U.S. patent application number 16/801806 was filed with the patent office on 2020-07-02 for fluid delivery and measurement systems and methods.
This patent application is currently assigned to Valeritas, Inc.. The applicant listed for this patent is Valeritas, Inc.. Invention is credited to Robert R. Gonnelli, Steven F. Levesque, David Lipson, Peter F. Marshall.
Application Number | 20200206418 16/801806 |
Document ID | / |
Family ID | 27575279 |
Filed Date | 2020-07-02 |
View All Diagrams
United States Patent
Application |
20200206418 |
Kind Code |
A1 |
Gonnelli; Robert R. ; et
al. |
July 2, 2020 |
Fluid Delivery and Measurement Systems and Methods
Abstract
Fluid delivery and measurement systems and methods are
disclosed.
Inventors: |
Gonnelli; Robert R.;
(Mahwah, NJ) ; Levesque; Steven F.; (North
Pembroke, MA) ; Lipson; David; (North Andover,
MA) ; Marshall; Peter F.; (Lancaster, MA) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Valeritas, Inc. |
Bridgewater |
NJ |
US |
|
|
Assignee: |
Valeritas, Inc.
Bridgewater
NJ
|
Family ID: |
27575279 |
Appl. No.: |
16/801806 |
Filed: |
February 26, 2020 |
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11219944 |
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60250295 |
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60324412 |
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60250403 |
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61M 5/16831 20130101;
A61M 5/14593 20130101; A61M 2005/14204 20130101; A61M 5/158
20130101; A61M 2205/276 20130101; A61M 5/155 20130101; A61M
2205/8206 20130101; A61M 5/14526 20130101; A61M 2005/14264
20130101; A61M 5/16804 20130101; A61M 5/14248 20130101; A61M
2005/14252 20130101; A61M 5/145 20130101; A61M 5/14244 20130101;
A61M 5/1483 20130101; A61M 2205/8231 20130101 |
International
Class: |
A61M 5/155 20060101
A61M005/155; A61M 5/145 20060101 A61M005/145; A61M 5/168 20060101
A61M005/168; A61M 5/142 20060101 A61M005/142; A61M 5/158 20060101
A61M005/158 |
Claims
1. A fluid delivery device comprising: a first housing having an
interior; a flexible member within the interior of the first
housing and mechanically coupled to the first housing, the flexible
member forming first and second chambers within the interior of the
first housing; a gas generator in fluid communication with the
flexible member via the first chamber of the first housing; a
microprobe connected to the first housing such that when the gas
generator produces a gas pressure sufficient to move the flexible
member a portion of a fluid disposed in the second chamber is
ejected via the microprobe; a second housing in fluid communication
with the first chamber of the first housing so that the second
housing is capable of increasing the pressure in the first chamber
of the first housing to increase a rate of fluid ejection via the
microprobe.
2. The device of claim 1, wherein the microprobe is mechanically
coupled to the flexible member.
3. The device of claim 1, wherein the microprobe comprises a
needle.
4. The device of claim 1, wherein the microprobe comprises a
microneedle.
5. The device of claim 1, wherein the flexible member comprises a
septum.
Description
RELATED APPLICATIONS
[0001] This application is a divisional of U.S. application Ser.
No. 11/219,944, filed on Sep. 6, 2005, which is a divisional of
U.S. application Ser. No. 10/006,526 (U.S. Pat. No. 6,939,324),
filed on Nov. 30, 2001, which claims the benefit of U.S.
Provisional Patent Application Ser. Nos. 60/250,538, 60/250,408,
60/250,295, 60/250,927, 60/250,422, 60/250,413, and 60/250,403, all
filed on Nov. 30, 2000; and of U.S. Provisional Patent Application
Ser. No. 60/324,412, filed on Sep. 24, 2001. The entire contents of
these applications are hereby incorporated by reference.
FIELD OF THE INVENTION
[0002] The invention relates to fluid delivery and measurement
systems and methods.
BACKGROUND
[0003] Fluid delivery systems can be used to deliver a fluid, such
as a pharmacological compound (e.g., a therapeutic agent), from a
reservoir to a subject, such as a human. In some embodiments, a
fluid delivery system includes a housing containing a deformable
membrane and a fluid reservoir. The needle is in fluid
communication with the fluid reservoir so that as a force is
exerted against the deformable membrane, the fluid can exit the
system via the needle. The needle is inserted into a subject (e.g.,
a human) so that the fluid is injected into the subject as the
fluid leaves the system.
SUMMARY
[0004] The invention relates to fluid delivery and measurement
systems and methods.
[0005] In one aspect, the invention features a device that includes
a housing and a flexible member within the interior of the housing
and mechanically coupled to the housing. The flexible member forms
first and second chambers within the interior of the housing. The
device further includes a fluid reservoir within the first chamber
of the housing and a microprobe extending from the fluid reservoir,
through the flexible member and into the second chamber of the
housing.
[0006] In some embodiments, the microprobe is configured to move
substantially freely in three mutually perpendicular directions. In
certain embodiments, the microprobe is configured to translate in a
first direction and rotate substantially freely in plane
perpendicular to the first direction.
[0007] In another aspect, the invention features a device that
includes a housing and a flexible member within the interior of the
housing and mechanically coupled to the housing. The flexible
member forms first and second chambers within the interior of the
housing. The device also includes a fluid reservoir within the
first chamber of the housing, and a flexible tube having a first
end and a second end. The first end of the flexible tube is
connected to the flexible member and in fluid communication with
the fluid reservoir via the flexible member. The device also
includes a microprobe connected to the second end of the flexible
tube. The microprobe can be configured to move substantially freely
in three mutually perpendicular directions. The microprobe can be
configured to translate in a first direction and rotate
substantially freely in plane perpendicular to the first
direction.
[0008] Embodiments can have one or more of the following
features.
[0009] The first end of the microprobe can be in the fluid
reservoir, and the second end of the microprobe can be capable of
extending to the exterior of the housing.
[0010] The microprobe can be mechanically coupled to the flexible
member.
[0011] The microprobe can be a needle or a microneedle.
[0012] The flexible member can be a septum.
[0013] The device can further include a pump in fluid communication
with the fluid reservoir. The pump can be configured to draw a
fluid from the microprobe into the fluid reservoir. The pump can be
configured to deliver a fluid from the fluid reservoir to the
microprobe. The pump can be a gas generating source. The pump can
be an electrochemical cell.
[0014] The device can be a device for delivering a fluid from the
fluid reservoir to the exterior of the device via the
microprobe.
[0015] The device can be a device for delivering a fluid to the
fluid reservoir from the exterior of the device via the
microprobe.
[0016] The microprobe can be capable of moving a distance in a
first direction that is at least about two percent (e.g., at least
about five percent, at least about 10 percent, at least about 20
percent, at least about 30 percent, at least about 40 percent, at
least about 50 percent, at least about 60 percent, at least about
70 percent, at least about 80 percent, at least about 90 percent)
of a distance the microprobe is capable of moving in a second
direction perpendicular to the first direction. The microprobe can
be capable of moving a distance in a third direction that is at
least about two percent (e.g., at least about five percent, at
least about 10 percent, at least about 20 percent, at least about
30 percent, at least about 40 percent, at least about 50 percent,
at least about 60 percent, at least about 70 percent, at least
about 80 percent, at least about 90 percent) of the distance the
microprobe is capable of moving in the second direction, the third
direction being perpendicular to the first and second
directions.
[0017] In another aspect, the invention features a fluid delivery
device that includes a first housing and a flexible member within
the interior of the first housing and mechanically coupled to the
first housing. The flexible member forms first and second chambers
within the interior of the first housing. The device also includes
a gas generator in fluid communication with the flexible member via
the first chamber of the first housing and a microprobe connected
to the first housing so that when the gas generator produces a gas
pressure sufficient to move the move the flexible member a portion
of a fluid disposed in the second chamber is ejected via the
microprobe. The device additionally includes a second housing in
fluid communication with the first chamber of the first housing so
that the second housing is capable of increasing the pressure in
the first chamber of the first housing to increase a rate of fluid
ejection via the microprobe.
[0018] In a further aspect, the invention features a fluid delivery
device that includes a housing and a flexible member within the
interior of the housing and mechanically coupled to the housing.
The flexible member forms first and second chambers within the
housing. The device also includes a microprobe connected to the
housing and in fluid communication with the first chamber of the
housing and a gas generator in fluid communication with the second
chamber of the housing. The gas generator is capable of increasing
the pressure in the second chamber to move the flexible member
thereby ejecting a fluid disposed in the first chamber out of the
housing via the microprobe. The device further includes a current
generator in electrical communication with the gas generator. The
current generator is configured so that when a current output by
the current generator is varied, the gas output by the gas
generator is correspondingly varied and the rate of fluid ejected
by the microprobe is also correspondingly varied.
[0019] In one aspect, the invention features a fluid delivery
device that includes a housing and a flexible member disposed in
the interior of the housing and mechanically coupled to the
housing. The flexible member forms first and second chambers within
the housing. A microprobe is connected to the housing and in fluid
communication with the first chamber of the housing. The device
also includes a gas generator in fluid communication with the
second chamber of the housing. The gas generator is capable of
increasing the pressure in the second chamber to move the flexible
member thereby ejecting a fluid disposed in the first chamber out
of the housing via the microprobe. The device further includes at
least one pressure relief valve in fluid communication with the
second chamber of the housing. The pressure relief valve(s) is(are)
able to compensate for a difference between a pressure of the
interior of the housing and a pressure of the exterior of the
housing.
[0020] In another aspect, the invention features a fluid delivery
device that includes a housing and a flexible member disposed in
the interior of the housing and mechanically coupled to the
housing. The flexible member forms first and second chambers within
the housing. A microprobe connected to the housing and in fluid
communication with the first chamber of the housing, and a gas
generator is in fluid communication with the second chamber of the
housing. The gas generator is capable of increasing the pressure in
the second chamber to move the flexible member thereby ejecting a
fluid disposed in the first chamber out of the housing via the
microprobe. The device also includes a second housing, a diluent
reservoir in the second housing, a piston in fluid communication
with the diluent reservoir and a powder chamber in fluid
communication with the diluent reservoir and the first chamber of
the first housing. The piston is configured so that it is capable
of applying a pressure to urge a fluid from the diluent reservoir
to the powder chamber, thereby mixing the fluid with a powder
contained in the powder reservoir to form a mixture and to urge the
mixture into the first chamber of the first housing.
[0021] In a further aspect, the invention features a sensor system
that includes a microprobe, a sensor and a pump. The pump is
configured to apply a suction to the microprobe so that the
microprobe can withdraw a fluid from a body and pass the fluid to
the sensor for detection. The sensor system can further include a
flow restriction device between the microprobe and the sensor along
a fluid flow path from the microprobe to the sensor and a re-fill
device in fluid communication between the pump and the sensor along
a fluid flow path from the pump to the sensor.
[0022] In one aspect, the invention features a fluid delivery
device that includes a housing a piston in the interior of the
housing, and a gas source in fluid communication with the interior
of the housing. The gas source is configured to exert a pressure
against the piston in a first direction. The device also includes a
resilient device configured to exert a pressure against the piston
in a second direction opposite the first direction, an arm, an
actuation device and a valve having an open position and a closed
position.
[0023] In another aspect, the invention features a device that
includes a fluid reservoir capable of containing a fluid and a
first drive mechanism configured to remove a predetermined amount
of the fluid from the fluid reservoir when the first drive
mechanism is actuated. The device is configured to prevent the
first drive mechanism from being re-actuated until the
predetermined amount of the fluid is removed. The device can
further include a second drive mechanism configured to remove fluid
from the fluid reservoir at a first predetermined rate. The first
drive mechanism can enable fluid to be removed from the fluid
reservoir at a second predetermined rate different than the first
predetermined rate. The second predetermined rate can be higher
than the first predetermined rate. The second drive mechanism can
be a gas generating source. The gas generating source can be in
fluid communication with a movable member. The first drive
mechanism can be a compressive force. The first drive mechanism can
be a spring.
[0024] In one aspect, the fluid delivery systems can be designed to
provide improved flexibility and/or patient comfort. For example,
the device is designed so that a rigid microprobe (e.g., a
microneedle or a rigid needle) can be inserted into a subject
(e.g., a human) while the device maintains several degrees of
freedom so that the subject can move while feeling reduced pain
because the system responds to the subject's movement.
[0025] In some embodiments, the invention features a device that
includes a fluid reservoir, a septum, a rigid microprobe (e.g., a
needle or a microneedle), and a housing having an orifice.
[0026] Embodiments may include one or more of the following
features. The device can have several degrees of freedom of
movement. The device can move relative to a subject. The septum can
move, or it can be stationary. The device can include flexible
tubing mechanically coupled to the rigid microprobe. The device can
be a component of an electrochemical cell system.
[0027] The systems and methods can deliver a fluid to a subject
with greater subject comfort, e.g., with a rigid member, and high
reliability.
[0028] In another aspect, the invention features systems and
methods that include delivering a fluid from a reservoir to a
patient at a first rate, then delivering the fluid from the
reservoir to the patient at a second rate different than the first
rate.
[0029] In some embodiments, the systems and methods can provide
both fluid (e.g., a pharmacological compound, such as a therapeutic
agent, such as insulin) delivery to a patient (e.g., a human) at a
relatively constant period of time and fluid delivery at an
increased rate for a desired period of time. In certain
embodiments, this can correspond to a basal delivery rate and a
bolus delivery rate, respectively.
[0030] In one embodiment, the invention provides a device that
includes a delivery device, an auxiliary gas source and a conduit
that provides fluid communication between the delivery device and
the auxiliary gas source.)
[0031] The delivery device can include a gas source, a deformable
layer, a fluid reservoir and a needle or microneedle in fluid
communication with the fluid reservoir. The components of the
delivery device can be arranged so that as the gas source creates a
gas within the delivery device the created gas exerts a pressure
against the deformable layer causing the deformable layer to exert
a pressure against the fluid reservoir, causing the fluid in the
fluid reservoir to exit the delivery device via the needle or the
microneedle.
[0032] The fluid can be a pharmacological compound (e.g., a
therapeutic agent, such as insulin). The gas source in the delivery
device can be an electrochemical cell (e.g., a fuel cell). The
auxiliary gas source can house a gas mixture at a pressure higher
than the pressure of the gas in the delivery device. The auxiliary
gas source can include a gas source. The gas source in the
auxiliary gas source can be an electrochemical cell (e.g., a fuel
cell).
[0033] In another aspect, the invention features a device that can
deliver a fluid, such as a therapeutic agent, variably, for
example, by varying the current output from a current source.
[0034] In one embodiment, the invention features a device having a
first chamber, a second chamber, and a deformable membrane between
the first and second chambers. The second chamber includes a
variable and controllable current source electrically connected to
a gas generator.
[0035] In another aspect, the invention features systems and
methods that compensate for a gas pressure differential between an
interior and exterior gas pressure to a fluid delivery device.
[0036] Compensation can be achieved using one or more valves. For
example, compensation can be achieved by having one or more valves
open or close as a result of the gas pressure differential.
[0037] The systems and methods can reduce overdelivery and/or
underdelivery of fluid to a subject (e.g., a human) when the gas
pressure differential between the interior and exterior of the
delivery device meets or exceeds some predetermined level.
[0038] The systems and methods can reduce overdelivery or
underdelivery of fluid to a subject (e.g., a human) when the gas
pressure external to the delivery device undergoes a relatively
rapid decrease or increase, respectively (e.g., when ascending or
descending, respectively, in an airplane).
[0039] In some embodiments, the invention features a device that
includes a housing, a gas source, a deformable layer, a fluid
reservoir, a valve, and a transmission device. The valve can be
designed to provide fluid communication between the interior and
exterior of the housing when the valve is in a first position,
and/or to prevent fluid communication between the interior and
exterior of the housing when the valve is in a different position.
The device can include more than one valve.
[0040] The gas source can create a gas that exerts a force against
the deformable layer to cause a fluid contained in the fluid
reservoir to exit the device via the transmission device. The gas
source can be an electrochemical cell, such as, for example, a fuel
cell. The transmission device can be a needle or a microneedle.
[0041] In some embodiments, the invention features a device that
includes a housing, a gas source, a piston, a spring, a valve, and
an actuation arm.
[0042] Embodiments include one or more of the following features.
The components of the device can be assembled so that the gas
source can form a gas that exerts a pressure against the piston to
move the piston in a direction away from the gas source. The piston
and actuation arm can be mechanically coupled. The spring can be
disposed within the housing so that it exerts a force in a
direction opposite to the direction of the force created when the
gas source forms a gas. The actuation arm can be coupled to a
pumping mechanism. The actuation arm can be coupled to a deformable
membrane so that the actuation arm can exert a force against the
deformable membrane. The deformable membrane can be coupled to a
fluid reservoir so that the deformable membrane can exert a force
against a fluid contained in the fluid reservoir. The fluid
reservoir can be in fluid communication with a needle or a
microneedle. The actuation arm can exert a force against the
deformable membrane, which can exert a force against a fluid in the
fluid reservoir, and the fluid can exit the device via the needle
or the microneedle.
[0043] In another aspect, the invention features a device that
includes two housings, the first housing can be used to mix a
diluent and a powder to form a mixture, and the second housing can
be used to transfer the mixture to a subject.
[0044] Embodiments include one or more of the following features.
The first housing can include a diluent chamber and a powder
chamber. The diluent and powder chambers can be in fluid
communication. The first and second housings can be in fluid
communication via a seal, which prevents fluid communication
between the first and second housings until the seal is opened or
broken. The second housing can include a reservoir in fluid
communication with the powder chamber via the seal. The second
housing can further include a gas source and a deformable layer.
The second housing can further include a transmission device so
that fluid can exit the fluid reservoir via the transmission
device.
[0045] In another aspect, the invention features a method that
includes transferring diluent from a diluent chamber in a first
housing to a powder chamber in the first housing to form a mixture,
and transferring the mixture to a fluid reservoir in a different
housing.
[0046] Embodiments include one or more of the following features.
The method can further include transferring the mixture from the
fluid reservoir to a subject via a transmission device. The methods
and devices can include an electrochemical cell (e.g., a fuel
cell).
[0047] In another aspect, the invention features sensors, such as,
for example, pumps that can be used, for example, to detect an
analyte (e.g., glucose) in a patient, as well as systems containing
such sensors and methods. A device, such as an indwelling
biosensor, can be used to monitor certain physiological conditions,
such as, for example, the amount and/or concentration of an analyte
(e.g., glucose) in a patient's blood.
[0048] In some embodiments, the invention features a system having
a microprobe, a sensor and a pump. The microprobe, sensor and pump
are in fluid communication.
[0049] Embodiments include one or more of the following features.
The pump can be an electrochemical cell. The electrochemical cell
can be capable of operating in a mode that removes oxygen from the
system. The microprobe can be in fluid communication with a
subject. The devices and methods can be used to withdraw, to
measure and/or to detect a sample, e.g., an analyte of interest, in
a subject without exposing (e.g., without directly exposing) the
sensor to the subject's tissue.
[0050] In one aspect, the invention features a fluid delivery
system capable of delivering a basal dosage (e.g., over about 24
hours) of a fluid, such as a drug, and/or delivering a bolus dosage
of the fluid. A basal dosage can be, for example, about 0.5 to
about 3 units per hour, and a bolus dosage can be, for example, a
maximum of 15 units in a maximum time of 15 minutes.
[0051] In another aspect, the invention features a system and a
method capable of delivering a bolus dosage accurately and
reliably, for example, with minimized risk of under-dosage or
over-dosage. In one embodiment, after a user starts a first cycle
of bolus delivery, a dosage drive mechanism prevents the user from
starting a second cycle of bolus delivery until the first cycle is
completed. For example, the user is prevented from starting the
second cycle mid-way through the first cycle, which can result in a
one-and-a-half bolus dosage being delivered at the end of second
cycle, rather than an intended one bolus dosage. The system and
method ensure that the first cycle delivers the intended,
predetermined dosage without unwanted interruption, thereby
allowing the user to know what dosage was delivered, and minimizing
the risk of under-dosage or over-dosage.
[0052] In certain embodiments, the invention features a method of
sensing a fluid in a subject. The method includes creating suction
in the system using an electrochemical cell to withdraw the fluid
from the subject.
[0053] The devices and methods can provide sample measurement with
relatively low signal loss, relatively little signal drift, and/or
relatively little calibration loss. The devices and methods can
provide relatively high stability (e.g., by not exposing the sensor
to a tissue environment, such as a tissue environment of the
subject). The systems and methods can use a pump that is relatively
small, inexpensive, lightweight, compact and/or inexpensive.
[0054] Combinations of embodiments can be used.
[0055] Other features, objects, and advantages of the invention
will be apparent from the description and drawings, and from the
claims.
DESCRIPTION OF DRAWINGS
[0056] FIG. 1 is an exploded view of an embodiment of an
electrochemical cell system.
[0057] FIG. 2 is a cross-sectional view of an embodiment of an
electrochemical system.
[0058] FIG. 3 is a partial perspective view of an embodiment of a
fluid delivery system.
[0059] FIG. 4 is a partial perspective view of an embodiment of a
fluid delivery system.
[0060] FIG. 5 is a cross-sectional view of an embodiment of a fluid
delivery system.
[0061] FIG. 6 is a cross-sectional view of an embodiment of an
auxiliary gas source.
[0062] FIG. 7 is a cross-sectional view of an embodiment of an
auxiliary gas source.
[0063] FIG. 8 is a cross-sectional view of an embodiment of an
auxiliary gas source.
[0064] FIG. 9 is a cross-sectional, schematic view of an embodiment
of a fluid delivery device.
[0065] FIG. 10 is a schematic diagram of a current controller.
[0066] FIG. 11 is a schematic diagram of a current controller.
[0067] FIG. 12 is a plot of fluid delivery as a function of
time.
[0068] FIG. 13 is a cross-sectional view of an embodiment of a
fluid delivery system.
[0069] FIG. 14 is a cross-sectional view of an embodiment of an
auxiliary gas source.
[0070] FIG. 15 is a cross-sectional view of an embodiment of a
fluid delivery system.
[0071] FIG. 16 is a cross-sectional view of an embodiment of a
fluid delivery device.
[0072] FIG. 17 is a schematic representation of an embodiment of a
sensor system.
[0073] FIG. 18 is a schematic representation of an embodiment of a
sensor system.
[0074] FIGS. 19A, 19B, and 19C are graphical representations of the
performance of an embodiment of a sensor.
[0075] FIG. 20 is a partial, schematic diagram of an embodiment of
a fluid delivery system.
[0076] FIG. 21 is a partial, schematic diagram of an embodiment of
a fluid delivery system.
[0077] FIG. 22 is a partial, schematic diagram of an embodiment of
a fluid delivery system.
[0078] FIG. 23 is a partial, schematic diagram of an embodiment of
a fluid delivery system.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
[0079] The invention relates to fluid delivery and measurement
systems and methods.
[0080] FIGS. 1 and 2 show a fluid delivery system 100 used to
deliver one or more fluids such as pharmacological compounds, e.g.,
one or more therapeutic agents. System 100 includes a button
stopper 102, a button 104, a microprobe (e.g., a needle or a
microneedle) 106, a spring 108, a shell 110, a bladder 112, a
delivery septum 114, a positive battery contact 116, an
electrochemical cell 118, a base 120, a filling septum 122, a
septum capture ring 124, a negative battery contact 126, a battery
128, a battery spacer 130, a vent 132, a drive volume 134, a fluid
volume 136, and a delivery path 138. Various features and/or
combinations can be incorporated into system 100 as described
herein.
[0081] In some embodiments, a force is used to urge fluid from the
fluid reservoir, into the microprobe and into a subject (e.g., a
human). In certain embodiments, the force is created using an
electrochemical cell, such as a fuel cell. Examples of
electrochemical cells are disclosed, for example, in U.S. Pat. Nos.
4,402,817; 4,522,698; 4,902,278; and 4,687,423, which are hereby
incorporated by reference.
[0082] FIG. 3 shows a portion of an embodiment of fluid delivery
system 101. System 101 includes a septum 140, a fluid reservoir 142
(e.g., containing a pharmacological compound), a microprobe 144
(e.g., a rigid microprobe, such as a microneedle or a rigid needle)
and a housing 146 having an orifice 148. In certain embodiments,
microprobe 144 can pierce septum 110 so that microprobe 144 is in
fluid communication with fluid reservoir 142. Septum 140,
microprobe 144, and housing 146 can move in the directions
indicated by the respective bold arrows (A, B, and C), providing
system 101 to have these degrees of freedom.
[0083] FIG. 4 shows a portion of a delivery system 150 in which a
flexible portion 152 (e.g., a flexible tubing) connects microprobe
144 with a septum 154. Septum 154 is stationary, but housing 146
and microprobe 144 can move as indicated by the respective bold
arrows (X and Y), providing system 150 with these degrees of
freedom.
[0084] In certain embodiments, housing 146 can further include a
breakable membrane, such as a polymeric membrane, extending across
orifice 148. The membrane can be connected to microprobe 144 to
hold the microprobe in place, e.g., centered in orifice 148, during
packing and storage of system 100. When system 100 is applied to a
subject, this causes microprobe 144 to move, e.g., upward, thereby
pulling the membrane from orifice 148 and allowing the microprobe
to move with multiple degrees of freedom.
[0085] Under certain circumstances, it can be desirable for a fluid
delivery system to deliver fluid to the subject at a relatively
constant rate. Under some circumstances, however, it can be
desirable for the system to deliver (at least for a period of time)
fluid to the subject at a relatively high rate.
[0086] FIG. 5 shows a system 160 including a fluid delivery device
162 and an auxiliary gas source 164. Fluid delivery device 162
includes a transport device (e.g., a microprobe or a microneedle or
a needle) 166, a deformable layer (e.g., a deformable membrane)
168, a fluid reservoir (e.g., a reservoir containing
pharmacological compound) 170, and a gas source 172. Fluid delivery
device 162 is connected to auxiliary gas source 164 via conduit 174
that includes valve 176.
[0087] Under certain circumstances when it is desirable for
delivery device 160 to deliver fluid to the subject via device 162
at a relatively constant rate, valve 176 is generally closed so
that device 160 and auxiliary gas source 164 are not in fluid
communication. When valve 174 is closed, fluid delivery device 162
delivers fluid from reservoir 168 to the subject via device 162 as
follows. Gas source 172 forms a gas inside device 162 between gas
source 172 and layer 168, As the amount of gas formed by source 172
increases, layer 168 is deformed and exerts a pressure against
fluid in reservoir 170, thereby forcing the fluid through device
166. Gas source 172 can be, for example, an electrochemical cell,
such as a fuel cell that generates oxygen in device 110, as
described above.
[0088] Under circumstances when it is desirable to deliver (at
least for a period of time) fluid to the subject via device 166 at
a relatively high rate, the pressure of gas in auxiliary gas source
164 is held at and/or increased to a pressure higher than the gas
pressure in device 162. Valve 176 is then opened, allowing gas to
flow from source 164 into device 162 via conduit 174. This
increases the pressure exerted on layer 168, thereby increasing the
rate at which fluid is delivered from reservoir 170 to the subject
via device 166.
[0089] Auxiliary gas source 164 can be a body of gas held at a
relatively high pressure. Alternatively or additionally, gas source
164 can include a piston 178 that is depressed in conjunction with
the opening of valve 176 and a portion 180 that moves as piston 178
is depressed (FIG. 6). FIG. 7 shows another embodiment in which
auxiliary gas source 164 includes a gas source 182 that generates a
gas within the auxiliary gas source, such as described above with
respect to device 162. For example, gas source 182 can be an
electrochemical cell as described above. In certain embodiments,
auxiliary gas source 164 can provide an increased pressure via
chemical reactions (e.g., relatively rapid chemical reactions) that
occur within the auxiliary gas source (e.g., reactions between
vinegar and sodium bicarbonate). The gases created can be directly
added into device 162, or an increased pressure can be achieved in
device 162 by allowing the gases created in the chemical reactions
to push, for example, a syringe plunger 184 that increases the gas
in device 162 (FIG. 8).
[0090] In some embodiments, the gas pressure can be held at a
relatively high value in auxiliary gas source 164. In certain
embodiments, the gas pressure in auxiliary gas source 164 is
increased just prior to, or at the same time as, valve 176 is
opened.
[0091] Valve 176 may be manually opened as desired. Valve 176 may
be opened at predetermined intervals. Valve 176 may be opened based
upon the value of some parameter (e.g., the concentration of an
analyte, such as glucose, in a patient).
[0092] Alternatively or in addition, in some embodiments, it is
desirable for a fluid delivery system to deliver a fluid at a
predetermined rate, e.g., a variable rate of delivery.
[0093] FIG. 9 shows a fluid delivery device 190 that includes a
housing 192 and a deformable member (e.g., a deformable membrane)
194 inside the housing. Housing 192 and member 194 define a first
chamber 196 and a second chamber 198. Device 190 includes a
microprobe 199, such as a needle or a microneedle, having a lumen
in fluid communication with first chamber 196 and an environment
outside housing 192.
[0094] First chamber 196 includes a pharmacological compound 200,
such as a, e.g., insulin.
[0095] Second chamber 198 includes a button 202, a current
generator 204, e.g., a DC current generator, in electrical
communication with the button, and a gas generator 206 in
electrical communication with the generator. Gas generator 206 is
generally as described above. When a user presses button 202, this
activates generator 204, which in turn sends a current to gas
generator 206 to create a gas (e.g., oxygen gas) in second chamber
198. As gas is generated, pressure in second chamber 198 increases,
which exerts a force on membrane 194 (e.g., pushes membrane toward
microprobe 199). This, in turn, pushes compound 200 out through the
lumen of microprobe 199 to, for example, a subject.
[0096] In some embodiments, the rate at which compound 200 is
delivered through microprobe 199 is controlled by controlling the
amount of current that generator 204 produces. This, in turn,
controls the amount of gas generated by gas generator 206, the
amount of pressure created in second chamber 198, and the amount of
force exerted on membrane 194. For example, an increase in current
output from current generator 204 increases compound delivery; and
a decrease in current output decreases compound delivery.
[0097] The current from current generator 204 can be controlled or
altered by using a standard current generator having a selector
switch configured to alter the resistance in the circuitry of the
generator. Current can be increased by switching to a low
resistance resistor, and current can be decreased by switching to a
high resistance resistor. FIGS. 10 and 11 show a FET and LM334
current controller, respectively, that can be used to control
current by changing resistors. With these current generator
systems, the active device can regulate current even with decay in
the voltage of the battery.
[0098] In some embodiments, the current control generator or system
can be combined with a software system, e.g., one having a
microprocessor, for remote control by the user. Accordingly, a
variety of configurations can be implemented depending on the
clinical need of the patient and the properties of a therapeutic
agent. For example, the therapeutic agent can be delivered
according to a circadian schedule, such as high dosage when the
patient is asleep. Thus, this system permits an "electronic
formulation" or adjustment of therapeutic agent dosage or delivery
over the period of ambulation in a delivery system that can, for
example, be disposable.
[0099] FIG. 12 is a plot of fluid, e.g., a therapeutic agent,
delivery (in units per hour) as a function of time. FIG. 12 shows
that the amount of fluid delivery can be controllably varied at
least over 24 hours by varying the applied current to current
generator 204. For example, from 10-12 pm, a constant current (CC)
of about 1,070 microamps was applied, which delivered about 30
units per hour. When the current was reduced to about 167
microamps, the rate of delivery decreased to about 3-4 units per
hour. Then, the rate of delivery can be increased again by
increasing the current. The current output from generator 204 can
be controlled by a variety of ways, including using constant
current and/or using constant voltage.
[0100] Under certain circumstances, there can be a relatively rapid
change in the ambient gas pressure external to a fluid delivery
system (e.g., during ascent or descent of an airplane). This can
result in a change in the rate of deliver of the fluid to the
subject.
[0101] FIG. 13 shows a fluid delivery system 210 including a
housing 212, a gas source 214, a deformable layer 216, a
transmission device (e.g., a microprobe, a microneedle or a needle)
218, a fluid reservoir 220 containing a fluid, and a valve 222.
System 210 delivers fluid from reservoir 220 to a subject when
valve 222 is closed and gas source 214 forms a gas inside housing
212 between the gas source and layer 216. As the amount of gas
formed by source 214 increases, layer 216 is deformed and exerts a
pressure against fluid in reservoir 220, thereby forcing the fluid
through device 218. In certain embodiments, the gas pressure inside
housing 212 between gas source 214 and layer 216 can be slightly
higher than the ambient gas pressure external to system 210.
[0102] Without wishing to be bound by theory, it is believed that
the change in delivery rate that is due to the change in the gas
pressure differential between the ambient gas pressure external to
system 210 and the gas pressure inside housing 212 between gas
source 214 and layer 216. For example, assuming an ideal gas forms
the ambient environment external to system 210 and an ideal gas
forms the gas pressure inside housing 212 between gas source 214
and layer 216, a change in the ambient gas pressure from 14.7
pounds per square inch (approximate ambient gas pressure at sea
level) to 10 pounds per square inch (approximate ambient gas
pressure at 15,000 feet), can correspond to an almost 50% increase
in the gas volume. This can result in overdelivery of the fluid
from reservoir 220 to the subject. Similarly, underdelivery of the
fluid from reservoir 220 to the subject can occur as the ambient
gas pressure external to system 210 undergoes a relatively rapid
decrease (e.g., when a plane descends).
[0103] Accordingly, valve 222 is designed to open to assist in
decreasing a gas pressure differential between the ambient gas
pressure external to system 210 and the gas pressure inside housing
212 between gas source 214 and layer 216. For example, valve 222
can be a bi-directional valve designed so that when this gas
pressure differential meets or exceeds some predetermined value the
valve allows gas to flow from the relatively high gas pressure
environment to the relatively low gas pressure environment, thereby
assisting in decreasing the gas pressure differential. Such valves
are commercially available from, for example, Vernay.
[0104] FIG. 14 shows a fluid delivery system 230 that contains
valves 232 and 234, each of which is a one-way valve (e.g., a
"pop-off" valve, a "mushroom-capped" valve). Valves 232 and 234 are
designed so that, if the ambient external gas pressure to system
210 exceeds the gas pressure inside housing 212 between gas source
214 and layer 216 by some predetermined value, valve 232 opens so
that the gas pressure differential decreases. Valves 232 and 234
are also designed so that, if the gas pressure inside housing 212
between gas source 214 and layer 216 exceeds the ambient external
gas pressure to system 210 by some predetermined value, valve 234
opens so that the gas pressure differential decreases.
[0105] Various combinations of pressure relief valves can be used.
Generally, the combination(s) of relief valve(s) is designed to
reduce the gas pressure differential between the internal and
external gas pressures of the delivery system when the gas pressure
differential meets or exceeds some predetermined value.
[0106] In certain embodiments, the internal pressure differential
at which the device works to provide a desired fluid flow can be
relatively low (e.g., about 0.2 PSIG or less). In some embodiments,
one or more components can be included in the device to provide a
resistive force to increase the internal pressure differential at
which the device works to provide the desired fluid flow. For
example, a spring can be disposed beneath the flexible member. This
can, for example, decrease the absolute and/or relative pressure
differential used for pressure relief valve(s) to operate relative
the internal pressure differential used to provide desired fluid
flow for the device, thereby enhancing the overall sensitivity of
the device to changes in the internal/external pressure
differential (e.g., due to a change in altitude).
[0107] Other embodiments for minimizing overdelivery and/or
underdelivery are possible. FIG. 15 shows a fluid delivery system
240 including a housing 242, a gas source 244, a resilient device
246 (e.g., a spring), an arm 248 (e.g., a drive arm, a cam, a
linkage, a ratchet device), a piston 250, seals 252 and 254 (e.g.,
O-rings), an actuation device 256 (e.g., a valve actuation arm),
and a valve 258. Arm 248 is in mechanically coupled to a pumping
mechanism 260 (e.g., a deformable layer) that delivers a fluid to a
patient via a transmission device, such as a microprobe, a
microneedle or a needle.
[0108] When valve 258 is closed, gas source 244 forms a gas, which
urges piston 250 against device 246 and which moves arm 248 away
from source 244. When the piston reaches a position at a
predetermined distance from gas source 244, device 256 causes valve
258 to open, decreasing the gas pressure differential between the
interior of housing 242 and the exterior of the housing.
Alternatively, the position of valve 258 (e.g., open or closed) can
be selected manually, or can be determined based upon some measured
parameter (e.g., the differential between the gas pressure inside
housing 242 and the gas pressure outside the housing).
[0109] The rate at which piston 250 moves distally from gas source
244 can depend upon the differential between the gas pressure
inside housing 242 and the gas pressure outside the housing. For
example, the amount of time it takes for piston 250 to move a given
distance away from gas source 244 can vary proportionally with the
variation in the differential in the gas pressure inside housing
242 and the gas pressure outside the housing (e.g., if at a given
gas pressure differential it takes piston 250 one second to move a
given distance from gas source 244, then at half that gas pressure
differential, it will take piston twice as long to move that
distance from the gas source).
[0110] In some embodiments, the piston and seals assembly can be
replaced with a bellows sealed to the gas source. In certain
embodiments, the circuitry of the gas source can be connected to
flip/flop polarity so that it switches, for example, from oxygen
generation mode to oxygen removal mode. The polarity can be
reversed by, for example, a timed response, a mechanical limit
switch, or both. In these embodiments, the system can be designed
to not include the return spring or valve actuation arm, and the
valve could be replaced with valves described above.
[0111] Referring to FIG. 20, a fluid delivery system 10 includes
base 11 positioned thereon, a fluid housing 12, a needle or
microneedle housing 14, and a movement system 16 for moving the
fluid housing. Fluid housing 12, e.g., a glass cylinder vial,
contains a fluid 18 (e.g., a pharmacological compound, such as a
drug) between a sealed end 20 and an open end 22 sealed with a
pierceable member 24, such as a rubber stopper or septum. Member 24
provides fluid housing 12 with a fluid-tight seal so that fluid 18
does not leak from the housing, but member 24 and housing 14 can
slide within the housing. That is, fluid housing 12 is configured
to slidably receive member 24 and housing 14, as described below.
Housing 14, which includes a double-pointed needle 26, is fixedly
attached to base 11. Examples of housings, including a needle or a
microneedle, are described herein.
[0112] Movement system 16 includes a gear rack 28, a pinion gear
30, a spur gear 32, and a pawl 34. Gear rack 28 has two projections
36 that engage, e.g., hold, ends 20 and 22 of fluid housing 12 to
couple the fluid housing to the gear rack. Gear rack 28 further
includes teeth 38 that engage pinion gear 30, and the pinion gear
is rotatably connected to spur gear 32. The gear ratios of gear
rack 28, pinion gear 30 and spur gear 32 are selected to provide a
predetermined amount of movement of the gear rack in response to a
predetermined movement of the spur gear, e.g., sufficient for drug
delivery. Pawl 34 is attached to base 11 at one end and engages
with the teeth of spur gear 32 at the other end. Pawl 34 serves as
an anti-reverse mechanism that allows spur gear 32 to rotate in
only one direction, here clockwise (arrow A). Pawl 34 also
maintains a load on fluid housing 12 as a drive mechanism (describe
below) is reset.
[0113] During use, fluid 18 is delivered from fluid housing 12
through needle or microneedle 26 by translating fluid housing 12
toward housing 14 (arrow B). Spur gear 32 is rotated clockwise,
which rotates pinion gear 30 clockwise. Pawl 34 prevents spur gear
32 from rotating counter-clockwise. As pinion gear 30 rotates, its
teeth engage with teeth 38 of gear rack 28, which translates the
gear rack in the direction of arrow B. Since gear rack 28 is
coupled to fluid housing 12 by projections 36, the fluid housing is
also translated in the direct of arrow B toward housing 14. As
fluid housing 12 is moved toward housing 14, one end of needle or
microneedle 26 pierces through member 24, and the other end of the
needle or microneedle pierces a subject, e.g., a human. Fluid 18 is
delivered through needle or microneedle 26 by continuing to move
fluid housing 12 toward housing 14 with member 24 sliding inside
the fluid housing, e.g., like a piston. In some embodiments, it is
preferable that needle or microneedle 26 pierces member 24, and
fluid 18, e.g., a drop or less, flows entirely through the needle
or the microneedle before the needle or the microneedle pierces the
subject. This can prevent or minimize contamination of fluid 18,
e.g., if the needle or the microneedle pierces the subject first
and the subject's bodily fluid can enter fluid housing 12.
[0114] FIG. 21 shows an embodiment of fluid delivery system 10
having a drive mechanism 40 capable of delivering a basal dosage of
fluid 18. Mechanism 40 includes an inlet port 42, a piston system
44, and a driver 46. Port 42 is interfaced with a gas-generating
source (not shown) such as an electrochemical cell, e.g., an
electrolytic cell. Gas-generating sources are disclosed in U.S.
Pat. Nos. 4,402,817; 4,522,698; 4,902,278; and 4,687,423. Gas from
the gas source is provided to drive piston system 44, which
includes a piston 48 and an exhaust port 50. Piston 48 is connected
to a torsion spring 49 configured to force the piston toward inlet
port 42. Piston 48 is also connected to driver 46 and linked to
exhaust port 50, e.g., a valve, by a linkage 52. Driver 46 is
configured to engage with spur gear 32 such that as piston 48 moves
away from inlet port 42, the driver can rotate the spur gear, e.g.,
clockwise. Linkage 52 is provided to open exhaust port 50 when
piston 48 reaches a predetermined position along its upstroke,
e.g., at the end of its stroke, and triggers the linkage. Opening
exhaust port 50 vents gas in piston system 44 so that spring 49 can
force piston 48 back to an initial stroke position, e.g., adjacent
to port 42. After gas is vented from piston system 44 and piston 48
completes its downstroke, linkage 52 closes exhaust port 50.
[0115] During use, gas is continuously introduced via port 42 into
piston system 44. With piston 48 at the initial stroke position and
port 50 closed, as the gas pressure increases in system 44 and
overcomes the force of spring 49, the gas advances the piston and
driver 46 toward spur gear 32, thereby rotating the spur gear. As
described above, rotation of spur gear 32 delivers fluid 18 through
needle or microneedle 26. Piston 48 continues to advance until it
reaches a predetermined position where it causes linkage 52 to open
exhaust port 50. Opening port 50 vents gas in system 44, and allows
spring 49 to force piston 48 to its initial stroke position (and
retracts driver 46), where linkage 52 now closes the exhaust port.
Since gas is continuously introduced into piston system 44, the
stroke cycle of piston 48 and driver 46 is repeated, thereby
continuing to deliver fluid 18 through needle or microneedle
26.
[0116] FIG. 22 shows an embodiment of fluid delivery system 10
having a drive mechanism 54 capable of delivering a bolus dosage of
fluid 18. Mechanism 54 is shown in an untriggered condition.
Mechanism 54 includes a shaft 56, a button release lever 58, and a
button lock-up bar 60.
[0117] Shaft 56 includes positioned thereon a button 62, a button
extension spring 64, a bolus actuator 66, and a bolus drive spring
68. Button 62 and actuator 66 are slidably positioned on shaft 56.
Button 62 is a square, hollow member having a notch 70. Springs 64
and 68 are positioned on shaft 56 such that they can be compressed
and extended on the shaft when button 62 and actuator 66 are moved
along the shaft. Actuator 66 is also a square, hollow member that
includes an actuator tab 72, e.g., spring steel, that can engage
with the teeth of spur gear 32 to rotate the spur gear, e.g., drive
the gear in the direction of arrow A. Shaft 56 is connected to base
11 on one end.
[0118] Button release lever 58 is pivotally connected to base 11 at
connection 74. Lever 58 is biased in the direction of arrow C by a
lever spring 76. Lever includes a portion 88 that can engage with
notch 70.
[0119] Button lock-up bar 60 is also pivotally connected to base
11, at connection 78. Button lock-up bar 60 is biased in the
direction of arrow D by a spring (not shown). Button lock-up bar 60
includes an edge 80 that is chamfered, e.g., at about 45.degree.,
and that contacts an end 82 of bolus actuator 66 when mechanism 54
is in an untriggered condition. Lock-up bar 60 further includes an
end 84 that can engage with an end 86 of button 62.
[0120] As shown in FIG. 22, in an untriggered condition, button
release lever 58 is spring-biased in the direction of arrow C, and
button lock-up bar 60 is spring-biased in the direction of arrow D.
Springs 64 and 68 are extended.
[0121] During use, for example, when a user wants to deliver a
bolus dose of fluid 18, the user first depresses button 62 (shown
extended in FIG. 22) in the direction of arrow E along shaft 56
until notch 70 engages with portion 88 of button release lever 58.
Portion 88 locks button 62 in a depressed position. Depressing
button 62 also compresses springs 64 and 68 along shaft 56 and
moves bolus actuator 66 and tab 72 in the direction of arrow E. Tab
72 deflects as it travels over the teeth of spur gear 32. Since
lock-up bar 60 is biased in the direction of arrow D, and bolus
actuator 66 has been moved out of contact with edge 80 by
depressing button 62, the lock-up bar rotates (arrow D) about
connection 78, and end 84 rotates to contact the side of the
button. With button 62 depressed and locked, drive mechanism 54 is
in a "cocked" condition.
[0122] To trigger drive mechanism 54, the user rotates button
release lever 58 about connection 74 in the direction opposite
arrow C, here clockwise. This releases the locking engagement
between notch 70 and portion 88, and allows button 62 to be
returned to its untriggered position by the spring force of spring
64. Similarly, bolus actuator 66 is returned to its untriggered
position by the controlled and predetermined spring force of spring
68. As bolus actuator 66 returns (in the direction opposite arrow
E) actuator tab 72 engages spur gear 32 at a controlled force and
rotates the spur gear, thereby delivering a bolus dose at a
controlled rate. When bolus actuator 66 returns to its untriggered
position, edge 82 contacts edge 80 to rotate lock-up bar 60 in the
direction opposite arrow D, thereby moving end 84 away from end 86
and allowing button 62 to be depressed. Before bolus actuator 66 is
returned to its untriggered position, however, lock-up bar 60 is
biased in the direction of arrow D (upwardly as shown in FIG. 22);
such that, if the user tried to depress button 62, end 84 would
butt against end 86 and prevent the button from being depressed.
This mechanism prevents the user from re-cocking and re-triggering
the bolus delivery mechanism before the bolus dosage is completed.
As a result, the risk that a user can deliver an unwanted bolus
dosage--over-dosage or under-dosage--is minimized. Each trigger of
drive mechanism 54 can provide a predetermined bolus dosage at a
controlled rate, so the risk of under-dosage is minimized. The user
is prevented from re-triggering the drive mechanism until the
predetermined dosage is delivered, so the risk of over-dosage is
minimized.
[0123] While drive mechanisms 40 and 54 are described above
separately, in certain embodiments, the drive mechanisms are
integrated in a fluid delivery system such that the delivery system
can deliver a basal dosage and a bolus dosage on demand.
[0124] While certain embodiments have been disclosed, the invention
is not limited in this sense. For example, FIG. 23 shows an
embodiment of a piston system 1100 that can be used in drive
mechanism 40 described above. System 1100 includes a piston
assembly 1102, a linkage assembly 1104, and a valve 1106, e.g., a
T-shape valve. Piston assembly 1102 includes a piston 1108, a
piston housing 1110, and a spring 1111. Spring 1111 is configured
to bias piston 1108, e.g., with linear force, in the direction of
arrow F, for example, to bias the piston to a position adjacent to
valve 1106. In some embodiments, piston 1108 is connected to driver
46 in the drive mechanism described above to delivery fluid 18.
Piston assembly 1102 further includes a gas inlet 1113 that is in
fluid communication with the interior of housing 1110 and a gas
source (not shown), such as an electrochemical cell described
above.
[0125] Linkage assembly 1104 includes a first lever arm 1112, a
linkage bar 1114, and a second lever arm 1116. First lever arm 1112
is connected to linkage bar 1114 by a freely pivoting connection;
and the linkage bar is connected to second lever arm 1116 by a
slotted connection 1118 and to valve 1106. First lever arm 1112 is
further engaged to a ball plunger 1120 via a first detent 1124 or a
second detent 1126 on the first lever arm. At one end, ball plunger
1120 includes a ball 1122 that can rest in first detent 1124 or
second detent 1126. At the other end, plunger 1120 is fixedly
connected, for example, to a housing of system 1100 via a spring or
a rigid connection. Linkage assembly 1104 is connected to piston
1108 at one end of first lever arm 1112, for example, by a spring
or a rigid connection such as a rod.
[0126] In operation, piston 1108 is at an initial position, e.g.,
adjacent to valve 1106. Linkage assembly 1104 is configured such
that the pivoting and lever action of lever arms 1112 and 1116 and
linkage bar 1114 causes the valve to be closed. Piston housing 1110
is sealed. Ball 1122 is at rest in first detent 1124.
[0127] As gas is continuously introduced via inlet 1113 into
housing 1110, the gas pressure inside the housing 1110 increases
and overcomes the spring force of spring 1111. Piston 1108 is moved
away from valve 1106. The movement of piston 1108 can be used to
drive driver 46 to deliver a fluid.
[0128] When piston 1108 reaches a predetermined position, e.g., at
the end of its upstroke, the piston pushes on first lever arm 1112
such that ball 1122 is displaced from first detent 1124 to second
detent 1126. This action causes linkage assembly 104 (by pivoting
and lever action) to open valve 1106. Opening valve 1106 vents gas
from piston housing 1110, and the spring force of spring 1111
causes piston 1108 to return to its initial position. As piston
1108 travels back to its initial position, ball 1122 is still in
second detent 1126, thereby ensuring that valve 1106 stays open
until the piston returns to a predetermined position, e.g., its
initial position, i.e., for the entire return stroke. For example,
if valve 1106 were just "cracked" or closed during the return
downstroke, piston 1108 could be stalled midway through the entire
stroke cycle. When piston 1108 reaches its initial position, the
piston pushes and closes valve 1106, and the mechanical action of
linkage assembly 1104 displaces ball 1122 from second detent 1126
to first detent 1124. The stroke cycle of the piston is repeated as
gas is introduced into housing 1110.
[0129] Thus, system 1100 is generally configured to ensure that
piston 1108 completes its stroke cycle, e.g., from an initial
position to a final position and back to the initial position,
without restarting its cycle during the cycle. When coupled, for
example, to a fluid delivery system, system 1100 can provide an
accurate and reliable drive mechanism.
[0130] FIG. 16 shows a system 270 that includes a first chamber 272
and a second chamber 274. Chamber 272 contains a diluent reservoir
276 coupled to a button 278 via a piston 280 so that when the
button is depressed, the piston moves in the direction shown by the
arrows. This causes the diluent to move along a path 282 and enter
a powder chamber 284, which contains a dried powder, such as, for
example, a pharmacological compound (e.g., a lyophilized
therapeutic agent). When the diluent enters chamber 284, the dried
powder is reconstituted. The reconstituted mixture (e.g.,
therapeutic agent/diluent mixture) can move along a path 286 to a
seal 288. Seal 288 can be, for example, a sterility seal. If seal
288 is broken (e.g., by being sheared as system 270 is mounted on,
for example, a subject), then the reconstituted mixture can pass
into a reservoir 290 contained in chamber 274. Chamber 274 also
includes a gas source 292 as described above, a deformable layer
294, and a transmission device 296 (e.g., a needle or a
microneedle).
[0131] When gas source 292 is activated (e.g., by the user pressing
a button), the gas source creates a gas in housing 274 between the
gas source and deformable layer 294. This exerts a force on
deformable layer 294, which, in turn, causes fluid (e.g., a fluid
and the therapeutic agent/diluent mixture) in reservoir 290 to exit
housing 274 via device 296. In some embodiments, the fluid is
transferred into a subject (e.g., a human) (e.g., when device 296
is inserted into the subject).
[0132] In certain embodiments, the user can press a button that
activates (e.g., simultaneously activates) both the electrochemical
cell and causes the transmission device to be inserted into the
subject so that a fluid path is connected between the fluid
reservoir and the subject. In some embodiments, such as when it is
desirable to have a long stroke on the button, the actions can be
performed sequentially using detents or partial mechanical stops
during travel of the button.
[0133] In some embodiments, a fluid delivery system can be adapted
for use as a sensor.
[0134] FIG. 17 shows an embodiment of a sensor system 300 including
a microprobe 302, a sensor 304, a pump 306 and a subject (e.g., a
human) 308. Microprobe 302 is in fluid communication with sensor
304 via a fluid path (e.g., tubing) 310, and the sensor is in fluid
communication with pump 306 via a fluid path (e.g., tubing)
312.
[0135] During use of system 300, pump 306 creates a suction or
partial vacuum that can remove a sample (e.g., a fluid sample, such
as a blood sample) from subject 308. The sample passes through
microprobe 302 (e.g., a needle or a microneedle) and along path 310
to sensor 304 (e.g., a blood glucose sensor), where one or more
species of interest (e.g., analytes of interest, such as glucose)
is measured. The sample then moves along path 312 to pump 306 and
exits system 300 via an exhaust 314 (e.g., a gas exhaust) and/or
exhaust 316 (e.g., a waste exhaust). Exhaust 314 and/or 316 can be
in fluid communication with, for example, a disposable bag.
[0136] In some embodiments, pump 306 is an electrochemical cell
that operates in reverse mode so that it removes oxygen present
between microprobe 302 and sensor 304 (e.g., in microprobe 302,
path 310, the sensor, path 312 and/or the pump) and exhausts via
exhaust 314. By using up this oxygen, pump 306 reduces the pressure
between microprobe 302 and sensor 304, thereby creating suction or
a partial vacuum and allowing the sample to be removed from subject
308. Because there is only about 20% oxygen in air, the suction
created by the electrochemical cell can be limited. An example of
an electrochemical cell is a symmetrical Pt/NAFION.RTM. fuel cell.
Examples of electrochemical cells are described above.
[0137] FIG. 18 shows an embodiment of a sensor system 320 that
includes a flow restriction device (e.g., a valve clamp) 322 and a
re-fill device (e.g., a re-fill valve) 324.
[0138] During use of system 320, pump 306 creates a suction or
partial vacuum that can remove a sample (e.g., a fluid sample, such
as a blood sample) from subject 308. The sample passes through
microprobe 302 and along a path 326 (e.g., tubing) to flow
restriction device 322. The sample then passes along a path 328
(e.g., tubing) to sensor 304. The sample then passes along a path
330 (e.g., tubing) to re-fill device 324. The sample then passes
along a path (e.g., tubing) 332 to pump 306, and then out of system
320 via exhaust 314 and/or 316.
[0139] Device 324 can be used to periodically (e.g., at
predetermined and/or timed intervals, and/or at intervals
determined in response to a signal, such as a measurement of the
amount of oxygen in fluid communication with path 330, path 332
and/or device 324) re-fill air into system 320, thereby allowing
continuous or semi-continuous extraction of fluid from subject 308
via microprobe 302. When device 324 is opened to re-fill air into
system 320, device 322 can be closed to prevent fluid communication
between subject 304 and sensor 304.
[0140] FIG. 19A shows an embodiment of oxygen values as a function
of time for system 320. FIGS. 19B and 19C show the corresponding
values of the position (i.e., open/closed) of devices 322 and 324,
respectively, as a function of time for system 320.
[0141] In other embodiments, more than one electrochemical cell can
be used to provide suction in an alternating pattern to provide
continuous or semi-continuous extraction of fluid from subject
308.
[0142] Pump 306 can be placed in various positions so long as it is
capable of forming suction or a partial vacuum as discussed above.
For example, in some embodiments, pump 306 is between microprobe
302 and sensor 304.
[0143] Combinations of embodiments can be used.
[0144] Therapeutic agents that can be used in the devices and
methods described herein include, for example, vaccines,
chemotherapy agents, pain relief agents, dialysis-related agents,
blood thinning agents, and compounds (e.g., monoclonal compounds)
that can be targeted to carry compounds that can kill cancer cells.
Examples of such agents include, insulin, heparin, morphine,
interferon, EPO, vaccines towards tumors, and vaccines towards
infectious diseases.
[0145] The device can be used to deliver a therapeutic agent to any
primate, including human and non-human primates. The device can be
used to deliver an agent, e.g., a therapeutic agent to an animal,
e.g., a farm animal (such as a horse, cow, sheep, goat, or pig), to
a laboratory animal (such as a mouse, rat, guinea pig or other
rodent), or to a domesticated animal (such as a dog or cat). The
animal to which the therapeutic agent is being delivered can have
any ailment (e.g., cancer or diabetes). It is expected that the
device may be most useful in treating chronic conditions. However,
the device can also be used to deliver a therapeutic agent (such as
a vaccine) to an animal that is not suffering from an ailment (or
that is suffering from an ailment unrelated to that associated with
the therapeutic agent). That is, the device can be used to deliver
therapeutic agents prophylactically.
[0146] The devices and methods of the invention can be used to
individually tailor the dosage of a therapeutic agent to a
patient.
[0147] The devices and methods of the invention can allow for
outpatient treatment with increased convenience, such as, for
example, without the use of an I.V.
[0148] Devices and methods described herein can be advantageous
because they can be used to promote maintenance of the
concentration of a therapeutic agent in a patient's plasma within a
safe and effective range. Moreover, the device can release
therapeutic agents in response to the concentration of an analyte
in the patient's system. Thus, the rate of drug delivery can be
appropriate for the patient's physiological state as it changes,
e.g., from moment to moment.
[0149] Other embodiments are within the claims.
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