EP4422714A1

EP4422714A1 - Injection device

Info

Publication number: EP4422714A1
Application number: EP22801204.3A
Authority: EP
Inventors: Ian Hugh Quirk; Muhammad Rohaan SADIQ; Michael Peter Irvine
Original assignee: Active Needle Technology Ltd
Current assignee: Active Needle Technology Ltd
Priority date: 2021-10-28
Filing date: 2022-10-27
Publication date: 2024-09-04
Also published as: GB2612576A; GB202115495D0; WO2023073374A1; GB2612576B; KR20240110585A

Abstract

An injection device comprises a needle including an inlet and plural outlets, an oscillator coupled to the needle and configured to oscillate the needle, and an injectant supply device configured to supply injectant to the inlet of the needle such that injectant is emitted from the outlets of the needle while the oscillator oscillates the needle.

Description

INJECTION DEVICE

FIELD OF THE INVENTION

The present invention relates to an injection device, and operation methods thereof. Various embodiments relate to an oscillating needle assembly.

BACKGROUND

Needles are commonly used to inject injectant into an injection target, such as tissue. For example, a needle may be used to inject a nanoparticle radiosensitiser into a tumour prior to radiotherapy so as to enhance the efficacy of the radiotherapy treatment.

A needle typically comprises a tubular shaft, or cannula, that extends along a needle axis between an inlet end and an outlet end, or tip. The tubular shaft (i.e. cannula) typically has a bore, or lumen, that extends along the entire axial length of the shaft to form an injectant inlet at the inlet end and an injectant outlet at the outlet end (i.e. tip). The outlet end of the shaft typically has a sharp point formed by a bevel. In use, injectant passes axially through the bore (i.e. lumen) of the shaft from the inlet end to the outlet end, and axially out of the outlet, e.g. into tissue.

The inventors believe that there remains scope for improvements to injection devices.

SUMMARY

According to an aspect, there is provided an injection device comprising: a needle including an inlet and one or more outlets; an oscillator coupled to the needle and configured to oscillate the needle; and an injectant supply device configured to supply injectant to the inlet of the needle such that injectant is emitted from the one or more outlets of the needle while the oscillator oscillates the needle. Embodiments of the present invention relate to an oscillating needle assembly in which a hollow needle is provided with an injectant inlet and one or more injectant outlets.

The needle may comprise a tubular shaft (i.e. cannula) that extends along an axis between an inlet end of the needle and an outlet end (i.e. tip) of the needle, with the inlet being provided at or proximate to the inlet end, and one or more outlets being provided at or proximate to the outlet end. The shaft may have an internal bore (i.e. lumen) that extends along the needle axis, and through which injectant can pass from the inlet to (each of) the one or more outlets. The needle (and needle axis) (and bore) may extend along a substantially straight line, or may be curved or bent. For example, the needle may be manufactured as a straight or curved needle and/or may bend in use.

In use, injectant may pass into the bore through the inlet, axially through the bore from the inlet (proximal) end to the outlet (distal) end, and out of (each of) the one or more outlets, e.g. into an injection target, such as tissue. In particular embodiments, as will be discussed in more detail below, injectant passes out of each of plural outlets while the needle is being oscillated by the oscillator.

The inventors have found that when injectant is injected into tissue using conventional injection devices, it can be difficult to control the resulting distribution of injectant in the tissue. For example, they have found that injectant may sometimes travel back up the needle track. This can be a particular problem for injections where controllable injectant distribution is desirable, such as in the case of injecting nanoparticle radiosensitisers prior to radiotherapy, where it is desirable that the nanoparticles are distributed uniformly throughout the target tumour, e.g. so that the efficacy of the subsequent radiotherapy is enhanced.

As will be discussed in more detail below, the inventors have found that providing an oscillating needle from which injectant can be emitted as a result of a combination of pressure generated by an injectant supply device and oscillations can improve injectant distribution and controllability.

The one or more outlets may be a plurality of outlets, i.e. the needle may include a plurality of outlets.

Thus, according to an aspect, there is provided an injection device comprising: a needle; and an oscillator coupled to the needle and configured to oscillate the needle; wherein the needle includes an inlet and a plurality of outlets.

As will be discussed in more detail below, the inventors have found that providing an oscillating needle assembly with a plurality of injectant outlets can improve injectant distribution and controllability.

These aspects and embodiments can, and in embodiments do, include one or more, and in an embodiment all, of the features of other aspects and embodiments described herein, as appropriate. For example, the injection device may comprise an injectant supply device configured to supply injectant to the inlet of the needle such that injectant is emitted from some or all of the plurality of outlets of the needle while the oscillator oscillates the needle.

The needle may include a bore. The bore (i.e. lumen) may extend along an (longitudinal) axis of the needle between an inlet (proximal) end of the needle and an outlet (distal) end (i.e. tip) of the needle. The bore may be configured such that injectant can pass from the inlet to (each of) the one or more (such as plurality of) outlets.

The bore may extend axially along the needle to the inlet end to form the inlet at the inlet end of the needle, e.g. such that injectant can pass axially through the inlet and into the needle. The needle may thus be open at the inlet end.

The bore may extend axially along the needle to the outlet end to form an outlet of the one or more outlets at the outlet end, e.g. such that injectant can pass axially through the outlet and out of the needle at the outlet end. Thus, the bore may extend along the entire axial length of the needle to form the inlet at the inlet end and an axial outlet at the outlet end. The needle may thus be open at the outlet end. In this case, the one or more (such as plurality of) outlets may include one or more axial outlets at the outlet end and optionally one or more (such as a plurality of) other outlets proximate to (i.e. spaced axially away from) the outlet end of the needle.

Alternatively, the needle may be closed at the outlet end. In this case (each of) the one or more (such as plurality of) outlets may be provided proximate to (i.e. spaced axially away from) the outlet end of the needle.

An (each) outlet of the one or more (such as plurality of) outlets that is proximate to (i.e. spaced axially away from) the outlet end of the needle may comprise a passage through the needle through which injectant can pass (from the bore and) out of the needle. Such a passage may extend in a direction that has a least a component in a radial direction (perpendicular to the needle axis), e.g. as opposed to a conventional needle tip outlet through which injectant can pass axially.

Thus, a (and optionally each) outlet of the one or more (such as plurality of) outlets that is proximate to (i.e. spaced axially away from) the outlet end of the needle may be a radial outlet configured to allow injectant to pass out of the needle radially (in a radial direction) through the shaft or tip. A radial outlet may extend from an opening in a radially interior surface of the needle to an opening in a radially exterior surface of the needle.

Embodiments of the present invention extend to the idea of an oscillating needle with at least one radial outlet.

Thus, according to another aspect, there is provided an injection device comprising: a needle extending along an axis; and an oscillator coupled to the needle and configured to oscillate the needle; wherein the needle includes an inlet and one or more radial outlets configured to allow injectant to pass out of the needle radially through the needle.

These aspects and embodiments can, and in embodiments do, include one or more, and in an embodiment all, of the features of other aspects and embodiments described herein, as appropriate. For example, the injection device may comprise an injectant supply device configured to supply injectant to the inlet of the needle such that injectant is emitted from the one or more radial outlets of the needle while the oscillator oscillates the needle.

A (and optionally each) radial outlet may comprise a hole through the shaft of the needle. A (and optionally each) radial outlet may comprise a hole through the tip of the needle.

The needle may comprise a plurality of radial outlets (holes) that may be arranged circumferentially spaced around the needle and/or axially (longitudinally) spaced along the needle.

The radial outlets (holes) may be regularly spaced, such as substantially equidistantly spaced circumferentially around the needle and/or axially along the needle.

For example, the radial outlets (holes) may be helically spaced around the needle and/or the needle may comprise one or more rows of radial outlets (holes), with the radial outlets (holes) in a row of radial outlets being provided at substantially the same circumferential position, and optionally equidistantly spaced axially along the needle. The needle may comprise plural such rows of radial outlets (holes), with the rows optionally being equidistantly spaced circumferentially around the needle.

Alternatively, the radial outlets (holes) may be irregularly, such as randomly, spaced (circumferentially and/or axially).

A (each) hole may be formed by drilling or laser cutting. The needle may be formed of an impermeable material, such as stainless steel, titanium, nitinol (nickel titanium), or glass, e.g. quartz.

Additionally or alternatively, the needle may comprise at least a region formed of a porous (permeable) material, such as sintered metal. In this case a (each) radial outlet may comprise a pore (or pores) of the porous material. In these embodiments, radial outlets may have a substantial random distribution.

The oscillator (e.g. transducer) may comprise one or more vibratory materials, such as a piezoceramic or a piezocrystal material. The oscillator may comprise one or more electrodes configured such that application of one or more (AC) voltages (e.g. by a voltage supply of the oscillator) causes the vibratory material(s) to vibrate.

The oscillator may oscillate the needle axially, i.e. along the needle axis. The oscillator may oscillate the needle torsionally, i.e. about the needle axis.

The oscillator may be configured to oscillate the needle at any suitable frequency. The oscillator may be configured to oscillate the needle at a resonant frequency. The oscillator may be configured to oscillate the needle with ultrasonic frequencies, e.g. > 20 kHz, such as in the range 20 kHz and 70 kHz, such as in the range 40 kHz to 60 kHz, such as about 50 kHz.

The oscillator may be configured to oscillate the needle at any suitable amplitude. The oscillator may be configured to oscillate the needle with (e.g. axial) amplitudes in the range 0.1 to 50pm, and/or < 20pm, such as < 3pm, such as < 2pm. The (e.g. axial) amplitude may be less than or equal to a maximum value selected to reduce or avoid cavitation, such as < 20pm, such as < 3pm, such as < 2pm. The amplitude (maximum) may be selected based on viscosity of the injectant. For example, a larger amplitude (maximum), e.g. < 20pm, may be selected for a relatively viscous injectant, and a smaller amplitude (maximum), e.g. < 3pm, may be selected for a relatively non-viscous injectant. The oscillator may be directly coupled to the needle, e.g. by a weld, adhesive, screw fitting, push fit, snap fit, bayonet fitting or another other suitable connection. The connection may be other than (not) a crimp style connection.

The oscillator may be indirectly coupled to the needle, e.g. by one or more intermediate components, such as a by a hub. The hub may be configured (e.g. may have a suitable shape) to convert axial (longitudinal) vibrations of the oscillator to axial (longitudinal) and/or torsional vibration of the needle.

The hub may generally have the form of a horn. The hub may include one or more generally spiral or helical ridges and/or slits on an outer surface, such that axial vibrations of the oscillator are converted to axial and/or torsional vibration of the needle.

The needle may be removably coupled to the oscillator. For example, the needle may be attached to a boss which is removably connectable to the hub or the oscillator, e.g. by a screw fitting, bayonet fitting or another other suitable connection.

The injectant supply device and/or the oscillator is configured such that injectant can be emitted from the needle while the oscillator is oscillating the needle.

The injectant supply device may comprise an injectant reservoir. The injectant supply device may comprise an injectant expelling device configured to expel injectant from the injectant reservoir, such as a piston or plunger. The injectant expelling device may be furthermore configured to cause the injectant reservoir to be filled with injectant.

The injectant supply device may (further) comprise one or more conduits connecting the injectant reservoir to the inlet of the needle such that injectant in the reservoir can be supplied to the inlet via the one or more conduits.

The injectant supply device may comprise a syringe in fluid communication with the inlet of the needle.

The injectant supply device (e.g. syringe) may be configured to supply injectant to the inlet of the needle via one or more ports arranged in the oscillator and/or the hub, e.g. in a radially outer side of (a housing of) the oscillator and/or the hub. The injectant supply device may be configured to supply injectant to the inlet of the needle via one or more axial bores arranged in the oscillator and/or the hub. The reservoir and/or injectant expelling device and/or conduit may be arranged within (a housing of) the oscillator and/or the hub. The injectant supply device may thus be integral with the oscillator and/or the hub.

The oscillator may be configured to oscillate the reservoir, e.g. to thereby sonicate injectant in the reservoir.

The injectant may comprise liquids, mixtures, colloids, nano-colloids, suspensions, dispersions, emulsions, active agents, pharmaceuticals, fillers, or radiosensitizers, etc..

A retractable sheath may surround the needle. The retractable sheath may be configured to cover one or more, such as all, of the one or more (such as plurality of) (e.g. radial) outlets so as to prevent injectant being emitted therefrom. Retraction of the retractable sheath may allow injectant to be emitted from a (e.g. radial) outlet.

The (needle of the) injection device may comprise a plurality of (sub- )needles, each (sub-)needle having one or more outlets (e.g. as described above). The oscillator may be configured to oscillate the plurality of (sub-)needles. The plurality of (sub-)needles may share a common injectant inlet. The injectant supply device may be configured to supply injectant to the common inlet such that injectant is emitted from the (plural) outlets of the plurality of (sub-)needles while the oscillator oscillates the plurality of needles. Needles of the plurality of (sub- )needles may be controllable between a radially retracted configuration, and a radially extended configuration.

According to an aspect, there is provided a method of operating the injection device described above, the method comprising causing injectant to be emitted from the needle(s) through the one or more (e.g. plurality of) outlets while the oscillator oscillates the needle(s).

According to an aspect, there is provided a method of injecting an injectant into an injection target, the method comprising: inserting the needle(s) of the injection device as described above into the injection target; and causing injectant to be emitted from the needle(s) through the one or more (e.g. plurality of) outlets while the oscillator oscillates the needle.

The method may comprise the oscillator oscillating the needle(s) at an ultrasonic (e.g. > 20 kHz) and/or resonant frequency. The method may comprise rotating and/or withdrawing the needle(s) while causing injectant to be emitted from the needle(s). The needle may be rotatable (e.g. by a user), and/or configured to rotate (e.g. by a motor).

The method may comprise retracting a (the) retractable sheath that surrounds a (the) needle while causing injectant to be emitted from the needle, e.g. so as to sequentially uncover each outlet of a (the) plurality of outlets arranged along the needle.

BRIEF DESCRIPTION OF THE DRAWINGS

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

Figure 1A shows schematically a needle that may be used to inject injectant into a lesion or tumour, Figure 1B shows schematically a needle being used to inject injectant into a lesion or tumour, and Figure 1C shows schematically a needle being used to inject injectant into a lesion or tumour in accordance with embodiments of the present invention;

Figure 2 shows schematically an injection device in accordance with embodiments of the present invention;

Figure 3 shows schematically a needle in accordance with embodiments of the present invention;

Figure 4A shows schematically a needle being used to inject injectant into a lesion or tumour in accordance with embodiments of the present invention, Figure 4B shows schematically a needle being used to inject injectant into a lesion or tumour in accordance with embodiments of the present invention, and Figure 4C shows schematically a needle being used to inject injectant into a lesion or tumour in accordance with embodiments of the present invention;

Figure 5 shows needle tip configurations in accordance with embodiments of the present invention;

Figure 6 shows schematically a needle in accordance with embodiments of the present invention;

Figure 7A shows a needle in accordance with embodiments of the present invention, Figure 7B shows a needle in accordance with embodiments of the present invention, and Figure 7C shows a needle in accordance with embodiments of the present invention; Figure 8A shows schematically a needle being used to inject injectant into a lesion or tumour in accordance with embodiments of the present invention, Figure 8B shows schematically a needle being used to inject injectant into a lesion or tumour in accordance with embodiments of the present invention, and Figure 8C shows schematically a needle being used to inject injectant into a lesion or tumour in accordance with embodiments of the present invention;

Figure 9A shows schematically a needle being used to inject injectant into a lesion or tumour in accordance with embodiments of the present invention, Figure 9B shows schematically a needle being used to inject injectant into a lesion or tumour in accordance with embodiments of the present invention, and Figure 9C shows schematically a needle being used to inject injectant into a lesion or tumour in accordance with embodiments of the present invention;

Figure 10 shows schematically a connection mechanism of an injection device in accordance with embodiments of the present invention;

Figure 11 shows schematically an injection device in accordance with embodiments of the present invention;

Figure 12 shows schematically an injection device in accordance with embodiments of the present invention;

Figure 13 shows schematically an injection device in accordance with embodiments of the present invention;

Figure 14 shows schematically an injection device in accordance with embodiments of the present invention;

Figure 15A shows schematically an injection device in accordance with embodiments of the present invention, Figure 15B shows schematically an injection device in accordance with embodiments of the present invention, and Figure 15C shows schematically an injection device in accordance with embodiments of the present invention;

Figure 16A shows injectant emerging from an injection device without oscillations being applied, and Figure 16B shows injectant emerging from the injection device with oscillations being applied in accordance with embodiments of the present invention;

Figure 17A shows an injectant distribution resulting from injection by an injection device without oscillations being applied, and Figure 17B shows an injectant distribution resulting from injection by the injection device with oscillations being applied in accordance with embodiments of the present invention; and Figure 18A shows tissue staining resulting from injection by an injection device without oscillations being applied, and Figure 18B shows tissue staining resulting from injection by the injection device with oscillations being applied in accordance with embodiments of the present invention.

DETAILED DESCRIPTION

Needle-based injection is a common method of administering a liquid, especially a drug, into the body. As shown in Figure 1A, in these methods, a needle 10 is used to introduce an injectant into a tissue, such as a lesion or tumour.

In many cases, the effectiveness of the injection, and therefore of the treatment, relies on the distribution of the injectate media (injectant) in the tissue, e.g. tumour.

For example, radiotherapy is an effective cancer treatment, as it can be targeted on a tumour. However, radiotherapy relies on the presence of oxygen to generate cell killing free radicals, meaning that aggressive oxygen deficient (hypoxic) tumours cannot be treated without unacceptable off-target toxicity. Recently, nanoparticles have begun to be used as radiosensitisers to enhance the efficacy of radiotherapy treatment.

However, with direct intratumoral injection, it is difficult to know how far from the needle tip the nanoparticles disperse into the tumour, since as illustrated by Figure 1B, some of the injectate media usually travels back up the needle track. Furthermore, conventional injections provide little control of the distribution of the nanoparticles within the tumour.

Various embodiments provide an injection device in which high-frequency (in particular ultrasound) microscopic axial and/or torsional vibrations are induced in a needle 10 while injectant is emitted from the needle 10. This has been found to allow augmented distribution of the injectate media (injectant) in tissues, including tumours.

The vibrations may be induced at ultrasounds frequencies, such as 20 kHz up to around 60 kHz, thereby producing the small vibrations with an amplitude of around 0.1 to 50pm, such as < 20pm, such as < 3pm, such as around 2pm. These vibrations may aid needle insertion through reduced penetration forces and improved visibility, e.g. under ultrasound guidance. Moreover, as illustrated by Figure 1 C, it has been found that these vibrations have the effect of projecting the injectate media away from the needle tip. This phenomenon, essentially atomization of fluid or injectate media at the surface of the needle tip or exit hole, may be based on capillary wave dynamics, cavitation, or both, depending on the operating frequency (Hz) and energy intensity (W/m²). The inventors have found, however, that limiting oscillation amplitude, e.g. to < 3pm, can avoid the occurrence of cavitation, which could otherwise result in high pressures and temperatures, and thus tissue damage.

As illustrated by Figure 1 C, the vibrations can result in improved dispersion in the target area, and e.g. significantly less injectate media travelling back up the needle track. This can allow improved confidence that a desired quantity of injectate media is delivered to the desired target, e.g. tumour. This can then facilitate, for example, an improvement in treatment efficacy, or a smaller and/or more controlled injectant dose to be delivered to the target without degrading treatment efficacy.

Figure 2 shows an injection device 100 according to various embodiments. As shown in Figure 1A, the injection device 100 includes a needle 10 and an oscillator in the form of a transducer 20. The needle 10 is coupled to the transducer 20 such that oscillations generated by the transducer 20 cause the needle 10 to oscillate. In the present embodiment, the transducer 20 is an ultrasonic transducer, and thus can cause the needle to oscillate with ultrasonic frequencies, e.g. > 20 kHz, such as in the range 40 kHz to 60 kHz, such as about 50 kHz. A resonant frequency may be selected.

In the present embodiment, the needle 10 is coupled to the ultrasonic transducer 20 via a hub 30. However, in other embodiments the needle 10 may be directly coupled to the transducer 20. The hub 30 is attached to the transducer 20, and the needle 10 is then attached to the hub 30, such that oscillations generated by the transducer 20 cause the hub 30 to oscillate, which in turn cause the needle 10 to oscillate.

According to various particular embodiments, the inventors have furthermore found that combining (in particular ultrasonic) vibrations with multioutlet needle designs can unexpectedly further improve the dispersion of injectate media, thereby allowing coverage of the entire target area, including the area around the needle. Figure 3 shows a cross-sectional view of the needle 10 of the present embodiment. As illustrated in Figure 3, the needle 10 comprises a tubular shaft (i.e. cannula) 14 that extends along an (longitudinal) axis 11 between an inlet end 12 and an outlet end (tip) 13. The tubular shaft 14 has a bore (i.e. lumen) 15 that extends along most or all of the axial length of the shaft 14 to form an injectant inlet 16 at the inlet end 12 and an injectant outlet 17 at the outlet end 13. In the present embodiment, the outlet end 13 of the shaft 14 has a sharp point formed by a bevel. Figure 3 illustrates a straight needle, but a curved needle would be possible.

As shown in Figure 3, the needle 10 includes at least one further outlet, which in the present embodiment is in the form of a hole 18 that passes radially through the shaft 14. As described further below, the needle 10 may include plural such further outlets.

In use, injectant passes axially through the inlet 16, axially through the bore 15 from the inlet end 12 to the outlet end 13, and axially out of the axial outlet 17 and radially out of the radial outlet 18, and e.g. into tissue, while the transducer 20 vibrates the needle 10 axially and/or torsionally.

As illustrated by Figures 4A to 4C, various multi-hole configurations are contemplated, and in each case augmented injectant distribution may be achieved. For example, the needle 10 may be a needle with multiple outlet holes around the circumference of the needle, and/or a needle with multiple outlet holes around the needle tip 13 (e.g. in case of a trocar tip).

For example, in the arrangements of Figures 4A and 4B an outlet hole 18 passes through the needle shaft 14 in a radial direction. Figure 4A shows a row of four such holes that are spaced axially along the shaft 14, and Figure 4B shows two such rows of holes, with each row of holes being spaced circumferentially around the shaft 14. Other numbers of holes and hole spacings would be possible.

In the arrangement of Figure 4C, an outlet hole 18 passes through the needle tip 13, in a direction that has radial and axial components. Figure 4C illustrates four such holes spaced circumferentially around the needle tip 13. Again, other numbers of holes and hole spacings would be possible.

The needle 10 may include a combination of a multi-hole configuration and other tip profiles, including open-ended or closed-ended tips. For example, as illustrated in Figure 5, the tip could be a blunt tip with a chamfered edge (Figure 5A), a spherical tip (Figure 5B), a lancet point tip (Figure 5C), a closed pencil pint (Figure 5D) or a trocar tip (Figure 5E). Various other multi-outlet needle designs are contemplated. For example, as shown in Figure 6, the needle design may include a combination or plurality of needles (sub-needles) that share a common single inlet 12. As illustrated in Figure 6, needles of the plurality of needles may be flexible and controllable to flex from a radially retracted (“stowed”) configuration in which outlets at the needle tips 13 are directed substantially axially, e.g. for the purposes of target entry, to a radially extended (“deployed”) configuration in which (at least some of the) outlets at the needle tips 13 are directed in a radial direction, e.g. for the purposes of injectate delivery. This may have the effect of broadening the distribution of injectate within the target tissue.

In another example, a region (or all) of the needle shaft and/or tip may be formed from a porous material, such as sintered metal. In this case, pores in the porous material may function as injectant outlets. For example, some or all of the needle shaft 14 may comprise a sintered metal tube that is permeable to injectant.

Figures 7A to 7C illustrate various multi-hole configurations in more detail. Figures 7A to 7C show embodiments in which the needle 10 includes an axial inlet 16, an axial outlet 17 at the needle tip 13 (which in this case is a lancet point tip), and one or more (in this case, a plurality of) radial outlet holes 18 proximate to the tip 13. In these embodiments, the needle 10 is formed from stainless steel, with holes formed through the needle shaft 14 by laser cutting. However, other materials, such as glass, and hole forming methods, such as drilling, would be possible.

In these embodiments, the holes are arranged regularly in one or more rows of one or more holes. For example, Figure 7A shows an embodiment having a single row of holes 18A-E, Figure 7B shows an embodiment having two rows of holes 18A-E, 18’A-E, and Figure 7C illustrates an embodiment having four rows of holes 18A-E, 18’A-E, 18”A-E, 18”’A-E (some not shown).

In these embodiments, the holes of a row of holes have substantially the same circumferential position, and are equidistantly spaced axially along the needle shaft 14. As shown in Figures 7B and 7C, rows of holes may be equidistantly spaced circumferentially around the needle shaft 14. As shown in Figures 7A to 7C, each row of holes in these embodiments includes five holes. However, other numbers of holes and hole spacings would be possible. Moreover, other arrangements, such as helically arranged holes, and/or irregular (e.g. random) hole spacings (circumferentially and/or axially) would be possible. The needle dimensions, hole dimensions, and hole configuration may be selected based on properties of the injection target and injectant, e.g. so as to facilitate injection of the injectant into the injection target. For example, the needle 10 may have a total axial length in the range 5 to 30 mm, such as about 20mm. The outer diameter of the needle 10 may be in the range 0.1 to 4 mm, such as about 1mm. The bore diameter (inner diameter) may be in range 0.05 to 3mm, such as about 0.25mm. The axial distance between the needle tip and hole nearest to the tip may be in the range 1mm to 5mm, such as about 4mm. An axial spacing between adjacent holes may in the range 0.5 to 5mm, such as about 1mm. A hole may be substantially cylindrical with a diameter in the range 0.01 to 0.5mm, such as about 0.05mm.

In general, the needle 10 may comprise a first end, or proximal end 12, which may be connectable to an injectant supply device, and a second end, or distal end 13, through which the injectant is expelled. The proximal end 12 and the distal end 13 of the needle may be joined by an elongate body portion 14 incorporating a lumen 15. The distal end 13 of the needle 10 comprises a plurality of delivery outlets 17, 18 which are in fluid communication with the lumen 15. The distal end 13 of the needle 10 may be closed or open.

The delivery outlets 17, 18 may be formed by an arrangement of holes which pierce the wall of the needle body. The holes may be circular in crosssection, ovular or any other shape, to allow the passing of the injectant therethrough.

In a traditionally used medical injection devices, the delivery medium (injectant) is expelled from the distal end of the device, provided by a single opening. The plural delivery outlets 17, 18 of the present embodiments facilitate delivery of the injectant through multiple openings, which in turn, can provide a more even distribution of the injectant into the target area, e.g. as opposed to a concentrated delivery resulting from traditionally used delivery devices.

As illustrated by Figure 8, during operation, a user may rotate or move the needle 10 back and forth manually or with the help of a motorised stage (e.g. in the case of automated injection), or may simply withdraw the needle 10 while infusing or injecting to further improve dispersion in the target, e.g. tumour.

As illustrated by Figure 9, the needle assembly may also include a sheath or a cover 50. The sheath 50 may be retractable, and may be used to cover the exterior surface of the needle 10. This may protect the delivery outlets 17, 18 from being blocked or obstructed by tissue or other particles which may come into contact with the needle 10 during entry into the target.

As illustrated in Figure 9A, the sheath 50 may be configured to be inserted into the target in combination with the needle 10. Once inserted, the sheath 50 may be pulled back to expose the delivery outlet or outlets 17, 18 of the needle 10, thus allowing free flow of the injectant to the target. As illustrated in Figures 9A to 9C, the sheath 50 may be configured to expose the holes 17, 18 (in the case of a multihole needle configuration) sequentially, e.g. to maintain the injection pressure to allow for maximum coverage inside the target, e.g. tumour.

Figure 10 shows schematically detail of the injection device 100 according to various embodiments. Figure 10 illustrates a hub or horn 30 that the needle (not shown) may be coupled to the ultrasonic transducer 20 via.

The transducer 20 may include a rear mass 21, and a front mass 22, separated by a vibratory material 23. To generate the high frequency vibrations, any suitable vibratory material may be used, such as a piezoceramic or a piezocrystal material. The material 23 may have any suitable shape and size, e.g. comprising one or more rings and/or plates, or bars. In response to a stimulus, such as electricity at a defined frequency, e.g. applied to an electrode 24, the (vibratory material 23 of the) transducer 20 may vibrate/resonate the needle 10 at a desired frequency.

Although Figure 10 shows the vibratory material 23 being used in combination with metal masses 21 , 22, it would instead be possible to use the vibratory material 23 in a standalone form. Thus, the vibratory material 23 may be attached to the needle 10 itself. In these embodiments, the vibratory material 23 may be attached to the needle 10 via a medium, such as a sonically transmissive adhesive, or weld.

As also shown in Figure 10, the hub (or horn) 30 may be configured to amplify the vibration amplitude. The front mass 22 of the transducer 20 and/or the hub 30 may be designed with angular slits, e.g. configured to produce vibrations in an axial (longitudinal), torsional or a combination of axial and torsional mode of vibration. In particular, the transducer and/or hub 30 may have a slitted horn design, configured to convert axial (longitudinal) vibrations at the front mass 22 to axial (longitudinal) and/or torsional vibration at the face of the hub/horn 30.

In various embodiments, the interface(s) between the various components is designed to achieve good physical and acoustic coupling. Figure 11 illustrates an embodiment in which the needle 10 is attached directly to the transducer’s front mass or hub 30, e.g. using an adhesive or a welding technique. In this embodiment, the injectant supply device comprises a syringe 60 and tube 61 connected to a side port 40 located on the transducer’s front mass or horn 30. In this case injectate media (injectant) initially held in the syringe 60 may be introduced to the needle 10 via the side port 40.

Figure 12 illustrates an embodiment in which the needle 10 is removably attached to the hub 30. As shown in Figure 12, to facilitate this, the needle 10 is attached to boss 120 (e.g. using an adhesive or a welding technique), and the boss 120 is removably attached to the hub 30 by means of a screw fitting. Other connection methods, such as a bayonet fitting, are also possible. This facilitates convenient needle replacement, e.g. without having to replace the entire hub. As shown in Figure 12, in this embodiment, an O-ring 121 may provide a seal between hub 30 and boss 120 to prevent leakage of injectate media. The hub 30 may be attached to the transducer 20 by means of a screw 122. Again, other connection methods are possible. Figures 13 to 15 show alternative embodiments in which the injection device 100 includes an integral injectant supply device. These arrangements can reduce dead volume, e.g. as compared to the arrangement of Figures 11 and 12, thereby improving injection efficiency. As shown in Figures 13 to 15, the injection device 100 in these embodiments generally comprises a needle 10, a transducer portion 20 and a hub portion 30.

As shown in Figures 13 and 14, an injectant reservoir 80 may be provided within a housing of the hub 30. The reservoir could alternatively be provided within the transducer 20. In these embodiments, the injectate media may be dispensed from the reservoir 80 (and/or the reservoir 80 may be filled with injectate media) with the help of air pressure or hydraulic pressure and/or a plunger e.g. passing through the transducer 20. A reservoir 80 with good acoustic coupling with the ultrasonic device may help with sonicating and/or mixing ingredients of the drug, and/or with reducing loss of drug to dead space. Thus, the reservoir 80 may be filled with injectate media that has not been subjected to a mixing/sonication step, and appropriate mixing/sonication may be achieved by the transducer 20 inducing (ultrasonic) oscillations in the injectant reservoir 80.

Figure 13 shows an embodiment in which (positive) air pressure provides the force necessary to deliver an injectant through the hub 30 and needle 10, to the target. In this arrangement, the hub 30 may have an opening in its outer wall, into which an air delivery device 81 may be connected. The air delivery device 81 is shown in Figure 12 as a canister, however, the supply may be suitable supply such as for example a tube. The tube may be connected to an air delivery device such as a pump, compressor or pressurised canister separate to the injection device. In embodiments, a negative air pressure (vacuum) may provide the force necessary to fill the reservoir 80.

Figure 14 shows an embodiment in which the injection device comprises a plunger mechanism, which e.g. may comprise a plunger cap 83 and a plunger end 84 connected by an elongate shaft 85. The shaft 85 may pass through the central (longitudinal) axis of the transducer 20. The plunger may be actuated by pushing the plunger cap 83 towards the needle 10. The movement of the plunger cap 83 causes corresponding movement of the plunger end 84 towards the needle 10. The plunger end 84 may be located within the bore of the hub 30 such that as the plunger end 84 moves towards the needle 10, any delivery medium (injectant) within the hub 30 is pushed into the lumen 15 of the needle 10 where it may be delivered to the target.

The operation of the plunger may be reversed to fill the injection device with injectant. The plunger cap 83 may be pulled axially away from the needle 10, where the pulling creates an area of negative pressure within the hub 30. The distal end of the needle 10 may be submerged in injectant as the negative pressure is created within the hub 30, such that the injectant is drawn through the outlet(s) 17, 18, along the lumen 15 and into the hub 30, thereby filling the hub reservoir 80 with injectant.

The movement of the plunger may optionally be automated. The plunger cap 83 may alternatively be located at the hub 30 such that the shaft does not pass through the transducer 20.

In some embodiments, the reservoir 80 may be in the form of a pre-filled capsule provided in the hub 30 of the injection device 100. The capsule may be pre-filled and sealed to contain the delivery medium (injectant). An internal cavity of the hub 30 may provide at least one sharp point, such that when the capsule containing the delivery medium is pushed against the sharp point e.g. by means of actuation of the injection mechanism, the capsule seal is broken, allowing the delivery medium therein to be released into the needle 10.

Figures 15A and 15B illustrate embodiments in which, for the purpose of mechanical attachment and transmission of ultrasonic vibration from the transducer 20 to the hub 30 or reservoir, or from the hub 30 to the reservoir, the attachment(s) is via threaded engagement.

As illustrated in Figure 15A, the hub 30 or reservoir may have a thread on an inner surface, with the transducer 20 having a corresponding thread on an outer surface. Or, as illustrated in Figure 15B, the hub 30 or reservoir may have a thread on an outer surface, with the transducer 20 having a corresponding thread on an inner surface. Thus, the connection arrangement between the hub 30 and the transducer 20 may comprise a male connection member and a female connection member, configured to mate with each other. The female connection member may be an externally threaded portion which corresponds to an internally threaded male portion. The female connection member may be an internally threaded portion which corresponds to an externally threaded male portion.

As illustrated by Figure 15C, transmission of ultrasonic vibration may also be achieved with the help of one or more free-masses 91 between the contact surfaces. A free mass may be constrained between the hub 30 and the transducer 20. In this configuration, the transducer 20 does not need to be directly connected to the needle 10. The free mass 91 may be constrained in space between the transducer 20 and the hub 30 such that repeated impact from the transducer 20 causes the needle 10 and hub 30 to vibrate.

Experiments were conducted to compare injection with and without ultrasonic oscillations applied to a multi-outlet needle. A stainless-steel needle having a design substantially as described above with refence to Figure 7 was coupled to an ultrasonic transducer operable to induce longitudinal oscillations in the needle at a resonant frequency, with an amplitude of < 3pm (e.g. to avoid cavitation), and injections with the ultrasonic transducer powered on and off were compared.

Figure 16A shows injectate media emerging from the multiple outlets of the multi-outlet needle without ultrasonic oscillations being applied to the needle, and Figure 16B shows injectate media emerging from the multiple outlets of the same multi-outlet needle with longitudinal ultrasonic oscillations being applied to the needle. A comparison of Figures 16A and 16B shows that the application of ultrasonic oscillations results in injectate media emerging from the needle outlets with greater radial and/or axial kinetic energy. It is moreover believed that the combination of axial oscillation and radial outlets improves energy transfer and dispersion, e.g. as compared to oscillation of a conventional needle that does not have radial outlets. Figure 16B, in particular, demonstrates the formation of turbulent (mushroom cloud-like) flows in the vicinity of the axial and radial outlets.

Figure 17 demonstrates the effect of this on overall injectate distribution. Figure 17A shows an injectate media distribution from the multi-outlet needle without ultrasonic oscillations being applied to the needle, and Figure 17B shows an equivalent injectate media distribution from the same multi-outlet needle with longitudinal ultrasonic oscillations being applied to the needle during injection. As can be seen by comparing Figures 17A and 17B, the application of ultrasonic oscillations during injection using the multi-outlet needle results in a broader and more even (symmetrical) distribution of injected injectate media (particularly in the radial direction). The inventors have observed acoustic streaming induced by the ultrasonic oscillations, and it is believed that the observed improvements in injectant dispersion can be linked to such acoustic streaming.

Figure 18 illustrates the results of mice tumour staining. Figure 18A shows the results of mice tumour staining using the multi-outlet needle without ultrasonic oscillations being applied to the needle, and Figure 18B shows the results of mice tumour staining using the same multi-outlet needle with longitudinal ultrasonic oscillations being applied to the needle during injection. A comparison of Figures 18A and 18B demonstrates that the application of ultrasonic oscillations during injection using a multi-outlet needle results in improved tissue penetration and staining.

Although the above has been described with particular reference to injecting a radiosensitiser for radiotherapy purposes, any suitable injectant may be used such as, liquids, mixtures, colloids, nano-colloids, suspensions, dispersions, emulsions, active agents such as stem cells, virokines, pharmaceuticals or fillers. The purpose of the injectant may include, but is not limited to treating or preparing an area of a patient for treatment.

Although the present invention has been described with reference to preferred embodiments, it will be understood by those skilled in the art that various changes in form and detail may be made without departing from the scope of the invention as set forth in the accompanying claims.

Claims

1. An injection device comprising: a needle; and an oscillator coupled to the needle and configured to oscillate the needle; wherein the needle includes an inlet and a plurality of outlets.

2. The injection device of claim 1, wherein the needle comprises a tubular shaft extending between an inlet end and an outlet end, and the outlets include an outlet at the outlet end and one or more outlets proximate to the outlet end.

3. The injection device of claim 1 or 2, wherein the needle comprises a tubular shaft extending between an inlet end and an outlet end, the tubular shaft is closed at the outlet end, and the outlets are formed proximate to the outlet end.

4. The injection device of any one of the preceding claims, wherein the outlets include one or more outlets passing radially through the needle.

5. An injection device comprising: a needle extending along an axis; and an oscillator coupled to the needle and configured to oscillate the needle; wherein the needle includes an inlet and one or more radial outlets configured to allow injectant to pass out of the needle radially through the needle.

6. The injection device of any one of the preceding claims, wherein the outlets include one or more holes passing radially through a shaft or tip of the needle.

7. The injection device of any one of the preceding claims, wherein at least a region of the needle is formed from a porous material, and the outlets include one or more pores in the porous material.

8. The injection device of any preceding claim, wherein the oscillator is configured to oscillate the needle axially.

9. The injection device of any one of the preceding claims, wherein the oscillator is configured to oscillate the needle torsionally.

10. The injection device of any one of the preceding claims, wherein the oscillator is configured to oscillate the needle at a frequency of > 20 kHz.

11. The injection device of any one of the preceding claims, wherein the oscillator is configured to oscillate the needle with an amplitude less than or equal to a maximum value selected to reduce or avoid cavitation.

12. The injection device of any one of the preceding claims, further comprising a retractable sheath that surrounds the needle.

13. The injection device of any one of the preceding claims, wherein an injectant reservoir of the injection device is located within the oscillator; and/or wherein the needle is coupled to the oscillator via a hub, and wherein an injectant reservoir of the injection device is located within the hub.

14. The injection device of any one of the preceding claims, comprising a plurality of needles, wherein the oscillator is configured to oscillate the plurality of needles.

15. A method of operating the injection device claimed in any one of the preceding claims, the method comprising causing injectant to be emitted from the needle through the outlets while the oscillator oscillates the needle.

16. A method of injecting an injectant into an injection target, the method comprising: inserting the needle of the injection device as claimed in any one of claims 1 to 14 into the injection target; and causing injectant to be emitted from the needle through the outlets while the oscillator oscillates the needle.

17. The method of claim 16, further comprising the oscillator oscillating the needle at a frequency of > 20 kHz, and optionally with an amplitude of < 20pm.

18. The method of claim 16 or 17, further comprising rotating and/or withdrawing the needle while causing injectant to be emitted from the needle.

19. The method of claim 16, 17 or 18, further comprising retracting a retractable sheath that surrounds the needle while causing injectant to be emitted from the needle.

20. An injection device comprising: a needle including an inlet and one or more outlets; an oscillator coupled to the needle and configured to oscillate the needle; and an injectant supply device configured to supply injectant to the inlet of the needle such that injectant is emitted from the one or more outlets of the needle while the oscillator oscillates the needle.