HK1200536B - A test method for analyzing body fluid - Google Patents

Description

Test methods for testing body fluids

This application is a divisional application of the invention patent application with application date of February 18, 2010, application number 201080008165.3, and invention name “Testing method and testing equipment for testing body fluids”.

Technical Field

The present invention relates to a test method for testing body fluids, in particular for blood glucose determination, wherein a test strip, preferably in the form of a cassette, is inserted into a test device so that a plurality of analytical test fields stored on the test strip are successively provided via a tape transport mechanism, wherein the provided test fields are loaded with body fluid by a user and scanned photometrically by a device-side measuring unit while detecting a measurement signal. The present invention also relates to a corresponding test apparatus.

Background Art

A test tape device according to the preamble is known, for example, from the applicant's EP application No. 08166955.8, which describes a magnetic tape cassette with a test tape on which, in addition to the analysis test fields, positioning marks are also present in order to ensure reliable positioning in different functional positions for each relevant tape section.

DE 199 32 846 A1 discloses a method for detecting mispositioning of optically analyzable test strips, which is based on a comparison of two measured values from test points spaced apart from one another in the insertion direction of the test strip in a test device. However, in a test strip system, the situation is hardly comparable to a tape system, as the test strips are inserted individually into the device guides, whereas the tape transport and guidance take place on the consumable side.

Summary of the Invention

Based on this, the object of the present invention is to further improve the test methods and test devices proposed in the prior art and to ensure increased reliability against operating errors and measurement errors.

In order to achieve this object, the feature combinations specified in the independent claims are proposed. Advantageous developments and refinements of the invention are revealed in the dependent claims.

A first aspect of the present invention is based on the idea of deriving an error analysis from expected signal changes in the measurement signal that are correlated with the test result. Accordingly, the present invention proposes determining a control value from the time-dependent and/or wavelength-dependent changes in the measurement signal and, depending on a predetermined threshold value for the control value, either processing the measurement signal as valid or rejecting it as erroneous. This makes it possible to largely exclude external influences that could distort the measurement results. It should be understood that multiple potential error cases can also be checked in parallel.

Error detection based on sample application provides for detecting measurement signals at two different wavelengths and determining a control value from the signal difference of the measurement signals of different wavelengths. If the signal difference disappears, an error is detected on the device side and an error signal is triggered, if necessary. This also allows, in particular, the detection of manipulations in which a user, for example, presses the test field with a finger without applying a sample.

Advantageously, the signal difference of the measurement signals of different wavelengths, due to the wetting of the provided test field with body fluid, allows reliable false positive detection even at low analyte concentrations. In this regard, it is advantageous to obtain measurement signals of different wavelengths in the visible wavelength range and in the infrared range.

Another advantageous embodiment is to determine the control value from the signal difference of the measurement signals detected at the beginning and end of the measurement interval, wherein an error is detected when the signal difference disappears. This type of error detection is based on the specific reaction kinetics of the analyte on the color-changing test field, which can therefore be distinguished from mechanical strip manipulation.

According to another advantageous embodiment, the measurement signal is detected over the duration of a measurement interval, the control value being determined from the measurement signal change in an initial time section of the measurement interval, and an error being detected if the measurement signal change falls below a predetermined minimum value. This also allows for the exclusion of environmental influences that would only result in a significant reduction in the initial signal change compared to regular measurements.

In the preparation phase for liquid application, it is advantageous if a blank value is cyclically detected on a provided test field and a control value is determined by the change in the blank value relative to an initial blank value, wherein liquid application is detected when the blank value changes above a threshold value and an error situation is detected when the blank value changes below the threshold value.

Advantageously, a momentary blank value is taken into account when the blank value changes up to a predetermined limit value to determine a relative measured value for the analyte in the body fluid. This allows a referenced measured value to be obtained, while small changes in the reference amount lead to falsified results.

The advantages described above also result for a corresponding device for carrying out the method according to the invention.

Another aspect of the invention is that a batch control value is stored on a memory device associated with the test strip, so that the test field control value is determined from a blank measurement of a first test field that has not yet been used, and the usability of the first test field is determined by comparing this batch control value with the test field control value. This quality check can detect harmful effects on test materials that are consumables, such as those that are only used after a long storage period. As a result of this check, if the test field control value of the first test field on an entire test strip deviates from the batch control value by more than a predetermined tolerance, the entire test strip can also be classified as unusable.

Advantageously, the batch control value is determined during batch production of the test strips by measuring the test field and the calibration field on the test strip material. This can be reliably performed when producing the test strips due to the uniform processing.

In order to take into account tolerable variations of subsequent measurements, it is advantageous if the test field control values of the test tape that are provided and listed as available are stored on the device side as new tape control values and that the correspondingly determined test field control values of the subsequent test field are compared with the stored tape control values for the purpose of checking the availability of the subsequent test field.

Advantageous measured value referencing can be achieved by performing a calibration measurement by detecting a preferably white calibration field correlated with the corresponding test field using the measuring unit, and determining the test field control value as a relative value from the blank measurement and the calibration measurement.

For a process that is as automated as possible, it is also advantageous if the batch control value is stored in a storage device applied to the cassette, preferably in an RFID chip, so that a comparison can be performed on the device side without further user interaction.

A special aspect of the present invention is that the signal offset of the measuring unit is detected in a reference area of the test tape relative to the provided test field, and an error message is triggered if the signal offset exceeds a predetermined limit value. In this way, contamination or other changes in the optical beam path can be reliably detected.

Another development provides for detecting the signal offset on a darkened black field as a reference area of the test tape, wherein the black field is arranged on a tape section adjacent to the respective test field and is positioned in the detection area of the measuring unit by the tape transport mechanism.

BRIEF DESCRIPTION OF THE DRAWINGS

The invention is explained in more detail below with reference to an exemplary embodiment shown in the accompanying drawings, in which:

FIG1 shows in a cutaway perspective view an analytical test strip system for performing blood glucose determinations including a handheld device and a test cassette;

FIG2 shows an enlarged cross-sectional view of FIG1 in the region of the measuring tip;

FIG3 shows a test strip section in top view;

FIG4 shows a graph of measured values at different stages of the measurement process;

FIG. 5 shows a graph of measured values for two different wavelengths as a function of analyte concentration.

DETAILED DESCRIPTION

The test strip system shown in FIG1 enables the use of a cassette 12 with a retractable test strip 14 in a handheld device 10 as a consumable item for performing glucose tests, with functional checks being performed at various stages of the measurement process. The general device principle is described in EP application No. 02026242.4, to which reference is hereby made.

Handheld device 10 has a belt drive (electric motor 15 with drive shaft 16), a measuring unit 18, a microprocessor-supported control device 20, and an energy supply device 22. A display (not shown) enables the output of measurement results and device messages to the user.

The magnetic tape cassette 12, which can be inserted into a receiving compartment 23 of the device 10, comprises a supply reel 24 for unused test tapes 14 and a take-up reel 26 for used test tapes, which can be coupled to the drive 16, as well as a tape guide 25 with a deflection tip 34. The supply reel 24 is arranged in a storage chamber 28 that is sealed relative to the surroundings.

Test strip 14 is equipped with test fields 32 in sections, and these test fields 32 therefore seem to be arranged in a given order in the tape transport direction. In this case, it will be considered that removing the test fields 32 contaminated by the blood on the take-up reel 26 and therefore the rewinding of the tape is not feasible.

In each case, the provided or active test field 31 can be loaded with a sample liquid, in particular blood or tissue fluid, on the front side in the area of the deflection tip 34 accessible from the outside. Detection of the analyte (glucose) is achieved by detecting the color change of the test field 32 from the back side using a reflective photometric method with the aid of a measuring cell 18. For this purpose, the test field 32 is applied as a dry reagent layer on a transparent support film. The test fields 32 can be put into use one after another by corresponding forward movement of the belt. In this way, multiple tests can be performed for the patient's own control without having to frequently replace consumables.

As shown in Figure 2, the device-mounted test unit 18, which is engaged in the cartridge 12, has three light-emitting diodes 36, 38, and 40 as radiation sources and a photodiode 41 as a detector for signal detection using reflectometry. An optical device 43 enables a bundled optical path, imaging a light spot of defined size and intensity onto the back of the strip. The central light-emitting diode 38 radiates at approximately 650 nm in the visible (red) wavelength range, while the outer light-emitting diodes 36 and 40 operate in the infrared at 875 nm. The light scattered back from the test strip 48 is detected by the photodiode 41 at a predetermined time interval.

As illustrated in FIG3 , the spaced-apart test fields 32 are individually located on the associated tape segment 42, which is additionally provided with further inspection or control fields in the form of black fields 44 and white fields 46. The test field 32 has a central test strip 48 formed by a test chemical layer and laterally delimited by two hydrophobic edge strips 50. A sample liquid applied to the front of the test field 32 wets the test strip 48 in the form of a sample spot 52, which is scanned from the transparent tape backside by the light spots 36', 38', 40' of the light-emitting diodes 36, 38, 40 in the measuring position on the deflection tip 34. However, since the tape can only be transported in one direction (arrow 54), the inspection fields 44, 46 are first detected before the actual measurement, as explained further below.

In the standby position, the white field 46 of the unused tape section 42 is located on the deflection tip 34 upstream of the measuring unit 18. The white field 46, which is impressed in white onto the carrier tape 34, is metered so that the measuring window detected by the measuring unit 18 is completely covered. In the same way, the upstream black field 44 can also be positioned for measurement before assuming the standby position.

As can be seen from Figure 4, the measurement cycle for each tape segment 42 is divided into different phases. In phase 1a, the black field 44 is scanned for contamination detection and, if necessary, for device-side self-calibration, as will be explained in more detail below. In phase 1b, the white field 46 is measured for tape quality inspection and, if necessary, self-calibration. Phase 1c provides for obtaining the so-called dry blank value TLW on the unused test field 32. A request (Id) is then issued to the user for blood sampling. This concludes the preparation phase.

In phase II, wetting of the test field 32 is detected by means of the IR light-emitting diodes 36, 40. When the test strip 48 is wetted, a decrease in the signal intensity occurs.

The kinetics of the analyte-specific measurement signal is then tracked in phases III and IV, based on the color change of the test strip 48, with a measurement cycle of, for example, 0.2 seconds. Phase IIIb of the kinetic tracking ends when a signal change interruption threshold, which is attenuated according to the chemical reaction rate, is reached. Subsequently, in phase IV, a double measurement is performed using the LED 38 to determine the average final value EW. The glucose concentration is then determined using relative remission by taking the quotient of the final value EW and the dry blank value TLW (the relative remission is typically calculated from the ratio of the current measured value to the dry blank value). Phase V also provides for a homogeneity measurement of the sample spot 52 for underdose detection, which is based on a comparison of the quantitative signals of the two IR LEDs 36 and 40. Finally, the glucose concentration is displayed to the user on the display of the device 10.

In addition to the actual measurement for determining the glucose concentration, the aforementioned functionality or "fail-safe" is implemented as follows:

Contaminant identification is performed using the LED 38 after the cartridge 12 is inserted and subsequently after each glucose measurement by measuring the signal bias on the black field 44. This bias is generated by the entire measuring environment when the LED is switched on and does not participate in the test. This bias is thus used as an additive quantity when determining the measured value. Due to contamination or other optical changes in the light path, for example caused by foreign bodies, dust and scratches, the emitted light is partially reflected and directed to the detector 41. The black field 44 serves as a substitute for a black cavity that does not reflect light during bias identification. However, in principle, it is also possible to perform measurements by inserting a transparent support strip into the dark interior of the device.

The detected signal offset is compared with a limit value stored in the device 10, which limit value has been determined as a batch average value during product production. If the stored limit value is exceeded, an error message is triggered.

To check the quality of the magnetic tape cassette 12, which may be used as a disposable item after a longer storage period, a reference value WF is detected at least on the first white field 46 on the test strip 14. Subsequently, potential impairment of the chemical properties of the test strip, for example due to environmental influences, is detected by a corresponding change in the dry blank value TLW of the first test field 32. For this purpose, not absolute mitigation values are used, but relative mitigation values relative to the reference value WF.

The corresponding batch control value CC is determined during the batch production of the test strips 14 by measuring the test field 32 and the white field 46 on the test strip material. The strips are produced in a reel-to-reel process that allows for the determination of these control values for a coating that is as consistent as possible. The batch control value is stored in an RFID chip 56 on the cartridge 12 and is read and processed by the test electronics 20. The RFID chip 56 is applied to the outside of the cartridge 12 and is shown only symbolically in the cross-sectional illustration according to FIG. 2 .

The result of the test field quality check is negative if the following conditions are met:

TLW ₁ /WF ₁ ＜CC-ΔC (1),

ΔC is the tolerance value, while the subscript 1 relates to the first test strip section 42. In this case, a corresponding error message is issued and the cartridge 12 is discarded if necessary.

If the result is positive, it is also possible to perform a quality check within narrower limits for subsequent tests. To this end, the relative relief value Cn-1 of the currently used test field is stored in the device memory and is used instead of the batch control value CC according to the above equation (1). When the following conditions are met:

TLW _n /WF _n <C _n-1 -ΔC (2),

The subsequent quality check of the following test field n therefore has a negative result.

Typically, the manufacturer's calibration of the device 10 ensures that relevant measured values can only be generated within a specific measurement range for all optoelectronic components. In this case, the electrical and optical characteristic parameters of the three LEDs 36 , 38 , 40 are calibrated.

In principle, self-calibration methods or device-side calibration are also possible to minimize the specific influence of signal offsets and fluctuating absolute measured values on the measured value determination. Due to manufacturing, optical offsets vary from cartridge to cartridge. Furthermore, the separation of the device-side optics and the cartridge-side tape guide results in distance components with tolerances.

The black and white fields 44, 46 are again used for reference measurements and are located on the test strip 14 before each test field 32. These fields are measured during production and are assigned batch-number average values. These values are stored on the RFID chip 56 as reference values.

After inserting the cartridge 12, the black point value measured on the first black field 44 is checked to see whether it lies within a predefined tolerance around the manufacturer's batch average for the optical offset. If so, the batch average is retained. If the measured black point value deviates from this tolerance range, the difference from the batch average is determined and calculated as the optical offset. The optical offset is then subtracted from the gross measurement signal obtained on the test field 32.

However, the correction of the optical offset is only performed up to a certain limit value. When this limit is exceeded, an error message is triggered as described above. Before each subsequent test, the black field measurement is used only for contamination detection.

In the case of white field calibration, the individual sensitivity values of the cartridges are determined by comparing the measured values detected on the white field 46 with the batch mean values stored on the RFID chip 56 in absolute terms. If the measured white field value m _K is within the tolerance range around the batch mean value m _W , the batch mean value m _W is taken into account for the subsequent scaling of the offset-corrected gross measurement signal; otherwise, the individual cartridge sensitivity m _K is taken into account. However, if the limit values of the deviation are exceeded, an error message is output.

In order to largely exclude the generation of unwanted measured values due to operating errors, a control value can be determined from a time-dependent and/or wavelength-dependent change in the measurement signal, wherein the measurement signal is then processed further as valid or discarded as erroneous depending on a threshold value for the control value.

The first such error can be that, due to the distance-dependence of the measuring principle, pressing the deflection tip 34 without applying a sample can generate a measurement start and a false measurement result. To eliminate this, the measurement signals are detected at two different wavelengths in the measuring field 32, with the control value being determined from the signal difference of the measurement signals of the different wavelengths.

As shown in FIG5 , when measuring samples using different wavelengths, different values of relative sensitivity are obtained across the entire range of analyte or glucose concentrations to be tested. The signal difference is generated by wetting the test field 32 with body fluid (thus, a difference is detected even at a sample concentration of 0) and is intensified when the test chemistry system develops an increased reaction color. Therefore, if the measurement signal is generated solely by pressing, the usual difference between the two LEDs 38 and 40 with different wavelengths cannot be observed due to the lack of wetting and reaction color, thus identifying an error. The predetermined threshold value for the signal difference can be, for example, a relative sensitivity of 3%.

Another scenario for generating unwanted measured values is the misidentification of a blood draw caused by strip displacement. If the dark edge strip 50 of the test field 32 is displaced into the beam path of the measuring unit 18 by a user operation, high measured values are generated without the sample being applied.

However, above a glucose concentration of approximately 100 mg/dl, the typical reaction kinetics of the blood sample on the test field 32 exhibit a signal amplitude of approximately 10%, as determined in phase III ( FIG. 4 ) as the difference between the first and last kinetic measurements. If, however, the test strip is merely displaced in phase II as described above, a sudden darkening occurs and a constant signal is subsequently achieved (hence, no changed reaction kinetics and no significant signal amplitude are observed in phase III). Therefore, error detection can be performed by determining the control value from the signal difference of the measurement signals detected at the beginning and end of the measurement interval, and detecting an error when the signal difference approaches zero.

If the test field 32 is in the state of sample application detection before the optical device 43 (Phase II in FIG. 4 ), the control device 20 of the device 10 interprets a signal change of a certain magnitude as sample application and starts the analysis. High humidity and even sunlight, even under unfavorable circumstances, can lead to such a signal change and thus to the start of a measurement without sample application.

To prevent this, the time course of the blank signal change is monitored during the sample waiting phase. While a drop of a few percent occurs within half a second after applying the blood sample, this drop only occurs over time intervals of more than 20 seconds under the influence of sunlight or air humidity. This allows for cyclical blank value detection on a test field provided for sample application, and for control values to be determined based on the change in the blank value relative to the initial blank value. Liquid application is detected when the change in the blank value exceeds a predetermined threshold value (e.g., approximately 5%), and an error is detected when the change in the blank value falls below this predetermined threshold value, optionally after a predetermined waiting time.

Another measurement problem can be that the dry blank value of a test field 32 that is provided but not yet used changes, for example, due to light or humidity influences, and thus falsifies the reference variable for determining the relative relief. The measured values of the unused test fields can therefore be cyclically checked and/or updated while the sample is waiting, in order to prevent the measured value from being falsified or to terminate the measurement with an error message starting at a certain limit value, for example, a relative relief change of more than 0.5%/s.

Claims (6)

1. A testing method for analyzing bodily fluids, wherein a test strip (14) is inserted into a testing device (10) in the form of a cassette tape (12) to provide, sequentially via a tape transport mechanism, multiple analytical test fields (32) stored on the test strip (14), wherein each provided test field is scanned by a user loading bodily fluid and by means of a measuring unit (18) on the device side in a photometric manner, characterized in that, during the batch manufacturing of test strips, a batch number control value is determined by measuring the test fields (32) on the test strip material and the batch number control value is stored on a storage device (56) associated with the test strip (14) and applied to the cassette tape (12), and Furthermore, the test field control value is determined from the blank measurement of the first unused test field and compared with the batch control value. The test field control value provided by the test tape and listed as the test field control value of the available test field as a result of the comparison between the batch control value and the test field control value is stored on the device side as a new tape control value. In order to check the availability of the next test field, the corresponding determined test field control value of the next test field is compared with the stored tape control value. The calibration measurement is performed by detecting the calibration field (46) associated with the corresponding test field (32) by means of the measurement unit (18), and the test field control value is determined as a relative value by the blank measurement and the calibration measurement. 2. The testing method according to claim 1, wherein the testing method is used to determine blood glucose levels. 3. The test method according to claim 1, wherein the calibration field (44, 46) is also measured. 4. The test method according to claim 1, characterized in that when the test field control value of the first test field on the test strip (14) deviates from the batch number control value by more than a predetermined tolerance, the first test field (32) or the entire test strip (14) is listed as unusable. 5. The test method according to any one of claims 1 to 3, wherein the calibration field is white. 6. The testing method according to any one of claims 1 to 3, wherein the batch number control value is stored in an RFID chip.