Patent Publication Number: US-2021177650-A1

Title: Systems and devices for delivering fluids to the eye and methods of use

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS 
     This application claims the benefit of priority under 35 U.S.C. 119§ to co-pending U.S. Provisional Patent Application Ser. No. 62/946,727, filed Dec. 11, 2019. The disclosures of the provisional application is incorporated by reference in its entirety. 
    
    
     FIELD 
     The present technology relates generally to systems and devices for handling a fluid and for delivering fluids to the eye, more particularly to microdroplet delivery systems and devices for ophthalmic use. 
     BACKGROUND 
     Drug delivery to the eye using medical eye droppers presents a number of challenges. Medical eye droppers typically dispense single drops having relatively large volume (e.g. about 50 mL). The human eye can retain only a fraction of these large volume drops on the corneal surface (e.g. about 7 mL). Consequently, most of the drug may be wasted due to overflow with less than ideal amounts being delivered to the targeted tissue. In addition, large volume single drops of medication can cause the blinking reflex that also contributes to a large fraction of the delivered fluid being lost. Conventional medical eye droppers can cause discomfort due to these large volume drops triggering the blinking reflex. Discomfort is also worsened by the need for vertical delivery when using conventional medical eye droppers. Vertical delivery of eye drops requires the patient to angle their head upwards to prevent waste of the drop, which is particularly problematic for the elderly. These challenges ultimately contribute to poor patient compliance. 
     SUMMARY 
     In an aspect described is a device for delivering a volume of fluid to an eye. The device includes a base having a drive mechanism; and a disposable fluid cartridge configured to releasably couple to the base to form the device. The cartridge includes a piezoelectric-driven fluid ejector; a fluid container having a reservoir manifold having an exit port, a reservoir film movably coupled to the reservoir manifold; and a manifold film positioned within the exit port. The reservoir manifold, manifold film, and reservoir film define an internal volume of the container that is sized to hold a plurality of doses of a therapeutic agent. The cartridge includes a pump configured to draw a dose from the plurality of doses held in the container through the exit port and deliver the dose to the fluid ejector. 
     The fluid ejector can be configured to eject the dose as a horizontal stream of microdroplets to a cornea of an eye. The reservoir film can tent outward from the reservoir manifold and collapse inward toward the reservoir manifold dependent upon the plurality of doses contained within the internal volume. The reservoir film can collapse towards the reservoir manifold as the dose is drawn from the internal volume by the pump. The fluid container can include no vent. The internal volume of the container can remain sealed from ambient air during use. The reservoir film can be a flexible, non-permeable material. The flexible, non-permeable material can be a polymer or foil that is not elastic or stretchy. 
     The reservoir manifold can include a concave inner surface and a mating edge at an outer perimeter of the concave inner surface. The mating edge of the reservoir manifold can mate with a corresponding outer perimeter of the reservoir film. The exit port can be located on a lower end region of the reservoir manifold. The manifold film can separate the internal volume of the container from a pumping manifold of the pump. The drive mechanism can be a motor-driven cam configured to operatively couple with the pump. The device can further include a single actuator that, upon actuation, causes the pump to draw and deliver the dose to the fluid ejector, and activate the piezoelectric-driven fluid ejector to eject the dose to the eye. The device can further include a dose button. Penetration of the manifold film can occur only upon actuation of the dose button. The device can further include a protective shutter arranged to cover the dose button and the fluid ejector. Opening the protective shutter can electronically wake the base. 
     The therapeutic agent can be tropicamide, phenylephrine, atropine, latanoprost, or pilocarpine. The therapeutic agent can be for the treatment of glaucoma, presbyopia, myopia, or mydriasis. 
     In an interrelated implementation, provided is a device for delivering a volume of fluid to an eye that includes a base comprising a motor-driven cam; and a disposable fluid cartridge configured to releasably couple to the base to form the device. The cartridge includes a piezoelectric-driven fluid ejector; a fluid container defining an internal volume sized to hold a plurality of doses of a therapeutic agent; and a pump configured to draw a dose from the plurality of doses held in the container and deliver the dose to the fluid ejector. The pump includes a pumping manifold defining an inner bore; a drive spool slidingly positioned within the inner bore and operatively coupled to the motor-driven cam; and a floating spool movably coupled to the drive spool and slidingly positioned within the inner bore. 
     The fluid ejector can be configured to eject the dose as a horizontal stream of microdroplets to a cornea of an eye. The device can further include a single actuator that, upon actuation, causes the pump to draw and deliver the dose to the fluid ejector, and activate the piezoelectric-driven fluid ejector to eject the dose to the eye. The device can include a dose button. The device can include a protective shutter arranged to cover the dose button and the fluid ejector. Opening the protective shutter can electronically wake the base. 
     The therapeutic agent can include tropicamide, phenylephrine, atropine, latanoprost, or pilocarpine. The therapeutic agent can be for the treatment of glaucoma, presbyopia, myopia, or mydriasis. 
     The drive spool can include two sliding seals encircling a main body of the drive spool, the two sliding seals having an upper seal and a lower seal. The floating spool can include one sliding seal encircling a portion near an upper end of the floating spool. The sliding seal on the floating spool and the upper seal on the drive spool can seal a space between the spools so that the dose drawn by the pump from the fluid container is maintained within the space. Sliding motion of the drive spool can cause sliding motion of the floating spool when the floating spool is engaged with the drive spool. Reciprocal, linear motion of the drive spool can draw the dose from the fluid container and deliver the dose to the fluid ejector. A first amount of rotation by the motor-driven cam can cause the drive spool and the floating spool to be urged toward the fluid container. The floating spool can include a projection that penetrates by piercing or lifting a manifold film of the fluid container placing the internal volume of the fluid container in fluid communication with the pumping manifold. A second amount of rotation by the motor-driven cam can withdraw the drive spool away from the floating spool increasing a space between the drive spool and floating spool to draw the dose from the fluid container into the inner bore. A third amount of rotation can draw the drive spool away from the floating spool until the drive spool and floating spool engage with one another and the drive spool pulls the floating spool through the inner bore until the dose in the space is aligned with the fluid ejector. A fourth amount of rotation can urge the drive spool towards the floating spool collapsing the space between the spools and delivering the dose within the space to the fluid ejector. A volume of the dose can be about equal to a cross-sectional area of the inner bore multiplied by a length of displacement between the drive spool and the floating spool. The length of displacement between the drive spool and the floating spool can be about 0.100″ to about 0.300″ and the volume of the dose can be about 2 ul to about 15 ul. 
     In an interrelated implementation, provided is a device for delivering a volume of fluid to an eye. The device includes a base comprising a drive mechanism; and a disposable fluid cartridge configured to releasably couple to the base to form the device. The cartridge includes a piezoelectric-driven fluid ejector; a fluid container defining an internal volume sized to hold a plurality of doses of a therapeutic agent; and a pump configured to draw a dose from the plurality of doses held in the container and deliver the dose to the fluid ejector. The fluid container includes an exit port having a manifold film positioned within the exit port. The pump includes a pumping manifold defining an inner bore separated from the internal volume of the fluid container by the manifold film positioned within the exit port; and a drive spool having a first end region operatively coupled to the drive mechanism and a second end region movably coupled to a floating spool. The drive spool and floating spool are slidingly positioned within the inner bore. The floating spool includes a projection arranged to place the inner bore in fluid communication with the internal volume of the fluid container. 
     The projection can be configured to lift the manifold film relative to the exit port. The projection can have a cutting edge geometry configured to pierce the manifold film. The cutting edge geometry can allow for fluid to pass around the projection when the projection pierces the manifold film. The floating spool can include a sliding seal encircling an upper end portion of the floating spool. The sliding seal of the floating spool can seal with at least a first region of the inner bore of the pumping manifold. The pumping manifold can further include an upper inlet region that tapers from an inner diameter of the exit port to a smaller inner diameter of the first region. The upper inlet region can include a plurality of surface features allowing for fluid flow around the sliding seal of the floating spool when the floating spool is in its uppermost position within the inner bore. The sliding seal can be compressed between a surface of the floating spool and walls of the inner bore creating a complete seal. The complete seal can break when the sliding seal of the floating spool enters the upper inlet region of the pumping manifold. The drive spool and the floating spool can define a variable volume pumping chamber. Withdrawing the drive spool away from the floating spool can increase the variable volume pumping chamber and create a vacuum within the pumping chamber to draw fluid from the internal volume of the fluid container. The projection can be eccentric relative to an upper surface of the floating spool. A reservoir manifold of the fluid container can slope downwards towards the exit port. A wetted delivery flow path can extend between a lower end of the fluid container to the fluid ejector through the inner bore. The wetted delivery flow path can be L-shaped and have a length that is between about 0.5 inch and 1.0 inch. 
     In an interrelated implementation, provided is a microdroplet or an aqueous pharmaceutical composition that is one of (a) about 2.0 wt % to about 3.0 wt % phenylephrine and about 0.5 wt % to about 1.5 wt % tropicamide, and about 0.005 wt % to about 0.06 wt % benzalkonium chloride; (b) about 0.05 wt % to about 0.2 wt % atropine, about 0.10 wt % to about 0.15 wt % sodium phosphate, about 0.009 wt % to about 0.016 wt % benzalkonium chloride, and about 0.8 wt % to about 1.0 wt % sodium chloride; (c) about 0.005 wt % to about 0.006 wt % atropine, about 0.10 wt % to about 0.15 wt % sodium phosphate, about 0.009 wt % to about 0.016 wt % benzalkonium chloride, and about 0.8 wt % to about 1.0 wt % sodium chloride; (d) about 0.005 wt % to about 0.01 wt % latanoprost, about 0.10 wt % to about 0.15 wt % sodium phosphate, about 0.01 wt % to about 0.03 wt % benzalkonium chloride, about 0.8 wt % to about 1.0 wt % sodium chloride, and about 0.1 wt % to about 0.3 wt % of a polypropylene glycol/polyethylene glycol copolymer; (e) about 0.05 wt % to about 1.5 wt % pilocarpine, about 0.1 wt % to about 0.2 wt % sodium phosphate, about 0.001 wt % to about 0.02 wt % benzalkonium chloride, and about 0.2 wt % to about 0.6 wt % sodium chloride; (f) about 0.05 wt % to about 1.5 wt % pilocarpine, about 0.1 wt % to about 0.2 wt % sodium phosphate, about 0.001 wt % to about 0.02 wt % benzalkonium chloride, and about 0.6 wt % to about 1.0 wt % sodium chloride; (g) about 1.5 wt % to about 2.5 wt % pilocarpine, about 0.1 wt % to about 0.2 wt % sodium phosphate, about 0.001 wt % to about 0.02 wt % benzalkonium chloride, and about 0.2 wt % to about 0.6 wt % sodium chloride; and (h) about 1.5 wt % to about 2.5 wt % pilocarpine, about 0.1 wt % to about 0.2 wt % sodium phosphate, about 0.001 wt % to about 0.02 wt % benzalkonium chloride, and about 0.6 wt % to about 1.0 wt % sodium chloride. 
     The microdroplet or the aqueous pharmaceutical composition can be selected from one of: (a) about 2.5 wt % phenylephrine, about 1.0 wt % tropicamide, about 0.01 wt % benzalkonium chloride, and sodium chloride; (b) about 0.1 wt % atropine, about 0.136 wt % sodium phosphate, about 0.011 wt % benzalkonium chloride, and about 0.9 wt % sodium chloride; (c) about 0.01 wt % atropine, about 0.136 wt % sodium phosphate, about 0.011 wt % benzalkonium chloride, and about 0.9 wt % sodium chloride; (d) about 0.0075 wt % latanoprost, about 0.136 wt % sodium phosphate, about 0.02 wt % benzalkonium chloride, about 0.9 wt % sodium chloride, and about 0.2 wt % of a polypropylene glycol/polyethylene glycol copolymer; (e) about 1.0 wt % pilocarpine, about 0.136 wt % sodium phosphate, about 0.011 wt % benzalkonium chloride, and about 0.4% wt sodium chloride; (f) about 1.0 wt % pilocarpine, about 0.136% wt % sodium phosphate, about 0.011 wt % benzalkonium chloride, and about 0.8% wt sodium chloride; (g) about 2.0 wt % pilocarpine, about 0.136% wt % sodium phosphate, about 0.011 wt % benzalkonium chloride, and about 0.4% wt sodium chloride; and (h) about 2.0 wt % pilocarpine, about 0.136% wt % sodium phosphate, about 0.011 wt % benzalkonium chloride, and about 0.8% wt sodium chloride. 
     In some variations, one or more of the following can optionally be included in any feasible combination in the above devices, systems, compositions, and methods of using the devices, systems, and compositions herein. More details of the methods, apparatus, devices, systems, and compositions are set forth in the accompanying drawings and the description below. Other features and advantages will be apparent from the description and drawings. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIG. 1  is a box diagram illustrating a fluid delivery system including a cartridge and a base device; 
         FIG. 2A  shows an exploded perspective view of the fluid delivery system including a base device and a cartridge; 
         FIG. 2B  shows the system of  FIG. 2A  with the cartridge installed on the base device; 
         FIG. 2C  shows the system of  FIG. 2A  with the cartridge installed on the base device and a shutter on the base device in the open configuration revealing a dose button; 
         FIG. 3  is an exploded view of the base device of  FIG. 2A ; 
         FIG. 4  is an exploded view of the cartridge of  FIG. 2A ; 
         FIG. 5  is an exploded partial view of a fluid container of  FIG. 4 ; 
         FIGS. 6A and 6B  are cross-sectional, partial side views of a cartridge without a housing showing the pump in different pumping stages; 
         FIG. 6C  is a detailed view of the pump in  FIG. 6B  showing at least a portion of the pump in fluid communication with the reservoir; 
         FIG. 6D  is a downward view of an exit port from the reservoir showing an o-ring in an upper region of the pump; 
         FIG. 6E  is another view of the exit port from the reservoir showing a projection on an upper region of a portion of the pump. 
         FIG. 6F  is a perspective view of a floating spool incorporating a projection and sliding seal; 
         FIG. 7  is an exploded view of a cartridge without a housing; 
         FIG. 8A  is a perspective view of a rotary cam and cam follower of the pump drive system; 
         FIG. 8B  is a partial view of the rotary cam and cam follower of  FIG. 8A  engaged with each other and coupled to the pump of the cartridge; 
         FIG. 8C  is a simplified view of the rotary cam, cam follower and pump in engagement; 
         FIG. 9  illustrates timing of pump stroke with rotation of the rotary cam; 
         FIGS. 10A-1 and 10A-2  illustrate the base device and pump within a pumping chamber, respectively, while the base device is in a LOW position; 
         FIGS. 10B-1 and 10B-2  illustrate the base device and pump within a pumping chamber, respectively, while the base device is in a HOME position; 
         FIGS. 10C-1 and 10C-2  illustrate the base device and pump within a pumping chamber, respectively, at the start of a drawdown phase; 
         FIGS. 10D-1 and 10D-2  illustrate the base device and pump within a pumping chamber, respectively, at the end of the drawdown phase; 
         FIGS. 10E-1 and 10E-2  illustrate the base device and pump within a pumping chamber, respectively, at the start of an ejection phase; 
         FIGS. 10E-1 and 10E-2  illustrate the base device and pump within a pumping chamber, respectively, at the end of the ejection phase; 
         FIGS. 11A-11B  are exploded and assembled perspective views, respectively of an ejector system. 
         FIG. 12  illustrates a printed circuit board with cam position sensors. 
     
    
    
     Generally speaking, the figures are not to scale in absolute terms or comparatively, but are intended to be illustrative. Also, relative placement of features and elements may be modified for the purpose of illustrative clarity. It is to be understood that devices described herein may include features not necessarily depicted in each figure. 
     DETAILED DESCRIPTION 
     Described herein are systems, devices, and methods for handling a fluid and for delivering fluids to the eye. The systems and devices described herein are designed to deliver microdoses of a therapeutic, particularly ophthalmic formulations of a therapeutic to the eye (e.g., cornea) within a physiologic range of the tear film capacity using a uniform, collimated stream of micro droplets to coat an ocular surface. The systems and devices described herein can be used with a single hand in an intuitive, easy-to-operate manner. The systems and device described herein provide can provide direct corneal delivery along a horizontal axis or orientation to eliminate the need for angling the head in an unnatural position to receive a treatment. 
     The various features and functions of the devices described herein may be applied to one or more devices described herein even though they may not be expressly described in combination. It should also be appreciated that various features and functions of the devices described herein can be applied to conventional devices and systems known in the art also useful for delivery of a medicament to the eye. 
     Fluid Delivery System 
       FIG. 1  illustrates a block diagram of a fluid delivery system  100  according to an implementation. The fluid delivery system  100  can include a base device  105  and a cartridge  110 . The base device  105  can be a durable, reusable component that can be used for an extended period of time compared to the cartridge  110 . The cartridge  110  can be a disposable, non-reusable component that can be used for a limited period of time compared to the base device  105 . A single cartridge  110  can be used with the base device  105  to supply a user with medication over an extended period of days, for example between 1 to about 30 days. For example, the cartridge  110  can be a 30-day disposable whereas the base device  105  can be used for 1, 2, 3 or more years. The cartridge  110  can incorporate a container size of any of a variety of volumes to allow for treatment for more than 30 days The cartridge  110  can be disposed after a number of uses of the system including after at least 1, 2, 5, 10, 15, 20, 30, 50 up to about 100 doses delivered. The base device  105  can connect with different cartridges  110  containing different medications depending upon a user&#39;s need. Thus, the base device  105  is fully interchangeable with a plurality of different cartridges  110 . 
     The cartridge  110  generally incorporates the “wet” components and is configured to come into direct contact with the fluids to be delivered. The base device  105  generally includes the components of the system  100  that are configured to remain outside the fluid path. It should also be appreciated that both the base device  105  and the cartridge  110  can be either disposable or durable. For example, the entire system  100  may be disposable and manufactured of lower cost materials such that it is financially feasible for the base device  105  to also be disposed of after a short term use. 
     Still with  FIG. 1 , the base device  105  can include a housing  112  configured to substantially enclose a pump drive system  120 . The base device can also include electronics such as power  125 , control processor  130 , memory  135 , one or more input/outputs  140 , and optionally a communication module  142 . The control processor  130 , memory  135 , one or more input/outputs  140 , communication module  142 , as well as any storage devices, etc., can be interconnected via a system bus  143 . The base device  105  can optionally include visualization features  150  to aid in the delivery of fluid from the system  100  to the patient. The visualization features  150  can vary including lighting such as an LED connected to a light pipe  1151 , one or more mirrors  1152 , or other feature. The pump drive system  120  can include an electric motor  145  arranged to drive a rotary cam  147 . As will be discussed in more detail below, the cam  147  can be positioned within the housing  112  of the base device  105  as shown in  FIG. 1 . The cam  147  can also be positioned within the cartridge  110  and configured to couple with the motor  145  (e.g. via a motor coupler or other feature) that is available outside the housing  112  of the base device  105 . 
     Still with respect to  FIG. 1 , the cartridge  110  can include a housing  114  configured to substantially enclose a fluid container  155 , a pumping system  160 , and an ejector system  180 . The cartridge  110  can optionally incorporate a memory  167  or other data device. The fluid container  155  can be a non-evaporative primary drug container filled with a liquid medicament to be delivered to a user in droplet form. The pumping system  160  is arranged to draw discrete volumes or doses of medicament from the fluid container  155  and deliver those doses to the ejector system  180 . The ejector system  180  can be a piezoelectric ejector system configured to deliver the dose of medicament drawn by the pumping system from the fluid container in the form of microdroplets. 
       FIG. 2A  shows an exploded perspective view of the system  100  including the base device  105  and the cartridge  110 .  FIG. 2B  shows the system  100  with the cartridge  110  installed on the base device  105 .  FIG. 2C  shows the system  100  with the cartridge  110  installed on the base device  105  and a shutter  170  on the base device  105  in the open configuration revealing a dose button  172  and a spray aperture  118 . The cartridge  110  may be a reversibly removable and interchangeable element that can be inserted within a corresponding slot  113  formed by the housing  112  of the base device  105  (see  FIG. 2A ). The housing  114  of the cartridge  110  and the housing  112  of the base device  105  can incorporate complementary alignment and attachment features  116  on their respective external surfaces such that the cartridge  110  may be reversibly attached and detached from the base device  105 . The coupling between the cartridge  110  and the base device  105  ensures operative engagement between the drive system  120  of the base device  105  and the pumping system  160  of the cartridge  110 , which will be described in more detail below. 
     The implementation shown in  FIGS. 2A-2C  provides coupling between the cartridge  110  and the base device  105  in an orientation relative to the user where the cartridge  110  is positioned on an upper end region of the base device  105 . The location of coupling between the cartridge  110  on the base device  105  can vary and need not be exactly as shown. For example, other configurations are considered where the cartridge  110  couples to a back, lower, upper, or front side of the base device  105 . The cartridge  110  can also be fully enclosed by a slot  113  of the housing  112  of the base device  105 . Regardless of the coupling configuration of the cartridge  110  and the base device  105 , the fully assembled fluid delivery system  100  can have a smooth ergonomic feel such that the housing  114  of the cartridge  110  and the housing  112  of the base device  105  together form a single system housing. The single system housing (i.e., the housing formed by the cartridge  110  installed with the base device  105 ) can be of any suitable shape and size. For instance, the single system housing can be relatively tubular to fit easily and ergonomically within a palm of the user&#39;s hand. The shape can be cylindrical, rectangular, square, oval, and the like. The single system housing may be dimensioned so as to be comfortably associated with a user&#39;s hand. The size of the single system housing can be suitable for single-hand use and easy storage within a pocket or purse. In some implementations, the single system housing may have a width of about 30 mm to about 45 mm and a height of about 100 mm to about 150 mm. 
     The materials of the housings may vary. The housing  114  of the cartridge  110  can be typically formed of disposable plastic whereas the housing  112  of the base device  105  can be made of more durable plastic or metal. The housing  112  of the base device  105  may be taken apart for repairs. In some implementations, the housing  112  of the base device  105  may be a water-tight, plastic housing that is glued together permanently. 
     The base device  105  and cartridge  110  and their components will be described in more detail below. 
     Base Device 
     Again with respect to  FIG. 1 , the base device  105  can include the electronics of the system  100  and at least a portion of the pump drive system  120 . The electronics of the base device  105  can include a control processor  130 , a memory  135 , one or more input/outputs  140 , and power  125 . The control processor  130  can be in operative communication with one or more of the power  125  system, the drive system  120 , the ejector system  180 , and any electronics in the cartridge  110 . The control processor  130  can be capable of processing instructions for execution within the system  100 . Such executed instructions can implement one or more of the processes described herein related to the use of the system  100 . The control processor  130  can be a single-threaded processor or a multi-threaded processor. The control processor  130  can be capable of processing instructions stored in the memory  135  and/or on a storage device to provide an output of information to the user about operation of the system  100 . The control processor  130  can include software capable of being programmed. The software run by the control processor  130  can provide certain aspects of the system  100  without any user input during use. In an implementation, the adjustments or programming can be via the control processor  130  that is controlled by software. 
     Still with respect to  FIG. 1 , the control processor  130  can communicate with or otherwise control operation of the drive system  120 , input/output  140 , the memory  135 , the communication module  142 , and the like of the base device  105 . The control processor  130  can also include programming configured to control one or more components of the cartridge  110  upon coupling the cartridge  110  to the base device  105 . For example, the control processor  130  may include circuitry to control timing of the ejector system  180  relative to the state of the drive system  120 . The control processor  130 (s) can include programming that allows the processor(s)  130  to receive signal and/or other data from an input device  140 , such as a sensor, button, or slider. The processors  130  may receive the signals, for example, from a data device  167  or a transmitter/receiver on the cartridge  110  and store the signals in the memory  135 . The control processor  130  circuitry may include one or more clocks (oscillators), charging circuitry, I/O controllers, memory, etc.. Alternatively or in addition, the circuitry of the control processor  130  may include circuitry for one or more wireless communication modes, including Bluetooth, nearfield communication (NFC), WiFi, ultrasound, ZigBee, RFID, etc. 
     The memory  135  of the base device  105  may be part of the control processor  130  or otherwise in data communication with the control processor  130 . The memory  135  is configured for receiving and storing user input data. The memory  135  can be configured to store user information, history of use, compliance, drug information, verification of genuine cartridge or source or supplier, and the like. The memory  135  can be any type of memory capable of storing data and communicating that data to one or more other components of the system  100 , such as the control processor  130 . The memory  135  may be one or more of a Flash memory, SRAM, ROM, DRAM, RAM, EPROM, dynamic storage, and the like. The size of the memory  135  can vary as is known in the art. 
     The memory  135  of the base device  105  can also receive and store data from a memory or data device of a cartridge  110  coupled to the base device  105 . For example, the cartridge  110  can include a data device  167  that is an encoder or bar code type strip. The encoder may be configured to be scanned or read by a reader device on the base device  105  that is in operative communication with the control processor  130 . The encoder device  167  may be an RFID chip or the like that transmits data to the reader. Such encoder device  167  embodiments may include the ability to securely transmit and/or store data, such as via, encryption, to prevent unauthorized access or tampering with such data. 
     Again with respect to  FIG. 1 , the input/outputs  140  may be combined or the input may be separate from the output. The one or more input/outputs  140  of the base device  105  can include one or more triggers, buttons, sliders, dials, keypads, switches, touchscreens, or other input that can be retracted, pressed, squeezed, slid, tapped, or otherwise actuated to activate, modify, or otherwise cause a response of the system. The shutter  170  and dose button  172  are examples of input/outputs  140  of the system. As another example, the input/outputs  140  of the base device  105  can be one or more indicator lights  1174  that can provide, for example, information about status or power of base device  105  (see  FIGS. 2A-2C ). 
     The one or more input/outputs  140  of the base device  105  can also include sensors, accelerometers, motion sensors, capacitive sensors, flow sensors, or the like. These sensors can detect user handling and interaction. The one or more input/outputs  140  can be optical (LED, display), tactile (e.g. vibrational, etc.), sonic (e.g. speaker, etc.), or the like. The one or more input/outputs  140  of the base device  105  can also be more elaborate such as a GUI having an input. The type of visual output/display may include LCD displays, LED displays, plasma displays, OLED displays and the like. The output/display may also be an interactive or touch sensitive screen having an input device such as a touch screen, a capacitance screen, a resistive screen or the like. The one or more input/outputs  140  can also include a vibratory motor, speaker, warning, alarm, alert, clock, timer, or other features. 
     Power  125  can be supplied to the drive system  120  and/or the control processor  130 . In some implementations, the power  125  can be supplied by a battery incorporated within a region of the housing  112 , either internally or coupled to a region of the housing  112  such as within a modular, removable battery pack  127  (see  FIG. 3 ). The battery can have different chemical compositions or characteristics. For instance, batteries can include lead-acid, nickel cadmium, nickel metal hydride, silver-oxide, mercury oxide, lithium ion, lithium ion polymer, or other lithium chemistries. The base device  105  can also include rechargeable batteries using either a DC power-port, induction, solar cells, or the like for recharging. The base device  105  can include a power charging mechanism in some cases, such as a USB port, induction charger, or the like. As such, all data may be downloaded to a computer, network etc. using the USB port. The USB port may also provide the base with power charging. 
     In some implementations, the base device  105  can incorporate a communication module  142  in operative communication with one or more components of the system, such as the control processor  130 , as well as with one or more peripheral devices such as the one or more external computing devices. The connection between the base device  105  and other components can also include a wired communication port such as a RS22 connection, USB, Fire wire connections, proprietary connections, or any other suitable type of hard-wired connection configured to receive and/or send information. The communication can also include a wireless communication port such that information can be fed to/from the base device  105  via a wireless link. The wireless connection can use any suitable wireless system, such as Bluetooth, Wi-Fi, radio frequency, ZigBee communication protocols, infrared, or cellular phone systems, and can also employ coding or authentication to verify the origin of the information received. The wireless connection can also be any of a variety of proprietary wireless connection protocols. 
     The base device  105  may have wired or wireless communication capability such as for the sending and receiving of data as is known in the art. The wireless capability may be used for a variety purposes, including updating of any software or firmware for the processor of the device. The wireless communication capability may vary including, e.g., a transmitter and/or receiver, radiofrequency (RF) transceiver, WIFI connection, infrared or Bluetooth® communication device. The wired communication capability may also vary including, e.g., USB or SD port, flash drive port, or the like. In some embodiments, the cartridge  110  and the base device  105  may each have a transmitter/receiver, such as a radiofrequency (RF) transceiver, that allows them to communicate with one another and be used interchangeably without loss of data or information during use. A user can alternate cartridges  110  with the same base device  105  and the transfer of data between the two can be automatic. 
     The control processor  130  can also be in operative communication with one or more external computing devices. The external computing device can vary including, but not limited to, desktop computer, laptop computer, tablet computer, smartphone, or other device capable of communicating and receiving user input. 
     Again with  FIG. 1 , the pump drive system  120  can include a motor  145  positioned within the base device  105  that is configured to operatively couple with and drive the pumping system  160  of the cartridge  110 . The motor  145  can be an electric motor such as a stepper motor, continuous motor, or the like. The motor  145  can be a brushless DC motor or any type of motor or drive suitable for rotating a shaft. The motor  145  can be programmed to have variable pumping speeds and/or multiple rotations upon activation of the base device  105  via a single dose button press allowing for different delivery volumes from the same base device. In some implementations, the motor  145  is an electric motor that incorporates gear reduction via a gear box or other mechanism. In some implementations, the base device  105  incorporates a HarmonicDrive gear reduction. The drive system  120  can also include a hydraulic mechanism, pneumatic mechanism, piezoelectric mechanism, or other drive mechanism. 
     At least a portion of the drive system  120  can remain available outside the housing  112  of the base device  105  such that it can engage with the corresponding component of the cartridge  110 . For example, the motor  145  can engage with and rotate the rotary cam  147  (see  FIG. 3 ). At least a first portion of the rotary cam  147  can be positioned within the base device  105  such that at least another portion of the cam  147  is available outside the housing  112  of the base device  105  for operative coupling with the pumping system  160  of the cartridge  110  to drive fluid flow through the cartridge  110  when the cartridge  110  is installed on the base device  105 . 
     The motor  145  is part of the drive system  120  and is positioned at least partially within the base device  105 . The rotary cam  147 , however, can be positioned within a region of the base device  105  or within a region of the cartridge  110 . In some implementations, the cam  147  is positioned within the base device  105  and engages with the motor  145  within the base device. In other implementations, the cam  147  is positioned within the cartridge  110  and engages with the motor  145  (e.g., via a motor coupler) within the cartridge  110 . In an implementation, a gear head  146  of the motor  145  can couple to the rotary cam  147  via a motor coupler such that the rotary cam  147  rotates as the gear head rotates. Any of a variety of coupling configurations of the motor/cam/pumping system  160  coupling is considered herein. 
     The drive system  120  need not be a motorized system and can incorporate a manual mechanism of effecting pumping. An actuator can be coupled to a region of the base device  105  that is configured to be manually actuated that, in turn, rotates the cam  147 . In some implementations, the actuator can be a manually-rotatable ring that directly rotates the cam  147 . In still further implementations, the actuator can eliminate the need to convert rotational motion to linear motion and can drive linear motion of the pump without the cam  147 . For example, a lever-actuated feature can be incorporated to cause motion of the pump. A lockout feature can be incorporated to prevent multiple actuations. Other manual drive mechanisms are described in U.S. Publication No.  2020 / 019721 , filed June  11 ,  2018 , which is incorporated herein by reference. 
     As best shown in  FIG. 8A , the cam  147  can include a cam surface  149  extending around a central cam shaft  151  having a rotational axis R. The geometry of the cam surface  149  can vary including elliptical, eccentric, egg, snail-shaped, and the like. The geometry of the cam surface  149  is designed to translate the rotary motion of the motor  145  into reciprocal axial motion of a pump in the cartridge  110 . The geometry provides a specific motion profile and a particular timing of events within the pumping system  160 , which will be described in more detail below. 
     The cam  147  can engage with the pumping system  160  directly or can couple to the pumping system  160  indirectly via a cam follower  153  that, in turn, is coupled to the pumping system  160 . As best shown in  FIG. 8A , the cam follower  153  can include a bushing  154  coupled to a spool coupler  156 . The bushing  154  is aligned with the rotational axis R of the cam shaft  151  such that the cam shaft  151  extends through the bushing  154 . The spool coupler  156  extends outward away from axis R of the cam shaft  151  and from the bushing  154 . A lower surface of the spool coupler  156  can include a bearing  158  configured to slide along the cam surface  149  as the cam  147  rotates (see also  FIGS. 8B-8C ). An upper surface of the spool coupler  156  can include a recess configured to receive and mate with a corresponding structure of the pumping system  160  in the cartridge  110 . The recess of the spool coupler  156  can have a longitudinal axis that is coaxial with a longitudinal axis A of the pump in the pumping manifold. As the cam rotates  147  around the axis R, the bearing  158  of the spool coupler  156  travels along the cam surface  149 . The cam surface  149  has a geometry that causes the cam follower  153  to move up along the axis R of the cam shaft  151  as the bearing  158  travels along the cam surface  149  during cam  147  rotation. The bushing  154  of the cam follower  153  moves up the cam shaft  151  and the spool coupler  156  drives the pumping system  160  in a first direction. A cam follower return spring  152  can be positioned around the cam shaft  151  to urge the bushing  154  of the cam follower  153  towards the cam surface  149 . As the cam  147  rotates further and the cam surface  149  angles back downward, the spring  152  urges the bushing  154  of the of the cam follower  153  back down the cam shaft  151  and the spool coupler  156  drives the pumping system  160  in a second, opposite direction. The pumping system  160  will be described in more detail below. 
       FIG. 3  is an exploded view of the base device  105  showing the housing  112  can be divided into a front shell  1120  and a back shell  1122  that upon coupling to one another substantially enclose the components of the base device  105 , including the drive system  120  and other electronic components discussed above mounted to a printed circuit board (PCB)  1185 . An indicator aperture  1127  can be positioned to receive the indicator light  1174 . 
     The front shell  1120  can slideably couple with the shutter  170 . An outer surface of the front shell  1120  can include a pair of shutter tracks  1102  configured to couple with corresponding features on an inner surface of the shutter  170 . A shutter fascia  1104  can be positioned between the shutter  170  and the front shell  1120 . The shutter tracks  1102  can insert through a pair of corresponding slots  1108  on the shutter fascia  1104  in order to connect with the shutter  170 . 
     The front shell  1120  can include at least two apertures extending through it. An upper aperture  1124  can allow for delivery of fluid from the ejector system  180  to the patient. A lower aperture  1126  can receive the dose button  172  therethrough. The shutter fascia  1104  can also include an upper opening  1106  configured to align with the upper aperture  1124  of the front shell  1120  and a lower opening  1110  configured to align with the lower aperture  1126  of the front shell  1120 . The aligned upper opening  1106  and upper aperture  1126  form the spray aperture  118  and the aligned lower opening  1110  and lower aperture  1126  are sized to receive the dose button  172 . 
     The shutter  170  is configured slide along the shutter tracks  1102  of the front shell  1120  between a resting (closed) position and an active (open) position. The spray aperture  118  and the dose button  172  are covered by the shutter  170  when the shutter  170  is in the resting position. The spray aperture  118  and the dose button  172  are revealed by the shutter  170  when the shutter  170  is in the active position. The shutter  170  can include a central dose button opening  1175  positioned between an upper portion  1171  of the shutter  170  and a lower portion  1173  of the shutter  170 . When in the resting position (see  FIG. 2B ), the shutter  170  is arranged relative to the fascia  1104  and the front shell  1120  so that the upper portion  1171  of the shutter  170  covers the spray aperture  118  (i.e. the upper opening  1106  aligned with the upper aperture  1124 ). Additionally, the lower portion  1173  of the shutter  170  covers the dose button  172  extending through the lower opening  1110  aligned with the lower aperture  1126 . When the shutter  170  is urged into the active position (see  FIG. 2C ), the shutter  170  is urged downwards relative to the shutter fascia  1104  and the front shell  1120  so that the upper portion  1171  of the shutter  170  slides below the spray aperture  118  (i.e. the upper opening  1106  aligned with the upper aperture  1124 ). The dose button opening  1175  of the shutter  170  aligns with the lower opening  1106  and the lower aperture  1126  thus, revealing the dose button  172 . 
     The dose button  172  can be engaged with a spring  1176  that biases the dose button  172  outwards relative to the front shell  1120 . Additionally, the shutter  170  can be engaged with a spring element  1178  on the shutter fascia  1104  configured to bias the shutter  170  upwards in the resting position. As an example, the shutter  170  can be manually urged by a user into the active position (e.g. downward relative to the front shell  1120 ). The spring element  1178  upon sliding the shutter  170  downwards can be stretched or compressed depending on the configuration thereby storing energy. The dose button  172  is revealed through the aligned openings (i.e.  1175 ,  1110 , and  1126 ). The presence of the dose button  172  extending through the aligned openings maintains the shutter  170  in this active position. Pressing the dose button  172  can release the shutter  170  from the active position releasing the stored energy of the spring element  1178  to urge the shutter  170  back up to the resting position. The shutter fascia  1104  or another portion of the base device housing can include a retention feature  1179  configured to retain the shutter  170  in a closed position thereby preventing inadvertent sliding into the active position. As an example, the retention feature  1179  can be a protrusion corresponding in shape to the dose button aperture  1175  of the shutter  170  to thereby extend through the aperture  1175  when the shutter  170  is urged upwards relative to the fascia  1104 . Other configurations are considered herein. The shutter release need not be a function of the depression of a button. For example, the motor cam can automatically release the shutter  170  at the end of its rotation. 
     Actuating the shutter  170  and dose button  172  can be performed with a single hand. A user can, for example, manipulate the shutter  170  and/or dose button  172  with one or more digits while holding the base device  105  in the one hand. The base device  105  can be held such that the spray aperture is aimed in a manner to provide horizontal delivery to a user&#39;s eye. 
     Sliding the shutter  170  to the lowered position not only reveals the dose button  172  and the spray aperture, but also electronically “wakes” the base device  105  such that pressing the dose button  172  can initiate the pump/spray sequence as will be described in more detail below. The shutter  170  and/or the dose button  172  can interact with one or more sensors that communicate with the control processor  130  and wake the base device  105 . In an implementation, fully lowering the shutter  170  allows the dose button  172  to move outward away from the PCB  1185 . This lifting of the dose button  172  away from a button switch on the PCB  1185  sends a signal to the control processor  130  that the shutter  170  has lowered and the dose button  172  is ready to be depressed. In another implementation, the shutter  170  in the fully lowered position may engage with a switch or sensor that wakes the base device  105 . 
     Cartridge 
     As discussed above, the cartridge  110  may be a reversibly removable and interchangeable element that can be engaged with the base device  105  that is configured to come into direct contact with the fluids to be delivered. Again with respect to  FIG. 1 , the cartridge  110  can include the housing  114  configured to substantially enclose a fluid container  155 , a pumping system  160 , and an ejector system  180 . The fluid container  155  can be a non-evaporative primary drug container filled with a liquid medicament to be delivered to a user in droplet form. The pumping system  160  is arranged to draw discrete volumes or doses of medicament from the fluid container and deliver those doses to the ejector system  180 . The ejector system  180  can be a piezoelectric ejector system configured to deliver the dose of medicament drawn by the pumping system from the fluid container in the form of microdroplets. Each of these components will be described in more detail below. 
       FIG. 4  is an exploded view of the cartridge  110  showing the housing  114  formed of a relatively rigid, lightweight material(s) that can be divided into a front shell  1140  and a back shell  1142  and upon coupling to one another substantially enclose the fluid container  155 , the pumping system  160 , and the ejector system  180  within an inner chamber of the housing. The housing  114  need not fully enclose all the components of the cartridge  110  such that mating between respective components in the cartridge  110  and base device  105  is possible. For example, at least a portion of the pumping system  160  of the cartridge  110  can remain available outside the cartridge  110  housing  114  such that at least a portion of the drive system  120  of the base device  105  can operatively engage with the pumping system  160 . As another example, the front shell  1140  of the housing  114  of the cartridge  110  can include a spray aperture  1144  extending through it. When the cartridge  110  is installed on the base device  105 , the drive system  120  of the base device  105  can operatively engage with the pumping system  160  of the cartridge  110  and spray aperture  1144  of the front shell  1140  can align with the spray aperture  118  of the base device  105  so as to deliver fluid to the patient. 
     As discussed above, the arrangement of attachment between the cartridge  110  and the base device  105  can vary. In some implementations, the cartridge  110  and the base device  105  can be coupled in an orientation relative to the user where the cartridge  110  is positioned on an upper end region of the base device  105 . A rear-facing surface of the base device  105  front shell  1120  and an upper-facing surface of the base device  105  rear shell  1122  can form a the corresponding slot  113  configured to receive the housing  114  of the cartridge  110  thereby creating a singular housing for the system  100 . In this arrangement, a front-facing surface of the cartridge  110  front shell  1140  aligns with and abuts against the rear-facing surface of the base device  105  front shell  1120  and a lower-facing surface of the cartridge  110  front shell  1140  reversibly engages with the upper-facing surface of the base device  105  rear shell  1122 . 
     The cartridge  110  and base device  105  can couple together using a variety of attachment and alignment mechanisms  116  such as snap-lock, bayonet, or other type of reversible coupling. As an example, the lower-facing surface of the cartridge  110  front shell  1144  can incorporate a projection  1146  configured to insert within a corresponding slot  1123  in the upper-facing surface of the base device  105  back shell  1122 . The projection  1146  can mechanically link with the slot  1123  to prevent inadvertent removal of the cartridge  110  from the base device  105 . The projection  1146  and slot  1123  can also incorporate corresponding windows  1148 ,  1125  defined therethrough. The window  1148  in the projection  1146  allows for a lower end of the pumping system  160  in the cartridge  110  to be available for coupling with a portion of the drive system  120  in the base device  105  made available through the window  1125  in the slot  1123 . 
     The coupling between the cartridge  110  and the base device  105  can include a release button configured to uncouple the cartridge  110  from the base device  105 . The coupling between the cartridge  110  and base device  105  may be purely mechanical or may involve both mechanical and electronic couplings. For example, the cartridge  110  may incorporate an electronic input configured to electronically couple with a portion of the base device  105 . 
     Fluid Container 
       FIG. 5  is an exploded, partial view showing the fluid container  155  of the cartridge  110  to be filled with a medicament for delivery. Any liquid medicament for ophthalmic delivery may be contained within the fluid container  155 . Therapeutic agents considered herein are described in more detail below as well as in U.S. Publication No. 20170344714, which is incorporated herein by reference. 
     The fluid container  155  can have any suitable shape and size configured for receiving liquid medicament. Generally, the fluid container  155  is sized large enough to contain multiple doses. The fluid container  155  can be rigid walled or expandable. In some implementations, an interior volume of the fluid container  155  (in a fully expanded state) is about 1 ml to about 10 ml, more specifically, about 3 ml to about 5 ml, or about 2.5 ml to about 3.0 ml. The volume of the fluid container  155  can be at least 150 times the volume of a capacity of the ejector system  180 . 
     The fluid container  155  can include a reservoir manifold  1505  coupled on a lower end region to a pumping manifold  1605 . The reservoir manifold  1505  defines, in part, a reservoir  1510  for containing the medicament and the pumping manifold  1605  defines an inner bore containing a pump  1615  configured to draw and eject doses medicament from the fluid container  155 . 
     The fluid container  155  can include an expandable reservoir. In an implementation, the expandable reservoir is formed, in part, by a relatively rigid reservoir manifold  1505  coupled to a movable reservoir film  1520 . The reservoir manifold  1505  can have a concave inner surface  1515  and a mating edge  1517  at an outer perimeter of the concave inner surface  1515 . The edge  1517  is configured to mate with a corresponding outer perimeter of the collapsible reservoir film  1520 . The reservoir film  1520  tents outward or collapses inward depending on how much fluid is contained within the reservoir  1510 . Filling the reservoir  1510  with a liquid can cause the reservoir film  1520  to tent, expand, enlarge, or otherwise move outwards away from the reservoir manifold  1505 . As the liquid in the reservoir  1510  is consumed, the reservoir film  1520  may suck back down towards the reservoir manifold  1505  (see  FIG. 6A-6B ). The reservoir film  1520  may be expandable and collapsible such that it moves relative to the reservoir manifold  1505 , but is generally not elastic or stretchy. The reservoir film  1520  of the fluid container  155  means that no venting is necessary during use. The collapse of the reservoir film  1520  towards the manifold  1505  is what makes up for the volume of drug removed from the container during each cycle. It should be appreciated, however, that the system may include venting in the manifold  1505  to allow air to escape upon insertion of the spools into the pumping manifold  1605 . This venting can aid in eliminating any air bubbles from entering the drug reservoir  1510  upon a first actuation of the device following loading of the cartridge. As an example, venting of the reservoir  1510  can be accomplished via a one-way valve allowing air to escape the reservoir  1510 , but not enter the reservoir  1510 . 
     Again with respect to  FIG. 5 , the lower end region of the reservoir manifold  1505  can include an exit port  1525 . A manifold film  1530  can sit within the exit port  1525  of the reservoir manifold  1505  to isolate the interior of the reservoir  1510  from the interior of the pumping manifold  1605 . The reservoir  1510  is thus, defined collectively by the reservoir manifold  1505 , the reservoir film  1520 , and the manifold film  1530 . The reservoir film  1520  can have substantially similar outer dimension as the reservoir manifold  1505  such that an edge of the reservoir film  1520  can mate with the edge  1517  of the manifold  1505 . The manifold film  1530 , in contrast, can have a relatively small dimension such that it can sit within the exit port  1525 . Both the manifold film  1530  and the reservoir film  1520  feature very low vapor transmission rates to prevent drug evaporation prior to, and during product use. 
     The reservoir film  1520  can be a collapsible membrane having a thickness of about . 001  inch to about 0.030 inch, more specifically about 0.002 inch to about 0.004 inch. The material of the reservoir film  1520  can vary, but is generally a flexible, non-permeable material with good vapor barrier. In some implementations, the reservoir film  1520  can be made from polymers such as PET, SiO, linear low density polyethylene or the like. In some implementations, the reservoir film  1520  is a metalized plastic film or foil suitable for drug containment including flexible aluminum foil/Polyolefin film. 
     The manifold film  1530  can be the same material have the same material properties as the reservoir film  1520 , however the manifold film  1530  may also be a different material as the reservoir film  1520 . The materials of the reservoir manifold  1505  and reservoir film  1520  may be selected based on their biocompatibility, stability, sterility, and whether or not they are extractable/leachable. 
     In some implementations, the reservoir manifold  1505  is formed of plastic that is highly stable and suitable for drug fluid interaction, including cyclic olefin copolymer (COC). The reservoir film  1520  and the manifold film  1530  may be heat-welded onto the reservoir manifold  1505 . 
     The fluid container  155  can be sterilized and/or sterile-filled via a sterilization port, a fill port, or a single universal port. In some implementations, the fluid container  155  can incorporate a fill port  1535  located near the lower end region of the reservoir manifold  1505 , for example, positioned above the manifold film  1530 . The fill port  1535  can be penetrated by a needle or similar tool configured to inject fluid into the reservoir  1510  without damaging the film  1520 . The fill port  1535  can be sealed by one of, but not limited to, a plug, heat cut/seal, or other sealing element  1540 . In some implementations, the fluid container  155  can include more than a single port. For example, a first port can be configured for filling the fluid container  155  and a second port can be configured for venting such as for airing out the fluid container  155  following sterilization. This sort of configuration may be referred for VHP (vaporized hydrogen peroxide) sterilization method. Generally, the reservoir  1510  is not intended to be refilled after use and instead disposed of However, such a configuration is well within the scope of what is described and considered herein. 
     Pumping System 
       FIGS. 6A-6B  show a cross-sectional partial views and  FIG. 7  shows an exploded, partial view of the cartridge  110  without the housing. The fluid container  155  can be positioned relative to the pumping system  160  such that the pumping system  160  can draw discrete volumes or doses of fluid from the reservoir  1510  and deliver those doses to the ejector system  180 . As mentioned above, the pumping manifold  1605  defines an inner bore sized to contain the pump  1615 . The pumping manifold  1605  can be an extension of or coupled to the reservoir manifold  1505  of the fluid container  155 . 
     The pump  1615  can be a two-part, positive displacement pump where a first part of the pump  1615  can be moveably coupled to a second part of the pump  1615 . In an implementation, the first part can be a drive spool  1620  that is actively driven by the drive system  120  of the base device  105  to reciprocate the drive spool  1620  within the pumping manifold  1605 . For example, the drive spool  1620  can be operatively coupled to an electric motor of the drive system  120 . The second part can be a passive, floating spool  1625  moveably coupled or engaged with the drive spool  1620 . The floating spool  1625  can also reciprocate through the pumping manifold  1605 , but it reciprocates in response to drive spool movement. As best shown in  FIGS. 6A-6B , the drive spool  1620  can include a main body  1621  having an extension  1622  at an upper end region of the main body  1621  and a piston head  1623  at a lower end region of the main body  1621 . The extension  1622  on the drive spool  1620  can extend toward and interlock with a corresponding extension  1627  of the floating spool  1625 . The piston head  1623  on the drive spool  1620  can operatively engage with at least a portion of the drive system  120  (e.g. the rotary cam  147  via a cam follower  153 , etc.). The drive spool  1620  is driven by the drive system  120  and, in turn, drives the floating spool  1625  through the pumping cycles via engagement of the extensions with one another. 
     Two sliding seals  1630 , such as O-rings or quad-rings, can encircle the main body of the drive spool  1620 . The floating spool  1625  can include one sliding seal  1630  encircling a portion near an upper end of the floating spool  1625 . A cavity or space can be formed between the spools  1620 ,  1625  with the size of that space changing as the spools  1620 ,  1625  move toward and away from one another. Increasing the size of the space by separating the spools  1620 ,  1625  away from one another draws fluid from the reservoir  1510  into this space (see  FIG. 6A ). Decreasing the size of the space by urging the spools  1620 ,  1625  towards one another ejects fluid from the space into the ejector system  180  (see  FIG. 6B ). 
     The space separating the spools  1620 ,  1625  can have a volume commensurate with the dose volume of the fluid being drawn and delivered. A volume of an aliquot or dose of fluid dispensed by a complete and full dispense cycle of the spools  1620 ,  1625  may be approximately equal to the cross-sectional area of the pumping manifold  1605  bore multiplied by the length of displacement of the two spools  1620 ,  1625  and excluding the volume of the engagement ends of the spools  1620 ,  1625 . The maximum axial displacement between the drive spool  1620  and the floating spool  1625  may be about 0.100 inch to about 0.300 inch, or from about 0.100 inch to about 0.130 inch. A complete aliquot of fluid may be dispensed. The dose volume of fluid dispensed by a full cycle can be between 2 ul and 15 ul or between 5 ul and 9 ul. The dose volume can be smaller or can be larger than this range, but is within a micro-volume range. The dose volume delivered can also be adjustable such as via programming of the control processor. The dose volume approximates the physiologic tear film capacity, which maximizes the effective dose while minimizing the likelihood that the patient will blink out excess solution greater than the tear volume. 
     Each of the spools  1620 ,  1625  may be made from any suitable material or materials including polymers or plastics such as polycarbonate, PEEK, thermoplastics, cyclic olefin copolymer, and the like. The floating spool  1625  can be made of medical grade cyclic olefin copolymer (COC) that features low permittivity to prevent the drug from evaporating through the spool. The driven spool  1620  need not act as a vapor barrier, but is in contact with the drug and thus, should be a medical grade plastic such as Acrylonitrile butadiene styrene (ABS) or other medical grade plastic. The sliding seals  1630  on the spools  1620 ,  1625  may be formed of materials such as butyl, silicone, polyurethanes, or the like. It should be appreciated that the sliding seals  1630  can have any of a variety of configurations including O-ring, quad ring, and the like. The upper-most sliding seal  1630  (i.e. the seal on the floating spool  1625 ) protects the drug from leaking/evaporating out of the reservoir  1510 . Additionally, the sliding seal  1630  on the floating spool  1625  remains above the ejector system  180  (e.g. above the channel  1607  shown in  FIGS. 6A-6B ) during all stages of pumping. This ensures the reservoir  1510  remains sealed from ambient air. 
     The single sliding seal  1630  on the floating spool  1625  together with the upper sliding seal  1630  on the drive spool  1620  can seal the space between the spools  1620 ,  1625  so that the fluid drawn into the pumping manifold  1605  from the reservoir  1510  is maintained within the space so it can be delivered to the ejection system  180 . The single sliding seal  1630  on the floating spool  1625  also aids in ensuring relative movement between the two spools  1620 ,  1625  occurs. When the floating spool  1625  is engaged with the drive spool  1620 , sliding motion of the drive spool  1620  causes sliding motion of the floating spool  1625 . When the floating spool  1625  is not engaged with the drive spool  1620 , sliding motion of the drive spool  1620  does not cause sliding motion of the floating spool  1625  because the sliding seal  1630  on the floating spool  1625  provides enough friction to maintain the floating spool  1625  in place within the pumping manifold  1605  as the drive spool  1620  moves. Thus, the sliding seal  1630  of the floating spool  1625  is capable of translating through the pumping manifold  1605 , but also provides sufficient interaction with the wall of the pumping manifold  1605  to prevent fluid passage and also to remain in place within the pumping manifold  1605  when the floating spool  1625  is not engaged with and driving the drive spool  1620  through the pumping manifold  1605 . 
     Still with respect to  FIGS. 6A-6B , the pumping manifold  1605  can be divided into two portions, including a pumping chamber  1632  and a piston chamber  1634 . The pumping chamber  1632  can be in an upper region of the pumping manifold  1605  near where it couples with the reservoir manifold  1505 . The exit port  1535  of the reservoir manifold  1505  can be separated from the pumping chamber  1632  by the manifold film  1530 . The piston chamber  1634  can be in a lower region of the pumping manifold  1605  near where the drive spool  1620  couples with the drive system  120 . The lower sliding seal  1630  on the drive spool  1620  can seal the pumping chamber  1632  from the piston chamber  1634 . 
     The pumping chamber  1632  can have a substantially round transverse cross-section configured to receive at least a portion of the drive spool  1620  and the floating spool  1625 . The spools  1620 ,  1625 , in turn, may also have a substantially round transverse cross section and are slidingly disposed within the pumping chamber  1632 . 
     The piston chamber  1634  can also have a substantially round transverse cross-section configured to receive a return spring  1640 . The return spring  1640  can be positioned within the piston chamber  1634  such that the return spring  1640  surrounds the portion of the drive spool  1620  extending through the piston chamber  1634 . A lower end of the return spring  1640  can abut against the piston head  1623  of the drive spool  1620  and an upper end of the return spring  1640  can abut against an upper end of the piston chamber  1634 . The return spring  1640  can be biased to urge the piston head  1623  of the drive spool  1620  towards a lower end of the piston chamber  1634  (see  FIG. 6A ). As the drive spool  1620  is urged by the drive mechanism  120  upward towards the fluid container  155 , the return spring  1640  within the piston chamber  1634  gets compressed between the piston head  1623  and an upper end surface of the piston chamber  1634  (see  FIG. 6B ). 
     The pump is shown in  FIGS. 6A and 6B  in two different stages of pumping.  FIG. 6A  shows the drive spool  1620  urged by the return spring  1640  towards a lower end of the piston chamber  1634 . The extension  1622  of the drive spool  1620  is engaged with the extension  1627  of the floating spool  1625  thereby pulling the floating spool  1625  downwards through the pumping chamber  1632  away from the fluid container  155 . The space between the drive spool  1620  and the floating spool  1625  in this configuration is at its maximum size. The sliding seal  1630  of the floating spool  1625  and the upper sliding seal  1630  of the drive spool  1620  are shown sealing the space between the drive spool  1620  and the floating spool  1625  such that the space is in fluid communication with the ejector system  180  via a channel  1607  extending through the pumping manifold  1605  leading to the ejector system  180 .  FIG. 6B  shows the drive spool  1620  urged upwards through the pumping chamber  1632 . The space between the drive spool  1620  and the floating spool  1625  has collapsed. The drive spool  1620  has traveled back upwards through the pumping chamber  1632  until the upper and lower sliding seals  1630  of the drive spool  1620  are positioned on either side of the channel  1607 . The floating spool  1625  is urged upwards by the drive spool  1620  towards the fluid container  155 . 
     Use of directional terms such as “upward” and “upper” or “downward” and “lower” are intended to provide clarity with respect to what is shown in the drawings and are not intended to be limiting. Other configurations of the cartridge  110  and base device  105  are considered herein such that motion of the spools  1620 ,  1625  relative to the pumping manifold  160  is in a different orientation. For example, motion of the spools  1620 ,  1625  to draw fluid from the reservoir  1510  and eject fluid from the pumping manifold  160  can be reversed such that downward motion causes the spool  1625  to penetrate the manifold film  1530  and upward motion aligns the fluid with the ejector system  180  for ejection. Side-to-side motions of the pump portions are also considered herein. 
     An upper surface of the floating spool  1625  (i.e. above the sliding seal  1630 ) can include a projection  1645  (see  FIGS. 6C, 6E, and 6F ). The projection  1645  can be a spike having a cutting edge geometry configured to penetrate the manifold film  1530 . In some implementations, the projection  1645  can be a needle stylet having a tip with a variety of geometries including bevel tip, lancet point, back bevel, trocar tip, conical tip, diamond, or other geometry configured to cut or puncture the film when advanced through it. The projection  1645  need not penetrate the manifold film  1530  to place the inside of the reservoir  1510  in fluid communication with the pump. The projection  1645  can lift the film  1530  away from its sealing surface with the exit port  1525  such that the foil  1530  remains lifted into an open position. In still other implementations, the projection  1645  may penetrate or lift the foil  1530  relative to the exit port  1525  only when the projection  1645  is positioned in its upward-most position such that the reservoir  1510  reseals when the projection  1645  retracts away from the exit port  1525 . Where the projection  1645  is described herein as penetrating the manifold film  1530  it should be appreciated that the film  1530  need not be punctured and can be lifted or otherwise moved away from the exit port  1525  creating an open pathway. 
     The floating spool  1625  can be driven upwards until the projection  1645  on the upper end of the floating spool  1625  penetrates the manifold film  1530  in the exit port  1525  of the reservoir manifold  1505 . The geometry of the projection  1645  can ensure that upon penetration of the film  1530 , fluid within the reservoir  1510  can pass through the penetration location. Thus, the geometry of the projection  1645  preferably allowed for fluid to pass around the projection  1645  even while the projection  1645  is positioned within the reservoir  1510 . Thus, motion of the floating spool  1625  upward through the pumping manifold  1605  into the inlet location directly results in penetration of the film  1530  and placing the reservoir  1510  into fluid communication with the pumping manifold  1605 . The floating spool  1625  projection  1645  is removed from the reservoir film  1530  when the floating spool  1625  travels back down through the pumping manifold  1605  to deliver the drawn-down discrete dose to the ejector system  180 . The seal  1630  on the floating spool  1625  maintains a seal against the wall of the pumping manifold  1605  during this downward travel towards the ejector system  180  and ensures the region of the pumping manifold  1605  above the seal  1630  on the floating spool  1625  is sealed from the region of the pumping manifold  1605  below the seal  1630 . Once the floating spool  1625  is urged back to the upward-most position within the pumping manifold  1605 , the floating spool  1625  is positioned again relative to the reservoir  1510  so that fluid from the reservoir  1510  communicates with the region of the pumping manifold  1605  below the seal  1630 . 
     Puncturing the manifold film  1530  with the projection  1645  on the floating spool  1625  can allow the fluid to flow from the reservoir  1510  to the wetted path of the pumping manifold  160 .  FIG. 6C  shows a close-up view of the projection  1645  penetrating through the manifold film  1530 . This configuration places the pumping manifold  160  into fluid communication with the reservoir  1510 . As mentioned previously, the reservoir manifold  1505  includes an exit port  1525  within which the manifold film  1530  sits such that the manifold film  1530  isolates the reservoir  1510  from the pumping chamber  1632  of the pumping manifold  160 .  FIG. 6D  is a downward view of the exit port  1525  from the reservoir  1510  with the manifold film  1530  and floating spool  1625  removed leaving the sliding seal  1630  in position within the pumping chamber  1632 . An upper inlet region of the pumping chamber  1632  is positioned below the exit port  1525  where the manifold film  1530  is normally positioned.  FIG. 6C  shows the inlet region of the pumping chamber  1632  can taper from a larger inner diameter of the exit port  1525  to a smaller inner diameter of the pumping chamber  1632  in the inner bore. The tapered inlet region of the pumping chamber  1632  can have a plurality of surface features configured to ensure fluid communication between the reservoir  1510  and the pumping chamber  1632  when the projection  1645  penetrates the manifold film  1530 . The surface features can vary. In an implementation, the surface features include a plurality of peaks  1650  and valleys  1655 . The valleys  1655  prevent complete sealing between the sliding seal  1630  of the floating spool  1625  with the walls of the tapered inlet region of the pumping chamber  1632 . The plurality of valleys  1655  together with the geometry of the projection  1645  allow for fluid in the reservoir  1510  to pass around the projection  1645  and around the sliding seal  1630  of the floating spool  1625  into the pumping chamber  1632  when the floating spool  1625  penetrates the manifold film  1530 . The fluid is drawn into the pumping chamber  1632  due to the retraction of the drive spool  1620  and the vacuum created within the pumping chamber  1632  as the space between the drive spool  1620  and the floating spool  1625  increases. Additionally, the reservoir  1510  can be positioned above the variable volume pumping chamber  1632 . 
     As mentioned above, the projection  1645  of the floating spool  1625  can have a variety of geometries configured to puncture the manifold film  1630  sealing the reservoir  1510  from the pumping chamber  1632 . The position of the projection  1645  on the upper end of the floating spool  1625  can vary as well. The projection  1645  shown in  FIG. 6C  is positioned relatively central on the upper surface of the floating spool  1625 .  FIG. 6E  shows the upper end of the floating spool  1625  relative to the inlet region of the pumping chamber  1632  and  FIG. 6F  is a perspective view of a floating spool  1625  incorporating a projection  1645  and sliding seal  1630 . The projection  1645  shown in these figures is eccentric or off-set from the central axis of the spool  1625 . The projection  1645  can taper to a sharp tip at the perimeter of the floating spool  1625  such that the longest portion of the projection  1645  is positioned the furthest away from the central axis of the spool  1625 . The eccentric positioning of the projection  1645  relative to the upper surface of the spool  1625  as well as the tapering towards the outer edges or perimeter aids in preventing inadvertent penetration or snagging on the reservoir film  1520 , which is not intended to be punctured by the pump and could cause leakage of the reservoir  1510 .  FIG. 6E  shows the exit port  1525  in the reservoir manifold  1505 . The reservoir manifold  1505  can slope downwards towards the exit port  1525  such that as the reservoir  1510  empties the liquid in the reservoir  1510  collects towards the exit port  1525 . The floating spool  1625  is positioned within the pumping chamber  1632  of the pumping manifold  1605  so that the eccentric projection  1645  on the upper surface of the floating spool  1625  is positioned away from the edge  1517  where the reservoir manifold  1505  seals with the reservoir film  1520  and towards the fill port  1535 .  FIG. 6E  shows the eccentric projection  1645  positioned between a first peak  1650   a  and a second peak  1650   b  in the inlet region of the pumping chamber  1632  such that the projection  1645  is substantially aligned with the valley  1655  between them. The taper of the projection  1645  ensure the longest part of the projection  1645  is located towards in the inner wall of the inlet region. This positioning provides the greatest clearance between the tip of the projection  1645  and the reservoir film (not shown in  FIG. 6E ). 
     Still with respect to  FIGS. 6C, 6E, and 6F , the sliding seal  1630  of the floating spool  1625  can be positioned within a corresponding gland  1633  near an upper end of the floating spool  1625 . The sliding seal  1630  can be an elastomeric O-ring or similar toroid-shaped component configured to compress between the walls of the pumping chamber  1632  and the gland  1633  to effectively block flow of any fluid past the seal  1630 . This sealing occurs when the floating spool  1625  is positioned within the pumping chamber  1632  and the sliding seal  1630  is compressed between the walls of the pumping chamber  1632  and the gland  1633  of the floating spool  1625 . At its upper end of travel, however, the sliding seal  1630  of the floating spool  1625  enters into the tapered inlet region of the pumping chamber  1632 . The sliding seal  1630  is no longer able to create a complete seal with the walls of the inlet region and the complete seal breaks. The inlet region tapers to a larger inner diameter compared to the inner diameter of the pumping chamber  1632 . Also, the inlet region includes the valleys  1655  between the peaks  1650  that allow liquid from the reservoir  1510  to flow past the sliding seal  1630  into the pumping chamber  1632 . The upper sliding seal  1630  of the drive spool  1620  remains sealed within the pumping chamber  1632  thereby preventing the fluid from the reservoir  1510  from traveling past that sealing point. 
     The wetted delivery flow path can extend from the lower end of the reservoir  1510  where the projection  1645  penetrates the manifold film  1530  through the bore of the pumping chamber  1632  to the channel  1607  leading to the ejector system  180 . The delivery flow path of the cartridge  110  is a relatively simple and short flow path with few connections. This mitigates problems with air and fluid leaks. Because the delivery flow path is short, the dormant drug (drug between doses) is exposed to less surface area and has less chance to evaporate compared to a longer delivery flow path with larger surface area. A length of the delivery flow path between the reservoir  1510  and the ejector system  180  can be between about 0.5 inch and 1.0 inch, or roughly about 0.6″. In an implementation, the delivery flow path of the cartridge  110  can be a generally L-shaped path that is about 0.44 inch down and about 0.15″ horizontal from the inlet to the pumping chamber  1632  to the channel  1607  leading to the ejector system  180 . 
     The fluid may be delivered from the space between the spools at a relatively high velocity of at least about 0.5 meters/second (or with the pump delivering the fluid at a pressure of at least about 200 psi) to “fire” the droplet into the ejector system  180 . 
     As discussed above, the pump/spray sequence can be controlled by the drive system  120 , which can include a motor-driven rotary cam  147 . The drive spool  1625  of the pumping system  160  can connect with the cam surface  149  of the rotary cam  147  directly or indirectly via a coupler. For example, the cam follower  153  (see  FIGS. 8A-8C ) can be positioned between the rotary cam  147  and the drive spool  1620  of the pumping system  160 . The piston head  1623  of the drive spool  1620  can be received within the recess of the spool coupler  156  on the cam follower  153 , as described above, such that upon rotation of the cam  147  the drive spool  1620  moves with the cam follower  153  to various positions within the pumping chamber  1623 . The reciprocal, linear motion of the drive spool  1620  can draw a dose of fluid from the reservoir  1510  into the pumping chamber  1623  to deliver the dose to the ejector system  180 . 
       FIG. 9  illustrates a pumping sequence of the drive spool  1620  as the rotary cam  147  rotates around a rotation axis R of the cam shaft  151 . A first amount of rotation around the rotation axis R of the rotary cam  147  away from a HOME position (box  500 ) causes the projection  1645  on the floating spool  1625  to pierce the manifold film  1530  (see  FIG. 6B ). This is the start of a drawdown (box  505 ). Further rotation of the cam  147  causes an increase in the space between the drive spool  1620  and the floating spool  1625  to fill the space with fluid. After a second amount of rotation the drawdown ends (box  510 ) and the two spools  1620 ,  1625  with the space between them are pulled through the pumping chamber  1632  towards the channel  1607  leading to the ejector system  180 . A third amount of rotation initiates the start of ejector system  180  filling (box  515 ) ( FIG. 6A ). The space containing the fluid between the upper and lower sliding seals  1630  of the drive spool  1620  is aligned with the channel  1607 . The drive spool  1620  is urged upward while the floating spool  1625  remains in place ejecting the fluid from the space. A fourth amount of rotation terminates filling of the ejector system  180  (box  520 ) as the space is fully collapsed and the drive spool  1620  urges the floating spool  1625  towards the manifold film  1530  once again. Timing of ejection from the ejector system  180  can be programmed electronically to fire at a specified point in the pumping cycle. For example, the ejector system  180  can be programmed to fire after the ejector system  180  is completely filled with the dose. In some implementations, the ejector system  180  can be programmed to start firing while the drug is delivered to the ejector system  180 . A first optic sensor  1190  (e.g., the LOW optic sensor  1190   a  shown in  FIG. 12 ) can be triggered to initiate firing of the ejector system  180  upon being occluded with an optic flag  157  on the cam follower  153 . In other implementations, the ejector system  180  can be programmed to start firing once the pumping action is completed when the space between the spools  1620 ,  1625  is collapsed and the microcup is at least partially filled. A second optic sensor  1190  (e.g., the HOME optic sensor  1190   b  shown in  FIG. 12 ) can be triggered to initiate firing. 
     The pumping sequence is illustrated in more detail below and with respect to  FIG. 10A-1  through  FIG. 10E-2 . 
       FIG. 10A-1  shows a cut-away view of the rotary cam  147  having its cam shaft  151  coupled to the cam follower  153 . The PCB  1185  with a plurality of position sensors  1190   a ,  1190   b  is shown positioned behind the rotary cam  147  and cam follower  153 .  FIG. 10A-1  shows the base device  105  in a LOW position with the cam follower  153  occluding the low position sensor  1190   a.    FIG. 10A-2  shows the position of the spools  1620 ,  1625  within the pumping chamber  1632  of the pumping manifold  1605 . The base device  105  can be stored with the rotary cam  147  in the LOW position during shipping or during exchange of cartridges  110 . The low optic  1190   a  positioned on the PCB  1185  can be occluded by the cam follower  153  when the rotary cam  147  is in the LOW position. 
     When a user connects a cartridge  110  to the base device  105  and the shutter  170  on the base device  105  is lowered for the first time after cartridge  110  installation, the system  100  can “wake up.” The rotary cam  147  can rotate around its rotation axis R into a HOME position. The rotary cam  147  is shown in  FIG. 10B-1  having rotated from the LOW position of  FIG. 10A-1  into the HOME position. The HOME position can be a location along the cam surface  149  that is higher than the LOW position, but not so high as to cause manifold film puncture.  FIG. 10B-2  shows the position of the spools  1620 ,  1625  within the pumping chamber  1632  when the base device  105  is in the HOME position. The cam follower  153  can travel along the cam surface  149  and be lifted away from occluding the low optic  1190   a  into a position that occludes an upper home optic  1190   b . on the PCB  1185 . The drive spool  1620 , which can be coupled to the cam follower  153 , is driven through upward through the pumping chamber  1632  urging the floating spool  1625  towards the upper end of pumping chamber  1632 . 
     In addition to waking up the system, lowering of the shutter  170  reveals the dose button  172 . When a user presses the dose button  172 , the rotary cam  147  can rotate further around its rotation axis R. The cam follower  153  can travel further along the cam surface  149  and be lifted further upward (see  FIG. 10C-1 ). The drive spool  1620  is driven further through the pumping chamber  1632  urging the projection  1645  on the floating spool  1625  to pierce the manifold film  1530  of the fluid container  155  (see  FIG. 10C-2 ). Fluid from the reservoir  1510  of the fluid container  155  can enter the inlet of the pumping chamber  1632  and pass the top sliding seal  1630  of the floating spool  1625  as discussed above. This position is the start of fluid drawdown into the pumping manifold  1605 . Penetration of the reservoir  1510  occurs only upon actuation of the shutter  170 /dose button  172  and is directly linked to spool  1620 ,  1625  movement through the pumping chamber  1632 . 
       FIG. 10D-1  shows the rotary cam  147  rotating further and the cam follower  153  traveling down the cam path  149 . The drive spool  1620  also moves downward. The floating spool  1625  can remain stationary within the pumping chamber  1632  due to friction between its sliding seal  1630  and the wall of the pumping chamber  1632 . The space between the drive spool  1620  and floating spool  1625  increases as the spools spread further apart thereby creating a vacuum that draws fluid from the reservoir  1510  around the sliding seal  1630  of the floating spool  1625  and down into the pumping chamber  1632 . The space between the drive spool  1620  and floating spool  1625  increases until the spool engagement ends  1622 ,  1627  engage with one another (see  FIG. 10D-2 ). 
       FIG. 10E-1  shows the rotary cam  147  rotating further and the cam follower  153  traveling down the cam path  149  to the lowest point. The low optic  1190   a  is once again occluded. The drive spool  1620  has pulled the floating spool  1625  along with the fluid-filled space between the spools  1620 ,  1625  to travel down through the pumping chamber  1632 . The sliding seal  1630  of the floating spool  1625  seals with the wall of the pumping chamber  1632  closing off the vacuum and fluid communication with the reservoir  1510 . The fluid-filled space between the spools  1620 ,  1625  is exposed to the ejector system  180  via channel  1607  (see  FIG. 10E-2 ). This is the start of the ejector system  180  filling. The ejector system  180  can be programmed to start firing at the start of filling. 
       FIG. 10E-1  shows the end of the ejector system  180  filling. The rotary cam  147  has rotated further around its axis R and the cam follower  153  traveled back up the cam path  149 . This urges the drive spool  1620  to begin its upward motion stroke. Once again, the floating spool  1625  remains stationary due to friction between its sliding seal  1630  and the pumping chamber  1632  wall. The space between the drive spool  1620  and floating spool  1625  decreases as the drive spool  1620  is urged upward pushing the fluid from the space between the spools  1620 ,  1625  into the channel  1607  towards the ejector system  180 . The full dose volume has been delivered to the ejector system  180  once the drive spool  1620  engages again with the floating spool  1625  as shown in  FIG. 10E-2 . 
     Further rotation of the rotary cam  147  can urge the cam follower to travel back to the HOME position as shown in  FIG. 10B-1 . The base device  105  can return to the HOME position automatically after a dose is delivered and can remain at rest until another delivery is desired. If the cam follower  153  ever gets knocked out of the HOME position and the cam  147  rotates back into the LOW position (or any other “non-home” position) while the base device  105  is at rest, the motor  145  can move it back into the HOME position in anticipation of a dose button  172  press the next time the shutter  170  is lowered. Lowering of the shutter  170  can automatically trigger the motor  145  to position the cam  147  and cam follower  153  into the HOME position. 
     When a cartridge  110  is disconnected from the base device  105 , the rotary cam  147  can rotate from the HOME position to the LOW position in anticipation of a new cartridge  110  to be installed. The low optic  1190   a  can be occluded when in this LOW position. The cartridge  110  and the base device  105  can be connected or disconnected from one another regardless of filling of the fluid container  155 . However, in order to remove a cartridge  110  from the base device  105 , the pumping system  160  is preferably in the HOME position. 
     Ejector System 
     In addition to the fluid container  155  and the pumping system  160 , the cartridge  110  can include an ejector system  180 . The pumping system  160  is arranged to draw discrete volumes or doses of medicament from the reservoir  1510  of the fluid container  155  and deliver those discrete doses to the ejector system  180  through the channel  1607  extending through a wall in the pumping manifold  1605  at the location of the ejector system  180 . The ejector system  180  can be a piezoelectric ejector system configured to deliver those discrete doses of medicament in the form of microdroplets. 
       FIG. 4  is an exploded view of the cartridge  110  showing the ejector system  180 .  FIGS. 6A-6B  are cross-sectional, partial side views and  FIG. 7  is an exploded view of the cartridge  110  with the housing removed showing the relative arrangement of the fluid container  155 , the pumping system  160 , and the ejector system  180  of the cartridge  110 . The ejector system  180  can include a microcup  1860  and a piezoelectric ejector  1865  ( FIG. 4 ). The piezoelectric ejector  1865  can include a piezoelectric disc  1870 , a pannulus  1875 , a flex circuit  1880 , and an ejector O-ring  1885 . The piezoelectric disc  1870 , pannulus  1875 , flex circuit  1880 , and ejector O-ring  1885  of the piezoelectric ejector  1865  can be sandwiched between a back plate  1887  and a front plate  1889  ( FIGS. 6A-6B  and  FIG. 7 ). In an implementation, the ejector  1865  can include a combined flex circuit—pannulus, which can be referred to as a “fannulus”, such that the pannulus is incorporated into the flex circuit as a laminated layer on the back side of the flex circuit.  FIG. 11A  is another exploded view of the ejector system  180  including the piezoelectric disc  1870 , the flex circuit  1880 , the pannulus  1875 , and the microcup  1860 .  FIG. 11B  shows the components of  FIG. 11A  assembled together with solder  1890  on a solder tab  1892  on the flexible circuit  1880 . The solder tab  1892  can be folded over the inner diameter of the piezoelectric disc  1870  and soldered onto the surface of the piezoelectric disc  1870  during assembly. The pannulus  1875  can include a plurality of openings  1894  extending through it that are configured to generate droplets between 20 um and 100 um, or between 30 um and 90 um, or between 40 um and 90 um, or between 50 um and 70 um, or about 60 um. In some implementations, the droplet size is about 40 um. The plurality of openings  1894  can be approximately 40 um in diameter. 
     The pannulus  1875  is vibrated with the piezoelectric disc  1870  coupled to the pannulus  1875 . The piezoelectric disc  1870  can be coupled to either a delivery side (front-facing) or a fluid side (rear-facing) of the pannulus  1875  with the openings  1894  positioned in an open central region  1871  of the piezoelectric disc  1870 . 
     The term “fluid” as used herein refers to any flowable substance and does not refer only to the liquid state of a material. 
     The piezoelectric disc  1870  may be made of any suitable material (such as ceramic, Lead zirconate titanate (PZT) having the chemical formula Pb[Zr x Ti1 −x ]O 3 , or another intermetallic inorganic compound having piezoelectric effect when an electric field is applied. The pannulus  1875  can be formed of plastic such as PEEK, polyamide, or other materials. The pannulus  1875  can be designed to be completely planar, particular the nozzle area near the openings  1894 . 
     The piezoelectric disc  1870  may be bonded, adhered, molded or otherwise coupled to the pannulus  1875  in any suitable manner as is known in the art. The flexible circuit  1880  can be in electrical communication with the piezoelectric disc  1870  to control the piezoelectric disc  1870 . The flexible circuit  1880  can be coupled to the control processor  130  that controls the piezoelectric disc  1870  to induce vibrations in the piezoelectric disc  1870  to vibrate the pannulus  1875  and eject fluid from the openings  1894 . The pannulus  1875  can be vibrated at a frequency of 100 to 160 khz, which may be a resonant frequency. The resonant frequency may be predetermined, measured, determined or tuned as is known in the art. The driving frequency of the piezoelectric disc  1870  is described further below. 
     The rear-facing, fluid side of the pannulus  1875  at the openings  1894  can be in contact with the fluid to be delivered and eject the fluid to the front-facing, delivery side. Fluid can be ejected through the openings  1894  toward the eye when the pannulus  1875  is vibrated. The openings  1894  can taper from the fluid side to the delivery side. For example, the openings  1894  at the fluid side may have a diameter of 160-240 microns (and may be 200 microns) while the diameter at the delivery side may be 20-60 microns (and may be 40 microns). A column of consistent diameter (20-60 microns) can extend to the delivery side and can have a length of 10-40 microns and can be about 25 microns in length. The openings  1894  can have a curved wall between the fluid and delivery sides with a radius of curvature of 100 microns. The openings  1894  at the fluid side and the delivery side can have a circular cross-sectional shape. As used herein, the cross-sectional area (or other dimension) may be defined by an effective diameter (or effective radius) for a circle having the same area. 
     The pannulus  1875  can have a thickness of 100 to 180 microns, or 120-160 microns, and can be about 140 microns. The pannulus  1875  can be made of any suitable material such as PEEK or Polyimide, with additional layers consisting of copper, polyimide, nickel, and/or gold. The pannulus  1875  can have a thickness of 125 microns and the coating/plating having a total thickness of about 15 microns so that the pannulus  1875  has thickness of about 140 microns. Other configurations of the pannulus  1875  and piezoelectric disc  1870  are considered herein including other dimensions of the openings. 
     Fluid can be ejected so that an average ejection velocity is 2.5 m/s to 15 m/s, as it leaves the opening at the delivery side and may be about 5-6 m/s. In some implementations, the velocity of droplets can be between 1 meter/second and 10 meters/second, or between about 4 meters/second and 5 meters/second. The pannulus  1875  can define a central axis CA, which is a central orientation of the plurality of openings  1894  defined by a geometric center of the ejection orientation of the plurality of openings. For a circular pattern of openings  1894  of even density distribution with a flat pannulus  1875  the central axis CA can extend perpendicular to plane of pannulus  1875  at the center of the circular pattern of openings  1894 . Stated another way, the central axis CA can be perpendicular to a plane defined by the pannulus  1875  and can be aligned with the geometric center of the ejection direction that the openings  1894  are aligned or with a geometric center of a spray pattern created by the plurality of openings  1894 . The central axis CA may be defined by an average or geometric center when, for example, the openings  1894  are clustered or an irregular or asymmetrical shape or varying density of openings  1894  (number of openings)/mm2 as used herein. 
     Individual doses of the fluid can be delivered by the pumping system  160  to the microcup  1860  and the pannulus  1875 . The microcup  1860  can be substantially dry after delivery of the fluid and dry when stored which may provide advantages over “wet” systems which may suffer from undesirable contamination or evaporation. Implementations of the microcup  1860  of the ejector system  180  are described in more detail in PCT Publication No. WO2018/227190, which is incorporated herein by reference. 
     The volume of fluid delivered may fill the microcup  1860  only 75-90% full, which may provide room during delivery to encourage all of the fluid to gather in the microcup  1860  due to surface tension forces. Delivering the fluid at a velocity of at least 0.5 m/s (or at least 1.0 m/s) to the microcup  1860  may also encourage substantially all of the fluid ejected from the channel to collect in the microcup  1860  rather than being left behind as residual. Stated another way, the pump can deliver the fluid at a pressure of at least 200 psi (and may be about 300 psi) which may be sufficient to achieve the velocities desired for many fluids delivered to the eye. In this manner, the small fluid amount remains a single fluid “droplet” which is fired into the microcup  1860 . 
     The fluid delivery completes a delivery of a single dose leaving the microcup  1860  substantially dry and free of residual fluid between activations. For example, the pannulus  1875  may deliver the fluid from the microcup  1860  so that no more than 5%, or no more than 2%, of a total volume of the microcup  1860  is occupied by residual fluid from a previous fluid delivery or less than about 1 microliter remains. Stated another way, the pannulus  1875  can be operated to dispense substantially the entire volume of fluid in communication with the openings  1894  so that no more than 5%, or no more than 2%, of the fluid volume (or less than 1 microliter) remains in the microcup  1860  after the fluid is ejected and a single actuation for fluid ejection. In this manner, the microcup  1860  is substantially empty after a single application of the fluid (a single firing actuation). The microcup  1860  can receive a single dose that is nearly completely delivered to leave the microcup  1860  substantially dry and free of residual fluid between activations. Contamination and degradation of the fluid may be reduced compared to “wet” systems that maintain the fluid in contact with the pannulus  1875  between uses or which have incomplete delivery. 
     The microcup  1860  can be sized so that the microcup  1860  is at least 70-95% full with the fluid volume as mentioned above, which may help the fluid to gather in the microcup  1860  as a single droplet. The microcup  1860  can define a relatively small volume such as less than 14 microliters or 10-14 microliters. The fluid volume may be 7-12 microliters or 10-12 microliters. 
     The ejector system  180  drives delivery of the drug through the spray aperture  118  in a microvolume dose (e.g. about 8 ul) with less than 100 milliseconds between the time the first droplet hits the corneal surface of the completion of the dose delivery. The entire event of pumping fluid from the fluid container  155  and delivering a full dose to the eye can occur in less than 200 milliseconds. The time is takes for a dose of fluid to be dispensed from the time the dose button is pressed until the last drop is delivered can be less than about 200 millisecond, less than about 150 milliseconds, or less than about 100 milliseconds. The pump sequence can begin upon dose button press. Within about 100 milliseconds after dose button press, the dosing begins, even if the pump sequence has not completed. If the ejector starts spraying before the full dose is delivered to the microcup  1860  from the pumping chamber  1632 , the spray will last for no more than 100 milliseconds to ensure the full dose enters the eye quicker than a blink is possible. In some implementations, the pumping action can last a maximum of about 100 milliseconds and then the dosing can last a maximum of about 100 milliseconds. In another implementation, upon lowering the shutter  170 , the dispenser can automatically pump drug to the microcup  1860  in anticipation of a dose button press. Then, once the dose button is pressed, the ejector sprays the full volume into the eye. In this implementation, the pump action (i.e. motion of the spools  1620 ,  1625 ) can be separated from the spray action (i.e. firing of the piezoelement). This separation of pump action from spray action aids in preventing missed doses due to flinching by the user upon hearing a noise during pumping. Pumping a dose prior to the dose button press can reduce potential flinch time even further. The microcup does not necessarily have to fill completely before ejecting the drug. In an implementation, the piezo can start firing before or during the act of drug being delivered to the microcup. The delivery can be so quick that a user observes it as a simultaneous pump/fire as one instantaneous ejection. 
     In use, fluid delivery to the eye may also be relatively rapid to reduce the likelihood of interference from a blink during delivery. The fluid delivery may take less than 200 ms and may even be less than 150 ms or even 100 ms. The pannulus  1875  can be operated with a pause between periods of vibration during a single actuation. For example, the pannulus  1875  can be driven by the piezoelectric disc  1870  for a first period of operation of about 26 ms with a pause of about 3.65 ms followed by a second period of operation of about 26 ms. The pannulus  1875  can be driven by the piezoelectric disc  1870  with two pauses with the piezoelectric disc  1870  being energized or activated for a first period of time, a second period of time and a third period of time with the first and second periods separated by the first pause and the second and third separated by a second pause in driving vibration of the pannulus  1875 . The first and second pauses in driving vibration may be 0.5 ms to 4.0 ms. Each of the first, second and third time periods may be 20-40 ms and the overall time of delivery may be less than  150  and even less than 100 ms and may be about 85.3 ms. Each of the first, second and third periods of vibration may be further subdivided into periods of activation for about  816 us and deactivated for about 586 us for the piezoelectric disc  1870 . During the deactivated time, the pannulus  1875  may continue to vibrate and eject fluid although not being actively driven by the piezoelectric disc  1870 . Similarly, during each pause in activation of the piezoelectric disc  1870  the pannulus  1875  may continue to eject the fluid. The “pause” may be defined as a continuous deactivation of at least 2% of the total time and the total pause time for a plurality of pauses being at least 6% and may be about 8.5% of the total delivery time. The deactivated times are defined distinct from the pause in that the pause is at least 2% of the time continuous while the deactivated time is shorter and may be defined as a continuous time of 0.5-1.0% of the total delivery time and a total of the deactivated times being at least 30% of the total delivery time. Stated another way, the deactivated time is a continuous time of 2.0 to 2.5% of the first period of time (and second and third as well) and a total deactivated time of at least 30% of the first period of time. The activation times and patterns may change depending on the surface tension of the ejected fluids. 
     An alternating current of electricity can be delivered to the piezoelectric disc  1870  via the flexible circuit  1880 . The polarization of the piezo-electric disc  1870  can be fixed. In other words, there is a positive side and a negative side. When the alternating current is applied to both sides, electrical energy is transformed into physical energy in the form of a wave. This wave passes through the pannulus  1875  and imparts its physical energy to the fluid contained in the microcup  1860 . 
     The trajectory of the fluid can be controlled by the geometry of the micronozzles or openings  1894  and moves in a straight path. The continual supply of fluid available can be propelled in multiple waves. 
     As mentioned above, the frequency of the alternating signal used to activate the piezoelectric disc  1870  and subsequently activate and vibrate the pannulus  1875  can be induced at a drive frequency between 100 kHz to 160 kHz. Furthermore, the frequency can be selected by the control processor  130  as a randomized frequency centered about the drive frequency (ranging from 100 kHz to 160 kHz, or between 110 kHz and 145 kHz, or a center frequency target of about 132 kHz with dithering) for each of the plurality of activations during a single delivery and may be randomized at least 20 and may be at least 40 times. Stated another way, the vibration frequency can be changed (randomly in a manner centered on the drive frequency) on average at least 33 times for a single firing actuation so that the piezoelectric disc  1870  is driven at a frequency for no more than 3% of the delivery time (average) before being changed. It is believed that the chaotic nature of the randomization of the drive signal may aid in ejecting fluid. The randomized nature may be provided by a predetermined randomized set of values that are applied to the centered operating frequency or the randomized values uniquely generated by the control processor  130 . 
     The frequency of operation may be at a frequency other than a resonant frequency of the piezoelectric disc  1870 . Tuning the frequency to be slightly off the resonant frequency can allow control of the ejection velocity and plume shape for a given applied voltage. Thus, the piezoelectric disc  1870  can be driven so it is near, but off its resonant frequency. The drive frequency can vary +/−2 k Hz around the center drive frequency. Dithering can improve droplet formation and mitigate issues with back-splatter on the ejector face when drops fail to break off cleanly. In some implementations, a relatively random dither frequency generator is used that is at least about 50%, 55%, 60%, 65%, 70%, or 75% below the nominal drive frequency (e.g., 123 kHz) with the balance above such that all frequencies chosen are within the +/−2 kHz window, but very little at the window edges. 
     The pannulus  1875  can also be designed to vibrate with a relatively low maximum amplitude. For example, the pannulus  1875  can vibrate with a maximum amplitude of less than 2 microns, less than 1.5 microns or within a range of 0.5-1.5 microns, 0.8-1.2 microns or may be about 0.8 microns. The maximum amplitude of the pannulus  1875  can also be relatively small compared to the size of the openings in the pannulus  1875 . For example, the maximum amplitude may be no more than 5%, or no more than 3%, of an effective diameter of the cross-sectional shape of the openings at the delivery side. For example, when the maximum amplitude is 1.0 microns and the average diameter of the openings at the delivery side is 40 microns the maximum amplitude is only 2.5% of the average diameter or about 2.5% of the average diameter of the fluid droplets ejected. The maximum amplitude also represents a relatively small amount compared to the thickness such as no more than 5.0% or even no more than 3.0% of the thickness of the pannulus  1875  (measured from the fluid side to the delivery side). As used herein, the thickness may be an average thickness for the area bounded by the openings. Operation at low amplitude may also contribute to venting through the openings in that air may be admitted through some of the openings having even low displacements. Operation at low amplitude may also help maintain fluid containment between the microcup  1860  and the pannulus  1875 . When the edge of the microcup  1860  is spaced apart from the pannulus  1875 , the edge may be spaced apart an average distance greater than the maximum amplitude of the pannulus  1875  during vibration. Stated another way, the maximum amplitude is less than an average separation distance between the surface of the edge of the microcup  1860  and the pannulus  1875 . 
     Therapeutic Agents 
     The systems described herein can be used to delivery any of a variety of therapeutic agents or combinations of therapeutic agents to a patient to treat a condition. Examples of conditions include: myopia, presbyopia, dry eye, glaucoma, allergies, infections, bacterial infections, viral infections, and other infections, rosacea keratitis, chronic inflammatory conditions such as thyroiditis and blepharitis, selected retinal conditions such as diabetic retinopathy, age-related macular degeneration, and other retinal conditions, postoperative, amblyopia, etc. 
     The drug families used for the treatment of the aforementioned conditions include: steroids, anti-inflammatory agents, antibiotics, compounds for the treatment of glaucoma, antihistamines, dry eye treatments, neuroprotective agents, retinoids, anti-neoplastics Vascular agents, antioxidants, and biologics. 
     Any medicament showing a desired ophthalmic activity may be administered. In an aspect, the medicament is available by prescription. In another aspect, the medicament is available over-the-counter. In an aspect, the medicament is or comprises a biologic agent. In an aspect, the biologic agent is selected from the group consisting of a full-length antibody, an active fragment of a full-length antibody, a peptide, a pegylated peptide, and an enzymatic ingredient. In another aspect, the biologic ingredient is selected from the group consisting of bevacizumab, ranibizumab, FV fragments, bi-specific antibodies, fusion molecules, pegaptanib, plasmin and microplasmin. In a further aspect, the biologic agent is selected from the group consisting of ranibizumab antibody FAB (including Lucentis™), VEGF Trap fusion molecule (including VEGF Trap-Eye™), microplasmin enzyme (including Ocriplasmin™), macugen pegylated polypeptide (including Pegaptanib™), and bevacizumab (including Avastin™) 
     In an aspect, the medicament to be delivered comprises a medicament selected from the group consisting of atropine, pirenzepine, 7-methylxanthine, pilocarpine, diclofenac, carbachol, brimonidine, NSAID, phenylephrine, nepafenac, pheniramine, napthazoline, carboxymethylcellulose sodium, tetrahydrozoline HCl, pheniramine maleate, ketotifen fumarate, oxymetazoline HCl, naphazoline HCl, pheniramine maleate, moxifloxacin hydrochloride, bromfenac, proparacaine hydrochloride, difluprednate, gatifloxacin, travoprost, bepotastine besilate, gatifloxacin, loteprednol etabonate, timolol ophthalmic, olopatadine hydrochloride, phenylephrine hydrochloride, levofloxacin, ketorolac tromethamine, letanoprost, bimatoprost and BAK free latanoprost. In another aspect, the medicament is selected from the group consisting of Refresh Tears™, Visine Advanced Relief™, Naphcon A™, Sensitive Eyes™, Renu™, Opti-Free™ rewetting drops, Visine A.C.™, Hypo Tears™ Alaway™, Visine Visine™ original, Rohto Cool™, Soothe XP™, Zaditor™, Bausch &amp; Lomb Advanced Eye Relief Redness™, Visine A™, Opcon-A™, Walgreens artificial tears, Visine™ dry eye relief, Advanced Eye Relief Dry Eye™, Opti-free Replenish™, Clear Eyes™ redness relief, Vigamox™, Bromday™, Durezol™, Zymaxid™, Travatan Z™, Tropicamide™, Bepreve™, Zymar™, Lotemax™, Istalol™, Pataday™, AK-Dilate™, Toradol™, Xalatan™, and Lumigan™. 
     In another aspect, the medicament to be delivered comprises a medicament selected from the group consisting of fluorosilicone acrylate, sodium carboxymethylcellulose, hydroxypropyl methylcellulose, tetrahydrozoline HCl, carboxymethylcellulose sodium, propylene glycol, hypromellose, zinc sulfate, dorzolamide HCl timolol maleate, azithromycin, brimonidine tartrate, nepafenac, brinzolamide, besifloxacin, dorzolamide HCl, prenisone acetate, loteprednol etabonate, tobramycin/dexamethasone, and cyclosporine. In a further aspect, the medicament is selected from the group consisting of Tears Naturale II™, Optimum NWN™, Thera Tears™, Systane Ultra™, GenTeal™, Systane Lubricant Eye Drops™, Blink™ tears, Visine Max Redness Relief™, Refresh Optive™, Muro128™, Systane Balance™, Rohto Hydra™, Rohto Ice™, Walgreens sterile artificial tears, Rohto Arctic™, Clear Eyes™ natural tears lubricant, Similasan™ pink eye relief, Similasan™ allergy eye relief, Cosopt™, AzaSite™ Alphagan P™ Nevanac™, Azopt™, Besivance™ Trusopt™ Alrex™, Alrex™, and Restasis™. 
     In an aspect, an ophthalmic medicament to be delivered is used to treat glaucoma. In an aspect, a glaucoma medicament is selected from the group consisting of travoprost, timolol ophthalmic, latanoprost, bimatoprost, dorzolamide HCl timolol maleate, brimonidine tartrate, brinzolamide, dorzolamide HCl, and BAK free latanoprost. In a further aspect, a medicament is selected from the group consisting of travoprost, timolol ophthalmic, latanoprost, bimatoprost, and BAK free latanoprost. In another aspect, a medicament is selected from the group consisting of dorzolamide HCl timolol maleate, brimonidine tartrate, brinzolamide, and dorzolamide HCl. In an aspect, a glaucoma medicament is selected from the group consisting of Travatan™, Istalol™, Xalatan™, Lumigan™, Cosopt™, Alphagan P™, Azopt™, and Trusopt™. In another aspect, a medicament is selected from the group consisting of Travatan™, Istolol™, Xalatan™ and Lumigan™. In a further aspect, a medicament is selected from the group consisting of Cosopt™, Alphagan P™, Azopt™, and Dorzolamide HCL™. 
     In an aspect, the concentration of an active ingredient in a medicament is measured as a percentage of the active ingredient in solution. In an aspect, the concentration of active ingredient ranges from about 0.0001% to about 5%. In another aspect, the concentration of active ingredient in a medicament ranges from about 0.0005% to about 1%. In other aspects, the concentration of active ingredient ranges from about 0.0005% to about 0.0001%, from about 0.0001% to about 0.001%, or from about 0.0005% to about 0.001%. In other aspects, the concentration of active ingredient ranges from about 0.005% to about 0.001% or from about 0.001% to about 0.01%. In another aspect, the concentration of active ingredient ranges from about 0.001% to about 0.5%. In various other aspects, the concentration of active ingredient is selected from the group consisting of about 0.0001%, about 0.0005%, about 0.001%, about 0.0025%, about 0.005%, about 0.01%, about 0.025%, about 0.05%, about 0.1%, about 0.2%, about 0.3%, about 0.4%, about 0.5%, about 0.75%, about 1%, about 1.5%, about 2%, about 2.5%, about 3%, about 4%, and about 5% measured as a percentage of the solution. However, given the lower dosing amounts afforded by the methods of the present disclosure, higher concentrations may be used depending on the intended use. For examples, about 10%, about 20%, about 25%, of the active ingredient in the medicament, measured as a percentage of the solution, may be utilized. 
     In an aspect, the medicament comprises a medicament selected from the group consisting of between about 0.02% and about 0.03% carboxymethylcellulose sodium, between about 0.4% and about 0.6% carboxymethylcellulose sodium, between about 0.04% and about 0.06% tetrahydrozoline HCl, between about 0.04% and about 0.06% tetrahydrozolinc HCl, between about 0.24% and about 0.36% pheniramine maleate, between about 0.02% and about 0.03% ketotifen fumarate, between about 0.028% and about 0.042% ketotifen fumarate, between about 0.02% and about 0.03% oxymetazoline HCl, between about 0.0096% and about 0.0144% naphazoline HCl, between about 0.024% and about 0.036% naphazoline HCl, between about 0.24% and 0.36% pheniramine maleate, between about 0.4% and about 0.6% moxifloxacin hydrochloride, between about 0.072% and about 0.108% bromfenac, between about 0.4% and about 0.6% proparacaine hydrochloride, between about 0.04% and about 0.06% difluprednate, between about 0.4% and about 0.6% gatifloxacin, between about 0.0032% and about 0.0048% travoprost, between about 1.2% and about 1.8% bepotastine besilate, between about 0.24% and about 0.36% gatifloxacin, between about 0.4% and about 0.6% loteprednol etabonate, between about 0.4% and about 0.6% timolol ophthalmic, between about 0.16% and about 0.24% olopatadine hydrochloride, between about 2% and about 3% phenylephrine hydrochloride, between about 0.4% and about 0.6% levofloxacin, between about 0.32% and about 0.48% ketorolac tromethamine, between about 0.004% and about 0.006% letanoprost, and between about 0.024% and about 0.036% bimatoprost. 
     In an aspect, the medicament comprises a medicament selected from the group consisting of 0.025% carboxymethylcellulose sodium, 0.5% carboxymethylcellulose sodium, 0.05% tetrahydrozoline HCl, 0.5%, tetrahydrozoline HCl, 0.3% pheniramine maleate, 0.025% ketotifen fumarate, 0.035% ketotifen fumarate, 0.025% oxymetazoline HCl, 0.012% naphazoline HCl, 0.03% naphazoline HCl, 0.3% pheniramine maleate, 0.5% moxifloxacin hydrochloride, 0.09% bromfenac, 0.5% proparacaine hydrochloride, 0.05% difluprednate, 0.5% gatifloxacin, 0.004% travoprost, 1.5% bepotastine besilate, 0.3% gatifloxacin, 0.5% loteprednol etabonate, 0.5% timolol ophthalmic, 0.2% olopatadine hydrochloride, 2.5% phenylephrine hydrochloride, 0.5% levofloxacin, 0.4% ketorolac tromethamine, 0.005% letanoprost, and 0.03% bimatoprost. 
     In another aspect, the medicament to be delivered comprises a medicament selected from the group consisting of between about 0.02% and about 0.3% sodium carboxymethylcellulose, between about 0.04% and about 0.06% tetrahydrozoline HCl, between about 0.4% and about 0.6% carboxymethylcellulose sodium, between about 0.48% and about 0.72% propylene glycol, between about 0.24% and about 0.36% hypromellose, between about 0.2% and about 0.3% zinc sulfate, between about 0.8% and about 1.2% azithromycin, between about 0.08% and about 0.12% brimonidine tartrate, between about 0.08% and about 0.12% nepafenac, between about 0.8% and about 1.2% brinzolamide, between about 0.48% and about 0.72% besifloxacin, between about 1.6% and about 2.4% dorzolamide HCl, between about 0.8% and about 1.2% prenisone acetate, between about 0.16% and about 0.24% loteprednol etabonate, between about 0.32% and about 0.48% tobramycin/dexamethasone, and between about 0.04% and about 0.06% cyclosporine. 
     In another aspect, the medicament to be delivered comprises a medicament selected from the group consisting of 0.025% sodium carboxymethylcellulose, 0.05% tetrahydrozoline HCl, 0.5% carboxymethylcellulose sodium, 0.6% propylene glycol, 0.3% hypromellose, 0.25% zinc sulfate, 1% azithromycin, 0.1% brimonidine tartrate, 0.1% nepafenac, 1% brinzolamide, 0.6% besifloxacin, 2% dorzolamide HCl, 1% prenisone acetate, 0.2% loteprednol etabonate, 0.4% tobramycin/dexamethasone, and 0.05% cyclosporine. 
     The terms “microdroplet” or “pharmaceutical microdroplet” are used interchangeably and refer to a droplet of the medicament in the form of an aqueous solution that is ejected through the openings  1894  toward the eye when the pannulus  1875  is vibrated. In embodiments, the microdroplet is a piezo-enabled aqueous solution capable of causing fluid movement. In embodiments, the microdroplet has a diameter from about 20 microns to about 60 microns. In embodiments, the microdroplet has a diameter from about 30 microns to about 50 microns. In embodiments, the microdroplet has a diameter from about 35 microns to about 45 microns. In embodiments, the microdroplet has a diameter of about 40 microns. In embodiments, any of the medicaments described herein is in the form of a microdroplet. In embodiments, any of the medicaments described herein is in the form of a plurality of microdroplets. 
     In embodiments, the medicament is a microdroplet or an aqueous pharmaceutical composition comprising phenylephrine and tropicamide. In embodiments, the microdroplet or aqueous pharmaceutical composition comprises from about 1.0 wt % to about 4.0 wt % phenylephrine and about 0.1 wt % to about 2.0 wt % tropicamide. In embodiments, the microdroplet or aqueous pharmaceutical composition comprises from about 2.0 wt % to about 3.0 wt % phenylephrine and about 0.5 wt % to about 1.5 wt % tropicamide. In embodiments, the microdroplet or aqueous pharmaceutical composition comprises about 2.5 wt % phenylephrine and about 1.0 wt % tropicamide. In embodiments, the microdroplet or aqueous pharmaceutical composition further comprises benzalkonium chloride. In embodiments, the microdroplet or aqueous pharmaceutical composition further comprises from about 0.001 wt % to about 0.1 wt % benzalkonium chloride. In embodiments, the microdroplet or aqueous pharmaceutical composition further comprises from about 0.005 wt % to about 0.06 wt % benzalkonium chloride. In embodiments, the microdroplet or aqueous pharmaceutical composition further comprises about 0.01 wt % benzalkonium chloride. In embodiments, the microdroplet or aqueous pharmaceutical composition further comprises sodium chloride. In embodiments, the microdroplet or aqueous pharmaceutical composition comprises about 2.5 wt % phenylephrine, about 1.0 wt % tropicamide, about 0.01 wt % benzalkonium chloride, and sodium chloride. In embodiments, the microdroplet or aqueous pharmaceutical composition further comprises an acid (e.g., HCl) or a base (e.g., NaOH) to adjust the pH of the solution from about 7 to about 7.3 In embodiments, the microdroplet or aqueous pharmaceutical composition is a solution. In embodiments, the medicament is a microdroplet. In embodiments, the medicament is an aqueous pharmaceutical composition having a volume from about 1 ml to about 10 ml. In embodiments, the aqueous pharmaceutical composition has a volume from about 2 ml to about 5 ml. In embodiments, the aqueous pharmaceutical composition has a volume from about 2.5 ml to about 3 ml. In embodiments, the microdroplet or aqueous pharmaceutical composition is a piezo-enabled formulation capable of causing fluid movement. Throughout, the term “wt %” refers to weight/volume percentage concentration. 
     In embodiments, the medicament is a microdroplet or an aqueous pharmaceutical composition comprising atropine. In embodiments, the microdroplet or aqueous pharmaceutical composition comprises from about 0.01 wt % to about 1 wt % atropine. In embodiments, the microdroplet or aqueous pharmaceutical composition comprises from about 0.01 wt % to about 1 wt % atropine, sodium phosphate, benzalkonium chloride, and sodium chloride. In embodiments, the microdroplet or aqueous pharmaceutical composition comprises from about 0.05 wt % to about 0.2 wt % atropine, about 0.10 wt % to about 0.15 wt % sodium phosphate, about 0.009 wt % to about 0.016 wt % benzalkonium chloride, and about 0.8 wt % to about 1.0 wt % sodium chloride. In embodiments, the microdroplet or aqueous pharmaceutical composition comprises about 0.1 wt % atropine, about 0.136 wt % sodium phosphate, about 0.011 wt % benzalkonium chloride, and about 0.9 wt % sodium chloride. In embodiments, the microdroplet or aqueous pharmaceutical solution comprises about 0.1 wt % atropine, about 0.136 wt % sodium phosphate, about 0.011 wt % benzalkonium chloride, and about 0.9 wt % sodium chloride. In embodiments, the microdroplet or aqueous pharmaceutical composition further comprises an acid (e.g., HCl) or a base (e.g., NaOH) to adjust the pH of the solution from about 7 to about 7.3. In embodiments, the microdroplet or aqueous pharmaceutical composition is a solution. In embodiments, the medicament is a microdroplet. In embodiments, the medicament is a plurality of microdroplets. In embodiments, the medicament is an aqueous pharmaceutical composition having a volume from about 1 ml to about 10 ml. In embodiments, the aqueous pharmaceutical composition has a volume from about 2 ml to about 5 ml. In embodiments, the aqueous pharmaceutical composition has a volume from about 2.5 ml to about 3 ml. In embodiments, the microdroplet or aqueous pharmaceutical composition is a piezo-enabled formulation capable of causing fluid movement. 
     In embodiments, the microdroplet or aqueous pharmaceutical composition comprises from about 0.005 wt % to about 0.006 wt % atropine, about 0.10 wt % to about 0.15 wt % sodium phosphate, about 0.009 wt % to about 0.016 wt % benzalkonium chloride, and about 0.8 wt % to about 1.0 wt % sodium chloride. In embodiments, the microdroplet or aqueous pharmaceutical composition comprises about 0.01 wt % atropine, about 0.136 wt % sodium phosphate, about 0.011 wt % benzalkonium chloride, and about 0.9 wt % sodium chloride. In embodiments, the microdroplet or aqueous pharmaceutical composition is a solution. In embodiments, the microdroplet or aqueous pharmaceutical solution comprises about 0.01 wt % atropine, about 0.136 wt % sodium phosphate, about 0.011 wt % benzalkonium chloride, and about 0.9 wt % sodium chloride. In embodiments, the microdroplet or aqueous pharmaceutical composition further comprises an acid (e.g., HCl) or a base (e.g., NaOH) to adjust the pH of the solution from about 7 to about 7.3. In embodiments, the microdroplet or aqueous pharmaceutical composition is a solution. In embodiments, the medicament is a microdroplet. In embodiments, the medicament is a plurality of microdroplets. In embodiments, the medicament is an aqueous pharmaceutical composition having a volume from about 1 ml to about 10 ml. In embodiments, the aqueous pharmaceutical composition has a volume from about 2 ml to about 5 ml. In embodiments, the aqueous pharmaceutical composition has a volume from about 2.5 ml to about 3 ml. In embodiments, the microdroplet or aqueous pharmaceutical composition is a piezo-enabled formulation capable of causing fluid movement. 
     In embodiments, the medicament is a microdroplet or an aqueous pharmaceutical composition comprising latanoprost. In embodiments, the aqueous pharmaceutical compositions comprise latanoprost, sodium phosphate, benzalkonium chloride, sodium chloride, and a polypropylene glycol/polyethylene glycol copolymer. In embodiments, the aqueous pharmaceutical compositions comprises from about 0.005 wt % to about 0.01 wt % latanoprost, about 0.10 wt % to about 0.15 wt % sodium phosphate, about 0.01 wt % to about 0.03 wt % benzalkonium chloride, about 0.8 wt % to about 1.0 wt % sodium chloride, and about 0.1 wt % to about 0.3 wt % of a polypropylene glycol/polyethylene glycol copolymer. In embodiments, the aqueous pharmaceutical compositions comprises from about 0.0075 wt % latanoprost, about 0.136 wt % sodium phosphate, about 0.02 wt % benzalkonium chloride, about 0.9 wt % sodium chloride, and about 0.2 wt % of a polypropylene glycol/polyethylene glycol copolymer. In embodiments, the sodium phosphate comprises monobasic sodium phosphate, dibasic sodium phosphate, or a mixture thereof In embodiments, the sodium phosphate comprises monobasic sodium phosphate. In embodiments, the sodium phosphate comprises dibasic sodium phosphate. In embodiments, the sodium phosphate comprises monobasic sodium phosphate and dibasic sodium phosphate. In embodiments, the polypropylene glycol/polyethylene glycol copolymer is a triblock copolymer having a central hydrophobic block of polypropylene glycol flanked by two hydrophilic blocks of polyethylene glycol. In embodiments, the approximate lengths of the two polyethylene glycol blocks is about 90 to about 110 repeat units, while the approximate length of the propylene glycol block is about 50 to about 60 repeat units. In embodiments, the approximate lengths of the two polyethylene glycol blocks is about 101 repeat units, while the approximate length of the propylene glycol block is about 56 repeat units. In embodiments, the polypropylene glycol/polyethylene glycol copolymer is poloxamer  407 . In embodiments, the microdroplet or aqueous pharmaceutical composition further comprises an acid (e.g., HCl) or a base (e.g., NaOH) to adjust the pH of the solution from about 7 to about 7.3. In embodiments, the microdroplet or aqueous pharmaceutical composition is a solution. In embodiments, the medicament is a microdroplet. In embodiments, the medicament is a plurality of microdroplets. In embodiments, the medicament is an aqueous pharmaceutical composition having a volume from about 1 ml to about 10 ml. In embodiments, the aqueous pharmaceutical composition has a volume from about 2 ml to about 5 ml. In embodiments, the aqueous pharmaceutical composition has a volume from about 2.5 ml to about 3 ml. In embodiments, the microdroplet or aqueous pharmaceutical composition is a piezo-enabled formulation capable of causing fluid movement. 
     In embodiments, the medicament is a microdroplet or an aqueous pharmaceutical composition comprising pilocarpine. In embodiments, the microdroplet or aqueous pharmaceutical composition comprises pilocarpine, sodium phosphate, and benzalkonium chloride. In embodiments, the microdroplet or aqueous pharmaceutical composition comprises pilocarpine, sodium phosphate, benzalkonium chloride, and sodium chloride. In embodiments, the microdroplet or aqueous pharmaceutical composition comprises from about 0.01 wt % to about 3 wt % pilocarpine. In embodiments, the microdroplet or aqueous pharmaceutical composition comprises from about 0.01 wt % to about 3 wt % pilocarpine, about 0.1 wt % to about 0.2 wt % sodium phosphate, about 0.001 wt % to about 0.02 wt % benzalkonium chloride, and about 0.2 wt % to about 0.6 wt % sodium chloride. In embodiments, the microdroplet or aqueous pharmaceutical composition comprises from about 0.01 wt % to about 3 wt % pilocarpine, about 0.1 wt % to about 0.2 wt % sodium phosphate, about 0.001 wt % to about 0.02 wt % benzalkonium chloride, and about 0.6 wt % to about 1.0 wt % sodium chloride. In embodiments, the microdroplet or aqueous pharmaceutical composition comprises from about 0.05 wt % to about 1.5 wt % pilocarpine. In embodiments, the microdroplet or aqueous pharmaceutical composition comprises from about 0.05 wt % to about 1.5 wt % pilocarpine, about 0.1 wt % to about 0.2 wt % sodium phosphate, about 0.001 wt % to about 0.02 wt % benzalkonium chloride, and about 0.2 wt % to about 0.6 wt % sodium chloride. In embodiments, the microdroplet or aqueous pharmaceutical composition comprises from about 0.05 wt % to about 1.5 wt % pilocarpine, about 0.1 wt % to about 0.2 wt % sodium phosphate, about 0.001 wt % to about 0.02 wt % benzalkonium chloride, and about 0.6 wt % to about 1.0 wt % sodium chloride. In embodiments, the microdroplet or aqueous pharmaceutical composition comprises about 1.0 wt % pilocarpine, about 0.136% wt % sodium phosphate, about 0.011 wt % benzalkonium chloride, and about 0.4 wt % sodium chloride. In embodiments, the microdroplet or aqueous pharmaceutical composition comprises about 1.0 wt % pilocarpine, about 0.136 wt % sodium phosphate, about 0.011 wt % benzalkonium chloride, and about 0.8 wt % sodium chloride. In embodiments, the sodium phosphate comprises monobasic sodium phosphate, dibasic sodium phosphate, or a mixture thereof. In embodiments, the sodium phosphate comprises monobasic sodium phosphate. In embodiments, the sodium phosphate comprises dibasic sodium phosphate. In embodiments, the sodium phosphate comprises monobasic sodium phosphate and dibasic sodium phosphate. In embodiments, the microdroplet or aqueous pharmaceutical composition comprises is a solution. In embodiments, the microdroplet or aqueous pharmaceutical composition further comprises an acid (e.g., HCl) or a base (e.g., NaOH) to adjust the pH of the solution from about 7 to about 7.3. In embodiments, the microdroplet or aqueous pharmaceutical composition is a solution. In embodiments, the medicament is a microdroplet. In embodiments, the medicament is a plurality of microdroplets. In embodiments, the medicament is an aqueous pharmaceutical composition having a volume from about 1 ml to about 10 ml. In embodiments, the aqueous pharmaceutical composition has a volume from about 2 ml to about 5 ml. In embodiments, the aqueous pharmaceutical composition has a volume from about 2.5 ml to about 3 ml. In embodiments, the microdroplet or aqueous pharmaceutical composition is a piezo-enabled formulation capable of causing fluid movement. 
     In embodiments, the microdroplet or aqueous pharmaceutical composition comprises from about 1.5 wt % to about 2.5 wt % pilocarpine. In embodiments, the microdroplet or aqueous pharmaceutical composition comprises from about 1.5 wt % to about 2.5 wt % pilocarpine. In embodiments, the microdroplet or aqueous pharmaceutical composition comprises from about 1.5 wt % to about 2.5 wt % pilocarpine, about 0.1 wt % to about 0.2 wt % sodium phosphate, about 0.001 wt % to about 0.02 wt % benzalkonium chloride, and about 0.2 wt % to about 0.6 wt % sodium chloride. In embodiments, the microdroplet or aqueous pharmaceutical composition comprises about 2.0 wt % pilocarpine, about 0.136% wt % sodium phosphate, about 0.011 wt % benzalkonium chloride, and about 0.4 wt % sodium chloride. In embodiments, the microdroplet or aqueous pharmaceutical composition comprises about 2.0 wt % pilocarpine, about 0.136 wt % sodium phosphate, about 0.011 wt % benzalkonium chloride, and about 0.8% wt sodium chloride. In embodiments, the sodium phosphate comprises monobasic sodium phosphate, dibasic sodium phosphate, or a mixture thereof In embodiments, the sodium phosphate comprises monobasic sodium phosphate. In embodiments, the sodium phosphate comprises dibasic sodium phosphate. In embodiments, the sodium phosphate comprises monobasic sodium phosphate and dibasic sodium phosphate. In embodiments, the microdroplet or aqueous pharmaceutical composition comprises is a solution. In embodiments, the microdroplet or aqueous pharmaceutical composition further comprises an acid (e.g., HCl) or a base (e.g., NaOH) to adjust the pH of the solution from about 7 to about 7.3. In embodiments, the microdroplet or aqueous pharmaceutical composition is a solution. In embodiments, the medicament is a microdroplet. In embodiments, the medicament is a plurality of microdroplets. In embodiments, the medicament is an aqueous pharmaceutical composition having a volume from about 1 ml to about 10 ml. In embodiments, the aqueous pharmaceutical composition has a volume from about 2 ml to about 5 ml. In embodiments, the aqueous pharmaceutical composition has a volume from about 2.5 ml to about 3 ml. In embodiments, the microdroplet or aqueous pharmaceutical composition is a piezo-enabled formulation capable of causing fluid movement. 
     Additional medicaments and their formulations are described in detail in U.S. Publication No. 20170344714, which is incorporated herein by reference. 
     Aspects of the subject matter described herein may be realized in digital electronic circuitry, integrated circuitry, specially designed ASICs (application specific integrated circuits), computer hardware, firmware, software, and/or combinations thereof. These various implementations may include an implementation in one or more computer programs that are executable and/or interpretable on a programmable system including at least one programmable processor, which may be special or general purpose, coupled to receive signals, data and instructions from, and to transmit signals, data, and instructions to, a storage system, at least one input device, and at least one output device. 
     These computer programs (also known as programs, software, software applications, or code) include machine instructions for a programmable processor, and may be implemented in a high-level procedural and/or object-oriented programming language, and/or in assembly/machine language. As used herein, the term “machine-readable medium” refers to any computer program product, apparatus, and/or device (e.g., magnetic discs, optical disks, memory, Programmable Logic Devices (PLDs)) used to provide machine instructions and/or data to a programmable processor, including a machine-readable medium that receives machine instructions as a machine-readable signal. The term “machine-readable signal” refers to any signal used to provide machine instructions and/or data to a programmable processor. 
     In various implementations, description is made with reference to the figures. However, certain implementations may be practiced without one or more of these specific details, or in combination with other known methods and configurations. In the description, numerous specific details are set forth, such as specific configurations, dimensions, and processes, in order to provide a thorough understanding of the implementations. In other instances, well-known processes and manufacturing techniques have not been described in particular detail in order to not unnecessarily obscure the description. Reference throughout this specification to “one embodiment,” “an embodiment,” “one implementation,” “an implementation,” or the like, means that a particular feature, structure, configuration, or characteristic described is included in at least one embodiment or implementation. Thus, the appearance of the phrase “one embodiment,” “an embodiment,” “one implementation,” “an implementation,” or the like, in various places throughout this specification are not necessarily referring to the same embodiment or implementation. Furthermore, the particular features, structures, configurations, or characteristics may be combined in any suitable manner in one or more implementations. 
     The use of relative terms throughout the description may denote a relative position or direction. For example, “distal” or “lower” or “downwards” may indicate a first direction away from a reference point. Similarly, “proximal” or “upper” or “upwards” may indicate a location in a second direction opposite to the first direction. However, such terms are provided to establish relative frames of reference, and are not intended to limit the use or orientation of the device to a specific configuration described in the various implementations. 
     The word “about” means a range of values including the specified value, which a person of ordinary skill in the art would consider reasonably similar to the specified value. In embodiments, about means within a standard deviation using measurements generally acceptable in the art. In embodiments, about means a range extending to +/−10% of the specified value. In embodiments, about includes the specified value 
     While this specification contains many specifics, these should not be construed as limitations on the scope of what is claimed or of what may be claimed, but rather as descriptions of features specific to particular embodiments. Certain features that are described in this specification in the context of separate embodiments can also be implemented in combination in a single embodiment. Conversely, various features that are described in the context of a single embodiment can also be implemented in multiple embodiments separately or in any suitable sub-combination. Moreover, although features may be described above as acting in certain combinations and even initially claimed as such, one or more features from a claimed combination can in some cases be excised from the combination, and the claimed combination may be directed to a sub-combination or a variation of a sub-combination. Similarly, while operations are depicted in the drawings in a particular order, this should not be understood as requiring that such operations be performed in the particular order shown or in sequential order, or that all illustrated operations be performed, to achieve desirable results. Only a few examples and implementations are disclosed. Variations, modifications and enhancements to the described examples and implementations and other implementations may be made based on what is disclosed. 
     In the descriptions above and in the claims, phrases such as “at least one of” or “one or more of” may occur followed by a conjunctive list of elements or features. The term “and/or” may also occur in a list of two or more elements or features. Unless otherwise implicitly or explicitly contradicted by the context in which it is used, such a phrase is intended to mean any of the listed elements or features individually or any of the recited elements or features in combination with any of the other recited elements or features. For example, the phrases “at least one of A and B;” “one or more of A and B;” and “A and/or B” are each intended to mean “A alone, B alone, or A and B together.” A similar interpretation is also intended for lists including three or more items. For example, the phrases “at least one of A, B, and C;” “one or more of A, B, and C;” and “A, B, and/or C” are each intended to mean “A alone, B alone, C alone, A and B together, A and C together, B and C together, or A and B and C together.” 
     Use of the term “based on,” above and in the claims is intended to mean, “based at least in part on,” such that an unrecited feature or element is also permissible.