Pumping unit for modular application device

Abstract

The invention provides for a pumping unit for the application of a liquid to an ocular surface of a subject, wherein the pumping unit comprises a liquid inlet fluidically connected or connectable to a reservoir for holding the liquid and a liquid outlet through which the liquid can exit the pumping unit, wherein the pumping unit (60) is adapted to convey the liquid in a downstream direction from the liquid inlet to the liquid outlet and to apply the liquid to the ocular surface of the subject by ejection of the liquid in the form of a liquid stream through the liquid outlet towards the ocular surface of the subject. The invention further provides for a device for the application of a liquid to an ocular surface of a subject by ejection of the liquid from the device towards the ocular surface comprising such pumping unit as well as for a system comprising the device of the present invention and a portable electronic device.

Description

[0001] TITLE: PUMPING UNIT FOR MODULAR APPLICATION DEVICE

[0002] Description

[0003] FIELD OF THE INVENTION

[0004] The present invention relates to devices for the application of a liquid such as a liquid for cosmetic or pharmaceutical purposes to an ocular surface of a subject, specifically to a pumping unit for such application devices. More specifically, the invention relates to a modular application device comprising such pumping unit as well as to a system comprising such modular application device and a portable electronic device such as a tablet computer or smartphone.

[0005] BACKGROUND OF THE INVENTION

[0006] Devices for the application of liquids to ocular surfaces of a subject may have a broad variety of application fields, especially however, may be used for decorative, cosmetic or pharmaceutical purposes. In these fields of application, it is common to apply liquids such as liquid compositions, for example liquid pharmaceutical compositions and the like to a targeted area of an ocular surface of a subject.

[0007] US 10,646,373 B2 discloses an ejector device and method of delivering repeatable dosages to a subject for topical, oral, nasal, or pulmonary use. The ejector device includes a housing, a reservoir disposed within the housing for receiving a volume of fluid, and an ejector mechanism in fluid communication with the reservoir and configured to eject a plurality of droplets, the ejector mechanism comprising an ejector plate coupled to a generator plate and a piezoelectric actuator; the piezoelectric actuator being operable to oscillate the ejector plate, and thereby the generator plate, at a frequency and generate the plurality of droplets.

[0008] Due to the broad variety of application fields as well as due to the increasing need for the application of the abovementioned liquid preparations to ocular surfaces of subjects, for example, due to increasing stress exerted by environmental influences or due to the increasing use of electronic displays and devices or due to advancements in the medical or ophthalmological field, there is an increased demand for application devices that allow for the application of liquids to a targeted ocular surface in an advantageous manner, for example with regard to economical but also environmental aspects. In view of this, it is highly desirable that such application devices can be provided to the user at low cost and in form that is easy to use as well as in a form that allows for the maximum avoidance of waste and other environmental impacts which usually increases the acceptance of such devices by the user.

[0009] Furthermore, there is an increased demand for technical means that allow for the flexible application of liquids or liquid compositions to an ocular surface of a subject that, contrary to the exiting technical solutions such as traditional eye droppers or devices comprising piezoelectric pumps, allow for high flexibility regarding the modalities of the application of such liquids to an ocular surface, for example with regard to the amount, pressure, and / or flow rate at which such liquid is applied or administered to the ocular surface.

[0010] It is thus an obj ect of the present invention to provide for a pumping unit and / or device for the application of a liquid to an ocular surface of a user or subject, that can be provided to the user in a form that is very cost-effective, easy to use and that provides for a high user acceptance, also due to the avoidance of waste materials generated by the repeated use of such an application device and that allows for the readily adjustment of the fluidic characteristics or performance of such pumping unit and / or device by simple technical means or modifications. Further objects of the invention will be clear on the basis of the following description of the invention, examples and claims.

[0011] SUMMARY OF THE INVENTION

[0012] In a first aspect, the present disclosure relates to a pumping unit for the application of a liquid to an ocular surface of a subject, wherein the pumping unit comprises a liquid inlet fluidically connected or connectable to a reservoir for holding the liquid and a liquid outlet through which the liquid can exit the pumping unit, wherein the pumping unit is adapted to convey the liquid in a downstream direction from the liquid inlet to the liquid outlet and to apply the liquid to the ocular surface of the subject by ejection of the liquid in the form of a liquid stream through the liquid outlet towards the ocular surface of the subject, wherein the pumping unit comprises:

[0013] - a metering chamber in fluidic connection with the liquid inlet and the liquid outlet, wherein the metering chamber comprises an inlet opening fluidically connected to and located downstream of the liquid inlet for the influx of the liquid into the metering chamber, and an outlet opening fluidically connected to and located upstream of the liquid outlet for the release of the liquid from the metering chamber;

[0014] - a piston reciprocally movable within the metering chamber and being adapted to suck the liquid from the liquid inlet into the metering chamber by a repulsive movement and to convey the liquid towards the liquid outlet by a propulsive movement;

[0015] - an inlet checkvalve located downstream of the liquid inlet and upstream of the inlet opening of the metering chamber and being transmissive in the downstream direction; and

[0016] - an outlet checkvalve located downstream of the outlet opening of the metering chamber and upstream of the liquid outlet and being transmissive in the downstream direction.

[0017] In a second aspect, the present disclosure provides for a modular device for the application of a liquid to an ocular surface of a subject, wherein the device is adapted to apply the liquid to the ocular surface by ejection of the liquid in the form of a liquid stream, wherein the device comprises a pumping unit according to the first aspect of the invention.

[0018] In a third aspect, the present invention provides for a kit comprising the device according to the second aspect of the disclosure and instructions for use of the device.

[0019] In a fourth aspect, the present disclosure provides for a replaceable module adapted to be releasably connected to a base module thereby forming the device according to the second aspect of the disclosure, the replaceable module comprising:

[0020] - a reservoir for holding a liquid to be applied to the ocular surface of a subject by ejection of the liquid from the device towards the ocular surface; and

[0021] - an ejection unit for the ejection of the liquid. In a fifth aspect, the disclosure provides for a kit comprising the replaceable module according to the fourth aspect of the disclosure and instructions for use of the replaceable module.

[0022] In a sixth aspect, the present disclosure provides for a system for the application of a liquid to an ocular surface of a subject by ejection of the liquid from an application device towards the ocular surface, wherein the system comprises: a) the device according to the second aspect of the disclosure, and b) a portable electronic device.

[0023] BRIEF DESCRIPTION OF THE DRAWINGS

[0024] Fig. 1 shows a schematic cross-sectional view of a pumping unit (60) according to the first aspect of the disclosure;

[0025] Fig. 2 depict the same pumping unit (60) as depicted in Fig. 1, however, in a status in which piston (66) is in a retracted position;

[0026] Fig. 3 depicts a pumping unit (60) corresponding to the one depicted in Figs. 1 and 2 with a motor (73) connected to a propeller shaft for driving spindle (74);

[0027] Fig. 4 shows the embodiment of pumping unit (60) as depicted in Fig. 3 in a status in which piston (66) is in its maximally retracted position

[0028] Fig. 5 depicts a schematic sideview representation of a system (200) comprising a modular application device (10) according to the present disclosure;

[0029] Fig. 6 depicts the present modular administration device (10) in the connected state;

[0030] Fig. 7 shows an alternative embodiment of the present modular application device (10) in the connected state;

[0031] Fig. 8 depicts an embodiment of modular device (10) in which the base module (20) and the replaceable module (30) are not connected to each other; Fig. 9 shows an embodiment of the device (10) as depicted in Fig. 8 with the mechanical energy storage device (71) comprised by base module (20);

[0032] Fig. 10 depicts an embodiment of the present modular application device (10) in which the replaceable module (30) is not connected to the base module (20); and

[0033] Fig. 11 depicts the finally assembled system (200) comprising the present modular application device (10) with base module (20) connected to replaceable module (30) and the resulting device (10) in the connected state coupled to portable electronic device (1).

[0034] DETAILED DESCRIPTION OF THE INVENTION

[0035] The following terms or expressions as used herein should normally be interpreted as outlined in this section, unless defined otherwise by the description or unless the specific context indicates or requires otherwise:

[0036] The words “comprise”, “comprises” and “comprising” and similar expressions are to be construed in an open and inclusive sense, as “including, but not limited to” in this description and in the claims. In contrast to this, the terms "consist of", "consists of" and "consisting of" as used herein are so-called closed language meaning that only the mentioned components are present.

[0037] The terms “a” or “an” do not exclude a plurality; i.e. the singular forms “a”, “an” and “the” should be understood as to include plural referents unless the context clearly indicates or requires otherwise. In other words, all references to singular characteristics or limitations of the present disclosure shall include the corresponding plural characteristic or limitation, and vice versa, unless explicitly specified otherwise or clearly implied to the contrary by the context in which the reference is made. The terms “a”, “an” and “the” hence have the same meaning as “at least one” or as “one or more” unless defined otherwise.

[0038] The expressions, “one embodiment”, “an embodiment”, “a specific embodiment” and the like mean that a particular feature, property or characteristic, or a particular group or combination of features, properties or characteristics, as referred to in combination with the respective expression, is present in at least one of the embodiments of the invention. The occurrence of these expressions in various places throughout this description do not necessarily refer to the same embodiment.

[0039] Moreover, the particular features, properties or characteristics may be combined in any suitable manner in one or more embodiments.

[0040] The terms “essentially”, “about”, “approximately”, “substantially” and the like in connection with an attribute or value include the exact attribute or the precise value, as well as any attribute or value typically considered to fall within a normal range or variability accepted in the technical field concerned. For example, the term “about” in connection with a value or range of values as used herein shall mean that such value or range of values includes typical deviations from such values of up to + / - 5% (abs.j, or up to about + / -4%, or up to + / - 3% up to + / - 2%, up to + / - 1%, up to + / - 0.5%.

[0041] In a first aspect, the present disclosure relates to a pumping unit for the application of a liquid to an ocular surface of a subject, wherein the pumping unit comprises a liquid inlet fluidically connected or connectable to a reservoir for holding the liquid and a liquid outlet through which the liquid can exit the pumping unit, wherein the pumping unit is adapted to convey the liquid in a downstream direction from the liquid inlet to the liquid outlet and to apply the liquid to the ocular surface of the subject by ejection of the liquid in the form of a liquid stream through the liquid outlet towards the ocular surface of the subject, wherein the pumping unit comprises:

[0042] - a metering chamber in fluidic connection with the liquid inlet and the liquid outlet, wherein the metering chamber comprises an inlet opening fluidically connected to and located downstream of the liquid inlet for the influx of the liquid into the metering chamber, and an outlet opening fluidically connected to and located upstream of the liquid outlet for the release of the liquid from the metering chamber;

[0043] - a piston reciprocally movable within the metering chamber and being adapted to suck the liquid from the liquid inlet into the metering chamber by a repulsive movement and to convey the liquid towards the liquid outlet by a propulsive movement; - an inlet checkvalve located downstream of the liquid inlet and upstream of the inlet opening of the metering chamber and being transmissive in the downstream direction; and

[0044] - an outlet checkvalve located downstream of the outlet opening of the metering chamber and upstream of the liquid outlet and being transmissive in the downstream direction.

[0045] The pumping unit according to the first aspect of the present invention is adapted to and suitable for the application of a liquid, particularly for the application of a metered dose of such liquid, to an ocular surface of a subject. The term “ocular surface” as used herein, unless otherwise stated, refers to a surface of an eye of a subject, for example a sclera or a cornea of an eye of a subject. Such ocular surface may be intact, or diseased, such as damaged, inflamed or infected.

[0046] The term “subject” as used herein, unless otherwise stated, preferably refers to human or animal, preferably a warm-blooded animal, especially to a human.

[0047] The term “liquid” as used herein is to be understood in a broad sense and means, unless otherwise stated, a liquid or liquid composition comprising a liquid vehicle or solvent and at least one further ingredient dissolved or dispersed (for example in the form of a suspension or colloidal dispersion). In some embodiments, the liquid may be a physiologically or pharmaceutically acceptable liquid, especially an ophthalmologically acceptable liquid. In some embodiments, the liquid may be an aqueous liquid or liquid composition comprising at least one of an excipient and an active pharmaceutical ingredient, for example an ophthalmic active pharmaceutical ingredient. The term “excipient” as used herein means, unless otherwise stated, means a substance that is formulated alongside with an active pharmaceutical ingredient in a pharmaceutical composition and includes, for example, salts, preservatives, antioxidants, buffers or pH-modifiers, viscosity enhancers, tonicity modifiers, surfactants, adjuvants, colorants and others. The term “active pharmaceutical ingredient” (API) as used herein means, unless otherwise stated, means a compound or combination of compounds which are pharmaceutically active against an undesired condition (of a subject). In particular embodiments, the liquid may be an ophthalmologically acceptable liquid for the (ophthalmic) application of the liquid to an ocular surface as discussed above. In particular embodiments, the liquid to be applied to an ocular surface of a subject is provided in sterilized or, in other words, aseptic form.

[0048] In some embodiments, the liquid or the active pharmaceutically ingredients optionally comprised by the liquid to be dispensed by the pumping unit and / or device according to the present invention are suitable for the prevention, delay or treatment of an ophthalmic disease or disorder and for the topical administration to the eye of a subject in need thereof.

[0049] In some embodiments, the liquid may comprise an ophthalmologically acceptable solvent, for example water, ethanol, glycerol, 1,2-propanediol, propylene glycol, polyethylene glycol, mineral oils, flaxseed oil, castor oil or mixtures thereof (for example compositions sometimes referred to as “artificial tears” which may comprise a demulcent such as carboxymethylcellulose (CMC), hydroxypropyl methylcellulose (hypromellose), hydroxyethylcellulose, methylcellulose, dextran 70, gelatin, glycerol, polyethylene glycol (300, 400), polysorbate 80, polyvinyl alcohol and / or polyvinyl pyrrolidone (povidone)), either in the form of an aqueous mixture or solution or in non-aqueous form. Examples of such liquid compositions are also commercially available and are commercialized, for example as Systane® (Alcon; for example, Systane® Hydration, Systane® Complete, Systane® Ultra, Systane® Balance, with or without preservatives). In some embodiments, the liquid, specifically the ophthalmologically acceptable liquid as referred to herein may be an ophthalmic composition comprising one or more APIs and may also be commercially available. Exemplary embodiments of such ophthalmic liquids comprise, but are not limited to Roclanda® (Santen), Cequa® (Sun Ophthalmics), Xiidra® (Novartis), Tryvaya® (Viatris), Eyreida® (Aspire Pharma), and others.

[0050] Furthermore, the term “liquid” as used herein is to be understood broadly to include liquids with a broad range of viscosities such as liquids with a very low viscosity in the range of, for example, from about 0.1 cP (centipoise) to about 1 cP as well as liquids with a very high viscosity in the range of, for example, from about 100 to about 200 cP. In some embodiments, the liquid to be dispensed by the device according to the present invention may have a viscosity in the range of from about 1 cP to about 100 cP or to about 75 cP or to about 60 cP (whereas 1 cP corresponds to 0.001Pa*s (pascal-second)).

[0051] The term “application” as used herein as used herein in connection with the term “liquid” means, unless otherwise stated, the activity of transferring such liquid onto an ocular surface of a subject or of bringing such liquid in contact with such ocular surface of a subject. In specific embodiments, the term “application” may also mean the administration, specifically the topical administration of such liquid or liquid pharmaceutical and / or ophthalmic composition to an ocular surface of a subject. Such application, in some embodiments may be a contactless application of the liquid to the ocular surface of the subject, whereas the term “contactless” as used herein means that the pumping unit or any of its constituents does not contact the ocular surface of the user during application of the liquid.

[0052] The term “metered dose” as used herein, unless otherwise stated refers to an amount or volume of the liquid as described above to be applied to an ocular surface of an eye of a subject in a single operation or in one working cycle of the present pumping unit or application device as described in further detail below. Typically, a metered dose corresponds to a volume of the liquid of from about 1 pL to about 50 pL, or from about 5 pL to about 25 pL or even from about 10 pL to about 20 pL.

[0053] The pumping unit according to this first aspect of the present invention (hereinafter also sometimes referred to as “present pumping unit”) comprises a liquid inlet fluidically connected or connectable to a reservoir for holding the liquid. The liquid inlet of the present pumping unit may be understood in a broad sense as an opening on the most upstream end of pumping unit which is connected, specifically fluidically connected, or which may be fluidically connected to a reservoir for holding the liquid, through which the liquid can enter into the pumping unit from the reservoir, specifically when conveyed or sucked from the reservoir by the pumping unit as described in further detail below.

[0054] Furthermore, the present pumping unit comprises a liquid outlet through which the liquid can exit the pumping unit. The liquid outlet of the present pumping unit may be understood in a broad sense as an opening on the most downstream end of pumping unit which is connected, specifically fluidically connected, or which may be fluidically connected to further functional units, such as an ejection unit as described in further detail below, for example a nozzle, through which the liquid can exit the pumping unit, specifically when conveyed or pumped from the reservoir by the pumping unit as described in further detail below.

[0055] The present pumping unit is adapted to convey and, in some embodiments, to pressurize the liquid in a downstream direction from the liquid inlet to the liquid outlet. In some embodiments, the present pumping unit may also be adapted to pressurize the liquid while conveying it towards the liquid outlet. The present pumping unit, furthermore, is adapted to apply the liquid to the ocular surface of the subject by ejection of the liquid in the form of a liquid stream through the liquid outlet towards the ocular surface of the subject. The term “ejection” as used herein in connection with the liquid to be applied means that a continuous or discontinuous stream of such liquid, preferably in the form of a metered portion of such liquid, is generated and conveyed towards the ocular surface of the subject, preferably in a pointed, or, in other words, targeted manner. The term “stream” as used herein, unless otherwise stated means a flow of liquid traveling along a trajectory, preferably a pointed trajectory, from the origin of the stream (here the present pumping unit or another functional unit downstream of the pumping unit such as an ejection unit) to the ocular surface of the subject to which the liquid is to be applied. In some embodiments, such liquid stream may be a continuous stream, for example in the form of a jet, or a discontinuous stream, such as a pulsed stream of consecutive separate portions of the liquid, for example in the form of droplets. In some embodiments, such droplet may be generated by disintegration of an originally continuous jet of liquid, for example by the Raleigh instability. In these embodiments, such droplets may be in the form of a consecutive series of droplets traveling along a pointed trajectory, preferably essentially along the same pointed trajectory, in extension of the trajectory of the initial liquid jet. In some embodiments, such droplets may have a size or, more specifically, a mean diameter selected within the range of from about 10 pm to about 1000 pm or from about 15 pm to about 100 pm or from about 20 pm to about 50 pm, wherein the mean diameter preferably means the mass medium diameter. Accordingly, in some embodiments, the present pumping unit is adapted is adapted to convey the liquid in the form of a continuous or discontinuous liquid stream.

[0056] In some embodiments, the liquid stream as provided by the present pumping unit does not comprise a plurality of droplets of such liquid in the form of a mist or plume of droplets, whereas the term mist or plume of droplets refer to a plurality of droplets which are not generated and propelled in a consecutive manner and which are typically not arranged in the form of a pointed stream as it is typically the case for a mist or plume of droplets generated by a vibrating mesh or membrane.

[0057] The present pumping unit comprises a metering chamber in fluidic connection with the liquid inlet and the liquid outlet as described above. In some embodiments, the metering chamber may be a hollow space provided by and located within a solid member surround the metering chamber, wherein the inner surfaces of such member form the boundaries of the metering chamber. In some embodiments, the metering chamber may have a generally cylindrical shape, specifically a longitudinal cylindrical shape having a longitudinal main axis. The metering chamber, in some embodiments, may have a round cross-sectional shape (perpendicular to the longitudinal main axis), for example an oval, circular or even irregular but rounded shape. In alternative embodiments, the metering chamber may have a rectangular or square or other symmetric (such as star-shaped) or asymmetric shape. In preferred embodiments, the metering chamber has a circular cross-sectional shape. The metering chamber comprises an inlet opening fluidically connected to and located downstream of the liquid inlet (of the pumping unit) for the influx of the liquid into the metering chamber. Furthermore, the metering chamber comprises an outlet opening fluidically connected to and located upstream of the liquid outlet (of the pumping unit) for the release of the liquid from the metering chamber. In some embodiments, the metering chamber or, more specifically, the solid member surrounding the metering chamber may comprise or essentially consist of glass, a metal, such as stainless steel, a ceramic material or a polymeric material, for example polyethylene (PE), polypropylene (PP), 3-Ethyl-6-vinyltetrahydro-2H-pyran-2-one (EVP), and / or polyetheretherketone (PEEK). The present pumping unit further comprises a piston reciprocally movable within the metering chamber and being adapted to suck the liquid from the liquid inlet into the metering chamber by a repulsive movement of the piston and to convey or, in other words, propel the liquid towards the liquid outlet by a propulsive movement (of the piston). In some embodiments, the reciprocal movements of the piston within metering chamber may be consecutive repulsive and propulsive movements or, in other words back and forth movements of the piston within the metering chamber, thereby reducing or enlarging the volume of the metering chamber. In some embodiments, the piston may comprise a sealing element for sealing the gap (if present) between the piston and the walls of the metering chamber, for example, in the form of a sealing ring or a plurality of sealing rings surrounding the circumference of the piston or in the form of a sealing cap mounted on or close to the end of the piston which is (under operating conditions) located within the metering chamber. In some embodiments, the piston may comprise or essentially consist of glass, a metal, such as stainless steel, a ceramic material or a polymeric material, for example polyethylene (PE), polypropylene (PP), 3-Ethyl-6-vinyltetrahydro-2H-pyran-2-one (EVP), and / or polyetheretherketone (PEEK).

[0058] In some embodiments, the metering chamber with the piston located in the metering chamber in its maximum retracted position (i.e. after a full repulsive movement) may have a volume within the range of from about 1 pL to about 100 pL or from about 5 pL to about 25 pL or from about 10 pL to about 20 pL, thereby defining the (maximum) volume of a metered dose of the liquid to be dispensed by the present pumping unit in one working cycle of the pumping unit. In some embodiments, the metering chamber with the piston located in the metering chamber in its maximum introduced position (i.e. after a full propulsive movement) may have a volume (or, in other words a “dead volume”) which remains filled with the liquid to be ejected, even after complete propulsive movement of the piston.

[0059] The present pumping unit further comprises an inlet checkvalve located downstream of the liquid inlet and upstream of the inlet opening of the metering chamber or, in other words, between the liquid inlet (of the pumping unit) and the inlet opening of the metering chamber (thereby fluidically connecting the liquid inlet of the pumping unit with the inlet opening of the metering chamber) and being transmissive (for the liquid) in the downstream direction. The term “inlet checkvalve” as used herein may be understood in abroad sense as a structure, specifically a fluidic structure that allows the liquid to pass such fluidic structure in one direction only, specifically in the downstream direction from the inlet of the present pumping unit towards the outlet. In some embodiments, the inlet checkvalve may be, for example, in the form of a ball valve, gate valve, butterfly valve, needle valve or diaphragma valve, preferably in the form of a ball valve.

[0060] Furthermore, the present pumping unit comprises an outlet checkvalve located downstream of the outlet opening of the metering chamber and upstream of the liquid outlet (thereby fluidically connecting the liquid outlet of the metering chamber with the outlet opening of the pumping unit) and being transmissive (for the liquid) in the downstream direction. The term “outlet checkvalve” as used herein may be understood in abroad sense as a structure, specifically a fluidic structure that allows the liquid to pass such fluidic structure substantially in one direction only, specifically in the downstream direction from the outlet of metering chamber towards the outlet of the present pumping unit. In some embodiments, the outlet checkvalve may be, for example, in the form of a ball valve, gate valve, butterfly valve, needle valve or diaphragma valve, preferably in the form of a ball valve. In some embodiments, the outlet checkvalve, however, may be comprised by or provided with a further fluidic structure potentially located downstream of the present pumping unit, for example in the form of a very narrow fluidic channel, connector or nozzle, through which the pressurized liquid is conveyed, which, however, does not allow for the backflow of such liquid (for example during the subsequent working or pumping cycle of the pumping unit, specifically during repulsive movement of the piston).

[0061] In some embodiments, the metering chamber may have a longitudinal cylindrical shape, a first end and a second end located opposite of the first end, wherein the piston enters the metering chamber via the first end and wherein the inlet opening and the outlet opening of the metering chamber are located adjacent to the second end of the metering chamber. The term “adjacent” to the second end of the metering chamber means that both, the inlet opening as well as the outlet opening are located close to the end of the longitudinal metering chamber such that they do not interfere or contact the piston, even in its maximally introduced position within the metering chamber (i.e. after complete propulsive movement and before start of the following repulsive movement).

[0062] In particular embodiments, the present pumping unit may comprise one or more mechanical limiting elements, for example mechanical limiting elements such as one or more stoppers which may be provided and positioned to constrain or limit the reciprocal movement, specifically at least one of the repulsive and propulsive movement) of the piston within the metering chamber.

[0063] In some embodiments, the pumping unit may further comprise a drive unit for driving the reciprocal movement of the piston within the metering chamber. The drive unit as referred to herein may provide the pumping unit as described above with sufficient energy, for example kinetic or electric energy to exert its pumping activity. In some embodiments, the drive unit may comprise a motor, for example an electrical motor or a mechanical energy storage device. Furthermore, the drive unit may comprise means for transferring the energy to be supplied to the pumping unit, specifically the kinetic energy or the electric energy to the pumping unit, for example circuitry for the transfer of electrical energy or mechanical means such as plungers, shafts, joints, gears and the like for the transfer of kinetic energy.

[0064] In some embodiments, the drive unit comprises a mechanical energy storage device or, in other words, a device adapted for the storage and release of energy. In some embodiments, the mechanical energy storage device may be adapted to store energy in the form of potential energy and to release such energy partially or entirely, for example in the form of kinetic energy. In particular embodiments, the mechanical energy storage device comprises at least one of a deformable elastic element, for example a spring, a reservoir for a compressed gas and or gas generating unit. In further particular embodiments, the term “deformable elastic element” as used herein may be interpreted broadly and may comprise, for example a spring, such as a leaf spring or spiral spring or other suitable form of a spring which may comprise or consist of an elastic material such as a metal, for example steel, or an elastomeric material, for example a polymeric elastomeric material. Accordingly, in some embodiments, the mechanical energy storage device as may be comprised by the optional drive unit may comprise a spring, for example a spiral spring or a leaf spring. In yet further particular embodiments, such deformable elastic element may be an elastic body in a form or shape different from a spring, for example in the form of an elastic block or cylinder which, for example, may comprise an elastomeric material.

[0065] In yet further particular embodiments, the mechanical energy storage device may be in the form of a reservoir (other than the reservoir for holding the liquid) holding a compressed gas and may further comprise a valve for the partial or entire release of the compressed gas in order to generate kinetic energy. In yet further particular embodiments, the mechanical energy storage device may comprise a gas generating unit, for example, a miniaturized unit for the electrochemical generation of a gas such as hydrogen which may be used to drive the pumping unit of the present application device.

[0066] In some embodiments, the optional drive unit, especially when comprising a mechanical energy storage device, may comprise an actuator for tensioning the mechanical energy storage device. Such actuator for tensioning the drive unit, especially when comprising a mechanical energy storage device, may be provided in a broad variety of different embodiments, ranging from, for example, a simple handle or lever to manually tension the mechanical energy storage device to more complex embodiments, in which the actuator may, for example, comprise a motor and a rotatable spindle associated to or driven by such motor. In some embodiments, the drive unit may comprise a motor and a mechanical energy storage device. In these embodiments, for example, the motor may be adapted to prime or tension the mechanical energy storage device, for example, by means of a rotatable spindle as mentioned above. In cases, for example in which such mechanical energy storage device comprises or is provided in the form of a spring, the actuator may comprise a handle, lever, button or other element that may be manually operated by a user to compress or expand such spring (for example in the case of a helical spring) or a leaf spring). In other embodiments, for example in embodiments in which the mechanical energy storage device comprises a compressed gas, the actuator the actuator may comprise a handle, lever, button or other element that may be manually operated by a user to compress or expand such gas. In some embodiments, the present pumping unit or, more specifically the optional drive unit of the present pumping unit may comprise a trigger mechanism. Such trigger mechanism, in some embodiments, may be adapted to and may allow for the activation of the drive unit and, thereby, initiation of the driving of the present pumping unit by the drive unit. In case, for example, in which the drive unit comprises a mechanical energy storage device, the trigger mechanism may comprise mechanical means for releasably holding such mechanical energy storage device, for example a spring, in a tensioned state and for releasing such mechanical energy storage device from such tensioned state to an non-tensioned or partially tensioned state, thereby releasing mechanical energy to drive the optional drive unit of the present pumping unit. In other exemplary embodiments, especially when the drive unit comprises a motor, such as an electrical motor as described above, such triggering unit may comprise switches and corresponding circuitry to provide such motor with electrical energy. In some embodiments, the triggering unit may comprise a switch or button that may be operated manually to trigger the optional drive unit as described above. In alternative embodiments, the trigger mechanism may comprise means adapted to automatically trigger the optional drive unit, without separate (manual) operation by a user.

[0067] In some embodiments of the present pumping unit, the reciprocal movement of the piston within the metering chamber may be monitored by measuring the power consumption of the optional drive unit, for example by using a control unit as described in further detail below in connection with the second aspect of the present disclosure.

[0068] In some embodiments, the present pumping unit comprises a reservoir for holding or holding the liquid, preferably in the form of an ophthalmologically acceptable liquid comprising at least one of an ophthalmic excipient and an ophthalmic active pharmaceutical ingredient to be applied to an ocular surface of a subject as described in detail above. The term “reservoir” as used herein is to be interpreted broadly and may refer to any type of disposable or reusable container that is suitable for holding the liquid to be applied to a ocular surface of a user by the present application device. In some embodiments, the reservoir may comprise a collapsible bag, such as a tube or a laminated pouch, or a container with at least one movable wall, a collapsible container such as a concertina-like container, or a dimensionally stable container, optionally with a gas exchange and ventilation opening. In some embodiments, the reservoir allows for the storage and withdrawal of the liquid in sterilized form, especially in cases in which the liquid is a pharmaceutically acceptable liquid to be applied to a damaged, diseased, inflamed or infected or intact ocular surface. In these embodiments, it may be advantageous that the container comprises a sterile filter in connection with an optional gas exchange and ventilation opening. In some embodiments, the reservoir has an inner volume or, in the case of a collapsible container, a maximum inner volume of up to about 10 mL, or up to about 7.5 or up to about 5 mL or up to about 2.5 mL, for example from about 0.1 mL or from about 0.2 mL to about 10 mL or to about 5 mL or to about 2.5 mL or to about 1 mL. In embodiments in which the container is provided in a dimensionally stable form, it may be advantageous that such container may have a generally conical shape narrowing towards the bottom of the container which may be advantageous to allow for improved and / or complete emptying of such container.

[0069] As described above, the present pumping unit is adapted or arranged for is adapted for conveying and, in some embodiments, thereby pressurizing, the liquid in a downstream direction from the liquid inlet to the liquid outlet and to apply the liquid to the ocular surface of the subject by ejection of the liquid in the form of a liquid stream as described in detail above. In some embodiments, the present pumping unit is adapted to convey the liquid at a flow rate of from about 0.5 mL / min to about 150 mL / min, such as from about 1 mL / min to about 100 mL / min, or from about 2 mL / min to about 75 mL / min, or from about 2.5 mL / min to about 50 mL / min or to about 60 mL / min, or from about 3 mL / min to about 30 mL / min or to about 40 mL / min, preferably from about 4 mL / min to about 25 mL / min or to about 20 mL / min or to about 15 mL / min or to about 10 mL / min (with regard to the ejected stream of liquid). In some embodiments, the present pumping unit is adapted to convey the liquid at a pressure (overpressure) of from about 100 mbar or from about 500 mbar or from about 1000 mbar to about 6000 mbar.

[0070] Accordingly, the present pumping unit is particularly suitable to provide streams, specifically pointed stream or jets of a liquid, specifically of an ophthalmic liquid in the form of a stream, specifically a pointed stream or jet as described above to the surface of an eye of a subject. In such embodiments, depending of the design or cross- sectional diameter of the outlet opening of the present pumping unit and / or the optional ejection unit or nozzle as further described below, such pointed jet or stream of liquid may have a cross-sectional diameter (perpendicular to the trajectory of the jet or stream) selected within the range of from about 0,05 mm or from about 0.1 mm to about 1.0 mm or to about 0.75 mm or to about 0.5 mm or to about 0.4 mm, or from about 0.05 mm to about 0.5 mm, preferably from about 0.1 mm or from about 0.18 mm or from about 0.2 mm to about 0.3 mm, specifically of 0.25 mm. In view of the broad variety of constituents and physical parameters in which such ophthalmic liquid may be applied, for example regarding amount, density, viscosity, specific physico-chemical parameters such as pH-values and others, the present pumping unit allows for an technically simple and straightforward adaptation to such characteristics of the liquid, for example by varying the dimensions of the metering chamber, the travel of the piston within the metering chamber and the forces exerted to the piston by the drive unit. Furthermore, due to the straightforward design and availability of its components, the present pumping unit may be provided in commercially very advantageous manner which allows, for example, that the pumping unit may be designed to exactly match the physico-chemical characteristics and or requirements of a specific liquid to be applied at low manufacturing costs. Inter alia, this allows for reduced periods of use of such a pumping unit which has been proven especially important an advantageous for the application of ophthalmic liquids to ocular surfaces or tissues, as this field of application usually requires a very high degree of purity and sterility, which is often difficult to achieve when such liquids are in contact with functional elements having a prolonged period of use. Finally, it has been found that the pumping unit according to this first aspect of the disclosure allows for the generation of a stream liquid to be applied to an ocular surface of a subject at a required pressure as well as at a required flow rate as described above. This advantageous combination of pressure and flow rate of the stream of liquid required for the successful application of such stream of liquid to an ocular surface of a subject which has not been achieved with other pumping unit designs. In a second aspect, the present disclosure provides for a device for the application of a liquid to an ocular surface of a subject, wherein the device is adapted to apply the liquid to the ocular surface by ejection of the liquid in the form of a liquid stream, wherein the device comprises a pumping unit according to the first aspect of the disclosure as described in detail above.

[0071] For the avoidance of doubt and in order to prevent repetitions, it should be noted that all embodiments, features, explanation and combinations thereof as described herein in connection with the pumping unit according to the first aspect of the disclosure apply to the device according to this second and all further aspects, accordingly.

[0072] In particular embodiments, the device according to this aspect of the disclosure, may be a modular device adapted to be releasably coupled to a portable electronic device and wherein the device comprises a base module and a replaceable module, wherein the replaceable module is adapted to be releasably connected to the base module, the device comprising a reservoir for holding the liquid, an ejection unit for the ejection of the liquid, the pumping unit according to the first aspect of the disclosure in fluid connection with the reservoir and the ejection unit and being adapted to convey the liquid from the reservoir to the ejection unit, a drive unit for driving the pumping unit, a control unit for controlling the ejection of the liquid, a coupling unit for releasably coupling the device to the portable electronic device, and a receiving unit for releasably connecting the replaceable module with the base module.

[0073] The device according to this aspect of the disclosure (herein sometimes also referred to as “present device” or “application device”), in some embodiments, is suitable for the application of a liquid to an ocular surface of a subject by ejection of the liquid from the device towards the ocular surface, or, in other words, by topical application. Such application, in some embodiments may be a contactless application of the liquid to the ocular surface of the subject, whereas the term “contactless” as used herein means that the device or any of its constituents does not contact the ocular surface of the subject during application of the liquid, wherein the term “ejection” is to be understood as described above in connection with the pumping unit of the first aspect of the disclosure.

[0074] Furthermore, for the avoidance of doubt, some functional units of the device according to this second aspect of the disclosure such as the reservoir the drive unit and the ejection unit have been described above in connection with the pumping unit of the first aspect of the invention already and may be understood to be comprised by either one of both, the pumping unit and the present device, whereas preferably in the device according to this second aspect of the disclosure only one of functional unit is comprised.

[0075] The device according to this aspect of the invention, in some embodiments, may be adapted to be releasably coupled or, in other words, releasably “docked” to a portable electronic device. In some embodiments, the device according to this aspect of the invention is releasably couplable or, in other words, “dockable” to a portable electronic device.

[0076] The terms “releasably coupled” as used herein in connection with the device according to this aspect of the present disclosure and the portable electronic device means, unless otherwise stated, that the present device can be coupled (or, in other words, attached or docked) to a portable electronic device by a releasable mechanical connection as described in further detail below in connection with the coupling unit of the device while the term “releasable” means that such connection, once established, may be released and re-established in a non-destructive manner. In some embodiments, such releasable mechanical connection results in an arrangement in which the present device and the portable electronic device are in a stable and defined position relative to each other. In some embodiments, the releasable coupling of the present application device to the portable electronic device allows for the for the transfer of data and / or energy between the application device and the portable electronic device as also described in further detail below.

[0077] The term “portable electronic device” as used herein may also be understood in a broad sense and may mean, unless otherwise stated, a tablet computer or smartphone, a (handheld) gaming console, a basic phone, a flip phone, a slider phone, a QWERTY phone, a rugged phone, a phablet, a folding phone, a netbook, a laptop computer, a digital media player, a handheld personal computer, a wearable computer, a smartwatch and others, preferably a tablet computer or a smartphone, especially a smartphone.

[0078] In some embodiments, the device of the present disclosure may be coupled to the portable electronic device by and a non-mechanical connection in order to establish a (wireless) connection between the device according to the invention and the portable electronic device in order to allow for the transfer of data and / or energy between the device according to the present invention and the portable electronic device.

[0079] As will be discussed in further detail below, the present application device, in some embodiments, may comprise a base module and a replaceable module, wherein the replaceable module may be adapted to be releasably connected to the base module. The base module and the replaceable module, when connected to each other, may form the application device according to the present invention in its operational state in which it allows, inter alia, for the application of the liquid to an ocular surface of a subject. It should be noted that either one of the base module and the releasable module alone or, in other words, disconnected from each other are not adapted to serve this purpose. In some embodiments, the base module or the replaceable module may have a separate housing. In further embodiments, both, the base module and the replaceable module has its own separate housing.

[0080] This optional modular design allows for the advantageous allocation of the particular constituents and functional units of the present device as described further below in one of the two modules or in both modules, where applicable. The replaceable module may be adapted or arranged for being releasably connected to the base module, thereby forming the device according to the present invention in a connected state (hereinafter referred to as “connected state”) or, in other words, in an operational state of the present device in which the liquid can be preferably applied to an ocular surface of a subject by ejection of the liquid from the device towards the ocular surface after being coupled to the portable electronic device as further discussed below. In particular embodiments, accordingly, the present device in the connected state comprising the base module and the replaceable module is not suitable for the application of liquid to an ocular surface unless coupled to the portable electronic device.

[0081] In some embodiments, in the connected state of the present device, the base module and the replaceable module may be in an arrangement in which the base module and the replaceable module are in a stable and defined position relative to each other. Furthermore, in the connected state the base module and the replaceable module may be in an arrangement, which allows for the operative interaction of the particular constituents or functional units of the present device, for example by mechanical, electro-mechanical and / or fluidic connections between the base module and the replaceable module and the corresponding constituents or functional units comprised by the respective modules. In this context as well the term “replaceable" means that such connection, once established, may be released and re-established in a nondestructive manner, if necessary repeatedly. To establish this connected state, as will be described in further detail below, at least one of the base module and the replaceable module may comprise a receiving unit.

[0082] The device according to this aspect of the disclosure may comprise a reservoir for holding or actually holding the liquid as escribed above in connection with the pumping unit of the first aspect of the disclosure. As discussed in further detail below, the reservoir may be comprised by the replaceable module of the present device and may be provided in a form in which it can be removed and, if necessary, replaced within the replaceable module. In some embodiments, however, the reservoir may be comprised by the replaceable module in a form in which it can only be replaced together with replaceable module, if necessary, for example when the liquid contained in the reservoir needs to be refilled or replaced.

[0083] As a further functional unit, the device according to this aspect of the present disclosure may comprise an ejection unit for the ejection of the liquid, specifically for the ejection of the liquid towards the ocular surface of the subject. The ejection unit, in some embodiments, may be in fluidic connection with the reservoir via the pumping unit of the first aspect of the disclosure to allow for the ejection of the liquid pumped from the reservoir by the pumping unit towards the selected or, in other words, targeted ocular surface of a subject.

[0084] The ejection unit, in some embodiments, may be orientable to the ocular surface of a subject to which the liquid is to be applied by the present application device. In some embodiments, the ejection unit is therefore used for targeted dispensing and application of liquid, preferably in the form of a continuous or discontinuous stream or separate dose or portion of liquid to the chosen ocular surface as described in detail above in connection with the pumping unit of the first aspect of the disclosure. In some embodiments, the ejection unit may comprise a nozzle or an array of a plurality of nozzles for the ejection of the liquid, optionally in the form of a single fluid nozzle, for example a solid stream nozzle, a full or hollow cone nozzle, a nozzle with multiple exits, an impinging or non-impinging nozzle, a swirl nozzle or a nozzle plate, preferably a solid stream nozzle, a full or hollow cone nozzle. In some embodiments, the ejection unit may comprise a single nozzle or an array of a plurality of nozzles.

[0085] In some embodiments, the ejection unit may comprise a nozzle that allows the liquid to leave the present application device at a certain speed, for example at a speed of from about 0.5 to about 10 m / s. This speed may be achieved by means of the pumping unit of the first aspect of the disclosure as described in detail above adapted to pump the liquid from the reservoir and to pressurize or accelerate the liquid. In some embodiments, the nozzle may have a single or a plurality, such as 2 to 10 or 2 to 5 openings, preferably a single opening, through which the liquid may be ejected. In some embodiments such nozzle opening may have a diameter selected within the range of from about 0,05 mm or from about 0.1 mm to about 1.0 mm or to about 0.75 mm or to about 0.5 mm or to about 0.4 mm, or from about 0.05 mm to about 0.5 mm, preferably from about 0.1 mm or from about 0.18 mm or from about 0.2 mm to about 0.3 mm, specifically of 0.25 mm. Orientation of the ejection unit may be achieved in the simplest case by manual movement of the entire present device, especially in the coupled state along with the portable electronic device by the user, but can also be achieved jointly with a few components thereof, or by separate orientation of merely the dispensing unit, and here in particular the nozzle or the nozzle array. In particular embodiments, the reservoir and the ejection unit of the present device may be comprised by the replaceable module.

[0086] As a further functional unit, the preferably modular application device according to this second aspect of the present disclosure comprises a pumping unit according to the first aspect of the disclosure in fluid connection with the reservoir and the ejection unit and being adapted to pump or, in other words, convey the liquid from the reservoir to the ejection unit, specifically in the connected state of the present device in which the base module is connected to the replaceable module. The pumping unit may further comprise further mechanical or fluidic elements as necessary to allow the pump to pressurize, accelerate or convey the liquid as described above, for example, fluidic connections in the form of liquid-tight tubing, valves or other microfluidic elements.

[0087] As a further functional unit, the device according to the present invention may comprise a drive unit for driving the pumping unit as described in detail above as an optional component of the pumping unit of the first aspect of the disclosure.

[0088] As a further functional unit, the application device according to this aspect of the present disclosure may comprise a control unit for controlling the ejection of the liquid. The term “control unit” as used herein is to be understood in a broad sense as a unit which is adapted or arranged or suitable for controlling the processes necessary for the implementation of the ejection of the liquid from the present device towards the targeted ocular surface, specifically the process of controlling or monitoring the pumping unit, specifically the controlling or monitoring of the pump comprised by the pumping unit and the associated drive unit as described above. Furthermore, the control unit may electronically cooperate and communicate with the portable electronic device to which the present application device is coupled (in the coupled state). In further embodiments, the control unit may provide for the electronic connection between the portable electronic device (in the coupled state) and the drive and pumping unit and potentially further functional units of the present application device. In some embodiments, the control unit may comprise suitable and, in some embodiments, miniaturized circuitry such as one or more printed circuit bords (PCBs) equipped with electronic components such as transistors, diodes, integrated circuits, processors, electronic storage devices, for example electronic data storage devices, optoelectronic devices, sound generators and other known to those of skill in the art.

[0089] As a further functional unit, the administration device according to this aspect of the present disclosure, in some embodiments, may comprise a coupling unit for releasably coupling the present modular application device to the portable electronic device. The term “coupling unit” as used herein is also to be understood in a broad sense as a functional unit adapted or suitable for establishing a releasable connection between the present application device and the portable electronic device, wherein the term “releasable” as used in this context means that such connection may be formed and released and, if necessary, formed again in a non-destructive manner. In some embodiments, the coupling unit comprises coupling means adapted to form a releasable connection, preferably a releasable electro-mechanic connection between the base module and the portable electronic device (in the coupled state). In specific embodiments, the coupling unit may be comprised by the base module of the present device and, in further specific embodiments, may not be comprised by the replaceable module of the device.

[0090] In further embodiments, the coupling device may be adapted for the transfer of data and / or energy between the portable electronic device and the present preferably modular application device and may be provided in the form of a mechanical connection, specifically in the form comprising a plug connection. In some embodiments, plug connectors may be provided that allow for both, the transfer of data and energy in both directions between the portable electronic device and the present modular application device. Suitable plug connectors in this regard comprise but are not limited to, for example, interfaces of the USB-type, especially micro-USB and USB-C as well as Lightning®. Accordingly, in particular embodiments, the coupling unit may comprise USB or Lightning connectors, specifically USB-C connectors. In specific embodiments, such corresponding Lightning or USB-C connectors may be provided on the portable electronic device as well as on the present application device, specifically the base module of the present application device. In this regard, however, it should be noted that the connectors as referred to herein may be replaced by future connectors suitable for the exchange of data and / or energy, accordingly.

[0091] In specific embodiments, the present modular application device, specifically the base unit thereof may comprise a male (USB, USB-C or Lightning) connector and the portable electronic device may comprise a female (USB, USB-C or Lightning) connector. Accordingly, in particular embodiments, the coupling unit of the present modular application device may be adapted to form a releasable connection between the base module of the device and the portable electronic device comprise a plug connector, preferably a male connector (USB-C, Lightning, micro-USB).

[0092] In some embodiments, the coupling unit may comprise means for establishing a mechanical connection between the portable electronic device and the present, preferably modular application device, specifically the base module thereof and may furthermore comprise means for establishing a wireless electronic connection between the portable electronic device and the present modular application device, specifically the base module thereof. In these embodiments, the term “mechanical connection” is to be understood as a connection between the portable electronic device and the present, preferably modular application device, specifically the base module thereof, in which the portable electronic device and the present modular application device, specifically the base module thereof, are in a positionally stable relationship to each other such that the portable electronic device and the present modular application device can be operated by a user as one single unit or system (in the coupled state). Furthermore, in these embodiments, the portable electronic device and the present modular application device may be connected to each other for the exchange of data and / or energy by a wireless connection, for example by a Bluetooth®, WLAN or other near-filed connection (NFC) or suitable future wireless connections.

[0093] As a further functional unit, the device according to this aspect of the present disclosure may comprise a receiving unit for releasably connecting the replaceable module with the base module. The receiving unit of the present modular application device may be provided in order to establish a releasable connection between the base module and the replaceable module by which the present preferably modular application device is formed in its connected state or, in other words, in a state in which it can be operated by a user for the application of a liquid to a targeted ocular surface after being coupled to the portable electronic device (thereby forming the device of this aspect of the present disclosure in the operational state). In some embodiments, the receiving unit may be (partly) comprised by both, the receiving unit of the base module and the replaceable module.

[0094] In some embodiments, the receiving unit of the base module and the replaceable module comprise corresponding connecting means adapted to form a releasable connection, preferably a releasable electro-mechanical and / or mechanical connection and / or fluidic connection between the base module and the replaceable module of the present device. In this context as well, the term “releasable” may mean that such connection may be formed and released and, if necessary, formed again in a nondestructive manner. In some alternative embodiments, however, in this context the term “releasable” may mean that such connection may be formed and released only once and that, in other words, such replaceable module may only be connected (and disconnected) once to or from the base module. In some embodiments, the base module and the replaceable module in the connected state may form a mechanically stable assembly or, in other words, an assembly in which both modules are in a positionally stable relationship to each other. This may be implemented, for example, by a broad variety of suitable connecting means provided on either one or both of the base module and the replaceable module, for example by a form-fit or force-fit or snap-fit connection such as by corresponding plug connectors, fastening rails, hooks with corresponding eyelets, magnetic connectors or even hook and loop connectors (Velcro® connectors) which may be, for example provided, on the outer surface of the corresponding housings of the base module and the replaceable module.

[0095] In preferred embodiments, the replaceable module of the present preferably modular application device may comprise the reservoir and the ejection unit. It has been found by the inventors that the specific, preferably modular design of the present application device allows for the maximum flexibility and particularly advantageous designs of the present device especially in case in which the replaceable module comprises both the reservoir and the ejection unit as both described in detail above. This has been proven especially advantageous in connection with the general functional layout of the device as being adapted to form a functional assembly or system with a portable electronic device which offers the possibility to co-operate with and share technical resources and capabilities between the portable electronic device and the present modular application device. For example, either one of or a subset of all of the following elements of the portable electronic device may be used or co-used by the present modular application device, for example the CPU, the reloadable battery, the display, the camera(s), other sensors such as position sensors, temperature sensors, humidity sensors, vibrating elements, the microphone, the loudspeaker and / or identification means.

[0096] The specific design of the present preferably modular application device, especially when having the reservoir and the ejection unit comprised by the replaceable module, allows for the advantageous design in which both, the reservoir and the ejection unit can be replaced along with the replaceable unit, for example, when the reservoir is empty and needs to be exchanged by a corresponding replacement module having a filled or partially filled reservoir. Furthermore, this design allows for the use of a particular base unit with different exchangeable units comprising different liquids to be applied to an ocular surface. Especially due to the fact that an ejection unit is often specifically designed with regard to the physico-chemical properties of a specific liquid or constituents contained therein, such as density, viscosity, specific chemical parameters such as pH-values and others, in many cases a specific ejection unit is used with a particular liquid and, accordingly, has to be exchanged when switching to a different liquid to be applied. Furthermore, the integration of ejection unit and reservoir within the replaceable module allows to reduce the risk of cross-contaminations with different liquids which is especially relevantin the field of the application of pharmaceutical liquids. In particular embodiments, the replaceable module is (initially) provided in sterilized form. In yet further embodiments, the replaceable module is (initially) provided in individually packaged form, for example sealed by a foil or blister pack.

[0097] In some embodiments, the functional units as described above other than the reservoir and the ejection unit may be comprised by or, in other words, allocated in either one of the base module and the replaceable module as outlined in further detail below, or, in some embodiments may be comprised by both, the base module and the replaceable module.

[0098] In some embodiments, the base module of the present modular application device may comprise the control unit and the coupling unit as described above. In further embodiments, the base module of the present modular application device may comprise the control unit, the coupling unit and the receiving unit. In yet further embodiments as already described above, however, the receiving unit may be comprised by both, comprise the base module and the replaceable module.

[0099] In some embodiments, the base module may also comprise the pumping unit comprising the pump as described in detail above in connection with the pumping unit of the first aspect of the disclosure. In further embodiments, the pumping unit may be comprised by the base unit and is not comprised by the replaceable unit. In these embodiments, accordingly, the pumping unit is not replaced once the replaceable module of the present application device is replaced and can be used repeatedly, independent of the exchange of the replaceable unit. This allows for economically advantageous embodiments of the present application device in which the pumping unit can be used repeatedly, independent of the preplacement of the replaceable unit.

[0100] In alternative and preferred embodiments, however, the replaceable module of the present application device comprises the pumping unit, specifically the pumping unit of the first aspect of the disclosure. In further embodiments, the pumping unit may be comprised by the replaceable module and not by the base module. In these embodiments, accordingly, the pumping unit is replaced once the replaceable module of the present application device is replaced and, accordingly, cannot be used repeatedly. This design allows for advantageous embodiments of the present application device in which the reservoir, the pumping unit and the ejection unit are replaced when the replaceable module is replaced or exchanged by another replaceable module. In further embodiments, the replaceable module further comprises tubing for the fluidic connection of the reservoir with the ejection unit. In these preferred embodiments, accordingly the pumping unit is replaced along with the replaceable module of the preferably modular application device which is commercially advantageous due to the simplified and commercially beneficial mechanical design of the pumping unit according to the first aspect of the disclosure.

[0101] In yet further embodiments, the replaceable module may comprise all components that are contact with the liquid (under standard operating conditions). Especially in these embodiments, the present preferably modular application device allows for the exchange of the replaceable module along with all components which (under standard operating conditions) are in contact with the liquid to be applied to an ocular surface of a subject. This, however, may be especially advantageous in cases in which liquids are to be ejected and applied to an ocular surface which are sensitive to cross-contamination, or which have to be applied in very pure or even sterile form as it is the case for many ophthalmic applications. In these embodiments, it has been proven advantageous, if the pumping unit, specifically the pump of the pumping unit has a lower technical complexity such that it can be provided in an economically advantageous form as it is the case for the pumping unit according to the first aspect of the disclosure.

[0102] In some embodiments, the base module may also comprise the drive unit as described in detail above. In further embodiments, the drive unit is comprised by the base unit and is not comprised by the replaceable unit. In these embodiments, accordingly, the drive unit is not replaced once the replaceable module of the present application device is replaced and can be used repeatedly, independent of the exchange of the replaceable unit. This allows for economically advantageous embodiments of the present application device, especially in cases in which technically or mechanically complex and, accordingly, expensive drive units are to be implemented, for example electrical drive units such as electrical motors.

[0103] In alternative embodiments, however, the replaceable module may be comprised by the drive unit. In further embodiments, the drive unit may be comprised by the replaceable module and not by the base module. In these embodiments, accordingly, the drive unit is replaced once the replaceable module of the present application device is replaced and, accordingly, cannot be used repeatedly. This design allows for advantageous embodiments of the present application device, especially when the drive unit comprises a mechanical energy storage device as discussed in detail above, such as deformable elastic element, for example a spring. In some embodiments, the energy storage device may be comprised by the replaceable module.

[0104] In these embodiments, the mechanical energy storage device may be charged with (potential) energy, for example by deformation, compression or extension of the mechanical energy storage device, for example when the replaceable module is inserted, introduced or attached to the base module. In these advantageous embodiments, no additional electrical or mechanical storage device would be necessary to provide the energy necessary for driving the pump of the pumping unit. In some embodiments, the exchangeable module may be provided in a form, in which the mechanical energy storage is already loaded with energy or, in other words, is provided in a loaded state. In these embodiments, after connection of the releasable module with the base module the resulting device is ready for use without the need of further loading or charging the mechanical energy storage device.

[0105] In alternative embodiments, however, it is also possible to provide for a priming unit (as a separate unit or as a part of the drive unit) to prime the drive unit or, in other words, to introduce energy to the drive unit, specifically the mechanical energy storage device such as a spring or other elastic element as described above, whereas such priming unit may be comprised by either one or both of the base unit and the replaceable unit, preferably, however, by the base unit. In particular embodiments, the replaceable module may comprise a mechanical energy storage, for example in the form of a spring, and the base unit may comprise a priming unit for priming or tensioning the spring prior to use.

[0106] In further embodiments, the application device according to this aspect of the disclosure may comprise s trigger mechanism as described in detail above, either in the form of a separate unit or as a part of the drive unit.

[0107] In particular embodiments, especially in cases in which the drive unit comprises a mechanical energy storage device, the replaceable module may comprise the energy storage device, or, in some embodiments, may comprise the energy storage device, the pumping unit, the reservoir and the ejection unit. This co-location of the mechanical energy storage device, pumping unit, reservoir and ejection unit allows for the advantageous alignment of the specific parameters of these functional units with regard to a specific liquid and specific amount thereof to be dispensed, for example regarding different sizes or volumes of the reservoir, different (spring) forces depending on the volume or viscosity of the specific liquid and / or different designs of the ejection unit and nozzle.

[0108] In further particular embodiments, the replaceable module may comprise a closing device, for example comprising a closing cap or cover to close, cover and / or protect the ejection unit in a non-use state and / or to prevent clogging and / or gelification of the ejection unit, specifically the nozzle of the ejection unit. In some embodiments, such closing device may, for example, comprise a slidable cover arranged for reciprocal slide movement thereby covering or uncovering the ejection unit towards the surroundings of the device. In other exemplary embodiments, such closing device may, for example, comprise a cap, such as a hinging cap arranged for reciprocal hinging movement thereby covering or uncovering the ejection unit towards the surroundings of the device. In further embodiments, such closing device may be linked to the drive mechanism or, more specifically to the priming mechanism, for example, such that opening or closing the covering means by a user may (simultaneously) prime or tension the drive mechanism.

[0109] In some embodiments, the present preferably modular application device may further comprise indicating means for indicating the tensioning / loading state of the drive unit. In some embodiments, such indicating means may comprise a display or optical indicator. Such indicating means may also be provided on either one or both of the base module and the replaceable module, preferably however, on the particular module which also comprises the respective energy storage device, preferably the mechanical energy storage device, if present. Accordingly, in some embodiments, the base module comprises the indicating means. In alternative embodiments the exchangeable module comprises the drive unit and the indicating means.

[0110] In further embodiments, the present preferably modular application device comprises means for identifying the replaceable module in the connected state of the base module and the replaceable module. Such identifying means may be comprised by the either one of the base module and the replaceable module or, in some embodiments, may be comprised (partly) by both, the base unit and the replaceable unit. In some embodiments, such means are suitable for at least one of a) identifying the replaceable module and b) providing information related to the liquid comprised by the reservoir of the exchangeable module, for example related to the constituents of the liquid, amount and / or concentration of liquid comprised, data related to the manufacture, expiration dates and others. In some embodiments, the identifying means may be, for example, in the form specific patterns provided on (the surface) of the exchangeable module that may be read by a corresponding sensor on the base pattern. In other embodiments, such identifying means may comprise a device for the storage of electronic data that may be read by a corresponding reading device, either via a wired or contactless connection. In particular embodiments, the replaceable module may comprise a data storage device, for example an RFID chip or a passive NFC tag, and the base module may comprise a corresponding RFID or NFC reader. In alternative embodiments, as already mentioned, wired connections for the exchange of data may also be provided. In some embodiments, the replaceable unit may comprise a data storage or memory unit, interacting with the control unit. On the basis of the data provided accordingly, in some embodiments, the specific commands necessary for the ejection of the liquid to the targeted ocular surface may be calculated by the control unit and provided to the other units as described above, specifically the drive unit and the pumping unit. In some embodiments such calculation by the drive unit may comprise an interaction between the control unit and the portable electronic device as described in further detail below.

[0111] The preferably modular application device of this aspect of the present disclosure may be provided along with directions for the use of the device, including but not limited to the connection and disconnection of the replaceable module to the base module, the coupling of the base module to a portable electronic device as well as other instructions for use of the device, specifically with regard to the intended application of the liquid to a targeted ocular surface.

[0112] Accordingly, in a third aspect, the present invention provides for a kit comprising the device according to the second aspect of the disclosure and instructions for use of the device. In a fourth aspect, the present disclosure provides for a replaceable module adapted to be releasably connected to a base module thereby forming the modular application device according to the second aspect of the disclosure, the replaceable module comprising: a reservoir for holding a liquid to be applied to an ocular surface of a subject by ejection of the liquid from the device towards the ocular surface, and an ejection unit for the ejection of the liquid (towards the ocular surface of the subject).

[0113] In some embodiments, the replaceable module according to this aspect of the disclosure may further comprise a pumping unit according to the first aspect of the disclosure in fluid connection with the reservoir and the ejection unit and being adapted to convey the liquid from the reservoir to the ejection unit (in the connected state). In further embodiments, the replaceable module may further comprise a drive unit for driving the pumping unit. In yet further embodiments, the replaceable module may be provided in sterilized form and / or in individually packaged form, for example sealed by a foil or blister pack. In some embodiments, the replaceable module may comprise means for identifying the replaceable module as described in detail above in connection with the preferably modular device of the second aspect of the disclosure.

[0114] The replaceable module according to this aspect may also be provided along with directions for the use of the replaceable module, including but not limited to the connection and disconnection of the replaceable module to the base module, as well as other instructions for use of the device, specifically with regard to the intended application of the liquid to a targeted ocular surface.

[0115] Accordingly, in a fifth aspect, the disclosure provides for a kit comprising the replaceable module according to the fourth aspect of the invention and instructions for use of the replaceable module.

[0116] The present preferably modular application device as described in connection with the second aspect of the invention may be coupled to a portable electronic device via the coupling unit as described in detail above to form an assembly or system comprising the present modular administration device and the portable electronic device in a positionally stable arrangement in which it can be used, handled and manipulated as a single assembly by a user for the application of the liquid to a targeted ocular surface, such as an ocular surface of a subject. In this context, it should be noted that, in some embodiments, said user may be identical to the subject to which the liquid is applied. In alternative embodiments, however, however, such user as referred to above may be different from the subject to which the liquid is applied.

[0117] Accordingly, in a sixth aspect, the present invention provides for a system for the preferably contactless application of a liquid to an ocular surface of a subject by ejection of the liquid from an application device towards the ocular surface, wherein the system comprises: a) the device according to the second aspect of the disclosure, and b) a portable electronic device.

[0118] In particular embodiments, as outlined in connection with the device of the second aspect of the disclosure already, the portable electronic device may be a tablet computer or smartphone, a (handheld) gaming console, a basic phone, a flip phones, a slider phone, a QWERTY phone, a rugged phone, a phablet, a folding phone, a netbook, a laptop computer, a digital media player, a handheld personal computer, a wearable computer, a smartwatch and others, preferably a tablet computer or a smartphone, especially a smartphone.

[0119] As also outlined in connection with the second aspect, such portable electronic device may be releasably coupled to the preferably modular device of the second aspect, specifically to the base module of the modular device, via the coupling unit of the device and in the coupled state, data and / or energy may be transferred from the electronic mobile device to the (base module) of the modular application device and vice versa. This design allows for the use and cooperation of the technical resources of the portable electronic device, for example the processor(s), the data storage, the battery, sensors, such as the camera(s), sensors, for example, sensors for the position or location, acceleration, temperature and others, the display and other functional elements in the finally assembled state. This contributes to the overall advantageous design of the preferably modular application device of the present disclosure in which a large number of technical elements can be provided by a (reusable) portable electronic device and in which a further considerable number of technical elements are comprised by a (reusable) base module and in which only a small number of technical elements is comprised by a (non-reusable, disposable) replaceable module, preferably including the pumping unit according to the first aspect of the disclosure. Furthermore, this overall design allows for maximum flexibility also with regard to the specific liquid to be applied or, in other words, allows for abroad variety of different liquids and application purposes to be performed with the same components of the system, specifically with the same portable electronic device and the same base module of the present modular application device. This, however, is not only especially advantageous with regard to economic but also with regard to environmental considerations.

[0120] In some embodiments, in order to provide for a defined spatial relationship between the portable electronic device and the present modular application device in the coupled state, the modular application device, specifically the base module of the modular application device, may comprise means for determining the position of the base module in relation to the portable electronic device (in the coupled state). In some embodiments, such means for determining the position of the base module in relation to the portable electronic device (in the coupled state) may comprise, for example, a stylus or a plurality of styluses adapted to interact with a touch-sensitive screen of the portable electronic device, preferably the smartphone or tablet computer. In some embodiments, such stylus may be connected to and / or interact with the control unit as described above.

[0121] In further aspects, the present disclosure provides for the use of the pumping unit according to the first aspect of the disclosure as well as of the device comprising such pumping unit according to the second aspect of the disclosure as well as of the replaceable module, kits and system according to the further aspects of the disclosure for the for the application of a liquid to an ocular surface of a subject, specifically by ejection of the liquid in the form of a liquid stream through the liquid outlet of the pumping unit towards the ocular surface of the subject. In yet further aspects, the present disclosure provides for a method for the application of a liquid to an ocular surface of a subject, specifically by ejection of the liquid in the form of a liquid stream through the liquid outlet of a pumping unit towards the ocular surface (S) of the subject, the method comprising the use of the pumping unit according to the first aspect of the disclosure as well as of the device comprising such pumping unit according to the second aspect of the disclosure as well as of the replaceable module, kits and system according to the further aspects of the disclosure. The following is a list of exemplary numbered embodiments El to E45 comprised by the present invention:

[0122] El. A pumping unit (60) for the application of a liquid (L) to an ocular surface (S) of a subject, wherein the pumping unit (60) comprises a liquid inlet (61) fluidically connected or connectable to a reservoir (40) for holding the liquid (L) and a liquid outlet (62) through which the liquid (L) can exit the pumping unit (60), wherein the pumping unit (60) is adapted to convey the liquid (L) in a downstream direction from the liquid inlet (61) to the liquid outlet (62) and to apply the liquid (L) to the ocular surface (S) of the subject by ejection of the liquid (L) in the form of a liquid stream through the liquid outlet (62) towards the ocular surface (S) of the subject, wherein the pumping unit (60) comprises:

[0123] - a metering chamber (63) in fluidic connection with the liquid inlet (61) and the liquid outlet (62), wherein the metering chamber (63) comprises an inlet opening (64) fluidically connected to and located downstream of the liquid inlet (61) for the influx of the liquid (L) into the metering chamber (63), and an outlet opening (65) fluidically connected to and located upstream of the liquid outlet (62) for the release of the liquid (L) from the metering chamber (63);

[0124] - a piston (66) reciprocally movable within the metering chamber (63) and being adapted to suck the liquid (L) from the liquid inlet (61) into the metering chamber (63) by a repulsive movement and to convey the liquid (L) towards the liquid outlet (62) by a propulsive movement; - an inlet checkvalve (67) located downstream of the liquid inlet (61) and upstream of the inlet opening (64) of the metering chamber (63) (and fluidically connecting the liquid inlet with the inlet opening) and being transmissive in the downstream direction; and

[0125] - an outlet check valve (68) located downstream of the outlet opening (65) of the metering chamber (63) and upstream of the liquid outlet (62) and being transmissive in the downstream direction.

[0126] E2. The pumping unit (60) according to embodiment El, wherein the pumping unit is adapted is adapted to convey the liquid (L) in the form of a continuous or discontinuous liquid stream.

[0127] E3. The pumping unit (60) according to embodiment El or E2, wherein the metering chamber (63) has a longitudinal cylindrical shape, a first end (63a) and a second end (63b) located opposite of the first end (63a), wherein the piston (66) enters the metering chamber (63) via the first end (63a) and wherein the inlet opening (64) and the outlet opening (65) of the metering chamber (63) are located adjacent to the second end (63b) of the metering chamber (63).

[0128] E4. The pumping unit (60) according to any one of embodiments El to E3, wherein the pumping unit (60) further comprises a drive unit (70) for driving the reciprocal movement of the piston (66) within the metering chamber (63).

[0129] E5. The pumping unit (60) according to embodiment E4, wherein the drive unit (70) comprises a mechanical energy storage device (71).

[0130] E6. The pumping unit (60) according to embodiment E5, wherein the mechanical energy storage device (71) comprises a spring.

[0131] E7. The pumping unit (60) according to any one of embodiments E4 to E6, wherein the drive unit (71) comprises an actuator (72) for tensioning the mechanical energy storage device (71).

[0132] E8. The pumping unit (60) according to embodiment E7, wherein the actuator (72) comprises an (electrical) motor (73) and a spindle (74). E9. The pumping unit (60) according to any one of embodiments E4 to E8, wherein the drive unit (70) comprises a trigger mechanism.

[0133] E10. The pumping unit (60) according to any one of the preceding embodiments, wherein the liquid (L) is an aqueous liquid or liquid composition comprising at least one of an ophthalmic excipient and an ophthalmic active pharmaceutical ingredient.

[0134] Ell. The pumping unit (60) according to any one of the proceeding embodiments, wherein the pumping unit comprises a reservoir (40) holding the liquid (L), preferably in the form of an ophthalmologically acceptable liquid comprising at least one of an ophthalmic excipient and an ophthalmic active pharmaceutical ingredient.

[0135] E12. The pumping unit (60) according to any one of the preceding embodiments, wherein the liquid (L) is in sterilized form.

[0136] E13. The pumping unit (60) according to any one of the preceding embodiments, wherein the pumping unit (60) is adapted to convey the liquid at a flow rate of from about 0.5 mL / min to about 150 mL / min, such as from about 1 mL / min to about 100 mL / min, or from about 2 mL / min to about 75 mL / min, or from about 2.5 mL / min to about 50 mL / min or to about 60 mL / min, or from about

[0137] 3 mL / min to about 30 mL / min or to about 40 mL / min, preferably from about

[0138] 4 mL / min to about 25 mL / min or to about 20 mL / min or to about 15 mL / min or to about 10 mL / min (with regard to the ejected stream of liquid).

[0139] E14. The pumping unit (60) according to any one of the preceding embodiments, wherein the pumping unit (60) is adapted to convey the liquid (L) at a pressure of from about 100 mbar or of from about 500 mbar or from about 1000 mbar to about 6000 mbar.

[0140] E15. A device (10) for the application of a liquid (L) to an ocular surface (S) of a subject, wherein the device is adapted to apply the liquid (L) to the ocular surface (S) by ejection of the liquid (L) in the form of a liquid stream, wherein the device (10) comprises a pumping unit (60) according to any one of embodiments El to E14. E16. The device (10) according to embodiment E15, wherein the device (10) is a modular device adapted to be releasably coupled to a portable electronic device (1) and wherein the device (10) comprises a base module (20) and a replaceable module, wherein the replaceable module (30) is adapted to be releasably connected to the base module (20), the device (10) comprising: a reservoir (40) for holding the liquid (L), an ejection unit (50) for the ejection of the liquid (L), a pumping unit (60) according to any one of embodiments El to E14 in fluid connection with the reservoir (40) and the ejection unit (50) and being adapted to convey the liquid (L) from the reservoir (40) to the ejection unit (50), a drive unit (70) for driving the pumping unit (60), a control unit (80) for controlling the ejection of the liquid (L), a coupling unit (90) for releasably coupling the device (10) to the portable electronic device (1), and a receiving unit (100) for releasably connecting the replaceable module (30) with the base module (20).

[0141] E17. The device according to embodiment E16, wherein the replaceable module (30) of the device comprises the reservoir (40) and the ejection unit (50).

[0142] E18. The device (10) according to any one of embodiments E15 to E17, wherein the base module (20) of the device (10) comprises the control unit (80), the coupling unit (90) and the receiving unit (100).

[0143] E19. The device (10) according to any one of embodiments E15 to E18, wherein the replaceable module (30) comprises the pumping unit (60).

[0144] E20. The device (10) according to any one of embodiments E15 to E19, wherein the base module (20) comprises the drive unit (70).

[0145] E21. The device (10) according to any one of embodiments E15 to E19, wherein the replaceable (30) module comprises the drive unit (70).

[0146] E22. The device (10) according to any one of embodiments E15 to E21, wherein the ejection unit (50) comprises a nozzle (51) for the ejection of the liquid (L), optionally in the form of a single fluid nozzle, for example a solid stream nozzle, a full or hollow cone nozzle, a nozzle with multiple exits, an impinging or non-impinging nozzle, a swirls nozzle or a nozzle plate.

[0147] E23. The device (10) according to any one of embodiments E15 to E22, wherein the replaceable module (30) further comprises tubing (31) for the fluidic connection of the reservoir with the ejection unit.

[0148] E24. The device (10) according to any one of embodiments E15 to E23, wherein the replaceable module (30) comprises all components that are contact with the liquid (L) (under standard operating conditions).

[0149] E25. The device (10) according to any one of embodiments E15 to E24, wherein the replaceable module (30) is (initially) provided in sterilized form.

[0150] E26. The device (10) according to any one of embodiments E15 to E25, wherein the replaceable module (30) comprises a closing cap (32) to protect the ejection unit (50) in a non-use state.

[0151] E27. The device (10) according to any one of embodiments E15 to E26, wherein the drive unit (70) comprises a motor and a mechanical energy storage device [71).

[0152] E28. The device (10) according to embodiment E27, wherein the mechanical energy storage device (71) comprises at least one of a deformable elastic element (e.g. a spring), a reservoir for a compressed gas and a gas generating unit.

[0153] E29. The device (10) according to embodiment E27 or E28, wherein the energy storage device (71) is comprised by the replaceable module (30).

[0154] E30. The device (10) according to any one of embodiments E15 to E29, wherein the device comprises a mechanical energy storage device (71) and wherein the replaceable module (30) comprises the energy storage device (71), the reservoir (40), the pumping unit (60) and the ejection unit (50).

[0155] E31. The device (10) according to any one of embodiments E15 to E30, wherein the receiving unit (100) of the base module (20) and the replaceable module (30) comprise corresponding connecting means (101) adapted to form a releasable connection, preferably a releasable electro-mechanical and / or mechanical and / or fluidic connection between the base module (20) and the replaceable module (30) of the device (10).

[0156] E32. The device (10) according to any one of embodiments E15 to E31, wherein the base module (20) and the replaceable module (30) in the connected state form a mechanically stable assembly.

[0157] E33. The device (10) according to any one of embodiments E15 to E32, wherein the coupling unit (90) comprises coupling means (91) adapted to form a releasable connection, preferably a releasable electro-mechanic connection between the base module (20) and the portable electronic device (1) (in the coupled state).

[0158] E34. The device (10) according to embodiment E33, wherein the coupling means (91) are adapted to form a releasable connection between the base module (20) of the device (10) and the portable electronic device (1) comprise a plug connector, preferably a male connector (USB-C, Lightning, micro-USB).

[0159] E35. The device (10) according to any one of embodiments E15 to E34, wherein the base module (20) comprises means for determining the position (21) of the base module (20) in relation to the portable electronic device (1) (in the coupled state).

[0160] E36. The device (10) according to embodiment E35, wherein the means for determining the position (21) of the base module (20) in relation to the portable electronic device (1) (in the coupled state) comprise a stylus adapted to interact with a touch-sensitive screen (2) of the portable electronic device (1), preferably the smartphone or tablet computer.

[0161] E37. The device (10) according to any one of embodiments E15 to E36, wherein the device (10) comprises means for identifying the replaceable module (30) in the connected state of the base module (20) and the replaceable module (30).

[0162] E38. A replaceable module (30) adapted to be releasably connected to a base (20) module thereby forming the device (10) according any one of embodiments E15 to E37, the replaceable module (30) comprising: a reservoir (40) for holding a liquid (L) to be applied to the ocular surface (S) of a subject by ejection of the liquid (L) from the device (10) towards the ocular surface (S); and an ejection unit (50) for the ejection of the liquid (L) (towards the ocular surface of the subject).

[0163] E39. The replaceable module according to item 38, further comprising:

[0164] - a pumping unit (60) according to any one of embodiments El to E 14 in fluid connection with the reservoir (40) and the ejection unit (50) and being adapted to convey the liquid (L) from the reservoir (40) to the ejection unit [50).

[0165] E40. The replaceable module (30) according to embodiment E39, wherein the replaceable module (30) further comprises a drive unit (70) for driving the pumping unit (60).

[0166] E41. The replaceable module (30) according to embodiment E39 or E40, wherein the replaceable module (30) is provided in sterilized form.

[0167] E42. The replaceable module (30) according to any one of embodiments E39 to E41, wherein the replaceable module (30) is provided in individually packaged form.

[0168] E43. The replaceable module (30) according to any one of embodiments E39 to E42, wherein the replaceable module (30) comprises means for identifying the replaceable module (30).

[0169] E44. A system (200) for the application of a liquid (L) to an ocular surface (S) of a subject by ejection of the liquid (L) from an application device (10) towards the ocular surface (S), wherein the system (200) comprises: a) the device (10) according to any one of embodiments E15 to E37, and b) a portable electronic device (1). E45. The system (200) according to embodiment E44, wherein the portable electronic device (1) is a tablet computer or smartphone, preferably a smartphone.

[0170] DETAILED DESCRIPTION OF THE DRAWINGS

[0171] Figure 1 shows a schematic cross-sectional view of a pumping unit (60) according to the first aspect of the disclosure. The pumping unit (60) comprises a liquid inlet (61) fluidically connected to a reservoir (40) for holding the liquid (L) via tubing (31). The liquid inlet (61) of pumping unit (60) is provided in the form of an opening on the most upstream end of pumping unit (60) which is fluidically connected to the reservoir (40) for holding the liquid (L), through which the liquid (L) can enter into the pumping unit (60) from the reservoir (40).

[0172] Furthermore, the shown pumping unit (60) comprises a liquid outlet (62) through which the liquid (L) can exit the pumping unit (60). The liquid outlet (62) of pumping unit (60) is provided in the form of an opening on the most downstream end of pumping unit (60) which is fluidically connected to ejection unit (50) as described in further detail below.

[0173] As already described in detail above, the pumping unit (60) a shown in Fig. 1 is adapted to convey and, in some embodiments, to pressurize the liquid (L) in a downstream direction from the liquid inlet (61) to the liquid outlet (62). The present pumping unit (60) is adapted to apply the liquid to the ocular surface (S) of a subject by ejection of the liquid (L) in the form of a liquid stream through the liquid outlet (62) and / or ejection unit (50) towards the ocular surface (S) of the subject as will described in further detail in connection with Fig. 10 below.

[0174] The present pumping unit (60) as shown in Fig. 1 comprises a metering chamber (63) in fluidic connection with the liquid inlet (61) and the liquid outlet (62). In the embodiment shown in Fig. 1, the metering chamber (63) is provided in the form of a hollow space provided by and located within a solid member (69) surrounding the metering chamber (63) wherein the inner surfaces of such member (69) form the boundaries of the metering chamber (63), which preferably has a circular cross- sectional shape. The metering chamber (60) comprises an inlet opening (64) fluidically connected to and located downstream of the liquid inlet (61) of pumping unit (60) for the influx of the liquid (L) into the metering chamber (63). Furthermore, the metering chamber (63) comprises an outlet opening (65) fluidically connected to and located upstream of the liquid outlet (62) of pumping unit (60) for the release of the liquid (L) from the metering chamber (63).

[0175] Pumping unit (60) further comprises a piston (66) reciprocally movable within the metering chamber (63) and being adapted to suck the liquid (L) from the liquid inlet (61) or, more specifically from reservoir (40) via liquid inlet (61), into the metering chamber (63) by a repulsive movement of the piston (66) and to convey the liquid (L) towards the liquid outlet (62) by a propulsive movement of piston (66). In the situation shown in Fig. 1, piston (66) is in its maximally or close to its maximally introduced position (i.e. after a full propulsive movement), thereby reducing the volume of the metering chamber (63) to a minimum.

[0176] The pumping unit (60) of Fig. 1 further comprises an inlet check valve (67) located downstream of the liquid inlet (61) and upstream of the inlet opening (64) of the metering chamber (63) or, in other words, between the liquid inlet (61) and the inlet opening (64) of the metering chamber (63) thereby fluidically connecting the liquid inlet (61) of the pumping unit (60) with the inlet opening (64) of the metering chamber (63) and being transmissive for the liquid (L) in the downstream direction.

[0177] Furthermore, the pumping unit (60) shown in Fig. 1 comprises an outlet checkvalve (68) located downstream of the outlet opening (65) of the metering chamber (63) and upstream of the liquid outlet (62) thereby fluidically connecting the liquid outlet

[0178] (65) of the metering chamber (63) with the outlet opening (62) of the pumping unit (60) and being transmissive for the liquid (L) in the downstream direction.

[0179] The metering chamber (63) as shown in Fig. 1 has a longitudinal cylindrical shape, a first end (63a) and a second end (63b) located opposite of the first end (63a). Piston

[0180] (66) enters the metering chamber (63) via the first end (63a) and the inlet opening (64) and the outlet opening (65) of the metering chamber (63) are located adjacent to the second end (63b) of the metering chamber (63). In the embodiment shown in Fig. 1, pumping unit (60) comprises a drive unit (70) for driving the reciprocal movement of the piston (66) within the metering chamber (63). The drive unit (70) as shown in Fig. 1 comprises a mechanical energy storage device (71) adapted for the storage and release of energy, here in the form of a compressible (spiral) spring. In the situation depicted in Fig. 1 in which the piston (66) is in its maximum introduced position, the mechanical energy storage device (71), here in the form of a spring, is in its maximally relaxed condition. The drive unit (70) as shown in Fig. 1 further comprises an actuator (72) for tensioning the mechanical energy storage device (71), here in the form of a handle or lever to manually tension the mechanical energy storage device (71).

[0181] The pumping unit (60) or, more specifically, the drive unit (70) as shown in Fig. 1 comprises a mechanical limiting element (75) provided and positioned to constrain or limit the reciprocal movement, specifically the repulsive movement of the piston (66) within the metering chamber (63). Of course, further limiting elements may also be present, for example to limit the propulsive movement of piston (66).

[0182] Furthermore, the shown pumping unit (60), specifically the drive unit (70) comprises a trigger mechanism (76), here in a form comprising a hook as a mechanical means for releasably holding the mechanical energy storage device (71) in a tensioned state and for releasing such mechanical energy storage device (71) from such tensioned state to a non-tensioned state.

[0183] The reservoir (40) as shown in the exemplary embodiment of Fig. 1 is in the form of a container, specifically a dimensionally stable container with a gas exchange and ventilation opening (41). Of course, alternative designs of such reservoir (40) as well as of the other functional elements depicted are possible as described in detail above.

[0184] Figure 2 shows the same pumping unit (60) as depicted in Fig. 1, however, in a status in which piston (66) is in its maximally or close to its maximally retracted position (i.e. after a full repulsive movement), thereby enlarging the volume of the metering chamber (63) to a maximum. In the situation depicted in Fig. 2 in which the piston (66) is in its maximum retracted position, the mechanical energy storage device (71), here in the form of a spring, is in its maximally tensioned condition and is held in position by trigger mechanism (76). Figure 3 shows a pumping unit (60) corresponding to the one depicted in Figs. 1 and 2 with the only difference that drive unit (70) or more specifically, actuator (72) interacts with a motor (73) for driving spindle (74) and to tension (or to relax) mechanical energy storage device (71) via actuator (72).

[0185] Figure 4 shows the same embodiment of pumping unit (60) as depicted in Fig. 3, however, in a status in which piston (66) is in its maximally or close to its maximally retracted position (i.e. after a full repulsive movement) with the volume of the metering chamber (63) at a maximum and mechanical energy storage device (71) in its maximally tensioned condition.

[0186] Figure 5 shows a schematic sideview representation of a system (200) comprising a modular application device (10) according to the second aspect of the present disclosure comprising a base module (20) and a replaceable module (30). In the embodiment shown, the replaceable module is not connected to the base module (20) but in a disconnected or dissembled state. The replaceable module (30) comprises a reservoir (40) holding a liquid (L) to be applied to an ocular surface of a subject by ejection of the liquid (L) from the device (10) towards the ocular surface.

[0187] Furthermore, the replaceable module comprises an ejection unit (50). Although shown in a disconnected state, replaceable module (30) is adapted to be releasably connected to base module (20) (thereby forming a connected state of the device).

[0188] In the embodiment as shown in Fig. 5, base module (20) is coupled to a portable electronic device (1) which may, for example be a tablet computer or smartphone and which comprises a screen (2) for the graphical display of information. In the embodiment of Fig. 5, the screen (2) of the portable electronic device (1) is located on the surface of the portable electronic device (1) facing the base module (20) of device (10) in the coupled state of the device, i.e. in the state in which at least the base module (20) of modular device (10) is coupled to the portable electronic device (1). The portable electronic device (1) may be releasably coupled to the (base module (20) of the) device (10) via a coupling unit (90) which may be comprised by the base module (20) of device (10). In the embodiment shown in Fig. 5, coupling unit (90) comprises coupling means (91), for example in the form of a plug connector such as a USB or Lightning® plug connector to be releasably plugged into the corresponding (female) connector of the portable electronic device (1).

[0189] As also shown in Fig. 5, device (10) furthermore comprises a pumping unit (60), specifically a pumping unit according to the first aspect of the disclosure, in fluid connection (not shown) with the reservoir (40) and the ejection unit (50) and being adapted to convey the liquid (L) from the reservoir (40) to the ejection unit (50) (in the connected state). As shown in Fig. 5, pumping unit (60) may be comprised by the base module (20) of device (10), however, as shown further below, may also be comprised by replaceable module (30). Device (10) as shown in Fig. 5 furthermore comprises a drive unit (70) for driving the pumping unit (60), a control unit (80) for controlling the ejection of the liquid (L) and a receiving unit (100) for releasably connecting the replaceable module (30) with the base module (20). In the embodiment shown in Fig. 5, the pumping unit (60), the drive unit (70), the control unit (80) and the receiving unit (100) are comprised by the base module (20) of the device (10). It should be noted, however, that especially the pumping unit (60) and / or the drive unit (70) may also be comprised by the replaceable module (30) of the device (10) and that, for example, the receiving unit (100) may be (partially) comprised by both, the base module (20) and the replaceable module (30). In the embodiment shown in Fig. 5, base module (20) of device (10) comprises means for determining the position (21) of the base module (20) or the device (10) relative to the portable electronic device (1), especially in the coupled state. Here, the means for determining the position (21) comprise a stylus that is in contact and interacts with screen (2), preferably a touch-sensitive screen, of portable electronic device (1).

[0190] Fig. 6 depicts the present modular administration device (10) in the connected state in which base module (20) is releasably connected to the replaceable module (30) (via receiving unit (100) (not shown) into which replaceable module (30) is inserted. The base module (20), in this Figure as well, comprises coupling unit (90) with coupling means (91) in the form of a plug as well as means for determining the position (21) of the device (10) relative to the portable electronic device (especially in the coupled state). It should be noted, however, that in this Fig. 6 the device (10) is shown in a state in which it is not coupled to a portable electronic device. In the device (10) as shown in Fig. 6, the base module (20) comprises pumping unit (60), for example pumping unit (60) according to the first aspect of the disclosure, drive unit (70) and control unit (80). Replaceable module (30) comprises reservoir (40) holding the liquid (L) to be applied as a well as ejection unit (50). Ejection unit (50), in this embodiment, is fluidically connected with reservoir (40) via pumping unit (60) and tubing (31) for providing a fluid connection between reservoir (40) and pumping unit (60) as well as from pumping unit (60) to ejection unit (50) through which the liquid (L) may be pumped from reservoir (40) towards ejection unit (50). In this embodiment, accordingly, pumping unit (60) is not comprised by the replaceable module (30) and, accordingly, will not be replaced together with replaceable unit (60) once necessary and, accordingly, can be used repeatedly with a plurality of different replaceable modules (30). It will be understood that in this schematic representation as well, additional functional elements may be present which are necessary for the operation of the device such as electrical, mechanical or fluidic connections or elements which are not shown here.

[0191] Fig. 7 shows an alternative embodiment of the present modular application device (10) according to the second aspect of the disclosure as well in the connected state in which base module (20) is connected to replaceable module (30). In this embodiment, however, pumping unit (60), preferably pumping unit (60) according to the first aspect of the disclosure, comprising pump (61) is comprised by the replaceable module such that all components with potential contact to liquid (L), namely reservoir (40), ejection unit (50), tubing (31) as well as pumping unit (60) with pump (61) are comprised by the replaceable module (30) of the present modular application device (10). In this embodiment, drive unit (70) and control unit (80) are still comprised by base module (20). It should be noted, however, that especially drive unit (70) may also be entirely or partly comprised by the replaceable unit (30).

[0192] Fig. 8 shows an embodiment of modular device (10) in which the base module (20) and the replaceable module (30) are not connected to each other. In this embodiment, replaceable module (30) comprises the reservoir (40) holding liquid (L) as well as the ejection unit (50) in fluidic connection with the reservoir (40) via pumping unit (60) and tubing (32). Furthermore, replaceable module (30) comprises drive unit (70) with a mechanical energy storage device (71), here in the form of a spring. The situation as depicted in Fig. 4 shows the replaceable module (20) before being connected to the base module (20) with the mechanical energy storage device (71) in a non-tensioned state. It should be noted, however, that the mechanical energy storage device (71) may also be comprised by the replaceable module (30) in a tensioned or, in other words, pre-tensioned state.

[0193] Fig. 9 shows another embodiment of the device (10) as depicted in Fig. 8, however, with the mechanical energy storage device (71) comprised by base module (20). In both embodiments of Figs. 8 and 9, however, the mechanical energy storage device (71) may be compressed and, accordingly, tensioned, by connection with or, in other words, insertion of the replaceable module (30) in the base module (20). In this tensioned state the mechanical energy storage device (71) may then provide the required (kinetic) energy to drive the pumping unit (60).

[0194] Fig. 10 depicts an embodiment of the present modular application device (10) in which the replaceable module (30) is not connected to the base module (20). In this embodiment, replaceable module (30) has the same general setup as in Fig. 8 and to avoid repetitions the common elements are not described here again. In addition to these elements, however, replaceable module (30) comprises a nozzle (51) which is comprised by ejection unit (50) and through which liquid (L) may be ejected. Furthermore, replaceable module (30) comprises a closing cap (32) for closing and protecting the ejection unit (30) (when not in use) to avoid or reduce contamination thereof. Replaceable module (30) also comprises connecting means (101) schematically shown in the form of hooks to interact with corresponding structures in the receiving unit (100) of the base module (20) in the connected state and for generating a releasable but tight connection between the modules. It should be noted, however, that these connecting means (101) may have a broad variety of forms that are suitable for generating a stable but releasable mechanical connection between the base module (20) and the replaceable module (30).

[0195] The embodiment of the present application device (10) as depicted in Fig. 10 also comprises a drive unit (70) comprising a mechanical energy storage device (71), here in the exemplary form of a spring comprised by the base unit (20). The drive unit (70) also comprises a priming unit (110) connected to the drive unit mechanical energy storage device (71) and adapted to interact with the replaceable module (30) upon insertion or connecting of the replaceable module (30) into or with the base module (20) to prime or tension the mechanical energy storage device (71).

[0196] Fig. 11 depicts an embodiment of the finally assembled system (200) according to the sixth aspect of the present disclosure comprising the present modular application device (10) according to the second aspect with base module (20) connected to replaceable module (30) and the resulting device (10) in the connected state coupled to portable electronic device (1) with screen (2) via coupling unit (90). Base unit (20) comprises mechanical energy storage device (71) in the exemplary form of a spring which, after insertion of replaceable module (30) into base module (20) and interaction with priming unit (110) is in a compressed or tensioned state. As also shown in the embodiment of Fig. 11, application device (10) comprises a closing cap (32) for protecting ejection unit (50), for example from contamination or mechanical stress, especially in the unused state when the closing cap (32) is closed. In the opened state as depicted in Fig. 7, closing cap (32) allows for liquid (L) to be ejected from nozzle (50) of injection unit (50) towards an ocular surface (S) of a subject, in the exemplary embodiment shown in Fig. 7 towards an ocular surface of a subject.

[0197] List of references:

[0198] 1 Portable electronic device

[0199] 2 Screen

[0200] 10 Application device

[0201] 20 Base module

[0202] 21 Means for determining the position

[0203] 30 Replaceable module

[0204] 31 Tubing

[0205] 32 Closing cap

[0206] 40 Reservoir

[0207] 41 Gas exchange and ventilation opening

[0208] 50 Ejection unit 51 Nozzle

[0209] 60 Pumping unit

[0210] 61 Liquid inlet

[0211] 62 Liquid outlet

[0212] 63 Metering chamber

[0213] 63a First end of metering chamber

[0214] 63b Second end of metering chamber

[0215] 64 Inlet opening

[0216] 65 Outlet opening

[0217] 66 Piston

[0218] 67 Inlet check valve

[0219] 68 Outlet check valve

[0220] 69 Solid member (of metering chamber)

[0221] 70 Drive unit

[0222] 71 Mechanical energy storage device

[0223] 72 Actuator

[0224] 73 Motor

[0225] 74 Spindle

[0226] 75 Mechanical limiting element

[0227] 76 Trigger mechanism

[0228] 80 Control unit

[0229] 90 Coupling unit

[0230] 91 Coupling means

[0231] 100 Receiving unit

[0232] 101 Connecting means

[0233] 110 Priming unit

[0234] 200 System

[0235] L Liquid

[0236] S Ocular surface

Claims

Claims1. A pumping unit (60) for the application of a liquid (L) to an ocular surface (S) of a subject, wherein the pumping unit (60) comprises a liquid inlet (61) fluidically connected or connectable to a reservoir (40) for holding the liquid (L) and a liquid outlet (62) through which the liquid (L) can exit the pumping unit (60), wherein the pumping unit (60) is adapted to convey the liquid (L) in a downstream direction from the liquid inlet (61) to the liquid outlet (62) and to apply the liquid (L) to the ocular surface (S) of the subject by ejection of the liquid (L) in the form of a liquid stream through the liquid outlet (62) towards the ocular surface (S) of the subject, wherein the pumping unit (60) comprises:- a metering chamber (63) in fluidic connection with the liquid inlet (61) and the liquid outlet (62), wherein the metering chamber (63) comprises an inlet opening (64) fluidically connected to and located downstream of the liquid inlet (61) for the influx of the liquid (L) into the metering chamber (63), and an outlet opening (65) fluidically connected to and located upstream of the liquid outlet (62) for the release of the liquid (L) from the metering chamber (63);- a piston (66) reciprocally movable within the metering chamber (63) and being adapted to suck the liquid (L) from the liquid inlet (61) into the metering chamber (63) by a repulsive movement and to convey (propel) the liquid (L) towards the liquid outlet (62) by a propulsive movement;- an inlet checkvalve (67) located downstream of the liquid inlet (61) and upstream of the inlet opening (64) of the metering chamber (63) and being transmissive in the downstream direction; and- an outlet check valve (68) located downstream of the outlet opening (65) of the metering chamber (63) and upstream of the liquid outlet (62) and being transmissive in the downstream direction.

2. The pumping unit (60) according to claim 1, wherein the metering chamber (63) has a longitudinal cylindrical shape, a first end (63a) and a second end (63b) located opposite of the first end (63a), wherein the piston (66) enters the metering chamber (63) via the first end (63a) and wherein the inletopening (64) and the outlet opening (65) of the metering chamber (63) are located adjacent to the second end (63b) of the metering chamber (63).

3. The pumping unit (60) according to claim 1 or 2, wherein the pumping unit (60) further comprises a drive unit (70) for driving the reciprocal movement of the piston (66) within the metering chamber (63).

4. The pumping unit (60) according to claim 3, wherein the drive unit (70) comprises a mechanical energy storage device (71).

5. The pumping unit (60) according to claim 4, wherein the mechanical energy storage device (71) comprises a spring.

6. The pumping unit (60) according to any one of claims 3 to 5, wherein the drive unit (71) comprises an actuator (72) for tensioning the mechanical energy storage device (71).

7. The pumping unit (60) according to claim 6, wherein the actuator (72) comprises an (electrical) motor (73) and a spindle (74).

8. The pumping unit (60) according to any one of the preceding claims, wherein the liquid (L) is an aqueous liquid or liquid composition comprising at least one of an ophthalmic excipient and an ophthalmic active pharmaceutical ingredient.

9. The pumping unit (60) according to any one of the preceding claims, wherein the pumping unit (60) is adapted to convey the liquid at a flow rate of from about 2 mL / min to about 75 mL / min, or from about 2.5 mL / min to about 50 mL / min or to about 60 mL / min, or from about 3 mL / min to about 30 mL / min or to about 40 mL / min.

10. The pumping unit (60) according to any one of the preceding embodiments, wherein the pumping unit (60) is adapted to convey the liquid (L) at a pressure of from about 100 mbar or of from about 500 mbar or from about 1000 mbar to about 6000 mbar.

11. A device (10) for the application of a liquid (L) to an ocular surface (S) of a subject, wherein the device is adapted to apply the liquid (L) to the ocular surface (S) by ejection of the liquid (L) in the form of a liquid stream, whereinthe device (10) comprises a pumping unit (60) according to any one of claims1 to 10.

12. The device (10) according to claim 11, wherein the device (10) is a modular device adapted to be releasably coupled to a portable electronic device (1) and wherein the device (10) comprises a base module (20) and a replaceable module, wherein the replaceable module (30) is adapted to be releasably connected to the base module (20), the device (10) comprising a reservoir (40) for holding the liquid (L), an ejection unit (50) for the ejection of the liquid (L), the pumping unit (60) according to any one of claims 1 to 10 in fluid connection with the reservoir (40) and the ejection unit (50) and being adapted to convey the liquid (L) from the reservoir (40) to the ejection unit [50), a drive unit (70) for driving the pumping unit (60), a control unit (80) for controlling the ejection of the liquid (L), a coupling unit (90) for releasably coupling the device (10) to the portable electronic device (1), and a receiving unit (100) for releasably connecting the replaceable module (30) with the base module (20).

13. The device (10) according to claim 12, wherein the replaceable module (30) of the device (10) comprises the reservoir (40) and the ejection unit (50).

14. The device (10) according to any one of claims 11 to 13, wherein the replaceable module (30) comprises the pumping unit (60).

15. A system (200) for the (contactless) application of a liquid (L) to an ocular surface (S) of a subject by ejection of the liquid (L) from an application device (10) towards the ocular surface (S), wherein the system (200) comprises: a) the device (10) according to any one of claims 11 to 14, and b) a portable electronic device (1).

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