KR20140105864A - Accurate analyte measurements for electrochemical test strip based on sensed physical characteristic(s) of the sample containing the analyte and derived biosensor parameters - Google Patents

Abstract

Methods of allowing for more accurate analyte concentrations with a biosensor by determining at least one physical property of a sample containing the analyte, typically a hematocrit, and deriving parameters relating to the biosensor from these characteristics to obtain an accurate glucose concentration Various embodiments are disclosed.

Description

[0001] ACCURATE ANALYTE MEASUREMENTS FOR ELECTROCHEMICAL TEST STRIP BASED ON SENSED PHYSICAL CHARACTERISTIC (S) OF [0002] METHOD FOR MEASURING ANALYZED PHYSICAL CHARACTERISTIC (S) SAMPLE CONTAINING THE ANALYTE AND DERIVED BIOSENSOR PARAMETERS}

preference

This application claims priority from U.S. Provisional Patent Application No. 61 / 581,087 (Attorney Docket No. DDI5220USPSP) filed on December 29, 2011, all of which are incorporated herein by reference. 61 / 581,089 (Attorney Docket No. DDI5220USPSP1); 61 / 581,099 (Attorney Docket No. DDI5220USPSP2); And 61 / 581,100 (Attorney Docket DDI5221 USPSP) filed on May 31, 2012, and US Patent Application No. 61 / 654,013 (Attorney Docket DDI5228 USPSP) filed May 31, 2012, ("Priority Claims") are hereby incorporated by reference in their entirety for all purposes as if fully set forth herein, as claimed in patent application PCT / GB2012 / 053276 (Attorney Docket DDI5220WOPCT) and PCT / GB2012 / 053277 (Attorney Docket DDI5228WOPCT) Are hereby incorporated by reference as if set forth.

An electrochemical glucose test strip, such as that used in the OneTouch TM Ultra (TM) whole blood test kit available from LifeScan, Inc., It is designed to measure the concentration of glucose in physiological fluid samples. Measurement of glucose can be based on the selective oxidation of glucose by the enzyme glucose oxidase (GO). The reactions that can occur in the glucose test strip are summarized below in Equations (1) and (2).

[Equation 1]

Glucose + GO _(ox) → gluconic acid + GO _(red)

&Quot; (2) "

GO _(red) + 2 Fe (CN) ₆ ^3- GO _(ox) + 2 Fe (CN) ₆ ^4-

As illustrated in equation (1), glucose is oxidized to gluconic acid by the oxidized form of glucose oxidase (GO _(ox) ). It should be noted that GO _{( ox )} may also be referred to as "oxidized enzyme ". During the reaction of equation (1 ₎ , the oxidized enzyme GO _{( ox )} is converted to its reduced state represented by GO _{( red )} (i.e., the "reduced enzyme"). Next, the reduced enzyme GO _(red) is reoxidized to GO _(ox) by reaction with Fe (CN) ₆ ^3- (referred to as oxidized mediator or ferricyanide) as illustrated in equation do. During regeneration of GO _(red) with its oxidized state GO _(ox) , Fe (CN) ₆ ^3- is reduced to Fe (CN) ₆ ^4- (referred to as reduced medium or ferrocyanide).

When the reactions described above are carried out by an inspection signal in the form of a potential applied between two electrodes, an inspection signal of the current type can be generated by the electrochemical reoxidation of the reduced medium at the electrode surface. Thus, in an ideal environment, the amount of ferrocyanide produced during the above-described chemical reaction is directly proportional to the amount of glucose in the sample located between the electrodes, so that the resulting test output signal will be proportional to the glucose content of the sample. Mediators such as ferricyanide are compounds that accept electrons from enzymes such as glucose oxidase and then donate electrons to the electrodes. As the concentration of glucose in the sample increases, the amount of reduced mediator formed also increases, thus there is a direct relationship between the glucose concentration and the test output signal resulting from the reoxidation of the reduced medium. In particular, the transfer of electrons across the electrical interface results in a flow of the test output signal (two moles of electrons per mole of glucose to be oxidized). Therefore, an inspection output signal due to the introduction of glucose can be referred to as a glucose output signal.

Electrochemical biosensors can be adversely affected by the presence of certain blood components which can have undesirable effects on the measurement and lead to inaccuracies in the detected signal. Such inaccuracies can lead to inaccurate glucose readings, for example, preventing the patient from perceiving potentially dangerous blood glucose levels. As an example, the blood hematocrit level (i.e., the percentage of blood volume occupied by erythrocytes) may have an adverse effect on the obtained analyte concentration measurements.

Fluctuations in the volume of red blood cells in the blood can lead to variations in glucose readings measured with disposable electrochemical test strips. Typically, a negative bias (i.e., a lower calculated analyte concentration) is observed at a higher hematocrit while a positive bias at a lower hematocrit (i.e., a higher calculated analyte concentration) . In high hematocrit, for example, erythrocytes can interfere with the reaction of enzymes and electrochemical mediators, reduce the rate of chemical dissolution because of the small plasma volume that solutes the chemical reactants, and slow the diffusion of the mediator. These factors can cause lower currents than anticipated glucose readings because less current is generated during the electrochemical process. Conversely, at low hematocrit, less red blood cells can affect the electrochemical reaction than expected, and a higher measured output signal can be obtained. In addition, the physiological fluid sample resistance is also a hematocrit dependency, which can affect voltage and / or current measurements.

Several methods have been used to reduce or prevent hematocrit-based fluctuations in blood glucose. For example, test strips include a variety of compounds or formulations designed to include a mesh to remove red blood cells from a sample, or designed to increase the viscosity of red blood cells and weaken the effects of low hematocrit on concentration determination . Other test strips included cytolytic agents and systems configured to determine hemoglobin concentration in an attempt to correct the hematocrit. The biosensor may also be used to measure a hematocrit by irradiating a physiological fluid sample with light and then measuring the electrical response of the fluid sample through a change in optical variation or alternating signal, It was configured to measure hematocrit. These sensors have certain disadvantages. A common technique for methods involving the detection of hematocrit is to use the measured hematocrit values to calibrate or change the measured analyte concentration, which techniques are generally described in each of the following US patents Published Application No. 2010/0283488; 2010/0206749; 2009/0236237; 2010/0276303; 2010/0206749; 2009/0223834; 2008/0083618; 2004/0079652; 2010/0283488; 2010/0206749; 2009/0194432; Or U.S. Patent Nos. 7,972,861 and 7,258,769.

Applicants have discovered that between the batch gradient and physical properties (e.g., hematocrit) to derive such a new batch gradient that can be used to determine the analyte concentration based on the derived new batch slope of the electrochemical biosensor ≪ / RTI > provided a variety of embodiments of techniques for allowing improved glucose measurements using the relationship. Advantageously, these new techniques do not rely on correction (s) or correction (s) to be made in analyte measurements, thereby improving accuracy while shortening inspection time.

In a first aspect of Applicants' invention, a method is provided for allowing a user to obtain results of analyte concentration with greater accuracy. The method includes applying a signal to a sample to determine a physical property of the sample; Introducing another signal into the sample to cause a physical conversion of the sample; Measuring at least one output signal from the sample; Obtaining an estimated analyte concentration from at least one predetermined parameter of the biosensor and at least one output signal at one time position of the plurality of predetermined time positions from the start of the test sequence; Generating a first parametric factor of the biosensor based on the physical characteristics of the sample; Calculating a first analyte concentration based on a first parameter coefficient of the biosensor and at least one output signal measured at a time position of one of a plurality of predetermined time positions from the start of the test sequence; Generating a second parameter coefficient of the biosensor based on the estimated analyte concentration and the physical characteristics of the sample; Calculating a second analyte concentration based on a second parameter coefficient of the biosensor and at least one output signal measured at a time position of one of a plurality of predetermined time positions from the start of the test sequence; Generating a third parameter coefficient of the biosensor based on the first analyte concentration and physical characteristics; Calculating a third analyte concentration based on the third parameter coefficient of the biosensor and at least one output signal measured at one time position from a plurality of predetermined time positions from the start of the test sequence; And notifying at least one of the first, second and third analyte concentrations.

In another aspect, a method is provided that allows a user to obtain results of analyte concentration with greater accuracy. The method includes initiating an analyte test sequence upon deposition of a sample; Applying a signal to the sample to determine a physical property of the sample; Introducing another signal into the sample to cause a physical conversion of the sample; Measuring at least one output signal from the sample; Deriving an estimated analyte concentration from at least one output signal measured at one time position of a plurality of predetermined time positions from the start of the test sequence; Obtaining new parameters of the biosensor based on the estimated analyte concentration and the physical characteristics of the sample; Calculating an analyte concentration based on a new parameter of the biosensor and an output signal measured at one time position or a different time position from a plurality of predetermined time positions from the start of the test sequence; And notifying the analyte concentration.

In another aspect of the present invention, a method is provided that allows a user to obtain results of analyte concentration with greater accuracy. The method includes initiating an analyte test sequence upon deposition of a sample on a biosensor; Applying a signal to the sample to determine a physical property of the sample; Introducing another signal into the sample to cause a physical conversion of the sample; Measuring at least one output signal from the sample; Generating a first new batch parameter of the biosensor based on the physical characteristics of the sample; Calculating a first analyte concentration based on a first new batch parameter of the biosensor and an output signal measured at a time position of one of a plurality of predetermined time positions from the start of the test sequence; And notifying the first analyte concentration.

In the above-described aspects of the present invention, the steps of determining, estimating, computing, computing, deriving and / or using (possibly with mathematical expressions) may be performed by an electronic circuit or processor. These steps may also be implemented as executable instructions stored on a computer readable medium; These instructions, when executed by a computer, may perform any of the methods of the methods described above.

In a further aspect of the present invention there is a computer-readable medium comprising instructions executable by the computer, when executed by a computer, to perform the steps of any of the methods described above.

In a further aspect of the present invention there is an apparatus such as a test meter or an analyte test apparatus wherein each apparatus or meter comprises an electronic circuit or processor configured to perform any of the methods of the methods described above.

These and other embodiments, features, and advantages will be apparent to those skilled in the art, when read in conjunction with the following more detailed description of an exemplary embodiment of the invention in connection with the accompanying drawings, which are briefly depicted first.

BRIEF DESCRIPTION OF THE DRAWINGS The accompanying drawings, which are incorporated in and form a part of this specification, illustrate presently preferred embodiments of the invention and, together with the general description provided and the detailed description given below, serve to explain the features of the invention , And the same reference numerals denote the same elements).
≪ 1 >
Figure 1 illustrates an analyte measurement system.
≪
2A is a diagram illustrating the components of the measuring device 200 in a simplified schematic form.
2b,
2B is a simplified schematic diagram of a preferred embodiment of a variant of the meter 200. Fig.
3A,
FIG. 3A illustrates a test strip 100 of the system of FIG. 1 with two physical property sensing electrodes upstream of the measurement electrode; FIG.
3b,
Figure 3b illustrates a variation of the test strip of Figure 3a in which a shield or ground electrode is provided proximate the entrance of the test chamber.
3C,
Figure 3c illustrates a variation of the test strip of Figure 3b, wherein the reagent region extends upstream to include at least one physical property sensing electrode.
≪
FIG. 3D illustrates a variation of the test strip 100 of FIGS. 3A, 3B and 3C in which certain elements of the test strip are integrated together into a single unit.
3b,
Fig. 3b shows the test of Fig. 3a in which one physical property sensing electrode is located close to the inlet and the other physical property sensing electrode is at the end of the inspection cell, Fig.
3C and 3D,
Figures 3c and 3d illustrate variations of Figure 3a or Figure 3b in which the physical property sensing electrodes are positioned adjacent to one another at the end of the inspection chamber, wherein the measurement electrode is upstream of the physical property sensing electrode.
3E and 3F,
Figures 3e and 3f illustrate a physical property sensing electrode arrangement similar to that of Figure 3a, Figure 3b, Figure 3c or Figure 3d with the pair of physical property sensing electrodes proximate the entrance of the inspection chamber.
4A,
Figure 4A is a graph of applied potential versus time for the test strip of Figure 1;
4 (b)
Figure 4b is a graph of output signal versus time from the test strip of Figure 1;
5,
5 is a diagram illustrating the relationship between the parameters of a biosensor and the physical properties of a fluid sample;
6,
Figure 6 is a complete system diagram of various modules implementing at least three techniques for determining analyte concentration.
7,
Figure 7 illustrates an alternative fourth technique, where Figure 7 is a template in which any of the techniques of Figure 6 may be used.
8A and 8B,
Figures 8A and 8B illustrate the accuracy of the various lots of the biosensor used in Table 5 in the known art.
9A and 9B,
Figures 9A and 9B illustrate an improvement in the accuracy of the various lots of the biosensor of Table 5 for a first novel technique.
10A and 10B,
Figures 10A and 10B illustrate an improvement in the accuracy of the various lots of the biosensor used in Table 5 for the second new technique.
11A and 11B,
Figures 11A and 11B illustrate an improvement in the accuracy of the various lots of the biosensor used in Table 5 for the third new technique.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS The following detailed description should be understood with reference to the drawings, wherein like elements are denoted by the same reference numerals in different drawings. The drawings that are not necessarily drawn to scale illustrate selected embodiments and are not intended to limit the scope of the present invention. The detailed description exemplifies the principles of the invention by way of example and not limitation. This description will clearly make apparent to those skilled in the art the manufacture and use of the invention and describes some embodiments, adaptations, variations, alternatives and uses of the present invention, including what are presently considered to be the best modes of carrying out the invention.

As used herein, the term " about "or" roughly " for any numerical value or range is intended to encompass any suitable number of elements, Indicates dimensional tolerance. More specifically, "about" or "about" may refer to a range of values of ± 10% of the values listed, for example, "about 90%" may refer to ranges of values from 81% to 99%. Also, as used herein, the terms "patient," "host," "user," and "subject" refer to any person or animal subject, While not intending to be limited for use, the use of the invention for human patients represents a preferred embodiment. As used herein, an "oscillating signal" includes voltage signal (s) or current signal (s), respectively, that change polarity, alternate the direction of current, or are multi-directional. Also as used herein, the phrase "electrical signal" or "signal" is intended to include any signal within a direct current signal, alternating current signal or electromagnetic spectrum. The terms "processor "," microprocessor ", or "microcontroller" are intended to have the same meaning and are intended to be used interchangeably. As used herein, the term "notified " and variations on its root terms indicate that the notification may be provided to the user via text, audible, visual or any combination of communication modes or media. In order to inform the user of the qualitative aspect of the results, a cover may be provided to indicate by green indicia or the like, if the result is outside the desired range, through a red indicia (or flashing message) or within range.

FIG. 1 illustrates a test meter 200 for testing an analyte (e.g., glucose) level in an individual's blood with a test strip prepared by the methods and techniques illustrated and described herein. The test meter 200 may include user interface inputs 206, 210 and 214, which may be in the form of buttons, for input of data, navigation of a menu, and execution of an instruction. The data may include a value indicative of the analyte concentration, and / or information relating to the routine lifestyle of the individual. Information related to the daily lifestyle may include an individual's food intake, drug use, occurrence of a health checkup, general health status, and exercise level. The test meter 200 may also include a display 204 that may be used to report the measured glucose level and to facilitate input of lifestyle related information.

The test meter 200 may include a first user interface input unit 206, a second user interface input unit 210, and a third user interface input unit 214. The user interface inputs 206, 210, and 214 facilitate the input and analysis of data stored in the testing device, enabling the user to navigate through the displayed user interface on the display 204. [ The user interface inputs 206, 210 and 214 include a first marking 208, a second marking 212 and a third marking 216 that help to correlate the user interface input to the character on the display 204 do.

The test meter 200 may be configured to receive a test strip 100 (or its variant in a priority application) by inserting it into the strip port connector 220, by pressing and holding the first user interface input 206 for a moment, Lt; RTI ID = 0.0 > data traffic. ≪ / RTI > The test meter 200 searches for and selects the meter off option from the main menu screen by depressing and holding the first user interface input 206 by removing the test strip 100 (or its variant in the priority application) , Or can be turned off by not pressing any buttons for a predetermined period of time. Display 104 may optionally include a backlight.

In one embodiment, the test meter 200 may be configured to not receive, for example, a calibration input from any external source when switched from a first test strip batch to a second test strip batch . Thus, in one exemplary embodiment, the meter includes a user interface (e.g., input 206, 210, 214), an embedded test strip, a separate code key or code strip, And is configured not to receive the calibration input from an external source, such as data port 218. [ Such a calibration input is not necessary if all of the test strip arrangements have substantially uniform calibration characteristics. The calibration input may be a set of values due to a particular test strip placement. For example, the calibration input may include placement slope and placement slice values for a particular test strip layout. Calibration inputs, such as placement slope and slice values, can be preset within the meter as described below.

Referring to FIG. 2A, an exemplary internal layout of the test meter 200 is shown. The test meter 200 may include a processor 300 that is a 32-bit RISC microcontroller in some embodiments described and illustrated herein. In the preferred embodiment described and illustrated herein, the processor 300 is preferably selected from the MSP 430 series of ultra low power microcontrollers manufactured by Texas Instruments, Dallas, Texas, USA. The processor may be bidirectionally connected via an I / O port 314 to a memory 302 that is an EEPROM in some embodiments described and illustrated herein. The data port 218, the user interface inputs 206, 210 and 214 and the display driver 320 are also connected to the processor 300 via the I / O port 214. The data port 218 may be connected to the processor 300 to enable transfer of data between the memory 302 and an external device, such as a personal computer. The user interface inputs 206, 210, and 214 are directly connected to the processor 300. The processor 300 controls the display 204 via the display driver 320. During manufacture of the test meter 200, calibration information, such as batch slope and batch slice values, may be pre-loaded into the memory 302. This pre-loaded calibration information may be accessed and used by the processor 300 upon receipt of a suitable signal (e.g., current) from the strip through the strip port connector 220 to provide a calibration input from any external source The corresponding analyte level (e. G., Blood glucose concentration) can be calculated using the signal and calibration information without an inbox.

In an embodiment described and illustrated herein, test meter 200 is used to measure glucose levels in blood applied to test strip 100 (or its variants in a priority application) inserted into strip port connector 220 An Application Specific Integrated Circuit (ASIC) 304 may be included to provide an electronic circuit to be implemented. The analog voltage may be passed to or from the ASIC 304 by an analog interface 306. [ The analog signal from the analog interface 306 can be converted into a digital signal by the A / D converter 316. [ The processor 300 further includes a core 308, a ROM 310 (including computer code), a RAM 312, and a clock 318. In one embodiment, the processor 300 is configured to disable all of the user interface inputs except for a single input, upon display of analyte values by the display unit, such as for a predetermined period of time after analyte measurement (Or programmed). In an alternative embodiment, the processor 300 is configured (or programmed) to ignore any input from all of the user interface inputs, except for a single input, when displaying the analyte values by the display unit. The detailed description and examples of the meter 200 are shown and described in International Patent Application Publication No. WO2006040200, which is incorporated herein by reference as if fully set forth herein.

FIG. 3A is an exemplary exploded perspective view of a test strip 100 that may include seven layers disposed on a substrate 5. FIG. The seven layers disposed on the substrate 5 include a first conductive layer 50 (which may also be referred to as an electrode layer 50), an insulating layer 16, two overlapping reagent layers 22a and 22b, An adhesive layer 60 comprising adhesive portions 24,26 and 28, a hydrophilic layer 70 and a top layer 80 forming a cover 94 for the test strip 100. [ The test strip 100 is fabricated such that the conductive layer 50, the insulating layer 16, the reagent layer 22 and the adhesive layer 60 are sequentially deposited on the substrate 5 using, for example, a screen- And can be manufactured in a series of steps. Note that the electrodes 10,12 and 14 are arranged to contact the reagent layers 22a and 22b while the physical property sensing electrodes 19a and 20a are spaced apart and not in contact with the reagent layer 22. The hydrophilic layer 70 and the top layer 80 may be laminated from the roll stock and laminated onto the substrate 5 as integrated laminate or separate layers. The test strip 100 has a distal portion 3 and a proximal portion 4 as shown in Figure 3A.

The test strip 100 may include a sample-receiving chamber 92 (FIG. 3B) through which a physiological fluid sample 95 can be aspirated or deposited. The physiological fluid sample discussed herein may be blood. The sample-receiving chamber 92 may include an inlet at the proximal end and an outlet at the side edge of the test strip 100, as illustrated in FIG. 3A. A fluid sample 95 can be applied to the inlet along axis L-L (FIG. 3B) to fill the sample-receiving chamber 92, allowing glucose to be measured. 3A, each of the side edges of the first adhesive pad 24 and the second adhesive pad 26 positioned adjacent to the reagent layer 22 define a wall of the sample-receiving chamber 92 do. 3A, the lower portion or "floor" of the sample-receiving chamber 92 may include a portion of the substrate 5, the conductive layer 50, and the insulating layer 16 . As illustrated in FIG. 3A, the upper portion or "roof" of the sample-receiving chamber 92 may include a distal hydrophilic portion 32. In the case of the test strip 100, as illustrated in FIG. 3A, the substrate 5 may be used as a foundation to help support the subsequently applied layers. The substrate 5 may be in the form of a polyester sheet, such as a polyethylene terephthalate (PET) material (Hostaphan PET supplied by Mitsubishi). The substrate 5 may be in roll form, nominally 350 microns in thickness, 370 mm in width, and approximately 60 meters in length.

Conductive layers are needed to form electrodes that can be used for electrochemical measurements of glucose. The first conductive layer 50 may be made from carbon ink that is screen-printed on the substrate 5. In the screen-printing process, carbon ink is loaded onto the screen and then transferred through a screen using a squeegee. The printed carbon ink can be dried using hot air at about < RTI ID = 0.0 > 140 C. < / RTI > The carbon ink may comprise one or more solvents for VAGH resin, carbon black, graphite (KS15), and resin, carbon and graphite mixtures. More specifically, the carbon ink may include a ratio of carbon black: VAGH resin of about 2.90: 1 in the carbon ink, and a ratio of graphite: carbon black of about 2.62: 1.

3A, the first conductive layer 50 includes a reference electrode 10, a first working electrode 12, a second working electrode 14, a third and a third working electrode 14, 4 physical property sensing electrodes 19a and 19b, a first contact pad 13, a second contact pad 15, a reference contact pad 11, a first working electrode track 8, a second working electrode track 9 ), A reference electrode track (7), and a strip detection bar (17). The physical property sensing electrodes 19a and 20a are provided with respective electrode tracks 19b and 20b. The conductive layer may be formed from carbon ink. The first contact pad 13, the second contact pad 15, and the reference contact pad 11 can be configured to electrically connect to the test meter. The first working electrode track (8) provides an electrical continuous path from the first working electrode (12) to the first contact pad (13). Similarly, the second working electrode track 9 provides an electrical continuous path from the second working electrode 14 to the second contact pad 15. Similarly, the reference electrode track 7 provides an electrical continuous path from the reference electrode 10 to the reference contact pad 11. The strip detection bar 17 is electrically connected to the reference contact pad 11. [ The third and fourth electrode tracks 19b and 20b are connected to the respective electrodes 19a and 20a. As illustrated in FIG. 3A, the test meter can detect whether the test strip 100 has been properly inserted by measuring the continuity between the reference contact pad 11 and the strip detection bar 17. FIG.

61 / 581,087, filed December 29, 2011, all of which are incorporated herein by reference in their entirety; 61 / 581,089; 61 / 581,099; And 61 / 581,100, filed May 31, 2012, and in United States Patent Application No. 61 / 654,013, filed May 31, Applicant's intent is that the scope of the invention claimed herein is also applicable to the various strips described in these earlier filed applications.

In the embodiment of Figure 3b, which is a variation of the test strip of Figure 3a, a further electrode 10a is provided as an extension of any of the plurality of electrodes 19a, 20a, 14, 12, It should be noted that this built-in shielding or grounding electrode 10a is used to reduce or eliminate any capacitive coupling between the user's finger or body and the characteristic measuring electrodes 19a, 20a. The ground electrode 10a allows any capacitance to be directed away from the sensing electrodes 19a, 20a. To this end, the ground electrode 10a may be connected to any one of the other five electrodes, or via one of the tracks 7, 8, 9, instead of one or more of the contact pads 15, To a separate contact pad (and track) of its own for connection to the contact pad. In a preferred embodiment, the ground electrode 10a is connected to one of the three electrodes on which the reagent 22 is disposed. In the most preferred embodiment, the ground electrode 10a is connected to the electrode 10. Because it is a ground electrode, it is advantageous to connect the ground electrode to the reference electrode 10 so as not to provide any additional current that may come from the background interference compound in the sample to the working electrode measurement. It is also believed that by connecting the shielding or ground electrode 10a to the electrode 10, this effectively increases the size of the counter electrode 10, which can be particularly limited in high signals. In the embodiment of Figure 3b, the reagents are arranged such that they do not come into contact with the measuring electrodes 19a, 20a. Alternatively, in the embodiment of Figure 3c, the reagent 22 is arranged so that the reagent 22 contacts at least one of the sensing electrodes 19a, 20a.

3D, an upper layer 38, a hydrophilic film layer 34 and a spacer 29 may be formed such that the reagent layer 22 ' Are combined together to form an integrated assembly for mounting to the substrate 5 in a state in which they are arranged close to the substrate 16 '.

In the embodiment of Figure 3b, the analyte measurement electrodes 10, 12 and 14 are arranged in substantially the same configuration as in Figures 3a, 3c or 3d. Alternatively, an electrode for sensing a physical property (e.g., hematocrit) level may be configured such that one electrode 19a is close to the inlet 92a of the test chamber 92 and the other electrode 20a is close to the entrance of the test chamber 92 (As shown in Fig. 3B of the priority application), or both are on the circle from the inlet 92a (shown in Figs. 3c and 3d of the priority application). At least one of the electrodes on the biosensor is arranged to contact the reagent layer (22).

3c, 3d, 3e and 3f, the physical properties (e.g., hematocrit) sensing electrodes 19a, 20a are disposed adjacent to each other, and at the opposite end of the inlet 92a of the examination chamber 92, (Fig. 3A-3E and 3F) adjacent to and downstream of the electrode 14 along the inlet 14a and adjacent the inlet 14a. In both of these embodiments, the physical property sensing electrode is configured such that the reagent layer 22 is not affected by the electrochemical reaction of the reagent when these physical property sensing electrodes are in the presence of a fluid sample containing glucose (e. G., Blood or interstitial fluid) Respectively.

As is known, conventional electrochemical-based analyte test strips facilitate the electrochemical reaction with an analyte of interest to determine the presence and / or concentration of the analyte, And an enzyme reagent layer. For example, an electrochemically-based analyte test strip for determination of the glucose concentration in a fluid sample may comprise an enzymatic reagent comprising an enzymatic glucose oxidase and a mediator ferricyanide (reduced to the intermediate ferrocyanide during the electrochemical reaction) Can be adopted. Such conventional analyte test strips and enzyme reagent layers are described, for example, in U.S. Patent Nos. 5,708,247, each of which is incorporated herein by reference; 5,951, 836; 6,241,862; And 6,284,125. In this regard, the reagent layer employed in the various embodiments provided herein may comprise any suitable sample-soluble enzyme reagent, wherein the choice of enzyme reagent depends on the analyte and the body fluid sample to be determined. For example, if glucose is to be determined in a fluid sample, the enzyme reagent layer 22 may comprise a glucose oxidase or a glucose dehydrogenase with other components necessary for functional operation.

Generally, the enzyme reagent layer 22 comprises at least an enzyme and an agent. Examples of suitable intermediates include, for example, ruthenium, hexamethylruthenium (III) chloride, ferricyanide, ferrocene, ferrocene derivatives, osmium bipyridyl complexes, and quinone derivatives. Examples of suitable enzymes include glucose oxidase, glucose dehydrogenase (GDH) using pyrroloquinoline quinone (PQQ) cofactor, GDH using nicotinamide adenine dinucleotide (NAD) cofactor, and flavin adenine dinucleotide (FAD) And GDH using cofactors. The enzyme reagent layer 22 can be applied during manufacture using any suitable technique including, for example, screen printing.

Applicants have found that the enzyme reagent layer can also be used in combination with suitable buffers such as Tris HCL, citraconate, citrate and phosphate, hydroxyethylcellulose [HEC], carboxymethylcellulose, ethylcellulose and alginate, , ≪ / RTI > and the like.

Although there are no phase-change measuring electrodes, analytical test strips and related methods described herein, additional details regarding the use of electrodes and enzyme reagent layers for determining the concentration of an analyte in a body fluid sample are fully disclosed in the present application U.S. Patent No. 6,733,655, incorporated herein by reference.

In various embodiments of the test strip, there are two measurements performed on the fluid sample deposited on the test strip. One measurement is a measurement of the concentration of an analyte (e.g., glucose) in a fluid sample and the other is a measurement of a physical property (e.g., a hematocrit) in the same sample. Measurement of physical properties (e.g., hematocrit) is used to correct or correct glucose measurements to eliminate or reduce the effect of erythrocytes on glucose measurements. Both measurements (glucose and hematocrit) can be performed sequentially, simultaneously or with overlapping durations. For example, physical properties (e.g., hematocrit) may be performed first, followed by glucose measurement; First, glucose measurements may be performed following physical properties (e.g., hematocrit) measurements; Both measurements can be performed simultaneously; The duration of one measurement can overlap the duration of another. Each measurement is discussed in detail below with respect to Figures 4A and 4B.

4A is an exemplary chart of test signals applied to the test strip 100 and its variations shown in Figs. 3A-3F herein. Before the fluid sample is applied to the test strip 100 (or its variation in the priority application), the test meter 200 determines that a first test signal of about 400 millivolts is applied to the fluid to be applied between the second working electrode and the reference electrode Detection mode. Preferably, a second test signal 401 of about 400 millivolts is applied to the first working electrode (e.g., electrode 12 of strip 100) and the reference electrode (e.g., electrode 10 of strip 100) Respectively. Alternatively, the second test signal may also be applied at the same time so that the time interval for applying the first test signal overlaps the time interval for applying the second test voltage. The test meter may be in the fluid detection mode during the fluid detection time interval T _FD prior to detection of the physiological fluid at a start time of zero. In the fluid detection mode, the test meter 200 applies a fluid to the test strip 100 (or its variation in the priority application) so that the fluid is either one of the first working electrode 12 or the second working electrode 14 And the reference electrode 10 to wet. Once the test meter 200 has detected a sufficient increase in the measured test current in either (or both of) the first working electrode 12 or the second working electrode 14, for example with respect to the reference electrode 10 Recognizing that the physiological fluid has been applied, the test meter 200 allocates a second marker of 0 at time zero "0 " and starts the test sequence time period T _S. The test meter 200 may sample the transient current output at a suitable sampling rate, such as every 1 millisecond to every 100 milliseconds. When the test time interval T _S is completed, test signals are removed. For simplicity, FIG. 4A shows only the first test signal 401 applied to the test strip 100 (or its variation in the priority application).

In the following, from the known transient current (e. G., Measured current response in nano-amperes as a function of time) measured when the test voltage of Figure 4A is applied to the test strip 100 (or its variation in the priority application) How the glucose concentration is determined is explained.

In FIG. 4A, the first and second test voltages applied to the test strip 100 (or variations thereof in the priority application) are generally about +100 millivolts to about +600 millivolts. In one embodiment where the electrode comprises a carbon ink and the medium is a pericyanide, the test signal is about +400 millivolts. As is known to those skilled in the art, other media and combinations of electrode materials will require different test voltages. The duration of the test voltage is generally about 1 to about 5 seconds after the reaction period, typically about 3 seconds after the reaction period. Typically, the test sequence time T _S is measured for time t ₀ . Voltage 401 in this Figure 4a in accordance with the maintained for the duration of T _S, the specification and the output signal shown in Figure 4b occurs in the, at this time of the transient (402) on the first working electrode 12 is zero, And the transient current 404 for the second working electrode 14 is also generated for a time of zero. Although the transient signals 402 and 404 have been placed on the same reference zero point to account for the process, it is believed that, due to fluid flow in the chamber toward each of the working electrodes 12 and 14 along the longitudinal axis LL, It should be noted that there is a slight time difference. However, the transients are sampled and configured in the microcontroller to have the same start time. In Figure 4b, the transient current increases to a peak close to the peak time Tp , at which the current slowly decreases to one of approximately 2.5 seconds or 5 seconds after the time of zero. At point 406, at approximately 5 seconds, the output signal for each of the working electrodes 12,14 can be measured and summed. Alternatively, the signal from only one of the working electrodes 12, 14 may be doubled. From the knowledge of the particular test strip 100 and the parameters of the test strip (e.g., batch correction code offset and batch slope) for its variants, the analyte (e.g., glucose) concentration can be calculated. The transient outputs 402 and 404 may be sampled to derive the signal I _E at various time positions during the test sequence (by summing each of the currents I _WE1 and I _WE2 or by doubling one of I _WE1 or I _WE2 ).

It should be noted that "slice" and "slope" are parameter values of the biosensor obtained by measuring calibration data from lots or batches of test strips. Typically about 1500 strips are randomly selected from the lot or batch. The physiological fluid (e.g., blood) from the provider is spiked at various analyte levels, typically six different glucose concentrations. Typically, blood from twelve different providers is spiked into each of the six levels. Blood from the same donor and level is provided in 8 strips, allowing a total of 12 x 6 x 8 = 576 tests to be performed on the lot. They are benchmarked against the actual analyte level (e. G., Blood glucose concentration) by measuring them using standard laboratory analyzers such as the Yellow Springs Instrument (YSI). The plot of measured glucose concentration is plotted against the actual glucose concentration (or the measured current versus YSI current), the formula y = mx + c is least squared fitted to this graph to determine the batch slope m And placement intercept c. Applicants have also provided a method and system in which the batch slope is derived during determination of analyte concentration. Thus, a "batch gradient" or "slope" can be defined as a measured or derived gradient of an optimal fitting line for a plot of measured glucose concentration (or measured current vs. YSI current) plotted against actual glucose concentration. Thus, a "batch segment" or "segmentation" can be defined as the point at which the best fit line for a graph of the measured glucose concentration (or measured current vs. YSI current) plotted against the actual glucose concentration meets the y axis.

It is worth noting here that the various components, systems and procedures previously described allow applicants to provide an analytical measurement system that was not previously available in the art. In particular, the system includes a test strip having a substrate and a plurality of electrodes connected to respective electrode connectors. The system also includes a housing, a test strip port connector configured to connect to a respective electrode connector of the test strip, and an analyte meter 200 having a microcontroller 300, as shown here in FIG. 2B. The microprocessor 300 is in electrical communication with the test strip port connector 220 to apply an electrical signal or to sense an electrical signal from a plurality of electrodes.

Referring to FIG. 2B, a detailed view of a preferred embodiment of a meter 200 having the same reference numerals in FIGS. 2A and 2B has a common description. 2B, the strip port connector 220 includes an impedance sense line (EIC) for receiving a signal from the physical property sensing electrode (s), an ac signal line (AC) for introducing a signal to the physical characteristic sensing electrode Is connected to the analog interface 306 by a reference line for a reference electrode and five lines including a current sense line from each working electrode 1 and working electrode 2. [ A strip detection line 221 may also be provided to the connector 220 to indicate insertion of the test strip. The analog interface 306 has four inputs to the processor 300: (1) the actual impedance Z '; (2) a virtual impedance Z "; (3) an output signal sampled or measured from the working electrode 1 of the biosensor, that is, I _we1 ; (4) an output signal sampled or measured from the working electrode 2 of the _biosensor , There is one output from the processor 300 to the interface 306 to introduce an oscillating signal AC of any value between 25 kHz and about 250 kHz or more into the physical property sensing electrode. If the phase difference P (in degrees) Impedance Z 'and virtual impedance Z ", where: < RTI ID = 0.0 >

[Mathematical Expression 3.1]

P = tan ^-1 {Z '' / Z '}

, The magnitude M (expressed in ohms and typically expressed as Z) from lines Z 'and Z "of interface 306 may be determined, where

[Equation 3.2]

In this system, the microprocessor is configured to: (a) apply a first signal to a plurality of electrodes to derive a placement gradient defined by the physical properties of the fluid sample; and (b) And to apply a second signal to the plurality of electrodes to be determined. In such a system, the plurality of electrodes of the test strip or biosensor comprises at least two electrodes for measuring physical properties and at least two other electrodes for measuring the analyte concentration. For example, at least two electrodes and at least two other electrodes are disposed in the same chamber provided on the substrate. Alternatively, at least two electrodes and at least two other electrodes are disposed in different chambers provided on the substrate. It should be noted that, for some embodiments, all of the electrodes are disposed on the same plane defined by the substrate. In particular, in some of the embodiments described herein, a reagent is placed close to at least two other electrodes, and no reagent is placed on at least two electrodes. One important feature of this system is its ability to provide accurate analyte measurements within about 10 seconds after deposition of a fluid sample (which may be a physiological sample) on the biosensor as part of the test sequence.

As an example of an analyte calculation (e.g., glucose) for strip 100 (Figures 3A-3F and variations thereof in priority applications), sampling at 406 for first working electrode 12 in Figure 4B The output signal at 406 for the second working electrode 14 is about 1300 nanoamperes and the calibration code of the test strip is about 500 nanoamperes and the slope is about < RTI ID = 0.0 >Lt; RTI ID = 0.0 > mg / dL. ≪ / RTI > The glucose concentration G ₀ can then be determined from equation 3.3 as follows:

[Equation 3.3]

G ₀ = [(I _E ) - intercept] / slope

here,

I _E is the _{impedance of the} working electrode 12, 14 (I _E = I _{we 1} + I _we 2 or I _E = 2 * (from all five electrodes in the sensor 100) from all electrodes in the biosensor Can be the total current from one of the working electrodes if I _E = 2 * I _{we 1} or I _E = 2 * I _we 2, or from I _{W 1} + I _we 2) / 2) Signal (e. G., A current proportional to the analyte concentration);

I _we1 is the signal (e.g., current) measured for the first working electrode at the set sampling time;

I _we2 is the signal (e.g., current) measured for the second working electrode at the set sampling time;

The slope is a value obtained from a calibration check of the placement of test strips that produce this particular strip;

The intercept is a value obtained from a calibration check of the placement of test strips that produce this particular strip.

From Equation 3.3, G ₀ = [(1600 + 1300) -500] / 18, and therefore G ₀ to 133 mg / dL.

Here, a biosensor having two working electrodes (12 and 14 of FIGS. 3A-3F and their variations in the priority application) to sum the measured signals from each working electrode to provide a total measured current I _E 100 and a signal derived from only one of the two working electrodes in the deformation of the test strip 100 when there is only one working electrode (either one electrode 12 or 14) It should be noted that Instead of the total measured signal, the average of the signals from each working electrode may be used as the total measured signal I _E in Equations 3.3, 5, 6, 6.1, 7 and 7.1 described herein, (As known to those skilled in the art) by modifying the computation coefficients appropriately to process the low total measured signal I _E compared to the embodiment in which the filtered signals are summed. Alternatively, the mean of the measured signal may be multiplied by 2 and used as I _E in Equations 3.3, 5, 6, 6.1, 7, and 7.1 without having to derive a computation factor as in the previous example . Where the predetermined offset does not _{exceed the} signal values I _we1 and < RTI ID = _0.0 > I < / _RTI &_gt; I &_lt; / RTI &_gt; _we2 . Temperature compensation may also be used to ensure that the result is calibrated to a reference temperature, such as, for example, room temperature of about 20 ° C.

It has been found that conventional glucose test strips manufactured by LifeScan (marketed as Ultra Brand) have variations in transient current output depending on glucose concentration and hematocrit. These variations can be seen in FIG. 5, where at high glucose levels 502a, 504a, 506a or intermediate glucose levels 502b, 504b, 506b, transient currents vary significantly as a function of the level of physical properties (e.g., hematocrit) , At low glucose levels (502c, 504c, 506c), the transient current does not change markedly as in high glucose or medium glucose as a function of the hematocrit. Specifically, at high glucose levels, the transients 502a, 504a, and 506a (for 30%, 42%, and 55% Hct) are approximately equal to the current output as a function of time after peak at about 1.5 seconds after the start of the test sequence Maintain consistent spacing. Similarly, at the intermediate glucose level, the transients 502b, 504b, 506b (for 30%, 42% and 55% Hct) are consistent with the current output after the peak at about 1.5 seconds after the start of the test sequence Keep spacing. At low glucose levels, the transients 502c, 504c, and 506c (for 30%, 42%, and 55% Hct) converge together after a peak at about 1.5 seconds after the start of the test sequence.

Based on these observations, Applicants have found that the parameters of these test strips tested at low glucose levels, intermediate glucose levels (502b, 504b, 506b) and high glucose levels for 30%, 42% and 55% hematocrit levels , Batch intercept or batch slope). In particular, Applicants have found from regression analysis that test strip parameters (e.g., batch intercept or batch slope) are associated with hematocrit levels. As a result, by knowing the physical properties of the sample (e.g., hematocrit) and the regression analysis for the biosensor, it has been found that this relationship has not been previously available for this type of biosensor, (E.g., batch intercept or batch slope) may be utilized to accommodate different levels of physical properties (e.g., hematocrit).

Since the glucose concentration (G ₀₎ can be determined from the signal I _E, the physical properties of the fluid sample IC (e.g., hematocrit, temperature, viscosity, density, etc.) of the technique of the Applicant describes for determining is provided with respect to Figure 2b . In FIG. 2B, system 200 (FIGS. 2A and 2B) applies a first oscillation input signal AC (FIG. 2B) at a first frequency (eg, greater than about 25 kilohertz) to at least one sensing electrode. The system also is configured to measure or detect the first oscillating output signal EIC, which involves in particular measuring a first time difference Δt ₁ between the first input and the output oscillating signal. At the same time or during the overlap time duration, the system also includes a second oscillation input signal AC (not shown for brevity) of a second frequency (e.g., from about 100 kilohertz to about 1 megahertz, preferably about 250 kilohertz) ) for applying to the electrodes of the pair, and then the second can measure or detect the oscillation output signal, which involves measuring the second time difference Δt ₂ (not shown) between the first input and the output oscillating signal can do. From these signals (AC and EIC), the system estimates the first and second time difference between the physical properties of the fluid sample based on Δt ₁ and Δt ₂ (e. G., Hematocrit, viscosity, temperature, density, etc.). Estimation of physical properties can be achieved by applying the following formulas.

[Mathematical Expression 4.1]

here

Each of C1, C2, and C3 is an operational constant for the test strip,

m ₁ represents the parameter from the regression data.

The details of this exemplary technique are described in the Attorney Docket No. DDI-5124USPSP, which is incorporated herein by reference, and is entitled "Hematocrit Corrected Glucose Measurements for Electrochemical Test Strips Using a Time Difference of Signal for example, in U.S. Provisional Patent Application No. 61 / 530,795, filed September 2, 2011, entitled " Electrochemical Test Strip Using Time Differential of Signals ".

Other techniques for determining physical properties (e.g., hematocrit) may be by two independent measurements of physical properties (e.g., hematocrit). This can be achieved by (a) determining the phase angle of the fluid sample at a second frequency that is significantly higher than the first frequency and (b) the impedance of the fluid sample at the first frequency. In this technique, a fluid sample is modeled as a circuit with unknown reactance and unknown resistance. In this model, the impedance for measurement (a) (as denoted by the symbol "Z |") corresponds to the applied voltage, the voltage across a known resistor (e.g., the inherent strip resistor), and the unknown impedance Vz Can be determined from the voltage across it; Similarly, for measurement (b) the phase angle can be measured by a person skilled in the art from the time difference between the input and output signals. The details of these techniques are shown and described in pending patent application Serial No. 61 / 530,808 (Attorney Docket DDI5215PSP), filed September 2, 2011, which is incorporated by reference. See, for example, U.S. Patent No. 4,919,770, U.S. Patent No. 7,972,861, U.S. Patent Application Publication Nos. 2010/0206749, 2009/0223834, or http://www.idealibrary.com Cell-Substrate Impedance Sensing (ECIS) as a Noninvasive Means to Monitor the Kinetics of Cell Spreading to Artificial Surfaces "by Joachim Wegener, Charles R. Keese, and Ivar Giaever and published by Experimental Cell Research 259, 158-166 (2000) doi : 10.1006 / excr.2000.4919]; Utilization of AC Impedance Measurements for Electrochemical Glucose Sensing Using Glucose Oxidase to Improve Detection Selectivity "by Takuya Kohma, Hidefumi Hasegawa, Daisuke Oyamatsu, and Susumu Kuwabata and published by Bull. Chem. Soc. Jpn. Vol. 80, No. Other suitable techniques for determining the physical properties (e.g., hematocrit, viscosity, or density) of a fluid sample, such as, e. G., 1, 158-165 (2007), may also be used, all of which are incorporated by reference.

Other techniques for determining physical properties can be obtained by knowing the magnitude and phase difference (e.g., phase angle) of the impedance of the sample. In one example, the following relationship is provided for estimating the physical or impedance characteristics of a sample ("IC"):

[Equation 4.2]

here:

M represents the magnitude of the measured impedance │Z│ (in ohms);

P represents the phase difference between input and output signals (in degrees);

y ₁ may be about -3.2e-08 and +/- 10%, 5%, or 1% of the provided numerical value (and may be 0 depending on the frequency of the input signal);

y ₂ can be about 4.1e-03 and +/- 10%, 5%, or 1% of the provided numerical value (and can be 0 depending on the frequency of the input signal);

y ₃ may be about -2.5 e + 01 and +/- 10%, 5% or 1% of the numerical value provided;

y ₄ may be about 1.5e-01 and +/- 10%, 5% or 1% of the provided numerical value (and may be 0 depending on the frequency of the input signal);

y ₅ may be about 5.0 and +/- 10%, 5% or 1% of the provided numerical value (and may be 0 depending on the frequency of the input signal).

Here, if the frequency of the input AC signal is high (e.g., greater than 75 kHz), the parameter terms y ₁ and y ₂ for the impedance magnitude M can be ± 200% of the exemplary values given here, 0.0 > 0 < / RTI > or even negative. On the other hand, if the frequency of the AC input signal is low (e.g., less than 75 kHz), the parameter terms y ₄ and y ₅ for the phase angle P can be ± 200% of the exemplary values given here, Each of the terms may contain zero or even negative values. Here, it should be noted that the size of H or HCT as used herein is substantially the same as the size of IC. In one exemplary embodiment, H or HCT is the same as IC when H or HCT is used in the present application.

In another alternative embodiment, Equation 4.3 is provided. Equation 4.3 is an accurate derivation of the quadratic relationship without using the phase angle as in Equation 4.2.

[Mathematical Expression 4.3]

here:

IC is an impedance characteristic [%];

M is the magnitude of the impedance [ohm];

y ₁ is about 1.2292 e ₁ and +/- 10%, 5% or 1% of the provided numerical value;

y ₂ is about -4.3431e2 and +/- 10%, 5%, or 1% of the provided numerical value;

y ₃ is about 3.5260e4 and +/- 10%, 5% or 1% of the provided numerical value.

By way of various components, systems and understandings provided herein, at least four techniques (and variations of such methods) for determining analyte concentration from a fluid sample (which may be a physiological sample) Accuracy was achieved.

One of the embodiments of the present invention may be understood with reference to FIG. 6 and in particular to the system module 600. In the system module 600, it is assumed that the user has deposited a fluid sample in module 602 and an output signal sufficient to initiate the test sequence timer T _N has been detected (FIG. 4B). In module 604, the system (FIG. 2B) includes a plurality of viewpoints or locations T ₁ , T ₂ , T ₃ , ... T _N to drive the signal to measure or sample the output signal I _E from at least one of the working electrodes (12, 14). As can be seen in FIG. 4B, the time position may be any time or section within the test sequence T _S. For example, the time position at which the output signal is measured may be a single time position T _1.5 of 1.5 seconds, or a period 408 overlapping the time position T _2.8 , which is close to 2.8 seconds (e.g., Or more).

Referring again to FIG. 6, the system may also apply another signal to measure the physical characteristics IC of the sample in module 606, concurrently with, subsequent to, or even before, the driving of the signal in module 604 . The signal IC may be a look-up table or a matrix that is configured to provide a new parameter x ₁ of the biosensor, which may be a new placement slope or placement intercept for the biosensor 100 And is provided to a biosensor parametric generator 608. The output of the generator 608 is provided to the calculation module 610 along with the measured output signal I _E at one of a plurality of predetermined time positions. The calculation module 610 is configured to provide a first analyte concentration to an annunciator 612 to inform the user of the first analyte result.

For the generator module 608, the system may use the following exemplary table 1. In Table 1, is correlated with the case of the estimated percent of the impedance characteristics of the sample, it referred to as the hematocrit a new biosensor based on the history regression analysis of the arrangement of the biosensor parameter coefficient x ₁ (placed on the inclination).

[Table 1a]

Once an alternative version of the IC of Equation 4.3 is used, it is not necessary to use an IC as expressed in% in Table 1a. That is, the IC can be replaced by the magnitude | Z | of the impedance expressed in ohms. This eliminates the computation of the IC from the system or instrument (which saves code space and computation time, allowing the lower cost meter to better cope with immediate task). In this case, Table 1a can be changed to Table 1b:

[Table 1b]

On the other hand, the calculation module 610 is configured to use Equation 5 of the form:

&Quot; (5) "

here

G ₁ represents the first analyte concentration;

I _E comprises a plurality of predetermined time positions T ₁ , T ₂ , T 3, ... (E.g., current) from at least one electrode measured at one of T _N to a test sequence interval (T ₁ to 1.0 second, T ₂ to 1.01 second, T ₃ to 1.02 second);

P1 represents the segmentation parameter of the biosensor;

P2 represents the slope parameter of the biosensor;

x ₁ represents the first biosensor parameter coefficient based on the physical properties of the sample (in Table 1a or Table Ib).

In Equation 5, for the particular embodiment described herein, P1 is about 475 nanoamperes and P2 is about 9.5 nanoamperes / (mg / dL).

It is believed that the results provided by modules 606, 608, 610 are more accurate than existing techniques, but still improvements in accuracy can be obtained. Specifically, the present inventor has provided a second alternative technique shown herein as modules 602, 604, 606, 614, 616, 618 in FIG. Since the modules 604 and 606 have been described above as providing the output signal IE and the physical characteristic signal IC, these modules need not be mentioned in the second technique.

In module 614, the system obtains the estimated analyte concentration (G _EST ) based on the measured output signal (e.g., at 2.5 seconds) at one of the predetermined time positions. The estimated analyte concentration G _EST is used in conjunction with the physical property signal IC for module 616 to generate a second biosensor parameter coefficient x ₂ . The parameter coefficient x ₂ is based on both the physical characteristic IC and the estimated analyte G _EST to arrive at the multiplication factor of the existing biosensor parameter (s) (e.g., the parameter is slope or intercept) in Equation 3.3.

The biosensor parameter coefficient x ₂ is determined by a hysteresis regression analysis of the biosensor described in this specification. Thus, a curve fitting mathematical, matrix or look-up table may be used for the module 616 to generate the required biosensor parameter coefficient x ₂ . For ease of calculation, a look-up table is used to reduce the computational load of the processor 300. An exemplary look-up table is recalled in Table 2 herein:

[Table 2a]

Similar to the case of Table 1a, if an alternative version of the IC of Equation 4.3 is used, it is not necessary to use an IC as expressed in% in Table 2a. That is, the IC can be replaced by the magnitude | Z | of the impedance expressed in ohms. This eliminates the computation of the IC from the system or instrument (which saves code space and computation time, allowing the lower cost meter to better cope with immediate task). In this case, Table 2a can be changed to Table 2b:

[Table 2b]

As is well known to those skilled in the art, where the glucose estimates do not match the table, interpolation may be used between the data provided in all of the tables described herein.

Referring again to FIG. 6, the module 618 calculates the second analyte concentration G ₂ using both the parameter coefficient x ₂ (of Table 2a or Table 2b) and the measured or sampled output signal I _E. Module 618 is configured to use Equation 6 of the form:

&Quot; (6) "

here

G ₁ represents the first analyte concentration;

I _E comprises a plurality of predetermined time positions T ₁ , T ₂ , T 3, ... (E.g., current) from at least one electrode measured at one of the .T _N to the test sequence interval (T ₁ to 1.0 second, T ₂ to 1.01 second, T ₃ to 1.02 second);

P1 represents the segmentation parameter of the biosensor;

P2 represents the slope parameter of the biosensor, where P2 is about 9.5 nanoamperes / (mg / dL);

x ₂ represents a physical property of the sample and a second biosensor parameter coefficient based on the estimated analyte concentration G _EST ,

here:

[Equation 6.1]

I _E comprises a plurality of predetermined time positions T ₁ , T ₂ , T ₃ , ... The total output signal (e.g., current) from the biosensor measured at one of the time points T _N to the test sequence interval (T ₁ to 1.0 second, T ₂ to 1.01 second, T ₃ to 1.02 second) Lt; / RTI >

P1 represents the slice parameter of the biosensor,

P2 represents the slope parameter of the biosensor.

In certain embodiments of the strips described in this specification and in the priority application, the time position for both Equations 6 and 6.1 is about 5 seconds from the beginning of the test sequence, P1 is about 475 nanoamperes, P2 is about 9.5 nano Ampere / (mg / dL).

Once the module 618 has acquired the second analyte concentration G2, the indicator module 620 can provide the results to the user.

In the third alternative shown here with respect to modules 602, 604, 606, 608, 610, 622, 624, 626, this third technique produces a greater improvement compared to the first and second techniques .

Since modules 602, 604, 606, 608, 610 have been described above, these modules need not be mentioned in the third technique. 6, the module 622 is configured to receive both the first analyte concentration result G1 from the module 610 and the physical properties from the module 606 such that a third parameter coefficient x3 can be generated . As in module 616, for example, a lookup table as shown in Table 3 may be used, but the present inventor is not intended to be limited to the lookup table described herein. In Table 3a, the system can obtain the required coefficient by correlating the physical properties analyte concentration and G _1. For example, if the first analyte concentration is 225 mg / dL and the estimated hematocrit is about 57%, the parameter coefficient x ₃ is determined from Table 3a to 0.82.

[Table 3a]

Similar to the case of Table 2a, if an alternative version of the IC of Equation 4.3 is used, it is not necessary to use an IC as expressed in% in Table 3a. That is, the IC can be replaced by the magnitude | Z | of the impedance expressed in ohms. This eliminates the computation of the IC from the system or instrument (which saves code space and computation time, allowing the lower cost meter to better cope with immediate task). In this case, Table 3a can be changed to Table 3b:

[Table 3b]

Then, the coefficient x ₃ (Table 3a or Table 3b), the third analyte concentration is used in Equation (7) as part of step 716 to obtain a G _3.

&Quot; (7) "

here

G ₃ represents the first analyte concentration;

I _E comprises a plurality of predetermined time positions T ₁ , T ₂ , T ₃ , ... Represents the total output signal (e.g., current) from the biosensor measured at one of T _N to a test sequence interval (T ₁ to 1.0 second, T ₂ to 1.01 second, T ₃ to 1.02 second);

P1 represents the segmentation parameter of the biosensor;

P2 represents the slope parameter of the biosensor;

x ₃ represents a physical characteristic of the sample and a third biosensor parameter coefficient based on the first analyte concentration G ₁ .

In Equation 7, for the particular embodiment described herein, P1 is about 475 nanoamperes and P2 is about 9.5 nanoamperes / (mg / dL).

By the description provided herein, a method for obtaining accurate analyte concentration has been achieved by the Applicant. The method includes applying a signal to the sample to determine a physical property of the sample in step 606; Introducing another signal into the sample to cause a physical conversion of the sample; Measuring at least one output signal from the sample in step 604; At least one predetermined parameter P1 or P2 of the biosensor at step 614 and a plurality of predetermined time positions T _PRED from the beginning of the test sequence are at least one of T ₁ , T ₂ , T ₃ ... T _N Obtaining an estimated analyte concentration (G _EST ) from at least one output signal (I _E ) Generating a first parameter coefficient (x ₁ ) of the biosensor based on a physical characteristic (IC) of the sample in step 608; Based on at least one output signal I _E measured at one of the plurality of predetermined time positions T _PRED from the beginning of the test sequence and the first parameter coefficient x ₁ of the biosensor at step 610 Calculating a first analyte concentration; Generating a second parameter coefficient (x ₂ ) of the biosensor based on the estimated analyte concentration (G _EST ) and the physical characteristic (IC) of the sample (95) in step 616; Based on the second parameter coefficient (x ₂ ) of the biosensor at step 618 and at least one output signal I _E measured at one of a plurality of predetermined time positions T _PRED from the start of the test sequence the method comprising: calculating a second analysis of the water concentration (G _2); Generating a third parameter coefficient (x ₃ ) of the biosensor based on the first analyte concentration (G ₁ ) and the physical property (IC) in step 622; Based on the at least one output signal I _E measured at one of the plurality of predetermined time positions T _PRED from the start of the test sequence and the third parameter coefficient x ₃ of the biosensor at step 624 comprising the steps of: 3 analysis calculated water concentration (G _3); And notifying at least one of the first, second and third analyte concentrations (G _1, G _2, G ₃ ) in step 626.

Figure 7 illustrates a variation of the second technique (modules 602, 604, 606, 614, 616, 618, 620 of Figure 6). In this technique, it is assumed that the user turns on the biosensor (e.g., inserts the strip into the meter's port connector). In step 702, a sample is deposited on the biosensor while the voltage is applied (Fig. 4A). As the sample wets the electrode, an output signal is generated from the working electrode (FIG. 4B). Once the output signal increases to zero, the system assumes that the test is in progress and starts the test sequence at step 704. It should be noted that during application of the sample, before or after the start of the test sequence, at step 706 the system may apply the signal AC to the sample to measure or estimate the physical properties of the sample. At step 708, a timer may be started at approximately the same time as step 704 to ensure that the output signal from the working electrode is sampled at the appropriate time position during the test period T. [ In step 710, another signal may be introduced into the sample to measure an output signal (e.g., an output signal in the form of a nano-ampere) from the working electrode. The estimated analyte concentration is derived at step 712 by measuring the output signal (s) at an appropriate time position from one of the time positions within the test period T with equation 6.1. In a preferred embodiment, the time position for deriving the estimated analyte concentration is about 2.5 seconds or about 5 seconds, and any suitable time interval overlapping each of these time points may be used and P1 (i. E. Fragment) is about 792 nanoamperes and P2 (i.e., slope) is about 10.08 nA / (mg / dL). In step 714, both the physical characteristic IC and the estimated analyte concentration can be used by the system to determine the new biosensor parameter P2 _NEW for the biosensor. This parameter P2 _NEW can be generated by regression analysis of the biosensor as described above and can be obtained by a curve fitting, matrix or look-up table. To reduce the computational load on the processor 300, a lookup table as shown in Table 4 may be used.

[Table 4]

Once the system can be made a new biosensor Once you obtain a parameter or _New P2, as used in equation (7), these parameters calculation for the analyte concentration G _2A using the _New P2:

&Quot; (7) "

here

G _2A represents the second analyte concentration;

I _E represents the total output signal (e.g., current) from the biosensor measured at one of a plurality of predetermined time positions;

P1 represents the segmentation parameter of the biosensor;

P2 _NEW represents the slope parameter of the biosensor based on the physical characteristic IC and the estimated analyte concentration G _EST ,

Here :

[Mathematical expression 7.1]

I _E represents the total output signal (e.g., current) from the biosensor measured at one of a plurality of predetermined time positions or at another time position;

P1 represents the slice parameter of the biosensor,

P2 represents the slope parameter of the biosensor.

In the particular embodiment described herein, P1 for (7) is about 400 nanoamperes; The signal I _E is measured at about 5 seconds; P1 for Equation 7.1 is about 792 nanoamperes; P2 for Equation 7.1 is about 10.1 nA / (mg / dL); The signal I _E for Equation 7.1 is measured or sampled at about 2.5 seconds.

It should be noted that for the new technique described above, instead of estimates of analyte concentrations in Tables 2 and 3, the measured signal at a predetermined time (e.g., about 2.5 or 5 seconds) can be used. This is due to the fact that the analyte estimates in these tables are the result of the measured signal, and hence the estimation, by multiplying and dividing by the biosensor parameter coefficients P1 and P2. Thus, the measured signal may be used as a raw value in the table instead of further mathematical manipulations with coefficients P1 and P2 for the estimates of such a table.

In order to demonstrate the improvement obtained by the present inventor, a lot of lots of 10 strips for a total of 13234 strips for a biosensor were tested in comparison with the first to third techniques of the present invention. The results are summarized in Table 5.

[Table 5]

It should be noted that the quantification of improvement can be indicated by "bias" at different hematocrit levels. The bias, which is an estimate of the relative error of glucose measurements, was calculated for each glucose concentration determined by the method described in this example. The bias for each glucose concentration was determined by the following formulas:

Bias _Absolute = G _Calculation - G _criteria (for G _criteria below 100 mg / dL glucose)

(In the case of G _standard of 100 mg / dL glucose or more)

here

The bias _absolute is an absolute bias,

Bias _% is percent biased,

G _calculation is the glucose concentration determined by the method herein,

The G _standard is the baseline glucose concentration.

The results from the experiment are plotted and shown in Figures 8-11. Figure 8a shows that in the known art glucose results below 100 mg / dL are biased out of the top border of 15 mg / dL below 35% hematocrit and below the bottom border of -15 mg / dL at the higher hematocrit above 45% As a graph. Figure 8b graphically illustrates how glucose results above 100 mg / dL in the known art are biased out of the top border of 15% below 35% hematocrit and biased below the bottom border of -15% at the higher hematocrit above 45% do.

On the other hand, when the first technique was used in the same sample set, the results were much better than the known technique (FIG. 8A), with results using the first technique (FIG. 9A) for analyte concentrations of less than 100 mg / Lt; / RTI > Similarly, for analyte concentrations above 100 mg / dL, the results of the first technique (Figure 9b) were also superior to the known technique (Figure 8b).

For the second technique (Figs. 10A and 10B) as compared to the known techniques (Figs. 8A and 8B), the results are impressive or even farther great.

It should be noted that, for the third technique (Figs. 11A and 11B), there is no significant difference between the second technique and the third technique (see Table 5), which is mainly given by the sizes of the correction tables 1 and 2 . It is believed that if a finer resolution of "bin" is used for glucose and hematocrit, an improvement in results for the third technique can be obtained.

As can be seen in the second or third technique, for glucose concentrations below 100 mg / dL, at least 95% of the final analyte concentration value of the batches of test strips is within ± 15 mg / dL of the reference analyte concentration .

The step of applying the first signal and driving the second signal may be such that the order is the second signal following the first signal or the order of both signals is superimposed; Alternatively, it should be noted that the first signal follows the second signal first, or that the order of both signals may overlap, which occurs in a sequential order. Alternatively, the application of the first signal and the driving of the second signal may occur simultaneously.

It should be noted that in a preferred embodiment, the measurement of the signal output to glucose concentration is performed prior to the estimation of physical properties (e.g., hematocrit). Alternatively, physical properties (e.g., hematocrit) levels may be estimated, measured, or obtained prior to measurement of glucose concentration.

Although the method may specify only one sampling point, the method may be performed continuously for at least about 10 seconds after the start of the test sequence, for example, until the results are stored for processing at the end of the test sequence (e.g., Sampling at as many points in time as desired, such as sampling the signal output at a time, e.g., every 1 millisecond to 100 milliseconds. Applicants note that although the appropriate sampling time is measured from the beginning of the test sequence, any suitable data can be used to determine when to sample the output signal. In practice, the system can be programmed to sample the output signal in a suitable time sampling period, such as one sampling, for example every 100 milliseconds or even about every 1 millisecond in the entire test sequence. In this variant, the sampled signal output at the specified sampling time T is the value used to calculate the analyte concentration.

The measurement time positions T ₁ , T ₂ , T _3, ... At which the system samples the output signal of the biosensor. The T _N is predetermined based on a regression analysis of the large sample size of the actual physiological fluid sample, based on both the qualitative category of the estimated analyte and the measured or estimated physical properties. Applicants note that although the appropriate sampling time is measured from the beginning of the test sequence, any suitable data can be used to determine when to sample the output signal. In practice, the system can be programmed to sample the output signal in a suitable time sampling period, such as one sampling, for example every 100 milliseconds or even about every 1 millisecond in the entire test sequence. By sampling the full transient signal output during the test sequence, the system can perform all necessary calculations near the end of the test sequence rather than trying to synchronize the set point and sampling time, which can introduce timing errors due to system delay.

With the description and teachings provided herein, Applicants have been able to devise a glucose test strip having a substrate, a plurality of electrodes disposed on the substrate and connected to respective electrode connectors. The test strip (100) includes a reagent disposed on at least one of the plurality of electrodes, wherein at least one of the electrodes is configured to sense a physical property of a fluid sample deposited on at least one electrode, At least another electrode is configured to measure the output signal from the sample upon application of the input signal to the sample. An instruction for use with a glucose meter is included with the test strip. The indicia includes a cover that is embedded within a suitable communication medium (e.g., paper, computer, internet, auditory or visual media, etc.) to insert the electrode connector of the test strip into the test strip port of the glucose meter. A meter designated for use with a glucose test strip comprises a test strip port connector configured to connect to a respective electrode connector of the test strip and a plurality of electrodes of the test strip connected to each electrode connector of the test strip during the test sequence, And a microprocessor in electrical communication with the test strip port connector to sense a signal or apply an electrical signal. The indicia may also be used by the microprocessor 300 to (a) initiate the analyte test sequence upon deposition of the sample; (b) applying a signal to the sample to determine a physical property of the sample; (c) introduce a different signal into the sample; (d) measuring at least one output signal from at least one of the electrodes; (e) deriving an estimated analyte concentration from at least one output signal at a time position of the plurality of predetermined time positions from the start of the test sequence; (f) acquiring new parameters of the biosensor based on the estimated analyte concentration and the physical characteristics of the sample; (g) calculating the analyte concentration based on the new parameters of the biosensor and the output signal measured at one time position or at another time position from a plurality of predetermined time positions from the start of the test sequence; (E.g., paper, a computer, the Internet, an auditory or visual medium, etc.) to deposit a fluid sample proximate to at least one of the plurality of electrodes, And the like.

Although the technique described herein is directed to the determination of glucose, this technique may also be applied to other analytes that are affected by the physical property (s) of the fluid sample in which the analyte (s) are placed in the fluid sample With appropriate modifications). For example, the physical properties (e.g., hematocrit, viscosity, or density, etc.) of a physiological fluid sample can be considered in the determination of ketone or cholesterol in a fluid sample, which may be a physiological fluid, calibration or control fluid. Other biosensor configurations may also be used. See, for example, U.S. Patent No. 6179979, which is incorporated herein by reference in its entirety; 6193873; 6284125; 6413410; 6475372; 6716577; 6749887; 6863801; 6890421; 7045046; 7291256; The biosensors shown and described in U.S. Pat. No. 7498132 may be used in conjunction with the various embodiments described herein.

As is known, the detection of physical properties need not be performed by an alternating signal, but can be performed with other techniques. For example, a suitable sensor can be used to determine viscosity or other physical properties (e.g., U.S. Patent Application Publication No. 20100005865 or EP1804048 B1). Alternatively, the viscosity was determined and determined according to the method of Blood Rheology and Hemodynamics by Oguz K. Baskurt, MD, Ph.D., 1 and Herbert J. Meiselman, Sc.D., Seminars in Thrombosis and Hemostasis , volume 29, number 5, 2003], based on the known relationship between hematocrit and viscosity.

As previously described, a microcontroller or equivalent microprocessor (and a related component that allows the microcontroller to function for its intended purpose in an intended environment, such as, for example, the processor 300 of FIG. 2B) And may be used with computer code or software instructions to carry out the methods and techniques described in the specification. Applicants have discovered that the exemplary microcontroller 300 of FIG. 2B (along with the appropriate components for functional operation of the processor 300) is loaded with computer software that represents the logic diagrams of FIGS. 6 and 7, Microcontroller 300, along with associated connector 220 and interface 306 and equivalents thereof,

(a) means for applying first and second input signals to a sample deposited on a biosensor during a test sequence;

(b) means for measuring a physical characteristic of a sample from output signals of one of the first and second input signals;

(c) means for deriving an estimated glucose concentration at one of a plurality of predetermined time points from the beginning of the test sequence based on the other of the first and second input signals;

(d) means for generating a new parameter of the biosensor based on the physical property and the estimated glucose concentration; And

(e) is a means for calculating the glucose concentration based on the new parameters of the biosensor and the output signal at one of the plurality of predetermined time positions or at another time position.

In particular, the means (602, 604, 606, 608, 610) for the first technique for performing functions (a) through (e) (and the hardware or software equivalent thereof); Modules 602, 604, 606, 614, 616, 618 for the second technique; And modules 602, 604, 606, 608, 610, 622, 624 for the third technique.

Furthermore, while the present invention has been described with reference to specific variations and illustrative figures, those skilled in the art will recognize that the invention is not limited to the described variations or drawings. It will also be appreciated that where the above-described methods and steps represent certain events that occur in a predetermined order, certain steps need not be performed in the order described, and that the steps may be performed in any order so long as the embodiment allows the embodiment to function for its intended purpose As shown in FIG. Thus, where there are variations of the invention that are within the spirit of the invention or equivalent to the invention as identified in the claims, the patent is also intended to include such variations.

Example

The following Examples include  It may or may not be billed:

1. A method for determining analyte concentration from a fluid sample with a biosensor having reagents disposed on at least two of the electrodes and at least one of the electrodes,

Depositing a fluid sample on at least one electrode to initiate an analyte test sequence; Applying a signal to the sample to determine a physical property of the sample;

Introducing another signal into the sample to cause a physical conversion of the sample; Measuring at least one output signal from at least one of the electrodes due to physical conversion of the sample;

Obtaining an estimated analyte concentration from at least one predetermined parameter of the biosensor and at least one output signal at one time position of a plurality of predetermined time positions from the start of the test sequence;

Generating a first parameter coefficient of the biosensor based on the physical characteristics of the sample;

Calculating a first analyte concentration based on a first parameter coefficient of the biosensor and at least one output signal measured at a time position of one of a plurality of predetermined time positions from the start of the test sequence;

Generating a second parameter coefficient of the biosensor based on the estimated analyte concentration and the physical characteristics of the sample;

Calculating a second analyte concentration based on a second parameter coefficient of the biosensor and at least one output signal measured at a time position of one of a plurality of predetermined time positions from the start of the test sequence;

Generating a third parameter coefficient of the biosensor based on the first analyte concentration and physical characteristics;

Calculating a third analyte concentration based on the third parameter coefficient of the biosensor and at least one output signal measured at one time position from a plurality of predetermined time positions from the start of the test sequence; And

And reporting at least one of the first, second, and third analyte concentrations.

Example 2. A method for determining analyte concentration from a fluid sample with a biosensor having reagents disposed on at least two of the electrodes and at least one of the electrodes,

Initiating an analyte test sequence upon deposition of the sample; Applying a signal to the sample to determine a physical property of the sample;

Introducing another signal into the sample to cause a physical conversion of the sample;

Measuring at least one output signal from at least one of the electrodes due to physical conversion of the sample;

Deriving an estimated analyte concentration from at least one output signal measured at one time position of a plurality of predetermined time positions from the start of the test sequence;

Obtaining new parameters of the biosensor based on the estimated analyte concentration and the physical characteristics of the sample;

Calculating an analyte concentration based on a new parameter of the biosensor and an output signal measured at one time position or a different time position from a plurality of predetermined time positions from the start of the test sequence; And

And notifying the analyte concentration.

Example 3. A method for determining analyte concentration from a fluid sample with a biosensor having a reagent disposed on at least two of the electrodes and at least one of the electrodes,

Initiating an analyte test sequence upon deposition of a sample on a biosensor; Applying a signal to the sample to determine a physical property of the sample;

Introducing another signal into the sample to cause a physical conversion of the sample;

Measuring at least one output signal from at least one of the electrodes due to physical conversion of the sample;

Generating a first new deployment parameter of the biosensor based on the physical characteristics of the sample;

Calculating a first analyte concentration based on a first new batch parameter of the biosensor and an output signal measured at one of a plurality of predetermined time positions from the start of the test sequence; And

And reporting the first analyte concentration.

Example 4. In the method of Example 3,

Generating a third parameter of the biosensor based on the physical property and the first analyte concentration;

Calculating a third analyte concentration based on a third parameter of the biosensor and an output signal measured at a time position of one of a plurality of predetermined time positions from the start of the test sequence; And

Further comprising notifying the third analyte concentration instead of the first analyte concentration.

5. The method of any one of embodiments 1 to 3, wherein the parameters of the biosensor include a placement slope and the new parameters of the biosensor include a new placement slope.

Embodiment 6. The method of embodiment 5, wherein the application of the first signal and the introduction of the second signal can be performed in a sequential order.

Embodiment 7: The method of any one of embodiments 1 to 3, wherein the application of the first signal overlaps the introduction of the second signal.

Embodiment 8: The method of any one of embodiments 1 to 3, wherein the application of the first signal comprises directing an alternating signal to a sample so that the physical properties of the sample can be determined from the output of the alternating signal , The physical properties include at least one of the viscosity, hematocrit, temperature and density of the sample, or a combination thereof.

9. The method of embodiment 5 wherein the physical property comprises an impedance characteristic indicative of a hematocrit of the sample and the analyte comprises glucose.

10. The method of embodiment 9, wherein the impedance characteristic of the sample can be determined by a formula of the form:

[Equation 4.2]

here:

The IC exhibiting impedance characteristics;

M is the magnitude of the measured impedance | Z | (in ohms);

P represents the phase difference between input and output signals (in degrees);

y ₁ may be about -3.2e-08 and +/- 10%, 5%, or 1% of the provided numerical value (and may be 0 depending on the frequency of the input signal);

y ₂ is (with and be zero or even negative, depending on the frequency of the input signal) of about 4.1e-03 and that can be ± 10% of the given numerical value, 5% or 1% and;

y ₃ may be about -2.5 e + 01 and +/- 10%, 5% or 1% of the numerical value provided;

y ₄ can be about 1.5e-01 and +/- 10%, 5% or 1% of the provided numerical value (and can be zero or even negative depending on the frequency of the input signal);

y ₅ can be about 5.0 and +/- 10%, 5% or 1% of the provided numerical value (and can be zero or even negative depending on the frequency of the input signal).

11. The method of embodiment 9, wherein directing comprises driving first and second alternating signals of different respective frequencies, wherein the first frequency may be lower than the second frequency.

12. The method of embodiment 11 wherein the first frequency may be at least one order of magnitude lower than the second frequency.

13. The method of embodiment 11 or 12, wherein the first frequency comprises any frequency in the range of about 10 kHz to about 250 kHz.

14. The method of embodiment 5 wherein the time position of one of the plurality of predetermined time positions for measuring at least one output signal during the test sequence may be approximately 2.5 seconds after the start of the test sequence.

15. The method of embodiment 14 wherein the time position of one of the plurality of predetermined time positions comprises a time period overlapping with a time point of 2.5 seconds after the start of the test sequence.

16. The method of embodiment 5 wherein the time position of the other of the plurality of predetermined time positions for measuring at least one output signal during the test sequence may be a time point of about 5 seconds after the start of the test sequence .

17. The method of embodiment 5 wherein the time position of one of the plurality of predetermined time positions comprises any time less than 5 seconds from the start of the test sequence.

18. The method of embodiment 5 wherein the time position of the other of the plurality of predetermined time positions comprises any time less than 10 seconds from the start of the test sequence.

19. The method of embodiment 17 or 18, wherein the time position of one of the plurality of predetermined time positions includes a time period overlapping with a time point of 2.5 seconds after the start of the test sequence, Wherein the other time position of the positions comprises a time period overlapping with a 5 second time point after the start of the test sequence.

Example 20. In the method of Example 1 or Example 2, the calculation of the estimated analyte concentration can be calculated from the following formulas:

here

G ₁ represents the first analyte concentration;

I _E represents the total output signal from the biosensor measured at one of the plurality of predetermined time positions;

P1 represents the slice parameter of the biosensor, where P1 may be about 475 nanoamperes;

P2 represents the slope parameter of the biosensor, where P2 may be about 9.5 nanoamperes / (mg / dL).

Example 21. In the method of Example 1, the calculation of the first analyte concentration can be calculated from the following formulas:

here

G ₁ represents the first analyte concentration;

I _E represents the total output signal from the biosensor measured at one of the plurality of predetermined time positions;

P1 represents the slice parameter of the biosensor, where P1 may be about 475 nanoamperes;

P2 represents the slope parameter of the biosensor, where P2 may be about 9.5 nanoamperes / (mg / dL);

x ₂ represents the biosensor parameter coefficient based on the physical characteristics of the sample.

Example 22. In the method of Example 1 or Example 2, the calculation of the second analyte concentration can be calculated by the following formulas:

G ₂ represents the second analyte concentration;

I _E represents the total output signal from the biosensor measured at one of a plurality of predetermined time positions or at another time position;

P1 represents the slice parameter of the biosensor, where P1 may be about 475 nanoamperes;

P2 represents the slope parameter of the biosensor, where P2 may be about 9.5 nanoamperes / (mg / dL);

x ₃ represents the coefficient from the matrix based on both the physical properties of the sample and the estimated analyte concentration.

Example 23. In the method of Example 1 or Example 4, the calculation of the third analyte concentration can be calculated by the following formulas:

G ₃ represents the third analyte concentration;

I _E represents the total output signal from the biosensor measured at one of a plurality of predetermined time positions or at another time position;

P1 represents the slice parameter of the biosensor, where P1 may be about 475 nanoamperes;

P2 represents the slope parameter of the biosensor, where P2 may be about 9.5 nanoamperes / (mg / dL);

x ₃ represents the coefficient from the matrix based on both the physical properties of the sample and the first analyte concentration.

24. The method of embodiment 5, wherein at least two electrodes and at least two other electrodes are disposed in the same chamber provided on the substrate.

25. The method of any one of the preceding embodiments, wherein the at least two electrodes comprise two electrodes for measuring physical properties and analyte concentration.

Embodiment 26. The method of any one of the preceding embodiments, wherein the at least two electrodes comprise a first set of at least two electrodes for determining the physical properties of the sample and at least two different And a second set of electrodes.

Embodiment 27. The method of embodiment 25 or 26, wherein all of the electrodes are disposed on the same plane defined by the substrate of the biosensor.

Embodiment 28. The method of embodiment 26, wherein a third electrode is disposed proximate to the first set of at least two electrodes and can be connected to the second set of at least two other electrodes.

Embodiment 29. The system of any one of embodiments 25-27, wherein the reagent may be disposed proximate to at least two other electrodes, and no reagent may be disposed on at least two electrodes.

Embodiment 31. An analyte measurement system,

As a test strip,

Board;

A plurality of electrodes connected to the respective electrode connectors; And

As an analyzer,

housing;

A test strip port connector configured to be connected to each of the electrode connectors of the test strip; And

And an analyte meter comprising a microprocessor in electrical communication with a test strip port connector for sensing electrical signals from a plurality of electrodes or applying electrical signals during a test sequence,

During the test sequence,

(a) initiating an analyte test sequence upon deposition of the sample;

(b) applying a signal to the sample to determine a physical property of the sample;

(c) introduce a different signal into the sample;

(d) measuring at least one output signal from at least one of the electrodes;

(e) deriving an estimated analyte concentration from at least one output signal at a time position of the plurality of predetermined time positions from the start of the test sequence;

(f) acquiring new parameters of the biosensor based on the estimated analyte concentration and the physical characteristics of the sample;

(g) calculating the analyte concentration based on the new parameters of the biosensor and the output signal measured at one time position or at another time position from a plurality of predetermined time positions from the start of the test sequence; And

(h) the analyte concentration.

Embodiment 32. The system of embodiment 31, wherein the plurality of electrodes comprises at least two electrodes for measuring physical properties and at least two other electrodes for measuring analyte concentrations.

Embodiment 33. The system of embodiment 32 wherein at least two electrodes and at least two other electrodes are disposed in the same chamber provided on the substrate.

[0214] [00200] Embodiment 34. The system of embodiment 31, wherein the plurality of electrodes comprises two electrodes for measuring physical properties and analyte concentration.

[0060] 35. The system of any of embodiments 31-34, wherein all of the electrodes are disposed on the same plane defined by the substrate.

Embodiment 36. The system of any one of embodiments 31-35, wherein the reagent may be disposed proximate to at least two other electrodes, and no reagent may be disposed on at least two electrodes.

[0099] Embodiment 37. The system of embodiment 31 wherein the time position of one of the plurality of predetermined time positions for measuring at least one output signal during the test sequence may be approximately 2.5 seconds after the start of the test sequence.

[0099] Embodiment 38. The system of embodiment 31 wherein the time location of one of the plurality of predetermined time positions comprises a time period overlapping with a time of 2.5 seconds after the start of the test sequence.

Embodiment 39. The system of embodiment 31, wherein the time position of the other of the plurality of predetermined time positions for measuring at least one output signal during the test sequence may be a time point of about 5 seconds after the start of the test sequence .

40. The system of embodiment 31, wherein the time location of one of the plurality of predetermined time positions comprises any time less than 5 seconds from the start of the check sequence.

[0099] 41. The system of embodiment 31, wherein the time location of the other of the plurality of predetermined time locations comprises any time less than 10 seconds from the start of the test sequence.

Embodiment 42. The system of embodiment 40 or embodiment 41, wherein the time position of one of the plurality of predetermined time positions includes a time period overlapping with a time point of 2.5 seconds after the start of the test sequence, Wherein the other time position of the positions comprises a time period overlapping with a 5 second time point after the start of the test sequence.

Example 43. As a glucose meter,

housing;

A test strip port connector configured to be connected to each of the electrode connectors of the biosensor; And

(a) means for applying first and second input signals to a sample deposited on a biosensor during a test sequence;

(b) means for measuring a physical characteristic of a sample from output signals of one of the first and second input signals;

(c) means for deriving an estimated glucose concentration at one of a plurality of predetermined time positions from the beginning of the test sequence based on the other of the first and second input signals;

(d) means for generating a new parameter of the biosensor based on the physical property and the estimated glucose concentration; And

(e) means for calculating a glucose concentration based on a new parameter of the biosensor and an output signal at a time position or at another time position of the plurality of predetermined time positions; And

And an indicator for providing an output of glucose concentration from said means.

[0080] 44. The meter of embodiment 43, wherein the means for measuring comprises means for applying a first AC signal to the biosensor and means for applying a second constant signal to the biosensor.

Embodiment 45. The meter of embodiment 43, wherein the means for deriving comprises means for estimating analyte concentration based on a predetermined sampling time from the beginning of the test sequence.

Embodiment 46. The meter of embodiment 43, wherein the means for generating comprises means for correlating physical properties with the estimated glucose concentration and the new parameters of the biosensor.

[0099] Embodiment 47. The meter of embodiment 43, wherein the means for calculating comprises determining the glucose concentration from the measured current at a different one of the plurality of predetermined time positions and the new parameters of the biosensor.

Embodiment 48. The apparatus of embodiment 47, wherein one of the plurality of time points includes a time point of about 2.5 seconds from the start of the test sequence, and the other time position among the plurality of predetermined time positions is about A meter containing a 5 second point of view.

[0215] Embodiment 49. The meter of embodiment 47, wherein one of the plurality of time points includes a time period of about 2.5 seconds from the beginning of the test sequence, and the other time position of the plurality of predetermined time positions is from the start of the test sequence A meter comprising a time interval of about 5 seconds.

Example 50. A method for demonstrating increased accuracy of a test strip,

Providing an arrangement of test strips;

Introducing a reference sample containing an analyte of reference concentration to each test strip of batches of test strips to initiate a test sequence;

Reacting the analyte with a reagent on each test strip to cause physical conversion of the analyte proximate to the two electrodes;

Applying a signal to the reference sample to determine a physical property of the reference sample;

Introducing a different signal into the reference sample; Measuring at least one output signal from the test strip;

Deriving an estimated analyte concentration of the reference sample from at least one output signal measured at a time position of the plurality of predetermined time positions from the start of the test sequence;

Obtaining a new parameter of the test strip based on the estimated analyte concentration of the reference sample and the physical characteristics of the reference sample;

Based on the new parameters of the test strip and the output signal measured at different one of the plurality of predetermined time positions from the start of the test sequence to provide an analyte concentration value for each test strip of the batch of test strips, Calculating the analyte concentration of the sample, wherein calculating at least 95% of the final analyte concentration values of the batches of test strips is within ± 15% of the reference analyte concentration.

Example 51. The method of embodiment 50, wherein at least 86% of the glucose concentration is within +/- 15% of these glucose concentrations above 100 mg / dL.

[0213] 52. The method of embodiment 50 or 51, wherein the parameters of the biosensor include a placement slope, and the new parameters of the biosensor include a new placement slope.

[0099] Embodiment 53. The method of embodiment 52, wherein the application of the first signal and the introduction of the second signal can be performed in a sequential order.

[0216] 54. The method as in embodiment 50 or embodiment 51, wherein the application of the first signal overlaps with the introduction of the second signal.

Embodiment 55. The method of embodiment 50 or 51, wherein the application of the first signal comprises directing an alternating signal to a sample so that the physical property of the sample can be determined from the output of the alternating signal, The viscosity of the sample, the hematocrit, the temperature and the density, or a combination thereof.

[0323] Embodiment 56. The method of embodiment 52, wherein the physical property comprises an impedance characteristic indicative of a hematocrit of the sample, and the analyte comprises glucose.

[0099] Embodiment 57. The method of embodiment 56, wherein directing comprises driving first and second alternating signals of different respective frequencies, wherein the first frequency may be lower than the second frequency.

[0099] Embodiment 58. The method of embodiment 57, wherein the first frequency may be at least one order of magnitude lower than the second frequency.

[0099] Embodiment 59. The method of embodiment 57 or 58, wherein the first frequency comprises any frequency in the range of about 10 kHz to about 250 kHz.

[0075] [0069] 60. The method of embodiment 52, wherein the time position of one of the plurality of predetermined time positions for measuring at least one output signal during the test sequence may be about 2.5 seconds after the start of the test sequence.

[0099] Embodiment 61. The method of embodiment 60, wherein the time position of one of the plurality of predetermined time positions comprises a time period overlapping with a time point of 2.5 seconds after the start of the test sequence.

[0452] Embodiment 62. The method of embodiment 61, wherein the time position of the other of the plurality of predetermined time positions for measuring at least one output signal during the test sequence may be about 5 seconds after the start of the test sequence .

[0099] Embodiment 63. The method of embodiment 52, wherein the time position of one of the plurality of predetermined time positions comprises any time less than 5 seconds from the start of the test sequence.

[0099] Embodiment 64. The method of embodiment 52, wherein the time position of the other of the plurality of predetermined time positions comprises any time less than 10 seconds from the start of the test sequence.

[0075] 65. The method of embodiment 63 or 64, wherein the time location of one of the plurality of predetermined time positions comprises a time period overlapping with a time of 2.5 seconds after the start of the test sequence, Wherein the other time position of the positions comprises a time period overlapping with a 5 second time point after the start of the test sequence.

Example 66. A glucose test strip,

Board:

A plurality of electrodes disposed on the substrate and connected to the respective electrode connectors;

A reagent disposed on at least one of the plurality of electrodes, wherein at least one of the electrodes is configured to sense a physical property of a fluid sample deposited on at least one electrode, A reagent configured to measure an output signal from a sample upon application of a signal; And

An indicator for use with a glucose meter, the indicator comprising a label for allowing the user to insert the electrode connectors of the test strip into the test strip port of the glucose meter, the meter being connected to the respective electrode connectors of the test strip And a plurality of electrodes of the test strip connected to the respective electrode connectors of the test strip during the test sequence and for electrically communicating with the test strip port connectors to sense electrical signals or to apply electrical signals Wherein the instructions cause the microprocessor to: (a) initiate an analyte test sequence upon deposition of the sample; (b) applying a signal to the sample to determine a physical property of the sample; (c) introduce a different signal into the sample; (d) measuring at least one output signal from at least one of the electrodes; (e) deriving an estimated analyte concentration from at least one output signal at a time position of the plurality of predetermined time positions from the start of the test sequence; (f) acquiring new parameters of the biosensor based on the estimated analyte concentration and the physical characteristics of the sample; (g) calculating the analyte concentration based on the new parameters of the biosensor and the output signal measured at one time position or at another time position from a plurality of predetermined time positions from the start of the test sequence; And (h) a marker for causing the user to actuate to notify the analyte concentration of depositing a fluid sample proximate to at least one of the plurality of electrodes.

Embodiment 67. The method, system, instrument, test strip or biosensor of any one of embodiments 1-66, wherein the physical properties, denoted by H, are substantially equal to the impedance characteristics determined by the following formulas: Same method, system, meter, test strip or biosensor:

here:

The IC exhibiting impedance characteristics;

M is the magnitude of the measured impedance | Z | (in ohms);

P represents the phase difference between input and output signals (in degrees);

y ₁ is about -3.2e-08;

y is from about ₂ 4.1e-03 and;

y ₃ is about -2.5 e + 01;

y ₄ is about 1.5e-01;

y ₅ is about 5.0.

Embodiment 68. The method, system, meter, test strip or biosensor of any one of embodiments 1-66, wherein the physical properties, denoted by H, are substantially equal to the impedance characteristics determined by the following formulas: Same method, system, meter, test strip or biosensor:

here;

IC represents the impedance characteristic [%]; M represents the magnitude of the impedance [ohm];

y is from about ₁ 1.2292e1 gt;

y ₂ is between about -4.3431e2;

y3 is about 3.5260e4.

Further aspects of the present invention

Section "A"

The following aspects, which were originally proposed in U.S. Provisional Patent Application No. 61 / 581,087 (Attorney Docket DDI5220USPSP), form part of this disclosure:

1. A method for determining an analyte concentration from a physiological sample with a biosensor having reagents disposed on at least two of the electrodes and at least one of the electrodes,

Depositing a physiological sample on at least two electrodes to initiate an analyte test sequence;

Applying a first electrical signal to the sample to measure a physical characteristic of the sample;

Deriving a batch gradient for the reagent based on the measured physical properties from an equation of the form:

x = aH ²  + bH + c

Where x represents the derived gradient of placement,

H is the measured or estimated hematocrit,

a represents about 1.4e-6,

b represents about -3.8e-4,

c represents about 3.6e-2;

Introducing a second electrical signal into the sample;

Measuring an output current from at least one of the at least two electrodes; And

Calculating an analyte concentration based on the measured output current and the resulting batch slope in the following form of equation:

here

G _o represents the analyte concentration,

I _E represents the current (proportional to the analyte concentration) determined from the sum of the terminal currents measured at a predetermined time,

The slice represents a calibration parameter for the placement of the biosensors,

x represents the derived gradient from the derivation step.

2. A method of determining analyte concentration from a physiological sample with a biosensor having reagents disposed on at least two of the electrodes and at least one of the electrodes,

Depositing a physiological sample on at least two electrodes to initiate an analyte test sequence;

Applying a first electrical signal to the sample to measure a physical characteristic of the sample;

Deriving a batch gradient for the reagent based on the measured physical properties;

Introducing a second electrical signal into the sample;

Measuring an output current from at least one of the at least two electrodes; And

And calculating the analyte concentration based on the measured output current and the derived batch slope from the measured physical properties of the sample.

3. The method according to claim 1, wherein the application of the first signal and the introduction of the second signal are performed in a sequential order.

4. The method of claim 1, wherein the application of the first signal overlaps with the introduction of the second signal.

5. The method of claim 1, wherein the application of the first signal directs the alternating signal to a sample so that the physical properties of the sample are determined from the output of the alternating signal.

6. The method of claim 1, wherein the application of the first signal directs the optical signal to a sample such that the physical property of the sample is determined from the output of the optical signal.

7. The method according to claim 5, wherein the physical property comprises hematocrit and the analyte comprises glucose.

8. The method of claim 1, wherein the physical property comprises at least one of viscosity, hematocrit and density of the sample.

9. The method of embodiment A5, wherein directing comprises driving first and second AC signals of different respective frequencies, wherein the first frequency is lower than the second frequency.

10. The method of claim 9, wherein the first frequency is at least one order of magnitude lower than the second frequency.

11. The method of embodiment A10, wherein the first frequency comprises any frequency in the range of about 10 kHz to about 90 kHz.

12. The method according to claim 1, wherein deriving comprises calculating a placement slope from a formula of the form:

x = aH ²  + bH + c

Where x represents the derived gradient from the derivation step,

H is the measured or estimated hematocrit,

a represents about 1.4e-6,

b represents about -3.8e-4,

c represents about 3.6e-2.

13. In the method of solar A12, the calculation of the analyte concentration comprises the step of using an equation of the following form:

here

G _o represents the analyte concentration,

I _E represents the current (proportional to the analyte concentration) determined from the sum of the measured terminal currents at a predetermined time of about 5 seconds after the start of the test sequence,

The slice represents a calibration parameter for the placement of the biosensors,

x represents the derived gradient from the derivation step.

14. An analyte measurement system,

As a test strip,

Board;

A plurality of electrodes connected to the respective electrode connectors; And

As an analyzer,

housing;

A test strip port connector configured to be connected to each of the electrode connectors of the test strip; And

And a microprocessor in electrical communication with a test strip port connector to sense electrical signals from a plurality of electrodes during a test sequence or to apply electrical signals, the microprocessor comprising: (a) Applying a first electrical signal to a plurality of electrodes to derive a placement gradient defined by the physical properties of the physiological fluid sample and (b) applying a first electrical signal to the plurality of electrodes such that the analyte concentration is determined based on the derived placement gradient. And to apply a second electrical signal.

15. The system of embodiment A14, wherein the plurality of electrodes comprises at least two electrodes for measuring physical properties and at least two other electrodes for measuring analyte concentrations.

16. The system of embodiment A14, wherein at least two electrodes and at least two other electrodes are disposed in the same chamber provided on the substrate.

17. The system of embodiment A14, wherein at least two electrodes and at least two other electrodes are disposed in different chambers provided on the substrate.

18. The system of embodiment A14, wherein at least two electrodes comprise two electrodes for measuring physical properties and analyte concentration.

19. In a system of solar A16, solar A17 or solar A18, all the electrodes are arranged on the same plane defined by the substrate.

20. The system of embodiment A17 or A18, wherein the reagent is disposed close to at least two other electrodes, and no reagent is disposed on at least two electrodes.

21. In the system of solar A14, the placement gradient is calculated from the following equation:

x = aH ²  + bH + c

Where x represents the derived gradient from the derivation step,

H represents the measured or estimated hematocrit,

a represents about 1.4e-6,

b represents about -3.8e-4,

c represents about 3.6e-2.

22. In the system of solar A21, the analyte concentration is determined from an equation of the form:

here

G _o represents the analyte concentration,

I _E represents the current (proportional to the analyte concentration) determined from the sum of the terminal currents measured at a predetermined time,

The slice represents the calibration parameters for the placement of the test strips,

x represents the derived gradient from the derivation step.

23. An analyte measurement system,

As a test strip,

Board;

A plurality of electrodes connected to the respective electrode connectors; And

As an analyzer,

housing;

A test strip port connector configured to be connected to each of the electrode connectors of the test strip; And

And a microprocessor in electrical communication with a test strip port connector to sense electrical signals from a plurality of electrodes or to apply electrical signals, the microprocessor comprising: (a) Applying a first electrical signal to a plurality of electrodes to derive a placement gradient defined by the physical properties of the sample and (b) applying a first electrical signal to the plurality of electrodes at a derived placement slope obtained from the physical properties of the sample within about 10 seconds of the start of the test sequence And to apply a second electrical signal to the plurality of electrodes such that an analyte concentration is determined based on the second electrical signal.

24. The system of embodiment A23, wherein the plurality of electrodes comprises at least two electrodes for measuring physical properties and at least two other electrodes for measuring analyte concentrations.

25. The system of embodiment A23, wherein at least two electrodes and at least two other electrodes are disposed in the same chamber provided on the substrate.

26. The system of embodiment A23, wherein at least two electrodes and at least two other electrodes are disposed in different chambers provided on the substrate.

27. In a system of solar A23, at least two electrodes include two electrodes for measuring physical properties and analyte concentration.

28. In a system of solar A24, solar A25 or solar A26, all of the electrodes are arranged on the same plane defined by the substrate.

29. A system as in Sun A23 or Solar A24, wherein the reagent is disposed close to at least two other electrodes, and no reagent is disposed on at least two electrodes.

30. In the system of Solar A23, the placement gradient is calculated from the following equation:

x = aH ²  + bH + c

Where x represents the derived gradient from the derivation step,

H represents the measured or estimated hematocrit,

a represents about 1.4e-6,

b represents about -3.8e-4,

c represents about 3.6e-2.

31. In the system of solar A30, the analyte concentration is calculated from the equation of the form:

here

G _o represents the analyte concentration,

I _E represents the current (proportional to the analyte concentration) determined from the sum of the terminal currents measured at a predetermined time,

The slice represents the calibration parameters for the placement of the test strips,

x represents the derived gradient from the derivation step.

32. A method for obtaining increased accuracy of a test strip,

Providing an arrangement of test strips;

Introducing a reference sample containing an analyte of reference concentration into each batch of test strips to initiate a test sequence;

Reacting the analyte with a reagent on the test strip to cause physical conversion of the analyte between the two electrodes;

Determining a physical property of the reference sample;

Deriving a placement slope for the placement of the test strips based on the determined physical properties of the reference sample;

Sampling the electrical output of the reference sample at a predetermined time during the test sequence;

Calculating an analyte concentration based on the batch slope and the sampled electrical output to provide a final analyte concentration value for each batch of test strips, wherein at least 95% of the final analyte concentration values of the batches of test strips Lt; RTI ID = 0.0 > 15% < / RTI > of the reference analyte concentration.

33. The method of claim 32, wherein the application of the first signal and the introduction of the second signal are performed in a sequential order.

34. The method of claim 32, wherein the application of the first signal overlaps with the introduction of the second signal.

35. The method of embodiment A32, wherein the application of the first signal comprises directing an alternating signal to a sample so that the physical properties of the sample are determined from the output of the alternating signal.

36. The method of embodiment A32, wherein the application of the first signal directs the optical signal to a sample such that the physical properties of the sample are determined from the output of the optical signal.

37. The method of claim 36 wherein the physical property comprises hematocrit and the analyte comprises glucose.

38. The method of claim 36, wherein the physical properties comprise at least one of viscosity, hematocrit and density.

39. The method of embodiment A34, wherein directing comprises driving first and second AC signals of different respective frequencies, wherein the first frequency is lower than the second frequency.

40. The method of A39, wherein the first frequency is at least one order of magnitude lower than the second frequency.

41. The method of embodiment A40, wherein the first frequency comprises any frequency in the range of about 10 kHz to about 90 kHz.

42. The method of embodiment A32, wherein deriving comprises calculating a placement slope from an equation of the form:

x = aH ²  + bH + c

Where x represents the derived gradient from the derivation step,

H represents the measured or estimated hematocrit,

a represents about 1.4e-6,

b represents about -3.8e-4,

c represents about 3.6e-2.

43. The method of embodiment A42, wherein the calculation of the analyte concentration comprises the step of using an equation of the form:

here

G _o represents the analyte concentration,

I _E represents the current (proportional to the analyte concentration) determined from the sum of the terminal currents measured at a predetermined time,

The slice represents the calibration parameters for the placement of the test strips,

x represents the derived gradient from the derivation step.

44. A method for determining analyte concentration from a physiological sample,

Depositing a physiological sample on the biosensor;

Applying electrical signals to the sample to convert the analyte to a different material;

Measuring the physical properties of the sample;

Obtaining a signal output from the sample;

Deriving parameters of the biosensor from measured physical properties; And

Determining an analyte concentration based on the derived parameters of the biosensor and the signal output of the sample.

45. The method of embodiment A44, wherein the measuring step comprises applying a first electrical signal to the sample to measure a physical property of the sample.

46. The method of embodiment A44, wherein obtaining comprises introducing a second electrical signal to the sample.

47. The method of embodiment A46, wherein the application of the first signal and the introduction of the second signal are performed in a sequential order.

48. The method of embodiment A46, wherein the application of the first signal overlaps the introduction of the second signal.

49. The method of embodiment A46, wherein the application of the first signal comprises directing an alternating signal to a sample so that the physical properties of the sample are determined from the output of the alternating signal.

50. The method of embodiment A44, wherein the application of the first signal directs the optical signal to a sample such that the physical properties of the sample are determined from the output of the optical signal.

51. The method according to any one of the preceding claims, wherein the physical property comprises hematocrit and the analyte comprises glucose.

52. The method of embodiment A49 or A50, wherein the physical property comprises at least one of viscosity, hematocrit and density.

53. The method of embodiment A49, wherein the directing comprises driving first and second alternating signals of different respective frequencies, wherein the first frequency is lower than the second frequency.

54. The method of Solar A53, wherein the first frequency is at least one order of magnitude lower than the second frequency.

55. The method of Solar A54, wherein the first frequency comprises any frequency within the range of about 10 kHz to about 90 kHz.

56. The method of embodiment A44, wherein deriving comprises calculating a placement slope from an equation of the form:

x = aH ²  + bH + c

Where x represents the derived gradient from the derivation step,

H represents the measured or estimated hematocrit,

a represents about 1.4e-6,

b represents about -3.8e-4,

c represents about 3.6e-2.

57. The method of embodiment A56, wherein the calculation of the analyte concentration comprises the step of using an equation of the form:

here,

G _o represents the analyte concentration,

I _E represents the current (proportional to the analyte concentration) determined from the sum of the terminal currents measured at a predetermined time,

The slice represents the calibration parameters for the placement of the test strips,

x represents the derived gradient from the derivation step.

Section "B"

The following aspects, which were originally proposed in U.S. Provisional Patent Application No. 61 / 581,089 (Attorney Docket DDI5220USPSP1), form part of this disclosure:

1. A method for determining analyte concentration from a physiological sample with a biosensor having reagents disposed on at least two electrodes and at least one of the electrodes,

Depositing a physiological sample on at least two electrodes to initiate an analyte test sequence;

Applying a first electrical signal to the sample to derive a physical characteristic of the sample;

Obtaining physical characteristics of the sample;

Specifying a sampling time based on the obtained physical characteristics;

Introducing a second electrical signal into the sample;

Measuring an output current at a specified sampling time from at least one of the at least two electrodes; And

And calculating an analyte concentration based on the measured output current.

2. The method of claim 1, wherein the application of the first signal and the introduction of the second signal are performed in a sequential order.

3. The method of claim 1, wherein the application of the first signal overlaps with the introduction of the second signal.

4. The method of claim 1, wherein the application of the first signal directs the alternating signal to a sample so that the physical properties of the sample are determined from the output of the alternating signal.

5. The method of claim 1, wherein the application of the first signal comprises directing the optical signal to a sample such that the physical properties of the sample are determined from the output of the optical signal.

6. The method according to claim 4, wherein the physical property comprises hematocrit and the analyte comprises glucose.

7. The method of claim 1, wherein the physical property comprises at least one of viscosity, hematocrit and density of the sample.

8. The method of embodiment B4, wherein directing comprises driving first and second AC signals of different respective frequencies, wherein the first frequency is lower than the second frequency.

9. The method of embodiment B8, wherein the first frequency is at least one order of magnitude lower than the second frequency.

10. The method of claim 9, wherein the first frequency comprises any frequency in the range of about 10 kHz to about 90 kHz.

11. In the method of solar B1, the designated sampling time is calculated using the following form:

Here, the " designated sampling time " is designated as the time from the start of the test sequence for sampling the output signal of the test strip,

H represents the physical properties of the sample in the form of a hematocrit;

x ₁ is about 4.3e5;

x ₂ is about -3.9;

x ₃ is about 4.8.

12. In the method of sun B11, the calculation of the analyte concentration is calculated by the following form:

here,

G _o represents the analyte concentration,

I _E represents the current (proportional to the analyte concentration) determined from the sum of the measured end currents at the specified sampling time ;

The slope represents the value obtained from the calibration check of the placement of the test strip producing this particular strip;

The segment represents the value obtained from the calibration check of the placement of the test strip to produce this particular strip.

13. An analyte measurement system,

As a test strip,

Board;

A plurality of electrodes connected to the respective electrode connectors; And

As an analyzer,

housing;

A test strip port connector configured to be connected to each of the electrode connectors of the test strip; And

And a microprocessor in electrical communication with a test strip port connector to sense electrical signals from a plurality of electrodes during a test sequence or to apply electrical signals, the microprocessor comprising: (a) (B) applying a second electrical signal to a plurality of electrodes, and (c) applying a second electrical signal to the plurality of electrodes, And to measure the current output from one of the plurality of electrodes at a designated sampling time such that the concentration is determined.

14. The system of embodiment B13, wherein the plurality of electrodes comprises at least two electrodes for measuring physical properties and at least two other electrodes for measuring analyte concentrations.

15. The system of embodiment B14, wherein at least two electrodes and at least two other electrodes are disposed in the same chamber provided on the substrate.

16. The system of embodiment B14, wherein at least two electrodes and at least two other electrodes are disposed in different chambers provided on the substrate.

17. The system of embodiment B14, wherein at least two electrodes comprise two electrodes for measuring physical properties and analyte concentration.

18. The system of any one of the preceding claims, wherein the electrodes are arranged on the same plane defined by the substrate, in the system of solar B15, solar B16 or solar B17.

19. The system of embodiment B16 or B17, wherein the reagent is disposed close to at least two other electrodes, and no reagent is disposed on at least two electrodes.

20. In the system of embodiment B13, the designated sampling time is calculated using an equation of the form:

Here, the " designated sampling time " is designated as the time from the start of the test sequence for sampling the output signal of the test strip,

H represents the physical properties of the sample in the form of a hematocrit;

x ₁ represents about 4.3e5;

x ₂ represents about -3.9;

x ₃ represents about 4.8.

21. In a system of sun B20, the analyte concentration is determined from an equation of the form:

here

G _o represents the analyte concentration,

I _E represents the current (proportional to the analyte concentration) determined from the sum of the measured end currents at the specified sampling time ;

The slope represents the value obtained from the calibration check of the placement of the test strip producing this particular strip;

The segment represents the value obtained from the calibration check of the placement of the test strip to produce this particular strip.

22. An analyte measurement system,

As a test strip,

Board;

A plurality of electrodes connected to the respective electrode connectors; And

As an analyzer,

housing;

A test strip port connector configured to be connected to each of the electrode connectors of the test strip; And

And a microprocessor in electrical communication with a test strip port connector to sense electrical signals from a plurality of electrodes or to apply electrical signals, the microprocessor comprising: (a) (B) applying a second electrical signal to the plurality of electrodes, and (c) applying a first electrical signal to the plurality of electrodes so as to derive a specific sampling point determined from the physical characteristics of the sample, And to measure the current output from one of the plurality of electrodes at a designated sampling time so that the analyte concentration of the sample is determined based on a specific sampling time within about 10 seconds.

23. The system of embodiment B22, wherein the plurality of electrodes comprises at least two electrodes for measuring physical properties and at least two other electrodes for measuring analyte concentration.

24. The system of embodiment B23, wherein at least two electrodes and at least two other electrodes are disposed in the same chamber provided on the substrate.

25. The system of embodiment B23, wherein at least two electrodes and at least two other electrodes are disposed in different chambers provided on the substrate.

26. The system of embodiment B23, wherein at least two electrodes comprise two electrodes for measuring physical properties and analyte concentration.

27. A system according to any of the preceding claims, wherein in the system of Sun B23, Sun B24, Sun B25, or Sun B26, all the electrodes are disposed on the same plane defined by the substrate.

28. The system of embodiment B22 or B23, wherein the reagent is disposed proximate to at least two other electrodes, and no reagent is disposed on at least two electrodes.

29. In the system of embodiment B22, the designated sampling time is calculated using the following form:

Here, the " designated sampling time " is designated as the time from the start of the test sequence for sampling the output signal of the test strip,

H represents the physical properties of the sample in the form of a hematocrit;

x ₁ represents about 4.3e5;

x ₂ represents about -3.9;

x ₃ represents about 4.8.

30. The system of embodiment B29, wherein the analyte concentration is calculated from an equation of the form:

here,

G _o represents the analyte concentration,

I _E represents the current (proportional to the analyte concentration) determined from the sum of the measured end currents at the specified sampling time ;

The slope represents the value obtained from the calibration check of the placement of the test strip producing this particular strip;

The segment represents the value obtained from the calibration check of the placement of the test strip to produce this particular strip.

31. A method for determining analyte concentration from a physiological sample,

Depositing a physiological sample on the biosensor on which the reagent is deposited;

Applying electrical signals to the sample and the reagent to convert the analyte into a different material;

Obtaining physical characteristics of the sample;

Designating a time for sampling the current output based on the obtained physical characteristics;

Measuring a signal output at a designated sampling time; And

And determining an analyte concentration based on the measured signal output of the sample.

32. The method of embodiment B31, wherein acquiring includes introducing a second electrical signal into the sample to derive a physical characteristic of the sample.

33. The method of aspect B44, wherein applying comprises applying a first electrical signal to a sample to derive a physical property of the sample, wherein the application of the first signal and the introduction of the second signal are performed in a sequential order How it is done.

34. The method of embodiment B33, wherein the application of the first signal overlaps the introduction of the second signal.

35. The method of aspect B33, wherein the application of the first signal comprises directing an alternating signal to a sample so that the physical properties of the sample are determined from the output of the alternating signal.

36. The method of embodiment B33, wherein applying the first signal directs the optical signal to a sample such that the physical properties of the sample are determined from the output of the optical signal.

37. The method of claim 36, wherein the physical property comprises hematocrit and the analyte comprises glucose.

38. The method of embodiment B36 or B37, wherein the physical property comprises at least one of viscosity, hematocrit and density.

39. The method of embodiment B36, wherein directing comprises driving first and second alternating signals of different respective frequencies, wherein the first frequency is lower than the second frequency.

40. The method of embodiment B39, wherein the first frequency is at least one order of magnitude lower than the second frequency.

41. The method of embodiment B40, wherein the first frequency comprises any frequency within the range of about 10 kHz to about 90 kHz.

42. The method of embodiment B31, wherein the designated sampling time is calculated using the following form:

Here, the " designated sampling time " is designated as the time from the start of the test sequence for sampling the output signal of the test strip,

H represents the physical properties of the sample in the form of a hematocrit;

x ₁ represents about 4.3e5;

x ₂ represents about -3.9;

x ₃ represents about 4.8.

43. The method of aspect B42, wherein the calculation of the analyte concentration comprises the step of using an equation of the form:

here

G _o represents the analyte concentration,

I _E represents the current (proportional to the analyte concentration) determined from the sum of the measured end currents at the specified sampling time ;

The slope represents the value obtained from the calibration check of the placement of the test strip producing this particular strip;

The segment represents the value obtained from the calibration check of the placement of the test strip to produce this particular strip.

Section "C"

The following aspects, which were originally proposed in U.S. Provisional Patent Application Serial No. 61 / 581,099 (Attorney Docket DDI5220USPSP2), form part of this disclosure:

1. A method for determining analyte concentration from a physiological sample with a biosensor having reagents disposed on at least two electrodes and at least one of the electrodes,

Depositing a physiological sample on at least two electrodes to initiate an analyte test sequence;

Applying a first electrical signal to the sample to derive a physical characteristic of the sample;

Obtaining physical characteristics of the sample;

Specifying a sampling time based on physical characteristics from the acquiring step;

Deriving a batch gradient for the reagent based on the physical properties from the acquiring step;

Introducing a second electrical signal into the sample;

Measuring an output signal at a specified sampling time from at least one of the at least two electrodes; And

Calculating an analyte concentration based on the measured output signal at a specified sampling time and the derived batch slope.

2. The method of claim 1, wherein the application of the first signal and the introduction of the second signal are performed in a sequential order.

3. The method of claim 1, wherein the application of the first signal overlaps with the introduction of the second signal.

4. The method of claim 1, wherein the application of the first signal comprises directing an alternating signal to a sample so that the physical properties of the sample are determined from the output of the alternating signal.

5. The method of claim 1, wherein the application of the first signal directs the optical signal to a sample such that the physical properties of the sample are determined from the output of the optical signal.

6. The method according to claim 4, wherein the physical property comprises hematocrit and the analyte comprises glucose.

7. The method of claim 1, wherein the physical property comprises at least one of viscosity, hematocrit and density of the sample.

8. The method of claim 4, wherein directing comprises driving first and second AC signals of different respective frequencies, wherein the first frequency is lower than the second frequency.

9. The method of embodiment C8, wherein the first frequency is at least one order of magnitude lower than the second frequency.

10. The method of claim 9, wherein the first frequency comprises any frequency in the range of about 10 kHz to about 90 kHz.

11. In the method of sun C1, the designated sampling time is calculated using the following form:

Here, the " designated sampling time " is designated as the time from the start of the test sequence for sampling the output signal of the test strip,

H represents the physical properties of the sample in the form of a hematocrit;

x ₁ is about 4.3e5;

x ₂ is about -3.9;

x ₃ is about 4.8.

12. In the method of Sun C11, the derived slope is determined from the following equation:

Where H is measured or estimated physical properties (e.g., hematocrit);

a is about 1.35e-6,

b is about -3.79e-4,

c is about 3.56e-2.

13. In the method of sun C12, the calculation of the analyte concentration is calculated by the equation of the form:

here

G _o represents the analyte concentration,

I _E represents the signal (proportional to analyte concentration) determined from the sum of the terminal signals measured at the specified sampling time ;

The new slope represents a value derived from the measured physical properties;

The segment represents the value obtained from the calibration check of the placement of the test strip to produce this particular strip.

14. An analyte measurement system,

As a test strip,

Board;

A plurality of electrodes connected to the respective electrode connectors; And

As an analyzer,

housing;

A test strip port connector configured to be connected to each of the electrode connectors of the test strip; And

And a microprocessor in electrical communication with a test strip port connector to sense electrical signals from a plurality of electrodes during a test sequence or to apply electrical signals, the microprocessor comprising: (a) (B) applying a second electrical signal to the plurality of electrodes, and (c) applying a second electrical signal to the plurality of electrodes so as to apply a first electrical signal to the plurality of electrodes so as to derive a specific sampling time and a placement gradient determined from the physical properties of the physiological fluid sample, ) Is configured to measure the signal output from one of the plurality of electrodes at a specified sampling time such that the analyte concentration is determined based on the measured signal and the placement gradient at the specified point in time.

15. The system of embodiment C14, wherein the plurality of electrodes comprises at least two electrodes for measuring physical properties and at least two other electrodes for measuring analyte concentrations.

16. The system of embodiment C15, wherein at least two electrodes and at least two other electrodes are disposed in the same chamber provided on the substrate.

17. The system of claim 15, wherein at least two electrodes and at least two other electrodes are disposed in different chambers provided on the substrate.

18. The system of clause C15, wherein at least two electrodes comprise two electrodes for measuring physical properties and analyte concentration.

19. The system of claim 16, wherein all of the electrodes are disposed on the same plane defined by the substrate.

20. The system of embodiment C17 or C18, wherein the reagent is disposed close to at least two other electrodes, and no reagent is disposed on at least two electrodes.

21. In the system of embodiment C14, the designated sampling time is calculated using the following form:

Here, the " designated sampling time " is designated as the time from the start of the test sequence for sampling the output signal of the test strip,

H represents the physical properties of the sample in the form of a hematocrit;

x ₁ represents about 4.3e5;

x ₂ represents about -3.9;

x ₃ represents about 4.8.

22. The method of embodiment C21, wherein the derived slope is determined from an equation of the form:

Where H is measured or estimated physical properties (e.g., hematocrit);

a is about 1.35e-6,

b is about -3.79e-4,

c is about 3.56e-2.

23. The method of embodiment C22, wherein the calculation of the analyte concentration is calculated by the formula:

here,

G _o represents the analyte concentration,

I _E represents the signal (proportional to analyte concentration) determined from the sum of the terminal signals measured at the specified sampling time ;

The new slope represents a value derived from the measured physical properties;

The segment represents the value obtained from the calibration check of the placement of the test strip to produce this particular strip.

24. An analytical measurement system,

As a test strip,

Board;

A plurality of electrodes connected to the respective electrode connectors; And

As an analyzer,

housing;

A test strip port connector configured to be connected to each of the electrode connectors of the test strip; And

And a microprocessor in electrical communication with a test strip port connector to sense electrical signals from a plurality of electrodes or to apply electrical signals, the microprocessor comprising:

(a) applying a first electrical signal to a plurality of electrodes such that a specific sampling time determined from the physical properties of the physiological fluid sample and a placement gradient of the test strip are derived,

(b) applying a second electrical signal to the plurality of electrodes, and

(c) measure the signal output from one of the plurality of electrodes at a designated sampling time so that the analyte concentration of the sample is determined based on the specific sampling time and the placement slope within about 10 seconds of the start of the test sequence.

25. The system of embodiment C24, wherein the plurality of electrodes comprises at least two electrodes for measuring physical properties and at least two other electrodes for measuring analyte concentrations.

26. The system of embodiment C24, wherein at least two electrodes and at least two other electrodes are disposed in the same chamber provided on the substrate.

27. The system of embodiment C24, wherein at least two electrodes and at least two other electrodes are disposed in different chambers provided on the substrate.

28. The system of embodiment C24, wherein at least two electrodes include two electrodes for measuring physical properties and analyte concentration.

29. A system in which all the electrodes are arranged on the same plane defined by the substrate, in the system of solar C24, solar C25, solar C26 or solar C27.

30. The system of embodiment C23 or C24, wherein the reagent is disposed close to at least two other electrodes, and no reagent is disposed on at least two electrodes.

31. In the system of embodiment C24, the designated sampling time is calculated using the following equation:

Here, the " designated sampling time " is designated as the time from the start of the test sequence for sampling the output signal of the test strip,

H represents the physical properties of the sample in the form of a hematocrit;

x ₁ represents about 4.3e5;

x ₂ represents about -3.9;

x ₃ represents about 4.8.

32. The system of clause C31, wherein the derived slope is determined from an equation of the form:

Wherein the new slope represents the derived slope;

H is a measured or estimated physical property (e.g., hematocrit);

a is about 1.35e-6,

b is about -3.79e-4,

c is about 3.56e-2.

33. In the method of sun C32, the calculation of the analyte concentration is calculated by the formula of the form:

here

G _o represents the analyte concentration,

I _E represents the signal (proportional to analyte concentration) determined from the sum of the terminal signals measured at the specified sampling time ;

The new slope represents a value derived from the measured physical properties;

The segment represents the value obtained from the calibration check of the placement of the test strip to produce this particular strip.

34. A method for obtaining increased accuracy of a test strip,

Providing an arrangement of test strips;

Introducing a reference sample containing an analyte of reference concentration into each batch of test strips to initiate a test sequence;

Reacting the analyte to cause physical conversion of the analyte between the two electrodes;

Determining a physical property of the reference sample;

Deriving a placement slope of the arrangement of test strips based on the determined physical properties;

Sampling the electrical output of the reference sample at a point in time during a test sequence defined by the measured physical properties;

Calculating the analyte concentration based on the placement slope and the designation point derived to provide a final analyte concentration value for each batch of test strips, wherein at least 95% of the final analyte concentration values of the batches of test strips are based on a baseline analysis Gt; 15% < / RTI > of the water concentration.

35. The method of aspect C34, wherein the step of reacting comprises introducing a second electrical signal into the sample and the step of determining comprises applying a first electrical signal to the sample to derive the physical properties of the sample And the application of the first signal and the introduction of the second signal are performed in a sequential order.

36. The method of embodiment C35, wherein the application of the first signal overlaps with the introduction of the second signal.

37. The method of embodiment C34, wherein the application of the first signal comprises directing an alternating signal to a sample such that the physical properties of the sample are determined from the output of the alternating signal.

38. The method of embodiment C34, wherein the application of the first signal comprises directing the optical signal to a sample such that the physical properties of the sample are determined from the output of the optical signal.

39. The method of any one of the preceding claims, wherein the physical property comprises hematocrit and the analyte comprises glucose.

40. The method of any preceding claim, wherein the physical properties comprise at least one of viscosity, hematocrit and density.

41. The method of embodiment C37, wherein directing comprises driving first and second AC signals of different respective frequencies, wherein the first frequency is lower than the second frequency.

42. The method of embodiment C41, wherein the first frequency is at least one order of magnitude lower than the second frequency.

43. The method of claim 41, wherein the first frequency comprises any frequency in the range of about 10 kHz to about 90 kHz.

44. The method of embodiment C34, wherein the designated sampling time is calculated using an equation of the form:

Here, the " designated sampling time " is designated as the time from the start of the test sequence for sampling the output signal of the test strip,

H represents the physical properties of the sample in the form of a hematocrit;

x ₁ represents about 4.3e5;

x ₂ represents about -3.9;

x ₃ represents about 4.8.

45. The method of embodiment C44, wherein the derived slope is determined from an equation of the form:

Where H is measured or estimated physical properties (e.g., hematocrit);

a is about 1.35e-6,

b is about -3.79e-4,

c is about 3.56e-2.

46. The method of embodiment C45, wherein the calculation of the analyte concentration is calculated by the equation of the form:

here

G _o represents the analyte concentration,

I _E represents the signal (proportional to analyte concentration) determined from the sum of the terminal signals measured at the specified sampling time ;

The new slope represents a value derived from the measured physical properties;

The segment represents the value obtained from the calibration check of the placement of the test strip to produce this particular strip.

47. A method for determining analyte concentration from a physiological sample,

Depositing a physiological sample on the biosensor on which the reagent is deposited;

Applying electrical signals to the sample and the reagent to convert the analyte into a different material;

Obtaining physical characteristics of the sample;

Designating a time point for sampling the signal output based on physical characteristics from the designation step;

Deriving a placement gradient of the biosensor;

Measuring a signal output at a designated sampling time; And

And determining the analyte concentration based on the measured signal output of the sample at the specified sampling time and the derived placement slope.

48. The method of embodiment C47, wherein acquiring comprises introducing a second electrical signal into the sample to derive a physical property of the sample.

49. The method of embodiment C48, wherein applying comprises applying a first electrical signal to a sample to derive a physical characteristic of the sample, wherein the application of the first signal and the introduction of the second signal are performed in a sequential order How it is done.

50. The method of embodiment C49, wherein the application of the first signal overlaps with the introduction of the second signal.

51. The method of claim 50, wherein the application of the first signal directs the alternating signal to a sample so that the physical properties of the sample are determined from the output of the alternating signal.

52. The method of embodiment C50, wherein the application of the first signal directs the optical signal to a sample such that the physical properties of the sample are determined from the output of the optical signal.

53. The method of claim 51, wherein the physical property comprises hematocrit and the analyte comprises glucose.

54. The method of sun C52 or sun C53, wherein the physical property comprises at least one of viscosity, hematocrit and density.

55. The method of claim 53, wherein directing comprises driving first and second AC signals of different respective frequencies, wherein the first frequency is lower than the second frequency.

56. The method of embodiment C55, wherein the first frequency is at least one order of magnitude lower than the second frequency.

57. The method of embodiment C56, wherein the first frequency comprises any frequency in the range of about 10 kHz to about 90 kHz.

58. The method of embodiment C47, wherein the designated sampling time is calculated using an equation of the form:

Here, the " designated sampling time " is designated as the time from the start of the test sequence for sampling the output signal of the test strip,

H represents the physical properties of the sample in the form of a hematocrit;

x ₁ represents about 4.3e5;

x ₂ represents about -3.9;

x ₃ represents about 4.8.

59. The method of embodiment C58, wherein the derived slope is determined from an equation of the form:

Where H is measured or estimated physical properties (e.g., hematocrit);

a is about 1.35e-6,

b is about -3.79e-4,

c is about 3.56e-2.

60. The method of embodiment C59, wherein the calculation of the analyte concentration is calculated by the formula:

here

G _o represents the analyte concentration,

I _E represents the signal (proportional to analyte concentration) determined from the sum of the terminal signals measured at the specified sampling time ;

The new slope represents a value derived from the measured physical properties;

The segment represents the value obtained from the calibration check of the placement of the test strip to produce this particular strip.

61. The method or system of each of Sun C12, Sun C22, Sun C32, Sun C44 or Sun C59, wherein a is about -1.98e-6; b is about -2.87e-5; and c is about 2.67e-2.

Section "D"

The following aspects, which were originally presented in U.S. Provisional Patent Application No. 61 / 581,100 (Attorney Docket DDI5221USPSP), form part of this disclosure:

1. A method for determining an analyte concentration from a physiological sample with a biosensor having reagents disposed on at least two of the electrodes and at least one of the electrodes,

Depositing a physiological sample on at least two electrodes to initiate an analyte test sequence;

Applying a first electrical signal to the sample to measure a physical characteristic of the sample;

Introducing a second electrical signal into the sample to cause an enzyme reaction of the analyte and the reagent;

Estimating the analyte concentration based on a predetermined sampling time from the start of the test sequence;

Wherein different qualitative categories of the estimated analyte are listed in the leftmost column of the matrix and different qualitative categories of measured physical properties are listed in the top row of the matrix and sampling times are provided to the remaining cells of the matrix, Selecting a sampling point from a table;

Measuring a signal output from the sample at a selected sampling time from a look-up table;

Calculating an analyte concentration from a measured output signal sampled at the selected sampling time according to an equation of the form:

Where G _o represents the analyte concentration;

I _T denotes the signal (proportional to the analyte concentration) determined from the sum of the terminal signals measured at the specified sampling time T;

The slope represents the value obtained from the calibration check of the placement of the test strip producing this particular strip;

The segment represents the value obtained from the calibration check of the placement of the test strip to produce this particular strip.

2. A method of determining analyte concentration from a physiological sample with a biosensor having reagents disposed on at least two of the electrodes and at least one of the electrodes,

Depositing a physiological sample on at least two electrodes to initiate an analyte test sequence;

Applying a first electrical signal to the sample to measure a physical characteristic of the sample;

Introducing a second electrical signal into the sample to cause an enzyme reaction of the analyte and the reagent;

Estimating the analyte concentration based on a predetermined sampling time from the start of the test sequence;

Selecting a sampling time point based on both the measured physical property and the estimated analyte concentration;

Measuring a signal output from the sample at a selected sampling time;

And calculating the analyte concentration from the measured output signal sampled at the selected sampling time.

3. The method of claim 1, wherein the application of the first signal and the introduction of the second signal are sequential.

4. The method of claim 1, wherein the application of the first signal overlaps the introduction of the second signal.

5. The method of claim 1, wherein the application of the first signal directs the alternating signal to a sample so that the physical properties of the sample are determined from the output of the alternating signal.

6. The method of claim 1, wherein the physical property comprises hematocrit and the analyte comprises glucose.

7. The method according to any one of the preceding claims, wherein the physical properties comprise at least one of viscosity, hematocrit and density.

8. The method of embodiment D5, wherein directing comprises driving first and second AC signals of different respective frequencies, wherein the first frequency is lower than the second frequency.

9. The method of embodiment D8, wherein the first frequency is at least one order of magnitude lower than the second frequency.

10. The method of Solar D8, wherein the first frequency comprises any frequency within the range of about 10 kHz to about 90 kHz.

11. The method of claim 1, wherein the measuring step comprises continuously sampling the signal output for at least about 10 seconds after the start of the test sequence at the beginning of the test sequence.

12. The method of sun D2, further comprising estimating analyte concentration based on a measure of the output signal at a predetermined time.

13. The method of embodiment D12, wherein the predetermined time comprises about 5 seconds from the beginning of the test sequence.

14. The method of embodiment D12, wherein the step of estimating comprises determining the physical properties of the sample indexed for different sample measurement times and the difference in analyte concentration Comparing the measured physical properties and the estimated analyte concentration for a look-up table having a range.

15. The method of embodiment D2, wherein the calculating step comprises using an equation of the form:

Where G _o represents the analyte concentration;

I _T denotes the signal (proportional to the analyte concentration) determined from the sum of the terminal signals measured at the specified sampling time T;

The slope represents the value obtained from the calibration check of the placement of the test strip producing this particular strip;

The segment represents the value obtained from the calibration check of the placement of the test strip to produce this particular strip.

16. An analyte measurement system,

As a test strip,

Board;

A plurality of electrodes connected to the respective electrode connectors; And

As an analyzer,

housing;

A test strip port connector configured to be connected to each of the electrode connectors of the test strip; And

And a microprocessor in electrical communication with a test strip port connector for sensing electrical signals from a plurality of electrodes or applying electrical signals, wherein the microprocessor is configured to: (a) determine a physical property of a physiological fluid sample To apply a first electrical signal to the plurality of electrodes so that the first electrical signal is determined; (b) estimate the analyte concentration based on a predetermined sampling time during the test sequence; And (c) applying a second electrical signal to the plurality of electrodes at a sampling time during a test sequence indicated by the determined physical property to cause analyte concentration to be calculated from the second electrical signal.

17. The system of claim 16, wherein the plurality of electrodes comprises at least two electrodes for measuring physical properties and at least two other electrodes for measuring analyte concentrations.

18. The system of embodiment D17, wherein at least two electrodes and at least two other electrodes are disposed in the same chamber provided on the substrate.

19. The system of embodiment D17, wherein at least two electrodes and at least two other electrodes are disposed in different chambers provided on the substrate.

20. In a system of solar D18 or solar D19, all of the electrodes are arranged on the same plane defined by the substrate.

21. In a system of solar D18 or solar D19, a reagent is placed close to at least two other electrodes, and no reagent is placed on at least two electrodes.

22. An analyte measurement system,

As a test strip,

Board;

A plurality of electrodes connected to the respective electrode connectors; And

As an analyzer,

housing;

A test strip port connector configured to be connected to each of the electrode connectors of the test strip; And

An analyte meter comprising a microprocessor in electrical communication with a test strip port connector to sense electrical signals from a plurality of electrodes or to apply electrical signals, the microprocessor comprising: (a) a physiological fluid sample To apply a first electrical signal to the plurality of electrodes such that a physical characteristic of the first electrical signal is determined; (b) estimate the analyte concentration based on a predetermined sampling time during the test sequence; And (c) applying a second electrical signal to the plurality of electrodes at a sampling time during a test sequence indicated by the determined physical characteristics to cause the analyte concentration to be determined from the second electrical signal within about 10 seconds of the start of the test sequence The system to be configured.

23. The system of embodiment D23, wherein the plurality of electrodes comprises at least two electrodes for measuring physical properties and at least two other electrodes for measuring analyte concentration.

24. The system of embodiment D23, wherein at least two electrodes and at least two other electrodes are disposed in the same chamber provided on the substrate.

25. The system of embodiment D23, wherein at least two electrodes and at least two other electrodes are disposed in different chambers provided on the substrate.

26. In a system of solar D24 or solar D25, all of the electrodes are disposed on the same plane defined by the substrate.

27. The system of embodiment D24 or D25, wherein the reagent is disposed close to at least two other electrodes, and no reagent is disposed on at least two electrodes.

28. A method for obtaining increased accuracy of a test strip,

Providing an arrangement of test strips;

Introducing a reference sample containing an analyte of reference concentration into each batch of test strips to initiate a test sequence;

Reacting the analyte with a reagent disposed on each of the test strips to cause physical conversion of the analyte between the two electrodes;

Estimating the analyte concentration based on the measured signal output of the sample at a predetermined time from the start of the test sequence;

Determining a physical property of the reference sample;

Sampling the electrical output of the reference sample at a point in time indicated during the test sequence defined by the measured physical properties and the estimated analyte concentration;

Calculating the analyte concentration based on the indicated point in time to provide a final analyte concentration value for each batch of test strips, wherein at least 95% of the final analyte concentration values of the batches of test strips are from about 30% to about 55 % Of the hematocrit of the sample to be within ± 10% of the reference analyte concentration.

29. The method of embodiment D28, wherein the application of the first signal and the introduction of the second signal are sequential.

30. The method of embodiment D28, wherein the application of the first signal overlaps with the introduction of the second signal.

31. The method of embodiment D28, wherein applying the first signal includes directing an alternating signal to a sample so that the physical properties of the sample are determined from the output of the alternating signal.

32. The method of embodiment D28, wherein the application of the first signal comprises directing the electromagnetic signal to a sample such that the physical properties of the sample are determined from the output of the electromagnetic signal.

33. The method of any preceding claim, wherein the physical property comprises hematocrit and the analyte comprises glucose.

34. The method of any preceding claim, wherein the physical properties comprise at least one of viscosity, hematocrit and density.

35. The method of embodiment D30, wherein directing comprises driving first and second AC signals of different respective frequencies, wherein the first frequency is lower than the second frequency.

36. The method of embodiment D35, wherein the first frequency is at least one order of magnitude lower than the second frequency.

37. The method of claim 36, wherein the first frequency comprises any frequency in the range of about 10 kHz to about 90 kHz.

38. The method of embodiment D29, wherein the measuring step comprises successively sampling the signal output for at least about 10 seconds after the start of the test sequence at the start.

39. The method of embodiment D29, further comprising estimating analyte concentration based on measurements of the output signal at a predetermined time.

40. The method of embodiment D39, wherein the step of estimating comprises determining the physical properties of the sample indexed for the different sample measurement times and the difference in the analyte concentration Comparing the measured physical properties and the estimated analyte concentration for a look-up table having a range.

41. A method for determining analyte concentration from a physiological sample,

Depositing a physiological sample on the biosensor to initiate a test sequence;

Causing the analyte in the sample to undergo an enzymatic reaction;

Estimating the analyte concentration in the sample;

Measuring at least one physical property of the sample;

Defining a point in time from the beginning of the test sequence for sampling the output signal of the biosensor based on at least one physical characteristic from the measuring step and the estimated analyte concentration;

Sampling the output signals of the biosensor at a prescribed time point;

Determining an analyte concentration from the sampled signals at a specified point in time.

42. The method of embodiment D41, wherein the measuring step comprises applying a first electrical signal to the sample to measure a physical property of the sample; Wherein the triggering step comprises introducing a second electrical signal into the sample; The measuring step includes obtaining an output signal from at least two electrodes at a point in time after the start of the test sequence, the point being set as a function of at least the measured physical properties; Wherein the step of determining comprises calculating the analyte concentration from the measured output signal at the time point.

43. The method of embodiment D41, wherein the application of the first signal and the introduction of the second signal are sequential.

44. The method of embodiment D41, wherein the application of the first signal overlaps with the introduction of the second signal.

45. The method of embodiment D41, wherein applying the first signal directs the alternating signal to a sample so that the physical properties of the sample are determined from the output of the alternating signal.

46. The method of embodiment D41, further comprising estimating analyte concentration based on a predetermined sampling time from the beginning of the test sequence.

47. The method of embodiment D46, wherein the defining step comprises selecting a defined time point based on both the measured physical properties and the estimated analyte concentration.

48. The method of any preceding claim, wherein the physical property comprises hematocrit and the analyte comprises glucose.

49. The method of any preceding claim, wherein the physical properties comprise at least one of viscosity, hematocrit and density.

50. The method of embodiment D46, wherein directing comprises driving first and second AC signals of different respective frequencies, wherein the first frequency is lower than the second frequency.

51. The method of Solar D50, wherein the first frequency is at least one order of magnitude lower than the second frequency.

52. The method of embodiment D51, wherein the first frequency comprises any frequency in the range of about 10 kHz to about 90 kHz.

53. The method of embodiment D41, wherein the step of measuring comprises continuously sampling the signal output for at least about 10 seconds after the beginning of the start of the test sequence.

54. The method of Solar D53, further comprising estimating analyte concentration based on a measure of the output signal at a predetermined time.

55. The method of embodiment D54, wherein the step of estimating comprises determining the physical properties of the sample indexed for different sample measurement times and the difference in the analyte concentration of each of the analytes concentration, such that the time for the measurement of the output from the sample of the second signal is obtained during the calculation step Comparing the measured physical properties and the estimated analyte concentration for a look-up table having a range.

56. The method or system of any one of clauses D1 to D55 wherein the sampling times are such that different qualitative categories of the estimated analyte are listed in the leftmost column of the matrix and different qualitative categories of measured physical properties are stored in the top Wherein the sampling times are selected from a lookup table comprising a matrix provided in the remaining cells of the matrix.

Section "E"

The following aspects, which were originally proposed in U.S. Provisional Patent Application No. 61 / 654,013 (Attorney Docket DDI5228USPSP), form part of this disclosure:

1. A method for determining analyte concentration from a physiological sample with a biosensor having reagents disposed on at least two electrodes and at least one of the electrodes,

Depositing a physiological sample on at least two electrodes to initiate an analyte test sequence;

Applying a first electrical signal to the sample to derive a physical characteristic of the sample;

Introducing a second electrical signal to the sample during a first sampling time duration overlapping the test sequence to obtain a first transient signal output from the sample, the first transient signal having a time and magnitude Correlating both with each other;

Extracting a specific sampling time during a test sequence in a first sampling time duration based on physical characteristics of the sample;

Defining a second sampling time duration based on a specific sampling time such that a second sampling time duration overlaps with a first sampling time duration;

Obtaining a second transient signal based on a second sampling time duration from the first transient signal;

Dividing the second transient signal into separate intervals for a second sampling time duration;

Deriving respective magnitudes of the second transient signals in distinct selected intervals within a second sampling time duration; And

Determining an analyte concentration based on the respective magnitudes of the second transient signals in distinct selected time intervals.

2. A method of determining analyte concentration from a physiological sample with a biosensor having reagents disposed on at least two electrodes and at least one of the electrodes,

Depositing a physiological sample on at least two electrodes to initiate an analyte test sequence;

Applying a first electrical signal to the sample to derive a physical characteristic of the sample;

Introducing a second electrical signal to the sample during a first sampling time duration overlapping the test sequence to obtain a first transient signal output from the sample, the first transient signal having a time and magnitude Correlating both with each other;

Extracting a specific sampling time during a test sequence in a first sampling time duration based on physical characteristics of the sample;

Obtaining a second transient signal from a first transient signal over a second sampling time duration;

Deriving respective magnitudes of the second transient signals in selected intervals within a second sampling time duration; And

And determining the analyte concentration based on the respective magnitudes of the second transient signals in the selected time intervals.

3. A method of determining analyte concentration from a physiological sample with a biosensor having reagents disposed on at least two electrodes and on at least one of the electrodes,

Depositing a physiological sample on at least two electrodes to initiate an analyte test sequence;

Applying a first electrical signal to the sample to derive a physical characteristic of the sample;

Extracting a specific sampling time in a first sampling time duration;

Applying or introducing a second signal into the sample during a first sampling time duration and measuring or sampling a first transient signal output from the sample during a duration of the first sampling time duration;

Defining a specific time range including a specific sampling time within a first sampling time duration;

Obtaining a plurality of magnitudes of a first transient signal in respective distinct intervals within a specific time range; And

Determining an analyte concentration based on the magnitudes of the first transient signal from the acquiring step.

4. A method of determining an analyte concentration from a physiological sample with a biosensor having reagents disposed on at least two electrodes and at least one of the electrodes,

Depositing a physiological sample on at least two electrodes to initiate an analyte test sequence;

Applying a first electrical signal to the sample to derive a physical characteristic of the sample;

Extracting a specific sampling time in a first sampling time duration;

Applying or introducing a second signal into the sample during a first sampling time duration and measuring or sampling a first transient signal output from the sample during a duration of the first sampling time duration;

Obtaining a plurality of magnitudes of a first transient signal output at approximately a specific sampling time and at different time intervals; And

Determining an analyte concentration based on the plurality of sizes of the first transient signal from the acquiring step.

5. A method of determining analyte concentration from a physiological sample with a biosensor having reagents disposed on at least two electrodes and on at least one of the electrodes,

Depositing a physiological sample on at least two electrodes to initiate an analyte test sequence for each of the plurality of biosensors;

Applying a first electrical signal to the sample to derive a physical property of the sample for each of the plurality of biosensors;

Extracting a specific sampling time in a first sampling time duration for each of the plurality of biosensors;

Applying or introducing a second signal into the sample for a first sampling time duration for each of the plurality of biosensors;

Measuring or sampling a first transient signal output from the sample for a duration of a first sampling time duration for each of the plurality of biosensors;

Defining a specific time range including a specific sampling time within a first sampling time duration for each of the plurality of biosensors;

Obtaining a plurality of sizes of first transient signals for each of the plurality of biosensors in respective distinct intervals within a specific time range; And

Determining an analyte concentration based on magnitudes of a first transient signal from acquiring for each of the plurality of biosensors, wherein the analyte concentration is determined between a plurality of analyte concentrations determined by determining for a plurality of biosensors Of error is less than +/- 15% relative to a reference value at each of 30%, 42% and 55% of the hematocrit.

6. The method according to any of the preceding claims, wherein in the method of sun E1, sun E2 or sun E3, the specific time range comprises the magnitudes of the first transient signal measured before a specific sampling time.

7. In the method of solar E1, solar E2, solar E3, solar E4 or solar E5, the step of extracting a specific sampling time calculates a specific sampling time defined in the first sampling time duration based on the physical characteristics of the sample Lt; / RTI >

8. The method of embodiment E6, wherein the step of calculating for a specified specific sampling time comprises using an equation of the form:

Here, the " designated sampling time " is designated as the time from the start of the test sequence for sampling the output signal of the biosensor,

H represents the physical properties of the sample in the form of a hematocrit;

x ₁ is about 4.3e5;

x ₂ is about (-) 3.9,

x ₃ is about 4.8.

9. The method of clause E8, wherein the step of defining the second sampling time duration is between a predetermined sampling time and a predetermined sampling time defined to define a start time (T1) and an end time (T2) substantially equal to the designated sampling time Wherein the first sampling time duration comprises no more than about 10 seconds from the step of depositing the sample.

10. The method of clause E8, wherein the acquiring step is a second sampling time duration overlapping a first sampling time duration, the first transient signal including a portion of its magnitude relative to the time of the second sampling time duration Further comprising the step of defining a second sampling time duration for the first transient signal, wherein the portion is designated as a second transient signal.

11. The method of claim 9, wherein acquiring the second transient signal comprises extracting a portion of the first transient signal designated as the second transient signal that is within a second sampling time duration from the first transient signal Way.

12. The method of clause E11, wherein deriving respective magnitudes of the second transient signals in distinct selected time intervals comprises calculating a magnitude of a second transient signal during each selected time interval.

13. The method of clause E12, wherein the dividing step comprises dividing the second transient signal into at least 22 intervals starting from interval 1 at approximately the start time, .

14. In the method of the solar E13, the determination of the analyte concentration is obtained using the following form:

here:

G comprises the analyte concentration; I ₁ ? Is the magnitude of the second transient signal at interval 17; I ₂ ? Is the magnitude of the second transient signal in interval 13; I ₃ ? Is the magnitude of the second transient signal in interval 5; I ₄ ? Is the magnitude of the second transient signal in interval 3; I ₅ ? Is the magnitude of the second transient signal at interval 22; x ₁ ? 0.75; x ₂ ? 337.27; x ₃ ? (-) 16.81; x ₄ ? 1.41; x ₅ ? 2.67.

15. In the method of Solar E10, the determination of the analyte concentration is obtained using the following form:

here:

G comprises the analyte concentration; I ₁ ? Is the magnitude of the second transient signal at interval 11; I ₂ ? Is the magnitude of the second transient signal at interval 7; x ₁ ? 0.59; x ₂ ? 2.51; x ₃ ? ( -) 12.74; x ₄ ? (-) 188.31; x ₅ ? 9.2.

16. In the method of solar E13, the determination of the analyte concentration is obtained using the following form:

Where G comprises the analyte concentration; I ₁ ? Is the magnitude of the second transient signal at interval 20; I ₂ ? Is the magnitude of the second transient signal at interval 22; I ₃ ? Is the magnitude of the second transient signal at interval 19; x ₁ ? 20.15; x ₂ ? 1.0446; x ₃ ? 0.95; x ₄ ? 1.39; x ₅ ? (-) 0.71; x ₆ ? 0.11.

17. In the method of the solar E13, the determination of the analyte concentration is obtained by using an equation of the form:

here:

I ₁ ? Is the magnitude of the second transient signal in interval 5; I ₂ ? Is the magnitude of the second transient signal in interval 1; I ₃ ? Is the magnitude of the second transient signal in interval 2; I ₄ ? Is the magnitude of the second transient signal in interval 10; I ₅ ? Is the magnitude of the second transient signal at interval 22; x ₁ ? 0.70; x ₂ ? 0.49; x ₃ ? 28.59; x ₄ ? 0.7; x ₅ ? 15.51.

18. In the method of solar E10, the determination of analyte concentration is obtained using the following form:

here:

G includes glucose concentration ; I ₁ ? Is the magnitude of the second transient signal at interval 19; I ₂ ? Is the magnitude of the second transient signal at interval 16; I ₃ ? Is the magnitude of the second transient signal in interval 11; I ₄ ? Is the magnitude of the second transient signal in interval 5; x ₁ ? (-) 1.68; x ₂ ? 0.95; x ₃ ? (-) 4.97; x ₄ ? 6.29; x ₅ ? 3.08; x ₆ ? (-) 5.84; x ₇ ? (-) 0.47; x ₈ ? 0.01.

19. In the method of embodiment E10, the determination of analyte concentration is obtained using the following form:

here:

G includes glucose concentration ; I ₁ ? Is the magnitude of the second transient signal at interval 16; I ₂ ? Is the magnitude of the second transient signal at interval 5; I ₃ ? Is the magnitude of the second transient signal at interval 12; I ₄ ? Is the magnitude of the second transient signal in interval 14; x ₁ ? 1.18; x ₂ ? 0.97; x ₃ ? (- ) 11.32; x ₄ ? 38.76; x ₅ ? (-) 39.32; x ₆ 0.0928; x ₇ ? (-) 0.85; x ₈ ? 1.75; x ₉ ? (-) 9.38; x ₁₀ ? 0.25.

20. The method of any one of clauses E14 to E19, wherein the magnitude of the second transient signal in each of the plurality of distinct intervals comprises an average magnitude of the measured magnitudes in each of the distinct intervals.

21. The method according to any of the preceding claims, wherein in the method of solar E1, solar E2 or solar E3, the application of the first signal and the introduction of the second signal are performed in a sequential order.

22. The method of claim 21, wherein the application of the first signal overlaps with the introduction of the second signal.

23. A method as in Sun E1, Sun E2, or Sun E3, wherein applying a first signal directs an alternating signal to a sample so that the physical properties of the sample are determined from the output of the alternating signal.

24. The method of any one of the preceding claims, wherein the application of the first signal directs the optical signal to a sample so that the physical properties of the sample are determined from the output of the optical signal.

25. The method of embodiment E24, wherein the physical property comprises hematocrit and the analyte comprises glucose.

26. The method according to any one of the preceding claims, wherein the physical properties comprise at least one of the viscosity, hematocrit or density of the sample.

27. The method of embodiment E24, wherein directing comprises driving first and second AC signals of different respective frequencies, wherein the first frequency comprises a different frequency than the second frequency.

28. The method of Solar E25, wherein the first frequency is at least one order of magnitude lower than the second frequency.

29. The method of embodiment E26, wherein the first frequency comprises any frequency in the range of about 10 kHz to about 90 kHz.

30. The method of clause E1, E2 or E3, wherein the obtaining comprises extracting a second transient signal based on a second sampling time duration from the first transient signal.

31. The method of clause E1, E2 or E3, wherein the obtaining step removes from the first transient signals signals that are outside a second sampling time duration to leave a second transient signal within a second sampling time duration Lt; / RTI >

32. The method of clause E30 or E31, wherein deriving comprises storing magnitudes of a second transient signal for each distinct interval in a second sampling time duration.

33. An analyte measurement system,

As a test strip,

Board;

A test strip disposed on the substrate and comprising a plurality of electrodes connected to respective electrode connectors; And

As an analyzer,

housing;

A test strip port connector configured to be connected to each of the electrode connectors of the test strip; And

And a microprocessor in electrical communication with a test strip port connector to sense electrical signals from a plurality of electrodes during a test sequence or to apply electrical signals, the microprocessor comprising: (a) (B) applying a second electrical signal to the plurality of electrodes, (c) applying a first electrical signal to the plurality of electrodes to provide a first transient output (D) to extract a second transient output signal from the first output signal, (e) to determine a magnitude of the second transient output signal over at least 22 distinct time intervals, and (f) And to calculate analyte concentrations from the magnitudes of the second transient output signal in selected intervals of at least 22 distinct time intervals.

34. An analyte measurement system,

As a test strip,

Board;

A test strip disposed on the substrate and comprising a plurality of electrodes connected to respective electrode connectors; And

As an analyzer,

housing;

A test strip port connector configured to be connected to each of the electrode connectors of the test strip; And

And a microprocessor in electrical communication with a test strip port connector to sense electrical signals from a plurality of electrodes during a test sequence or to apply electrical signals, the microprocessor comprising: (a) (B) applying a second electrical signal to the plurality of electrodes, (c) applying a first electrical signal to the plurality of electrodes to provide a first transient output (D) to extract a second transient output signal from the first output signal, (e) to determine a magnitude of the second transient output signal over at least 22 distinct time intervals, and (f) The magnitude of the second transient output signal at selected intervals of at least 22 distinct time intervals to notify the analyte concentration within about 10 seconds of the start of the test sequence It is configured to calculate an analyte concentration from.

35. A system as in Sun E33 or E34, wherein the plurality of electrodes comprises at least two electrodes for measuring physical properties and at least two other electrodes for measuring analyte concentration.

36. The system of embodiment 35 wherein at least two electrodes and at least two other electrodes are disposed in the same chamber provided on the substrate.

37. The system of embodiment E35, wherein at least two electrodes and at least two other electrodes are disposed in different chambers provided on the substrate.

38. The system of embodiment E37, wherein the different chambers are disposed adjacent to one another on an edge of the substrate.

39. The system of embodiment E35, wherein at least two electrodes and at least two other electrodes are disposed in a common chamber that receives a fluid sample.

40. The system of embodiment E35, wherein at least two electrodes comprise two electrodes for measuring physical properties and analyte concentration.

41. The system of any one of clauses E33 to E40, wherein all of the electrodes are disposed on the same plane defined by the substrate.

42. The system of any one of clauses < RTI ID = 0.0 > E33 < / RTI > to E40, wherein the reagent is disposed proximate to at least two other electrodes and no reagent is disposed on at least two electrodes.

43. In the system of solar E33 or solar E34, the specified sampling time is calculated using the following form:

Here, the " designated sampling time " is designated as the time from the start of the test sequence for sampling the output signal of the test strip,

H represents the physical properties of a sample in the form of a hematocrit,

x ₁ represents about 4.3e5,

x ₂ represents about (-) 3.9,

x ₃ represents about 4.8.

44. In a system of solar E33, solar E34 or solar E41, the microprocessor is a system for calculating analyte concentration in the following form:

here

G comprises the analyte concentration; I ₁ ? Is the magnitude of the second transient signal at interval 17; I ₂ ? The magnitude of the second transient signal in interval 13; I ₃ ? Is the magnitude of the second transient signal in interval 5; I ₄ ? Is the magnitude of the second transient signal in interval 3; I ₅ ? Is the magnitude of the second transient signal at interval 22; x ₁ ? 0.75; x ₂ ? 337.27; x ₃ ? (-) 16.81; x ₄ ? 1.41; x ₅ ? 2.67.

45. In a system of solar E33, solar E34 or solar E44, the microprocessor is a system for calculating the analyte concentration in the following form:

here

G comprises the analyte concentration; I ₁ ? Is the magnitude of the second transient signal at interval 11; I ₂ ? Is the magnitude of the second transient signal at interval 7; x ₁ ? 0.59; x ₂ ? 2.51; x ₃ ? (-) 12.74; x ₄ ? (-) 188.31; x ₅ ? 9.2.

46. In a system of solar E33, solar E34 or solar E41, the microprocessor is a system for calculating analyte concentration in the following form:

Where G comprises the analyte concentration; I ₁ ? Is the magnitude of the second transient signal at interval 20; I ₂ ? Is the magnitude of the second transient signal at interval 22; I ₃ ? Is the magnitude of the second transient signal at interval 19; x ₁ ? 20.15; x ₂ ? 1.0446; x ₃ ? 0.95; x ₄ ? 1.39; x ₅ ? (-) 0.71; x ₆ ? 0.11.

47. In a system of solar E33, solar E34 or solar E41, the microprocessor is a system for calculating analyte concentration in the following form:

here:

I ₁ ? Is the magnitude of the second transient signal in interval 5; I ₂ ? Is the magnitude of the second transient signal in interval 1; I ₃ ? Is the magnitude of the second transient signal in interval 2; I ₄ ? Is the magnitude of the second transient signal at interval 10; I ₅ ? Is the magnitude of the second transient signal at interval 22; x ₁ ? 0.70, x ₂ ? 0.49, x ₃ ? 28.59, x ₄ ? 0.7, and x ₅ ? 15.51.

48. In a system of solar E33, solar E34 or solar E41, the microprocessor is a system for calculating the analyte concentration in the following form:

here:

G includes glucose concentration ; I ₁ ? Is the magnitude of the second transient signal at interval 19; I ₂ ? Is the magnitude of the second transient signal at interval 16; I ₃ ? Is the magnitude of the second transient signal in interval 11; I ₄ ? Is the magnitude of the second transient signal in interval 5; x ₁ ? (-) 1.68; x ₂ ? 0.95; x ₃ ? (-) 4.97; x ₄ ? 6.29; x ₅ ? 3.08; x ₆ ? (-) 5.84; x ₇ ? (-) 0.47; x ₈ ? 0.01.

49. In a system of solar E33, solar E34 or solar E41, the microprocessor is a system for calculating analyte concentration in the following form:

here:

G includes glucose concentration ; I ₁ ? Is the magnitude of the second transient signal at interval 16; I ₂ ? Is the magnitude of the second transient signal at interval 5; I ₃ ? Is the magnitude of the second transient signal at interval 12; I ₄ ? Is the magnitude of the second transient signal in interval 14; x ₁ ? 1.18; x ₂ ? 0.97; x ₃ ? (-) 11.32; x ₄ ? 38.76; x ₅ ? (-) 39.32; x ₆ ≒ 0.0928 gt; x ₇ ? (-) 0.85; x ₈ ? 1.75; x ₉ ? (-) 9.38; x ₁₀ ? = 0.25.

50. The system of clause E33, E34 or E41, wherein the magnitude of the second transient signal in each of the plurality of distinct time intervals comprises an average magnitude of the sampled signal over each section.

51. In a system of solar E33, solar E34 or solar E41, the error between the plurality of analyte concentrations calculated by the microprocessor is less than +/- 15% as compared to the reference value at 30% hematocrit.

52. In a system of solar E33, solar E34 or solar E41, the error between the plurality of analyte concentrations calculated by the microprocessor is less than +/- 15% relative to a reference value at 42% hematocrit.

53. In a system of solar E33, solar E34 or solar E41, the error between the plurality of analyte concentrations calculated by the microprocessor is less than +/- 15% relative to a reference value at 55% hematocrit.

Section "F"

The following aspects, which were originally proposed in U.S. Patent Application No. 13 / 250,525 (Attorney Docket DDI5209USNP) and PCT / GB2012 / 052421 (Attorney Docket DDI5209WOPCT), form part of the present disclosure and are incorporated herein by reference:

1. A handheld test meter for use with an assay strip to determine an analyte in a body fluid sample,

housing;

A microcontroller block disposed in the housing; And

A phase-change-based hematocrit measurement block, wherein the phase-change-based hematocrit measurement block comprises

A signal generating sub-block;

A low pass filter sub-block;

Analysis test strip sample cell interface sub-block;

A trans-impedance amplifier sub-block; And

A phase detector sub-block,

The phase-change-based hematocrit measurement block and microcontroller block are configured to measure a phase change of a body fluid sample in a sample cell of an assay strip inserted in a handheld test meter,

Wherein the microcontroller block is configured to calculate the hematocrit of body fluids based on the measured phase change.

2. In a handheld test instrument of Solar F1, the phase-change-based hematocrit measurement block and the microcontroller block are configured to measure the phase change using a signal of a first frequency and a second signal of a second frequency, Measuring instrument.

3. In a handheld test instrument of sun F2, the body fluid sample is a whole blood sample, wherein the first frequency is in the range of 10 kHz to 25 kHz and the second frequency is in the range of 250 kHz to 500 kHz.

4. The handheld test meter of claim 1, wherein the phase detector sub-block is configured as a rising edge acquisition phase detector.

5. The handheld test meter of claim 1, wherein the phase detector sub-block is configured as a dual edge capture phase detector.

6. The handheld test meter of claim 1, wherein the phase detector sub-block is configured as an XOR phase detector.

7. The handheld test meter of claim 1, wherein the phase detector sub-block is configured as a synchronous modulated phase detector.

8. Handheld test meter further comprising a calibrated load sub-block in parallel with the analysis test strip sample cell interface sub-block, in the hand-held test meter of Sun F1.

9. The handheld test meter of claim 1, wherein the signal generating sub-block is configured to generate a first electrical signal of at least a first frequency and a second electrical signal of a second frequency.

10. In the handheld test instrument of the Sun F1, the phase-change-based hematocrit measurement block and microcontroller block insert the signal in the handheld test meter by measuring the phase-change of the signal, And configured to measure a phase change of a body fluid sample in a sample cell of the assayed test strip.

11. In the handheld test instrument of solar F9, the first frequency is in the range of 10 kHz to 25 kHz, the second frequency is in the range of 250 kHz to 500 kHz,

Wherein the phase-change-based hematocrit measurement block and the microcontroller block are configured such that the signal of the first frequency is used as a reference signal during measurement of the phase change of the body fluid sample.

12. In the handheld test instrument of the solar F9, the signal generating block is integrated with the microcontroller block.

13. In a handheld test instrument of Solar F1, the assay test strip sample cell interface block is configured to operatively interface with a sample cell of an assay test strip via a first electrode and a second electrode of an assay test strip disposed in the sample cell Handheld inspection meter.

14. In a handheld test instrument of solar F1, the assay test strip is an electrochemical-based assay test strip configured to determine glucose in a whole blood sample.

15. The handheld test meter of claim 1, wherein the phase detector sub-block is configured as a Quadrature DEMUX phase detector.

16. A method for using a handheld test meter and an assay test strip,

Introducing a whole blood sample into a sample cell of the assay strip;

Measuring a phase change of a body fluid sample in a sample cell using a phase-change-based measurement block and a microcontroller block of a handheld test meter; And

Calculating the hematocrit of the whole blood sample based on the measured phase change using the microcontroller block.

17. In the method of solar F16,

Further comprising the step of determining the analyte in the bodily fluid sample introduced using the analytical test strip, the hand held test meter and the calculated hematocrit.

18. The method of aspect F17, wherein the assay strip is an electrochemical-based assay strip and the assay is glucose.

19. The method of aspect F16, wherein the measuring step comprises measuring a phase change with a phase-change based measurement circuit block, wherein the phase-change based measurement circuit block

A signal generating sub-block;

A low pass filter sub-block;

Analysis test strip sample cell interface sub-block;

A trans-impedance amplifier sub-block; And

Phase detector sub-block.

20. The method of embodiment F19, wherein the phase detector sub-block is configured as a rising edge acquisition phase detector.

21. The method of embodiment F19, wherein the phase detector sub-block is configured as a dual edge acquisition phase detector.

22. The method of embodiment F19, wherein the phase detector sub-block is configured as an XOR phase detector.

23. The method of embodiment F19, wherein the phase detector sub-block is configured as a synchronous modulated phase detector.

24. The method of embodiment F19, wherein the phase detector sub-block is configured as a quadrature demultiplexed phase detector.

25. The method of aspect F16, wherein the phase-change-based hematocrit measurement block and the microcontroller block are configured to measure a phase change using a signal of a first frequency and a second signal of a second frequency.

26. The method of Sun F25, wherein the body fluid sample is a whole blood sample, wherein the first frequency is in the range of 10 kHz to 25 kHz and the second frequency is in the range of 250 kHz to 500 kHz.

Appendix

U.S. Provisional Patent Application No. 61 / 581,087, which was originally filed and filed in U.S. Patent Application No. 13 / 250,525 (Attorney Docket DDI5209USNP) and PCT / GB2012 / 052421 (Attorney Docket DDI5209WOPCT) (Attorney Docket No. DDI5220USPSP); 61 / 581,089 (Attorney Docket No. DDI5220USPSP1); 61 / 581,099 (Attorney Docket No. DDI5220USPSP2); And 61 / 581,100 (Attorney Docket No. DDI5221USPSP) and 61 / 654,013 (Attorney Docket No. DDI5228USPSP), each of which is incorporated herein by reference in its entirety.

BACKGROUND OF THE INVENTION [0002] The following disclosure generally relates to medical devices, particularly test instruments and related methods.

Measurement (e.g., detection and / or concentration measurement) of an analyte in a fluid sample is of particular interest in the medical field. For example, it may be desirable to determine the concentration of glucose, ketone, cholesterol, lipid protein, triglyceride, acetaminophen, and / or HbA1c in a sample of body fluids such as urine, blood, plasma or interstitial fluid . Such determination can be accomplished using a handheld test meter in combination with an analytical test strip (e.g., an electrochemical-based analytical test strip).

The novel features of the present invention are particularly described in aspect "F ". A more thorough understanding of the features and advantages of the present invention will be obtained by reference to the following detailed description, which describes exemplary embodiments in which the principles of the invention are employed, and the accompanying drawings, wherein like reference numerals designate like elements.

Figure 12 is a simplified diagram of a handheld test meter in accordance with an embodiment of the present invention.

Figure 13 is a simplified block diagram of various blocks of the handheld test meter of Figure 12;

Figure 14 is a simplified block diagram of a phase-change-based hematocrit measurement block as may be used in an embodiment in accordance with the present invention.

Figure 15 is a simplified schematic diagram of a simplified low-pass filter sub-block block as may be used in an embodiment of the present invention.

Figure 16 is a simplified schematic diagram of a simplified annotation of a transimpedance amplifier (TIA) sub-block as may be used in an embodiment of the present invention.

Figure 17 illustrates a dual low-pass filter sub-block, a calibration load sub-block, an analysis test strip sample cell interface sub-block, a transimpedance amplifier sub-block, Block diagram of a simplified annotated diagram showing a block, an XOR phase change measurement sub-block and an orthogonal demultiplexed phase-change measurement sub-block.

18 is a flow chart illustrating steps in a method for using a hand held test meter in accordance with an embodiment of the present invention.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS The following detailed description should be understood with reference to the drawings, wherein like elements are denoted by the same reference numerals in different drawings. The drawings, which are not necessarily drawn to scale, illustrate exemplary embodiments for purposes of illustration only and are not intended to limit the scope of the invention. The detailed description exemplifies the principles of the invention by way of example and not by way of limitation. This description clearly makes several modifications, alterations, alternatives, and uses of the present invention that will enable those skilled in the art to make and use the present invention and that are presently considered to be the best modes of carrying out the invention.

As used herein, the term " about "or" roughly " for any numerical value or numerical range means that any portion or aggregate of elements may have any suitable dimensional tolerance to enable it to function for its intended purpose .

Generally, a handheld test meter for use with an assay strip to determine an analyte (such as glucose) in a body fluid sample (i.e., a whole blood sample), according to an embodiment of the present invention, includes a housing, A microcontroller block, and a phase-change-based hematocrit measurement block (also referred to as a phase-change-based hematocrit circuit). In such a handheld test meter, the phase-change-based hematocrit measurement block comprises a signal generating sub-block, a low pass filter sub-block, an analysis test strip sample cell interface sub-block, a transimpedance amplifier sub- Block. The phase-change-based hematocrit measurement block and the microcontroller block are also configured to measure the phase change of the bodily fluid sample in a sample cell of the analysis test strip inserted in the hand held test meter, And calculate the hematocrit of the body fluid sample based thereon.

A handheld test meter according to an embodiment of the present invention provides improved accuracy of analyte determinations (such as glucose determinations) in whole blood samples by allowing them to measure the hematocrit of a whole blood sample and then use the measured hematocrit during analyte determinations It is advantageous in point.

Once a person skilled in the art becomes aware of the present invention, those skilled in the art will readily understand that a handheld test meter that can be easily modified as a handheld test meter in accordance with the present invention is a one-touch (registered) device available from LifeScan Inc, Milpitas, CA Lt; RTI ID = 0.0 > Ultra < / RTI > 2 glucose meter. Further examples of handheld test instruments that can be modified are described in U.S. Patent Application Publication 2007/0084734 (published April 19, 2007) and 2007/0087397 (2007 (Published April 19, 2010) and International Patent Publication No. WO 2010/1049669 (published May 6, 2010).

12 is a simplified diagram of a handheld test meter 100 in accordance with one embodiment of the present invention. 13 is a simplified block diagram of the various blocks of the handheld test meter 100. FIG. FIG. 14 is a simplified, combined block diagram of a phase-change-based hematocrit measurement block of the handheld test meter 100. FIG. FIG. 15 is a simplified schematic diagram of a simplified annotation of a dual low pass filter sub-block of a handheld test meter 100. FIG. 16 is a simplified schematic diagram of a simplified annotation of the transimpedance amplifier sub-block of the handheld test meter 100. FIG. 17 is a simplified block diagram of a simplified annotation of portions of the phase-change-based hematocrit measurement block of the handheld test meter 100. FIG.

12-17, the handheld test meter 100 includes a display 102, a plurality of user interface buttons 104, a strip port connector 106, a USB interface 108, and a housing 110 (See FIG. 12). 13, the handheld test meter 100 also includes a microcontroller block 112, a phase-change-based hematocrit measurement block 114, a display control block 116, a memory block 118, Other electronic components for applying the test voltage to the strip (indicated by TS in Fig. 12) and for determining the electrochemical response (e.g., a plurality of test current values) and determining the analyte based on the electrochemical response (Not shown). To simplify the present description, the drawings do not show all such electronic circuits.

Display 102 may be, for example, a liquid crystal display or a bistable display configured to display a screen image. Examples of screen images may include a glucose concentration, date and time, error messages, and a user interface to inform the end user how to perform the test.

The strip port connector 106 is configured to operatively interface with an assay strip TS, such as an electrochemical-based assay strip configured to determine glucose in a whole blood sample. Thus, the analytical test strip is configured to be operatively inserted into the strip port connector 106 and operatively interfaced with the phase-change-based hematocrit measurement block 114, for example, via suitable electrical contacts.

USB interface 108 may be any suitable interface known to those skilled in the art. USB interface 108 is essentially a passive component that is configured to supply power to handheld test meter 100 and provide data lines to the meter.

Once the assay strip is interfaced with or prior to the handheld test meter 100, a body fluid sample (e.g., a whole blood sample) is introduced into the sample chamber of the assay strip. Analytical test strips may include enzyme reagents that selectively and quantitatively convert an analyte to another desired chemical form. For example, an assay test strip may include an enzyme reagent with ferricyanide and glucose oxidase so that the glucose can be physically converted into an oxidized form.

The memory block 118 of the handheld test meter 100 includes an appropriate algorithm and is coupled with the microcontroller block 112 to determine the analyte based on the electrochemical response of the hematocrit and analytical test strip of the introduced sample Lt; / RTI > For example, in the determination of the analyte blood sugar, the hematocrit may be used to compensate for the effect of the hematocrit on the electrochemically determined blood glucose concentration.

The microcontroller block 112 may be located within the housing 110 and may include any suitable microcontroller and / or microprocessor known to those skilled in the art. One such suitable microcontroller is a microcontroller with part number MSP430F5138 available from Texas Instruments, Dallas, Texas. Such a microcontroller can produce a square wave of 25 to 250 kHz and a 90 degree phase-shifted wave of the same frequency, thereby serving as a signal generating s-block, described further below. The MSP430F5138 also has analog-to-digital (A / D) processing capability suitable for measuring the voltage generated by the phase change based hematocrit measurement block used in embodiments of the present invention.

14, the phase-change-based hematocrit measurement block 114 includes a signal generating sub-block 120, a low pass filter sub-block 122, an analysis test strip sample cell interface sub-block 124, Block 126, a transimpedance amplifier sub-block 128, and a phase detector sub-block 130 (in the dotted line of Fig. 14).

As described further below, the phase-change-based hematocrit measurement block 114 and the microcontroller block 112 measure the phase change of one or more high frequency electrical signals driven through, for example, a body fluid sample, And to measure the phase change of the body fluid sample in the sample cell of the assay strip inserted into the test meter. In addition, the microcontroller block 112 is configured to calculate the hematocrit of body fluids based on the measured phase change. The microcontroller 112 may, for example, use an A / D converter to measure the voltage received from the phase-detector sub-block and convert the voltage to a phase-change, and then convert the phase-change to a hematocrit value The hematocrit can be calculated by using an algorithm or a lookup table. Those skilled in the art will recognize that the algorithm and / or look-up table will be configured to take into account various factors such as strip geometry (including electrode area and sample chamber volume) and signal frequency once the present invention is known.

It has been found that there is a predetermined relationship between the reactance of the whole blood sample and the hematocrit of the sample. Electrical modeling of a body fluid sample (i. E., A whole blood sample) as parallel capacitive and resistive components requires that the phase change of the AC signal when passing an alternating current (AC) signal through the body fluid sample is at both the hematocrit of the sample and the frequency of the AC voltage It will depend on it. The modeling also indicates that the hematocrit has a relatively minor influence on the phase change when the frequency of the signal is in the range of approximately 10 kHz to 25 kHz and the phase change when the frequency of the signal is within the range of approximately 250 kHz to 500 kHz ≪ / RTI > Thus, the hematocrit of a body fluid sample can be measured, for example, by passing an AC signal of known frequency through a body fluid sample and detecting their phase change. For example, a phase-change of a signal having a frequency in the range of 10 kHz to 25 kHz may be used as a reference reading in such a hematocrit measurement while a phase change of a signal having a frequency in the range of 250 kHz to 500 kHz Can be used as the main measure.

Referring specifically to Figures 14-17, the signal generating sub-block 120 may be any suitable signal generating block and is configured to generate a square wave of the desired frequency (0 V to Vref). Such a signal generating sub-block may be integrated into the microcontroller block 112 if necessary.

The signal generated by the signal generation sub-block 120 is passed to a dual low-pass filter sub-block 122 configured to convert the square-wave signal into a sinusoidal signal of a predetermined frequency. The dual LPF of FIG. 15 includes a signal of a first frequency (such as a frequency in the range of 10 kHz to 25 kHz) to the sample chamber of the analysis test strip (also referred to as the HCT measurement cell) and the analysis test strip sample cell interface sub- (Such as a frequency in the range of 250 kHz to 500 kHz). The selection of the first and second frequencies is achieved using the switch IC7 of Fig. The dual LPF of FIG. 15 includes the use of two suitable operational amplifiers (IC4 and IC5), such as operational amplifiers available from Texas Instruments, Dallas, Texas, as part of the high speed, voltage feedback, CMOS op amp OPA354.

Referring to Fig. 15, F-DRV represents a low frequency or high frequency (e.g. 25 kHz or 250 kHz) square wave input and is connected to both IC4 and IC5. The signal Fi-HIGH / LOW (from the microcontroller) selects the output of the dual low-pass filter sub-block 122 via switch IC7. C5 of FIG. 15 is configured to block the operating voltage of the dual low pass filter sub-block 122 from the HCT measurement cell.

Although a particular dual LPF is shown in FIG. 15, the dual low-pass filter sub-block 122 may be any suitable low-pass filter, such as any suitable multi-feedback low pass filter, or any of the well known to those skilled in the art including a Sallen- Lt; RTI ID = 0.0 > sub-block. ≪ / RTI >

The sinusoidal wave generated by the lowpass filter sub-block 122 is passed to the analysis test strip sample cell interface sub-block 124, which is driven across the sample cell of the analysis test strip (also referred to as the HCT measurement cell) do. The analysis test strip sample cell interface block 124 may include an interface block configured to operatively interface with a sample cell of an analysis test strip through, for example, a first electrode and a second electrode of an analysis test strip disposed in a sample cell. Lt; / RTI > In such a configuration, the signal can be driven into the sample cell via the first electrode (from the low-pass filter sub-block), as shown in Fig. 17, and the sample can be driven through the second electrode (by the transimpedance amplifier sub- Can be picked up from the cell.

The current generated by driving the signal across the sample cell is picked up by the transimpedance amplifier sub-block 128 and converted into a voltage signal for communication with the phase detector sub-block 130.

The transimpedance sub-block 128 may be any suitable transimpedance sub-block known to those skilled in the art. Figure 16 is a simplified block diagram of a simplified annotation of one such transimpedance amplifier sub-block (based on two OPA354 operational amplifiers, IC3 and IC9). The first stage of the TIA sub-block 128 operates, for example, at 400 pF, which limits the AC amplitude to +/- 400 pF. The second stage of TIA sub-block 128 operates at Vref / 2, which allows the generation of the output of the full span of the microcontroller A / D input. C9 of TIA sub-block 128 serves as a blocking component that allows only AC sinusoidal signals to pass.

The phase detector sub-block 130 can be read back by the microcontroller block 112 using a digital frequency or analog-to-digital converter that can be read back by the microcontroller block 112 using the acquisition function Block may be any suitable phase detector sub-block that generates an analog voltage. 17 is a block diagram of two such phase detector sub-blocks: an XOR phase detector (in the upper half of FIG. 17, including IC22 and IC23) and a phase detector (in the lower half of FIG. 17, ) Orthogonal demultiplexing phase detector.

Figure 17 also shows a calibration load sub-block 126 that includes a switch IC 16 and a dummy load R7 and C6. The calibration load sub-block 126 is configured for dynamic measurement of the phase offset for a known phase change of 0 degrees produced by the resistor R7, thus providing a phase offset for use during calibration. C6 is configured to compensate for some pre-set phase shift, for example, the phase delay caused by the parasitic capacitance in the signal trace to the sample cell, or the phase delay in the electrical circuits (LPF and TIA).

The orthogonal demultiplexed phase detector circuit of Figure 17 includes two portions, one for the resistive portion of the incoming AC signal and one for the reactive portion of the incoming AC signal. The use of such two portions enables simultaneous measurement of both the resistive and reactive portions of the AC signal and a measurement range including 0 degrees to 360 degrees. The orthogonal demultiplexer circuit of Fig. 17 generates two separate output voltages. One of these output voltages represents "in phase measurement" and is proportional to the "resistive" portion of the AC signal, the other output voltage represents "Quadrature Measurement" do. The phase change is calculated as follows:

Φ = tan ^-1 (V _QUAD-PHASE / V _IN-PHASE )

Such an orthogonal demultiplexing phase detector circuit can also be used to measure the impedance of the body fluid sample in the sample cell. Without limitation, it is assumed that an impedance can be used to determine the hematocrit of the body sample, with phase-change, or independent of the phase-change. The amplitude of the signal passed through the sample cell can be calculated using the two voltage outputs of the orthogonal demultiplexing circuit as follows:

Amplitude = SQR ((V _QUAD-PHASE ) ² + (V _IN-PHASE ) ² )

This amplitude can then be compared to the measured amplitude for the known resistor of the calibration load block 126 to determine the impedance.

The XOR phase detector portion has a measurement range of 0 DEG to 180 DEG, or alternatively from -90 DEG to + 90 DEG, depending on whether the "square wave input from mu C" Lt; / RTI > The XOR phase detector always produces an output frequency that is twice the input frequency, but the duty cycle varies. If both inputs are perfectly equal, the output is LOW; if both inputs are 180 °, the output is always HIGH. By integrating the output signal (e.g., via a simple RC element), a voltage that is directly proportional to the phase change between both inputs can be generated.

Once the present invention is known, those skilled in the art will appreciate that the phase detector sub-block used in embodiments of the present invention can take any suitable form and can be implemented using any suitable technique, including, for example, a rising edge capture technique, a double edge capture technique, Quot; and " using " techniques.

Since the low-pass filter sub-block 122, the transimpedance amplifier sub-block 128 and the phase detector sub-block 130 can introduce the residual phase change into the phase-change-based hematocrit measurement block 114, The calibration load block 126 may optionally be included in the phase-change-based hematocrit measurement block. The calibration load block 126 is configured to be substantially resistive (e.g., a 33 k-ohm load), so that a phase change between the excitation voltage and the generated current is not induced. The calibration load block 126 is configured to switch across the circuit to provide a "0" calibration reading. Once calibrated, the handheld test meter can measure the phase change of the body fluid sample, subtract the "0" reading to calculate the modified phase change, and calculate the body sample hematocrit based on the subsequently modified phase change .

18 is a flow chart illustrating steps in a method 200 for using a handheld test meter and an analysis test strip (e.g., an electrochemical-based analysis test strip). At step 210, the method 200 includes introducing a whole blood sample into a sample cell of an assay strip.

In step 220, the phase change of the whole blood sample in the sample cell is measured using the microcontroller block and the phase-change-based measurement block of the handheld test meter. The method 200 further comprises calculating a hematocrit of the whole blood sample based on the measured phase change using the microcontroller block (see step 230 of FIG. 18).

Those skilled in the art will appreciate that the method according to embodiments of the present invention, including method 200, may be applied to any of the techniques, advantages and features of the handheld test meter described herein and in accordance with embodiments of the present invention. It will be appreciated that the present invention can be easily modified to incorporate such features. For example, if necessary, the analyte is determined in the bodily fluid sample introduced using the analytical test strip, the handheld test meter and the calculated hematocrit.

Claims (51)

A method for determining analyte concentration from a fluid sample with a biosensor having at least two electrodes and a reagent disposed on at least one of the electrodes,
Depositing a fluid sample on at least one electrode to initiate an analyte test sequence;
Applying a signal to the sample to determine a physical property of the sample;
Introducing another signal to the sample to cause a physical conversion of the sample;
Measuring at least one output signal from the sample;
Obtaining an estimated analyte concentration from at least one predetermined parameter of the biosensor and at least one output signal at one time position of the plurality of predetermined time positions from the start of the test sequence;
Generating a first parametric factor of the biosensor based on the physical characteristics of the sample;
Calculating a first analyte concentration based on the first parameter coefficient of the biosensor and at least one output signal measured at one time position of the plurality of predetermined time positions from the start of the test sequence ;
Generating a second parameter coefficient of the biosensor based on the estimated analyte concentration and the physical characteristics of the sample;
Calculating a second analyte concentration based on the second parameter coefficient of the biosensor and at least one output signal measured at one time position of the plurality of predetermined time positions from the start of the test sequence ;
Generating a third parameter coefficient of the biosensor based on the first analyte concentration and the physical property;
Calculating a third analyte concentration based on the third parameter coefficient of the biosensor and at least one output signal measured at one time position of the plurality of predetermined time positions from the start of the test sequence ; And
And reporting at least one of the first, second and third analyte concentrations. A method for determining an analyte concentration from a fluid sample with a biosensor having at least two electrodes and a reagent disposed on at least one of the electrodes,
Initiating an analyte test sequence upon deposition of the sample;
Applying a signal to the sample to determine a physical property of the sample;
Introducing another signal to the sample to cause a physical conversion of the sample;
Measuring at least one output signal from the sample;
Deriving an estimated analyte concentration from the at least one output signal measured at one time position of the plurality of predetermined time positions from the start of the test sequence;
Obtaining new parameters of the biosensor based on the estimated analyte concentration and the physical characteristics of the sample;
Calculating an analyte concentration based on the new parameter of the biosensor and an output signal measured at the one of the plurality of predetermined time positions or at another time position from the start of the test sequence; And
And notifying the analyte concentration. A method for determining an analyte concentration from a fluid sample with a biosensor having at least two electrodes and a reagent disposed on at least one of the electrodes,
Initiating an analyte test sequence upon deposition of the sample on the biosensor;
Applying a signal to the sample to determine a physical property of the sample;
Introducing another signal to the sample to cause a physical conversion of the sample;
Measuring at least one output signal from the sample;
Generating a first new batch parameter of the biosensor based on the physical characteristics of the sample;
Calculating a first analyte concentration based on the first new batch parameter of the biosensor and an output signal measured at one of a plurality of predetermined time positions from the start of the test sequence; And
And reporting the first analyte concentration. The method of claim 3,
Generating a third parameter of the biosensor based on the physical property and the first analyte concentration;
Calculating a third analyte concentration based on the third parameter of the biosensor and an output signal measured at a time position of one of a plurality of predetermined time positions from the start of the test sequence; And
Further comprising reporting the third analyte concentration instead of the first analyte concentration. 4. The method according to any one of claims 1 to 3, wherein the parameter of the biosensor comprises a batch slope and the new parameter of the biosensor comprises a new batch slope. 6. The method of claim 5, wherein the applying step of the first signal and the introducing step of the second signal can be performed in a sequential order. 4. The method of any one of claims 1 to 3, wherein the applying step of the first signal overlaps the introducing step of the second signal. 4. The method of any one of claims 1 to 3, wherein the applying step of the first signal includes directing an alternating signal to the sample so that the physical property of the sample can be determined from the output of the alternating signal and,
Wherein the physical properties include at least one of viscosity, hematocrit, temperature and density of the sample or a combination thereof. 6. The method of claim 5, wherein the physical property comprises an impedance characteristic indicative of a hematocrit of the sample, and wherein the analyte comprises glucose. 10. The method of claim 9, wherein the impedance characteristic of the sample can be determined by an equation of the form:
[Equation 4.2]

here:
The IC exhibiting the impedance characteristic;
M is the magnitude of the measured impedance | Z | (in ohms);
P represents the phase difference between input and output signals (in degrees);
y ₁ may be about -3.2e-08 and +/- 10%, 5%, or 1% of the numerical value provided (and may be zero or even negative depending on the frequency of the input signal);
y ₂ is (with and be zero or even negative, depending on the frequency of the input signal) can be about 4.1e-03 and ± 10% of those given a numerical value of 5% or 1% and;
y ₃ may be about -2.5 e + 01 and +/- 10%, 5% or 1% of the numerical value provided;
y ₄ may be about 1.5e-01 and +/- 10%, 5%, or 1% of the provided numerical value (and may be zero or even negative depending on the frequency of the input signal);
y ₅ may be about 5.0 and +/- 10%, 5% or 1% of the provided numerical value (and may be zero or even negative depending on the frequency of the input signal). 10. The method of claim 9, wherein the physical property, denoted by H, is substantially the same as the impedance property determined by an equation of the form:

here:
IC represents the above impedance characteristic, [%],
M represents the above-mentioned magnitude of the impedance, and [ohm]
y ₁ is between about 1.2292e1,
y ₂ is about -4.3431e2,
y ₃ is about 3.5260e4. 10. The method of claim 9, wherein the directing comprises driving first and second AC signals of different respective frequencies, wherein the first frequency may be lower than the second frequency. 13. The method of claim 12, wherein the first frequency may be at least one order of magnitude lower than the second frequency. 14. The method of claim 12 or 13, wherein the first frequency comprises any frequency in the range of about 10 kHz to about 250 kHz. 6. The method of claim 5, wherein the one of the plurality of predetermined time positions for measuring at least one output signal during the test sequence may be about 2.5 seconds after the start of the test sequence. 16. The method of claim 15, wherein the one of the plurality of predetermined time positions comprises a time period overlapping with a time point of 2.5 seconds after the start of the test sequence. 6. The method of claim 5, wherein the other one of the plurality of predetermined time positions for measuring at least one output signal during the test sequence may be at a time point of about 5 seconds after the start of the test sequence . 6. The method of claim 5, wherein said one of said plurality of predetermined time positions comprises an arbitrary time less than 5 seconds from the beginning of said check sequence. 6. The method of claim 5, wherein the other one of the plurality of predetermined time positions comprises an arbitrary time less than 10 seconds from the start of the test sequence. 20. The method of claim 18 or 19, wherein the one of the plurality of predetermined time positions comprises a time period overlapping with a time point of 2.5 seconds after the start of the test sequence, Wherein the other one of the positions comprises a time period overlapping with a 5 second time point after the start of the test sequence. 3. The method according to claim 1 or 2, wherein said calculating step of said estimated analyte concentration can be calculated from the following form:

here
G ₁ represents the first analyte concentration;
I _E represents the total output signal from at least one electrode measured at said one of said plurality of predetermined time positions;
P1 represents the intercept parameter of the biosensor, where P1 may be about 475 nanoamperes;
P2 represents the slope parameter of the biosensor, where P2 may be about 9.5 nanoamperes / (mg / dL). 2. The method of claim 1, wherein the step of calculating the first analyte concentration can be calculated from the following form:

here
G ₁ represents the first analyte concentration;
I _E represents the total output signal from at least one electrode measured at said one of said plurality of predetermined time positions;
P1 represents the segmentation parameter of the biosensor, where P1 may be about 475 nanoamperes;
P2 represents the slope parameter of the biosensor, where P2 may be about 9.5 nanoamperes / (mg / dL);
x ₂ represents a biosensor parameter coefficient based on the physical characteristics of the sample. 3. The method of claim 1 or 2, wherein the step of calculating the second analyte concentration can be calculated by the following form:

G ₂ represents the second analyte concentration;
I _E represents the total output signal from at least one electrode measured at said one of said plurality of predetermined time positions or at another time position;
P1 represents the segmentation parameter of the biosensor, where P1 may be about 475 nanoamperes;
P2 represents the slope parameter of the biosensor, where P2 may be about 9.5 nanoamperes / (mg / dL);
x ₃ represents a coefficient from a matrix based on both the physical property of the sample and the estimated analyte concentration. 5. The method of claim 1 or 4, wherein said calculating step of said third analyte concentration can be calculated by an equation of the form:

G ₃ represents the third analyte concentration;
I _E represents the total output signal from at least one electrode measured at said one of said plurality of predetermined time positions or at another time position;
P1 represents the segmentation parameter of the biosensor, where P1 may be about 475 nanoamperes;
P2 represents the slope parameter of the biosensor, where P2 may be about 9.5 nanoamperes / (mg / dL);
x ₃ represents a coefficient from a matrix based on both the physical property of the sample and the first analyte concentration. 6. The method of claim 5, wherein the at least two electrodes and at least two other electrodes are disposed in the same chamber provided on the substrate. 26. The method of any one of claims 1 to 25, wherein the at least two electrodes comprise two electrodes for measuring the physical properties and analyte concentration. 27. A method according to any one of the preceding claims wherein the at least two electrodes comprise a first set of at least two electrodes for determining the physical properties of the sample and at least two And a second set of other electrodes. 28. The method of claim 26 or 27, wherein all of the electrodes are disposed on the same plane defined by the substrate of the biosensor. 27. The method of claim 26, wherein a third electrode is proximate the first set of at least two electrodes and is connectable to the second set of at least two other electrodes. 29. A system according to any one of claims 26 to 28, wherein a reagent can be placed close to the at least two other electrodes, and no reagent can be placed on the at least two electrodes. An analyte measurement system,
As a test strip,
Board;
A plurality of electrodes connected to respective electrode connectors; And
As an analyte meter,
housing;
A test strip port connector configured to connect to the respective electrode connectors of the test strip; And
And a microprocessor in electrical communication with the test strip port connector to sense electrical signals or apply electrical signals from the plurality of electrodes during a test sequence,
The microprocessor, during the test sequence,
(a) initiating an analyte test sequence upon deposition of the sample;
(b) applying a signal to the sample to determine a physical property of the sample;
(c) introducing another signal into the sample;
(d) measuring at least one output signal from at least one of the electrodes;
(e) deriving an estimated analyte concentration from the at least one output signal at one of a plurality of predetermined time positions from the start of the test sequence;
(f) acquiring a new parameter of the biosensor based on the estimated analyte concentration and the physical characteristics of the sample;
(g) calculating an analyte concentration based on the new parameter of the biosensor and the output signal measured at the one or the other one of the plurality of predetermined time positions from the start of the test sequence ; And
(h) can be configured to notify the analyte concentration. 32. The analyte measurement system of claim 31, wherein the plurality of electrodes comprises at least two electrodes for measuring the physical properties and at least two other electrodes for measuring the analyte concentration. 33. The analyte measurement system of claim 32, wherein the at least two electrodes and the at least two other electrodes are disposed in the same chamber provided on the substrate. 32. The analyte measurement system of claim 31, wherein the plurality of electrodes comprises two electrodes for measuring the physical properties and the analyte concentration. 35. An analyte measurement system as claimed in any one of claims 31 to 34, wherein all of said electrodes are disposed on the same plane defined by said substrate. 36. An analyte measurement system according to any one of claims 31 to 35, wherein a reagent can be placed close to the at least two other electrodes, and no reagent can be placed on the at least two electrodes, . 32. The method of claim 31, wherein the one of the plurality of predetermined time positions for measuring at least one output signal during the test sequence is about 2.5 seconds after the start of the test sequence, system. 32. The analyte measurement system of claim 31, wherein the one of the plurality of predetermined time positions comprises a time period overlapping with a point of time of 2.5 seconds after the start of the test sequence. 32. The method of claim 31, wherein the other one of the plurality of predetermined time positions for measuring at least one output signal during the test sequence may be at a time point of about 5 seconds after the start of the test sequence Water measuring system. 32. The analyte measurement system of claim 31, wherein the one of the plurality of predetermined time positions comprises an arbitrary time less than 5 seconds from the start of the test sequence. 32. The analyte measurement system of claim 31, wherein the other one of the plurality of predetermined time positions comprises an arbitrary time less than 10 seconds from the start of the test sequence. 42. The method of claim 40 or claim 41, wherein said one of said plurality of predetermined time positions comprises a time period overlapping with a time point of 2.5 seconds after said start of said test sequence, Wherein the other one of the positions comprises a time period overlapping with a 5 second time point after the start of the test sequence. As a glucose meter,
housing;
A test strip port connector configured to be connected to each of the electrode connectors of the biosensor; And
(a) means for applying first and second input signals to a sample deposited on the biosensor during a test sequence;
(b) means for measuring a physical characteristic of the sample from one of the first and second input signals;
(c) means for deriving an estimated glucose concentration at one of a plurality of predetermined time positions from the beginning of the test sequence based on the other of the first and second input signals;
(d) means for generating a new parameter of the biosensor based on the physical characteristic and the estimated glucose concentration; And
(e) means for calculating a glucose concentration based on the new parameter of the biosensor and an output signal at a time position or another time position of the plurality of predetermined time positions; And
And an indicator (annunciator) for providing an output of said glucose concentration from said means. 44. The glucose meter of claim 43, wherein the means for measuring comprises means for applying a first AC signal to the biosensor and means for applying a second constant signal to the biosensor. 44. The glucose meter of claim 43, wherein the means for deriving comprises means for estimating analyte concentration based on a predetermined sampling time from the start of the test sequence. 44. The glucose meter of claim 43, wherein said means for generating comprises means for correlating said physical properties with said estimated glucose concentration and said new parameters of said biosensor. 44. The glucose meter of claim 43, wherein the means for calculating comprises determining a glucose concentration from the new parameter of the biosensor and the current measured at another of the plurality of predetermined time positions. 48. The method of claim 47, wherein the one of the plurality of views includes a time of about 2.5 seconds from the start of the test sequence, and wherein the other one of the plurality of predetermined time positions And a time point of about 5 seconds from the start. 48. The method of claim 47, wherein the one of the plurality of views includes a time period of about 2.5 seconds from the start of the test sequence, and wherein the other one of the plurality of predetermined time locations is the test sequence Wherein the glucose meter comprises a time interval of about 5 seconds from the start of the glucose meter. CLAIMS What is claimed is: 1. A method for proving increased accuracy of a plurality of test strips,
Providing a batch of glucose test strips;
Introducing a reference sample containing glucose of a reference concentration into each test strip of the batch of test strips to initiate a test sequence;
Reacting the glucose with reagents on each test strip to cause physical conversion of the glucose between the two electrodes;
Applying a signal to the reference sample to determine a physical property of the reference sample;
Introducing a different signal to the reference sample;
Measuring at least one output signal from the test strip;
Deriving an estimated glucose concentration of the reference sample from the at least one output signal measured at one of a plurality of predetermined time positions from the start of the test sequence;
Obtaining a new parameter of the test strip based on the estimated glucose concentration of the reference sample and the physical characteristics of the reference sample;
And wherein the controller is further adapted to determine an output of the test strip at a different one of the plurality of predetermined time positions from the start of the test sequence and the new parameter of the test strip to provide a glucose concentration value for each test strip of the batch of test strips Calculating a glucose concentration of the reference sample based on the signal such that at least 95% of the glucose concentration values of the batches of test strips are within ± 15 mg / dL of the reference glucose concentration. 51. The method of claim 50, wherein greater than or equal to 86% of the glucose concentration is within +/- 15% of those glucose concentrations above 100 mg / dL.

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