WO2014068024A1 - Systems and methods for multiple analyte analysis - Google Patents
Systems and methods for multiple analyte analysis Download PDFInfo
- Publication number
- WO2014068024A1 WO2014068024A1 PCT/EP2013/072757 EP2013072757W WO2014068024A1 WO 2014068024 A1 WO2014068024 A1 WO 2014068024A1 EP 2013072757 W EP2013072757 W EP 2013072757W WO 2014068024 A1 WO2014068024 A1 WO 2014068024A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- concentration
- analyte
- hydroxybutyrate
- indication
- providing
- Prior art date
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- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/145—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
- A61B5/14532—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue for measuring glucose, e.g. by tissue impedance measurement
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- A61B5/145—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
- A61B5/1486—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue using enzyme electrodes, e.g. with immobilised oxidase
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/54—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving glucose or galactose
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- G01N27/00—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
- G01N27/26—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating electrochemical variables; by using electrolysis or electrophoresis
- G01N27/28—Electrolytic cell components
- G01N27/30—Electrodes, e.g. test electrodes; Half-cells
- G01N27/327—Biochemical electrodes, e.g. electrical or mechanical details for in vitro measurements
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- G01N27/26—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating electrochemical variables; by using electrolysis or electrophoresis
- G01N27/28—Electrolytic cell components
- G01N27/30—Electrodes, e.g. test electrodes; Half-cells
- G01N27/327—Biochemical electrodes, e.g. electrical or mechanical details for in vitro measurements
- G01N27/3271—Amperometric enzyme electrodes for analytes in body fluids, e.g. glucose in blood
- G01N27/3272—Test elements therefor, i.e. disposable laminated substrates with electrodes, reagent and channels
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N27/00—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
- G01N27/26—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating electrochemical variables; by using electrolysis or electrophoresis
- G01N27/28—Electrolytic cell components
- G01N27/30—Electrodes, e.g. test electrodes; Half-cells
- G01N27/327—Biochemical electrodes, e.g. electrical or mechanical details for in vitro measurements
- G01N27/3271—Amperometric enzyme electrodes for analytes in body fluids, e.g. glucose in blood
- G01N27/3273—Devices therefor, e.g. test element readers, circuitry
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N27/00—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
- G01N27/26—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating electrochemical variables; by using electrolysis or electrophoresis
- G01N27/416—Systems
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
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- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/483—Physical analysis of biological material
- G01N33/487—Physical analysis of biological material of liquid biological material
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- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
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- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/483—Physical analysis of biological material
- G01N33/487—Physical analysis of biological material of liquid biological material
- G01N33/49—Blood
- G01N33/492—Determining multiple analytes
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/66—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving blood sugars, e.g. galactose
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- G—PHYSICS
- G08—SIGNALLING
- G08C—TRANSMISSION SYSTEMS FOR MEASURED VALUES, CONTROL OR SIMILAR SIGNALS
- G08C17/00—Arrangements for transmitting signals characterised by the use of a wireless electrical link
- G08C17/02—Arrangements for transmitting signals characterised by the use of a wireless electrical link using a radio link
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- A61B2562/02—Details of sensors specially adapted for in-vivo measurements
- A61B2562/0295—Strip shaped analyte sensors for apparatus classified in A61B5/145 or A61B5/157
Definitions
- SYSTEMS AND METHODS FOR MULTIPLE ANALYTE ANALYSIS Background The use of disposable test elements has become commonplace to measure the presence and/or concentrations of selected analytes in test samples. For example, patients suffering from diabetes and similar medical conditions often engage in self-monitoring of blood glucose where the patient monitors his or her blood glucose levels. The purpose of monitoring blood-glucose levels is to determine the concentration level, and if necessary to take corrective action if the level is too high or too low in order to bring the level back within an acceptable range. In addition, blood glucose levels are determined to calculate a pre-meal insulin bolus often with the help of a bolus calculator with the goal of minimizing glucose increases from consumption of the meal.
- Glucose monitoring is a fact of everyday life for diabetic individuals, and the accuracy of such monitoring can literally mean the difference between life and death. Failure to maintain blood glucose at acceptable levels on a regular basis can result in serious diabetes-related complications, including cardiovascular disease, kidney disease, nerve damage and blindness.
- the Diabetes Control and Complications Trial was a clinical study conducted from 1983 to 1993 by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK).
- the DCCT compared intensive to conventional treatments. Patients on intensive treatment kept glucose levels as close to normal as possible with at least three insulin injections a day or an insulin pump, and frequent self-monitoring of blood glucose levels.
- Intensive treatment aimed to keep hemoglobin Ale (HbAlc), which reflects average blood glucose over a 2- to 3-month period, as close to normal as possible.
- Conventional treatment consisted of one or two insulin injections a day with once-a-day urine or blood glucose testing.
- a number of analytical instruments or biosensors such as glucose meters, are currently available that permit an individual to test the glucose level in a small sample of blood.
- Many of the meter designs currently available make use of a disposable test element which, in combination with the meter, measures the amount of glucose in the blood sample electrochemically or optically.
- the information displayed as a consequence of a successful blood glucose measurement is the respective blood glucose value, typically shown in mg/dL or mmol units, and perhaps the time and date the measurement was performed.
- This information in combination with calculation of planned or known intake of carbohydrates or planned or known activities and knowledge of other situational or individual factors, is in most cases sufficient to allow diabetics to adjust or derive their dietary intake and/or an immediate dose of insulin to inject to control blood glucose level on the short-term. Also, in case of low glucose values, diabetics can detect the need for intake of sugar to avoid hypoglycemia.
- DKA diabetic ketoacidosis
- ketone reducing treatment since symptoms related to a DKA episode may not present until the DKA episode has onset or ketone levels are otherwise undesirably high, it is generally preferred for ketone reducing treatment not to begin as a response to these symptoms.
- Prevention of DKA episodes can be achieved by measuring ketone levels and seeking medical attention if they rise above a certain concentration.
- the ADA website recommends that ketone levels should be checked every 4-6 hours when a diabetic has an illness (such as a cold or the flu), or when his or her blood glucose is more than 240 mg/dl. (See
- Urine tests can be utilized to determine ketone levels. However, for diabetics who perform multiple blood glucose tests per day, performing separate urine tests in addition to their blood glucose tests is time consuming and burdensome.
- a diabetic By having a dual test to measure glucose and ketone levels on the same test strip, a diabetic is better enabled to comply with testing recommendations and safer therapy by detecting high ketone levels early. For example, it is recommended to avoid exercise when ketone and blood glucose are high because elevated levels of these analytes may be indicative of unsatisfactory diabetes management.
- most diabetics do not have ketone tests readily available for testing, and often do not have information readily available for how to handle such situations.
- the symptoms of diabetic ketoacidosis usually evolve over about a 24 hour period, meaning useful information and instruction typically require the perspective of trending analysis.
- ketone levels are commonly determined by measuring the concentration of hydroxybutyrate, which is the predominate ketone in blood.
- Hydroxybutyrate concentrations below 0.6 mM in blood are considered normal, while hydroxybutyrate concentrations that are between 0.6 mM and 1.5 mM indicate that a problem may develop and greater than 1.5 mM indicate a risk for developing DKA. Hydroxybutyrate concentrations above 3 mM in blood are indicative of DKA and require emergency medical treatment.
- test elements suitable for detecting blood glucose and blood ketone levels Other techniques for determining ketone levels from blood involve test elements suitable for detecting blood glucose and blood ketone levels. In these current test elements however, blood glucose levels are measured more quickly than blood ketone levels such that the blood ketone test results are delayed and provided after the blood glucose test results. Alternatively, the results of both the blood glucose and blood ketone tests are not provided until the latter completion of the blood ketone test. In either case, waiting for the results of one or both tests until the blood ketone test is completed can become quite burdensome and time consuming for a diabetic who performs a relatively high magnitude of tests each day, particularly when considering that in some instances the blood ketone test can take almost twice as long to complete as the blood glucose test.
- a method includes determining concentrations of first and second analytes in a sample.
- the first and second analytes may be, for example, glucose and a ketone such as hydroxybutryate.
- ketone is understood to refer to and include ketone bodies such as hydroxybutyrate.
- an indication related to the measured concentration of hydroxybutyrate is provided in response to determining that the
- a concentration of hydroxybutyrate is above a predetermined value.
- a quantitative indication representative of the measured glucose concentration is automatically provided regardless of the value of the measured glucose concentration.
- each measured concentration of hydroxybutyrate is stored or otherwise retained regardless of whether that measured concentration is above a predetermined value in order to permit trending analysis to be conducted with respect to all measured concentrations of hydroxybutyrate.
- a system includes a meter configured to interact with a test element to assess first and second analytes in a sample. Other aspects of the subject application are directed to unique techniques for analyzing analytes in a sample. Further embodiments, forms, objects, features, advantages, aspects, and benefits shall become apparent from the description and drawings.
- a method includes providing a test element configured for analyzing first and second analytes in a sample; contacting the test element with the sample; determining concentration of the first analyte in the sample and providing an indication in response to determining the first analyte concentration is above a predetermined value; and determining concentration of the second analyte in the sample.
- the method further includes displaying information corresponding to the second analyte concentration.
- the first analyte is hydroxybutyrate and the second analyte is glucose.
- the predetermined value is 0.6 mM.
- the step of providing the indication in response to determining the first analyte concentration is above a predetermined value includes at least one of displaying the first analyte concentration, providing a warning, providing a list of actions to take in response to the first analyte concentration being above the predetermined value, and transmitting a message to at least one of a user of the test element, healthcare provider, caregiver and parent or guardian.
- providing the indication in response to determining the first analyte concentration is above the predetermined level includes transmitting a message to a mobile device or computer. In one aspect of this form, providing the indication in response to determining the first analyte concentration is above the predetermined level further includes displaying a message related to the first analyte concentration on a test meter. In another form, providing the indication in response to determining the first analyte concentration is above the predetermined level includes displaying a message related to the first analyte concentration. In one other form, providing the indication in response to determining the first analyte concentration is above the predetermined level includes changing a color or a shading of at least a portion of a display screen or textual display. In still another form, providing the indication in response to determining the first analyte concentration is above the predetermined level includes displaying an information icon on a display screen. In still another form, providing the indication in response to determining the first analyte concentration is above the predetermined level is above the
- a system includes a test element configured for analyzing first and second analytes in a sample.
- the system also includes a meter configured to interact with the test element and including a controller structured to: determine concentration of the first analyte in the sample and, if the concentration of the first analyte is above a
- the predetermined value includes at least one of outputting information corresponding to the concentration of the first analyte, providing a warning, providing a list of actions to take in response to the first analyte concentration being above the predetermined value, and transmitting information related to the concentration of the first analyte to at least one of a user of the system, healthcare provider, caregiver and parent or guardian.
- the first analyte is hydroxybutyrate and the second analyte is glucose.
- the predetermined value is in the range of 0.5 mM to 3.0 mM.
- the meter further includes a display responsive to the first signal to display the indication related to the concentration of the first analyte.
- the display is responsive to the first signal to provide an icon related to the concentration of the first analyte.
- at least a portion of the display is configured to change color or shading in response to the first signal.
- the display is configured to provide an information icon in response to the first signal.
- the display is further configured to provide a message in response to a selection of the information icon, the message including at least one of a description of the first analyte concentration, a list of actions to take in response to the first analyte concentration being above the predetermined level, and contact information of a healthcare provider.
- the meter further includes a communication module configured to transmit a message to a mobile device or computer in response to the first signal.
- the controller is further structured to provide a third signal for providing an approval indication if the concentration of the first analyte is below the predetermined value.
- a method includes performing a plurality of tests to determine concentrations of first and second analytes in a sample.
- Each of the tests includes applying the sample to a test element configured for analyzing the first and second analytes in the sample.
- the method also includes storing the first analyte concentration determined from each test performed; analyzing the stored concentrations of the first analyte to monitor for an existence of any trends in the stored concentrations, such as toward a predetermined value or upwardly increasing over time, or as between common time periods such as specific time of day, weekend trends, or after specific events like meals, exercise or illness, and any interesting rate-of-change trends suggesting concerning changes in ketone/hydroxybutyrate levels regardless of whether any such levels are measured to be above a predetermined value; and providing a first indication in response to detecting the existence of the trend.
- the rate- of-change value to trigger a trend can be a preselected value or one that can be set by a person with diabetes or health care providers within reasonable ranges.
- the method also includes providing a second indication in response to determining the first analyte concentration is above the predetermined value in any one or more of the plurality of tests.
- the method further includes automatically providing a third indication related to the concentration of the second analyte after performing each of the tests.
- the first analyte is hydroxybutyrate and the second analyte is glucose.
- the first indication includes one of a graphical illustration of the trend and an information icon.
- providing the first indication includes displaying an information icon on a meter display.
- the method further includes providing a graphical illustration of the trend in response to a selection of the information icon.
- a graphical illustration of a trend is shown automatically if the trend meets some pre-specified criteria.
- Such criteria could be for example: one or more measured values coming close to or exceeding a pre- specified hydroxybutyrate value, the max/min hydroxybutyrate level over the past days/weeks/months is greater than a pre-specified value, or other criteria such as initiation of a "ketone watch” or measured values trending toward initiation of a "ketone watch”.
- a ketone watch may be set by the meter whenever a measured glucose value greater than or equal to a predetermined value, such as 240 mg/dL, is recorded. The ketone watch would recommend testing glucose and hydroxybutyrate every 4-6 hours as long as the glucose value exceeds the predetermined value.
- the meter may automatically display measured glucose and hydroxybutyrate levels regardless of their relationship with any pre-specified values.
- a ketone watch may also start a new trending set of data to determine if
- hydroxybutyrate levels are beginning to rise even if still below the threshold of a high hydroxybutyrate level.
- a ketone watch may also be started if the user has indicated they have an illness such as a cold or the flu.
- a method in still another embodiment, includes providing a hand held device including a display, a processor and a storage memory. The device is operative to engage one or more test elements and to determine concentration of at least first and second analytes in a fluid sample provided on the one or more test elements.
- the method also includes: using the device, recording in the storage memory the value of the determined concentration of each of the at least first and second analytes; using the device, determining whether the determined concentration for the first analyte is above a first predetermined value; using the device, determining whether the determined concentration for the second analyte is above a second predetermined value; and using the device, activating a watch mode when the determined concentration for either of the first and second analytes is above the respective first and second predetermined values.
- the storage memory includes a plurality of recorded values of determined concentrations for each of the first and second analytes
- the method further includes: selecting at least one of the first and second analytes for monitoring trending information; using the device, determining whether the trending information for the analyte selected for monitoring generally matches predetermined criteria for recommending an increased frequency for determining the concentration for the analyte selected; and using the device, activating the watch mode regardless of the determined concentration for either of the first and second analytes being above the respective first and second predetermined values when the trending information generally matches the predetermined criteria.
- the first analyte is hydroxybutyrate and the second analyte is glucose
- the analyte selected for monitoring comprises hydroxybutyrate.
- the watch mode comprises the device providing at least one recommendation for an increased frequency for determining the concentration for at least one of the first and second analytes.
- the method further includes, when the watch mode is activated, displaying a visual indication on the display, the visual indication configured to indicate the activation of the watch mode.
- the first analyte is hydroxybutyrate and the second analyte is glucose.
- one or more of the embodiments described above may involve a test element that includes a first coenzyme-dependent enzyme or a substrate for the first enzyme and a second coenzyme-dependent enzyme or a substrate for the second enzyme.
- the test element also includes a coenzyme selected from the group consisting of thio-NAD, thio-NADP, and a compound according to formula (I):
- A adenine or an analog thereof
- T in each case independently denotes O or S,
- U in each case independently denotes OH, SH, BH 3 , or BCNH 2 ,
- V in each case independently denotes OH or a phosphate group
- W COOR, CON(R) 2 , COR, or CSN(R) 2 in which R in each case independently denotes H or Ci-C 2 -alkyl,
- Z a residue comprising a cyclic group with 5 C atoms which optionally contains a heteroatom selected from O, S and N and optionally one or more substituents, and a residue CR4 2 wherein CR4 2 is bound to the cyclic group and to X 2 , and
- R4 in each case independently denotes H, F, CI, or CH 3 , provided that Z and the pyridine residue are not linked by a glycosidic bond,
- the first analyte is hydroxybutyrate and the first enzyme is a hydroxybutyrate dehydrogenase.
- the hydroxybutyrate dehydrogenase is 3 -hydroxybutyrate dehydrogenase.
- the second enzyme is a
- dehydrogenase selected from the group consisting of glucose dehydrogenase, lactate dehydrogenase, malate dehydrogenase, glycerol dehydrogenase, alcohol dehydrogenase, sorbitol dehydrogenase, and an amino acid dehydrogenase comprising L-amino acid dehydrogenase.
- the second analyte is glucose and the second enzyme is a glucose dehydrogenase or a glucose oxidase.
- the coenzyme is a compound according to formula (I)
- V in each case denotes OH
- R5 CR4 2
- the coenzyme is a compound according to formula (I)
- U in each case denotes OH
- V in a first case denotes OH and in a second case denotes a phosphate group
- W CON(R) 2 in which R denotes H
- R5 CR4 2
- the coenzyme is thio-NAD. In another further aspect, the coenzyme is thio-NADP.
- the test element includes a first reagent material which includes the first enzyme or the substrate for the first enzyme, and the coenzyme selected from the group consisting of thio-NAD, thio-NADP and the compound according to formula (I) or a salt or optionally a reduced form thereof.
- the test element also includes a second reagent material which includes the second enzyme or the substrate for the second enzyme, and a coenzyme selected from the group consisting of FAD, NAD, NADP and the compound according to formula (I) or a salt or optionally a reduced form thereof.
- the test element includes a test strip configured to carry the first and second reagent materials.
- the test strip includes a first electrode system associated with the first reagent material and a second electrode system associated with the second reagent material.
- the first reagent material further includes an electrochemical mediator or mediator precursor such as one of nitrosoaniline, potassium ferricyanide, a phenazine derivative, or hexaammineruthenium chloride or a combination thereof.
- Another aspect of the present application is a unique technique for measuring the presence and/or concentration of multiple analytes in test samples.
- Other aspects include unique methods, systems, devices, kits, assemblies, equipment, and/or apparatus related to analyte detection in a sample.
- FIG. 1 is a perspective view of a first embodiment test element.
- FIG. 2 is an exploded, perspective view of various features of the test element of FIG.
- FIG. 3 is an exploded, perspective view of a second embodiment test element.
- FIG. 4 is a fragmentary, sectional view of the test element of FIG. 3.
- FIG. 5 is a schematic illustration of an analytical instrument structured for use with the test element of FIG. 1.
- FIGS. 6A-6B are schematic illustrations of one non- limiting display configuration for the analytical instrument.
- FIGS. 7A-7B are schematic illustrations of another non-limiting display configuration for the analytical instrument.
- FIG. 8 is a schematic illustration of yet another non-limiting display configuration for the analytical instrument.
- FIG. 9 is a schematic illustration of the analytical instrument communicating with other devices.
- FIGS. 10A-E are schematic illustrations of another display configuration for the analytical instrument.
- a method includes determining concentrations of first and second analytes in a sample.
- the first and second analytes may be, for example, glucose and hydroxybutyrate.
- an indication related to the measured concentration of hydroxybutyrate is provided in response to determining that the concentration of hydroxybutyrate is above a predetermined value.
- a quantitative indication representative of the measured glucose concentration is automatically provided regardless of the value of the measured glucose concentration.
- a system includes a meter configured to interact with a test element to assess first and second analytes in a sample. This assessment may range from detecting the presence of the first and second analytes to determining the concentration of the first and second analytes. Further aspects and features of the present application are described with respect to the illustrated embodiments as follows.
- Test element 10 is provided as an electrochemical sensor including a sample-receiving chamber for the sample fluid, and first and second reagent materials for producing electrochemical signals in the presence of the first and second analytes.
- test element 10 extends between a meter insertion end 12 and a dosing end 14.
- the shape of dosing end 14 may be distinguishable from meter insertion end 12 so as to aid users in proper handling and use of test element 10.
- Test element 10 may also include one or more graphics (not shown) to provide a user guidance on proper handling and use.
- Test element 10 is provided in the form of a disposable test strip which has a laminar construction including a base substrate 16, a spacing layer 18, a body cover 20 and a chamber cover 22. Further details of test elements including a similar laminar construction are provided in U.S. Patent No. 7,727,467, the contents of which are incorporated herein by reference in their entirety.
- Spacing layer 18 includes a void portion 24 to provide a sample- receiving chamber 26 extending between base substrate 16 and body cover 20 and chamber cover 22. In this configuration, sample-receiving chamber 26 opens at dosing end 14 of test element 10 through an opening 28 which is configured to facilitate passage of a sample fluid into sample-receiving chamber 26.
- sample-receiving chamber 26 opens through an opening positioned along a side of test element 10 are also contemplated. Further, forms in which the sample-receiving chamber 26 opens through an opening positioned along the full length or width of the dosing end 14 and including a portion of the sides are also contemplated.
- Slot 30 is located at a position relative to sample- receiving chamber 26 that is interior of the location of the electrode systems (described below) positioned in sample-receiving chamber 26. Sample fluid entering sample-receiving chamber 26 will progress as far as the vent opening, but no further. When viewed from the top, the slot provides a visual indication of a "fill-line" to confirm that the electrode systems in sample-receiving chamber 26 have been properly wetted or covered to function properly.
- dose sufficiency electrodes may also be positioned adjacent slot 30 to detect when the sample fluid has progressed to slot 30 to assure that wetting of the measuring electrodes has occurred.
- Other alternative configurations of test strip architectures are also anticipated that would include the required electrodes for two assays and the application of a sample with means for venting.
- the alternative architectures may include additional features such as means for detecting sample sufficiency or other electrodes for corrections or failsafes.
- sample-receiving chamber 26 may be empty or may alternatively include a sorbent material. Suitable sorbent materials include polyester, nylon, cellulose, and cellulose derivatives such as nitrocellulose. When included, a sorbent material helps facilitate uptake of the sample fluid by assisting in wicking the fluid into sample-receiving chamber 26. The use of a sorbent material would also serve to further reduce the void volume of sample-receiving chamber 26 for reception of the sample fluid. In one form, the filling of sample-receiving chamber 26 occurs by capillary action.
- sample-receiving chamber 26 can also be augmented by other means, such as by applying a pressure on the sample fluid to push it into sample -receiving chamber 26, and/or creating a vacuum on sample-receiving chamber 26 to pull the sample fluid into sample -receiving chamber 26.
- one or more surfaces of sample-receiving chamber 26 can be formed from a hydrophilic material, provided with a coating of a hydrophilic material, or subjected to a hydrophilicity increasing treatment in order to facilitate filling of sample-receiving chamber 26 with the test sample.
- Test element 10 is configured to detect the presence of, and/or measure the concentration of, first and second analytes by way of electrochemical oxidation and reduction reactions. These reactions are transduced to an electrical signal that can be correlated to an amount or concentration of the analyte.
- substrate 16 carries a first electrode system 32 that includes a plurality of electrodes 34 and electrode traces 36 terminating in contact pads 38. Electrodes 34 are defined as those portions of electrode traces 36 that are positioned within sample- receiving chamber 26.
- Substrate 16 also carries a second electrode system 46 that includes a plurality of electrodes 48 and electrode traces 50 terminating in contact pads 52.
- Electrodes 48 are defined as those portions of electrode traces 50 that are positioned within sample- receiving chamber 26. It should be understood that the illustrated configurations of electrode systems 32, 46 are not limiting, and that alternative configurations are contemplated.
- Test element 10 also includes a first reagent material 60 which overlies at least a portion of electrodes 34 of first electrode system 32 within sample-receiving chamber 26, and a second reagent material 62 which overlies at least a portion of electrodes 48 of second electrode system 46 within sample-receiving chamber 26.
- First and second reagent materials 60, 62 are suitable for producing electrochemical signals in the presence of respective first and second test analytes, and are disposed within sample-receiving chamber 26 in position to provide the electrochemical signal to electrodes 34, 48 in sample-receiving chamber 26.
- a space 64 extends between first and second reagent materials 60, 62, although forms in which space 64 is absent and first and second reagent materials form a continuous layer over electrodes 34, 48 are also contemplated. Further details regarding first and second reagent materials 60, 62 will be provided herein below.
- Electrodes 34 of first electrode system 32 include a set of measuring electrodes in the form of working electrode 40 and counter electrode 42 which includes portions 44a and 44b spaced on opposite sides of working electrode 40.
- a "working electrode” is an electrode at which an analyte is electrooxidized or electroreduced with or without the agency of a redox mediator
- counter electrode refers to an electrode that is paired with the working electrode and through which passes an electrochemical current equal in magnitude and opposite in sign to the current passed through the working electrode.
- counter electrode is meant to include counter electrodes which also function as reference electrodes (i.e., counter/reference electrodes).
- Electrodes 48 of second electrode system 46 include a set of measuring electrodes in the form of working electrode 54 and counter electrode 56 which includes portions 58a and 58b spaced on opposite sides of working electrode 54.
- sample-receiving chamber 26 is configured such that sample fluid entering sample-receiving chamber 26 is placed in electrolytic contact with working electrodes 40 and 54 and counter electrodes 42 and 56. This arrangement also allows electrical current to flow between the measuring electrodes to affect the
- test element 110 for assessing first and second analytes in a sample is illustrated in FIGS. 3 and 4.
- Test element 110 is produced utilizing a head to head manufacturing technique. Further details of this technique, and of test element 110 generally, are found in International Patent Publication No. WO 2012/003306, the contents of which are incorporated herein by reference in their entirety.
- electrode patterns 112 are arranged in two columns (one set of electrode patterns in column A and one set in column B) on an elongated layer (tape) of a substrate 114.
- Test element 110 also includes sample chamber electrode patterns 1 16 located near each other and near the center of substrate 114 and contact pads 118 spaced apart from one another and located near the opposite edges of substrate 114.
- the electrode patterns are all similar; however in alternative forms at least some of the electrode patterns may be different from other electrode patterns.
- a first reagent material 120 is applied over the sample chamber electrodes 116 in column A and a second reagent material 122 is applied over the sample chamber electrodes 116 in column B.
- a spacer layer 124 is attached to the top of substrate 114 with an adhesive layer 126.
- one elongated strip or tape forms spacer layer 124 to cover the electrode patterns of both columns A and B, although forms in which two separate strips of spacer layer 124 are individually attached to substrate 114 in column A and column B and aligned along centerline 128 are also possible.
- Spacer layer 124 includes a plurality of cutout portions 130 arranged along centerline 128. When spacer layer 124 is assembled with substrate 114, cutout portions 130 will form the perimeters of sample chambers 132 (FIG. 4).
- a single, continuous upper substrate layer 134 is attached to the top of spacer layer 124 with an adhesive layer 136 and includes a plurality of vent openings 142, 144 to facilitate venting of sample chambers 132 as they are filled with a sample fluid.
- adhesive layers 126, 136 include a plurality of cutout portions 138, 140, respectively, arranged along centerline 128 and corresponding to cutout portions 130 of spacer layer 124.
- adhesive layer 136 may be a solid layer without any openings or cutouts.
- test strips in column A are not fully separated from the test strips in column B, and test strip pairs are formed with each pair of test strips arranged in a head-to-head manner.
- Each test strip pair may be folded to place contact pads 118 of the test strip from column A adjacent contact pads 118 of the test strip from column B, and to place the sampling end of the test strip from column A adjacent to and facing the same direction as the sampling end of the test strip from column B.
- a dual-use biosensor is provided in which a user can apply a sample of bodily fluid to both test strips simultaneously in order to test for first and second different analytes using a single sample.
- a blood filtering media may be provided within dual sample chambers 132 prior to folding the pair together in order to prevent blood and reagent mixing between chambers 132.
- one of the substrate layers e.g. top layer 134
- the substrate 114 is either unmodified or modified to predictably bend about centerline 128.
- one of the substrate layers is modified, such as through perforations or partial cutting to be easily separated by the user along centerline 128 while the other substrate is modified, such as by scoring, denting or crimping, to predictably bend or separate about a straight line, for example, centerline 128.
- both top layer 134 and lower substrate 114 are modified to allow the head-to-head test strips to be folded in either direction, i.e., the user may choose to bend the head-to-head pair of test strips to have top layers 134 of the two test strips positioned adjacent one another or to have substrates 114 of the two test strips positioned adjacent one another.
- Substrates 16, 114 may be formed of an insulating material on which electrode systems 32, 46 and electrode patterns 112, respectively, are positioned.
- plastics such as vinyl polymers, polyimides, polyesters, and styrenes provide the electrical and structural properties which are required.
- the material for substrates 16, 114 can be selected as a flexible polymeric material such as polyester, including high temperature polyester materials; polyethylene naphthalate (PEN); and polyimide, or mixtures of two or more of these.
- Polyimides are available commercially, for example under the trade name Kapton®, from E.I. duPont de Nemours and Company of Wilmington, Del. (duPont).
- Kapton® from E.I. duPont de Nemours and Company of Wilmington, Del.
- One specific material possible for substrates 16, 114 is MELINEX® 329 available from duPont.
- the working and counter electrodes, and the remaining portions of the electrode systems 32, 46 and electrode patterns 112 may be formed from a variety of materials.
- the electrodes should have a relatively low electrical resistance and should be electrochemically inert over the operating range of the test elements.
- Suitable conductors for the working electrode include gold, palladium, platinum, carbon, titanium, ruthenium dioxide, and indium tin oxide, and iridium, as well as others.
- the counter electrode may be made of the same or different materials, e.g., silver/silver chloride. In one specific embodiment, the working and counter electrodes are both gold electrodes.
- Electrode systems 32, 46 and electrode patterns 1 12 may be applied to substrates 16, 114, respectively, in any fashion that yields electrodes of adequate conductivity and integrity. Exemplary processes include sputtering and printing, just to provide a few non-limiting possibilities.
- gold electrodes are provided by coating the materials of substrates 16, 114 and then removing selected portions of the coating to yield the electrode systems 32, 46 and electrode patterns 112.
- One particular method for removing portions of the coating include laser ablation, and more particularly broad field laser ablation, as disclosed in U.S. Patent No. 7,073,246, the contents of which are incorporated herein by reference in their entirety.
- Laser ablative techniques typically include ablating a single metallic layer or a multilayer composition that includes an insulating material and a conductive material, e.g., a metallic-laminate of a metal layer coated on or laminated to an insulating material.
- the metallic layer may contain pure metals, alloys, or other materials, which are metallic conductors.
- metals or metallic-like conductors include: aluminum, carbon (such as graphite), cobalt, copper, gallium, gold, indium, nickel, palladium, platinum, silver, titanium, mixtures thereof, and alloys or solid solutions of these materials.
- the materials are selected to be essentially unreactive to biological systems, non-limiting examples of which include gold, platinum, palladium, carbon and iridium tin oxide.
- the metallic layer may be any desired thickness which, in one particular form, is about 500 nm.
- a dual function test element may include a sandwich-type of configuration where a first substrate that carries a first electrode system is positioned over a second substrate that carries a second electrode system.
- the first and second substrates are spaced apart from one another by an intermediate layer that includes a capillary channel or a capillary channel is otherwise formed between the first and second substrates.
- sample fluid that enters into the capillary channel is directed toward the first and second electrode systems such that simultaneous or near simultaneous covering of the first and second electrode systems occurs.
- the first substrate is provided with a first reagent material suited for determination of a first analyte and that the second substrate is provided with a second reagent material suited for determination of a second analyte.
- one technique for producing test elements having this configuration involves separately producing the first substrate carrying the first reagent material and the first electrode system and the second substrate carrying the second reagent material and the second electrode system and then assembling the first and second substrates together.
- a dual function test element may include a slightly different sandwich-type of configuration. In this configuration, a first substrate that carries a first electrode system is positioned over a second substrate that carries a second electrode system.
- the first and second substrates are joined by an adhesive layer and each includes a separate sample chamber positioned over its respective electrode system in lieu of a single capillary channel.
- the test element includes a configuration that facilitates simultaneous or near simultaneous filling of the individual sample chambers such that simultaneous or near simultaneous covering of the first and second electrode systems also occurs.
- the first substrate is provided with a first reagent material suited for determination of a first analyte and that the second substrate is provided with a second reagent material suited for determination of a second analyte.
- This test element may also be produced utilizing the technique discussed above in connection with the other sandwich-type of configuration described herein. Further details of one non-limiting test element having this form are provided in International Patent Publication No. WO 2012/003306 (incorporated herein above).
- test elements 10, 110 may be useful for the determination of a wide variety of first and second analytes from a biological fluid.
- test elements 10, 110 may be readily adapted for use with reagent materials 60, 62 and 120, 122 having any suitable chemistry that can be used to assess the presence and/or concentration of the first and second analytes.
- Reagent materials 60, 62 and 120, 122 are operable for reacting with the first and second analytes to produce the electrochemical signals that represent the presence and/or concentration of the first and second analytes in the sample fluid.
- reagent materials 60, 62 and 120, 122 can include a variety of active components selected to determine the presence and/or concentration of various first and second analytes.
- the test chemistries of reagent materials 60, 62 and 120, 122 are therefore selected in respect to the first and second analytes to be assessed.
- Such analytes may include, for example, glucose, cholesterol, HDL cholesterol, triglycerides, glycerine, lactates, lactate dehydrogenase, malates, alcohol, uric acid, sorbitol, amino acids, 1,5-anhydroglucitol and analytes representative of ketone bodies, such as hydroxybutyrate.
- test elements 10, 110 include reagent materials 60, 62 and 120, 122, respectively, which are selected to determine the presence and/or concentration of
- Non-limiting examples of biological fluids in which the first and second analytes can be assessed include any bodily fluid in which the analytes can be measured, such as interstitial fluid, tears, urine, and blood.
- blood in the context of this document includes whole blood and its cell-free components, namely plasma and serum.
- the sample fluid may specifically include, for example, fresh capillary blood obtained from the finger tip or approved alternate sites (e.g., forearm, palm, ear lobe, upper arm, calf and thigh), fresh venous blood or urine.
- the test elements may also be useful in connection with control fluids that are used in conventional fashion to verify the integrity of the system for testing.
- the bodily fluid containing the analyte to be assessed may be acquired and delivered to the test elements in any fashion.
- a blood sample may be obtained in conventional fashion by incising the skin, such as with a lancet, and then contacting the test element with fluid that appears at the skin surface.
- the test elements are operable for assessing the targeted analyte while only using very small fluid samples.
- Reagent materials 60, 120 include a first coenzyme-dependent enzyme or a substrate for the first enzyme and a suitable coenzyme. These components are typically dissolved or suspended in a matrix. The liquid test sample hydrates or dissolves the matrix, and the first analyte diffuses through the matrix to react with one or more of the active components.
- Suitable enzymes that could be included in reagent materials 60, 120 are for example dehydrogenases selected from glucose dehydrogenase (E.C.
- HBDH HBDH
- 3-hydroxybutyrate dehydrogenase or beta-hydroxybutyrate dehydrogenase alpha-hydroxybutyrate dehydrogenase and gamma-hydroxybutyrate dehydrogenase
- sorbitol dehydrogenase amino acid dehydrogenase e.g. L-amino acid dehydrogenase
- oxidases such as glucose oxidase (E.C.1.1.3.4) or cholesterol oxidase (E.C.1.1.3.6) or aminotransferases such as aspartate or alanine
- potential coenzymes suitable for use in reagent materials 60, 120 include FAD, NAD, NADP, thio-NAD, thio-NADP, and a compound according to formula (I)
- A adenine or an analog thereof
- T in each case independently denotes O or S,
- U in each case independently denotes OH, SH, BH 3 , or BCNH 2 ,
- V in each case independently denotes OH or a phosphate group
- W COOR, CON(R) 2 , COR, or CSN(R) 2 in which R in each case independently denotes H or Ci-C 2 -alkyl,
- Xi, X 2 in each case independently denote O, CH 2 , CHCH 3 , C(CH 3 ) 2 , NH, or NCH 3
- Y NH, S, O, or CH 2
- Z a residue comprising a cyclic group with 5 C atoms which optionally contains a heteroatom selected from O, S and N and optionally one or more substituents, and a residue CR4 2 wherein CR4 2 is bound to the cyclic group and to X 2
- Xi, X 2 in each case independently denote O, CH 2 , CHCH 3 , C(CH 3 ) 2 , NH, or NCH 3
- Y NH, S, O, or CH 2
- Z a residue comprising a cyclic group with 5 C atoms which optionally contains a heteroatom selected from O, S and N and optionally one or more substituents, and a residue CR4 2 wherein CR4 2 is bound to the cyclic group and to X 2
- R4 in each case independently denotes H, F, CI, or CH 3 , provided that Z and the pyridine residue are not linked by a glycosidic bond,
- W CONH 2 or COCH 3 .
- substituents on Z are selected from the group consisting of OH, F, CI, and Ci-C 2 alky which are optionally fluorinated or chlorinated and/or OH-substituted, O— Ci-C 2 - alkyl.
- a first residue V is OH and a second residue V is a phosphate group.
- the one OH group and the one phosphate group can form a ring together with the carbon atoms to which they are bound.
- Non-limiting examples of adenine analogues include Cg-substituted and N 6 - substituted adenine, deaza variants such as 7-deaza aza variants such as 8-aza or
- the compounds contain adenosine analogues which contain for example 2-methoxydeoxyribose, 2'-fluorodeoxy-ribose, hexitol, altritol or polycyclic analogues such as bicyclic, LNA and tricyclic sugars instead of ribose.
- R5 CR4 2
- carba-NAD has the following structure:
- R5 CR4 2
- carba-NADP has the following structure:
- reagent materials 60, 120 are operable to facilitate detection of the presence and/or concentration of hydroxybutyrate and include a hydroxybutyrate dehydrogenase.
- hydroxybutyrate dehydrogenase include alpha- hydroxybutyrate dehydrogenase, beta or 3 -hydroxybutyrate dehydrogenase, and gamma- hydroxybutyrate dehydrogenase.
- the hydroxybutyrate dehydrogenase is 3 -hydroxybutyrate dehydrogenase.
- reagent materials 60, 120 further include a coenzyme selected from thio-NAD, thio-NADP, and a compound according to formula (I) or a salt or optionally a reduced form thereof.
- reagent materials 60, 120 include 3 -hydroxybutyrate dehydrogenase and one of carbaNAD and carbaNADP.
- the first reagent material includes a hydroxybutyrate dehydrogenase and a coenzyme selected from thio-NAD, thio-NADP, and a compound according to formula (I) or a salt or optionally a reduced form thereof, it has been surprisingly discovered that detection of the presence and/or concentration of
- hydroxybutyrate can be completed in or about five seconds after the test element has been contacted with the sample, which generally corresponds to state of the art glucose testing which takes about five seconds. Further details in this regard and in connection with preparation of related reagent materials are provided in a U.S. Patent Application filed on the same date herewith, entitled “Reagent Materials and Associated Test Elements” and having Serial No. 13/667,057, the contents of which are incorporated herein by reference in their entirety. It should be understood that the use of reagent materials that require more than five seconds to complete detection of the presence and/or concentration of hydroxybutyrate are also suitable for use in test elements of the subject application.
- reagent material does not require any additional enzymes, such as diaphorase, to be operable for the detection of presence and/or concentration of hydroxybutyrate in forms where it includes a hydroxybutyrate dehydrogenase and a coenzyme selected from thio-NAD, thio-NADP, and a compound according to formula (I) or a salt or optionally a reduced form thereof.
- additional enzymes such as diaphorase
- the first reagent material may also include a mediator.
- the mediator can be selected as any chemical species (generally electroactive) which can participate in a reaction scheme involving the enzyme, the first analyte, and the coenzyme, and reaction products thereof, to produce a detectable electroactive reaction product.
- participation of the mediator in the reaction involves a change in its oxidation state (e.g., a reduction), upon interaction with any one of the first analyte, the enzyme, or the coenzyme, or a species that is a reaction product of one of these (e.g., a coenzyme reacted to a different oxidation state).
- a variety of mediators exhibit suitable electrochemical behavior.
- a mediator can preferably also be stable in its oxidized form, may optionally exhibit reversible redox electrochemistry, can preferably exhibit good solubility in aqueous solutions, and preferably reacts rapidly to produce an electroactive reaction product.
- mediators include benzoquinone, meldola blue, transition metal complexes such as potassium ferricyanide and osmium derivatives (see International Patent Publication No. WO 98/35225), a phenazine derivative, and
- the first reagent material may also include a nitrosoaniline-based compound that acts as a mediator precursor (see e.g. U.S. Patent No. 5,286,362).
- the nitrosoaniline- based mediator precursor breaks down into reversible mediator components when it contacts an analyte sample such as blood.
- mediators and nitrosoaniline-based mediator precursors include N-(2-hydroxyethyl)-N'-p-nitrosophenyl-piperazine, N,N-bis-(2-hydroxyethyl)-p- nitrosoaniline, o-methoxy-[N,N-bis-(2-hydroxyethyl)]-p-nitrosoaniline, p- hydroxynitrosobenzene, N-methyl-N'-(4-nitrosophenyl)-piperazine, p-quinone dioxime, N,N- dimethyl-p-nitrosoaniline, N,N-diethyl-p-nitrosoaniline, N-(4-nitrosophenyl)-morpholine, N- benzyl-N-(5 '-carboxypentyl)-p-nitrosoaniline, N,N-dimethyl-4-nitroso- 1 -naphthylamine, N,N,3
- Reagent materials 62, 122 include a second coenzyme-dependent enzyme or a substrate for the second enzyme and a suitable coenzyme. These components are typically dissolved or suspended in a matrix. The liquid test sample hydrates or dissolves the matrix, and the analyte diffuses through the matrix to react with one or more of the active components.
- Suitable enzymes that could be included in reagent materials 62, 122 are for example dehydrogenases selected from glucose dehydrogenase (E.C.1.1.1.47), lactate dehydrogenase (E.C.1.1.1.27, 1.1.1.28), malate dehydrogenase (E.C.1.1.1.37), glycerol dehydrogenase (E.C.1.1,1.6), alcohol dehydrogenase(E.C.1.1.1.1), hydroxybutyrate dehydrogenase (HBDH), such as 3-hydroxybutyrate dehydrogenase or beta-hydroxybutyrate dehydrogenase, alpha-hydroxybutyrate dehydrogenase and gamma-hydroxybutyrate dehydrogenase, sorbitol dehydrogenase, and amino acid dehydrogenase e.g.
- dehydrogenases selected from glucose dehydrogenase (E.C.1.1.1.47), lactate dehydrogenase
- L-amino acid dehydrogenase (E.C.1.4.1.5).
- oxidases such as glucose oxidase (E.C.1.1.3.4) or cholesterol oxidase (E.C.1.1.3.6) or aminotransferases such as aspartate or alanine aminotransferase, 5 '-nucleotidase or creatine kinase.
- potential coenzymes suitable for use in reagent materials 62, 122 include FAD, NAD, NADP, thio-NAD, thio-NADP, and a compound according to formula (I) or a salt or optionally a reduced form thereof.
- reagent materials 60, 120 are operable to facilitate detection of the presence and/or concentration of hydroxybutyrate
- reagent materials 62, 122 are operable to facilitate detection of the presence and/or concentration of glucose and include an enzyme for glucose.
- the enzyme is a glucose
- reagent materials 62, 122 further include a coenzyme selected from FAD, NAD, NADP and the compound according to formula (I) or a salt or optionally a reduced form thereof.
- a coenzyme selected from FAD, NAD, NADP and the compound according to formula (I) or a salt or optionally a reduced form thereof.
- forms in which reagent materials 60 and 62 have a common coenzyme, e.g., a compound according to formula (I) or a salt or optionally a reduced form thereof, and are merged together to form a single reagent layer such that space 64 therebetween is eliminated are contemplated.
- the reagent materials described herein for detecting the presence and/or concentration of glucose are not limiting, and that other forms for the same are known in the art.
- the second reagent material may also include a mediator.
- the mediator can be selected as any chemical species
- mediator (generally electroactive) which can participate in a reaction scheme involving the second enzyme, the second analyte, and the coenzyme, and reaction products thereof, to produce a detectable electroactive reaction product.
- participation of the mediator in the reaction involves a change in its oxidation state (e.g., a reduction), upon interaction with any one of the second analyte, the second enzyme, or the coenzyme, or a species that is a reaction product of one of these (e.g., a coenzyme reacted to a different oxidation state).
- mediators exhibit suitable electrochemical behavior.
- a mediator can preferably also be stable in its oxidized form, may optionally exhibit reversible redox electrochemistry, can preferably exhibit good solubility in aqueous solutions, and preferably reacts rapidly to produce an electroactive reaction product.
- mediators include benzoquinone, meldola blue, transition metal complexes such as potassium ferricyanide and osmium derivatives (see International Patent Publication No. WO 98/35225), a phenazine derivative, and
- the second reagent material may also include a nitrosoaniline-based compound that acts as a mediator precursor (see e.g. U.S. Patent No. 5,286,362).
- the nitrosoaniline- based mediator precursor breaks down into reversible mediator components when it contacts an analyte sample such as blood.
- mediators and nitrosoaniline-based mediator precursors include N-(2-hydroxyethyl)-N'-p-nitrosophenyl-piperazine, N,N-bis-(2-hydroxyethyl)-p- nitrosoaniline, o-methoxy-[N,N-bis-(2-hydroxyethyl)]-p-nitrosoaniline, p- hydroxynitrosobenzene, N-methyl-N'-(4-nitrosophenyl)-piperazine, p-quinone dioxime, N,N- dimethyl-p-nitrosoaniline, N,N-diethyl-p-nitrosoaniline, N-(4-nitrosophenyl)-morpholine, N- benzyl-N-(5 '-carboxypentyl)-p-nitrosoaniline, N,N-dimethyl-4-nitroso- 1 -naphthylamine, N,N,3
- the reagent materials may also include a variety of adjuvants to enhance various properties or characteristics thereof. See e.g., U.S. Patent No. 7,749,437 referred to hereinabove.
- reagent materials 60, 62 and 120, 122 may include materials to facilitate their placement onto respective substrates 16, 114 and to improve their adherence thereto, or for increasing the rate of hydration of the reagent materials by the sample fluid.
- the reagent materials can include components selected to enhance the physical properties of the resulting dried reagent layer, and the uptake of a liquid test sample for analysis.
- adjuvant materials to be used with the reagent materials include thickeners, viscosity modulators, film formers, stabilizers, buffers, detergents, gelling agents, fillers, film openers, coloring agents, and agents endowing thixotropy.
- Non-limiting examples of thickeners that may be included in the reagent materials include (1) starches, gums (e.g., pectin, guar gum, locust bean (carob seed) gum, konjac gum, xanthan gum, alginates, and agar), casein, gelatin, and phycocolloids; (2) cellulose and semisynthetic cellulose derivatives (carboxymethyl-cellulose, methyl cellulose,
- thickeners include a combination of a xanthan gum sold under the trade name Keltrol F by CP Kelco US, Inc., and carboxylmethyl cellulose sold under the trade name AQUALON® CMC 7F PH by Hercules Inc., Aqualon Division.
- Film forming and thixotropic agents that can be included in the reagent materials include polymers and silica.
- One more specific thixotropic agent includes silica sold under the trade name Kieselsaure Sipemate FK 320 DS by Degussa AG, while a more specific film forming agent includes polyvinylpyrrolidone, sold under the trademark polyvinylpyrrolidone Kollidon 25, by BASF, and polyvinyl propionate dispersion.
- Stabilizers for the enzymes in the reagent materials can be selected from sacchhrides and mono-or di-fatty acid salts. More specific stabilizers include trehalose sold under the trade name D-(+)-Trehalose dihydrate by Sigma Chemical Co. and sodium succinate.
- Non-limiting examples of detergents that can be included in the reagent materials include water-soluble soaps, as well as water-soluble synthetic surface-active compounds such as alkali, earth alkali or optionally substituted ammonium salts of higher fatty acids, e.g., oleic or stearic acid, mixtures of natural fatty acids, for example, from coconut or tallow oil, fatty sulphates, esters of sulphonic acids, salts of alkyl sulphonic acids taurine salts of fatty acids, fatty acid amides, and ester amides.
- water-soluble soaps as well as water-soluble synthetic surface-active compounds such as alkali, earth alkali or optionally substituted ammonium salts of higher fatty acids, e.g., oleic or stearic acid, mixtures of natural fatty acids, for example, from coconut or tallow oil, fatty sulphates, esters of sulphonic acids, salts of alkyl sulphonic acids
- More specific forms of detergents include an ester amide, n-octanoyl-N-methylglucamide, sold under the trade name Mega-8 by Dojindo Molecular Technologies, Inc., and a fatty acid salt, N-methyl oleyl taurate sodium salt, sold under the trade name Geropon T77 by Rhodia HPCII (Home, Personal Care and Industrial Ingredients).
- the reagent materials are formulated as a viscous solution that includes thickeners and thixotropic agents to enhance its physical properties.
- the thickeners are selected to provide a thick, liquid matrix having the remaining components homogeneously dispersed therein.
- the thickening and thixotropic agents also inhibit the liquid or semi -paste material from running or spreading over the surface of substrates 16, 114 after it has been deposited and before it dries. After the reagent materials are deposited, they quickly dry to a readily hydratable matrix.
- the first reagent material includes a hydroxybutyrate dehydrogenase and a coenzyme selected from thio-NAD, thio- NADP, and a compound according to formula (I) or a salt or optionally a reduced form thereof.
- Current state of the art for glucose testing facilitates the detection of the presence and/or concentration of glucose to be completed in or about five seconds after the test element has been contacted with the sample.
- detection of the presence and/or concentration of hydroxybutyrate and glucose can be completed within five seconds after the test element has been contacted by the sample when the test element includes a first reagent material that has a hydroxybutyrate dehydrogenase and a coenzyme selected from thio-NAD, thio-NADP, and a compound according to formula (I) or a salt or optionally a reduced form thereof, and a second reagent material that is suitable for detection of glucose and appropriately formulated.
- the timing for completing the detection of hydroxybutyrate and glucose with these test elements is also possible and dependent on, for example, the specific formulation of the reagent materials, amongst other aspects.
- the detection of hydroxybutyrate and glucose is completed within 10 seconds after the test element has been contacted by the sample.
- the detection of hydroxybutyrate and glucose is completed within 7.5 seconds after the test element has been contacted by the sample.
- the timing for completion of the hydroxybutyrate detection and the glucose detection may be different. For example, in one or more of the foregoing or other forms the hydroxybutyrate detection is completed within 4 seconds before or after completion of the glucose detection.
- the hydroxybutyrate detection is completed within 2 seconds before or after completion of the glucose detection. In still another variant, the hydroxybutyrate detection is completed at or near the same time the glucose detection is completed. It should be understood however that other variations in the timeframe for completion of hydroxybutyrate and glucose detection are contemplated.
- FIG. 5 further details of one non- limiting analytical instrument in the form of a test meter 210 suitable for use with test element 10 will be provided. While test meter 210 is described for use with test element 10, it should be understood that it could be readily altered to accommodate use with test element 110 while retaining the general operating principles discussed below.
- Test meter 210 generally includes a controller 212, memory 214 associated with controller 212, and a programmable processor 216 associated with controller 212 and connected with memory 214.
- Test meter 210 also includes a display 218 connected with processor 216 with, for example, a display driver, and operable to provide a user readable display of output from processor 216.
- Processor 216 is connected with test element port 224 and operable to process and record data in memory 214 relating to the detection of the presence and/or concentration of the first and second analytes obtained through use of test element 10.
- Test element port 224 includes connectors 226 configured to engage with contact pads 38 of first electrode system 32 and connectors 228 configured to engage with contact pads 52 of second electrode system 46.
- Test meter 210 further includes user entry means 220 connected with processor 216 and accessible by a user to provide input to processor 216 and processor 216 is further programmable to receive input commands from user entry means 220 and provide an output that responds to the input commands.
- Processor 216 is also connected with a communication module or link 222 to facilitate wireless transmissions with test meter 210.
- communication link 222 may be used to exchange messages, warnings, or other information between test meter 210 and another device or party, such as a caseworker, caregiver, parent, guardian or healthcare provider, including nurses, pharmacists, primary or secondary care physicians and emergency medical professionals, just to provide a few possibilities.
- Communication link 222 can also be utilized for downloading programming updates for test meter 210.
- communication link 222 may be configured for sending and receiving information through mobile phone standard technology, including third-generation (3G) and fourth-generation (4G) technologies, or through Bluetooth, Zigbee, Wibree, ultra-wide band (UWB), wireless local area network (WLAN), General Packet Radio Service (GPRS), Worldwide Interoperability for Microwave Access (WiMAX or WiMAN), Wireless Medical Telemetry (WMTS), Wireless Universal Serial Bus (WUSB), Global System for Mobile communications (GSM), Short Message Service (SMS) or WLAN 802.1 lx standards.
- 3G Third-generation
- 4G fourth-generation
- Controller 212 may be comprised of one or more components configured as a single unit or of multi-component form. Controller 212 may be programmable, a state logic machine or other type of dedicated hardware, or a hybrid combination of programmable and dedicated hardware. One or more components of controller 212 may be of the electronic variety defining digital circuitry, analog circuitry, or both. As an addition or alternative to electronic circuitry, controller 212 may include one or more mechanical or optical control elements.
- controller 212 includes an integrated processor 216 operatively coupled to one or more solid-state memory devices defining, at least in part, memory 214.
- memory 214 contains operating logic to be executed by processor 216 that is a microprocessor and is arranged for reading and writing of data in memory 214 in accordance with one or more routines of a program executed by microprocessor 216.
- Memory 214 may include one or more types of solid-state electronic memory and additionally or alternatively may include the magnetic or optical variety.
- memory 214 may include solid-state electronic Random Access Memory (RAM),
- SAM Sequentially Accessible Memory
- FIFO First-In, First-Out
- LIFO Last-In First-Out
- PROM Programmable Read Only Memory
- EPROM Electrically Programmable Read Only Memory
- EEPROM Electrically Erasable Programmable Read Only Memory
- memory 214 may be volatile, nonvolatile or a hybrid combination of volatile and nonvolatile varieties. Some or all of memory 214 can be of a portable type, such as a disk, tape, memory stick, cartridge, code chip or the like. Memory 214 can be at least partially integrated with processor 216 and/or may be in the form of one or more components or units.
- test meter 210 may utilize a removable memory key that is pluggable into a socket or other receiving means (not shown), and which communicates with the memory or controller of the meter 210 to provide information relating to calibration codes, measurement methods, measurement techniques, and information management.
- removable memory keys are disclosed in U.S. Pat. Nos. 5,366,609 and 5,053,199, the disclosures of which are incorporated herein by reference in their entireties.
- Controller 212 may also include signal conditioners, filters, limiters, Analog-to-
- Entry means 220 may be defined by a plurality of push-button input devices, although entry means 220 may include one or more other types of input devices like a keyboard, mouse or other pointing device, touch screen, touch pad, roller ball, or a voice recognition input subsystem.
- Display 218 may include one or more output means like an operator display that can be of a Cathode Ray Tube (CRT) type, Liquid Crystal Display (LCD) type, plasma type, Organic Light Emitting Diode (OLED) type, a printer, or the like.
- Other input and display means can be included such as loudspeakers, voice generators, voice and speech recognition systems, haptic displays, electronic wired or wireless communication subsystems, and the like.
- test element port 224 includes connectors 226 configured to engage with contact pads 38 of first electrode system 32 and connectors 228 configured to engage with contact pads 52 of second electrode system 46.
- the connection between test meter 210 and test element 10 is utilized to apply a potential or a series of potentials across the electrodes of first and second electrode systems 32, 46, and to subsequently receive electrochemical signals that are produced by first and second reagent materials 60, 62 in the presence of the first and second analytes and can be correlated to the concentration of the first and second analytes.
- Processor 216 is configured to evaluate the electrochemical signals in order to assess the presence and/or concentration of the first and second analytes, and the results of the same may be stored in memory 214.
- processor 216 may also be configured to assess electrochemical signals associated therewith to determine that the sample fluid has been received by the test element, and/or that the amount of sample fluid is sufficient for testing.
- processor 216 is generally configured to automatically or seamlessly produce a signal for providing an indication from meter 210 related to the presence and/or concentration of the first and second analytes after the relevant electrochemical signals have been evaluated.
- processor 216 may be configured such that test meter 210 is capable of providing the indication related to hydroxybutyrate and glucose analysis at the same time and with no or only minimal delay after the completion of either test.
- the indication provided by test meter 210 may be in the form of one or more tactile, aural and/or visual alarms, warnings, messages or other representations, just to provide a few possibilities.
- processor 216 provides a signal to which display 218 is responsive to produce an indication related to the presence and/or concentration of the first and second analytes after the relevant electrochemical signals have been evaluated.
- the indication produced by display 218 may include, for example, one or more of a quantitative indication or representation of the concentration of one or both of the first and second analytes, a qualitative indication or representation that one or both of the first and second analyte concentrations is acceptable, and a warning indication or representation that one or both of the first and second analyte concentrations is not acceptable.
- processor 216 is configured to compare the measured values for the concentrations of the first and second analytes with a predetermined value or range of values for the first and second analytes stored in memory 214 for example, and determine if the concentrations of the first and second analytes are acceptable.
- processor 216 might determine that the measured concentration of one or both of the first and second analytes is acceptable if it independently falls below a respective predetermined value or within a respective range of predetermined values, or that the concentration of one or both of the first and second analytes is unacceptable if it falls above the respective predetermined value or outside of the respective range of predetermined values. It should be understood that a single quantitative, qualitative or warning indication could be provided that covers the relevant analysis of the first and second analytes or that separate quantitative, qualitative or warning indications could be provided that independently cover the relevant analysis of the first and second analytes.
- the qualitative indication may be in the form of an icon indicative of approval, such as a check mark, relevant text, relevant emoticon (e.g., smiley face), or thumbs up, or in the form of an icon indicative of disapproval or unacceptability, such as an "X"-mark, relevant text, relevant emoticon (e.g., frown face), or thumbs down, just to provide a few non-limiting possibilities.
- the qualitative indication may involve the use of a first color, shading or design of display 218 when the concentration of the first and second analytes is acceptable and a second color, shading or design of display 218 when the concentration of one or both of the first and second analytes is unacceptable.
- the background of display 218 may be green when the concentration of the first and second analytes is acceptable and then change to red if and when the concentration of one or both of the first and second analytes is not acceptable.
- the background of display 218 may include a non-patterned configuration when the concentration of the first and second analytes is acceptable and a patterned configuration when the concentration of one or both of the first and second analytes is not acceptable.
- display 218 may include a first section associated with analysis of the first analyte and a second section associated with analysis of the second analyte.
- a color or pattern change of the background of display 218 may be associated with a single one of the first and second sections in the event only one of the first and second analyte concentrations is not acceptable.
- a color or pattern change of the background of display 218 will be associated with both of the first and second sections if the concentration of both of the first and second analytes is not acceptable.
- the first and second sections may utilize a common color or pattern change, or the color or pattern change associated with the first and second sections could be independent.
- the warning indication may be accompanied by a tactile or aural alarm and/or a notice instructing the user of test meter 210 to seek immediate medical attention and/or to take one or more actions to address the unacceptable concentration of the first and/or second analytes.
- the warning indication includes an information icon and in response to its selection by a user of test meter 210, additional information such as an explanation of the reason for the warning, contact information for one or more healthcare providers or medical professionals, and/or a list of actions that need to be taken due to the unacceptable concentration of one or both of the first and second analytes may be provided on display 218.
- additional information such as an explanation of the reason for the warning, contact information for one or more healthcare providers or medical professionals, and/or a list of actions that need to be taken due to the unacceptable concentration of one or both of the first and second analytes may be provided on display 218.
- the information icon is not provided and this additional information may be automatically provided without any specific action required of the user of test meter 210.
- test meter 210 may be configured to provide the indication related to the presence and/or concentration of the first and second analytes to another device or party via communication link 222.
- processor 216 provides a signal to which communication link 222 is responsive to transmit a message including information related to the presence and/or concentration of the first and second analytes.
- This message may be sent to one or more other devices of the user of test meter 210 and/or to one or more devices of one or more third parties, such as a healthcare provider, caregiver, parent or guardian, just to provide a few non-limiting possibilities.
- devices to which this message may be sent include PDA's, tablets, computers, pagers, and cellular and landline phones.
- the message may be sent directly to the one or more other devices of the user of test meter 210 and/or to the one or more devices of the one or more third parties, although forms in which the user of test meter 210 is first prompted to transmit the message are also envisioned.
- the message may additionally or alternatively be sent to a central computer or data processing unit which may store the message and/or transmit it on to one or more of the various devices identified above belonging to the user of test meter 210 or one or more other parties.
- the information included in the message transmitted by communication link 222 may generally correspond to the indication that is described above and produced by display 218, and likewise may include one or more of the quantitative, qualitative and warning indications related to the presence and/or concentration of one or both of the first and second analytes.
- the devices to which the message is sent by communication link 222 may be configured to display this information in a manner corresponding to that described above in connection with display 218, although forms in which this information is alternatively displayed and/or reproduced are possible. It should be understood however that the message transmitted by communication link 222 may include information in addition to or in lieu of these
- the message may include a notice that the user of test meter 210 is in need of emergency medical assistance.
- the message may also include information regarding the location and/or contact information of the user of test meter 210.
- the third party to which the message is sent may directly or indirectly contact or locate the user of test meter 210 to provide assistance as necessary.
- Communication link 222 may also be configured to receive input from one or more of the devices of the one or more third parties. Similarly, in response to receiving a message including information related to the
- processor 216 is configured to provide signals or instructions for execution of different actions or functions by test meter 210 depending on, for example, the concentration determined for the first and second analytes. For example, in one form where the first and second analytes are hydroxybutyrate and glucose, processor 216 is configured to
- Display 218 could also be responsive to this signal to further provide a qualitative or warning indication related to the glucose concentration.
- one or more other components of test meter 210 such as communication link 222, audio speakers or other output means, may be responsive to this signal to provide a quantitative or qualitative output representative of the glucose concentration.
- processor 216 is further configured to provide a signal for test meter 210 to provide quantitative, qualitative or warning information related to the measured hydroxybutyrate concentration.
- processor 216 may be responsive to this signal to provide quantitative, qualitative or warning information related to the measured hydroxybutyrate concentration.
- display 218 is responsive to the signal to produce a qualitative or warning indication related to the measured hydroxybutyrate concentration. As illustrated in FIG.
- display 218 produces a qualitative indication that includes a first background color of display 218, such as green, and relevant text 230 specifying "Ketone OK" when the measured hydroxybutyrate concentration is acceptable; e.g., it is below a predetermined value or falls within a range of predetermined values.
- display 218 produces a warning indication that involves a change in background color of display 218 from the first color to a second color such as red, and in relevant text 230 to specify "Warning High Ketone (Take Action)".
- Display 218 could also provide a quantitative representation of hydroxybutyrate concentration with the warning indication.
- FIGS. 7 A and 7B Another variation in displaying the qualitative and warning indications related to the measured hydroxybutyrate concentration is shown in FIGS. 7 A and 7B.
- display 218 includes a first section 232a associated with the quantitative representation of the glucose concentration, and a second section 232b associated with the qualitative and warning indications related to the measured hydroxybutyrate concentration.
- second section 232b of display 218 produces a qualitative indication that includes a first background color of display 218 at second section 232b, such as green, and a relevant emoticon 234a in the form of a smiley face indicating an acceptable hydroxybutyrate concentration when the hydroxybutyrate concentration is acceptable.
- second section 232b of display 218 produces a warning indication that involves a change in background color of display 218 at second section 232b from the first color to a second color such as red, and from emoticon 234a to an emoticon 234b indicative of disapproval, such as a frown face.
- Display 218 could also provide a quantitative representation of hydroxybutyrate concentration with the warning indication in this configuration.
- the qualitative and warning indications related to the measured hydroxybutyrate concentration could include an information icon that is selectable by a user of test meter 210. In response to selecting this icon, test meter 210 provides additional information related to the unacceptable hydroxybutyrate concentration, such as the contact information for one or more healthcare providers or medical professionals who should be contacted in light of the unacceptable hydroxybutyrate concentration, and/or a list of actions that need to be taken or activities to avoid in order to correct or otherwise address the unacceptable hydroxybutyrate concentration.
- processor 216 may be configured to provide a signal to which communication link 222 is responsive to transmit a message, as described above, related to the qualitative and warning indications associated with the measured hydroxybutyrate concentration.
- processor 216 is configured to automatically or seamlessly provide a signal to which one or more components of test meter 210, such as communications link 222, display 218, audio speakers or other output means, is responsive to provide a quantitative output representative of the glucose concentration
- processor 216 is further configured to produce a signal to which one or more components of test meter 210 is responsive to provide an output related to the hydroxybutyrate concentration if and only if it is not acceptable; e.g., it is above a predetermined value or falls outside a range of predetermined values.
- the concentration of hydroxybutyrate is determined for each test performed by test meter 210, but the user of test meter 210 is only bothered or burdened by indications or information related to the hydroxybutyrate concentration if there is a health concern.
- the system may record into memory or otherwise store both the glucose and hydroxybutyrate concentrations with appropriate context such as date, time, and marked notes from the user.
- meter 210 or another device may also be configured to monitor for trends in the measured analyte concentrations through review of historical data. Such monitoring may look for a variety of different trends, including for example, trends suggestive of the onset or likely onset of DKA and more subtle trends such as higher glucose and/or hydroxybutyrate levels on the weekends and better control during the week.
- this may be a lifestyle driven result and indicate that the patient does not watch or maintain his or her diabetes well during the relevant timeframe, and providing notice of the same may help a diabetic user modify their behavior during these times.
- This advanced functionality that searches or monitors for various trends could be a feature of a meter that runs automatically, by request of the patient or user, or a feature that is managed by a health care professional through data that is downloaded to an EMR.
- Such retrospective data analysis could also be run on a secondary device such as a smart phone application that receives the data from the analytical device.
- test meter 210 is configured such that display 218 includes a first section 236 where a quantitative representation of the glucose concentration is produced in response to the signal automatically provided by processor 216.
- First section 236 could also be responsive to this signal to further provide a qualitative or warning indication related to the glucose concentration.
- Display 218 also includes a second section 238 which is only provided or activated if and when the hydroxybutyrate concentration is not acceptable.
- the second section 238 provides a warning indication that includes relevant text specifying "Ketone High Alert (Take Action)".
- the warning indication of second section 238 also includes a different background color relative to that of first section 236.
- second section 238 may provide a quantitative representation of hydroxybutyrate concentration in addition to or in lieu of the warning indication if and when the hydroxybutyrate concentration is not acceptable. Still, it should be appreciated that other variations in first and second sections 236, 238 of display 218 are possible.
- second section 238 could include an information icon that is selectable by a user of test meter 210. In response to selecting this icon, test meter 210 provides additional information related to the unacceptable
- processor 216 may be configured to provide a signal to which communication link 222 is responsive to transmit a message, as described above, related to the measured hydroxybutyrate concentration when it is not acceptable. For example, in the form shown in FIG. 9, communication link 222 transmits a message related to the measured hydroxybutyrate concentration to a separate device 240 in the form of a cellular phone which may belong to the user of test meter 210 or a third party.
- Device 240 could also be of a form other than a cellular phone, including those listed above, or the message could be transmitted to a plurality of devices having a variety of forms and belonging to a variety of different parties.
- Communication link 222 also transmits the message to a central computer or data processing unit 242 that may store the message and/or transmit it on to one or more of the other various devices. It should be appreciated that forms in which communication link 222 transmits the message to a single one of device 240 and data processing unit 242 are possible.
- the illustrated form shows the message being transmitted in conjunction with the warning indication of second section 238 of display 218, forms in which the message is transmitted without production of the warning indication of second section 238 are possible.
- the information included in the message transmitted by communication link 222 may generally correspond to the information displayed by display 218. It should be understood however that the message transmitted by communication link 222 may include information in addition to or in lieu of that displayed by display 218.
- the message may include a notice that the user of test meter 210 is in need of emergency medical assistance due to the unacceptable hydroxybutyrate concentration and the possible onset of an episode of DKA.
- the message may also include information regarding the location (such as by providing GPS coordinates) and/or contact information of the user of test meter 210.
- the third party to which the message is sent may directly or indirectly contact or locate the user of test meter 210 to provide assistance as necessary.
- Communication link 222 may also be configured to receive input or instructions from one or more of the devices of the one or more third parties as discussed above.
- meter 210 may be configured to go into a "ketone watch" mode of recommending and/or prompting a user to test hydroxybutyrate every 4-6 hours. In one non-limiting form, upon initiation of and during the ketone watch, meter 210 may automatically display measured glucose and
- meter 210 also begins to monitor for further increases or other notable trends in hydroxybutyrate levels before providing further notice. In such embodiments, the
- meter 210 may be configured to monitor for specific criteria to activate a "ketone watch dog" mode in order to remind the user to perform tests at some frequency and/or at certain times to decrease the likelihood of or avoid an onset of DKA and/or to detect for the same.
- display 218 includes at least one segment in which a visual indication is provided to a user to indicate that meter 210 is in the ketone watch mode or otherwise operating as a "ketone watch dog.”
- meter 210 may also be further configured to analyze measured glucose or hydroxybutyrate concentrations to monitor for the existence of any trends.
- trends may include, without limitation, one or more of a trend moving toward a predetermined value or upwardly increasing over time toward an unacceptable level, trends between common time periods such as specific time of day, weekend trends, or after specific events like meals, exercise or illness, and any interesting rate-of-change trends suggesting concerning changes in glucose or
- test meter 210 may be configured to store the results of each hydroxybutyrate concentration test in memory 214.
- Processor 216 is structured to analyze these results by, for example, producing a graphical representation of the measured hydroxybutyrate concentrations over time and monitoring for, amongst others, a trend in the graphical representation toward an unacceptable,
- first section 236 of display 218 includes a quantitative representation of the measured glucose concentration and second section 238 of display 218 has been provided due to the observation of the upward trend in the hydroxybutyrate concentrations.
- Second section 238 includes relevant text specifying "Ketone Trend Noted”.
- It also includes an information icon 244 and an emoticon 246 in the form of a frown face indicative of the undesired trend in hydroxybutyrate concentration.
- an information icon 244 and an emoticon 246 in the form of a frown face indicative of the undesired trend in hydroxybutyrate concentration.
- information icon 244 When information icon 244 is present as illustrated in FIG. 10A, it may be selected by a user of test meter 210 to provide additional information. For example, in the illustrated form, selection of information icon 244 results in the production of a graphical display 248 which shows increasing ketone or hydroxybutyrate levels over time. Graphical display 248 may also be automatically provided in addition to or in lieu of the information of second section 238. Graphical display 248 includes ranges representative of normal and high ketone levels, although it should be appreciated that other forms for graphical display 248 are possible. Test meter 210 may also provide information in addition to or in lieu of graphical display 248, including that described above in connection with the selection of an information icon. It should also be understood that second section 238 of display 218 can include a warning indication as described above if and when any test yields an unacceptable hydroxybutyrate concentration.
- test meter 210 is additionally or alternatively configured to provide indications related to the hydroxybutyrate concentration even when the same is deemed acceptable.
- FIG. 10B graphical display 248 is illustrative of an observed trend where measured hydroxybutyrate concentrations are relatively consistent over time.
- graphical display 248 is illustrative of an observed trend where a number of spikes or increases in hydroxybutyrate concentration occur over time, while graphical display 248 in FIG. 10D is illustrative of an observed trend where measured hydroxybutyrate concentrations are moving toward an unacceptable value over time.
- graphical display 248 may provide positive reinforcement to a user of test meter 210 that their diabetes management is on an acceptable track.
- FIG. 10B In the case of FIG. 10B, graphical display 248 may provide positive reinforcement to a user of test meter 210 that their diabetes management is on an acceptable track.
- the observed increases or spikes in measured hydroxybutyrate concentrations shown in graphical display 248 may correspond to a certain event (such as a meal or exercise) or timeframe (such as the weekend) and provide notice to a user of meter 210 that a different management approach may be necessary at these times to avoid the intermittent increases.
- the consistent increase shown by graphical display 248 provides notice to a user of meter 210 that continuing along the current trajectory will result in the onset of DKA and that remedial actions must be taken to avoid the same.
- graphical display 248 shows that the upward trajectory has reached above the recommended high level at which DKA is likely imminent, and display 218 provides a clear alert warning that immediate action is required.
- meter functionality discussed in connection with FIGS. 10A-D and elsewhere is also applicable to measured glucose concentrations.
- information related to any observed trend(s) of the hydroxybutyrate or glucose concentrations could also be transmitted by communication link 222 to one or more devices belonging to the user of test meter 210 or other third parties so that appropriate actions can be taken by necessary parties to address the observed trend(s).
- processor 216 may be structured in various forms to provide signals or instructions for the execution of certain actions based on the measured
- processor 216 may be structured such that a) the output provided by test meter 210 changes from a qualitative indication of acceptability of the measured hydroxybutyrate concentration to a warning indication of unacceptability of the measured hydroxybutyrate concentration when the hydroxybutyrate concentration exceeds a predetermined value or falls outside of a
- test meter 210 only provides an output related to the measured hydroxybutyrate concentration if and only if it is above a predetermined value or falls outside a range of predetermined values and is therefore not acceptable; and/or c) test meter 210 provides an output related to the observation of an upward trend of
- the predetermined value for triggering processor 216 to provide signals or instructions for the execution of certain actions based on the measured hydroxybutyrate concentration is in the range of 0.6 mM 3.0 mM. In another aspect, the predetermined value is 0.6 mM.
- processor 216 may be structured such that a) the output provided by test meter 210 changes from a qualitative indication of acceptability to a warning indication of unacceptability of the measured hydroxybutyrate concentration when the hydroxybutyrate concentration exceeds 0.6 mM; b) test meter 210 only provides an output related to the measured hydroxybutyrate concentration if and only if it is above 0.6 mM; and/or c) test meter 210 provides an output related to the observation of an upward trend of hydroxybutyrate concentrations toward 0.6 mM.
- processor 216 may be structured to provide signals or instructions for the execution of different actions or functions based on different hydroxybutyrate concentrations.
- processor 216 may be configured to provide instructions for prompting execution of certain actions once the hydroxybutyrate concentration is at or exceeds 0.6 mM and other actions as the hydroxybutyrate concentration continues to rise above 0.6 mM. For example, when the hydroxybutyrate concentration is at or exceeds 0.6 mM but below 1.5 mM, processor 216 may be configured to provide instructions for activating, amongst other things, warning indications representative of an unacceptable ketone or hydroxybutyrate concentration.
- the actions executed in response to the instructions generated by processor 216 may also further include the transmittal of a message by communication link 222 to a caregiver, parent, guardian and/or non-emergency medical professional indicating, for example, that a risk is present for developing DKA.
- the actions executed in response to the instructions generated by processor 216 may also further include the transmittal of a message to an emergency medical professional that the user of test meter 210 requires immediate medical treatment.
- the actions executed in response to the instructions generated by processor 216 may also further include transmittal of a message to a caregiver, parent, guardian and/or non-emergency medical professional indicating that the user of test meter 210 requires immediate medical attention. It should also be understood that the values provided above for having processor 216 generate instructions for the execution of the various different actions are exemplary only, and that one or more of the above-described actions may be executed in response to different hydroxybutyrate concentrations.
- processor 216 in one embodiment is configured to cause conveyance of a message on display 218 indicating a "low" ketone level and that no action is required. In other embodiments, at such levels processor 216 causes the display to further convey the recommendation to monitor ketone change if the user is ill, and/or to perform both glucose and ketone tests every 4 hours. In another illustrative example, for hydroxybutyrate levels between 0.6 mM and 1.5 mM, processor 216 in one embodiment is configured to cause conveyance of a message on display 218 indicating a "medium" ketone level, and that a problem may be developing. In other embodiments, at such levels processor 216 causes display 218 to further convey the recommendation to consider instructions from the user's healthcare provider to notify him/her when such levels are detected. In yet another illustrative example, for
- processor 216 in one embodiment is configured to determine whether high glucose levels are also present and to cause
- processor 216 is configured to cause conveyance of a message on display 218 instructing the user to contact the healthcare provider immediately and/or to proceed to the emergency department of a clinic or hospital.
- hydroxybutyrate concentrations do not exceed 1 mM for Type I diabetic patients.
- the mean hydroxybutyrate concentration is about 7 mM but can range between 3 mM and 12 mM.
- those concentrations should be expected to fall by 1 mM per hour, otherwise the treatment is likely inadequate and insulin and fluid infusion rates should be reviewed by the healthcare provider.
- processor 216 is additionally or alternatively configured to provide instructions for executing one or more of the actions discussed above in response to determining that the hydroxybutyrate
- a method comprising:
- test element configured for analyzing first and second analytes in a sample
- the predetermined value is 0.6 mM. 5. The method of embodiment 1, wherein the step of providing the indication in response to determining the first analyte concentration is above a predetermined value includes at least one of displaying the first analyte concentration, providing a warning, providing a list of actions to take in response to the first analyte concentration being above the predetermined value, and transmitting a message to at least one of a user of the test element, healthcare provider, caregiver and parent or guardian.
- providing the indication in response to determining the first analyte concentration is above the predetermined level further includes displaying a message related to the first analyte concentration on a test meter.
- providing the indication in response to determining the first analyte concentration is above the predetermined level includes displaying a message related to the first analyte concentration.
- providing the indication in response to determining the first analyte concentration is above the predetermined level includes changing a color of at least a portion of a display screen.
- providing the indication in response to determining the first analyte concentration is above the predetermined level includes displaying an information icon on a display screen.
- the message includes at least one of a description of the first analyte concentration, a list of actions to take in response to the first analyte concentration being above the predetermined level, and contact information of a healthcare provider.
- a system comprising:
- test element configured for analyzing first and second analytes in a sample
- meter configured to interact with the test element and including a controller structured to:
- concentration of the first analyte in the sample and, if the concentration of the first analyte is above a predetermined value, provide a first signal for providing an indication related thereto; and determine concentration of the second analyte in the sample and provide a second signal for outputting information related to the concentration of the second analyte.
- the indication includes at least one of outputting information corresponding to the concentration of the first analyte, providing a warning, providing a list of actions to take in response to the first analyte concentration being above the predetermined value, and transmitting information related to the concentration of the first analyte to at least one of a user of the system, healthcare provider, caregiver and parent or guardian.
- the meter further includes a display responsive to the first signal to display the indication related to the concentration of the first analyte.
- the display is configured to provide an information icon in response to the first signal.
- the meter further includes a communication module configured to transmit a message to a mobile device or computer in response to the first signal.
- controller is further structured to provide a third signal for providing an approval indication if the concentration of the first analyte is below the predetermined value.
- a method comprising:
- each of the tests includes applying the sample to a test element configured for analyzing the first and second analytes in the sample;
- a method comprising:
- a hand held device comprising a display, a processor and a storage memory, the device being operative to engage one or more test elements and to determine
- the watch mode comprises the device providing at least one recommendation for an increased frequency for determining the concentration for at least one of the first and second analytes.
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Abstract
Description
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