Source: https://patents.com/us-8298400.html
Timestamp: 2019-10-24 04:23:06
Document Index: 280466272

Matched Legal Cases: ['Application No. 09007943', 'Application No. 09007942', 'Application No. 09007944', 'Application No. 01998816', 'Application No. 2000', 'Application No. 2001']

US Patent # 8,298,400. Method of measuring quantity of substrate - Patents.com
United States Patent 8,298,400
Miyazaki , et al. October 30, 2012
Inventors: Miyazaki; Shoji (Matsuyama, JP), Tokunaga; Hiroyuki (Onsen-gun, JP), Tokuno; Yoshinobu (Iyo-gun, JP)
Appl. No.: 12/803,253
11378944 Mar., 2006 7850839
10182236 7232510
PCT/JP01/10525 Nov., 2001
Nov 30, 2000 [JP] 2000-364225
Nov 22, 2001 [JP] 2001-357144
Current U.S. Class: 205/792 ; 204/403.02; 204/406; 204/408
Field of Search: 204/403.01,403.02,406,408 205/777.5,792
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This application is a divisional of U.S. patent application Ser. No. 11/378,944, filed Mar. 16, 2006, now U.S. Pat. No. 7,850,839, which is a divisional of U.S. patent application Ser. No. 10/182,236, filed Nov. 21, 2002, now U.S. Pat. No. 7,232,510, which is a 35 U.S.C. .sctn.371 U.S. National Phase of PCT Application No. PCT/JP01/10525, filed Nov. 30, 2001, and claims priority to Japanese Application No. 2000-364225, filed Nov. 30, 2000, and Japanese Application No. 2001-357144, filed Nov. 22, 2001, the contents of all of which are hereby incorporated by reference.
1. A method of measuring a quantity of a substrate, comprising the steps of: i) providing a biosensor which includes a reagent layer reacting specifically with a substrate included in a measurement sample; ii) providing a measuring device for measuring the quantity of the substrate, wherein the measuring device includes: a temperature measuring section for measuring a temperature while the reaction between the reagent layer and the measurement sample progresses; and a temperature compensation data memory having a plurality of measurement compensation tables which are different in different temperature ranges; iii) selecting one of the compensation tables according to a combination of a temperature measured by the temperature measuring section and a concentration of the substrate; iv) calculating a compensation value corresponding to a measured value of the substrate; and v) compensating the measured value of the substrate with the calculated compensation value.
2. The method of claim 1, wherein the biosensor further includes an insulating board and an electrode section formed on at least a part of the insulating board, the electrode section including a counter electrode and a measuring electrode, and wherein the measuring device applies a voltage to the electrode section, and detects an electric current flowing from the electrode section.
3. The method of claim 1, wherein the temperature measuring section comprises a plurality of temperature measuring sections for measuring values of the temperature, said method further comprising: determining a difference between the values of the temperature; and determining whether or not the difference exceeds a given threshold.
4. The method of claim 3, wherein said selecting one of the compensation tables according to the temperature comprises: providing an average of the measured values of the temperature; and selecting the one of the compensation tables according to the average of the measured values of the temperature if the difference does not exceed the given threshold.
5. The method of claim 1, wherein the biosensor comprises a counter electrode, a measuring electrode, and a detecting electrode that are arranged along a flow direction of the measurement sample such that the detecting electrode is most downstream of the electrodes; the method further comprising the steps of: determining a lapse between a time when a current or voltage that is measured between the measuring electrode and the counter electrode reaches a first given level and a time when a current or voltage that is measured between the measuring electrode and the detecting electrode reaches a second given level; and compensating the measured quantity of the substrate depending on the lapse of time.
6. The method of claim 5, wherein voltage is provided by a current-to-voltage converter.
Next, components forming biosensor 30 will be described with reference to FIG. 2, an exploded perspective view of biosensor 30. Insulating board 31 (hereinafter called simply "board") is made of, e.g., polyethylene terephthalate. On a surface of board 31, a conductive layer, which is made of a noble metal such as gold and palladium, or an electrically conductive substance such as carbon, is formed by screen printing or sputtering evaporation. The conductive layer may be formed on the entire or at least a part of the surface. Reference numeral 32 denotes an insulating board having air hole 33 formed at its center. Spacer 34 having a notch is disposed between boards 31 and 32, so that board 32 is integrated to board 31.
In measuring device 10, reference numerals 12, 13, 14, 15, 16 and 17 denote connectors connected to areas A, B, C, D, E and F, respectively, which are produced by dividing recognizing section 42 of biosensor 30 into six areas. The six areas are grouped such that the groups correspond to slits 41d, 41f and slits 41g, 41h. Area A corresponds to measuring electrode 38, area C corresponds to detecting electrode 39, and area E corresponds to counter electrode 37. Area A is integrally formed with area B, and areas D and F correspond to compensating sections 43 and 44 shown in FIG. 3, respectively. Switches 18, 19, 20, 21 and 22 are provided between respective connectors 13, 14, 15, 16, 17 and a grounding (meaning a constant voltage, not necessarily "0"V. This definition is applicable to this description hereinafter.) Voltage to be applied to respective electrodes can be controlled at the grounding. Connectors 13, 14, 15, 16 and 17 are connected in parallel to the grounding. Switches 18 to 22, upon being turned on and off under control, select a necessary connector out of connectors 13 to 17 which is used for the measurement.
If it is determined that the voltage detected between area A and areas C is greater than 5 mV (step S4, Yes), it is recognized that biosensor 30 which is used is inserted, and the measuring process terminates due to an error of an used sensor (step S5). If being detected, the error of used sensor is preferably displayed on display 11, or noticed to a user as an alarm sound from a speaker. This prevents the user easily from dripping blood to biosensor 30 by mistake while used biosensor 30 is inserted. Next, when the voltage detected between area A and areas C, E is not greater than 5 mV (step S4: No), the patterns of the slits is recognized by recognizing section 42 of biosensor 30 which is detected to be inserted at step S1. According to the recognizing result, CPU 25 changes data and a program into appropriate ones for output characteristics of the sensor (steps S6 to S10). In the first embodiment, three patterns of the slits are available, as shown in FIGS. 3(e), 3(f), and 3(g), for a blood-sugar-level sensor which measures a glucose concentration. Specifically, first, conductivity between areas A and D is tested (step S6). Switch 20 is turned on, and then the conductivity between areas A and D is tested, so that it may be determined whether or not biosensor 30 is proper to measure a blood sugar level and not proper to measure a quantity of lactic acid or cholesterol.
Next, a concentration of the substrate selected in step S35, S36 or S37 is compensated by a compensation coefficient corresponding to the delay time which has been found in steps S14 and S17 and stored in the memory (step S38). Specifically, the concentration is compensated by the following equation (1): D1=(concentration of substrate).times.[{100-(sensitivity compensation coefficient)}/100] where D1 is a compensated concentration of the substrate. This compensation eliminates a measurement error due to adding sample liquid by a user.
FIG. 13 shows temperature compensation tables. Compensation table T10 is used for the temperature of 10.degree. C. In the same manner, table T15 is for the temperature of 15.degree. C., and table T20 is for the temperature of 20.degree. C. The compensation tables specifies a relation between substrate concentration D1 in the sample liquid and a temperature compensation coefficient is specified. The temperature compensation coefficient is determined based on a concentration at 25.degree. C. as a reference, and shows a coefficient for compensation with respect to the concentration. Specifically, the compensation for temperature is performed according to the following equation (2): D2=D1.times.(100-Co)/100 where D2 is a compensated concentration, D1 is the concentration calculated in step S38, and Co is the temperature compensation coefficient specified by referring to the temperature compensation table.
The inventors found experimentally that measurement accuracy was influenced by a combination of a measured temperature and a concentration of a substrate. The influence will be described hereinafter. FIG. 14 shows relations between the measured temperature and measurement dispersion (bias) at each concentration of glucose. The measurement dispersion in FIG. 14 is defined by a coefficient of a change of a concentration of glucose measured at 25.degree. C. according to a change of the measured temperature. FIG. 14(a) shows a relation between the dispersion and the measured temperature in the case of glucose concentration of 50 mg/dl at 25.degree. C. Similarly, FIG. 14(b) shows the relation for the glucose concentration of 100 mg/dl and the temperature of 25.degree. C. FIG. 14(c) shows the relation for the glucose concentration of 200 mg/dl and the temperature of 25.degree. C. FIG. 14(d) shows the relation for the glucose concentration of 300 mg/dl and the temperature of 25.degree. C. FIG. 14(e) shows the relation for the glucose concentration of 420 mg/dl and the temperature of 25.degree. C. FIG. 14(f) shows the relation for the glucose concentration 550 mg/dl and the temperature of 25.degree. C.
These experimental data point out the following two tendencies. First, for the same glucose concentration, the measuring dispersion increases as a difference between a measured temperature and reference temperature 25.degree. C. becomes greater. In detail, the dispersion increases in a negative direction as a measured temperature decreases from the reference temperature, and the dispersion increases in a positive direction as a measured temperature rises from the reference temperature. Second, the dispersion converges at the glucose concentration of 300 mg/dl, which seems a boundary, even though the glucose concentration increases. Specifically, FIG. 14(a) indicates the dispersion of approximately 28% at 40.degree. C., FIG. 14(c) indicates approximately 50%, FIG. 14(d) indicates approximately 60%, and FIG. 14(f) indicates approximately 50%. A similar tendency is found in a low temperature range such as a measured temperature of 10.degree. C.
This tendency is reflected to the tables shown in FIG. 13. First, the measuring dispersion increases as a difference between a measured temperature and reference temperature of 25.degree. C. becomes greater for the same glucose concentration. Second, the dispersion starts converging at the glucose concentration of 300 mg/dl as a boundary even though the glucose concentration increases. These two aspects are taken into consideration for preparing the tables. The measurement accuracy is remarkably improved by compensating a concentration referring to the temperature compensation table, in which combinations of measured temperatures and concentrations of the substrate are well considered, rather than compensating a concentration only based on a measured temperature.
In an operable temperature range of biosensor 30 (10.degree. C. to 40.degree. C. in this embodiment), a temperature compensation table for every 1.degree. C. may be prepared, or the table for every given temperature range (e.g. 5.degree. C.). If a temperature at a middle of the given temperature range is detected, a temperature compensation coefficient may be calculated by a linear interpolation with a temperature compensation table including the detected temperature.
FIG. 15 shows temperature changes in measuring device 10. A temperature change in device 10 moving from a place at a temperature of 10.degree. C. to another place at a temperature of that of 25.degree. C. is shown in FIG. 15. A temperature change in device 10 moving from a place at a temperature of 40.degree. C. to a place of a temperature of 25 C is also shown in FIG. 15. FIG. 15 shows that it takes approximately 30 minutes to stabilize the temperature changes in an ambient temperature ranging from 10 to 40.degree. C. If the temperature compensation is carried while the temperature changes, an exact temperature compensation may not be expected.
TABLE-US-00001 TABLE 1 S Blood Supply (mm) Angle (deg.) 1 2 3 4 5 Conventional 0 0 X X X X X Sensor 15 .DELTA. X X .DELTA. X 30 .DELTA. .DELTA. .DELTA. X .DELTA. 45 .largecircle. .largecircle. .largecircle. .largecircle. .DELTA. 90 .largecircle. .largecircle. .largecircle. .largecircle. .largecircle.- Sensor 0.1 0 .largecircle. .DELTA. .DELTA. .largecircle. .DELTA. According 15 .largecircle. .DELTA. .largecircle. .largecircle. .DELTA. to Present 30 .largecircle. .largecircle. .largecircle. .largecircle. .DE- LTA. Invention 45 .largecircle. .largecircle. .largecircle. .largecircle. .lar- gecircle. 90 .largecircle. .largecircle. .largecircle. .largecircle. .largecircle.- 0.25 0 .largecircle. .largecircle. .largecircle. .largecircle. .largecirc- le. 15 .largecircle. .largecircle. .largecircle. .largecircle. .largecircle.- 30 .largecircle. .largecircle. .largecircle. .largecircle. .largecircle.- 45 .largecircle. .largecircle. .largecircle. .largecircle. .largecircle.- 90 .largecircle. .largecircle. .largecircle. .largecircle. .largecircle.- 0.5 0 .largecircle. .largecircle. .largecircle. .largecircle. .largecircl- e. 15 .largecircle. .largecircle. .largecircle. .largecircle. .largecircle.- 30 .largecircle. .largecircle. .largecircle. .largecircle. .largecircle.- 45 .largecircle. .largecircle. .largecircle. .largecircle. .largecircle.- 90 .largecircle. .largecircle. .largecircle. .largecircle. .largecircle.- 1.0 0 .largecircle. .largecircle. .largecircle. .largecircle. .largecircl- e. 15 .largecircle. .largecircle. .largecircle. .largecircle. .largecircle.- 30 .largecircle. .largecircle. .largecircle. .largecircle. .largecircle.- 45 .largecircle. .largecircle. .largecircle. .largecircle. .largecircle.- 90 .largecircle. .largecircle. .largecircle. .largecircle. .largecircle.- 2.0 0 .largecircle. .largecircle. .largecircle. .largecircle. .largecircl- e. 15 .largecircle. .largecircle. .largecircle. .largecircle. .largecircle.- 30 .largecircle. .largecircle. .largecircle. .largecircle. .largecircle.- 45 .largecircle. .largecircle. .largecircle. .largecircle. .largecircle.- 90 .largecircle. .largecircle. .largecircle. .largecircle. .largecircle.- Definitions of the marks in the table: .largecircle.: The blood is sucked by one sucking. .DELTA.: The blood is sucked by two or three sucking operations. X: The blood is not sucked at all.
TABLE-US-00002 TABLE 2 S Blood Supply (mm) Angle (deg.) 1 2 3 4 5 Conventional 0 0 X X X X X Sensor 15 X X X X X 30 X X X X X 45 X X X X X 90 X X X X X Sensor 0.1 0 X .DELTA. .DELTA. .DELTA. X According 15 .DELTA. .DELTA. .DELTA. X .DELTA. to Present 30 .DELTA. .largecircle. .DELTA. .largecircle. .DELTA. Invention 45 .largecircle. .largecircle. .largecircle. .largecircle. .lar- gecircle. 90 .largecircle. .largecircle. .largecircle. .largecircle. .largecircle.- 0.25 0 .largecircle. .largecircle. .largecircle. .largecircle. .largecirc- le. 15 .largecircle. .largecircle. .largecircle. .largecircle. .largecircle.- 30 .largecircle. .largecircle. .largecircle. .largecircle. .largecircle.- 45 .largecircle. .largecircle. .largecircle. .largecircle. .largecircle.- 90 .largecircle. .largecircle. .largecircle. .largecircle. .largecircle.- 0.5 0 .largecircle. .largecircle. .largecircle. .largecircle. .largecircl- e. 15 .largecircle. .largecircle. .largecircle. .largecircle. .largecircle.- 30 .largecircle. .largecircle. .largecircle. .largecircle. .largecircle.- 45 .largecircle. .largecircle. .largecircle. .largecircle. .largecircle.- 90 .largecircle. .largecircle. .largecircle. .largecircle. .largecircle.- 1.0 0 .largecircle. .largecircle. .largecircle. .largecircle. .largecircl- e. 15 .largecircle. .largecircle. .largecircle. .largecircle. .largecircle.- 30 .largecircle. .largecircle. .largecircle. .largecircle. .largecircle.- 45 .largecircle. .largecircle. .largecircle. .largecircle. .largecircle.- 90 .largecircle. .largecircle. .largecircle. .largecircle. .largecircle.- 2.0 0 .largecircle. .largecircle. .largecircle. .largecircle. .largecircl- e. 15 .largecircle. .largecircle. .largecircle. .largecircle. .largecircle.- 30 .largecircle. .largecircle. .largecircle. .largecircle. .largecircle.- 45 .largecircle. .largecircle. .largecircle. .largecircle. .largecircle.- 90 .largecircle. .largecircle. .largecircle. .largecircle. .largecircle.- Definitions of the marks in the table: .largecircle.: The blood is sucked by one sucking. .DELTA.: The blood is sucked by two or three sucking operations. X: The blood is not sucked at all.
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