Patent Publication Number: US-9889253-B2

Title: Dosing unit for an ambulatory infusion device

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS 
     This application is a continuation of U.S. patent application Ser. No. 14/193,074, filed Feb. 28, 2014, which is a continuation of International Application No. PCT/EP2012/065972, filed Aug. 15, 2012. U.S. patent application Ser. No. 14/193,074, filed Feb. 28, 2014, is a continuation of International Application No. PCT/EP2011/065242, filed Sept. 2, 2011. The contents of each of these applications are hereby incorporated by reference in their entirety into this disclosure. 
    
    
     TECHNICAL FIELD 
     The invention relates to dosing units for infusion pump devices, and infusion pump devices with such a dosing unit. 
     BACKGROUND 
     Devices for the automated release of liquid medicaments are normally used with patients who have a continuous and in the course of the day varying need of a liquid medicine which can be administered by infusion. Specific applications are, for example, certain pain therapies, cancer therapies and the treatment of diabetes mellitus, in which computer controlled infusion pump devices are used. Such devices are particularly useful for ambulatory therapy, and are generally carried attached on or near the body of a patient. The medicine reservoir often comprises medicine supply sufficient for one or several days. The liquid medicament is supplied to the patient&#39;s body from the medicine reservoir through an infusion cannula or an injection needle. 
     Ambulatory infusion pump devices are typically of the syringe driver type, where the liquid medicament to be administered to the patient is stored in a cylindrical glass cartridge or ampoule acting as the liquid medicament reservoir, and is conveyed to the body of the patient by displacing a plunger within the cylinder. An example of such an infusion pump device is disclosed for example in WO 01/83008 A1. A cylinder of the dosing unit comprises the complete reservoir of liquid medicament of the infusion pump device. A plunger plug arranged in the cylinder is unidirectionally displaced along the cylinder axis by a drive system via a shaft or threaded spindle. 
     EP 2163273 A1 of the applicants, the disclosure of which is hereby included by reference in its entirety, discloses a piston pump based dosing unit for an infusion pump device with a 4/3 or 3/3 way valve system arranged at a front end of the cylinder of the dosing unit. A plunger arranged in the cylinder of the dosing unit can the bidirectionally displaced along the cylinder axis by a spindle drive system. In one state of the valve, an inlet conduit fluidly connected to the primary reservoir is fluidly connected to the cylinder cavity, and an outlet conduit fluidly connected to the infusion tubing is disconnected from the dosing unit. This state of the valve is applied during the refill mode, when the dosing unit retracts the plunger and sucks liquid medicament from the primary reservoir into the pump cylinder/secondary reservoir. In a second state of the valve, the cylinder of the dosing unit is fluidly connected to the outlet conduit, thereby establishing a fluid connection to the body of the patient. The inlet conduit is disconnected from the dosing unit. This valve state is applied during the pump mode, when liquid medicament is conveyed from the secondary reservoir in the cylinder of the dosing unit to the subcutaneous tissue of the patient. The valve thus either allows the dosing unit to retrieve liquid from the primary reservoir, or to convey liquid from the secondary reservoir of the dosing unit toward the patient. 
     The valve is realized as a rotatable cylinder acting as a valve member, mounted in a fixed valve seat. The cylinder member of the valve is frictionally connected to the plunger. By rotating the plunger along the cylinder axis, the actuating means of the plunger indirectly actuate also the valve member, by rotating the cylinder/valve member within the stationary valve seat. Thus no separate actuator is needed for the valve. Furthermore the valve system and the piston pump are coupled such that in the pump mode, the valve will automatically be in the pump state, and in the refill mode, the valve will automatically be in the retrieving state. Thus also no additional control means is needed for the valve. 
     In order to rotate the cylinder and to switch the valve, the plunger has to exert a rotational torque on the cylinder member. At the same time the rotational torque exerted on the plunger by a drive unit has to be translated into a linear displacement of the plunger along the cylinder axis. For that purpose the plunger shaft is provided with an outer thread that interacts with an inner thread provided on the cylinder. The dosing unit is designed such that the static frictional force between plunger and cylinder member (including friction between plunger plug and cylinder wall and friction of the thread) is larger than the static friction between cylinder member and valve seat. When the drive unit rotates the shaft into one direction, the cylinder is frictionally coupled to the rotating plunger and rotates in the valve seat until finally reaching an end position, where its further rotation is mechanically blocked by a stopper. The plunger is now frictionally decoupled from the cylinder member, and any further rotation of the plunger is translated by the threads into a linear displacement along the cylinder axis. When the rotation of the plunger is reversed, the cylinder member is no longer rotationally blocked in the valve set, and plunger and cylinder member are frictionally coupled again. The cylinder member thus rotates in the valve seat in the reverse direction, actuated by the drive unit via the plunger, until a second stopper is reached, corresponding to the second valve state. The plunger is decoupled again from the blocked cylinder member, and is now linearly displaced along the cylinder axis in the opposite direction. The design of such a combined piston pump/valve system is named “valve before plunger” design, since the valve is actuated before the plunger is actuated. 
     In an infusion pump device as discussed above, all parts that come into contact with liquid medicament, as well as parts that are subject to friction, may be arranged in a disposable subunit. Prior to use of the infusion pump device, a fresh disposable subunit is coupled to a reusable subunit, comprising for example the electronics, the drive system, the battery, and all other parts that are not prone to contamination or wear, and can be used over a longer time period. 
     Since the spindle that actuates the plunger of the pump is typically made from a polymer material, and thus would be subject to wear if used over a long time period, it is advantageously also part of the disposable subunit. However, if a simple threaded rod coupled to the plunger would be used as the spindle of the spindle drive, the length of the disposable subunit would depend on the plunger position. Such a design would complicate the coupling of the disposable subunit to the reusable subunit, namely the coupling of the spindle to the drive motor. 
     In the dosing unit shown in EP 2163273 A1, the length of the disposable subunit is hold constant. The plunger spindle of the dosing unit comprises a plunger shaft attached to the plunger, and a coaxial plunger driving rod arranged in a longitudinal bore along its axis of the plunger shaft. The driving rod can be linearly shifted along the longitudinal bore. The cross-section of the driving rod and the longitudinal bore are chosen such that a rotational torque is effectively transmitted from the driving rod to the plunger shaft. The coupler element can be coupled to a driving unit of a reusable subunit. The linear displacement of the plunger during the spindle actuation is compensated by the two-part spindle. While the plunger shaft is linearly shifted together with the plunger, the driving rod remains on place in regard to the drive unit. The transmission of the rotational torque from the drive unit to the plunger shaft is effected by the rotational coupling between plunger shaft and driving rod. 
     A spindle drive, as it is also present in the above-referenced dosing unit, unavoidably has a certain thread lash. When spindle rotation is reversed, the flanks of the inner thread and the outer thread are slightly shifted in regard to each other along the longitudinal axis. In a standard single-reservoir syringe-type infusion pump, thread lash is not relevant, since the spindle drive in unidirectional. Thus after priming of the pump system there is no reversal of the spindle rotation direction. Thread lash can be potentially detrimental to metering precision for secondary-reservoir piston pump dosing units, where the rotation direction is repeatedly reversed after priming. After switching the rotational direction of the plunger, for a small rotation angle of the plunger the threads are not coupled, resulting in a rotation of the plunger without linear displacement. Furthermore the linear force exerted on the plunger may have to counteract an opposite force due to a pressure differential in the cylinder cavity. Depending on the circumstances this can lead to a small linear displacement of the plunger within the cylinder, without rotation. As a result, the metering precision of such a dosing unit may be restricted. 
     This precision reducing effect of the thread lash is particularly relevant when the rotation angle and/or the linear displacement of the plunger are used to determine the position of the plunger plug within the cavity and/or the volume of retrieved/conveyed liquid volume. Although such a metering measurement method is very precise, and can take into account various effects, it cannot counterbalance thread lash, since thread lash cannot be detected such a method. 
     Counter spindle drives are used to avoid thread lash in high precision linear motors, for example for machining devices such as lathes. However, such complex drives are not applicable for infusion pump devices, since they are too voluminous and complex. 
     SUMMARY 
     In at least one embodiment of the present disclosure, a dosing unit for an infusion pump device is disclosed. In an exemplary embodiment, a dosing unit for an infusion pump device comprises a piston pump with a pump cylinder and a plunger arranged within said cylinder, coaxially arranged along a longitudinal axis. The plunger has a shaft with a thread and the cylinder has a threaded sleeve part with a thread. One of the two threads is an outer thread and the other one is an inner thread, said two threads engaging with each other in such a way that a rotational movement of the plunger around the longitudinal axis results in an additional linear displacement of the plunger along said longitudinal axis. A separate bias force element biases the two threads in regard to each other along the longitudinal axis, such that the threaded engagement of inner thread and outer thread is free of play independent of a direction of a rotational movement and linear displacement of the plunger in regard to the cylinder. The plunger thread may optionally be an outer thread and the cylinder thread may be an inner thread. 
     In at least one embodiment of the dosing unit, the bias force element subjects the plunger shaft to a force perpendicular to the longitudinal axis, thereby pressing a portion of the plunger thread onto a portion of the cylinder thread. Such a bias force element may comprise a radially biased flat surface that abuts the lateral surface of an outer one of the two threads. 
     In at least one embodiment of the dosing unit, one or more portions of the cylinder thread or the plunger thread are pivotably mounted on the cylinder, or on the plunger shaft, respectively. Additionally, a spring element may also be included in the dosing unit. The exemplary spring element may be a tension ring, which radially biases the pivotably mounted thread portions toward the other thread. 
     In at least one embodiment of the dosing unit, the bias force element comprises a tensioned segment of wire that is mounted to the cylinder or the plunger and is arranged in such a way that it is located in a groove segment of the outer thread and exercises a bias force perpendicular to the longitudinal axis. 
     In at least one embodiment of the dosing unit, the bias force element comprises a threaded element, which is coaxially mounted on the first threaded sleeve or on the plunger shaft, and is longitudinally shiftable in regard to the first threaded sleeve or the plunger shaft, respectively. The threaded element has a thread portion engaging with the plunger thread or the cylinder thread, respectively. Further the threaded element may have a spring element that subjects the threaded element to an axial bias force in regard to the first threaded sleeve or the plunger shaft, respectively. 
     In at least one embodiment of the dosing unit, the bias force element comprises one or more spring elements with inner or outer thread segments, such that said inner or outer thread segments are radially biased toward the outer or inner thread. The inner or outer thread segments act as the inner or outer thread, respectively. In at least one embodiment of the present disclosure, the bias force element is elastic. 
     The bias force element, in at least one embodiment, is made from a material that is different from the material of the cylinder and/or the plunger. Further, the bias force element can be made from metal, and alternatively or in addition the cylinder and/or the plunger can be made from polymer. 
     In at least one embodiment of the dosing unit, the plunger driving part is provided for transmitting rotational torque from a driving unit to the plunger without itself being linearly displaced. The cylinder, the plunger and the plunger driving part are coaxially arranged along a longitudinal axis and are rotatable around said axis in regard to static parts of the dosing unit. The plunger has a shaft with a thread and the cylinder has a threaded sleeve part with a thread. One of the two threads is an outer thread and the other one is an inner thread, said two threads engaging with each other in such a way that a rotational movement of the plunger around the longitudinal axis results in an additional linear displacement of the plunger along said longitudinal axis. The plunger driving part has a driving rod that is arranged in a longitudinal bore of the plunger shaft, the driving rod being linearly displaceable within the longitudinal bore along the longitudinal axis, and being rotationally engaged with the plunger shaft. 
     In at least one embodiment of the present disclosure, the one or more first coupling parts are mounted to or integral with the cylinder, and the one or more second coupling parts are mounted to or integral with the plunger driving part and/or the plunger. The first and second coupling parts interact in such a way that upon a reversal of the rotation direction of the plunger driving part the cylinder is rotationally coupled to the plunger driving part if it was previously not rotationally coupled, and vice versa. Alternatively, or in addition, the one or more first coupling parts may be mounted to or integral with the cylinder and/or the plunger driving part, and one or more second coupling parts are mounted to or integral with the plunger driving part and/or the plunger. The cylinder is rotationally coupled to the plunger on certain linear positions of the plunger in regard to the cylinder and being not rotationally coupled to the plunger on the other position. 
     In at least one embodiment of the dosing unit of the present disclosure, the coupling parts may, at least partly, be part of the plunger driving part and do a direct (selective) torque transmission from the plunger driving part to the cylinder. Alternatively the coupling parts may, at least partly, be part of the plunger and do an indirect (selective) torque transmission from the plunger driving part to the cylinder, via the plunger. The plunger driving part is distinct from both cylinder and plunger. 
     In at least one embodiment of the present disclosure, the plunger driving part receives a rotational torque from some drive and provides that torque either to the plunger only (decoupled state) or to both plunger and cylinder (coupled state). The plunger driving part may fulfils the functions of transforming a pure rotational drive movement into a screw-like combined rotational and linear movement of the plunger, and selectively rotationally coupling the cylinder to the drive. 
     In at least one embodiment of the present disclosure, the dosing unit has reduced energy consumption, since the cylinder can be decoupled from the drive unit, as long as the valve does not have to be switched. 
     In at least one embodiment of the present disclosure, the one or more first coupling parts are mounted to or integral with the cylinder, and one or more second coupling parts are mounted to or integral with the plunger driving part and/or the plunger. The first and second coupling parts may interact in such a way that the first and second coupling parts are bidirectionally switchable between a first state and a second state, by reversing the rotation direction of the plunger driving pan; the first and second coupling pans are unidirectionally switchable from the first state to the second state, by mechanically blocking cylinder rotation or actuating the first coupling part; and the cylinder is rotationally coupled to the plunger driving part in the first state of the first and second coupling parts; and not rotationally coupled in the second state. 
     In at least one embodiment of the present disclosure, a first coupling part is mounted to or is integral with the cylinder, and a second coupling part is mounted to or is integral with the plunger driving part. The first and/or the second coupling parts may comprise one or more bistable elements that can be in a first configuration where the bistable elements rotationally couple the first and second coupling parts by static friction or positive locking when the plunger driving part rotates clockwise, and do not rotationally couple the first and second coupling parts when the plunger driving part rotates counter-clockwise. In a second configuration the bistable elements rotationally couple the first and second coupling parts by static friction or positive locking when the plunger driving part rotates counter-clockwise, and do not rotationally couple the first and second coupling parts when the plunger driving part rotates clockwise. 
     In at least one embodiment of the present disclosure, the bistable elements are friction elements that are switchable between two configurations, and that the rotational coupling is a static frictional coupling. Further, the bistable friction elements may be switchable between the two configurations by reversing the rotation direction of the plunger driving part in case the first and second coupling parts are not rotationally coupled; and by reversing the rotation direction of the plunger driving part and blocking cylinder rotation in case the first and second coupling parts are rotationally coupled. Additionally, the cylinder rotation may be blocked on certain angular orientations of the cylinder in regard to the static parts of the dosing unit. 
     In at least one embodiment of the dosing unit, where the first and second coupling parts are unidirectionally switchable front a first state to a second state, by mechanically blocking cylinder rotation, such a change occurs, more generally spoken, if the torque for rotating the cylinder exceeds a maximum torque that can be transmitted via the coupling from the bistable friction elements to the cylinder. In at least one embodiment, such a change occurs only in the mechanically blocked state, where the torque for further rotating the cylinder becomes essentially infinite. 
     The bistable elements may also be ratchet mechanisms that are switchable between two configurations, and that the rotational coupling is given when the ratchet mechanism is locked. Additionally, the bistable ratchet mechanisms may switchable between the two states by reversing the rotation direction of the plunger driving part in case the ratchet mechanism is locked; and by reversing the rotation direction of the plunger driving part and additionally actuating the ratchet mechanism in case the ratchet mechanism is not locked. In at least one embodiment, the ratchet mechanism is actuated by switching elements mounted to or being integral with the static parts of the dosing unit. 
     In at least one embodiment of the present disclosure, one or more first coupling parts are mounted to or integral with the cylinder and/or the plunger driving part, and one or more second coupling parts are mounted to or integral with the plunger driving part and/or the plunger. The first and second coupling parts may interact in such a way that the cylinder is rotationally coupled to the plunger on certain linear positions of the plunger in regard to the cylinder and is not rotationally coupled to the plunger on the other positions. 
     In at least one embodiment of the present disclosure, the first coupling parts comprise first ramps provided on the plunger driving rod, and the second coupling parts comprise second ramps provided on a structure pivotably mounted on the plunger shaft. The structure carries portions of the outer thread. The first and second ramps are arranged such that on certain linear positions of the plunger in regard to the cylinder some of the first ramps abut some of the second ramps, and press the outer thread portions radially outwards onto the inner thread of the cylinder, thereby frictionally coupling the cylinder and the plunger. 
     In at least one embodiment of the present disclosure, the one or more first coupling parts are first friction elements mounted to or being integral with the cylinder, and the one or more second coupling parts are second friction elements mounted to or being integral with the plunger. At certain longitudinal positions of the plunger in regard to the cylinder one of the first friction elements frictionally engages with one of the second friction elements, thereby frictionally coupling the cylinder and the plunger. Further, the one or more first friction element may be a hollow cylinder, and the one or more second friction element may be a friction cylinder, which frictionally engages with the hollow cylinder when the friction cylinder is located in the hollow cylinder. 
     In at least one embodiment of the present disclosure, the one or more first coupling parts are first stopper elements mounted to or being integral with the cylinder, and the one or more second coupling parts are second stopper elements mounted to or being integral with the plunger. In at least one longitudinal position of the plunger in regard to the cylinder one of the first stopper elements abuts with one of the second stopper elements, thereby blocking the further linear displacement of the plunger, and releasably jamming the inner thread of the cylinder and the outer thread of the plunger. The stopper elements are in at least one embodiment may be disks. 
     In at least one embodiment of the present disclosure, the dosing unit has a cylinder coupling part as the first coupling part and a plunger coupling part as the second coupling part. The cylinder coupling part comprises first locking elements and the plunger coupling part comprises second locking elements, which releasably lock the plunger to the cylinder at certain longitudinal positions of the plunger in regard to the cylinder. 
     In at least one embodiment of the present disclosure, the one or more first coupling parts are mounted to or being integral with the cylinder, and one or more second coupling parts are mounted to or being integral with the plunger driving part. The first and second coupling parts in at least one embodiment interact in such a way that the cylinder is rotationally decoupled from the plunger driving part on certain angular orientations of the cylinder in regard to static parts of the dosing unit, and is rotationally coupled on the other orientations. 
     In at least one embodiment of the present disclosure, the first coupling part is mounted to or is integral with the cylinder, and a second coupling part is mounted to or is integral with the plunger driving part. The two coupling parts are frictionally coupled. The frictional coupling is releasable by switching elements mounted to or being integral with the static parts of the dosing unit. 
     In at least one embodiment, an infusion pump device according to the disclosure comprises a dosing unit according to the disclosure. 
    
    
     
       DRAWINGS 
       The features and advantages of the present disclosure, and the manner of attaining them, will be more apparent and better understood by reference to the following descriptions taken in conjunction with the accompanying figures, wherein: 
         FIG. 1  schematically shows a possible embodiment of a dosing unit according to at least one embodiment of the disclosure, (a) in a longitudinal section along the cylinder axis, and (b) in a cross section through the plunger shaft and the plunger driving rod along plane A-A. 
         FIG. 2  schematically shows a detail view of at least one embodiment of a thread lash reducing arrangement as shown in  FIG. 1 . 
         FIG. 3  schematically shows at least one embodiment thread lash reducing arrangements in a dosing unit according to the present disclosure. 
         FIG. 4  depicts at least one embodiment of an dosing unit of the present disclosure without thread lash, with a ring-like metal spring element as a radial bias element, (a) in a top view, (b) in a longitudinal section along plane B-B, and in a cross-section along plane A-A, (c) with the plunger shaft, and (d) without the plunger shaft. The plunger is shown (e) without the plug sealing element material in top view, (f) in a cross-section along plane C-C, and (g) in side view with view along the longitudinal axis on the bore. The radial bias force element is shown in (h). 
         FIG. 5  depicts at least one embodiment of a dosing unit, with a ring-like metal spring element as a radial bias element, (a) in top view, (b) in a longitudinal section along plane A-A, and (c) in a cross-section along plane B-B. The radial bias force element is shown in (d). 
         FIG. 6  schematically shows a further embodiment of a radial bias force element, (a) in a longitudinal view on the split end of the plunger shaft, and (b) in a side view on the end of the plunger shaft. 
         FIG. 7  depicts at least one embodiment of a plunger according to the present disclosure with thread lash reduction, having three pivotably mounted thread portions, (a) in a perspective view, (b) in a longitudinal view, (c) in a longitudinal section along plane A-A, and (d) in a cross-section along plane B-B. 
         FIG. 8  shows at least one embodiment of a thread lash reduction arrangement according to the present disclosure, with four threaded claws at the distal end of the cylinder engaging with a threaded plunger shaft, (a) in a side view with view on the distal end, and (b) in a longitudinal section along plane A-A. 
         FIG. 9  schematically depicts at least one embodiment of a dosing unit with thread lash reduction arrangement, in which three biased spring elements act as an radially biased outer thread, with the dosing unit (a) in a perspective view, and (b) in a detail view of a longitudinal section, with a distal sleeve (c) in a longitudinal view, and (d) in a perspective view, and with an axial bias force element with three radially biased spring elements (e) in a longitudinal view, and (f) in a perspective view. 
         FIG. 10  shows at least one embodiment of a thread lash reduction arrangement according to the present disclosure, in which a biased wire is used as a radial bias force element. The interaction of the biased wire, the threaded plunger shaft, and the thread portion on the cylinder surface is schematically depicted in (a). A distal portion of the cylinder is shown in (b), and a cross-section along plane A-A in (c). 
         FIG. 11  shows at least one embodiment of a thread lash reduction arrangement according to the present disclosure, with an axially biased threaded sleeve, (a) in a longitudinal section though plunger shaft, threaded sleeve and axial bias force element, and (b) in a schematical detail view of the interacting thread portions, (c) discloses yet a further variant of a thread lash reduction arrangement, with an axially biased threaded plunger shaft, a longitudinal section through plunger shaft, threaded sleeve and axial bias force element. 
         FIG. 12  schematically shows a longitudinal section of at least one embodiment of a dosing unit with controlled friction between plunger and cylinder, (a) with the plunger in a start position, (b) with the plunger in a medium position, and (c) with the plunger in a maximum position. A detail of  FIG. 12( a )  is shown in (d), explaining how the driving rod controls the friction between plunger and cylinder. 
         FIG. 13  schematically shows the plunger of  FIG. 12 , (a) in a longitudinal section along plane A-A, (b) in a cross-section along plane B-B, and (c) in a cross-section along plane C-C. 
         FIG. 14  schematically shows the driving rod of  FIG. 12 , (a) in a side view, (b) in a top view, and (c) in a cross-section along plane D-D. 
         FIG. 15  schematically shows a longitudinal section of at least one embodiment of a plunger shaft and driving rod that allows valve switching in intermediate positions according to the present disclosure. 
         FIG. 16  schematically shows at least one embodiment of a dosing unit with controlled friction between plunger and cylinder according to the present disclosure, (a) with the plunger in a start position, and (b) with the plunger in a maximum position. A detail of  FIG. 16( a )  is shown in (c), explaining how the driving rod controls the friction between plunger and cylinder. 
         FIG. 17  schematically shows at least one embodiment of a dosing unit with controlled friction between plunger and cylinder, (a) with the plunger in a start position, and (b) with the plunger in a maximum position. A detail of  FIG. 17( a )  is shown in (c), explaining how the driving rod controls the friction between plunger and cylinder. 
         FIG. 18  schematically shows at least one embodiment of a dosing unit of the present disclosure with controlled friction between plunger and cylinder, (a) with the plunger in a start position, and (b) with the plunger in a maximum position. 
         FIG. 19  schematically shows at least one embodiment of a dosing unit of the present disclosure with controlled friction between plunger and cylinder, and thread lash reduction, with the plunger in an intermediate position. 
         FIG. 20  schematically depicts a longitudinal section of at least one embodiment of a dosing unit of the present disclosure, in which the cylinder is positively locked to the plunger at certain longitudinal positions, (a) with the plunger in a start position, (b) with the plunger in a medium position, and (c) with the plunger in a maximum position. 
         FIG. 21  schematically depicts at least one embodiment of a dosing unit of the present disclosure: (a) in a longitudinal section with the plunger in a start position, (b) in a longitudinal section perpendicular with the plunger in a maximum position, (c) in a detail view of (a), and (d) in a detail view of (b). 
         FIG. 22  schematically depicts a longitudinal section of at least one embodiment of a dosing unit or the present disclosure with the plunger in the start position, in which the cylinder can be releasably positively locked to the plunger at certain longitudinal positions. 
         FIG. 23  schematically shows at least one embodiment of a coupling system of the present disclosure that allows switching the valve of a dosing unit at any longitudinal position of the plunger, (a) in a cross section, and (b) to (e) in detail views of different steps during the valve switching. 
         FIG. 24  schematically shows at least one embodiment of a coupling system of the present disclosure that allows switching the valve of a dosing unit at any longitudinal position of the plunger, (a) in a bottom view of the driving rod, (b) in a side view of the driving rod, and (c) in a detail of a cross-section of the coupling part of the driving rod coupled to the cylinder wall, (d) to (g) show detail views of different steps during the valve switching. 
         FIG. 25  schematically shows cross-sections of at least one embodiment of plunger shafts and driving rods, (a) without and (b) to (d) with rotational play. 
         FIG. 26  shows a perspective view of at least one embodiment of a dosing unit with the cylinder/plunger combination with thread lash reduction arrangement as shown in  FIG. 5 , and with a cylinder/driving rod coupling arrangement similar to  FIG. 24 . 
         FIGS. 27( a )-( m )  shows the different steps during valve switching with the dosing unit of  FIG. 26 . 
         FIG. 28  schematically shows subsequent steps of at least one approach to realize a controlled coupling between cylinder and driving rod, based on a bistable ratchet mechanism. 
         FIG. 29  schematically shows at least one embodiment of a controlled coupling between cylinder and driving rod, (a) in a perspective view on the interacting coupling parts, and (b) in a perspective view of the cylinder coupling part alone. 
     
    
    
     DETAILED DESCRIPTION 
     A dosing unit without thread-lash is advantageous for several reasons. The metering precision is increased due to the reduction of metering errors due to uncontrolled plunger displacement. Furthermore the separation in time of the valve switching process and the plunger displacement process is more precise, since the thread friction force, adding to the friction force between cylinder valve member and plunger, remains essentially constant when the plunger rotation direction is reversed. 
     A self-biasing polymer plunger shall for thread-lash reduction has the disadvantage that its bias force deteriorates over time in an irreproducible manner, which eventually reduces the acceptable shelf time of a disposable dosing unit prior to first use in an ambulatory infusion pump device. In an advantageous dosing unit according to this disclosure, a separate bias force element is provided, thereby allowing using a plunger without detrimental mechanical stress. 
     At least one embodiment of a dosing unit  1  according to the present disclosure is schematically depicted in  FIG. 1 . A cylinder valve member  2  is rotatably mounted in a stationary valve seat  12 . A plunger  3  with a plug  31  and a shaft  32  is arranged in the cylinder  2 . The plunger plug  31  sealingly closes the cylinder, thereby defining a metering cavity  11  between the cylinder head  21  and the plug. In the figure, the valve formed by the valve seat  12  and the cylinder valve member  2  is in one of its two operational valve states, where an inlet  121  is fluidly connected to the metering cavity  11  through an opening  211  in the cylinder head. The inlet  121  is fluidly connected to a primary reservoir of an infusion pump device (not shown). A downstream outlet  122  toward an infusion set (not shown) is disconnected from the metering cavity  11 . 
     The plunger plug  31  is attached to a plunger shaft  32 , which is provided with an outer thread  33  that interacts with an inner thread  23  arranged on the cylinder. The plunger shaft  32  is provided with a longitudinal bore  322  along its axis, having a square cross-section, in which a rod  41  of a plunger driving part  4  is arranged. The plunger driving rod  41  has a square cross-section corresponding to the longitudinal bore  322  of the plunger shaft. Thus the rod  41  can be shifted with only minimum friction in the longitudinal bore  322 , while at the same time efficiently transmitting a rotational torque around the axis  20  from the plunger coupler to the plunger  3 . Plunger shaft and plunger driving rod are designed such that the bore  322  is vented toward atmosphere. 
     The plunger shaft  32  and the plunger driving rod  41  together form the plunger spindle of the dosing unit. The plunger driving part  4  is rotationally coupled to a driving unit of the infusion pump device (not shown). In case the dosing unit is designed as a disposable element, which is intended to be replaced in regular intervals, the plunger driving part is advantageously provided with a drive unit coupling  42  for releasably coupling the plunger coupler to the drive unit. During operation, the drive unit (not shown) exerts a rotational force on the plunger coupler via the drive unit coupling  42 , and the plunger coupler transmits this rotational torque to the plunger  3 . While the plunger driving rod remains stationary along the longitudinal axis, the plunger is linearly displaced along the axis. 
     Since the frictional coupling between plunger and cylinder is larger than between cylinder and valve seat, the plunger is frictionally coupled to the cylinder member, as long as the cylinder has not yet rotated to a blocking position, corresponding to an operational valve state. In the blocking position of the valve, the now decoupled rotational movement of the plunger is translated into a linear movement of the plunger, by the spindle drive realized by the outer thread  33  of the plunger and the inner thread  23  of the cylinder. 
     In at least one embodiment shown in  FIG. 1 , the thread lash is minimized by an advantageous thread lash reduction arrangement. The inner thread of the cylinder is realized as a single thread segment  23  having a segment angle of 180° or less. A separate radial bias force element  5  is provided on the cylinder wall, on the side opposite to the inner thread segment  23 . Said bias force element  5  is realized in the given embodiment with a radially biased flat surface element  56  pressing on the outer thread  33  of the shaft  32 , thereby pressing the outer thread  33  on the opposite side of the shaft radially onto the thread segment  23 . A defined bias force is generated by a spring element  52  or other suitable resilient element, which in the figure is shown only schematically. 
     The principle of the applied thread lash reduction arrangement is shown in more detail in  FIGS. 2( a ) and ( b ) , schematically depicting a longitudinal section through a portion of a plunger shaft  32  with outer trapezoid thread  33 , interacting with a trapezoid thread segment  23  on the cylinder wall  22 . On the opposite side of the thread segment  23 , a radial bias force element  5  is arranged, exerting a radial bias force F bias  perpendicular to the cylinder axis  20 . The radial bias force element  5  is here realized as a flat element  56 , abutting the outer surface  331  of the spindle  32 ,  33 , and biased by a helical spring  52 . The bias element exerts a radial force on the outer thread  33  surface and the shaft  32 , without directly interacting with the thread  33 . As a result, there is a radial force F bias  between thread  33  and thread segment  23 , resulting to which the two threads closely abut each other, without a thread lash. Thus with at least one exemplary arrangement there will be no undefined plunger motion upon reversal of the rotation direction, or pressure differentials in the metering chamber. 
     The parameters of at least one exemplary thread as such, namely thread form, flank angle, and helical angle are mainly defined by the intended application, namely a self-locking spindle drive. With a thread having a flank angle α, and neglecting the comparably small helix angle of the thread, an axial force F ax  acting on the plunger shaft  32  will have a force component F a =cos(α)F ax  parallel to the surface of the thread flank. Similarly there acts a force component F b =sin(α)F bias  parallel to the flank surface, in the opposite direction. Thus as long as biasing force component F b  is larger than an axial force component F a  exerted on the plunger, or sin(α)F bias &gt;cos(α)F ax , the axial force cannot overcome the bias force, and the outer thread flank cannot slide along the flank of the thread segment  23 , which would lead to a axial shift of the plunger. 
     In at least one embodiment, the biasing force should be properly adjusted to avoid increased thread friction, and tints for the battery life time of a corresponding infusion pump device. 
     The maximum axial force F ax,max  that may occur on the plunger during normal operation can be estimated. Based on that upper limit an appropriate minimum radial force of the bias force element is determined, as F bias,min =cot(α)F ax . The smaller the flank angle the smaller is thread friction during operation, which is advantageous in regard to energy consumption. On the other hand it considerably increases the necessary bias force. An advantageous compromise in a dosing unit according to the disclosure is for example a trapezoid thread with flank angle 60° (cot 60°=0.58) and helical angle 3.4°. 
     In at least one embodiment, the bias force is generated by a spring element, for example a metal helical spring. Other types of resilient elements are possible. The material of the resilient element is chosen such that it does not deteriorate over time in regard to the spring force, thereby allowing a long shelf time prior first use. 
     The plunger shaft and the cylinder wall including thread segment  23  of at least one embodiment may be manufactured from a thermoplastic polymer material compatible for medicinal applications. It should furthermore provide elasticity parameters suitable for application in self-locking spindle drives. Exemplary materials that may be used in at least one embodiment include for example poly-amide (PA), polypropylene (PP), methyl methacrylate butadiene styrene terpolymer (MBS), and polybutylene terephthalate (PBT). 
     At least one embodiment of a thread lash reducing arrangement is shown in  FIG. 3( a ) , where the bias force element  5  is realized as a biased thread segment  51 , interacting with the outer thread  33 . A further embodiment is shown in  FIG. 3( b ) , where three parallel thread segments  23  are provided. Such a variant with more than one thread flank interacting is less advantageous than the variants discussed before, since the actual forces acting on the thread can be determined less precisely due to manufacturing tolerances. 
     At least one embodiment of a dosing unit of the present disclosure is disclosed in  FIG. 4 . The pump cylinder/valve member  2  comprises two parts  28 ,  26 , and is rotatably arranged in the valve seat  12 . The plunger plug  31  is arranged in a proximal (proximal meaning “toward the valve”) cavity part  28  of the cylinder, together defining the variable metering cavity. The plug  31  comprises a plug sealing element  311 , sealingly closing the metering cavity. The sealing element  311  is advantageously made from an elastic thermoplastic polymer. The plunger can be manufactured e.g. by two component injection moulding of plunger sealing element and plunger rod. In the longitudinal section given in  FIG. 4( b ) , in which the valve seat  12  is shown, the radial opening  211  in the cylinder head wall  21  is fluidly connected to inlet  121 , while the outlet  122  is disconnected from the metering cavity. 
     The threaded  33  plunger shaft  32  is arranged in a distal (distal meaning “away from the valve, toward the drive unit”) threaded sleeve part  26  of the cylinder, where the outer thread  33  interacts with two inner thread segments  23  of the threaded sleeve  26 . The proximal cylinder part  22  and the distal part/threaded sleeve  26  of the cylinder are attached together with a suitable locking mechanism, for example by ultrasonic welding. Assembling the cylinder front two separate parts has the advantage that the single pieces are easier to manufacture. Furthermore it allows optimising of the materials used. The material of the proximal cylinder part  22  can be chosen in regard to compatibility with medical liquids and the interaction with the material of the plug sealing element  311 . The material of the distal threaded sleeve  26  can be chosen in regard to a reliable thread interaction with the plunger shaft  32 . 
     The plunger shaft  32  is provided with a longitudinal bore  322  along its axis, in which a rod of a plunger driving part (not shown) can be arranged. Four longitudinal cams or rips  34  are arranged along the bore  322  of the plunger shaft, intended to interact with corresponding slots on the plunger driving rod. The cams  34  in at least one embodiment allow for efficiently transmitting a rotational torque from the plunger coupler to the plunger. At the same time there is only low friction along the longitudinal axis  20 . 
     The necessary bias force to remove tread lash is provided by a radial bias force element  5  in the form of a half-ring-like metal spring  52 , having a flat portion  56  at one end of the spring  52 , and a locking structure  53  on the other end. When mounted to the cylinder, the locking structure is arranged in a corresponding recession on the outer cylinder wall. The flat element  56  is arranged in an opening  221  in the threaded sleeve  26 , and abuts the thread  33  of the plunger shaft  32 . 
     During assembly, the spring element  52  may be slightly deformed. When the locking structure  53  and the flat portion  56  snap into the corresponding recessions and openings, the spring element is positively locked to the distal cylinder element, with a spring force due to the remaining radial deformation. Due to this remaining spring force the radial bias force element  5  generates a radial biasing force between the two inner thread segments  23  of the threaded sleeve  26  and the outer thread  33 . 
     Since the bias spring element  52  in at least one embodiment has a very simple structure and can be easily mounted to the cylinder, the dosing unit can be manufactured and assembled very efficiently. At the same time the spring element provides a reliable and constant radial bias force F bias . The spring element  52  may in at least one embodiment be made from spring band steel, for example spring band steel 1.4310. 
     The use of two inner thread segments  23  in combination with a single biased flat surface element  56  is particularly advantageous, compared to a single threaded segment as described for  FIG. 1 . Since said two inner thread segments and the flat surface element provide a three-point mounting (instead of two mounting points), the outer thread of the plunger shaft  32  is more stably mounted. 
     In at least one embodiment of a dosing unit is depicted in  FIGS. 5 and 26 , where the embodiment has a radial bias force element  5 . Here the spring element  52  is a metal spring having the basic shape of an open ring, with two locking structures  53  at the two ends of the open ring, and a straight segment  56  in the middle. When mounted to the cylinder, the locking structures  53  are located in corresponding recessions. The straight segment  56  is located in an opening  221  of the cylinder wall, through which the flat portion  56  abuts the thread  33  of the plunger shaft  32 . The two arms of the spring element  52  between the locking structures  53  and the central flat portion  56  remain slightly deformed when mounted to the cylinder, providing a constant radial bias force F bias . 
     In at least one embodiment plunger shaft  32  has been provided with a continuous outer thread, while the inner thread has been reduced to a single segment ( FIG. 2 ) or two segments ( FIG. 5 ). Such a configuration may be advantageous in regard to reproducibility of thread lash reduction (see also discussion of  FIGS. 2 and 3 ). Alternatively it is also possible to provide the shaft  32  with a single outer thread segment  22 , and the inner surface of the cylinder with a continuous inner thread  23 , as for example shown in  FIG. 6 . The distal end of the plunger shaft  32  is split into two shaft arms  321 ,  321 ′. On one shaft arm  321  a single outer thread segment  33  is arranged, interacting width the inner thread  23  of the cylinder. On the other shaft arm  321 ′ of the plunger shaft, a flat cylinder segment  56  is arranged, abutting the surface of the inner thread  23 . A spring element  52  in the form of a single metal leaf spring is arranged between the two shaft arms  321 ,  321 ′, providing a radial force directed outwards. As a result the outer thread segment  23  is constantly biased against the inner thread  23 , thereby removing the thread lash. The two shaft arms  321 ,  321 ′ of the plunger as such are not biased, since the corresponding force is provided by the spring element  52 . Thus such an embodiment does not suffer from creep deformation as in the state of the art. 
     At least one additional embodiment of a plunger with thread lash reduction is given in  FIG. 7 . The outer thread  33  of the plunger shaft is divided into three rectangular portions  33   a ,  33   a ′,  33   a ″, equally distributed on the shaft  32 . The threads are provided such that the outer thread is stably arranged and runs smoothly in a continuous inner thread of the cylinder. The thread portions are arranged in corresponding rectangular openings on the shaft, connected to the shaft only by a longitudinal hinge structure  323 , e.g. a film hinge or a longitudinal area with reduced wall thickness. The thread portions thus are pivotable along the axis of said hinges, abut a small angle. The three outer thread portions are radially biased toward the inner thread, thereby efficiently removing thread lash. 
     The necessary bias force can be obtained by one or more suitable spring elements, e.g. a slotted metal ring spring (not shown) arranged in a circular groove in the bore  322  of the shaft. A suitable way to manufacture such a plunger is insert injection moulding, where the ring spring is over-moulded with the thermoplastic polymer material of the plunger shaft. 
     In at least one additional embodiment, the dimensions of the shaft are chosen such that the pivotably mounted thread portions are slightly compressed inwards when introduced into the inner thread. In that case the spring force is generated by the shaft/thread structure itself. 
     At least one approach is shown in  FIG. 8 , where a plunger  3  having a shaft  32  with continuous outer thread  33  is arranged in a threaded sleeve  26  with four threaded claws  25 ,  25 ′,  25 ″,  25 ′″, separated by slots  251 . In the given embodiment a slotted tension ring  27  is arranged as a radial bias force element  5  around the distal end of the claws  26 , Said tension ring is dimensioned such that the claws are slightly biased inwards, toward the outer thread  33  of the plunger shaft, the inner and outer thread thereby engaging without thread lash. 
     At least one embodiment of a thread lash reducing arrangement with radial bias force is shown in  FIG. 9 . A sleeve element  263  is mounted to the distal end of the cylinder  2 . A radial bias force is provided by radial bias force element  5  with three spring biased inner thread segments  59   a . The radial bias force element is mounted to the distal end of the sleeve element  263 , and comprises a mounting sleeve  57  with three openings  58 , and three spring elements  59 . Together the sleeve element  263  and the radial bias force element  5  form a threaded sleeve  26 , the inner thread segments acting as the inner thread  23  of the threaded sleeve. 
     Assembling the threaded sleeve  26 , the mounting sleeve  57  is put over the sleeve element  263 , such that three protrusions  262  lock into the openings  58 , thereby positively locking the mounting sleeve  57  on the sleeve element  263 . The three spring elements  59  are located in three longitudinal slots  261  of the sleeve element  263 . 
     Sleeve element  263  and bias force element  5  are designed such that the thread segments  59   a  of the three spring elements  59  engage with the outer thread  33  of a plunger shaft  32  that is engaged with the threaded sleeve  26 . The thread segments  59   a  thus act as short thread segments  23  of the threaded sleeve  26 . In the assembled state, the thread segments  59   a  are radially biased, with a spring force F bias  acting radially inwards. The three spring elements are symmetrically arranged around the longitudinal axis. As a result the radial force components acting on the plunger shaft stun to zero. 
     The flanks of the thread segments  59   a  of the spring elements  59  of the radial bias force element  5  abut the flanks of the plunger shaft thread  33 . Thread lash is removed, similar to  FIG. 2 , as long as the relation F bias,min =cot(α)F ax  applies for the minimum radial bias force F bias,min  and the external axial force F ax . 
     In at least one embodiment, a similar radial bias force element  5  is mounted to the plunger shaft, its spring biased outer thread segments  59   b  acting as the outer thread  33  of the plunger shaft, engaging with the inner thread  23  of the cylinder without thread lash. 
     In at least one embodiment of a thread lash reduction arrangement is depicted in  FIG. 10 . In contrast to the embodiment shown in  FIG. 3( a ) , where a radially biased inner thread segment provides the radial bias force, a short wire segment  55  is used as the radial bias force element  5 . 
     The wire segment  55  is mounted on a threaded sleeve, parallel to the other threads  33  of the plunger. Two inner thread segments  23  are arranged on the sleeve  26  opposite to the wire  55 . During operation the bias wire  55  is arranged in a groove of the outer thread  33 . The wire is attached on its two ends to the sleeve in such a way that it is strained when the plunger shaft tread  33  is introduced into the threaded sleeve  26 . The strained wire exerts a radial bias force on the plunger shaft, resulting in a radial bias force between outer thread  33  and thread segments  23 . In the embodiment as shown in  FIG. 10( a ) , the wire abuts the groove of the thread  33 . 
     In at least one embodiment discussed so far the bias force providing the thread lash free engagement of plunger thread and cylinder thread was directed radially. Inner thread and outer thread were subject to a force perpendicular to the longitudinal axis. 
     In at least one embodiment of the present disclosure, the bias force is directed axially, along the longitudinal axis  20 , as for example in  FIG. 11 . A continuously threaded  33  plunger shaft  32  is arranged in a threaded sleeve  26  at the distal end of a cylinder. A separate threaded element  64  with an inner thread  65  is coaxially mounted behind the threaded sleeve  26 , connected to the latter via a helical spring  62 . 
     Together the threaded element  64  and the helical spring  62  act as a spring biased axial bias force element  6 . The helical spring  62 , arranged coaxially to the plunger  32 , provides an axial force F bias , pushing the threaded element  64  away from the threaded sleeve  26  along the longitudinal axis  20 . As a result, during normal operation the distal flanks of the threaded portion  65  of the threaded element  64  abut the proximal flanks of the plunger shaft thread  33 , and the proximal flanks of the static threaded sleeve  26  abut the distal flunks of the plunger shall thread. Independently from any reversal of the rotation direction of the plunger, or any external axial force due to a pressure differential in the metering chamber, the plunger  3  will be positively locked in the cylinder thread, without thread lash. 
     In at least one embodiment, the roles of the inner  23  and outer  33  threads are exchanged, as shown in  FIG. 11( c ) . A threaded sleeve  26  comprises a continuous inner thread  23 . A plunger shaft  32  is provided with an outer thread  33 . A threaded element  64 ′ with an outer thread  66  is shiftably arranged on the plunger shaft  32 . A spring element in the form of a helical spring  62  is coaxially arranged between the end of the outer thread portion  33  and the threaded element  64 ′. Together the threaded element  64 ′ and the helical spring  62  form a spring biased axial bias force element  6 . The helical spring  62  provides an axial force F bias , pushing the threaded sleeve  64 ′ away from the outer thread portion  33  along the longitudinal axis  20 . As a result, during normal operation the proximal flanks of the outer thread portion  66  of the threaded element  64 ′ abut the distal flanks of the cylinder thread  23 , and the distal flanks of the outer thread  33  abut the proximal flanks of the cylinder thread  23 . Independently from any reversal of the rotation direction of the plunger, or any external axial force, the plunger  3  will be positively locked in the cylinder thread  23 , without thread lash. 
     In the dosing unit as known from prior art EP 2163273 A1, the friction force between cylinder valve member and plunger, which is necessary for reliably switching the valve before the plunger is linearly displaced, is constant. As a result the corresponding rotational torque that is necessary for actuating the plunger is also constant. 
     To reduce energy consumption of the drive unit actuating the plunger, the friction force between cylinder valve element and plunger during linear plunger displacement may be reduced, where the valve is in one of its operational states. At least one embodiment of a dosing unit that allows controlling the friction between cylinder valve member  2  and plunger  3  is shown in  FIGS. 12, 13, and 14 . The valve seat of the dosing unit  1  is not shown for simplicity. The threads  33 ,  23  are only schematically indicated. The plunger  3  is coaxially arranged in the cylinder valve member  2 , defining a metering cavity  11 . The plunger  3  comprises a plunger plug  31  and a plunger shaft  32 . Said plunger shaft is longitudinally split into two shaft arms  321 ,  321 ′, pivotably connected to the plunger plug  31  by a hinge region  323 . A coupler element  4 , releasably coupled to a drive unit (not shown) of an infusion pump device, has a driving rod  41 , essentially comprising a distal part stem  412 , to be connected to the drive unit, and a proximal part  411  that is arranged in a longitudinal bore  322  of the plunger shaft. The proximal part  411  comprises two cams  43 ,  43 ′, slidably arranged in the slot  37  that divides the shaft  32  into the two shaft arms  321 ,  321 ′. Rotational torque is primarily transferred from the driving rod  41  to the plunger shaft  32  via said cams  43 ,  43 ′. Two other cams  44 ,  44 ′ are arranged perpendicular to the first cams  43 ,  43 ′, each having a long cut-out  441  that leaves a proximal ramp  71  and a distal ramp  71 ′. 
     Along each of the two shaft arms  321 ,  321 ′ a longitudinal slot  38  is arranged, on the proximal side limited by the hinge region  323  of the shaft  32 , and on the other side by a bridge structure  39  bearing an outer thread element  33   a .  33   a ′. The two bridge structures  39  comprise a proximal ramp  72  and a distal ramp  72 ′. When assembled the bridge structures are arranged in the cut-out  441  of the coupling rid  41 , between the two ramps  71 ,  71 ′. During operation the linear orientation of the driving rod  41  in regard to the cylinder valve member  2 , as well as the rotational orientation of the driving rod  41  in regard to the plunger  3 , remain constant. 
     As will be shown, the elements of the plunger shaft  32  and the driving rod  41  engage in such a way that friction between plunger and cylinder valve element is increased to a high value when the plunger shaft and the driving rod are in certain positions to each other, thereby frictionally coupling cylinder and plunger. In the other positions friction is on a lower level. This functional principle is explained in more detail in  FIG. 12 , and Table 1. 
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 1 
               
               
                   
               
               
                   
                   
                   
                 Frictional 
                   
               
               
                   
                   
                   
                 coupling 
                   
               
               
                   
                   
                   
                 between 
               
               
                 Plunger 
                   
                   
                 Cylinder valve 
               
               
                 rotation 
                   
                   
                 member and 
               
               
                 direction 
                 Valve State 
                 Metering cavity 
                 plunger 
                 FIG. 
               
               
                   
               
             
            
               
                 Pump direction 
                 Pump state 
                 Partially filled 
                 None 
                 12(b) 
               
               
                 Pump direction 
                 Pump state 
                 Empty 
                 Yes 
                 12(a) 
               
               
                 Refill direction 
                 Undefined, 
                 Empty 
                 Yes 
                 12(a) 
               
               
                   
                 valve rotates 
               
               
                   
                 until the other 
               
               
                   
                 stopper is 
               
               
                   
                 reached. 
               
               
                 Refill direction 
                 Refill state 
                 Partially filled 
                 None 
                 12(b) 
               
               
                 Refill direction 
                 Refill state 
                 Maximum 
                 Yes 
                 12(c) 
               
               
                   
                   
                 capacity 
               
               
                 Pump direction 
                 Undefined, 
                 Maximum 
                 Yes 
                 12(a) 
               
               
                   
                 valve rotates 
                 capacity 
               
               
                   
                 until the other 
               
               
                   
                 stopper is 
               
               
                   
                 reached. 
               
               
                 Pump direction 
                 Pump state 
                 Partially filled 
                 None 
                 12(b) 
               
               
                   
               
            
           
         
       
     
     Assuming that the valve of the dosing unit is in the pump state, the valve member abutting a corresponding stopper of the valve seat, and the outlet being connected to an infusion set, and that the metering cavity is partially filled (see the situation in  FIG. 12( b ) ), the drive unit will rotate the plunger such that it is linearly shifted to the left, thereby conveying liquid medicament toward the infusion set. The friction between plunger  3  and cylinder  2 , namely thread friction and friction between plunger plug and cylinder wall, is chosen such that is as small as possible, in order to minimize energy consumption of the drive. 
     When the plunger reaches the cylinder head, and the metering cavity is completely emptied (see  FIG. 12( a ) ), the proximal ramp  72  of the bridge structure  39  of the plunger shaft  32 , shifting to the left, engages with the proximal ramp  71  of the driving rod  41  and forces the bridge structure  39  radially outward toward the cylinder wall. As a result the thread segment  33   a  on the bridge structure is radially pressed onto the inner thread  23 , which increases thread friction until finally the outer thread is jammed in the inner thread. 
     To continue the administration of liquid medicament it will be necessary to retrieve new liquid medicament from the primary reservoir of the infusion pump. For that the valve has to be switched from the pump state to the refill state, which requires a reversal of the rotation direction of the plunger and a frictional coupling between cylinder valve member and plunger. Since the inner and outer threads are jammed, friction between cylinder and plunger is considerably larger than friction between cylinder and valve seat. The rotating plunger grips and rotates the cylinder in the valve seat until it reaches the stopper that defines the valve&#39;s refill state, where the inlet conduit is connected to the primary reservoir. Since cylinder rotation is now mechanically blocked, the drive unit can overcome the thread jamming. The proximal ramp  72  of the bridge structure  39 , now shifting to the right, disengages from the proximal ramp  71  of the driving rod, until thread friction and thus energy consumption is minimal again. 
     During the following refill mode, the plunger is displaced to the right and the metering cavity is refilled (see  FIG. 12( b ) ), until finally maximum filling capacity is reached (see  FIG. 12( c ) ). When the plunger reaches this maximum position at the right, the distal ramp  72 ′ of the bridge structure  39  engages with the distal ramp  71 ′ of the driving rod, forcing the bridge structure and the outer thread segment radially outwards toward the inner thread  23 , until the thread is jammed. The valve has now to be switched back to the pump position, disconnecting the primary reservoir and connecting the infusion set. Since cylinder and plunger are again temporarily frictionally coupled, rotating the plunger in the reversed direction (pump direction) will rotate the cylinder in the valve seat until the stopper is reached that defines the pump state of the valve. Further rotation of the plunger disengages the ramps  71 ′,  72 ′ and removes the thread jam, and the plunger can be moved again to the left with minimum friction. 
     As can be seen, at least one embodiment of the dosing unit allows controlling the friction between plunger and cylinder valve member. The interaction between the ramps  72 ,  72 ′ of the bridge structures  39  and the ramps  71 ,  71 ′ of the driving rod  41  provides the possibility of temporarily radially biasing the outer thread segments toward the inner thread  23 , thereby increasing thread friction. Thus a dosing unit optimizes energy consumption by restricting friction to a minimum level during pumping and refilling. Although this increase may go up to an actual temporary jamming of the thread, it is also possible just to increase friction to a value that is sufficient for the valve switching. 
     The example discussed above provides opportunities to switch the valve at two distinct positions, namely when the metering cavity is either completely empty or completely full. An advantageous variant that allows the switching of the valve also in intermediate positions is explained in  FIG. 15 . In addition to the two ramps  71 ,  71 ′ at the proximal and distal end of the driving rod  41 , two elevations  71   a  arranged on the driving rod between the ramps provide two other positions where bridge structures  39  and thread segments  33   a ,  33   a ′ are radially biased (see position I). The height of the elevations is chosen such that although friction is increased, no jamming takes place. Thus the dosing unit may continue in the mode it currently is in, for example pumping. The only effect will be a temporary increase of energy consumption until the end of the elevation is reached, due to the temporary increase of thread friction. If on the other hand the valve should be switched at this intermediate position, the dosing unit may do so by reversing the plunger rotation and rotating the frictionally coupled cylinder in the valve seat until the stopper is reached, and frictional coupling is released. Between the elevations and/or ramps, the bridge structure is not biased (see position II). When the bridge structure reaches one of the outer ramps (see position III), the friction can be increased up to thread jamming, although this is not actually necessary. 
     The exemplary dosing units discussed in  FIGS. 12 to 15  may also be combined with thread lash reduction. For example may the two shaft arms of the plunger shaft be pre-biased, due to radial dimensions that are slightly larger than the dimensions of the inner thread, or a radial bias force element as shown for example in the embodiments in  FIG. 6 or 7  can be applied. 
     At least one embodiment of a dosing unit  1  with controlled friction is shown in  FIG. 16 , with the valve seat not shown for simplicity. The cylinder valve member comprises a cavity part  28  and a threaded sleeve part  26 , mounted together. The threaded sleeve part  26  has an inner thread  23 , which may be some few windings, or even only a thread segment, particularly if one of the thread-lash reduction schemes is applied that have been discussed further above. 
     The plunger  3  with plunger plug  31  and plunger shaft  32  is coaxially arranged in the cylinder  2 . The plunger shaft  32  comprises a continuous outer thread  33 , engaging with the inner thread  23  of the threaded sleeve  26 . In the figure the threads are only schematically indicated for simplicity. The plunger shaft comprises a longitudinal bore  322 , in which a driving rod  41  of a plunger driving pan  4  is shiftably arranged. 
     The plunger and the cylinder are realized in such a way that friction is minimal during the pump mode and refill mode, in order to restrict energy consumption by the drive unit (not shown). In order to temporarily increase friction and thereby enabling the valve switching functionality by the drive unit, two friction cylinders  74 ,  74 ′ are arranged on the proximal and the distal end of the plunger shaft  32 . Said two friction cylinders may frictionally engage with two corresponding hollow friction cylinders  74   a ,  74   a ′ that are arranged on the proximal and the distal side of the inner thread  23  of the threaded sleeve  26 . When the plunger is in the position where the metering cavity  11  is completely empty ( FIG. 16( a ) ) or completely filled ( FIG. 16( b ) ), the abutting cylinder surfaces of the engaging friction cylinders cause increased friction. This provides the necessary additional friction between plunger and cylinder to reliably actuating the valve and rotating the cylinder valve member in the valve seat upon reversal of the plunger rotation direction. This can be seen in more detail in  FIG. 16( c ) . When the spindle drive rotates the plunger toward the maximum distal position, the friction cylinder  74  continuously shifts to the right into the cavity of the hollow friction cylinder  74   a , thereby linearly increasing friction. The dimensions of the interacting elements and the materials used are chosen such that latest when the plunger is in the maximum filling position, the friction between cylinder valve member and plunger, namely between the friction between the engaging friction cylinders and the constant friction due to the thread and the plunger plug, are sufficiently large to actuate the cylinder valve member in the valve seat when the plunger rotation direction is reversed. 
     When the plunger rotation direction is reversed, the plunger grips the cylinder and rotates it in the valve seat, until the cylinder abuts the stopper of the valve set. The static friction force is overcome, and the plunger starts again to rotate and to displace in the cylinder. The overlapping area of the friction cylinders, and thus the additional friction force, decreases linearly to zero. 
     As in the example discussed before, the friction between cylinder and plunger is mechanically controlled, depending on the relative position of the plunger in the cylinder. However, the element controlling the additional friction (the hollow friction cylinders  74   a ,  74   a ) are in this case located on the cylinder, while in  FIG. 12  the cams as the controlling element are located on the driving rod. In both cases the relative position of the linearly static elements (cylinder and driving rod) in regard to the displaceable element (the plunger) is the parameter used to control the amount of friction between plunger and cylinder. 
     At least one embodiment of dosing unit  1 , using a similar principle for controlling the friction, is described in  FIG. 17 . Again the valve seat is not shown for simplicity. Two stopper disks  73 ,  73 ′ are mounted on the plunger shaft  32 , on a proximal and a distal end of the continuous outer thread  33 . The threaded sleeve  26  comprising the inner thread  23  is also realized as a stopper disk  73   a.    
     The additional friction that is necessary for switching the valve in the end positions of the plunger is generated when one of the two stopper disks, e.g. the proximal stopper disk  73  as shown in  FIGS. 17( a ) and ( c ) , abuts the stopper disk  73   a  mounted to the cylinder. Since the plunger is actually mechanically blocked front a further linear displacement, the thread friction force exponentially increases with any further rotation, immediately jamming the plunger thread  33  in the cylinder thread  23  and frictionally coupling the plunger and the cylinder. When now the plunger rotation direction is reversed, the static friction between cylinder and plunger is large enough to actuate and rotate the cylinder in the valve seat (not shown) of the dosing unit. When the cylinder abuts the stopper of the valve seat the thread jamming is removed and frictional coupling is released. Thread friction is back to a minimum level. A dosing unit embodiment as discussed in the example above is very robust and reliable. 
     A further variant of such a dosing unit is shown in  FIG. 18 , having two stopper disks  73   a ,  73   a ′ mounted in the cylinder  2 , while one stopper disk  73  is mounted on the plunger shaft  32  on a distal end of the continuous outer thread  33 , and located between the two other stopper disks  73   a .  73   a ′. The inner thread  23  of the cylinder is arranged on the proximal stopper disk  73   a . Similar to the example above, the spindle thread  23 ,  33  jams when the central stopper disk  73  reaches one of the peripheral stopper disks  73   a ,  73   a ′. The resulting frictional coupling between plunger and cylinder then allows rotating the cylinder and switching the valve when the rotation direction is reversed. 
     The inner thread  23  of the cylinder may also be arranged on the distal stopper disk  73   a ′, when the outer thread  33  is arranged on the other side of the central stopper disk  73 . In such a case, however, the necessary length of the plunger shaft and the driving rod, and thus the overall length of the dosing unit, is increased. 
     Such a dosing unit can be further modified by arranging an outer thread  33 ,  33 ′ on both sides of the central stopper disk, each engaging with an inner thread  23 ,  23 ′ on a stopper disk  73   a .  73   a ′, as disclosed in  FIG. 19 . The linear and angular orientation of the engaging threads is advantageously realized in such a way that the two thread sets longitudinally bias each other, thereby effectively removing thread lash. 
     Instead of achieving the temporary locking of cylinder and plunger via jamming the spindle threads, as discussed above, it is also possible to positively lock the plunger and the cylinder at certain longitudinal positions, as for example shown in the dosing unit in  FIG. 20 . The cylinder  2  of the depicted embodiment comprises a cylinder part  28  and a threaded sleeve  26 . The valve seat of the dosing unit, in which the cylinder valve member  2  is rotatably arranged, is not shown. 
     An embodiment of the threaded sleeve comprises a cylinder coupling part  75  in the form of a circumferential ring with a multitude of locking holes  751 . Attached to a distal end of the plunger shaft  32 , a plunger coupling part  76  is provided, having locking elements  761 ,  761 ′ in the form of spring biased balls, arranged on both sides of the cylinder locking element  75 . The plunger locking element  76  can be realized as a cylinder-like element, having a multitude of circumferentially distributed locking elements  761 ,  761 ′, or as two or more arms bearing the locking elements. 
     During pumping and refilling the position of the cylinder coupling part with the multitude of locking holes  751  remains in a fixed position, since the cylinder remains in a fixed position. The plunger coupling part  76  rotates and linearly shifts together with the plunger  3 , to which it is attached. When the plunger  3  arrives at one of its two terminal positions, the spring-biased balls of one end of the plunger locking structure start to slide and roll over the ring  75  surface, with minimum friction. However, when they finally arrive at their corresponding locking holes  751 , the balls  761 ,  761 ′ snap into the holes and positively lock the cylinder to the plunger. When now the plunger rotation direction is reversed, the plunger  3  actuates and rotates the cylinder valve member  2  in the valve seat, until the cylinder abuts the stopper of the valve seat. The valve has switched. Due to continuing rotation, the ball overcomes the spring force and slides under the ring  65 , and the temporary locking of cylinder and plunger is released. 
       FIG. 21  discloses another advantageous variant of a dosing unit  1 , in which a cylinder coupling part in the form of a cylindrical sleeve  75  is coaxially arranged on the cylinder part  28  and attached to the threaded sleeve  26 . Alternatively said cylinder coupling part may also be realized as an integral part of the cylinder  28 , or as a separate part. A plunger locking structure  76  that is attached to a distal end of the plunger shaft  32  comprises cams  762  that are pivotably mounted on the locking structure  76 , by pivot arms  763 . Two sets of depressions  751 ,  751 ′ are located on a proximal and a distal end of the cylinder coupling part  75 . The two coupling parts  75 ,  76  are realized in such a way that the cams  762  slide on the surface of the cylinder coupling part  75  when the cams are located between the two depressions  751 ,  751 ′, and snap into the depressions when the plunger arrives at a terminal position, corresponding to an empty metering cavity  11  ( FIG. 21( a ) ) or a completely filled metering cavity ( FIG. 21( b ) ). The cams are radially biased inwards, since the pivot arms  763  are deformed outwards when the cams slide on the surface during operation. 
     The depressions  751 ,  751 ′ are formed such that a perpendicular wall on the outer side (toward the end of the dosing unit) provides a clearly defined stopping position for the cam  762 , thereby mechanically blocking the further linear displacement of the cam and the attached plunger, which as a results leads to a thread jam. Plunger and cylinder are now coupled by static friction. Upon reversal of the plunger rotation direction, the plunger rotates the cylinder and switches the valve. When the valve has been switched and the further rotation of the cylinder valve member is blocked by a stopper of the valve seat, the thread jam is released, and plunger and cylinder are decoupled. An embodiment of the ramp, on the opposite side of the stopper wall of the depression, forces the pivotably mounted cam outwards, until it slides on the surface. The plunger can now move to the other terminal position, with minimal friction. 
     At least one embodiment of a dosing unit is given in  FIG. 22 , where the pivotably mounted cam is replaced by a spring-biased ball as the locking element  761 , mounted on the plunger locking structure  76 . A number of locking holes  751  are distributed on the cylinder coupling part  75  in the form of a sleeve attached to the threaded part  26  of the cylinder. 
     During normal operation, in the pump mode or the refill mode, the plunger is linearly displaced along the axis, at the same time rotating about the axis. The spring-biased ball rolls and slides on the surface of the sleeve  75 , providing minimum friction. At certain positions, the spring ball  761  snaps into a locking hole  751 , positively locking plunger and cylinder. However, since the valve is in a switched state, the cylinder being mechanically blocked from further rotation, the ball is immediately forced out of the hole upon further rotation of the plunger, and rolls and slides on the surface of the sleeve  75 , providing minimum friction. 
     If on the other hand in such a position the rotation direction is reversed, the positive locking of cylinder and plunger is strong enough to rotate the cylinder valve member in the valve seat, until the other stopper is reached and further cylinder rotation is mechanically blocked. Again the ball is forced out of the hole upon further rotation of the plunger, and rolls and slides on the surface of the sleeve. 
     At least one advantage of such an embodiment is the possibility to define intermediate positions on which the friction between plunger and cylinder is increased, and the valve can be switched. At these positions of positive locking, the drive unit may or may not reverse the plunger rotation direction and thereby switching the valve. 
     In the embodiments of dosing units discussed so far the friction between plunger and cylinder valve member is may be controlled based on the linear position of the plunger. Thus valve switching is enabled at certain relative linear positions of the plunger within the cylinder. 
     At least one embodiment of a dosing unit achieves cylinder valve member actuation by temporary frictional coupling between the cylinder and the driving rod, upon each reversal of the rotation direction of the driving rod. The coupling friction is nut controlled by the position of the plunger in the cylinder, but by the change of the driving rod rotation direction and the relative angular orientation of cylinder and static valve seat. Such an embodiment may allow switching the valve at any longitudinal position of the plunger. 
     An example of such an embodiment is given by the dosing unit schematically disclosed in  FIG. 23 . As can be seen in the schematic cross-section, a cylindrically shaped driving rod coupling part  77  is arranged coaxially to a cylindrically shaped cylinder coupling part  79 . The driving rod coupling part  77  is attached to the driving rod (not shown) of the dosing unit, while the cylinder coupling part  79  is attached to the cylinder of the dosing unit (not shown). Thus during operation of the dosing unit, the two coupling parts  79 ,  77  rotate in regard to each other, while at the same time being fixed in regard to each other in the longitudinal direction. 
     The coupling parts  79 ,  77  are coupled to each other by three friction elements  770  attached to the driving rod coupling part  77 , symmetrically distributed along its circumference. The friction elements  770  have an O-like cross-section and are made from a flexible, elastic material. The materials of the friction elements  770  and the cylinder coupling elements  79  are advantageously chosen such that they provide a large static friction force. 
     The functional principle of the disclosed embodiment is that during normal operation of the dosing unit, where the plunger is either advanced or retreated within the cylinder, the inner driving rod coupling part  77  (attached to the rotating driving rod) rotates counter-clockwise in regard to the cylinder coupling part  79  (attached to the cylinder valve member), as shown in  FIGS. 23( a ) and ( b ) . The cylinder valve member is mechanically blocked from counter-clockwise rotation in the static valve seat, which is schematically shown by a cam  29  of the cylinder abutting a stopper  123  of the valve seat. The elastic friction elements  770  are deformed and are dragged along by the inner coupling part  77 , sliding on the inner surface  792  of the outer cylinder coupling part  79 , which results in a minimum sliding friction force. 
     For switching the valve, the rotation direction of the driving rod is reversed to clockwise. The deformed friction elements  770  are now oriented opposite in regard to the rotation direction ( FIG. 23( c ) ). The cylinder coupling part  79  is not mechanically blocked from clockwise rotation. The rotating driving rod coupling part  77  presses the friction elements into the surface  792  of the coupling part  79  and jams them in regard to the coupling part  79 . The resulting static friction force between surface  792  and frictions elements  770  allows the inner coupling part  77  gripping the outer coupling part  79  and rotating it clockwise in the valve seat, until the cam  29  reaches the other stopper  123 ′ of the valve seat, and is mechanically blocked again. 
     Since the cylinder coupling part cannot rotate any longer, the still frictionally coupled friction elements  770  of the inner coupling part  77  are deformed, and flip via an intermediate state ( FIG. 23( d ) ) to an opposite conformation ( FIG. 23( e ) ). In this conformation the friction elements again slide over the surface  792 , with minimum sliding friction. 
     To achieve high static friction, the materials of the friction elements  770  and the surface  792  are chosen accordingly. For example may at least one of said two elements be made or covered by a rubber-like material. Furthermore the elastic friction element is realized such that the force necessary to deform and flip the friction element is larger than the force due to the torque between the inner and outer coupling parts  77 ,  79 . To adjust the friction forces in the given setup, the different elements may be further modified. For example may the outer cylinder  79  be provided with a roughened or teethed surface. The friction elements can also be arranged on the cylinder coupling part  79  instead of the driving rod coupling part  77 , or on both parts. 
     At least one embodiment of a dosing unit having dynamic friction control is disclosed in  FIG. 24 . Shown is the plunger driving part  4  of the dosing unit, having a driving rod  41  with four longitudinal cams  43 . On a distal end of the driving rod, opposite to the end that is to be located in the longitudinal bore of a plunger shaft (not shown) of the dosing unit, a driving rod coupling part  77  is arranged, having the form of a disk. On the circumference of said disk  77 , three mounting arms  776  are provided, for attaching the plunger driving part  4  to a cylinder in such a way that it is remains freely rotatable along the longitudinal axis  20 . The mounting arms  776  are provided with two distance rips  775  and a cam  774 . 
     During assembly the driving rod  41  is inserted into the plunger shaft bore. Forced by the ramp of the cam  774 , the three mounting arms  776  are forced outwards, until a distal rim  222  of the cylinder wall snaps into the gap provided between the cam  774  and the two distance rips  775 . The dimensions of the gap are chosen such that the rim and thus also the cylinder  2  is positively locked in regard to the plunger driving part  4  with minimum play, but can be rotated around axis  20  with minimum friction. The distal surface  792  of the cylinder rim also acts as the cylinder coupling part  79 . 
     On the surface of disk  77  facing the cylinder, three friction elements  770  are arranged, comprising a pivoting arm  771  that is connected to the driving rod coupling part  77  by a hinge  772 , and that has a tip  775  facing the cylinder. The length of the friction element  770  is chosen such that in the assembled state, during normal operation of the dosing unit, the arm  771  is tilted to one side away from the direction of rotation, as shown in  FIG. 24( d ) . The disk  77  rotates together with the driving rod  41 , symbolized by the arrow to the left. The cylinder  79  is mechanically blocked in the valve seat, symbolized by the crossed-out arrow to the left. During rotation of the driving rod, the lip  775  of the friction element  770  is dragged along and slides on the distal surface  792  of the cylinder coupling part  79  with minimum friction. 
     In order to turn the cylinder valve member  2  in the valve seat and to switch the valve, the rotation direction of the driving rod  41  is reversed. In this direction the cylinder  2  is not mechanically blocked in the valve seat. The friction element is now tilted toward the direction of rotation (arrow to the right). Upon rotation of the driving rod  41 , the tip  775  of the friction element is pressed into the surface  792  of the cylinder coupling part  79 , jamming the frictional element  770  (high static friction, gripping the cylinder and pushing it in the same rotation direction ( FIG. 24( e ) ). 
     When the cylinder has rotated in the static valve seat for a certain rotation angle to the second stopper that corresponds to the other valve state, further rotation of the cylinder is mechanically blocked. Forced by the continuingly rotating driving rod  41  and disk  77 , the hinge region  772  of the friction element  77  is compressed ( FIG. 24( f ) ), allowing the pivoting arm to flip to the other side ( FIG. 24( g ) ). The friction element  770  is now again dragged along by the driving rod coupling part, with minimum sliding friction. 
     Also in this embodiment of a dosing unit, the friction elements can be arranged on the cylinder coupling part  79  instead on the driving rod coupling part  77 , or on both parts. To increase friction, the interacting elements  770 ,  792  may be modified. For example can the surface  792  be provided with teeth that allow a stronger grip of the tip  773  of the friction element  770 , or the surface  792  can be provided with an adhesive or compressible coating. The use of teeth makes the coupling parts unsusceptible to contamination of the surfaces by oil or similar substances. At the same time the teeth define discrete steps of the rotation angle. 
     In at least one embodiment shown in  FIGS. 23 and 24 , the driving rod, and not the plunger, actuates the cylinder valve member in the valve seat. To avoid that the plunger already gets linearly displaced during the valve switching process, the coupling between plunger shaft and driving rod is advantageously temporarily released during valve switching. This is achieved by realizing the longitudinal bore  322  and the driving rod  41  with a certain predefined play. In such an embodiment there is a reduction of friction between driving rod and plunger shaft during linear displacement. 
       FIG. 25  depicts in a cross-sectional view different variants of interacting plunger shafts  32  and driving rods  41 . In  FIG. 25( a ) , the longitudinal bore of the plunger shaft  32  has essentially the shape of the driving rod  41 , the four longitudinal cams  43  of the driving rod being slidably arranged in corresponding slots of the longitudinal bore. Such an embodiment provides essentially no rotational play between driving rod and plunger shaft, and is advantageously used for dosing units as for example shown in  FIGS. 14 to 22 . 
     In  FIG. 25( b ) , the longitudinal bore of the plunger shaft  32  provides rotational play. The slots between the cams  34  of the plunger shaft are designed such that upon reversal of the rotation direction of the driving rod, in the given Figure from clockwise to counter-clockwise, for a certain predefined rotation play angle α, the cams  43  do not rotationally engage with the cams  34  of the plunger rod, until the cams  43  have reached the cants  34  on the other side of the slot ( FIG. 25( c ) ). The angle α is chosen such that the friction elements  770  of  FIG. 23 or 24  can completely switch before the driving rod  41  and the plunger shalt  32  rotationally engage again. This ensures that in a dosing unit as for example shown in  FIGS. 23 and 24 , the friction element does not remain for a longer time in an intermediate state ( FIGS. 23( d ), 24( f ) ), which could lead to irreversible deformation. 
     In at least one embodiment, as shown in  FIG. 25( d ) , the predefined rotation angle β is chosen larger than the angle that is necessary for switching the valve. This ensures that it is geometrically impossible to resume plunger displacement before the valve has been switched. 
     At least one embodiment of dosing unit  1  is disclosed in  FIG. 26 . The cylinder  2  and the plunger (not visible) are identical to the embodiment shown in  FIG. 5 . Visible is the threaded sleeve part  26  of the cylinder  2 , with the radial bias force element  5  mounted to the threaded sleeve part. A plunger driving part  4  similar to the one shown in  FIG. 5  is attached to the distal end of the threaded sleeve part  26  with three mounting arms  776 . The driving rod coupling part  77 , to which the driving rod (not visible) and the friction elements  77  are mounted, provides additional functionality. 
     The friction elements  770 /pivoting arms  771  are attached to the driving rod coupling part  77  by hinge structures  772 , which are mounted to spring element structures  777 . Said spring element structures  777  provide certain elasticity and flexibility in the longitudinal and radial direction. 
     The distal end of the coupling part  77 , opposite to the driving rod and facing toward the driving unit (not shown), is realized as a concave, self-centering drive unit coupling  42 , with three protruding cams  421  that are intended to engage with corresponding elements of the drive unit. 
     In  FIG. 26  the friction elements  770  are shown in the intermediate state, as shown in  FIG. 24( f ) .  FIGS. 27( a )-( m )  shows the different steps during valve switching. Only the most distal end of the cylinder  2  is shown. The depicted different steps are as follows:
       FIG. 27( a ) : The valve is in a first valve state. The driving rod coupling part  77  with the piston rod (not visible) is in the counter-clockwise freewheel mode, and the friction elements  770  are dragged along the surface  792  of the rim  222 . The plunger (not shown) is linearly displaced, driven by the rotating driving rod.     FIG. 27( b ) : The plunger (not visible) has reached a stop position (completely empty or completely full), or the control system of the dosing unit decides to switch the valve for another reason.     FIG. 27( c ) : The valve switching process begins. The rotation direction is reversed from counter-clockwise to clockwise. The friction elements jam with the surface of the rim of the cylinder, and actuate the cylinder clockwise in the valve seat.     FIG. 27( d ) : The cylinder valve member, rotating in the valve seat (not shown) reaches the stopper (not shown) that defines the second valve position. The valve has been switched to its second state.     FIG. 27( e ) : The cylinder valve member is blocked from further rotation.     FIG. 27( f ) : Upon further rotation of the driving rod, the friction elements flips over, and the jamming between driving rod and cylinder valve member is released.     FIG. 27( g ) : The valve is in the second valve state. The driving rod coupling part with the piston rod (not visible) is in the clockwise freewheel mode. The friction elements are dragged along the surface of the rim. The plunger (not shown) is linearly displaced upon rotation of the driving rod.     FIG. 27( h ) : The plunger (not visible) has reached the other stop position (completely full or completely empty), or the control system of the dosing unit decides to switch the valve for another reason.     FIG. 27( i ) : The valve switching process begins. The rotation direction is reversed from clockwise to counter-clockwise. The friction elements jam with the surface of the rim of the cylinder, and actuate the cylinder clockwise in the valve sear.     FIG. 27( j ) : The cylinder valve member, rotating in the valve seat (not shown) reaches the stopper (not shown) that defines the first valve position. The valve has been switched to its first state.     FIG. 27( k ) : The cylinder valve member is blocked from further rotation.     FIG. 27( l ) : Upon further rotation of the driving rod, the friction elements flips over, and the jamming between driving rod and cylinder valve member is released.     FIG. 27( m ) : The valve is in the first valve state again. The driving rod coupling part with the piston rod (not visible) is in the counter-clockwise freewheel node. The friction elements are dragged along the surface of the rim. The plunger (not shown) is linearly displaced upon rotation of the driving rod. The step in  FIG. 27( m )  is essentially identical to step 1, except for the angular orientation of the driving rod.   

     In at least one dosing unit is schematically depicted in  FIG. 28 , where a controlled coupling between cylinder  2  and driving rod  41  is realized with a bistable ratchet mechanism  78 . All figures are shown with the cylinder valve member remaining static, and the driving rod  41  and valve seat moving in relation to the cylinder valve member. 
     A cog wheel  781  is mounted on the driving rod  41  at a distal end. A double pawl element  785  with two opposite pawls  787 ,  787 ′ is pivotably mounted on an axis bearing  784 , which itself is mounted on the cylinder valve member  2 . The double pawl element  785  is provided with an arm  788 . A tension spring  786  is arranged between a first suspension point at the end of the arm and a second suspension point  783 . To provide symmetrical operational conditions, said second suspension point  783  has to be located somewhere on a straight line through the driving rod&#39;s rotation axis and the pivotal axis  784  of the double pawl element  785 . 
     In  FIG. 28( a )  the driving rod  41  is in the counter-clockwise freewheel mode (symbolized by an arrow). The plunger can be linearly displaced in the corresponding direction. The bistable ratchet mechanism is in one of its stable states, driven by the spring force of the tension spring  786 . The teeth  782  of the cog wheel  781 , rotating counter-clockwise together with the driving rod, can pass the pawl  787  without switching the ratchet mechanism. 
     For switching the valve, the rotation direction of the driving rod  41  is reversed, in the given case from counter-clockwise to clockwise ( FIG. 28( b ) . The tooth right of the pawl  787 ′ abuts the pawl, and the ratchet is jammed. The driving rod  41  and the cylinder valve member  2  are now rotationally coupled via the pawl  787  and the bearing axis  784 , and the rotating driving rod rotates the cylinder valve member clockwise (dashed arrow). 
     The rotation of the cylinder is stopped when a first switching element  124  mounted to the valve seat (dotted arrow) reaches the bistable ratchet mechanism, as shown  FIG. 28( c ) . The switching element  124  pushes the first pawl  787  toward the cogwheel. The double pawl element  785  pivots around the axis bearing  784 , the tension spring  786  is expanded, and when the arm  788  passes the line defined by suspension point  783  and axis bearing  784 , the bistable ratchet switches to the other state. The cylinder valve member  2  is now rotationally decoupled from the driving rod  41 . The driving rod  41  is in the clockwise freewheel mode again. The teeth of the cogwheel can pass the ratchet mechanism without engaging, and the plunger is linearly displaced in the opposite direction. 
     To switch the valve back to the first state, the process is repeated ( FIG. 28( d ) ), by reversing the rotation direction from clockwise to counter-clockwise. The ratchet and the cogwheel jam, rotationally coupling the cylinder valve member and the driving rod. The driving rod rotates the cylinder valve member counter-clockwise, until the second switching element  124 ′ mounted to the valve seat reaches the ratchet mechanism, and flips over the double pawl element to its first state, as shown in  FIG. 28( a ) , thereby decoupling again the cylinder valve member and the driving rod. 
     The angular position of the switching elements  124 ,  124 ′ is chosen such that the ratchet switching positions correspond to the two valve positions. Thus no additional stopper elements are necessary, delimiting the rotation of the cylinder valve member in the valve seat. Advantageously they are nevertheless provided, to define clear valve end positions. 
     Instead of using a separate cogwheel the driving rod itself may be used as the cogwheel, with its cams  43  acting as the teeth, if a sufficient number of cams  43  are provided to realize the ratchet mechanism. 
     At least one embodiment of a controllable coupling between driving rod  41  and cylinder valve member  2  is disclosed in  FIG. 29 . A driving rod  41  is arranged within the cylinder  2 , operationally engaging with the plunger shaft (not visible). Only the distal end  412  of the driving rod is visible in  FIG. 29( a ) . The driving rod is provided with a driving rod coupling part  77 , in the form of a hollow cylinder  778 . The distal end of the cylinder is provided with a cylinder coupling part  79 , intended to be arranged in the hollow cylinder  778 . The cylinder coupling part  79  comprises two clamp arms  793 ,  793 ′ that are pivotably connected to the cylinder  2  via hinges  794 ,  794 ′. One clamp arm  793  has one clamp finger  795 , having a radial protrusion on the outside toward the inner side of the hollow cylinder  778 . The other clamp arm  794 ′ has two clamp fingers  795 ′ with a radial protrusion. Alternatively both clamp arms may be provided with an equal number of clamp fingers. 
     The dimensions of the two coupling parts  79 ,  77  are chosen such that in the assembled state of the dosing unit the clamp fingers  795 ,  795 ′ are radially biased against the inner surface of the hollow cylinder  778 . As a result the driving rod  41  and the cylinder valve member  2  are frictionally coupled, the rotating driving rod being able to actuate the cylinder valve member. 
     To minimize friction during the linear displacement of the plunger within the cylinder, the cylinder coupling part  79  is provided with means  796 ,  796 ′ to rotationally decouple the two coupling parts  79 ,  77 . Each of the two clamp arms is provided with a release element arranged  796 ,  796 ′ outside of the hollow cylinder  778 . Two switching elements (nor visible) mounted on the valve seat are arranged on such angular positions that in each of the two valve states, one of the switching elements engages with one of the decoupling elements  796 ,  796 ′. The resulting force presses the corresponding clamp arm  793 ,  793 ′ inwards, thereby decoupling the two coupling parts  79 ,  77 , and thus the driving rod  41  and the cylinder valve member  2 . Upon further rotation of the driving rod in the same direction, friction is minimal, and the cylinder valve member remains on place. 
     To switch the valve, the rotation direction of the driving rod is reversed. The switching element disengages the release element, and the clamp arms engage again with the hollow cylinder. The frictionally coupled cylinder valve member rotates together with the driving rod, until the second switching element reaches the second release element, and coupling element and driving rod are decoupled again. 
     Instead of coupling arms engaging with a hollow cylinder, another embodiment of such a controllable coupling can be realised with a coiled spring, connected to the cylinder. The coil spring is looped around a cylindrical portion of the driving rod, and frictionally couples the cylinder and the driving rod. Switching elements of the valve seat can engage with the ends of the coil spring, increasing the radius of the coil spring and temporarily decoupling cylinder and driving rod. 
     While various embodiments of dosing units and methods for their use have been described in considerable detail herein, the embodiments are merely offered by way of non-limiting examples of the disclosure described herein. It will therefore be understood that various changes and modifications may be made, and equivalents may be substituted for elements thereof, without departing from the scope of the disclosure. Indeed, this disclosure is not intended to be exhaustive or to limit the scope of the disclosure. 
     Further, in describing representative embodiments, the disclosure may have presented a method and/or process as a particular sequence of steps. However, to the extent that the method or process does not rely on the particular order of steps set forth herein, the method or process should not be limited to the particular sequence of steps described. Other sequences of steps may be possible. Therefore, the particular order of the steps disclosed herein should not be construed as limitations of the present disclosure. In addition, disclosure directed to a method and/or process should not be limited to the performance of their steps in the order written. Such sequences may be varied and still remain within the scope of the present disclosure. 
     Having described the present disclosure in detail and by reference to specific embodiments thereof, it will be apparent that modifications and variations are possible without departing from the scope of the disclosure defined in the appended claims. More specifically, although some aspects of the present disclosure are identified herein as preferred or particularly advantageous, it is contemplated that the present disclosure is not necessarily limited to these preferred aspects of the disclosure. 
     LIST OF REFERENCE NUMERALS 
     
         
           1  dosing unit 
           11  metering cavity 
           12  valve seat 
           121  inlet 
           122  outlet 
           123 ,  123 ′ stopper elements 
           124 ,  124 ′ switching element 
           2  pump cylinder/cylinder valve member 
           20  cylinder axis 
           21  cylinder head 
           211  opening 
           212  guide ring 
           22  cylinder wall 
           221  opening in the cylinder wall 
           222  rim 
           23 ,  23 ′ threaded portion of the cylinder, cylinder thread 
           25 ,  25 ′,  25 ″,  25 ′″ threaded claw 
           251  slot 
           26  threaded sleeve par 
           261  slot 
           262  protrusion 
           263  sleeve element 
           27  tension ring 
           271  slot 
           28  cavity part 
           29  cam 
           3  plunger 
           31  plunger plug 
           311  plug sealing element 
           312  plug protrusion 
           32  plunger shaft 
           321 ,  321 ′ shaft arm, split portion of plunger shaft 
           323  hinge 
           322  longitudinal bore 
           33 ,  33 ′ threaded portion of the plunger, plunger thread 
           33   a ,  33   a ′,  33   a ″ portions of the thread 
           331  lateral surface of the thread 
           34  cam 
           35  plunger coupling element 
           37  slot 
           38  slot 
           39  bridge structure 
           4  plunger driving part 
           41  plunger driving rod 
           411  proximal part 
           412  distal part 
           42  drive unit coupling 
           421  cam 
           43 ,  43 ′ cam 
           44 ,  44 ′ cam 
           441  cut-out 
           5  radial bias force element 
           51  threaded element 
           52  spring element 
           53  locking structure 
           55  wire 
           56  flat surface element 
           57  mounting sleeve 
           58  opening 
           59  spring element 
           59   a  inner thread segment 
           59   b  outer thread segment 
           6  axial bias force element 
           62  spring element 
           64 ,  64 ′ threaded element 
           65  inner thread portion of threaded element 
           66  outer thread portion of threaded element 
           7  friction control element 
           71 ,  71 ′ ramp 
           71   a  elevation 
           72 ,  72 ′ ramp 
           73 ,  73 ′ stopper disk 
           73   a ,  73   a ′ stopper disk 
           74 ,  74 ′ friction cylinder 
           74   a ,  74   a ′ friction cylinder 
           75  cylinder coupling part 
           751  locking hole 
           76  plunger coupling part 
           761 ,  761 ′ spring-biased ball, locking element 
           762  cam, locking element 
           763  pivot arm 
           77  driving rod coupling part 
           770  friction element 
           771  pivoting arm 
           772  hinge 
           773  tip 
           774  snap lock cam 
           775  distance rip 
           776  mounting arm 
           777  spring element 
           778  hollow cylinder 
           78  bistable ratchet mechanism 
           781  cog wheel 
           782  tooth 
           783  suspension point 
           784  axis bearing 
           785  double pawl element 
           787 ,  787 ′ pawl 
           786  tension spring 
           788  arm 
           79  cylinder coupling part 
           792  surface 
           793 ,  793 ′ clamp arm 
           794 ,  794 ′ hinge 
           795 ,  795 ′ clamp finger 
           796 ,  796 ′ release element 
         F bias  bias force 
         F bias,ax  axial component of the bias force 
         F ax  axial force acting on the plunger