WO2008029110A2

WO2008029110A2 - Electrochemical device with 3 detection areas

Info

Publication number: WO2008029110A2
Application number: PCT/GB2007/003322
Authority: WO
Inventors: Oliver Davies
Original assignee: Suresensors Ltd
Priority date: 2006-09-04
Filing date: 2007-09-04
Publication date: 2008-03-13
Also published as: GB0617276D0; WO2008029110A3

Abstract

A device for measuring the amount of analyte in a fluid sample, typically glucose in blood. The device comprises three detection areas. The first detection area (10) comprises an analyte specific signal generating component reactable with the analyte to generate a response. The second detection area (12) comprises a predetermined amount of an analyte of interest, typically the same analyte as that being measured, for example glucose, for generating a first calibration or correction response. The third detection area (16) is absent an analyte specific signal generating component and generates a second calibration or correction response.

Description

The present invention relates to a method and device for measuring an analyte, preferably in a physiological fluid from a patient. Typically the method and device of the present invention are for use by diabetics to measure the amount of glucose in a blood sample.

Background of the Invention

Diabetes is one of most widespread non-infectious diseases. It is estimated that around 100 million people suffer from diabetes, equivalent to around 4% of the world's population. Furthermore, the prevalence of diabetes is increasing, particularly in developed countries due, in part, to increased obesity rates. The complications associated with diabetes include an increased risk of suffering a heart attack, stroke, blood circulation disorders, kidney damage, blindness and nerve conduction disorders that can result in foot or leg amputations.

Managing diabetes effectively can reduce the risk of complications such as those listed above. Effective management involves maintaining the blood sugar level of a diabetic to within a narrow window of those of a non-sufferer. Various methods of controlling blood sugar levels are well known including adjusting the sugar levels in the diet, increasing exercise, and administering insulin. An essential aspect of these methods is monitoring blood sugar levels to determine whether action should be taken to increase or decrease the amount of sugar in the blood stream by, for example, adjustments to diet, exercise regime or levels of insulin administered.

Diabetics, in particular insulin-dependent diabetics, are advised to monitor their blood sugar levels several times a day in order to adapt and improve treatment plans. Due to the number of times blood sugar levels should be measured, it is highly preferable that diabetics are able to self-monitor blood sugar levels without the need for medical supervision. In recent years self-monitoring glucose measuring devices have been developed, typically including a sensor element that generates a signal, commonly an electrochemical signal, in proportion to the level of glucose in a sample, and an electronic reader device, that converts the generated signal into a readable glucose level. 7 003322

Self-monitoring sensors are commonly calibrated during manufacture in an attempt to insure that these devices provide accurate test results when used by patients. This calibration process aims to assess the sensitivity of these devices to glucose and to assess the level of glucose independent response that is generated by these devices in a typical test. The glucose sensitivity of the device is the calibration slope and the glucose independent response is the calibration intercept. By calibrating these devices prior to sale a calibration slope and intercept can be assigned to each batch. Typically this information is entered in the device in the form of a calibration code that allows the system to convert the raw measured system response to calibrated readings. This calibration information may then be programmed in the electronic test meter by the patient for each separate batch of test strips prior to use. However, during any particular test many post-manufacture factors may affect the blood glucose sensitivity and glucose independent response of these self-monitoring devices leading to inaccurate results. Under such circumstances the calibration information assigned to the product and programmed in the test meter may cease to be correct.

Possible error inducing factors are many and varied and include: compromised product storage leading to damaged reagents in the product; unusually low or high red cell count blood samples; variation in the temperature at which the product is used; addition of insufficient test sample to test strip; the presence of substances in the test sample that interfere with the reaction mechanism eg vitamin C, paracetamol, aspirin; incorrectly handled test strips resulting in product damage; the use of test strips beyond their stated expiry date; test strip and or sample contamination: eg resulting from the user not washing the skin area to be lanced prior to obtaining the blood sample and variation in the humidity at which the product is used.

In order to account for error inducing factors many devices seek to measure parameters that correlate to the presence of commonly occurring error generating factors. Such parameter measurements are then used to correct the device readings for the effects of these error inducing factors. This is only possible if the level of error caused by such error causing parameters can be previously determined experimentally. In this case, a correction algorithm for such error factors can be programmed in to the electronic meter prior to sale. In the case of temperature, for example, the level of error caused by a one degree increase in temperature can be calculated and thus when the temperature at which a test is carried out is measured an appropriate error correction can be applied to the test result. Such an approach can also be used for variations in test sample haematocrit, i.e. red cell count, where an increase in red cell count typically results in a decrease in system response for any given glucose value. Such a correction depends firstly on the system's ability to measure a parameter that correlates to the red cell count of the blood sample in question and secondly on having an algorithm that accurately reflects the effects of increasing red cell count on the system's performance.

A problem with this approach is that it is critical that the correction parameter applied by the electronic meter accurately reflects the actual error experienced as a result of the error causing parameter under all testing conditions. If this is not the case then the system accuracy may deteriorate as a result of the correction rather than improve. Even when the correction parameter correlates well to the cause of a system error it is typically the case that precision is significantly worsened, because errors in the measurement of the correction parameter are added to errors in the initial reading. This is a particular problem where a scaling factor is applied to the correction factor. Additionally, these systems are very sensitive to a variety of production, material and environmental changes that may cause variations in the correlation of the correction parameter to the system error. This sensitivity to a wide variety of error inducing factors can, particularly in combination, cause dramatically inaccurate results.

WO 2005/080970 describes a device for measuring the level of a clinically relevant analyte in a sample of biological origin, for example blood glucose levels. The device has two measuring electrodes, the first of which is exposed to a predetermined amount of the analyte of interest, typically glucose. Both electrodes are contacted with the sample to be tested. The response generated from the known amount of analyte can be calculated and is compared to an expected reading for this known amount of analyte. By comparing the actual reading generated by this known amount of analyte to the expected reading an estimate of the analyte the level measurement error can be determined and used to correct the analyte reading generated by the second measuring electrode. This device cannot, however, distinguish between errors relating to the sensitivity of the device to the analyte of interest and the response generated by the device due to other, interfering substances, in particular acetaminophen, ascorbate, gentisic acid, uric acid, therapeutic drugs, such as vitamin C, paracetamol, aspirin, and haemoglobin. Accordingly, measurements include a variable interference term and are likely to give variably inaccurate glucose readings.

Summary of the Invention

According to a first aspect of the present invention there is provided an analyte measuring device for measuring the amount of analyte in a fluid sample, typically a biological fluid, comprising: a first detection area comprising an analyte specific signal generating component reactable with the analyte to generate a response; a second detection area comprising a predetermined amount of an analyte of interest, wherein upon or following contact with the fluid a first calibration or correction response is generated, and a third detection area, absent the analyte specific signal generating component, wherein upon or following contact with the fluid a second calibration or correction response is generated.

Using the present invention, the total error experienced by each and every test result can be measured, so that it is unnecessary to measure the causes of measurement error. This is a significant advantage.

In a preferred embodiment, the second detection area comprises a predetermined amount of the same analyte as measured on the first detection area, for example glucose, or a predetermined amount of a different analyte. The predetermined amount may be controlled to the nearest 3% or less; suitably to the nearest 2% or less; more suitably to the nearest 0.5% or less; advantageously to the nearest 0.1% or less.

The second detection area may comprise an analyte specific signal generating component. Where the second detection area comprises a predetermined amount of the analyte to be measured in the fluid sample the second detection area typically comprises the same analyte specific generating component as the first detection area. Where the second detection area comprises a predetermined amount of a different analyte than that to be measured in the fluid sample, the second detection area may comprise an analyte specific signal generating component specific to the different analyte.

The second detection area may comprise a predetermined amount of an analyte such as potassium ferrocyanide, ferrocene, acetaminophen, ascorbic acid, gentisic acid, and may be absent an analyte specific signal generating component.

The analyte specific signal generating component may be an enzyme that reacts with an analyte, such as glucose, to cause the generation of a measurable response, typically an electrochemical response. Advantageously the enzyme is Glucose Oxidase, Glucose dehydrogenase, cholesterol esterase, alcohol dehydrogenase or β-hydroxybutarase.

The third detection area may be formed from the same material as the first detection device. The third detection area may be identical to the first detection area except that it does not contain any analyte specific signal generating component.

The relationship between the amount of analyte in the sample and the response generated by the first detection area is typically proportional.

The second detection area may comprise more than one detection element. Each detection element may comprise the same predetermined amount of an analyte of interest, or a different predetermined amount of an analyte of interest. Each detection element may comprise an analyte specific signal generating component. Typically the detection elements comprise predetermined amounts of the analyte to be measured. Accordingly the response generated for different amounts of analyte can be calculated, allowing the slope of the sample specific calibration curve to be calculated more accurately.

Where the increase in the response of the device does not have a linear relationship to the concentration of the analyte, the second detection area suitably comprises two or more detection elements wherein each of these detection elements may comprise the analyte specific signal generating component and a predetermined amount of the analyte of interest where each detection element comprises a different predetermined amount of the analyte of interest.

The first, second and third detection areas may have the same surface area. Variations in surface area between the detection areas may be less than 2%; more suitably less than 1%; advantageously less than 0.1%; more advantageously less than 0.05% of the total surface area of one of the detection areas. The shape of the first, second and third detection areas may be the same.

The first, second and third detection areas may have different surface areas, and the exact relationship between the surface areas of the first, second and third detection areas is known, and is taken into account during calibration of the device. The shape of the first, second and third detection areas may be the same.

The detection areas may be formed by screen printing techniques, lamination techniques, photolithography or by using laser ablation techniques. Laser ablation techniques may provide greater control of the areas of the first second and third detection areas than is possible with more traditional screen printing or lamination techniques. The areas of the detection areas can be maintained extremely precisely using laser ablation.

The detection areas are preferably formed from the same materials. The materials used to form the detection areas preferably exhibit little variation throughout the detection device. In particular, variables such as resistance, oxidation potential, electrochemical area and topology (i.e. roughness) of the material are minimised. Suitably there is a variation of less than 5% in the abovementioned properties of the materials used to form the first, second and third detection areas; more suitably a variation of less than 1%; advantageously a variation of less than 0.5%; most advantageously a variation of less than 0.05% of the abovementioned properties of the material used to form the detection areas. The detection areas may be formed from materials including carbon, gold, platinum or palladium. Using pure gold, platinum or palladium allows reproducible and controlled electrochemistry. The electrodes may be formed using thin layer deposition techniques such as sputtering and metal evaporation.

The first and second detection areas may comprise the same amount of analyte specific signal generating compound. Variations in the amount of analyte specific signal generating compounds may be limited to less than 5%; more suitably less than 1%; advantageously less than 0.5%.

Where the response detected by the detection areas is generated by the reaction between an enzyme and the analyte, the, or each, enzyme is suitably present in the first and second detection areas in excess; typically 10 to 200% in excess.

Where a reduced mediator is used to convert the response generated by the analyte and/or the enzyme to a response detectable by the detection areas very little variation in the amount of reduced mediator should be tolerated. Suitably variations in the amount of reduced mediator are less than 1%; suitably less than 0.5%; advantageously less than 0.01%.

The predetermined amount of the analyte may be put on to the second detection area using highly controlled dosing technology such as ink jet technology. The control of the amount and position of the predetermined amount of analyte will be far more accurate using such technology than for traditional deposition techniques such as screen printing and syringe dosing.

The first, second and third detection areas may be present in the same device. Alternatively the first, second and third detection areas may be separate from each other and the device constitutes a kit of parts.

The device may comprise a display, upon which the measurement of the analyte in the fluid is displayed. The analyte specific signal generating component of the device is preferably in a dry form. The analyte specific signal generating component is generally any compound that has a specific affinity to the analyte of interest. The analyte specific signal generating component is suitably an enzyme, an antibody, a fragment thereof or a DNA strand. In particular the analyte specific signal generating component is an enzyme that reacts with an analyte, such as glucose, to cause the generation of a measurable response, typically an electrochemical response. Advantageously the enzyme is Glucose Oxidase, Glucose dehydrogenase, cholesterol esterase, alcohol dehydrogenase or β-hydroxybutarase.

In one embodiment the analyte specific generating component may comprise an enzyme, antibody, fragment thereof or DNA strand and a mediator to cause the generation of an electrochemical response. The mediator allows the transfer of electrons from the analyte specific signal generating component to the electrode surface thus allowing a response to be measured. Alternatively, the analyte specific generating component may comprise an enzyme, antibody, fragment thereof or DNA strand and a dye to cause the generation of a colourimetric response. Suitably the analyte is glucose, cholesterol, alcohol, β hydroxybutarate or free fatty acids. Preferably the analyte is β-D-Glucose.

The fluid is typically blood, urine, interstitial fluid, plasma, serum, saliva fluid, breath condensate or spinal fluid.

In one embodiment, the responses generated are electrochemical responses. Alternatively, the device may be a colourimetric system and the response generated may be a change in colour.

The first, second and third detection areas are suitably transduction devices such as electrodes, in combination with appropriate circuitry.

Where the device is an electrochemical system the first, second and third detection areas are at the same voltage when the measurements are taken. In one embodiment the currents generated by the first, second and third detection areas are measured.

Where the first, second and third detection areas are in the form of electrodes, the current generated from the first electrode may be subtracted from the current generated from the second electrode to determine the current generated by the predetermined amount of analyte present on the second electrode and this current may then be used, via an algorithm, to calibrate the device. This value is associated with the slope of the sample specific calibration curve for the device. The current generated from the third electrode may be subtracted from the current generated from the first electrode to calibrate the device. This value is associated with the intercept of the sample specific calibration curve for the device.

Where the first, second and third detection areas are in the form of electrodes and the surface area of the three detection areas differs, appropriate scaling factors are used to calculate the current generated per unit surface area before calibration of the device. For instance, if the third detection area has twice the surface area of the first and second detection areas, the current generated from the third detection area is halved before calibration of the device. The current generated from the third electrode may be subtracted from the current generated by the first electrode to determine the true current generated by the analyte in the fluid. In this way the effects of interfering substances may be taken into account.

The device may be a single-use device. After one measurement has been taken, the device may be discarded. The device may be a capillary fill device.

According to a further aspect of the present invention there is provided a method of measuring the amount of analyte in a fluid sample from a patient comprising the steps of: obtaining a fluid sample from a patient; contacting the fluid sample with a first detection area comprising an analyte specific signal generating component reactable with the analyte to generate a response; contacting the fluid with a second detection area including one or more detection elements comprising an analyte specific signal generating component and one or more predetermined amounts of an analyte wherein upon contact with the fluid a first calibration response is generated, and contacting the fluid with a third detection area absent the analyte specific signal generating component, wherein upon contact with the fluid a second calibration response is generated.

There may be a delay of less than 10 minutes between contacting the analyte measuring device with the fluid and obtaining the measurement of the amount of analyte in the fluid sample. Where the analyte to be measured is glucose there is suitably a delay of 5 to 15 seconds between contacting the analyte measuring device with the fluid and obtaining the measurement of the amount of glucose in the fluid; advantageously 1 to 5 seconds.

Approximately 1 to 10 μl of fluid may be contacted with the detection devices; suitably 1 to 3 μl where the analyte is glucose. Suitably sufficient quantities of blood may be obtained through the patient pricking his finger where the analyte is glucose.

Where the device is used to measure an immunological response 8 to 10 μl of the fluid, typically blood, plasma or serum, may be contacted with the detection areas.

Brief Description of the Drawings Various aspects of the invention are described by way of reference only in the accompanying drawings, of which:

Figure 1 is a schematic diagram of a first device for measuring an analyte in a physiological fluid from a patient;

Figure 2 is a typical calibration plot of measured signal versus glucose levels for a self-test device, in the absence of interfering substances or other factors that may cause errors;

Figure 3 is an estimated calibration curve showing the impact of interfering substances and factors that affect the analyte sensitivity, or calibration slope, of the device; Figure 4 is a flow diagram of the steps that have to be taken to correct for errors in the reading of the analyte of interest in the sample; Figure 5 shows the results of various measurement taken at three different measurement points on the device of Figure 1; and

Figure 6 is a schematic diagram of another device for measuring an analyte in a physiological fluid from a patient.

Specific Description of the Drawings

Figure 1 shows a device having a disposable test strip on which are located four distinct areas for detecting the amount of analyte in a physiological fluid. These areas include a first detection area or working electrode 10, a second detection area 12, a counter/reference area or electrode 14 and a third detection area 16. In this example, each detection area has the same surface area. Each detection area is electrically insulated from the other such areas and the reference electrode. Each discrete area is connected to a measurement electrode 18, 20, 22 and 24 so that signals generated by the various detection areas can be measured relative to the counter/reference electrode 14.

The device of Figure 1 is adapted for use in co-operation with a measurement meter (not shown). Sample fluid flows into the device from the end at which the first detection area 10 is located, so that the fluid is incident first on the first detection area and then successively on the second electrode, the reference electrode and the third electrode. Alternatively, the sample may be placed on the device such that all of the detection areas are covered at the same time

The first electrode 10 has an analyte specific signal generating component reactable with the analyte to generate a measurable electrochemical response. The analyte specific signal generating component is typically an enzyme, such as Glucose Oxidase, Glucose dehydrogenase, cholesterol esterase, alcohol dehydrogenase or β-hydroxybutarase. The second detection area 12 acts as an internal standard and includes one or more detection elements each comprising a predetermined amount of the analyte of interest, wherein upon or following contact with the fluid a first correction response is generated. The first detection area 10 and the second detection area 12 are identical to each other except that the second detection area 12 also contains a predetermined amount of the analyte to be measured. The third detection area 16 acts as a background electrode and does not have the analyte specific signal generating component, but upon or following contact with the fluid generates a second correction response. Preferably, the third detection area 16 is identical to the first detection area except that it is absent the analyte specific signal generating component, for example the enzyme. In a preferred embodiment, the analyte that is being measured is glucose and the first detection area 10 includes Glucose Oxidase as the analyte specific signal generating component, and the analyte present on the second detection area 12 is also glucose.

To obtain a measure of the analyte of interest, a pre-determined calibration slope and intercept are used to calculate the analyte reading. The calibration slope and intercept curve represents the expected relationship between the level of analyte in the fluid and the signal generated by the first detection area 10 of the device in response to the analyte in the fluid when tested under standard conditions and with a standard test sample. Figure 2 shows an example of a typical calibration curve. This shows a linear relationship between the sample response measured in μA and the level of glucose in the sample, with an offset of Y on the y-axis. However, because of a variety of errors due, for example, to interfering substances and unusually high haematocrit levels, in practice, the actual response may be closer to that shown in Figure 3. Again this shows a linear relationship between the sample response measured in μA and the level of glucose in the sample, but in this case the offset is Y' is greater than expected whilst the gradient is lower than for the predetermined curve.

Figure 4 shows the steps that are taken to reduce the effect of all measurement errors, in accordance with the present invention. Firstly, three measurements are taken simultaneously relative to the reference electrode using the first detection area 10, the second detection area 12 and the third detection area 16. The response, Rl, generated by the first detection area 10 is the response generated by the analyte to be measured in the fluid sample and is subject to all error factors present, whether environmental or related to the sample itself, at the time of the test. The response, R2, generated by the second detection area 12 comprises the response generated by the analyte to be measured in the fluid sample and the response generated by the predetermined amount of analyte of interest present on or at the second detection area 12. The response, R2, from the second detection area 12 is also subject to all error factors present at the time of the test. Where the second detection area 12 comprises a predetermined amount of the analyte to be measured and has the same area as the first detection area 10, a first sample specific calibration response is calculated by subtracting the reading, Rl, of the first detection area 10 from the reading, R2, of the second detection area 12. This calculation provides the response SRM generated from the known amount of analyte of interest present on the second detection area 12. The response generated by the predetermined amount of analyte present on the second detection area 12 can then be compared to the expected response SRX for the predetermined amount of analyte present on the second detection area 12. Comparison of the actual response generated by the predetermined amount of analyte with the expected response provides sample specific calibration information relating to the slope of the calibration curve of the device for the particular fluid sample tested. More specifically, the measured internal standard reading is divided by the expected internal standard reading SRX to give a slope correction factor SCF.

The third detection area 16 provides a measure, R3, of the background response generated by the fluid sample to be measured. By measuring the response, R3, at the third detection area 16, a value of the intercept of the sample specific calibration curve can be determined. The non-analyte related test response generated by the third detection area 16 has a fixed and predictable relationship to the non analyte related component of the response generated by the first and second detection area 12. The third detection area 16 identifies a second sample specific correction response for all of the responses from substances other than the analyte in the fluid or interfering substances to be compensated for. The second calibration response is associated with the intercept of the sample specific calibration curve for the device. The reading from the third detection area 16 can be subtracted from the reading provided by the first detection area 10 to provide an intercept corrected sample reading, Rl '. The resulting intercept corrected reading from the first detection area 10 can then be corrected by the slope correction factor SCF calculated from the second detection area as described above to give a slope and intercept corrected analyte reading Rl ". Figure 5 shows an example that illustrates the benefits of the present invention. In this case, the measurement at the first detection area, Rl, is 10, the measurement at the second detection area, R2, is 23 and the measurement at the third detection area, R3, is 5. Hence, the contribution of the predetermined amount of the analyte at the second detection area, SRM, is the measurement at the second detection area minus the measurement at the first detection area, or (R2 - Rl) = SRM; which in this case would be 13.

Let us assume that the expected response for the predetermined amount of analyte present on the second detection area, SRX is 12. For this example the sample specific slope related correction factor, SCF, that needs to be applied to the result from the first detection area is the expected result from the predetermined amount of analyte on second detection area divided by the actual result from predetermined amount of analyte on second detection area, i.e. SCF = SRX / SRM = 12 / 13 = 0.92

The measurement at the first detection area, Rl, has to be corrected to take into account any intercept error, which is determined at the third detection area. This is done by subtracting the measurement at the third detection area, R3, from measurement at the first detection area, Rl . In this case, this would result in the intercept error corrected value being (10-5) = 5.

The final corrected and accurate amount of analyte in the sample is:

(measurement at the 1st detection area - measurement at the 3rd detection area) x SCF=

(Rl - R3) x SCF

(10-5) x 0.92 = 4.6

Figure 6 shows a variation on the device of Figure 1. In this case, the second detection area 12 includes two detection elements 11 and 13. Each of these detection elements 11, 13 comprises an analyte specific signal generating component and different predetermined amounts of an analyte. Preferably, the analyte on the detection elements 11, 13 is the same as the analyte to be measured. In this case, the response generated for different amounts of analyte can be calculated, allowing the slope of the sample specific calibration curve to be calculated more accurately. Whilst only two elements are shown in Figure 6, using three or more elements may be useful where the device response does not have a linear relationship to the concentration of the analyte.

Each of the devices described above may include a mediator substance. Where the devices include electrodes the mediator may transfer the electrons generated by the reaction of the analyte of interest with an enzyme to the electrode surface. Alternatively, the mediator substance may generate a change in colour as a result of contact with electrons generated by the analyte of interest. Typically the electrons are generated by the analyte of interest through contact with an enzyme. The incorporation of a mediator compound is particularly desirable where the device is a glucose monitor device and the analyte specific signal generating component is an enzyme such as Glucose Oxidase. The mediator substance may be potassium ferricyanide.

Suitably the first, second and third detection areas comprise the same amount of mediator substance. Where the mediator is in an oxidised form, the variation in the amount of mediator substance in contact with the first, second and third detection areas may vary by 5% or less, suitably 2% or less, more suitably 1% or less of the total amount of mediator substance in contact with any one of the detection areas. Where the system employs a mediator in reduced form the variation in the amount of mediator substance in contact with the first, second and third detection areas may vary by less than 1%, typically less than 0.5%, suitably less than 0.1%, advantageously less than 0.05%.

Where electrochemical responses are generated the analyte specific signal generating component may become reduced upon contact with the analyte. The mediator will in turn become reduced by oxidising the analyte specific signal generating component. Upon application of an appropriate specific voltage the mediator substance may become reoxidised at the electrode surface, thus generating an electrical current that is typically proportional to the concentration of the analyte of interest. The electrical current, and therefore the presence and amount of analyte, is thus detected by the detection areas in the form of an electrochemical response.

The present invention allows for the measurement and correction of errors for each and every test, without measuring any parameters that are considered to correlate to the overall system error, thereby removing the need to measure multiple parameters that correlate to test errors. Instead the device measures the actual overall system error itself. Using this error information the test result can be corrected. Because the measurement errors are measured during use and for every test, inaccuracies are minimised. The present invention allows for correction of errors that affect the system's glucose sensitivity and errors that affect the system's background glucose-independent reading. In other words each test strip is individually and automatically calibrated using the sample to be assayed at the same time as the test assay is carried out. By doing this, all errors that affect the system's accuracy can be taken in to account thus allowing an accurate result to be provided by the system to the user.

All documents referred to in this specification are hereby incorporated by reference. Various modifications and variations to the described embodiments of the invention will be apparent to those skilled in the art without departing from the scope and spirit of the invention. For example, although in the specific description the second detection area comprises the same analyte as that to be measured in the fluid sample, another different analyte could be used. In this case, the second detection area may comprise an analyte specific signal generating component specific to that different analyte. Although the invention has been described in connection with specific preferred embodiments, it should be understood that the invention as claimed should not be unduly limited to such specific embodiments. Indeed, various modifications of the described modes of carrying out the invention obvious to those skilled in the art are covered by the present invention.

Claims

1. An analyte measuring device for measuring the amount of analyte in a fluid sample comprising: a first detection area comprising an analyte specific signal generating component readable with the analyte to generate a response; a second detection area comprising a predetermined amount of an analyte of interest, wherein upon or following contact with the fluid a first calibration or correction response is generated, and a third detection area, absent an analyte specific signal generating component, wherein upon or following contact with the fluid a second calibration or correction response is generated.

2. A device as claimed in claim 1 wherein the second detection area comprises a second analyte specific signal generating component.

3. A device as claimed in claim 2 wherein the analyte of interest on the second detection area is the analyte to be measured, and the second analyte specific signal generating component is the same as the analyte specific signal generating component of the first detection area.

4. A device as claimed in any of the preceding claims wherein the second detection area comprises more than one detection element, each detection element comprising a different or the same predetermined amount of an analyte of interest.

5. A device as claimed in any of the preceding claims wherein the analyte is glucose.

6. A device as claimed in any of the preceding claims wherein the analyte specific signal generating component is an enzyme, an antibody, an antibody fragment or a DNA strand.

7. A device as claimed in claim 6 wherein the enzyme is Glucose dehydrogenase or Glucose Oxidase.

8. A device as claimed in any of the preceding claims wherein the fluid is blood, urine, plasma, serum, saliva, spinal fluid or interstitial fluid.

9. A device as claimed in any of the preceding claims wherein the responses generated are electrochemical responses. I

10. A device as claimed in claim 9 wherein the first, second and third detection areas are electrochemical electrodes.

11. A device as claimed in any of the preceding claims wherein the first second and third detection areas comprise a mediator substance or a dye allowing the responses generated to be measured through the generation of an electrochemical or colourimetric response.

12. A device as claimed in claim 11 wherein the first, second and third detection areas comprise the same amount of mediator substance.

13. A device as claimed in any of the preceding claims wherein the second detection area is identical to the first detection area except that the second detection area comprises a predetermined amount of an analyte to be measured.

14. A device as claimed in any of the preceding claims wherein the third detection area is identical to the first detection area except that the third detection area does not contain an analyte specific signal generating component.

15. A device as claimed in any of the preceding claims wherein the first, second and third detection areas have the same surface area.

16. A device as claimed in any of the preceding claims wherein the first, second and third detection areas are manufactured using laser ablation techniques.

17. A device as claimed in any of the preceding claims wherein the first, second and third detection areas are formed from carbon, gold, platinum, rhodium or palladium.

18. A device as claimed in any of the preceding claims wherein the predetermined amount or amounts of analyte of the second detection device are provided using ink jet technology.

19. A method of measuring the amount of analyte in a fluid sample comprising the steps of: contacting a fluid sample with a first detection area comprising an analyte specific signal generating component reactable with the analyte to generate a response; contacting the fluid with a second detection area comprising a predetermined amount of an analyte of interest, wherein upon or following contact with the fluid a first calibration or correction response is generated; contacting the fluid with a third detection area absent an analyte specific signal generating component, wherein upon or following contact with the fluid a second calibration response is generated.

20. A method as claimed in claim 19 wherein the method is performed using the device of any one of Claims 1 to 18.

21. A method as claimed in claim 19 or 20 wherein there is a delay often minutes or less between contacting the detection areas with the fluid and obtaining the measurement of the amount of analyte in the fluid sample.