WO2018015499A1

WO2018015499A1 - Needle-free skin piercing system and method

Info

Publication number: WO2018015499A1
Application number: PCT/EP2017/068383
Authority: WO
Inventors: Filip ANDREI; Eduard Matheus Johannes NIESSEN
Original assignee: Koninklijke Philips N.V.
Priority date: 2016-07-22
Filing date: 2017-07-20
Publication date: 2018-01-25

Abstract

A system for needle-free skin piercing comprises a removable head and a pressurizing system. The head comprises a body comprising a channel which comprises a distal opening at a distal end and a proximal opening at a proximal end. A filling port is for at least partially filling the channel with a liquid through a fill opening separate from the distal and proximal openings. The pressurizing apparatus is for applying pressure to the proximal 5 opening thereby to expel under pressure the liquid in the channel from the distal opening. The liquid may be used to pierce the skin for drawing blood or it may be used to administer a dose of a biological agent beneath the skin surface or it may be used for skin rejuvenation.

Description

NEEDLE-FREE SKIN PIERCING SYSTEM AND METHOD

FIELD OF THE INVENTION

This invention relates to needle-free systems for piercing skin, for example for drawing blood for testing or analysis, for injection, or for skin rejuvenation. BACKGROUND OF THE INVENTION

Presently, there are various devices and methods for drawing blood samples from patients that are commercially available. For example, regular measurement of blood glucose levels is necessary for monitoring the body's ability to metabolize glucose, particularly when it comes to diabetes management.

A typical blood sample collection apparatus usually involves a syringe comprising a hypodermic needle, a plunger, and a cylindrical barrel. When the needle punctures the skin, a suction force is generated as the plunger is pulled by the operator. Blood is then drawn by the suction force into the cylindrical barrel through a nozzle connected to the hypodermic needle. A blood lancet is another device that can be used for drawing a small amount of blood for diagnostic tests. A blood lancet includes a needle that is punctured into the ball of the finger, and a small amount of blood is allowed to freely drop onto a sample holder, such as a glass slide.

However, the applicability of these blood drawing devices are limited because they are usually not reusable, which could make the products expensive because multiple products are needed repeatedly in cases where constant monitoring is necessary. Importantly, this traditional blood drawing apparatus requires the use of a needle, which most patients would rather avoid if possible.

US 2015/0342509 discloses a system for needle-free drawing of blood. The device comprises a negative-pressure barrel with a membrane sealing an outlet aperture which is adapted to be placed in contact with the dermal tissue. The negative-pressure barrel defines a chamber. The device also includes an accelerator barrel positioned within the negative-pressure barrel chamber, with an open end aligned with the aperture. The chamber is filled with pressurized gas, and a particle positioned within the accelerator barrel is accelerated by an abrupt gas surge initiated by releasing a trigger valve. The particle thus attains enough momentum to pierce the aperture membrane and penetrates the adjacent dermal tissue. As a result, a micro-emergence of blood can be drawn into the negative- pressure barrel.

There is limited control of the blood drawing phase, in that it simply relies on a pressure difference between the outside and the inside of the chamber. The device also has limited control of the pressurizing phase. Furthermore, to provide a sterile solution, a single use device is proposed, which may be price prohibitive.

There are also known systems for needle-free injection. One area of interest for needle-free injection is for skin rejuvenation. The human skin is composed of three primary layers including the epidermis, the dermis and the hypodermis. The epidermis forms a waterproof, protective cover, which also serves as a barrier to infection. A major problem with known creams and lotions for skin care is that active ingredients for skin rejuvenation do not penetrate the epidermis effectively. While skin care creams provide a level of hydration to the epidermis, expensive active ingredients in high-end products provide little improvement to skin rejuvenation due to poor penetration into the deeper skin layers.

In particular, the skin of vertebrate animals, including that of humans, provides a substantial barrier to chemical permeation; the stratum corneum of the epidermis can be likened to a wall-like brick and mortar structure. The corneocytes of keratin comprise the bricks, while the lipid bilayers, fatty acids, cholesterol comprise the mortar. Within this application, needle-free skin piercing shall mean needle free penetration of a liquid at least through the stratum corneum of the epidermis. If the skin piercing depth extends at least to the dermis layer reaching the blood vessels in the skin, it could be used for blood drawing in a subsequent phase.

For skin rejuvenation, what would be of interest would be a system able to simultaneously provide fast and repetitive injection of liquid droplets containing one or more active ingredients into the skin for treating a large skin surface.

WO 2006/086742 discloses a needle-free injector for injecting a microstream containing a biologically active agent into an injection site. The needle-free injector comprises a microfluidic transport assembly configured to form a microfluidic flow path originating in a reservoir, and terminating at an external opening of an ejecting tube. The microfluidic transport assembly further includes valves in the form of parallel plates, wherein each plate includes holes to allow a contiguous microfluidic flow to the ejecting tubes that range in diameter from about 0.5 μηι to about 40 μηι. The fluid for the microstream is held in a reservoir, and is then passed to the ejecting tubes by a pressurizing arrangement. There is still a need for a system which enables low cost multiple injections or blood samples to be taken without risk of contamination.

SUMMARY OF THE INVENTION

The invention is defined by the claims.

According to examples in accordance with an aspect of the invention, there is provided a removable head assembly for a needle-free skin piercing system, comprising:

a body comprising a channel which comprises a distal opening at a distal end and a proximal opening at a proximal end;

a filling port for only partially filling the channel with a liquid through a fill opening separate from the distal and proximal openings, such that a first unfilled region remains adjacent the distal opening and a second unfilled region remains adjacent the proximal opening; and

pressurizing apparatus for applying pressure to the proximal opening thereby to expel under pressure the liquid in the channel from the distal opening.

In this arrangement, a liquid in a channel is ejected as a particle for piercing the skin, driven by an applied pressure, for example a gas pressure. By providing filling through an opening which is additional to the distal and proximal openings, the channel can be refilled for multiple skin piercing operations. These skin piercing operations may be performed as discrete individual events.

The liquid in the channel is part of the removable head assembly so that the remote pressurizing apparatus may be reused with multiple removable head assemblies. The liquid may be used simply to pierce the skin, or it may be a drug to be administered beneath the skin.

This design may be used to provide fast repetitive injection from a head assembly and also injection of multiple liquids with different active ingredients. The design may also be adapted to allow fast treatment based on local microinjection for large skin surfaces.

The fill opening may extend laterally into the channel. This means there is side filling of the channel, in the manner of a breach loader. This can be performed repeatedly.

The filling port is adapted to only partially fill the channel. The unfilled region at the distal end provides an acceleration path for the liquid particle to reach a desired velocity at which it can penetrate the outer layer of the skin. The or each channel for example has a diameter in the range 50 μηι to 200 μηι.

The body may comprise an array of channels, for example at least 25 channels, for example at least 100 channels, for example at least 1000 channels.

In one set of examples, the body comprises a first plate and a second plate arranged parallel to each other and spaced by a predetermined distance, arranged for receiving a liquid film between the first and second plates, wherein the proximal opening is in the first plate and the distal opening is in the second plate, thereby to define the channel between.

This design of removable head assembly enables a liquid particle to be formed as a portion of a liquid film that is blown out of a liquid film by an applied pressure.

The first and second plates may each comprise an array of openings, thereby to define an array of channels, for example at least 25 channels, for example at least 100 channels, for example at least 1000 channels. This enables multiple (micro) injections to take place, for example for skin rejuvenation. Each array of openings may comprise at least 25 openings, for example at least 100 openings, for example at least 1000 openings.

The removable head assembly may further comprise at least a third plate such that there is a number N of plates which define a number N- 1 of spacings for receiving different liquid films. The multiple liquid films for example may comprise different biological agents. Each liquid film may be present at locations aligned with some of the openings of the array and not present at locations aligned with others of the openings. In this way, different sets of injection sites may be defined for different films, and the pressure is only used to release a portion from one film at any given location. Thus, the full pressure is applied across a single film at any particular location, and different locations enable different agents to be injected.

First barrier regions may be formed between the first and second plates and second barrier regions may be formed between the second and third plates. These barrier portions each shield a set of openings, such as rows or columns, such that each liquid film is only present at some of the opening locations.

The removable head assembly may comprise part of a blood collection chamber. The particle is used to penetrate the skin and then allow a blood sample to be drawn. The blood sample may for example be drawn by applying suction using the pressurizing apparatus.

The removable head assembly may instead be part of a system for delivering a biologically active agent. The removable head assembly may instead be part of a skin rejuvenation system.

The removable head assembly may further comprise a reservoir for the liquid, the reservoir having an output which is connectable to the filling port, and a fluid delivery system for delivering the liquid from the reservoir to the filling port. This enables the liquid in the channels to be replenished after the liquid portions have been removed. The liquid may form the film by capillary action, so that a low pressure fluid delivery system is needed. The negative pressure created during piston retraction may be used as the fluid delivery system.

Examples in accordance with another aspect of the invention provide a pressurizing apparatus for a system for needle-free skin piercing, comprising:

a coupling interface adapted to removably couple the apparatus to a removable head assembly as defined above;

a pressurizing chamber having a release opening on a distal side, wherein the pressurizing chamber is adapted to apply a pressure to the removable head assembly thereby to expel under pressure the liquid in the channel of the removable head assembly.;

The apparatus preferably comprises a piston arranged to reciprocate in the pressurizing chamber; and

an electrically-controlled actuator coupled to the piston for controlling a reciprocating motion of the piston.

This apparatus is used to provide a pressure pulse for releasing a liquid from a channel to define a liquid particle which is used to pierce the skin.

The invention also provides a system for needle-free skin piercing comprising: a removable head assembly as defined above; and

a pressurizing apparatus as defined above.

The invention also provides a needle-free skin piercing method comprising: pressurizing a pressurizing chamber of a pressurizing apparatus during a skin piercing mode;

using a gas flow resulting from the pressurizing to expel a liquid portion from a channel within a removable head assembly; and

driving the liquid portion into the skin.

The method further comprises replenishing the channel from a filling port, wherein the channel is replenished laterally. Replenishing the channel comprises only partially filling the channel such that a first unfilled region remains adjacent a distal opening of the channel and a second unfilled region remains adjacent a proximal opening of the channel.

Pressurizing the pressurizing chamber may comprise using an electrically- controlled actuator to drive a piston of the pressurizing apparatus towards a distal side.

Expelling the liquid from the channel may comprise expelling a portion of a liquid film which is between a first plate and a second plate arranged parallel to each other, wherein the channel is defined between a proximal opening in the first plate and a distal opening in the second plate.

The method may comprise a cosmetic skin rejuvenation method, in particular a non-therapeutic cosmetic treatment method.

Alternatively, the method may comprises a blood drawing method. In this case the method may further comprise using the electrically-controlled actuator to drive the piston of the pressurizing apparatus away from release opening thereby depressurizing a

pressurizing chamber to draw blood.

BRIEF DESCRIPTION OF THE DRAWINGS

Examples of the invention will now be described in detail with reference to the accompanying drawings, in which:

Figure 1 is an example device for a needle-free blood drawing or injection system;

Figure 2 is a block diagram of a needle-free blood drawing or injection system with removable head;

Figure 3 illustrates some different channel designs;

Figure 4 illustrates a longitudinal section view of a needle-free injection system for injecting a liquid into a skin layer;

Figure 5 illustrates a side view of two parallel plates for containing a liquid film layer; Figure 6 illustrates a bottom view of a removable head assembly;

Figure 7 illustrates a side view of three parallel plates for containing two liquid film layers;

Figure 8 illustrates a top view of a second plate of three plates for containing a first liquid film layer; Figure 9 illustrates a top view of a third plate of three plates for containing a second liquid film layer;

Figure 10 is a flowchart illustrating a method of needle-free injection or blood drawing; and

Figure 1 1 is a flowchart illustrating a method of needle-free injection.

DETAILED DESCRIPTION OF THE EMBODIMENTS

The invention provides a system for needle-free skin piercing, having a removable head and a pressurizing system. The head comprises a body comprising a channel which comprises a distal opening at a distal end and a proximal opening at a proximal end. A filling port is for at least partially filling the channel with a liquid through a fill opening separate from the distal and proximal openings. The pressurizing apparatus is for applying pressure to the proximal opening thereby to expel under pressure the liquid in the channel from the distal opening.

The expelled liquid may be used to pierce the skin for drawing blood or it may be used to administer a dose of a biological agent beneath the skin surface or it may be used for skin rejuvenation.

The following are definitions of terms as used in the various embodiments of the present invention.

The terms "proximal" and "distal" as used herein refer to the upstream and downstream side of the needle-free blood drawing or injection device, respectively. These terminologies also indicate the direction of both the piston, fluid, or particle motion. As used herein, "fluid" refers to a liquid or gas.

The term "reciprocate" as used herein refers to an up-and-down or back-and- forth motion of the piston inside the pressurizing apparatus.

The term "micro-emergence" as used herein refers to the appearance of a small volume, preferably in microliters (μί), of blood or blood and interstitial fluid resulting from the piercing of the skin.

Figure 1 shows an example of a system for providing injection or for drawing a micro-emergence blood sample with a removable head. The device 10, preferably handheld, may be operated by a medical personnel or a patient. The device 10 is shown in simplified form for illustrating the form and dimensions. The cylindrical form of the device 100 is illustrated as a representative shape. Also, in terms of size, the device 10 is presented relative to the patient's arm 1 1. As shown in Figure 1, the device 10 comprises a pressurizing apparatus 16, a removable head assembly 12, aperture 14 and a power button 18.

Figure 2 is a block diagram of the device. Note that the sizes of the

components and their relative sizes are not necessarily shown to scale.

During operation, the distal end of the removable head 12 is positioned against the skin 22 of a subject from whom a blood sample is to be taken or to whom an injection is to be given.

As Figure 2 shows, the device 20 has an elongated form and comprises a proximal and a distal end. In addition, the orientation of the components is presented with respect to the proximal and distal sides of the device 20 and with respect to each other. The device 20 comprises the pressurizing apparatus 10 at the proximal side (the upper

component) and the removable head 12 at the distal side (the lower component). The pressurizing apparatus 10 and removable head 12 are connected by coupling elements and are separable such that a new removable head may be used with the same pressurizing apparatus 10. The pressurizing apparatus 10 comprises a pressurizing chamber 24 (labeled "C"), a piston 26 (labeled "P"), and an electrically-controlled actuator 28 (labeled "A"). The pressurizing apparatus may initially be sealed from the removable head by a puncturable membrane 23, which is ruptured in use. This may be part of the head or part of the pressurizing apparatus.

As shown in Figure 2, the removable head 12 comprises a body 30 which defines a channel 32 which comprises a proximal opening 34 at a proximal end and a distal opening 35 at a distal end. A filling port 36 is provided for at least partially filling the channel with a liquid. The liquid in the channel 32 may be replenished after use so that the removable head may be used many times in succession to the same patient.

In use, pressure from the pressurizing apparatus 10 is used to expel the liquid in the channel to form a liquid particle which is accelerates such that it can penetrate the skin 22.

The channel is filled from a lateral direction. Thus, there are three openings in fluid communication with the channel.

Figure 3A shows a most basic design. The channel 32 comprises a capillary tube formed within the body 30. The filling port 36 connects to a lateral filling channel which communicates with the inside of the channel 32 via a fill opening 36'.

Figure 3B shows an alternative design. The removable head 12 in this design comprises first and second plates 37, 38 parallel to each other and spaced by a predetermined distance. A liquid film 39 is received between the first and second plates. The first plate has the proximal opening 34 and the second plate has the distal opening 35, with the opening of the first plate aligned with the opening of the second plate. The channel 32 is thus formed between the top of the proximal opening 34 in the first plate 37 and the bottom of the distal opening 35 in the second plate 38.

In this design, instead of using a fill channel extending from the filling port to the fill opening, a film of liquid provides a fill opening circumferentially all around the channel. The liquid film is in fluid communication with the filling port 36.

In use, pressure from the pressurizing apparatus 10 is in this case used to separate the portion of the liquid film 39 which is between the openings 34, 35 to form a liquid particle.

The use of a fill opening for side filling, and which is thus additional to the distal and proximal openings, means that discrete particles can be formed. Once a liquid particle is formed and expelled, there is a high pressure in the channel coming from the pressurizing apparatus 10, but there is low pressure in the filling port channel which is connected to the lower pressure reservoir. Hence, additional liquid to that which was initially present in the channel is blocked from entering. Thus, instead of injecting a continuous jet, a discrete particle can be formed, in particular for example for skin piercing.

This discrete operation means that multiple injections may be performed with a pause in between. For skin rejuvenation applications, the interest is not in injecting a large volume into one spot, but rather very small volumes are desired in as many spots as possible.

Figure 3C shows that the channel 32 does not need to be completely filled with liquid. Instead, the channel is only partially filled such that a first unfilled region 40 remains adjacent the distal opening 35 and a second unfilled region 42 remains adjacent the proximal opening 34. This feature means that the channel acts as a barrel. A liquid meniscus is formed as shown in Figure 3C so the liquid fills completely the channel in the lateral direction, but it does not extend far into the openings.

The presence of an empty channel portion at the distal (ejection) end provides a gun barrel functionality, whereby the liquid particle is accelerated to a skin penetration velocity. The barrel function may be provided as part of the body 30 for example by having a smaller thickness on the proximal end compared to the thickness at the distal end, as shown in Figure 3C. Alternatively, an external barrel may be provided extending

downwards. The required barrel length will effectively depend on the pressurizing power at the proximal end. A high power requires a low barrel length so that an external barrel can be avoided. A lower power design may favor an external barrel design to reduce the amount of material needed.

The barrel function can be implemented based on the geometrical properties of the design, such as the ratio of opening sizes and shapes along the proximal/distal axis compared to the shape along the side axis, in combination with surface wetting properties. The channel typically has the same wetting properties as the side filling channel as it is made from the same material. By selecting the appropriate shape, it can be ensured that a full film is obtained along the side axis, but the film does not enter the barrel portion. Control of wetting properties may be achieved by adding a small amount of surfactant to the liquid.

Instead of, or in addition to, adding surfactants to the liquid, the inner side of the head may be coated to achieve the desired wetting properties.

A liquid may be selected which is hydrophobic to the channel surface, so it would not normally create the liquid particle and the full film would not be formed. By applying a suitable pressure from the reservoir, the channel then becomes partially filled as desired (as shown in Figure 3C). If the filling channel is larger than the main channel 32, the force needed to partially fill the channel as desired is lower than the force required to completely fill the channel, so that a range of forces (or pressures) may be used in which the channel is only partially filled, i.e. in the lateral direction but not in the proximal-distal direction.

For some applications, such as skin rejuvenation, an average effect over the skin surface is desired, and the precise liquid amount in the channel (or in different channels of an array of channels) is less important. For medical treatments, a more accurate solution may be used, as described below.

Different surface wetting properties may be used instead of (or as well as) pressure control and geometric design. The barrel part may be made hydrophobic such that the liquid does not enter the barrel while the channel portion to be filled is hydrophilic. The liquid then has a natural tendency to partially fill the channel. In this way, the range of forces where the desired partial filling is achieved is increased, hence the system reliability is improved.

In order to enable multiple injections from the same head, a reservoir function is provided. Fundamentally there are two ways to provide such a reservoir function.

A first approach is to connect a side reservoir to the filling port 36, and to provide a pressurizing means for the reservoir to drive liquid into the channel, as explained above. A second approach is to use the volume of the liquid film 39 in the plate design, for example the design of Figure 3B, to act as the reservoir. The total volume of liquid between plates may be much larger than the volume in the openings, and thus acts as a reservoir.

Figure 3D shows that the plates may also have enlarged regions 44 at the injection points, or there may be constrictions in an otherwise thick liquid film at the locations of the channels. This provides a larger reservoir.

Figure 3 shows a single channel. There may instead be an array of channels. For the plate design, this simply requires the formation of arrays of openings in the first and second plates. For the capillary tube design, there may be an array of the capillary tubes, with all tubes connected to the same reservoir, or there may even be different reservoirs and supply channels for different groups of capillary tubes.

An example of the invention will now be described in more detail in connection with its possible use as a needle-free injection system, for example for skin rejuvenation, and based on the plate design explained above.

Figure 4 shows longitudinal section view of a needle- free injection system for injecting a liquid into a skin layer.

The needle-free injection system for injecting a liquid into a skin layer 142 includes a pressurizing unit 1 18 that comprises an electrical connector plug 100, a rear cap 102, a portable power source 104, electrodes 106, a ferromagnetic material 108, a piston rod 1 10, an electrically-controlled actuator 1 12, a piston 1 14, a pressurizing chamber 1 16, , a pressurizing unit distal opening 120, a pressurizing unit coupling means 124, a safety measure 146, a graphical user interface (GUI) 150, electrical connections 152, and a processor 154.

The system further includes a removable head assembly 122,that comprises a removable head assembly first coupling means 126, a fluid containment edge 128, a first plate 130, a liquid film 132, a second plate 134, a second plate hole 136, a liquid particle 138, a first plate hole 140, a removable head assembly second coupling means 144, and a removable head assembly proximal opening 148

As shown in Figure 4, the needle-free injection system includes two main components, namely the removable head assembly 122 and the pressurizing unit 1 18. The pressurizing unit distal opening 120 is coupled to the removable head assembly proximal opening 148 via a locking mechanism of the first coupling means 126 of removable head assembly to the pressurizing unit coupling means 124, wherein the locking mechanism is obtained by friction, a screw mechanism, or any type of locking mechanism. Preferably, the locking mechanism includes a safety measure 146 comprising a means to detect a coupling quality between the removable head assembly 122 and the pressurizing unit 1 18, and a coupling indicator such as an LED light, or an audio indicator.

The pressurizing unit 1 18 houses a movable piston 1 14 in the pressurizing chamber 1 16, wherein the pressurizing chamber 1 16 is preferably filled with ambient air. Connected to the piston 1 14 is the piston rod 1 10 for moving the piston 1 14 along the pressurizing chamber 1 16.

The ferromagnetic material 108 is attached at the end of the piston rod 1 10 to allow the piston to respond to the electrically-controlled actuator 1 12. The electrically- controlled actuator 1 12 is preferably a solenoid connected to the portable power source 104, and is able to generate a magnetic field when a current is passed through it. The solenoid 1 12 surrounds the piston rod and is fixed in the pressurizing unit 1 18. When a current of a first direction is applied to the electrically-controlled actuator 1 12, the electrically-controlled actuator 1 12 creates a first direction of the magnetic field and moves the piston 1 14 along a first direction in the pressurizing chamber 1 16, driven by the force exerted on the

ferromagnetic material 108. When a current of a second direction is applied to the electrically-controlled actuator 1 12, the electrically-controlled actuator 1 12 creates a corresponding second direction of the magnetic field and moves the piston 1 14 along a second direction, opposite to the first direction of the piston movement, in the pressurizing chamber 1 16.

One of the two movement directions of the piston 1 14 creates a positive pressure inside the pressurizing chamber 1 16 while the other movement creates a negative pressure inside the pressurizing chamber 1 16. The portable power source 104 is preferably a rechargeable battery. A power cable connected to an external alternating current (AC) or direct current (DC) power source is used for recharging via the plug 100. Alternatively, the rear cap 102 is removable to allow a replacement of the battery when the battery reaches full discharge.

The piston may be operated as a coil gun. For this purpose, multiple coils may be provided in series (not shown). The voltage that needs to be applied on the coil to generate a certain force will be proportional to the inductance, which depends linearly on coil length. Hence, since most systems will have a limit on the total voltage they can generate, a higher kinetic energy (e.g. velocity) can be reached by using multiple coils in series. Note that the ability to actively retract the piston is optional in the case of a skin rejuvenation system. A suction phase is needed for blood drawing, but for skin rejuvenation, no suction is needed, hence a non-reversible mechanism may be used.

Examples of non-reversible mechanisms are a simple air gun (mechanical compression followed by release) or cartridges with compressed air and a coupling valve.

On the external side of the pressurizing unit 1 18 is the GUI 150 for initiating an injection of a liquid into a skin layer 142. The GUI 150 preferably includes a power button, an actuating button to trigger the needle-free injection of a liquid, depth setting buttons, and an increase and decrease button to adjust the depth settings.

In this example, the removable head assembly 122 includes a first plate 130 and a second plate 134 that are parallel to each other, and a fluid containment edge 128. On one side of the removable head assembly 122 is the removable head assembly second coupling means 144 for coupling to a reservoir containing a liquid. The liquid in the coupled reservoir forms a liquid film 132 between the first plate 130 and the second plate 134. At least one first plate hole 140 is provided for the first plate 130, and at least one second plate hole 136 is provided for the second plate 134, wherein the at least one first plate hole 140 is preferably aligned to the at least one second plate hole 136. In this example, two first plate holes 140 are shown for the first plate 130, and two second plate holes 136 are shown for the second plate 134.

Preferably, an array of up to an order of 100 x 100 holes is provided for the first plate 130 and the second plate 134. The holes preferably range in diameter from about 50 micrometers to 200 micrometers.

When pressure is applied over the liquid film 132, a liquid particle 138 is formed, wherein the formed liquid particle 138 is preferably micrometer-sized. The first plate 130 and the second plate 134 preferably have the same cross sectional shape as the pressurizing unit distal opening 120. Alternatively, the cross sectional shape of the first plate 130 and the second plate 134 is different from the cross section shape of the pressurizing unit distal opening 120 as long as the removable head assembly proximal opening 148 is the same cross section shape as the pressurizing unit distal opening 120 to allow coupling of the pressurizing unit 1 18 and the removable head assembly 122 e.g., the first plate 130 and the second plate 134 are rectangular, while the pressurizing unit distal opening 120 and the removable head assembly proximal opening 148 are circular.

Figure 5 illustrates a side view of two parallel plates for containing a liquid film layer. An applied pressure 200 is shown, as well as a first plate hole 202, a first plate 204, a liquid film layer 206, a predetermined distance 208, a skin layer 210, a liquid particle

212, a second plate 214, and a second plate hole 216.

As shown in Figure 5, the first plate 204 and the second plate 214 are set at a predetermined distance 208 such that when a liquid comes into contact at the edge of the two parallel plates the liquid preferably fills a predetermined volume set by the predetermined distance 208 via capillary action and forms a liquid film layer 206 between the two parallel plates. The first plate hole 202 and the second plate hole 216 are preferably aligned with each other and are termed to be in a hole position. The hole position allows a pressurization via the applied pressure 200 of the liquid film layer 206, and formation of a liquid particle 212. In one example, the second plate hole 216 has a nozzle of either a conical or cylindrical shape to direct or modify the injection of the liquid particle 212.

Figure 6 illustrates a bottom view of a removable head assembly. The bottom view of the removable head assembly shows a reservoir 300 for the liquid of the liquid film, a removable head assembly second coupling means 302, fluid containment edges 304, an injection hole 306, a bottom plate 308, and a hole array 310. The second coupling means

302 functions as a filling port for filling the space between the first and second plates with the liquid from the reservoir 300.

As shown in Figure 6, the reservoir 300 is coupled to the removable head assembly and this may be via a lock mechanism including friction, a screw mechanism, or any type of locking mechanism. The bottom plate 308 is provided with at least one injection hole 306. Preferably, as mentioned above a hole array 310 of up to an order of 100 x 100 holes is provided to allow an injection of a liquid into a larger skin surface area. In one example, the removable head assembly second coupling means 302 includes a valve to allow a controlled reception of the liquid to the removable head assembly.

The example above has two plates with a single liquid film. There may be a third plate or further plates such that there is a number N of plates which define a number N-

1 of spacings for receiving different liquid films.

Figure 7 illustrates a side view of three parallel plates for containing two liquid film layers. The at least two liquid film layers may comprise the same type of liquid containing the same active ingredient, or they may comprise the same base liquid having different active ingredients, or they may comprise different liquids having different active ingredients.

The figure shows an applied pressure 400, a first plate hole 402, a second plate hole 404, a first plate 406, a first liquid film layer 408, first layer walls 410, a first predetermined distance 412, a second predetermined distance 414, a second plate 416, a second liquid film layer 418, a third plate 420, a second liquid particle 422, a second hole position 424, a third plate hole 426, second layer walls 428, a first liquid particle 430, and a first hole position 432.

As shown in Figure 7, the first liquid film layer 408 is disposed between the first plate 406 and the second plate 416, while the second liquid film layer 418 is disposed between the second plate 416 and the third plate 420. Preferably, the first predetermined distance 412 and the second predetermined distance 414 are set to be equal. Alternatively, the first predetermined distance 412 and the second predetermined distance 414 can be set to different values. In this example, two hole positions are illustrated. A hole position or location is preferably assigned to an alignment of a first plate hole 402, second plate hole 404, and a third plate hole 426. The first hole position or location 432 allows a pressurization and formation of a first liquid particle 430 via the applied pressure 400 over the first liquid film layer 408, while the second hole position or location 424 allows a pressurization and formation of a second liquid particle 422 via the applied pressure 400 over the second liquid film layer 418.

In the first hole position 432, the second plate hole 404 and third plate hole 426 are isolated from the second liquid film layer 418 via second layer walls 428. These second layer walls form second barrier regions between the second and third plates 416, 420. In the second hole position or location 424, the first plate hole 402 and second plate hole 404 are isolated from the first liquid film layer 408 via first layer walls 410. These first layer walls form first barrier regions between the first and second plates 406, 416.

In this way, each liquid film is present at locations aligned with some of the openings of the array and not present at locations aligned with others of the openings. Thus, each fluid layers is assigned to its own respect set of opening locations.

Figure 8 illustrates a top view of a second plate of three plates for containing a first liquid film layer. The top view of the second plate 512 comprises a hole array 514 having a plurality of injection holes 510, a first layer wall 504, fluid containment edges 506, and a space 508. The hole array 514 includes first position holes 500 and second position holes 502.

The second plate 512 in Figure 8 and a first plate positioned on top of the second plate contains a first liquid film layer. In this example, the first position holes 500 are enclosed by the first layer wall 504, preferably with a width equal to at least a diameter of the injection hole 510. The length of the first layer wall 504 preferably extends along a column of first position holes 500 such that a space 508 is left at the edge of the second plate 512.

Preferably, the height of the first layer wall 504 is equal to the predetermined distance between the second plate 512 and the first plate. Alternatively, a cylindrical wall is provided for each of the first position holes 500. The diameter of the cylindrical wall is preferably equal to a diameter of a first position hole, and the height of the cylindrical wall is preferably equal to the predetermined distance between the second plate 512 and the first plate. In this example, the first liquid film layer is positioned over the second position holes 502 and isolated from the first position holes 500 by the first layer walls 504.

Figure 9 illustrates a top view of a third plate of three plates for containing a second liquid film layer. The top view of the third plate 612 comprises a hole array 614 having a plurality of injection holes 610, a second layer wall 604, fluid containment edges 606, and a space 608. The hole array 614 includes first position holes 600, second position holes 602.

The third plate 612 in Figure 9 and a second plate positioned on top of the third plate together contain a second liquid film layer. The second position holes 602 are enclosed by a second layer wall 604, preferably with a width equal to at least a diameter of the injection hole 610. The length of the second layer wall 604 preferably extends along a column of second position holes 602 such that a space 608 is left at the edge of the third plate 612. Preferably, the height of the second layer wall 604 is equal to the predetermined distance between the third plate 612 and the second plate. Alternatively, a cylindrical wall is provided for each of the second position holes 602. The diameter of the cylindrical wall is preferably equal to a diameter of a second position hole, and the height of the cylindrical wall is preferably equal to the predetermined distance between the third plate 612 and the second plate.

In this example, the second liquid film layer is positioned over the first position holes 600 and isolated from the second position holes 602 by the second layer wall 604.

The use of multiple layers gives a uniform distribution of liquids when different (non-compatible) liquids are used. If two layers are used, each may be formed as a checkerboard pattern, with the two checkerboard patterns interleaved ("pixel interleaving"). In such as case, if the x is the distance between two channels, the effective distance between channels allocated to the same liquid layer is xV2.

A less uniform distribution is achieved with line interleaving within a single layer (i.e. one row of channels of one liquid followed by a row of channels of the other liquid). An advantage of line interleaving is that all channels for one liquid can be connected together at one side to a first filling port, and all channels for other liquid can be connected together at an opposite side to a second filling port, within the same layer. The effective distance between channels of the same liquid in different rows becomes 2 x where x is the distance between rows. This has the advantage that all channels have the same barrel length (because there can be multiple channel types within a single layer rather than multiple layers). There can however also be different barrel lengths for different lines by position the fill channel at different depths.

The same approach of forming a skin piercing liquid particle from a liquid film may be used for a blood sampling apparatus. In this case, the removable head assembly may comprise part of a blood collection chamber which forms a removable cartridge. The injected particle passes through an outlet of the chamber (which may initially be closed by a membrane), and by providing depressurization of the pressurizing apparatus, blood may be drawn into the chamber.

The distal end of the removable head assembly for example has a membrane which covers an output aperture. The membrane preferably comprises a thin metallic foil or Mylar.

In an example, the removable head includes a hydrophobic surface at its proximal end and a hydrophilic surface at its distal end so that the blood is not drawn toward the removable head's proximal end. The hydrophilic surface can be in the form of a pad, wad, or any absorbent material.

The liquid particle is then a biodegradable or biocompatible liquid. A liquid with a negligible evaporation rate (e.g. fat/oil based) and a very low saturation pressure is preferably used. However, the liquid film may be water.

In an initial particle shooting phase, an electrical current is applied to the electromagnetic coils, which attracts the ferromagnetic material 108 resulting in the movement of the piston towards the distal end of the pressurizing apparatus. The resulting pressurized gas from the piston's downward motion exerts a downward force on the liquid film to cause a liquid particle to be ejected from the (or each) opening. By way of example, the particle may be ejected with a flow velocity in the region of lOOm/s to 300 m/s. The particle, having gained sufficient momentum, pierces the aperture membrane if present and penetrates the skin at a sufficient depth. The particle penetration causes a micro-emergence of blood at the skin. In a subsequent blood drawing phase, an electrical current is applied to the electromagnetic coils, in a reverse direction, causing the repulsion of the ferromagnetic material and the movement of the piston towards the proximal side of the pressurizing apparatus. The piston movement leads to a suction mechanism and depressurizes the chamber in which the plates are housed. The at least partial vacuum within the chamber is configured to draw at least a portion of the blood from the micro-emergence into the chamber.

One-way valves may be included in the pressurizing apparatus such that they only open during the blood drawing phase. This is creates a large pressure difference in the skin piercing phase, leading to a higher acceleration power. In addition, one-way valves ensure that the pressure in the pressurizing chamber and in the removable head are equal during the drawing phase, since suction efficiency is controlled by the vacuum efficiency in the removable head. The one-way valves are aligned with holes in the removable head.

The removable head may be integrated with a removable cap. The removable head may then be used as a storage container for the blood sample. The removable cap can seal the head using a mechanical locking mechanism.

If the removable head is transparent and it has a pad or wad with suitable reagents, then blood analysis may be done through spectroscopic measurements. The head is for example integrated with a glucose meter.

Figure 10 shows a needle-free blood sampling method or injection method. It comprises in step 620, using an electrically-controlled actuator to drive a piston of a pressurizing apparatus towards a distal side thereby pressurizing a pressurizing chamber during a skin piercing mode.

In step 630, a gas flow resulting from the pressurizing is used to dislodge a portion of a liquid film, wherein the liquid film is between a first plate and a second plate arranged parallel to each other and spaced by a predetermined distance, wherein the liquid portion is aligned with at least one opening of the first plate and with at least one opening of the second plate.

In step 640 the portion is driven into the skin.

This may either be used to administer an agent or to promote (micro) bleeding for collection of a blood sample.

Figure 1 1 is a flowchart illustrating in more detail a method of needle-free injection.

A removable head assembly is coupled via a first coupling means to a pressurizing unit in step 700. The removable head assembly is coupled via a second coupling means to a reservoir containing an at least one liquid with an at least one active ingredient in step 702. Then, the at least one liquid is received in the removable head assembly in step 704. A liquid film is disposed between the at least two parallel plates in step 706 preferably via capillary action.

To initiate an injection of the liquid, an actuating button is pressed and, subsequently, a current is applied to an electrically-controlled actuator to move a piston in the pressurizing unit in step 708.

During the injection of the liquid, a positive pressure is applied to the removable head assembly via a movement of the piston in step 710. The applied pressure forms at least one liquid particle from the liquid film in step 712 for each of the at least one hole. Preferably, micrometer-sized liquid particles carrying the active ingredient are formed by the applied pressure. After the at least one liquid particle is formed, the applied pressure accelerates the at least one particle through the at least one hole such that the at least one particle is injected into the skin at a skin layer in step 714.

The pressurizing unit preferably includes a coupling means to which the first coupling means of the removable head assembly connected. The coupling between the removable head assembly and the pressurizing unit is a locking mechanism including friction, screw mechanism, or any type of locking mechanism. Preferably, the locking mechanism includes a safety measure to prevent triggering an injection when the removable head assembly is not securely coupled to the pressurizing unit. The safety measure is preferably provided with a means to detect the coupling quality between the removable head assembly and the pressurizing unit, and a coupling indicator such LED light, or audio indicator.

In one example, when the removable head assembly is not securely coupled to the pressurizing unit, the LED light emits a red color, and when the removable head assembly is securely coupled to the pressurizing unit, the LED light emits a green color. In another example, no triggering of an injection when the actuating button is pressed unless a valid removable head assembly is detected to be coupled to a pressurizing unit by the safety measure. The second coupling means of the removable head assembly to the reservoir is positioned preferably at an edge of the at least two plates.

As explained above, for blood drawing, a negative pressure is used as part of the process. For the injection system, the ability to drive the piston in the backward direction is mainly so that the device may be reset after the full stroke of the piston has been used. In this case, the negative pressure does not need to be used as part of the injection procedure. Note that one full forward stroke of the piston may correspond to a single injection (so that there is a reset after each injection) or else multiple injection events may be achieved with one full stroke of the piston (so that there is a reset after a set of injections).

However, the negative pressure may be used in the injection system to implement the fluid delivery from the reservoir to the parallel plates or channels. After the injection of the liquid particle, the liquid film is refilled in the at least two parallel plates or channels preferably via capillary action. In one example, the negative pressure enables an automatic mechanism. Since the pressurizing unit and removable head assembly are coupled, the negative pressure created draws the liquid contained in the reservoir into the at least two parallel plates.

Preferably, a depth of the skin layer that the at least one liquid particle penetrates is controlled by the applied pressure. In a preferred embodiment, a user can select using a GUI a given applied pressure corresponding to a desired skin depth penetration by the liquid particle formed from the liquid film unto which the pressure was applied. The selected pressure setting is then transmitted to a processor, and a corresponding pressure is applied by the piston via the electrically-controlled actuators.

The example above is based on a coil gun arrangement, namely one or more coils arranged along a shaft, so the path of the accelerating piston is along the central axis of the coils. The current direction controls the travel direction and the current intensity controls the force being applied. The current pulse duration controls the motion travel distance.

Advantageously, complex pulse shapes (current intensity vs. time) can be used.

Other arrangements are possible. For example a rail gun has a direction of acceleration at right angles to the central axis of a current loop formed by conducting rails. Rail guns usually require the use of sliding contacts to pass a large current through the projectile whereas coil guns do not necessarily require sliding contacts. Some simple coil gun concepts can use ferromagnetic projectiles or even permanent magnet projectiles, but most designs for high velocities incorporate a coupled coil as part of the projectile.

Another example is a piezoelectric arrangement making use of piezo actuators. These have the advantage of very fast response (hence high pressures are possible) but the travel distance may be limited. A gear system or difference between piston surface and removable head surface may be needed to enhance travel or increase the amount of blood being drawn. By way of example, known coil gun designs for pistols are able to accelerate a 2 - 4 mm steel ball to subsonic speeds of the order of 200 - 300 m/s. Such particle velocity can easily penetrate skin up to cm depths.

For injection, particles with diameter in the order of 50-200 micrometers are desired. This diameter reduction compared to 2 - 4 mm gives a corresponding mass or kinetic energy reduction. Hence much smaller and portable mechanisms are possible. A handheld device may for example simultaneously power an array of 1000 to 10,000 injection holes simultaneously. In this way, simultaneous skin piercing and local microinjection can take place in arrays of 1000 to 10,000 points. However, for larger skin surfaces multiple injections from the whole array would be required. An advantage is therefore the ability to recharge the removable head.

The liquid film between the two plates may be coupled to the reservoir during use, together with a pressure source or else making use of the negative pressure created by the pressurizing apparatus, so that the hole array can be easily recharged in real time. A single head can then be used for injection at multiple spots to improve process efficiency.

The example above which makes use of multiple liquid film layers addresses a problem in medicine of the poor mixing or compatibility of various active ingredients. Many active ingredients are only soluble in a limited range of solvents, while certain active ingredients may be intrinsically unstable unless stabilizing agents are provided or they may react with other active ingredients.

For example, certain active substances may be fatty oils (e.g. vitamin A or vitamin E) which require oil based solvents while other active substances are water soluble. Hence it can be advantageous that incompatible agents are provided in different layers. Each injection hole is assigned to one of the liquid layers. In the simple example of 2 layers, holes vary alternatively between a bottom and a top layer.

It will be understood from the description above that the invention is of particular interest for a skin rejuvenation application in which an array of channels is used. Skin rejuvenation requires treatment of large surfaces, which is equivalent to multiple injections. For cost and efficiency of the process, a single head can then be used by the person receiving the full cosmetic treatment, by enabling multiple injections by injecting and then side refilling from the reservoir.

When no medically active compounds are used within the liquid, the skin rejuvenation method is an entirely non-therapeutic method. Commercially available professional skin rejuvenation solutions are instead based on laser skin resurfacing. The skin resurfacing is based on the principle of micro- thermal treatment zones which penetrate deep into the skin removing the epidermis and upper dermis but leaving the surrounding tissues untouched and intact. The treated regions

("pixels") trigger the body's natural healing process stimulating the growth of new healthy skin tissue and increased collagen formation. The small bridges of untreated areas act as a reservoir for more effective and rapid tissue healing and collagen production.

The system described above provides a replacement for the laser by using injected particles to create the local damage to the epidermis. There are several advantages over a laser-based treatment. The treatment may include injection of relevant active substances to actively promote the healing effect (for example active substance such as Q10, vitamins A and C etc.) and also enables the use of substances to avoid development of skin infection (e.g. antibiotics).

Thermal issues influence the possible treatment size in a laser based system, and these issues are not present in the system described above. The effectiveness of the treatment provided is also independent of the skin complexion. A large number of channels may be used in the system, for example of the order of 20x20 to 100x100 with a good uniformity. Furthermore the penetration depth can easily be controlled by pressure, and thereby adapted to the skin thickness and level of treatment required.

Other variations to the disclosed embodiments can be understood and effected by those skilled in the art in practicing the claimed invention, from a study of the drawings, the disclosure, and the appended claims. In the claims, the word "comprising" does not exclude other elements or steps, and the indefinite article "a" or "an" does not exclude a plurality. The mere fact that certain measures are recited in mutually different dependent claims does not indicate that a combination of these measures cannot be used to advantage. Any reference signs in the claims should not be construed as limiting the scope.

Claims

CLAIMS:

1. A removable head assembly (12) for a needle-free skin piercing system, comprising:

a body (30) comprising a channel (32) which comprises a distal opening (35) at a distal end and a proximal opening (34) at a proximal end;

a filling port (36) for only partially filling the channel with a liquid through a fill opening (36') separate from the distal and proximal openings, such that a first unfilled region remains adjacent the distal opening and a second unfilled region remains adjacent the proximal opening; and

a coupling interface for removably coupling the removable head assembly to a pressurizing apparatus (10) for applying pressure to the proximal opening thereby to expel under pressure the liquid in the channel from the distal opening.

2. A removable head assembly as claimed in claim 1, wherein the fill opening (36') extends laterally into the channel.

3. A removable head assembly as claimed in any preceding claim, wherein the or each channel has a diameter in the range 50 μηι to 200 μηι.

4. A removable head assembly as claimed in any preceding claim, wherein the body comprises an array of channels, for example at least 25 channels, for example at least 100 channels, for example at least 1000 channels.

5. A removable head assembly as claimed in any one of claims 1 to 3, wherein the body comprises a first plate (37) and a second plate (38) arranged parallel to each other and spaced by a predetermined distance, arranged for receiving a liquid film between the first and second plates, wherein the proximal opening is in the first plate and the distal opening is in the second plate, thereby to define the channel between, and wherein preferably the first and second plates each comprise an array of openings, thereby to define an array of channels, for example at least 25 channels, for example at least 100 channels, for example at least 1000 channels.

6. A removable head assembly as claimed in claim 4 or 5, further comprising at least a third plate such that there is a number N of plates which define a number N-l of spacings for receiving different liquid films.

7. A removable head assembly as claimed in claim 6, wherein each liquid film is present at locations aligned with some of the openings of the array and not present at locations aligned with others of the openings, and wherein preferably first barrier regions are formed between the first and second plates and second barrier regions are formed between the second and third plates.

A removable head assembly as claimed in any preceding claim, comprising part of a blood collection chamber; or

part of a system for delivering a biologically active agent; or

part of a skin rejuvenation system.

A removable head assembly as claimed in any preceding claim, further comprising a reservoir for the liquid, the reservoir having an output which is connectable to the filling port, and a fluid delivery system for delivering the liquid from the reservoir to the filling port.

10. A pressurizing apparatus for a system for needle-free skin piercing, comprising:

a coupling interface adapted to removably couple the apparatus to a removable head assembly as claimed in any preceding claim;

a pressurizing chamber having a release opening on a distal side, wherein the pressurizing chamber is adapted to apply a pressure to the removable head assembly thereby to expel under pressure the liquid in the channel of the removable head assembly.

1 1. An apparatus as claimed in claim 10, further comprising:

a piston arranged to reciprocate in the pressurizing chamber; and an electrically-controlled actuator coupled to the piston for controlling a reciprocating motion of the piston.

12. A system for needle-free skin piercing comprising:

a removable head assembly as claimed in any one of claims 1 to 9; and a pressurizing apparatus as claimed in claim 10 or 1 1.

13. A needle-free skin piercing method comprising:

pressurizing a pressurizing chamber of a pressurizing apparatus during a skin piercing mode;

driving the liquid portion into the skin;

replenishing the channel from a filling port, wherein the channel is replenished laterally, and wherein replenishing the channel comprises only partially filling the channel such that a first unfilled region remains adjacent a distal opening of the channel and a second unfilled region remains adjacent a proximal opening of the channel.

14. A method as claimed in claim 13, wherein expelling the liquid from the channel comprises expelling a portion of a liquid film which is between a first plate and a second plate arranged parallel to each other, wherein the channel is defined between a proximal opening in the first plate and a distal opening in the second plate.

15. A method as claimed in any one of claims 13 to 14 comprising a non- therapeutic cosmetic skin rejuvenation method.