Patent Publication Number: US-2019167523-A1

Title: Medicament dispenser

Description:
TECHNICAL FIELD 
     This disclosure generally relates to a medicament dispenser comprising a piston-cylinder assembly, a valve assembly, and actuator assembly configured to receive and dispense a source of medicament. 
     BACKGROUND 
     Conventionally drops are applied to the eye, mouth or other mucus membranes with a dropper generally by squeezing a plastic container fitted with a tapered nozzle. This manner of application has a number of disadvantages such as the requirement to align the tapered nozzle precisely with the eye as well as from anticipation of the drop and involuntary blinking, both of which may result in the drop of medicament not being delivered to the ocular space. Furthermore, and particularly applicable to self-administration of eye drops, is the problem of uncertain dosage originally applied and the indeterminate fraction thereof that is squeezed out of the eye by reflex blinking. 
     Continued use of eye drops in certain instances is required for medical treatment. Thus, for example, in the treatment of glaucoma it is conventional to require the administration to the ocular space a number of times per day for life. The necessity of continued usage of eye drops as in the foregoing instance usually requires the drops to be self-administered and the present disclosure is particularly adapted to improve this application. 
     SUMMARY 
     In a first embodiment, a valve assembly comprising a piston-cylinder assembly configured to receive and dispense a liquid from a container, the piston-cylinder assembly having at least one fluid inlet, at least one vent inlet, and at least one fluid outlet; a cannula in fluidic communication with the vent inlet; a sheath surrounding the cannula and providing a fluid path between the cannula and the sheath, the sheath in fluid communication with the fluid inlet and the fluid outlet; an actuator assembly providing stored energy and release of the stored energy, the actuator assembly coupled to the piston; and a container manipulation system configured to align and present a container with the cannula and the sheath. 
     In a second embodiment, a dispensing device is provided, the dispensing device comprising: a piston-cylinder assembly, a fluidic system fluidically coupled to the piston-cylinder assembly, the fluidic system comprising a valve assembly, the valve assembly comprising: a cannula having a piercing distal end; a proximal end separated by a length; and at least one side port in proximity to the piercing distal end; and the at least one side port fluidically coupled to a vent; a one-way valve fluidically coupled to the vent; a sheath surrounding the length of cannula, the sheath having a distal end; a proximal end; at least one side opening; and a fluid path between the at least one side opening and a portion of the length of the cannula; a one-way valve fluidically coupled to the flow path; an outlet in fluid communication with the cylinder and the flow path; the piston configured to draw an amount of liquid through the valve assembly into the cylinder, and to expel the amount of liquid; and an actuator assembly coupled to and biasing the piston with stored energy. 
     In a third embodiment, a dispensing device is provided, the dispensing device comprising: a housing comprising: a piston-cylinder assembly; a fluidic system fluidically coupled to the piston-cylinder assembly; a container manipulation assembly for receiving and fluidically coupling contents of a container to the fluidic system; the fluidic system comprising a valve assembly, the valve assembly comprising: a cannula having a piercing distal end; a proximal end separated by a length; and at least one side port in proximity to the piercing distal end; and the at least one side port fluidically coupled to a vent; a one-way valve fluidically coupled to the vent; a sheath surrounding the length of cannula, the sheath having a distal end; a proximal end; at least one side opening; and a fluid path between the at least one side opening and a portion of the length of the cannula; a one-way valve fluidically coupled to the flow path; an outlet in fluid communication with the cylinder and the flow path; the piston configured to draw an amount of liquid through the valve assembly into the cylinder, and to expel the amount of liquid; the container manipulation assembly configured for arranging the cannula and the sheath to access contents of the container; and an actuator assembly coupled to and biasing the piston with stored energy. 
     In a third aspect, alone or in combination with any of the previous aspects of the first embodiment, the actuator operably coupled to a stored energy source. 
     In a fourth aspect, alone or in combination with any of the previous aspects of the first embodiment, the actuator assembly is configured with a first configuration and a second configuration, the first configuration capable of urging the piston in a first direction within the cylinder and activating a stored energy source; the second configuration capable of releasing the stored energy activated by the first configuration and urging the piston in a second direction within the cylinder opposite the first direction. 
     In order to understand the invention and to see how it may be carried out in practice, embodiments will now be described, by way of non-limiting example only, with reference to the accompanying drawings, in which: 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIG. 1A  and  FIG. 1B  depict perspective views of an embodiment of the present disclosure. 
         FIG. 2  depicts an exploded view of the device of  FIG. 1A . 
         FIG. 3  depicts an exploded view of a fluid flow system of the present disclosure. 
         FIG. 4A  and  FIG. 4B  depict a plan and side view, respectively, of the device of  FIG. 1A . 
         FIG. 5  depicts a sectional view of  FIG. 4B  along section line  5 - 5 . 
         FIG. 6A  and  FIG. 6B  depict a plan and side view, respectively, of the device of  FIG. 1A  with a medicament container. 
         FIG. 7  depicts a sectional view of  FIG. 6B  along section line  7 - 7 . 
         FIG. 8A  and  FIG. 8B  depict a plan and side view, respectively, of the device of  FIG. 1B . 
         FIG. 9  depicts a sectional view of  FIG. 8B  along section line  9 - 9 . 
         FIG. 10  depicts a sectional view of  FIG. 4A  along section line  10 - 10 . 
         FIG. 11  depicts a sectional view of  FIG. 6A  along section line  11 - 11 . 
         FIG. 12  depicts a sectional view of  FIG. 8A  along section line  12 - 12  in a primed, activated state. 
         FIG. 13  depicts a sectional view of  FIG. 8A  along section line  12 - 12  during activation. 
         FIG. 14  depicts a sectional view of  FIG. 8A  along section line  12 - 12  with an alternate activation embodiment. 
         FIG. 15A  and  FIG. 15B  depict perspective views of an embodiment of the present disclosure. 
         FIG. 16A  depicts an exploded view of the device of  FIG. 15A . 
         FIG. 16B  depicts a partial exploded view of the activation mechanism of the present disclosure. 
         FIG. 17  depicts an exploded view of a fluid flow system of the present disclosure. 
         FIG. 18A ,  FIG. 18B ,  FIG. 18C , and  FIG. 18D  depict a first perspective view, a second perspective view rotated about 90 degrees from the first perspective view, a top view, and a bottom view, respectively, of a container manipulation system of the present disclosure. 
         FIG. 19A  depicts a side view of the device of  FIG. 15A . 
         FIG. 19B  depicts a sectional view along section line  19 A- 19 A of the device of  FIG. 19A  without a medicament container. 
         FIG. 20A  depicts a top plan view of the device of  FIG. 15A . 
         FIG. 20B  is a side view of the device of  FIG. 15A . 
         FIG. 21  is a sectional view of  FIG. 20B  along section line  21 - 21 . 
         FIG. 22  is a sectional view of  FIG. 20A  along section line  22 - 22 . 
         FIG. 23  is a sectional view of  FIG. 20A  along section line  23 - 23 . 
         FIG. 24  is a sectional view of  FIG. 20A  along section line  24 - 24 . 
         FIG. 25A  is a top plan view of  FIG. 15B . 
         FIG. 25B  is a side view of  FIG. 15B . 
         FIG. 26  is a sectional view of  FIG. 25B  along section line  26 - 26 . 
         FIG. 27  is a sectional view of  FIG. 25A  along section line  27 - 27 . 
         FIG. 28  is a sectional view of  FIG. 27  along section line  28 - 28 . 
         FIG. 29A  is a top plan view of the device of  FIG. 15B  in an activated state. 
         FIG. 29B  is a side view of the device of  FIG. 15B  in an activated state. 
         FIG. 30  is a sectional view of  FIG. 29B  along section line  30 - 30 . 
         FIG. 31  is a sectional view of  FIG. 29A  along section line  31 - 31 . 
         FIG. 32  is a partial sectional view of section  32  of  FIG. 29A . 
         FIG. 33  is a sectional view of  FIG. 29A  along section line  33 - 33 . 
         FIG. 34  is a sectional view of  FIG. 29A  along section line  34 - 34 . 
         FIG. 35A  is a top plan view of the device of  FIG. 15B  in a final state. 
         FIG. 35B  is a side view of the device of  FIG. 15B  in a final state. 
         FIG. 36  is a sectional view of  FIG. 35B  along section line  36 - 36 . 
         FIG. 37  is a sectional view of  FIG. 35A  along section line  37 - 37 . 
         FIG. 38  is a sectional view of  FIG. 35A  along section line  38 - 38 . 
         FIG. 39  is a sectional view of  FIG. 35A  along section line  39 - 39 . 
         FIG. 40  is a side view of the device of  FIG. 15B  in an inverted state. 
         FIG. 41  is a sectional view of the device of  FIG. 40  along section line  41 - 41 . 
         FIG. 42  is a partial sectional view of section  42  of  FIG. 41 . 
         FIG. 43  is a partial cutaway view of  FIG. 40 . 
     
    
    
     DETAILED DESCRIPTION 
     An apparatus and method for applying medicament to the eye by urging an amount of fluid from a medicament container through an inlet into a cylinder via a flow control valve. The medicament is urged with sufficient velocity from the cylinder with a piston through a one-way valve to minimize delivery loss via blinking of the eye during self-administration. In one aspect of the present disclosure, the present device is devoid of a pressurized gas source to assist in the dispensing of the medicament. 
     The embodiments herein are exemplarily described in the context of a device comprising a modular system in which the device and the medicament liquid source are provided separately, or at least independent of each other. A liquid medicament source can then be independently selected, and coupled to the present device as desired. This enables the same device to be used repeatedly and/or for different treatments. Such a device, if used for institutional use, can be at least partially automated or provided as a kit or combination, so as to provide for such medicament selection. It is understood that the present disclosure can be provided as a single unit, or a single use device, the medicament or its container integral with the device. 
     Devices disclosed herein can be for personal or hand held use, or for use on a more regular basis in healthcare settings. For whatever use, the device is configured for ensuring a proper spacing between the device and the eye to be targeted, and this can be adjusted, particularly in the devices adapted for institutional use. In this respect, it will be noted that the dispensing mechanisms disclosed and described in the present disclosure are capable of discharging a form of liquid medicament, e.g., droplets, substantially horizontally or vertically over a minimum distance so as not requiring a user or healthcare provider to operate the device directly above an eye, e.g., not requiring solely the use of gravity to target drops of medicament. 
     With reference to  FIGS. 1A and 1B , dispenser  100  is shown in perspective views comprising a carriage receiving member  110  presenting an opening for receiving a carriage manipulation system comprising a carriage member  103 , the carriage member  103  configured for receiving medicament container  99 , the carriage receiving member  110  integral with housing  101 . Device  100  further comprises optional projection  112 . Projection  112  is configured for assisted locating and/or positioning the dispensing device  100  in proximity to a target location, for example, an eye or mucous membrane. Projection  112  can be configured in a variety of sizes and may be readily removed at collar  109  and attached to device  100 . 
     Carriage member  103  is shown engaged with carriage receiving member  110  that is integral with dispenser  100 . In one aspect, device  100  can be provided with carriage member  103  separate and apart from carriage receiving member  110 . In one aspect, as shown in  FIGS. 1A and 1B , carriage receiving member  110  projects from the longitudinal axis A-A of device  100 . In one aspect, as shown, carriage receiving member  100  projects at an angle less than 90° from the longitudinal axis A-A of device  100 . In other aspects, carriage receiving member  110  can project essentially perpendicular to the longitudinal axis A-A of device. Button  105  is operably coupled to an actuating system  111  internal to the housing  101 . 
     With reference to  FIG. 1A , carriage member  103  is shown receiving medicament container  99 . With reference to  FIG. 1B , upon receipt of the medicament container  99  by carriage member  103 , the carriage member is configured for engaging with the carriage receiving member  110 , for example, with corresponding external and internal threading. 
     With reference to  FIGS. 2 and 3 , an exploded view of the device of  FIG. 1A  (without medicament container  99 ) is provided, showing carriage member  103  received by carriage receiving member  110 , and that it at least partially surrounds a portion of a cannula  410  having sheath  408 . 
     In one aspect, cannula  410  is configured to be essentially centered in carriage receiving member  110 . In one aspect, cannula  410  is configured to be essentially centered in carriage receiving member  110  and carriage member  103 . 
     Valve assembly  400  positioned between housing components  101   a  and  101   b , fluidically couples a fluidic system comprising valve assembly  400  to piston-cylinder components of an actuating assembly  333 . Valve assembly  400  comprises an upper valve housing  405  being coupled on one (lower) side to a lower valve housing  401  and a flange seal  409  on the other (upper) side. 
     With reference to  FIG. 3 , flange seal  409  comprises seat  412  for receiving proximal end  455  of cannula  410  and proximal end  472  of sheath  408 . Flange seal  409  couples with upper valve housing  405  to provide a fluid reservoir  414 . Fluid reservoir  414  contains coupling  406   a  and ferrule  413  spatially separated from coupling  406   a . Upper valve housing  405  comprises an isolated filter compartment  402   a  and filter  402  adjacent the flange seal  409 . 
     Upper valve housing  405  is couplable to lower valve housing  401  and together with partition  441  provides a fluid compartment  440  isolated from vent compartment  442  in between the respective valve housings, each respective compartment having associated there with flow control valves  406  and  404 , respectively. Coupling  406   a  secures flow control valve  406  in-between upper and lower valve housing components. Flow control valve  406  fluidically couples fluid reservoir  414  and fluid compartment  440  with sheath  408  and the at least one side opening  470 . Flow control valve  404  fluidically couples vent compartment  442  and vent filter housing  402   a  with cannula  410  and the at least one side-port  460 . In this configuration, the venting of device  100  is essentially isolated from the liquid flow path. 
     Lower housing  405  comprises opposing flange ends  458 ,  459 . Flange  458  couples with flange cap  419  and encloses a one-way dispensing valve  407 . Opposite flange  459  couples flow path  190  with actuator system  333  discussed below. 
     With specific reference to the expanded exploded view of  FIG. 3 , fluidic cannula  410  has a pointed distal end  450 , at least one side-port  460 , and a proximal end  455 . Proximal end  455  of cannula  410  is received by a sheath  408  having a distal opening  471  and a proximal opening  472 . Sheath  408  comprises at least one side opening  470  positioned between is distal opening  471  and proximal opening  472 . In one aspect, the outer diameter of cannula  410  is configured such that it is smaller than the inner diameter of sheath  408  such that fluid may freely flow between the outer diameter of the cannula and the inner diameter of the sheath. In some aspects, the spacing between the inner diameter of the sheath and the outer diameter of the cannula can be between about 0.0005 inches (about 0.00127 centimeter) to about 0.005 inches (about 0.0127 centimeter). Other spacing of the inner diameter of the sheath and the outer diameter of the cannula can be used. The inner diameter of sheath  408  from its distal opening  471  and proximal opening  472 , surrounds cannula  410  from its proximal end  455  up to but not including or otherwise obfuscating or blocking the one or more side-port  460  or the pointed distal end  450 . In other words, the at least one side-port  460  is spatially (e.g., vertically from the housing, with reference to axis B-B of  FIG. 1B ) separated from the at least one side opening  470  of sheath  408 . The spatial separation of the at least one side-port  460  and the at least one side opening  470  can be determined, for example, based on the physical parameters of the medicament container and other physical parameters of the device, as further discussed below. 
     In one aspect, distal opening  471  is reduced in inner diameter so as to secure and/or seal outer diameter of cannula  410  with sheath  408  and thus direct liquid flow essentially through the at least one side opening  470 . Securing distal opening  471  with cannula can be by press-fit, welding, adhesive, sonic, and the like. In one aspect, there can be no intentional sealing of opening  471  and the cannula. In this configuration, side-port  460  of cannula  410  functions efficiently as an air vent while the at least one side opening  470  of sheath  408  functions to receive liquid from the medicament container  99  about the inner diameter of the sheath and allows the liquid to flow around the outer diameter of cannula  410  into fluid reservoir  414 . In one aspect, liquid flow between the at least one side-port  460  and proximal end  455  of cannula  410  is prevented. In another aspect, liquid flow between the at least one side-port  460  and proximal end  455  of cannula  410  is prevented and liquid flow is restricted to the space between sheath  408  cannula  410 . In one aspect, the side-port  460  is arranged to be about 180 degrees rotated from the side opening  470  to maximize fluid draw and venting exchange. In other aspects, using longitudinal axis B-B as reference, the side-port  460  is positioned such that it is vertically above the side opening  470 , relative to the housing. In one aspect, the side-port  460  is arranged to be about 180 degrees rotated from the side opening  470 , and, using longitudinal axis B-B as reference, the side-port  460  is positioned such that it is vertically above the side opening  470 , relative to the housing. 
     With specific reference to the expanded exploded view of  FIG. 3 , proximal end  455  of cannula within sheath  408  is received by seat  412  of flange seal  409 , whereas the proximal end  455  of cannula proceeds thru seat  412  to ferrule  413  and further extends into vent compartment  442 , terminating at vent seat  456  so as to provide an isolated vent path from the at least one side-port  460  of the cannula and the vent compartment  442 . Vent seat  456  may be an elevated protrusion projecting from a surface of vent compartment  442  or may be a depression in the surface of the vent compartment, and maybe of a size and shape so as not to completely obstruct the distal end  450  of the cannula  410  and to allow for venting. 
     Proximal opening  472  of sheath  408  seats in seat  412  of the flange seal  409  so as to provide an isolated fluid path to fluid reservoir  414 . In one aspect, outer diameter of sheath  408  is secured to seat  412  with an adhesive. Seat  412  is designed to receive proximal opening  472  of sheath  408  so as to avoid contamination of the fluid path (the inner diameter of sheath  408 ) by the adhesive. Tapering and other design features can also be used to provide a liquid tight seal between the outer diameter of sheath  408  and seat  412 . 
     With reference back to exploded view  FIG. 2 , actuating system  333  is shown fluidically coupled to flow channel  190  of flow path  190   a  and flange end  459  of lower valve housing  401 , comprises a piston  530  sealably engaged to the fluid flow path  190   a  of lower valve housing  401 . Piston  530  and fluid flow path  190   a  provide a piston-cylinder arrangement. In one aspect, a portion of fluid flow path  190   a  provides a cylinder  190   b  within lower valve housing  401  for receiving piston  530  and allowing for reversible translation of the piston within the cylinder essentially parallel with the longitudinal axis A-A and essentially opposed to longitudinal axis B-B. O-ring  534  provides a liquid-tight seal of piston  530  in cylinder  190   b . Gasket  532  provides adjustment of piston stroke length and medicament dosing/dispensing amount and can also provide a reduction or elimination of sound and/or vibration. Piston  530  is attached or otherwise integral at its opposing end to member  527 . Member  527  is generally an elongated structure of two parallel projecting surfaces providing a opening there between terminating at one end, as shown, in an annular ring configured for pulling, in a generally lateral direction parallel to the longitudinal axis A-A of device  100 , for example, by a digit of a human hand. Stored energy  525 , exemplified as a spring, is configured within opening between parallel projecting surfaces of member  527 . Upper surface  520  is raised from the parallel projecting surfaces of member  527  and terminates in a lip  536  proximal to piston  530 . 
     Member  527  and actuating button  105  are configured to be positioned within the housing  101 . Actuating button  105  comprises pivot points pivotally configured in housing  101 . Biasing means  528  are positioned at end  105   b  of button  105  so as to allow the button to reversibly operate in a direction essentially perpendicular to the longitudinal axis A-A of device  100 . Button  105  comprises, at its opposite end, a projecting lip  519  that engages lip  536  of member  527  and allows for control of the stored energy  525  and the dispensing of medicament by the device  100 . Projecting lip  519  can be presented as gear teeth with complementary teeth presented on upper surface  520  of member  527 . 
     The function and structural relationships of carriage receiving member  110  and carriage member  103  are now discussed. With reference to  FIGS. 1A ,1B, 4A, 4B , and  FIG. 5 , depicting a sectional view of  FIG. 4B  along section line  5 - 5 , carriage member  103  is shown as an elongated cylinder having a first end  102   a  and a second end  102   b  that is generally centered and aligned with longitudinal axis B-B. Male threads  103   a , in proximity to the second end  102   b , is configured to partially encircle the outer diameter of carriage member  103  and provide edges  103   c  at both terminal ends of the male threads  103   a . Male threads  103   a  is configured to be received by female threads  110   a  of housing  101 . 
     With reference to perspective views  FIGS. 4A, 4B, 6A, 6B, and 8A and 8B , and their corresponding sectional views of  FIGS. 5, 7, and 9 , along sectional lines  5 - 5 ,  7 - 7 , and  9 - 9 , respectively, the device  100  is depicted without medicament container  99 , with medicament container  99  inserted in carriage member  103 , and with medicament container and carriage member  103  fully threaded into carriage receiving member  110 , respectively. The structural and functional interaction between the carriage member  103 , carriage receiving member  110 , and the medicament container  99 , carriage member  103 , are now described. 
     With reference to  FIGS. 1A, and 5 , depicting a sectional view of  FIG. 4B  along section line  5 - 5 , device  100  is shown in an initial configuration, without medicament container  99 . Upon assembly, at least a portion of elongated members  150  is presented in a cavity formed through carriage member  103 . Elongated members  150  are approximately attached to carriage member  303  and project parallel to longitudinal axis B-B. As shown, each of the 2 two elongated members  150  terminate in a distal end corresponding to projecting protrusions  150   a , shown projecting essentially horizontally. Protrusions  150   a  project into the interior of carriage member  103 . The width of the cavity containing elongated members  150 , measured along the outer perimeter of carriage member  103  are sized to receive the total width of protrusions  152   a  of the carriage receiving member  110 . In this assembled configuration, cavity wall edge  103   e , exposed by the inward inflection of elongated members  150  by elongated retaining members  152 , engages with edge surfaces  152   b  of protrusions  152   a  of retaining members  152 , preventing carriage member  103  from threading (either clockwise or counterclockwise) with carriage receiving member  110  in the absence of an inserted medicament container  99 , as further discussed below. Upon assembly, and in this initial configuration, second end  102   b  and male threads  103   a  of carriage member  103  extends into carriage receiving member  110  to at least partially engage female threads  110   a . The pre-engagement of male threads  103   a  and a lip formed on the interior diameter of the opening of carriage receiving member  110  prevents carriage member  103  from being completely removed, either before or after medicament container  99  is inserted. 
     With reference now to  FIGS. 7 and 11 , depicting a sectional view of  FIG. 6B  along section line  7 - 7  and a sectional view of  FIG. 6A  along section line  11 - 11 , respectively, device  100  is depicted in a first configuration, where a medicament container  99  has been introduced to carriage member  103 . Inwardly, facing projecting protrusions  150   a  of elongated members  150  allow an annular collar  98  of medicament container  99  to slidably pass and slightly outwardly bias protrusions  150   a  and elongated members  150  along a portion of their length. After the annular collar  98  has passed the protrusions  150   a . elongated members  150  partially return to their initial configuration and restrain or prohibit the medicament container  99  from being withdrawn from carriage member  103 , but are no longer flush along the entire length with the outer diameter of carriage member  103 , and now extends slightly past cavity wall edge  103   e . The bias applied to elongated members  150  by the inserted container  99  provides for a portion of elongated member  150  to engage with a portion of inwardly projecting protrusions  152   a  of corresponding retaining members  152  of carriage receiving member  110  so as to allow edges  103   c  of cavity of carriage member to freely rotate without engaging edge surfaces  152   b  of projecting protrusions  152   a  and thus allow one way threading of carriage member  103  with carriage receiving member  110 . The composition, bias and flexibility of elongated members  150  and/or elongated retaining members  152  can be adjusted for a desired amount of flexibility/bias for repeated use as well as, for example, by tapering or providing step changes in thickness along the length of the member. 
     Still referencing  FIG. 7 , device  100  provides for retaining of medicament container  99  and aligning tapered nozzle  97  in carriage member  103  and for threading the carriage member into carriage receiving member  110 . Distal end  450  of cannula  410  is aligned with tapered nozzle  97  of medicament container  99  such that threading of carriage member  103  into carriage receiving member  110  introduces distal end  450  of cannula  410  into tapered nozzle  97  of medicament container  99 , thus, eliminating possible deflection and/or misalignment of the cannula with a rather small diameter orifice typical of such tapered nozzles of such medicament containers. 
     With reference now to  FIGS. 9 and 12 , depicting a sectional view of  FIG. 8B  along section line  9 - 9  a sectional view of  FIG. 8A  along section line  12 - 12 , respectively, device  100  is presented in a second configuration with medicament container  99  and carriage member  103  fully threaded into carriage receiving member  110 . In this second configuration, distal end  450  and side-port  460  of cannula  410 , as well as side opening  470  of sheath  408 , having been properly aligned with tapered nozzle  97 , are urged through opening  96  of medicament container  99 . As the opening  96  of a typical medicament container is of a small-diameter and generally constructed of a thermoplastic polymer such as polyethylene or polypropylene, in one aspect, cannula  410  is of metal or of an engineering grade plastic having higher tensile strength than that of such polyolefins. Distal end  450  of cannula  410  can be sharpened and/or beveled in a variety of ways suitable for advancing through opening  96 . Likewise, distal end  471  of sheath  408  can be constructed of a rigid polymer of suitable tensile properties and/or tapered so as to engage and transverse opening  96 . 
     Upon completion of the threading of carriage member  103  with carriage receiving member  110 , protrusions  152   a  of the carriage receiving member are permitted to engage openings  103   b  adjacent section  103   d  of the carriage member and thus effectively reduce or prevent the reverse threading of the carriage member. In addition, projections  150   a  of elongated members  150  of carriage member  103  maintain the securement of medicament container  99  and prevent or eliminate its removal while providing one or more uses of the device  100 . Window  101   d  provides for an indication of complete threading of carriage member  103  with carriage receiving member  110 , for example, where male threads  103   a  and/or a portion of the carriage member are brightly or fluorescently colored. 
     In one aspect, device  100  is designed for dedicated use with a single medicament container  99  and/or whereas forcing release of either the carriage member  103  from the carriage receiving member  110  or the medicament container  99  from the carriage member  103  would cause damage, including non-operability, of the device. Device  100  and one medicament container  99  can be collectively provided as a kit. Alternatively, device  100  can be configured such that projections  150   a  and  152   a  can accept one or more special tools designed to release carriage member  103  from protrusions  152   a  so as to permit reverse threading of carriage member  103  as well as allowing release the medicament container  99  from protrusions  150   a , so that a medicament regimen using different medicament containers can be employed. Device  100  and two or more medicament containers  99  can be collectively provided as a kit. 
     With the side-port  460  of cannula  410  and side opening  470  of sheath  408  introduced into medicament container  99 , the operation of device  100  can now be described with reference to  FIGS. 12-13 . In this activated configuration, device  100  is configured such that the actuating system  333  can be engaged by the user and prepare device  100  for the dispensing of an amount of medicament from medicament container  99 . 
     Thus, referencing  FIGS. 12-13 , that depict a sectional view of  FIG. 8A  along section line  12 - 12  in a primed, activated state; and a sectional view of  FIG. 8A  along section line  12 - 12  during activation, respectively, the use of device  100  can now be described. 
       FIG. 12  shows piston  530  and will ring  534  slidably received in cylinder  190   b . Flow channel  190  of lower valve housing  401  is fluidically coupled to cylinder  190   b  and fluid compartment  440  via first flow control valve  404  that is fluidically coupled to fluid reservoir  414  that is fluidically coupled to side opening  470  of sheath  408 . 
     First and second flow control valves  404 ,  406  can be check valves arranged together in opposite flow control arrangement such that liquid medicament from container  99  is restricted to flowing in one direction through fluid reservoir  414  and fluid compartment  440  by flow control valve  406  into cylinder  190   b , and air is restricted to flow in the opposite direction from filter  402 , vent compartment  442 , flow control member  404 , through cannula  410  and side-port  460 . Distal end  105   b  of user actuating button  105  is pivotally coupled to lip  519  for engagement with lip  536  of surface  520 . Stored energy  525  is positioned in space  526  of member  527  and is secured with member stop  527   a.    
     In preparation for use, ring member  107  is urged rearward towards distal end  101   c  of housing  101  by a user or healthcare provider, as shown by directional arrow  197 , causing stored energy  525  to compress against member stop  527   a , drawing piston  530  in a first direction opposite that of the direction the medicament is to be dispensed and generally parallel to the longitudinal axis A-A, while drawing an amount of fluid from medicament container  99  into side opening  470  of sheath  480 , into fluid reservoir  414  of upper valve housing  405 . Flow control valve  406  is thus caused to open and release the fluid from the fluid reservoir  414  into flow channel  190  of fluid compartment  440  of lower valve housing and then into cylinder  190   b . Urging of member  527  rearward causes surface  520  to pass under lip  519 , whereas spring  528  biases lip  519  in front of lip  536  thus holding stored energy  525  in preparation for activation. 
     Cap  283 , connected by tether  280  secured to housing by tab  284  thru orifice  284   a , can be removed from flange cap  419  using pull-tab  282 , before or after preparation for use. To activate the device  100 , a user or healthcare provider pushes on button  105  in a direction generally perpendicular to the longitudinal axis A-A as shown by arrow  198 , causing lip  519  to deflect upward such that lip  536  of surface  520  is free to travel forward past and under lip  519  urged by released energy of stored energy  525 , sending piston  530  forward in cylinder  190   b  generally parallel to the longitudinal axis A-A and in the direction of one-way dispensing valve  407 , causing the amount medicament to exit flange cap  419 . 
     In one aspect, one-way flow control valve  407  is a duck-bill valve with a predetermined cracking pressure of between about 0.2 to about 1.5 pounds per square inch (psi) (about 1379 to about 10,340 newtons/square meter). Other cracking pressures can be chosen. Other one-way flow control valves can be used. The one-way flow control valve  407  provides for an aseptic delivery system. Biasing member  528  repositions user actuating button  105  after activation. 
     After dispensing an amount of liquid from the device  100 , the device returns to the second configuration described above. Thus, device  100  provides a “dual-action” mode of operation where the device is first placed in a first state by the user by pulling back on ring member  107  and charging the device with an amount of medicament from medicament container  99 . Dispensing of the amount of medicament requires the pressing of user-actuating button  105  in a separate action, which places the device in a dynamic state whereby the stored energy is released to piston-cylinder assembly expelling the amount of medicament. Prior to first use, the user may purge the system or may squeeze medicament container  99  to urge medicament into reservoir  414  and/or fluid compartment  440  and/or flow channel  190  or fluid flow path  190   a.    
     Device  100  further includes, as an optional feature, a mechanism or “gravity stop” provided to prevent the device from attempting to withdrawal fluid from the medicament container  99  unless or until the device is properly oriented for the fluidic system to access the liquid contained in the medicament container  99 . If not properly oriented, device  100  may allow the introduction of an amount of air into the cylinder  190   b  when member  527  is drawn back for priming of the device, as one or more side opening  470  may not be in contact with liquid in medicament container  99 . By “properly oriented” it is at least meant that the at least one side opening  470  of sheath  480  is in the liquid or below the surface  94 , defined by longitudinal axis F-F, of the liquid within the container  99 , such that the one or more of side opening  470  has access to the liquid or would otherwise draw air into the cylinder. 
     Thus, as shown in  FIGS. 11-12 , ball  580  is floatably positioned in cavity  581  of housing  101 , the cavity sized to receive the entirety of ball  580 . If device  100  is not properly aligned, at least a portion of ball  580  can enter a socket  582  in member  527 , where the socket  582  is slightly larger than cavity  581  so as to readily receive ball  580 , and of a shallow depth of no more than half the diameter of ball  580 , so that when member  527  is moved such that there is alignment of cavity  581  and socket  582 , at least a portion of ball  580  can be received in socket  582  with at least a portion of the ball protruding from the socket thus restricting member  527  and piston  530  from advancing and withdrawing fluid from medicament container  99 . If the device  100  is properly oriented, ball  580  is not introduced into socket  582  even though cavity  581  may be aligned with socket  582 . 
       FIG. 14  depicts a sectional view of  FIG. 8A  along section line  12 - 12  with an alternate activation embodiment whereby biasing member  528  is replaced with flexible member  205  capable of storing energy, flexible member  205  having a first end  207  in proximity to surface  105   a . Opposite end of flexible member  205  is secured under member  528   a  and cavity  209   a  in contact with surface  527   b . Member  205  can have bends  209  and be contained in housing in cutout  527   c  All other operational, functional, and structural elements being the same as previously described for device  100 . 
     Other activation systems may be employed with the carriage member/carriage receiving member and fluidic system described above for device  100 , for example, as disclosed in PCT application number PCT/US2015/058855, incorporated herein by reference in its entirety. 
     A second embodiment of the device of the present disclosure is provided in  FIGS. 15A-43  is now described. In the second embodiment, a modified carriage member and carriage receiving member are provided. While aspects of the piston cylinder arrangement of the first embodiment are maintained, the second embodiment provides for a modified actuating system, where the piston is drawn back using a perpendicularly directed force rather than a parallel directed force. The second embodiment also uses a “dual-action” mode of operation, where the device is first placed in a first state by the user by providing a perpendicular force relative to the longitudinal transitioning of the piston in the cylinder for charging the device with an amount of medicament from medicament container  99 . 
     Dispensing of the amount of medicament requires the pressing of user-actuating button  105  in a separate action, which places the device in a second dynamic state whereby the stored energy is released to piston-cylinder assembly expelling the amount of medicament. In addition, the second embodiment may provide a device suitable for one-handed operation and control and having less total material and a smaller footprint. Such a configuration may prevent or eliminate accidently giving or receiving a “double dose” as each dose has to be loaded/primed by pulling the piston back (directly or indirectly) before it can be delivered with an activation event, as each dose has to be manually chambered with a separate action. 
       FIG. 15A  and  FIG. 15B  depict perspective views of the second embodiment of the present disclosure depicting device  300  and an initial state and a first state, respectively, having cap  325  of carriage member  303  cooperatively engaged with carriage manipulation system comprising a carriage member  303  and carriage receiving member  310 . Carriage receiving member  310  is shown projecting from housing  301  essentially perpendicular to the longitudinal axis C-C. Housing  301  is shown as components  301   a  and  301   b  joined together to form housing  301 . Carriage member  303  is provided in an initial state partially threaded with carriage receiving member  310  along longitudinal axis D-D. Slider  307  cooperates with button  305  to prime the device  300  with an amount of liquid from medicament container  99  and to activate the device for dispensing the amount of liquid. Slider  307  and button  305  transverse essentially parallel to the longitudinal axis D-D during normal operation. Optional positioner  311 , cap  283 , tether  280 , and distal end  282  are structurally and functionally equivalent to that described above for the first embodiment. 
     With reference to  FIG. 16A , which depicts an exploded view of the device  300  of  FIG. 15A , as well as  FIG. 16B , which depicts a partial exploded view of the activation mechanism, fluidic system and housing of the present disclosure, medicament container  99  with tapered nozzle  97  is configured to be received by opening  325   a  in cap  325  of carriage member  303 . 
     With reference to  FIG. 17 , an exploded view of a fluid flow system  400   a  of the present disclosure is shown, where cannula  410 , sheath  408 , seat  412 , flange seal  409 , upper valve housing  405 , filter  402 , filter housing  402   a , valve  407 , flow control valves  404 ,  406 , ferrule  413 , fluid reservoir  414 , coupling  406   a , and flange seal cap  419 , are structurally and functionally equivalent to that as described above as in  FIG. 2 . Device  300  comprises a lower valve housing  501  with vent compartment  442 , fluid compartment  440 , partition  441 , and flow channel  190  and flow path  190   a  as described above as in  FIG. 2 . Lower valve housing  501  has parallel arms  503 ,  504  extending from housing  501  essentially parallel with longitudinal axis C-C and the piston  630 -cylinder  190   b  path. Arms  503 ,  504  are received by button  305  between parallel sidewalls  306 , and the arms are positioned above and below member  627 , respectively, and are received by slider  307  between a pair of extending parallel surfaces  307   a.    
     Referring now to  FIG. 16B  and  FIG. 17 , post  505  extends perpendicular to the longitudinal axis C-C and receives spring  305   a . Parallel sidewalls  306  of button  305  comprises guide track  341  configured to receive a portion of opposed projecting element  629  of member  627 . Guide track  341  can be a cutout and/or opening in parallel sidewalls  306 . Guide track  341  can be stepped, with an upper region  329   a  and a lower region  329   b  parallel to the longitudinal axis C-C, as shown, the upper region includes engagement teeth  328  for receiving corresponding teeth  628  of lower surface of projecting element  629  and lower region  329   b  without engagement teeth. In one aspect, guide track  341  comprises a vertical surface  629   c  perpendicular to longitudinal axis C-C separating the upper region  329   a  and lower region  329   b  of the guide track  341 . 
     Slider  307  receives projecting elements  629  such that cam following surfaces  629   a  engage with corresponding cam surfaces  307   b  of parallel surfaces  307   a  when button  305  is traversed (in a direction essentially perpendicular to longitudinal axis D-D and the piston  630 -cylinder  190   b  axis). In one aspect, slider  307  receives projecting element  629  such that cam following surfaces  629   a  engage with corresponding cam surfaces  307   b  when slider  307  is traversed in only one direction (e.g. down) so as to urge the piston rearward in the cylinder so as to draw fluid from the medicament container  99 , as discussed further below. Slider  307  is designed to accommodate one or more digits of a human hand to facilitate its operation of being biased downwardly (e.g., in a direction perpendicular to the piston-cylinder longitudinal axis corresponding to longitudinal axis C-C and in a direction away from carriage member  303 ). 
       FIG. 18A  and  FIG. 18B  depict perspective views, and  FIG. 18C  and  FIG. 18D  depicts a top view, and a bottom view, respectively, of a container manipulation system of the present disclosure comprising a container carriage member  303 . Carriage member  303  provides for retention and proper alignment of tapered nozzle  97  of medicament container  99  with distal penetrating end  450  of cannula  410 . Opening  325   a  in cap  325  receives medicament container  99  with tapered nozzle  97  pointing generally towards housing  301 . Carriage member  303  comprises male thread segment  303   a , and at least one edge surface  303   b  at either end of the male thread  303   a . Male thread  303   a  is configured for engagement with female threads  310   a  of carriage receiving member  310 . Carriage receiving member  310  provides for, upon assembly, retention of carriage member  303  by way of engaging male thread  303   a  of carriage member  303  with female threads  310   a  of carriage receiving member  310  and lip about inner diameter opening of carriage receiving member. 
     One or more tabs  315  of each of the locking members  318  are positioned between the opposing ends of carriage member  303  and each project inwardly into the interior of carriage member  303 , for receiving and retaining annular collar  98  of container  99 . During insertion of medicament container  99 , locking members  318  and tabs  315  deflect outwardly. Tabs  315  of locking members  318  are shown with angled surfaces on a container receiving side proximal to the opening of cap  325  so as to facilitate deflection of the locking members  318  upon engagement with annular collar  98  of medicament container  99  during insertion into the carriage member  303 , and flat surfaces on the opposing side to engage and retain annular collar upon restoration of the deflection of the projecting tabs  315  so as to retain medicament container  99  in the carriage member  303 . 
     Carriage member  303  comprises at least two elongated container locking members  318  that are arranged approximately 180° apart about the outer perimeter of carriage member  303  projecting parallel to longitudinal axis E-E. Locking members  318  each terminate at tabs  315  distal from male thread  303   a  in proximity to cap  325 . Locking members  318  are provided in an initial configuration generally unbiased, but are configured to deflect slightly outward from the outer diameter of carriage member  303  during insertion of medicament container  99 , and to essentially return to the initial configuration. One or more tabs  315  of each of the locking members  318  are positioned between the opposing ends of carriage member  303  and project outwardly for receiving and retaining annular collar  98  of container  99 . Inwardly projecting tabs  315  of locking members  318  are shown with angled surfaces on one side proximal to the opening of cap  325  so as to facilitate deflection of the locking members  318  upon engagement with annular collar  98  of medicament container  99  during insertion into the carriage member  303 , and flat surfaces on the opposing side to engage and retain annular collar upon restoration of the deflection of the projecting tabs  315  so as to retain medicament container  99  in the carriage member  303 . One or more anti-reverse tabs  317  are arranged on outer perimeter of carriage member  303 , shown projecting outwardly from surface of locking members  318  and outer perimeter of carriage member  303  ( FIG. 18A, 18B ). 
     With reference to  FIG. 18A ,  FIG. 18B ,  FIG. 18C  and  FIG. 18D , as well as  FIG. 28 , which is a sectional view of the device  300  of  FIG. 27 , and top plan view  FIG. 20A , anti-reverse tabs  317 , configured for preventing reverse rotation of the carriage member  303  from carriage receiving member  310 , are shown. Tabs  317  are positioned on the outer perimeter of carriage member  303  between male thread  303   a  and lip  326  of cap  325 . With reference to  FIG. 28 , Tabs  317  are exemplary shown as projections having a tapered surface  317   a  and a flat surface  317   b , the tapered surface configured to slidably engage female threads  310   a  of carriage receiving member  310 , and the flat surface configured to prevent reverse rotation of the carriage member  303  by engaging a surface between female threads  310   a . Tabs  317  are shown on locking members  318 , but alternatively can be positioned about the outer perimeter of carriage member  303 . 
     Carriage member  303  further comprises at least two elongated deflecting members  319  arranged approximately 180° apart within a cavity formed through carriage member  303 , and the deflecting members are arranged parallel to longitudinal axis E-E, and are shown approximately 90° apart from elongated locking members  318 . Other spatial arrangements of the deflecting members  319  and locking members  318  about the carriage member  303  may be employed. Deflecting members  319  each terminate at ends  321  distal from cap  325  in proximity to male thread  303   a . Deflecting members  319  are shown having a tapered thickness along their longitudinal length corresponding with longitudinal axis E-E, with a thicker section  319   a  distal from opening in  325  proximal to end  321 . Upon assembly with carriage receiving member  310 , at least a portion of the distal end of deflecting members  319  are deflected inward exposing an edge  319   b  in wall of carriage member  303 . Edge  319   b  is configured to engage edge  352   a  of projections  352  in the absence of medicament container  99  and prevent rotation (clockwise or counterclockwise). In one aspect, thicker section  319   a  is stepped from thin section  319   c  to engage neck  95  of medicament container  99  to assist in the deflecting of end  321  outwardly from the outer perimeter of carriage member  303  and engage and deflect projections  352  of flexible member  350  of carriage receiving member  310 , so as to deflect projections  352  and members  350  outwardly from carriage receiving member. Members  350  are proximal to housing  301  and project along axis D-D and distally terminate at opening  310   b  of carriage receiving member  310 . By deflecting projection  352  and members  350  upon insertion of container  99 , edges  352   a  of projections  352  do not engage edges  319   b  of carriage member  303  during rotation of carriage member  303  allowing male thread  303   a  of carriage member  303  to fully engage and thread with female threads  310   a  of carriage receiving member  310 . 
     With reference to  FIG. 19A , depicting a side view of the device of  FIG. 15A , and  FIG. 19B , depicting a sectional view along section line  19 A- 19 A of the device of  FIG. 19A , the arrangement of carriage member  303  and carriage receiving member  310  are shown in an initial configuration, partially threaded together but otherwise not capable of further threading without an inserted medicament container  99 , whereas inwardly projecting members  352  of the elongated members  350  occupy a portion of carriage member  303  between male thread segments  303   a  preventing the segments from fully threading with corresponding female threads  310   a  of carriage receiving member. 
     With reference now to  FIG. 20B , which is a side view of the device of  FIG. 15A , and  FIG. 21 , which is a sectional view of  FIG. 20B  along section lines  21 - 21 , the structure and functional relationships between the carriage member  303  and carriage receiving member  310  after insertion of medicament container  99  in carriage member  303  are shown with the container  99  fully received by carriage member  303 . Neck  95  of container  99  deflects end  321  of deflecting member  319  which in turn deflects inwardly projecting intrusions  352  of elongated members  350  outwardly from outer perimeter of carriage receiving member  310 . 
     In this first configuration state with the container  99  introduced to carriage member  303 , male thread  303   a  are configured to be fully received by corresponding female threads  310   a  so as to allow a continuous one-way threading of carriage member  303  with carriage receiving member  310  and to align the opening in tapered nozzle  97  with penetrating and  450  of cannula  410 . 
     With reference now to  FIGS. 25A, 25B, 26 and 27 , a second configuration of device  300  is shown, whereby carriage member  303  has been fully threaded with carriage receiving member  310  such that tapered nozzle  97  and opening  96  of medicament container  99  has been properly aligned and penetrated by penetrating end  450  of cannula  410  such that liquid in medicament container  99  is fluidically coupled to fluidic system  400   a .  FIGS. 20A, 20B, 22, 23 and 24  are similar in presentation to that of  FIGS. 25A-27 , but with the medicament container  99 , and shows that activation system  333  is unchanged by the insertion of the container  99  and the threading of carriage member  303  with carriage receiving member  310 . In this configuration, device  300  is in preparation for priming by a user or healthcare professional. 
     The activation system  333  is now described. With reference to  FIGS. 22 and 24 , sidewall  306  of button  305  having upper region  329   a  and engagement teeth  328  cooperatively engaged with corresponding teeth  628  of lower surface of projecting element  629  above lower region  329   b  of guide track  341 , as shown, having upper region with engagement teeth  628  for receiving corresponding teeth  628 . A portion of cam following surfaces  629   a  of element  629  is shown engaged with cam surface  307   b.    
     Other activation systems may be employed with the carriage member/carriage receiving member and fluidic system described above for device  300 , for example, as disclosed in PCT application number PCT/US2015/058855, incorporated herein by reference in its entirety. 
       FIG. 23  shows the internal structure of piston  630  positioned between extending arms  505  and  504  of fluidic system so as to guide plunger rod in cylinder in a lateral path parallel with longitudinal axis C-C. Piston  630  is biased by spring  525  secured to housing and contained in the plunger rod and aligned with the longitudinal axis C-C. Post  505  positions spring  305   a  for biasing distal end of button  305  in reversible paths of motion perpendicular to longitudinal axis C-C and parallel with longitudinal axis D-D. Distal end  535  of piston  630  is shown in a sealing relationship with one-way dispensing valve  407 . Distal end  535  configured for sealing with dispensing valve  407  provides aseptic integrity and/or minimizes or reduces contamination of the fluid flow path  190   a  by minimizing dead volume and/or preventing a backflow of air or vapor into the flow channel. 
     With reference now to  FIG. 25A , which is a top plan view of  FIG. 15B ,  FIG. 25B , which is a side view of  FIG. 15B ,  FIG. 26 , which is a sectional view of the device of  FIG. 25B  along section line  26 - 26 , and  FIG. 27 , which is a sectional view of the device of  FIG. 25A  along section line  27 - 27 , and with reference to  FIG. 29A , which is a top plan view of the device of  FIG. 15B ,  FIG. 29B , which is a side view of the device of  FIG. 15B ,  FIG. 30 , which is a sectional view of  FIG. 29B  along section line  30 - 30 ,  FIG. 31 , which is a sectional view of  FIG. 29A  along section line  31 - 31 ,  FIG. 32 , which is a partial sectional view of  FIG. 29A  along section line  32 - 32 ,  FIG. 33 , which is a sectional view of  FIG. 29A  along section line  33 - 33 , and  FIG. 34 , which is a sectional view of  FIG. 29A  along section line  34 - 34  in a final configuration where the device  300  is in preparation for dispensing (in a pre-activated state) an amount of liquid removed from the medicament container  99  and presented to flow channel  190  and cylinder  190   b.    
     Referring to  FIGS. 29B, 31, 32 and 33 , to arrive at the final configuration, a user or healthcare provider would apply a force to slider  307  that is perpendicular to the longitudinal axis C-C of the device and in a direction generally away from the carriage member  303  and carriage receiving member  310  in the direction of arrow A. In doing so, cam surface  307   b  engages cam following surface  629   a  and withdraws piston  630  against bias from spring  525  from cylinder  190   b  along a path parallel to longitudinal axis C-C and in the direction of slider  307 . Vacuum created in post  505  causes fluid from medicament container  99  to enter side opening  470  of sheath  408  and into fluid reservoir  414 , through flow control valve  406  into fluid compartment  443  so as to provide an amount of fluid to enter flow channel  190  and fluid flow path  190   a  in preparation for dispensing. 
     Cam surface  307   b  engages cam following surface  629   a  until element  629  is urged past vertical surface  329   c  of guide track  341 . Upon clearing vertical surface  329   c , button  305  is biased upwardly, arrow B, in a perpendicular path to that of longitudinal axis C-C (a path generally parallel with longitudinal axis D-D and in the general direction of carriage member  303 ) by spring  305   a . Lateral protrusions  314  ( FIG. 16B ) on opposite sides of button  305  are configured to stop the travel of button  305  against housing elements  301   c . Vertical surfaces  329   c  of button  305  are positioned against vertical surfaces  629   d  of element  629 , which is biased by spring  525  in the 3 rd  configuration e.g., a primed and loaded configuration ready to dispense an amount of liquid upon activation (depression) of button  305 . With reference to  FIG. 32 , the angle of cam following surface  629   a  may be optimized so as to facilitate the force needed on slider  307 . In one aspect, the angle “alpha” (α) can be between 20 and 60°, or between 30 and 50°, or between 35 to 45°. Likewise, engagement teeth  328  and  629   6  can be configured to maximize engagement during the cam action and to minimize engagement during activation, as discussed below. 
     Referring now to  FIG. 35A , which is a top plan view of the device of  FIG. 15B ,  FIG. 35B , which is a side view of the device of  FIG. 15B ,  FIG. 36 , which is a sectional view of  FIG. 35B  along section line  36 - 36 ,  FIG. 37 , which is a sectional view of  FIG. 35A  along section line  37 - 37 ,  FIG. 38 , which is a sectional view of  FIG. 35A  along section line  38 - 38 , and  FIG. 39 , which is a sectional view of  FIG. 35A  along section line  39 - 39 , device  300  has partially withdrawn piston  630  from cylinder containing an amount of liquid for dispensing, piston  630  biased from spring  525  along a path parallel to longitudinal axis C-C and releasable in the direction of one-way dispensing valve  407 . Button  305  now protrudes partially from housing  301  and slider  307  has returned to its initial configuration due to bias from spring  305   b . In one aspect, the side surfaces of button  350  that are protruding from housing  301  may be brightly colored (e.g., fluorescent red, green, or orange) so as to indicate to the user or healthcare provider that device  300  is primed and activated for dispensing amounts of fluid from medicament container  99 . 
     As an advantage, device  300  is configured such that the user cannot actuate the device or be given an indication that the device has been activated until a sequence of steps are performed. This is to avoid a “false administration event” Small amounts of liquids, especially clear liquids may not be readily visible to the user or healthcare provider to otherwise confirm administration. For example, button  305  is presented in a raised position only when device  300  is primed and an amount of liquid is present in the cylinder  190   b  for dispensing. Otherwise, button  305  is essentially flush with the housing  301 , e.g., a dead button, and does not respond to pushing by the user, in contrast to the primed configuration where button  305  is raised from housing  301 . In one aspect, the shape of the surface of button  305  is concave and mostly recessed in housing  301  when the device is not primed. 
     Upon depression of button  305  in a downward direction, arrow C, (e.g., a path generally parallel with longitudinal axis D-D and in the general direction away from carriage member  303 ) vertical face  329   c  is urged passed the engagement teeth  628  of elements  629  releasing the bias from spring  525  and urging the piston  630  in a direction away from slider  307  and a path in the cylinder  190   b  generally parallel with longitudinal axis C-C so as to dispense the amount of liquid. Engagement teeth  328  and  629  are configured at an angle such that accidental engagement is avoided during activation when the piston  630  is driven towards the dispensing valve  407 . After dispensing an amount of liquid from the device  300 , the device returns to the second configuration described above. 
     With reference to  FIGS. 16A, 16B, 19B, 21, 26, 33 ,  FIG. 40 , which is a side view of the device of  FIG. 15B  in an inverted state,  FIG. 41 , which is a sectional view of the device of  FIG. 40  along section line  41 - 41 ,  FIG. 42 , which is a partial sectional view of section  42  of  FIG. 41 , and  FIG. 43 , which is a partial cutaway view of  FIG. 40 , a gravity break/gravity stop member  330  of device  300  is depicted which functions to prevent the piston  630  from being withdrawn from the cylinder  190   b  and drawing and air into cylinder  190   b  when the device  300  is oriented such that the at least one side-port  470  of sheath  480  is above the liquid or the liquid surface  94 , defined by longitudinal axis F-F, in the medicament container  99 , however, this stop feature member  330  of the present embodiment is structurally adapted for the smaller footprint and modifications of device  300  and that of the activation system  400   a . Thus, member  330  which is shown having generally a pendulum shape, has a weighted end  330   a  and a pivoting member  330   b  adapted to be configured with housing elements  331   a  so as to swing freely about pivoting member. A portion of member  330  is configured to have a first configuration where the device  300  is properly oriented as defined above such that protruding members  308   a  of slider  307  when traveling in a path perpendicular to longitudinal axis C-C are not blocked by member  330 . If device  300  is not properly oriented such that member  330  is in a second configuration relative to protruding members  308  of slider  307  such that slider is prevented from fully traveling in a path perpendicular to the longitudinal axis C-C. Various alternative shapes and configurations of member  330  are possible so as to provide a similar function as described. 
     Thus, the fixed fluidic path dimensions of the above devices  100 ,  300  are adapted to introduce a medicament liquid of approximately uniform amounts, for example in one or more droplets. The droplets can be of a size in the range 20 to 200 micron in diameter, or can be smaller or larger. The droplet size can be adjusted based on the viscosity of the medicament and the sizing of the exit valve and fluidic system dimensions. 
     To assemble dispenser  100 , first, valve assembly  400  is built up, valve  407  is located into flange seal cap  419  and welded to flange  458  of lower valve housing  401 . The weld may be the hermetic seal or the compression of the valve flange between the tip and chamber flange. Flange seal  409  is attached to upper valve housing  405  by an ultrasonic bond or alternately an adhesive, chemical bond, or mechanical press fit. Valves  404  and  406  are pressed into upper valve housing  405 , and that sub-assembly is then attached to valve housing  401  by a weld, adhesive or mechanical fitment, which can be carried out in discrete steps can happen concurrently, before or after the previous step. 
     The following assembly steps may be performed in any order, but could be performed after the previously discussed steps to reduce risk of damage to non-plastic parts, where sheath  408  is seated into flange seal  409  in seat  412 , this fitment may be a press fit, solvent bond or adhesive bond. Filter  402  is attached by heat bond, press fit or adhesive. Cannula  410  is inserted as a last step to reduce risk of damage to tip  450 . Alternatively, cannula  410  is attached to upper valve housing  405  prior to  405  being attached to  401 . This allows for an adhesive bond to be used in such a way that adhesive remains in vent compartment  442  and is prevented or eliminated from entering any fluid pathways. 
     As a separate sub-assembly, O-ring  534  can be assembled to piston  530 . Gasket  532  would be positioned on piston  530 . This sub-assembly can then be placed into the fluid path chamber subassembly of  FIG. 3 . Spring  525  may be added and held captive on post  527 . 
     All remaining assembly steps would start with housing  101   a  being placed in a nest/fixture and the previously described sub-assemblies being located into receiving features in the housing. Ball  580  would be placed in cavity  581 . Additionally, carriage member  103  would be placed into the housing and rotationally oriented to its start position. Edge  103   c  establishes rotational orientation of the carriage in the housing. Button  105  would be placed into the housing, spring  528  would be place with button  105  and held captive on post  529 . Feature  284  of cap tether  280  would be placed into its slot in the housing. Housing  101   b  would then be place over housing  101   a , which together hold all of the inserted elements. The housings halves could be snap fit together, press fit, glued, screwed or welded, or some combination. Cap  283  would then be placed over flange seal cap  419 . 
     In one aspect, device  300  is designed for dedicated use with a single medicament container  99  and/or whereas forcing release of either the carriage member  303  from the carriage receiving member  310  or the medicament container  99  from the carriage member  303  would cause damage, including non-operability, of the device. Device  300  and one medicament container  99  can be collectively provided as a kit. Device  300  and two or more medicament containers  99  can be collectively provided as a kit. 
     The assembly of devices  100 ,  200 , and  300  are similar and can be automated or performed by hand, performed aseptically or subsequently followed by sterilization. For example, assembly  400   a  is similar to  400 . Thus, starting with subassembly  400   a  button  305  is added, followed by slider  307  and piston  627  with O ring  534  applied. Orifice  327   a  allows for assembly of piston  627  after slider  307  and button  305  are assembled. Spring  525  is positioned in pocket  627   a . All these parts being assembled in a common direction allows for high speed automated assembly without need for reorientation of the assembly. Spring  305   a  is placed on post  505 . Spring  305   b  is placed in pocket  505   b . This now built up sub assembly can be placed into housing  301   b . Gravity stop member  330  is placed into receiving feature  331   b . Carriage member  103  can then be placed into the housing and rotationally oriented to its start position. Edge  103   c  establishes rotational orientation of the carriage  303  in the housing  301 . Housing  301   a  is placed over housing  301   b  thus locating all of the sub-assemblies and components. The housings can be snapped, glued, welded, press fit, screwed together or by some combination thereof. Alternative assembly methods can be used. 
     To pierce, penetrate or otherwise insert a cannula through the small opening of the container  99 , a force of between about 20-30 pounds (about 9.072-13.61 kilograms) or more may be required. In one aspect, the male threads  103   a  and the female threads  110   a  of the container manipulation system are configured to provide a reduction of the force required. In one aspect, the devices  100 ,  200 ,  300  herein provide a reduction of force of about 2-10 times is provided to pierce, penetrate or otherwise insert a cannula through the small opening of the container  99  requiring about 2-10 lbs (about 0.9072-4.536 kilogram). This reduction in force required is provided by, for example, the pitch and/or thickness of the male/female threads, and/or the sharpness of the piercing distal end  450  of cannula  410 , among other parameters. 
     The components of the devices disclosed may be injection molded, 3D printed, or machined. Anti-microbial material, chemical coatings, and/or lubricants can be added to the molded components of the device to impart microbial control and/or other function, for example, the flow path components, that come into contact the liquid of the medicament container during use, can be coated with anti-absorbing and/or repellant coatings. The velocity of the piston during expulsion of liquid from the device can be adjusted in the present devices such that large molecule or biomolecules, or otherwise sensitive medicinal formulations are not subject to excessive shear or other stress. Furthermore, while certain embodiments of the present disclosure have been illustrated with reference to specific combinations of elements, various other combinations may also be provided without departing from the teachings of the present disclosure. While the devices disclosed provide for application to use for ophthalmological applications, other applications, for example, to mucus membranes, mouth, nose, or ear are envisioned. 
     Because of the disclosed function of the devices disclosed, a much greater proportion of treatment liquid medicament will actually make contact with the eye, leading to less waste, reduced risk of systemic absorption, less flooding of the eye, and a reduced risk of non-administration because of blinking. 
     Devices according to the present disclosure may also include a number of additional safety features which are already well established in dosing devices of various kinds, for example, the medicament container  99  will of course have a finite capacity, and a dose recorder may be included to provide an indication of the number of doses remaining or delivered. 
     Thus, the present disclosure should not be construed as being limited to the particular exemplary embodiments described herein and illustrated in the Figures, but may also encompass combinations of elements of the various illustrated embodiments and aspects thereof.