Note: Descriptions are shown in the official language in which they were submitted.
CA 02564800 2012-12-18
ELECTROKIINE'TIC DELIVERY SYSTEMS, DEVICES AND METHODS
BACKGROUND OF THE INVENTION
In many diagnostic and therapeutic medical applications (including drug
delivery
and analyte sampling/monitoring), precise transport of a drug, blood and/or
other bio-fluid
is important. However, with most conventional diagnostic and therapeutic
medical systems,
precise movement of large and small aqueous volumes of drugs and other bio-
fluids is
difficult to achieve. This difficulty arises because conventional systems
employ mechanical
components to effect fluid transport and delivery. Re-configuration of these
systems, to
enable highly precise movement of small and large aqueous volumes of a
solution
containing biomaterials, would be impractical, as the complexity of such
systems would
make their manufacture expensive, time consuming and labor intensive.
Presently, electrokinetic ("EK") or electro-osmotic manipulations of fluids
represent
the state-of-the art in controlled, high precision, small volume fluid
transport and handling.
Electro-osmosis involves the application of an electric potential to an
electrolyte, in contact
with a dielectric surface, to produce a net flow of the electrolyte.
While electro-osmosis has found widespread and wide ranging applications in
chemical analysis (e.g., high-speed liquid chromatography and other chemical
separation
procedures), its medical applications, such as for drug delivery and analyte
sampling, have
been limited, despite its advantages over conventional, mechanical approaches.
Design
challenges, including gas generation in the EK pump fluid, insufficient
hydraulic pressure
generation, and chemical degradation of the transported material caused by an
applied
electrical field, need to be overcome. When configured for non-medical use,
these
drawbacks do not pose tnajor issues because the consequences are minimal,
unlike in
medical applications.
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Accordingly, the present invention is directed to low-cost, high precision,
reliable and
compact EK pumps and systems adapted for medical applications, including, but
not limited
to, drug delivery and/or analyte sampling.
SUMMARY OF THE INVENTION
Generally, the present invention contemplates the use of controlled
electrokinetic
fluid flow techniques for efficient, reliable and highly precise movement of a
pump fluid. In
addition, various low-cost, precise, reliable and compact medical systems and
device for drug
delivery and analyte sampling are provided.
In some embodiments, the invention is a method of pumping fluid including the
steps
of providing an electrokinetic pump comprising a pair of double-layer
capacitive electrodes
having a capacitance of at least 10-2 Farads/cm2 and being connectable to a
power source, a
porous dielectric material disposed between the electrodes, a first reservoir
containing pump
fluid, a second reservoir, and a third reservoir containing a dispensed fluid;
connecting the
electrodes to a power source; moving pump fluid out of the first reservoir
into the second
reservoir at a pump fluid flow rate substantially without the occurrence of
Faradaic processes
in the pump; and moving dispensed fluid out of the third reservoir and through
a pump outlet
at a dispensed fluid flow rate as the pump fluid moves from the first
reservoir into the second
reservoir, the dispensed fluid flow rate being between about .1 times and 10
times the pump
fluid flow rate.
In other embodiments, the invention is a method of pumping fluid including the
steps
of providing an electrokinetic pump comprising a pair of double-layer
capacitive electrodes
having a capacitance of at least 10-2 Farads/cm2 and being connectable to a
power source, a
porous dielectric material disposed between the electrodes, a first reservoir
containing pump
fluid, a second reservoir, and a third reservoir containing a dispensed fluid,
the electrokinetic
pump having a volume no greater than 250% of an initial volume of dispensed
fluid;
connecting the electrodes to a power source; moving pump fluid out of the
first reservoir into
the second reservoir substantially without the occurrence of Faradaic
processes in the pump;
and moving dispensed fluid out of the third reservoir and through a pump
outlet as the pump
fluid moves from the first reservoir into the second reservoir.
In still other embodiments, the invention is a method of pumping fluid
including the
steps of providing an electrokinetic pump comprising a pair of double-layer
capacitive
electrodes having a capacitance of at least 10-2 Farads/cm2 and being
connectable to a power
source, a porous dielectric material disposed between the electrodes, a first
reservoir
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containing pump fluid, a second reservoir, and a syringe containing a
dispensed fluid;
connecting the electrodes to a power source; moving pump fluid out of the
first reservoir into
the second reservoir substantially without the occurrence of Faradaic
processes in the pump;
and moving dispensed fluid out of the syringe and into a patient as the pump
fluid moves
from the first reservoir into the second reservoir. This embodiment may also
include the step
of adding dispensed fluid to the syringe prior to the moving step.
Still other embodiments of the method include the following steps: providing
a first electrokinetic pump comprising a pair of double-layer capacitive
electrodes having a
capacitance of at least 10-2 Farads/cm2 and being connectable to a power
source, a porous
dielectric material disposed between the electrodes, a first reservoir
containing pump fluid, a
second reservoir, and a third reservoir containing a dispensed fluid;
connecting the electrodes
to a power source; moving pump fluid out of the first reservoir into the
second reservoir
substantially without the occurrence of Faradaic processes in the pump; moving
dispensed
fluid out of the third reservoir and through a first electrokinetic pump pump
outlet into a
patient as the pump fluid moves from the first reservoir into the second
reservoir; providing a
second electrokinetic pump comprising a pair of double-layer capacitive
electrodes
connectable to a power source, a porous dielectric material disposed between
the electrodes, a
first reservoir of pump fluid, a second reservoir, a third reservoir and a
dispensed fluid
disposed in the third reservoir; connecting the electrodes of the second
electrokinetic pump to
a power source; and moving dispensed fluid out of the third reservoir and
through a second
electrokinetic pump outlet into the patient as pump fluid of the second
electrokinetic pump
moves from the first reservoir into the second reservoir of the second
electrokinetic pump
substantially without the occurrence of Faradaic processes in the second pump.
The step of
moving dispensed fluid from the first electrokinetic pump may be performed at
a first rate
and the step of moving dispensed fluid from the second electrokinetic pump may
be
performed at a second rate different than the first rate. The first
electrokinetic pump and the
dispensed fluid of the second electrokinetic pump may be the same kind of
fluid or different
kinds of fluid.
Other embodiments of the invention provide a method of pumping fluid including
the
steps of providing a first electrokinetic pump comprising a pair of double-
layer capacitive
electrodes having a capacitance of at least 10-2 Farads/cm2 and being
connectable to a power
source, a porous dielectric material disposed between the electrodes, a first
reservoir
containing pump fluid, a second reservoir, and a third reservoir containing a
dispensed fluid;
connecting the electrodes to a power source; moving pump fluid out of the
first reservoir into
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the second reservoir substantially without the occurrence of Faradaic
processes in the pump;
moving dispensed fluid out of the third reservoir and through a pump outlet
into a patient as
the pump fluid moves from the first reservoir into the second reservoir;
providing a second
electrokinetic pump comprising a pair of double-layer capacitive electrodes
connectable to a
power source, a porous dielectric material disposed between the electrodes, a
first reservoir of
pump fluid, a second reservoir, a third reservoir and a dispensed fluid
disposed in the third
reservoir; connecting the electrodes of the second electrokinetic pump to a
power source; and
moving dispensed fluid out of the second electrokinetic pump third reservoir
and through the
pump outlet into the patient as pump fluid of the second electrokinetic pump
moves from the
first reservoir into the second reservoir of the second electrokinetic pump
substantially
without the occurrence of Faradaic processes in the second pump. The first
electrokinetic
pump and the dispensed fluid of the second electrokinetic pump may be the same
kind of
fluid or different kinds of fluid.
Yet other embodiments of the invention provide a method of pumping fluid
including
the steps of providing a first electrokinetic pump comprising a pair of double-
layer capacitive
electrodes having a capacitance of at least 10-2 Farads/cm2 and being
connectable to a power
source, a porous dielectric material disposed between the electrodes, a first
reservoir
containing pump fluid, a second reservoir, and a third reservoir containing a
dispensed fluid;
connecting the electrodes to a power source; moving pump fluid out of the
first reservoir into
the second reservoir substantially without the occurrence of Faradaic
processes in the pump;
moving dispensed fluid out of the third reservoir and through a pump outlet
into a patient as
the pump fluid moves from the first reservoir into the second reservoir;
providing a second
electrokinetic pump comprising a pair of double-layer capacitive electrodes
connectable to a
power source, a porous dielectric material disposed between the electrodes, a
first reservoir of
pump fluid and a second reservoir; connecting the electrodes of the second
electrokinetic
pump to a power source; and moving dispensed fluid out of the third reservoir
and through
the pump outlet into the patient as pump fluid of the second electrokinetic
pump moves from
the first reservoir into the second reservoir of the second electrokinetic
pump substantially
without the occurrence of Faradaic processes in the second pump.
Still other aspects of the invention include a method of pumping fluid
including the steps of
providing an electrokinetic pump comprising a pair of double-layer capacitive
electrodes
having a capacitance of at least 10-2 Farads/cm2 and being connectable to a
power source, a
porous dielectric material disposed between the electrodes, a first reservoir
containing pump
fluid, a second reservoir, and a third reservoir containing a dispensed fluid;
connecting the
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electrodes to a power source; determining a patient's need for a dispensed
fluid; moving
pump fluid out of the first reservoir into the second reservoir substantially
without the
occurrence of Faradaic processes in the pump; and moving dispensed fluid out
of the third
reservoir and through a pump outlet into the patient as the pump fluid moves
from the first
reservoir into the second reservoir in response to the determined need. The
dispensed fluid
may be insulin and the determining step may include determining the patient's
blood glucose
concentration, with the moving step comprising injecting a quantity of insulin
into the patient
in response to the determined blood glucose concentration. The moving step may
also
include automatically injecting a quantity of insulin into the patient in
response to the
determined blood glucose concentration. The determining step may include
sampling a fluid
taken from the patient with a second electrokinetic pump.
Other aspects of the invention provide a method of pumping fluid including the
steps
of providing an electrokinetic pump comprising a pair of double-layer
capacitive electrodes
having a capacitance of at least 10-2 Farads/cm2 and being connectable to a
power source, a
porous dielectric material disposed between the electrodes, a first reservoir
containing pump
fluid, a second reservoir, and a third reservoir containing a dispensed fluid;
connecting the
electrodes to a power source; moving pump fluid out of the first reservoir
into the second
reservoir substantially without the occurrence of Faradaic processes in the
pump; moving
dispensed fluid out of the third reservoir and through a pump outlet as the
pump fluid moves
from the first reservoir into the second reservoir; and monitoring a parameter
related to an
amount of dispensed fluid moved out of the third reservoir during the moving
step (e.g., flow
rate, position of a pump element). The monitored parameter may be used to
provide
feedback control of the moving step, to provide an indication related to the
dispensed fluid, to
calculate a desired amount of dispensed fluid to be dispensed, and/or to
indicate the presence
of an occlusion in the pump outlet.
Yet other aspects of the invention provide a method of pumping fluid including
the
steps of providing an electrokinetic pump comprising a pair of double-layer
capacitive
electrodes having a capacitance of at least 10-2 Farads/cm2 and being
connectable to a power
source, a porous dielectric material disposed between the electrodes, a first
reservoir
containing pump fluid, a second reservoir, and a third reservoir containing a
dispensed fluid;
connecting the electrodes to a power source; moving pump fluid out of the
first reservoir into
the second reservoir substantially without the occurrence of Faradaic
processes in the pump;
and moving dispensed fluid out of the third reservoir and through a pump
outlet for a fixed
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time interval to dispense a fixed volume of dispensed fluid as the pump fluid
moves from the
first reservoir into the second reservoir.
Still other aspects of the invention provide a method of pumping fluid
including the
steps of providing an electrokinetic pump comprising a pair of double-layer
capacitive
electrodes having a capacitance of at least 10-2 Farads/cm2 and being
connectable to a power
source, a porous dielectric material disposed between the electrodes, a first
reservoir
containing pump fluid, a second reservoir, and a third reservoir containing a
dispensed fluid;
connecting the electrodes to a power source; moving pump fluid out of the
first reservoir into
the second reservoir substantially without the occurrence of Faradaic
processes in the pump;
moving dispensed fluid out of the third reservoir and through a pump outlet as
the pump fluid
moves from the first reservoir into the second reservoir; and adjusting an
amount of
dispensed fluid moved out of the third reservoir.
Yet another aspect of the invention is a method of pumping fluid including the
steps
of providing an electrokinetic pump comprising a pair of double-layer
capacitive electrodes
having a capacitance of at least 10-2 Farads/cm2 and being connectable to a
power source, a
porous dielectric material disposed between the electrodes, a first reservoir
containing pump
fluid, a second reservoir, and a third reservoir containing a dispensed fluid;
connecting the
electrodes to a power source; loading a dispensed fluid into the third
reservoir; treating the ,
electrokinetic pump to alter a characteristic of the dispensed fluid; moving
pump fluid out of
the first reservoir into the second reservoir substantially without the
occurrence of Faradaic
processes in the pump; and moving dispensed fluid out of the third reservoir
and through a
pump outlet as the pump fluid moves from the first reservoir into the second
reservoir. The
treating step may include irradiating the electrokinetic pump.
Still another aspect of the invention provides a method of pumping fluid
including the
steps of providing an electrokinetic pump comprising a pair of double-layer
capacitive
electrodes having a capacitance of at least 10-2 Farads/cm2 and being
connectable to a power
source, a porous dielectric material disposed between the electrodes and a
reservoir
containing pump fluid; connecting the electrodes to a power source; and moving
substantially
all of the pump fluid out of the reservoir substantially without the
occurrence of Faradaic
processes in the pump at a flow rate of less than about 1 microliter/minute
and with a steady
state flow rate error of no more than about 5% over the entire method step.
Yet another aspect of the invention provides a method of pumping fluid
including the
steps of providing an electrokinetic pump comprising a pair of double-layer
capacitive
electrodes having a capacitance of at least 10-2 Farads/cm2 and being
connectable to a power
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source, a porous dielectric material disposed between the electrodes and a
reservoir
containing pump fluid; connecting the electrodes to a power source; generating
a pump fluid
pressure between about 1 and about 1000 psi; and moving pump fluid out of the
reservoir
substantially without the occurrence of Faradaic processes in the pump.
Another aspect of the invention provides a method of pumping fluid including
the
steps of providing an electrokinetic pump comprising a pair of double-layer
capacitive
electrodes having a capacitance of at least 10-2 Farads/cm2 and being
connectable to a power
source, a porous dielectric material disposed between the electrodes and a
reservoir
containing pump fluid, a power source connectable to the electrodes and a
housing containing
the electrodes, dielectric material, reservoir and power source, the
electrokinetic pump having
a volume of at most about 11 cm3; connecting the electrodes to a power source;
and moving
at least about 0.2 milliliters of pump fluid out of the reservoir
substantially without the
occurrence of Faradaic processes in the pump. The moving step may include
moving the
pump fluid at a rate of less than about 10 nanoliters/min. and may also
include the step of
moving the pump fluid substantially continuously for about 30 days.
Still another aspect of the invention provides a method of pumping fluid
including the
steps of providing an electrokinetic pump comprising a pair of double-layer
capacitive
electrodes having a capacitance of at least 10-2 Farads/cm2 and being
connectable to a power
source, a porous dielectric material disposed between the electrodes and a
reservoir
containing pump fluid; supporting the electrokinetic pump on a patient;
connecting the
electrodes to a power source; and moving pump fluid out of the reservoir
substantially
without the occurrence of Faradaic processes in the pump. This method may also
include
implanting the electrokinetic pump in a patient. In embodiments in which the
electrokinetic
pump has a shape, the implanting step includes placing the electrokinetic pump
adjacent to an
anatomical feature of the patient having a shape complementary to the
electrokinetic pump
shape.
Another aspect of the invention provides a method of pumping fluid including
the
steps of providing a first electrokinetic pump comprising a pair of double-
layer capacitive
electrodes having a capacitance of at least 10-2 Farads/cm2 and being
connectable to a power
source, a porous dielectric material disposed between the electrodes and a
reservoir
containing pump fluid; connecting the electrodes to a power source; moving
pump fluid out
of the reservoir at a first rate into a patient substantially without the
occurrence of Faradaic
processes in the first pump; providing a second electrokinetic pump comprising
a pair of
double-layer capacitive electrodes connectable to a power source, a porous
dielectric material
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disposed between the electrodes and a reservoir of a pump fluid; connecting
the electrodes of
the second electrokinetic pump to a power source; and moving pump fluid out of
the second
electrokinetic pump reservoir at a second rate into the patient substantially
without the
occurrence of Faradaic processes in the second pump. The first electrokinetic
pump and the
pump fluid of the second electrokinetic pump may be the same kind of fluid or
different kinds
of fluid.
Still another aspect of the invention provides a method of pumping fluid
including the
steps of providing an electrokinetic pump comprising a pair of double-layer
capacitive
electrodes having a capacitance of at least 10-2 Farads/cm2 and being
connectable to a power
source, a porous dielectric material disposed between the electrodes and a
reservoir
containing pump fluid; connecting the electrodes to a power source in a time
modulated
manner; and moving pump fluid out of the reservoir substantially without the
occurrence of
Faradaic processes in the pump.
Yet another aspect of the invention provides a method of pumping fluid
including the
steps of providing an electrokinetic pump comprising a pair of double-layer
capacitive
electrodes having a capacitance of at least 10-2 Farads/cm2 and being
connectable to a power
source, a porous dielectric material disposed between the electrodes and a
reservoir
containing pump fluid; connecting the electrodes to a power source by
alternating the power
source between an on state and an off state; and moving pump fluid out of the
reservoir
substantially without the occurrence of Faradaic processes in the pump.
Another aspect of the invention is a method of pumping fluid including the
steps of
providing an electrokinetic pump comprising a pair of double-layer capacitive
electrodes
having a capacitance of at least 10-2 Farads/cm2 and being connectable to a
power source, a
porous dielectric material disposed between the electrodes and a reservoir
containing pump
fluid; connecting the electrodes to a power source by alternating the power
source between a
normally off state and a periodic on state in response to a computer program;
and moving
pump fluid out of the reservoir substantially without the occurrence of
Faradaic processes in
the pump.
Still another aspect of the invention provides an electrokinetic pump system
including
a pair of double-layer capacitive electrodes having a capacitance of at least
10-2 Farads/cm2;
a porous dielectric material disposed between the electrodes; a first
reservoir containing
pump fluid; a second reservoir; a third reservoir containing dispensed fluid
and a pump
outlet; a power source connected to the electrodes; the electrodes, dielectric
material and
power source being adapted to move the pump fluid out of the first reservoir
into the second
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reservoir substantially without the occurrence of Faradaic processes in the
pump and to move
the dispensed fluid out of the pump outlet as the pump fluid moves from the
first reservoir
into the second reservoir; and a controller adapted to control delivery of
power from the
power source to the electrodes to move a fixed volume of dispensed fluid out
of the third
reservoir.
Yet another aspect of the invention is an electrokinetic pump system including
a pair
of double-layer capacitive electrodes having a capacitance of at least 10-2
Farads/cm2; a
porous dielectric material disposed between the electrodes; a first reservoir
containing pump
fluid; a second reservoir; a third reservoir containing dispensed fluid and a
pump outlet; a
power source connected to the electrodes; the electrodes, dielectric material
and power source
being adapted to move the pump fluid out of the first reservoir into the
second reservoir
substantially without the occurrence of Faradaic processes in the pump and to
move the
dispensed fluid out of the pump outlet as the pump fluid moves from the first
reservoir into
the second reservoir; and a controller adapted to control delivery of power
from the power
source to the electrodes to move dispensed fluid for a fixed period of time.
Still another aspect of the invention provides an electrokinetic pump system
including
a pair of double-layer capacitive electrodes having a capacitance of at least
10-2 Farads/cm2; a
porous dielectric material disposed between the electrodes; a first reservoir
containing pump
fluid; a second reservoir; a third reservoir containing dispensed fluid and a
pump outlet; a
power source connected to the electrodes; the electrodes, dielectric material
and power source
being adapted to move the pump fluid out of the first reservoir into the
second reservoir
substantially without the occurrence of Faradaic processes in the pump and to
move the
dispensed fluid out of the pump outlet as the pump fluid moves from the first
reservoir into
the second reservoir; and a controller adapted to control delivery of power
from the power
source to the electrodes to move dispensed fluid out of the third reservoir at
a fixed time
interval.
Another aspect of the invention is an electrokinetic pump system including a
pair of
double-layer capacitive electrodes having a capacitance of at least 10-2
Farads/cm2; a porous
dielectric material disposed between the electrodes; a first reservoir
containing pump fluid; a
second reservoir; a third reservoir containing dispensed fluid and a pump
outlet; a power
source connected to the electrodes; the electrodes, dielectric material and
power source being
adapted to move the pump fluid out of the first reservoir into the second
reservoir
substantially without the occurrence of Faradaic processes in the pump and to
move the
dispensed fluid out of the pump outlet as the pump fluid moves from the first
reservoir into
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the second reservoir; and a controller adapted to control delivery of power
from the power
source to the electrodes to move an amount dispensed fluid out of the third
reservoir in
response to a user input.
Yet another aspect of the invention is an electrokinetic pump system including
a first
electrokinetic pump comprising a pair of double-layer capacitive electrodes
having a
capacitance of at least 10-2 Farads/cm2; a porous dielectric material disposed
between the
electrodes; a first reservoir containing pump fluid; a second reservoir; a
third reservoir
containing dispensed fluid and a first pump outlet; and a power source
connected to the
electrodes; the electrodes, dielectric material and power source being adapted
to move the
pump fluid out of the first reservoir into the second reservoir substantially
without the
occurrence of Faradaic processes in the pump and to move the dispensed fluid
out of the first
pump outlet into a patient as the pump fluid moves from the first reservoir
into the second
reservoir; and a second electrokinetic pump comprising a second pair of double-
layer
capacitive electrodes connectable to a power source, a porous dielectric
disposed between the
second pair of electrodes, a fourth reservoir containing pump fluid, a second
reservoir and a
sixth reservoir containing a dispensed fluid, and a second pump outlet, the
second
electrokinetic pump electrodes and dielectric material being adapted to move
the second
electrokinetic pump fluid out of the fourth reservoir into the fifth reservoir
tò move the
second electrokinetic pump dispensed fluid through the second pump outlet into
the patient
when the second electrokinetic pump electrodes are connected to a power source
without the
occurrence of Faradaic processes in the second pump, the system further
comprising a
controller adapted to control the first and second electrokinetic pumps. The
first
electrokinetic pump may be further adapted move dispensed fluid at a first
rate and the
second electrokinetic pump is further adapted to move dispensed fluid at a
second rate
different than the first rate.
Another aspect of the invention is an electrokinetic pump system including a
first
electrokinetic pump comprising a pair of double-layer capacitive electrodes
having a
capacitance of at least 10-2 Farads/cm2; a porous dielectric material disposed
between the
electrodes; a first reservoir containing pump fluid; a second reservoir; a
third reservoir
containing dispensed fluid and a pump outlet; and a power source connected to
the
electrodes; the electrodes, dielectric material and power source being adapted
to move the
pump fluid out of the first reservoir into the second reservoir substantially
without the
occurrence of Faradaic processes in the pump and to move the dispensed fluid
out of the
pump outlet into a patient as the pump fluid moves from the first reservoir
into the second
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reservoir; and a second electrokinetic pump comprising a pair of double-layer
capacitive
electrodes connectable to a power source, a porous dielectric disposed between
the
electrodes, a fourth reservoir containing pump fluid, a fifth reservoir and a
sixth reservoir
containing a dispensed fluid, the second electrokinetic pump electrodes and
dielectric
material being adapted to move the second electrokinetic pump fluid out of the
fourth
reservoir into the fifth reservoir to move the second electrokinetic pump
dispensed fluid
through the pump outlet into the patient when the second electrokinetic pump
electrodes are
connected to a power source substantially without the occurrence of Faradaic
processes in the
second pump. The first electrokinetic pump may be further adapted move
dispensed fluid at
a first rate and the second electrokinetic pump is further adapted to move
dispensed fluid at a
second rate different than the first rate.
Still another aspect of the invention is an electrokinetic pump system
including a pair
of double-layer capacitive electrodes having a capacitance of at least 10-2
Farads/cm2; a first
electrokinetic pump comprising a porous dielectric material disposed between
the electrodes;
a first reservoir containing pump fluid; a second reservoir; a third reservoir
containing
dispensed fluid and a pump outlet; and a power source connected to the
electrodes; the
electrodes, dielectric material and power source being adapted to move the
pump fluid out of
the first reservoir into the second reservoir substantially without the
occurrence of Faradaic
processes in the pump and to move the dispensed fluid out of the pump outlet
into a patient as
the pump fluid moves from the first reservoir into the second reservoir; and a
second
electrokinetic pump comprising a pair of double-layer capacitive electrodes
connectable to a
power source, a porous dielectric disposed between the electrodes, a fourth
reservoir
containing pump fluid and a fifth reservoir, the second electrokinetic pump
electrodes and
dielectric material being adapted to move the second electrokinetic pump fluid
out of the
fourth reservoir into the fifth reservoir to move the dispensed fluid through
the pump outlet
into the patient when the second electrokinetic pump electrodes are connected
to a power
source substantially without the occurrence of Faradaic processes in the
second pump.
Yet another aspect of the invention provides an electrokinetic pump system
including
a pair of double-layer capacitive electrodes having a capacitance of at least
10-2 Farads/cm2; a
porous dielectric material disposed between the electrodes; a first reservoir
containing pump
fluid; a second reservoir; a third reservoir containing dispensed fluid and a
pump outlet; a
power source connected to the electrodes; the electrodes, dielectric material
and power source
being adapted to move the pump fluid out of the first reservoir into the
second reservoir
substantially without the occurrence of Faradaic processes in the pump and to
move the
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dispensed fluid out of the pump outlet as the pump fluid moves from the first
reservoir into
the second reservoir; and a movable member comprising a hydraulic amplifier
disposed
between the second reservoir and the third reservoir adapted to move as pump
fluid moves
from the first reservoir into the second reservoir to move the dispensed fluid
out of the third
reservoir.
Another aspect of the invention is an electrokinetic pump system including a
pair of
double-layer capacitive electrodes having a capacitance of at least 10-2
Farads/cm2; a porous
dielectric material disposed between the electrodes; a first reservoir
containing pump fluid; a
second reservoir; a third reservoir containing dispensed fluid and a pump
outlet; a power
source connected to the electrodes; the electrodes, dielectric material and
power source being
adapted to move the pump fluid out of the first reservoir into the second
reservoir
substantially without the occurrence of Faradaic processes in the pump and to
move the
dispensed fluid out of the pump outlet as the pump fluid moves from the first
reservoirinto
the second reservoir; and a sensor adapted to determine a patient's need for
the dispensed
fluid. The system may also include a controller adapted to control delivery of
power from the
power source to the electrodes in response to a signal from the sensor. In
some embodiments,
the sensor comprises an electrokinetic pump adapted to sample a fluid from the
patient.
Still another aspect of the invention provides an electrokinetic pump system
including
a pair of double-layer capacitive electrodes having a capacitance of at least
10-2 Farads/cm2; a
porous dielectric material disposed between the electrodes; a first reservoir
containing pump
fluid; a second reservoir; a third reservoir containing dispensed fluid and a
pump outlet; an
external port communicating with the third reservoir; a movable member
disposed between
the second reservoir and the third reservoir adapted to change an effective
volume of the third
reservoir as an effective volume of the second reservoir changes; a power
source connected to
the electrodes; the electrodes, dielectric material and power source being
adapted to move the
pump fluid out of the first reservoir into the second reservoir substantially
without the
occurrence of Faradaic processes in the pump and to move the dispensed fluid
out of the
pump outlet as the pump fluid moves from the first reservoir into the second
reservoir; and a
laminated housing, the electrokinetic pump system having a volume no greater
than 250% of
the largest effective volume of the third reservoir.
Yet another aspect of the invention is an electrokinetic pump system including
a pair
of double-layer capacitive electrodes having a capacitance of at least 10-2
Farads/cm2; a
porous dielectric material disposed between the electrodes; a first reservoir
containing pump
fluid; a second reservoir; a third reservoir containing dispensed fluid and a
pump outlet; an
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external port communicating with the third reservoir; a movable member
disposed between
the second reservoir and the third reservoir adapted to change an effective
volume of the third
reservoir as an effective volume of the second reservoir changes; a power
source connected to
the electrodes; the electrodes, dielectric material and power source being
adapted to move the
pump fluid out of the first reservoir into the second reservoir substantially
without the
occurrence of Faradaic processes in the pump and to move the dispensed fluid
out of the
pump outlet as the pump fluid moves from the first reservoir into the second
reservoir; and a
sensor adapted to monitor a parameter (e.g., flow rate, syringe position
using, e.g., a magnet
and a magnetostrictive sensor) related to an amount of fluid dispensed from
the third
reservoir. The system may also include a feedback control element adapted to
control power
delivered to the electrodes by the power source in response to a signal from
the sensor, a
controller adapted to control application of power from the power source to
the electrodes in
response to a sensor output signal, and/or an indicator adapted to provide an
indication
related to fluid dispensed from the third reservoir, such as the existence of
an occlusion of the
external port.
Another aspect of the invention provides an electrokinetic pump system
including a
pair of double-layer capacitive electrodes having a capacitance of at least 10-
2 Farads/cm2; a
porous dielectric material disposed between the electrodes; a reservoir
containing pump fluid;
and a power source connected to the electrodes; the electrodes, dielectric
material and power
source being adapted to move the pump fluid out of the reservoir substantially
without the
occurrence of Faradaic processes in the pump at a flow rate of less than about
1
microliter/minute and with a steady state flow rate error of no more than
about 5%.
Still another aspect of the invention provides an electrokinetic pump system
including
a pair of double-layer capacitive electrodes having a capacitance of at least
10-2 Farads/cm2; a
porous dielectric material disposed between the electrodes; a reservoir
containing pump fluid;
and a power source connected to the electrodes; the electrodes, dielectric
material and power
source being adapted to move the pump fluid out of the reservoir substantially
without the
occurrence of Faradaic processes in the pump at a pump fluid pressure between
about 1 and
about 1000 psi.
Yet another aspect of the invention provides an electrokinetic pump system
including
a pair of double-layer capacitive electrodes having a capacitance of at least
10-2 Farads/cm2; a
porous dielectric material disposed between the electrodes; a reservoir
containing pump fluid;
a power source connected to the electrodes; the electrodes, dielectric
material and power
source being adapted to move the pump fluid out of the reservoir substantially
without the
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occurrence of Faradaic processes in the pump; and a housing having a volume of
at most
about 11 cm3 and wherein the electrodes, dielectric material and power source
are further
adapted to move at least about 0.2 milliliters of pump fluid from the
reservoir. The
electrodes, dielectric material and power source may be further adapted to
move pump fluid
from the reservoir at a rate of less than 10 nanoliters/min. The electrodes,
dielectric material
and power source may be still further adapted to move pump fluid from the
reservoir from the
reservoir substantially continuously for about 30 days. The housing may be a
laminated
housing.
Yet another aspect of the invention provides an electrokinetic pump system
including
a pair of double-layer capacitive electrodes having a capacitance of at least
10-2 Farads/cm2; a
porous dielectric material disposed between the electrodes; a reservoir
containing pump fluid;
and a power source connected to the electrodes; the electrodes, dielectric
material and power
source being adapted to move the pump fluid out of the reservoir substantially
without the
occurrence of Faradaic processes in the pump; wherein the electrodes,
dielectric material and
power source are further adapted to be implanted in a patient.
Another aspect of the invention is an electrokinetic pump system including a
pair of
double-layer capacitive electrodes having a capacitance of at least 10-2
Farads/cm2; a porous
dielectric material disposed between the electrodes; a reservoir containing
pump fluid; a
power source connected to the electrodes; the electrodes, dielectric material
and power source
being adapted to move the pump fluid out of the reservoir substantially
without the
occurrence of Faradaic processes in the pump; and an indicator adapted to
indicate an amount
of pump fluid present in the reservoir.
Still another aspect of the invention provides an electrokinetic pump system
including
a pair of double-layer capacitive electrodes having a capacitance of at least
10-2 Farads/cm2; a
porous dielectric material disposed between the electrodes; a reservoir
containing pump fluid;
a power source connected to the electrodes; the electrodes, dielectric
material and power
source being adapted to move the pump fluid out of the reservoir substantially
without the
occurrence of Faradaic processes in the pump; and a controller adapted to
provide power
from the power source to the electrodes in a time modulated manner.
Another aspect of the invention is an electrokinetic pump system including a
pair of
double-layer capacitive electrodes having a capacitance of at least 10-2
Farads/cm2; a porous
dielectric material disposed between the electrodes; a reservoir containing
pump fluid; a
power source connected to the electrodes; the electrodes, dielectric material
and power source
being adapted to move the pump fluid out of the reservoir substantially
without the
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occurrence of Faradaic processes in the pump; and a controller adapted to
alternate the power
source between an on state and an off state.
Still another aspect of the invention is an electrokinetic pump system
including a pair
of double-layer capacitive electrodes having a capacitance of at least 10.'2
Farads/cm2; a
porous dielectric material disposed between the electrodes; a reservoir
containing pump fluid;
a power source connected to the electrodes; the electrodes, dielectric
material and power
source being adapted to move the pump fluid out of the reservoir substantially
without the
occurrence of Faradaic processes in the pump; and a controller adapted to
alternate the power
source between a normally off state and a periodic on state in response to a
computer
program.
Yet another aspect of the invention is an electrokinetic pump system including
a pair
of double-layer capacitive electrodes having a capacitance of at least 10-2
Farads/cm2; a
porous dielectric material disposed between the electrodes; a reservoir
containing pump fluid;
a power source connected to the electrodes; the electrodes, dielectric
material and power
source being adapted to move the pump fluid out of the reservoir substantially
without the
occurrence of Faradaic processes in the pump; and a housing containing the
electrodes,
reservoir, dielectric material and power source, the housing being adapted to
be worn on a
human or animal body.
Another aspect of the invention provides a displacement pump including a
dispensed
fluid reservoir; a pump outlet; a displacement mechanism; a power source
adapted to operate
the displacement mechanism; and a housing containing the reservoir, pump
outlet, power
source and displacement mechanism, the housing having a volume no more than
250% of the
volume of the dispensed fluid reservoir; the displacement mechanism and power
source being
further adapted to dispense substantially all of dispensed fluid from the
reservoir through the
pump outlet at a flow rate no more than 1 microliter/minute with a steady
state flow rate error
of no more than about 5%. The displacement mechanism may include a movable
member,
and the pump may further include an electrokinetic assembly comprising a pair
of electrodes
connectable to the power source, a porous dielectric material disposed between
the
electrodes; and pump fluid in contact with the electrodes, such as double-
layer capacitive
electrodes.
Yet another aspect of the invention is a pump including a reservoir of pump
fluid; a
pump mechanism operable on the pump fluid; a pump outlet; a power source
connectable to
the pump mechanism to move pump fluid from the reservoir through the pump
outlet at a
flow rate no more than 1 microliter/minute with a steady state flow rate error
of no more than
=
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about 5%; and a housing containing the reservoir, electrodes, pump outlet and
power source, the
housing having a volume no more than 150% of the volume of the reservoir. The
electrodes may be
a pair of double-layer capacitive electrodes having a capacitance of at least
10-2Farads/cm2.
In another aspect there is provided a displacement pump comprising: a
dispensed fluid
reservoir; a pump outlet; a displacement mechanism; a power source adapted to
operate the
displacement mechanism; and a housing containing the reservoir, pump outlet,
power source and
displacement mechanism, the housing having a volume no more than 250% of the
volume of the
dispensed fluid reservoir; wherein the displacement mechanism comprises a pair
of double-layer
capacitive electrodes connectable to the power source and having a capacitance
of at least 10-2
Farads/cm2; and wherein the displacement mechanism and power source is further
adapted to
dispense substantially all of dispensed fluid from the reservoir through the
pump outlet at a flow
rate no more than 1 microliter/minute with a steady state flow rate error of
no more than about 5%.
The displacement mechanism may further comprise a movable member.
The displacement mechanism may further comprise an electrokinetic assembly
comprising
the pair of double-layer capacitive electrodes, a porous dielectric material
disposed between the pair
of double-layer capacitive electrodes; and pump fluid in contact with the pair
of double-layer
capacitive electrodes.
In another aspect, there is provided a pump comprising: a reservoir of pump
fluid; a pump
mechanism operable on the pump fluid, the pump mechanism comprising a pair of
double-layer
capacitive electrodes having a capacitance of at least 10-2 Farads/cm2; a pump
outlet; a power
source connectable to the pump mechanism to move pump fluid from the reservoir
through the
pump outlet at a flow rate no more than 1 microliter/minute with a steady
state flow rate error of no
more than about 5%; and a housing containing the reservoir, electrodes, pump
outlet and power
source, the housing having a volume no more than 150% of the volume of the
reservoir.
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BRIEF DESCRIPTION OF THE DRAWINGS
The novel features of the invention are set forth with particularity in the
appended claims.
A better understanding of the features and advantages of the present invention
will be obtained by
reference to the following detailed description that sets forth illustrative
embodiments, in which the
principles of the invention are utilized, and the accompanying drawings of
which:
FIG. 1 illustrates a cross-section view of one embodiment of a direct EK pump;
FIG. 2 illustrates a cross-sectional view of a direct EK pump comprising a
split reservoir
design;
FIG. 3 illustrates a cross-section view of an indirect EK pump;
FIGS 4a ¨ 4c schematically illustrate operation of the EK pump provided with
FIG. 3;
FIGS 5a ¨ Sc schematically illustrate controlled collapse of impermeable
membranes
during operation of the EK pump illustrated in FIGS. 3 and 4;
FIG. 6 illustrates a cross-sectional view of another indirect EK pump
embodiment;
FIG. 7 illustrates a cross-sectional of one embodiment of a hydraulic
amplifier;
FIG. 8 illustrates one embodiment of an EK delivery system comprising a
syringe;
FIG. 9 illustrates the dependence of fluid flow rates on voltage of an EK
pump;
FIG. 10 illustrates the relationship of pressure and fluid flow rate of an EK
pump;
FIG. lla illustrates one embodiment of a flow indicator;
FIG. 111J illustrates one embodiment of a flow meter;
FIG. 12a illustrates an exploded, enlarged view of one embodiment of n EK
delivery
system;
FIG. 12b illustrates a schematic view of the EK delivery system illustrated in
FIG. 12a;
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FIG. 13a illustrates an exploded, view of another EK delivery system
embodiment;
FIG. 13b illustrates a schematic view of the EK delivery system illustrated in
FIG.
13a;
FIG. 14 illustrates a schematic view of one embodiment of a shielded delivery
system;
FIG. 15 illustrates a schematic view of one embodiment of an EK sampling
system;
FIG. 16 illustrates a system block diagram of a dual drug delivery and
sampling
system;
FIG. 17 illustrates system block diagram of a multi-drug delivery and sampling
system;
FIG. 18 illustrates a system block diagram of a multi-drug, multi-pump
externally
controllable delivery system;
FIG. 19 illustrates a system block diagram of a distributed, multi-drug, multi-
pump
externally controllable delivery system; and
FIGS. 20 ¨ 24 illustrate pump performance wherein:
FIG. 20 graphically illustrates rapid loading and delivery flow rates of an EK
pump;
FIG. 21 graphically illustrates the constant steady-state flow rates during
operation of
an EK pump at any instantaneous time; and
FIGS. 22 and 23 graphically illustrate constant steady-state flow rates during
operation of an EK pump configured to operate over a period of hours or days.
DETAILED DESCRIPTION OF THE INVENTION
The invention described herein provides EK systems for efficient, reliable and
precise
movement of a pump fluid for drug delivery and/or analyte sampling. Before
describing
these systems, the designs and characteristics of a few exemplary EK pumps
suitable for use
in said systems are provided below.
FIG. 1 is a cross-sectional view of a small, compact EK pump 100. In this
example,
EK pump 100 comprises a first fluid reservoir 102 and a second fluid reservoir
104. First
fluid reservoir 102 is coupled to second fluid reservoir 104 by through-vias
106, 110 and
porous dielectric material 108. Through-vias 106 and 110, along with porous
dielectric
material 108, provide a fluidic path between first reservoir 102 and second
reservoir 104. In
this example, porous dielectric material 108 is encapsulated within a bonding
material 114,
between upper and lower substrates 116a and 116b, respectively, as further
described in Ser.
No. 10/198,223.
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Each fluid reservoir further comprises a fluid port 118 (which can be an inlet
or outlet
port) and capacitive electrode 120a and 120b. An electrical lead (not shown)
is placed in
contact with electrodes 120a, 120b to couple them to a power supply (not
shown). During
operation, reservoirs 102 and 104, including the space between porous
dielectric material 108
and electrodes 120a and 120b, is filled with an electrolyte or pump fluid 122.
The fluid 122
may flow though or around electrodes 120a and 120b. As a voltage (correlated
to the desired
flow rate and pressure profile of pump 100) is applied, pump fluid 122 is
moved from one
fluid reservoir to the other via electro-osmosis, without electrolysis, gas
generation or
substantial capacitive de-ionization during operation of the pump 100. As will
be recognized
by one skilled in the art, gas formation or pH change due to changes in pump
components
(e.g., the pump fluid and/or electrodes), can introduce system error and
decrease the precision
of a fluid transport system or prevent the pump from working altogether.
Generally, the problem of gas formation and pH change in prior EK pumps
results
from electrochemical changes in the pump components, which are induced when a
high
enough electric field or voltage is applied to create a desired EK flow. For
example, the
pump fluid may be oxidized or reduced and produce gas and/or change the pH.
Additionally,
the electrodes of prior art EK pumps can be changed by oxidation-reduction
reactions at the
electrode-pump fluid interface. As will be recognized by one skilled in the
art, these Faradaic
processes decrease the precision and operability of EK pumps over time. To
prevent or
minimize Faradaic processes, several techniques can be employed in this
invention, including
but not limited to, implementing drive strategies to limit Faradaic processes
and careful
material selection of pump electrodes.
For example, a system voltage and the duration of the applied system voltage
should
be maintained sufficient to charge the electrodes and generate current flow to
support a
desired fluid flow rate for a given length of time, but below an electrode
charging potential
beyond which Faradaic reactions (such as oxidation/reduction) are induced.
However,
current flow is required in order to provide pump fluid flow. What is needed
is a non-
Faradaic process for maintaining current flow and fluid flow. This challenge
can be met by
employing electrodes having high double layer capacitance. Use of high double
layer
capacitance electrodes ensures that an applied system voltage will be
sufficiently high to
charge the electrodes and support the desired current and fluid flow of most
pump fluids
(such as water, saline, etc.) but be below an electrode charging potential
beyond which
oxidation-reduction is induced. Accordingly, configuration of an EK pump to
move a pump
fluid without the occurrence of Faradaic processes includes the incorporation
of electrodes
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made of materials having a high double-layer capacitance of at least 104
Farads/cm2, more
preferably of at least 10-2 Farads/cm2, and most preferably of at least 1
F/cm2. Preferably,
these high double-layer capacitance electrodes are compatible with a wide
range of pump
fluids.
In general, high capacitance of double-layer materials arises from their
comparatively
large microscopic surface area. In one example, carbon paper impregnated with
a carbon
aerogel can be used as a high capacitance double-layer electrode. Other forms
of carbon also
have very large microscopic surface areas and exhibit double-layer high
capacitances, and
thus may be employed herein. For example, shaped carbon aerogel foam, carbon
mesh,
carbon fiber (e.g., pyrolized poly(acrylonitrile) or cellulose fiber), carbon
black and carbon
nanotubes, all of which have significant double layer capacitances.
While double-layer capacitive electrodes may also be formed of materials other
than
carbon, carbon is the preferred electrode material, as it is also inert and
inhibits or slows
reactions detrimental to EK transport of a fluid, i.e., Faradaic reactions
(such as oxidation
reduction of the electrodes or pump fluid). Further, the use of carbon based
electrodes (for
example, carbon paper) provides flexibility in EK pump design and
configuration, as these
materials are shapeable and conformable into a variety of shapes (e.g., can be
punched, cast
or cut easily into a variety of shapes) and are inexpensive, thus lowering the
production costs
of the EK pumps provided herein.
With respect to drive strategies to minimize Faradaic processes, a pump can be
operated at system voltages, and the system voltages applied for durations,
below a potential,
or threshold, beyond which Faradaic processes such as electrolysis of the pump
fluid is
induced. Pump fluid electrolysis potentials for most pump fluids are less than
a few volts;
for example, the electrolysis potential for water is about 1.2 V while the
electrolysis potential
for propylene carbonate pump fluid is about 3.4 V. By maintaining a voltage
drop across the
electrodes of a pump below this electrolysis potential, pump fluid
electrolysis can be
prevented or minimized. The use of double layer high capacitance electrodes
allows high or
low system voltages to be used to support EK fluid flow through the pump
without causing
Faradaic processes in the pump fluid or electrodes. If the threshold for
electrode oxidation or
reduction is lower than that of the pump fluid, driving strategies can be
employed that apply a
system voltage and the duration of the applied system voltage sufficient to
charge the
electrodes and generate current flow to support a desired fluid flow rate for
a given length of
time, but below an electrode charging potential beyond which Faradaic
reactions (such as
oxidation/reduction) of the electrodes are induced.
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In addition, to prevent capacitive deionization of a pump fluid (which is a
non-
Faradaic process but can still impact pump performance), it may also be
preferable to employ
a pump fluid having a sufficiently high enough ionic strength, so that during
operation, the
pump fluid's ionic strength does not fall below a minimum pump fluid ionic
strength needed
to support electro-osmotic flow since deionization of a pump fluid occurs over
time, reducing
the conductivity of the pump fluid. Yet another approach can be to limit the
volume of pump
fluid (or other fluid) in a pump reservoir that can be transported during a
given run time of a
pump before complete deionization of the pump fluid occurs.
In yet another embodiment, the pump design itself can be adapted to minimize
the
effect of deionization processes that can decrease the operability of a pump
over time. For
example, in the embodiment illustrated in FIG. 2, the shape of the first fluid
reservoir 102
may be tapered in the portion of said reservoir immediately surrounding an
electrode,
creating a low volume fluidic path over the electrode. As will be recognized
by those skilled
in art, this low volume reservoir 124 configuration creates a steady state ion
concentration
adjacent to the electrode 120a, as the rate of ions passing into a low volume
reservoir 124 is
generally proportional to the rate of deionization of the pump fluid 122 which
usually occurs
during operation of a pump. In this way, the effects of deionization of the
pump fluid 122 on
pump flow rate and current can be minimized and controlled during pump
operation.
FIG. 3 illustrates yet another embodiment of an EK pump 200 in accordance with
the
present invention. In this example, pump 200 is configured as an indirect
pump. As
provided herein, an indirect pump is a pump where movement of a pump fluid 122
causes
flow of a second fluid in a separate part of the pump. This second fluid is
referred to herein
as a working fluid 126, which may be a drug or other fluid to be dispensed by
pump 200.
In this embodiment, EK pump 200 generally comprises a first chamber 202
comprising: a first flexible barrier 204 separating first reservoir 206 and
second reservoir
208; and a second chamber 210 comprising a second flexible barrier 212 that
separates third
reservoir 214 and fourth reservoir 216. Either of ports 118 may be an outlet
for the working
fluid, an inlet for the working fluid and/or a vent for one of the working
fluid reservoirs.
Preferably, flexible barriers 204 and 212 are impermeable to prevent mixing of
a pump fluid
122 (disposed in second 208 and fourth 216 reservoirs) and working fluid 126.
This pump
configuration may be used when a working fluid (e.g., drug, reagent, etc.) is
not compatible
with electrokinetic flow; when the working fluid does not support a zeta
potential, has a low
electrolysis potential, has a high viscosity, or has or carries suspended
particles or cells; or in
cases where long-term storage, or useable lifetime, of the working fluid
requires that it be
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separate from the pump fluid. In pump 200, a fluidic pathway exists between
second 208 and
fourth 216 fluid reservoirs by means of porous dielectric material 108, which
may be
encapsulated within a bonding material disposed between upper and lower
substrates (as in
FIG. 1) or disposed within a conduit, or plurality of conduits. Electrodes
120a and 120b
surround openings leading to and from porous dielectric material 108.
FIGS. 4a ¨ 4c are provided to illustrate what happens during operation of pump
200
as a voltage is applied across electrodes 120a and 120b disposed within second
208 and
fourth 216 reservoirs respectively. In general, as pump fluid 122 is pumped
from second
reservoir 208, through porous dielectric material 108, and into fourth
reservoir 216, first
flexible member 204 is collapsed while second flexible member 212 disposed
with the
second chamber 210 is distended. As the second flexible member 212 is
distended working
fluid 126 (which may be a drug, etc) disposed within the third reservoir 214
will be displaced
and pumped out of third reservoir 214 through a fluid port 118b. The volume in
first
reservoir 206 may be filled through port 118a with additional working fluid,
air, etc., as
flexible member 204 moves to expand first reservoir 206 and contract second
reservoir 208.
In pump configurations where flexible members 204, 212 are employed, it may be
advantageous to utilize flexible members having highly ordered movement during
collapse or
expansion as depicted in FIGS. 5a ¨ 5c. As illustrated in FIGS. 5a-c, a pump
may be
configured to comprise a flexible member that has a single flexure joint 300
(indicated by
arrows) giving rise to a simple geometry during collapse (or expansions), as
shown in FIG.
5a, or multiple or compound geometries during collapse, as pictured in FIGS.
5b and 5c. As
will be appreciated by those skilled in the art, this feature will ensure
precise and maximal
fluid movement effected by the pump, especially if the pump is adapted for
small volume
movement of liquids, low flow rates or low pressures.
In general, the pumps provided herein (including both direct and indirect pump
embodiments) are highly compact and not much larger than the volume of a fluid
to be
transported by the pump. Accordingly, in the present invention the various
systems
incorporating these pumps for fluid transport can be correspondingly small.
For example, for
a drug delivery pump system (i.e., the electrodes, dielectric conduit, and
reservoirs without
the power supply or control electronics), the volume of said system need not
be greater than
about 250% of the largest effective volume of a drug reservoir if an indirect
pump
configuration is employed. For a pump system comprising a direct pump
configuration such
as the one shown in FIGS. 1 and 2, the volume of a pump system need no be more
than
150% of the largest effective volume of a drug reservoir.
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FIG. 6 illustrates another technique that can be employed to ensure maximal
and
precise fluid delivery from an EK pump. Through-vias 106 and 110 extend
through a
laminated substrate 116a and 116b to form upper and lower parts 208a, 208b,
216a, 216b of
the pump fluid reservoirs. In this example, the flexible members 204 and 212
define the
upper reservoir parts 208a and 216a while the electrodes 120a and 120b of pump
300 are
placed within lower reservoir parts 208b and 216b so that flexible members 204
and 212 are
not in contact with the electrodes 120a and 120b during collapse. As will be
appreciated by
one skilled in the art, this placement of electrodes inside of reservoirs 208
and 214 increases
the fluid volume/capacity of the pump. Filling ports 119 are used to fill the
reservoirs 208a
and 208b and reservoirs 216a and 216b with pump fluid 122 during pump
manufacture and
are sealed during pump operation.
FIG. 7 illustrates another feature that may be incorporated to modulate fluid
flow
rates from an EK pump, a hydraulic amplifier 400. In one embodiment, hydraulic
amplifier
400 comprises a first piston 402 having a first cross-sectional area Al and
diameter D1 and a
rigid shaft 404 that couples first piston 402 to second piston 406 having a
second cross-
sectional area A2 and diameter D2.
During operation, fluid (e.g., a pump fluid) from a pump may be directed
against the
first piston 402, which displaces the first piston 402 and the second piston
406 in a first
direction. Alternatively, fluid may be directed against the second piston 406
to displace it
and the first piston 402 in the opposite direction. As will be recognized by
those skilled in
the art, hydraulic amplifier 400 may be used to create pressure amplification
or de-
amplification as well as flow reduction or increase as may be needed.
Accordingly, by
appropriately choosing the relative piston sizes, the pressure and flow
characteristics of a
pump may be modulated.
In the embodiment shown in FIG. 7, linear displacement of the pistons 402 and
406 is
generally equal. However, because of the differing cross-sectional areas of
the respective
pistons provided by the differences in diameters of the pistons, pressure
amplification (or de-
amplification) proportional to the ratio of the cross-sectional areas is
created. In one
example, the use of hydraulic amplifier can be used to alter the flow rate of
a dispensed fluid
vs. the flow rate of a pump fluid; for example a hydraulic amplifier can be
used so that a
dispensed fluid flow rate of a drug is between about .1 times and 10 times a
pump fluid flow
rate.
Further detailed descriptions of various compact, precise and low-cost medical
systems for drug delivery and/or analyte systems are provided below. As
further described
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herein, these EK systems are smaller, lighter and more cost-effective than
comparable prior
systems and offer advantages in design flexibility and simplicity due to the
incorporation of
EK pumps for general fluid transport to effect drug delivery, analyte
sampling, etc.,
FIG. 8 is a schematic diagram of one embodiment of an EK delivery system 500
in
accordance with the present invention. EK delivery system 500 preferably
comprises EK
pump 502 having an inlet 504 and outlet 506 fluid port; a reservoir 508; a
syringe 510 having
a pump fluid chamber 512, plunger 514, a syringe port 516; a power source 518;
and a
system controller 520 having one ore more feedback sensors 522. In this
embodiment, inlet
fluid port 504 is coupled to reservoir 508 and outlet fluid port 506 is
coupled to a syringe
510, containing, for example, a drug such as insulin, pain medication or other
therapeutic or
diagnostically useful agent.
In one embodiment of system 500, pump 502 is configured to move a drug out of
syringe 510 and into a patient. Reservoir 508 can contain a pump fluid 122
while syringe 510
may be loaded with a drug. During operation, EK pump 502 (via direction of
controller 520)
causes movement of the pump fluid 122 into pump fluid chamber 512 of syringe
510 and
creates hydraulic pressure that pushes against syringe plunger 514, causing
movement of the
plunger 514 and effecting drug delivery.
As will be recognized by those skilled in the art, syringe 510 can be
configured to
couple to any patient access device, such as a conventional infusion set, port-
a-catheter, IV
needle and the like, for transdermal, transvascular, intramuscular delivery of
a drug into a
patient. Alternatively, system 500 can be configured as a small ambulatory
system contained
in a bio-compatible, preferably inert housing, which is hermetically sealed to
prevent leakage
of any system components. As will be appreciated by one skilled in the art,
because the EK
systems of the present invention do not require mechanical components to cause
fluid
transport and drug delivery, these devices are small and lightweight and can
be configured in
any shape so that they can be easily carried or worn by a patient and hidden
from view.
Moreover, syringe 510 and reservoir 508 can be adapted to be refillable. In
yet another
embodiment, system 500 can be coupled to a transcutaneous adhesive pad having
a plurality
of micro-needles to adapt system 500 as a transdermal delivery system.
As will be further appreciated by those skilled in the art, system controller
520 serves
to control the operation of pump 502 (e.g., to effect fluid flow rates,
pressures, etc.),
preferably in response to one or more system feedback sensors 522. These
feedback sensors
522 can be installed in any location, and their signals can be transmitted
through a sensing
circuitry, which can be integrated into system controller 520. Various signals
from these
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feedback sensors 522 can be configured to provide feedback regarding drug
volume
displacement; measurements of flow rate or delivery rate over time; battery
life; drug and
pump reservoir conditions; system component malfunctions; the presence of an
occlusion or
other flow obstruction or failure; and other data. Preferably, the feedback
data is transmitted
quickly so that dynamic responses by the system controller 520 in response to
feedback data
can be initiated.
In one specific embodiment, a feedback sensor 522 can be coupled to syringe
plunger
514 to detect and monitor displacement of plunger 514. In one exemplary
embodiment,
feedback sensor 522 may be a magnetostrictive sensor available from MTS
Sensors, of Cary,
North Carolina, and the plunger 514 may contain an embedded permanent magnet.
As will
be recognized by one skilled in the art, these sensors can provide absolute
distance
measurements of plunger 514 without needing to be zeroed to an external
reference. By
monitoring the distance moved by plunger 514 at a given time, the amount of a
substance
delivered by system 500 can be compared to the desired amount of a substance
to be
delivered and the operation of the pump modulated at selected time intervals
to ensure precise
accurate delivery. Pump modulation may involve modifying drive voltage,
current or
duration of pump operation. Preferably, data from feedback sensor 522 is
relayed to
controller 520 where displacement of the plunger 514 can be correlated to the
amount of
agent/drug delivered by system 500. Depending on the desired drug dosage
regime, the
controller 520 can modulate operation of pump 502 (by regulating current and
voltage
applied to the pump) to achieve the appropriate drug delivery profile. In one
embodiment,
depending on whether less or more drug delivery is required, operational
parameters of the
pump may be modulated.
For example, flow rates can increase or decrease based on feedback from
sensors 522
disposed on plunger 514 by altering the voltage applied to the electrodes
disposed in pump
502. FIG. 9 graphically illustrates this concept and depicts the direct
relationship of an EK
pump voltage with the pump flow rate. FIG. 10 is provided to illustrate the
relationship
between pressure and flow rate. FIGS. 9 and 10 also depict performance aspects
of the EK
and demonstrate the precision and consistent flow rates and pressures during
steady state
fluid flow using the EK pumps of the present invention. Alternatively,
controller 520 can
simply apply power to the electrodes according to a preset on and off cycle
(e.g., where the
power is normally off and is turned on to dispense fluid from the syringe)
according to a
computer program, timer or other control. Use of a timing circuit or other
timing control to
turn the power on for a period of time can be used to deliver a fixed volume
or bolus from the
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syringe. The system controller can also be provided with a user interface so
that a user can
indicate or change the volume or size of the bolus delivered.
In yet another embodiment, as illustrated in FIGS. lla and 11b, flow
indicators 600
and flow meters 602 may be disposed in, or coupled to, one or more fluid paths
of an EK
system, to provide indication of the amount (volume) of a drug dispensed, the
amount of
agent still remaining in a syringe, the amount of fluid pump fluid remaining
in a system
reservoir, flow rate, etc., In some examples, said flow indicators 600 and
flow meters 602
can provide a visual indication to a system user, or can be functionally
coupled to a controller
and adapted to supply electronic signals indicative of such information to
enable modulation
of a EK pump, as needed. In yet another embodiment, pump chamber 512 can be
adapted as
a hydraulic amplifier to alter the flow rate of a drug from syringe 510 and/or
the flow rate of
the pump fluid into pump chamber 512.
In yet another embodiment, feedback mechanisms can be employed in order to
create
a feedback loop directly to the EK pump to control activation of a voltage
from a battery or
power source to the electrodes. For example, a small processor can be designed
to produce
an activation signal for a selected signal duration, e.g., 1-4 seconds, at
selected time intervals
to run the EK pump directly,
FIGS. 12a-12b illustrate an exploded, enlarged view and a schematic view,
respectively, of a self-contained indirect EK pump delivery system 700 in
accordance with
the present invention. In this example, delivery system 700 is enclosed within
housing 702,
which includes a first cover 704 and a second cover 706, which can be
adhesively bonded
together. First cover 704 comprises a first pump fluid aperture 708 and a
second pump fluid
aperture 712. Apertures 708 and 712 each have a silicone septum which may be
pierced by
a needle for adding pump fluid to the system. After filling the system with
pump fluid,
apertures 708 and 712 may be sealed, such as by covering with epoxy.
Second cover 706 houses the internal circuitry of the system in the cavity
715,
including a system controller disposed on circuit board 718 and a power source
720. Second
cover 706 also houses a first pump fluid reservoir 709 communicating with a
second pump=
fluid reservoir 724 through a through-via 728b, a third pump fluid reservoir
726
communicating with a fourth pump fluid reservoir 713 via a through-via 728a
(located in the
first cover 704¨not shown in FIG. 12a). Apertures 708 and 712 communicate with
reservoirs 724 and 726, respectively. Porous double layer capacitive
electrodes 120a and
120b are disposed in reservoirs 726 and 724, respectively, and the pump fluid
in those
reservoirs can be moved between reservoirs 726 and 724 (and through reservoirs
709 and
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713) through a porous dielectric material 730 (such as packed bed of silica
beads) disposed in
channel 732 extending between reservoirs 726 and 724 by applying a voltage to
electrodes
120a and 120b from the power source via electrical connections (not shown).
Flexible impermeable diaphragms 734a and 734b are disposed in second cover 706
to
form fifth and sixth reservoirs 710 and 714 adjacent the first and fourth
reservoirs 709 and
713, respectively. A vent 799 communicates fifth reservoir 710 with the
exterior of the
pump, and a cannula 722 serves as an outlet from sixth reservoir 714. In
addition, fluid
aperture 798 with a silicone septum on the underside of cover 706 provides a
way to fill the
sixth reservoir 714 with a drug or other fluid to be delivered.
In operation, after filling reservoirs 709, 713, 724 and 726 with pump fluid
via, e.g.,
ports 708 and 712, and sixth reservoir 714 via aperture 798 with a drug, power
may be
supplied to electrodes 120a and 120b to move pump fluid from reservoirs 709
and 724 into
reservoirs 726 and 713, thereby moving flexible diaphragm 734b to dispense the
drug from
reservoir 714 through cannula 722.
In accordance with this embodiment of the invention, the system 700 is small,
having
an overall dimension of about 2 x 0.8 x 0.4 inches and is configured to
deliver about 300
microliters of a drug employing about 300 microliters of a pump fluid. As
exemplified in this
embodiment, generally the overall size or volume of system 700, (i.e., the
volume of the
pump less the volume of the power source and circuit board) need not be much
greater than
the volume of drug to be delivered or the volume of the drug reservoir 714.
FIGS. 13a and 13b illustrate yet another embodiment of an EK pump delivery
system
800 in accordance with the present invention. In this embodiment, the system
is adapted for
high flow-rate (about 1-10mL/min) transport of fluid and which generally
comprising
electrodes having a porous dielectric material disposed, preferably laminated,
between the
electrodes so that pump fluid movement is through or perpendicular to the face
of the pump
as best illustrated in FIG. 13b.
FIG. 13a illustrates exploded view of one embodiment of EK pump system 800. A
flexible diaphragm 820 held between a top housing 812 and a spacer 816 defines
a first fluid
reservoir 808 and a second fluid reservoir 810. A second flexible diaphragm
830 held
between a bottom housing 824 and spacer 828 defines a third fluid reservoir
811 and a fourth
fluid reservoir 821. A porous dielectric material 802 separates the second and
third
reservoirs, which contain EK pump fluid.
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Fluid reservoirs 808 and 821 each have fluid inlet and a fluid outlet ports,
which
couple reservoirs 808 and 821 to fluid pathway 832 (best illustrated in FIG.
13b) comprising
a plurality of check valves 834, 836, 838 and 840.
As best shown in FIG. 13b, system 800 is configured to provide high flow rate
unidirectional transport along fluid pathway 832, e.g., movement of fluid from
a drug source
846 (such as, e.g., a collapsible IV bag) to system inlet port 842 to system
outlet port 844
(which may be coupled to a patient access member 848, such as a needle,
infusion set, etc.)
and to a patient. As will be appreciated by one skilled in the art,
unidirectional fluid transport
through system 800 is aided by the one-way check valves 834, 836, 838 and 840
coupled to
fluid pathway 832.
In this configuration, voltage from power source 850 is applied to electrodes
(not
shown) disposed in reservoirs 810 and 811 to cause movement of pump fluid (as
indicated by
shading) disposed between flexible diaphragms 820 and 830, i.e., from fluid
reservoir 810 to
fluid reservoir 811, and the direction of flow may be reversed by reversing
the polarity of the
applied voltage. Movement of the pump fluid from reservoir 810 to reservoir
811 will cause
flexible member 820 to move downward, which in turn will draw fluid from drug
source 846
to system inlet port 842 and through fluid pathway 832 into reservoir 808.
Check valve 836
prevents fluid from being drawn into reservoir 808 from outlet 844. Likewise,
fluid in
reservoir 821 will be expelled as flexible member 830 moves downward, and
check valve
838 prevents the expelled fluid from flowing toward drug source 846. The
operation is then
reversed by reversing the polarity of the applied voltage, so that pump fluid
flows from
reservoir 811 into reservoir 810 and diaphragms 820 and 830 move upward. This
movement
draws the drug into reservoir 821 via check valve 838 and expels drug from
reservoir 808 via
check valve 836. Check valves 840 and 834 prevent the fluid from flowing in an
undesired
direction.
The operation of this pump system can be controlled by a controller coupled to
the
pump, which modulates operation of the pump (by regulating current and
voltage, for
example amplitude and period or duration, applied to the pump, electrodes,
etc.). As will be
appreciated by one skilled in the art, the voltage and current applied to the
pump and
electrodes can be accomplished employing simple or complex drive strategies so
that the
appropriate pressure, fluid flow rates, drug delivery regimes of the system
can be
accomplished. Continuous oscillation provides for continuous flow of drug from
the drug
source to the outlet.
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In one exemplary embodiment, system 800 is a small (about 1.6 x 1.2 x 1.7
inches)
ambulatory system configured to deliver fluids at flow rates of about 1 mL/min
at about 1-2
psi. System 800 can be used in place of conventional infusion pump, for
example PCA
pumps and the like, which are typically coupled to 1L saline bags. Also, the
high accuracy of
a low flow rate EK pump can be used to deliver a concentrated version of a
drug to a saline
stream provided by a higher flow rate pump to provide accurate dosing. EK
system 800 can
be used similarly and configured for continuous fluid delivery or operation or
for intermittent
fluid delivery (e.g., by intermittent activation of a system voltage from a
battery coupled to
turn the system 800 on and off). EK system 800 may also be controlled by
feedback (e.g.
vary voltage and or current based on a flow sensor reading).
FIG. 14 illustrates yet another embodiment of drug delivery system 900,
wherein
delivery system 900 is adapted for the delivery of radioactive drugs or other
toxic diagnostic
or therapeutic compounds that require special handling to minimize a patient
or user's
exposure to those compound(s). In this example, delivery system 900 comprises
a protective
or shielded housing 902, which surrounds an EK pump 904; a power source 906;
and
controller 908. Delivery system 900 further comprises a patient access means
910, which can
be a cannula or needle adapted to provide subcutaneous, transvascular or other
access to a
patient, dosimeter 913, which can be disposed and coupled to a fluid path,
reservoir or the
like of EK pump 904 to provide indication to a patient/or user regarding a
substances
delivered, etc., Preferably, the patient access means 910 is shielded to
protect the patient or
user from the radioactive or toxic material while it is being pumped into a
patient.
Delivery system 900 further comprises an internal liner 912, preferably a
removable
liner, adapted to shield the patient or user from the radioactive or toxic
compound contained
within the system. To further minimize the need to handle the system during
operation,
system 900 can further comprise other system components, such as a flow
indicator or meter
914; dosimeter 913 (as mentioned above); or other indicator to signal the
amount of the toxic
substance that has been delivered, how much is left, etc., in order to obviate
or minimize the
need to handle the system 900 during operation. In one example, indicator 914
can be
adapted to be easily viewable by a user or can optionally be omitted and
instead an electronic
flow meter employed. Moreover, pump 904 and system 900 can be configured to be
remotely activated and/or programmable in response to user or automatic
control by a pre-
programmed controller with feedback control provided by a dosimeter 912, flow
indicator
dosimeter 914 or the like.
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In yet another embodiment, system 900 can be adapted to withstand irradiation
to
activate a non-radioactive drug preloaded into system 900. Upon irradiation of
a preloaded
drug within system 900, it is converted into a radioactive form. Therefore,
radioactive
materials do not need to be handled in order to load a radioactive drug or
substance into
delivery system 900. Moreover, because of the low cost of the delivery system
and EK
pump, the entire system 900 can be discarded after use. Yet another advantages
to system
900 is that radioactive waste can be minimized because the systems provided
efficient fluid
delivery where no significant residual amount of a radioactive drug left
within system 900.
Table 1 provides a list of some radiopharmaceuticals that may be delivered
using a
system of this invention.
TABLE 1
¨
_
Radiopharmaceutical Trade Name
Primary Uses
Cobalt-57 cyanocobalamin Rubratope; Dicopac
Schilling test
1
_ _ _ _ . . _
= ...
Cobalt -58 cyanocobalamin Dicopac
Schilling test
Chromium-51sodium chromate
Chromotope for labeling
RBCs
_
Flourine-18 FDG positron
emission
tomography imaging ,
Gallium-67 Neoscan
soft-tissue tumor and I
1 inflammatory
process
imaging
_
Indium-111 chloride Indiclor for labeling
monoclonal
; antibodies and
peptides
(OncoScint & Octreoscan)
_______________________________________________________ 1
_____________________
Indium-111 pentetate (DTPA)
imaging of CSF kinetics
Indium-111 oxyquinoline (oxine)
for labeling leukocytes and
platelets
Indium-111 Capromab pendetide ProstaScint monoclonal antibody
for
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_
. .. . ,
._
1 ' imaging prostate
cancer
I
. _____________________________ 1 ,
.,1 monoclonal antibody for i
,
.-.
. Indium-111 Imciromab pentetate Myoscint diagnosis of
myocardial
. I
.. I
necrosis .
. , . .
...
__________________________________________________ I
Indium-111 pentetreotide Octreoscan imaging of
neuroendocrine
, I
.. 1
,
tumors
_______________________________ I ________________________________ .
'
. ..... . ._...
:
:
. Indium-111 satumomab pendetide OncoScint CR/OV 1
imaging of metastatic
,
.
disease associated with ,
. i
i
, 1 colorectal and
ovarian
,
1
, I
i
cancer
. . ...... _ ... . .. . .
i . I
!: 1-123 sodium iodide I ________________ ,
i= thyroid imaging & uptake
. !
"
. I-125 iothalamate I Glofil i
measurement of .
õ
õ
. ,
,
:
.: .
. glomerular filtration
_______________________________ I. .
.. .. _ .
: 1-125 human serum albumin (RISA) I Isoj ex plasma
volume
1
1
, determinations
;
I-131sodium iodide I , thyroid uptake, imaging,
& =
. 1 I
= therapy
i
- _________________________________________________
,
I-131 iodohippurate 1 Hippuran; Hipputope renal imaging and
function ,
:
I 1 studies
'
,
1
_ _ . ...
I-131 iodomethylnorcholesterol I i
adrenal imaging i
1 =
(NP-59)
1 _________________________________________________ ,
. ,
...... . . . . . õ .. .. __ ......_ . . _ . .
.. . .._ ..... . . ........ . . .. . .. ..
. _______________________________________________ , ______________________
I-131 metaiodobenzylguanidine i I-131 MIBG ,
õ imaging
of
i
. 1 1
(MIBG) I : pheochromocytomas and
1
. i
neuroblastomas
,
;
Krypton-81m gas (from Rb-81 I pulmonary ventilation
,
! generator) ,,' imaging
_ 1
__; ,
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......_
1
P-32 chromic phosphate
Phosphoco16P32 ? therapy of intracavitary 1
. I malignancies
! " _______ ,
P-32 sodium phosphate 1 I therapy of polycythemia
1
i I vera
_______________________________ i ________________________________________ I
Rubidium-82 (from Sr-82/Rb-82 1 Cardio-Gen-82
positron positron emission
1 1
generator) , I tomography imaging
1
Samarium-153 Lexidronam ! palliative treatment of
bone
I Quadramet
1 (Sm-153 EDTMP) , pain of skeletal
metastases
i .
Strontium-89 i Metastron 1 palliative treatment of
bone
' ! ; pain of skeletal
metastases
il I
Tc-99m pertechnetate
1 I
imaging of thyroid,
,
. I I salivary glands,
ectopic
, gastric mucosa,
i
i
parathyroid glands, '
P
..
I ;
,
dacryocystography,
11
icystography
i _____________________________ I ________________ i ______________________
Tc-99m Apcitide AcuTect 1 peptide imaging of DVT :
1I. __________________________________________________ monoclonal antibody for
Tc-99m Arcitumomab CEA-Scan
1 I colorectal cancer
I
___________________________________________________________________________ ,
Tc-99m albumin colloid I Microlite -no longer i imaging of RES
:
I
on market 1 I
(liver/spleen)
I
. Tc-99m bicisate (ECD) Neurolite 1 cerebral perfusion
imaging :
..
. Tc-99m Depreotide I
Neotect-7
somatostatin receptor-
bearing pulmonary masses
I
. .
Tc-99m disofenin (DISIDA) I Hepatolite hepatobiliary imaging
,
. i _______________ 1 _____________________
1 1
Tc-99m exametazine (HMPAO) Ceretec ! cerebral perfusion
imaging
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1 ! _____________________ :
Tc-99m Gluceptate Glucoscan renal imaging
I 1 I
- . - .... . - - . -- ..-= - . .
-.---, - _ , õ _
I
1l' . Tc-99m Human Serum Albumin I imaging
of cardiac '
,
I I '
'
i (HSA) 1 1 chambers
i
I _______________________________________ ;
. i
. hepatobiliary imaging Tc-99m Lidofenin (HIDA) i
Technescan HIDA ,
, ;
Tc-99m Macroaggregated Albumin 1 Pulmolite; Macrotec i pulmonary perfusion
!
,
(MAA) .
1 . ,
_1 i
,
,
,
. Tc-99m Mebrofenin i Choletec
hepatobiliary imaging
I i
- -
7
Tc-99m Medronate (MDP) i bone imaging
.. ,
, 1 '
! _____________________
Tc-99m Mertiatide Technescan MAG3 ' renal imaging
i 1
monoclonal antibody Fab '
. ,
,
Tc-99m Nofetumomab Merpentan !
i Verluma 1 fragment for imaging small
NR-LU-10
I
-
= , cell lung cancer
,
. _ .. . . ....... _ . .. _ ,
___________________________________________________ , _____________________
Tc-99m Oxidronate (HDP) Osteoscan HDP
bone imaging .
_______________________________ I _________________________________________ '
I
Tc-99m Pentetate (DTPA) Techneplex, renal imaging
and function !
11
1 Technescan DTPA i studies; radioaerosol
- ,
L I I
ventilation imaging =
,
1
__________________________ k _________________
g Tc-99m Pyrophosphate (PYP)
1 i avid infarct imaging i
i
1
õ
1 _________________
imaging of GI bleeds,
Tc-99m Red Blood Cells (RBCs) I Ultratag 1
. , I
.. ,
. .
. .
cardiac chambers
, ,
õ Tc-99m Sestamibi
I Cardiolite , myocardial perfusion i
1 Miraluma i imaging
breast tumor imaging
______________________________________________________________
_____.........__ _ ... _.... ,
Tc-99m Succimer (DMSA)1 renal imaging :
! =
'
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- ______________________________________________________
Tc-99m Sulfur Colloid (SC)
imaging of RES
(liver/spleen), gastric
emptying, GI bleeds
Tc-99m Teboroxime Cardiotec myocardial
perfusion
1
imaging
Tc-99m Tetrofosmin Myoview
myocardial perfusion 1
imaging
_
Thallium-201 myocardial
perfusion
imaging; parathyroid &
tumor imaging
Xenon-133
! pulmonary
ventilation
imaging
.;.
,
FIG. 15 illustrates yet another aspect of the invention, specifically an EK
sampling
system 1000, which can be adapted to draw, analyze and/or store (within the
system) a
physiological fluid, such as blood (e.g., for glucose monitoring) or other
body fluid
containing a target analyte from a patient. In this embodiment, sampling
system 1000
comprises an indirect EK pump 1002, which is coupled to a sampler 1004 and an
analyzer
1006, which are fluidly coupled to EK pump 1002 via external fluid loop 1008.
During use,
pump can be operated to effect transport of a physiological fluid taken from a
patient by
sampler, 1004 to analyzer 1006 where the physiological fluid may be evaluated
for the
analyte. In one example, the Ringers solution, saline or other appropriate
fluid can be
pumped through fluid loop 1008 where the solution can be mixed with the
extracted
physiological fluid at sampler 1004 and transported to analyzer 1006.
Sampler 1004 may be any conventionally known system or device for obtaining a
physiological fluid. In one embodiment, sample 1004 may comprise a EK pump
adapted to
hydraulically draw a physiological fluid from a patient. One embodiment of an
EK pump
system and pump configuration suitable for such an application is described
with reference to
FIGS. 13a ¨ 13b. Likewise analyzer 1006 may be any conventionally known system
for
testing the obtained sample. For example, analyzer 1006 can be reagent system
for
determination of a patient's glucose concentrations in the sampled
physiological fluid, as
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further described in U.S. Pat. No. 3,298, 789, and U.S. Pat. No. 3,630,957,
the entire contents
of which are hereby incorporated by reference.
FIG. 16 illustrates a system block diagram of another embodiment, wherein the
EK
system 2000 is a dual analyte sampling and drug delivery system. In this
example, system
2000 broadly comprises a system controller 2002; an analyte sampling subsystem
2004
comprising a first EK pump 2006; and a drug delivery subsystem 2008 comprising
a second
EK pump 2010. The system controller 2002 serves to control the operation of
the sampling
and delivery subsystems 2004 and 2008 by controlling voltage being applied to
the EK
pumps.
In a preferred embodiment, system 2000 comprises two separate fluid paths 2012
and
2014. Fluid path 2014 is coupled the second EK pump 2010 and adapted to
electro-
osmotically pump a drug from within drug reservoir 2016 to a patient. Fluid
path 2012 is
coupled to the first EK pump 2006 and adapted to electro-osmotically pump a
physiological
fluid from sampler 2018 to analyzer 2020 where it can be evaluated. However,
while the
fluid paths are preferably configured to be separate, the control of drug
delivery subsystem
2008 by controller 2002 is based on feedback from sampling subsystem 2004.
Controller
2002 is adapted to send and/or receive data to and from the sampling and drug
delivery
subsystems 2004 and 2008 to modulate drug delivery and determine an
appropriate drug
delivery profile or regime depending on monitoring and analysis of a patient's
physiological
and/or chemical state by sampling subsystem 2004.
As will be appreciated by those skilled in the art, in this embodiment, the
sampling
subsystem 2004 can be configured to measure a specific analyte and/or a change
in analyte
parameter and to compare it to a known values stored within a memory component
of
controller 2002, so that the EK system 2000 can effect drug delivery in
response to any
physiological, physiochemical or chemical changes in a patient. In one
example, depending
on input from the sampling subsystem 2004, controller 2002 can execute a
command signal
to the delivery subsystem 2008 to initiate, control and/or terminate of an
operation.
For example, system 2000 can be configured for the treatment of diabetes and
adapted
to deliver insulin. Insulin delivery can be initiated after a patient's blood
glucose
concentration has been determined by sampling subsystem 2004. Delivery
subsystem 2008
can be configured to deliver a quantity of insulin into the patient in
response to the
determined blood glucose concentration. Delivery of insulin in response to the
determined
blood glucose concentration may comprise automatically effecting delivery of
insulin or can
be configured to require user initiation of insulin delivery or both. In
addition, delivery
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subsystem can be adapted to deliver more than one type of insulin, insulin at
different
delivery rates to effect basal and bolus delivery. In addition, the system can
be adapted to
deliver a frequent micro-volumes or microboluses of insulin in order to
maintain a constant
glucose concentrations in a patient to effect better or effective diabetes
management.
In yet another embodiment, the various systems and pumps provided herein may
be
multiplexed to provide delivery of more than one drug, comprise more than one
fluid path,
flow rate or EK pump as schematically depicted in FIGS. 17 ¨ 19. For example,
FIG. 17
illustrates a system block diagram for a multi-pump, multi-reservoir drug
delivery system
3000. In this embodiment, the various EK pumps of the invention may be
multiplexed and
adapted to provide a system capable of delivering more than one drug Di...D.,
for example,
in order to deliver a drug cocktail or for delivering one or more drugs at
differing flow rates
FRi....FR. or for delivering one drug at differing flow rates (e.g., for
basal, bolus delivery) or
the like.
In one embodiment, for example, EK system 3000 can be adapted to deliver more
than one compound, to mimic or functionally augment or replace diseased or
organ, such as a
pancreas. In this example, drug delivery subsystem can comprise one or more EK
delivery
pumps 3002 that can be configured to deliver one or more compounds or drugs
(e.g., trypsin,
steapsin, amylolytic ferment) and which are coupled to a sampling subsystem
3010 for
providing feedback control of the multi-pump delivery subsystem 3012 (through,
e.g.,
diagnostics sampling blood or other biological fluids) controlling how much of
each
substance is needed. Other organs may be mimicked or augmented in this way.
Alternatively, system 3000 can be configured to deliver a single drug from
drug reservoir
3014 which is common to all pumps 3002, for delivery at differing flow rates,
etc.,
FIG. 18 illustrates yet another embodiment of a multi-reservoir, multi-pump
drug
delivery system 4000 comprising an external controller 4002. Operation of the
implanted
delivery system 4000 can be operationally controlled by external controller
4002 having a
user interface 4004. Signals (such as RF, lR or other electronic
transmissions) between
external controller and implanted delivery system 4000 are provided to allow
interface with,
and/or control, by external controller 4002 of one or more of the components
of the delivery
system 4006 such as a controller, battery, electrodes, feedback sensors, etc.
Signal
transmission lines 4008 illustrate one method of controlling the multiple
pumps 4010 system
4000. In this embodiment, the fluid paths 4012 of system 4000 are illustrated.
As shown, the
various fluids (e.g., drugs) can be combined for delivery to a target
treatment site inside a
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body. Alternatively, an external pump or pumps located outside of the patient
may be
remotely controlled to deliver one or more fluids to the patient.
As will be appreciated by one skilled in the art, this embodiment may be
useful for
medical applications where the delivery of multiple agents is required, e.g.,
for diagnostic
imaging studies, for cancer treatment where multiple chemotherapeutic agents
need to be
delivered simultaneously or in a particular timing or order, where one agent
counteracts
unwanted side effects of another agent, etc., For example, Agent A is a
chemotherapy
cocktail called Taxotere used in early or late stage breast cancer. The
unwanted side effect is
a reduction in white blood cells. Agent B is an antibiotic that is provided in
proportion to the
reduction in white blood cell activity or white blood cell count. Agent B
could be provided at
a first, higher rate immediately following the highest dosage of chemotherapy,
then tapered
off as the body's ability to produce white blood cells improves or is
restored.
Other examples include a multi-drug cocktail to treat AIDS (reservoirs contain
AZT,
reverse transcriptase inhibitors and protease inhibitors) and multi-drug
cocktails to treat
tuberculosis, hepatitis B, hepatitis C, and tissue rejection after an organ
transplant.
Generally, because of their small size, and because they may be formed in a
variety of
shapes, the EK pumps of this invention may be implanted in proximity to the
portion of a
body being treated by the agent delivered by the pump. For example, the pump
may have a
form factor adapted to the shape of the liver and may be implanted to treat
hepatitis B. Other
potential organs include the kidneys, the gall bladder, etc., FIG. 19 is a
system block
diagram of an implantable "distributed" drug delivery system 5000 comprising
one or more
implantable drug delivery subsystems 5002 and an external controller 5004. As
illustrated,
the various delivery subsystems 5002 can be implanted at different locations
inside a
patient's body for drug delivery at more than one treatment site. In this
embodiment, each of
the subsystems 5002 is configured to be operable by external controller 5004.
Alternatively,
an external pump or pumps located outside of the patient may be remotely
controlled to
deliver one or more fluids to the patient.
Other embodiments of indirect pumps may be provided. For example, instead of
using a diaphragm or syringe to isolate a reservoir, the drug or other fluid
to be delivered may
be loaded into a collapsible bag placed within a rigid chamber. Delivery of
the EK pump
fluid into the portion of the rigid chamber outside the bag collapses the bag
to dispense the
drug out through an outlet, such as a plastic tube. This approach may be used
to deliver high
viscosity drugs, for example.
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In addition, dried (e.g., lyophilized) versions of drugs may be preloaded into
the
pump's drug delivery reservoir for shipment and storage of the pump and drug,
then
reconstituted immediately prior to use.
Pumping system embodiments of the present invention may include electronics
and
communications that allow for various level of control authority, for example
the prescribing
physician may have a greater authority over dosing, while the patient has a
lesser authority.
This authority my include electronic key authentication for granting such
authority as well as
for activation (e.g., for cases where the device dispenses controlled
substances requires
specific license to prescribe/distribute, such as for a scheduled narcotic).
As another
example, the device can be configured to deliver only a total amount of drug
over a period of
time, regardless of how much drug is delivered at each of one or more times
during that
period. Alternatively, the device can be controlled to operate for only a set
period of time, no
matter how much drug has been delivered. The device can also provide a display
showing
the amount of drug remaining in the reservoir, the amount of dose delivered at
one time or
overall, etc.,
Other manners of automatic feedback control of the EK pumps of this invention
may
be provided. For example, physiological inputs, such as limb movement during
Parkinson's-
induced tremor or epileptic seizure, may trigger the release of a drug from
the EK pump to
treat the condition.
The device may include electronics and communications that provide for making
a
historical record of device operation that may be complemented with records of
various
physiological responses or conditions (e.g., heart rate, blood pressure, EKG,
blood gases,
serum levels of specific compounds). These records can be downloaded for
analysis and use
in optimizing treatment and/or judging response to treatment. Various levels
of authority can
be included if desired to allow some, all or none of the download features. =
FIGS. 20-23 are provided to illustrate the performance aspects of the EK
systems and
pumps provided herein. For example, FIG. 20 is provided to illustrate fast
loading and
delivery flow rates plotted over time for a typical EK pump in accordance with
the present
invention. As illustrated it is possible to configure the various EK pumps and
systems to
provide fast loading and delivery of a pump fluid to effect transport and
movement of fluid
out of or through an EK fluid system.
FIG. 21 is provided to illustrate the overall reliability and precision of
fluid transport
by the EK pumps of the present invention. In this example, constant fluid flow
rates can be
maintained during pump operation, little or no error in flow rates at any
given time. As
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previously described above, by employing certain techniques (e.g., controlled
release of and
uptake of ions in the pump fluid, controlling the voltage applied below a pump
fluid voltage
potential, careful selection of electrode materials), flow rate errors can be
maintained at less
than 5% during steady-state flow. FIGS. 22 and 23 are provided to illustrate
the constant and
precise steady-state flow rate can be maintained over a period of hours or
over a period of
days as may be required.
Pumps of the present invention may be advantageously used to dispense agents
of
wide ranging physical characteristics. For example, embodiments of the present
invention
may be used to pump agents having a viscosity of 10 to 100 poise, 100 to 1,000
poise or
1,000 to 10,000 poise. In each of these various viscosity ranges, pumps of the
present
invention maintain the precision and micro-delivery aspects described herein.
For example,
pumps of the present invention may provide 1-10 microliters per hour flow
rates for agents
ranging from 10 to 10,000 poise.
The EK pump systems of this invention may be used to deliver many different
drugs
or other substances to treat a variety of disorders. For example, in a patient
diagnosed with a
disorder in the autonomic and/or somatic motor nervous systems or whose
treatment requires
agent or agents that have a therapeutic effect on the autonomic and/or somatic
motor nervous
systems, the agent (or agents in a co-treatment embodiment) dispensed by the
pump may
include by way of illustration and not limitation: muscarinic receptor
agonists and
antagonists; anticholinesterase agents; agents acting at the neuromuscular
junction and/or
autonomic ganglia; catecholamines, sympathominmetic drugs, and adrenergic
receptor
antagonists; and 5-hydroxytryptamine (5-HT, serotonin) receptor agonists and
antagonists.
In a patient diagnosed with a disorder in the central nervous system (CNS) or
whose
treatment requires agent or agents that have a therapeutic effect on the
central nervous system
and/or act at synaptic and/or neuroeffector junction sites, the agent
dispensed by the pump
may include by way of illustration and not limitation: general anesthetics,
local anesthetics,
analogs of benzodiazepine and barbiturates, a hypnotic, a sedative, aliphatic
alcohols,
ethanol, nonbenzodiazepine sedative-hypnotic drugs, sedative-hypnotic agents
of diverse
chemical structure (e.g., paraldehyde, chloral hydrate), CNS depressants,
antidepressant
therapeutic agents, antipsychotic and antimanic agents, norepinephrine
inhibitors,
monoamine oxidase inhibitors, selective serotonin-reuptake inhibitors,
benodiazepine
sedative-antianxiety agents, serotonin 5-HT1A-receptor partial agonists,
buspirone, agents that
block D2-dopamine receptors, agents that reduce dopamine neurotransmission in
forebrain,
tricyclic phenothiazines, thioxanthenes, dibenzepines, butyrophenones and
congeners,
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heterocyclics, benzamides, agents that interact with D1- and D4- dopaminergic,
5-HT2A- and
5-HT2c-serotonergic, and a-adrenergic receptors, clozapine, olanzapine,
quetiapine,
risperidone, fluphenazine, haloperidol, chlorpromazine, lithium, lithium
carbonate, lithium
citrate, sedative-anticonvulsant benzodiazepines, sodium divalproex,
carbamazepine,
antiseizure drugs that promote an inactivated state of voltage-activated No+
channels,
antiseizure drugs that enhance gamma-aminobutyric acid (GABA)-mediated
synaptic
inhibition, antiseizure drugs that enhance gamma-aminobutyric acid (GABA)-
mediated
synaptic inhibition by an action presynaptically, antiseizure drugs that
enhance gamma-
aminobutyric acid (GABA)-mediated synaptic inhibition by an action
postsynapically,
cholinergic agents, levodopa, dopamine-receptor agonists, catechol-O-
methyltransferase
(COMT) inhibitors, acetylcholinesterase (AChE) inhibitors, NMDA-receptor
antagonists, and
opioid analgesics.
In a patient having a condition, such as injury or inflammation, causing a
physiological or pathophysiological response to the condition or whose
treatment requires
agent or agents that have a therapeutic effect on the physiological or
pathophysiological
response to injury or inflammation, the agent (or agents in a co-treatment
embodiment)
dispensed by the pump may include by way of illustration and not limitation:
histamine and
histamine antagonists, bradykinin and bradykinin antagonists, 5-
hydroxytryptamine
(serotonin), lipid substances that are generated by biotransformation of the
products of the
selective hydrolysis of membrane phospholipids, eicosanoids, prostaglandins,
thromboxanes,
leukotrienes, aspirin, nonsteriodal anti-inflammatory agents, analgesic-
antipyretic agents,
agents that inhibit the synthesis of prostaglandins and thromboxanes,
selective inhibitors of
the inducible cyclooxygenase, selective inhibitors of the inducible
cyclooxygenase-2,
autacoids, paracrine hormones, somatostatin, gastrin, cytokines that mediate
interactions
involved in humoral and cellular immune responses, lipid-derived autacoids,
eciosanoids, 13-
adrenergic agonists, ipratropium, glucocorticoids, methylxanthines, and
leukotriene
inhibitors.
In a patient diagnosed with a disorder affecting renal and/or cardiovascular
function
or whose treatment requires agent or agents that have a therapeutic effect on
the renal and/or
cardiovascular function, the agent (or agents in a co-treatment embodiment)
dispensed by the
pump may include by way of illustration and not limitation: diuretics,
vasopressin, agents
affecting the renal conservation of water, rennin, angiotensin, agents useful
in the treatment
of myocardial ischemia, anthihypertensive agents, angiotensin converting
enzyme inhibitors,
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0-andrenergic receptor antagonists, agents for the treatment of
hypercholesterolemia, and
agents for the treatment of dyslipidemia.
In a patient diagnosed with a disorder in the gastrointestinal system and/or
function or
whose treatment requires agent or agents that have a therapeutic effect on the
gastrointestinal
system or function, the agent (or agents in a co-treatment embodiment)
dispensed by the
pump may include by way of illustration and not limitation: agents used for
control of gastric
acidity, agents for the treatment of peptic ulcers, agents for the treatment
of gastroesophageal
reflux disease, prokinetic agents, antiemetics, agents used in irritable bowel
syndrome, agents
used for diarrhea, agents used for constipation, agents used for inflammatory
bowel disease,
agents used for biliary disease, agents used for pancreatic disease.
In a patient diagnosed with a disorder requiring chemotherapy of a parasitic
infection
or whose treatment requires agent or agents that have a chemotherapeutic
effect on an
infection in the patient, the agent (or agents in a co-treatment embodiment)
dispensed by the
pump may include by way of illustration and not limitation: drugs used to
treat protozoal
infections, drugs used to treat Malaria, Amebiasis, Giardiasis,
Trichomoniasis,
Trypanosomiasis, and/or Leishmaniasis, and/or drugs used in the chemotherapy
of
helminthiasis.
= In a patient diagnosed with a disorder requiring chemotherapy of
neoplastic diseases
or whose treatment requires agent or agents that have a chemotherapeutic
effect on a
neoplastic disease or infection in the patient, the agent (or agents in a co-
treatment
embodiment) dispensed by the pump may include by way of illustration and not
limitation:
antineoplastic agents.
In a patient diagnosed with a disorder requiring chemotherapy of microbial
diseases
or whose treatment requires agent or agents that have a chemotherapeutic
effect on microbial
diseases or infections in the patient, the agent (or agents in a co-treatment
embodiment)
dispensed by the pump may include by way of illustration and not limitation:
antimicrobial
agents, sulfonamides, trimethoprim-sulfamethoxazole quinolones, and agents for
urinary tract
infections, penicillins, cephalosporins, and other, P-Lactam antibiotics, an
agent comprising
an aminoglycoside, protein synthesis inhibitors, drugs used in the
chemotherapy of
tuberculosis, mycobacterium avium complex disease, and leprosy, antifungal
agents, antiviral
agents including nonretroviral agents and antiretroviral agents. Additional
disorders
requiring chemotherapy or whose treatment requires agent or agents that have a
chemotherapeutic effect in the patient are described in the Handbook of
Chemotherapy (Sixth
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Edition), Roland T. Skeel, M.D. Editor, Physicians Cancer Chemotherapy Drug
Manual 2003
by Edward Chu, Vincent T. DeVita, Lippincott's Cancer Chemotherapy Handbook by
Delia
C. Baquiran, Jean Gallagher, each of which is incorporated herein by reference
in their
entirely and for all purposes.
In addition, agents may include drugs used for immunomodulation, such as
immunomodulators, immunosuppressive agents, tolerogens, and immunostimulants.
In addition, agents may include drugs acting on the blood and the blood-
forming
organs, hematopoietic agents, growth factors, minerals, and vitamins,
anticoagulant,
thrombolytic, and antiplatelet drugs.
In addition, agents may include hormones and hormone antagonists, pituitary
hormones and their hypothalamic releasing factors, thyroid and antithyroid
drugs, estrogens
and progestins, androgens, adrenocorticotropic hormone; adrenocortical
steroids and their
synthetic analogs; inhibitors of the synthesis and actions of adrenocortical
hormones, insulin,
oral hypoglycemic agents, and the pharmacology of the endocrine pancreas,
agents affecting
calcification and bone turnover: calcium, phosphate, parathyroid hormone,
vitamin D,
calcitonin, and other compounds.
In addition, agents may include vitamins such as water-soluble vitamins,
vitamin B
complex, ascorbic acid, fat-soluble vitamins, vitamins A, K, and E. In
addition, agents may
include drugs suited to dermatological pharmacology and ocular pharmacology.
Additional disorders and their treatments may be found in Goodman and Gilman's
"The Pharmacological Basis of Therapeutics" Tenth Edition edited by Hardman,
Limbird and
Gilman or the Physician's Desk Reference, both of which are incorporated
herein by
reference in their entirety. It is to be appreciated therefore that the
embodiments of the
present invention are not limited merely to the agent, agents or disorders
listed above but that
embodiments of the present invention may be used to advantage for the delivery
of agents,
including diagnostic and testing agents for the purpose of detecting,
treating, managing, or
diagnosing any of the above listed disorders as well as those disorders
mentioned in
Goodman and Gilman's "The Pharmacological Basis of Therapeutics" Tenth Edition
edited
by Hardman, Limbird and Gilman or mentioned in the Physician's Desk Reference.
Agents may be used alone or in formulations comprising a pharmaceutically
acceptable carrier. The formulation may also comprise a solvent. The agent may
be a
biological molecule or a pharmaceutical drug, DNA, RNA or a protein.
It is to be appreciated that the EK functionality of pumps of the present
invention do
not provide any perceptible indication of operation. As used herein,
perceptible indication of
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operation refers to a any outward sign that the pump is operating. For
example, conventional
piezoelectric pumps have a distinct buzz resulting from the vibration of the
piezoelectric
elements. Conventional mechanical and peristaltic pumps have distinct
mechanical noises
that indicate the pump is operating. Such perceptible indications, especially
noises, are
undesirable for pump systems worn on the person or to be operated in public,
for example, to
dispense insulin prior or during a meal. Embodiments of the present invention
are capable of
dispensing or administering an agent without a perceptible indication of pump
operation. For
example, embodiments of the present invention may operate and generate noise
levels below
20 db, or in some embodiments below 10 db or in still other embodiments
generate noise
inaudible or barely audible to a human being.
The pump and pumping systems described herein are useful in methods for the
treatment of animal subjects. The term "animal subject" as used herein
includes humans as
well as other mammals. The methods generally involve the administration of one
or more
agents for the treatment of one or more diseases. Combinations of agents can
be used to treat
one disease or multiple diseases or to modulate the side-effects of one or
more agents in the
combination.
The term "treating" and its grammatical equivalents as used herein includes
achieving
a therapeutic benefit and/or a prophylactic benefit. By therapeutic benefit is
meant
eradication or amelioration of the underlying disorder being treated. For
example, in a cancer
patient, therapeutic benefit includes eradication or amelioration of the
underlying cancer.
Also, a therapeutic benefit is achieved with the eradication or amelioration
of one or more of
the physiological symptoms associated with the underlying disorder such that
an
improvement is observed in the patient, notwithstanding that the patient may
still be afflicted
with the underlying disorder. For example, administration of a
chemotherapeutic agent to a
patient suffering from cancer provides therapeutic benefit not only when the
patient's tumor
marker level is decreased, but also when an improvement is observed in the
patient with
respect to other complications that accompany the cancer like pain and
psychiatric disorders.
For prophylactic benefit, the combination of phosphate binder and gastric pH
modulator may
be administered to a patient at risk of developing a particular disease, like
cancer, or to a
patient reporting one or more of the physiological symptoms of a disease, even
though a
diagnosis of this disease may not have been made.
In some of the embodiments of the present invention the agent is a drug. Drugs
are
any compounds of any degree of complexity that perturb a biological state,
whether by
known or unknown mechanisms and whether or not they are used therapeutically.
Drugs thus
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include: typical small molecules of research or therapeutic interest;
naturally-occurring
factors, such as endocrine, paracrine, or autocrine factors or factors
interacting with cell
receptors of all types; intracellular factors, such as elements of
intracellular signaling
pathways; factors isolated from other natural sources; pesticides; herbicides;
and insecticides.
The biological effect of a drug may be a consequence of, inter alia, drug-
mediated changes in
the rate of transcription or degradation of one or more species of RNA, the
rate or extent of
translation or post-translational processing of one or more polypeptides, the
rate or extent of
the degradation of one or more proteins, the inhibition or stimulation of the
action or activity
of one or more proteins, and so forth. In fact, most drugs exert their affects
by interacting
with a protein. Drugs that increase rates or stimulate activities or levels of
a cellular
constituent are called herein "activating drugs", while drugs that decrease
rates or inhibit
activities or levels of cellular constituents are called herein "inhibiting
drugs".
The agents used in the pumps described herein may be used alone or in
combination
with one or more pharmaceutically acceptable carrier. Examples of suitable
carriers are
known in the art, for example, see Remington: The Science and Practice of
Pharmacy by
A.R. Gennaro (Editor), 20th Edition, 2000. Preferably the carrier improves the
delivery of the
agent to the subject. It is also preferable that the carrier does not hinder
the delivery of the
agent. In some of the embodiments, the carrier has sufficient ionic properties
to support the
electro-osmotic functioning of the pump.
In some embodiments, the pump is used to detect the presence of one or more
markers
of a disease. If a marker of a disease is detected as being present, the pump
is used to deliver
one or more agents to treat the disease. The term marker as used herein is
intended to
encompass biological markers and also measurable phenotypic characteristics
like
temperature, pressure, etc., Examples of biological markers include, but are
not limited to,
DNA, RNA, proteins, enzymes, hormones, cells, portions of cells, tissues, or
organs,
subcellular organelles like mitochondria, nucleus, Golgi complex, lysosome,
endoplasmic
reticulum, and ribosome, chemically reactive molecules like H+, superoxides,
and ATP.
Examples of markers include, but are not limited to, prostate specific antigen
for prostate
cancer, glucose and/or insulin levels for diabetes, and blood pressure
measurements for
hypertension.
While preferred embodiments of the present invention have been shown and
described herein, it will be obvious to one skilled in the art that such
embodiments are
provided by way of example only. Numerous variations, changes, and
substitutions will now
occur to those skilled in the art without departing from the invention. For
example, the
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systems of the invention may comprise for example any of the features of
conventional drug
delivery or analyte monitoring devices including for example alarms or other
indicators for
notifying a user of when drug delivery is complete. In yet another example,
various retention
members and the like may be coupled to the various device and systems in aid
in the
portability of the various devices and system. In addition, the intended uses
of the present
invention include a variety of medical applications as well as other
applications where highly
precise, compact devices for fluid transport are needed. It should be
understood that various
alternatives to the embodiments of the invention described herein may be
employed in
practicing the invention. It is intended that the following claims define the
scope of the
invention and that methods and structures within the scope of these claims and
their
equivalents be covered thereby.
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