EP1740497A2 - Elektrokinetisches abgabesystem, vorrichtungen und verfahren - Google Patents

Elektrokinetisches abgabesystem, vorrichtungen und verfahren

Info

Publication number
EP1740497A2
EP1740497A2 EP05779953A EP05779953A EP1740497A2 EP 1740497 A2 EP1740497 A2 EP 1740497A2 EP 05779953 A EP05779953 A EP 05779953A EP 05779953 A EP05779953 A EP 05779953A EP 1740497 A2 EP1740497 A2 EP 1740497A2
Authority
EP
European Patent Office
Prior art keywords
pump
reservoir
fluid
electrodes
power source
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP05779953A
Other languages
English (en)
French (fr)
Other versions
EP1740497A4 (de
Inventor
Deon S. Anex
Phillip H. Paul
David W. Neyer
Edwin K. Hvalka
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Eksigent Technologies LLC
Original Assignee
Eksigent Technologies LLC
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Eksigent Technologies LLC filed Critical Eksigent Technologies LLC
Publication of EP1740497A2 publication Critical patent/EP1740497A2/de
Publication of EP1740497A4 publication Critical patent/EP1740497A4/de
Withdrawn legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
    • A61M5/14—Infusion devices, e.g. infusing by gravity; Blood infusion; Accessories therefor
    • A61M5/142—Pressure infusion, e.g. using pumps
    • A61M5/145—Pressure infusion, e.g. using pumps using pressurised reservoirs, e.g. pressurised by means of pistons
    • A61M5/148—Pressure infusion, e.g. using pumps using pressurised reservoirs, e.g. pressurised by means of pistons flexible, e.g. independent bags
    • A61M5/1483—Pressure infusion, e.g. using pumps using pressurised reservoirs, e.g. pressurised by means of pistons flexible, e.g. independent bags using flexible bags externally pressurised by fluid pressure
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
    • A61M5/14—Infusion devices, e.g. infusing by gravity; Blood infusion; Accessories therefor
    • A61M5/142—Pressure infusion, e.g. using pumps
    • A61M5/14244—Pressure infusion, e.g. using pumps adapted to be carried by the patient, e.g. portable on the body
    • A61M5/14248—Pressure infusion, e.g. using pumps adapted to be carried by the patient, e.g. portable on the body of the skin patch type
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
    • A61M5/14—Infusion devices, e.g. infusing by gravity; Blood infusion; Accessories therefor
    • A61M5/142—Pressure infusion, e.g. using pumps
    • A61M5/14244—Pressure infusion, e.g. using pumps adapted to be carried by the patient, e.g. portable on the body
    • A61M5/14276—Pressure infusion, e.g. using pumps adapted to be carried by the patient, e.g. portable on the body specially adapted for implantation
    • F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
    • F04—POSITIVE - DISPLACEMENT MACHINES FOR LIQUIDS; PUMPS FOR LIQUIDS OR ELASTIC FLUIDS
    • F04B—POSITIVE-DISPLACEMENT MACHINES FOR LIQUIDS; PUMPS
    • F04B19/00—Machines or pumps having pertinent characteristics not provided for in, or of interest apart from, groups F04B1/00 - F04B17/00
    • F04B19/006—Micropumps
    • F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
    • F04—POSITIVE - DISPLACEMENT MACHINES FOR LIQUIDS; PUMPS FOR LIQUIDS OR ELASTIC FLUIDS
    • F04B—POSITIVE-DISPLACEMENT MACHINES FOR LIQUIDS; PUMPS
    • F04B43/00—Machines, pumps, or pumping installations having flexible working members
    • F04B43/02—Machines, pumps, or pumping installations having flexible working members having plate-like flexible members, e.g. diaphragms
    • F04B43/04—Pumps having electric drive
    • F04B43/043—Micropumps
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
    • A61M5/14—Infusion devices, e.g. infusing by gravity; Blood infusion; Accessories therefor
    • A61M5/142—Pressure infusion, e.g. using pumps
    • A61M5/145—Pressure infusion, e.g. using pumps using pressurised reservoirs, e.g. pressurised by means of pistons
    • A61M2005/14513—Pressure infusion, e.g. using pumps using pressurised reservoirs, e.g. pressurised by means of pistons with secondary fluid driving or regulating the infusion
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M2205/00—General characteristics of the apparatus
    • A61M2205/50—General characteristics of the apparatus with microprocessors or computers
    • A61M2205/52—General characteristics of the apparatus with microprocessors or computers with memories providing a history of measured variating parameters of apparatus or patient
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M2230/00—Measuring parameters of the user
    • A61M2230/20—Blood composition characteristics
    • A61M2230/201—Glucose concentration
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
    • A61M5/14—Infusion devices, e.g. infusing by gravity; Blood infusion; Accessories therefor
    • A61M5/168—Means for controlling media flow to the body or for metering media to the body, e.g. drip meters, counters ; Monitoring media flow to the body
    • A61M5/172—Means for controlling media flow to the body or for metering media to the body, e.g. drip meters, counters ; Monitoring media flow to the body electrical or electronic
    • A61M5/1723—Means for controlling media flow to the body or for metering media to the body, e.g. drip meters, counters ; Monitoring media flow to the body electrical or electronic using feedback of body parameters, e.g. blood-sugar, pressure

Definitions

  • 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.
  • 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.
  • the present invention contemplates the use of controlled electrokinetic fluid flow techniques for efficient, reliable and highly precise movement of a pump fluid.
  • various low-cost, precise, reliable and compact medical systems and device for drug delivery and analyte sampling are provided.
  • the invention is a method of pumping fluid including the steps of providing an electrokinetic pump comprising a pair of double-layer capacitive electrodes having a capacitance of at least 10 '2 Farads/cm 2 and being connectable to a power source, a porous dielectric material disposed between the electrodes, a first reservoir containing pump fluid, a second reservoir, and a third reservoir containing a dispensed fluid; connecting the electrodes to a power source; moving pump fluid out of the first reservoir into the second reservoir at a pump fluid flow rate substantially without the occurrence of Faradaic processes in the pump; and moving dispensed fluid out of the third reservoir and through a pump outlet at a dispensed fluid flow rate as the pump fluid moves from the first reservoir into the second reservoir, the dispensed fluid flow rate being between about .1 times and 10 times the pump fluid flow rate.
  • the invention is a method of pumping fluid including the steps of providing an electrokinetic pump comprising a pair of double-layer capacitive electrodes having a capacitance of at least 10 " Farads/cm and being connectable to a power source, a porous dielectric material disposed between the electrodes, a first reservoir containing pump fluid, a second reservoir, and a third reservoir containing a dispensed fluid, the electrokinetic pump having a volume no greater than 250% of an initial volume of dispensed fluid; connecting the electrodes to a power source; moving pump fluid out of the first reservoir into the second reservoir substantially without the occurrence of Faradaic processes in the pump; and moving dispensed fluid out of the third reservoir and through a pump outlet as the pump fluid moves from the first reservoir into the second reservoir.
  • the invention is a method of pumping fluid including the steps of providing an electrokinetic pump comprising a pair of double-layer capacitive electrodes having a capacitance of at least 10 " Farads/cm and being connectable to a power source, a porous dielectric material disposed between the electrodes, a first reservoir containing pump fluid, a second reservoir, and a syringe containing a dispensed fluid; connecting the electrodes to a power source; moving pump fluid out of the first reservoir into the second reservoir substantially without the occurrence of Faradaic processes in the pump; and moving dispensed fluid out of the syringe and into a patient as the pump fluid moves from the first reservoir into the second reservoir.
  • This embodiment may also include the step of adding dispensed fluid to the syringe prior to the moving step.
  • Still other embodiments of the method include the following steps: providing a first electrokinetic pump comprising a pair of double-layer capacitive electrodes having a capacitance of at least 10 "2 Farads/cm and being connectable to a power source, a porous dielectric material disposed between the electrodes, a first reservoir containing pump fluid, a second reservoir, and a third reservoir containing a dispensed fluid; connecting the electrodes to a power source; moving pump fluid out of the first reservoir into the second reservoir substantially without the occurrence of Faradaic processes in the pump; moving dispensed fluid out of the third reservoir and through a first electrokinetic pump pump outlet into a patient as the pump fluid moves from the first reservoir into the second reservoir; providing a second electrokinetic pump comprising a pair of double-layer capacitive electrodes connectable to a power source, a porous dielectric material disposed between the electrodes, a
  • the step of moving dispensed fluid from the first electrokinetic pump may be performed at a first rate and the step of moving dispensed fluid from the second electrokinetic pump may be performed at a second rate different than the first rate.
  • the first electrokinetic pump and the dispensed fluid of the second electrokinetic pump may be the same kind of fluid or different kinds of fluid.
  • FIG. 1 A block diagram illustrating an exemplary embodiment of the invention.
  • FIG. 1 A block diagram illustrating an exemplary embodiment of the invention.
  • FIG. 1 A block diagram illustrating an exemplary embodiment of the invention.
  • FIG. 1 A block diagram illustrating an exemplary embodiment of the invention.
  • FIG. 1 A block diagram illustrating an exemplary embodiment of the invention.
  • FIG. 1 A block diagram illustrating an exemplary embodiment of the invention.
  • FIG. 1 A first electrokinetic pump comprising a pair of double-layer capacitive electrodes having a capacitance of at least 10 " Farads/cm and being connectable to a power source, a porous dielectric material disposed between the electrodes, a first reservoir containing pump fluid, a second reservoir, and a third reservoir containing a dispensed fluid; connecting the electrodes to a power source; moving pump fluid out of the first reservoir into the second reservoir substantially without the occurrence of Faradaic processes in the pump; moving dispensed fluid out of the third reservoir and through a pump outlet
  • the first electrokinetic pump and the dispensed fluid of the second electrokinetic pump may be the same kind of fluid or different kinds of fluid.
  • a method of pumping fluid including the steps of providing a first electrokinetic pump comprising a pair of double-layer capacitive electrodes having a capacitance of at least 10 " Farads/cm and being connectable to a power source, a porous dielectric material disposed between the electrodes, a first reservoir containing pump fluid, a second reservoir, and a third reservoir containing a dispensed fluid; connecting the electrodes to a power source; moving pump fluid out of the first reservoir into the second reservoir substantially without the occurrence of Faradaic processes in the pump; moving dispensed fluid out of the third reservoir and through a pump outlet into a patient as the pump fluid moves from the first reservoir into the second reservoir; providing a second electrokinetic pump comprising a pair of double-layer capacitive electrodes connectable to a power source, a porous dielectric material disposed between the electrodes
  • Still other aspects of the invention include a method of pumping fluid including the steps of providing an electrokinetic pump comprising a pair of double-layer capacitive electrodes having a capacitance of at least 10 "2 Farads/cm 2 and being connectable to a power source, a porous dielectric material disposed between the electrodes, a first reservoir containing pump fluid, a second reservoir, and a third reservoir containing a dispensed fluid; connecting the electrodes to a power source; determining a patient's need for a dispensed fluid; moving pump fluid out of the first reservoir into the second reservoir substantially without the occurrence of Faradaic processes in the pump; and moving dispensed fluid out of the third reservoir and through a pump outlet into the patient as the pump fluid moves from the first reservoir into the second reservoir in response to the determined need.
  • the dispensed fluid may be insulin and the determining step may include determining the patient's blood glucose concentration, with the moving step comprising injecting a quantity of insulin into the patient in response to the determined blood glucose concentration.
  • the moving step may also include automatically injecting a quantity of insulin into the patient in response to the determined blood glucose concentration.
  • the determining step may include sampling a fluid taken from the patient with a second electrokinetic pump.
  • a method of pumping fluid including the steps of providing an electrokinetic pump comprising a pair of double-layer capacitive electrodes having a capacitance of at least 10 "2 Farads/cm 2 and being connectable to a power source, a porous dielectric material disposed between the electrodes, a first reservoir containing pump fluid, a second reservoir, and a third reservoir containing a dispensed fluid; connecting the electrodes to a power source; moving pump fluid out of the first reservoir into the second reservoir substantially without the occurrence of Faradaic processes in the pump; moving dispensed fluid out of the third reservoir and through a pump outlet as the pump fluid moves from the first reservoir into the second reservoir; and monitoring a parameter related to an amount of dispensed fluid moved out of the third reservoir during the moving step (e.g., flow rate, position of a pump element).
  • a parameter related to an amount of dispensed fluid moved out of the third reservoir during the moving step e.g., flow rate, position of a pump element.
  • the monitored parameter may be used to provide feedback control of the moving step, to provide an indication related to the dispensed fluid, to calculate a desired amount of dispensed fluid to be dispensed, and/or to indicate the presence of an occlusion in the pump outlet.
  • Yet other aspects of the invention provide a method of pumping fluid including the steps of providing an electrokinetic pump comprising a pair of double-layer capacitive electrodes having a capacitance of at least 10 "2 Farads/cm 2 and being connectable to a power source, a porous dielectric material disposed between the electrodes, a first reservoir containing pump fluid, a second reservoir, and a third reservoir containing a dispensed fluid; connecting the electrodes to a power source; moving pump fluid out of the first reservoir into the second reservoir substantially without the occurrence of Faradaic processes in the pump; and moving dispensed fluid out of the third reservoir and through a pump outlet for a fixed time interval to dispense a fixed volume of dispensed fluid as the pump fluid moves from the first reservoir into the second reservoir.
  • Still other aspects of the invention provide a method of pumping fluid including the steps of providing an electrokinetic pump comprising a pair of double-layer capacitive electrodes having a capacitance of at least 10 "2 Farads/cm 2 and being connectable to a power source, a porous dielectric material disposed between the electrodes, a first reservoir containing pump fluid, a second reservoir, and a third reservoir containing a dispensed fluid; connecting the electrodes to a power source; moving pump fluid out of the first reservoir into the second reservoir substantially without the occurrence of Faradaic processes in the pump; moving dispensed fluid out of the third reservoir and through a pump outlet as the pump fluid moves from the first reservoir into the second reservoir; and adjusting an amount of dispensed fluid moved out of the third reservoir.
  • Yet another aspect of the invention is a method of pumping fluid including the steps of providing an electrokinetic pump comprising a pair of double-layer capacitive electrodes having a capacitance of at least 10 " Farads/cm and being connectable to a power source, a porous dielectric material disposed between the electrodes, a first reservoir containing pump fluid, a second reservoir, and a third reservoir containing a dispensed fluid; connecting the electrodes to a power source; loading a dispensed fluid into the third reservoir; treating the electrokinetic pump to alter a characteristic of the dispensed fluid; moving pump fluid out of the first reservoir into the second reservoir substantially without the occurrence of Faradaic processes in the pump; and moving dispensed fluid out of the third reservoir and through a pump outlet as the pump fluid moves from the first reservoir into the second reservoir.
  • the treating step may include irradiating the electrokinetic pump.
  • Still another aspect of the invention provides a method of pumping fluid including the steps of providing an electrokinetic pump comprising a pair of double-layer capacitive electrodes having a capacitance of at least 10 "2 Farads/cm 2 and being connectable to a power source, a porous dielectric material disposed between the electrodes and a reservoir containing pump fluid; connecting the electrodes to a power source; and moving substantially all of the pump fluid out of the reservoir substantially without the occurrence of Faradaic processes in the pump at a flow rate of less than about 1 microliter/minute and with a steady state flow rate error of no more than about 5% over the entire method step.
  • Yet another aspect of the invention provides a method of pumping fluid including the steps of providing an electrokinetic pump comprising a pair of double-layer capacitive 9 9 electrodes having a capacitance of at least 10 " Farads/cm and being connectable to a power source, a porous dielectric material disposed between the electrodes and a reservoir containing pump fluid; connecting the electrodes to a power source; generating a pump fluid pressure between about 1 and about 1000 psi; and moving pump fluid out of the reservoir substantially without the occurrence of Faradaic processes in the pump.
  • Another aspect of the invention provides a method of pumping fluid including the steps of providing an electrokinetic pump comprising a pair of double-layer capacitive 9 9 electrodes having a capacitance of at least 10 " Farads/cm and being connectable to a power source, a porous dielectric material disposed between the electrodes and a reservoir containing pump fluid, a power source connectable to the electrodes and a housing containing the electrodes, dielectric material, reservoir and power source, the electrokinetic pump having a volume of at most about 11 cm ; connecting the electrodes to a power source; and moving at least about 0.2 milliliters of pump fluid out of the reservoir substantially without the occurrence of Faradaic processes in the pump.
  • the moving step may include moving the pump fluid at a rate of less than about 10 nanoliters/min. and may also include the step of moving the pump fluid substantially continuously for about 30 days.
  • Still another aspect of the invention provides a method of pumping fluid including the steps of providing an electrokinetic pump comprising a pair of double-layer capacitive 9 9 electrodes having a capacitance of at least 10 " Farads/cm and being connectable to a power source, a porous dielectric material disposed between the electrodes and a reservoir containing pump fluid; supporting the electrokinetic pump on a patient; connecting the electrodes to a power source; and moving pump fluid out of the reservoir substantially without the occurrence of Faradaic processes in the pump.
  • This method may also include implanting the electrokinetic pump in a patient.
  • the implanting step includes placing the electrokinetic pump adjacent to an anatomical feature of the patient having a shape complementary to the electrokinetic pump shape.
  • Another aspect of the invention provides a method of pumping fluid including the steps of providing a first electrokinetic pump comprising a pair of double-layer capacitive electrodes having a capacitance of at least 10 "2 Farads/cm and being connectable to a power source, a porous dielectric material disposed between the electrodes and a reservoir containing pump fluid; connecting the electrodes to a power source; moving pump fluid out of the reservoir at a first rate into a patient substantially without the occurrence of Faradaic processes in the first pump; providing a second electrokinetic pump comprising a pair of double-layer capacitive electrodes connectable to a power source, a porous dielectric material disposed between the electrodes and a reservoir of a pump fluid; connecting the electrodes of the second electrokinetic pump to a power source; and moving pump fluid out of the second electrokinetic pump
  • the first electrokinetic pump and the pump fluid of the second electrokinetic pump may be the same kind of fluid or different kinds of fluid.
  • Still another aspect of the invention provides a method of pumping fluid including the steps of providing an electrokinetic pump comprising a pair of double-layer capacitive electrodes having a capacitance of at least 10 "2 Farads/cm 2 and being connectable to a power source, a porous dielectric material disposed between the electrodes and a reservoir containing pump fluid; connecting the electrodes to a power source in a time modulated manner; and moving pump fluid out of the reservoir substantially without the occurrence of Faradaic processes in the pump.
  • Yet another aspect of the invention provides a method of pumping fluid including the steps of providing an electrokinetic pump comprising a pair of double-layer capacitive electrodes having a capacitance of at least 10 "2 Farads/cm 2 and being connectable to a power source, a porous dielectric material disposed between the electrodes and a reservoir containing pump fluid; connecting the electrodes to a power source by alternating the power source between an on state and an off state; and moving pump fluid out of the reservoir substantially without the occurrence of Faradaic processes in the pump.
  • Another aspect of the invention is a method of pumping fluid including the steps of providing an electrokinetic pump comprising a pair of double-layer capacitive electrodes having a capacitance of at least 10 "2 Farads/cm 2 and being connectable to a power source, a porous dielectric material disposed between the electrodes and a reservoir containing pump fluid; connecting the electrodes to a power source by alternating the power source between a normally off state and a periodic on state in response to a computer program; and moving pump fluid out of the reservoir substantially without the occurrence of Faradaic processes in the pump.
  • Still another aspect of the invention provides an electrokinetic pump system including a pair of double-layer capacitive electrodes having a capacitance of at least 10 "2 Farads/cm 2 ; a porous dielectric material disposed between the electrodes; a first reservoir containing pump fluid; a second reservoir; a third reservoir containing dispensed fluid and a pump outlet; a power source connected to the electrodes; the electrodes, dielectric material and power source being adapted to move the pump fluid out of the first reservoir into the second reservoir substantially without the occurrence of Faradaic processes in the pump and to move the dispensed fluid out of the pump outlet as the pump fluid moves from the first reservoir into the second reservoir; and a controller adapted to control delivery of power from the power source to the electrodes to move a fixed volume of dispensed fluid out of the third reservoir.
  • an electrokinetic pump system including a pair of double-layer capacitive electrodes having a capacitance of at least 10 "2 Farads/cm 2 ; a porous dielectric material disposed between the electrodes; a first reservoir containing pump fluid; a second reservoir; a third reservoir containing dispensed fluid and a pump outlet; a power source connected to the electrodes; the electrodes, dielectric material and power source being adapted to move the pump fluid out of the first reservoir into the second reservoir substantially without the occurrence of Faradaic processes in the pump and to move the dispensed fluid out of the pump outlet as the pump fluid moves from the first reservoir into the second reservoir; and a controller adapted to control delivery of power from the power source to the electrodes to move dispensed fluid for a fixed period of time.
  • Still another aspect of the invention provides an electrokinetic pump system including a pair of double-layer capacitive electrodes having a capacitance of at least 10 "2 Farads/cm 2 ; a porous dielectric material disposed between the electrodes; a first reservoir containing pump fluid; a second reservoir; a third reservoir containing dispensed fluid and a pump outlet; a power source connected to the electrodes; the electrodes, dielectric material and power source being adapted to move the pump fluid out of the first reservoir into the second reservoir substantially without the occurrence of Faradaic processes in the pump and to move the dispensed fluid out of the pump outlet as the pump fluid moves from the first reservoir into the second reservoir; and a controller adapted to control delivery of power from the power source to the electrodes to move dispensed fluid out of the third reservoir at a fixed time interval.
  • Another aspect of the invention is an electrokinetic pump system including a pair of double-layer capacitive electrodes having a capacitance of at least 10 "2 Farads/cm 2 ; a porous dielectric material disposed between the electrodes; a first reservoir containing pump fluid; a second reservoir; a third reservoir containing dispensed fluid and a pump outlet; a power source connected to the electrodes; the electrodes, dielectric material and power source being adapted to move the pump fluid out of the first reservoir into the second reservoir substantially without the occurrence of Faradaic processes in the pump and to move the dispensed fluid out of the pump outlet as the pump fluid moves from the first reservoir into the second reservoir; and a controller adapted to control delivery of power from the power source to the electrodes to move an amount dispensed fluid out of the third reservoir in response to a user input.
  • an electrokinetic pump system including a first electrokinetic pump comprising a pair of double-layer capacitive electrodes having a capacitance of at least 10 "2 Farads/cm 2 ; a porous dielectric material disposed between the electrodes; a first reservoir containing pump fluid; a second reservoir; a third reservoir containing dispensed fluid and a first pump outlet; and a power source connected to the electrodes; the electrodes, dielectric material and power source being adapted to move the pump fluid out of the first reservoir into the second reservoir substantially without the occurrence of Faradaic processes in the pump and to move the dispensed fluid out of the first pump outlet into a patient as the pump fluid moves from the first reservoir into the second reservoir; and a second electrokinetic pump comprising a second pair of double-layer capacitive electrodes connectable to a power source, a porous dielectric disposed between the second pair of electrodes, a fourth reservoir containing pump fluid, a second reservoir and a sixth reservoir containing a disp
  • the first electrokinetic pump may be further adapted move dispensed fluid at a first rate and the second electrokinetic pump is further adapted to move dispensed fluid at a second rate different than the first rate.
  • Another aspect of the invention is an electrokinetic pump system including a first electrokinetic pump comprising a pair of double-layer capacitive electrodes having a 9 9 capacitance of at least 10 " Farads/cm ; a porous dielectric material disposed between the electrodes; a first reservoir containing pump fluid; a second reservoir; a third reservoir containing dispensed fluid and a pump outlet; and a power source connected to the electrodes; the electrodes, dielectric material and power source being adapted to move the pump fluid out of the first reservoir into the second reservoir substantially without the occurrence of Faradaic processes in the pump and to move the dispensed fluid out of the pump outlet into a patient as the pump fluid moves from the first reservoir into the second reservoir; and a second electrokinetic pump comprising a pair of double-layer capacitive electrodes
  • the first electrokinetic pump may be further adapted move dispensed fluid at a first rate and the second electrokinetic pump is further adapted to move dispensed fluid at a second rate different than the first rate.
  • Still another aspect of the invention is an electrokinetic pump system including a pair 9 9 of double-layer capacitive electrodes having a capacitance of at least 10 " Farads/cm ; a first electrokinetic pump comprising a porous dielectric material disposed between the electrodes; a first reservoir containing pump fluid; a second reservoir; a third reservoir containing dispensed fluid and a pump outlet; and a power source connected to the electrodes; the electrodes, dielectric material and power source being adapted to move the pump fluid out of the first reservoir into the second reservoir substantially without the occurrence of Faradaic processes in the pump and to move the dispensed fluid out of the pump outlet into a patient as the pump fluid moves from the first reservoir into the second reservoir; and a second electrokinetic pump comprising a pair of double-layer capacitive electrode
  • an electrokinetic pump system including a pair of double-layer capacitive electrodes having a capacitance of at least 10 "2 Farads/cm 2 ; a porous dielectric material disposed between the electrodes; a first reservoir containing pump fluid; a second reservoir; a third reservoir containing dispensed fluid and a pump outlet; a power source connected to the electrodes; the electrodes, dielectric material and power source being adapted to move the pump fluid out of the first reservoir into the second reservoir substantially without the occurrence of Faradaic processes in the pump and to move the dispensed fluid out of the pump outlet as the pump fluid moves from the first reservoir into the second reservoir; and a movable member comprising a hydraulic amplifier disposed between the second reservoir and the third reservoir adapted to move as pump fluid moves from the first reservoir into the second reservoir to move the dispensed fluid out of the third reservoir.
  • Another aspect of the invention is an electrokinetic pump system including a pair of double-layer capacitive electrodes having a capacitance of at least 10 "2 Farads/cm 2 ; a porous dielectric material disposed between the electrodes; a first reservoir containing pump fluid; a second reservoir; a third reservoir containing dispensed fluid and a pump outlet; a power source connected to the electrodes; the electrodes, dielectric material and power source being adapted to move the pump fluid out of the first reservoir into the second reservoir substantially without the occurrence of Faradaic processes in the pump and to move the dispensed fluid out of the pump outlet as the pump fluid moves from the first reservoir into the second reservoir; and a sensor adapted to determine a patient's need for the dispensed fluid.
  • the system may also include a controller adapted to control delivery of power from the power source to the electrodes in response to a signal from the sensor.
  • the sensor comprises an electrokinetic pump adapted to sample a fluid from the patient.
  • Still another aspect of the invention provides an electrokinetic pump system including 9 9 a pair of double-layer capacitive electrodes having a capacitance of at least 10 " Farads/cm ; a porous dielectric material disposed between the electrodes; a first reservoir containing pump fluid; a second reservoir; a third reservoir containing dispensed fluid and a pump outlet; an external port communicating with the third reservoir; a movable member disposed between the second reservoir and the third reservoir adapted to change an effective volume of the third reservoir as an effective volume of the second reservoir changes; a power source connected to the electrodes; the electrodes, dielectric material and power source being adapted to move the pump fluid out of the first reservoir into the second reservoir substantially without the occurrence of Faradaic processes in the pump and to move the dispensed fluid out of
  • an electrokinetic pump system including a pair of double-layer capacitive electrodes having a capacitance of at least 10 "2 Farads/cm 2 ; a porous dielectric material disposed between the electrodes; a first reservoir containing pump fluid; a second reservoir; a third reservoir containing dispensed fluid and a pump outlet; an external port communicating with the third reservoir; a movable member disposed between the second reservoir and the third reservoir adapted to change an effective volume of the third reservoir as an effective volume of the second reservoir changes; a power source connected to the electrodes; the electrodes, dielectric material and power source being adapted to move the pump fluid out of the first reservoir into the second reservoir substantially without the occurrence of Faradaic processes in the pump and to move the dispensed fluid out of the pump outlet as the pump fluid moves from the first reservoir into the second reservoir; and a sensor adapted to monitor a parameter (e.g., flow rate, syringe position using, e.g., a magnet and
  • the system may also include a feedback control element adapted to control power delivered to the electrodes by the power source in response to a signal from the sensor, a controller adapted to control application of power from the power source to the electrodes in response to a sensor output signal, and/or an indicator adapted to provide an indication related to fluid dispensed from the third reservoir, such as the existence of an occlusion of the external port.
  • a feedback control element adapted to control power delivered to the electrodes by the power source in response to a signal from the sensor
  • a controller adapted to control application of power from the power source to the electrodes in response to a sensor output signal
  • an indicator adapted to provide an indication related to fluid dispensed from the third reservoir, such as the existence of an occlusion of the external port.
  • an electrokinetic pump system including a pair of double-layer capacitive electrodes having a capacitance of at least 10 "2 Farads/cm 2 ; a porous dielectric material disposed between the electrodes; a reservoir containing pump fluid; and a power source connected to the electrodes; the electrodes, dielectric material and power source being adapted to move the pump fluid out of the reservoir substantially without the occurrence of Faradaic processes in the pump at a flow rate of less than about 1 microliter/minute and with a steady state flow rate error of no more than about 5%.
  • Still another aspect of the invention provides an electrokinetic pump system including 9 9 a pair of double-layer capacitive electrodes having a capacitance of at least 10 " Farads/cm ; a porous dielectric material disposed between the electrodes; a reservoir containing pump fluid; and a power source connected to the electrodes; the electrodes, dielectric material and power source being adapted to move the pump fluid out of the reservoir substantially without the occurrence of Faradaic processes in the pump at a pump fluid pressure between about 1 and about 1000 psi.
  • an electrokinetic pump system including a pair of double-layer capacitive electrodes having a capacitance of at least 10 "2 Farads/cm 2 ; a porous dielectric material disposed between the electrodes; a reservoir containing pump fluid; a power source connected to the electrodes; the electrodes, dielectric material and power source being adapted to move the pump fluid out of the reservoir substantially without the occurrence of Faradaic processes in the pump; and a housing having a volume of at most about 11 cm and wherein the electrodes, dielectric material and power source are further adapted to move at least about 0.2 milliliters of pump fluid from the reservoir.
  • the electrodes, dielectric material and power source may be further adapted to move pump fluid from the reservoir at a rate of less than 10 nanoliters/min.
  • the electrodes, dielectric material and power source may be still further adapted to move pump fluid from the reservoir from the reservoir substantially continuously for about 30 days.
  • the housing may be a laminated housing.
  • an electrokinetic pump system including a pair of double-layer capacitive electrodes having a capacitance of at least 10 "2 Farads/cm 2 ; a porous dielectric material disposed between the electrodes; a reservoir containing pump fluid; and a power source connected to the electrodes; the electrodes, dielectric material and power source being adapted to move the pump fluid out of the reservoir substantially without the occurrence of Faradaic processes in the pump; wherein the electrodes, dielectric material and power source are further adapted to be implanted in a patient.
  • Another aspect of the invention is an electrokinetic pump system including a pair of double-layer capacitive electrodes having a capacitance of at least 10 "2 Farads/cm 2 ; a porous dielectric material disposed between the electrodes; a reservoir containing pump fluid; a power source connected to the electrodes; the electrodes, dielectric material and power source being adapted to move the pump fluid out of the reservoir substantially without the occurrence of Faradaic processes in the pump; and an indicator adapted to indicate an amount of pump fluid present in the reservoir.
  • Still another aspect of the invention provides an electrokinetic pump system including a pair of double-layer capacitive electrodes having a capacitance of at least 10 "2 Farads/cm 2 ; a porous dielectric material disposed between the electrodes; a reservoir containing pump fluid; a power source connected to the electrodes; the electrodes, dielectric material and power source being adapted to move the pump fluid out of the reservoir substantially without the occurrence of Faradaic processes in the pump; and a controller adapted to provide power from the power source to the electrodes in a time modulated manner.
  • an electrokinetic pump system including a pair of double-layer capacitive electrodes having a capacitance of at least 10 "2 Farads/cm 2 ; a porous dielectric material disposed between the electrodes; a reservoir containing pump fluid; a power source connected to the electrodes; the electrodes, dielectric material and power source being adapted to move the pump fluid out of the reservoir substantially without the occurrence of Faradaic processes in the pump; and a controller adapted to alternate the power source between an on state and an off state.
  • Still another aspect of the invention is an electrokinetic pump system including a pair of double-layer capacitive electrodes having a capacitance of at least 10 "2 Farads/cm 2 ; a porous dielectric material disposed between the electrodes; a reservoir containing pump fluid; a power source connected to the electrodes; the electrodes, dielectric material and power source being adapted to move the pump fluid out of the reservoir substantially without the occurrence of Faradaic processes in the pump; and a controller adapted to alternate the power source between a normally off state and a periodic on state in response to a computer program.
  • an electrokinetic pump system including a pair 9 9 of double-layer capacitive electrodes having a capacitance of at least 10 " Farads/cm ; a porous dielectric material disposed between the electrodes; a reservoir containing pump fluid; a power source connected to the electrodes; the electrodes, dielectric material and power source being adapted to move the pump fluid out of the reservoir substantially without the occurrence of Faradaic processes in the pump; and a housing containing the electrodes, reservoir, dielectric material and power source, the housing being adapted to be worn on a human or animal body.
  • a displacement pump including a dispensed fluid reservoir; a pump outlet; a displacement mechanism; a power source adapted to operate the displacement mechanism; and a housing containing the reservoir, pump outlet, power source and displacement mechanism, the housing having a volume no more than 250% of the volume of the dispensed fluid reservoir; the displacement mechanism and power source being further adapted to dispense substantially all of dispensed fluid from the reservoir through the pump outlet at a flow rate no more than 1 microliter/minute with a steady state flow rate error of no more than about 5%.
  • the displacement mechanism may include a movable member, and the pump may further include an electrokinetic assembly comprising a pair of electrodes connectable to the power source, a porous dielectric material disposed between the electrodes; and pump fluid in contact with the electrodes, such as double-layer capacitive electrodes.
  • a pump including a reservoir of pump fluid; a pump mechanism operable on the pump fluid; a pump outlet; a power source connectable to the pump mechanism to move pump fluid from the reservoir through the pump outlet at a flow rate no more than 1 microliter/minute with a steady state flow rate error of no more than about 5%; and a housing containing the reservoir, electrodes, pump outlet and power source, the housing having a volume no more than 150% of the volume of the reservoir.
  • the electrodes may be a pair of double-layer capacitive electrodes having a capacitance of at least 9 9
  • FIG. 1 illustrates a cross-sectional view of one embodiment of a direct EK pump
  • FIG. 2 illustrates a cross-sectional view of a direct EK pump comprising a split reservoir design
  • FIG. 3 illustrates a cross-sectional view of an indirect EK pump
  • FIGS. 4a - 4c schematically illustrate operation of the EK pump provided in FIG. 3
  • FIGS. 4a - 4c schematically illustrate operation of the EK pump provided in FIG. 3
  • FIG. 5a - 5c schematically illustrate controlled collapse of impermeable membranes during operation of the EK pump illustrated in FIGS. 3 and 4;
  • FIG. 6 illustrates a cross-sectional view of another indirect EK pump embodiment;
  • FIG. 7 illustrates a cross-sectional view of one embodiment of a hydraulic amplifier;
  • FIG. 8 illustrates one embodiment of an EK delivery system comprising a syringe;
  • FIG. 9 illustrates the dependence of fluid flow rates on voltage of an EK pump;
  • FIG. 10 illustrates the relationship of pressure and fluid flow rate of an EK pump;
  • FIG. 11a illustrates one embodiment of a flow indicator;
  • FIG. lib illustrates one embodiment of a flow meter;
  • FIG. 12a illustrates an exploded, enlarged view of one embodiment of an EK delivery system;
  • FIG. 12b illustrates a schematic view of the EK delivery system illustrated in FIG. 12a
  • FIG. 13a illustrates an exploded, view of another EK delivery system embodiment
  • FIG. 13b illustrates a schematic view of the EK delivery system illustrated in FIG. 13a
  • FIG. 14 illustrates a schematic view of one embodiment of a shielded delivery system
  • FIG. 15 illustrates a schematic view of one embodiment of an EK sampling system
  • FIG. 16 illustrates a system block diagram of a dual drug delivery and sampling system
  • FIG. 17 illustrates system block diagram of a multi-drug delivery and sampling system
  • FIG. 18 illustrates a system block diagram of a multi-drug, multi-pump externally controllable delivery system
  • FIG. 19 illustrates a system block diagram of a distributed, multi-drug, multi-pump externally controllable delivery system
  • FIGS.20 - 24 illustrate pump performance wherein: FIG. 20 graphically illustrates rapid loading and delivery flow rates of an EK pump; FIG. 21 graphically illustrates the constant steady-state flow rates during operation of an EK pump at any instantaneous time; and FIGS. 22 and 23 graphically illustrate constant steady-state flow rates during operation of an EK pump configured to operate over a period of hours or days.
  • FIG. 1 is a cross-sectional view of a small, compact EK pump 100.
  • EK pump 100 comprises a first fluid reservoir 102 and a second fluid reservoir 104.
  • First fluid reservoir 102 is coupled to second fluid reservoir 104 by through-vias 106, 110 and porous dielectric material 108.
  • porous dielectric material 108 is encapsulated within a bonding material 114, between upper and lower substrates 116a and 116b, respectively, as further described in Ser. No. 10/198,223.
  • Each fluid reservoir further comprises a fluid port 118 (which can be an inlet or outlet port) and capacitive electrode 120a and 120b.
  • An electrical lead (not shown) is placed in contact with electrodes 120a, 120b to couple them to a power supply (not shown).
  • reservoirs 102 and 104 including the space between porous dielectric material 108 and electrodes 120a and 120b, is filled with an electrolyte or pump fluid 122.
  • the fluid 122 may flow though or around electrodes 120a and 120b.
  • pump fluid 122 is moved from one fluid reservoir to the other via electro-osmosis, without electrolysis, gas generation or substantial capacitive de-ionization during operation of the pump 100.
  • electro-osmosis As will be recognized by one skilled in the art, gas formation or pH change due to changes in pump components
  • the pump fluid and/or electrodes can introduce system error and decrease the precision of a fluid transport system or prevent the pump from working altogether.
  • the problem of gas formation and pH change in prior EK pumps results from electrochemical changes in the pump components, which are induced when a high enough electric field or voltage is applied to create a desired EK flow.
  • the pump fluid may be oxidized or reduced and produce gas and/or change the pH.
  • the electrodes of prior art EK pumps can be changed by oxidation-reduction reactions at the electrode-pump fluid interface. As will be recognized by one skilled in the art, these Faradaic processes decrease the precision and operability of EK pumps over time.
  • Faradaic processes include but not limited to, implementing drive strategies to limit Faradaic processes and careful material selection of pump electrodes.
  • a system voltage and the duration of the applied system voltage should be maintained sufficient to charge the electrodes and generate current flow to support a desired fluid flow rate for a given length of time, but below an electrode charging potential beyond which Faradaic reactions (such as oxidation/reduction) are induced.
  • Faradaic reactions such as oxidation/reduction
  • current flow is required in order to provide pump fluid flow. What is needed is a non- Faradaic process for maintaining current flow and fluid flow. This challenge can be met by employing electrodes having high double layer capacitance.
  • configuration of an EK pump to move a pump fluid without the occurrence of Faradaic processes includes the incorporation of electrodes made of materials having a high double-layer capacitance of at least 10 "4 Farads/cm 2 , more preferably of at least 10 "2 Farads/cm 2 , and most preferably of at least 1 F/cm 2 .
  • these high double-layer capacitance electrodes are compatible with a wide range of pump fluids.
  • high capacitance of double-layer materials arises from their comparatively large microscopic surface area.
  • carbon paper impregnated with a carbon aerogel can be used as a high capacitance double-layer electrode.
  • Other forms of carbon also have very large microscopic surface areas and exhibit double-layer high capacitances, and thus may be employed herein.
  • shaped carbon aerogel foam, carbon mesh, carbon fiber (e.g., pyrolized poly(acrylonitrile) or cellulose fiber), carbon black and carbon nanotubes all of which have significant double layer capacitances.
  • double-layer capacitive electrodes may also be formed of materials other than carbon
  • carbon is the preferred electrode material, as it is also inert and inhibits or slows reactions detrimental to EK transport of a fluid, i.e., Faradaic reactions (such as oxidation reduction of the electrodes or pump fluid).
  • Faradaic reactions such as oxidation reduction of the electrodes or pump fluid.
  • carbon based electrodes for example, carbon paper
  • a pump can be operated at system voltages, and the system voltages applied for durations, below a potential, or threshold, beyond which Faradaic processes such as electrolysis of the pump fluid is induced .
  • Pump fluid electrolysis potentials for most pump fluids are less than a few volts; for example, the electrolysis potential for water is about 1.2 V while the electrolysis potential for propylene carbonate pump fluid is about 3.4 V.
  • pump fluid electrolysis can be prevented or minimized.
  • the use of double layer high capacitance electrodes allows high or low system voltages to be used to support EK fluid flow through the pump without causing Faradaic processes in the pump fluid or electrodes.
  • driving strategies can be employed that apply a system voltage and the duration of the applied system voltage sufficient to charge the electrodes and generate current flow to support a desired fluid flow rate for a given length of time, but below an electrode charging potential beyond which Faradaic reactions (such as oxidation/reduction) of the electrodes are induced.
  • a pump fluid which is a non- Faradaic process but can still impact pump performance
  • Yet another approach can be to limit the volume of pump fluid (or other fluid) in a pump reservoir that can be transported during a given run time of a pump before complete deionization of the pump fluid occurs.
  • the pump design itself can be adapted to minimize the effect of deionization processes that can decrease the operability of a pump over time.
  • the shape of the first fluid reservoir 102 may be tapered in the portion of said reservoir immediately surrounding an electrode, creating a low volume fluidic path over the electrode.
  • this low volume reservoir 124 configuration creates a steady state ion concentration adjacent to the electrode 120a, as the rate of ions passing into a low volume reservoir 124 is generally proportional to the rate of deionization of the pump fluid 122 which usually occurs during operation of a pump.
  • FIG. 3 illustrates yet another embodiment of an EK pump 200 in accordance with the present invention.
  • pump 200 is configured as an indirect pump.
  • an indirect pump is a pump where movement of a pump fluid 122 causes flow of a second fluid in a separate part of the pump.
  • This second fluid is referred to herein as a working fluid 126, which may be a drug or other fluid to be dispensed by pump 200.
  • EK pump 200 generally comprises a first chamber 202 comprising: a first flexible barrier 204 separating first reservoir 206 and second reservoir 208; and a second chamber 210 comprising a second flexible barrier 212 that separates third reservoir 214 and fourth reservoir 216.
  • Either of ports 118 may be an outlet for the working fluid, an inlet for the working fluid and/or a vent for one of the working fluid reservoirs.
  • flexible barriers 204 and 212 are impermeable to prevent mixing of a pump fluid 122 (disposed in second 208 and fourth 216 reservoirs) and working fluid 126.
  • This pump configuration may be used when a working fluid (e.g., drug, reagent, etc.) is not compatible with electrokinetic flow; when the working fluid does not support a zeta potential, has a low electrolysis potential, has a high viscosity, or has or carries suspended particles or cells; or in cases where long-term storage, or useable lifetime, of the working fluid requires that it be separate from the pump fluid.
  • a fluidic pathway exists between second 208 and fourth 216 fluid reservoirs by means of porous dielectric material 108, which may be encapsulated within a bonding material disposed between upper and lower substrates (as in FIG. 1) or disposed within a conduit, or plurality of conduits.
  • Electrodes 120a and 120b surround openings leading to and from porous dielectric material 108.
  • FIGS. 4a - 4c are provided to illustrate what happens during operation of pump 200 as a voltage is applied across electrodes 120a and 120b disposed within second 208 and fourth 216 reservoirs respectively.
  • first flexible member 204 is collapsed while second flexible member 212 disposed with the second chamber 210 is distended.
  • working fluid 126 which may be a drug, etc
  • first reservoir 206 may be filled through port 118a with additional working fluid, air, etc., as flexible member 204 moves to expand first reservoir 206 and contract second reservoir 208.
  • a pump may be configured to comprise a flexible member that has a single flexure joint 300 (indicated by arrows) giving rise to a simple geometry during collapse (or expansions), as shown in FIG. 5a, or multiple or compound geometries during collapse, as pictured in FIGS. 5b and 5c.
  • the pumps provided herein are highly compact and not much larger than the volume of a fluid to be transported by the pump. Accordingly, in the present invention the various systems incorporating these pumps for fluid transport can be correspondingly small.
  • the volume of said system need not be greater than about 250% of the largest effective volume of a drug reservoir if an indirect pump configuration is employed.
  • FIG. 6 illustrates another technique that can be employed to ensure maximal and precise fluid delivery from an EK pump.
  • Through-vias 106 and 110 extend through a laminated substrate 116a and 116b to form upper and lower parts 208a, 208b, 216a, 216b of the pump fluid reservoirs.
  • the flexible members 204 and 212 define the upper reservoir parts 208a and 216a while the electrodes 120a and 120b of pump 300 are placed within lower reservoir parts 208b and 216b so that flexible members 204 and 212 are not in contact with the electrodes 120a and 120b during collapse.
  • this placement of electrodes inside of reservoirs 208 and 214 increases the fluid volume/capacity of the pump.
  • Filling ports 119 are used to fill the reservoirs 208a and 208b and reservoirs 216a and 216b with pump fluid 122 during pump manufacture and are sealed during pump operation.
  • FIG. 7 illustrates another feature that may be incorporated to modulate fluid flow rates from an EK pump, a hydraulic amplifier 400.
  • hydraulic amplifier 400 comprises a first piston 402 having a first cross-sectional area Al and diameter Dl and a rigid shaft 404 that couples first piston 402 to second piston 406 having a second cross- sectional area A2 and diameter D2.
  • fluid e.g., a pump fluid
  • first piston 402 which displaces the first piston 402 and the second piston 406 in a first direction.
  • second piston 406 may be directed against the second piston 406 to displace it and the first piston 402 in the opposite direction.
  • hydraulic amplifier 400 may be used to create pressure amplification or de- amplification as well as flow reduction or increase as may be needed.
  • linear displacement of the pistons 402 and 406 is generally equal.
  • pressure amplification or de- amplification proportional to the ratio of the cross-sectional areas is created.
  • the use of hydraulic amplifier can be used to alter the flow rate of a dispensed fluid vs. the flow rate of a pump fluid; for example a hydraulic amplifier can be used so that a dispensed fluid flow rate of a drug is between about .1 times and 10 times a pump fluid flow rate.
  • FIG. 8 is a schematic diagram of one embodiment of an EK delivery system 500 in accordance with the present invention.
  • EK delivery system 500 preferably comprises EK pump 502 having an inlet 504 and outlet 506 fluid port; a reservoir 508; a syringe 510 having a pump fluid chamber 512, plunger 514, a syringe port 516; a power source 518; and a system controller 520 having one ore more feedback sensors 522.
  • inlet fluid port 504 is coupled to reservoir 508 and outlet fluid port 506 is coupled to a syringe 510, containing, for example, a drug such as insulin, pain medication or other therapeutic or diagnostically useful agent.
  • pump 502 is configured to move a drug out of syringe 510 and into a patient.
  • Reservoir 508 can contain a pump fluid 122 while syringe 510 may be loaded with a drug.
  • EK pump 502 (via direction of controller 520) causes movement of the pump fluid 122 into pump fluid chamber 512 of syringe 510 and creates hydraulic pressure that pushes against syringe plunger 514, causing movement of the plunger 514 and effecting drug delivery.
  • syringe 510 can be configured to couple to any patient access device, such as a conventional infusion set, port-a-catheter, IV needle and the like, for transdermal, transvascular, intramuscular delivery of a drug into a patient.
  • system 500 can be configured as a small ambulatory system contained in a bio-compatible, preferably inert housing, which is hermetically sealed to prevent leakage of any system components.
  • a bio-compatible, preferably inert housing which is hermetically sealed to prevent leakage of any system components.
  • these devices are small and lightweight and can be configured in any shape so that they can be easily carried or worn by a patient and hidden from view.
  • syringe 510 and reservoir 508 can be adapted to be refillable.
  • system 500 can be coupled to a transcutaneous adhesive pad having a plurality of micro-needles to adapt system 500 as a transdermal delivery system.
  • system controller 520 serves to control the operation of pump 502 (e.g., to effect fluid flow rates, pressures, etc.), preferably in response to one or more system feedback sensors 522.
  • These feedback sensors 522 can be installed in any location, and their signals can be transmitted through a sensing circuitry, which can be integrated into system controller 520.
  • Various signals from these feedback sensors 522 can be configured to provide feedback regarding drug volume displacement; measurements of flow rate or delivery rate over time; battery life; drug and pump reservoir conditions; system component malfunctions; the presence of an occlusion or other flow obstruction or failure; and other data.
  • the feedback data is transmitted quickly so that dynamic responses by the system controller 520 in response to feedback data can be initiated.
  • a feedback sensor 522 can be coupled to syringe plunger 514 to detect and monitor displacement of plunger 514.
  • feedback sensor 522 may be a magnetostrictive sensor available from MTS Sensors, of Cary, North Carolina, and the plunger 514 may contain an embedded permanent magnet.
  • these sensors can provide absolute distance measurements of plunger 514 without needing to be zeroed to an external reference. By monitoring the distance moved by plunger 514 at a given time, the amount of a substance delivered by system 500 can be compared to the desired amount of a substance to be delivered and the operation of the pump modulated at selected time intervals to ensure precise accurate delivery.
  • Pump modulation may involve modifying drive voltage, current or duration of pump operation.
  • data from feedback sensor 522 is relayed to controller 520 where displacement of the plunger 514 can be correlated to the amount of agent/drug delivered by system 500.
  • the controller 520 can modulate operation of pump 502 (by regulating current and voltage applied to the pump) to achieve the appropriate drug delivery profile.
  • operational parameters of the pump may be modulated. For example, flow rates can increase or decrease based on feedback from sensors 522 disposed on plunger 514 by altering the voltage applied to the electrodes disposed in pump 502. FIG.
  • controller 520 can simply apply power to the electrodes according to a preset on and off cycle (e.g., where the power is normally off and is turned on to dispense fluid from the syringe) according to a computer program, timer or other control. Use of a timing circuit or other timing control to turn the power on for a period of time can be used to deliver a fixed volume or bolus from the syringe.
  • a preset on and off cycle e.g., where the power is normally off and is turned on to dispense fluid from the syringe
  • timer or other control Use of a timing circuit or other timing control to turn the power on for a period of time can be used to deliver a fixed volume or bolus from the syringe.
  • the system controller can also be provided with a user interface so that a user can indicate or change the volume or size of the bolus delivered.
  • flow indicators 600 and flow meters 602 may be disposed in, or coupled to, one or more fluid paths of an EK system, to provide indication of the amount (volume) of a drug dispensed, the amount of agent still remaining in a syringe, the amount of fluid pump fluid remaining in a system reservoir, flow rate, etc.
  • said flow indicators 600 and flow meters 602 can provide a visual indication to a system user, or can be functionally coupled to a controller and adapted to supply electronic signals indicative of such information to enable modulation of a EK pump, as needed.
  • pump chamber 512 can be adapted as a hydraulic amplifier to alter the flow rate of a drug from syringe 510 and/or the flow rate of the pump fluid into pump chamber 512.
  • feedback mechanisms can be employed in order to create a feedback loop directly to the EK pump to control activation of a voltage from a battery or power source to the electrodes.
  • a small processor can be designed to produce an activation signal for a selected signal duration, e.g., 1-4 seconds, at selected time intervals to run the EK pump directly
  • FIGS. 12a-12b illustrate an exploded, enlarged view and a schematic view, respectively, of a self-contained indirect EK pump delivery system 700 in accordance with the present invention.
  • delivery system 700 is enclosed within housing 702, which includes a first cover 704 and a second cover 706, which can be adhesively bonded together.
  • First cover 704 comprises a first pump fluid aperture 708 and a second pump fluid aperture 712.
  • Apertures 708 and 712 each have a silicone septum which may be pierced by a needle for adding pump fluid to the system. After filling the system with pump fluid, apertures 708 and 712 may be sealed, such as by covering with epoxy.
  • Second cover 706 houses the internal circuitry of the system in the cavity 715, including a system controller disposed on circuit board 718 and a power source 720.
  • Second cover 706 also houses a first pump fluid reservoir 709 communicating with a second pump fluid reservoir 724 through a through- via 728b, a third pump fluid reservoir 726 communicating with a fourth pump fluid reservoir 713 via a through- via 728a (located in the first cover 704 — not shown in FIG. 12a). Apertures 708 and 712 communicate with reservoirs 724 and 726, respectively.
  • Porous double layer capacitive electrodes 120a and 120b are disposed in reservoirs 726 and 724, respectively, and the pump fluid in those reservoirs can be moved between reservoirs 726 and 724 (and through reservoirs 709 and 713) through a porous dielectric material 730 (such as packed bed of silica beads) disposed in channel 732 extending between reservoirs 726 and 724 by applying a voltage to electrodes 120a and 120b from the power source via electrical connections (not shown).
  • Flexible impermeable diaphragms 734a and 734b are disposed in second cover 706 to form fifth and sixth reservoirs 710 and 714 adjacent the first and fourth reservoirs 709 and 713, respectively.
  • a vent 799 communicates fifth reservoir 710 with the exterior of the pump, and a cannula 722 serves as an outlet from sixth reservoir 714.
  • fluid aperture 798 with a silicone septum on the underside of cover 706 provides a way to fill the sixth reservoir 714 with a drug or other fluid to be delivered.
  • power may be supplied to electrodes 120a and 120b to move pump fluid from reservoirs 709 and 724 into reservoirs 726 and 713, thereby moving flexible diaphragm 734b to dispense the drug from reservoir 714 through cannula 722.
  • the system 700 is small, having an overall dimension of about 2 x 0.8 x 0.4 inches and is configured to deliver about 300 microliters of a drug employing about 300 microliters of a pump fluid.
  • the overall size or volume of system 700 i.e., the volume of the pump less the volume of the power source and circuit board
  • FIGS. 13a and 13b illustrate yet another embodiment of an EK pump delivery system 800 in accordance with the present invention.
  • the system is adapted for high flow-rate (about 1-lOmL/min) transport of fluid and which generally comprising electrodes having a porous dielectric material disposed, preferably laminated, between the electrodes so that pump fluid movement is through or perpendicular to the face of the pump as best illustrated in FIG. 13b.
  • FIG. 13a illustrates exploded view of one embodiment of EK pump system 800.
  • a flexible diaphragm 820 held between a top housing 812 and a spacer 816 defines a first fluid reservoir 808 and a second fluid reservoir 810.
  • a second flexible diaphragm 830 held between a bottom housing 824 and spacer 828 defines a third fluid reservoir 811 and a fourth fluid reservoir 821.
  • a porous dielectric material 802 separates the second and third reservoirs, which contain EK pump fluid.
  • Fluid reservoirs 808 and 821 each have fluid inlet and a fluid outlet ports, which couple reservoirs 808 and 821 to fluid pathway 832 (best illustrated in FIG. 13b) comprising a plurality of check valves 834, 836, 838 and 840. As best shown in FIG.
  • system 800 is configured to provide high flow rate unidirectional transport along fluid pathway 832, e.g., movement of fluid from a drug source 846 (such as, e.g., a collapsible IV bag) to system inlet port 842 to system outlet port 844 (which may be coupled to a patient access member 848, such as a needle, infusion set, etc.) and to a patient.
  • a drug source 846 such as, e.g., a collapsible IV bag
  • system inlet port 842 to system outlet port 844 (which may be coupled to a patient access member 848, such as a needle, infusion set, etc.) and to a patient.
  • patient access member 848 such as a needle, infusion set, etc.
  • voltage from power source 850 is applied to electrodes (not shown) disposed in reservoirs 810 and 811 to cause movement of pump fluid (as indicated by shading) disposed between flexible diaphragms 820 and 830, i.e., from fluid reservoir 810 to fluid reservoir 811, and the direction of flow may be reversed by reversing the polarity of the applied voltage. Movement of the pump fluid from reservoir 810 to reservoir 811 will cause flexible member 820 to move downward, which in turn will draw fluid from drug source 846 to system inlet port 842 and through fluid pathway 832 into reservoir 808.
  • Check valve 836 prevents fluid from being drawn into reservoir 808 from outlet 844.
  • fluid in reservoir 821 will be expelled as flexible member 830 moves downward, and check valve 838 prevents the expelled fluid from flowing toward drug source 846.
  • the operation is then reversed by reversing the polarity of the applied voltage, so that pump fluid flows from reservoir 811 into reservoir 810 and diaphragms 820 and 830 move upward. This movement draws the drug into reservoir 821 via check valve 838 and expels drug from reservoir 808 via check valve 836.
  • Check valves 840 and 834 prevent the fluid from flowing in an undesired direction.
  • the operation of this pump system can be controlled by a controller coupled to the pump, which modulates operation of the pump (by regulating current and voltage, for example amplitude and period or duration, applied to the pump, electrodes, etc.).
  • system 800 is a small (about 1.6 x 1.2 x 1.7 inches) ambulatory system configured to deliver fluids at flow rates of about 1 mL/min at about 1-2 psi.
  • System 800 can be used in place of conventional infusion pump, for example PCA pumps and the like, which are typically coupled to IL saline bags.
  • EK system 800 can be used similarly and configured for continuous fluid delivery or operation or for intermittent fluid delivery (e.g., by intermittent activation of a system voltage from a battery coupled to turn the system 800 on and off). EK system 800 may also be controlled by feedback (e.g. vary voltage and or current based on a flow sensor reading).
  • FIG. 14 illustrates yet another embodiment of drug delivery system 900, wherein delivery system 900 is adapted for the delivery of radioactive drugs or other toxic diagnostic or therapeutic compounds that require special handling to minimize a patient or user's exposure to those compound(s).
  • delivery system 900 comprises a protective or shielded housing 902, which surrounds an EK pump 904; a power source 906; and controller 908.
  • Delivery system 900 further comprises a patient access means 910, which can be a cannula or needle adapted to provide subcutaneous, transvascular or other access to a patient, dosimeter 913, which can be disposed and coupled to a fluid path, reservoir or the like of EK pump 904 to provide indication to a patient/or user regarding a substances delivered, etc.
  • the patient access means 910 is shielded to protect the patient or user from the radioactive or toxic material while it is being pumped into a patient.
  • Delivery system 900 further comprises an internal liner 912, preferably a removable liner, adapted to shield the patient or user from the radioactive or toxic compound contained within the system.
  • system 900 can further comprise other system components, such as a flow indicator or meter 914; dosimeter 913 (as mentioned above); or other indicator to signal the amount of the toxic substance that has been delivered, how much is left, etc., in order to obviate or minimize the need to handle the system 900 during operation.
  • indicator 914 can be adapted to be easily viewable by a user or can optionally be omitted and instead an electronic flow meter employed.
  • pump 904 and system 900 can be configured to be remotely activated and/or programmable in response to user or automatic control by a preprogrammed controller with feedback control provided by a dosimeter 912, flow indicator dosimeter 914 or the like.
  • system 900 can be adapted to withstand irradiation to activate a non-radioactive drug preloaded into system 900. Upon irradiation of a preloaded drug within system 900, it is converted into a radioactive form. Therefore, radioactive materials do not need to be handled in order to load a radioactive drug or substance into delivery system 900. Moreover, because of the low cost of the delivery system and EK pump, the entire system 900 can be discarded after use.
  • FIG. 15 illustrates yet another aspect of the invention, specifically an EK sampling system 1000, which can be adapted to draw, analyze and/or store (within the system) a physiological fluid, such as blood (e.g., for glucose monitoring) or other body fluid containing a target analyte from a patient.
  • sampling system 1000 comprises an indirect EK pump 1002, which is coupled to a sampler 1004 and an analyzer 1006, which are fluidly coupled to EK pump 1002 via external fluid loop 1008.
  • pump can be operated to effect transport of a physiological fluid taken from a patient by sampler 1004 to analyzer 1006 where the physiological fluid may be evaluated for the analyte.
  • the Ringers solution, saline or other appropriate fluid can be pumped through fluid loop 1008 where the solution can be mixed with the extracted physiological fluid at sampler 1004 and transported to analyzer 1006.
  • Sampler 1004 may be any conventionally known system or device for obtaining a physiological fluid.
  • sample 1004 may comprise a EK pump adapted to hydraulically draw a physiological fluid from a patient.
  • EK pump system and pump configuration suitable for such an application is described with reference to FIGS. 13a - 13b.
  • analyzer 1006 may be any conventionally known system for testing the obtained sample.
  • analyzer 1006 can be reagent system for determination of a patient's glucose concentrations in the sampled physiological fluid, as further described in U.S. Pat. No.
  • FIG. 16 illustrates a system block diagram of another embodiment, wherein the EK system 2000 is a dual analyte sampling and drug delivery system.
  • system 2000 broadly comprises a system controller 2002; an analyte sampling subsystem 2004 comprising a first EK pump 2006; and a drug delivery subsystem 2008 comprising a second EK pump 2010.
  • the system controller 2002 serves to control the operation of the sampling and delivery subsystems 2004 and 2008 by controlling voltage being applied to the EK pumps.
  • system 2000 comprises two separate fluid paths 2012 and
  • Fluid path 2014 is coupled the second EK pump 2010 and adapted to electro- osmotically pump a drug from within drug reservoir 2016 to a patient.
  • Fluid path 2012 is coupled to the first EK pump 2006 and adapted to electro-osmotically pump a physiological fluid from sampler 2018 to analyzer 2020 where it can be evaluated.
  • the control of drug delivery subsystem 2008 by controller 2002 is based on feedback from sampling subsystem 2004.
  • Controller 2002 is adapted to send and/or receive data to and from the sampling and drug delivery subsystems 2004 and 2008 to modulate drug delivery and determine an appropriate drug delivery profile or regime depending on monitoring and analysis of a patient's physiological and/or chemical state by sampling subsystem 2004.
  • the sampling subsystem 2004 can be configured to measure a specific analyte and/or a change in analyte parameter and to compare it to a known values stored within a memory component of controller 2002, so that the EK system 2000 can effect drug delivery in response to any physiological, physiochemical or chemical changes in a patient.
  • controller 2002 can execute a command signal to the delivery subsystem 2008 to initiate, control and/or terminate of an operation.
  • system 2000 can be configured for the treatment of diabetes and adapted to deliver insulin. Insulin delivery can be initiated after a patient's blood glucose concentration has been determined by sampling subsystem 2004.
  • Delivery subsystem 2008 can be configured to deliver a quantity of insulin into the patient in response to the determined blood glucose concentration. Delivery of insulin in response to the determined blood glucose concentration may comprise automatically effecting delivery of insulin or can be configured to require user initiation of insulin delivery or both.
  • delivery subsystem can be adapted to deliver more than one type of insulin, insulin at different delivery rates to effect basal and bolus delivery.
  • the system can be adapted to deliver a frequent micro-volumes or microboluses of insulin in order to maintain a constant glucose concentrations in a patient to effect better or effective diabetes management.
  • the various systems and pumps provided herein may be multiplexed to provide delivery of more than one drug, comprise more than one fluid path, flow rate or EK pump as schematically depicted in FIGS.
  • FIG. 17 illustrates a system block diagram for a multi-pump, multi-reservoir drug delivery system 3000.
  • the various EK pumps of the invention may be multiplexed and adapted to provide a system capable of delivering more than one drug D ⁇ ...Dminister, for example, in order to deliver a drug cocktail or for delivering one or more drugs at differing flow rates FR ⁇ ....FRabel or for delivering one drug at differing flow rates (e.g., for basal, bolus delivery) or the like.
  • EK system 3000 can be adapted to deliver more than one compound, to mimic or functionally augment or replace diseased or organ, such as a pancreas.
  • drug delivery subsystem can comprise one or more EK delivery pumps 3002 that can be configured to deliver one or more compounds or drugs (e.g., trypsin, steapsin, amylolytic ferment) and which are coupled to a sampling subsystem 3010 for providing feedback control of the multi-pump delivery subsystem 3012 (through, e.g., diagnostics sampling blood or other biological fluids) controlling how much of each substance is needed. Other organs may be mimicked or augmented in this way.
  • system 3000 can be configured to deliver a single drug from drug reservoir 3014 which is common to all pumps 3002, for delivery at differing flow rates, etc., FIG.
  • FIG. 18 illustrates yet another embodiment of a multi-reservoir, multi-pump drug delivery system 4000 comprising an external controller 4002.
  • Operation of the implanted delivery system 4000 can be operationally controlled by external controller 4002 having a user interface 4004.
  • Signals (such as RF, IR or other electronic transmissions) between external controller and implanted delivery system 4000 are provided to allow interface with, and/or control, by external controller 4002 of one or more of the components of the delivery system 4006 such as a controller, battery, electrodes, feedback sensors, etc.
  • Signal transmission lines 4008 illustrate one method of controlling the multiple pumps 4010 system 4000. In this embodiment, the fluid paths 4012 of system 4000 are illustrated.
  • the various fluids can be combined for delivery to a target treatment site inside a body.
  • an external pump or pumps located outside of the patient may be remotely controlled to deliver one or more fluids to the patient.
  • this embodiment may be useful for medical applications where the delivery of multiple agents is required, e.g., for diagnostic imaging studies, for cancer treatment where multiple chemotherapeutic agents need to be delivered simultaneously or in a particular timing or order, where one agent counteracts unwanted side effects of another agent, etc.
  • Agent A is a chemotherapy cocktail called Taxotere used in early or late stage breast cancer. The unwanted side effect is a reduction in white blood cells.
  • Agent B is an antibiotic that is provided in proportion to the reduction in white blood cell activity or white blood cell count. Agent B could be provided at a first, higher rate immediately following the highest dosage of chemotherapy, then tapered off as the body's ability to produce white blood cells improves or is restored.
  • Other examples include a multi-drug cocktail to treat AIDS (reservoirs contain AZT, reverse transcriptase inhibitors and protease inhibitors) and multi-drug cocktails to treat tuberculosis, hepatitis B, hepatitis C, and tissue rejection after an organ transplant.
  • FIG. 19 is a system block diagram of an implantable "distributed" drug delivery system 5000 comprising one or more implantable drug delivery subsystems 5002 and an external controller 5004. As illustrated, the various delivery subsystems 5002 can be implanted at different locations inside a patient's body for drug delivery at more than one treatment site.
  • each of the subsystems 5002 is configured to be operable by external controller 5004.
  • an external pump or pumps located outside of the patient may be remotely controlled to deliver one or more fluids to the patient.
  • Other embodiments of indirect pumps may be provided.
  • the drug or other fluid to be delivered may be loaded into a collapsible bag placed within a rigid chamber. Delivery of the EK pump fluid into the portion of the rigid chamber outside the bag collapses the bag to dispense the drug out through an outlet, such as a plastic tube. This approach may be used to deliver high viscosity drugs, for example.
  • Pumping system embodiments of the present invention may include electronics and communications that allow for various level of control authority, for example the prescribing physician may have a greater authority over dosing, while the patient has a lesser authority.
  • This authority my include electronic key authentication for granting such authority as well as for activation (e.g., for cases where the device dispenses controlled substances requires specific license to prescribe/distribute, such as for a scheduled narcotic). As.
  • the device can be configured to deliver only a total amount of drug over a period of time, regardless of how much drug is delivered at each of one or more times during that period.
  • the device can be controlled to operate for only a set period of time, no matter how much drug has been delivered.
  • the device can also provide a display showing the amount of drug remaining in the reservoir, the amount of dose delivered at one time or overall, etc.,
  • physiological inputs such as limb movement during Parkinson' s- induced tremor or epileptic seizure, may trigger the release of a drug from the EK pump to treat the condition.
  • the device may include electronics and communications that provide for making a historical record of device operation that may be complemented with records of various physiological responses or conditions (e.g., heart rate, blood pressure, EKG, blood gases, serum levels of specific compounds). These records can be downloaded for analysis and use in optimizing treatment and/or judging response to treatment. Various levels of authority can be included if desired to allow some, all or none of the download features.
  • FIGS. 20-23 are provided to illustrate the performance aspects of the EK systems and pumps provided herein. For example, FIG. 20 is provided to illustrate fast loading and delivery flow rates plotted over time for a typical EK pump in accordance with the present invention.
  • FIG. 21 is provided to illustrate the overall reliability and precision of fluid transport by the EK pumps of the present invention.
  • constant fluid flow rates can be maintained during pump operation, little or no error in flow rates at any given time.
  • flow rate errors can be maintained at less than 5% during steady-state flow.
  • Pumps of the present invention may be advantageously used to dispense agents of wide ranging physical characteristics.
  • embodiments of the present invention may be used to pump agents having a viscosity of 10 to 100 poise, 100 to 1,000 poise or 1,000 to 10,000 poise.
  • pumps of the present invention maintain the precision and micro-delivery aspects described herein.
  • pumps of the present invention may provide 1-10 microliters per hour flow rates for agents ranging from 10 to 10,000 poise.
  • the EK pump systems of this invention may be used to deliver many different drugs or other substances to treat a variety of disorders.
  • the agent (or agents in a co-treatment embodiment) dispensed by the pump may include by way of illustration and not limitation: muscarinic receptor agonists and antagonists; anticholinesterase agents; agents acting at the neuromuscular junction and/or autonomic ganglia; catecholamines, sympathominmetic drugs, and adrenergic receptor antagonists; and 5-hydroxytryptamine (5-HT, serotonin) receptor agonists and antagonists.
  • muscarinic receptor agonists and antagonists may include by way of illustration and not limitation: muscarinic receptor agonists and antagonists; anticholinesterase agents; agents acting at the neuromuscular junction and/or autonomic ganglia; catecholamines, sympathominmetic drugs, and adrenergic receptor antagonists; and 5-hydroxytryptamine (5-HT, serotonin) receptor agonists and antagonists.
  • the agent dispensed by the pump may include by way of illustration and not limitation: general anesthetics, local anesthetics, analogs of benzodiazepine and barbiturates, a hypnotic, a sedative, aliphatic alcohols, ethanol, nonbenzodiazepine sedative-hypnotic drugs, sedative-hypnotic agents of diverse chemical structure (e.g., paraldehyde, chloral hydrate), CNS depressants, antidepressant therapeutic agents, antipsychotic and antimanic agents, norepinephrine inhibitors, monoamine oxidase inhibitors, selective serotonin-reuptake inhibitors, benodiazepine sedative-antianxiety agents, serotonin 5-HTi A -receptor partial
  • the agent (or agents in a co-treatment embodiment) dispensed by the pump may include by way of illustration and not limitation: histamine and histamine antagonists, bradykinin and bradykinin antagonists, 5-hydroxytryptarnine (serotonin), lipid substances that are generated by biotransformation of the products of the selective hydrolysis of membrane phospholipids, eicosanoids, prostaglandins, thromboxanes, leukotrienes, aspirin, nonsteriodal anti-inflammatory agents, analgesic-antipyretic agents, agents that inhibit the synthesis of prostaglandins
  • the agent (or agents in a co-treatment embodiment) dispensed by the pump may include by way of illustration and not limitation: diuretics, vasopressin, agents affecting the renal conservation of water, rennin, angiotensin, agents useful in the treatment of myocardial ischemia, anthihypertensive agents, angiotensin converting enzyme inhibitors, ⁇ -andrenergic receptor antagonists, agents for the treatment of hypercholesterolemia, and agents for the treatment of dyslipidemia.
  • the agent (or agents in a co-treatment embodiment) dispensed by the pump may include by way of illustration and not limitation: agents used for control of gastric acidity, agents for the treatment of peptic ulcers, agents for the treatment of gastroesophageal reflux disease, prokinetic agents, antiemetics, agents used in irritable bowel syndrome, agents used for diarrhea, agents used for constipation, agents used for inflammatory bowel disease, agents used for biliary disease, agents used for pancreatic disease.
  • the agent (or agents in a co-treatment embodiment) dispensed by the pump may include by way of illustration and not limitation: drugs used to treat protozoal infections, drugs used to treat Malaria, Amebiasis, Giardiasis, Trichomoniasis,
  • the agent (or agents in a co-treatment embodiment) dispensed by the pump may include by way of illustration and not limitation: antineoplastic agents.
  • the agent (or agents in a co-treatment embodiment) dispensed by the pump may include by way of illustration and not limitation: antimicrobial agents, sulfonamides, trimethoprim-sulfamethoxazole quinolones, and agents for urinary tract infections, penicillins, cephalosporins, and other, ?-Lactam antibiotics, an agent comprising an aminoglycoside, protein synthesis inhibitors, drugs used in the chemotherapy of tuberculosis, mycobacterium avium complex disease, and leprosy, antifungal agents, antiviral agents including nonretroviral agents and antiretroviral agents.
  • agents may include drugs used for immunomodulation, such as immunomodulators, immunosuppressive agents, tolerogens, and immunostimulants.
  • agents may include drugs acting on the blood and the blood-forming organs, hematopoietic agents, growth factors, minerals, and vitamins, anticoagulant, thrombolytic, and antiplatelet drugs.
  • agents may include hormones and hormone antagonists, pituitary hormones and their hypothalamic releasing factors, thyroid and antithyroid drugs, estrogens and progestins, androgens, adrenocorticotropic hormone; adrenocortical steroids and their synthetic analogs; inhibitors of the synthesis and actions of adrenocortical hormones, insulin, oral hypoglycemic agents, and the pharmacology of the endocrine pancreas, agents affecting calcification and bone turnover: calcium, phosphate, parathyroid hormone, vitamin D, calcitonin, and other compounds.
  • agents may include vitamins such as water-soluble vitamins, vitamin B complex, ascorbic acid, fat-soluble vitamins, vitamins A, K, and E.
  • agents may include drugs suited to dermatological pharmacology and ocular pharmacology. Additional disorders and their treatments may be found in Goodman and Gilman's
  • the agent may be a biological molecule or a pharmaceutical drug, DNA, RNA or a protein.
  • perceptible indication of operation refers to a any outward sign that the pump is operating.
  • conventional piezoelectric pumps have a distinct buzz resulting from the vibration of the piezoelectric elements.
  • Conventional mechanical and peristaltic pumps have distinct mechanical noises that indicate the pump is operating.
  • Such perceptible indications, especially noises are undesirable for pump systems worn on the person or to be operated in public, for example, to dispense insulin prior or during a meal.
  • Embodiments of the present invention are capable of dispensing or administering an agent without a perceptible indication of pump operation.
  • embodiments of the present invention may operate and generate noise levels below 20 db, or in some embodiments below 10 db or in still other embodiments generate noise inaudible or barely audible to a human being.
  • the pump and pumping systems described herein are useful in methods for the treatment of animal subjects.
  • the term "animal subject" as used herein includes humans as well as other mammals.
  • the methods generally involve the administration of one or more agents for the treatment of one or more diseases. Combinations of agents can be used to treat one disease or multiple diseases or to modulate the side-effects of one or more agents in the combination.
  • treating includes achieving a therapeutic benefit and/or a prophylactic benefit.
  • therapeutic benefit is meant eradication or amelioration of the underlying disorder being treated.
  • therapeutic benefit includes eradication or amelioration of the underlying cancer.
  • a therapeutic benefit is achieved with the eradication or amelioration of one or more of the physiological symptoms associated with the underlying disorder such that an improvement is observed in the patient, notwithstanding that the patient may still be afflicted with the underlying disorder.
  • administration of a chemotherapeutic agent to a patient suffering from cancer provides therapeutic benefit not only when the patient's tumor marker level is decreased, but also when an improvement is observed in the patient with respect to other complications that accompany the cancer like pain and psychiatric disorders.
  • the combination of phosphate binder and gastric pH modulator may be administered to a patient at risk of developing a particular disease, like cancer, or to a patient reporting one or more of the physiological symptoms of a disease, even though a diagnosis of this disease may not have been made.
  • the agent is a drug.
  • Drugs are any compounds of any degree of complexity that perturb a biological state, whether by known or unknown mechanisms and whether or not they are used therapeutically.
  • Drugs thus include: typical small molecules of research or therapeutic interest; naturally-occurring factors, such as endocrine, paracrine, or autocrine factors or factors interacting with cell receptors of all types; intracellular factors, such as elements of intracellular signaling pathways; factors isolated from other natural sources; pesticides; herbicides; and insecticides.
  • the biological effect of a drug may be a consequence of, inter alia, drug-mediated changes in the rate of transcription or degradation of one or more species of RNA, the rate or extent of translation or post-translational processing of one or more polypeptides, the rate or extent of the degradation of one or more proteins, the inhibition or stimulation of the action or activity of one or more proteins, and so forth. In fact, most drugs exert their affects by interacting with a protein.
  • activating drugs drugs that increase rates or stimulate activities or levels of a cellular constituent
  • inhibitorting drugs drugs that decrease rates or inhibit activities or levels of cellular constituents
  • activating drugs drugs that decrease rates or inhibit activities or levels of cellular constituents
  • inhibitorting drugs drugs that decrease rates or inhibit activities or levels of cellular constituents
  • the agents used in the pumps described herein may be used alone or in combination with one or more pharmaceutically acceptable carrier. Examples of suitable carriers are known in the art, for example, see Remington: The Science and Practice of Pharmacy by
  • the carrier improves the delivery of the agent to the subject. It is also preferable that the carrier does not hinder the delivery of the agent.
  • the carrier has sufficient ionic properties to support the electro-osmotic functioning of the pump.
  • the pump is used to detect the presence of one or more markers of a disease. If a marker of a disease is detected as being present, the pump is used to deliver one or more agents to treat the disease.
  • marker as used herein is intended to encompass biological markers and also measurable phenotypic characteristics like temperature, pressure, etc.
  • biological markers include, but are not limited to, DNA, RNA, proteins, enzymes, hormones, cells, portions of cells, tissues, or organs, subcellular organelles like mitochondria, nucleus, Golgi complex, lysosome, endoplasmic reticulum, and ribosome, chemically reactive molecules like H + , superoxides, and ATP.
  • markers include, but are not limited to, prostate specific antigen for prostate cancer, glucose and/or insulin levels for diabetes, and blood pressure measurements for hypertension.
  • the systems of the invention may comprise for example any of the features of conventional drug delivery or analyte monitoring devices including for example alarms or other indicators for notifying a user of when drug delivery is complete.
  • various retention members and the like may be coupled to the various device and systems in aid in the portability of the various devices and system.
  • the intended uses of the present invention include a variety of medical applications as well as other applications where highly precise, compact devices for fluid transport are needed. It should be understood that various alternatives to the embodiments of the invention described herein may be employed in practicing the invention. It is intended that the following claims define the scope of the invention and that methods and structures within the scope of these claims and their equivalents be covered thereby.

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CA2564800C (en) 2014-04-15
CN101365885B (zh) 2011-08-03
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EP1740497A4 (de) 2015-11-11

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