Patent Publication Number: US-11642456-B2

Title: Hydraulically actuated pump for fluid administration

Description:
CROSS REFERENCE TO RELATED APPLICATIONS 
     The present application is a continuation of U.S. application Ser. No. 15/299,678 filed Oct. 21, 2016, which is a continuation of U.S. application Ser. No. 14/809,436 (now U.S. Pat. No. 9,511,187), filed on Jul. 27, 2015 which is a continuation of U.S. application Ser. No. 12/762,307 (now U.S. Pat. No. 9,125,983), filed Apr. 17, 2010 which is a continuation of U.S. application Ser. No. 12/336,363 (now U.S. Pat. No. 8,070,726), filed Dec. 16, 2008, which is a continuation of U.S. application Ser. No. 10/831,354 (now U.S. Pat. No. 7,530,968), filed Apr. 23, 2004, which claims the benefit of U.S. Provisional Application No. 60/465,070, filed on Apr. 23, 2003, all of which are expressly incorporated herein by reference in their entirety. 
    
    
     BACKGROUND OF THE INVENTION 
     The systems and methods described herein relate to a hydraulic pump system that can be used in medicament pumps for injectables, specifically to low-cost, miniature, single-use pump systems. 
     Various people, such as diabetics, require continuous or near continuous infusion of certain drugs or medicines (broadly referred to herein as medicaments). 
     Many attempts have been made to provide continuous or near continuous dosing of medicaments, such as insulin, using pump systems. For example, one known pumping technique uses gas generated by various means to advance a plunger in a syringe, thereby injecting the medicament through an infusion set. The infusion sets is a means for conveying medicament through the patient skin and may comprise a standard needle, a microneedle, a microneedle array, and a catheter and cannula system. 
     Although these systems can work quite well, patients using these systems, particularly in continuous dose mode, need to monitor closely or deactivate these devices under circumstances where the ambient air pressure may vary greatly, such as in an airplane. In particular, patients need to be careful that the infusion pump does not deliver a dangerously increased dosage in airplanes at high altitudes, where the ambient pressure is significantly reduced. 
     What is needed is a simple, inexpensive, single-use only medicament pump system. Such a system must have the capacity to provide variable dosing under patient control as well as safety and consistency in the metered dose at any range of ambient pressures or operating conditions. 
     SUMMARY 
     In an exemplary embodiment, the systems described herein include, inter alia, a pump device, which may be single use, and that provides for sustained low volume (preferably high potency) medicament application, such as for use by insulin-dependent diabetics and other patients. The pump may employ as an actuator a spring-compressed bellows crank, hinged plate, paired roller set, or other peristaltic mechanisms to force a volume of hydraulic fluid through a flow restrictor, such as an aperture, thereby expanding one chamber of a two chamber hydraulic cylinder. The second (fluid storage) chamber, containing a medicament, is vented through a conventional orifice as the hydraulic chamber is expanded by introduction of additional hydraulic fluid. The medicament thus expelled may then be injected or infused into a patient via any suitable injection and/or infusion mechanism. 
     The restrictor, in one embodiment, may be a hydraulic fluid aperture and may be a fixed micro-aperture of approximately 0.1-10 μm in diameter, or about 1-5 μm in diameter, and one ten-thousandths of an inch (0.0001″, or about 2.5 μm) in diameter. In another embodiment, the hydraulic fluid aperture may be an adjustable aperture providing either continuous orate p-wise diameter variations of approximately 0.1-10 μm in diameter, or about 1-5 μm in diameter, preferably one ten-thousandths of an inch (0.0001″, or about 2.5 μm) in diameter. Combined with a hydraulic fluid of appropriate viscosity, the micro-aperture provides precise pressure regulation that is insensitive to ambient pressure or other environmental conditions. This insensitivity, in turn, allows for highly accurate dosing and dose regulation under a wider range of conditions than previously seen in the arts. 
     Thus one aspect of the invention provides a hydraulically actuated fluid delivery system for sustained delivery of a liquid component, comprising: a pump chamber, and a fluid storage chamber having an orifice and being functionally connected to said pump chamber by a moveable barrier; a hydraulic fluid reservoir for storing a high viscosity fluid, said reservoir being connected to said pump chamber, via a restrictor, such as an aperture, which may be less than 10 μm in diameter, and the largest insoluble particle, if any, in said hydraulic fluid may optionally be no more than the size of said aperture; and, an actuator functionally connected to said hydraulic fluid reservoir to cause said hydraulic fluid to flow into said pump chamber through said aperture, thereby expanding the volume of said pump chamber, displacing said moveable barrier and causing a quantity of said liquid component stored in said fluid storage chamber to be delivered at a sustained rate. 
     In one embodiment, the pump chamber and the fluid storage chamber are both within a compartment. 
     In one embodiment, the moveable barrier is a piston or plunger plate. 
     In one embodiment, the movement of the piston or plunger plate is guided such that the piston or plunger plate does not flip or generate leakage when moving. 
     In one embodiment, the moveable barrier is one or more deformable membranes separating the pump and the fluid storage chambers. 
     In one embodiment, the liquid component is a medicament, and the wall of the fluid storage chamber is composed of bio-inert materials. 
     In one embodiment, the aperture has a fixed size. 
     In one embodiment, the aperture is adjustable in size to allow variable hydraulic pressure. 
     In one embodiment, the size of the aperture is adjusted by a thumbwheel control/dial. 
     In one embodiment, the thumbwheel control activates a miniaturized valve or iris device. 
     In one embodiment, the quantity of said liquid component is expelled at a rate selected from: about 100 nl-1 μl per minute, about 1-10 μl per minute, or about 10-100 μl per minute. 
     In one embodiment, the actuator is a miniaturized bellows crank, paired rollers, one or more piezoelectric elements, a ratchet or stepper motor driven unit, a two-plate hinged peristaltic mechanism, an electrically driven or piezoelectric mechanism. 
     In one embodiment, the actuator employs one or more external springs having a constant spring coefficient over its full range of motion. 
     In one embodiment, the fluid delivery system further comprises a connective passage linking the hydraulic fluid reservoir to the pump chamber through the aperture. 
     In one embodiment, the liquid component is a solution of a medicament. 
     In one embodiment, the medicament is insulin, an opiate, a hormone, a psychotropic therapeutic composition. 
     In one embodiment, the orifice of the fluid storage chamber is connected to an infusion set for delivering the liquid component to a patient. 
     In one embodiment, the patient is a mammalian patient selected from human or non-human animal. 
     In one embodiment, the infusion set is a needle, a lumen and needle set, a catheter-cannula set, or a microneedle or microneedle array attached by means of one or more lumens. 
     In one embodiment, the pump is manufactured with inexpensive material for single-use. 
     In one embodiment, the inexpensive material is latex-free and is suitable for use in a latex-intolerant patient. 
     In one embodiment, the inexpensive material is disposable or recyclable. 
     In one embodiment, the inexpensive material is glass or medical grade PVC. 
     In one embodiment, the fluid delivery system further comprises a second hydraulic reservoir. 
     In one embodiment, the second hydraulic reservoir is separately and independently controlled by a second actuator. 
     In one embodiment, the second hydraulic reservoir and the original reservoir are both connected via a common connective passage and through the aperture to the pump chamber. 
     In one embodiment, the second hydraulic reservoir is connected to the pump chamber through a second aperture. 
     In one embodiment, one of the two hydraulic reservoirs is used for sustained delivery of the liquid component, and the other of the two hydraulic reservoir is used for a bolus delivery of the liquid component at predetermined intervals. 
     In one embodiment, both apertures are independently adjustable. 
     In one embodiment, one of the two apertures are adjustable. 
     In one embodiment, the sustained delivery is over a period of: more than 5 hours, more than 24 hours, more than 3 days, or more than one week. 
     In one embodiment, the viscosity of the hydraulic fluid is at least about ISO VG 20, or at least about ISO VG 32, or at least about ISO VG 50, or at least about ISO VG 150, or at least about ISO VG 450, or at least about ISO VG 1000, or at least about ISO VG 1500 or more. 
     Another aspect of the invention provides a hydraulically actuated pump system comprising: a pump chamber functionally connected to a moveable barrier; a hydraulic fluid reservoir for storing a high viscosity fluid, said reservoir being connected to said pump chamber via an aperture of less than 10 and in some embodiments less than 3 μm in diameter, and the largest insoluble particle, if any, in said hydraulic fluid is no more than the size of said aperture; and, an actuator functionally connected to said hydraulic fluid reservoir to cause said hydraulic fluid to flow into said pump chamber through said aperture, thereby expanding the volume of said pump chamber, displacing said moveable barrier. 
     Another aspect of the invention provides a method of administering a medicament, comprising: compressing a hydraulic fluid reservoir to force said hydraulic fluid through a connection means; passing said hydraulic fluid through an adjustable aperture into a pump chamber, wherein said pump chamber is separated from an adjacent fluid storage chamber by a moveable barrier and wherein said fluid storage chamber is filled with a medicament; displacing said moveable barrier into said fluid storage chamber by filling said pump chamber with said hydraulic fluid, wherein said displacing causes a quantity of said medicament to be expelled from said fluid storage chamber through an output orifice. 
     In one embodiment, the passing is regulated by the adjustable aperture varying the flow of the hydraulic fluid and thus the quantity of the medicament expelled through the orifice. 
     In one embodiment, the method further comprises injecting a quantity of the medicament into a patient through an infusion set connected to the orifice. 
     In one embodiment, the compressing employs peristaltic compaction of the reservoir at a constant rate. 
     In one embodiment, the compressing employs peristaltic compaction of the reservoir at a variable rate. 
     In one embodiment, the method further comprises rapidly compressing a second hydraulic reservoir fluidly connected to the pump chamber to displace the moveable barrier and thus cause a bolus of the medicament to be expelled through the orifice. 
     In one embodiment, the method further comprises passing the hydraulic fluid from the second hydraulic reservoir through a second aperture into the pump chamber. 
     It should be understood that the individual embodiments described above are meant to be freely combined with one another, such that any particular combination may simultaneously contain two or more features described in different embodiments whenever appropriate. In addition, all embodiments described for one aspect of the invention (such as device) also applies to other aspects of the invention (e.g. method) whenever appropriate. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       The present disclosure may be better understood and its numerous features and advantages made apparent to those skilled in the art by referencing the accompanying drawings. 
         FIG.  1    is a high-level functional schematic drawing of a hydraulic pump system, according to one embodiment of the invention. 
         FIG.  2    is a high-level functional schematic drawing of a fluid delivery system comprising the hydraulic pump system, according to one embodiment of the invention. 
         FIGS.  3 A- 3 B  are schematic drawings illustrating one of the advantages of the fluid delivery system comprising the hydraulic pump system. 
         FIGS.  4 A- 4 C  are high-level functional schematic drawings of several fluid delivery system with various barriers. 
         FIG.  5    is a high-level functional schematic drawing of an alternative fluid delivery system, according to one embodiment of the invention. The alternative fluid delivery system in this embodiment features arrayed microneedles on an transdermal patch. 
         FIGS.  6 A- 6 C  are high-level functional schematic drawings of several actuator mechanisms that can be used with the fluid delivery system employing the hydraulic pump, according to one embodiment of the invention. 
         FIG.  7    is a high-level functional schematic drawing of the adjustable control for aperture opening size. 
         FIGS.  8 A- 8 B  are a high-level functional schematic drawings of several fluid delivery system with multiple actuators, according to one embodiment of the invention. 
     
    
    
     The use of the same reference symbols in different drawings indicates similar or identical items. 
     DETAILED DESCRIPTION 
     Described herein is a drug delivery system, uses thereof and methods for making the same. In one embodiment, the systems described herein provide pump devices for delivering a medicant, agent, fluid or some other material to a patient, typically through the skin. To this end, the system includes an actuator that operates on a reservoir of viscous fluid. The actuator causes the viscous fluid to apply pressure to the medicant being delivered. The viscous fluid is controlled by a restrictor that, in one practice, controls the rate of flow of the fluid so that an uneven application of pressure to the reservoir is mediated, and a controlled rate of fluid movement is achieved. This controlled rate of fluid movement is employed to cause a medicant to be delivered at a selected rate. 
     In one embodiment the systems and methods described herein include a hydraulic pump system that may include a chamber (the “pump chamber”) that can be filled with high viscosity fluid, which, when forced by pressure, enters the pump chamber through a restrictor, for example an opening/aperture, which is dimensionally adapted to control the rate of fluid flow therethrough. In one embodiment, the aperture is about the size of a 1-100 μm diameter circle (but not necessarily circular in shape). However, those of skill in the art will understand that any suitable restrictor may be employed, and that the size and the shape of the restrictor can vary to achieve the desired flow rate of the fluid being mediated under the expected conditions, including temperature and ambient pressure. 
     The increase in volume of the working fluid inside the pump chamber triggers the movement of a barrier mechanism, which can be coupled to other devices, such as a second (fluid storage) chamber. 
     One advantage of the instant hydraulic pump system resides with the restrictor through which the high viscosity working fluid flows. For example, when the restrictor is an aperture, when subjected to varying pressure, the working fluid enters the chamber through the aperture at a slow, yet relatively constant rate, thus mostly eliminating the potentially large variations in the force generating the pressure, while ensuring a substantially less variable expansion in volume of the working fluid in the chamber. This in turn leads to a relatively smooth and constant movement of the coupled barrier mechanism. 
     An additional advantage of the hydraulic pump system is that its relatively low requirement for a constant pressure source, or its high ability to tolerate relatively large variations in force generated by the pressure source. This is especially useful in manufacturing simple and inexpensive devices, such as single-use, disposable devices for medical use. 
     Partly because of the over-pressure employed in the hydraulic pump system, a further advantage is that the hydraulic pump is relatively insensitive to environmental changes, such as ambient temperature, altitude, or external pressure. 
     An illustrative embodiment of the hydraulic fluid system described herein is shown in the high-level functional drawing of  FIG.  1   . The pump chamber  110  may be shaped like, but is not limited to, a cylinder. The hatched lines represent a moveable barrier  130 , which may (but need not (o) be at the distal end of aperture  152 . Hydraulic fluid  112  enters aperture  152  on pump chamber wall  150  into pump chamber  110 , optionally via a connective passage  116 . 
     As used herein, the term “ultrapure” is understood to encompass, although not be limited to, a fluid wherein the largest insoluble impurity particle in the working fluid is smaller than the aperture size (which may be for example about 2-3 μm in diameter, but could be smaller or larger, and may be adjustable). In those embodiments wherein the restrictor is an aperture, the aperture need not be circular in shape, and could be an oval, a square, a rectangle, a triangle, a polygon, or irregular in shape. In those embodiments wherein the restrictor is a tube, valve, sieve, or other mechanism or combination of mechanisms, the size and shape of the restrictor may be determined empirically by testing the fluid flow of selected fluids at conditions of interest. In one particular embodiment, the largest impurity particle is no more than 1 mm in diameter, or no more than 500 nm in diameter, or no more than 100 nm in diameter. In addition, the total amount of insoluble impurity particle is less than 0.1%, or 0.01%, or 0.001% in volume. 
     Viscosity is ordinarily expressed in terms of the time required for a standard quantity of the fluid at a certain temperature to flow through a standard orifice. The higher the value, the more viscous the fluid. Since viscosity varies inversely with temperature, its value is less meaningful unless accompanied by the temperature at which it is determined. As used herein, “high viscosity” means the working fluid has a viscosity grade of at least about ISO VG 20, or at least about ISO VG 32, or at least about ISO VG 50, or at least about ISO VG 150, or at least about ISO VG 450, or at least about ISO VG 1000, or at least about ISO VG 1500. 
     The hydraulic pump system can be employed in a fluid delivery system that can be manufactured inexpensively, and could take advantage of the slow, yet relatively constant delivery rate associated with the hydraulic pump system. Partly due to the slow rate of delivery, the fluid delivery system can be used to continuously deliver a fluid over a long period of time, e.g. 6 hrs, 12 hrs, 1 clay, 3 days, 5 days, 10 days, one month, etc. The fluid delivery system comprises the hydraulic pump, coupled to a separate chamber for storing fluid to be delivered (the “fluid storage chamber” or “fluid chamber” in short). There could be various mechanisms coupling the movement of the barrier mechanism in the hydraulic pump to the fluid chamber, such that a small amount of fluid (ideally equal to, or at least proportional to the amount of the working fluid entering the hydraulic pump chamber) is expelled from the fluid chamber, through one or more orifice, in response to the movement of the barrier. 
     One embodiment of the fluid delivery system is illustrated in a high-level schematic drawing in  FIG.  2    (see detailed description below). This type of fluid delivery system/device can be used for a broad range of applications, including but are not limited to biomedical research (e.g. microinjection into cells, nuclear or organelle transplantation, isolation of single cells or hybridomas, etc.), and clinical applications (administration of medicaments, etc.). 
     For example, to provide a low level or variable dose of medicine over a long period of time (e.g., hours or even days), the fluid delivery system may form a portion of a single-use dispenser for a medicament to be applied through any of the standard infusions sets available on the market today or likely to be available in the future. The fluid delivery system, formed in some embodiments as low-cost plastic parts, may comprise a hydraulic cylinder containing two chambers, one function as the pump chamber described above, the other the fluid chamber for storing medicaments. In those embodiments, the hydraulic cylinder may be configured similarly to most conventional hydraulic cylinders, and the wall, especially the inner wall of at least the chamber for storing a liquid medicament to be delivered, may be composed of bio-inert and inexpensive materials. 
     The following description is for principal illustration only and should not be construed as limiting in any respect. Various illustrative alternative embodiments are described further below. 
     Hydraulic cylinder  100 , as described in  FIG.  2   , consists of two chambers,  110  and  120 . Chamber  110  (corresponding to the pump chamber) is filled by hydraulic working fluid  112  from a hydraulic reservoir  114 . Filling is accomplished by means of a connective passage  116 , such as (but not limited to) a tube or lumen either flexibly or rigidly connecting hydraulic reservoir  114  and hydraulic cylinder  100 . As hydraulic fluid  112  is forced out of reservoir  114  by actuator  135  (consisting, in an exemplary embodiment, of peristaltic compression plates  135 A and  135 B and hinge  135 C), chamber  110  fills with hydraulic fluid expanding its volume and thus forcing piston element  130  (barrier mechanism) into chamber  120  (corresponding to the fluid chamber). The dotted lines in the actuator and the piston in  FIG.  2    represent the later-in-time position of a plate-hinge actuating mechanism, and the later-in-time position of the barrier/piston. 
       FIGS.  3 A- 3 B  are schematic diagrams illustrating one advantage of the fluid delivery system, e.g., its ability to tolerate relatively large variations in force generating the over-pressure, to create a relatively constant fluid delivery rate over time or distance traveled by the barrier piston. It is apparent that without the hydraulic pump system, any direct use of force to expel fluid in the fluid chamber will be hard to control, and will be subjected to a large variation in delivery rate of the fluid ( FIG.  3 A ). In contrast, with the hydraulic pump, the delivery rate is much more constant ( FIG.  3 B ). 
     Chambers  110  and  120  can be, but are not necessarily separate, physical chambers, since both chambers can exist within the confines of a hydraulic cylinder such as the one in  FIG.  2    (hydraulic cylinder  100 ). The chambers are separated by a moveable barrier, such as the piston element  130  in  FIG.  2   , where piston  130  may be a fluid-tight barrier that prevents hydraulic fluid  112  from entering the second medicament fluid storage chamber  120 . However, the invention is not limited in the type of hydraulic cylinder  100  or the contours, dimensions or finishes of the interior surfaces of cylinder  100 , chamber  110 , or chamber  120 . Furthermore, the invention is not limited to particular configurations of piston element  130 . The following description illustrates several of many possible alternative embodiments that can be employed in the subject fluid delivery system. 
     In one embodiment, as shown in  FIG.  4 A , the piston element  130  in  FIG.  2    is replaced by a flexible membrane  132  separating the pump chamber  110  and the fluid chamber  120 . The flexible membrane can expand in response to the increased pressure from the pump chamber  110 , due to the increase in volume of the working fluid entering the pump chamber  110  through aperture  152 . This in turn expels fluid from the fluid chamber  120  via orifice  140 . 
     In another embodiment, as shown in  FIG.  4 B , chambers  110  and  120  may each have a separate wall unit  134  and  136 , respectively (such as expandable bags made from flexible materials). By virtue of being within the limited confinement of cylinder  100 , the expansion in volume of chamber  110  necessarily leads to the decrease in volume of chamber  120 , creating a force to expel liquid from chamber  120  via orifice  140 . 
     In yet another embodiment, as shown in  FIG.  4 C , the pump chamber  110  and the fluid chamber  120  may be separated from each other, but are mechanically coupled through a barrier mechanism  138  that transmits movements in pump chamber  110  to that in the fluid chamber  120 . The coupling mechanism  138  can either augment or diminish the magnitude of the initial movement in the pump chamber  110 , such that the corresponding movement in the fluid chamber  120  is increased, or decreased, respectively, resulting in expelling a larger or smaller amount of medicament fluid from the fluid chamber  120 . For example, the coupling mechanism  138  can be two pistons linked by a shaft, as shown in  FIG.  4 C . In one embodiment, the fluid chamber  120  may be detached from the pump chamber  110 , so that a new fluid chamber ( 120 ′, not shown) may be re-attached. 
     As noted above, chamber  120  is to be initially filled with a quantity of liquid component to be delivered, such as a medicament. In the case of a medicament, the quantity would typically be determined by a medical professional in order to provide the necessary dosing over a pre-determined period of time. The volume of the fluid chamber may be about 100 μl, 500 μl, 1 ml, 3 ml, 5 ml, 10 ml, 30 ml, 50 ml, 100 ml or more. 
     The depicted hydraulic cylinder  100  in  FIG.  2    can be further connected to an infusion set  160  through orifice  140  at the distal end of chamber  120  (distal here meaning the end of chamber  120  distant from piston  130 ). In other words, the output orifice  140  of hydraulic cylinder  100  is on the opposite end of the cylinder from hydraulic fluid input aperture  152 , as one would commonly expect in a hydraulic system. However, this is merely one of the preferred designs. The output orifice  140  could be located on the wall of cylinder  100  at the chamber  120  portion if desired (see  FIG.  5    below). 
     Attached to orifice  140 , in some embodiments, is an infusion device or “set”  160  selected from any of the infusion means conventionally known and used in the medical arts. Examples of infusion devices include: a needle, such as depicted in  FIG.  1   ; a lumen and needle set; a catheter-cannula set; or a microneedle or microneedle array attached by means of one or more lumens. One of ordinary skill in the art will readily appreciate that many devices exist to convey medicaments into a body. Accordingly, the invention is not limited in the types of infusion or injection devices used therewith. 
     In an illustrative embodiment, as shown here in a high-level schematic drawing in  FIG.  5   , the fluid delivery system is affixed to a delivery area of a patient, e.g. skin  200 , by an adhesive means, such as a transdermal patch. The fluid chamber  120  is connected to a microneedle or an array of microneedles  180 , such as those described in U.S. Pat. No. 6,503,231 (incorporated herein by reference). Unlike what is shown in  FIG.  5   , the microneedle(s) need not completely enter the skin layer  200 . To achieve a low profile, both the pump chamber  110  and the fluid chamber  120  may be flat in shape (rather than shaped like a cylinder), and the outer-surfaces may hug the contour of the attached skin layer  200 . The orifice(s) (not shown) connecting the fluid chamber and the microneedle(s) preferably opens on a side-wall of the fluid chamber  120 . Alternatively, a connective passage may link the orifice on fluid chamber  120  to the microneedle or microneedle(s) array. Barrier  130  and aperture  152  are as described above. Also shown is one embodiment of the actuator, where plates  135  actuated by spring mechanism squeeze the hydraulic fluid reservoir  114  to inject hydraulic working fluid into the pump chamber  110 . Other actuators, such as those described in other parts of the specification, may be adapted for use in this embodiment. 
     As exemplified in  FIG.  2   , in operation, the fluid (e.g. medicament) is administered by compressing hydraulic fluid reservoir  114  in a controlled manner with actuator  135 .  FIG.  2    shows an exemplary peristaltic mechanism actuator  135 . However, the actuator may be alternatively selected from any of a number of squeeze devices that apply a force on the reservoir, such as a miniaturized bellows crank or paired rollers bearing on reservoir  114  (see  FIG.  6    below). Moreover, in other embodiments, the reservoir can be acted on by an expanding gas volume, thermal energy, or any other device or process that will be capable of causing the fluid to apply a pressure, either directly or indirectly, to the medicant being delivered. 
     In the embodiment shown in  FIG.  2   , plates  135 A and  135 B are attached by hinge  135 C and forced together by means of a spring or, in some embodiments, one or more piezoelectric elements, such that flexible (e.g., elastomeric) hydraulic fluid reservoir  114  is squeezed between them. Squeezing an elastomeric reservoir forces the contents of the reservoir out through whatever aperture exists in the reservoir. In some embodiments, an aperture  152  is provided by the coupling tube  116  and the adjustable aperture  150 , further described below. 
     Actuator  135  may also take on other forms. Ratchet or stepper motor driven units that compress plates or other structures bearing on hydraulic reservoir  114  that move hydraulic fluid may also be used without departing from the present invention. Additionally, for a two-plate hinged peristaltic mechanism such as that represented by reference designator  135  in  FIG.  2   , springs mounted internally or externally to the plates (not shown) may be used to force the plates together. Electrically driven or piezoelectric mechanisms, such as those described in the prior art, may also be employed. 
     In one embodiment, as shown in  FIG.  6 A , one or more external spring(s)  135 D having a constant spring coefficient over its full range of motion is (are) employed, (For the sake of simplicity, a single spring configuration is described. But multiple springs may be used to adjust forces.) This spring is disposed so as to connect portions of plates  135 A and  135 B distant from hinge  135 C and to draw them together (inwardly), thus bearing on reservoir  114 . Thus, when the system is initially prepared for use, the spring is extended (i.e., placed in tension) by forcing plates  135 A and  135 B apart. The plates are then held in place with a removable brace or other device (not shown) to keep them from compressing hydraulic reservoir  114 . Once the pump is in place and connected through infusion means  160  (see  FIG.  2   , but not shown here) to inject the medicament into the patient, the brace may be removed. The constant spring tension placed on plates  135 A and  135 B of actuator  135  will then slowly force the plates together and squeeze hydraulic fluid  112  out of reservoir  114  in a peristalsis-like action. 
     In another embodiment, as illustrated in  FIG.  6 B , a compressed spring or set of springs  260  may be used to push a piston element  250  through a guided-path to compress the hydraulic fluid reservoir  114 . At the end of the reservoir, distal to the piston element  250 , is an aperture  152  that allows the hydraulic fluid  112  to enter the adjacent pump chamber  110 , so that barrier  130  may move accordingly. In a more simplified version, the spring mechanism  250  and  260  may be replaced by thumb force  300 , just like in a traditional syringe ( FIG.  6 C ). In both  FIGS.  6 B and  6 C , there is no connective passage separating the fluid reservoir  114  from the pump chamber  110 . 
     The adjustable aperture provides regulation of the hydraulic pressure and flow rate in the pump chamber  110 . This regulation may be effected by allowing the aperture  152  (in  FIG.  2   ) to be adjusted to extremely small dimensions, for example, to a diameter of one-ten thousandths of an inch (0.0001 inches, or about 2.5 μm) or less. 
     In one embodiment, the aperture  152  has a fixed size. It does not have to be round/circular in shape. For example, it could be roughly a square, a triangle, an oval, an irregular shape, or a polygon. Whatever the shape, the area of the opening will be sized to achieve the flow rate desired. In example, the opening may be about one-tenth thousandths of an inch (or 2-3 μm) in diameter. Depending on use, the opening size can be anything, including an opening between 200 nm-500 nm, or 500 nm-1000 nm, or 1-2 μm, or 5-10 μm. Other sizes and dimensions can be selected and the size and dimension selected will depend upon the application at hand. 
     In other embodiments, as shown in  FIG.  7   , the aperture  152  may be adjustable in size, as by means of a conventional iris mechanism (see  FIG.  7   ), miniature valve, or paired gating slits (for example and not by way of limitation) currently known in the arts. For example, the adjustable aperture  152  may be adjusted by means of a simple thumb wheel  150  that activates the conventional, miniaturized valve or iris device discussed above. In an alternate embodiment, an electrical motor or piezoelectric device may be used to open or close the aperture, thus affecting the rate at which hydraulic fluid  112  flows into chamber  110  and moves barrier  130 . 
     Regardless of whether the aperture is adjustable or not, the flow rate of the hydraulic fluid can be controlled to suit different needs. In certain embodiments, the quantity of the fluid in the fluid chamber is expelled at a rate selected from: about 100 nl-1 μl per minute, about 1-10 μl per minute, or about 10-100 μl per minute. In other embodiments, the fluid rate is mediated and controlled to be from 0.001 μl per hour to 100 milliliters per hour. The rate selected will depend upon the application at hand, and those of skill in the art will be able to determine the proper dosage rate for a given application. 
     One feature of aperture  152 , whether adjustable or not, is that it can be made extremely small so that hydraulic fluid  112  enters chamber  110  at very low rates, such as but not limited to rates as low as ones or tens of micro-liters per minute. When used with a hydraulic fluid of appropriate viscosity (further discussed below), the configuration of aperture  152  enables precise pressure regulation that is insensitive to ambient pressure or other environmental conditions. This insensitivity, in turns, allows for highly accurate dosing and dose regulation under a wider range of conditions than previously seen in the arts. 
     Hydraulic fluid  112  is, in some embodiments, an ultrapure, high viscosity, bio-inert material. Viscosity is limited at its upper bound by the amount of force developed by the actuator. In certain embodiments, the force generated by the actuator is about 10 lb, 5 lb, 3 lb, 2 lb, 1 lb, 0.5 lb, 0.1 lb, 0.001 lb or less. At its lower bound, the fluid must be viscous enough so that the flow can remain highly regulated by the combination of actuator pressure and aperture diameter in all environment conditions, especially in the presence of low atmospheric pressure and/or high ambient temperature (where viscosity tends to decrease). A simple test may be performed to roughly determine the average flow rate of the hydraulic fluid, by fixing an aperture size and the pushing force exerted on the fluid reservoir, and determining the amount of hydraulic fluid remaining in the reservoir (and thus the amount exited) after a period of time. Consecutive periods of hydraulic fluid loss (e.g. fluid loss in consecutive 5-minute periods, etc.) may be measured to determine if the rate of hydraulic fluid loss from the reservoir is constant over time under the condition used. 
     Medicaments suitable for use with the system presently disclosed include: insulin, opiates and/or other palliatives, hormones, psychotropic therapeutic composition, or any other drug or chemical whose continuous low volume dosing is desirable or efficacious for use in treating patients. Note too that “patients” can be human or non-human animal; the use of continuous dosing pumps is not confined solely to human medicine, but can be equally applied to veterinarian medicines. 
     In an alternate embodiment of the system, two or more hydraulic reservoirs and actuators are provided ( FIGS.  8 A- 8 B ). In an illustrative embodiment shown in  FIG.  8 A , the first reservoir  400  and actuator  235  are the same as or similar to items  114  and  135  in  FIG.  2   . The second reservoir  500  and actuator  235 , which may use the same peristaltic actuator  135  as shown in  FIG.  2    or any other conventional alternative, such as those described above, are provided with a separate control. In other words, the second actuator may be controlled independently of the first. Both fluid reservoirs are connected to the pump chamber wall  150 , through apertures  154  and  156 , respectively. The connection may optionally go through connective passages  116 . Such a configuration is useful in situations where special, discrete doses of the medicament may be necessary. For example, an insulin-dependent diabetic may often find it necessary to receive an additional booster dose or bolus of insulin immediately after meals, in addition to and along with continuously supplied insulin during the day. The second actuator control may thus be operated independently of the first actuator control mechanism to deliver the bolus. 
     In an alternative embodiment, shown in  FIG.  8 B , hydraulic fluid  112  from both reservoirs  400  and  500  may pass together through a common lumen  116  and thence through adjustable aperture  152  ( FIG.  8 B ). Alternatively, as described above, the two reservoirs may lead into hydraulic chamber  110  by way of separate lumens and separately adjustable apertures  154  and  156  ( FIG.  8 A ). In this latter configuration, the rate of dosing affected by either reservoir may be independently controlled through their respective adjustable apertures. 
     In a further alternative, one of the reservoirs may lead to a fixed aperture while the other leads to an adjustable aperture. In this embodiment, useful in cases such as the insulin-dependent diabetic described above, the fixed-aperture-connected hydraulic reservoir can be actuated to provide bolus dosing at discrete intervals, while the adjustable-aperture-connected hydraulic reservoir can be used to provide continuous slow dosing. 
     Exemplary Embodiment of Using the Fluid Delivery System 
     In one exemplary embodiment, there is provided a method of administering a medicament, comprising: compressing a hydraulic fluid reservoir to force said hydraulic fluid through a connection means; passing said hydraulic fluid through an adjustable aperture into a first, pump chamber, wherein said pump chamber is separated from an adjacent fluid storage chamber, for example, by a moveable barrier, and wherein said fluid storage chamber is filled with a medicament; displacing said moveable barrier into said fluid storage chamber by filling said pump chamber with said hydraulic fluid, wherein said displacing causes a quantity of said medicament to be expelled from said fluid storage chamber through an orifice. 
     Said passing may be regulated by said adjustable aperture varying the flow of said hydraulic fluid and thus the quantity of said medicament expelled through said orifice. Furthermore, the method may further comprise injecting a quantity of said medicament into a patient through an infusion set connected to said orifice. 
     In some embodiments, the step of compressing may employ peristaltic compaction of said reservoir at a constant rate. Alternatively, the compressing step may employ peristaltic compaction of said reservoir at a variable rate. 
     In yet another alternate embodiment, the method may further comprise rapidly compressing a second hydraulic reservoir fluidly connected to said pump chamber to displace said moveable barrier and thus cause a bolus of said medicament to be expelled through said orifice. This embodiment may further comprise passing said hydraulic fluid from said second hydraulic reservoir through a second aperture into said pump chamber. 
     Alternate Embodiments 
     The order in which the steps of the present method are performed is purely illustrative in nature, and the steps may not need to be performed in the exact sequence they are described. In fact, the steps can be performed in any suitable order or in parallel, unless otherwise indicated as inappropriate by the present disclosure. 
     While several illustrative embodiments of the hydraulic pump system and its use in the fluid delivery system have been shown and described, it will be apparent to those skilled in the art that changes and modifications may be made without departing from this invention in its broader aspect and, therefore, the appended claims are to encompass within their scope all such changes and modifications as fall within the true spirit of this invention.