WO2014118585A2

WO2014118585A2 - Dispensing electrically charged liquids

Info

Publication number: WO2014118585A2
Application number: PCT/GB2014/050315
Authority: WO
Inventors: Lukasz GROSZKOWSKI; Hua Ye; Pierre Alexis MOUTHUY
Original assignee: Isis Innovation Limited
Priority date: 2013-02-04
Filing date: 2014-02-04
Publication date: 2014-08-07
Also published as: GB201301941D0; WO2014118585A3

Abstract

A cordless liquid dispensing apparatus (100) for hand held use comprises a mount (116) for a reservoir of liquid (112), an electrically driven pump (106) arranged to deliver liquid from the reservoir (112) to a discharge tip (120) at a liquid delivery rate, and a high voltage power source (104) arranged to charge the liquid at the discharge tip (120). A microcontroller is arranged to control the pump speed (106), so as to adjust a non-zero value of the liquid delivery rate.

Description

Dispensing electrically charged liquids The present invention relates to apparatus for dispensing electrically charged liquid(s), e.g. electrospraying an aerosol of liquid droplets or electrospinning fibres from a liquid, and in particular to cordless apparatus for handheld use.

When a charged liquid is emitted through a discharge tip, the electrical field establishes waves along the surface of the liquid that create a jet. The jet may either break up into liquid droplets which are radially dispersed due to Coulomb repulsion to form a fine aerosol (i.e.

electrospraying), or the jet may convey the liquid so as to form fibres (i.e. electrospinning). Electrospun fibres are typically formed by applying a high voltage to a polymer solution as it is discharged from a nozzle. The difference between electrospinning and electrospraying is determined by the interplay between the surface tension and the viscosity of the solution. If the viscosity is high, entanglements between polymer chains prevent a break-up into droplets due to surface tension and cause the liquid solution to remain as a jet that will later become solidified fibres due to solvent evaporation.

Electrospinning has become a widespread method of producing very small polymer fibres, e.g. nanofibres, for a range of applications in many different areas such as filtration, protective materials, electrical and optical applications, sensors, environment e.g. gas/water filters, etc. In the biomedical field, electrospinning can also be used to produce scaffolds for tissue engineering and drug delivery vehicles. Drugs ranging from antibiotics and anti-cancer agents to proteins, DNA, and RNA can be incorporated into electrospun scaffolds. Suspensions containing living cells have even been electrospun successfully.

The main components found in a standard electrospinning setup are a high voltage DC power supply (typically 5 to 50 kV) connected to a nozzle (also known as a spinneret) and a pump or header tank to feed liquid to the nozzle. The fibres spun out of the nozzle are collected on a grounded surface.

A standard electrospinning apparatus is designed for large-scale industrial production or bench top use and is therefore not well suited for depositing fibres directly onto a site of interest in situ, for example if it is desired to deposit biologically active nanofibres onto a site belonging to a living specimen. There have been some attempts to design a portable apparatus for dispensing charged liquids that is small and/or light enough for handheld use. US 6,753,454 discloses an electrospinning apparatus that may be small enough to be portable for treatment of wounds. The device houses a power source and batteries together with a liquid reservoir to feed the electrospinning liquid to a discharge tip under gravity. US 6,252,129 also suggests a portable version of a liquid dispensing device with an onboard voltage source and liquid reservoir. WO 2010/059127 discloses a portable device in the shape of a gun using batteries as a power supply and a battery-powered or manually pressured pump to transfer polymer solution from an internal reservoir to an outlet. However such devices may suffer from the problem that the liquid dispensing conditions, e.g. liquid flow rate and/or voltage, can not readily be controlled in the same manner as is expected from a larger bench top apparatus, especially for

electrospinning applications.

It is an aim of the present invention to provide an improved apparatus for dispensing electrically charged liquid(s) that is portable.

According to a first aspect of the present invention there is provided a cordless liquid dispensing apparatus for handheld use comprising: a mount for a reservoir of liquid; an electrically driven pump arranged to deliver liquid from the reservoir to a discharge tip at a liquid delivery rate; a high voltage power source arranged to charge the liquid at the discharge tip; and a microcontroller arranged to control the pump, and optionally the high voltage power source; wherein the microcontroller is arranged to adjust a non-zero value of the liquid delivery rate.

Firstly, it will be appreciated that such a handheld apparatus combines the benefits of an onboard power source with a microcontroller that can be used to adjust the liquid delivery rate e.g. during use, and optionally controlling the voltage applied at the discharge tip too. This increases the range of applications of the device as the liquid delivery rate can be varied to suit various different liquids, which can be particularly important when electrospinning fibres. It has been recognised that previous proposals for a portable liquid dispensing apparatus have the drawback that the liquid delivery rate is not controllable, especially when relying on a gravity feed, but also when a pump is used to provide a constant or steady flow rate. The present invention is unique in terms of using a microcontroller to adjust the value of the liquid delivery rate rather than simply turning a pump on and off. Furthermore it is advantageous to combine electronic control of the liquid delivery rate with electronic control of the voltage source. A user of such apparatus can therefore adjust the main liquid dispensing parameters so as to more precisely control the production of an aerosol or fibres from a particular liquid.

The Applicant has realised that it is not straightforward to integrate a microcontroller into a cordless apparatus that has a pump connected to a reservoir of liquid and a high voltage source arranged to charge the liquid, especially one that preferably allows the reservoir to be replaced or replenished e.g. between uses. Previous attempts to design a portable apparatus have kept the number and complexity of components housed in the device to a minimum, for example choosing a simple analogue control circuit based on resistor-capacitor networks and/or potential dividers to adjust the voltage supplied. Replenishment of the liquid may require disconnection of the pump and/or high voltage power source, and this is further complicated by the presence of a microcontroller also requiring connection to an onboard power supply and to the component(s) that it controls. The inventors have devised a particularly practical solution that uses a modular construction.

In one set of embodiments, preferably the cordless apparatus comprises a first compartment that is physically separable from a second compartment, the first compartment preferably housing (at least) the microcontroller, the high voltage power source and the pump and the second compartment preferably housing (at least) the mount for the liquid reservoir.

Advantageously, the second compartment can be separated from the first compartment to allow a user to mount a reservoir of liquid therein or to refill a reservoir already mounted therein.

In another set of embodiments, preferably the cordless apparatus comprises a first compartment housing (at least) the microcontroller, the high voltage power source and the pump, and a second compartment housing (at least) the mount for the liquid reservoir, wherein the second compartment is physically accessible independently of the first compartment.

Advantageously, a user can access the second compartment to mount, remove or refill a liquid reservoir without coming into contact with the electrical components in the first compartment. The second compartment may include a removable cover to provide for access. The first compartment may be separated from the second compartment by a physical barrier that prevents a user e.g. human fingers from reaching inside. Accordingly the first compartment may be substantially closed.

In both sets of embodiments, the liquid may therefore be replenished without disturbing the microcontroller and its connection to the high voltage power source and/or the pump in the first compartment. In this way the integrity of the control electronics can be protected while enabling the apparatus to be re-used, potentially with one or more different liquids. If the liquid in the reservoir is changed than a user can take advantage of the microcontroller to adjust the voltage and/or liquid delivery rate accordingly.

A reservoir of liquid may be the only component mounted in the second compartment, e.g. with the discharge tip provided in the first compartment for ease of connection to the high voltage power source. The second compartment may simply provide a mount for one or more reservoirs, for example interchangeable reservoirs or liquid cartridges. However this would require a liquid delivery connection from the second compartment to the first compartment, and it could be difficult to ensure a liquid-tight path if the connection is to be opened and closed when the compartments are physically separated. A permanent liquid delivery connection between the compartments would prevent them from being entirely separable from one another. While it is envisaged that the compartments could be partially separated e.g. with a hinged connection, in embodiments where the compartments are physically separable it is preferable that the compartments are entirely separable from one another (i.e. they can be physically separated without any mechanical connection between them). In order to avoid the problems of providing liquid delivery between the physically separable compartments, it is therefore preferred that liquid is arranged to be delivered from the reservoir to a discharge tip in the second compartment. This may also be preferable in embodiments where the second compartment is physically accessible independently of the first compartment, for example with a physical barrier therebetween. The second compartment may therefore keep the liquid reservoir and its delivery separate from the microcontroller and electrical components in the first compartment. Advantageously the components in the first compartment are not disturbed when the second compartment is removed or accessed so as to access the mount for a liquid reservoir.

This is considered novel and inventive in its own right, and thus when viewed from a further aspect the present invention provides a cordless liquid dispensing apparatus for handheld use comprising a first compartment that is physically separable from a second compartment, the second compartment housing a mount for a reservoir of liquid and a discharge tip for the liquid, and the first compartment housing at least an electrically driven part of a pump arranged to deliver liquid from the reservoir to the discharge tip and a high voltage power source arranged to charge the liquid at the discharge tip via an electrical connection between the first and second compartments.

It has been recognised that it may not always be necessary for the two compartments to be physically separable, as long as the mount for the liquid reservoir is physically accessible without a user coming into contact with the electrical components housed in the first

compartment. Thus when viewed from a yet further aspect the present invention provides a cordless liquid dispensing apparatus for handheld use comprising a first compartment and a second compartment that is physically accessible independently of the first compartment, the second compartment housing a mount for a reservoir of liquid and a discharge tip for the liquid, and the first compartment housing at least an electrically driven part of a pump arranged to deliver liquid from the reservoir to the discharge tip and a high voltage power source arranged to charge the liquid at the discharge tip via an electrical connection between the first and second compartments.

An electrically driven pump has benefits over a manually operable pump or gravity feed delivery as it means that the delivery rate of liquid can be more precisely controlled. It will be appreciated that it seems counter-intuitive to house any part of the pump in the first compartment while the liquid reservoir and discharge tip are housed in the second compartment. However the inventors have recognised that there are benefits to keeping the electrical components that rarely need to be accessed (i.e. the high voltage power source and at least the electrically driven part of the pump) in one compartment separate from the other compartment that may be accessed regularly e.g. to replace or refill the liquid reservoir and/or to unblock or clean the discharge tip. It may be preferable for the first compartment to be substantially closed, and even substantially sealed, while the second compartment is preferably open e.g. for ease of access. As is mentioned above, it is preferable that the first and second compartments are not just partially separable, e.g. with a hinged connection, but fully separable such that there is no mechanical connection between them (although an electrical connection may remain in some embodiments).

While the electrically driven part of the pump is housed in the first compartment, the pump must also be able to act on the liquid provided by a reservoir mounted in the second

compartment. In a preferred set of embodiments a moving part of the pump is arranged to extend between the first and second compartments i.e. so as to interact with the reservoir when the compartments are connected together. The pump could, for example, comprise an electrically driven diaphragm or a piezoelectric actuator. Preferably the pump comprises an electrically driven motor housed in the first compartment and a mechanical actuator that extends into the second compartment. The mechanical actuator could be a rotary actuator e.g. a cam or a linear actuator e.g. a ram. The mechanical actuator is preferably arranged to act on the reservoir of liquid. The reservoir may take the form of a deformable chamber, for example a collapsible bag.

In a preferred set of embodiments the reservoir is provided by a syringe and the mechanical actuator, preferably a linear actuator, is arranged to act on a piston of the syringe.

This has been found to be an ideal design as the linear actuator can be arranged to pass through a relatively small aperture in the first compartment while it remains substantially closed. The linear actuator can preferably be retracted when the two compartments are separated to allow access to the reservoir of liquid. The range of movement and speed of a linear actuator can be electronically controlled so that the liquid delivery rate can be accurately controlled by the microprocessor. It is preferable for the microcontroller to be housed in the first compartment and arranged to control the mechanical actuator so as to adjust a non-zero value of the liquid delivery rate. The combination of a linear actuator with a syringe as the liquid reservoir effectively results in a syringe pump - which has already been proven to be suitable for delivering liquids at the extremely low rates typically required for electrospinning e.g. in the range of 0.1 -10 ml/h.

However it should be noted that syringe pumps have not previously been housed in a cordless apparatus for handheld use and combined with microprocessor control of the syringe piston, hence the combination of a micro linear actuator with a small syringe (e.g. 1 -5 ml) and electronic control of the syringe piston results in a novel system that is more compact and reliable than existing designs (which may e.g. rely on mechanical control of the piston). Pre-f illed syringes can also provide a convenient way of exchanging the liquid reservoir.

It will be appreciated that an electrical connection is required between the high voltage power source in the first compartment and the discharge tip in the second compartment. This electrical connection may be a permanent one so as to ensure that there is no leakage of the high voltage, both for safety reasons and to guarantee the desired voltage is applied to the discharge tip. The electrical connection could take the form of a flexible cable, for example, that does not unduly hinder physical separation of the two compartments or physical access to the second compartment. Such an electrical cable could run through the second compartment, from the high voltage power source in the first compartment, to reach the discharge tip. However such a cable may need to be flexible or extendable to enable physical separation of the compartments.

In embodiments where the mount in the second compartment is physically accessible, a user may come into contact with the high voltage electrical cable. Thus in a preferred set of embodiments an electrical cable extends from the high voltage power source in the first compartment to the discharge tip while bypassing the second compartment. This makes the apparatus safer for handheld use. For example, the electrical cable may be arranged to run along an outer surface e.g. underside of the second compartment. This may be facilitated by splitting the first compartment into two separate compartments, so that the first compartment houses the electrically driven part of the pump and a third compartment houses the high voltage power source. The first and second compartments may be aligned to enable a mechanical actuator to extend therebetween, while the third compartment may be physically offset from the second compartment. The electrical cable may then conveniently run out of the third

compartment and along the outside of the second compartment to reach the discharge tip.

In other embodiments, where the first and second compartments are physically separable, it is preferable for the electrical connection to also be separable e.g. a separable electrical connector (plug/socket). Inductive coupling or other wireless connections may be considered, but are unlikely to be suitable for transmitting a high voltage, in particular from a high voltage DC power source.

It is an advantage of the electrically driven part of the pump being housed in the first compartment that it can share a common power supply, such as a battery pack, with the high voltage power source - as is described in more detail below. The liquid delivery rate to be provided by the pump and/or the high voltage to be supplied to the discharge tip may be preset. This could take place during manufacture or if the apparatus is connected e.g. docked to a controller when not in use. However it is advantageous that the pump and/or high voltage power source can be electronically controlled in the first compartment. Thus in a preferred set of embodiments a microcontroller is housed in the first compartment and arranged to control the pump and/or high voltage power source. Preferably the microcontroller is arranged to adjust a non-zero value of the liquid delivery rate. As is discussed above in relation to the first aspect of the invention, this can provide a handheld apparatus with enhanced functionality never before found in a portable device. The cordless apparatus may be used to manually access deposition sites not previously accessible with a bench top apparatus, but with the additional benefit of adjustable liquid delivery rate and, optionally a controllable voltage, e.g. to suit different liquids and applications - such as electrospinning of fibres in situ. According to a preferred set of embodiments the cordless liquid dispensing apparatus is an electrospinning apparatus. The cordless apparatus according to either aspect of the present invention may be used to deposit biologically active nanofibres directly onto a site on the body e.g. "skin printing" or to form a patch at the site of a wound rather than applying a pre-formed fibrous patch. This can not only offer better adhesion of the fibrous patch, but also help to preserve the activity of the biological agents carried by the liquid for as long as possible by allowing storage in optimum conditions before applying the liquid to the site as needed. The device may permit the use of more fragile materials such as pure collagen and/or coating thinner layers of bioactive materials than would be possible when pre-forming a fibrous patch to be transferred to a wound site. Such direct "printing" of electrospun fibres and fibrous patches onto a site may promote faster tissue repair and minimise scar formation. In another example, such apparatus may be used to enable in situ repair of nanofibre webs such as gas or water filters. In another example, the device might be used to deliver a charged liquid to a moveable e.g.

automated print head.

The cordless apparatus may find further application(s) in depositing fibres for the manufacture of materials in the textile industry or for the treatment of various materials. Coating a surface (plastic, textile, wood, paper, metal, ceramic, etc.) with fibres is generally called flocking. Rather than spraying pre-formed fibres onto an adhesive surface, the apparatus could be used to directly deposit electrospun fibres onto a surface that has been treated with a conductive adhesive. Electrostatic flocking is already used extensively in the automotive industry for coating vehicle interiors. Other potential applications include a flocked finish for textiles, jewellery, furniture, and packaging. As before, the liquid delivery rate being controlled by a microcontroller means that the fibre deposition process can be tailored during use to a particular liquid and/or application of the electrospun fibres.

A further advantage of a handheld apparatus is that a user can control the distance between the discharge tip and the deposition site. If the apparatus is used for electrospinning, then relatively large changes in this distance can be used to control the fibre diameter. The closer the discharge tip is to the deposition site, the less the jet of charged liquid can stretch and the larger the fibre diameter. If the distance is increased then the jet is stretched further and the fibre diameter is decreased. However it is beneficial that most electrospun fibres are not overly sensitive to separation distance so that relatively small variations, e.g. of the order of several centimetres, typically do not significantly affect fibre diameter. This means that a particular fibre diameter will be reproducible as long as a user holds the apparatus so that the discharge tip is approximately the same distance from a deposition site. The cordless apparatus is preferably suitable for delivering charged liquid, droplets and/or fibres to a collection surface that is spaced at a relatively large distance from the discharge tip, e.g. of the order of 1 -100 cm rather than 1 - 100 mm. For example, the discharge tip of the apparatus may be held at distance of 1 -30 cm, preferably 4-30 cm, from a collection surface.

There will now be described various preferred features that are applicable to

embodiments according to any of the foregoing aspects of the invention.

For the apparatus to be cordless the high voltage power source preferably comprises an onboard power supply, in particular a DC power supply. The power supply may generate its own electrical power e.g. using one or more solar cells and/or it may comprise a store of electrical power e.g. one or more batteries. As it is desirable for the apparatus to have a constant and reliable reservoir of electrical power in use, the high voltage power source preferably comprises a battery pack as a power supply. Since a compact battery pack is unlikely to be able to supply the high voltages required in particular for electrospinning (typically 5-20 kV), it is preferable that the high voltage power source further comprises a high voltage converter. Very compact high voltage converters, e.g. having dimensions of less than 10 cm, are available that can convert input voltages of 5-20 V to high voltages of 5-12 kV. A suitable high voltage converter is the F series from Emco (www.emcohiqhvoltaqe.com). It is preferable that the battery pack is not only connected to the high voltage converter to provide the high voltage power source, but also connected to the pump (or electrically driven part thereof). Where a microcontroller is provided, it may have its own power supply, but preferably it is connected to the same battery pack as the high voltage power source and/or pump.

Where the apparatus has a modular design, the battery pack may be housed in either of the compartments. In a set of embodiments the battery pack may be housed in the first compartment so as to be co-located with the converter of the high voltage power source and directly connected to the electrically driven part of the pump (and to a microcontroller, where provided). This means that a single high voltage electrical connection can be made with the second compartment e.g. connecting the high voltage power source to the discharge tip. It may be convenient for the first compartment to include a charging port for the battery pack to be recharged from the mains.

In another set of embodiments the battery pack may be housed in the second

compartment so as to be more easily accessible, either for recharging from the mains supply or for removing and replacing the battery pack. While this requires an additional electrical connection to be made between the battery pack and the components e.g. high voltage converter in the first compartment, this can be readily achieved without affecting the separability of the two compartments or accessibility of the second compartment. The inventors have found that a particularly compact arrangement houses the battery pack in the second compartment in a cylindrical geometry surrounding the mount for a reservoir of electrospinning liquid (such as a syringe, for example). In such embodiments the first compartment may house the rarely accessed components - high voltage converter, electrically driven part of the pump (e.g. linear actuator) and microcontroller - while the second compartment houses the liquid reservoir and battery pack that may require more frequent access.

Where a microcontroller is arranged to control the pump, and optionally the high voltage power source, it is preferably provided on the same printed circuit board (PCB) as control circuit(s) for the pump (and optionally for the high voltage power source). It is preferable for the microcontroller to be connected to a user interface (Ul) providing means for a user to adjust the voltage supplied to the discharge tip and/or the liquid delivery rate of the pump. The user interface may include a display e.g. LCD. The user interface may be arranged economically to facilitate adjustment of the liquid dispensing parameters during handheld use. In a set of embodiments it is preferable for the microcontroller to be arranged to control the high voltage power source as well as the liquid delivery rate.

As is mentioned above, where the apparatus is used for electrospinning the pump is preferably arranged to deliver liquid from the reservoir at rates of 0.1 to 10 ml/hour, preferably between 0.1 ml/h and 5 ml/h, e.g. around 1 ml/h. The liquid jet may break up into separate fibrils or form fibres that extend to the nearest grounded surface. Of course it is not necessary for the collection surface (or electrode) to be grounded, as long as there is a negative potential difference. For example, instead of the liquid being charged to +10 kV and then collected at ground, the liquid may be charged to +5 kV and the collection surface held at -5 kV, or vice versa. Often the most practical choice is to ground the collection surface (or electrode).

Where the apparatus is used for electrospraying, the liquid is likely to be much less viscous and it is typical for the liquid delivery rate to be a least an order of magnitude greater, often at least two orders of magnitude greater, e.g. the liquid delivery rate may be at least 1000 ml/hour (i.e. 1 l/hr) and up to 20 l/hr, 25 l/hr or 30 l/hr. The liquid delivery rate may be chosen depending on the liquid and any solvent it may include. It will be appreciated that the sprayed droplets may not remain liquid for but can solidify so as to be at least partially solid or gel-like, for example due to solvent evaporation. The apparatus may therefore be used to spray liquid droplets and/or solid droplets or particles.

The mount may be arranged to receive any suitable reservoir of liquid, for example a cartridge, collapsible bag, syringe, etc. containing the liquid. The mount preferably allows a reservoir of liquid to be removed and replaced e.g. having been refilled or exchanged for a different liquid. The mount may of course receive more than one reservoir of liquid. The mount may be arranged such that liquids from different reservoirs can be delivered to the discharge tip at the same time (e.g. a coaxial flow) or sequentially.

The high voltage power source can be arranged to charge the liquid at the discharge tip by applying the high voltage to the discharge tip itself e.g. the discharge tip may comprise a metallic needle or spinneret. Alternatively the high voltage may be applied to the liquid itself (if the liquid is sufficiently conductive) e.g. in a charging head just upstream of the discharge tip. The charging head may be made of brass to ensure good electrical conductivity. The discharge tip may then be formed of an electrically insulating material so that there is less risk of a user receiving an electric shock. Whether or not the discharge tip is conductive, in a set of embodiment it is preferably shielded for increased safety and also to help direct the emerging jet. For example, a conical lip or shielding cone may surround the discharge tip to control the trajectory of the liquid jet as it travels through the air. The discharge tip may be made of any suitable material e.g. metal, glass, ceramic or plastics material (e.g. PTFE for ease of cleaning).

The high voltage power source may be arranged to apply a voltage of at least 1 kV and typically up to 5 kV, and further up to 10 kV, 15 kV or 20 kV for electrospraying micro- and nano- particles and electrospinning applications, or even up to about 50 kV for at least some electrospinning applications. It will be appreciated that the liquid may be charged to a higher voltage for electrospinning than for electrospraying as the liquid is likely to be more viscous. For safety purposes, the discharge tip and any charging head, as well as any other conductive parts in contact with the charged liquid, are preferably earthed or shielded so as to avoid the risk of electric shock. In such embodiments the apparatus may include an earthing cable that can be connected to a surface onto which it is desired to deposit electrosprayed particles (e.g. liquid droplets) or electrospun fibres. In other words, the apparatus may provide an earth cable to connect to a collection surface for fibres or particles/droplets emitted from the discharge tip. Of course the deposition site could instead be earthed through external means.

The charged liquid emerging from the discharge tip forms a jet and if it does not break up into electrosprayed droplets then the solidifying jet continues across the air gap to a grounded (or lower potential) surface where electrospun fibres are deposited. As the cordless apparatus is designed to be handheld, a user can easily move the apparatus so as to position the discharge tip where desired and deposit electrospun fibres onto a surface of interest, for example a wound site on a living body. However, in at least some embodiments it may be preferable to access sites that are hard to reach even using a cordless electrospinning apparatus. In one set of embodiments the apparatus may further comprise a liquid delivery device that has its own second discharge tip and an elongated channel for delivering charged liquid from the first discharge tip of the apparatus to the second discharge tip, wherein at least a portion of the elongated channel has an electrically insulating sheath to enable manual manipulation of the device. The elongated channel is preferably at least partially flexible to aid with manual manipulation. In particular, the elongated channel may be formed from flexible tubing. The flexible tubing may be made from a plastics material such as PTFE (e.g. Teflon) or alternatives such as PFA, FEP or PVDF. Such flexible tubing can be safely used to deliver a wide range of charged liquids from the cordless apparatus to a remote discharge tip that can more easily be manoeuvred to a particular location e.g. for in situ repair using nanofibres. For example, the cordless apparatus may be held in one hand while the liquid delivery device may be manipulated using the other hand. Such a device is described in more detail in the applicant's co-pending application(s) claiming priority from GB1301939.3.

The apparatus can be used with any suitable liquid such as water, a liquid solution (aqueous solution, alcohol solution, etc.), a particulate suspension in liquid, or even a liquid or molten metal. For example, electrospraying may be used for micro- or nano-particle production or the production of fine metal powder from liquid metal. The apparatus may be used to spray an aerosol of a printing liquid. In a set of embodiments particularly suitable for electrospinning, the liquid is a polymer solution, sol-gel, particulate suspension, emulsion or melt. A polymer solution may include one or more polymers, one or more solvents, and optionally one or more crosslinking compounds. Polymers suitable for forming an electrospinning liquid include, for example, polyamides, polyimides, polyesters, polyacrylates, polysulfones, polycarbamides, polyolefins, polyurethanes, fluoropolymers, collagen, cellulose and cellulose acetate. Polymer mixtures, blends, copolymers and terpolymers may be used. Any suitable solvent may be used, either organic or inorganic. The solvent may be selected depending on the polymer(s) used. In a set of embodiments the solvent is an aqueous solvent so that evaporation poses less of a hazard to a user of the handheld apparatus. The solvent may be water, or an aqueous solution of a water-miscible solvent such as acetic acid, hydrochloric acid, acetone, tetrahydrofuran, ethanol or another alcohol.

For applications such as wound treatment using electrospun fibres, the liquid is preferably biologically compatible. In a set of embodiments the liquid comprises a polymer solution made from one or more polymeric materials suitable for electrospinning fibres for biological use. Such materials may include, for example, those inert polymeric substances that are absorbable and/or biodegradable, that react well with selected organic or aqueous solvents, or that dry quickly. Essentially any organic or aqueous soluble polymer or any dispersions of such polymer with a soluble or insoluble additive suitable for topical therapeutic treatment of a wound may be employed. Examples of suitable polymers include, but are not limited to, linear polyethylenimine, cellulose acetate, and other preferably grafted cellulosics, poly(L-lactic acid), polycaprolactone (PCL), polyethyleneoxide, and polyvinylpyrrolidone. In a set of embodiments where the apparatus or delivery device is used to deposit electrospun fibres for wound healing applications, the liquid may comprise: a water-soluble polymer solution of poly(ethylene glycol) (PEG), polyvinyl alcohol) (PVA), or po!y(viny! pyrrolidone) (PVP); or a non-water soluble polymer solution of biodegradable polyesters such as poly(iactic acid) (PLLA), poiy(!actic-co-giycolic acid) (PLGA), or polycaprolactone (PCL).

In a set of embodiments the liquid comprises a polymer solution that uses a solvent which is compatible with the skin or other tissue to be treated with electrospun fibres. Examples of such solvents include water, alcohols, and acetone. Similarly, the types of polymers that are used may be limited to those that are soluble in a skin- or tissue-compatible solvent. Biocompatible polymer/solvent combinations include, for example, poly(ethylenimine)/ethanol, poly(vinylpyrrolidone)/ethanol, polyethylene oxide/water, and poly(2- hydroxymethacrylate)/ethanol+acid.

Furthermore the liquid may contain one or more active components chosen from one or more of the following: pharmaceutical compounds such as analgesics, anesthetics, antiseptics, antibiotics, bactericides or bacteriostats, fungicides, antiparasitics, anti-inflammatory agents, vasodilators, analgesic compounds, thrombogenic compounds or antithrombotics e.g. Dextran, nitric oxide releasing compounds such as sydnonimines; agents such as proteolytic enzymes for debridement; tissue repair-promoting materials such as cytokines or NO-complexes that promote wound healing; growth factors such as fibroblast growth factor (FGF), epithelial growth factor

(EGF), transforming growth factor (TGF); cells; peptides, polypeptides, polysacharrides; insulin; immune suppressants or stimulants; vaccines. Other possible active components are DNA or other genetic matter for gene therapy, surface binding or surface recognising agents such as surface protein A, and nucleic acids. The types of active components that may be added to a particular polymer solution may be limited to those that are soluble in the particular solvent used.

While there is described herein a cordless apparatus for handheld use, it will be appreciated that the apparatus is suitable for handheld use but not limited to handheld use. For example, the apparatus may include a handle to assist a user in lifting, carrying and/or holding the apparatus. At other times the apparatus may rest on a surface or be mounted in position during use. It is an advantage of the cordless functionality that the apparatus can be manually moved and positioned at a desired distance from a collection surface, but once positioned the apparatus does not have to be held by user while liquid is being dispensed.

Some embodiments of the present invention will now be described, by way of example only, and with reference to the accompanying drawings, in which:

Fig. 1 a is an exploded view of a cordless liquid dispensing apparatus for handheld use according to a first embodiment;

Fig. 1 b is a cross-sectional view of the same apparatus;

Fig. 2a is an optical micrograph of nanofibres spun using the cordless apparatus at 6.5 kV and Fig 2b is an optical micrograph of nanofibres spun using a conventional benchtop apparatus at 6.5 kV;

Fig. 2c is an optical micrograph of nanofibres spun using the cordless apparatus at 9.5 kV and Fig 2d is an optical micrograph of nanofibres spun using a conventional benchtop apparatus at 9.5 kV;

Figs 3a and 3b are perspective views of a cordless liquid dispensing apparatus for handheld use according to a second embodiment;

Fig. 4a is a cross-sectional view of the same apparatus and Fig. 4b is an exploded view of the same apparatus; Figs. 5a and 5b are SEM images of biodegradable polyester (PDO) fibres electrospun with a cordless handheld apparatus;

Figs. 6a and 6b are SEM images of biodegradable polyester (PDO) fibres electrospun with a cordless handheld apparatus using different parameters to create a mixture of microfibres and nanofibres;

Figs. 7a to 7d are SEM images of some materials spun or sprayed using a cordless handheld apparatus;

Fig. 8 shows a patch of PDO fibres deposited onto pig skin using a pen-like delivery device connected to the cordless handheld apparatus; and

Fig. 9 shows a patch of PEO fibres deposited onto human skin using a pen-like delivery device connected to the cordless handheld apparatus.

There is seen in Figs. 1 a and 1 b a cordless liquid dispensing apparatus 1 for handheld use. In an upper compartment 2 there is housed a high voltage power source 4 (e.g. Emco F101 ) and a micro linear actuator 6 (e.g. Zaber T-NA08A25-S). A microcontroller for these two components is mounted on a PCB 8 located on top of the upper compartment 2. The PCB 8 is double-sided with a user interface on its top side (e.g. to display cathode voltage and liquid delivery rate) and the microcontroller on its bottom side. The PCB 8 also mounts a power jack for connection to the power supply.

In a lower compartment 10 there is housed a mount 16 for a syringe 12 containing liquid and a battery pack 14 as a power supply. The battery pack 14 comprises two packs of AA batteries (1 .2-1.5 V NiMH rechargeable batteries) each containing 10 batteries in a cylindrical arrangement aligned along the axis of the compartment 10 and surrounding the mount 16. The two packs of batteries are connected in parallel to provide a 12 V DC power supply with a capacity of 4000-5000 mAh. This ensures that the apparatus 1 can be operated continuously for around one hour based on the expected power consumption of the high voltage power source 4 (1.5 A) and the linear actuator 6 (0.35 A). The battery pack 14 is connected to a PCB (not shown) provided either in the top of the lower compartment 10 or in the bottom of the upper compartment 2, which may transform the power supply to provide 5 V to the microcontroller and 12 V to the high voltage power source 4 and linear actuator 6. This PCB may have pins for connecting a power jack from the main PCB 8 and from both the high voltage power source 4 and linear actuator 6.

It can be seen from Fig. 1 b that the ram of the linear actuator 6 extends through an aperture in the bottom of the upper compartment 2. A disc 18 is arranged on the end of the ram to prevent the piston of the syringe 12 from slipping away. This disc 18 has an indentation on its bottom side to locate over the piston of the syringe 12 and a hole on its top side to receive the ram of the linear actuator 6. During use, the linear actuator 6 pushes the disc 18 downwardly to depress the plunger of the syringe 12 and deliver liquid through a discharge needle 20. There is an electrical cable (not shown) running from the needle 20 to the high voltage power source 4. The needle 20 is arranged to protrude through an aperture in the bottom of the lower

compartment 10. A conical lip 22 surrounds the needle 20 to allow the formation of a Taylor cone and to help prevent a user from touching the needle 20. The conical lip 22 is made of an electrically insulating material such as acetal.

The two compartments 2, 10 may be made of a lightweight metallic material such as Dural. Since the main body of the apparatus 1 is conductive, it can be grounded to ensure user safety. However it is also envisaged that the apparatus may instead be made mostly of insulating plastics materials, so as to further reduce its weight. The high voltage supply cable (not shown) extending from the power source 4 to the needle 20 is suitably electrically isolated e.g. with a silicone sheath or the like.

It will be understood that the handheld apparatus 1 is entirely cordless, i.e. it does not require a connection to the mains power supply, as it has the battery pack 14 as an onboard power supply. The choice of miniaturised components and compact design using a

microcontroller on a PCB allows the apparatus 1 to be small enough for handheld use while still providing the functionality of adjusting the high voltage applied and/or the liquid delivery rate.

The apparatus 1 preferably has a modular construction that allows the upper

compartment 2 to be separated from the lower compartment 10. The battery pack 14 may have a separable connection to the electrical components in the upper compartment 2, for example a PCB in the top of the lower compartment 10 may be unplugged from the various power supply jacks when the compartments are separated. If the battery pack is directly connected to the main PCB 8 (e.g. without an intervening PCB) then a simple electrical connector (plug/socket) may be arranged between the two compartments 2, 10. The high voltage supply cable (not shown) extending from the power source 4 to the needle 20 may be flexible enough to allow the two compartments 2, 10 to be physically separated. It is then easy for a user to access the lower compartment 10 to exchange or refill the syringe 12 and/or to replace or recharge the battery pack 14.

There is seen in Figs. 3 and 4 another cordless liquid dispensing apparatus 100 for handheld use. This apparatus 100 includes a dedicated handle 101 rather than a user simply gripping the outside of the housing. The apparatus 100 has a unitary appearance on the outside, but inside it has a modular construction separated into multiple compartments, as will be explained below. In Fig. 3a it can be seen that a removable cover 124 enables a user to access a front compartment 1 10. A discharge needle 120 protrudes through an aperture in the front compartment 1 10. A cone 122 (seem in Fig. 4b) surrounds the needle 120 to prevent a user from touching the charged needle. While gripping the handle 101 , a user can orientate the apparatus 100 so as adjust the angle at which fibres are spun (or an aerosol is sprayed) from the discharge needle 120. In Fig. 3b it can be seen that a rear compartment 102 carries a user interface, which includes an LCD 126 to display the liquid flow rate and/or magnitude of the high voltage supply, a charging port 128, a control dial 130 for the high voltage power source, a control dial 132 for the liquid flow rate, and a high voltage return jack 134. Buttons 136, 138 provide user functions such as start and stop.

From Figs. 4a and 4b it can be seen that the front compartment 1 10 houses a mount 1 16 for a syringe 1 12 containing liquid. The syringe is in fluid connection with the discharge needle 120. The cover 124, which may be hinged or completely removable, is positioned above the mount 1 16 so that a user can easily access the syringe 1 12 to replace the liquid. The front compartment 1 10 is separated from the rear compartment 102 by an internal wall 105. The rear compartment 102 is split into an upper compartment 102a in line with the front compartment 1 10 and a lower compartment 102b. The upper rear compartment 102a houses a linear actuator 106. The ram of the linear actuator 106 extends though an aperture in the internal wall 105 to act on the plunger of the syringe 1 12 in the front compartment 1 10. The lower rear compartment 102b houses a high voltage power source 104 and a battery pack 1 14. Mounted to the back of the rear compartment 102 is a PCB 108 carrying a microcontroller on one side and the user interface on the other. A high voltage electrical cable 140 connected to the power source 104 extends from the lower rear compartment 102b to the discharge needle 120, bypassing the front compartment 1 10.

Operation of the apparatus 100 will now be described. The apparatus 100 is turned on using the high voltage (HV) dial 130. The microcontroller runs through an initialisation sequence, which will retract the linear actuator 106 to its home position. Once initialisation is complete, the apparatus 100 waits in an idle state, displaying the HV voltage on the LCD 126. A user can adjust the voltage and/or the dispensing speed using the dials 130, 132. Once set up is complete then a dispensing cycle can be started by pressing the button 136. The linear actuator 106 will begin to travel forwards, displacing the plunger of the syringe 1 12. The dispensing state may be indicated on the LCD 126 by a character "D" in the bottom right of the display. Pressing the start button 136 will halt the linear actuator 106 and a pause in dispensing is indicated by the absence of a "D" on the LCD 126. Dispensing can be resumed by pressing the start button 136 again. When the linear actuator 106 reaches the limit of its travel, the LCD 126 displays a request to retract the actuator 106. The user can action this by pressing the 'return' button 138. The flow rate can be adjusted during a dispensing cycle using the dial 132.

As the apparatus 100 is cordless, a user can hold or position it at a desired distance from a collection surface. Fibres may be spun directly from the discahrge nozzle 120. Although not seen in the drawings, an pen-like applicator may instead be connected to the nozzle 120, in particular an applicator including a flexible tubing and an electrically insulating sheath enabling a user to manually manipulate the applicator while charged liquid is being dispensed. Example 1

A cordless apparatus substantially as described above was used to perform

electrospinning using polycaprolactone (PCL) dissolved at 8% (%w/v) in HFIP. The same solution was loaded into a benchtop apparatus so as to compare the results. Electrospinning was performed with a cathode voltage (i.e. applied to the discharge needle) of 9.5 kV and 6.5 kV and with a polymer delivery rate of 1 ml/h. In all tests the discharge needle was located 10 cm away from the collector plate (metallic, grounded plate covered with aluminium foil). The fibres deposited on the collector plate were transferred to a glass slide for optical microscopy. Photos of the fibres are shown in Figure 2. All images were taken using 10x ocular with 10x lens (left side) or 40x lens (right side). The images have been scaled to 50% of their height/width, resulting in a magnification of 10x10x0.5 = 50x (left side) or 10x40x0.5 = 200x (right side).

There is seen in Fig. 2a the fibres produced by the handheld apparatus at 6.5 kV and in Fig. 2b the fibres produced by the benchtop apparatus at 6.5 kV. There is seen in Fig. 2c the fibres produced by the handheld apparatus at 9.5 kV and in Fig. 2d the fibres produced by the benchtop apparatus at 9.5 kV. It can be seen that the results for nanofibre generation by the handheld apparatus and the benchtop apparatus are similar. The only difference is that the mesh is slightly thicker for the fibres deposited from the benchtop apparatus, as a result of this apparatus being allowed to operate for longer than the handheld apparatus.

Example 2

A handheld liquid charging apparatus as seen in Figs. 3 and 4 was used to spin fibres from a solution of biodegradable PDO (9% w/v in HFIP; viscosity 1.5-2.2 dl/g) at a voltage of 10 kV and the results are seen in Figs. 5a and 5b. The fibres were collected on a flat surface at a distance of 20 cm from the discharge nozzle and the total duration of spinning was 30 minutes. The liquid dispensing rate was adjusted to 1 ml/h.

Figs. 6a and 6b show the fibres resulting from the same concentration PDO solution and flow rate, but with the electrospinning voltage and distance to the collector being adjusted so as to create a mixture of thicker microfibres and thinner nanofibres. The thicker fibres were generated at a voltage of 10 kV and collected at a distance of about 15 cm. The thinner fibres were generated at a voltage of 13.5 kV and collected at a distance of about 25 cm.

Example 3

The same handheld liquid charging apparatus was used to spin fibres or particles from a number of different polymer solutions.

Fig. 7a shows the microparticles collected at a distance of 15 cm using PVA (mol. weight:

89,000-987,000 Da; 99% hydrolysed) solution, 8% w/v in deionised water, charged to 13.5 kV and dispensed at a flow rate of 1 ml/h. Fig. 7b shows the fibres collected at a distance of 20 cm using PCL (mol. weight: 80,000 Da) solution, 8% w/v in HFIP, spun at 1 1 kV and a flow rate of 1 ml/h.

Fig. 7c shows the fibres collected at a distance of 20 cm using PEO (mol. weight: 900,000 Da) solution, 4% w/v in deionised water, spun at 10 kV and a flow rate of 1 ml/h.

Fig. 7d shows the microparticles collected at a distance of 20 cm using PLGA (mol. weight: 66,000-107,000 Da) solution, 5% w/v in HFIP, charged to 13.6 kV and dispensed at a flow rate of 1 ml/h.

Example 4

The apparatus used for Examples 2 and 3 was then connected to a pen-like delivery device and an earthing cable connected between the apparatus and a sample of pig skin. Using the PDO solution of Ex. 2, fibres were collected directly onto the pig skin to form a patch, as seen in Fig. 8. The patch adhered to the skin, but could also be detached without causing any damage to the underlying skin. It was found that applying alcohol to the electrospun patch made it transparent, enabling an underlying skin wound to be observed without removing the patch.

PDO in an organic solution (9% w/v in HFIP as per Ex. 2) was used, mainly for visual purposes as the resultant fibres appear whiter than PEO in a water-based solvent. However, the aqueous PEO solution of Ex. 3 was also delivered using the pen-like device at a distance of 15 cm to form a patch directly onto human skin, as is seen in Fig. 9.

Claims

1 . A cordless liquid dispensing apparatus for handheld use comprising:

a mount for a reservoir of liquid;

an electrically driven pump arranged to deliver liquid from the reservoir to a discharge tip at a liquid delivery rate;

a high voltage power source arranged to charge the liquid at the discharge tip; and a microcontroller arranged to control the pump, and optionally the high voltage power source;

wherein the microcontroller is arranged to adjust a non-zero value of the liquid delivery rate.

2. A cordless liquid dispensing apparatus according to claim 1 , comprising a first compartment and a second compartment that is physically accessible independently of the first compartment, the first compartment housing the microcontroller, the high voltage power source and the electrically driven pump and the second compartment housing the mount for the liquid reservoir.

3. A cordless liquid dispensing apparatus according to claim 2, wherein the second compartment further comprises the discharge tip.

4. A cordless liquid dispensing apparatus for handheld use comprising a first compartment and a second compartment that is physically accessible independently of the first compartment, the second compartment housing a mount for a reservoir of liquid and a discharge tip for the liquid, and the first compartment housing at least an electrically driven part of a pump arranged to deliver liquid from the reservoir to the discharge tip and a high voltage power source arranged to charge the liquid at the discharge tip via an electrical connection between the first and second compartments.

5. A cordless liquid dispensing apparatus according to claim 1 , comprising a first compartment that is physically separable from a second compartment, the first compartment housing the microcontroller, the high voltage power source and the electrically driven pump and the second compartment housing the mount for the liquid reservoir.

6. A cordless liquid dispensing apparatus according to claim 5, wherein the second compartment further comprises the discharge tip.

7. A cordless liquid dispensing apparatus for handheld use comprising a first compartment that is physically separable from a second compartment, the second compartment housing a mount for a reservoir of liquid and a discharge tip for the liquid, and the first compartment housing at least an electrically driven part of a pump arranged to deliver liquid from the reservoir to the discharge tip and a high voltage power source arranged to charge the liquid at the discharge tip via an electrical connection between the first and second compartments.

8. A cordless liquid dispensing apparatus according to any of claims 5, 6 or 7, wherein the first and second compartments are entirely separable from one another.

9. A cordless liquid dispensing apparatus according to any of claims 2 to 8, wherein the first compartment is substantially closed.

10. A cordless liquid dispensing apparatus according to any of claims 2 to 9, wherein the pump comprises an electrically driven motor housed in the first compartment and a mechanical actuator that extends into the second compartment.

1 1 . A cordless liquid dispensing apparatus according to claim 10, wherein the mechanical actuator is arranged to act on a reservoir of liquid mounted in the second compartment.

12. A cordless liquid dispensing apparatus according to claim 1 1 , wherein the reservoir comprises a syringe and the mechanical actuator comprises a linear actuator that extends into the second compartment to act on a piston of the syringe.

13. A cordless liquid dispensing apparatus according to any of claims 10, 1 1 or 12, wherein a or the microcontroller is housed in the first compartment and arranged to control the mechanical actuator so as to adjust a non-zero value of the liquid delivery rate.

14. A cordless liquid dispensing apparatus according to any of claims 2 to 13, further comprising an electrical cable extending from the high voltage power source in the first compartment to the discharge tip, the electrical cable bypassing the second compartment.

15. A cordless liquid dispensing apparatus according to any of claims 2 to 13, further comprising a separable electrical connection between the first and second compartments.

16. A cordless liquid dispensing apparatus according to any preceding claim, wherein a or the microcontroller is arranged to control the high voltage power source.

17. A cordless liquid dispensing apparatus according to any preceding claim, wherein the high voltage power source comprises a battery pack.

18. A cordless liquid dispensing apparatus according to any preceding claim, wherein the high voltage power source comprises a high voltage converter.

19. A cordless liquid dispensing apparatus according to any of claims 2 to 17, wherein a or the battery pack is housed in the second compartment.

20. A cordless liquid dispensing apparatus according to any preceding claim, wherein the high voltage power source is arranged to apply a voltage of at least 1 kV and up to 5 kV, 10 kV, 15 kV or 20 kV.

21 . A cordless liquid dispensing apparatus according to any preceding claim, including an earthing cable that can be connected to a collection surface.

22. A cordless liquid dispensing apparatus according to any preceding claim, including a handle.

23. A cordless liquid dispensing apparatus according to any preceding claim, further comprising a liquid delivery device comprising an elongated channel arranged to deliver charged liquid from the discharge tip of the apparatus to a second discharge tip at the end of the elongated channel, wherein at least a portion of the elongated channel has an electrically insulating sheath to enable manual manipulation of the device.

24. A cordless liquid dispensing apparatus according to claim 23, wherein the elongated channel is at least partially flexible.

25. A cordless liquid dispensing apparatus according to any preceding claim, comprising a reservoir of liquid mounted therein.

26. A cordless liquid dispensing apparatus according to any preceding claim, comprising a syringe of liquid mounted in the second compartment.

27. A cordless liquid dispensing apparatus according to claim 25 or 26, wherein the liquid is a polymer solution.

28. A cordless liquid dispensing apparatus according to any preceding claim, wherein the apparatus is an electrospinning apparatus.