U.S. patent application number 13/091047 was filed with the patent office on 2012-02-16 for electrolytically driven drug pump devices.
This patent application is currently assigned to MiniPumps, LLC. Invention is credited to SEAN CAFFEY, Mark Humayun, Michelle Journey, Alice Lai, Po-Ying Li, Jason Shih, Yu-Chong Tai.
Application Number | 20120041427 13/091047 |
Document ID | / |
Family ID | 44121015 |
Filed Date | 2012-02-16 |
United States Patent
Application |
20120041427 |
Kind Code |
A1 |
CAFFEY; SEAN ; et
al. |
February 16, 2012 |
ELECTROLYTICALLY DRIVEN DRUG PUMP DEVICES
Abstract
Electrolytically driven drug pump devices may be configured so
as to ensure sustained contact of the electrolysis electrodes with
the electrolyte, thereby improving the reliability and/or pump
capacity of the devices.
Inventors: |
CAFFEY; SEAN; (Manhattan
Beach, CA) ; Li; Po-Ying; (Los Angeles, CA) ;
Tai; Yu-Chong; (Pasadena, CA) ; Humayun; Mark;
(Glendale, CA) ; Lai; Alice; (Upland, CA) ;
Shih; Jason; (Yorba Linda, CA) ; Journey;
Michelle; (Carlsbad, CA) |
Assignee: |
MiniPumps, LLC
Manhattan Beach
CA
|
Family ID: |
44121015 |
Appl. No.: |
13/091047 |
Filed: |
April 20, 2011 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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61326047 |
Apr 20, 2010 |
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61367686 |
Jul 26, 2010 |
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61423945 |
Dec 16, 2010 |
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61449899 |
Mar 7, 2011 |
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Current U.S.
Class: |
604/891.1 ;
604/151 |
Current CPC
Class: |
A61M 5/14526 20130101;
A61M 2005/14204 20130101; A61M 2205/3523 20130101; A61M 5/14248
20130101; A61M 5/16886 20130101; A61M 2210/0612 20130101; A61M
5/14276 20130101; A61M 2205/3569 20130101; A61M 5/14593 20130101;
A61M 2205/3592 20130101; A61M 2205/3584 20130101; A61M 5/1684
20130101 |
Class at
Publication: |
604/891.1 ;
604/151 |
International
Class: |
A61M 5/145 20060101
A61M005/145; A61M 37/00 20060101 A61M037/00 |
Claims
1. A drug pump device comprising: a vial comprising a drug
reservoir therein, the drug reservoir being fluidically connectable
to a cannula for conducting liquid from the reservoir; an
electrolytically driven piston, movable within the vial, for
forcing liquid from the reservoir into the cannula, a first side of
the piston facing the drug reservoir; and an electrolysis pump
comprising an electrolysis chamber in contact with a second side of
the piston and, contained within the chamber, at least one coaxial
electrode pair in contact with electrolyte absorbed within a
matrix.
2. The device of claim 1, comprising multiple coaxial electrode
pairs in a parallel arrangement.
3. The device of claim 2, wherein the coaxial electrode pairs are
arranged in a close-packing pattern.
4. The device of claim 3, wherein the electrode pairs have
hexagonal cross sections and are arranged in a honeycomb
fashion.
5. The device of claim 1, wherein the at least one electrode pair
comprises a surface coating inhibiting gas formation.
6. The device of claim 5, wherein a surface portion of the
electrode pair proximate to the piston is not coated so as to allow
gas formation thereat.
7. The device of claim 1, wherein the coaxial electrode pair is
sealed with a gas-permeable membrane.
8. The device of claim 1, wherein the matrix comprises a solid
phase of a gel.
9. The device of claim 8, wherein the gel comprises a hydrogel.
10. The device of claim 1, wherein the matrix comprises a
hydrophilic absorbent material.
11. The device of claim 1, wherein the matrix comprises a sponge,
cotton, or superabsorbent polymer.
12. The device of claim 1, wherein the vial is formed from a
conventional drug vial.
13. The device of claim 1, wherein the vial comprises at least one
of glass or a polymer.
14. The device of claim 1, wherein the electrolysis pump is
attached to the vial by a clamp-fit mechanism and sealed by a
rubber O-ring.
15. The device of claim 1, further comprising an electrical circuit
and associated power supply.
16. The device of claim 15, wherein the electrolysis pump comprises
a back-end comprising at least one of ceramics, polymer, anodized
metal, or glass, with feed-throughs for connection to the external
electrical circuit and associated power supply without loss of
electrolyte fluid and without electrical shorting of the electronic
circuit or battery.
17. The device of claim 15, wherein the electrical circuit and
associated power supply are sized based on a diameter of the
electrolysis pump so as to fit as a cap thereon.
18. The device in claim 15, wherein the electrical circuit and
associated power supply are located adjacent the vial and
wire-connected to the electrolysis pump.
19. The device of claim 1, further comprising a controller for
facilitating device operation by an electronic handheld device via
a wireless connection.
20. The device of claim 1, further comprising a mechanical selector
for setting a drug dose to be delivered from the drug
reservoir.
21. A drug pump device comprising: a vial comprising a drug
reservoir therein, the drug reservoir being fluidically connectable
to a cannula for conducting liquid from the reservoir; an
electrolytically driven piston, movable within the vial, for
forcing liquid from the reservoir into the cannula, a first side of
the piston facing the drug reservoir; and an electrolysis pump
comprising (i) an electrolysis chamber in contact with a second
side of the piston, and (ii) cathode and anode structures arranged
to remain at least partially submerged in liquid electrolyte
partially filling the chamber notwithstanding variations in
orientation of the device.
22. The device of claim 21, wherein the cathode structure comprises
first and second cathode portions and the anode structure comprises
first and second anode portions, the first cathode and anode
portions being in contact with the piston and the second cathode
and anode portions being attached to an opposed wall of the
electrolysis chamber.
23. The device of claim 22, wherein the cathode and anode
structures further comprise flexible wires electrically connecting
the respective first and second portions notwithstanding variations
in the distance therebetween.
24. The device of claim 22, wherein at least one of the first or
second cathode and anode portions are two-dimensional and
interdigitated.
25. The device of claim 22, wherein the first cathode and anode
portions extend parallel to the second side of the piston and the
second cathode and anode portions extend parallel to the opposed
wall of the electrolysis chamber.
26. The device of claim 22, wherein the first cathode and anode
portions extend at an angle with respect to the second side of the
piston and the second cathode and anode portions extend at an angle
to the opposed wall of the electrolysis chamber.
27. The device of claim 22, wherein each of the first cathode and
anode portions comprises multiple wire sections attached to the
piston at different locations and each of the second cathode and
anode portions comprises multiple wire sections attached to the
opposing wall at different locations.
28. The device of claim 21, wherein the cathode and anode
structures extend in three dimensions through the electrolysis
chamber.
29. The device of claim 21, wherein the cathode and anode
structures comprise a pair of parallel wires.
30. The device of claim 29, wherein the parallel wires are
separated by insulating spacers.
31. The device of claim 29, wherein the parallel wires are
flexible.
32. The device of claim 29, wherein the parallel wires are in the
form of spring coils.
33. The device of claim 121, wherein the vial is formed from a
conventional drug vial.
34. A drug pump device comprising: a vial comprising a drug
reservoir therein, the drug reservoir being fluidically connectable
to a cannula for conducting liquid from the reservoir; an
electrolytically driven piston, movable within the vial, for
forcing liquid from the reservoir into the cannula, a first side of
the piston facing the drug reservoir; and an electrolysis pump
comprising an electrolysis chamber and a gas-permeable separator
partitioning the chamber into first and second compartments, the
first compartment containing a pair of electrodes immersed in
electrolyte, and the second compartment being in contact with a
second side of the piston.
35. The device of claim 34, wherein the gas-permeable separator is
fixed within the electrolysis chamber so that a volume of the first
compartment remains constant.
36. The device of claim 35, wherein, during operation of the
device, the second compartment expands as the piston moves.
37. A drug pump device comprising: a refillable drug reservoir; an
electrolytically driven displaceable member for forcing liquid from
the reservoir, a first side of the displaceable member facing the
drug reservoir; and an electrolysis pump comprising an electrolysis
chamber in contact with a second side of the displaceable member,
and, contained within the chamber, electrodes in contact with
liquid electrolyte absorbed within a matrix that substantially does
not expand during electrolysis.
38. The device of claim 37, wherein the displaceable member is one
of a piston or a diaphragm.
39. The device of claim 37, wherein the device is implantable.
40. The device of claim 37, wherein the device is an ophthalmic
drug pump.
41. The device of claim 40, wherein an underside of the device
conforms to a patient's eyeball.
42. The drug pump device of claim 37, further comprising an
adhesive patch for adhesion to a patient's skin.
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application claims priority to and the benefit of, and
incorporates herein by reference in its entirety, U.S. Provisional
Patent Applications No. 61/326,047, filed on Apr. 20, 2010, No.
61/367,686, filed on Jul. 26, 2010, No. 61/423,945, filed on Dec.
16, 2010, and No. 61/449,899, filed on Mar. 7, 2011.
TECHNICAL FIELD
[0002] The invention relates, generally, to drug pump devices, and,
in various embodiments, to electrolysis-driven piston or diaphragm
pump devices.
BACKGROUND
[0003] As patients live longer and are diagnosed with chronic and
often debilitating ailments, there is an increased need for
improvements to the speed, convenience, and efficacy of drug
delivery. For example, many chronic conditions, including multiple
sclerosis, diabetes, osteoporosis, and Alzheimer's disease, are
incurable and difficult to treat with currently available
therapies: oral medications have systemic side effects; injections
may require a medical visit, can be painful, and risk infection;
and sustained-release implants must typically be removed after
their supply is exhausted, and offer limited ability to change the
dose in response to the clinical picture. In recent decades,
several types of wearable drug delivery devices have been
developed, including battery-powered miniature pumps, implantable
drug dispensers, and diffusion-mediated skin patches.
[0004] Treatments for a number of chronic diseases currently
require subcutaneous administration of a drug or therapeutic agent
either continuously or at specific times or time intervals in
highly controlled doses. Subcutaneous injections take advantage of
the lack of blood flow to the subcutaneous layer, which allows the
administered drug to be absorbed more slowly over a longer period
of time (compared with direct injection into the bloodstream).
Additional advantages to subcutaneous delivery of some drugs (i.e.,
vaccines, tuberculin tests, immunostimulents, etc.) to the tissue
region are the targeting of lymph tissue and lymphatic drainage for
subsequent antigen presentation to the body. Traditionally, these
types of injections have been administered either by the patient or
a medical practitioner anywhere from several times a day to once
every few weeks. Such frequent injections can result in discomfort,
pain, and inconvenience to the patient. Self-administration further
poses the risk of non-compliance or errors in dosage events.
[0005] These problems can be at least partially overcome by
wearable, electronically controlled drug pump devices capable of
delivering highly controlled dosages of drug continuously or
intermittently, depending on the needs of the patient. Such pumps
often employ electrolysis to evolve gas from a liquid electrolyte,
and thereby to generate pressure inside a pump chamber. The pump
chamber imparts the pressure onto an adjacent drug reservoir, from
where liquid drug is conducted to a subcutaneous injection site.
The drug delivery rate can, generally, be accurately controlled via
the electric current supplied to the electrolysis electrodes. In
conventional electrolysis pumps with liquid electrolyte, however,
the electrolyte level decreases as more and more gaseous
electrolysis products develop in and thereby expand the pump
chamber. As a result, the electrodes may gradually lose contact
with the electrolyte, which affects the rate of electrolysis and,
eventually, causes the electrolysis process to cease entirely. Not
only does this negatively affect the drug-delivery capacity of a
pump device with a given electrolyte volume, but it also undermines
the reliability of drug delivery because the effect tends to depend
on the orientation of the device, and is, therefore, highly
unpredictable (in particular, in patient-worn devices).
Accordingly, there is a need for alternative electrolysis pump
configurations that ensure stable pump operation throughout all
stages of the drug delivery.
SUMMARY
[0006] The instant invention generally provides electrolytically
driven drug pump devices with configurations that ensure sustained
physical contact between the electrolysis electrodes and the
electrolyte notwithstanding changes in device orientation. In some
embodiments, the anode and cathode each consists of two or more
portions placed at different locations in the pump chamber such
that at least part of each electrode remains submerged in the
electrolyte regardless of the orientation of the drug pump device.
The device may, for example, have a pen-injection pump
configuration including a linear arrangement of a drug reservoir,
an electrolytically driven piston facing the drug reservoir at one
side, and an electrolyte-filled electrolysis chamber in contact
with the other side of the piston. One portion of each electrode
may be attached to the piston, and the other portion to an opposing
wall of the pump chamber; the corresponding portions may be
electrically connected by flexible wires. In alternative
embodiments, a pair of electrodes extends three-dimensionally
through the pump chamber, e.g., in the form of a pair of spring
coils or flexible wires supported by a series of electrically
insulating spacers.
[0007] Another approach involves compartmentalizing the pump
chamber by a gas-permeable separator into a back-end portion of
constant volume that contains the electrodes and electrolyte, and a
front-end portion in contact with the piston that is expanded by
the gaseous electrolysis products. In this configuration, the
electrolyte-level in the back-end compartment decreases only
minimally as the front-end compartment expands and drives the
piston forward.
[0008] In yet another group of embodiments, the liquid electrolyte
is absorbed in a three-dimensionally networked material
(hereinafter referred to as a "matrix"), such as a gel, cotton, a
sponge, a superabsorbent polymer, or a combination thereof, that
fills the electrolysis chamber. The electrodes are embedded in or,
in the case of tubular electrodes, filled with the matrix. The
matrix maintains a persistent distribution of the electrolyte, and
thus ensures that the electrodes remain in contact with the
electrolyte. In one aspect, the invention is directed to a drug
pump device including a vial, an electrolytically driven piston,
and an electrolysis pump containing an electrolysis chamber and a
coaxial electrode pair in contact with electrolyte absorbed within
a matrix contained therein. The vial includes a drug reservoir
therein, which is fluidically connectable to a cannula for
conducting liquid from the reservoir. The piston is movable within
the vial, and serves to force liquid from the reservoir into
cannula. It faces the drug reservoir with a first side and is in
contact with the electrolysis chamber in contact with a second
side. The device may further include an electrical circuit and
associated power supply.
[0009] The pump may include multiple coaxial electrode pairs
arranged in parallel and, in certain embodiments, in a
close-packing pattern. For example, the electrode pairs may have
hexagonal cross sections and be arranged in a honeycomb fashion.
One or more of the electrode pairs may have a surface coating
inhibiting gas formation; a surface portion of the electrode
pair(s) proximate to the piston may lack the coating so as to allow
gas formation at this portion. The coaxial electrode pair may be
sealed with a gas-permeable membrane. The matrix may include or
consist of the solid phase of a gel (e.g., a hydrogel), a sponge,
cotton, or superabsorbent polymer, or, generally, a hydrophilic
absorbent material.
[0010] The vial may be formed from a conventional drug vial, and
may be made of glass and/or a polymer. The electrolysis pump may be
attached to the vial by a clamp-fit mechanism and sealed by a
rubber O-ring. The electrolysis pump may have a back-end made of
polymer, ceramics, anodized metal, or glass, with feed-throughs for
connection to the external electrical circuit and associated power
supply without loss of electrolyte fluid and without electrical
shorting of the electronic circuit or battery. In some embodiments,
the electrical circuit and associated power supply are sized based
on a diameter of the electrolysis pump so as to fit as a cap
thereon. In other embodiments, they are located adjacent the vial
and are wire-connected to the electrolysis pump. The device may
include a controller for facilitating device operation by an
electronic handheld device via a wireless connection, or a
mechanical selector for setting the drug dose to be delivered from
the drug reservoir.
[0011] In another aspect, a drug pump device in accordance with
various embodiments includes a vial and electrolytically driven
piston as above, and an electrolysis pump having an electrolysis
chamber in contact with a second side of the piston (the first side
of the piston facing the drug reservoir) as well as cathode and
anode structures arranged to remain at least partially submerged in
liquid electrolyte partially filling the chamber notwithstanding
variations in orientation of the device.
[0012] In some embodiments, the cathode and anode structures
comprises respective first and second cathode and anode portions.
The first cathode and anode portions are in contact with the
piston, and the second cathode and anode portions are attached to
an opposed wall of the electrolysis chamber. The cathode and anode
structures may also include flexible wires that electrically
connect the respective first and second portions notwithstanding
variations in the distance therebetween. The first and/or second
cathode and anode portions may extend parallel to, or,
alternatively, at an angle with respect to, the second side of the
piston and the opposed wall of the electrolysis chamber,
respectively, In some embodiments, each of the first cathode and
anode portions comprises multiple wire sections attached to the
piston at different locations and each of the second cathode and
anode portions comprises multiple wire sections attached to the
opposing wall at different locations. In certain embodiments, the
first cathode and anode portions and/or the second cathode and
anode portions are two-dimensional and interdigitated.
[0013] In some embodiments, the cathode and anode structures extend
in three dimensions through the electrolysis chamber. They may
include a pair of parallel wires, which may be separated by
insulating spacers. The wires may be flexible or in the form of
spring coils.
[0014] In yet another aspect, the invention provides a drug pump
device including a vial and electrolytically piston as described
above, and an electrolysis pump including a gas-permeable separator
that partitions the electrolysis chamber into first and second
compartments. The first compartment contains a pair of electrodes
immersed in electrolyte, and the second compartment is in contact
with the second side of the piston (the first side of the piston,
again, facing the drug reservoir). The gas-permeable separator may
be fixed within the electrolysis chamber so that a volume of the
first compartment remains constant. The second compartment may
expand during operation of the device, as the piston moves. In a
further aspect, the invention provides a drug pump device including
a refillable drug reservoir, an electrolytically driven
displaceable member (e.g., a piston or diaphragm) for forcing
liquid from the reservoir and having a first side facing the drug
reservoir, and an electrolysis pump comprising an electrolysis
chamber in contact with a second side of the displaceable member.
The electrolysis chamber contains electrodes in contact with liquid
electrolyte absorbed within a matrix that substantially does not
expand during electrolysis. The drug pump device may be
implantable, or include an adhesive patch for adhesion to a
patient's skin. The device may be an ophthalmic drug pump device,
and may have an underside that conforms to a patient's eyeball.
[0015] As used herein, the term "substantially" means .+-.10% and,
in some embodiments, .+-.5%.
BRIEF DESCRIPTION OF THE DRAWINGS
[0016] The foregoing and the following detailed description of the
invention may be more readily understood in conjunction with the
drawings, in which:
[0017] FIG. 1 is a block diagram illustrating the functional
components of drug pump devices in accordance with various
embodiments;
[0018] FIG. 2 is a perspective view of a piston pump device in
accordance with one embodiment;
[0019] FIGS. 3A and 3B illustrate, in isometric views, the assembly
of a piston pump device with a hydrogel-based electrolysis pump in
accordance one embodiment;
[0020] FIGS. 4A-4C are drawings of a piston pump device with a
liquid-electrolyte-based electrolysis pump at various stages during
drug delivery, illustrating the location of an electrode pair
relative to the electrolyte level in the electrolysis chamber;
[0021] FIGS. 5A-5F are drawings of piston pump devices with
liquid-electrolyte-based electrolysis pumps in accordance with
various embodiments, illustrating various electrode arrangements
that ensure contact of the electrodes with the electrolyte
regardless of the orientation of the devices;
[0022] FIG. 6 is a schematic drawing of a piston pump device
including a gas-permeable separator in the electrolysis chamber in
accordance with one embodiment;
[0023] FIGS. 7A and 7B are schematic isometric and side views,
respectively, of a piston pump device with a honeycomb electrode
structure in accordance with one embodiment;
[0024] FIG. 7C shows the honeycomb electrode structure of FIGS. 7A
and 7B in cross section;
[0025] FIG. 7D shows a membrane-sealed honeycomb electrode
structure with a gas-inhibiting surface coating in accordance with
one embodiment;
[0026] FIG. 8D is a schematic drawing of a piston pump vial with an
interior surface coating in accordance with one embodiment;
[0027] FIG. 9 is a schematic drawing of a magnetic-induction-based
piston velocity sensor in accordance with one embodiment;
[0028] FIGS. 10A-10E are schematic drawings of piston position
sensors in accordance with various embodiments;
[0029] FIGS. 11A and 11B are side and perspective views,
respectively, of a diaphragm drug pump device in accordance with
one embodiment; and
[0030] FIGS. 12A-12C are side views of a diaphragm drug pump device
with a secondary pump chamber in accordance with one
embodiment.
DETAILED DESCRIPTION
[0031] FIG. 1 illustrates, in block diagram form, the components of
a drug pump device 100 in accordance with various embodiments of
the present invention. In general, the pump device 100 includes a
drug reservoir 102 that interfaces with a pump 104 via a
displaceable member 106. The displaceable member 106 may be, for
example, a piston, diaphragm, bladder, or plunger. In use, the drug
reservoir 102 is filled with medication in liquid form, and
pressure generated by the pump 104 moves or expands the
displaceable member 106 so as to push the liquid drug out of the
reservoir 102. A cannula 108 connected to an outlet of the drug
reservoir 102 conducts the liquid to an infusion set 109. The
cannula 108 may be made of substantially impermeable tubing, such
as medical-grade plastic. The infusion set 109 may include a
catheter that is fluidically connected to the cannula 108 and
delivers the drug to a subcutaneous tissue region. A lancet and
associated insertion mechanism may be used to drive the catheter
through the skin. Alternatively, the infusion set 109 may include
another type of drug-delivery vehicle, e.g., a sponge or other
means facilitating drug absorption through the skin surface.
[0032] The pump 104 may utilize any suitable pumping mechanism such
as, for example, electrochemical, osmotic, electroosmotic,
piezoelectric, thermopneumatic, electrostatic, pneumatic,
electrohydrodynamic, magnetohydrodynamic, acoustic-streaming,
ultrasonic, and/or electrically driven (e.g., motorized) mechanical
actuation. In certain embodiments, electrolysis provides the
mechanism that mechanically drives drug delivery. An electrolysis
pump generally includes an electrolyte-containing chamber
(hereinafter also referred to as the "pump chamber") and, disposed
in the chamber, one or more pairs of electrodes that are driven by
a direct-current power source to break the electrolyte into gaseous
products. Suitable electrolytes include water and aqueous solutions
of salts, acids, or alkali, as well as non-aqueous ionic solutions.
The electrolysis of water is summarized in the following chemical
reactions:
##STR00001##
The net result of these reactions is the production of oxygen and
hydrogen gas, which causes an overall volume expansion of the drug
chamber contents. This gas evolution process proceeds even in a
pressurized environment (reportedly at pressures of up to 200 MPa).
As an alternative (or in addition) to water, ethanol may be used as
an electrolyte, resulting in the evolution of carbon dioxide and
hydrogen gas. Ethanol electrolysis is advantageous due to its
greater efficiency and, consequently, lower power consumption,
compared with water electrolysis. Electrolysis pumps in accordance
with several embodiments are described in detail further below.
[0033] The pressure generated by the drug pump 104 may be regulated
via a pump driver 110 by a system controller 112. For example, in
an electrolytic pump, the controller 112 may set the drive current
and thereby control the rate of electrolysis, which, in turn,
determines the pressure. In particular, the amount of gas generated
is proportional to the drive current integrated over time, and can
be calculated using Faraday's law of electrolysis. For example,
creating two hydrogen and one oxygen molecule from water requires
four electrons; thus, the amount (measured in moles) of gas
generated by electrolysis of water equals the total electrical
charge (i.e., current times time), multiplied by a factor of 3/4
(because three molecules are generated per four electrons), divided
by Faraday's constant. The volume of the gas can be determined,
using the ideal gas law, based on the pressure inside the pump
chamber (and the temperature). Accordingly, by monitoring the
pressure inside the pump chamber, it is possible to control the
electrolysis current and duration so as to generate a desired
volume of electrolysis gas, and thereby displace the same volume of
liquid drug from the reservoir 102.
[0034] In certain low-cost embodiments, the dose of drug to be
delivered from the reservoir 102 is dialed into the device using a
mechanical switch (e.g., a rotary switch), which then activates the
pump 104, via the controller 112, to deliver the dose. In various
alternative embodiments, the controller 112 executes a
drug-delivery protocol programmed into the device or commands
wirelessly transmitted to the device, as further described
below.
[0035] The system controller 112 may be responsive to one or more
sensors that measure an operational parameter of the drug pump
device 100, such as the pressure or flow rate in the drug reservoir
102 or cannula 108, the pressure inside the pump chamber,
barometric pressure changes, or the position of the displaceable
member 106. For example, the controller 112 may adjust the
electrolysis based on the pressure inside the pump chamber, as
described above; due to the inexpensiveness of pressure sensors,
this option is particularly advantageous for pumps designed for
quick drug delivery. Two or more pressure sensors may be placed in
the pump chamber to simultaneously monitor pressure therein, which
provides additional feedback to the controller 112, improves
accuracy of information, and serves as a backup in case of
malfunction of one of the sensors.
[0036] In pump devices that are intended to operate over multiple
days, typically in accordance with a non-uniform delivery protocol
(e.g., insulin delivery devices that are designed for 3-7 days of
continuous drug delivery), a flow sensor is preferably used to
measure drug flow out of the cannula in real-time, and compute the
total dose delivered by integrating the flow rate over time. For
safety, the device may include, in addition to the flow sensor, a
pressure sensor inside the pump chamber. This ensures that, in case
the flow sensor fails, the pressure sensor would be able to detect
high drug delivery rates, and shut the pump down to avoid
administering an overdose to the patient. It also provides extra
safety by preventing chamber explosion at very high pressure when a
failure mode occurs. Conversely, the combination of flow and
pressure sensors can also detect a violation in the drug reservoir
102 if pressure is measured in the pump chamber but no flow is
measured in the cannula 108, indicating a potential leak.
[0037] In general, the sensors used to measure various pump
parameters may be flow, thermal, time of flight, pressure, or other
sensors known in the art, and may be fabricated (at least in part)
from parylene--a biocompatible, thin-film polymer. Multiple
pressure sensors may be used to detect a difference in pressure and
calculate the flow rate based on a known laminar relationship. In
the illustrated embodiment, a flow sensor 114 (e.g., a MEMS sensor)
is disposed in the cannula 108 to monitor drug flow to the infusion
site, and detect potential obstructions in the flow path,
variations in drug-pump pressure, etc. The cannula 108 may further
include a check valve 116 that prevents backflow of liquid into the
drug reservoir 112. Like the sensor 114, the check valve 116 may be
made of parylene. In other embodiments, silicon or glass are used
in part for the flow sensor 114 and valve 116 construction. The
drug pump device 100 may include electronic circuitry 118 (which
may, but need not, be integrated with the system controller 112)
for processing the sensor signal(s) and, optionally, providing pump
status information to a user by means of LEDs, other visual
displays, vibrational signals, or audio signals. In addition to
controlling the drug pump 104, the controller 112 may be used to
control other components of the drug pump system; for example, it
may trigger insertion of the lancet and catheter.
[0038] The system controller 112 may be a microcontroller, i.e., an
integrated circuit including a processor core, memory (e.g., in the
form of flash memory, read-only memory (ROM), and/or random-access
memory (RAM)), and input/output ports. The memory may store
firmware that directs operation of the drug pump device. In
addition, the device may include read-write system memory 120. In
certain alternative embodiments, the system controller 112 is a
general-purpose microprocessor that communicates with the system
memory 120. The system memory 120 (or memory that is part of a
microcontroller) may store a drug-delivery protocol in the form of
instructions executable by the controller 112, which may be loaded
into the memory at the time of manufacturing, or at a later time by
data transfer from a hard drive, flash drive, or other storage
device, e.g., via a USB, Ethernet, or firewire port. In alternative
embodiments, the system controller 112 comprises analog circuitry
designed to perform the intended function, e.g., to deliver the
entire bolus upon manual activation by the patient.
[0039] The drug-delivery protocol may specify drug delivery times,
durations, rates, and dosages, which generally depend on the
particular application. For example, some applications require
continuous infusion while others require intermittent drug delivery
to the subcutaneous layer. An insulin-delivery device may be
programmed to provide a both a continuous, low basal rate of
insulin as well as bolus injections at specified times during the
day, typically following meals. To implement a dinner pump, for
example, the instructions may cause the pump to administer a 150
.mu.L dose of insulin immediately after dinner, and to dispense
another 350 .mu.L at a basal rate over eight hours while the
patient sleeps. In general, drug pump devices 100 may be configured
to achieve sustained drug release over periods ranging from several
hours to several months, with dosage events occurring at specific
times or time intervals. Flow rates of fluid flowing through the
cannula 108 may range from nanoliters per minute to microliters per
minute. A clinician may alter the pump programming in system memory
120 if the patient's condition changes.
[0040] Sensor feedback may be used in combination with a
pre-programmed drug-delivery protocol to monitor drug delivery and
compensate for external influences that may affect the infusion
rate despite unchanged electrolysis (such as backpressure from the
infusion site or cannula clogging). For example, signals from the
flow sensor 114 may be integrated to determine when he proper
dosage has been administered, at which time the system controller
112 terminates the operation of the pump 104 and, if appropriate,
causes retraction of the delivery vehicle. The system controller
112 may also assess the flow through the cannula 108 as reported by
the flow sensor 114, and take corrective action if the flow rate
deviates sufficiently from a programmed or expected rate. If the
system controller 112 determines that a higher flow rate of drug is
needed, it may increase the current to the electrolysis electrodes
to accelerate gas evolution in the electrolysis chamber;
conversely, if the system controller 112 determines that a lower
flow rate of drug is needed, it may decrease the current to the
electrolysis electrodes.
[0041] The pump driver 110, system controller 112, and electronic
circuitry 118 may be powered by a battery 122. Suitable batteries
122 include non-rechargeable lithium batteries approximating the
size of batteries used in wristwatches, as well as rechargeable
Li-ion, lithium polymer, thin-film (e.g., Li-PON),
nickel-metal-hydride, and nickel cadmium batteries. Other devices
for powering the drug pump device 100, such as a capacitor, solar
cell or motion-generated energy systems, may be used either in
place of the battery 122 or supplementing a smaller battery. This
can be useful in cases where the patient needs to keep the
drug-delivery device 100 on for several days or more.
[0042] In certain embodiments, the drug pump device 100 includes,
as part of the electronic circuitry 118 or as a separate component,
a signal receiver 124 (for uni-directional telemetry) or a
transmitter/receiver 124 (for bi-directional telemetry) that allows
the device to be controlled and/or re-programmed remotely by a
wireless handheld device, such as a customized personal digital
assistant (PDA) or a smartphone 150. A smartphone is a mobile phone
with advanced computing ability that, generally, facilitates
bi-directional communication and data transfer. Smartphones
include, for example, iPhones.TM. (available from Apple Inc.,
Cupertino, Calif.), BlackBerries.TM. (available from RIM, Waterloo,
Ontario, Canada), or any mobile phones equipped with the
Android.TM. platform (available from Google Inc., Mountain View,
Calif.).
[0043] The smartphone 150 may communicate with the drug pump device
100 using a connection already built into the phone, such as a
Wi-Fi, Bluetooth, or near-field communication (NFC) connection.
Alternatively, a smartphone dongle 152 may be used to customize the
data-transfer protocol between the smartphone and the drug pump
device 100, which facilitates optimizing the sender and/or receiver
components 122 of the drug pump device 100, e.g., for reduced power
consumption, and may provide a layer of security beyond that
available through the smartphone. A smartphone dongle is a special
hardware component, typically equipped with a microcontroller,
designed to mate with a corresponding connector on the smartphone
(e.g., a Mini USB connector or the proprietary iPhone connector).
The connector may accommodate several power and signal lines
(including, e.g., serial or parallel ports) to facilitate
communication between the dongle and the smartphone and to power
the dongle via the phone.
[0044] In certain embodiments, the smartphone 150 and pump device
100 communicate over a (uni- or bidirectional) infrared (IR) link,
which may utilize one or more inexpensive IR light-emitting diodes
and phototransistors as transmitters and receivers, respectively.
Data transfer via the. IR link may be based on a protocol with
error detection or error correction on the receiving end. A
suitable protocol is the IrDA standard for IR data communication,
which is well-established and easy to implement. Communication
between the drug pump device 100 and the smartphone 150 may also
occur at radio frequencies (RF), using, e.g., a copper antenna as
the transmitter/receiver component 124. The transmitter/receiver
124 and associated circuitry, which may collectively be referred to
as the communication module of the drug pump device 100, may be
powered by the battery 122 and/or by the signal transmitted from
the smartphone 150 or other communication device. In some
embodiments, the communication module remains in a dormant state
until "woken up" by an external signal, thereby conserving
power.
[0045] In some embodiments, the smartphone 150 is used to send
real-time signals to the drug pump device 100, for example, to turn
the pump on or off, or to adjust an otherwise constant drug
delivery rate, and in some embodiments, the smartphone serves to
program or re-program the drug pump device 100 for subsequent
operation over a period of time in accordance with a drug-delivery
protocol. The communication link between the smartphone and the
drug pump device 100 may be unidirectional (typically allowing
signals only to be sent from the phone and received by the drug
pump device) or bi-directional (facilitating, e.g., transmission of
status information from the drug pump device 100 to be sent to the
smartphone). A special software application 154 (e.g., an iPhone
"app") executing as a running process on the smartphone 150 may
provide a user interface for controlling the drug pump device 100
via the smartphone display. As a security measure, the application
154 may be configured to be accessible only when the dongle 152 is
connected to the smartphone 150. The application may further
facilitate communication between the smartphone 150 and a remote
party. For example, a health-care provider may communicate with his
patient's smartphone 150 to obtain status updates from the drug
pump device 100 and, based on this information, push a new
drug-delivery protocol onto the patient's smartphone, which in turn
uploads this new protocol to the drug pump device 100.
[0046] The functional components of drug pump devices as described
above may be packaged and configured in various ways. In certain
preferred embodiments, the drug pump device may be integrated into
a patch adherable to the patient's skin. Suitable adhesive patches
are generally fabricated from a flexible material that conforms to
the contours of the patient's body and attaches via an adhesive on
the backside surface that contacts a patient's skin. The adhesive
may be any material suitable and safe for application to and
removal from human skin. Many versions of such adhesives are known
in the art, although utilizing an adhesive with gel-like properties
may afford a patient particularly advantageous comfort and
flexibility. The adhesive may be covered with a removable layer to
preclude premature adhesion prior to the intended application. As
with commonly available bandages, the removable layer preferably
does not reduce the adhesion properties of the adhesive when
removed. In some embodiments, the drug pump device is of a shape
and size suitable for implantation. For example, certain pump
devices in accordance herewith may be used to deliver drug to a
patient's eye or middle ear. Ophthalmic pump devices may be shaped
so as to conform to the patient's eyeball, and may include a
suitable patch for adhesion to the eyeball.
[0047] The various components of the drug pump device may be held
within a housing mounted on the skin patch. The device may either
be fully self-contained, or, if implemented as discrete,
intercommunicating modules, reside within a spatial envelope that
is wholly within (i.e., which does not extend beyond in any
direction) the perimeter of the patch. The housing may provide
mechanical integrity and protection of the components of the drug
pump device 100, and prevent disruption of the pump's operation
from changes in the external environment (such as pressure
changes). The control system components 110, 112, 118, 120, 122 may
be mounted on a circuit board, which is desirably flexible and/or
may be an integral part of the pump housing. In some embodiments,
the electrodes are etched, printed, or otherwise deposited directly
onto the circuit board for cost-savings and ease of
manufacturing.
[0048] The housing may contain the infusion set 109. Alternatively,
the infusion set 109 may be separately housed, mounted on a second
skin-adhesive patch, and tethered to the drug pump device 100 via
the cannula 108. Such a tethered infusion set 109 may be
advantageous because it generally provides greater flexibility for
the placement and orientation of the insertion set 109 and drug
pump device 100 son the patient's skin. Further, it allows leaving
the insertion set 109 in place while removing the pump device 100,
for example, for the purpose of replacing or refilling the drug
reservoir 102.
[0049] In some embodiments, the drug reservoir 102 and pump 104 are
stacked in a double-chamber configuration, in which the drug
reservoir 102 is separated from the pump chamber by a flexible
diaphragm. Typically, the pump chamber is formed between the skin
patch and the diaphragm, and the drug reservoir 102 is disposed
above the pump 104 and formed between the diaphragm and a
dome-shaped portion of the housing. In alternative embodiments, the
drug pump device has a pen-injector configuration, i.e., the
reservoir 102, a piston movable in the reservoir, and the pump 104
driving the piston are arranged in series in an elongated (e.g.,
substantially cylindrical) housing. A pump device with this
configuration may be integrated horizontally into a skin patch for
prolonged drug infusion. Alternatively, it may be used as a
handheld injection device that is oriented substantially
perpendicularly during injection, much like a conventional pen
injector. Compared with the conventional injector that is
mechanically activated by the patient, a digitally controlled
electrolysis-based pump device as described herein provides the
advantage of better dosage control. Various diaphragm pump and
piston pump configurations are described in more detail below.
[0050] The drug-delivery device 100 may be manually activated,
e.g., toggled on and off, by means of a switch integrated into the
pump housing. In some embodiments, using the toggle switch or
another mechanical release mechanism, the patient may cause a
needle to pierce the enclosure of the drug reservoir 102 (e.g., the
septum of a drug vial) to establish a fluidic connection between
the reservoir 102 and the cannula 108; priming of the pump can then
begin. Coupling insertion of the needle into the reservoir 102 with
the activation of the pump device ensures the integrity of the
reservoir 102, and thus protects the drug, up to the time when the
drug is injected; this is particularly important for pre-filled
drug pump devices. Similarly, the lancet and catheter may be
inserted by manually releasing a mechanical insertion mechanism. In
some embodiments, insertion of the lancet and catheter
automatically triggers electronic activation of a pump, e.g., by
closing an electronic circuit. Alternatively, the pump and/or
insertion set may be activated remotely by wireless commands. Drug
pump devices integrated into skin patches may also be configured to
automatically turn on once the skin, patch 102 is unwrapped and
moisture is sensed. When drug delivery is complete, the device 100
may automatically retract the catheter and turn off the pump.
[0051] Drug pump devices 100 in accordance herewith may be designed
for single or repeated use. Multi-use pumps generally include a
one-way check valve and a flow sensor, as described above, in the
cannula. Further, the drug reservoir of a multi-use pump may be
refillable via a refill port, using, e.g., a standard syringe. In
some embodiments, the drug pump device 100 is removed from the
patient's skin for re-filling. The patient may, for example, place
the drug pump device 100 and cartridge containing the new drug into
a home refill system, where the pump device and cartridge may be
aligned using, e.g., a press-machine mechanism. The patient may
then press a button to trigger automatic insertion of a needle that
draws liquid drug from the cartridge to the cannula in order to
activate the electronics and begin priming the pump. In a further
embodiment, a two-channel refill system may be used to aspirate old
drug using one channel as well as load new drug into the drug pump
device 100 using the other channel. One channel of the two-channel
refill system is configured to regulate the flow and storage of
drug, while the other one is configured to regulate the flow and
storage of waste liquid. The system may use pneumatic pressure
and/or vacuum control to direct the infusion and suction of liquid
in and out of the drug pump, and may include sensors to monitor the
pressures, and sterile filters to keep air from contaminating new
drug. The drug pump device need not necessarily be removed from the
patient for refilling with the two-channel system, as the system
may provide sufficient and flow and pressure control to prevent
accidental drug infusion into the target region (e.g., by infusing
liquid below the cracking pressure of a check valve).
[0052] In some embodiments, multiple drug pump devices are
integrated into one skin-adhesive patch. The devices may be
arranged in an array on the same surface, stacked on top of one
another, or a combination of both. They may share the same
insertion set, or, alternatively, each device may have its own
insertion set and drug outlet. A multiple-outlet arrangement
facilitates administering several smaller doses over a larger
surface area using multiple delivery vehicles, which may help to
reduce systemic side effects (such as scarring and damage to
subcutaneous tissue) that results from drug deliver at high
concentrations to a small target area. In some embodiments, the
multi-pump system includes, in addition to the drug reservoirs of
the individual devices, a shared reservoir. During operation of any
one of the pump devices, drug may be expelled from the respective
reservoir into the shared reservoir, from where it is conducted to
the infusion site.
[0053] The volume of drug stored in the various pump devices may be
the same or varied, and may be as little as 50 .mu.L or less. The
pumps may function separately or collectively to deliver variable
dosage volumes, essentially achieving controllable dosage
resolution equal to an average dosage delivered by each pump.
Parallel operation of the pumps may lead to faster response times
and better control over the overall flow rate. For example, if a
high flow rate is desired, all of the pumps may simultaneously be
active. Further, the use of multiple, independently operable pumps
provides redundancy, should any of the pumps fail.
[0054] In some embodiments, the individual drug reservoirs store
different drugs, facilitating variable drug mixing through
selective pump activation. Different drugs may be administered
together as part of a drug "cocktail" or separately at different
times, depending on the treatment regimen. Multiple reservoirs may
also facilitate mixing of agents. For example, one reservoir may
store, as a first agent, a drug that is in a "dormant" state with a
half-life of several months, and another reservoir may contain, as
a second agent, a catalyst required for activating the dormant
drug. By controlling the amount of the second agent that reacts
with the first agent, the drug delivery device is able to regulate
the potency of the delivered dosage. The pumps may be operated by a
single controller, which may be programmed to deliver the various
drugs in accordance with a user-selected drug-delivery protocol. As
explained above, pump operation may be altered through wireless
reprogramming or control.
1. Piston Pump Devices
[0055] FIG. 2 shows an exemplary drug pump system 200 including a
piston pump device 202 and an associated tethered infusion set 204,
both mounted to skin-adhesive patches 206. The pump device 202
includes a cylindrical (or, more generally, tubular) vial 208 with
a piston 210 movably positioned therein and an electrolysis
electrode structure 212 mounted to one end. The structure 212 may
be made of any suitable metal, such as, for example, platinum,
titanium, gold, or copper. In another embodiment, the structure 212
may include a support made from plastic or glass containing the
electrodes inside a sealed pump chamber. The piston 210 separates
the interior of the vial 208 into a drug reservoir 214 and a pump
chamber 216. A cannula 218 connects the drug reservoir 214 to the
infusion set 204. The piston pump device 202 is enclosed in a
protective housing 220, e.g., made of a hard plastic.
[0056] The vial 208 may be fabricated from a glass, polymer, or
other materials that are inert with respect to the stability of the
drug and, preferably, biocompatible. Glass is commonly used in
commercially available and FDA-approved drug vials and containers
from many different manufacturers. As a result, there are
well-established and approved procedures for aseptically filling
and storing drugs in glass containers, which may accelerate the
approval process for drug pump devices that protect the drug in a
glass container, and avoid the need to rebuild a costly aseptic
filling manufacturing line. Using glass for the reservoir further
allows the drug to be in contact with similar materials during
shipping. Polymer vials, e.g., made of polypropylene or parylene,
may be suitable for certain drugs that degrade faster when in
contact with glass, such as protein drugs.
[0057] Suitable glass materials for the vial may be selected based
on the chemical resistance and stability as well as the
shatterproof properties of the material. For example, to reduce the
risk of container breakage, type-II or type-III soda-lime glasses
or type-I borosilicate materials may be used. To enhance chemical
resistance and maintain the stability of enclosed drug
preparations, the interior surface of the vial may have a
specialized coatings. Examples of such coatings include chemically
bonded, invisible, ultrathin layers of silicone dioxide or
medical-grade silicone emulsions. In addition to protecting the
chemical integrity of the enclosed drugs, coatings such as silicone
emulsions may provide for easier withdrawal of medication by
lowering internal resistance and reducing the amount of pressure
needed to drive the piston forward and expel the drug.
[0058] In certain embodiments, the drug pump device is manufactured
by fitting a conventional, commercially available glass or polymer
drug vial, which may already be validated for aseptic filling, with
the piston and electrolysis pump, as shown in FIG. 3A. The piston
300 may be disposed inside the vial 302 near one end, leaving room
for the electrolysis pump 304, and a septum 306 may be disposed at
the other end to seal the vial. Both the piston 300 and the septum
304 may be made of an elastomeric polymer material, such as a
synthetic or natural rubber; in some embodiments, silicone rubber
is used. A screw-in needle cassette 308 may be placed over the
septum 304, as illustrated in FIG. 3B, and a mechanical actuation
mechanism may serve to screw the cassette into the vial 302 such
that the cassette needle punctures the septum 304 and establishes a
connection with the cannula at the time the patient desires to use
the pump. To accommodate the electrolysis pump 304, the vial 302
is, in some embodiments, longer than typical commercially available
vials, but maintains all other properties such that validated
filling methods and the parameters of existing aseptic filling
lines need not be changed. The drug pump device may be furnished
with a prefilled vial. If a glass vial is used, the drugs can be
stored in the pump device for long-term shelf life without the need
to change the labeling on the drug.
[0059] In applications involving dry-powder or lyophilized drug
preparations, dual-compartment vials, also known as mix-o-vials,
may be employed in the drug pump device. These vials may
incorporate a top compartment containing a diluent solution and a
bottom compartment containing a powdered or lyophilized drug. The
two compartments may be separated by a rubber stopper. Electrolysis
may be used to actuate a mixing system that triggers the piercing
of the stopper to cause the top and bottom contents to mix before
or during infusion. For lyophilized and powder medications, vials
of borosilicate glass are particularly suitable. The vial bottom
may be specially designed to optimize cake formation and enhance
the efficiency of the reconstitution process. Borosilicate vials
also offer good hydrolytic resistance and small pH shifting, and
are not prone to delamination. They are commercially available in
both clear and amber varieties, with capacities ranging currently
from 1.5 to 150 cm.sup.3.
[0060] FIG. 4A illustrates schematically a piston pump device 400
having a conventional electrolysis pump chamber 402 filled with
liquid electrolyte. As gaseous electrolysis products are generated,
they push the piston 404 towards the outlet end of the drug
reservoir 406 (see FIG. 4B). Movement of the piston 404 increases
the volume of the electrolysis chamber 402, causing a decrease in
the level of the electrolyte 408. Depending on the orientation of
the device, one or both electrodes 410 may, as a result, gradually
emerge from the electrolyte and become surrounded by the gas,
eventually forming an open circuit (FIG. 4C). This causes the
electrolysis reaction to cease. Various drug pump embodiments that
avoid this problem are described below.
[0061] In some embodiments, the electrodes are arranged such that
at least a portion of each electrode remains submerged in
electrolyte partially filling the electrolysis chamber regardless
of the device orientation. For example, as illustrated in FIG. 5A,
electrode pairs 500, 502 may be located on both ends of the
electrolysis chamber 504, i.e., at or near the interface of the
electrolysis chamber 504 with the piston 506 as well as at the
opposite wall 508 sealing the vial. The cathodes 500 and anodes 502
on either side of the electrolysis chamber 504 may be connected by
a flexible wire 506 of sufficient length to accommodate separation
of the two walls of the electrolysis chamber 504 as electrolysis
proceeds and the contents of the vial are expelled. As illustrated
by the five depicted device orientations at 0.degree.,
.+-.45.degree., and .+-.90.degree. with respect to a horizontal
plane, this electrode arrangement ensures at least partial
submergence of the electrodes 500, 502 in the electrolyte 510
regardless of orientation. Changes in orientation as depicted
arise, as a practical matter, from different patient orientations
during sleep or activity, throughout which drug delivery needs to
continue. FIG. 5B shows a modification of this electrode
arrangement, in which the electrode pairs 520, 522 are angled
relative to the walls of the electrolysis chamber 504. In the
example shown in FIG. 5C, multiple electrode pairs 530, 532 are
positioned on each side of the electrolysis chamber 504.
[0062] FIG. 5D shows an embodiment in which two parallel electrode
spring coils 540, 542 are utilized. These two coils 540, 542 may be
supported by a series of electrically isolating spacers 544 in a
ladder-like configuration that prevents short circuits between the
two coils 540, 542. This double coil set is compressed into the
electrolysis chamber 504 so that, as the piston moves forward, the
coils extend to keep part of the coil pair submerged in electrolyte
510. This arrangement may be modified by disposing multiple coil
pairs 540, 542 in the electrolysis chamber 504 to provide
redundancy in case of a short circuit between the coils of any coil
pair. In yet another embodiment, illustrated in FIG. 5E, a flexible
parallel pair of wires 550, 552 separated by multiple spacers 544
in a ladder-like configuration is utilized. One end of this wire
pair 550, 552 is affixed to the piston 506, and the other end is
attached to the opposing wall of the electrolysis chamber 504. As
the piston 506 moves, at least part of the wire pair 550, 552 will
remain submerged in electrolyte for continuous and steady gas
generation.
[0063] In another embodiment, illustrated in FIG. 5F, two pairs of
interdigitated microelectrodes 560, 562 are used, one attached to
the piston 506 and the other one located at the opposite, fixed
wall of the electrolysis chamber 504. The cathodes 560 of the
microelectrode sets on both ends of the electrolysis chamber 504
may be connected with a flexible wire 564, as may the two opposed
anodes 562. In this arrangement, as in the previous examples, part
of the electrode pair 560, 562 will be submerged in electrolyte 510
to continuously produce electrolysis gases irrespective of the
orientation of the pump device. As will be evident to those skilled
in the art, other electrode designs may also be used to ensure
immersion of at least a portion of an electrode pair in the
electrolyte.
[0064] In some embodiments, schematically illustrated in FIG. 6, a
gas-permeable separator 600 partitions the pump chamber 602 into an
electrolyte-filled compartment 604 at the back end and a gas
compartment 606 adjacent the piston 608. The gas-permeable
separator 600 is generally impermeable to liquid electrolyte, but
allows gaseous electrolysis products to pass. Suitable separators
are known to persons of skill in the art, and include, for example,
thin silicone membranes, polymer membranes (e.g., made of
polyurethane, carboxylated poly(vinyl chloride), or parylene),
microporous polymer films with polymeric coatings, or porous metal
films. The separator 600 is fixedly mounted within the pump chamber
602; as a result, the electrolyte compartment 604 has a constant
volume. As an electrode pair 610 disposed in the electrolyte
compartment 604 breaks down liquid electrolyte into gas products,
the gas penetrates the separator 600, entering the gas compartment
606 and driving the piston 608 forward; consequently, the volume of
the gas compartment 606 increases. Due to the large expansion ratio
associated with the phase transition from liquid electrolyte to
gaseous products, the volume of the gas compartment 606 generally
increases orders of magnitude (e.g., hundreds- or thousandfold)
faster than the volume of liquid electrolyte in the electrolyte
compartment 604 decreases. As a result, the electrodes 610 remain
submerged in the electrolyte throughout significant displacement
distances of the piston 608. The volume of the electrolyte
compartment may be chosen, based on the expansion ratio of the
employed electrolyte and the initial drug reservoir volume, such
that contact between the electrodes and the electrolyte is ensured
until the drug has been fully expelled.
[0065] Yet another approach involves absorbing the electrolyte
within a matrix that fills the interior of the pump chamber, or at
least a portion of the chamber containing the electrodes. The
matrix may be any absorbent, three-dimensionally networked
material, for example, the solid phase of a gel, cotton, a
superabsorbent polymer, a sponge material, or any combination
thereof (such as, e.g., a gel absorbed within a sponge). Its
function is to maintain a persistent distribution of the
electrolyte throughout the matrix, thereby ensuring that the
electrodes, which are embedded in or filled with the matrix, remain
in contact with electrolyte.
[0066] Additional examples of suitable matrix materials include
other fibers such as natural or synthetic cellulose based materials
(e.g., rayon), acetate fiber, nylon fiber, hemp, bamboo fabric,
wool, carbon based fibrous material, silk, polyester, or other
cotton-blend fibers. Ultra-fine cellulose nanofibers (with
diameters of 1-50 nm), made using, for example, a combination of
TEMPO, NaBr, and/or NaClO oxidation of natural cellulose (e.g.,
wood pulp), in different nanofibrous composite formats include
small diameter, high surface-to-volume ratio, easy surface
functionality, good mechanical properties, and good chemical
resistance. Fibers with hydrophilic and water-absorbent properties
tend to be preferable; they include "polymer molecules" that are
linked up in repetitive patterns or chains, negative charged
materials that help attract and absorb "dipolar" water molecules,
and fibers with capillary action, where the fibers are able to draw
or suck in water like a straw through the interior of the fiber.
Capillary action is present both in the fiber of the cotton plant
and cotton fabric. Once drawn in through the fibers, the water is
then stored in the interior cell walls.
[0067] A particularly advantageous matrix material is hydrogel, a
highly water-absorbent network of hydrophilic polymer chains.
Hydrogels can contain large fractions (e.g., more than 99% by
weight) of water or an aqueous solution. They are highly
biocompatible, and their absorbed liquid maintains most of its
original liquid properties (e.g., density, phase change, and
incompressibility), which makes the gels stable for mechanical
operation. Using hydrogel also facilitates easier packaging in
low-cost manufacturing.
[0068] Electrolytes used with the hydrogel system may generally be
aqueous solutions, i.e., solutes dissolved in water. Examples of
solutes include salts (e.g., sodium chloride, magnesium sulfate, or
sodium sulphate), dilute acids (e.g., sulfuric acid, hydrochloric
acid, or amino acid), and dilute alkali (e.g., sodium hydroxide,
potassium hydroxide, calcium hydroxide). Instead of water, other
liquids, such as oil or ethanol, may be used as solvents. Depending
on the electrolyte used, the electrolysis gas includes a
combination of hydrogen, oxygen, and/or carbon dioxide. For
example, electrolysis of water results in oxygen and hydrogen gas,
whereas electrolysis of ethanol results in carbon dioxide and
hydrogen gas. The use of ethanol may lower the power consumption of
the electrolysis pump and extend the life of the battery.
[0069] In some embodiments, the water contained in the hydrogel
itself serves as the electrolyte. The volume expansion from liquid
water to hydrogen and oxygen gas is more than a thousand times.
Consequently, a pump chamber volume of less than 1/1000 that of the
drug reservoir may, at least theoretically, suffice to expel all
the drug from the reservoir. However, to increase the reliability
of the electrolysis pump, a volume ratio such as 1 to 5
(electrolysis chamber to drug reservoir) may be preferable. For
example, for drug reservoir volumes of 0.5 mL, 3 mL, or 5 mL, the
corresponding volume of electrolysis chamber may be 0.1 mL, 0.6 mL,
or 1 mL, respectively. Still, use of an electrolysis pump permits
the size of the pump to be reduced significantly compared with
conventional drug pumps, such as, e.g., motorized drug pump
devices.
[0070] The matrix material may be placed next to electrodes in a
single pump chamber, or in multiple electrolysis cells (e.g., as
described with respect to FIGS. 7A-7D below). FIG. 3A shows a basic
single-chamber configuration of a gel-based electrolysis pump, in
which a pair of electrode poles breaks the electrolyte contained in
the gel into gas bubbles (e.g., hydrogen bubbles and oxygen
bubbles), which cause expansion of the bubble-gel mixture. The
expanding gel mechanically couples the pump chamber to the piston.
In place of electrode poles, more complex electrode structures,
such as planar interdigitated electrodes (as shown in FIG. 11B in
the context of a diaphragm pump device) may be used. In an
alternative embodiment, a coaxial electrode pair having a
pole-shaped core electrode arranged along the axis of a tubular
(e.g., cylindrical) sleeve electrode may be used.
[0071] In some embodiments, multiple coaxial electrode pairs, which
are preferably arranged in parallel in a close-packed pattern, are
used to compartmentalize the pump chamber into several electrolytic
cells. The individual cells may be driven separately or in
combination, which facilitates precise and smooth actuation of the
piston. Operating the cells consecutively may contribute to
maintaining contact between the hydrogel and the respective active
electrode pair while gas is generated over time. A multi-cell
electrode structure also increases the reliability of the pump
device due to redundancy: because of the large volume expansion
ratio, a single cell may be able to drive the piston from the
beginning to the end of drug delivery. In some embodiments, the
electrolysis cells are activated in a serial fashion, one after the
other as electrolyte in the respective active cells dries out, to,
prolong the overall lifetime of the pump; cell activation may be
controlled by the electronic circuitry and based, for example, on a
measured electrolysis or flow rate.
[0072] FIGS. 7A and 7B illustrate drug pump embodiments that
include multiple electrolytic cells 700. Here, seven co-axial
electrode pairs with hexagonal cross sections are arranged in a
honeycomb structure 701, which is shown in front-view in FIG. 7C.
The tubular sleeve electrodes may (but need not) form a contiguous
hexagonal latticework 702, and may be manufactured from
off-the-shelf metallic micro-honeycomb tubes. Typically (although
not necessarily), the core electrodes 704 serve as the anodes and
the latticework 702 serves as the cathodes of the respective
cells.
[0073] At the beginning of drug delivery from a filled reservoir
706, the honeycomb electrode structure may extend through the drug
pump chamber, from the back wall 708 of the chamber to the piston
710, as illustrated in FIG. 7B. As electrolysis gases are
generated, the drug chamber expands and the piston 710 moves
towards the drug outlet. In some embodiments, the expanding gel 712
flows out of the tubular electrolysis cells 700 and enters the
space between the cells 700 and the piston 710. In the alternative
embodiment shown in FIG. 7D, the electrode cells 700 are sealed by
a porous membrane or other gas-permeable filter 714, which may be,
as described above, a thin silicone membrane, a polymer membrane or
a microporous polymer film. The filter 714 serves to retain the gel
712 and electrolyte inside the electrolysis cells 700 while
allowing gas to leave the cells 700 and fill and expand the space
between the cells and the piston 710.
[0074] In some embodiments, large portions of the interior surfaces
of the honeycomb electrodes 702 and portions of the core electrodes
704 are coated with a material that inhibits gas formation, such as
epoxy, while surface portions of the electrodes near the
gas-permeable filter 714 are exposed (see FIG. 7D). For example,
10% or less of the electrode surface area may be uncoated. As a
result of the coated and uncoated areas, gas will be generated
proximally to the filter 714, allowing hydrogel (and/or
electrolyte) to be preserved inside the electrolytic cells 700 for
longer periods.
[0075] Some electrolysis pumps, such as smaller implantable pumps
for drug delivery to the eye or the middle ear, or refillable drug
pumps (where a diaphragm or piston collapses back to its initial
state after the drug has been refilled) desirably use a
non-expanding fibrous material for the matrix. Otherwise, expansion
of the matrix could limit the collapse of the piston or diaphragm,
and prevent the drug reservoir from being fully refilled A
non-expanding fibrous material can keep electrolyte near the
electrodes, but does not interfere with the piston or diaphragm
motion.
[0076] Electrolysis pumps as described above generally facilitate
continuous control of the drug-delivery rate via the drive voltage
or current applied to the electrodes. However, as the piston moves
inside the drug vial, sudden changes in friction between the piston
and the vial may cause the drug delivery rate to deviate from the
intended delivery protocol, resulting, for example, in a
non-uniform delivery rate despite a constant rate of electrolysis,
or in undesired spikes in an otherwise smooth uniform or
non-uniform delivery protocol. Such changes in friction typically
occur at the onset of piston movement as a consequence of the
difference between static and dynamic coefficients of friction: the
static coefficient of friction between the piston and vial
generally exceeds the dynamic coefficient of friction (usually by a
factor of about two or three), so that the force needed to start
the piston in motion is greater than that needed to keep it moving.
In addition, if the piston stops moving for a short period of time,
a larger force is needed to re-initiate piston movement.
[0077] Furthermore, the dynamic friction itself may be affected by
variations in the surface properties of the piston and/or the vial
along their lengths, and/or by changes in the surface properties
resulting from the interaction between piston and vial. For
example, if the inner diameter of the vial and/or the outer
diameter of the piston vary slightly along their lengths, the
frictional forces generally depend on the piston position. Further,
surface roughness may be smoothened out in time, in particular, if
a refillable drug pump device is used repeatedly. Conversely,
discrete surface defects, e.g., a peck sticking out from the
interior surface of a glass vial, may roughen and/or damage the
other surface, e.g., the surface of a soft rubber piston. In
general, the variations in dynamic friction due to these and other
effect are highly unpredictable.
[0078] The difference between static and dynamic friction may be
reduced by applying a suitable surface coating to the interior
surface of the vial and/or to the piston. In some embodiments, the
vial (which may be made, e.g., of glass) is coated with a
low-friction material such as, for example, parylene or
polytetrafluoroethylene (commonly known under the brand name
Teflon.TM.), which reduces static friction without significantly
changing dynamic friction. Because vial surface coatings may be in
contact with drugs or drug solutions, the coating materials are
preferably biocompatible to facilitate long-term drug stability.
FIG. 8 illustrates a drug vial 800 with an interior surface coating
802.
[0079] While the friction drop at the onset of piston movement can
be mitigated with friction-reducing coatings, and variations in
dynamic friction can be minimized through high-precision
manufacturing and selection of suitable combinations of piston and
vial materials, in general they cannot be eliminated entirely. This
problem may be addressed by using pressure variations in the drug
chamber to match the applied force to the friction profile in order
to maintain a desired piston velocity (or to change the piston
velocity according to a desired protocol). For this purpose, some
drug pump embodiments include one or more sensors to continuously
monitor a parameter indicative of or affecting drug delivery. For
example, a flow or pressure sensor placed inside the cannula may be
used to measure the drug delivery rate directly, and feedback
circuitry can be employed to adjust the rate of electrolysis in
response to sensed variations that deviate from the delivery
protocol.
[0080] Alternatively, the movement of the piston may be monitored
with a position or velocity sensor. For example, in one embodiment,
illustrated in FIG. 9, a magnet 900 is embedded in the piston 902,
and an induction coil or coil sleeve 904 is wound around the drug
vial such that, as the magnet 900 moves relative to the coil 904,
an electric voltage proportional to the piston velocity is induced
in the coil 904. To ease manufacturing, the piston 902 may be
molded or otherwise manufactured to accommodate the magnet 900 in a
small pocket, allowing the magnet to be press-fit into place in a
simple assembly step. A lip may be included to hold the magnet in
place. In yet another embodiment, the pressure inside the pump
chamber is measured continuously, allowing a sudden friction
decrease or increase to be detected via a pressure drop or spike,
respectively.
[0081] In response to the measured flow, pressure, position, or
other parameter, the system controller 112 may adjust the
electrolysis rate in real-time (or near real-time, e.g., within 1
ms of the friction change) to compensate for any variations in
friction. Alternatively or additionally, for changes in friction
that are relatively predictable (such as the drop in friction at
the onset of piston motion), the necessary adjustments to the
electrolysis may be determined empirically. For example, to avoid
flow rate spikes as the piston begins to move, the transition from
static to dynamic friction may be repeated multiple times while the
electrolysis rate and piston position and/or flow rate in the
cannula are measured simultaneously. From this data, the
electrolysis rate, as a function time, that is required to assure a
smooth onset of piston motion may be calculated, and then
programmed into the pump device. The friction compensation
techniques and features described above apply similarly to a piston
pump device that employs a pump mechanism other than electrolysis,
i.e., the pump rate may, generally, be controlled based on a
measured drug delivery parameter to reduce or eliminate the effect
of changes in friction on the drug delivery rate.
[0082] When operating a drug pump device to inject liquid drug into
a patient, it is often desirable to monitor the rate or volume of
the injection or to track the filling status of the device, e.g.,
to alert the patient of the need to refill the device soon. This
can be accomplished by monitoring the position of the piston inside
the vial. One approach utilizes the magnet 900 and one or more
induction coils 904, as shown in FIG. 9. As the voltage induced due
to the motion of the magnet 900 relative to the coil 904 is
proportional to the momentary velocity of the piston 902,
integration of the voltage over time yields the piston position.
Integrator circuits are well known in the art and can be
implemented without undue experimentation. This embodiment can be
useful when a simple, inexpensive pump is needed.
[0083] Rather than continuously monitoring the position of the
piston, it often suffices to detect and signal certain threshold
piston positions corresponding to incremental amounts of drug
remaining inside the vial, as depicted in FIGS. 10A-E. For example,
an electronic display may indicate when the drug reservoir is
completely filled (corresponding to a piston position at the
farthest possible distance from the drug outlet to the cannula),
75% filled, 25% filled, or empty.
[0084] For example, FIG. 10A shows a low-cost embodiment in which
the piston position is mechanically sensed with strings of
different lengths. The strings 1000 may be tethered from the back
wall or electronics end 1002 of the drug pump chamber to the piston
1004. As the piston 1004 moves to push liquid out of the drug
reservoir, the strings 1000 are stretched until they break. Based
on the ultimate tensile strengths of the string material, the
lengths of the strings are chosen such that each string ruptures
when the piston 1004 reaches a corresponding predetermined
position. For example, the string that is intended to break when
the drug device is 75% filled has a length, immediately prior to
breakage, that is the sum of the length of the drug chamber and a
quarter of the maximum length of the drug reservoir. The strings
1000 may be, for example, nylon strings or fine metal (e.g., copper
or lead) wires. If the vial and drug pump housing are transparent,
string rupture may be observed by eye. Alternatively, if the
strings are electrically conductive (as is the case with metal
wires), their breakage may be detected electronically. For example,
the several wires of different lengths may be part of respective
electronic circuits, and their rupture may cause a detectable
open-circuit condition.
[0085] Position sensing may also be accomplished using multiple
Hall effect sensors, optical sensors, induction coils, and/or
capacitive sensors placed at different locations along the drug
vial in combination with a magnet or optical component embedded in
or attached to the piston; several embodiments are illustrated in
FIGS. 10B-10D. For example, when a magnet 1010 associated with the
piston 1004 passes a Hall effect sensor 1012 (FIG. 10B), the
magnetic field strength detected by the sensor peaks, resulting in
a voltage signal at that sensor. Similarly, as the magnet 1010
passes an induction coil 1014 (FIG. 10C), a voltage signal is
detected, enabling precise location of the piston. To detect the
piston motion optically, an LED may be attached to the piston and
phototransistors may be placed alongside the vial to detect LED
light as the piston passes. Alternatively, as shown in FIG. 10D,
the piston may include a reflector 1016 (e.g., a piece of metal),
and pairs of LEDs and phototransistor 1018 positioned along the
vial may serve, respectively, to emit light and to measure the
amount of reflected light, which reaches a maximum when the
reflector 1016 is closest to the phototransistor.
[0086] To detect the piston motion using capacitive sensing, one or
multiple pairs of plate-electrodes 1020 are positioned along the
length of the vial such that the piston 1004 moves between
consecutive pairs of plate-electrodes as the drug is dispensed. As
the piston moves between a pair of plate-electrodes, the dielectric
medium between those particular plate-electrodes changes, thereby
producing a detectable change in capacitance between the two
plate-electrodes 1020. The piston 1004 may be made from or contain
material(s) that maximize the detectable change in capacitance,
e.g., the piston may possess significantly different dielectric
properties than the drug in the vial.
[0087] Piston drug pump devices as described above may be
manufactured from various readily available components, and
prefilled using existing fill/finish lines with few modifications.
For example, as explained above, a conventional, FDA-approved drug
glass vial may be used to house the drug reservoir. A rubber
stopper, optionally having a magnet attached thereto, may be placed
into the vial to serve as the piston. The electrolysis chamber may
be housed in a container that is open on one side so as to allow
mechanical coupling between its contents and the piston. A circuit
board including the pump driver, system controller, memory, any
other electronic circuitry, and battery (or other power supply) may
be attached to the back-end of the electrolysis chamber, which may
be made of ceramics or plastics and include electrical feedthroughs
that allow electrical connections between the electrodes and the
circuit board components. The circuit board may have the same or a
similar diameter as the drug vial and pump, and may form, or be
integrated into, a cap that fits onto the pump. Alternatively, if
the circuit board is larger than the pump diameter, it may be
placed to the side of the drug vial and pump assembly. The chamber
may be filled with electrolyte-absorbed hydrogel, and then fitted
into (or onto) the back-end of the vial, thereby closing the
vial.
[0088] The pump container may be made of glass. Its back-end may be
sealed by heating it, e.g., in an oven or with a torch, and then
crimping, twisting, or otherwise closing it, by hand or with a
specially designed jig, while the glass is molten. The electrolysis
electrodes may be positioned and sealed in place as the glass is
crimped. In some embodiments, the glass container holding the pump
may be placed over a portion of the open drug vial like an end-cap.
In other embodiments, the glass container is slid partially into
the vial. Either way, the overlapping wall portions of the vial and
pump container may be bonded with an adhesive sealant or through
application of heat. In embodiments that utilize a honeycomb
electrode or similar structure, this structure may, itself, serve
to contain the other drug pump components (such as the hydrogel or
other matrix material), and may be placed into the glass vial and
secured, e.g., by a clamp-fit or screw mechanism. To prevent
leakage of the electrolyte out of the electrolyte chamber (which
could cause a short circuit in the circuit board), the electrolysis
chamber may be sealed with a rubber O-ring.
[0089] Once the vial, piston, and pump are assembled, they may be
sterilized, for example, by gamma-irradiation. One of the
advantages of hydrogel and electrolysis fluid is that they can
readily be gamma-irradiated after assembly. Sterilization serves to
protect the patient from infection by preventing bacteria and
pyrogens from entering the final fluid pathway of the device. The
drug vial may initially be sterilized through standard techniques,
for example, the use of heat or radiation. In one embodiment, a
metal barrier is placed over the septum before sterilization of the
vial (using, e.g., heat or radiation) to serve as a barrier during
final sterilization steps using ethylene oxide or gases, preventing
the gases from penetrating the septum.
[0090] Following assembly and sterilization of the vial, the vial
may be filled with liquid drug in a standard aseptic fill and
finish line. For that purpose, the glass vial may be oriented
vertically, with its back-end (where the piston is) at the bottom,
and filled through the front opening. After the filling step, the
front-end of the vial is sealed, e.g., by placing a silicone septum
in the opening and crimping a metal ring cap to hold the septum in
place. Finally, the vial assembly may be enclosed in an
injection-molded protective housing, which may optionally have an
adhesive on its underside. The housing may have separate front and
back portions (shown in FIG. 7B), which may be connected by a
clip-mechanism. The front portion of the housing may include a
needle to pierce the drug vial's septum at time of use, and a
cannula including a flow sensor and check valve for one-way
flow.
[0091] Assembling the device (e.g., adding the pump chamber and
outer casing), packaging the device in an outer sterile barrier,
and boxing it for shipping may be performed with non-sterile
techniques, before a final sterilization is used to sterilize the
rest of the pump (including the outer areas of the drug vial). This
outer sterilization is particularly important for any surfaces that
are in contact with the drug. Post-sterilization processes such as
treatment with ethylene-oxide gas or gas plasma, e-beam treatment,
steam autoclaving, radiation treatment, chemical treatment, or dry
heat treatment can all be used. In one embodiment, the resulting
drug device has a pump with a sterile drug vial that has an
aluminum barrier over its pierceable silicone septum, and a loading
needle that can be mechanically driven through the vial's septum
and the metal barrier into the drug reservoir, which simultaneously
activates the electronics and primes the pump.
[0092] Precisely controlled piston pump devices as described herein
may be advantageous over traditional body-adhered syringe systems,
for example, because they can supply a larger overall volume of
drug to a patient while reducing the flow rate from a rapid
injection rate to a slower rate of infusion over time. Due to the
lower flow rate, a smaller needle may be used to deliver the drug
to the patient, resulting in less pain to the patient. Further, in
comparison with conventional, manually operated pen injectors,
electrolytically driven pump devices in accordance herewith provide
greater accuracy and precision in drug dosage, thus increasing
patient safety and treatment efficacy.
2. Diaphragm Pump Devices
[0093] FIGS. 11A and 11B illustrate an exemplary diaphragm pump
device 1100 in cross-sectional and perspective views. The device
1100 contains, within a housing 1102 (which is partially removed in
FIG. 11B for illustrative purposes only), a drug reservoir 1104 and
an electrolysis pump. The pump includes an electrolyte-filled pump
chamber 1106 formed between a lower portion of the housing 1100 and
a diaphragm 1108. The reservoir 1104 is located on the other side
of the diaphragm 1108, above the electrolysis chamber 1106, and is
enclosed by the diaphragm 1108 and an upper, typically dome-shaped
portion of the housing 1102. The reservoir 1104 may include a
refill port that allows for the introduction of additional drug. In
some embodiments, the reservoir 1104 is capable of holding between
approximately one and ten mL of a drug and has an active
operational lifetime of, e.g., between 30 minutes and 75 hours. The
capacity and operational lifetime of the reservoir drug pump can
easily be adjusted by altering the size of the reservoir 1104 and
the rate at which the drug is administered.
[0094] The drug reservoir 1104 opens into a cannula 1110, which
conducts liquid drug to an infusion set 1112 (not shown in FIG.
11A). The cannula 1110 may contain a check valve 1113 to prevent
blood or interstitial fluid from entering the reservoir 1104 and
spoiling the drug, as well as a flow sensor 1114 for monitoring the
rate at which drug flows to the infusion set 1112. In some
embodiments, the infusion set 1112 is detachable from the drug pump
device 1100, allowing the infusion set 1112 to stay in place at the
infusion site (e.g., with the cannula inserted into the patient's
subcutaneous tissue) while the drug device 1100 is removed for
refilling or other purposes. Conversely, the pump can remain
attached to the patient when the infusion needle or catheter is
exchanged (which typically happens every few days). As illustrated
in FIG. 11B, the drug pump device 1100 and infusion set 1112 may be
mounted on two respective adhesive patches 1115 to be placed in
contact with the patient's skin.
[0095] A series of low-profile electrolysis electrodes 1116 are
disposed at the bottom of the electrolysis chamber 1106. The pump
control system may be disposed below the electrodes 1116, e.g.,
embedded in the lower housing portion 1102. As shown in FIG. 11 B,
the electrodes 1116 may form interdigitated comb-like structures--a
configuration that is advantages because it maximizes the opposing
electrode surface area and minimizes the distance between the
opposing electrodes, resulting in high electric field strengths in
the interjacent space. The electrodes 1116 are generally made of a
suitable metal, such as platinum, titanium, gold, or copper, among
others.
[0096] In operation, when current is supplied to the electrolysis
electrodes 1116, the electrolyte filling the pump chamber 1106
evolves gas 1120, expanding the diaphragm 1108 and moving it
upwards, i.e., towards the upper portion of the housing 1102. As a
result, liquid is displaced from the drug reservoir 1104 and forced
into and through the cannula 1110 to a delivery vehicle that is
part of the infusion set 1112. The diaphragm 1108 may be corrugated
or otherwise folded to permit a large degree of expansion without
sacrificing volume within the drug reservoir 1104 when the
diaphragm 1108 is relaxed. However, flat or bellows diaphragms may
also be used. The diaphragm 1108 may be molded or microfabricated
from, for example, parylene polymer. When the current is stopped,
the electrolyte gas 1120 condenses back into its liquid state, and
the diaphragm 1108 recovers its space-efficient corrugations. The
electrolysis pump may be smaller and more portable than other pumps
because of its lack of rigidly moving parts, and may be capable of
generating high pressures (e.g., greater than 20 psi), allowing the
drug pump device to overcome any biofouling or blockages in the
system.
[0097] The pump 1100 may include a magnet 1120 attached to the
underside of the diaphragm 1108. As the magnet 1120 approaches the
top of the drug dome 1102, a sensor 1124 determines the relative
distance between the magnet and the top of the drug dome, thus
indicating when the pump is, e.g., 80%, 90% and 100% empty. The
sensor 1124 may, for example, be a magnetic induction coil or a
Hall effect sensor. In one embodiment, the pump device alerts
(e.g., by means of LED flashes and/or an audio alert, or by
wirelessly signaling, for example, a smartphone) the patient when
the pump is almost empty (e.g., 80% to 90% empty), and again when
the pump is completely empty.
[0098] FIGS. 12A-12C illustrate another embodiment of a diaphragm
pump device in accordance herewith. The device 1200 includes an
electrolysis chamber 1202, a secondary pump chamber 1204 adjacent
the electrolysis chamber 1202, and a drug reservoir 1206 disposed
above the secondary pump chamber 1204 and opening into a cannula
1208. The electrolysis chamber 1202 and secondary pump chamber 1204
are connected via a fluid path that may be closed by a manually
controlled pressure-release valve 1210. This valve 1210 is closed
when the electrolysis pump is active, allowing gas to evolve and
pressure to build up inside the electrolysis chamber 1202, as shown
in FIG. 12B. At least a portion of the enclosure of the
electrolysis chamber 1202--as illustrated, the corrugated diaphragm
1212--has strong elastic properties. Therefore, when the
electrolysis pump is subsequently turned off and the valve to the
secondary chamber is opened, recoil of the elastic enclosure 1212
forces fluid from the pressurized electrolysis chamber 1202 into
the secondary pump chamber 1204. As a result, a diaphragm 1214
separating the secondary pump chamber 1204 from the drug reservoir
1206 expands, expelling drug from the reservoir 1206. A pressure
sensor inside the electrolysis chamber 1202 may be used to gauge
when the electrolysis pump needs to be turned on again. The pump
device 1200 facilitates delivering drug continuously while driving
the electrolysis only intermittently, which may allow building up a
level of pressure inside the pump chamber greater than that
achievable with sustained electrolysis. Consequently, this pump
configuration may be particularly useful for fast, high-pressure
drug injections.
[0099] Mechanical recoil may similarly be exploited for power
savings in a drug pump device that includes only a single pump
chamber, but primary and secondary drug reservoirs. The pump
chamber and primary drug reservoir may be arranged and function
substantially like the pump device 1100 shown in FIGS. 11A and 11B.
Rather than conducting drug from the primary reservoir directly to
the infusion site, however, the drug is pumped into the secondary
reservoir contained in a flexible bladder, which results in
expansion and pressurization of the bladder. The electrolysis pump
may then be turned off, and the pressurized bladder thereupon
slowly releases the drug for subcutaneous infusion.
[0100] Diaphragm pump devices in accordance herewith may include
various pump features described above with respect to piston pump
devices. For example, to ensure continuous contact between the
electrolysis electrode structure and the electrolyte despite
changes in the orientation of the device, the electrolyte may be
absorbed within a matrix material that is disposed on top of, or
otherwise placed in contact with, the electrode structure.
Preferably, the matrix material does not retain electrolysis gas
and, therefore, substantially does not expand during electrolysis.
This facilitates collapsing the expanded diaphragm to refill the
drug reservoir to its original volume. In other embodiments,
electrode structures (such as a pair of spring coils or flexible
wires) that remain in contact with liquid electrolyte regardless of
device orientation may be implemented in the electrolysis pump.
[0101] Having described certain embodiments of the invention, it
will be apparent to those of ordinary skill in the art that other
embodiments incorporating the concepts disclosed herein may be used
without departing from the spirit and scope of the invention. For
example, various features described with respect to one particular
device type and configuration may be implemented in other types of
device and alternative device configurations as well. Accordingly,
the described embodiments are to be considered in all respects as
only illustrative and not restrictive.
* * * * *