, and acrylonitrile butadiene styrene. Thedisplacement piston146 can be machined, although it is typically injection molded. Thedisplacement piston146 typically is about 0.450 inches in diameter and about 0.819 inches long.
• Theadjustable receiving chamber158 is typically formed on an inner surface of thedisplacement piston146, and it is typically about 0.230 inches in diameter by about 0.731 inches long, and can be machined or injection molded. The surface of theadjustable receiving chamber158 can be smooth to allow a seal to be formed between theadjustable receiving chamber158 and theforward portion166 of theengine housing163 using theelectrokinetic seal168, as illustrated inFIG. 6. Thelatch151, as shown inFIG. 9, can be attached to thedisplacement piston146 using thefirst latch pocket152. Thelatch151 is typically pressed into thefirst latch pocket152 without the use of adhesive, since it can be removed in subsequent steps, as discussed below relative toFIG. 24. Below thefirst latch pocket152 is anenlarged pocket153. Theenlarged pocket153 is adapted to allow the circular end of thelatch151 to clear thefirst latch pocket152 by pressing thelatch151 inwards, towards theenlarged pocket153, which allows thedisplacement piston146 to disengage from thelatch151.
• Referring toFIGS. 1, 6, and14, when theelectrokinetic infusion pump100 is filled with theinfusion liquid124 and theelectrokinetic solution114, a potential can be applied across thefirst electrode110 and thesecond electrode112 to cause theelectrokinetic solution114 to be pumped from thecollapsible supply reservoir160 and the fixedsupply reservoir162, across the electrokineticporous media108, and into the fixed receivingchamber154, the connectingchannel156, and theadjustable receiving chamber158. The pressure generated inside the fixed receivingchamber154, the connectingchannel156, and theadjustable receiving chamber158 causes thedisplacement piston146 to move in the direction of theinfusion reservoir outlet123, displacing a portion of theinfusion liquid124. In one exemplary embodiment, the diameter (D₁) of theadjustable receiving chamber158 is less than the diameter (D₂) of thecollapsible supply reservoir160 and the fixedsupply reservoir162, causing the volume ofinfusion liquid124 that is displaced to be greater than the volume ofelectrokinetic solution114 that is pumped by a factor (D₂/D₁)², referred to as the hydraulic amplification factor. Using a hydraulic amplification factor lesselectrokinetic solution114 is required to displaceinfusion liquid124, thus reducing the overall size of theelectrokinetic infusion pump100, and the size of thefirst electrode110 and thesecond electrode112. Similarly, since lesselectrokinetic solution114 is pumped, total energy consumption is reduced. A side effect of the hydraulic amplification factor is that force on thedisplacement piston146 is reduced by the same factor, (D₂/D₁)²but generating higher pressures with theelectrokinetic engine102 can compensate for this side effect. While the hydraulic amplification factor can vary, it is generally greater than 1 or 2, and in one embodiment, the hydraulic amplification factor (D₂/D₁)²is approximately 4. There are two additional advantages of designing electrokinetic infusion pumps100 with hydraulic amplification factors of greater than 1, as illustrated inFIGS. 5 through 29. First, a nonpressurized region167, illustrated inFIG. 6, is created between theelectrokinetic seal168 and thesecond infusion seal150, which reduces pressure buildup in the electrokinetic solution should it leak beyond theelectrokinetic seal168, and thus minimizes the chance of electrokinetic solution migrating into the infusion liquid. A second advantage of designing electrokinetic infusion pumps100 with hydraulic amplification factors of greater than 1 is that the wall thickness of thedisplacement piston146 can be increased, providing a stifferadjustable receiving chamber158 which results in more consistent delivery of theinfusion liquid124. Although the electrokinetic infusion pumps100 illustrated inFIGS. 5 through 29 were designed with a hydraulic amplification factor of 4, both higher and lower hydraulic amplification factors can be used. In some designs a factor of 1 is used, while in other designs factors of less than 1 or greater than 1 are used.
• FIG. 15 is another perspective view of thedisplacement piston146, as used in theelectrokinetic infusion pump100 ofFIG. 5. As shown inFIG. 15, thedisplacement piston146 can include thefirst infusion seal148 and thesecond infusion seal150.
• FIGS. 16 through 29 illustrate the operation of theelectrokinetic infusion pump100 shown inFIG. 5. InFIG. 16, theelectrokinetic engine102 and thedisplacement piston146 are in a completely forward position within theinfusion housing116. Thealignment tab176 and the alignment pin188 (not shown) are positioned at theaxial groove start175.
• InFIG. 17, thepositioning knob170 is pulled in the direction indicated byarrow200. Thealignment tab176 and the alignment pin188 (not shown) move slidably along theaxial groove174 in the direction indicated byarrow202. Thedisplacement piston146 and theelectrokinetic engine102 travel in the direction indicated byarrow200, which increases the volume of theadjustable infusion reservoir122. Althoughinfusion liquid124 is not shown inFIG. 17, the motion of thedisplacement piston146 and theelectrokinetic engine102 can be used to fill theinfusion reservoir122 with theinfusion liquid124 by way of theinfusion reservoir outlet123 when the infusion reservoir outlet is coupled to thevial134, as illustrated inFIG. 2. As mentioned previously, theinfusion liquid124 is not shown inFIGS. 16 through 29 to make the illustrations more clear.
• InFIGS. 18 and 19, thepositioning knob170 is pulled further in the direction indicated byarrow200, causing thealignment tab176 and the alignment pin188 (not shown) to continue to move slidably along theaxial groove174 in the direction indicated byarrow202. Thedisplacement piston146 and theelectrokinetic engine102 travel in the direction indicated byarrow200, which further increases the volume of theadjustable infusion reservoir122, which further fills theinfusion reservoir122 with theinfusion liquid124.
• InFIG. 20, thepositioning knob170 is pulled in the direction indicated byarrow200 until thealignment tab176 and the alignment pin188 (not shown) reach theaxial groove stop177. At this point, thedisplacement piston146 and theelectrokinetic engine102 have reached their maximum travel in the direction indicated byarrow200, and theadjustable infusion reservoir122 is expanded to its maximum size, enabling it to accommodate a maximum volume of theinfusion liquid124. Theinfusion tube138, as illustrated inFIG. 4, can then be attached to theelectrokinetic infusion pump100 and primed, as described below relative toFIGS. 21 through 23.
• InFIG. 21, thepositioning knob170 is turned in the direction indicated byarrow204, causing thealignment tab176 and the alignment pin188 (not shown) to move slidably along theperimeter groove192. Referring toFIG. 20, theperimeter groove192 is not perpendicular to theaxial groove174, but is angled back slightly towards the positioningknob170. While theperimeter groove174 can be positioned at a variety of angles with respect to theaxial groove174, theperimeter groove192 is typically angled about 80 degrees relative to theaxial groove174, as indicated by anangle callout193, illustrated inFIG. 20. The angle of theperimeter groove192 relative to theaxial groove174 allows thedisplacement piston146 and theelectrokinetic engine102 to travel in the direction indicated byarrow202 while thepositioning knob170 is turned in the direction ofarrow204. Because thedisplacement piston146 and theelectrokinetic engine102 travel in the direction indicated byarrow202 as a result of movement alongperimeter groove192, theinfusion liquid124 is dispensed through theinfusion reservoir outlet123, thus priming theinfusion tube138, as illustrated inFIG. 4, by displacing air, and the filling theinfusion tube138 with theinfusion liquid124. Theperimeter groove192 therefore provides precise, reproducible displacement while priming theinfusion tube138.
• InFIG. 22, thepositioning knob170 is turned further in the direction indicated by thearrow204. Thealignment tab176 and the alignment pin188 (not shown) move slidably along theperimeter groove192, causing movement of thedisplacement piston146 and theelectrokinetic engine102 in the direction indicated by thearrow202, which further displaces theinfusion liquid124 through theinfusion reservoir outlet123 and into theinfusion tube138.
• InFIG. 23, thepositioning knob170 is turned further in the direction indicated byarrow204 until thealignment tab176 and the alignment pin188 (not shown) reach theperimeter groove stop194. At this point, thepositioning knob170 is no longer turned, priming of theinfusion tube138 is complete, and theelectrokinetic infusion pump100 is inserted into thepump controller115, as illustrated inFIG. 4. Theinfusion tube138 can be connected to a users tissue, subcutaneously, as mentioned previously. Theelectrokinetic infusion pump100 is then ready to dispense theinfusion liquid124, as illustrated inFIGS. 24 through 29.
• FIG. 24 illustrates thelatch151 as being disengaged from thefirst latch pocket152 by pressing it inward. As discussed above in the description ofFIG. 14, thefirst latch pocket152 can include anenlarged pocket153 below its surface that allows the circular end of thelatch151 to clear thefirst latch pocket152 when thelatch151 is pressed inward towards the center of thedisplacement piston146, allowing thedisplacement piston146 to disengage from thelatch151. Once thedisplacement piston146 is disengaged from thelatch151, thedisplacement piston146 can move in the direction ofarrow202 while theelectrokinetic engine102 remains stationary. Thelatch151 can be disengaged either before or after insertion of theelectrokinetic infusion pump100 into thepump controller115. Thelatch151 can be pressed towards the center of the displacement piston146 (i.e., disengaged) by deflecting theinfusion housing116 in the vicinity of thelatch151, or an opening can be provided in theinfusion housing116 allowing direct contact with thelatch151. In designs where thelatch151 is pressed after theelectrokinetic infusion pump100 is inserted into thepump controller115, means can be provided in thepump controller115 that can press thelatch151.
• FIG. 25 is a cross sectional view of theelectrokinetic infusion pump100 ofFIG. 24 in which thedisplacement piston146 is shown in the fully back position, with theinfusion reservoir122 at its maximum volume. Theforward portion166 of theengine housing163 is positioned inside of thedisplacement piston146, sealed with theelectrokinetic seal168. Theinfusion reservoir122 is sealed with thefirst infusion seal148 and thesecond infusion seal150 to prevent the infusion liquid from flowing beyond thedisplacement piston146.
• InFIG. 26, an electrical potential is applied to theelectrokinetic engine102 by way of thefirst connector opening180 and thesecond connector opening182, causing thedisplacement piston146 to move in the direction indicated byarrow202, while theelectrokinetic engine102 remains stationary. The motion of thedisplacement piston146 in the direction ofarrow202 causes theinfusion liquid124 to be displaced from theinfusion reservoir122, through theinfusion reservoir outlet123, through an infusion tube, and into the user. InFIG. 27, thedisplacement piston146 has moved further in the direction indicated byarrow202, thus displacing additional infusion liquid.
• FIG. 28 is a cross sectional view of theelectrokinetic infusion pump100 illustrated inFIG. 27. As a result of the applied electrical potential, electrokinetic solution is pumped across the electrokineticporous media108 from thecollapsible supply reservoir160 and the fixedsupply reservoir162 to the electrokineticsolution receiving chamber118, the connectingchannel156, and theadjustable receiving chamber158. Pumping is caused by the electrical potential applied across thefirst electrode110 and thesecond electrode112 by the pump controller115 (illustrated inFIG. 4).
• InFIG. 29, thedisplacement piston146 has moved in the direction ofarrow202 and is in the fully forward position. Infusion liquid has been completely dispensed through theinfusion reservoir outlet123 and the operation of theelectrokinetic infusion pump100 is stopped. At this point theelectrokinetic infusion pump100 can be removed from pump controller115 (illustrated inFIG. 4) and discarded.
EXAMPLE
• As discussed previously with respect toFIG. 1, when designing electrokinetic infusion pumps100, theinfusion module104 and theelectrokinetic engine102 can be integrated, as illustrated inFIGS. 2 through 29, or they can be separate components connected with tubing, as illustrated inFIG. 30. As illustrated inFIG. 30, theelectrokinetic infusion pump100 includes theinfusion module104 and theelectrokinetic engine102, connected by connection atubing300. Further details regardingelectrokinetic engine102, including materials, designs, and methods of manufacturing, suitable for use in theelectrokinetic infusion pump100 illustrated inFIG. 30 are included in U.S. patent application Ser. No. 10/322,083, previously incorporated by reference. Using theelectrokinetic infusion pump100 that is illustrated inFIG. 30, basal and bolus infusion liquid delivery rates were determined. Basal infusion liquid delivery rates typically dispense smaller volumes at a higher frequency, whereas bolus infusion liquid delivery rates typically dispense larger volumes at a lower frequency. Basal and bolus infusion liquid delivery rates were determined by applying an electric field acrosselectrokinetic engine102 for a period of time (referred to as the pump on time), then switching the electric field off for a period of time (referred to as the pump off time). The sum of pump on time and pump off time is referred to as cycle time. The mass of infusion liquid pumped during each cycle time (referred to as the shot size) was determined with a Mettler Toledo AX205 electronic balance. The shot size was determined repeatedly, using the same the same pump on time and the same cycle time, giving an indication of shot size repeatability. Using the density of water (1 gram per cubic centimeter), the shot size volume was derived from the mass of infusion liquid pumped during each cycle time.Electrokinetic engine102 was connected toinfusion module104 usingconnection tubing300.Connection tubing300 was rigid PEEK tubing with an inside diameter of 0.040 inches, an outside diameter of 0.063 inches, and a length of approximately 3 inches. A similar piece of PEEK tubing, approximately 24 inches long, was connected toinfusion reservoir outlet123 on one end, and to glass capillary tubing on the other end. The glass capillary tubing had an inside diameter of 0.021 inches, an outside diameter of 0.026 inches, and a length of about 6 inches. The end of the glass capillary tubing not connected toinfusion reservoir outlet123 was inserted into a small vial being weighed by the Mettler Toledo AX205 electronic balance. A small amount of water was placed in the bottom of the small vial, covering the end of the glass capillary tubing, and a drop of oil was placed on top of the water in the bottom of the small vial to reduce evaporation of the water.Electrokinetic engine102 was also connected to a vented electrokinetic solution reservoir (not shown inFIG. 30) that provided electrokinetic solution toelectrokinetic engine102.Electrokinetic engine102, vented electrokinetic solution reservoir,infusion module104,connection tubing300, the glass capillary tubing, and the Mettler Toledo AX205 electronic balance, were placed inside a temperature-controlled box, held to +/−1 degree C., to eliminate measurement errors associated with temperature variations. The temperature-controlled box was placed on top of a marble table to reduce errors from vibration. A personal computer running LabView software controlledelectrokinetic infusion pump100 and collected data from the Mettler Toledo AX205 electronic balance.
• To determine basal delivery of infusion liquid,electrokinetic engine102 was connected toinfusion module104 withconnection tubing300 and driven with a potential of 75V. At 75V,electrokinetic engine102 delivered electrokinetic solution toinfusion module104 at a rate of approximately 3.6 microliters/minute.Infusion module104 includeddisplacement piston146 that was designed with the hydraulic amplification factor (D₂/D₁)²equal to 4, as described previously relative toFIG. 14.Electrokinetic infusion pump100 was run with an on time of 12 seconds and a cycle time of 60 seconds, over a 12-hour period. During 12 hours, 720 shots were delivered.FIG. 31 is a graph showing measured shot size as a function of time for basal delivery of infusion liquid. As can be seen inFIG. 31, the shot size asymptotically approached a shot size of approximately 0.55 microliters. The average shot size was 0.65 microliters with a standard deviation of 0.1 microliters. In this experiment, no attempt was made to control shot size by varying the potential applied toelectrokinetic engine102.
• To determine bolus delivery of infusion liquid,electrokinetic engine102 was connected toinfusion module104 withconnection tubing300 and driven with a potential of 75V. At 75V,electrokinetic engine102 delivered electrokinetic solution toinfusion module104 at a rate of approximately 3.6 microliters/minute.Infusion module104 includeddisplacement piston146 that was designed with the hydraulic amplification factor (D₂/D₁)²equal to 4, as described previously relative toFIG. 14. Theelectrokinetic infusion pump100 was run with an on time of 80 seconds and a cycle time of 10 minutes, over a period of 3 hours and 50 minutes. During 3 hours and 50 minutes, 23 shots were delivered.FIG. 32 is a graph showing measured shot size as a function of time. As can be seen inFIG. 32, the average shot size was 9.8 microliters with a standard deviation of 0.6 microliters. In this experiment, no attempt was made to control shot size by varying the potential applied toelectrokinetic engine102.
• Closed Loop Control
• As discussed above, in one exemplary embodiment, the electrokinetic infusion pump can use closed loop control.
• FIG. 33 is an illustration of an electrokinetic infusion pump with closed loop control1100 according to an additional embodiment of the present invention. The electrokinetic infusion pump with closed loop control1100 includes a closed loop controller1105 and an electrokinetic infusion pump1103. In the embodiments of electrokinetic infusion pump with closed loop control1100 illustrated inFIGS. 33, 35,36,37 and38, the electrokinetic infusion pump1103 and closed loop controller1105 can be handheld, or mounted to a user by way of clips, adhesives, or non-adhesive removable fasteners. The closed loop controller1105 can be directly or wirelessly connected to remote controllers that provide additional data processing and/or analyte monitoring capabilities. As outlined earlier, and referring toFIGS. 1 and 33, closed loop controller1105 andelectrokinetic infusion pump103 can include elements that enable the position ofmovable partition1120 to be determined. The closed loop controller1105 includes display1140, input keys1142, and insertion port1156. After filling electrokinetic infusion pump1103 with infusion liquid1124, electrokinetic infusion pump1103 is inserted into insertion port1156. Upon insertion into insertion port1156, electrical contact is established between the closed loop controller1105 and the electrokinetic infusion pump1103. An infusion set is connected to the infusion reservoir outlet1123 after electrokinetic infusion pump1103 is inserted into insertion port1156, or before it is inserted into insertion port1156. Various means can be provided for priming of the infusion set, such as manual displacement ofmoveable partition1120 towards infusion reservoir outlet1123. After determining the position ofmoveable partition1120, voltage and current are applied across electrokinetic porous media1108, and infusion liquid1124 is dispensed. The electrokinetic infusion pump with the closed loop control1100 can be worn on a user's belt providing an ambulatory infusion system. The display1140 can be used to display a variety of information, including infusion rates, error messages, and logbook information. The closed loop controller1105 can be designed to communicate with other equipment, such as analyte measuring equipment and computers, either wirelessly or by direct connection.
• As discussed above, the position of themovable partition1120 can be determined using a magnetic position sensor.FIG. 34 illustrates the principals of magnetic position sensor1176. A magnetic position sensor1176, suitable for use in this invention, can be purchased from MTS Systems Corporation, Sensors Division, of Cary, N.C. In the magnetic position sensor1176, a sonic strain pulse is induced in a magnetostrictive waveguide1177 by the momentary interaction of two magnetic fields. A firstmagnetic field178 is generated by a movable permanent magnet1149 as it passes along the outside of the magnetostrictive waveguide1177. A second magnetic field1180 is generated by a current pulse1179 as it travels down the magnetostrictive waveguide1177. The interaction of the first magnetic field1178 and the second magnetic field1180 creates a strain pulse. The strain pulse travels, at sonic speed, along the magnetostrictive waveguide1177 until the strain pulse is detected by a strain pulse detector1182. The position of a movable permanent magnet1149 is determined by measuring the elapsed time between application of the current pulse1179 and detection of the strain pulse at the strain pulse detector1182. The elapsed time between application of the current pulse1179 and arrival of the resulting strain pulse at the strain pulse detector1182 can be correlated to the position of the movable permanent magnet1149. Alternative magnetic sensors are disclosed in the co-pending application entitled “Infusion Pumps with a Position Sensor” (Attorney Docket No. 106731-18), filed concurrently herewith.
• FIGS. 35-36 illustrate portions of an electrokinetic infusion pump with closed loop control according to an embodiment of the present invention.FIGS. 35-36 include the electrokinetic infusion pump1103, the closed loop controller1105, the magnetic position sensor1176, and the position sensor control circuit1160. The position sensor control circuit1160 is connected to theclosed loop controller105 by way of afeedback138. The electrokinetic infusion pump1103 can include an infusion housing1116, an electrokinetic supply reservoir1106, an electrokinetic porous media1108, an electrokinetic solution receiving chamber1118, an infusion reservoir1122, and amoveable partition1120. Themoveable partition1120 includes a first infusion seal1148, a second infusion seal1150, and a moveable permanent magnet1149. The infusion reservoir1122 can be formed between themoveable partition1120 and a tapered end of the infusion housing1116. The electrokinetic supply reservoir1106, the electrokinetic porous media1108, and the electrokinetic solution receiving chamber1118 can contain electrokinetic solution1114, while the infusion reservoir1122 can contain an infusion liquid1124. An electrical potential, such as voltage, is controlled by theclosed loop controller105, and is applied across the first electrode1110 and the second electrode1112. The magnetic position sensor1176 includes the magnetostrictive waveguide1177, the positionsensor control circuit160, and thestrain pulse detector182. The magnetostrictive waveguide1177 and the strain pulse detector1182 are typically mounted on the position sensor control circuit1160.
• InFIG. 35, themoveable partition120 is in a first position1168. The position sensor control circuit1160 sends a current pulse down the magnetostrictive waveguide1177, and by interaction of the magnetic field created by the current pulse with the magnetic field created by the moveable permanent magnet1149, a strain pulse is generated and detected by the strain pulse detector1182. The first position1168 can be derived from the time between initiating the current pulse and detecting the strain pulse. InFIG. 36, the electrokinetic solution1114 has been pumped from the electrokinetic supply reservoir1106 to the electrokinetic solution receiving chamber1118, which pushes themoveable partition1120 toward a second position1172. The position sensor control circuit1160 sends a current pulse down the magnetostrictive waveguide1177, and by interaction of the magnetic field created by the current pulse with the magnetic field created by the moveable permanent magnet1149, a strain pulse is generated and detected by the strain pulse detector1182. The second position1172 can be derived from the time between initiating the current pulse and detecting the strain pulse. A change in position1170 can be determined using the difference between the first position1168 and the second position1172. As discussed above, the position of themoveable partition1120 can be used in controlling flow in the electrokinetic infusion pump1103.
• Although the electrokinetic infusion pumps with closed loop control described in this invention are described in respect to electrokinetic engines, embodiments using other engines are envisioned. These include the use of engines based on gas generation and expanding gels and polymers, used alone or in combination with electrokinetic engines. Closed loop control, as envisioned in this invention, is useful in many types of infusion pumps. While closed loop control and occlusion detection are described herein with respect to an electrokinetic infusion pump, the principals of closed loop control and occlusion detection are applicable to any actuator that generates pressure in a hydraulic medium which causes movement of a moveable partition.
• FIG. 37 is a block diagram of a circuit that can be used in an electrokinetic infusion pump with closed loop control according to another exemplary embodiment of the present invention. The electrokinetic infusion pump1103 includes the electrokinetic engine1102, and themoveable partition1120. Themoveable partition1120 includes the moveable permanent magnet1149. The position of moveablepermanent magnet149 in electrokinetic infusion pump1103 is detected by magnetostrictive waveguide1177. Alternative magnetic position sensors are disclosed in co-pending application entitled “Infusion Pumps with a Position Sensor” (Attorney Docket No. 106731-18), filed concurrently herewith. Electrokinetic infusion pump with closed loop control1100 includes master control unit1190 and master control software1191. Master control unit1190 and master control software1191 control various elements in electrokinetic infusion pump with closed loop control1100, including display1140, input keys1142, non-volatile memory1200, system clock1204, user alarm1212, radio frequency communication circuit1216, positionsensor control circuit160, electrokinetic engine control circuit1222, andsystem monitor circuit1220. A battery1208 powers master control unit1190, and is controlled by a power supply and management circuit1210. The user alarm1212 can be audible, vibrational, or optical.
• Referring again toFIG. 37, electrokinetic infusion pump1103 includes electrokinetic engine1102 andmoveable partition1120. Electrokinetic engine1102 displacesmoveable partition1120 by pumping electrokinetic solution114 (not shown) againstmoveable partition1120.Moveable partition1120 includes moveable permanent magnet1149, and the position of moveable permanent magnet1149 in electrokinetic infusion pump1103 is detected by magnetostrictive waveguide1177. Although in this illustration magnetic techniques are used to determine the position ofmoveable partition1120, other techniques can be used, as mentioned previously. Other techniques include the use of light emitters and photodetectors. Electrokinetic infusion pump with closed loop control1100 includes master control unit1190 and master control software1191. Master control unit1190 is typically mounted to a printed circuit board and includes a microprocessor. Master control software1191 controls the master control unit1190. Display1140 provides visual feedback to users, and is typically a liquid crystal display, or its equivalent. Display driver1141 controls display1140, and is an element of master control unit1190. Input keys1142 allow the user to enter commands into closed loop controller1105 and master control unit1190, and are connected to master control unit1190 by way of digital input and outputs1143. Non-volatile memory1200 provides memory for closed loop controller1105, and is connected to master control unit1190 by way of serial input and output1202. The system clock1204 provides a microprocessor time base and real time clock for master control unit1190. The user alarm1212 provides feedback to the user, and can be used to generate alarms, warnings, and prompts. Radio frequency communication circuit1216 is connected to the master control unit1190 by way of serial input and output1218, and can be used to communicate with other equipment such as self monitoring blood glucose meters, electronic log books, personal digital assistants, cell phones, and other electronic equipment. Information that can be transmitted via radio frequency, or with other wireless methods, include pump status, alarm conditions, command verification, position sensor status, and remaining power supply. The position sensor control circuit1160 is connected to the master control unit1190 by way of digital and analog input and output1161, and is connected to magnetostrictive waveguide1177 by way of connector1175. As discussed previously, position sensor control circuit1160 uses magnetostrictive waveguide1177 and moveable permanent magnet1149 to determine the position ofmoveable partition1120. Electrokinetic engine control circuit1222 is connected tomaster control unit190 by way of digital and analog input and output1224, and to electrokinetic engine1102 by way of connector1223. The electrokinetic engine control circuit1222 controls pumping of the electrokinetic solution1114 and the infusion liquid1124, as mentioned previously. The electrokinetic engine control circuit1222 relies upon input from the position sensor control circuit1160, and commands issued by the master control unit1190 and the master control software1191, via digital and analog input and output1224. Fault detection in the electrokinetic engine control circuit1222 is reported to the master control unit1190 and the master control software1191 by way of the digital input and output1226. Thesystem monitor circuit1220 routinely checks for system faults, and reports status to themaster control unit190 and the master control software1191 by way of the digital input and output1221. The battery1208 provides power to the master control unit1190 and is controlled by the power supply and management circuit1210.
• FIG. 38 is a block diagram of a position sensor signal processing circuit that can be used in an electrokinetic infusion pump with closed loop control according to an additional embodiment of the present invention. The block diagram illustrated inFIG. 38 includes the electrokinetic infusion pump1103, the magnetorestrictive waveguide1177, the position sensor control circuit1160, the voltage nulling device1228, the voltage amplifier1238, digital to analog converter1232, the analog to digital converter1236, and the microprocessor1234. The electrokinetic infusion pump1103 includesmoveable partition1120 and infusion liquid1124. Themoveable partition1120 includes the moveable permanent magnet1149, which interacts with the magnetostrictive waveguide1177 in determining the position of themoveable partition1120 in the electrokinetic infusion pump1103. When the position sensor signal processing circuit illustrated inFIG. 38 is used, the resolution of magnetostrictive waveguide1177 is increased. In operation, the magnetostrictive waveguide1177 yields a voltage that varies as a function of the position of moveable permanent magnet1149. When the position sensor signal processing circuit illustrated inFIG. 38 is not used, the voltage from the magnetostrictive waveguide1177 ranges from 0 to a maximum value that is determined by analog to digital converter1236. The resolution of magnetostrictive waveguide1177 is determined by the maximum voltage analog todigital converter236 can process divided by the length of the magnetostrictive waveguide1177. When the position sensor signal processing circuit illustrated inFIG. 6 is used, voltage nulling device1228 offsets the voltage from the magnetostricitive waveguide1177 to either zero, or a value near zero. After the voltage from the magnetostrictive waveguide1177 is offset by voltage nulling device1228, nulled voltage1229 can be multiplied using voltage amplifier1238 to a value less than the maximum voltage that can be processed by analog to digital converter1236. The combined effect of nulling device1228 and voltage amplifier1238 is to divide the maximum voltage that can be processed by analog to digital converter1236 by a smaller length, and in that way increase the voltage change per unit length of movement by moveable permanent magnet1149. To avoid exceeding the capacity of analog to digital converter1236, the nulling step is repeated by voltage nulling device1228 multiple times asmoveable partition1120 moves along the length of electrokinetic infusion pump1103. Larger voltage change per unit length of movement by moveable permanent magnet1149 allows smaller detectable volumes, and more sensitive determination of the position of moveable permanent magnet1149. Upon insertion of electrokinetic infusion pump1103 into closed loop controller1105, an amplification factor of approximately 1 can be used by voltage amplifier1238, with a nulling voltage of 0 volts. Once moveable permanent magnet1149 moves from its original position, voltage nulling device1228 can apply nulling voltage that results in a nulled voltage of approximately zero, and voltage amplifier1238 can amplify the voltage, while keeping the voltage in the range of analog to digital converter1236. If power to closed loop controller1105 is inadvertently lost, the nulling voltage and amplification factor can be recovered from non-volatile memory1200, if it has been previously stored. In alternative embodiments, a fixed amplification factor can be used, and the nulling voltage varied to keep the voltage within the range of analog to digital converter1236.
EXAMPLE
• As mentioned previously, when designing an electrokinetic infusion pump with closed loop control1100, the infusion module1104 and the electrokinetic engine1102 can be integrated, as illustrated inFIGS. 33, 35,36,37, and38, or they can be separate components connected with tubing, as illustrated inFIG. 39. InFIG. 39, electrokinetic infusion pump with closed loop control1100 includes infusion module1104 and electrokinetic engine1102, connected by connection tubing1244. Infusion module1104 includesmoveable partition1120 and infusion reservoir outlet1123. Themoveable partition1120 includes moveable permanent magnet1149. Further details regarding electrokinetic engine1102, including materials, designs, and methods of manufacturing, suitable for use in electrokinetic infusion pump with closed loop control1100 are included in U.S. patent application Ser. No. 10/322,083, previously incorporated by reference. Using electrokinetic infusion pump with closed loop control1100 illustrated inFIG. 39, basal and bolus infusion liquid delivery rates were determined, using a method similar to the one described above.
• To determine basal delivery of infusion liquid, electrokinetic engine1102 was connected to the infusion module1104 with theconnection tubing244 and driven with a potential of 75V. At 75V, electrokinetic engine1102 delivered electrokinetic solution to infusion module1104 at a rate of approximately 15 microliters/minute. The electrokinetic engine1102 was run with an on time of approximately 2 seconds and an off time of approximately 58 seconds, resulting in a cycle time of 60 seconds and a shot size of approximately 0.5 microliters. The on time of electrokinetic engine1102 was adjusted, based upon input from the magnetostrictive waveguide1177 and positionsensor control circuit160. For each cycle of basal delivery, the position of the moveable permanent magnet1149 was determined. If the moveable permanent magnet1149 did not move enough, the on time for the next cycle of basal delivery was increased. If the moveable permanent magnet1149 moved too much, the on time for the next cycle of basal delivery was decreased. The determination of position of the moveable permanent magnet1149, and any necessary adjustments to on time, was repeated for every cycle of basal delivery.
• To determine bolus delivery of infusion liquid, theelectrokinetic engine102 was connected to the infusion module1104 with the connection tubing1244 and driven with a potential of 75V. Once again, at 75V electrokinetic engine1102 delivered electrokinetic solution toinfusion module104 at a rate of approximately 15 microliters/minute. The electrokinetic engine1102 was run with an on time of approximately 1120 seconds and an off time of approximately 120 seconds, resulting in a cycle time of 4 minutes and a shot size of approximately 30 microliters. For each cycle of bolus delivery, the position of moveable permanent magnet1149 was determined while the electrokinetic engine1102 was on. Once the moveable permanent magnet1149 moved the desired amount, electrokinetic engine1102 was turned off. The position of the moveable permanent magnet1149 was used to control on time of the electrokinetic engine1102 for every cycle of bolus delivery.
• Basal and bolus delivery of infusion liquid were alternated, as follows. Thirty cycles of basal delivery was followed by one cycle of bolus delivery. Then, thirty-seven cycles of basal delivery, was followed by one cycle of bolus delivery. Finally, thirty-eight cycles of basal delivery was followed by a one cycle of bolus delivery and forty-nine additional cycles of basal delivery.FIG. 40 is a graph showing measured shot size as a function of time, for alternating basal delivery1243 and bolus delivery1245, as outlined above. In basal mode, the average shot size was about 0.5 microliters with a standard deviation of less than 2%.
• FIG. 41 is a flow diagram illustrating a method of detecting occlusions in an electrokinetic infusion pump with closed loop control1100 according to an embodiment of the present invention. With reference toFIG. 41, andFIGS. 33 through 40, closed loop controller1105 starts with a normal status1246. In the next step, closed loop controller1105 determines position1250 of themoveable partition1120. After determining the position1250 of themoveable partition1120, the closed loop controller1105 waits before dose1252. During this time, the pressure in electrokinetic infusion pump1103 decreases. After waiting before dose1252, a fixed volume is dosed1254. This is accomplished by activating the electrokinetic engine1102. As a result of dosing a fixed volume1254 (electrokinetic engine on time), the pressure in the electrokinetic infusion pump1103 increases as a function of time, as illustrated inFIG. 10. Multiple graphs are illustrated inFIG. 42, showing the effect of time between shots (electrokinetic engine off time) on pressure in the electrokinetic infusion pump1103. Waiting 1 minute between shots results in a rapid build up of pressure. Waiting 5 minutes between shots results in a longer time to build pressure. The rate at which pressure builds is the same in each graph, but the starting pressure decreases as a function of time between shots, and therefore results in longer times to build pressure. Each graph eventually reaches the same approximate pressure, in this case about 3.2 psi. This is the pressure needed to displacemoveable partition1120. Returning toFIG. 41, after dosing a fixed amount1254, and waiting after dose1256 (during which time the pressure in electrokinetic infusion pump1103 increases), the change in position1258 ofmoveable partition1120 is determined. The position ofmoveable partition1120 can be determined using a variety of techniques, as mentioned previously. After determining the change in position1258 ofmoveable partition1120, closed loop controller1105 determines ifmoveable partition1120 has moved as expected1260, or if it has not moved as expected1264. If themoveable partition1120 has moved as expected1260, then no occlusion1262 has occurred, and the closed loop controller1105 returns to normal status1246. If themoveable partition1120 has not moved as expected1264, then an occlusion1266 has occurred, and the closed loop controller1105 enters analarm status248.FIG. 43 is a graph illustrating the position ofmoveable partition1120 as a function of time when an occlusion occurs in an electrokinetic infusion pump with closed loop control1100, according to the embodiment described in the previous example. As can be seen inFIG. 43, after about 70 minutes the rate at which themoveable partition1120 moves as a function of time suddenly decreases in region1251, even though constant voltage is applied to electrokinetic engine1102. This indicates that an occlusion has occurred, blocking the movement of themoveable partition1120.
• Electrokinetic Infusion Pump with a Detachable Controller
• FIGS. 44A-44C illustrate a low profile electrokinetic infusion pump according to an additional embodiment of the present invention. InFIG. 44A, combined electrokinetic engine/infusion module2103 is in an initial state, ready to draw infusion liquid2124 from vial2107. The combined electrokinetic engine/infusion module2103 includes an infusion housing2116, an electrokinetic solution receiving chamber2118, an electrokinetic supply reservoir2106, an electrokinetic porous media2108, and an infusion reservoir2122. The electrokinetic supply reservoir2106 and the electrokinetic solution receiving chamber2118 include electrokinetic solution2114. The infusion reservoir2122 is empty initially. InFIG. 44B, the electrokinetic engine2102 has been moved by the user in the direction of arrow2328, drawing the infusion liquid2124 from a vial2107 and into the infusion reservoir2122. At the top of the infusion reservoir2122, a moveable partition2120 forms an interface between the infusion reservoir2122 and the electrokinetic solution receiving chamber2118. InFIG. 44C, electrical potential has been applied across the electrokinetic porous media2108, and the electrokinetic solution2114 has moved from the electrokinetic supply reservoir2106 to the electrokinetic solution receiving chamber2118, displacing the infusion liquid2124 from the infusion reservoir2122 and through an infusion reservoir outlet2123. As electrokinetic solution2114 is pumped through the electrokinetic porous media2108 into the electrokinetic solution receiving chamber2118, the electrokineticsolution receiving chamber118 expands and the moveable partition2120 pushes against the infusion liquid2124 in infusion reservoir2122. The infusion reservoir2122, electrokinetic solution receiving chamber2118, and the electrokinetic supply reservoir2106 can be fabricated using a variety of techniques, although a preferred embodiment includes flexible plastic films in compliant pouch-like configurations. Compliant pouch-like configurations allow infusion reservoir2122, electrokinetic solution receiving chamber2118, and electrokinetic supply reservoir2106 to readily expand and contract, and create minimal resistance to flow in electrokinetic solution2114. By using compliant pouch-like configurations with the infusion reservoir2122, the electrokinetic solution receiving chamber2118, and the electrokinetic supply reservoir2106, various cross sectional configurations can be used for combined electrokinetic engine/infusion module2103, including circular, oval, and rectangular. Non-circular cross sections can allow for a more compact configuration, and are desirable in some embodiments. Although not shown in this figure, electrodes (as illustrated inFIG. 1) allow electrical contact with electrokinetic solution2114, on both sides of the electrokinetic porous media2108. The electrodes can be disk shaped, cylindrically shaped, or shaped like wires, and allow electrical contact with the electrokinetic solution2114 from the outside of the electrokinetic supply reservoir2106 and the electrokinetic solution receiving chamber2118.
• FIGS. 44A45C are illustrations of a low profile electrokinetic infusion pump2101 according to an additional embodiment of the present invention. The low profile electrokinetic infusion pump2101 illustrated inFIGS. 44A-44C include a combined electrokinetic engine/infusion module2103, and a controller2105. InFIG. 45A, combined electrokinetic engine/infusion module2103 and controller2105 are detached. Electrokinetic engine/infusion module2103 includes a retaining clip2317 and pump contacts2331. The controller2105 includes input keys2142, a display2140, and controller contacts2333 (shown inFIG. 47). The retaining clip2317 secures the controller2105 to combined electrokinetic engine/infusion module2103 when they are attached. The retaining clip2317 can be a molded feature, as shown, or a separate mechanical piece, as long as it secures the controller2105 to combined electrokinetic engine/infusion module2103 and is easily fastened and unfastened. The pump contacts2331 interface with the controller contacts2333 (shown inFIG. 47), and enable electrical connection between the controller2105 and combined electrokinetic engine/infusion module2103. Among other things, this allows the controller2105 to control pumping action in combined electrokinetic engine/infusion module2103, and can allow controller2105 to determine the status of combined electrokinetic engine/infusion module2103 in respect to errors and remaining infusion liquid. In some embodiments, the display2140 includes at least one light emitting diode, and in other embodiments the display2140 includes a liquid crystal display. In embodiments where the display2140 includes at least one light emitting diode, different colors can be used to indicate the status of low profile electrokinetic infusion pump2101. In embodiments where the display2140 includes a liquid crystal display, text messages can be used to communicate the status of low profile electrokinetic infusion pump2101. The input keys2142 can be used to navigate messages provided by display2140, and in issuing commands to low profile electrokinetic infusion pump2101. Although two input keys2142 are illustrated, a single input key2142 can be used, or more than two input keys2142 can be used, depending upon their function. InFIG. 45B, combined electrokinetic engine/infusion module2103 and controller2105 are attached. The retaining clip2317 keeps controller2105 in place, but it can be displaced to allow detachment of controller2105 from combined electrokinetic engine/infusion module2103. The overall size of low profile electrokinetic infusion pump2101 can vary, but is typically the size of a small mobile phone, allowing for discrete placement by its user. InFIG. 4C, the perspective has been rotated, allowing infusion reservoir outlet2123 and contact surface2325 to be seen. InFIG. 45C, infusion reservoir outlet2123 is a fixed cannula that allows injection of infusion liquid2124 into the body of a user. When infusion reservoir outlet2123 is in the form of a fixed cannula, it penetrates the skin when low profile electrokinetic infusion pump2101 is attached to the user, eliminating the need for an additional infusion line. The fixed cannula can be permanently or removably attached to combined electrokinetic engine/infusion module2103. A removably attached fixed cannula allows periodic replacement. The combined electrokinetic engine/infusion module2103 includescontact surface325, providing a support for controller2105 and a surface for contact with a user. The contact surface2325 can optionally include an adhesive2326 (as illustrated inFIGS. 46A and 46B) or a mounting clip2335 (as illustrated inFIG. 47).
• FIGS. 46A and 46B are cross sectional illustrations of low profile electrokinetic infusion pump2101 illustrated inFIGS. 44A-45C. InFIG. 46A, combined electrokinetic engine/infusion module2103 is filled with infusion liquid2124. The electrokinetic supply reservoir2106 is filled with electrokinetic solution2114, while the electrokinetic porous media2108 and the electrokinetic solution receiving chamber2118 also contain small amounts of electrokinetic solution2114. In this embodiment, the infusion reservoir outlet2123 is a fixed cannula, and the contact surface2325 is covered with adhesive2326. The controller2105 is attached to combined electrokinetic engine/infusion module2103, and is fixed in place by retaining clip2317. The controller contacts2333 are connected to the pump contacts2331, establishing electrical contact between the controller2105 and the combined electrokinetic engine/infusion module2103. In the embodiment of low profile electrokinetic infusion pump2101 illustrated inFIGS. 46A and 46B, the controller2105 includes a battery2313 that can be reused when the combined electrokinetic engine/infusion module2103 is spent. In the embodiment of low profile electrokinetic infusion pump2101 illustrated inFIG. 47, the combined electrokinetic engine/infusion module2103 includes a battery2313 that can be disposed of when the combined electrokinetic engine/infusion module2103 is spent. InFIG. 46B, the low profile electrokinetic infusion pump2101 has dispensed a portion of infusion liquid2124. The electrokinetic solution2114 has been pumped from the electrokinetic supply reservoir2106, across the electrokinetic porous media2108, and into the electrokinetic solution receiving chamber2118. As the electrokinetic solution2114 flows into the electrokinetic solution receiving chamber2118, the electrokinetic solution receiving chamber2118 expands, forcing infusion liquid2124 out of the infusion reservoir2122, and through the infusion reservoir outlet2123, as indicated by arrow2329. The controller2105 applies potential across the electrokinetic porous media2108, causing the electrokinetic solution2114 to flow from the electrokinetic supply reservoir2106 into the electrokinetic solution receiving chamber2118. As previously mentioned, electrodes (as illustrated inFIG. 1) allow electrical contact with the electrokinetic solution2114, on both sides of the electrokinetic porous media2108. The electrodes can be of a variety of appropriate shapes, including disk shaped, cylindrical, or shaped like wires, and they are effective to allow electrical contact with the electrokinetic solution2114 from the outside of the electrokinetic supply reservoir2106 and the electrokinetic solution receiving chamber2118. In some embodiments, the display2140 includes indication that electrokinetic solution2114 is being pumped from the electrokinetic supply reservoir2106 into the electrokinetic solution receiving chamber2118, causing infusion liquid2124 to flow from the infusion reservoir2122 through the infusion reservoir outlet2123. The battery2313 provides power for the controller2105, allowing voltage to be applied across the electrokinetic porous media2108. To prime the infusion reservoir outlet2123, pumping of the electrokinetic solution2114 from the electrokinetic supply reservoir2106 into the electrokinetic solution receiving chamber2118 can occur before attaching low profile electrokinetic infusion pump2101 to the user. As mentioned previously, the electrokinetic supply reservoir2106, the electrokinetic solution receiving chamber2118, and the infusion reservoir2122 can be fabricated using compliant pouch-like configurations, allowing for compact design.
• FIG. 47 is an illustration of the low profile electrokinetic infusion pump illustrated inFIGS. 45A, 45B,45C,46A, and46B with an alternative infusion reservoir outlet2123 and mounting clip2335. InFIG. 47, combined electrokinetic engine/infusion module2103 and controller2105 are detached, and combined electrokinetic engine/infusion module2103 is partially filled with infusion liquid. In contrast to the design illustrated inFIGS. 46A and 46B, the design illustrated inFIG. 47 includes battery2313 as part of electrokinetic engine/infusion module2103. This can result in smaller battery size, since battery2313 provides power for a single use of electrokinetic engine/infusion module103. A smaller battery can result in smaller overall size for low profile electrokinetic infusion pump2101. Electrokinetic engine/infusion module2103 also includes mounting clip2335, as opposed to adhesive326 illustrated inFIGS. 46A and 46B. Mounting clip2335 can be connected to a user's belt or clothing, and can be repositioned, as needed. In the embodiment of low profile electrokinetic infusion pump2101 illustrated inFIG. 47, infusion reservoir outlet2123 includes an infusion line with infusion tip2337. When controller2105 applies electrical potential across electrokinetic porous media2108, electrokinetic solution2114 flows from electrokinetic supply reservoir2106, through electrokinetic porous media2108, and into electrokinetic solution receiving chamber2118, displacing infusion liquid2124 from infusion reservoir2122, through infusion reservoir outlet2123 and infusion tip2337. After priming the infusion line, infusion tip2337 can be placed under the skin of the user, and infusion liquid2124 can be pumped into the user by low profile electrokinetic infusion pump2101. The infusion line used as infusion reservoir outlet2123 can be any of those currently used with mechanical infusion pumps. The controller2105 includes controller contacts2333, input keys2142, and display2140, as described previously. When the controller2105 is connected to electrokinetic engine/infusion module2103, and fastened in place with retaining clip2317, electrical connection is made between controller contacts2333 and pump contacts2331, allowing controller2105 to control pumping in electrokinetic engine/infusion module2103. As previously mentioned, electrodes (as illustrated inFIG. 1) allow electrical contact with electrokinetic solution2114, on both sides of electrokinetic porous media2108. The electrodes can be disk shaped, cylindrically shaped, or shaped like wires, and allow electrical contact with electrokinetic solution2114 from the outside ofelectrokinetic supply reservoir106 and electrokinetic solution receiving chamber2118.
• FIG. 48 is an illustration of the low profile electrokinetic infusion pump2101 illustrated inFIGS. 46A and 46B attached to a user by way of adhesive2326. InFIG. 48, the low profile electrokinetic infusion pump2101 is in wireless communication with remote controller2343. The remote controller2343 can include various features, such as electronic log book entry, blood glucose or other analyte monitoring, additional pump control electronics and algorithms, alarms, and communication capabilities. Although the remote controller2343 and the low profile electrokinetic infusion pump2101 are illustrated in wireless communication, they can also be hard-wired. InFIG. 48, the low profile electrokinetic infusion pump2101 is fastened directly to a users skin by way of the adhesive2326 (shown inFIGS. 46A and 46B). This embodiment is particularly useful when the infusion reservoir outlet2123 is a fixed cannula, and the low profile electrokinetic infusion pump2101 remains in one location while dispensing infusion liquid2124. The low profile electrokinetic infusion pump2101 can be attached to a users skin, and covered with clothing, as desired. Once infusion liquid2124 is completely dispensed, the low profile electrokinetic infusion pump2101 can be removed from the skin, the controller2105 can be detached from the electrokinetic engine/infusion module2103, and the electrokinetic engine/infusion module2103 can be disposed of. In this way, the low profile electrokinetic infusion pump2101 provides a compact, discrete, and convenient infusion system.
• FIG. 49 is an illustration of the low profile electrokinetic infusion pump2101 illustrated inFIGS. 47, attached to a user by way of mounting clip a2335. InFIG. 49, the low profile electrokinetic infusion pump2101 is in wireless communication with the remote controller2343, as described previously. The low profile electrokinetic infusion pump2101 is fastened directly to a belt2345 by way of the mounting clip2335 (shown inFIG. 47). This embodiment is particularly useful when the infusion reservoir outlet2123 is an infusion line, and the low profile electrokinetic infusion pump2101 can be moved from one location to another while dispensing infusion liquid2124. The low profile electrokinetic infusion pump2101 can be attached to the belt2345, and covered with clothing, as desired. Once infusion liquid2124 is completely dispensed, the low profile electrokinetic infusion pump2101 can be removed from the belt2345, the controller2105 can be detached from the electrokinetic engine/infusion module2103, and the electrokinetic engine/infusion module2103 can be disposed of.
• In the low profile electrokinetic infusion pump embodiments described above, a variety of infusion reservoir outlets have been described. In some embodiments, an infusion reservoir outlet can include an insertion device and a cannula for delivering infusion liquid hypodermically. In other embodiments, infusion reservoir outlets include hollow needles for delivering infusion liquid hypodermically. In embodiments that include cannulas, insertion devices can be removed after the cannula is positioned under the epidermis, making the device more comfortable for the user. A variety of cannulas, hollow needles, and insertion devices can be used with low profile electrokinetic infusion pumps of the present invention. Insertion devices can include automatic or manual actuators. For some users, using infusion reservoir outlets as illustrated inFIGS. 45A-46B may limit their selection of cannulas and needles, preventing them from selecting a favorite design. In addition, the designs illustrated inFIGS. 45A-46B may pose difficulties in respect to insertion because of the inability to see the infusion reservoir outlet while it is being inserted into the tissue. To address these limitations, additional embodiments of the present invention are anticipated, and are illustrated inFIGS. 50-54.
• In the embodiments illustrated inFIGS. 50-54, a mounting plate2347 is fixed to the user's skin. The mounting plate can include an infusion tip, such as a hollow needle or a cannula, or can include a hole that allows an infusion tip to pass through. The mounting plate includes features that allow it to be attached and detached from a low profile electrokinetic infusion pump. The mounting plate can be made out of clear plastic, and can include a clear pressure sensitive adhesive for mounting to the user's skin. In embodiments where the mounting plate includes a through hole, an insertion device can be used to introduce a cannula and can be removed, leaving the cannula in place. The mounting plate can then be mounted to the skin over the cannula, with the cannula centered in the mounting plate hole. An electrokinetic infusion pump can then be fastened to the mounting plate, while establishing a seal between the pump components and the cannula. In embodiments where a hollow needle is used to deliver infusion liquid, the needle can be rigidly fixed to the mounting plate, penetrating the tissue while the mounting plate is fixed to the user. An electrokinetic infusion pump can then be fastened to the mounting plate, while establishing a seal between the pump components and the needle. The mounting plate can be made out of a variety of materials, including transparent plastic that enables visualization of the infusion site by the user.
• InFIG. 50, low profile electrokinetic infusion pump2101 is attached to mounting plate2347, as it would be when delivering infusion liquid. Although electrokinetic infusion pump2101 is illustrated as a single piece, in other embodiments it includes a separate controller2105 and combined electrokinetic engine/infusion module2103, as illustrated inFIGS. 45A-47. InFIG. 51, low profile electrokinetic infusion pump2101 is detached from mounting plate2347. Mounting plate2347 includes retaining clips2317, which interlock with features in low profile electrokinetic infusion pump2101 when mounting plate2347 and low profile electrokinetic infusion pump2101 are attached. Mounting plate2347 also includesinfusion tip337 andconnector349.Infusion tip337 can include a hollow needle, an insertion device, and/or a cannula, as described previously. InFIG. 51, infusion tip2337 andconnector349 are fixed to mounting plate2347, and are inserted into the user's tissue while mounting plate2347 is being fastened to the user. In the embodiment illustrated inFIG. 52, mounting plate2347 includes hole2355, and is not connected to infusion tip2337 or connector2349. This allows infusion tip2337 and connector2349 to be inserted into the tissue independently from mounting plate2347. Some users may prefer the embodiment illustrated inFIG. 52, as it allows better visualization of insertion of infusion tip2337 into the tissue, and more readily allows the use of a cannula (as infusion tip2337) and insertion device2359. After inserting a cannula (as infusion tip2337) into the user's tissue, insertion device2359 can be removed, and mounting plate2347 can be fixed to the user while centering infusion tip2337 in hole2355. This may help in forming a seal betweenconnector349 and low profileelectrokinetic infusion pump101 when low profile electrokinetic infusion pump2101 is fixed to mounting plate2347. InFIG. 53, mounting plate2347 and low profileelectrokinetic infusion pump101 are viewed from the bottom. Mounting plate2347 includes adhesive2326, while low profile electrokinetic infusion pump2101 includes retaining pocket2318, pump components2353, and connection port2351. Adhesive2326 can be made using a wide variety of adhesives, including pressure sensitive acrylic based adhesives. The adhesive2326 can completely cover the surface of mounting plate2347, or can partially cover the surface of mounting plate2347. As illustrated inFIG. 53, a portion of the surface of mounting plate2347 in the area of infusion tip2337 may be free of adhesive, improving visibility through mounting plate2347. This can be particularly advantageous when insertinginfusion tip337 into the skin, or when inspecting the infusion site. Retaining pocket2318 mates with retaining clip2317, securing low profile electrokinetic infusion pump2101 in place over mounting plate2347. When low profile electrokinetic infusion pump2101 is attached to mounting plate2347, connector2349 mates with connection port2351, forming a leak-proof seal. Although the embodiment illustrated inFIG. 53 does not include hole2355, as seen inFIG. 52, it optionally can include hole2355.
• In conventional infusion pumps, an infusion pump and infusion reservoir are connected to a user's infusion site by way of tubing, and either a needle or a cannula. An adhesive patch is often used to fasten the needle or cannula to the user's infusion site. The tubing, needle or cannula, and adhesive patch are often referred to as an infusion set, and is replaced every three days or so to prevent infection and scar tissue formation at the infusion site. Many different infusion sets are commercially available, allowing patients to choose an infusion set according to their personal preference. Features that vary from one infusion set to another include means for a connection between the tubing and the pump, means for disconnection between the tubing and the needle or cannula (particularly near the infusion site), the length of tubing, the insertion angle of the needle or cannula, means for inserting cannulas, means for manually or automatically inserting the needle or cannula, and variations in the shape and kind of adhesive for fastening the needle or cannula to the infusion site. In some embodiments of the present invention, a needle or cannula is connected directly to the infusion pump, eliminating the need for tubing. Eliminating tubing can be desirable in that many of the problems encountered by users of infusion pumps are related to the use of tubing. Tubing can become tangled with clothing or other objects, and can dislodge a needle or cannula when cleared. In addition, tubing can become kinked, causing an interruption in the flow of infusion liquid. While embodiments of the present invention that do not include tubing avoid tubing related problems, they may require removal of the needle or cannula when inspecting the infusion site or when inspecting the pump. To address this issue, the embodiment of the present invention illustrated inFIG. 54 is envisioned.
• In the embodiment of the present invention illustrated inFIG. 54, the low profile electrokinetic infusion pump is connected to an infusion tip by way of tubing. The tubing is retractable, and can be stored within the low profile electrokinetic infusion pump. A spring-loaded mechanism can be used to retract and coil the tubing around a tubing spool. The tubing spool releases tubing the low profile electrokinetic infusion pump is detached from the mounting plate, as is the case when the user wishes inspect the pump or the infusion site. When the low profile electrokinetic infusion pump is re-attached, the tubing recoils on the tubing spool. The embodiment illustrated inFIG. 54 prevents entanglement, disconnection, and kinking of the infusion set. As illustrated inFIG. 54, low profile electrokinetic infusion pump2101 includes retaining pocket2318, pump components2353, and tubing spool2357. Mounting plate2347 includes retaining clip2317, infusion tip2337, and connector2349. Although the embodiment illustrated inFIG. 54 showsinfusion tip337 and connector2349 fixed to mounting plate2347, they can be separate from mountingplate347 as illustrated inFIG. 52 and described previously. Tubing2356 is wound around tubing spool2357, and is connected to pump components2353 on one end and connector2349 on the other end. As low profile electrokinetic infusion pump2101 is detached and moved away from mounting plate2347, tubing2356 unwinds from tubing spool2357, allowing low profile electrokinetic infusion pump2101 to be inspected, as needed. When desired, low profile electrokinetic infusion pump2101 can be moved back towards mounting plate2347, while tubing2356 winds around tubing spool2357, re-attaching to mounting plate2347. While low profile electrokinetic infusion pump2101 is detached from mounting plate2347, infusion tip2337 and the user's infusion site can be inspected, and adjusted, as needed. Although tubing spool2357 is illustrated as part of low profile electrokinetic infusion pump2101, it can also be attached to mounting plate2347 in alternative embodiments. As mentioned in reference toFIGS. 50-53, low profile electrokinetic infusion pump2101 can be a single unit, or can include a separate controller and combined electrokinetic engine/infusion module. Since low profile electrokinetic infusion pump2101 is detachable in the embodiment illustrated inFIG. 54, it can be attached to mounting plate2347, or placed remotely, in a pocket, purse, or on a belt clip, for example. Although the system illustrated inFIG. 54 has been described in respect to a low profile electrokinetic infusion pump, elements can be used with conventional infusion systems. For instance, infusion tip2337, connector2349, tubing2356, and tubing spool2357 can be used as infusion sets for commercially available electromechanical based infusion pumps, such as those sold by Medtronic Diabetes, of Northridge, Calif.
• While this particular embodiment describes a bag-to-bag pump design, the electrokinetic pump described above is also applicable to a variety of other designs, including a removable pump with a movable seal.
• In another exemplary embodiment, the pump is adapted to allow a user to adjust the depth of the needle which is inserted into the skin of the user, as shown inFIGS. 55-62. One feature of this embodiment is that it allows the temporary removal of the pump from the skin of the user. In general, as shown inFIG. 55, an adjustment assembly3000 can include cannula channel mold3080, which includes a cannula channel3070 and cavities for top and bottom septum caps3050,3090. A needle inserter assembly3130 is provided which is adapted to insert a cannula3020 housing a needle3010 at a user selected depth. To adjust the depth of the cannula3020, an adjustment key3030 is provided, having multiple positions, such as a first, second, and third position corresponding to three depths for the needle inserter3130.
• FIG. 56 shows the adjustment key3030 at a first position in which the needle inserter and the cannula3020 are at a first position, for example, at a depth of 9 mm. In order to position the depth of the needle inserter3130, a first shoulder3110 is adapted to engage with a top surface of the adjustment key3030. This stops the needle inserter3130 at the first position.FIG. 57 shows the adjustment key3030 shifted from the first position3110 to a second position in which the needle inserter and cannula are at a second position, for example, at a depth of 12 mm. A second shoulder3120 is adapted to engage the adjustment key3030 is stop the adjustment key3030 at the second position3120.FIG. 58 shows the adjustment key3030 shifted from the second position to a third position in which the needle inserter3130 and the cannula3020 are at a third position, for example, at a depth of 15 mm. The first shoulder3110 engages with a top surface of the cannula channel mold3080 to stop the needle inserter3130 at the third position.
• FIG. 59 shows the needle inserter assembly3130 holding the cannula3020 which houses the needle3010. The cannula3020 can be press-fit within the cannula channel3070 as the needle inserter3130 moves through the channel3070. The needle inserter3130 can be removed after the needle insertion is completed, leaving the cannula3020 and the needle3010 held within the cannula channel3070. The cannula3020 can have a variety of configurations, as shown inFIGS. 60A-60B, which illustrate cannulas including a feature on a proximal end configured for allowing the cannula3020 to press-fit within the cannula channel3070.FIG. 60A illustrates a cannula3020ahaving a flange3022 disposed on the proximal end,FIG. 60B illustrates a cannula3020bhaving a flared proximal end3024,FIG. 60C illustrates a cannula3020chaving an extended flange3026 disposed on the proximal end, andFIG. 60D illustrates a cannula3020dhaving a squared flange3028 disposed on the proximal end. A person skilled in the art will appreciate that any feature disposed on the proximal end of the cannula3020, or any shape or configuration of the proximal end of the cannula, can be used to provide a press-fit of the cannula within the cannula channel.
• The top and bottom septums3040,3090 and septum caps3050,3100 can be used to provide a seal to prevent leaking of the infusion liquid. The top septum3040 and septum cap3050, shown inFIG. 61, provide a seal and a conduit for the infusion liquid from the reservoir3150 to the cannula channel3070. The top septum3040 maintains a water-tight seal for the reservoir needle, and can also self-seal after the reservoir3150 and/or a controller is temporarily removed, which allows a user to remove the pump for a short period of time, for example, for activities such as sports or bathing, or permanently removed. The top septum3040 also provides a water-tight seal after the removal of the needle inserter3130. The top septum cap3050 can latch into the top cavity of the cannula channel mold3080 and maintains a water-tight seal between the bottom of the top septum3040 and the top surface of the cannula channel mold3080. The bottom septum3090 and bottom septum cap3100, shown inFIG. 62, provides a seal for leaks between the cannula3020 and the cannula channel3070, and horizontally stabilizes the cannula3020. The bottom septum cap3100 latches into the bottom cavity of the cannula channel mold3080 and maintains a water-tight seal between the top of the bottom septum3090 and the bottom surface of the cannula channel mold3080.
• The electrokinetic infusion pumps described above can also be adapted to allow a user to modify the configuration of the infusion pump to achieve a variety of options for wearing the infusion pump. The infusion pump can include a dock having a cannula with a needle housed therein. The needle extends into the skin of the user to allow infusion liquid to pass from the infusion pump to the user. A variety of components can be removably coupled to the dock and the cannula and needle to allow for flexibility in wearing the infusion pump.
• As shown inFIG. 63, in one exemplary embodiment, a patch4002, disposed on the user's skin, is directly coupled to an infusion dock4004. The infusion pump4006 is coupled to the infusion dock4004, and the infusion pump4006 is controlled using a remote control4008. In another exemplary embodiment, shown inFIG. 64, the infusion pump4006 is coupled to the infusion dock4004 using a tubing4010, and the infusion pump4006 is controlled using a remote control4008. In yet another exemplary embodiment, shown inFIG. 65, the infusion pump4006 is coupled to the infusion dock4004 using a tubing4010, and the infusion pump4006 is controlled manually with controls disposed on the infusion pump4006.FIG. 66 shows another exemplary embodiment, the infusion pump4006 is coupled to the infusion dock4004, and the remote control4008 for controlling the infusion pump4006 is removably coupled to the infusion pump4006 for storage. A person skilled in the art will appreciate that any combination of the infusion dock, infusion pump, tubing, remote control, and any other component used with an infusion pump, can be used to attach the infusion pump to the user and to control the pump for deliver of infusion liquid to the user.
• One of ordinary skill in the art will appreciate further features and advantages of the invention based on the above-described embodiments. Accordingly, the invention is not to be limited by what has been particularly shown and described, except as indicated by the appended claims. All publications and references cited herein are expressly incorporated herein by reference in their entirety.

Claims (29)

1. An electrokinetic infusion pump comprising:

an infusion housing including an infusion reservoir, the infusion reservoir having an infusion outlet and being capable of containing an infusion liquid;

a plunger movably coupled to the infusion housing and adapted to be manually displaced relative to the infusion housing to load the infusion reservoir with infusion liquid;

a movable partition disposed within the infusion housing and having a first surface in communication with an electrokinetic solution and a second surface, isolated from the first surface, in communication with the infusion reservoir; and

an electrokinetic engine integrated within the plunger and adapted to selectively apply electric potential across an electrokinetic porous media to cause the electrokinetic solution within the electrokinetic engine to displace the movable partition to effect delivery of at least a portion of the infusion liquid through the infusion outlet.

2. The electrokinetic infusion pump ofclaim 1, wherein the movable partition forms part of a displacement piston that is adapted to be slidably disposed within the infusion housing to form, with an inner surface of the displacement piston, an adjustable receiving reservoir which is fluidly isolated from the infusion reservoir and capable of containing an electrokinetic solution.

3. The electrokinetic infusion pump ofclaim 2, wherein the adjustable receiving reservoir is formed by a chamber extending within the displacement piston.

4. The electrokinetic infusion pump ofclaim 2, wherein the plunger is in the form of a generally elongate member having a forward piston extending from a distal portion of an outer plunger housing.

5. The electrokinetic infusion pump ofclaim 4, wherein the electrokinetic engine further includes:

a fixed supply reservoir effective to contain an electrokinetic solution and having a first electrode in communication therewith and a fixed receiving chamber being capable of receiving a volume of the electrokinetic solution from the fixed supply reservoir and having a second electrode in communication therewith, the electrokinetic porous media being disposed between the fixed supply reservoir and the fixed receiving chamber; and

an inner channel formed in the forward piston and providing a fluid communication pathway between the adjustable receiving reservoir and a fixed receiving chamber.

6. The electrokinetic infusion pump ofclaim 5, wherein the forward piston is adapted to slidably mate within the chamber extending within the displacement piston.

7. The electrokinetic infusion pump ofclaim 6, wherein the application of electric potential across the porous media is effective to cause electrokinetic solution in the fixed supply chamber to flow through the porous media, into the fixed receiving chamber, through the inner channel of the forward piston and into the adjustable receiving chamber, causing a distally directed force to be placed on the displacement piston, thus resulting in distal movement of the movable partition which will effect dispensing of at least a portion of the infusion liquid through the infusion outlet.

8. The electrokinetic infusion pump ofclaim 5, wherein the diameter of the adjustable receiving chamber (D₁) is less then the diameter of the fixed supply reservoir (D₂) to allow for a larger volume of infusion liquid to be displaced than the volume of electrokinetic solution that is displaced within the electrokinetic engine.

9. The electrokinetic infusion pump ofclaim 8, wherein the ratio of (D₁/D₂)²defines an amplification factor and the amplification factor is greater than 1.

10. The electrokinetic infusion pump ofclaim 9, wherein the amplification factor is about 4.

11. The electrokinetic infusion pump ofclaim 1, wherein the plunger includes a knob disposed on a proximal end thereof, the knob being adapted for grasping by a user to enable rotational and longitudinal movement of the plunger.

12. The electrokinetic infusion pump ofclaim 1, wherein the electrokinetic infusion pump includes a latch disposed on a portion of the plunger, that latch being selectively movable between a latched condition in which it is coupled to the displacement piston to allow movement of the displacement piston and the movable partition with movement of the plunger, and an unlatched condition in which it is uncoupled from the displacement piston to permit movement of the displacement piston and the movable partition independent of the plunger.

13. The electrokinetic infusion pump ofclaim 12, wherein the latched condition allows for loading of the infusion liquid into the infusion reservoir, and wherein the unlatched condition allows for delivery of at least a portion of the infusion liquid through the infusion outlet when an electric potential is applied across the porous media to cause the electrokinetic solution within the electrokinetic engine to displace the movable partition.

14. The electrokinetic infusion pump ofclaim 11, wherein a surface of the outer plunger housing includes an axial groove formed along at least a portion of the length thereof and a perimeter groove extending transversely from a distal portion of the axial groove, the perimeter groove being angled towards a proximal end of the outer plunger housing.

15. The electrokinetic infusion pump ofclaim 14, wherein the infusion housing includes a surface feature slidably disposed within the axial and perimeter grooves of the outer plunger housing.

16. The electrokinetic infusion pump ofclaim 15, wherein the knob disposed on the plunger is adapted to move the plunger proximally to fill the infusion reservoir with infusion liquid, the plunger being adapted to move proximally until the surface feature reaches the distal end of the axial groove.

17. The electrokinetic infusion pump ofclaim 16, wherein the knob is able to be rotated to cause the surface feature to travel along the perimeter groove to allow at least a portion of the infusion liquid to be delivered through the infusion outlet to prime the infusion pump.

18. The electrokinetic infusion pump ofclaim 17, wherein a first locking feature provided on the infusion housing irreversibly engages a second locking features provided on the plunger to lock the plunger to the infusion housing.

19. An electrokinetic infusion pump comprising:

a base capable of being attached to a patient,

an electrokinetic engine infusion module adapted to selectively apply electric potential across an electrokinetic porous media to cause an electrokinetic solution within the module to displace a movable partition disposed adjacent to a deformable infusion reservoir that is adapted to contain an infusion liquid to effect delivery of at least a portion of the infusion liquid through an infusion outlet, the module being adapted to be detachably coupled to the base; and

a controller configured to control the application of electric potential across the electrokinetic porous media and adapted to be detachably coupled to the base.

20. The electrokinetic infusion pump ofclaim 19, wherein the base is attachable to the patient using an adhesive.

21. The electrokinetic infusion pump ofclaim 19, wherein the base further includes a clip to enable attachment of the base to an article of clothing worn by a user.

22. The electrokinetic infusion pump ofclaim 19, wherein the controller is integrated with the electrokinetic engine infusion module.

23. The electrokinetic infusion pump ofclaim 19, wherein the controller is separate from the electrokinetic engine infusion module.

24. The electrokinetic infusion pump ofclaim 23, further including a battery disposed within the controller.

25. The electrokinetic infusion pump ofclaim 23, further including a battery disposed within the electrokinetic engine infusion module.

26. The electrokinetic infusion pump ofclaim 19, wherein the electrokinetic porous media separates a collapsible supply chamber containing an electrokinetic solution and an expandable receiving chamber within the electrokinetic engine such that electrokinetic solution is able to flow from the supply chamber through the porous media and into the expandable receiving chamber when a voltage is applied to the electrokinetic solution infusion module.

27. The electrokinetic infusion pump ofclaim 26, wherein transfer of the electrokinetic solution from the collapsible supply chamber is effective to expand the expandable receiving chamber such that the expandable receiving chamber applies a compressive force to the deformable infusion reservoir to effect delivery of the infusion liquid.

28. The electrokinetic infusion pump ofclaim 19, wherein the infusion outlet comprises a needle that extends through an opening in the base.

29. The electrokinetic infusion pump ofclaim 19, wherein the infusion outlet comprises a catheter extending from a portion of the infusion pump.

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