# US 2011/0218516 A1 · Methods and Devices for Programmable Delivery of Microdoses of Liquid Drugs

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- Number: US 2011/0218516 A1
- Document ID: US20110218516A1
- Status: Published application
- Kind: A1
- Application number: 13/119,018
- Filed: 2009-09-14
- Published: 2011-09-08
- Earliest claimed: 2008-09-15
- Inventors: Leonid Grigorov
- Web page: https://patentgrep.com/patent/US20110218516A1

## CPC

- A61M 5/14248: {of the skin patch type}
- A61M 5/1456: {with a replaceable reservoir comprising a piston rod to be moved into the reservoir, e.g. the piston rod is part of the removable reservoir}
- A61M 5/16854: {by monitoring line pressure}
- A61M 5/16881: {Regulating valves}
- A61M 5/1413: {Modular systems comprising interconnecting elements}
- A61M 2005/14268: {with a reusable and a disposable component}
- A61M 2205/3355: Controlling downstream pump pressure
- A61M: DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY (introducing media into or onto the bodies of animals A61D7/00; means for inserting tampons A61F13/26; devices for administering food or medicines orally A61J; containers for collecting, storing or administering blood or medical fluids A61J1/05); DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY (surgery A61B; chemical aspects of surgical articles A61L); DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR {(Electrotherapy, e.g. producing anaesthesia by the use of alternating or intermittent currents A61N1/36021)}

## Abstract

Devices of this invention include replaceable cartridges for delivery of doses of fluids. Cartridges having a fluid supply reservoir comprising an expandable element are designed to be connected with non-disposable actuating module supplied with a sensor, a mechanism to apply a force to the fluid, thereby forcing a predetermined dose out of the reservoir, and a processor providing control outputs from a sensor system according to preprogrammed instructions. Methods of this invention include delivery of microdoses of fluids using devices of this invention.

## Claims

### Claim 1

A fluid delivery device, comprising:
(a) a replaceable cartridge located in a first housing, wherein the replaceable cartridge comprises:
a reservoir comprising at least one expandable element made of resilient material, said reservoir having at least two spatially separated sections connected so that hydraulic resistance between said two sections is not less than non-zero R1; and
a flow passage connecting an internal volume of said reservoir with at least one exit opening so that under conditions of fluid flow, hydraulic resistance to flow of said flow passage is not less than predetermined non-zero R2;
(b) an actuating module located in a second housing, said module comprising:
a driving force system; and
at least part of a sensor system, wherein said part of the sensor system is capable of producing an output associated with at least one geometric parameter of said expandable element;
(c) a connector to provide a temporary connection of said replaceable cartridge and said actuating module; and
(d) a programmable processor with fluid delivery instructions stored therein, said processor capable of acquiring said output of the sensor system and capable of producing an other output, said other output controlling the driving force system; whereas
when both housings are connected to each other, the driving force system is capable of applying a force changing over time to the fluid in the reservoir.

### Claim 2 (depends on 1)

The device of claim 1, wherein at least part of said processor is located in a third housing comprising:
a display; and
a system providing a exchange of data between said actuating module and said third housing.

### Claim 3 (depends on 1)

The device of claim 1, wherein the driving force system comprises at least one a mediatory element which, when said first and second housings are connected, said mediatory element operably transmits said force changing over time to a force receiving element of said reservoir in said replaceable cartridge.

### Claim 4 (depends on 3)

The device of claim 3, wherein both said mediatory element and said force receiving element are at least partially made of a ferromagnetic material.

### Claim 5 (depends on 3)

The device of claim 3, wherein both said mediatory element and said force receiving element each comprises a permanent magnet.

### Claim 6 (depends on 5)

The device of claim 5, wherein said magnets have an orientation such that the mediatory element applies said driving force remotely to said force receiving element.

### Claim 7 (depends on 1)

The device of claim 1, wherein said driving force system comprises a latch capable of switching between two stable states;
whereas in a first stable state the driving force applied to said force receiving element is a continuous compressive force applied to the fluid in said reservoir to urge said fluid out of said reservoir; and
whereas in a second stable state the driving force is a decompressive force applied to said fluid in the reservoir.

### Claim 8 (depends on 7)

The device of claim 7, wherein said latch comprises:
a permanently stressed spring to create said continuous compressive force;
at least one permanent magnet;
at least one electromagnet; and
a mechanism capable of switching a distance between two said magnets so that one stable state occurs at greater distance between said magnets, and
whereas said second stable state occurs at shorter distance between said magnets.

### Claim 9 (depends on 7)

The device of claim 7, wherein the actuating module further comprises a manual switch between said two stable states of said latch; and wherein said processor is programmed to initiate at least one signal to a patient.

### Claim 10 (depends on 9)

The device of claim 9, wherein said signal is at least one of visual, mechanical, and auditory.

### Claim 11 (depends on 1)

The device of claim 1, wherein said reservoir further comprises an additional section connected to said other two sections of said reservoir by a hydraulic element providing a resistance R0 so that R0 exceeds R1 when a compressive force is applied to a fluid in said reservoir, and more preferably R0 exceeds R1 at least one order of magnitude, and most preferably more than two orders of magnitude.

### Claim 12 (depends on 11)

The device of claim 11, wherein said hydraulic element is a pressure-dependent static hydraulic resistor capable of switching its resistance R0 so that R0 does not exceed R1 when a decompressive force is applied to the fluid.

### Claim 13 (depends on 1)

The device of claim 1, wherein said reservoir comprises an additional element made of resilient material, said element separating a movable piston from the internal volume of said reservoir, wherein said movable piston is adapted to transmit said driving force to said fluid.

### Claim 14 (depends on 13)

The device of claim 13, wherein said additional element is capable of expanding into a cavity made in said movable piston when fluid in said reservoir is subjected to an internal pressure exceeding external pressure.

### Claim 15 (depends on 14)

The device of claim 14, wherein said additional element is adapted to eliminate direct correspondence between displacement of said movable piston and a dose of the fluid delivered to said exit opening.

### Claim 16 (depends on 1)

The device of claim 1, wherein a ratio of R1/R2 is greater than about 0.05 and less than about 200, more desirably said ratio is in between about 0.25 and about 40, and most desirably said ratio is in between about 1 and about 10.

### Claim 17 (depends on 1)

The device of claim 1, wherein said flow passage connecting said internal volume of said reservoir with at least one exit opening further comprises a pressure-dependent valve capable of switching to an open state under conditions of fluid flow so that hydraulic resistance of said open valve is less than R2 at least by one order of magnitude when a pressure drop applied to said valve is equal or exceeds a predetermined value Pop, and wherein said pressure dependent valve is capable of switching into a closed state when said pressure drop is below such Pcl which is either equal or less than said Pop, whereas the hydraulic resistance of said closed valve exceeds R2 by at least one order of magnitude, and most desirable it exceeds R2 by more than two orders of magnitude.

### Claim 18 (depends on 1)

The device of claim 1, wherein at least one element of said sensor system comprises a piezoelectric sensor, and when said first and said second housings are connected, the device further comprises a direct or an indirect mechanical connection of said piezoelectric sensor with an external surface of said reservoir.

### Claim 19 (depends on 1)

The device of claim 1, wherein when said first and said second housings are connected together, the sensor system comprises at least one such electrically conducting area which is capable of forming a non-contact capacitor sensor so that said electrically conducting area is located in proximity to at least one other electrically conducting area which is attached to said reservoir and capable of relocating in response to deformation of said expandable element.

### Claim 20 (depends on 1)

The device of claim 1, wherein said sensor system comprises a magnetic detector adapted to form a non-contact magnetic sensor when said first and said second housings are connected, so that said magnetic detector is located in proximity to either a magnetic substance or a magnetized substance attached to said reservoir and capable of relocating in response to deformation of said expandable element.

### Claim 21 (depends on 1)

The device of claim 1, wherein at least one element of said sensor system is housed in said actuating module, said one element of said sensor system comprising a non-contact optical sensor comprising:
a light emitter directed onto said replaceable cartridge when said first and said second housings are connected together, and
at least one detector adapted to receive light emitted by said light emitter, either reflected by said replaceable cartridge or transmitted through said reservoir.

### Claim 22

A replaceable cartridge for a fluid delivery device, comprising:
(a) a reservoir adapted to be filled with a fluid, said reservoir having at least two spatially separated sections, a first section of said two sections comprising at least one expandable element made of resilient material, said two sections connected to each other so that under conditions of fluid flow, hydraulic resistance between them is not less than non-zero R1;
(b) a flow passage connecting at least one exit opening with an internal volume of said first section which comprises said at least one expandable element made of resilient material so that under conditions of fluid flow, hydraulic resistance of said flow passage is not less than predetermined non-zero R2; and
(c) at least a portion of a connector to at least temporarily operably connect said cartridge with a housing containing an actuator;
wherein said connector provides that relative locations of said reservoir and said housing containing said actuator to permit transfer a force from said actuator to internal surface of a second section of said two sections of said reservoir.

### Claim 23 (depends on 22)

The replaceable cartridge of claim 22, wherein under flow conditions, the ratio R1/R2 exceeds about 0.05 and is less than about 200, more desirably said ratio is in between about 0.25 and about 40, and most desirably said ratio is in between about 1 and about 10.

### Claim 24

An actuator module for a fluid delivery device, comprising:
(a) a housing having:
a driving force system; and
at least part of a sensor system, wherein said part of the sensor system is capable of producing an output associated with at least one geometric parameter of an expandable element of a replaceable cartridge having a reservoir;
(b) at least a portion of a connector to provide a temporary operable connection to a replaceable cartridge having a reservoir adapted to hold said fluid; and
(c) a programmable processor with fluid delivery instructions stored therein, said processor capable of acquiring said output of the sensor system and capable of producing an other output, said other output controlling said driving force system; wherein
when said actuator and said replaceable cartridge are connected to each other, said driving force system is capable of applying a force changing over time to a fluid in the reservoir.

### Claim 25 (depends on 24)

The actuator of claim 24, wherein said sensor system comprises at least one such electrically conducting area which is capable of forming a non-contact capacitor sensor when said actuator and a replaceable cartridge comprising a reservoir having an expandable element made of resilient material are connected, so that said electrically conducting area is located in proximity to at least one other electrically conducting area which is attached to said reservoir and capable of relocating in response to deformation of said expandable element.

### Claim 26 (depends on 24)

The actuator of claim 24, wherein said sensor system comprises a magnetic detector adapted to form a non-contact magnetic sensor when said actuator and a replaceable cartridge comprising a reservoir having an expandable element made of resilient material are connected, so that said magnetic detector is located in proximity to either a magnetic substance or a magnetized substance attached to said reservoir and capable of relocating in response to deformation of said expandable element.

### Claim 27 (depends on 24)

The actuator of claim 24, wherein at least one element of said sensor system is housed in said actuating module, said one element of said sensor system comprising a non-contact optical sensor comprising:
a light emitter directed onto said replaceable cartridge when said actuator and said replaceable cartridge are connected together, and
at least one detector, wherein said detector is adapted to receive light emitted by said light emitter, either reflected by said replaceable cartridge or transmitted through said reservoir.

### Claim 28 (depends on 1)

The actuator of claim 1, wherein said processor has instructions to calculate a dose of fluid delivered according to the following formula:
D

(
t
)
=
∫
0
t

F

(
t
)



t
=
∫
0
t

Δ


P
ind

(
t
)
R
exit



t

### Claim 29 (depends on 1)

The actuator of claim 1, wherein said processor has instructions to calculate a dose of fluid delivered according to the following formula:
D

(
t
)
=
1
R
exit

∫
0
t

Δ


P
ind

(
t
)



t
=
αβ
R
2

∫
0
t

S

(
t
)



t
.

### Claim 30 (depends on 1)

The actuator of claim 1, wherein said processor has instructions to calculate a dose of fluid delivered according to the following formula:
D

(
t
)
=
P
0
R
2

(
t
-
T
up
2
)
=
α


β


S
R
2

(
t
-
T
up
2
)
.

### Claim 31 (depends on 1)

The actuator of claim 1, wherein said processor has instructions to calculate a dose of fluid delivered according to the following formula:
D

(
t
)
=
α


β
R
2

∫
0
t



t


S

(
t
)
≅
α


β
f
0


R
2

∑
k
=
1
L

(
t
)


S

(
t
k
)
=
D

(
t
L
)
.

### Claim 32 (depends on 1)

The actuator of claim 1, wherein said processor has instructions to calculate a time needed to deliver a dose of fluid according to the following formula:
D
0

R
2
α


β


S
+
(
T
up
-
T
down
2
)
=
T
c
.

### Claim 33 (depends on 1)

The actuator of claim 1, wherein said processor has instructions to calculate a time needed to deliver a dose of fluid according to the following formula:
T
c
=
τ
act

D
0

R
1

S
atm
(
τ
oc
-
τ
act
)

P
atm

S
(
0
)
=
t
end
-
t
st
.

### Claim 34 (depends on 1)

The actuator of claim 1, wherein said processor has instructions to calculate a time needed to deliver a dose of fluid according to the following formula:
T
c
+
τ
act

S
1
S
max

exp

{
t
1
-
T
c
τ
act
}
=
t
1
+
τ
act

S
1
S
max
+
α
ini

τ
act

D
0
P
val

(
1
-
τ
act
τ
oc
)

(
S
max
S
1
-
1
)
.

### Claim 35 (depends on 1)

A method for a delivering of a dose of a fluid, comprising the steps:
(a) providing a device of claim 1;
(b) introducing said fluid into said reservoir;
(c) initiating a non-zero force urging said fluid out of the reservoir;
(d) acquiring at least one output from said sensor system associated with at least one geometric parameter of said resilient element;
(e) calculating a time tend, comprising treating said acquired output by a processor executing commands based upon instructions stored in said processor; and
(f) terminating said force at tend.

### Claim 36 (depends on 35)

The method of claim 35, further comprising the steps:
(i) before step (c) subjecting said fluid in the reservoir to a sufficiently low pressure to prevent said fluid from flowing out of said exit opening, said pressure in the reservoir close to an external pressure Pext;
(ii) the step (c) further comprising producing at least one starting electric output at a predetermined moment tst, said starting output resulting in producing:
said force urging said fluid out of said reservoir; and
subjecting said expandable element to a pressure Pind(t) within the range defined by the expression: Pmax+Pext>Pind(t)>Pmin+Pext wherein 25>Pmax/Pmin>1;
(iii) treating said output of said sensor, comprising determining a pressure difference Pind(t)−Pext, and further comprising determining a period Tc satisfying the condition Tc=tend−tst wherein Tc is of such duration of said force urging said fluid out of said reservoir to provide an equality of said predetermined dose and an actual dose delivered, said actual dose being an integral found by integrating over time from time tst of a ratio having a numerator being said pressure difference, and a denominator being a parameter expressing hydraulic resistance Rexit of said flow passage connecting the reservoir with said exit opening;
(v) the step (f) comprises producing at least one ending electric output at tend=Tc+tst, wherein said ending output results in either decreasing the force or changing a direction of the force or both so that the pressure of the fluid in said first section can relax in time up to about its initial value before step (c).

### Claim 37 (depends on 35)

The method of claim 35, wherein under flow conditions, hydraulic communication between said two spatially separated sections of the reservoir has a resistance R1≧0.05 R2;
wherein step (d) comprises acquiring at least two outputs from said sensor system;
wherein said step (e) further comprises:
determining an actual hydraulic resistance Rexit of said flow passage connecting the reservoir with said exit opening;
setting said denominator equal said actual Rexit;
producing an alarm signal if said actual Rexit exceeds a predetermined level; or
substituting said actual Rexit into an analytic expression of said integral if said
actual Rexit does not exceed said predetermined level.

### Claim 38 (depends on 35)

The method of claim 35, wherein said flow passage connecting the reservoir with said exit opening is further supplied with an element switching hydraulic resistance at a predetermined pressure drop Pop;
wherein step (d) comprises acquiring at least five outputs and desirably more than five outputs from said sensor system;
said treating of step (e) further comprising:
calibrating said device delivering the fluid;
checking current performance of components of said device;
determining the amount of the fluid remaining in the reservoir; and
producing one or more of a report and an alarm signal to inform a user if said amount of remaining fluid is below a predetermined amount or a malfunction is detected that cannot be self-compensated by said steps determining of the time tend.

### Claim 39 (depends on 35)

The method of claim 35, wherein step (c) further comprises creating a first emergency signal if after said starting electric output said force urging the fluid out of said reservoir is not produced, said first emergency signal resulting in the at least one of:
(i) prompting a patient to initiate a manual application of said force to said reservoir;
(ii) determining an actual starting time tst, when an appearance of manually created non-zero force urging the fluid out of said reservoir is detected by said sensor system;
(iii) said ending electric output of step (e) results in creating such second emergency signal at the moment tend which recommends the patient to terminate manually said application of said force, whereas both said first and second emergency signals are visual, mechanical or acoustic signals.

### Claim 40 (depends on 35)

The method of claim 35, wherein said predetermined R2 is substituted into said denominator in order to fulfill the role of said parameter expressing said Rexit, and said integral is proportional to a sum of all said outputs of said sensor system acquired since the time tst.

### Claim 41 (depends on 35)

The method of claim 35, further comprising:
transmitting at least one output of at least one bio-medical device analyzing a physiological feature of a patient to a control system, and
correcting the predetermined dose delivered by said device according to said transmitted output of said biomedical device.

### Claim 42

A method for a delivery of a predetermined dose of a fluid, comprising the steps:
(a) providing a device comprising a replaceable cartridge comprising a reservoir filled with the fluid, said reservoir having both at least one element made of resilient material and at least one exit opening, and a separable actuator module connected with said cartridge, said actuator module capable of switching between at least two stable states, wherein only one of two said states results in a continuous compressive force applied to the fluid;
(b) switching said module into a stable state which results in producing of a continuous compressive force applied to the fluid in said reservoir;
(c) acquiring at least one output from a sensor system associated with at least one geometric parameter of said resilient element;
(d) calculating a time tend, comprising treating said acquired output by a processor capable of executing commands stored in said processor; and
(e) switching said module into said other stable state at tend.

### Claim 43

A processor for a drug-delivery system, comprising:
said processor capable of processing computer implemented instructions for calculating an amount of fluid to be delivered, said instructions comprising a formula selected from the group consisting of equations 9 (Eq. 9), Eq. 11, Eq. 12, Eq. 13, Eq. 14, and Eq. 30.

### Claim 44

A computer readable medium, comprising:
a physical medium having computer implementable instructions thereon for calculating an amount of fluid to be delivered, said instructions comprising a formula selected from the group consisting of equations 9 (Eq. 9), Eq. 11, Eq. 12, Eq. 13, Eq. 14, and Eq. 30, wherein said medium is in physical form.