US20150176049A1 - Determining usability of analytical test strip - Google Patents

Abstract

A system for determining usability of an analytical test strip includes a sample chamber to receive a fluid sample, a reagent in the sample chamber having a moisture-varying impedance, and two detection electrodes contacting the reagent. A test meter applies an AC waveform across the reagent via the detection electrodes while measuring an impedance of the reagent. A processor automatically determines whether the measured impedance of the reagent meets a dryness criterion. The meter includes a housing, a strip port connector, an impedance measurement circuit and the processor. A method for determining usability of a strip inserted in a hand held meter includes applying an AC waveform across a reagent of the strip and measuring a first electrical signal, and determining whether the strip meets the dryness criterion based on the first electrical signal. The test strip and ways of determining an analyte are also described.

Description

TECHNICAL FIELD
• The present invention relates, in general, to the field of analyte measurement and, in particular, to test meters and related methods for detecting error conditions of analytical test strips based on specified criteria.
DESCRIPTION OF RELATED ART
• The determination (e.g., detection or concentration measurement) of an analyte in a fluid sample is of particular interest in the medical field. For example, it can be desirable to determine glucose, ketone bodies, cholesterol, lipoproteins, triglycerides, acetaminophen or HbA1c concentrations in a sample of a bodily fluid such as urine, blood, plasma or interstitial fluid. Such determinations can be achieved using a hand-held test meter in combination with analytical test strips (e.g., electrochemical-based analytical test strips). Analytical test strips generally include a sample chamber (also referred to herein as an “analyte chamber”) for maintaining a liquid analyte, e.g., whole blood, in contact with two or more electrodes. Analytes can then be determined electrochemically using signals conveyed by the electrodes.
• Since test meters are used to make care decisions relating to medical conditions, it is desirable that these devices measure with as much accuracy and precision as possible. However, conventional reagents used on analytical test strips can be affected by environmental conditions. For example, a measurement can be affected by the moisture content of the reagent, which is correlated with the relative humidity of the atmosphere around the analytical test strip. It is therefore desirable to measure the effect of humidity to notify a user in advance of obtaining an analyte reading if such an inaccuracy may be present.
BRIEF DESCRIPTION OF THE DRAWINGS
• Various novel features of the invention are set forth with particularity in the appended claims. A better understanding of the features and advantages of the present invention will be obtained by reference to the following detailed description that sets forth illustrative embodiments, in which the principles of the invention are utilized, and the accompanying drawings, in which like numerals indicate like elements, of which:
• FIG. 1 is a simplified depiction of a system according to an embodiment of the present invention;
• FIG. 2 is an exploded view of anexemplary test strip150 and a schematic of related components;
• FIG. 3 is a flow diagram depicting stages in an exemplary method for determining usability of an analytical test strip inserted in a hand-held test meter;
• FIGS. 4A and 4B show experimental data of a tested analytical test strip with a reagent; and
• FIG. 5 is a flow diagram depicting stages in an exemplary method for the determination of an analyte in a bodily-fluid sample.
DETAILED DESCRIPTION OF ILLUSTRATIVE EMBODIMENTS
• The following detailed description should be read with reference to the drawings, in which like elements in different drawings are identically numbered. The drawings, which are not necessarily to scale, depict exemplary embodiments for the purpose of explanation only and are not intended to limit the scope of the invention. The detailed description illustrates by way of example, not by way of limitation, the principles of the invention. This description will clearly enable one skilled in the art to make and use the invention, and describes several embodiments, adaptations, variations, alternatives and uses of the invention, including what is presently believed to be the best mode of carrying out the invention.
• As used herein, the terms “about” or “approximately” for any numerical values or ranges indicate a suitable dimensional tolerance that allows the part or collection of components to function for its intended purpose as described herein. In addition, the term “in”, as used throughout this description, does not necessarily require that one component or structure be completely contained within another, unless otherwise indicated.
• In general, portable test meters, such as hand-held test meters, for use with an analytical test strip in the determination of an analyte (such as glucose) in a bodily-fluid sample (i.e., a whole blood sample) according to embodiments of the present invention include a circuit and a processor configured to apply an AC waveform across a sample chamber of the test strip and measure the impedance of a reagent disposed on the strip while applying the waveform. This permits accurately determining whether reagent moisture is likely to affect an electrochemical measurement taken using the reagent.
• Hand-held test meters according to embodiments of the present invention are beneficial in that they provide a qualitative determination of test strip usability. For example, the detection of an unusually low resistance can indicate that the reagent is moist. It is desirable to avoid using such test strips, since the moisture may reduce the accuracy of the results.
• A problem solved by various embodiments is to determine the moisture content of a reagent. Various embodiments discussed herein can readily be incorporated by one of sufficient skill into a hand-held test meter. One example of a test meter that can be suitably configured is the commercially available OneTouch® Ultra® 2 glucose meter from LifeScan Inc. (Milpitas, Calif.). Additional examples of hand-held test meters that can also be modified are described in U.S. Patent Application Publication Nos. 2007/0084734 (published on Apr. 19, 2007) and 2007/0087397 (published on Apr. 19, 2007) as well as International Publication Number WO2010/049669 (published on May 6, 2010), incorporated by reference in their entirety.
• An experiment was performed to investigate the effect of moisture content on test strips. Control test strips were stored at room temperature in a vial. Experimental test strips were stored in an environmental chamber at 30° C. and 90% relative humidity (RH) for approximately 1.5 hours. Glucose assays were performed using a control solution in each group of test strips. The assay was conducted using a conventional hand-held blood-glucose test meter. The experimental test strips were tested directly after removal from the environmental chamber. The results were as given in Table 1.

• TABLE 1
  Assay #	Experiment	Control

  1	389	350
  2	400	361
  3	418	354
  4	413	367
  5	416	355
  6	411	348
  Average	407.8333	355.8333

  
  As can be seen, the experimental test strips read significantly higher than the control test strips.
• FIG. 1 shows anexemplary system10 for determining usability of ananalytical test strip150. Thesystem10 can determine whether thetest strip150 has areagent171 that has absorbed moisture. Thesystem10 includes theanalytical test strip150 having two spaced-apart detection electrodes151,152 connected in series with asample chamber140. Thesample chamber140 is adapted to receive a fluid sample. Thereagent171 is arranged at least partly in thesample chamber140, and thedetection electrodes151,152 are in contact with thereagent171. Thereagent171 has an impedance that varies with moisture content. An example of thesample chamber140 is an electrochemical sample cell, as discussed below with reference toFIG. 2. Thesample chamber140 can have a volume ranging, e.g., from about 0.1 microliters to about 5 microliters, or about 0.2 microliters to about 3 microliters, or about 0.3 microliters to about 1 microliter.
• The herein describedsystem10 also includes atest meter100 adapted to receive theanalytical test strip150. Thetest meter100 has an impedance-measurement circuit190 configured to apply an alternating-current (AC) waveform across thereagent171 via thedetection electrodes151,152 and concurrently measure an impedance of thereagent171. Thetest meter100 also includes aprocessor186 configured to automatically determine whether the measured impedance of thereagent171 meets a selected dryness criterion. The selected dryness criterion can be stored, e.g., in amemory block118.
• In at least one example, the selected dryness criterion is an impedance of about 00 to about 1 MΩ and the impedance-measurement circuit190 is configured to apply the AC waveform at a frequency of about 10 kHz, or at a frequency in the range from about 1 kHz to about 100 kHz. The AC waveform can have an amplitude of about 50 mVrms to about 500 mVrms.
• In at least one exemplary embodiment, thetest meter100 further includes auser interface189 including, e.g., adisplay181 and one or moreuser interface buttons180. In this exemplary embodiment, theprocessor186 is configured to, if the measured impedance does not meet the selected dryness criterion, present an error indication via theuser interface189. The error indication can, e.g., request the user to insert anew test strip150, or request the user to check the package of test strips and make sure it has not expired or been punctured, or inform the user that measurements may have reduced accuracy due to a high moisture level in thereagent171.
• Thedisplay181 can be, for example, a liquid crystal display or a bi-stable display configured to show a screen image. The exemplary screen image shown inFIG. 1 provides indications of glucose concentration (“120”) and of date and time (“3/14/15 8:30 am”), as well as a units indication (“mg/dL”). Thedisplay181 can also present error messages or instructions to a user on how to perform a test (analyte determination).
• In various embodiments, the impedance-measurement circuit190 includes a voltage supply, e.g., anAC voltage source191, configured to apply the alternating-current waveform. The voltage supply can be controlled by theprocessor186. In one version, theAC voltage source191 includes a low-pass filter that receives a square wave from theprocessor186 and provides a filtered voltage that is closer to a sinusoid as a result of the filtering. Exemplary low-pass filters for this purpose can include fourth-order filters, multiple feedback low pass filters, and Sallen and Key low pass filters.
• The impedance-measurement circuit190 can further include a transimpedance amplifier configured to detect a current through the reagent while the alternating-current waveform is applied. In the example shown, theAC voltage source191 is connected to thedetection electrode151. The transimpedance amplifier in the impedance-measurement circuit190 includes aresistor192 in series between thedetection electrode152 and theAC voltage source191. The voltage across theresistor192 is directly proportional to the current through theAC voltage source191 and thedetection electrodes151,152. Anamplifier193 amplifies the voltage across theresistor192 to provide a voltage signal to theprocessor186 that is representative of current through thedetection electrodes151,152.
• As noted, thetest meter100 can be a hand-held test meter for use with ananalytical test strip150 in the determination of at least one analyte in a bodily-fluid sample. Still referring toFIG. 1, theexemplary test meter100 can include ahousing104 and a strip port connector (SPC)106 that is configured to receive theanalytical test strip150, which is inserted into a port of thehousing104. TheSPC106 can include spring contacts arranged so that thetest strip150 can be slid into theSPC106 to electrically connect the spaced-apartdetection electrodes151,152 of the receivedanalytical test strip150 with the impedance-measurement circuit190 or other components of thetest meter100. TheSPC106 can also or alternatively include pogo pins, solder bumps, pin or other receptacles, jacks, or other devices for selectively and removably making electrical connections. The impedance-measurement circuit190 can thus apply the alternating-current waveform via theSPC106.
• Thetest meter100 can also include other electronic components (not shown) for applying test voltages or other electrical signals to theanalytical test strip150, and for measuring an electrochemical response (e.g., plurality of test current values) and determining an analyte based on the electrochemical response. To simplify the present descriptions, the figures do not depict all such electronic circuitry. Exemplary circuits for measuring electrochemical responses are discussed in greater detail in a later portion of this description with reference toFIG. 2.
• According to the exemplary embodiment, theprocessor186 is disposed within thehousing104. Theprocessor186 can be adapted to detect the fluid sample in thesample chamber140 and subsequently cause the impedance-measurement circuit190 to apply the excitation voltage signal. For the purposes described herein, theprocessor186 can include any suitable microcontroller or micro-processor known to those of skill in the art. One exemplary microcontroller is an MSP430F5138 microcontroller that is commercially available from Texas Instruments, Dallas, Tex. USA. Theprocessor186 can include, e.g., a field-programmable gate array (FPGA) such as an ALTERA CYCLONE FPGA, a digital signal processor (DSP) such as a Texas Instruments TMS320C6747 DSP, or another suitable processing device adapted to carry out various algorithm(s) as described herein, e.g., flowcharts or blocks shown inFIGS. 3 and 5. Theprocessor186 can include signal-generation and signal-measurement functions, e.g., D/A converters, pulse-train generators, or A/D converters.
• Thememory block118 of the hand-heldtest meter100 includes one or more storage device(s), e.g., a code memory (such as random-access memory, RAM, or Flash memory) for storing, e.g., program firmware or software; a data memory (e.g., RAM or fast cache); or a disk (such as a hard drive). Computer program instructions to carry out suitable algorithm(s), e.g., those shown inFIGS. 3 and 5, are stored in one of those device(s). Thememory block118 can also or alternatively be incorporated in theprocessor186. A Flash or other nonvolatile memory in thememory block118 can also contain, e.g., graphics to be displayed on thedisplay181, text messages to be displayed to a user, calibration data, user settings, or algorithm parameters.
• Throughout this description, some embodiments are described in terms that would ordinarily be implemented as software programs. Those skilled in the art will readily recognize that the equivalent of such software can also be constructed in hardware (hard-wired or programmable), firmware, or micro-code. Given the systems and methods as described herein, software or firmware not specifically shown, suggested, or described herein that is useful for implementation of any embodiment is conventional and within the ordinary skill in such arts.
• FIG. 2 is an exploded view of anexemplary test strip150 and a schematic of related components. Additional details of various exemplary test strips and measurement methods are provided in US Patent Application Publication No. 2007/0074977 and U.S. Pat. No. 8,163,162, each of which is incorporated herein by reference in its entirety. In the example shown, theexemplary test strip150 includes asample electrode253 arranged at least partly in thesample chamber140, and thedetection electrodes151,152. Theexemplary sample electrode253 is electrically insulated from thedetection electrodes151,152, e.g., by an electrically-insulatingspacer235 arranged between thesample electrode253 and thedetection electrodes151,152. Thesample chamber140 can be formed by removing a portion of thespacer235, or by disposing two separated portions of thespacer235 between the first andsecond electrodes151,152. In various embodiments, theelectrodes151,152,253 can be arranged spaced apart in a facing or opposing faced arrangement, or in other coplanar or non-coplanar configurations. In the example shown, thedetection electrodes151,152 are laterally adjacent to each other and are arranged on the opposite side of thesample chamber140 from thesample electrode253.
• In various aspects, theelectrodes151,152,253 include conductive thin films formed from materials such as gold, palladium, carbon, silver, platinum, tin oxide, iridium, indium, and combinations thereof (e.g., indium-doped tin oxide or “ITO”). Electrodes can be formed by disposing a conductive material onto electrically-insulatinglayers225,215 by a sputtering, electroless plating, thermal evaporation, or screen printing process. Suitable materials that can be employed in the electrically-insulatinglayers215,225 or thespacer235 include, for example, plastics (e.g. PET, PETG, polyimide, polycarbonate, or polystyrene), silicon, ceramic, glass, and combinations thereof. In an example, thesample electrode253 is a sputtered gold electrode disposed over the electrically-insulatinglayer215, and thedetection electrodes151,152 are sputtered palladium electrodes disposed over the electrically-insulatinglayer225. Thedetection electrodes151,152 can be deposited separately, or can be formed by, e.g., scribing or etching anisolation channel226 to separate a deposited film intoseparate electrodes151,152. Theisolation channel226 can be scribed into a gold layer, a palladium layer, or another conductor.
• Theanalytical test strip150 can be used by a patient or healthcare provider in various ways. For example, once theanalytical test strip150 is interfaced with the hand-heldtest meter100,FIG. 1, or prior thereto, a fluid sample (e.g., a whole blood sample or a control-solution sample) can be introduced into thesample chamber140 of theanalytical test strip150. Theanalytical test strip150 can includeenzymatic reagents171 that selectively and quantitatively transform an analyte in the fluid sample into another predetermined chemical form. For example, theanalytical test strip150 can be an electrochemical-based analytical test strip configured for the determination of glucose in a whole blood sample. Such atest strip150 can include theenzymatic reagent171 configured in the sample chamber such that the electrochemical response represents a glucose level in the fluid sample. For example, thereagent171 can include ferricyanide and glucose oxidase so that glucose can be physically transformed into an oxidized form. Movement of charge during this oxidation and related reactions provides a current that can be measured to determine the amount of glucose present in the fluid sample.
• Accordingly, in various aspects, thetest meter100 includes ananalyte measurement circuit290. Theprocessor186 is further configured to, if the measured impedance of the reagent does meet the dryness criterion, detect the presence of the fluid sample in thesample chamber140 of the receivedanalytical test strip150. Theprocessor186 can be further configured to, based upon (e.g., in response to) the detection, operate the analyte measurement circuit to apply a testing waveform across the fluid sample and measure a resulting electrochemical response.
• In various embodiments, theanalyte measurement circuit290 is electrically connected to the sample electrode and at least one of the spaced-apart detection electrodes, e.g., via theSPC106,FIG. 1. In various embodiments, theanalyte measurement circuit290 includes theimpedance measurement circuit190,FIG. 1, or uses components of theimpedance measurement circuit190 such as theAC voltage source191 and theamplifier193, bothFIG. 1. For example, theAC voltage source191 or291 can be shorted or bridged to provide a conductive path between thesample electrode253 and a reference potential, e.g., ground, during analyte measurement. Theanalyte measurement circuit290 can be configured to provide the testing waveform including an AC waveform, a DC level, or a waveform combining AC and DC waveform(s).
• In the example shown, avoltage source291 supplies an AC waveform to thesample electrode253, e.g., via a contact263 of thestrip port connector106,FIG. 1. Atransimpedance amplifier293 is connected to one or both of thedetection electrodes151,152, e.g., viarespective contacts261,262 of thestrip port connector106. Thevoltage source291 can alternatively be connected to the detection electrode(s)151,152 and thetransimpedance amplifier293 can be connected to thesample electrode253. Aswitch294 can be provided for selectively shorting thecontacts261,262. Closing theswitch294 permits a single input to thetransimpedance amplifier293 to be used to measure current traveling through both of thedetection electrodes151,152.
• Theprocessor186 can operate thevoltage source291 and receive data from thetransimpedance amplifier293. Theprocessor186 can use information stored in thememory block118,FIG. 1, in determining an analyte, e.g., in determining a blood glucose concentration, based on the electrochemical response of analytical test strip. For example, thememory block118 can store calibration tables to adjust for electrical parasitics on thetest strip150.
• In at least one exemplary embodiment, thetest meter100 includes two presence-detectcontacts265,266 configured to electrically contact a selected one of thedetection electrodes151,152 of the receivedanalytical test strip150. Thetest meter100, or a component thereof (e.g., the impedance-measurement circuit190), includes a presence-detection circuit285 configured to detect electrical continuity between the two presence-detect contacts. Theprocessor186 in this exemplary embodiment is further configured to automatically cause application of the alternating-current waveform subsequent to detection of the electrical continuity. Electrical continuity can be detected when the DC resistance between the presence-detectcontacts265,266 drops below a selected threshold, e.g., 100Ω. The threshold can be selected based on the resistivity of one or both of theelectrodes151,152. Although this particular example shows the presence-detectcontacts265,266 electrically connected through thedetection electrode152, electrical connection can also or alternatively be made through thedetection electrode151, thesample electrode253, or another electrode or conductive area of thetest strip150.
• In an example, theprocessor186 is programmed to sleep or otherwise enter a low-power-draw state when thetest meter100 is not in use by a patient. The presence-detection circuit185 can be connected to an interrupt or wakeup (“INT”) pin of theprocessor186 to wake up theprocessor186 when continuity is detected. When theprocessor186 resumes operation, it can test the impedance of the reagent, detect the fluid sample, or perform other processes described herein with respect to thetest strip150.
• In the exemplary embodiment shown, the presence-detection circuit285 includes a pullup resistor287 (e.g., a resistor wired at one end to a voltage supply) and a current sink288 (e.g., ground, or a voltage supply with a voltage lower than the voltage of the voltage supply of the pullup resistor287). A voltage or current source or other circuit for maintaining the voltage of a node within a selected range can be used in place of thepullup resistor287. A pulldown resistor or circuit and a voltage source can alternatively be used. When electrical continuity is not present between the presence-detectcontacts265,266, anelectrode289 is held at a relatively higher voltage by thepullup resistor287. When electrical continuity is present, theelectrode289 is held at a relatively lower voltage by thecurrent sink288 through the presence-detectcontact265, theelectrode152, and the presence-detectcontact266.
• In various aspects, the presence-detection circuit285 further includes a switch284 (here, a double-pole, single-throw switch) for selectively electrically isolating at least one of the two presence-detectcontacts265,266 from the receivedanalytical test strip150 when open, and theprocessor186 is further configured to automatically cause opening of theswitch284 after the impedance of thereagent171 is measured. This advantageously reduces noise on the analyte measurement that might otherwise be introduced by, e.g., thepullup resistor287.
• In an exemplary aspect for detecting the fluid sample, once a determination is made that thetest strip150 is electrically connected to thetest meter100, thetest meter100 can apply a test potential or current, e.g., a constant current, between thesample electrode253 and one or both of thedetection electrodes151,152. In an example, a constant DC current can be applied into thesample chamber140, and the voltage across thesample chamber140 can be monitored. When the fluid sample has filled thesample chamber140, the voltage across thesample chamber140 will fall below a selected threshold. AC signals, as described herein, can be measured before thesample chamber140 has filled with fluid, or after thesample chamber140 has filled with fluid.
• Thereagent171 can be disposed within thesample chamber140 using a process such as slot coating, coating by dispensing liquid from the end of a tube, ink jetting, and screen printing. Such processes are described, for example, in U.S. Pat. Nos. 6,676,995; 6,689,411; 6,749,887; 6,830,934; and 7,291,256; in U.S. Patent Application Publication No. 2004/0120848; and in PCT Application Publication No. WO/1997/018465 and U.S. Pat. No. 6,444,115, each of which is incorporated herein in relevant part by reference. The reagent layer Suitable mediators in thereagent171 include ferricyanide, ferrocene, ferrocene derivatives, osmium pipyridyl complexes, and quinone derivatives. Suitable enzymes in thereagent171 include glucose oxidase, glucose dehydrogenase (GDH) based on pyrroloquinoline quinone (PQQ) co-factor, GDH based on nicotinamide adenine dinucleotide (NAD) co-factor, and FAD-based GDH (EC 1.1.99.10).
• In at least one example, the electrochemical-basedanalytical test strip150 includes an electrically-insulatingbottom layer225. A patterned electrically-conductive layer (e.g., including thedetection electrodes151,152) is disposed on the electrically insulatingbottom layer225. The patterned electrically-conductive layer includes a first patterned portion (e.g., the detection electrode151) and a second patterned portion (e.g., the detection electrode152). An enzymatic reagent layer (e.g., the reagent171) is disposed on the first patterned portion (e.g., the detection electrode151), the second patterned portion (e.g., the detection electrode152) and the electrically-insulatingbottom layer225 such that the enzymatic reagent layer bridges the first patterned portion (e.g., the detection electrode151) and the second patterned portion (e.g., the detection electrode152). A patterned spacer layer (e.g., the spacer235) is arranged over the patterned electrically-conductive layer. A top electrically conductive layer (e.g., the sample electrode253) is arranged over thespacer235. An electrically-insulatingtop layer215 is arranged over the top electrically conductive layer (e.g., the sample electrode253). The terms “top” and “bottom” do not constrain the orientation of thetest strip150 during manufacturing or use, but are used for clarity of explanation.
• FIG. 3 is a flow diagram depicting stages in a method for determining usability of an analytical test strip inserted in a hand-held test meter. The steps can be performed in any order except when otherwise specified, or when data from an earlier step is used in a later step. In at least one example, processing begins withstep310. For clarity of explanation, reference is herein made to various components shown inFIGS. 1 and 2 that can carry out or participate in the steps of exemplary method(s). It should be noted, however, that other components can be used; that is, exemplary method(s) shown inFIG. 2 are not limited to being carried out by the identified components. An exemplary method includes performing below-described steps using theprocessor186 and at least one electrical circuit of the test meter, e.g., the impedance-measurement circuit190.
• Instep310, an alternating-current waveform is applied across areagent171 of the insertedanalytical test strip150 and a first electrical signal is measured. This can be performed by theprocessor186 commanding and receiving data from the impedance-measurement circuit190, as discussed above with reference toFIGS. 1 and 2.
• Indecision step320, theprocessor186 determines whether the insertedanalytical test strip150 meets a selected dryness criterion based on the first electrical signal. This can be as discussed above. If so,step330 is next. If not, step360 is next.
• Instep330, the insertedanalytical test strip150 meets the selected dryness criterion. A fluid sample is detected in a sample chamber of the inserted analytical test strip. This can be done, e.g., by applying a constant current across thesample chamber140 as described above, or in other ways. Step340 is next.
• Instep340, a voltage signal is applied across the detected fluid sample in the sample chamber and a second electrical signal is measured. The second electrical signal is mediated by the reagent. Examples are given above with respect to oxidation of glucose. Step350 is next.
• Instep350, a physiological property of the fluid sample, e.g., blood glucose level or hematocrit, is determined using the second electrical signal. The physiological property can be determined using, e.g., the change in phase or magnitude from the voltage signal to the second electrical signal. As discussed above, in various aspects, the reagent is configured so that the second electrical signal represents a blood glucose level in the fluid sample.
• If the measured impedance does not meet the selected dryness criterion,decision step320 is followed bystep360. Instep360, theprocessor186 automatically presents an error indication via theuser interface189. Step360 can include automatically computing or rendering a visual representation of the error indication and displaying the visual representation on thedisplay181,FIG. 1.
• FIGS. 4A and 4B show experimental data of a testedanalytical test strip150 with areagent171.FIG. 4A shows measured resistance in kΩ as a function of measurement frequency in Hz.FIG. 4B shows measured capacitance in pF as a function of measurement frequency (Hz). The tests that produced the illustrated results were carried out in a thermal chamber at 30° C. and 90% RH. At DC, the resistance (not shown inFIG. 4A) was 10 MΩ. As measurement frequency increased, themoist test strip150 showed a decrease of resistance (FIG. 4A) and a decrease of capacitance (FIG. 4B). In this example, both resistance and capacitance have significantly reduced values at 10 kHz compared to 100 Hz. Subsequent measurements outside the 90% RH condition demonstrated that AC impedance rose as the strip dried out.
• For comparison, tests were performed at lower RH levels. Tests were also performed on a control test strip that did not have a reagent. At an RH of 80%, both of the test strips150 (with and without reagent) showed a resistance of approx 6 MΩ at 10 kHz. At an RH below 80%, theexperimental test strip150 showed resistance above the limit of the ohmmeter and approx 156 pF capacitance. This capacitance was determined to be the result of the test setup.
• Characterization measurements similar to those shown inFIGS. 4A and 4B can be collected and processed or analyzed to determine the dryness criterion and alternating-current waveform frequency for a selected design of thetest strip150. The threshold can be chosen according to the resistivity of thedetection electrodes151,152. In an example, the threshold can be higher fordetection electrodes151,152 including carbon conductors than fordetection electrodes151,152 including sputtered Pd conductors. In some aspects, the geometry of thesample chamber140 and thereagent171 are constrained by the analyte measurement to be performed. The threshold can be selected for thetest strip150 conforming to those constraints on geometry. In various aspects, the geometry of thetest strip150 can be selected to provide desired thresholds. For example, the width of theisolation channel226 can be selected wider to increase AC impedance or narrower to decrease AC impedance.
• FIG. 5 is a flow diagram depicting stages in an exemplary method for the determination of an analyte in a bodily-fluid sample. The steps can be performed in any order, with exceptions noted above. In at least one example, processing begins withstep510. As discussed above, various components can be used in carrying out the exemplary method. The below-described steps can be carried out using theprocessor186 and at least one electrical circuit of the test meter, e.g., the impedance-measurement circuit190.
• Instep510, it is ascertained whether an enzymatic reagent layer of an electrochemical-based analytical test strip has been exposed to a predetermined humidity level by measuring an electrical characteristic of the enzymatic reagent layer. As discussed above, in at least one example the electrochemical-based analytical test strip has an electrically-insulating bottom layer; a patterned electrically-conductive layer disposed on the electrically insulating bottom layer and including a first patterned portion and a second patterned portion; an enzymatic reagent layer disposed on the first patterned portion, the second patterned portion and the electrically-insulating bottom layer such that the enzymatic reagent layer bridges the first patterned portion and the second patterned portion; a patterned spacer layer; a top electrically conductive layer; and an electrically-insulating top layer.
• Instep520, the bodily-fluid sample is applied to the electrochemical-based analytical test strip. For example, thesample chamber140 can be filled with the bodily-fluid sample.
• Instep530, the analyte (e.g., blood glucose level, or another physiological property) is determined based on an electrochemical response of the electrochemical-based analytical test strip. The electrochemical response can be mediated by thereagent171. The analyte can be determined, e.g., by measuring a current through thesample electrode253 and one or both of thedetection electrodes151,152 as the analyte reacts with thereagent171. Other ways of determining analytes are described, e.g., in the above-referenced patent documents. Analyte determination can be performed, e.g., using AC, DC, or combined waveforms; by applying voltages or currents; and by measuring currents, voltages, or impedances, any of which can be real- or complex-valued. For example, an AC excitation waveform can be applied across thesample chamber140 and AC measurements can be taken at one or more signal phase(s) with respect to the AC excitation waveform.
• Using various methods, devices or systems described herein advantageously permits determining moisture content of thereagent171 on theanalytical test strip150,FIG. 1. Various aspects permit notifying the user before a measurement is taken using a test strip that may be inaccurate due to the moisture content of thereagent171. Technical effects of various aspects including transducing moisture content into an electrical signal; quantitatively transforming an analyte in the fluid sample into another predetermined chemical form; carrying out an electrochemical reaction to permit measuring the analyte in the fluid sample; and computing and presenting visible representations informing a user that thetest strip150 is too moist.
PARTS LIST FOR FIGS.1-5
• 10 system
• 100 test meter
• 104 housing
• 106 strip port connector (SPC)
• 118 memory block
• 140 sample chamber
• 150 analytical test strip
• 151,152 detection electrodes
• 171 reagent
• 180 user interface button
• 181 display
• 185 presence-detection circuit
• 186 processor
• 189 user interface
• 190 impedance-measurement circuit
• 191 AC voltage source
• 192 resistor
• 193 amplifier
• 215,225 electrically-insulating layers
• 226 isolation channel
• 235 spacer
• 253 sample electrode
• 261,262,263 contacts
• 265,266 presence-detect contacts
• 284 switch
• 285 presence-detection circuit
• 287 pullup resistor
• 288 a current sink
• 289 electrode
• 290 analyte measurement circuit
• 291 voltage source
• 293 transimpedance amplifier
• 294 switch
• 310 step
• 320 decision step
• 330,340,350,360 steps
• 510,520,530 steps
• While preferred embodiments of the present invention have been shown and described herein, it will be obvious to those skilled in the art that such embodiments are provided in this description by way of example only. To that end, numerous variations, changes, and substitutions will be readily apparent to those skilled in the art without departing from the invention. In addition, it should be understood that various alternatives to the embodiments of the invention described herein can be employed in practicing the invention. References to “a particular embodiment” (or “aspect”) and the like refer to features that are present in at least one embodiment of the invention. Separate references to “an embodiment” (or “aspect”) or “particular embodiments” or the like, however, do not necessarily refer to the same embodiment or embodiments; however, such embodiments are not mutually exclusive, unless specifically indicated or as are readily apparent to one of skill in the art. The word “or” is used in this disclosure in a non-exclusive sense, unless otherwise explicitly noted. It is intended that the following claims define the scope of the invention and that devices and methods within the scope of these claims and their equivalents be covered thereby.

Claims (22)

What is claimed is:

1. A system for determining usability of an analytical test strip, the system comprising:

a) the analytical test strip having a sample chamber adapted to receive a fluid sample, a reagent arranged at least partly in the sample chamber, and two spaced-apart detection electrodes in contact with the reagent, wherein the reagent has an impedance that varies with moisture content; and

b) a test meter adapted to receive the analytical test strip, the test meter having an impedance-measurement circuit configured to apply an alternating-current waveform across the reagent via the detection electrodes and concurrently measure an impedance of the reagent, and having a processor configured to automatically determine whether the measured impedance of the reagent meets a selected dryness criterion.

2. The system according toclaim 1, wherein the test meter further includes a user interface, wherein the processor is configured to, if the measured impedance does not meet the selected dryness criterion, present an error indication via the user interface.

3. The system according toclaim 1, wherein the analytical test strip further includes a sample electrode arranged at least partly in the sample chamber and the test meter further includes an analyte measurement circuit electrically connected to the sample electrode and at least one of the spaced-apart detection electrodes.

4. The system according toclaim 3, wherein the processor is further configured to, if the measured impedance of the reagent meets the dryness criterion, detect the presence of the fluid sample in the sample chamber of the received analytical test strip and, based upon the detection, operate the analyte measurement circuit to apply a testing waveform across the fluid sample and measure a resulting electrochemical response.

5. The system according toclaim 4, wherein the reagent is configured in the sample chamber such that the electrochemical response represents a glucose level in the fluid sample.

6. The system according toclaim 4, wherein the testing waveform includes an alternating-current waveform.

7. The system according toclaim 3, wherein the detection electrodes are laterally adjacent to each other and are arranged on the opposite side of the sample chamber from the sample electrode.

8. The system according toclaim 1, wherein the impedance-measurement circuit includes a voltage supply configured to apply the alternating-current waveform and a transimpedance amplifier configured to detect a current through the reagent while the alternating-current waveform is applied.

9. The system according toclaim 1, wherein the test meter includes two presence-detect contacts configured to electrically contact a selected one of the detection electrodes of the received analytical test strip and a presence-detection circuit configured to detect electrical continuity between the two presence-detect contacts, and the processor is further configured to automatically cause application of the alternating-current waveform subsequent to detection of the electrical continuity.

10. The system according toclaim 9, wherein the test meter further includes a switch for selectively electrically isolating at least one of the two presence-detect contacts from the received analytical test strip when open, and the processor is further configured to automatically cause opening of the switch after the impedance of the reagent is measured.

11. The system according toclaim 1, wherein the selected dryness criterion is an impedance of about 0Ω to about 1 MΩ and the impedance-measurement circuit is configured to apply the alternating-current waveform at a frequency of about 10 kHz.

12. A hand-held test meter for use with an analytical test strip, the test meter comprising:

a) a housing;

b) a strip port connector configured to receive the analytical test strip and to electrically connect to two spaced-apart detection electrodes of the received analytical test strip;

c) an impedance-measurement circuit arranged in the housing and configured to apply an alternating-current waveform across a reagent in a sample chamber of the received analytical test strip via the strip port connector, and to concurrently measure an impedance of the reagent; and

d) a processor configured to automatically determine whether the measured impedance of the reagent meets a selected dryness criterion.

13. The meter according toclaim 12, wherein the strip port connector is further configured to electrically connect to a sample electrode of the received analytical test strip and the meter further includes an analyte measurement circuit electrically connected to the sample electrode and at least one of the spaced-apart detection electrodes.

14. The meter according toclaim 13, wherein the processor is further configured to, if the measured impedance of the reagent meets the dryness criterion, detect the presence of the fluid sample in the sample chamber of the received analytical test strip and, based upon the detection, operate the analyte measurement circuit to apply a testing waveform across the fluid sample and measure an electrochemical response to the testing waveform.

15. The meter according toclaim 14, wherein the reagent is configured so that the electrochemical response represents a glucose level in the fluid sample.

16. The meter according toclaim 12, further including a user interface, wherein the processor is configured to, if the measured impedance does not meet the selected dryness criterion, present an error indication via the user interface.

17. A method for determining usability of an analytical test strip inserted in a hand-held test meter, the method comprising performing the following steps using a processor and at least one electrical circuit of the test meter:

applying an alternating-current waveform across a reagent of the inserted analytical test strip and measuring a first electrical signal; and

determining whether the inserted analytical test strip meets a selected dryness criterion based on the first electrical signal.

18. The method according toclaim 17, further including, if the inserted analytical test strip meets the selected dryness criterion:

detecting a fluid sample in a sample chamber of the inserted analytical test strip;

applying a voltage signal across the detected fluid sample in the sample chamber and measuring a second electrical signal mediated by the reagent; and

determining a physiological property of the fluid sample using the second electrical signal.

19. The method according toclaim 18, wherein the reagent is configured so that the second electrical signal represents a blood glucose level in the fluid sample.

20. The method according toclaim 17, further including, if the measured impedance does not meet the selected dryness criterion, automatically presenting an error indication via a user interface.

21. An electrochemical-based analytical test strip comprising:

a) an electrically-insulating bottom layer;

b) a patterned electrically-conductive layer disposed on the electrically insulating bottom layer that includes a first patterned portion and a second patterned portion;

c) an enzymatic reagent layer disposed on the first patterned portion, the second patterned portion and the electrically-insulating bottom layer such that the enzymatic reagent layer bridges the first patterned portion and the second patterned portion;

d) a patterned spacer layer;

e) a top electrically conductive layer; and

f) an electrically-insulating top layer.

22. A method for the determination of an analyte in a bodily-fluid sample, the method comprising:

ascertaining whether an enzymatic reagent layer of an electrochemical-based analytical test strip has been exposed to a predetermined humidity level by measuring an electrical characteristic of the enzymatic reagent layer, the electrochemical-based analytical test strip having:

an electrically-insulating bottom layer;

a patterned electrically-conductive layer disposed on the electrically insulating bottom layer and including a first patterned portion and a second patterned portion;

an enzymatic reagent layer disposed on the first patterned portion, the second patterned portion and the electrically-insulating bottom layer such that the enzymatic reagent layer bridges the first patterned portion and the second patterned portion;

a patterned spacer layer;

a top electrically conductive layer; and

an electrically-insulating top layer;

applying the bodily-fluid sample to the electrochemical-based analytical test strip; and

determining the analyte based on an electrochemical response of the electrochemical-based analytical test strip.

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