The present invention relates to a sensor for real-time monitoring of a subject's metabolites and vital ion levels in bodily fluids. The present invention also relates to an electrochemical etching process for tapering a tip end of a metal blank such as the end of a metal wire.

The present invention is particularly concerned with a sensor capable of measuring blood glucose and lactate for physiological assessment in a subject in sport and critical care medicine. The present invention is more particularly concerned with a sensor capable of providing an output to a device in real time to trigger an event which will cause a device to deliver a therapeutic drug or reagent. BACKGROUND OF INVENTION

Blood lactate and glucose measurements have been previously used to assist in the physiological assessment of athletes. Lactate is a key metabolite in the anaerobic glycolic pathway and lactate levels in physiological fluids provide an indication of energy release under anaerobic conditions. When plotted against workload, blood lactate related thresholds provide key reference points for prescription of training intensity, for example. These reference points allow coaches and athletes to structure balanced training programs and to prevent over-reaching or over-training and physiological damage.

Methods of measuring blood lactate and glucose have previously involved the collection and analysis of blood samples from athletes. For example for lactate measurements, the LactatePro and Lactate Scout test strips enable readings to be obtained from lancet prick blood sampling. However, this process involves cessation of athlete's activity and discontinuity of activity could impact on the validity of the measurements.

Blood samples for glucose and lactate testing may be taken during activity by simulating the relevant activity in a laboratory or medical environment. However, a simulated environment may not adequately recreate a subject or athlete's normal operating environment. This being the case, the results of the testing may not accurately reflect the subject's or athlete's blood glucose or lactate levels during normal activity.

Further, for some sports such as rowing, where the athlete is using both legs and arms during the activity, it may still be the case that the nature of the activity requires rest period to allow the acquisition of blood.

Lactate measurement is also a useful tool in medicine for the assessment of:

1. Patients experiencing respiratory difficulties;

2. Patients recovering from a cardiac arrest or cardiac surgery; 3. Patients undergoing multiple organ failure, or monitoring of an organ transplant recipient;

4. Monitoring of prematurely born infants;

5. Patients suffering septic shock;

6. Patients with tumours; 7. Patients suffering drug or toxin overdoses.

Glucose measurement is a useful tool in sports medicine for the assessment of blood glucose levels in athletes for energy monitoring, and in clinical medicing for patients experiencing Type 1 Diabetes, Type 2 Diabetes, gestational Diabetes mellitus or other forms of diabetes including endocrine diseases, drug induced diabetes or immune disorders.

Sensors have been developed by others for in vivo glucose and/or lactate measurement. The sensors are typically invasive, often requiring minor surgery to be implanted and removed.

A sensor has been developed that utilises Fourier Transform Infrared spectroscopy to detect glucose for example. This involves the implantation of a optoelectronic device and glucose sensitive indicator by way of a large bore needle into the fatty layer beneath the skin of a subject. A Fourier Transform Infrared sensor is about the size of an oral medicine capsule with a light emitting diode as the light source. Sensors have also been manufactured on a biochip. Amperometric biosensors are imprinted onto a silicon wafer and the wafer inserted through a small incision made in the flesh. These sensors have dimensions typically of the order of 2mm x 4mm.

Another type of sensor termed a needle-type sensor is a probe like structure inserted into tissue and veins of a subject to detect target metabolites. The probes have a diameter of 0.5mm. Again these sensors are highly invasive and painful.

Needles with diameters of the order of 80μm, hereafter referred to as micro-needles, have been developed for use in the medical field. These needles are used to increase the permeability of the skin for transdermal drug delivery and to sample fluids from the stratum corneum painlessly, as an alternative to intravenous injection. These micro-needles have been developed using micro- electro-mechanical system (MEMS) technology and micro-needles with a diameter of the order of 80μm have been produced. Some of these needles have been solid needle like structures produced by etching silicon. These silicon needles are then coated with drugs and inserted into the skin delivering the drugs just below the tough outer layer of the skin painlessly.

Micro-needles should to be sufficiently robust to penetrate the stratum corneum but sufficiently short to avoid stimulating nerves. Techniques used in the past to fabricate micro-needles have been reactive ion etching of silicon to produce an array of needles. These needles were 150μm in length 80μm in diameter and radius of curvature less than 1μm, and comprised solid needles. However silicon is a fragile material resulting in microneedles being damaged or broken when inserted into the skin; in addition the fabrication of tips sufficiently sharp to penetrate the dermis has proven difficult as disclosed in Henry, S., et al., Microfabricated Microneedles: A Novel Approach to Transdermal Drug Delivery. J. Pharm. Sci., 1998. 87(8): p. 922-925.

Similar MEMS techniques have been applied to the fabrication of microneedles composed of the photoresist epoxy polymer SU-8, which requires fabrication onto a micro-layer of silicon dioxide on a silicon wafer. Although these micro-needles were able to be successfully fabricated so that they were hollow for microinjection and formed arrays, tests to date have shown that penetration through the epidermis layer of human skin samples is still problematic as disclosed in PoIIa, D. L., et al., Microdevices in medicine. Annu. Rev. of Biomed. Eng., 2000. 2: p. 551-576.

Micro-needles fabricated from metal substrates therefore are more suited for penetration of the dermis and upper layers of the skin. Metal needles having tips with a radius of curvature less than 100nm have been used in scanning tunnelling microscopy; scanning tunnelling spectroscopy; and field-ion microscopy. Metal needles have also been used in medical areas for neural stimulation and drug delivery, for example. These metal needles have tips that are reproducible and have a well defined geometry.

Conventional electrochemical etching and polishing techniques for producing needles generally involves the mechanical withdrawal of individual metal wires from an electropolishing solution. The radius of curvature of the needle tips formed by traditional electrochemical etching and polishing processes are not generally suitable for use in micro-needle formation.

Sharp metal tips have been previously produced by way of electrochemical etching and polishing. For example, sodium hydroxide etching has produced tungsten tips with a radius of curvature of about 10nm. Some examples of electrochemical techniques are described below. Silver tips for scanning tunnelling microscopy having a final curvature radius less than 200nm have previously been produced in a two step electrochemical process. An example of such a process is disclosed in Gorbunov, A.A. and B. Wolf, The Use of Silver Tips in Scanning Tunnelling Microscopy. Rev. Sci. Instrum., 1993. 64(8): p. 2393-2394. Platinum and platinum iridium tips suitable for use in scanning tunnelling microscopy have been previously produced by way of an etching method using CaCI2 followed by H2SO4 micro-polishing within a horizontal glass tube. This process is described in Libioulle, L., Y. Houbion, and J.-M. Gilles, Very Sharp Platinum Tips for Scanning Tunnelling Microscopy. Rev. Sci. Instrum., 1995. 66(1): p. 97-100. Silver tips with curvature radii of less than 100nm are typically used in laser scanning tunnelling microscopy and nano-structuring. Mechanical tip movement techniques to provide electronically controlled removal of the tip during electrochemical etching to achieve a high degree of tip reproducibility are described in Dickmann, K., F. Demming, and J. Jersch, New Etching Procedures for Silver Scanning Tunnelling Microscopy Tips. Rev. Sci. Instrum., 1996. 67(3): p. 845-846.

It is desirable to overcome or ameliorate one or more of the above- described difficulties, or at least provide a useful alternative. The invention takes the form of a number of different embodiments. These embodiments may be employed independently or in any combination. SUMMARY OF INVENTION

In accordance with one aspect of the invention resides the use of microneedles as ultramicroelectrodes for the detection of target metabolites or vital ions. According to this embodiment the invention provides an array of microneedles which have lengths up to 1mm long and diameters less than 80μm.

In accordance with one aspect of the present invention, there is provided an electrochemical etching process for producing a sharp tapering tip of a metal blank such as a wire, including the steps of : (a) providing an electrochemical cell having a voltage source, electrolyte solution, and a metal blank electrode and a counter electrode;

(b) generating ultrasonic waves on a surface of the electrolyte; and

(c) positioning the tip end of the blank in the path of said waves such that said tip end periodically contacts the waves. Preferably, the process step of generating is effected by an ultrasonic wave bath or ultrasonic wave probe and the step of positioning includes the step of positioning the tip end of the blank at substantially half the amplitude of the ultrasonic surface waves.

The blank preferably forms a micro-needle having a diameter in the range of approximately 8μm to 80μm. In one embodiment, said metal blank is a silver wire and the micro-needle has a length of substantially in the range of 100μm - 300μm and the tip end has a radius of curvature in the order of 100nm. In another embodiment the metal blank is a platinum wire and the micro-needle has a length in the order of about 100μm-300μm and the tip end has a radius of curvature of less than about 100nm. In yet another embodiment, the metal blank is a stainless steel wire and the micro-needle has a length in the order of 100μm-

300μm and the tip end has a radius of curvature of less than 100nm.

In accordance with another aspect of the present invention, there is provided a microneedle formed in accordance with the above-described process.

The micro-needle is preferably shaped for painless insertion into the skin of a subject and is sufficiently robust to penetrate the epidermis without significant deformation or fracture

In accordance with another aspect of the present invention, there is provided an electrochemical etching cell for tapering a tip end of a metal blank, including: (a) ultrasonic wave generating means for producing waves on a surface of an electrolyte; and (b) means for positioning the tip end of the blank in the path of said waves such that said tip end periodically contacts the electrolyte waves.

In accordance with another aspect of the present invention, there is provided an electrochemical etching cell for tapering a tip end of a metal blank such as a wire, including:

(a) a voltage source;

(b) electrolyte solution;

(c) a metal blank electrode, such as a wire;

(d) a counter electrode; (e) ultrasonic wave generating means for producing ultrasonic waves on a surface of an electrolyte; and

(f) means for positioning the tip end of the blank in the path of said waves such that said tip end periodically contacts the surface waves of the electrolyte.

In accordance with another aspect, the micro needles can be used as ultra-microelectrodes for the detection of target metabolites by a sensor. In accordance with another aspect of the present invention, there is provided a sensor for real-time monitoring of blood metabolite and vital ion levels in a subject, including a controller and a data acquisition facility in electrical communication with an array of micro-needles, wherein the controller is adapted to continuously measure blood variables in the dermal interstitial fluid of the subject by way of the array of micro-needles. Preferably, blood metabolites and vital ions such as lactate, glucose, potassium, calcium, sodium, carbon dioxide, oxygen and pH maybe measured with this sensor device. Preferably, the microneedles are converted to ultramicroelectrodes. In accordance with another aspect of the present invention, there is provided a sensor for monitoring blood metabolites and vital ions in a subject, including a controller and data acquisition facility in electrical communication with an array of micro-needles, wherein the controller is adapted to measure metabolite levels below the stratum corneum of the subject by way of the array of micro-needles.

The array of micro-needles are preferably implantable microelectrode sensors and each microelectrode of the array of microelectrodes is preferably a micro-needle formed in accordance with the above described process.

The controller may be a microcontroller that includes a program that controls measurement of said metabolite levels. Further, the data storage facility can store the results of the sampling in a computer readable data storage area. In addition, the microcontroller can communicate with a computer terminal using a mobile phone network to transfer the results of the sampling.

The microelectrodes are preferably mechanically coupled to a substrate containing the microelectronics.

The micro-needles are preferably sufficiently robust to penetrate the stratum corneum of the subject and sufficiently short to avoid stimulating nerves. In accordance with another aspect of the present invention, there is provided a sensor for monitoring concentrations of blood variables in a subject, including a controller in electrical communication with an array of micro-needles, wherein the controller is adapted to measure the concentration of blood variables from the stratum corneum of the subject by way of the array of micro-needles.

The micro-needles are preferably ultramicroelectrodes and the array of micro-needles are preferably implantable microelectrode sensors. Each micro- needle of the array of micro-needles is preferably a micro-needle formed in accordance with the above described process.

The controller is preferably a microcontroller that includes a program that controls measurement of said metabolite levels. The microcontroller can store the results of the sampling in a computer readable data storage area. Further, the microcontroller can communicate with a computer terminal to transfer the results of the sampling.

The micro-needles are preferably mechanically coupled to a substrate, to which the controller is also coupled. The micro-needles are preferably sufficiently robust to penetrate the stratum corneum of the subject and sufficiently short to avoid stimulating nerves. Preferably, the microneedles in the array range between 100μm to 1mm. More preferably, the miconeedles in the array range between 200μm and 600μm.

Advantageously, the micro-needles are sufficiently robust to penetrate the stratum corneum of the subject and sufficiently short to avoid stimulating nerves. In accordance with another aspect of the present invention provides a sensor capable of measuring blood glucose and lactate for physiological assessment in a subject in sport or critical care medicine.

In accordance with yet another aspect of the invention there is provided a sensor capable of providing an output to a device in real time. Such output being capable of triggering an event which will cause a device to deliver a therapeutic drug or reagent, wherein the event is a change in surface characteristics of the device enabling release.

More particularly the therapeutic drugs or reagents are nanostructured having preferred dimensions of between 10 nanometres and 200 nanometres and between 200 nanometres and 2 microns. The sensor in accordance with the invention advantageously provides real-time measurements of important aspects of blood chemistry and in this respect is different from current systems which require blood sampling, collection or medical insertion for measurement. DESCRIPTION OF PREFERRED EMBODIMENTS

Preferred embodiments of the present invention are hereafter described, by way of nonlimiting example only, with reference to the accompanying drawings, in which:

Figure 1 is a diagrammatic illustration of an ultrasonic electrochemical assembly in accordance with a preferred embodiment of the present invention;

Figure 2 is a diagrammatic illustration of an ultrasonic electrochemical assembly in accordance with a preferred embodiment of the present invention;

Figure 3 is a scanning electron microscope image of a needle formed by a process in accordance with a preferred embodiment of the present invention; Figure 4 is a scanning electron microscope image of a needle formed by a process in accordance with a preferred embodiment of the present invention;

Figure 5 is a scanning electron microscope image of a needle formed by a process in accordance with a preferred embodiment of the present invention;

Figure 6 is a scanning electron microscope image of a needle formed by a process in accordance with a preferred embodiment of the present invention;

Figure 7 is a scanning electron microscope image of the needle shown in Figure 6 after further processing;

Figure 8 is a scanning electron microscope image of a needle formed by a process in accordance with a preferred embodiment of the present invention; Figure 9 is a scanning electron microscope image of the needle shown in

Figure 8 at higher magnification showing the fine tip;

Figure 10 is a diagrammatic illustration of a blood chemistry patch sensor in accordance with a preferred embodiment of the present invention;

Figure 11 is another diagrammatic illustration of the blood chemistry patch sensor shown in Figure 10; Figure 12 is a scanning electron microscope image of an ultra- microelectrode of the sensor shown in Figures 10 and 11 illustrating the coating process; and

Figure 13 is a scanning electron microscope image of another ultra- microelectrode of the sensor shown in Figures 10 and 11 illustrating an alternate thicker coating process.

Ultrasonic Electrochemical Etching

The ultrasonic electrochemical assembly shown in Figures 1 or 2 are used to produce sharp tapered tip ends 12 on metal blanks 14 such as tips of wires. The process is effected by creating ultrasonic waves 16 on the surface of an electrolyte 18 and by arranging the tip 15 end 12 of the metal blank 14 in the path of the waves so that it is periodically immersed in the electrolyte 18. Electrochemical etching is effected by the periodical immersion of the tip end 12 of the metal blank in the electrolyte 18.

The ultrasonic electrochemical assembly 10 includes a voltage source 20 coupled to the blank 14 and to a counter electrode 22 by respective electrically conductive wires 24, 26 to effect the electrochemical etching of the blank 14. The electrolyte 18 is housed in a container 28 that is either seated in an ultrasonic bath 30 Figure 1 or has an ultrasonic probe in contact with the electrolyte 32 Figure 2. The ultrasonic bath 30 or probe 32 transfer energy to the container 28 and creates ultrasonic waves 16 on the surface of the electrolyte 18.

The electrochemical etching was effected using ultrasonic waves in the surface of the electrolyte by way of performing the following steps: 1. Arranging the tip end 12 of the blank 14 so that it is placed between 1mm and 2mm into the surface of the electrolyte, as shown in Figures 1 & 2;

2. Arranging the counter electrode 22 so that it is at least partially submerged in the electrolyte, as shown in Figures 1 & 2;

3. Connecting the blank 14 to the voltage source 20 using wire 24 as shown in Figures 1 & 2; 4. Connecting the counter electrode 22 to the voltage source 20 using wire 26 as shown in Figures 1 & 2;

5. Turning the ultrasonic bath 30 or probe 32 on;

6. Arranging the tip end 12 of the blank 14 at half the amplitude "A" of the ultrasonic waves on the surface of the electrolyte so that the tip end 12 is 10 periodically immersed in the electrolyte 18, as shown in Figures 1 & 2;

7. Turning voltage source 20 on;

8. Waiting for a predetermined period of time as defined by loss of surface contact; and 9. Removing the resultant sharp needle 14.

The above described process of ultrasonic electrochemical etching provides reproducible metal tip ends 12 for needles 14 and micro-needles, without the need for precisely controlled machinery for the withdrawal of the needles from the electrolyte 18. The needles 14 are uniformly tapered and can form micro-needles having diameters in the range of approximately 1μm to 20μm. Silver, platinum and stainless steel micro-needles formed using the described ultrasonic electrochemical etching technique have a length of about 300μm and have curvature radii less than approximately 100nm.

The stainless steel needle 34 shown in Figure 3 was produced by way of the above described ultrasonic electrochemical etching method. The radius of curvature of the tip end 34 is of the order of 100nm and the diameter of the needle at a length of about 150μm (a length designed to penetrate the stratum corneum, epidermis and about 30μm of the skin dermis) is approximately 20μm. The stainless steel micro-needle 34 is within the guidelines for painless insertion into the skin of a subject and is sufficiently robust to penetrate the dermis without deformation or fracture.

The Process

The ultrasonic electrochemical etching assembly 10, shown in Figure 1 or 2, was used for the platinum, silver and stainless steel electrochemical etching processes. Platinum 99.9+% and silver 99.9% wire of 0.1mm diameter was sourced from Sigma Aldrich (Australia) and Stainless Steel surgical Grade 316L 0.1mm diameter was sourced from Goodfellow (UK). All chemicals were of analytical grade.

1. Platinum

Platinum wire 14 was electrochemically etched in an acetone saturated calcium chloride solution 18. A 1 :1 solution of distilled water and acetone was mixed and CaCI2 was added to provide a concentration of 0.06M. The acetone was present to prevent the bubble stream produced disturbing the dissolution process and the tip end 12 shape.

To electrochemically etch the platinum wire 14, a peak to peak sinusoidal potential of 20V at 40Hz was applied between the platinum wire 14 and a glassy carbon electrode 22 using a Tektronix CFG253 3MHz function generator 20. This resulted in a stable hydrogen bubble stream at the metal interface indicating the occurrence of etching. This was continued until the tip end 12 no longer made contact with the solution and the bubble stream stopped.

The tip end 40 platinum wire 42 shown in Figure 4 was effected after 60 seconds exposure to ultrasonic electrochemical etching in the CaCI2 electrolyte 18. The initial etching process produced deposits of platinum black on the tip end 40 of the wire. The tip end 40 was subsequently cleaned and smoothed by immersing in the 0.5M sulfuric acid solution and applying +15V pulses between the tip and the glassy carbon electrode without ultrasonic input. This process provided a well defined sharp tip end 40 radius of curvature less than 100nm and length about 300μm, as shown in Figure 5.

2. Silver

Electrochemical etching of silver wire was carried out in a 25% ammonia solution. To electrochemically etch the silver wire 14, a 10V dc potential was applied between the silver wire 14 and a stainless steel counter electrode 22. The potential difference was applied using an Autolab PGSTAT 30 Potentiostat/Galvanostat 20 and again it was applied until the tip end 12 of the wire 14 no longer made contact with the electrolyte solution 18 and the bubble stream stopped. The tip end 44 of the silver wire 46 shown in Figure 6 was effected using the ultrasonic electrochemical process until no further bubble stream was visible indicating that the tip was no longer in contact with the solution 18. The silver tips 44 produced by ultrasonic electrochemical etching have a significantly higher degree of surface contamination than the platinum tips. Cleaning of the silver tips 44 in 0.5M sulfuric acid did not require the application of a potential nor ultrasonic input to produce the final clean surface with a very sharp tip 44 shown in Figure 7. The silver tips 44 produce by this process had a radius of curvature of around 100nm.

3. Stainless Steel To electrochemically etch the stainless steel wire 14, a 2.5V dc potential difference was applied again with the Autolab PGSTAT 30 Potentiostat/Galvanostat 20 until the tip no longer made contact with the electrolyte solution 18 and the bubble stream stopped.

The ultrasonic electrochemical etching of the stainless steel wire 14 was achieved in a 10% HCI electrolyte with an applied potential difference of 2.5V dc, applied between a stainless steel counter electrode 22 and the stainless steel wire 14, working electrode. During the etching process bubbles were produced at the counter electrode together with a yellow stain in the solution at the working electrode 14. Ultrasonic electrochemical etching continued until the bubble stream from the counter 22 ceased.

The stainless steel tip end 48 of the needle 50 shown in Figures 8 and 9 produced by the above described ultrasonic electro-chemical etching process, has a radius of curvature at the tip end 48 of an order less than 100nm and the diameter of the resultant needle, at a length of approximately 150μm, is about 8μm. Needles 50 of this length are suitable to penetrate the stratum corneum, epidermis and about 30μm of the skin dermis. The above-described process of ultrasonic electrochemical etching provides reproducible platinum, silver and stainless steel tips 12 for needles 14 without the need for precisely controlled mechanical withdrawal techniques. The tips 12 of the needles 14 are uniformly 10 tapered. The process of ultrasonic electrochemical etching provides needles 14 having diameters about 5 to 20 μm and the tips have radii of curvature less than 100nm for platinum, silver and stainless steel. The micro-needles have overall lengths of about 300μm.

Metabolite Sensor Patch

The lactate sensor patch 100 shown in Figures 10 and 11 is used to take blood metabolite or vital ion measurements in a subject. The patch 100 can be applied to a skin surface of a subject and, when so fitted, take a series of measurements or continuously measure metabolite or vital ion levels and stores the results of these measurements for later use.

After a period of use, the patch 100 can be removed from the subject and the results of the measurements can be analysed. The patch 100 facilitates realtime measurement of blood metabolite or vital ion levels in a subject in a non- intrusive manner. The patch 100 can be worn by an athlete, for example, and take blood lactate measurements during a period of normal activity. This data can provide important physiological information about true metabolic effect of the activity on the subject's body.

The patch 100 can also be used to monitor blood lactate levels in patients to detect increased blood lactate levels signalling distress in critical organs of the body.

The patch 100 can also be used to monitor blood glucose levels in patients to detect increased blood lactate levels signalling distress in critical organs of the body.

The Metabolite Sensor Patch 100 shown in Figure 10 includes microelectronics 112 consisting of a microcontroller and data acquisition facility connected to an array of ultra-microelectrode needles 110 via one or more cables. The microelectrode needles protrude from the underside side of the substrate. The needles 110 are mechanically held in position by the substrate. The electronics 112 are contained in a small box and connected via a cable. The electronics 112 are capable of being strapped onto the subject in close proximity to the placement of the microelectrode needle substrate. The metabolite sensor patch 100 includes a patch substrate with an adhesive side (which is preferably the underside of the substrate), and a non-adhesive side (which is preferably a topside of the substrate). The micro-needles protrude approximately 300-500μm from the adhesive underside of the patch. The patch 100 is fitted by applying the adhesive side to a skin surface of the subject. Dimensions of these needles allow painless insertion.

The Metabolite Sensor Patch shown in Figure 11 is the same as that shown in Figure 10 with the exception that in Figure 11 the microelectronics 114 are mounted on the top surface of the patch 100.

1. Ultra-microelectrode needles 110

The above-described ultrasonic electrochemical etching technique produces metal microneedles that can be used as substrates for preparation of ultra-microelectrodes 110. The metabolite sensor patch 100 utilises electrochemical detection principles and thin film technologies combined in a device to measure blood metabolite and vital ion levels in real time and or continuously. The patch 100 may utilise enzymes to catalyse chemical reactions and electrochemical reduction of the products for measurement. Example

The enzyme Lactate Oxidase (LOD) is used as a catalyst in the reaction below where lactic acid, oxygen and water in the presence of the LOD enzyme is converted to Pyruvate and hydrogen peroxide.

L-lactate+O ₂ +H ₂ O → Pyruvate+H ₂ O ₂ The hydrogen peroxide is then electrochemically oxidised usually at a platinum surface by:

The electrons produced are detected as a current proportional to the hydrogen peroxide concentration and therefore also the lactic acid concentration. The micro-needles 14 produced by the above-described ultrasonic electrochemical etching process are coated with a thin film for immobilization of the enzymes suitable for in vivo use. Implantable enzyme sensors can employ polymers to immobilise the enzymes.

However, many of these polymers, if degraded, are toxic in vivo. The patch 100 preferably uses an electrode coating based upon a non-toxic polymer. An example of such a non-toxic polymer system is an adaptation of the lectin- sucrose system as described and investigated by Anzai Layer-by-Layer Construction of Enzyme Multilayers on an Electrode for the Preparation of Glucose and Lactate Sensors: Elimination of Ascorbate Interference by Means of an Ascorbate Oxidase Multilayer. Analytical Chemistry, 1998. 70: p. 811-817 and Kobayashi Glucose and Lactate Biosensors Prepared by a Layer-by-Layer Deposition of Concanavalin A and Mannose-Labelled Enzymes: Electrochemical Response in the Presence of Electron Mediators. Chemical Pharmacy Bulletin, 2001. 49(6): p. 755-757.

Alternative electrochemical and/or enzymatic process maybe employed to continuously monitor other blood metabolites or vital ions of physiological and medical significance. The Micro-needles 14 fabricated using the above-described ultrasonic electrochemical etching technique are used to developed an array of ultra-microelectrodes 110. The working ultra-microelectrodes 110 are constructed utilizing thin films 116 of a suitable non-toxic polymer system, as shown in Figures 12 and 13. These enzyme films 116 are applied to the micro-needle substrates in varying thicknesses to give different life-times of the sensors. For example, a patch 100 having ultra-microelectrodes with a thin enzyme film 116, as shown in Figure 12, may have a life expectance of 1 hour. Further, a patch 100 having ultra-microelectrodes with a thick enzyme film 116, as shown in Figure 13, may have a life expectance of 3 hours. The films 116 will be suitable for in vivo applications without fear of toxicity.

2. Microelectronics 112 and 114

The microelectronics 112 and 114 are designed to interface with a personal computer, for example, to transfer data on blood chemistry measurements collected. This may be effected by coupling communications wires between the microelectronics 112 or 114 and the personal computer, or may be effected by any other suitable means.

The microelectronics 112 and 114 includes a program stored in memory that controls the process of taking continuous blood metabolite or vital ion measurements from a subject and storing the results of those measurements for later use. It will be understood by those skilled in the relevant art that the microcontroller 112 and 114 could alternatively be made up of a number of different components implemented entirely in hardware, firmware or any suitable combination thereof. The components, or parts thereof, may also be implemented by application specific integrated circuits (ASICs). The sensor patch 100 is preferably water proof. In the described embodiments the sensor continuously measures blood metabolites and vital ions, in the sense that it continuously executes a suitable routine to produce a series of measurements over time. Also these measurements are stored in the data acquisition facility. However, the manner in which one or more such measurements are made, over time is not critical to the invention.

Similarly, while storage in the data acquisition facility is suitable for many applications, it may not be necessary to so store the measurement, or it may alternatively be stored, such as in the controller itself. Further, the measurements may not be stored at all, or only stored in temporary memory. For example, the measurements may be passed to, eg an external computer terminal, or other device e.g. mobile phone using standard communications techniques such as wire, or wireless, communications link.

While we have shown and described specific embodiments of the present invention, further modifications and improvements will occur to those skilled in the art. We desire it to be understood, therefore, that this invention is not limited to the particular forms shown and we intend in the append claims to cover all modifications that do not depart from the spirit and scope of this invention.

Throughout this specification, unless the context requires otherwise, the word "comprise", and variations such as "comprises" and "comprising", will be understood to imply the inclusion of a stated integer or step or group of integers or steps but not the exclusion of any other integer or step or group of integers or steps. The reference to any prior art in this specification is not, and should not be taken as, an acknowledgment or any form of suggestion that the prior art forms part of the common general knowledge in Australia or any other country.