Microneedle device

Abstract

A microneedle device (100) having one or more microneedles (106) extending from a substrate (104), and for insertion into a target body. The microneedle device includes one or more piezoelectric micromachined ultrasound transducer (102), PMUT, elements formed on the substrate. Each of the one or more PMUT elements includes a moveable piezoelectric diaphragm. Control circuitry (110) is integrally formed with the substrate and electrically coupled to the one or more PMUT elements.

Description

[0001] MICRONEEDLE DEVICE

[0002] Field of the invention

[0003] The present invention relates to microneedle devices.

[0004] Background to the invention

[0005] Microneedle arrays are useful for a range of biomedical applications, such as transdermal drug delivery and fluid extraction. They can provide a less invasive way of delivering or extracting fluid compared to conventional hypodermic needles. They are also known for use in veterinary, cosmetic and agricultural applications.

[0006] Microneedle arrays include an arrangement of micron sized needles (typically around 50-1500 pm in length, 50-250 pm in width, and 1-25 pm in diameter). Various types of microneedles are known. For example, they may be solid, dissolvable, hollow and / or coated. Silicon is a commonly used material - but other options such as metals, ceramics, and polymers are also possible.

[0007] It is known to provide microneedle arrays coupled to an ultrasound transducer for drug delivery purposes. However, providing devices which are portable whilst also being convenient and cost-effective to manufacture is challenging.

[0008] It is in this context that the present invention has been devised.

[0009] Summary of the invention

[0010] According to an aspect of the invention, there is provided a microneedle device comprising: a substrate; one or more microneedles extending from the substrate, and for insertion into a target body; one or more piezoelectric micromachined ultrasound transducer, PMLIT, elements formed on the substrate, wherein each of the one or more PMLIT elements comprises a moveable piezoelectric diaphragm; and control circuitry integrally formed with the substrate and electrically coupled to the one or more PMLIT elements.

[0011] By providing one or more microneedles extending from a substrate having at least one PMLIT element formed thereon and having integrated control circuitry, it is possible to provide a highly integrated microneedle device having a small-form factor. This arrangement avoids or limits the need for separate electronics (not integrated with the control circuitry). Accordingly, it is made possible to provide microneedle devices which are portable whilst also having the high functionality (e.g., control / sensing) enabled by the combination of a PMLIT element and control circuitry.

[0012] Since each PMLIT element is formed on the substrate having the integrally formed control circuitry, the device is also relatively straightforward to manufacture (e.g., compared to other integrated devices where the MEMS components and control circuitry are manufactured separately before being bonded together).

[0013] The substrate may comprise a silicon wafer. The substrate may be a semiconductor substrate. An additional layer may be provided between the microneedle and the substrate - e.g., a valve seat / other sealing layer.

[0014] The term microneedle device will be understood to mean substantially any device having at least one micro-sized needle (e.g., 50-1500 pm in length, 50-250 pm in width, and 1-25 pm in diameter) for insertion into a target body.

[0015] Typically, the moveable piezoelectric diaphragm comprises a piezoelectric body, a first electrode and a second electrode. The piezoelectric body, a first electrode and a second electrode are typically stacked on a first surface of the substrate (e.g., between the substrate and at least one of the plurality of microneedles).

[0016] Typically, the moveable piezoelectric diaphragm defines at least part of a wall of a cavity. Typically, the cavity is defined in part by the moveable piezoelectric diaphragm and in part by the substrate.

[0017] Each PMLIT element is formed on (e.g., deposited on) the substrate. The PMLIT element may be deposited using one or more PVD methods. Importantly, the PMLIT element is formed on the substrate rather than being formed separately and later bonded.

[0018] It may be that the control circuitry is configured to control reception of signals resulting from the movement of the moveable piezoelectric diaphragm. It may be that the control circuitry is configured to control movement of the moveable piezoelectric diaphragm.

[0019] The microneedle device may be a microneedle array. The term microneedle array will be understood to mean substantially any device having an arrangement of micro-sized needles (e.g., 50-1500 pm in length, 50-250 pm in width, and 1-25 pm in diameter) for insertion into a target body.

[0020] It may be that there is uniform spacing between adjacent microneedles of the microneedle device. It may be that the control circuitry comprises CMOS control circuitry.

[0021] The CMOS control circuitry may be formed using conventional CMOS fabrication techniques (e.g. ion implantation, chemical vapour deposition (CVD), physical vapour deposition (PVD), etching, chemical-mechanical planarization (CMP) and / or electroplating).

[0022] The microneedle device may be configured to generate an electric field for application to part of a user’s body (e.g., a portion of the user’s tissue and / or skin).

[0023] The microneedle device may be configured to generate a static electric field. The microneedle device may be configured to generate one or more electric pulses (e.g., voltage pulses). The microneedle device may be configured to generate a plurality of electric pulses. The microneedle device may be configured to generate a series of electric pulses (e.g., with a pulse repetition frequency of between 10-5000 Hz). The microneedle device may be configured to generate a static electric field over a first time period and a pulsed electric filed over a second time period different from the first time period.

[0024] The inventors have realised that by providing a microneedle device configured to generate an electric field that it is possible to further improve the effectiveness of the microneedle device. In particular, improved drug delivery is made possible using iontophoresis and / or electroporation. Iontophoresis involves applying a potential difference over part of the user’s body to cause the flow of charged particles through part of the user’s tissue. For example, part of the microneedle device having a first polarity (e.g., an electrode) can be used to force charged drug particles having the same polarity through part of the user’s body. Iontophoresis typically involves low voltages / currents (typically less than 10 V and less than 5 mA) and the application of a static electric field. Electroporation involves applying high voltage electrical pulses (typically voltages of 50 V to 3000 V, and pulse durations of 5 ps to 100 ms) to part of the user’s body. This increases tissue permeability and therefore facilities improved drug transport / delivery. The microneedle device may comprise more than one electrode for generating the electric field. At least one of the one or more electrodes may be integrated with the substrate. At least one of the one or more electrodes may be formed on the substrate. At least one of the one or more electrodes may be separate from the microneedles and / or PMLITS on the substrate (e.g., separate entities). A surface of the electrode microneedle device may comprise a wall of a cavity for accommodating conductive fluid (e.g., conductive gel) between the electrode surface and the user.

[0025] One or more of the microneedles of the microneedle device may be configured to generate the electric field. That is, one or more of the microneedles may function as an electrode. One or more of the microneedles of the microneedle device may comprise a conductor. One or more of the PMLITS of the microneedle device may be configured to generate the electric field. It may be that at least one of the one or more microneedles and at least one of the one more PM UTS are configured to generate the electric field. For example, a PMUT may function as a cathode and a microneedle may function as the anode to provide a potential difference between them.

[0026] It may be that the control circuitry is configured to generate a control signal for generating the electric field. By controlling the electric field using the integrated control circuitry it is possible to provide a compact microneedle device with improved drug delivery functionality.

[0027] The microneedle device may be configured to apply a voltage of less than 1V. The microneedle device may be configured to apply a voltage of less than 5 V. The microneedle device may be configured to apply a voltage of less than 10 V. The microneedle device may be configured to apply a voltage of less than 20 V. The microneedle device may be configured to apply a voltage of greater than 5 V. The microneedle device may be configured to apply a voltage of greater than 10 V.

[0028] The microneedle device may be configured to generate a current of less than 5 mA.

[0029] The microneedle device may be configured to generate a current of less than 3 mA.

[0030] The microneedle device may be configured to generate a current of less than 1 mA.

[0031] The microneedle device may be configured to generate a current of greater than 0.1 mA. The microneedle device may be configured to generate a current of greater than 1 mA. Thus, charged particles can be forced through the user’s tissue using iontophoresis.

[0032] The microneedle device may be configured to apply a voltage of greater than 50 V. The microneedle device may be configured to apply a voltage of greater than 500 V. The microneedle device may be configured to apply a voltage of greater than 1000 V. The microneedle device may be configured to apply a voltage of greater than 2000 V.

[0033] The microneedle device may be configured to apply a voltage of less than 3500 V. The microneedle device may be configured to apply a voltage of less than 2000 V. The microneedle device may be configured to apply a voltage of less than 1000 V.

[0034] The microneedle device may be configured to apply an electrical pulse having a duration of greater than 5 ps. The microneedle device may be configured to apply an electrical pulse having a duration of greater than 100 ps. The microneedle device may be configured to apply an electrical pulse having a duration of greater than 1 ms. The microneedle device may be configured to apply an electrical pulse having a duration of greater than 10 ms. The microneedle device may be configured to apply an electrical pulse having a duration of greater than 50 ms.

[0035] The microneedle device may be configured to apply an electrical pulse having a duration of less than 1 ms. The microneedle device may be configured to apply an electrical pulse having a duration of less than 10 ms. The microneedle device may be configured to apply an electrical pulse having a duration of less than 50 ms. The microneedle device may be configured to apply an electrical pulse having a duration of less than 100 ms. Thus, tissue permeability can be increased using electroporation to provide improved drug delivery.

[0036] It may be that each of the one or more PMLIT elements is coupled to at least one microneedle of the one or more microneedles. It may be that each microneedle is coupled to a single PMLIT element. It may be that each PMLIT element is coupled to a corresponding single microneedle. The response of the PMLIT element (i.e., the response of the piezoelectric diaphragm of that PMLIT element) affects the microneedle coupled therewith (and vice versa).

[0037] In some embodiments, each microneedle is coupled to a corresponding single PMLIT element and each PMLIT element is coupled to a corresponding single microneedle (i.e., there is a one-to-one correspondence between microneedles and PMLIT elements).

[0038] By providing control circuitry integrated with the PMLIT elements as described herein, it is possible to provide a high number of microneedles coupled to PMLIT elements on a single substrate, whilst enabling functionality on the scale of individual microneedles.

[0039] It may be that the control circuitry is configured to receive electrical signals generated by the movement of the or each moveable piezoelectric diaphragm, and generate a signal based on the movement of the or each moveable piezoelectric diaphragm.

[0040] By providing control circuitry configured to receive electrical signals generated by each PMLIT element, it is possible to provide a microneedle device having integrated sensing capabilities. This in advantageous for a range of applications, as described herein.

[0041] It may be that the microneedle device further comprises a first circuit, wherein the first circuit is configured to determine a microneedle characteristic based on the signal. It may be that the microneedle characteristic is indicative of whether at least one of the one or more microneedles is correctly inserted in the target body. It may be that the first circuit is configured to determine a target body characteristic based on the signal. It may be that the target body characteristic is indicative of an internal pressure of the target body.

[0042] The inventors have realised that it is possible to use the sensed data to obtain characteristics of microneedles of the device, thereby facilitating improved device operation / performance. It may be that the microneedle device is configured such that characteristics are determinable on the scale of individual microneedles / PMUT elements.

[0043] It may be that a first PMLIT element is coupled to a first microneedle, wherein the first circuit is configured to determine a microneedle characteristic of the first microneedle based on the movement of the moveable piezoelectric diaphragm of the first PMLIT element.

[0044] It may be that the microneedle characteristic and / or the target body characteristic is determined in dependence on an oscillation of at least one of the moveable piezoelectric diaphragms. It may be that the microneedle characteristic and / or the target body characteristic is determined in dependence on a frequency of the oscillation.

[0045] The inventors have realised that the oscillations of the moveable piezoelectric diaphragms (including the frequency content of those oscillations) can provide an indication of characteristics of a microneedle and / or target body.

[0046] It will be understood that the signal comprises information indicative of the oscillation of at least one of the moveable piezoelectric diaphragms. The information indicative of the oscillation may be at least one of an amplitude and a frequency of the oscillation. The information may be indicative of the frequency of the oscillation. The information may be the frequency of the oscillation.

[0047] It may be that the first circuit is configured to generate an output signal based on the determined microneedle characteristic and / or target body characteristic. It may be that the output signal is for disabling at least one of the one or more microneedles. It may be that the output signal is for alerting the user that operation of the microneedle device is compromised.

[0048] Advantageously, the microneedle device may be configured to respond to the determined characteristic to disable a microneedle or alert the user that the operation of the microneedle device is compromised (e.g., a microneedle is blocked, or not correctly inserted in the target body), thereby facilitating more efficient and effective use of the microneedle device.

[0049] The microneedle device may be configured to extract liquid from the target body. The microneedle device may be configured to deliver liquid to the target body.

[0050] The fluid may be extracellular fluid (e.g., interstitial skin fluid). The liquid may be a pharmaceutical fluid (e.g., medication / medicinal drugs such as antibiotics, insulin or vaccines). The fluid may comprise cannabinoids (e.g., cannabidiol). The fluid may comprise small molecule ingredients.

[0051] By providing a microneedle device configured to extract / deliver liquid to a target body, convenient and cost-effective testing / treatment of the target body is enabled. A microneedle device for delivering / extracting liquid having a small form factor is particularly advantageous in settings where providing a less bulky device is important (e.g., for improved patient comfort / adherence in a medical setting or when testing / treating a small target body).

[0052] It may be that the microneedle device comprises one or more chambers for accommodating at least a portion of the fluid between the one or more microneedles and the one or more PMLIT elements (e.g., the one or more moveable piezoelectric diaphragms of the one or more PMLIT elements) such that a force can be transferred between the or each PMLIT element and the or each microneedle through the fluid (e.g., directly through the fluid). It may be that ultrasound can be transmitted between the one or more microneedles and the one or more PMLIT elements through the fluid (e.g., directly through the fluid). It may be that the one or more chambers are in fluidic communication with the one or more microneedles.

[0053] It may be that each microneedle is coupled to a corresponding single PMLIT element and each PMLIT element is coupled to a corresponding single microneedle via a respective chamber for accommodating the fluid.

[0054] It may be that the microneedle device is configured for use with a specific type of fluid. For example, it may be that the microneedle device is configured to preserve the integrity (e.g., to avoid degradation / denaturation) of the specific type of fluid (e.g., a specific type of pharmaceutical fluid) being delivered and / or extracted. For example, the or each microneedle may be sized and / or shaped to preserve the integrity of the fluid. It may be that the movement of the or each moveable piezoelectric diaphragm is controlled to preserve the integrity of the fluid - e.g., suitable amplitudes / frequencies of oscillation are chosen. Thus, the forces exerted on the fluid are reduced (relative to conventional microneedle arrays). Advantageously, it is possible to provide fluid delivery / extraction with high efficacy and efficiency.

[0055] The microneedle device can be used for medical applications in a domestic or clinical setting, by trained medical professionals, or by the patient themselves. The microneedle device may be used for veterinary applications. The microneedle device may be used in an agricultural setting.

[0056] The target body may be part of a plant. The target body may be part of a human body. The target body may be part of an animal body.

[0057] In some embodiments, the or each moveable piezoelectric diaphragm defines at least part of a wall of a respective cavity, the microneedle device further comprises an input for receiving the liquid into the cavity. The input may in fluidic communication with a channel - e.g., a channel extending parallel to the moveable piezoelectric diaphragm (when the moveable piezoelectric diaphragm is not in an actuated configuration). It may be that the input receives the liquid into the cavity via a valve.

[0058] Advantageously, the inclusion of valves enhances the extraction / delivery of liquid.

[0059] It some embodiments, the microneedle device further comprises an input for receiving the liquid above the cavity (and respective moveable piezoelectric diaphragm). The input may in fluidic communication with a channel extending substantially parallel to moveable piezoelectric diaphragm (when the moveable piezoelectric diaphragm is not in an actuated configuration).

[0060] In some embodiments, the or each moveable piezoelectric diaphragm comprises an opening for fluidic connection between the respective cavity and at least one of the plurality of microneedles. It may be that the opening is arranged at the periphery of the or each respective moveable piezoelectric diaphragm.

[0061] In some embodiments, the microneedle device further comprises the liquid within the cavity.

[0062] It may be that the microneedle device is configured so that, in use, when the or each moveable piezoelectric diaphragm is deformed in a first sense, the respective cavity is in fluidic communication with at least one microneedle of the one or more microneedles, and wherein the or each moveable piezoelectric diaphragm is deformed in a second sense, the respective cavity is not in fluidic communication with any of the one or more microneedles.

[0063] It may be that the control circuitry is configured to sense fluid characteristics. For example, it may be that the control circuitry is configured to sense fluid flow rates through the device and / or fluid viscosity. It may be that the control circuitry is configured to sense whether the device contains fluid.

[0064] It may be that each microneedle defines at least in part a respective fluid channel extending therethrough, wherein the microneedle characteristic is indicative of whether a bubble exists within the fluid channel of a respective microneedle. It may be that the first circuit is configured to generate an output signal based on the microneedle characteristic. It may be that the output signal is for triggering removal of the bubble. It may be that the output signal is for disabling a microneedle. It may be that the output signal is for alerting the user that operation of the microneedle device is compromised.

[0065] Bubbles within the microneedles can affect the operation of the microneedle device - e.g., by preventing fluid delivery / extraction. Advantageously, the first circuit can be configured to generate a signal (e.g., to trigger an alert, or a control strategy) in response to the detection of such bubbles, thereby facilitating more efficient and effective use of the microneedle device. The first circuit may be further configured to trigger removal of the bubble, thereby improving the operation of the microneedle device by facilitating improved fluid flow through the microneedle channel. The signal may trigger the generation of ultrasound to remove the bubble. For example, the signal may trigger movement of the moveable piezoelectric diaphragm of the PMLIT element coupled to the microneedle having the bubble in the respective fluid channel.

[0066] It may be that the control circuitry comprises the first circuit.

[0067] By providing the first circuit within the integrated circuitry, the overall size of the microneedle device can be reduced (e.g., compared to embodiments where the first circuit is not provided within the substrate), thereby facilitating more portable microneedle devices.

[0068] It may be that the control circuitry is configured to control ultrasound transmission by controlling movement of the or each moveable piezoelectric diaphragm. It may be that the control circuitry is configured to control ultrasound reception by receiving signals resulting from movement of the or each moveable piezoelectric diaphragm.

[0069] Transmitted ultrasound can be used to improve fluid extraction and / or delivery, thereby providing a more effective microneedle device. In particular, the characteristics of transmitted ultrasound may be chosen to enhance fluid delivery through the user’s skin. Without wishing to be bound by theory, this may involve increasing the permeability of the skin by disrupting cells / opening microscopic channels.

[0070] Received ultrasound can be used to detect microneedle characteristics (e.g., blockages) or characteristics of the target body (e.g., heart rate or pressure within the skin).

[0071] It may be that the control circuitry is configured to control ultrasound transmission.

[0072] It may be that the control circuitry is configured to control movement of the or each moveable piezoelectric diaphragm to extract liquid from the target body. It may be that the control circuitry is configured to control movement of the or each moveable piezoelectric diaphragm to deliver liquid to the target body. The inventors have further realised that PMLIT elements can be used to extract and / or deliver fluid to the target body. That is, the PMLIT elements can effectively be used as pumps. It is possible for individual microneedles to have a dedicated pump provided by a respective PMLIT element, thereby providing improved control of fluid delivery / extraction.

[0073] Typically, microneedle devices require external (i.e., non-integrated) pumps. By providing a microneedle device with integrated PMLIT elements and the associated control circuitry, it is possible to provide more portable fluid delivery / extraction systems.

[0074] It may be that the microneedle device further comprises a temperature sensor for measuring the liquid temperature, wherein the control circuitry is configured to control movement of the or each moveable piezoelectric diaphragm based on the liquid temperature.

[0075] It will be understood that liquid viscosity is generally temperature dependent. By providing integrated temperature sensors and control circuitry configured to control the movement piezoelectric diaphragms based on the measured temperatures, improved fluid delivery / extraction is facilitated.

[0076] It may be that microneedle device further comprises a reservoir for storing a liquid therein. It may be that the reservoir contains a liquid for delivery to the target body and / or a liquid extracted from the target body.

[0077] It may be that the substrate has a first surface, the one or more microneedles extending from the first surface and the one or more PMLIT elements formed on the first surface, wherein at least a portion of the control circuitry is integrally formed at the first surface.

[0078] By providing a microneedle device having one or more microneedles, one or more PMLIT elements and control circuitry formed on the same surface the form factor of the device is further reduced. It may be that the one or more PMLIT elements each comprise one or more materials processable at a temperature below 450°C. It may be that the or each moveable piezoelectric diaphragm comprises scandium aluminium nitride.

[0079] Typically, each moveable piezoelectric diaphragm comprises a piezoelectric body, a first electrode and a second electrode. It may be that the piezoelectric body comprises one or more piezoelectric materials processable at a temperature below 450°C. Examples of piezoelectric materials that are processable at temperatures below 450°C include aluminium nitride (AIN), zinc oxide (ZnO), and / or scandium aluminium nitride (ScAIN).

[0080] Some electronics (e.g., CMOS components) can be damaged at temperatures greater than 450°C. By using piezoelectric materials that are processable at a temperature below 450°C, MEMS and electronic components can be integrated whilst avoiding degradation of the electronics, thereby improving the operation and efficiency of the device.

[0081] In particular, the use of ScAIN facilitates the use of low powers to operate the microneedle device, thereby improving energy efficiency, portability, and safety.

[0082] According to another aspect of the invention, there is provided a valve comprising: a substrate; a piezoelectric actuator formed on the substrate, wherein the piezoelectric actuator comprises a moveable piezoelectric diaphragm; control circuitry integrally formed with the substrate for controlling the movement of the piezoelectric actuator; the valve having a first state for allowing fluid flow therethrough, wherein in the first state the moveable piezoelectric diaphragm is deformed in a first sense; and the valve having a second state for stopping fluid flow therethrough, wherein in the second state the moveable piezoelectric diaphragm is deformed in a second sense.

[0083] According to another aspect of the invention, there is provided a wearable patch comprising any of the microneedle devices or valves described herein. According to another aspect of the invention, there is provided a liquid suitable for use with any of the microneedle devices, valves or patches described herein.

[0084] It will be understood that liquids will typically require specific properties to be suitable to be used with the microneedle device described herein. In particular, the rheological properties must not be such that, for liquids comprising medically active components, damage is caused to the medically active components that inhibits or even substantially prevents the desired medical effect.

[0085] The liquid may comprise charged particles. The liquid may comprise ions (e.g., polyatomic ions). The liquid may comprise ionic drugs (e.g., charged drug particles). It may be that the liquid comprises a solute dissolved in a solvent. It may be that the charged particles comprise the ions of the solute. The liquid may have charged particles (e.g., nanoparticles / nanodrugs having a surface charge) provided within (e.g., in a suspension). The liquid may have chargeable particles provided therein.

[0086] The invention extends to any of the devices described herein, comprising the liquid.

[0087] According to an aspect of the invention, there is provided a microneedle device comprising: a substrate; one or more microneedles extending from the substrate, and for insertion into a target body; and one or more piezoelectric micromachined ultrasound transducer, PMLIT, elements formed on the substrate, wherein each of the one or more PMLIT elements comprises a moveable piezoelectric diaphragm.

[0088] It may be that control circuitry is integrally formed with the substrate and electrically coupled to the one or more PMLIT elements.

[0089] It will be understood that features described in conjunction with a particular aspect of the invention are to be understood to be applicable to any other aspect described herein unless incompatible therewith. All of the features disclosed in this specification may be combined in any combination, except combinations where at least some of such features and / or steps are mutually exclusive.

[0090] Description of the Drawings

[0091] An example embodiment of the present invention will now be illustrated with reference to the following Figures in which:

[0092] Figures 1-2 are schematic representations of a microneedle device, according to the invention;

[0093] Figure 3 is a schematic representation of part of a microneedle device according to the invention, showing a PMLIT element in more detail;

[0094] Figure 4 is a schematic representation of a microneedle array according to the invention;

[0095] Figure 5 is a schematic representation of a microneedle device according to the invention;

[0096] Figure 6A is a schematic representation of a microneedle device having a valve arrangement in a first configuration, according to the invention,

[0097] Figure 6B is a schematic representation of the same microneedle device as Figure 6A showing the valve arrangement in a second configuration, according to the invention;

[0098] Figure 7 is a schematic representation of a microneedle device configured to apply an electric field to a user according to the invention; and

[0099] Figure 8 is a schematic representation of a microneedle device configured to apply an electric field to a user according to the invention.

[0100] Detailed Description of an Example Embodiment

[0101] Figure 1 is a schematic representation of a microneedle device 100 having a PMLIT element 102 formed on a substrate 104. One microneedle 106 extends from the substrate 104 above the PMLIT element 102. An outlet valve seat 108 is provided between the microneedle 106 and the substrate 104. CMOS control circuitry 110 comprising a plurality of transistors is integrally formed with the substrate 104, and electrically couped to the PMLIT element 102 via conductive connections (not shown). A cavity 112 is defined in part by the moveable piezoelectric diaphragm 102 and in part by the substrate 104.

[0102] In use, fluid flows from the cavity 112 via the aperture 114 through the centre of the moveable piezoelectric diaphragm 102. The fluid is delivered to the user via a channel 118.

[0103] Further, in use, the moveable piezoelectric diaphragm of the PMLIT element 102 is configured to deform into the cavity 112. The CMOS control circuitry 110 is configured to receive electrical signals generated by the movement of the moveable piezoelectric diaphragm 102. According, the PMLIT element 102 together with the CMOS control circuitry 110 operates as a sensor to allow the status of the microneedle 106 to be sensed. The control circuitry 110 generates a signal which can be used to determine multiple operational conditions - e.g., whether the microneedle 106 is correctly inserted in a user’s skin or whether the microneedle 106 is blocked by an air bubble. In this embodiment, the operational conditions are determined based on the frequency of oscillation of the membrane when in contact with the fluid. The inventors have realised that the frequency of oscillation is affected by air bubbles blocking the channel 118 and the insertion status of the microneedle 106, for example. In other embodiments, the act of inserting the microneedle 106 into the user’s skin may cause a force to be transferred through fluid (between the microneedle 106 and the PMLIT element 102) and exerted on the moveable piezoelectric membrane. The resultant movement of the moveable piezoelectric membrane may be detected and used to identify correct insertion of the microneedle 106. In other embodiments, the PMLIT element 102 may be used to transmit ultrasound and receive a reflected signal. The received signal may be used to determine correct insertion of the microneedle 106 / presence of a blockage in the channel 118.

[0104] Figure 2 shows another schematic representation of a microneedle device 200 having a PMLIT element 202 formed on a substrate 204.

[0105] The microneedle device 200 is similar to the microneedle device 100 shown in Figure 1. In particular, the microneedle device 200 also comprises a microneedle 206 having a channel 218 therethrough, an outlet valve seat 208, CMOS control circuitry 210 and a cavity 212. One difference between the embodiment shown in Figure 1 and the embodiment shown in Figure 2, is that the PMLIT element 202 has a central aperture 214 through the moveable piezoelectric membrane in addition to peripheral apertures 216.

[0106] In the embodiment shown at Figure 2, the CMOS control circuitry 210 is configured to control movement of the moveable piezoelectric diaphragm of the PMLIT element 202 to force fluid through the channel 218 and, in a different operational mode, to extra fluid from a target body through the channel 218. That is, in use, the PMLIT element 202 functions as a pump for delivery and extraction of fluid through the microneedle 206 coupled therewith. In this embodiment, the CMOS control circuitry is also configured to provide sensing capabilities as described in relation to Figure 1.

[0107] Figure 3 shows one possible configuration of part of a microneedle device 300. The device 300 comprises a semiconductor substrate 310 having a first surface 312 opposite to a second surface 314. The device 300 includes CMOS control circuitry comprising a plurality of transistors 320 integrally provided within the substrate 310. A CMOS metallisation layer 330 is provided on the first surface 312. The PMLIT element comprises a moveable piezoelectric diaphragm including a piezoelectric body 350, a first electrode 352 and a second electrode 354 each arranged on the first surface 312. The moveable piezoelectric diaphragm also includes an additional layer 360 (made from the same material as the rest of the substrate, in this embodiment). A cavity 340 is defined in part by the moveable piezoelectric diaphragm and in part by the semiconductor substrate 310. In this embodiment, the CMOS metallisation layer 330 includes conductive connections 332, 334 extending from the plurality of transistors 320 to the first electrode 352. The device also includes a protective layer 370. In this embodiment, the moveable piezoelectric diaphragm does not extend across the full side of the cavity (i.e. , it is discontinuous). Each of the first electrode 352, the second electrode 354, and the piezoelectric body 350 are annular and arranged concentrically. The additional layer 360 and protective layer 370 are also discontinuous such that an aperture 390 is defined through the moveable piezoelectric diaphragm - thereby increasing the flexibility of the piezoelectric diaphragm and allowing the flow of fluid therethrough. Figure 4 shows a microneedle array 400 having a plurality of microneedles 406A-E extending from a substrate 404. Each of the microneedles 406A-E is coupled to a respective PMLIT element 402A-E. Control circuitry 410 is provided in the substrate 404 and coupled to each of PMLIT elements 402A-E. Accordingly it is possible to provide sensing / pumping capabilities on the level of individual microneedles, whilst still providing a compact microneedle array.

[0108] Figure 5 shows another schematic representation of a microneedle device 500. The microneedle device has a PMLIT element 502, having peripheral apertures 516 for allowing the flow of a fluid therethrough. The microneedle device 500 further comprises a microneedle 506, having a channel 518, extending from a substrate 504. The microneedle device 500 comprises an outlet valve seat 508, control circuitry 510 and a cavity 512. In this embodiment the cavity 512 is filled with a pharmaceutical fluid. The microneedle device 500 further comprises a channel extending parallel to the PMLIT element 502 for directing the pharmaceutical fluid into the cavity 512 from a reservoir (not shown).

[0109] In use, the microneedle 506 pierces a user’s skin. Pharmaceutical fluid can then flow from the cavity 512 through the apertures 516 into the user’s skin. In this embodiment, the control circuitry 510 is configured to control movement of the moveable piezoelectric diaphragm 502 to transmit ultrasound towards the microneedle. This transmitted ultrasound can help to drive the pharmaceutical fluid through the channel 518 and enhance drug absorption by increasing the permeability of the skin.

[0110] Figures 6A and 6B show schematic representations of a microneedle device 600 having a valve arrangement. The microneedle device 600 has a PMLIT element 602 formed on a substrate 604. A microneedle 606 has a channel 618 and extends from the substrate 604. The microneedle device 600 comprises an outlet valve seat 608, a check valve 620, an inlet valve seat 622, control circuitry 610, a cavity 612 and a passive valve 624.

[0111] Figure 6A shows the microneedle device 600 in a first configuration. In this configuration the moveable piezoelectric diaphragm of the PMLIT element 602 is deformed in a first sense. This movement is controlled by the control circuitry 610. This causes the valve 624 to open and for fluid to flow into the cavity 612. In the first configuration, fluid cannot flow through the PMLIT element 602 to access the channel 618 of the microneedle 600.

[0112] Figure 6B shows the microneedle device 600 in a second configuration. In this configuration the moveable piezoelectric diaphragm of the PMLIT element 602 is deformed in a second sense. This causes the valve 624 to close. In the second configuration, fluid can flow through the PMLIT element 602 to access the channel 618 of the microneedle 600.

[0113] That is, in this embodiment, the PMLIT element 602 operates as a valve.

[0114] Figure 7 shows a microneedle device 700 having a plurality of microneedles 706A-E extending from a substrate 704. Each of the microneedles 706A-E is coupled to a respective PMLIT element 702A-E. Control circuitry 710 is provided in the substrate 704 and coupled to each of PMLIT elements 702A-E. In use, this microneedle device 700 is configured to apply an electric field to a user. The microneedle 706A acts as a cathode and each of the PMLIT elements 702A-E function as anodes. This allows a potential difference to be set up between the electrodes. In this example, the potential different provided is around 10 V and the electric field is static. In use, the microneedle device can be used to supply a pharmaceutical fluid having charged particles to a user. The pharmaceutical fluid is pumped via the channels of each microneedle 706A-E using the PMLIT elements 702A-E. The electric field enhances transport of the charged particles which are forced through the user’s tissue to provide improved drug delivery (i.e., via iontophoresis).

[0115] Figure 8 shows a microneedle array 800 having a plurality of microneedles 806A-E extending from a substrate 804. Each of the microneedles 806A-E is coupled to a respective PMLIT element 802A-E. Control circuitry 810 is provided in the substrate 804 and coupled to each of PMLIT elements 802A-E. In this example separate cathodes 830 are integrated with the substate. Each of the PMLIT elements 802A-E function as anodes. In use, an electric field can be generated by the microneedle device. In this example the control circuitry 810 is used to generate control signals to cause the generation of high voltage pulses (e.g., 50 V to 3000 V, and pulse durations of 5 ps to 100 ms). This increases the permeability of the tissue leading to improved drug absorption (i.e., via electroporation).

[0116] Manufacturing the microneedle devices described herein typically involves a step of forming each required cavity within a substrate. Typically, the cavities are provided using a DRIE etch procedure from the backside of the substrate. Buried oxide and deep trench isolation structures can be used to define the cavity dimensions. The control circuitry can then be formed within the substrate. For example, transistors may be formed by standard CMOS processing methodologies including ion implantation on a p-type or n-type substrate. Metallisation layers can also formed by standard processes such as ion implantation chemical vapour deposition, physical vapour deposition, etching, chemical-mechanical planarization and / or electroplating.

[0117] Each moveable piezoelectric diaphragm can then be formed on the substrate. Forming each moveable piezoelectric diaphragms involves forming the respective electrodes and intervening piezoelectric body. Typically this step involves using successive thin film deposition techniques. Preferably, each piezoelectric body is formed of a material such as AIN or ScAIN which may be deposited at a temperature below 450°C by physical vapour deposition (including low-temperature sputtering). The electrodes are formed of, for example titanium, platinum, aluminium, tungsten or alloys thereof.

[0118] Each microneedle (or group of microneedles) can then be coupled to substrate (optionally via another layer).

[0119] Throughout the description and claims of this specification, the words “comprise” and “contain” and variations of them mean “including but not limited to”, and they are not intended to and do not exclude other components, integers, or steps. Throughout the description and claims of this specification, the singular encompasses the plural unless the context otherwise requires. In particular, where the indefinite article is used, the specification is to be understood as contemplating plurality as well as singularity, unless the context requires otherwise.

[0120] Features, integers, characteristics, or groups described in conjunction with a particular aspect, embodiment, or example of the invention are to be understood to be applicable to any other aspect, embodiment or example described herein unless incompatible therewith. All of the features disclosed in this specification (including any accompanying claims, abstract and drawings), and / or all of the steps of any method or process so disclosed, may be combined in any combination, except combinations where at least some of such features and / or steps are mutually exclusive. The invention is not restricted to the details of any foregoing embodiments. The invention extends to any novel one, or any novel combination, of the features disclosed in this specification (including any accompanying claims, abstract and drawings), or to any novel one, or any novel combination, of the steps of any method or process so disclosed.

Claims

Claims1 . A microneedle device comprising: a substrate; one or more microneedles extending from the substrate, and for insertion into a target body; one or more piezoelectric micromachined ultrasound transducer, PMLIT, elements formed on the substrate, wherein each of the one or more PMLIT elements comprises a moveable piezoelectric diaphragm; and control circuitry integrally formed with the substrate and electrically coupled to the one or more PMLIT elements.

2. The microneedle device according to claim 1 , wherein each of the one or more PMLIT elements is coupled to at least one microneedle of the one or more microneedles, and optionally wherein each microneedle is coupled to a single PMLIT element, and further optionally wherein each PMLIT element is coupled to a corresponding single microneedle.

3. The microneedle device according to any preceding claim, wherein the microneedle device is configured to generate an electric field for application to part of a user’s body.

4. The microneedle device according to claim 3, wherein the control circuitry is configured to generate a control signal for generating the electric field.

5. The microneedle device according to any preceding claim, wherein the control circuitry is configured to receive electrical signals generated by the movement of the or each moveable piezoelectric diaphragm, and generate a signal based on the movement of the or each moveable piezoelectric diaphragm.

6. The microneedle device according to claim 5, further comprising a first circuit, wherein the first circuit is configured to determine a microneedle characteristic based on the signal, and optionally wherein the microneedle characteristic is indicative ofwhether at least one of the one or more microneedles is correctly inserted in the target body; and / or wherein the first circuit is configured to determine a target body characteristic based on the signal, and optionally wherein the target body characteristic is indicative of an internal pressure of the target body.

7. The microneedle device according to claim 6, wherein the microneedle characteristic and / or the target body characteristic is determined in dependence on an oscillation of at least one of the moveable piezoelectric diaphragms, and optionally in dependence on a frequency of the oscillation.

8. The microneedle device according to claim 6 or 7 wherein the first circuit is configured to generate an output signal based on the determined microneedle characteristic and / or target body characteristic, and optionally wherein the output signal is for disabling at least one of the one or more microneedles and / or for alerting the user that operation of the microneedle device is compromised.

9. The microneedle device according to any preceding claim, wherein the microneedle device is configured to extract liquid from the target body and / or deliver liquid to the target body, and optionally wherein the fluid is extracellular fluid or a pharmaceutical liquid.

10. The microneedle device according to claim 9 when dependent on claim 6 or 7, wherein, in use, each microneedle defines at least in part a respective fluid channel extending therethrough, wherein the microneedle characteristic is indicative of whether a bubble exists within the fluid channel of a respective microneedle, and optionally, wherein the first circuit is configured to generate an output signal based on the microneedle characteristic, and further optionally, wherein the output signal is for triggering removal of the bubble, disabling a microneedle and / or for alerting the user that operation of the microneedle device is compromised.

11. The microneedle device according to any of claims 6-8 or 10, wherein the control circuitry comprises the first circuit.

12. The microneedle device according to any preceding claim wherein the control circuitry is configured to control ultrasound transmission by controlling movement of the or each moveable piezoelectric diaphragm and / or control ultrasound reception by receiving signals resulting from movement of the or each moveable piezoelectric diaphragm, and / or wherein the microneedle device further comprises a reservoir for storing a liquid therein, and optionally wherein the reservoir contains a liquid for delivery to the target body and / or a liquid extracted from the target body.

13. The microneedle device according to any preceding claim, wherein the control circuitry is configured to control movement of the or each moveable piezoelectric diaphragm to extract liquid from the target body and / or deliver liquid to the target body, and optionally wherein the microneedle device further comprises a temperature sensor for measuring the liquid temperature, wherein the control circuitry is configured to control movement of the or each moveable piezoelectric diaphragm based on the liquid temperature.

14. The microneedle device according to any preceding claim, the substrate having a first surface, the one or more microneedles extending from the first surface and the one or more PMLIT elements formed on the first surface, wherein at least a portion of the control circuitry is integrally formed at the first surface, and / or wherein the one or more PMLIT elements each comprise one or more materials processable at a temperature below 450°C, and optionally wherein the or each moveable piezoelectric diaphragm comprises scandium aluminium nitride.

15. A valve comprising: a substrate; a piezoelectric actuator formed on the substrate, wherein the piezoelectric actuator comprises a moveable piezoelectric diaphragm;control circuitry integrally formed with the substrate for controlling the movement of the piezoelectric actuator; the valve having a first state for allowing fluid flow therethrough, wherein in the first state the moveable piezoelectric diaphragm is deformed in a first sense; and the valve having a second state for stopping fluid flow therethrough, wherein in the second state the moveable piezoelectric diaphragm is deformed in a second sense.

16. A wearable patch comprising the microneedle device according to any of claims 1-14 or the valve according to claim 15.

17. A liquid suitable for use with the microneedle device according to any of claims 1-14, the valve according to claim 15, or the patch according to claim 16.

18. The liquid according to claim 17, wherein the liquid comprises charged particles and / or wherein the liquid has chargeable particles.

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