Microneedle device for diagnosis and / or health monitoring

Abstract

The invention provides improvements in the design of microneedles, microneedle arrays, microneedle patches or microarray patches. The invention combines a microneedle with a sensor for detecting physical parameters which relate to the receipt of fluid in the microneedle from a patient and a circuit in communication with the sensor for processing sensor data. It may be applied to the skin as a patch containing an array of microneedles to diagnose and / or monitor the health of a patient through contact between the microneedles which penetrate the epidermis to extract fluid from the patient.

Description

[0001] Title

[0002] Microneedle Device for Diagnosis and / or Health Monitoring

[0003] Field

[0004] The present disclosure relates to a microneedle and in particular, to microneedle array, microneedle patch or microarray patch suitable for diagnosis and / or health monitoring in a recipient.

[0005] Microneedles, also referred to as microneedle arrays, microneedle patches or microarray patches are micron-scaled medical devices for administering therapeutic agents for example, vaccines and drugs. They may also be used for diagnostic applications by interacting with the biomarker-laden interstitial fluid (ISF) that lies beneath the outermost skin layer.

[0006] Microneedles are usually applied as a single needle or small array. The arrays are a collection of microneedles, ranging from only a few microneedles to several hundred, attached to an applicator, sometimes a patch or other solid stamping device.

[0007] The main types of microneedles are solid, hollow, coated, dissolvable / dissolving, and hydrogel-forming.

[0008] Medical diagnosis is the process of determining which disease or condition explains a person's symptoms and signs. Diagnosis is often challenging because many signs and symptoms are nonspecific. For example, redness of the skin (erythema), by itself, is a sign of many disorders.

[0009] Laboratory diagnosis is a diagnosis based significantly on diagnostic test results, for example, the measurement of blood sugar. Another type of diagnosis is screening which may be defined as a medical test or series of tests used to detect or predict the presence of disease in at-risk individuals within a defined group such as a population, family, or workforce. Screenings may be performed to monitor disease prevalence, manage epidemiology, aid in prevention or for statistical purposes. Examples of screenings include measuring the level of TSH in the blood of a newborn infant as part of newborn screening for congenital hypothyroidism, checking for lung cancer in non-smoking individuals who are exposed to second-hand smoke in an unregulated working environment, and Pap smear screening for prevention or early detection of cervical cancer,

[0010] In medicine, monitoring is the observation of a disease, condition or one or several medical parameters over time. It can be performed by continuously measuring certain parameters by using a medical monitor (for example, by continuously measuring vital signs by a bedside monitor), and / or by repeatedly performing medical tests (such as blood glucose monitoring with a glucose meter in people with diabetes mellitus).

[0011] One example is the monitoring and diagnosis of pregnant mothers. Of the 140million born globally each year, around 15 million are born preterm. Complications during birth account for 40 % of perinatal and maternal deaths, and cause a severe cost burden to healthcare, not only due to immediate shortterm costs of intensive neonatal care but most importantly, long-term adverse effects and life-long complications. Many preterm births could be prevented with careful pregnancy monitoring and early prediction and detection of risks and complications.

[0012] Microneedle technologies, based around polymeric arrays that absorb interstitial fluid (ISF) from the skin, are known for the monitoring of biomarkers such as glucose, lactate and cortisol, amongst others. However, current solutions require the patch to be removed from the user for offline recovery and subsequent analysis of the absorbed ISF, which clearly limits the opportunities for deployment in low-cost, continuous monitoring applications.

[0013] Summary of the Invention

[0014] It is an object of the invention to overcome at least one of the above-referenced problems. It is an object of the present invention to provide improvements in the design of microneedles, microneedle arrays, microneedle patches or microarray patches.

[0015] It is another object of the present invention to provide high-value, intelligent systems which merge microelectronics and biodegradable materials suitable for insertion in the skin.

[0016] According to the invention there is provided a microneedle and or a microneedle array, as set out in the appended claims.

[0017] In accordance with a first aspect of the invention there is provided, a microneedle assembly for diagnosis and / or monitoring a patient comprising: a microneedle with a base, and a tip, the microneedle further comprising a sensor for detecting physical parameters which relate to the fluid transferred to the microneedle from the body of the patient and a circuit in communication with the sensor for processing sensor data.

[0018] In at least one embodiment, the invention further comprises an array of microneedles.

[0019] In at least one embodiment, the microneedles are adapted to extract fluid from the patient.

[0020] In at least one embodiment, the microneedles are adapted to absorb interstitial fluid (ISF) from the patient.

[0021] In at least one embodiment, the absorption of interstitial fluid creates a pathway in the microneedle

[0022] In at least one embodiment, the pathway extends from the base to the tip of the microneedle. In at least one embodiment, the fluid is interstitial fluid.

[0023] ISF is rich in biomarkers such as glucose, lactate and cortisol, and ISF sampling may be used to continuously and / or discreetly monitor the physiological status of the body without resorting to blood extraction procedures.

[0024] In at least one embodiment, the sensor is attached to the base of the microneedle.

[0025] In at least one embodiment, the sensor comprises a planar electrode.

[0026] In at least one embodiment, the sensor comprises one or more planar electrodes.

[0027] In at least one embodiment, the sensor comprises a planar, interdigitated electrode.

[0028] In at least one embodiment, the sensor measures impedance.

[0029] In at least one embodiment, the sensor measures capacitance.

[0030] In at least one embodiment, the sensor uses electrodes which are bio-modified to selected target biomarkers.

[0031] In at least one embodiment, the circuit is mounted on or near the base of the microneedle.

[0032] In at least one embodiment, the sensor is linked to the circuit by microconnectors.

[0033] In at least one embodiment, the sensor comprises a continuous monitoring sensor.

[0034] In at least one embodiment, the sensor comprises an electrochemical sensor. Suitably the electrochemical sensor is capable of detecting biomarkers in interstitial fluid for diagnostic purposes. These biomarkers include, but are not limited to, glucose, lactate, cortisol and the like.

[0035] In at least one embodiment, the microneedle further comprises a coating.

[0036] In at least one embodiment, the coating is a degradable coating which blocks the microneedle from interaction with the skin.

[0037] In at least one embodiment, the coating blocks the microneedle from interaction with the skin, for a predetermined period after which the microneedle is activated.

[0038] In at least one embodiment, the array of microneedles has microneedles with degradable coatings that degrade at different rates such that the one or more of the microneedle is activated at different times from initial skin contact.

[0039] In at least one embodiment, the coating is a bioresorbable material.

[0040] In at least one embodiment, the degradable coating is an electrically conductive degradable coating.

[0041] In at least one embodiment, the electrically conductive degradable coating is part of an electrical circuit which monitors degradation of the degradable coating.

[0042] In at least one embodiment, the rate of degradation of the degradable coating is dependent upon the thickness of the coating.

[0043] In at least one embodiment, the rate of degradation of the degradable coating is dependent upon the composition of the coating.

[0044] In at least one embodiment, the circuit comprises an adherence monitor which monitors coating degradation upon epidermal contact, to determine the time at which the microneedle interacts with the skin. In at least one embodiment, caused by epidermal contact.

[0045] In at least one embodiment, the adherence monitor facilitates controlled delivery.

[0046] In at least one embodiment, the microneedle further comprises a passivation layer applied to at least part of the base and or the degradable coating.

[0047] In at least one embodiment, the degradable layer further comprises storage protection for encapsulating the microneedle or microneedle array.

[0048] In at least one embodiment, the microneedle is dissolvable.

[0049] In at least one embodiment, the microneedle is swellable.

[0050] In at least one embodiment, the microneedle is made of a hydrogel.

[0051] In at least one embodiment, the present invention comprises a wearable patch which has microelectronic sensors integrated within biodegradable microneedles to create a painless gateway to the body for applications in transdermal diagnosis and / or monitoring.

[0052] In accordance with another aspect of the invention there is provided, a microneedle assembly for diagnosis and / or monitoring a patient comprising: a microneedle with a base, and a tip, the microneedle further comprising a sensor for detecting physical parameters which relate to the fluid transferred to the microneedle from the body of the patient and a circuit in communication with the sensor for processing sensor data. The microneedle further comprises a degradable coating which blocks the microneedle from interaction with the skin.

[0053] In at least one embodiment, the degradable coating blocks the microneedle from interaction with the skin, for a predetermined period after which the microneedle is activated. In at least one embodiment, the array of microneedles has microneedles with degradable coatings that degrade at different rates such that the one or more of the microneedle is activated at different times from initial skin contact.

[0054] In at least one embodiment, the coating is a bioresorbable material.

[0055] In at least one embodiment, the degradable coating is an electrically conductive degradable coating.

[0056] In at least one embodiment, the electrically conductive degradable coating is part of an electrical circuit which monitors degradation of the degradable coating.

[0057] In at least one embodiment, the rate of degradation of the degradable coating is dependent upon the thickness of the coating.

[0058] In at least one embodiment, the rate of degradation of the degradable coating is dependent upon the composition of the coating.

[0059] In at least one embodiment, the circuit comprises an adherence monitor which monitors coating degradation upon epidermal contact, to determine the time at which the microneedle interacts with the skin.

[0060] In at least one embodiment, the adherence monitor facilitates controlled delivery.

[0061] In at least one embodiment, the microneedle further comprises a passivation layer applied to at least part of the base and or the degradable coating.

[0062] In at least one embodiment, the degradable layer further comprises storage protection for encapsulating the microneedle or microneedle array.

[0063] In accordance with another aspect of the invention there is provided, a microneedle assembly for diagnosis and / or monitoring a patient comprising: a microneedle with a base and a tip, the microneedle further comprising a sensor for detecting physical parameters which relate to the fluid transferred to microneedle from the body of the patient and a circuit in communication with the sensor for processing sensor data., the microneedle further comprises an adherence monitor which monitors coating degradation upon epidermal contact, to determine the time at which the microneedle interacts with the skin.

[0064] In accordance with another aspect of the invention there is provided, a microneedle assembly for diagnosis and / or monitoring a patient comprising: a microneedle with a base and a tip, the microneedle further comprising a sensor for detecting physical parameters which relate to the fluid transferred to the microneedle from the body of the patient and a circuit in communication with the sensor for processing sensor data., the microneedle further comprises a passivation layer applied to at least part of the base and or the degradable coating.

[0065] In at least one embodiment, the degradable layer further comprises storage protection for encapsulating the microneedle or microneedle array.

[0066] Brief Description of the Drawings

[0067] The invention will be more clearly understood from the following description of an embodiment thereof, given by way of example only, with reference to the accompanying drawings, in which:-

[0068] Figure 1 is a schematic illustration of an example of a microneedle assembly in accordance with the present invention;

[0069] Figure 2a is an illustration of an example of a microneedle assembly in accordance with the present invention and figure 2b is an illustration of an example of a microneedle array which incorporates the microneedle of figure 2a; Figure 3 is a diagram of an example of a microneedle assembly in accordance with the present invention;

[0070] Figures 4a and 4b show an example of a microneedle array in accordance with the present invention which incorporates adherence monitoring;

[0071] Figures 5a, 5b and 5b show an example of a microneedle array in accordance with the present invention which incorporates controlled delivery;

[0072] Figures 6 shows an example of a microneedle array in accordance with the present invention which incorporates passivation;

[0073] Figures 7a and 7b show an example of a microneedle array in accordance with the present invention which incorporates storage protection;

[0074] Figures 8a and 8b show an example of a swellable microneedle for use in at least one embodiment of the present invention;

[0075] Figures 9a and 9b show an example of a degradable microneedle for use in at least one embodiment of the present invention; and

[0076] Figure 10 shows sensor field penetration in an example of a microneedle assembly in accordance with the present invention.

[0077] Detailed Description of the Drawings

[0078] The present invention provides improvements in the design of microneedles, microneedle arrays, microneedle patches or microarray patches. The invention combines a microneedle with a sensor for detecting physical parameters which relate to the receipt of fluid in the microneedle from a patient and a circuit in communication with the sensor for processing sensor data. In at least one embodiment, the present invention may be applied to the skin as a patch containing an array of microneedles to diagnose and / or monitor the health of a patient through contact between the microneedles which penetrate the epidermis to extract fluid from the patient.

[0079] Dissolvable microneedles and swellable microneedles may be used in diagnostic applications to extract interstitial fluid (ISF), the intracellular fluid present in the outermost skin layers, by absorption / extraction of the ISF by polymer-based microneedles. ISF is rich in biomarkers such as glucose, lactate and cortisol, and ISF sampling may be used to continuously and / or discreetly monitor the physiological status of the body without resorting to blood extraction procedures.

[0080] Hydrogel microneedles swell in the skin to produce continuous, unblockable conduits between the dermal microcirculation and the microneedle assembly.

[0081] The hydrogel microneedles swell significantly upon uptake of interstitial fluid for use as diagnostic sensors

[0082] This technique may be used in minimally invasive diagnostics, particularly with regard to improved patient compliance and the development of sophisticated theranostic platforms. It may also be used in the delivery of healthcare services using wearable technologies and communication devices. In wearable diagnostics, the present invention may be used to continuously monitor ISF-borne biomarkers, by embedding micro electrochemical sensors (ECS) within swellable hydrogel microneedles. In one example, the measurement of interstitial glucose, may be used in diabetes management by providing an unobtrusive method of continuously recording glucose levels.

[0083] Figure 1 shows a microneedle assembly which comprises a microneedle with a base 5 which supports a microneedle 3. The microneedle 3 comprises a body 7 and a tip 9. A sensor 1 1 for detecting physical parameters which relate to the transfer of fluid to the fluid pathway is mounted on the base 5 so as to be operatively connected to the body 7 of the microneedle 3. The circuit 13 is in communication with the sensor for processing sensor data. The sensor can be a nano-sensor.

[0084] Figure 2a shows microneedle assembly 1 1 with an electrochemical sensor 13 positioned above the microneedle 15. Figure 2b is an illustration of an example of a rectangular microneedle array 17 which incorporates a number of microneedle assemblies arranged in lines. The array has a central circuit 19 which processes data from sensors located in the microneedle assemblies 1 . Suitably the electrochemical sensor 13 is capable of detecting biomarkers in interstitial fluid for diagnostic purposes. These biomarkers include, but are not limited to, glucose, lactate, cortisol and the like.

[0085] Figure 3 is a diagram of an example of a microneedle assembly which forms part of a microneedle array in accordance with the present invention. It shows a microneedle assembly 21 which has a needle 23, supported by a base 25. The microneedle has a body 27 which extends from the base 25 to the tip 29. Sensors 31 are mounted in the base 25 and an adhesive 39 is used to fix the circuitry to the microneedle 23. In this example of the present invention a paper battery 33 is provided between the flexible circuitry 35 and the microneedle 23. Connectors 36 provide electrical connection between the various components.

[0086] In this and other examples of the present invention, a polymer moulding technology to create biodegradable and hydrogel microneedles. In one example Moulds 37 are formed from polydimethylsiloxane (PDMS) and silicon templates The moulds 37 are then filled with biodegradable materials and dried.

[0087] Planar electrodes / sensors 31 are attached at the base 25 of the microneedle 23. Sensors 31 may be selected to measure for example, capacitance or impedance which are both functions of the water content of the polymer and its environment. The circuitry is created using photolithographic techniques to pattern electrodes on to a flexible substrate such as polyimide, which is bonded to the needle array using medical tapes as the adhesive 39. Holes are die cut in these tapes to allow interaction between needle and sensor. In this and other examples of the present invention, the use of flexible materials allows the microneedle array to be incorporated into minimally invasive transdermal ‘smart’ tattoo-like patches with active delivery needles which can be used as a diagnostic tool.

[0088] The base of a microneedle is severely limited in area having a diameter of ~300pm. Alignment tolerances of 50pm between layers are met using advanced photolithography and / or e-beam lithography techniques. The semi-transparent nature of the microneedle polymer facilitates alignment.

[0089] In this example of the present invention, the sensor / needle layer is linked via microconnectors 36 to the flexible printed circuit 35 (FPC) incorporating miniaturized sensor conditioning circuitry and communications modules.

[0090] Surface mount components, such as the ADM350 on-chip potentiostat or AD7746 capacitance-to-digital converter, interrogate the sensors. Bluetooth Low Energy (BLE) or Near-Field Communication (NFC) standards may be used. Miniature systems-on-chip may be used, they have integrated functionality such as microcontrollers, sensors and antennae.

[0091] The flexible, disposable ‘paper’ battery is located between the needle / sensor assembly 23,31 and the circuit module 35 so that antenna performance will not be affected. The patch will be approximately 3 cm square, and a further advantage of using microconnectors is that both battery and sensor module will be detachable and incinerable, thereby allowing (a) reuse of the core circuit module if required and (b) separate sterilisation of the sensor module.

[0092] Capacitive dissolution sensors embedded within the microneedle may be used to characterise the skin / microneedle interaction. The sensor’s output capacitance depends on the relative dielectric permittivity, sr, of the material, which varies with water content (Er ~ 4 for a dry polymer, and Er ~ 80 for water). Using high-resolution capacitance-to-digital converters, microneedle moisture content is measured over the range from dry (0% moisture) to total dissolution (100 %).

[0093] The present invention also allows for the monitoring of moisture uptake and may detect when degradation of the microneedle has taken place before use.

[0094] The present invention provides a discreet device capable of continuously monitoring ISF biomarkers in-vivo. In at least one example there is provided a continuous monitoring sensor which uses electrodes which are bio-modified to selected target biomarkers, for example Interstitial glucose. In contrast, minimally invasive continuous glucose monitors (CGM), use a subcutaneous needle-like sensor and have issues with patient compliance and discomfort.

[0095] Electrochemical sensors are based on the measurement of a current flowing from an oxidation reaction at a working electrode, to a reduction reaction at a counter electrode. Three electrodes (working, counter and reference) are formed by photolithographically defining working and reference electrodes, along with a counter electrode. The electrodes are formed on a flexible substrate that is embedded at the base of the dissolvable microneedle.

[0096] Figures 4a and 4b show an example of a microneedle array 41 in accordance with the present invention which incorporates adherence monitoring. Figure 4a shows microneedles 43, base 45, body 47 and tip 49. The key shows the microneedle material 51 and bioresorbable material 53. The circuit 55 measures changes in impedance 57 which occur as a result of the degradation of the bioresorbable metal 53.

[0097] In this and other examples of the present invention, the bioresorbable metals will degrade when in contact with the moist epidermis when the microneedle array is applied to the skin. This degradation can be used to break an electrical circuit, which changes the impedance and therefore monitor the time at which the microneedle material interacts with the skin. Degradation 59 of the bioresorbable material is shown in figure 4b which also shows an increase in resistance. The application of the present invention to adherence monitoring may be used in drug delivery or diagnostics.

[0098] Figures 5a, 5b and 5b show an example of a microneedle array 61 in accordance with the present invention which incorporates controlled delivery. The microneedle 63 has a base 65, body 67 and tip 69. The key shows the microneedle material 71 and bioresorbable material 73. Of the three microneedles shown, different thicknesses of bioresorbable metal are applied to the surface. These are shown as increasing thickness 1 75, thickness 2, 77 and thickness 3 79. Layers of different thicknesses will degrade at different times and enable parts of the microneedle array to become activated at a pre-defined time. Figure 5b shows the bioresorbable metal of thickness 1 in figure 5a having completely degraded 81 . Bioresorbable metal of thicknesses 2 and 3 in figure 5a having partially degraded 83 and 85. Figure 5c shows the bioresorbable metal of thickness 2 in figure 5a having completely degraded 87. Bioresorbable metal of thickness 3 in figure 5a has partially degraded 89.

[0099] Figure 6 shows an example of a microneedle array 91 in accordance with the present invention which incorporates passivation. Figure 6 shows microneedles 93, base 95, body 49 and tip 99. The key shows the microneedle material 101 , bioresorbable material 103 and passivation layer 105. The circuit 107 measures changes in impedance and is used to monitor changes in impedance which may occur as a result of moisture on the skin interacting with the microneedle. In effect, the circuit is present to monitor whether the passivation layer is intact and operating correctly.

[0100] Figures 7a and 7b show an example of a microneedle array 121 in accordance with the present invention which incorporates storage protection. Figure 7a shows microneedles 123, base 125, body 127 and tip 129. The key shows the microneedle material 131 and bioresorbable material 133. The circuit 137 measures changes in impedance 137 which occur as a result of the degradation of the bioresorbable metal 53. These metal layers may be used to encapsulate microneedle arrays during shipping and storage, thereby enhancing the stability and shelf life of microneedle devices.

[0101] In this and other examples of the present invention, the bioresorbable metals will degrade when in contact with the moist epidermis when the microneedle array is applied to the skin. This degradation can be used to break an electrical circuit, which changes the impedance and therefore monitor the time at which the microneedle material interacts with the skin. Degradation 139 of the bioresorbable material is shown in figure 7b which also shows an increase in resistance. The application of the present invention to adherence monitoring may be used in drug delivery or diagnostics.

[0102] Figures 8a and 8b show an example of a swellable microneedle for use in at least one embodiment of the present invention. Figure 8a shows a hydrogel microneedle 141 . Figure 8b shows a swollen hydrogel microneedle 151 .

[0103] Hydrogel microneedles swell in the skin to produce continuous, unblockable conduits between the dermal microcirculation and an attached patch-type drug reservoir, through which therapeutic agents could diffuse thus allowing prolonged transdermal drug administration. Pulsatile or bolus delivery can be achieved under electrical control.

[0104] In addition, hydrogel microneedles swell significantly upon uptake of interstitial fluid and may be used as diagnostic sensors.

[0105] Figures 9a and 9b show an example of a degradable microneedle 161 for use in at least one embodiment of the present invention. The degradable microneedles of figure 9a degrades 171 to deliver its cargo to the epidermis as shown in figure 9b.

[0106] Figure 10 shows sensor field penetration in an example of a microneedle assembly in accordance with the present invention. It shows a microneedle 181 substrate 183, adhesive 185, the needle 187. Electric fields between sensor electrodes can be directed into the material and the ‘penetration depth’ of these fields, as shown by zones 193 and 195 corresponding to positions 189 and 191 across the base of the microneedle and is determined by the electrode spacing. Therefore, sensor capacitance will be altered by moisture in the body of the needle, but will remain insensitive to changes in the external environment (i.e. whether stored in air or placed in skin). Arrays of sensors, with varying spacing, may be used to map the three- dimensional diffusion pattern within the needle.

[0107] Where used herein and unless specifically indicated otherwise, the following terms are intended to have the following meanings in addition to any broader (or narrower) meanings the terms might enjoy in the art: Unless otherwise required by context, the use herein of the singular is to be read to include the plural and vice versa. The term "a" or "an" used in relation to an entity is to be read to refer to one or more of that entity. As such, the terms "a" (or "an"), "one or more," and "at least one" are used interchangeably herein.

[0108] As used herein, the term "comprise," or variations thereof such as "comprises" or "comprising," are to be read to indicate the inclusion of any recited integer (e.g. a feature, element, characteristic, property, method / process step or limitation) or group of integers (e.g. features, element, characteristics, properties, method / process steps or limitations) but not the exclusion of any other integer or group of integers. Thus, as used herein the term "comprising" is inclusive or open- ended and does not exclude additional, unrecited integers or method / process steps.

[0109] The foregoing description details presently preferred embodiments of the present invention. Numerous modifications and variations in practice thereof are expected to occur to those skilled in the art upon consideration of these descriptions. Those modifications and variations are intended to be encompassed within the claims appended hereto. The invention is not limited to the embodiments hereinbefore described but may be varied in both construction and detail.

Claims

Claims1. A microneedle assembly for diagnosis and / or monitoring a patient comprising: a microneedle with a base and a tip, the microneedle further comprising a sensor for detecting physical parameters which relate to fluid transferred to the microneedle from the body of the patient and a circuit in communication with the sensor for processing sensor data.

2. The microneedle assembly as claimed in claim 1 wherein, the sensor is attached to the base of the microneedle.

3. The microneedle assembly as claimed in any preceding claim wherein, the microneedle is adapted to extract interstitial fluid (ISF) from the patient.

4. The microneedle assembly as claimed in any preceding claim wherein, the microneedle is adapted to absorb fluid from the patient.

5. The microneedle as claimed in claim 4 wherein, the absorption of the fluid creates a pathway in the microneedle.

6. The microneedle as claimed in claim 5 wherein the pathway extends from the base to the tip of the microneedle.

7. The microneedle assembly as claimed in claim 4 wherein, the fluid is interstitial fluid (ISF).

8. The microneedle assembly as claimed in any preceding claim wherein, the sensor comprises a planar electrode9. The microneedle assembly as claimed in any preceding claim wherein, the sensor measures impedance.

10. The microneedle assembly as claimed in any preceding claim wherein, the sensor measures capacitance or resistance.11 . The microneedle assembly as claimed in any preceding claim wherein, the sensor uses electrodes which are bio-modified to selected target biomarkers.

12. The microneedle assembly as claimed in any preceding claim wherein, the circuit is mounted on or near the base of the microneedle.

13. The microneedle assembly as claimed in any preceding claim wherein, the sensor is linked to the circuit by microconnectors.

14. The microneedle assembly as claimed in any preceding claim wherein, the sensor comprises a continuous monitoring sensor.

15. The microneedle assembly as claimed in any preceding claim wherein, the sensor comprises an electrochemical sensor.

16. The microneedle assembly as claimed in any preceding claim wherein, the sensor comprises a nanosensor.

17. The microneedle assembly as claimed in any preceding claim wherein, the microneedle further comprises a coating.

18. The microneedle assembly as claimed in claim 17 wherein, the coating is a degradable coating which blocks the microneedle from interaction with the skin.

19. The microneedle assembly as claimed in claim 17 or claim 18 wherein, the coating blocks the microneedle from interaction with the skin, for a predetermined period after which the microneedle is activated.

20. The microneedle assembly as claimed in any of claims 17 to 19, comprising an array of microneedle assemblies which further comprises asmicroneedles with degradable coatings that degrade at different rates such that the one or more of the microneedle is activated at different times from initial skin contact.21 . The microneedle assembly as claimed in any of claims 17 to 20 wherein, the coating is a bioresorbable material.

22. The microneedle assembly as claimed in any of claims 17 to 21 wherein, the degradable coating is an electrically conductive degradable coating.

23. The microneedle assembly as claimed in claim 22 wherein, the electrically conductive degradable coating is part of an electrical circuit which monitors degradation of the degradable coating.

24. The microneedle assembly as claimed in any of claims 17 to 23 wherein, the rate of degradation of the degradable coating is dependent upon the thickness of the coating.

25. The microneedle assembly as claimed in any of claims 17 to 23 wherein, the rate of degradation of the degradable coating is dependent upon the composition of the coating.

26. The microneedle assembly as claimed in any preceding claim wherein, the circuit comprises an adherence monitor which monitors coating degradation upon epidermal contact, to determine the time at which the microneedle interacts with the skin.

27. The microneedle assembly as claimed in claim 26 wherein, the adherence monitor facilitates controlled delivery.

28. The microneedle assembly as claimed in any preceding claim, which further comprises a passivation layer applied to at least part of the base and or the degradable coating.

29. The microneedle assembly as claimed in any preceding claim, which further comprises storage protection for encapsulating the microneedle or microneedle array.

30. The microneedle assembly as claimed in any preceding claim wherein, the microneedle is dissolvable.

31. The microneedle assembly as claimed in any of claims 1 to 29 wherein, the microneedle is swellable.

32. The microneedle assembly as claimed in claim 31 wherein, the microneedle is made of a hydrogel.

33. A microneedle assembly comprising: a microneedle assembly for diagnosis and / or monitoring a patient comprising: a microneedle with a base, and a tip, the microneedle further comprising a sensor for detecting physical parameters which relate to the fluid transferred to the microneedle from the body of the patient and a circuit in communication with the sensor for processing sensor the microneedle further comprises a degradable coating which blocks the microneedle from interaction with the skin.

34. The microneedle assembly as claimed in claim 31 wherein, the degradable coating blocks the microneedle from interaction with the skin, for a predetermined period after which the microneedle is activated.

35. The microneedle assembly as claimed in claim 33 or claim 34 wherein, comprising an array of microneedle assemblies which further comprises as microneedles with degradable coatings that degrade at different rates such that the one or more of the microneedle is activated at different times from initial skin contact.

36. The microneedle assembly as claimed in claims 33 to 35 wherein, the coating is a bioresorbable material.

37. The microneedle assembly as claimed in claims 33 to 36 wherein, the degradable coating is an electrically conductive degradable coating.

38. The microneedle assembly as claimed in claim 37 wherein, the electrically conductive degradable coating is part of an electrical circuit which monitors degradation of the degradable coating.

39. The microneedle assembly as claimed in claims 33 to 38 wherein, the rate of degradation of the degradable coating is dependent upon the thickness of the coating.

40. The microneedle assembly as claimed in claims 33 to 38 wherein, the rate of degradation of the degradable coating is dependent upon the composition of the coating.41 . A microneedle assembly comprising: a microneedle assembly for diagnosis and / or monitoring a patient comprising: a microneedle with a base and a tip, the microneedle further comprising a sensor for detecting physical parameters which relate to the fluid transferred to microneedle from the body of the patient and a circuit in communication with the sensor for processing sensor data, the microneedle further comprises an adherence monitor which monitors coating degradation upon epidermal contact, to determine the time at which the microneedle interacts with the skin.

42. A microneedle assembly comprising: a microneedle assembly for diagnosis and / or monitoring a patient comprising: a microneedle with a base and a tip, the microneedle further comprising a sensor for detecting physical parameters which relate to the fluid transferred to microneedle from the body of the patient and a circuit in communication with the sensor for processing sensor data., the microneedle further comprises apassivation layer applied to at least part of the base and or the degradable coating.

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