WO2014118584A1

WO2014118584A1 - Delivering electrically charged liquids

Info

Publication number: WO2014118584A1
Application number: PCT/GB2014/050314
Authority: WO
Inventors: Hua Ye; Pierre Alexis MOUTHUY
Original assignee: Oxford University Innovation Ltd
Current assignee: Oxford University Innovation Ltd
Priority date: 2013-02-04
Filing date: 2014-02-04
Publication date: 2014-08-07
Anticipated expiration: 2015-08-04
Also published as: GB201301939D0

Abstract

Delivering electrically charged liquids A liquid delivery device comprising a discharge tip (6) and an elongated channel (2) for delivering charged liquid from an apparatus to the discharge tip (6), wherein at least a portion of the elongated channel (2) has an electrically insulating sheath (8) to enable manual manipulation of the device. The elongated channel (2) may be at least partially flexible e.g. formed from flexible tubing.

Description

Delivering electrically charged liquids The present invention relates to apparatus and methods for delivering electrically charged liquid(s), e.g. for electrospraying an aerosol of liquid droplets or electrospinning fibres from a liquid. In particular, the present invention may provide improved manual control over the deposition of fibres generated by electrospinning.

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 syringe pump or header tank to feed liquid to the charged 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 benchtop 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 electrospinning apparatus that is small and/or light enough for handheld use. WO 2010/059127 discloses a portable device in the shape of a gun comprising a battery-powered high voltage power supply and a battery-powered or manually pressured pump to transfer polymer solution from an internal reservoir to an outlet (Fig. 4). The outlet of the device is a metallic needle that is connected to the high voltage power supply so that liquid is charged as it exits. The charged liquid jet may optionally be focused by a hollow shroud that can be used to achieve a desired coating profile on the target substrate. However such a portable apparatus only provides a limited degree of manual control over liquid delivery, in particular when depositing electrospun fibres.

It is an aim of the present invention to provide improved apparatus and methods for charged liquid delivery that enable a higher degree of manual control over delivery, e.g.

increased control over fibre deposition or aerosol delivery.

According to a first aspect of the present invention there is provided a liquid delivery device for a liquid charging apparatus, the device comprising a discharge tip and an elongated channel for delivering charged liquid from the apparatus to the discharge tip, wherein at least a portion of the elongated channel has an electrically insulating sheath to enable manual manipulation of the device.

It will be appreciated that such a device allows the charged liquid that is usually emitted directly from the nozzle of a liquid charging apparatus, such as an electrospinning apparatus, to be delivered by the elongated channel to a location determined by manual manipulation of the device. The device therefore provides a manually operable extension to the conventional discharge nozzle of a liquid charging apparatus. The elongated channel could, for example, be used to deliver the charged liquid to a discharge tip that is positioned relatively distant from the liquid charging apparatus. The device may therefore find use in electrospraying an aerosol directly at a location away from the liquid charging apparatus.

For electrospinning, all that is required at the discharge location is a grounded (or lower potential) surface to collect the electrospun fibres. The jet formed as the charged liquid exits the tip is accelerated by the electric field gradient to the grounded (or lower potential) surface. In a conventional electrospinning apparatus the liquid is charged as it leaves a metal nozzle and the nozzle (or other tip) can not be handled due to the risk of electric shock. In fact the nozzle is usually shielded to prevent any manual contact. A device according to the present invention, on the other hand, can be manipulated by virtue of the electrically insulating sheath. This can be contrasted with a conventional electrospinning apparatus, in which the discharge nozzle is stationary while the collection electrode might be moved closer to the tip e.g. to vary the separation distance and adjust the formation of fibres.

The liquid delivery device may find many different applications where it is desirable to manually manipulate an elongated channel carrying charged liquid to a site of interest for electrospinning or electrospraying. This can enable direct deposition of fibres or an aerosol at locations not previously accessible by a discharge tip. For example, the device 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, the device 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 liquid delivery device 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. This may be assisted by treating the deposition surface 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. The manual

manipulability of the device means that flocking can be applied selectively by a user to certain areas.

A further advantage of being able to manually manipulate the deposition of electrospun fibres is that a user of the device can control the distance between the discharge tip and the deposition site. 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 the device is 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 the device is manipulated to bring the discharge tip to approximately the same distance from a deposition site. The liquid delivery device 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 liquid delivery device may be held at distance of 1 -30 cm, preferably 4-30 cm, from a collection surface.

As the elongated channel is carrying a charged liquid from an apparatus to the discharge tip, the insulating nature of the sheath is critical to ensure that the device can be safely manipulated by a user without suffering an electric shock. In one set of embodiments the sheath may be separate from the elongated channel. The material of the sheath can therefore be chosen to ensure that electrical insulation is achieved independently of the material of the channel. For example, the sheath may be made of a material having good electrical insulation properties while the channel may be made of a material that is less insulating or even electrically conductive e.g. metallic. Furthermore the sheath may be designed to be ergonomic e.g. easy to grip. In such embodiments the sheath may be provided at any convenient location along the length of the elongated channel. One or more such sheaths may be provided e.g. spaced along the channel to enable a user to grip at different positions. In one set of embodiments the insulating sheath is provided substantially along the entire length of the channel, e.g. providing a user with maximum flexibility in selecting where to hold the device. This may also make the device safer by ensuring that a user can not touch part of the channel that is not insulated.

In another set of embodiments the sheath may be integral with the elongated channel. For example, at least a portion of the elongated channel may itself be electrically insulating e.g. a portion made of insulating material or treated so as to be insulating. An insulating coating may be applied to at least a portion of the channel. In some embodiments the elongated channel may itself be electrically insulating e.g. a tube formed of a plastics material or the like. This can be particularly convenient as it means the channel can provide the dual functions of delivering charged liquid and allowing a user to manually manipulate the device without a separate sheath being required. As mentioned above, this ensures that a user can safely touch any part of the channel. Furthermore, an electrically insulated channel may be better able to carry the charged liquid without electrical leakage.

Whether the sheath is separate or integral, it may be preferable for at least part of the electrically insulating sheath to surround the discharge tip. This can be used to protect a user from coming into contact with the tip, for example if it is a metal needle carrying a risk of electric shock. In other embodiments the discharge tip may be shielded independently. 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 help control the trajectory of the liquid jet as it travels through the air. In yet other embodiments the discharge tip may be not need to be shielded, for example if it is formed of an electrically insulating material. The discharge tip may be integrally formed by the distal end of the elongated channel or it may be a separate component, for example a conventional nozzle, that is fitted to the distal end of the channel.

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 discharge tip may comprise a single outlet for an electrosprayed aerosol or electrospun fibres. The discharge tip may be designed in such way that it allows multi-jet spinning (e.g. comprising multiple outlets) or co-axial spinning (e.g. if fed by multiple channels that deliver different liquids). The electrically insulating sheath may be made of any suitable insulating material, for example a plastics material such as acetal, silicone, EPDM, PE, PP, PVC, ETFE, PTFE or Kapton

(polyimide film) and/or coated with such an insulating material. The sheath may also be made of glass, ceramic and/or composite polymer materials. The sheath may be substantially solid e.g. to provide a rigid grip or it may be at least partially flexible. In embodiments where the elongated channel is flexible it may be preferable that the sheath is also flexible, so that they can be manipulated together. Preferably the sheath substantially surrounds at least a portion of the elongated channel, i.e. extending around the circumference of the channel, so that a user can hold the device from any angle. However it will be appreciated that it is not essential for the sheath to extend fully around the circumference of the channel and it may take the form of a partial sheath in some less preferred embodiments.

The elongated channel can take any form, and be made of any material, suitable for conveying charged liquid from an upstream apparatus. The channel may, for example, be formed of a metallic, glass, ceramic, plastics and/or composite material. It is preferable for the material to have resistance to the liquid chemicals to which it is likely to be exposed. It will be understood that the choice of charged liquid may dictate the materials that are appropriate for the channel, which may in turn determine whether the sheath can be made from the same material or not. Preferably the elongated channel is able to convey a liquid that is charged at 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.

Preferably the elongated channel is able to convey a liquid that is flowing under pressure, in particular a liquid that is being pumped from the apparatus to the discharge tip. The internal diameter of the elongated channel may therefore be chosen to take into account the expected flow rate of the liquid, in addition to the viscosity of the liquid. Where the device is used to deliver an electrospinning liquid, for example, the elongated channel may be arranged to deliver charged liquid at flow 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 elongated channel may have an internal diameter ranging from 0.1 mm (e.g. for low viscosity solutions such as hexafluoroisopropanol (HFIP)) up to 1 .0 mm or 1 .5 mm (e.g. for very viscous solutions). In various embodiments, the elongated channel may have an internal diameter that is about 0.2 mm, 0.3 mm, 0.4 mm, 0.5 mm, 0.6 mm, 0.7 mm, 0.8 mm or 0.9 mm. At least in electrospinning applications, the internal diameter of the elongated channel adjacent to the discharge tip may slightly affect the electrospun fibre diameter. It will be appreciated that the internal diameter of the elongated channel may not be constant along its length, for example the diameter may be larger or smaller towards the end adjacent to the discharge tip. Furthermore, the elongated channel may have a non-porous internal surface so that liquid is conveyed through the channel by a pressure head provided by the apparatus. This may be contrasted with liquid delivery devices that use capillary action to carry the liquid, in particular tubing having a porous internal surface to help suck the liquid along.

While the elongated channel may be substantially rigid, to increase the range of movement available it is preferable for the channel to be at least partially flexible. 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 while enabling ease of manipulation, especially when it is desired to manoeuvre the discharge tip to a particular location e.g. for in situ repair using nanofibres.

It will be understood that an elongated channel is one having an aspect ratio (i.e. the ratio of length I to diameter d) that is much greater than unity. In order to increase the range of the device it is preferable for the elongated channel to have an aspect ratio defined by l/d > 10, 20, 30, or 40, preferably l/d > 50, and further preferably l/d > 100, 150, 200, 250, 300, 350, 400 or 450. In some embodiments the elongated channel may have an aspect ratio defined by l/d > 500. As long as the liquid is carried without losing its charge then there may not be a limit to the length of the channel. However it is envisaged that in various embodiments it will be possible to locate a liquid charging apparatus reasonably close to a site of interest e.g. belonging to a human body, and then use the device as a local extension with the elongated channel typically having a length I of at least 5 cm, 10 cm, 15 cm, 20 cm, 25 cm, 30 cm or even 50 cm and preferably up to about 100 cm. It may be desirable to limit the length of the device so that it does not become unwieldy, so as not to substantially reduce the flow rate of charged liquid from the apparatus, and also to avoid a wasted volume of potentially expensive liquid being left unused in the channel.

In a set of embodiments the liquid delivery device may comprise means for controlling the rate of liquid delivery through the elongated channel. Such control means may take the form of a manually operable valve that can be manipulated by a user to turn the liquid delivery on and off. In some embodiments the control means may allow a user to throttle the flow of liquid through the elongated channel so as to adjust a non-zero value of the liquid delivery rate. This control may be effected within the delivery device e.g. as liquid is passing along the elongated channel. In other embodiments the control means may be linked to the liquid charging apparatus upstream of the delivery device e.g. to adjust the delivery rate before liquid reaches the elongated channel. Such a control means may also be used to adjust the voltage applied to the liquid by the charging apparatus. In either case it is advantage for the control means to be operated by an interface provided on the liquid delivery device, preferably on the insulating sheath, as this component is designed to be handheld. A user may therefore operate the control means as the same time as manually manipulating the device.

The liquid delivery device can be connected to any suitable liquid charging apparatus e.g. a conventional bench top apparatus such as is commercially available from companies including Electrospinz, Fluence, KES Kato Tech Co., MECC, Nanospinner, NanoNC, Yflow, IME Technologies, Physics Instruments Co. and Linari Biomedical. The elongated channel may be connected to the usual discharge nozzle of the apparatus so as to provide an extension that delivers the charged liquid to a discharge tip remote from the apparatus. It will be understood that the device may not be compatible with other forms liquid charging apparatus that do not have a discharge nozzle, for example the nozzle-less electrospinning system offered by

Elmarco in which a rotating drum is dipped into a bath of liquid polymer (so-called "nanospider" technology).

It is an advantage that the liquid delivery device can be connected and/or disconnected to/from a wide range of different liquid charging apparatus, in particular electrospinning apparatus. The liquid delivery device may therefore be compatible for retrofitting to existing equipment. The liquid delivery device may be connected to a liquid charging apparatus that is fixed in position, for example on a production line, or to a liquid charging apparatus that is portable, for example a handheld apparatus. In addition, or alternatively, the elongated channel may be interchangeable, for example one or more different diameter channels may be used in combination with different liquid charging apparatus. As is described above, the internal diameter of the elongated channel may be chosen depending on the viscosity and/or flow rate of liquid supplied by the liquid charging apparatus.

In other embodiments the liquid delivery device may be built into a novel apparatus. According to a further aspect the present invention therefore provides a liquid charging apparatus comprising a mount for a liquid reservoir, a high voltage power source arranged to charge liquid from the reservoir, and an elongated channel arranged to deliver charged liquid from the apparatus to a remote discharge tip, wherein at least a portion of the elongated channel has an electrically insulating sheath for manual control of the position of the discharge tip.

It will be appreciated that such an apparatus is fundamentally different to a conventional dispensing system for charged liquid because the elongated channel with its sheath is provided to carry the charged liquid downstream of the point of voltage application to a discharge tip that may be remote from the bulk of the apparatus. As is described above, this enables a user to perform electrospinning or electrospraying at a location of their choice and allows direct aerosol or fibre deposition in situ onto various objects e.g. such as human skin for wound repair. Rather than a stationary discharge nozzle, as is conventional, the discharge tip is manually moveable by a user. ln one set of embodiments the elongated channel may deliver charged liquid directly from the point at which the high voltage power supply is arranged to charge the liquid e.g. in a charging head. For example, the elongated channel may be an integral extension of the tubing that is normally used to convey liquid to/from the charging head. The elongated channel may comprise one or more channels, for example a co-axial arrangement of multiple channels where two or more charged liquids are to be kept separate until they reach the discharge tip. In another set of embodiments the elongated channel may be connected to a discharge nozzle or capillary after the high voltage power supply is arranged to charge the liquid. This may enable the elongated channel to be removed e.g. for cleaning purposes. Furthermore, as is discussed above, the elongated channel may be retrofitted to the discharge nozzle(s) of an existing liquid charging apparatus, whether single or coaxial capillary delivery. It may therefore be preferable for the elongated channel to be removable e.g. so as to allow the use of a conventional discharge nozzle instead of the extension provided by the elongated channel. When the elongated channel is connected to a discharge nozzle, it is preferable for the elongated channel to be connected using a liquid-tight fitting such as a PEEK sleeve or PTFE tubing, and preferably a leak-free seal e.g. made of PTFE, so as to mitigate the risk of charged liquid leakage.

The apparatus may comprise any suitable liquid reservoir, including one or more liquid reservoirs. Where the apparatus is used for electrospinning, the liquid reservoir is preferably arranged to supply liquid at flow 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). The apparatus may conveniently comprise an earth cable to connect to a collection surface for fibres or liquid droplets emitted from the discharge tip.

Where the apparatus is used for electrospraying, the liquid is likely to be much less viscous and it is typical for the liquid flow rate to be a least an order of magnitude greater, often at least two orders of magnitude greater, e.g. the liquid may be supplied at flow rates of at least 1000 ml/hour (i.e. 1 l/hr) and up to 20 l/hr, 25 l/hr or 30 l/hr. The flow 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 liquid reservoir may provide a flow driven by a hydrostatic head or by an electrically driven pump. In preferred embodiments the liquid reservoir comprises one or more syringe pumps so that liquid can be delivered at a controllable rate. The apparatus may include means to adjust a non-zero value of the liquid delivery rate, for example a controller for the syringe pump, and preferably a microprocessor-based controller.

The high voltage power source is typically connected to a charging head through which liquid from the reservoir is delivered to the elongated channel. The charging head may be made of brass to ensure good electrical conductivity, or stainless steel can be suitable. As is described above, the elongated channel can be connected directly to the charging head or connected to a discharge nozzle of the head. In either case the elongated channel conveys the charged liquid downstream of the head and away from the high voltage power source. 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, or even up to about 50 kV. The high voltage power source is preferably a DC power supply. It may be run from a battery or from the mains supply (e.g. with an AC/DC converter).

For safety purposes, the charging head and any other conductive parts in contact with the charged liquid are preferably earthed or shielded so as to avoid the risk of electric shock. However, it is an advantage of the present invention that the elongated channel moves the actual discharge tip away from the liquid charging apparatus so that a user is less likely to come into contact with the high voltage power source and/or charging head. The electrically insulating sheath of the elongated channel ensures that a user can safely manipulate the device without receiving an electric shock from the charged liquid. Further preferred features of the sheath and/or elongated channel have already been described above in relation to the first aspect of the invention and may equally be applied to the apparatus described herein.

In addition to manual manipulation of the elongated channel, in one set of embodiments the whole apparatus may be cordless, that is, designed for handheld use. The cordless liquid charging apparatus may comprise an electrically driven pump arranged to deliver liquid from the reservoir to the discharge tip at a liquid delivery rate, a high voltage power source arranged to charge the liquid upstream of the elongated channel, and a microcontroller arranged to control the pump (and optionally the high voltage power source). Preferably the microcontroller is arranged to adjust a non-zero value of the liquid delivery rate. As is mentioned above, a user interface for the microcontroller may be provided on the elongated channel for ease of manual manipulation, or else somewhere else on the cordless apparatus.

In one set of embodiments the cordless apparatus comprises 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. 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. The first and second compartments may be entirely separable from one another (except for an electrical connection, which may or may not comprise a physically separable connector).

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.

In one set of embodiments a liquid reservoir in the form of a syringe is mounted in the second compartment and a mechanical actuator, preferably a linear actuator, extends from the first compartment into the second compartment to act on a piston of the syringe. 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 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 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 preferred 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 polyvinyl pyrrolidone) (PVP); or a non-water soluble polymer solution of biodegradable polyesters such as po!y(!actic acid) (PLLA), poly(lactic-co-glycolic acid) (PLGA), or polycaprolactone (PCL).

In a set of embodiments the liquid is 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.

The present invention extends to the use of a liquid delivery device or liquid charging apparatus to manually generate fibres from acharged liquid at a remote site of interest, in particular to manually generate a fibrous network at a biological site on the human body.

According to a further aspect of the present invention there is provided a method of delivering a charged liquid, in which the charged liquid is conveyed through an elongated channel to a discharge tip and the elongated channel is manually manipulated to control the position of the discharge tip.

According to a yet further aspect of the present invention there is provided a method of dispensing an electrically charged liquid, comprising: providing a liquid reservoir; applying a high voltage to charge liquid from the reservoir; conveying the charged liquid through an elongated channel to a remote discharge tip; and manually manipulating the elongated channel to control the position of the discharge tip.

Various preferred features of the methods outlined above will be apparent from the foregoing description. For example, it will be understood that in such methods a user can vary the distance between the discharge tip and a deposition site of interest. This may be facilitated by an elongated channel that is flexible and/or relatively long.

While it is described above that the electrically insulating sheath provides the advantage of enabling manual manipulation of a channel that is delivering charged liquid, it will be appreciated that the liquid delivery device is not limited to manual use. The electrically insulating sheath may equally provide a benefit if mounting the elongated channel within liquid delivery equipment, for example because it means that conductive e.g. metal parts can be put in contact with the sheath without the need for earthing. The liquid delivery device may therefore find use mounted in a fixed position or mounted in an automatically moveable machine head, such as a moveable print head.

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

Figure 1 is a schematic illustration of a charged liquid delivery device according to a first embodiment of the present invention;

Figure 2 is a schematic illustration of a charged liquid delivery device according to a second embodiment of the present invention;

Figure 3 is a schematic illustration of a charged liquid delivery device according to a third embodiment of the present invention; Fig. 4a is an optical micrograph of nanofibres spun using a cordless liquid charging apparatus at 6.5 kV and Fig 4b is an optical micrograph of nanofibres spun using a conventional bench top apparatus at 6.5 kV;

Fig. 4c is an optical micrograph of nanofibres spun using the same cordless liquid charging apparatus at 9.5 kV and Fig 4d is an optical micrograph of nanofibres spun using a conventional bench top apparatus at 9.5 kV;

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 pen applicator connected to the cordless handheld apparatus;

Fig. 7 shows a patch of PDO fibres deposited onto pig skin using a pen-like delivery device; and Fig. 8 shows a patch of PEO fibres deposited onto human skin using a pen-like delivery device.

There is seen in the Figures three embodiments of a liquid delivery device for a liquid charging apparatus, such as e.g. an electrospinning apparatus. In both embodiments the device comprises an elongated channel 2 for delivering charged liquid from the head 4 of an apparatus (not shown) to a discharge tip 6. Along most of its length, the elongated channel 2 is surrounded by an electrically insulating sheath 8 that can be gripped by a user for manual control of the position of the discharge tip 6. The elongated channel 2 with the sheath 8 is in the form of a pen-like extension that can be integrated with, or connected to, the charging head 4,4' of an upstream apparatus (e.g. as seen in Figs. 1 and 2). A high voltage power source 10 is connected to the head 4,4' to charge liquid as its passes therethrough. Further features of the apparatus are not described, although it may of course include the usual control components for the high voltage power source 10 (including adjustable voltage) and/or liquid delivery (including an adjustable liquid delivery rate).

Figure 1 shows an embodiment in which a liquid from a single reservoir (not shown) is fed into the charging head 4 e.g. by a syringe pump (not shown). The elongated channel 2 is an extension of the PTFE tubing that is connected to the charging head 4. Where the channel 2 is connected to the head 4 and to the sheath 8 a PTFE screw and leak-proof seal 12 is provided.

Figure 2 shows another embodiment in which liquid from two reservoirs (not shown) is fed into the charging head 4' e.g. by syringe pumps (not shown). A coaxial capillary tube 14 allows the two liquids, which may be the same or different, to be mixed and charged inside the head 4'. The elongated channel 2 is connected to the outlet of the capillary tube 14 by a PTFE screw and leak-proof seal 12. As before, the channel 2 may be formed by PTFE or other plastics tubing.

Figure 3 shows a further embodiment of a liquid delivery device in which the elongated channel 2' is a coaxial channel. The inner channel 2a delivers one liquid while the outer channel 2b delivers another liquid. Instead of two (or more) liquids being mixed in an upstream charging head as shown in Figure 2, the charged liquids are kept separate as they pass along the elongated channel 2'. The discharge tip 6' is a co-axial tip. Such a device may be used, for example, to form droplet or fibres having a core formed by one liquid and a coating formed by another.

In all of these embodiments the electrically insulating sheath 8 is shown as a separate pen-like sleeve through which the elongated channel 2, 2' passes. The sheath is wider than the tubing and easier for a user to grip. However, it will be understood that in other embodiments the sheath 8 may instead be integrated with the tubing of the elongated channel 2, 2'. Also in these embodiments the discharge tip 6, 6' is seen to be provided by the distal end of the tubing that forms the elongated channel 2, 2', but a separate tip could instead be used e.g. a metal nozzle connected to the end of the channel 2, 2'.

Example 1

The discharge tip 6, 6' has a similar diameter to the discharge tip of a cordless liquid charging apparatus used without the pen-like delivery device. It is therefore expected that a charged liquid can be delivered by the elongated channel and achieve the same results as observed using such apparatus. A cordless liquid charging apparatus was used to perform electrospinning using polycapro lactone (PCL) dissolved at 8% (%w/v) in HFIP. The same solution was loaded into a bench top 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 4. 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. 4a the fibres produced by the cordless apparatus at 6.5 kV and in Fig. 4b the fibres produced by the bench top apparatus at 6.5 kV. There is seen in Fig. 4c the fibres produced by the cordless apparatus at 9.5 kV and in Fig. 4d the fibres produced by the bench top apparatus at 9.5 kV. It can be seen that the results for nanofibre generation by the cordless apparatus and the bench top apparatus are similar. The only difference is that the mesh is slightly thicker for the fibres deposited from the bench top apparatus, as a result of this apparatus being allowed to operate for longer than the cordless apparatus. The same results are expected when using an elongated liquid delivery device connected to the discharge tip of either apparatus. Example 2

A handheld liquid charging apparatus was used to electrospin fibres from a solution of biodegradable PDO polyester (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.

The same apparatus was then connected to a pen-like delivery device as described above and the results are seen in Figs. 6a and 6b. The fibres were collected on a flat surface at a distance of 20 cm from the discharge tip of a 50 cm extension. The liquid dispensing rate was the same, namely 1 ml/h.

Comparing Figs. 5b and 6b, the results obtained with the pen-like delivery device are no different from what is observed without - in terms of fibre/mesh aspect. An expert would not make out a difference as long as the same parameters have been used both with and without the pen-like delivery device. In the SEM images the amount of fibres is slightly different but this results from the duration of spinning.

Example 3

Using the pen-like delivery device, an earthing cable was 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. 7. 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, in a further test the device was used to deliver fibres at a distance of 15 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, to form a patch directly onto human skin, as is seen in Fig. 8.

Claims

1 . A liquid delivery device for a liquid charging apparatus, the device comprising a discharge tip and an elongated channel for delivering charged liquid from the apparatus to the discharge tip, wherein at least a portion of the elongated channel has an electrically insulating sheath to enable manual manipulation of the device.

2. A liquid delivery device as claimed in claim 1 , wherein the sheath is separate from the elongated channel.

3. A liquid delivery device as claimed in claim 1 , wherein the sheath is integrated with the elongated channel.

4. A liquid delivery device as claimed in claim 1 , 2 or 3, wherein the sheath is provided substantially along the entire length of the elongated channel.

5. A liquid delivery device as claimed in any preceding claim, wherein the elongated channel is at least partially flexible e.g. formed from flexible tubing.

6. A liquid delivery device as claimed in any preceding claim, wherein the elongated channel is arrange to deliver a liquid that is charged at a voltage of at least 1 kV and up to 5 kV, 10 kV, 15 kV or 20 kV.

7. A liquid delivery device as claimed in any preceding claim, wherein the elongated channel has an aspect ratio (the ratio of length I to diameter d) that is defined by l/d > 10, 20, 30, 40, 50 or l/d > 100, 150, 200, 250, 300, 350, 400 or 450.

8. A liquid delivery device as claimed in any preceding claim, wherein the elongated channel has a length I of at least about 5 cm, 10 cm, 15 cm, 20 cm, 25 cm, 30 cm, 40 cm or 50 cm and up to about 100 cm.

9. A liquid delivery device as claimed in any preceding claim, further comprising a shield for the discharge tip.

10. A liquid delivery device as claimed in any preceding claim, further comprising means for controlling the rate of liquid delivery through the elongated channel.

1 1 . A liquid delivery device as claimed in claim 10, wherein the control is operated by an interface provided on the insulating sheath.

12. A liquid charging apparatus comprising a liquid delivery device as claimed in any preceding claim connected to a discharge nozzle of the apparatus.

13. An electrospinning apparatus comprising a liquid delivery device as claimed in any preceding claim connected to a discharge nozzle of the apparatus.

14. A liquid charging apparatus comprising a mount for a liquid reservoir, a high voltage power source arranged to charge liquid from the reservoir, and an elongated channel arranged to deliver charged liquid from the apparatus to a remote discharge tip, wherein at least a portion of the elongated channel has an electrically insulating sheath for manual control of the position of the discharge tip.

15. A liquid charging apparatus as claimed in claim 14, wherein the high voltage power source is connected to a charging head and the elongated channel is arranged to deliver liquid directly from the charging head.

16. A liquid charging apparatus as claimed in claim 14, wherein the high voltage power source is connected to a charging head and the elongated channel is connected to a discharge nozzle of the charging head.

17. A liquid charging apparatus as claimed in claim 16, wherein the elongated channel is removably connected to the discharge nozzle.

18. A liquid charging apparatus as claimed in any of claims 15-17, wherein the charging head receives liquid from one, two or more reservoirs.

19. A liquid charging apparatus as claimed in any of claims 14-18, wherein the sheath is separate from the elongated channel.

20. A liquid charging apparatus as claimed in any of claims 14-19, wherein the sheath is integrated with the elongated channel.

21 . A liquid charging apparatus as claimed in any of claims 14-20, wherein the sheath is provided substantially along the entire length of the elongated channel.

22. A liquid charging apparatus as claimed in any of claims 14-21 , wherein the elongated channel is at least partially flexible e.g. formed from flexible tubing.

23. A liquid charging apparatus as claimed in any of claims 14-22, wherein the elongated channel is arrange to deliver a liquid that is charged at a voltage of at least 1 kV and up to 5 kV, 10 kV, 15 kV or 20 kV.

24. A liquid charging apparatus as claimed in any of claims 14-23, wherein the elongated channel has an aspect ratio (the ratio of length I to diameter d) that is defined by l/d > 10, 20,

30, 40, 50 or l/d > 100, 150, 200, 250, 300, 350, 400 or 450.

25. A liquid charging apparatus as claimed in any of claims 14-24, wherein the elongated channel has a length I of at least about 5 cm, 10 cm, 15 cm, 20 cm, 25 cm, 30 cm, 40 cm or 50 cm and up to about 100 cm.

26. A liquid charging apparatus as claimed in any of claims 14-25, further comprising a shield for the discharge tip.

27. A liquid charging apparatus as claimed in any of claims 14-26, further comprising means for controlling the rate of liquid delivery through the elongated channel.

28. A liquid charging apparatus as claimed in claim 27, wherein the control is operated by an interface provided on the insulating sheath.

29. A liquid charging apparatus according to any of claims 14-28, comprising a reservoir of liquid mounted therein.

30. A liquid charging apparatus as claimed in claim 29, wherein the liquid is an

electrospinning liquid, e.g. the liquid is a polymer solution.

31 . A liquid charging apparatus as claimed in claim 29, wherein the liquid is a printing liquid.

32. A liquid charging apparatus as claimed in any of claims 13-31 , comprising a syringe pump to deliver liquid to the elongated channel.

33. A liquid charging apparatus as claimed in any of claims 13-32, wherein a or the high voltage power source is arranged to apply a voltage to the liquid of at least 1 kV and up to 5 kV, 10 kV, 15 kV or 20 kV.

34. A liquid charging apparatus as claimed in any of claims 13-33, comprising an earth cable to connect to a collection surface for fibres or liquid droplets emitted from the discharge tip.

35. A liquid charging apparatus as claimed in any of claims 13-34, wherein the apparatus is a cordless apparatus for handheld use.

36. A liquid charging apparatus as claimed in claim 35, comprising an electrically driven pump arranged to deliver liquid from the reservoir to the discharge tip at a liquid delivery rate and a microcontroller arranged to adjust a non-zero value of the liquid delivery rate.

37. A liquid charging apparatus as claimed in claim 36, wherein the microprocessor is arranged to control a or the high voltage power source so as to adjust the voltage applied to the liquid upstream of the elongated channel.

38. A liquid charging apparatus as claimed in claim 35, 36 or 37, wherein the cordless apparatus comprises a first compartment that is physically separable from a second

compartment, the first compartment housing a or the microcontroller, a or the high voltage power source and a or the electrically driven pump, and the second compartment housing a or the mount for the liquid reservoir.

39. A liquid charging apparatus as claimed in claim 35, 36 or 37, wherein the cordless apparatus comprises a first compartment and a second compartment that is physically accessible independently of the first compartment, the first compartment housing a or the microcontroller, a or the high voltage power source and a or the electrically driven pump and the second compartment housing a or the mount for the liquid reservoir.

40. A liquid charging apparatus as claimed in claim 38 or 39, wherein a liquid reservoir in the form of a syringe is mounted in the second compartment and a mechanical actuator, preferably a linear actuator, extends from the first compartment into the second compartment to act on a piston of the syringe.

41 . A liquid charging apparatus as claimed in claim 39 or 40, 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.

42. The use of a liquid delivery device or liquid charging apparatus according to any preceding claim to deposit a charged liquid at a remote site of interest.

43. The use of a liquid delivery device or liquid charging apparatus according to any preceding claim for electrospinning fibres or electrospraying an aerosol.

44. The use of a liquid delivery device or liquid charging apparatus to manually generate fibres from a charged liquid at a remote site of interest, in particular to manually generate a fibrous network at a biological site on the human body.

45. A method of delivering a charged liquid, in which the charged liquid is conveyed through an elongated channel to a discharge tip and the elongated channel is manually manipulated to control the position of the discharge tip.

46. A method according to claim 45, wherein the liquid is an electrospinning liquid, e.g. the liquid is a polymer solution.

47. A method according to claim 45, wherein the liquid is a printing liquid.

48. A method of dispensing an electrically charged liquid, comprising: providing a liquid reservoir; applying a high voltage to charge the liquid from the reservoir; conveying the charged liquid through an elongated channel to a remote discharge tip; and manually manipulating the elongated channel to control the position of the discharge tip.

49. A method as claimed in any of claims 45 to 48, further comprising varying the distance between the discharge tip and a deposition site.