HK1241019A1 - System and method for detecting used and dried sensors - Google Patents

Description

System and method for detecting used and dried-out sensors

CROSS-REFERENCE TO RELATED APPLICATIONS

The present application is a divisional application of chinese patent application No. 201280074692.3, and the application date of patent application No. 201280074692.3 is 2012, 8 and 31, entitled "system and method for detecting used and dried sensor".

This application claims benefit of filing date of U.S. provisional patent application No.61/676,549, filed on 27/7/2012, the disclosure of which is incorporated herein by reference.

Technical Field

The present disclosure relates generally to the field of medical devices. More particularly, the present disclosure relates to devices and methods for measuring the amount of an analyte in a bodily fluid sample, for example, for measuring glucose in a whole blood sample.

Background

Amperometric glucose biosensors typically use a sensor often referred to as a "test strip" having at least one pair of electrodes including a working electrode and a counter electrode. The test strip also includes a dry reagent in contact with the working electrode and the counter electrode and a capillary flow channel extending from the inlet aperture to the working electrode and the counter electrode. The reagent typically comprises an enzyme capable of oxidising glucose in the sample, such as glucose oxidase, and one or more mediators suitable for re-oxidising a reduced enzyme produced by the oxidation of glucose to form a reduced mediator. The test strip is inserted into the meter such that the working and counter electrodes are in electrical connection with components within the meter. After the test strip is inserted into the meter, a sample of bodily fluid, such as blood, is introduced into the capillary flow passage and contacts the working electrode, the counter electrode, and the reagent, whereupon components within the meter apply one or more voltages between the working electrode and the counter electrode and measure the current passing between the two electrodes. The reduced mediator is oxidized at the working electrode, thereby generating a measurable current related to the amount of reduced mediator present at the working electrode and thus related to the concentration of glucose in the body fluid. The measured current typically starts at a high value and then falls and approaches a constant value. For example, the current measured at a predetermined time during the application of the voltage may be used to determine the glucose content of the sample.

Occasionally, the user will attempt to conduct a blood glucose test with a previously used test strip. Such repeated use can produce erroneous readings. To prevent reuse, the test meter may be configured to measure the conductivity between the electrodes of the test strip prior to introducing the fluid sample. When the test strip is inserted into the meter, electrical components within the meter apply a voltage between the electrodes and measure the current. New, unused test strips have only dry reagent between the electrodes prior to application of the fluid sample, and therefore have a very high resistance between the electrodes. However, a previously used test strip that is still wetted with a previous sample may exhibit very low resistance and high current flow between the electrodes. The meter can easily recognize this and issue a warning and/or terminate the test. However, if the initial use of the test strip occurs many hours or days ago, the previous fluid sample has dried out. In this case, the conductivity test by the tester does not reveal the problem.

Repeated use of previously used dried test strips can result in erroneous readings. For example, readings from such used test strips are likely to have a very large negative bias due to the loss of working and/or counter electrode chemistry from previous uses. Thus, further improvements are desired.

Disclosure of Invention

Various aspects of the systems and methods disclosed herein may be implemented in hardware, software, or a combination of both. Systems and methods for detecting and reporting the reuse of previously inoculated dried test strips are provided. In various aspects, a system and method are provided for determining whether a test strip is a dried-out test strip that has been inoculated with one sample and then re-inoculated with another sample, determining a glucose reading obtained from a test strip inoculated with a blood sample, and correcting the measured glucose reading based on factors such as the ambient temperature of the blood sample and the amount of hematocrit determined from the blood sample.

The present invention provides a method for detecting reuse of a test strip in a biosensor. The method comprises the following steps: a test strip having a dry reagent and a plurality of electrodes including a bare electrode that is not normally in contact with the dry reagent is inoculated with a liquid such that the liquid contacts the dry reagent, the bare electrode, and one or more other electrodes. The method further comprises the following steps: applying an electrical potential between the bare electrode and the one or more other electrodes while the electrode is in contact with the liquid, and measuring a current between the bare electrode and the one or more other electrodes in response to the application of the electrical potential. The method further comprises the following steps: determining whether the sensor strip is a previously wetted and dried sensor strip prior to the inoculating step based on one or more parameters of the measured current.

In one aspect, the first current value may be measured at a first time during the potential applying step and the second current value may be measured at a second, later time during the potential applying step.

A ratio between the second current value and the first current value may be calculated, and the ratio may be compared with a boundary ratio. In one aspect, the boundary ratio may be selected based at least in part on a current value measured during the potential applying step. Further, the boundary ratio may be selected based at least in part on one of the first current value and the second current value.

In one aspect, the boundary ratio may be a ratio of the second current value divided by the first current value, and the sensor strip may be determined to be a previously wetted and dried sensor strip when the ratio is less than or equal to the boundary ratio.

In one embodiment, the one or more other electrodes on the test strip may include a working electrode and a counter electrode, and the method may further include: at least one input signal is applied between the working electrode and the counter electrode. At least one output signal generated in response to the application of the at least one input signal may be measured, and a concentration of the analyte in the sample may be determined based at least in part on the at least one output signal. In one aspect, the input signal may be an electrical potential and the output signal may be a current flowing between the working electrode and the counter electrode.

The determined concentration of the analyte in the sample may be corrected based at least in part on the at least one parameter of the measured current. In one embodiment, for example, the liquid may be blood and the concentration of the analyte may be corrected for hematocrit-related effects. According to this embodiment, the analyte may be glucose, and the dry reagent may further contain an enzyme and a mediator that react with glucose.

In another aspect, the method may include: the current value measured during the potential applying step is compared with a threshold current value. Then, it may be determined based on the comparison whether the sensor strip is a sensor strip that was previously wetted with blood and dried prior to the inoculating step, rather than a sensor strip that was previously wetted with water and dried prior to the inoculating step.

The present invention provides a reusable biosensor for detecting a test strip. The biosensor may include: a processor and a memory storing one or more executable instructions. When the instructions are executed by the processor, the processor may be configured to: applying an electrical potential between a bare electrode of a test strip and one or more other electrodes while an electrode of the test strip is in contact with a liquid, the test strip having a dry reagent and the bare electrode not normally in contact with the reagent; measuring a current between the bare electrode and the one or more other electrodes in response to an electrical potential application; and determining whether the sensor strip is a previously wetted and dried sensor strip prior to inoculating the test strip with the liquid based on the one or more parameters of the measured current.

The present invention provides a non-transitory computer-readable storage unit storing computer-readable instructions of a program. The instructions, when executed by the processor, may cause the processor to: applying an electrical potential between a bare electrode of a test strip and one or more other electrodes while an electrode of the test strip is in contact with a liquid, the test strip having a dry reagent and the bare electrode not normally in contact with the reagent; measuring a current between the bare electrode and the one or more other electrodes in response to an electrical potential application; and determining whether the sensor strip is a previously wetted and dried sensor strip prior to inoculating the test strip with the liquid based on the one or more parameters of the measured current.

Drawings

Fig. 1 is a schematic plan view of a test strip according to an embodiment of the present invention.

Fig. 2 is a block diagram of an amperometric biosensing test meter according to an embodiment of the invention.

FIG. 3 is a graph of voltage versus time depicting a series of input pulses applied to a test strip by a meter in a method according to one embodiment of the present invention.

FIG. 4 is a graph of current versus time depicting an example of output current between electrodes of a test strip in the method of FIG. 3.

FIG. 5 is a graph depicting some of the results measured using the method of FIG. 3.

FIG. 6 is a graph depicting some results according to another aspect of the present disclosure.

Detailed Description

FIGS. 1-2 illustrate examples of a test strip 100 and a test meter 200, respectively, according to various aspects of the present invention. Although a particular configuration of the meter and test strip is shown, the present disclosure is not limited to any particular configuration.

Test strip 100 used in one embodiment of the present invention includes a body 90 defining a capillary flow channel 92 extending from one edge 94 of the body. The flow passage has an inlet aperture 96 that forms the proximal end of the flow passage. In other words, as shown in fig. 1, the flow channel defines a proximal direction P and a distal direction D. For example, the body 90 may be configured as a laminate including a bottom layer, a separation layer having a gap defining a flow channel, and a top layer covering the separation layer. By way of example only, the capillary flow passage may have a width of about 1.2mm or less and a height (in a direction perpendicular to the plane of the drawing in fig. 1) of about 0.1mm or less.

The test strip also includes a plurality of electrodes carried on the body 90. For example, the electrode may be formed as a conductive metal film on the bottom layer of the body. For example, the metal membrane may comprise palladium on the face of the membrane that is exposed to the channels and thus to the sample fluid during use. The electrodes include a working electrode 102 and a counter electrode 104 extending across the flow channel 92 in close proximity to each other. In the particular embodiment depicted, counter electrode 104 includes a portion 104a disposed proximate to working electrode 102 and a portion 104b disposed distal to the working electrode. Electrodes 102 and 104 are connected to terminals 112 and 114, respectively. Chemical substances, such as dry reagents including enzymes (e.g., glucose oxidase) and mediators (compounds that are readily reduced and oxidized) that react with an analyte (e.g., glucose) in a biological sample (e.g., blood), are disposed within the predetermined area 118 of the test strip such that the reagents contact and desirably cover the working electrode 102 and the counter electrode 104 within the predetermined area. In another embodiment, the dry reagent can further include a glucose dehydrogenase with a FAD cofactor ("FAD-GDH"). Other enzymes suitable for measuring glucose include glucose dehydrogenase with NAD or PQQ cofactors and hexokinase.

Test strip 100 according to this embodiment also includes a bare electrode 106 (also referred to herein as a "hematocrit" electrode). The bare electrode 106 extends across the flow channel 92 at a location proximate the working electrode 102 and the counter electrode 104 and outside of the area 118 occupied by the dry reagent. Although the bare electrode 106 is disposed outside of the area 118 occupied by the dry reagent, the bare electrode is preferably proximate to the area 118. By way of example only, the distal edge of the bare electrode may be disposed less than about 0.3mm from the region 118 and less than about 0.6mm from the proximal edge of the working electrode 104. In the unused condition shown in fig. 1, the bare electrode 106 is devoid of any chemicals. There is no dry reagent on the bare electrode 106 in the region 118 before the test strip is inoculated with a liquid sample, such as blood. The bare electrode 106 is electrically connected to the contact terminal 116.

The test strip according to this embodiment also includes a detection electrode 107 disposed in the channel 92 at the distal edge of the counter electrode 104. The detection electrode is connected to the other terminal 117. The detection electrode is covered with dry reagent 118. The detection electrode can be used to determine when the liquid fills the channel 92 to a point away from the working and counter electrodes, and can also be used as part of the counter electrode 104.

In addition to the electrodes shown in fig. 1, test strip 100 may include other electrodes (not shown), such as additional counter, working, or bare electrodes.

Test meter 200 (fig. 2) includes a strip port 202 for receiving test strip 100. The strip port 202 is configured to electrically connect one or more components of the test meter 200 with the terminals 112, 114, 116, and 117 on the test strip, thus connecting the components of the test meter with the electrodes 102, 104, 106, and 107. As such, the strip port includes contacts (not shown) configured to engage with terminals of the test strip.

The test meter 200 may operate under the control of a processor 204. Processor 204 may be any commercially available general purpose microprocessor configured to execute and/or process instructions and data stored in memory 206. Processor 204 may be connected with various components of test meter 200 and may generally indicate and enable the functionality provided by test meter 200.

The memory 206 may be any computer readable memory such as a magnetic, optical, or semiconductor memory. The memory 206 may be implemented using fixed storage (e.g., flash memory) or removable storage (e.g., memory card). In various aspects, the memory 206 may include one or more regions of non-volatile memory (e.g., ROM or flash memory), one or more regions of volatile memory (e.g., RAM memory), or a combination of both. Memory 206 may include stored instructions or algorithms that, when executed by processor 204, cause test meter 200 to perform various operations as described below. Further, the processor 204 may store, retrieve, and process various data in the memory 206, such as information received via the input interface 210, information output onto the display 208, or information obtained and/or measured via the strip port 202 during operation of the test meter 200.

Input interface 210 may provide a mechanism for a user to interact with test meter 200. For example, the input interface 210 may include a power switch for activating the test meter. The input interface may also include one or more additional buttons for enabling a user to operate the test meter, such as a button for directing the start of a new test or restoring results obtained in a previous test.

Display 208 may be any display suitable for presenting information to a user. For example, the display 208 may include an LED or LCD display, a graphical display, a plasma display, a backlit display, a touch screen display, or a combined segmented/graphical display. In embodiments where the display 208 is a touch screen display, the display 208 may also be used by the user to provide input to the meter. The information displayed by the processor 204 on the display 208 may be in the form of alpha/numeric characters and/or images stored in the memory 206 and may include one or more icons representative of one or more types of information provided (or received) by the test meter. Some of the information that may be displayed to the user includes analyte concentration readings, time and data indications, hematocrit readings, indicia, error or warning information, and any combination thereof. For example, more than one error message may be output to the display 208, which may include an error message displayed upon detection of a previously inoculated test strip. As another example, upon successful completion of the test without any errors, a glucose reading may be displayed on the display 208.

The test meter 200 according to this embodiment also includes a temperature sensor (e.g., a thermistor or thermocouple) 212. The temperature sensor 212 is configured to measure and provide an ambient temperature reading indicative of the ambient temperature of the environment surrounding the meter. The processor 204 may periodically receive ambient temperature readings and store the readings in the memory 206 for further processing.

The test meter 200 also includes a signal generator and measurement unit 214. Unit 214 is electrically connected to strip port 202 such that when a test strip is inserted into the meter unit 214 will be electrically connected to the electrodes of the test strip. Unit 214 is configured to apply a voltage between the electrodes of the test strip, as described below, and is also configured to measure the current flowing between the electrodes, as described below. The unit 214 may include conventional electronic components such as regulated voltage sources, switches for connecting these voltage sources with appropriate contacts in the strip port 202, and conventional current measuring components.

As discussed further below, unit 214 is capable of measuring each current at a series of measurement times and of providing a signal indicative of the magnitude of the current at each measurement time. These signals are typically provided in digital form and may be provided directly to the processor 204 or stored in the memory 206 for further processing by the processor 204.

In a method according to one embodiment of the present invention, test strip 100 is engaged in strip port 202. The processor 204 performs an initialization routine that may include a diagnostic test of the meter components and may also include an initial check of the test strip. For example, in an initial examination, the unit 214 applies a low voltage of several hundred millivolts between the working electrode 102 and the counter electrode 104, and monitors the current flowing between the electrodes. Because no liquid is applied to the test strip at this stage, and because the reagent 118 should be dry and substantially non-conductive, there should be substantially no current flow. If the current between electrodes 102 and 104 exceeds a threshold, this indicates that the test strip is wet and contaminated with fluid left over from previous uses of the test strip. If this is the case, the processor 204 will issue an error message via the display 208 and terminate the testing process. The processor then activates unit 214 to apply a low voltage between bare electrode 106 and counter electrode 104. Here, if the current again exceeds the threshold, this indicates that there is moisture left from the previous use of the test strip and the processor issues an error message. It should be noted that these steps do not detect a used test strip that dries out after use. The dried used test strip will exhibit a high resistance and low or zero current between the electrodes during the above steps. Previously used and dried test strips can be tested using the additional steps described below.

If an error condition does not occur, the processor places the tester in a ready state. In this ready state, a message is displayed instructing the user to apply the liquid sample, and unit 214 applies a low voltage between bare electrode 106 and counter electrode 104, and repeatedly monitors the current. A sample of liquid to be analyzed, such as blood, or a control solution containing a known amount of glucose is applied to the inlet port 96 of the channel 92. When the current between electrodes 104 and 106 rises above a threshold value, this indicates that a sample has been applied to the test strip. The processor starts a timer and instructs unit 214 to apply a low voltage between working electrode 102 and detection electrode 106. When the current between these electrodes rises above a threshold, this indicates that fluid has filled the channel 92 to the detection electrode, thus completely covering those portions of the working electrode 102 and the counter electrode 104 disposed within the channel 92. If the timer started by the processor reaches a maximum value before this occurs, this indicates that the fluid sample is not filling the channel properly. The processor may issue an error message or instruct the user to apply more sample fluid. If the timer does not reach a maximum value before the channel is filled with fluid, the system is ready for a glucose and hematocrit measurement procedure.

When a fluid sample, such as blood or a control fluid, fills the channel and contacts the dry reagent 118, the components of the dry reagent, including the enzyme and mediator, are dispersed in the fluid. Glucose in the sample reduces the enzyme, and the enzyme reduces the mediator accordingly. Thus, the sample contains a concentration of reduced mediator that correlates with the concentration of glucose in the sample. The meter applies a potential between the working electrode 102 on the one hand and the counter electrode 104 and the detection electrode 107 on the other hand. In the processing at this stage, the detection electrode 107 is electrically connected to the counter electrode 104 and serves as a part of the counter electrode. The applied potential oxidizes the mediator in contact with the working electrode. That is, the reduced mediator gives up electrons to the working electrode. This produces a current, referred to herein as an output current in response to an applied potential. The output current is related to the amount of reduced mediator present and thus to the amount of glucose in the fluid sample. As is known in the art, the output current typically decreases over time during the application of the potential. The potential may be applied as one continuous potential or in multiple pulses, and the measurement of the current may comprise a single measurement or multiple measurements. In another known variant, the potential may be applied as an alternating potential, generating an alternating current. As is known in the art, currents of this nature are also affected by other factors such as temperature and hematocrit of the sample (i.e., the percentage of blood cells in the volume of blood).

By way of example only, as shown in FIG. 3, test meter 200 may apply an input signal consisting of a series of input potentials ("input pulses") shown as pulses 1 through 6. Each input pulse may be sequentially applied for a period tA to tB, where tA represents the start time of applying the potential (V) between the working electrode and the counter electrode, and tB represents the time when the potential is removed. The duration of each pulse 1-6 is typically less than 1 second. For example, the potential applied during these pulses is typically about half a volt or less. As further shown, there may be a pause period between input pulses during which no potential is applied between working electrode 102 and counter electrode 104.

Unit 214 measures output signals consisting of the magnitude of the current flowing between working electrode 102 and counter electrode 104 at various times and provides these values to processor 204. For example, when the output current produced may be at a maximum for a given period of time, the tester may first measure the output current flowing between the working electrode and the counter electrode at or immediately after the input pulse is applied at time tA. The meter may continue to periodically measure the value of the generated (and dropped) output current at various times during the period of time in which the input pulse is applied, such that the last reading is at or about time tB when the input pulse between the working electrode and the counter electrode is removed.

Immediately after pulse 6 (the last pulse applied between the working electrode and the counter electrode) ends, processor 204 instructs unit 214 to apply a potential between bare electrode 106 and one or more other electrodes (e.g., working electrode 102 or counter electrode 104) of test strip 100 and to monitor the current between the bare electrode and the other electrodes. Here, the detection electrode 107 again serves as a part of the counter electrode 104. As previously noted, the bare or hematocrit electrode 106 is located proximate to but spaced from the working electrode 102 and the counter electrode 104 and outside of the dry reagent containing region 118. Thus, the current between the bare electrode 106 and the working or counter electrode is the same as the current between the working and counter electrodes in the early pulses and is not affected by the glucose concentration. The current between the bare electrode and the working or counter electrode is less sensitive to glucose in body fluids such as blood, but sensitive to hematocrit.

In fig. 3, the potential applied between the bare electrode 106 and the working or counter electrode is depicted as pulse 7. The pulse 7 may be applied for a time period tC to tD (e.g., 0.4 seconds), where tC represents the start time of the applied potential and tD represents the time when the potential is removed. The potential applied between the bare electrode 106 and the working or counter electrode is typically greater than the potential applied between the working and counter electrodes. For example, the potential applied to the bare electrode may be on the order of 2-3 volts.

As shown in fig. 4, the output current 400 generated between the bare electrode 106 and the working electrode 102 or the counter electrode 104 in response to the applied potential may be measured at various times by a test meter. For example, the unit 214 may first measure the resulting output current at time t1 which is 0.1 seconds after the start time tC of the pulse. The meter may continue to periodically measure the output current at various times while pulse 7 is applied, with the last reading taken at or about time tD when pulse 7 was removed.

The processor 204 uses the information obtained from the above measurements along with other information such as the ambient temperature measured by the sensor 212 and calibration factors associated with the test strip to derive a value for the glucose concentration in the sample. For example, a rough estimate of glucose concentration may be calculated from one of the currents measured during pulses 1-6, whereas an estimate of hematocrit may be derived from one or more of the currents measured during pulse 7 and ambient temperature, with or without other information. The rough estimate of glucose may be corrected for hematocrit based on the estimate of hematocrit. The corrected glucose estimate may be further refined based on factors such as the individual current values measured during pulses 1-6 and the ambient temperature. Many algorithms for calculating and correcting glucose concentration are known in the art, and any such algorithm may be employed.

The processor 204 also executes the following programs: whether test strip 100 is a previously used and dried test strip is determined based on a measurement of the output current 400 generated in response to pulse 7 (i.e., the output current resulting from the application of a potential between bare electrode 106 and working electrode 102 or counter electrode 104).

In accordance with this aspect, the processor 204 utilizes a first current value measured at a first time during the application of a potential between the hematocrit electrode 106 and the working electrode 102 or the counter electrode 104 and a second current value measured at another, later time during the application of this potential. For example, as shown in fig. 4, the output current 400 may have a first value (referred to herein as i7,1) measured at or about immediately after the start time tC of the pulse 7. For example, i7,1 can be measured about 0.1 second after the potential is applied in pulse 7. The second or other current value (referred to herein as i7,4) may be measured about 0.4 seconds after the end time tD of pulse 7 (i.e., at or near the end of the pulse). As shown in fig. 4, the output current 400 during pulse 7 is decremented such that i7,4 is less than i7, 1.

The present disclosure is not limited to any specific example of measuring time; measurements made at other times during potential application may also be used as the first current value and the second current value.

The processor 204 calculates a ratio between the first current value and the second current value. For example, the processor may calculate a ratio of the second current value divided by the first current value. In the above example, this ratio is (i7,4)/(i7,1), and is referred to herein as R7. The ratio between the first value and the second value obtained from a previously used and dried test strip is significantly different from the ratio obtained from a normal, unused test strip. For example, the measured R7 value is exceptionally low for a previously used and dried test strip that is rewetted with blood compared to the corresponding measurement for a normal test strip. The designation "previously inoculated" test strip is also used herein to refer to a test strip that has been previously wetted with a liquid (e.g., blood or water) and then dried. This phenomenon is illustrated in the graph 500 of fig. 5, in which measurements of i7,4 and R7 are plotted for three types of blood-inoculated test strips at a given ambient temperature, including normal or previously uninoculated test strips, previously blood-inoculated dried test strips, and previously water-inoculated dried test strips.

As seen in fig. 5, the measured R7 values for the three types of blood-inoculated test strips are plotted on the vertical axis of the graph 500, and the corresponding i7,4 values that yield R7 values are plotted on the horizontal axis of the graph. In particular, the measured R7 and i7,4 values obtained by testing blood-inoculated test strips using a number of normal (or previously uninoculated) test strips are plotted with circles. The measured R7 and i7,4 values obtained by testing blood-inoculated test strips using dried test strips previously inoculated with blood are plotted using squares. Finally, the measured R7 and i7,4 values obtained by testing blood-inoculated test strips using dried test strips previously inoculated with water are plotted using triangles. As seen in graph 500, the measured R7 values (represented by triangles and squares, respectively) for the previously used and dried test strips were generally lower than the measured R7 values (represented by circles) for the normal test strips.

As can be appreciated from fig. 5, when testing blood in a particular test strip, a comparison between the value of the ratio between the first current value and the second current value and the fixed ratio threshold TH will provide a good distinction between normal and previously used test strips. In other words, in this method, the ratio R7 resulting from a particular test using blood is compared to a fixed threshold TH. If the value of R7 is greater than TH, then the test is considered to have been performed with a normal test strip that has not been used previously. If the value of R7 is below TH, the test is considered to have been performed with a previously used and dried test strip.

However, using a threshold value of the ratio as a function of a value of one current measured during the application of the potential between the bare electrode and the other electrode enables an even better discrimination. The ratio threshold, shown by point 506 on dashed line 502, is a function of the second current value i7,4 (denoted as 504). The ratio threshold increases with the second current value i7,4 within a certain range of the second current value and remains constant for second current values above this range. The precise value of the ratio threshold function that produces curve 502 varies with the composition of the test strip, the particular times when the first and second current values are measured, and other factors related to the composition of the meter and test strip. However, for a given configuration of test strip and a given configuration of meter, the ratio threshold curve 502 may be determined by using actual measurements of test strips and blood or control fluids that satisfy known conditions (i.e., used or unused). The ratios and second current values obtained in many tests with previously used dried and normal test strips were plotted in the same manner as shown by curve 502 in fig. 5. Using such a graph, a ratio threshold function that gives good discrimination can be determined by inspection. Once the ratio threshold function is established in this manner using a prototype meter having a given make-up, the ratio threshold function can be stored in other meters having the same make-up made in a mass production operation. The function defining the ratio threshold is stored in the memory 206 of the test meter 200 either as a look-up table giving the specific threshold value of the ratio R7 for a given value of the second current i7,4 or as a set of parameters that can calculate the threshold value for a given second current i7, 4.

The second current value generally varies with ambient temperature. The relationship between the second current value and the ambient temperature is constant for a given meter and test strip configuration. Thus, a given second current value or i7,4 measured at a known ambient temperature corresponds to a normalized second current value at a standard operating temperature. A look-up table relating the measured second current values and the measured ambient temperature to the normalized second current values at the standard temperature may be compiled and used through actual testing. Alternatively, the same information may be provided as a parameter of a normalization function that relates the measured second current value and the measured ambient temperature to the normalized second current value at the standard temperature. Such a normalization function or look-up table should be used to normalize the second current value or i7,4 used in the test to determine the ratio threshold curve. The value of i7,4 represented in fig. 5 is normalized to the standard operating temperature. The ratio between the first current value and the second current value, or R7, is generally insensitive to ambient temperature and therefore does not require normalization.

A fixed current threshold 508 (referred to herein as the "i7,4 threshold") for the second current value i7,4 can be used to further distinguish between measurements of previously blood-inoculated dried test strips (represented by squares) and previously water-inoculated dried test strips (represented by triangles). Again, the i7,4 threshold depends on the make-up of the instrument and test strip, but is fixed for a given make-up. As described above, the i7,4 threshold for a given configuration can be determined by actual measurement of a set of known samples. Again, as mentioned above, the value of i7,4 is preferably normalized. The threshold values of i7,4 are also stored in the memory 206 of the test meter.

Thus, a dried-out test strip that provides an i7,4 measurement that exceeds the i7,4 threshold 508 can be identified as an inoculated, dried-out test strip that was previously inoculated with water and subsequently dried out. For example, such test strips may be distinguished from other dried test strips that provide an i7,4 measurement less than or equal to an i7,4 threshold 508 (which may be determined as inoculated dried test strips that were previously inoculated with blood and subsequently dried).

In another aspect, test meter 200 may be configured to determine not only whether a given blood-inoculated test strip is a normal test strip or a dried test strip, but also whether the test strip is a control test strip. For example, a control test strip as described herein is a normal, previously uninoculated test strip that has been inoculated with a control solution, such as an aqueous glucose control solution, rather than blood. This is illustrated below with reference to fig. 6.

FIG. 6 is similar to FIG. 5, except that FIG. 6 also shows a number of measurements (indicated using ovals) obtained from a normal test strip inoculated with a test control solution rather than blood. As shown in fig. 6, the measurement of the control solution (represented by the oval) using a normal, previously unused test strip can be simultaneously distinguished from the measurements produced by a blood-inoculated normal test strip and a blood-inoculated dried test strip. This distinction may be based on ratio threshold curve 502 and current threshold 508. More specifically, a given test strip may be identified as a control test strip when the measured R7 value corresponding to a given i7,4 current value is greater than the applicable R7 value of the given i7,4 current value determined from the ratio threshold curve 502, while the given i7,4 current value is also less than the current threshold 508. This is possible because the measurement of the control solution may be configured to produce a lower current value between the bare electrode 106 and the other electrode than the current value obtained from the measurement of blood. In particular, the control test strip may be designed such that the second current or i7,4 value obtained by testing a normal test strip inoculated with a particular control solution is generally lower than the second current or i7,4 value produced by testing a normal test strip inoculated with blood for testing, while the measured R7 values obtained by testing such a control test strip are greater than those produced by testing a dried test strip that has been previously inoculated with blood or water and subsequently dried.

Note from fig. 6 that the current threshold 508 allows the control test strips inoculated with control solution (ovals) to be distinguished from the normal test strips inoculated with blood (circles). In addition, the same current threshold 508 also allows for distinguishing dried test strips previously inoculated with blood (squares) from dried test strips previously inoculated with water (triangles). However, it is understood that this is not limiting, and in other embodiments, there may be two (or more) different current thresholds, rather than one current threshold 508, one of which may be used to distinguish control test strips from normal test strips, and the other of which may be used to distinguish previously blood-inoculated dried test strips from previously water-inoculated dried test strips.

In operation of the above method, processor 204 obtains the ambient temperature from sensor 212 and the measured first current value i7,1 and second current value i7,4 from unit 214. The processor calculates a measured ratio R7 between the measured first current value and the second current value. The processor also determines a normalized value for i7,4 using the function or lookup table described above that relates the measured second current value to the normalized value. Using the normalized second current value i7,4, the processor determines the applicable boundary ratio value 506 of the ratio R7 using the lookup table or parameters described above that define the threshold function 502 (fig. 5).

The processor then compares the measured ratio R7 to the applicable boundary ratio value of the threshold. The processor may also compare the normalized second current value i7,4 to the i7,4 threshold 508. If the measured ratio R7 is below the applicable boundary ratio 506 of the ratio threshold curve 502, the processor may determine that the test strip used to make the measurement is a previously used and dried test strip rather than a normal test strip. In response to such a determination, the processor signals an error to the user via the display 208, inhibits the measured glucose value from being displayed on the display, or both. If the measured R7 value is greater than the applicable boundary ratio value 506 of the ratio threshold curve 502, then the processor may determine that the test strip used in the test is a normal unused test strip, rather than a dried test strip. In this case, the processor initiates the display 208 to display the glucose value without the above-mentioned warning. If the measured ratio R7 value is the same as the applicable boundary ratio 506 value of the ratio R7, then the processor preferably processes the test strip as a dried test strip. In other variations, the processor may process the test strip as a normal test strip, or may issue a warning that it is not certain whether the test strip is a used and dried test strip or a normal test strip.

If the normalized value of the second current i7,4 is below (or less than) the i7,4 threshold and the simultaneously measured R7 value is above (or greater than) the applicable boundary ratio value of the ratio threshold curve 502, then the processor can determine that the test was performed with a control solution (e.g., an aqueous glucose solution) rather than a blood-inoculated normal test strip (fig. 6). The processor activates the display to indicate that the control solution, rather than blood, is being tested.

It has been found that the above embodiments accurately detect previously used and dried test strips regardless of whether the dried test strips were previously blood or water inoculated. While the present invention is not limited by any theory of operation, it is believed that the prior inoculation of the dried test strip redistributes the chemical disposed on the working electrode 102 and the counter electrode 104 within the predetermined area 118 onto the bare electrode 106. It is believed that this redistribution or bleeding of chemicals from the working electrode 102 and counter electrode 104 onto the bare electrode 106 during the previous inoculation produces an abnormal signal in the current in response to the pulse applied to the bare electrode (i.e., pulse 7).

The ability to detect previously used and dried test strips provides a valuable safety function because testing of blood using previously used and dried test strips can provide erroneous glucose values. In addition, this functionality can be provided without requiring additional physical elements in the test strip or meter and without requiring any additional measurements to be taken during testing. As noted above, current measurements during the application of the potential to the bare electrode have been captured and used for the determination of hematocrit. Thus, additional security can be provided without adding any appreciable cost or adding any significant delay to the test. The additional time, if any, required by the processor to perform the calculations involved is negligible.

Many variations and combinations of the above-described functions may be employed. For example, in the above method, the ratio between the first current value and the second current value is the ratio of the second current value to the first current value, i.e., (i7,4)/(i7,1) or R7. The inverse ratio may be used. Thus, in the above example, the processor is able to calculate the ratio of the first current value to the second current value or (i7,1)/(i7, 4). If the inverse ratio is used, then testing with a normal test strip will yield a lower value than testing with a previously inoculated and dried test strip. In the above embodiment, the ratio threshold is a function of the second current value. However, the ratio threshold may be selected as a function of the first current value or the further current value measured during the application of the potential between the bare electrode and the further electrode.

In the above-described embodiment, the ratio between a first current value measured at a first time during the application of a potential between the bare electrode and the other electrode and a second current value measured at a later time during the application of the same potential is used to distinguish between a normal test strip and a dried test strip. However, more than one other parameter of the current between the bare electrode and the other electrode may be employed. The potential applied between the bare electrode and the other electrode may be an alternating or varying potential rather than the constant dc potential applied in the above example.

In the example shown in fig. 3, after applying potentials (pulse 1 to pulse 6) between the working electrode and the counter electrode, a potential (pulse 7) is applied between the bare electrode and the other electrode. In other embodiments, an electrical potential may be applied to the bare electrode before an electrical potential is applied between the working electrode and the counter electrode. In addition, the potential may be applied to the bare electrode during an interval in which the potential is applied between the working electrode and the counter electrode (e.g., during a pause period between pulse 1 and pulse 2 in the example of fig. 3). The application of the potential to the bare electrode preferably does not occur at the same time as the application of the other pulses, as this may lead to uncertain results.

In the above embodiments, the analyte is glucose and the analyte-containing target liquid applied to the test strip is blood. However, the invention may be applied to the measurement of other analytes in other liquids. The test strips used for such other measurements contain other known reagents, most typically an enzyme that reacts with the analyte and a mediator having a redox potential suitable for use with the enzyme. These reagents are provided in dry form in the area of the test strip in the same manner as described above.

In other embodiments, the electrochemical measurements may include the application of an input signal other than a potential between the electrodes and the measurement of an output signal other than a current passing between the electrodes. For example, current may be applied as an input signal and potential may be measured as an output signal. In other embodiments, the test strip may be configured to perform other measurements in addition to electrochemical measurements.

In the above embodiment, the bare electrode 106 (fig. 1) is disposed proximate to the counter electrode 104 and the working electrode 102. However, the bare electrode may be disposed away from the working and counter electrodes along the channel 92. Other locations may also be used, as long as the bare electrode is located where it is wetted by the liquid introduced into the test strip and outside the area 118 covered by the dry reagent applied during the manufacturing process. Preferably, the bare electrode is located adjacent to the working electrode and the counter electrode.

In other embodiments, the test strip may include more than two bare electrodes, both disposed outside of the area covered by the dry reagent. The two bare electrodes should be placed where they are wetted by the liquid introduced into the test strip. In this embodiment, the potential applied between the bare electrode and the other electrode may be a potential applied between two bare electrodes. Again, if a previously used and dried test strip is employed, one or more parameters of the current in response to such potential will be different.

As described above with reference to the control solution threshold 508 (fig. 6), it is not necessary to provide a distinction between a test using a control solution and a test using blood. This function may be omitted entirely.

While the present disclosure is shown with reference to particular embodiments, it is to be understood that these examples are merely illustrative of the principles and applications of the present disclosure. In addition, it should be understood that numerous other modifications may be made to the illustrative embodiments. These and other configurations, however, may be devised without departing from the spirit and scope of the present disclosure as defined by the appended claims.

Claims (19)

1. A method of analyzing a test strip in a biosensor, the method comprising:

displaying program information for applying a liquid sample to a test strip having a dry reagent, a working electrode, a counter electrode, a detection electrode, and a bare electrode that is not in contact with the dry reagent in an unused state of the test strip;

applying a first voltage between the working electrode and the counter electrode;

measuring a first current between the working electrode and the counter electrode;

determining an amount of the analyte based on the measured first current;

applying a second voltage between the bare electrode and the working electrode after applying the first voltage;

measuring a second current between the bare electrode and the working electrode followed by a third current; and at least one of the following steps:

displaying a first error message and inhibiting display of the measured amount of the analyte in response to the calculation based on the measured second and third currents being below the first threshold; and

the measured amount of the analyte is displayed in response to the calculation being above the first threshold.

2. The method of claim 1, wherein the first error message indicates that the test strip cannot be used because the test strip was previously wetted and dried.

3. The method of claim 1, wherein the second voltage is higher than the first voltage.

4. The method of claim 1, wherein applying the first voltage comprises applying the first voltage as one continuous potential or as a plurality of pulses.

5. The method of claim 1, wherein measuring the first current comprises measuring the first current in a single measurement or in multiple measurements.

6. The method of claim 1, wherein the amount of analyte comprises an amount of glucose.

7. The method of claim 1, further comprising determining a second analysis result based on the measured second current, the measured third current, or both.

8. The method of claim 7, wherein the determined second analysis result comprises an estimate of hematocrit.

9. The method of claim 1, further comprising, prior to displaying the program information:

applying a third voltage between the working electrode and the counter electrode;

measuring a fourth current between the working electrode and the counter electrode;

displaying a second error message in response to the measured fourth current being above a second threshold;

applying a fourth voltage between the bare electrode and the counter electrode in response to the measured fourth current being below a second threshold;

measuring a fifth current between the bare electrode and the counter electrode; and

displaying a second error message in response to the measured fifth current being above a third threshold.

10. The method of claim 9, wherein the second error message indicates that the test strip cannot be used because the test strip is wet and fluid-laden.

11. The method of claim 1, further comprising, after displaying the program information and before applying the first voltage:

applying a fifth voltage between the bare electrode and the counter electrode;

measuring a sixth current between the bare electrode and the counter electrode;

applying a sixth voltage between the working electrode and the detection electrode in response to the measured sixth current being above a fourth threshold;

measuring a seventh current between the working electrode and the detection electrode; and

displaying remedial information indicating that more liquid sample should be applied to the test strip in response to the measured sixth current being below the fourth threshold or the measured seventh current being below the fifth threshold.

12. A biosensor, comprising:

a processor;

a memory storing one or more executable instructions that, when executed by the processor, the processor is configured to:

applying a first voltage between the working electrode and the counter electrode;

measuring a first current between the working electrode and the counter electrode;

determining an amount of the analyte based on the measured first current;

applying a second voltage between the bare electrode and the working electrode after applying the first voltage;

measuring a second current between the bare electrode and the working electrode followed by a third current; and at least one of the following steps:

displaying a first error message and inhibiting display of the measured amount of the analyte in response to the calculation based on the measured second and third currents being below the first threshold; and

the measured amount of the analyte is displayed in response to the calculation being above the first threshold.

13. The biosensor of claim 12, wherein the first error message indicates that the test strip cannot be used because the test strip was previously wetted and dried.

14. The biosensor of claim 12, where the amount of analyte comprises an amount of glucose.

15. The biosensor of claim 12, wherein the instructions, when executed by the processor, are further configured to determine a second analysis result based on the measured second current, the measured third current, or both.

16. The biosensor of claim 15, where the determined second analysis result comprises an estimate of hematocrit.

17. The biosensor of claim 12, wherein the instructions, when executed by the processor, further configure the processor to:

applying a third voltage between the working electrode and the counter electrode;

measuring a fourth current between the working electrode and the counter electrode;

displaying a second error message in response to the measured fourth current being above a second threshold;

applying a fourth voltage between the bare electrode and the counter electrode in response to the measured fourth current being below a second threshold;

measuring a fifth current between the bare electrode and the counter electrode; and

displaying a second error message in response to the measured fifth current being above a third threshold.

18. The biosensor of claim 17, wherein the second error message indicates that the test strip cannot be used because the test strip is wet and fluid-laden.

19. The biosensor of claim 12, wherein the instructions, when executed by the processor, further configure the processor to:

applying a fifth voltage between the bare electrode and the counter electrode;

measuring a sixth current between the bare electrode and the counter electrode;

applying a sixth voltage between the working electrode and the detection electrode in response to the measured sixth current being above a fourth threshold;

measuring a seventh current between the working electrode and the detection electrode; and

displaying information indicating that more liquid sample should be applied to the test strip in response to the measured sixth current being below a fourth threshold or the measured seventh current being below a fifth threshold.