U.S. patent application number 09/943639 was filed with the patent office on 2002-11-07 for method for checking the fitness for purpose of analysis elements.
Invention is credited to Albrecht, Gertrud, Gaa, Otto, Loch-Leroux, Dieter.
Application Number | 20020164805 09/943639 |
Document ID | / |
Family ID | 7654945 |
Filed Date | 2002-11-07 |
United States Patent
Application |
20020164805 |
Kind Code |
A1 |
Gaa, Otto ; et al. |
November 7, 2002 |
Method for checking the fitness for purpose of analysis
elements
Abstract
For a simple and reliable check of the fitness for purpose of
analysis elements, it is proposed to check the deviation of the
quotient of a control value and a first standard reference value as
compared to a first reference quotient, formed by a control
reference value and the first standard reference value, and to
reject a checked analysis element, if the deviation is not within a
given tolerance range.
Inventors: |
Gaa, Otto; (Worms, DE)
; Albrecht, Gertrud; (Mannheim, DE) ; Loch-Leroux,
Dieter; (Carlsberg, DE) |
Correspondence
Address: |
Roche Diagnostics Corporation
9115 Hague Road, Bldg. D
P.O. Box 50457
Indianapolis
IN
46250-0457
US
|
Family ID: |
7654945 |
Appl. No.: |
09/943639 |
Filed: |
August 29, 2001 |
Current U.S.
Class: |
436/8 ;
436/43 |
Current CPC
Class: |
G01N 33/52 20130101;
Y10T 436/11 20150115; Y10T 436/10 20150115 |
Class at
Publication: |
436/8 ;
436/43 |
International
Class: |
G01N 035/00 |
Foreign Application Data
Date |
Code |
Application Number |
Sep 1, 2000 |
DE |
100 43 556.4 |
Claims
1. Method for checking the fitness for purpose of analysis
elements, in which method it is checked, whether a control value
measured for at least one control parameter of a checked analysis
element is within a tolerance range, wherein a) in a first step, a
first standard reference value is determined in a reference value
measurement at a reference control means which provides a
standardized reference value for the control parameter, b) in a
second step, the control parameter of a first analysis element is
determined as control reference value, c) in a third step, the
quotient from the control reference value and the first standard
reference value is calculated and set as first reference quotient
for analysis elements measured later, d) in a fourth step, the
control parameter of a second analysis element is determined as
control value for the second analysis element to be checked, e) in
a fifth step, the quotient from the control value and the first
standard reference value is calculated as the control quotient, f)
in a sixth step, the deviation between the control quotient and the
first reference quotient is determined and g) the checked second
analysis element is rejected if the deviation is not within a given
tolerance range.
2. Method according to claim 1, wherein the deviation is determined
using a relative difference between the control quotient and the
first reference quotient in step g).
3. Method according to claim 1, wherein the deviation is determined
using a difference between the control quotient and the first
reference quotient in step g).
4. Method according to claim 1, wherein the checked, second
analysis element is rejected in step g), if the control quotient is
smaller, by a given percentage, than the first reference
quotient.
5. Method according to claim 1, wherein the checked, second
analysis element is rejected in step g), if the control quotient is
smaller, by a given difference value, than the first reference
quotient.
6. Method according to claim 1, wherein a tolerance range is used
in step g) which is batch-specific for the current batch of
analysis elements.
7. Method according to claim 1 wherein the first analysis element
and the second analysis element, the one to be checked, are
comprised in a package or in a storage container, which contains
further similar analysis elements, showing a long-time packaging
common to all analysis elements.
8. Method according to claim 7, wherein the analysis elements in
the package or in the storage container are individually protected
by an individual packaging element.
9. Method according to claim 7, wherein the analysis element which
is the first one to be removed from a package or from a storage
container contained in the package, is chosen in step b).
10. Method according to claim 7, wherein steps a) to c) are
performed when a new package is used, when the first analysis
element of a package or a storage container is used or when a
long-time packaging is opened.
11. Method according to claim 1, wherein the steps a) to c) are
repeated, if a change which potentially influences the measured
value, was performed on the evaluation device which performs the
control measurement or the analytical measurement,
respectively.
12. Method according to claim 1, wherein in case of the
determination of a given deviation in step g), the control value
determined in step d) is used as new control reference value
according to step b), calculating a new reference quotient from
this according to step c), and that this new reference quotient is
used as basis for checking further analysis elements according to
steps d) to g).
13. Method according to claim 12, wherein a new reference quotient
is formed, if a control quotient determined in step e) exceeds the
current reference quotient by more than a fixed limit value.
14. Method according to claim 13, wherein a tolerance value is
used, which is batch-specific for the current batch of analysis
elements.
15. Method according to claim 1, wherein one or various method
steps are performed automatically.
16. Method according to claim 1, wherein a reference control means
is used, providing a high measured value for the control parameter
in step a).
17. Method according to claim 1, wherein such analysis elements are
used which comprise a control means for the measurement of the
control reference value or control value, as well as the reference
control means for the reference value measurement of step a).
18. Method according to claim 1, wherein the analysis element is a
test element for a substrate-based rapid test for the qualitative
or quantitative analysis of components of a solid or liquid sample,
in particular of body liquids of human beings or animals, in
particular for the determination of the blood glucose content.
19. Method according to claim 1, wherein the control parameter is
an optical measured value, in particular a remission value.
20. Evaluation device for measuring an analytic measured value with
an analysis element, wherein the evaluation device comprises means
to perform a method according to claim 1.
Description
[0001] The invention relates to a method for checking the fitness
for purpose of analysis elements, in which method a check is
performed whether a measured control value for at least one control
parameter of a checked analysis element is within a tolerance
range. Furthermore, the invention relates to a corresponding
evaluation device.
[0002] For the qualitative and quantitative analysis, by means of
chemical and biochemical processes for the analysis of sample
materials, in particular liquid samples, in particular of a body
liquid of human beings or animals, so-called substrate-based rapid
tests are used to a large extent, in laboratories specialized on
this, but in particular also for the use outside of fixed
laboratories. These substrate-based rapid tests are based on a
specially developed dry chemistry process, and can be performed
easily and without problems even by nonexperts, in spite of the
complex reaction occurring in many cases, using sensitive
reagents.
[0003] For this, analysis elements are used which have reagents
embedded in one or more test layers. For the execution of a
reaction, the analysis element is brought into contact with the
sample. The reaction of sample and reagent leads to a change of the
analysis element, which change is characteristic for the analysis
and can be evaluated visually or by means of an evaluation device
(in most cases, reflection-photometrically). The analysis elements
are also designated as test elements.
[0004] Generally, the evaluation device is appropriate for the
evaluation of a very certain type of analysis elements of a certain
manufacturer. For this, the analysis elements and the evaluation
device are components which are mutually adjusted to each other, as
a whole, they are commonly designated as analysis system.
[0005] A plurality of different analysis element types are known,
differentiated by the measuring principle (e.g. optical or
electrochemical) and the used reagents, as well as by their
structure, in particular by the arrangement and the fastening of
the test layers. In particular, strip-shaped analysis elements
(test strips) are common, consisting of an oblong plastic stripe
("basic stripe") and at least one test layer fixed to it. For
another common analysis element type, a plastic frame is used,
enframing at least one test layer.
[0006] A known example for substrate-based rapid tests are test
elements for the determination of the blood glucose content for
diabetics. Other known embodiments of stripe-shaped diagnostic test
elements are, e.g., one-field- or multi-field test stripes for
urinanalysis and different test papers. Analysis elements to be
evaluated with an apparatus, e.g. electrochemically or optically,
in particular analysis elements to be evaluated photometrically,
are comprehensively described in the prior art, and are known to
the persons skilled in the art in a plurality of embodiments.
[0007] It is known that the analytic function of the analysis
elements can be damaged by environment factors as e.g. light,
temperature or humidity. Such damages can lead to fault in
measuring when used; this can have dangerous consequences for a
diagnosis basing upon this, or can render the analysis elements
unusuable.
[0008] In the presence of light-sensitive, temperature-sensitive or
humidity-sensitive compounds, photometrically evaluated analysis
elements can change, even before use, their dry color in such an
extreme way that this can be recognized by an alert user. In these
cases, the analysis elements can be manually segregated. However,
the visual assessment is difficult and requires experience.
Moreover, due to the methodical difficulties, this is rarely
performed, or simply forgotten, in particular by nonexperts.
[0009] In order to protect the analysis elements from the impact of
light beams, the access of humidity, dirt, germs, dust, as well as
from mechanical deterioration, or in order to store them under
sterile conditions, the analysis elements are generally packaged.
For this, the analysis elements can be packaged individually, or be
comprised in a common packaging or in a storage container. However,
the packaging does not offer a 100% protection. For example, it can
be damaged during fabrication, transport or improper storage.
However, the most important factor is that the packaging offers
only very little protection against temperature influences and that
it does guarantee only little or no protection against aging
effects. The aging process proceeds in an increased way after a
package or a storage container has been opened, so the aging of
analysis elements in this period of time should receive special
consideration.
[0010] Thus, for checking the fitness for purpose of an analysis
element, for photometric measuring systems it is known, in the
prior art, before applying the sample to be measured, to determine
the so-called dry blank value of the measuring field, i.e. the
remission value of the analysis element, without the sample
applied. This dry blank value is compared to a comparative value;
the analysis element is rejected if the dry blank value serving as
control parameter is not within a given tolerance range.
[0011] For this known procedure, only a very inaccurate check is
possible, as the measuring devices used for the evaluation of the
analysis elements show individual tolerances during their
production, and as the differences between the devices even amplify
during service life, e.g. due to changes of the measurement device,
in particular for optical measurement systems. These changes can be
caused by mechanic charges leading to misadjustment, aging of the
illumination systems (e.g. light emitting diodes) or dust deposits
on the optical elements. Furthermore, batch fluctuations
influencing the dry blank value result in the fact that only
inaccurate checks are possible, unless these batch fluctuations are
considered by batch-specific information which is taken over from
the analysis elements or their respective packaging into the
evaluation device.
[0012] So far, no methods for checking or monitoring of the fitness
for purpose are known for electrochemical analysis elements, in
opposite to photometric analysis elements.
[0013] From the document U.S. Pat. No. 4,832,488, it is known to
consider the aging effects of optical analysis elements, which can
lead to a change of the calibration curve used in the analysis, by
parameters describing the aging process. The parameters are
determined by optical measurements of analysis elements, among
which also is, in some case constellations, the measurement of the
dry blank value; the rectification of the calibration using these
parameters leads to an improved measuring accuracy of the analysis.
However, this procedure is sophisticated with respect to its
practical application, and does not include any control of the
fundamental fitness for purpose of the analysis elements.
[0014] Test stripe elements are known from document DE 2800225 A1,
which show a reference field with comparison or compensation paper
pieces. These are exposed, just as the proper test field, to
radiation of different wavelengths, measuring the reflecting power.
The changes caused by samples on the reference field are detected;
with this, the influence of the measurement field caused by
characteristics of the sample, not based on the concentration of
the analyte, is compensated. This is a correction of sample-related
changes of the measurement conditions of an analysis device. There
is no control of the fitness for purpose of an analysis
element.
[0015] Taking into account this state of the art, the object of
this invention is to provide a simple and reliable method for
checking the fitness for purpose of analysis elements.
[0016] According to the invention, this object is achieved by a
method with the features of the appended claim 1. Preferred
embodiments and further developments of this invention can be taken
from the claims 2-20, and the subsequent description with the
corresponding drawings.
[0017] A method according to the invention, for checking the
fitness for purpose of analysis elements, in which method a check
is performed whether a control value measured for at least one
control parameter of a checked analysis element is within a
tolerance range, comprises the following steps:
[0018] a) In a first step, a first standard reference value is
determined in a reference value measurement, using a reference
control means. The reference control means provides a standardized
reference value for the control parameter.
[0019] b) In a second step, the control parameter of a first
analysis element is determined as control reference value.
[0020] c) In a third step, the quotient from the control reference
value and the first standard reference value is calculated and set
as first reference quotient for analysis elements measured
later.
[0021] d) In a fourth step, the control parameter of a second
analysis element is determined as control value for the second
analysis element to be checked.
[0022] e) In a fifth step, the quotient from the control value and
the first standard reference value is calculated as the control
quotient.
[0023] f) In a sixth step, the deviation between the control
quotient and the first reference quotient is determined.
[0024] g) The checked second analysis element is rejected if the
deviation is not within a given tolerance range.
[0025] Below, the invention is described, without limiting the
universality, using the example of photometrically evaluated
analysis elements. The explained principles can easily be applied
to other analysis elements, e.g. electrochemical ones.
[0026] For electrochemical analysis elements, an electronic
measured quantity, appropriate for the performance of the check,
can be used. For example, a blank value measurement with an AC
voltage, for which the impedance or the phase shift provide the
control parameter, can be considered for this. Other possible
control parameters are conductivity, capacitance, inductance, decay
times, frequency dependencies, or other functional correlations of
electronic measured quantities which can be expressed in
characteristic curves; e.g. a characteristic depending on current,
voltage or frequency. For cases in which the proper electrochemical
analysis element itself does not show an appropriate control
parameter, it is possible, in order to enable the possibility of
measuring, to add an additional component to the analysis element,
providing a characteristic which allows measurement and which is
appropriate for the check purposes according to this invention.
[0027] Thus, the method as according to this invention essentially
comprises two aspects. According to the first aspect, changes of
the optical measurement system are monitored. For this, a reference
value is measured using a standardized reference surface, e.g. a
white standard measurement, providing a standardized reference
value for the control parameter. No sample material is applied to
the reference surface. In the context of this invention, an optical
measurement value, in particular a remission value, is a very
appropriate control parameter. The first standard reference value
determined by this checks the current state of the evaluation
device, e.g. of the optical measurement system, and can be used for
a post-calibration of the evaluation device; however, this is not
necessary in the context of the invention; it is sufficient to use
the standard reference value as a reference value for subsequent
measurements.
[0028] The second aspect refers to the check of the fitness for
purpose of individual analysis elements, which could be impaired by
e.g. damaging influences or aging. For this, the control parameter
of a first analysis element is determined at the reactive
measurement field before applying the sample material, using it as
control reference value for analysis elements measured
subsequently. For this purpose, the quotient from the control
reference value of the first analysis element and the first
standard reference value is calculated, and the quotient is set as
the first reference quotient. For the subsequent check of a second
analysis element to be checked for its fitness for purpose, the
control parameter is determined at the reactive measurement field
before applying the sample material, i.e., for example, the dry
blank value of the second analysis element is determined as control
value, and the quotient of the determined control value of the
second analysis element and the first standard reference value is
calculated as the control quotient. Using the deviation between the
control quotient and the first reference quotient, it can then be
checked whether the checked second analysis element is fit for
purpose, or, if the deviation is not within a given tolerance
range, if it must be rejected due to deterioration.
[0029] With the method according to the invention it is possible to
check easily and reliably, before performing an analysis, without
expensive re-calibration processes, whether an analysis element can
be used for the performance of an analysis, or whether it must be
rejected due to the existence of deterioration, in particular in
case of aging after a package has been opened.
[0030] For this method, it is presupposed that the first analysis
element which has been used to determine the control reference
value, is undamaged and fit for purpose. The fitness for purpose of
the first analysis element is not controlled by the method
according to this invention. However, this can be checked, at least
in a coarse way, according to the method known in the state of the
art, using the dry blank value of the first analysis element; if
the control reference value determined for the first analysis
element is not within a given tolerance, the first analysis element
is not fit for purpose.
[0031] The method according to the invention principally works
without the reference measurement of step a), too. However, step a)
makes the method more sensitive, as it considers the differences of
different analysis devices, e.g. deviation due to the manufacturing
of the optical measuring systems. However, the coarse check of the
first analysis element is not the object of the invention; the
invention is focussed on the check of the analysis elements
following the first analysis element, proposing the method
described above.
[0032] Thus, the method according to the invention is advantageous
with respect to an additional aspect, in particular for such
application cases for which the first analysis element and the
second analysis element, the one to be checked, are comprised in a
package or in a storage container, which contains further similar
analysis elements, showing a long-time packaging common to all
analysis elements. For this, according to another advantageous
feature, the analysis elements in the package may be protected
additionally and individually by an individual packaging means.
[0033] In these application cases, the common long-time packaging
guarantees, with a high degree of safety, that the analysis
elements contained therein, and thus, the first analysis element,
are not deteriorated, except for possible deterioration caused by
temperature influences, which can be determined by means of the
known blank value tolerance measurement. After opening the
long-time packaging, the danger of damaging individual analysis
elements contained in the package by improper handling, is high.
However, a deterioration of the fitness for purpose of individual
analysis elements after opening the long-time packaging, can
advantageously be recognized by the check according to this
invention.
[0034] The invention has the advantage of enabling a simple and
reliable check of analysis elements. Another advantageous feature
is the fact that one or more of the method steps are performed
automatically, i.e. in a user-independent way. It must be noted
that the sequence of the steps according to the invention can be
modified conveniently--e.g., the order of the steps a) and b) can
be interchanged--thus, the designations "first" step etc. only
serve for the differentiation of the individual method steps
without determining the sequence; the method step sequence given in
claim 1, however, is a preferred embodiment.
[0035] Furthermore, the terms "first analysis element" and "second
analysis element" do not restrictively designate the first measured
analysis element (of a package), or the immediately subsequent
analysis element, respectively, but designate merely a conceptual
differentiation. The first analysis element is the one used for the
determination of the standard reference value. This is preferably,
but not necessarily, the first analysis element in the package. The
second analysis element is one of the analysis elements checked
subsequently, or checked in relation to the first analysis element.
These are preferably, but not necessarily, all analysis elements
following the first analysis element.
[0036] The invention will subsequently be explained in detail with
the help of an examplary embodiment shown in the figures. The
characteristics described can be used individually or in
combination, in order to create preferred embodiments of this
invention.
[0037] FIG. 1 shows an analysis element in the shape of a test
stripe.
[0038] FIG. 2 shows a package with test stripes contained in a
storage container.
[0039] FIG. 1 shows an analysis element 1 in the shape of a test
stripe which can be inserted into an evaluation device not shown;
the evaluation device and the analysis elements adapted thereto
form an analysis system. The analysis element comprises an elastic
basic layer 2, normally consisting of a plastic material. It
carries a test field 3, onto which a sample liquid to be analyzed
has to be applied. During the analysis, chemical reactions between
the sample liquid and the reagents contained in the test field 3
take place. A resulting, optically provable change can be detected
reflection-photometrically.
[0040] Many embodiments of test elements are known, differentiated
e.g. by the type of the chemical detection reaction, the layer
structure in the test field, the optical measurement method, and
the number of test fields 3 on a test stripe. All previously known
test stripes are appropriate in the scope of the check method
according to the invention.
[0041] The fitness for purpose of the analysis element 1 can
coarsely be checked with a so-called dry blank value measurement of
the test field 3, i.e. an optical measurement of the test field 3
without the application of sample liquid. For this, the analysis
element 1 is inserted into the evaluation device without a
preceding application of sample liquid, and the dry blank value is
measured. If the dry blank value, serving as control parameter, is
within a given tolerance range, which range can be determined
batch-specific, if necessary, there is an increased probability for
analysis element 1 to be not deteriorated, and thus fit for
purpose. Subsequently, the analysis element is taken off the
evaluation device, the sample liquid is applied to it, and then it
is re-inserted into the measurement unit of the evaluation device
for performing the proper analysis. The evaluation device can
conveniently be designed to allow the application of the sample
without the need to remove the analysis element 1 once again.
[0042] In order to perform the check method according to the
invention, the analysis element 1 advantageously comprises, in
addition to the test field 3 serving for the check of its fitness
for purpose and for performing the analysis, an integrated
reference control means, providing a standardized reference value
for the control parameter, e.g. the remission value. The reference
control means does not suffer any change caused by the sample
material; it is non-reactive, and no sample material adheres to it.
The reference control means is embodied in the shape of a reference
field 4, providing a standardized reference value for the
remission. In a preferred embodiment, the reference control means
consists of a white plastic foil or contains such a foil.
[0043] The remission value of the reference field is preferably
high, e.g. 80%, in order to allow a high measured value for the
remission control parameter, and thus, a relative high accuracy of
measuring. In the framework of the invention, however, there are no
very high requirements to the reference field 4, serving as
reference control means. For example, a less remitting gray surface
can be considered, too; the remission value of the reference field
4 does not need to be stable over a long period of time. However,
it is preferred if the characteristics of the reference field 4
are, to a large extent, independent from environment conditions
such as temperature and humidity.
[0044] FIG. 1 shows the reference field 4 as a specially designed
part of the analysis element 1. However, due to the uncritical
requirements to the characteristics of the reference field 4, as
explained above, it is also possible to use a section of the
analysis element 1 as reference control means, which is not
specially designed, e.g. a part of the surface of the preferably
white plastic the test stripe or its basic layer 2 is made of. In
these cases, the marking of reference field 4 in FIG. 1 only
illustrates which place of the analysis element 1 serves as
reference control means, without an existing difference of this
area with respect to neighboring areas.
[0045] The reference field 4 can be an integrated component of the
analysis element 1, as shown in FIG. 1. However, it is also
possible to provide the reference field 4 on a separate reference
test stripe not equipped with a test field 3, being added to the
evaluation device and/or to a package or batch of analysis elements
1. In other embodiments, the reference field 4, or the reference
control means in general, can be an integrated component of the
corresponding evaluation device.
[0046] The reference field 4 serves as a reference value allowing
to consider the current state of the evaluation device or its
optical system. It allows the detection of fluctuations of the
measurement conditions, caused by the apparatus. For this, as a
first step of a reference value measurement, a first standard
reference value W1 of a white standard value of e.g. 80% remission
is measured for reference field 4. For this, the analysis element 1
is brought into a position into the evaluation device where not the
test field 3, but the test field 4 is measured instead.
[0047] The white standard value W1 only results in a fixed and
constant value for a certain measuring apparatus with defined and
constant measuring properties. This cannot be realized in practice,
in particular not in measuring devices outside of laboratories,
resulting in the fact that the white standard value W1 is submitted
to apparatus-caused fluctuations of the evaluation device (and,
possibly, to fluctuations with respect to the characteristics of
the reference field 4). However, this is not disadvantageous in the
framework of the invention; exactly by referencing to a white
standard, using the quotient calculation according to this
invention, apparatus-caused changes, which can also arise in short
term, can be considered.
[0048] After that, or, if necessary, also before that, the dry
blank value L1 of the test field 3, brought into the measuring
position in the evaluation device, is determined in a second step.
For this, it can optionally be checked, at the same time, whether
the dry blank value L1 is within a given or, if necessary,
charge-specific tolerance range. In the exemplary embodiment it is
presupposed that the dry blank value of analysis elements 1 which
are fit for purpose shows a remission between 55% and 65%, and a
remission of 60% for the actual measurement.
[0049] In a third step, a quotient from the control reference value
L1 measured for the first analysis element and the first standard
reference value W1 is calculated and set as first reference
quotient Q1 for analysis elements measured later. Thus, in the
supposed example, the first reference quotient Q1 is
60/80=0.75.
[0050] The first analysis element, which has been used for
calculating the first reference quotient Q1, can subsequently be
used for performing an analysis. For this, it is taken off the
evaluation device, the sample to be analyzed is applied to the test
field 3, and the analysis element is inserted into the evaluation
device for analysis; or, the sample is applied to the analysis
element left in the evaluation device.
[0051] If a second analysis element is used, first the control
value L2, i.e. the dry blank value of test field 3 of the second
analysis element, which is to be checked, is determined. This dry
blank value L2 is divided by the first standard reference value W1,
forming the control quotient Q2; after that, the deviation .DELTA.
between the control quotient Q2 and the first reference quotient Q1
is checked. The checked second analysis element is rejected if the
deviation .DELTA. is not within a given tolerance range.
[0052] The decision whether the deviation .DELTA. is outside a
given tolerance range or not, can be made, e.g. using the quotient
Q1/Q2, i.e. the relative difference between the first reference
quotient Q1 and the control quotient Q2, using an (absolute)
difference Q1-Q2 or using a functional or parametrical evaluation
of the deviation .DELTA.,.
[0053] If, for example, the dry blank value L2 in the supposed
example is 56.4%, and the tolerance range for the admissible
deviation is a relative .DELTA. 6% , referred to the first
reference quotient Q1, or an absolute 0.045, referred to the
difference of Q1 and Q2, the control quotient Q2 of 56.4/80=0.705
of the second analysis element is just within the admissible range,
allowing the second analysis element to be used for analysis.
However, if the measurement of the control value L2 results in a
dry blank value of 50% for the second analysis element, a control
quotient Q2 of 50/80=0.625, and a deviation .DELTA. of a relative
16% or an absolute 0.125 come out. In this case, the checked second
analysis element in question is not admitted to be used for
analysis and must be rejected.
[0054] The tolerance range for the admissible deviation .DELTA. can
be batch-specific for the current batch of analysis elements. This
can be realized by providing the analysis elements or their
packaging with a bar code, which can be read by the measuring
device and be considered for the check or for the analysis. A
modification of this can be the storage of a set of tolerance
ranges in the evaluation device, from which one value is selected
for the batch in question via the bar code readout.
[0055] The measurement of the standard reference value W1 could
principally be performed for each analysis element. However, this
is not necessary in the framework of the invention, so time is
saved if the measurement is only performed in case of
necessity.
[0056] For some analysis elements, in particular for test elements
for a substrate-based rapid test for the qualitative or
quantitative analysis of components of a solid or liquid sample, in
particular of body liquids of human beings or animals, in
particular for the determination of the blood glucose content, the
checked second analysis element may be rejected in step g), if the
control quotient Q2 is smaller, by more than a given percental
value or more than a given difference value, than the first
reference quotient Q1. The reason for this is that it was found out
in the framework of the invention, that, in particular for the test
elements mentioned above, aging and deterioration influences lead,
in most cases, to a decrease of the remission value, and thus, to a
decrease of the control quotient Q2 as compared to the reference
quotient Q1, and that, for this reason, the decrease can be used
for checking purposes.
[0057] According to another preferred feature, in particular for
the test elements mentioned above, it may be provided that in case
of the determination of a given deviation .DELTA. in step g), the
control value L2 determined in step d) is used as new control
reference value according to step b), calculating a new reference
quotient from this according to step c), and that this new
reference quotient is used as basis for checking further analysis
elements according to steps d) to g). A given deviation .DELTA. in
this respect, which leads to the replacement of the first reference
quotient Q1 by the later measured control quotient Q2, replacing it
for the purpose of subsequent checks, can be the observation that
the control quotient Q2 determined in step e) exceeds the current
(first) reference quotient Q1 by more than a fixed limit value
.delta..
[0058] In the example mentioned above, for example, the measurement
of a control value or dry blank value L2 of an analysis element to
be checked, of more than 61.8%, leads to a control quotient Q2
bigger than 0.7725, and thus to the replacement of the first
reference quotient Q1 of 0.75 by the control quotient Q2, if a
value of 3%, referred to the first reference quotient Q1, or 0.0225
as deviation of Q1, is given for the admissible limit value
.delta.. In an additional advantageous embodiment, it may be
provided that the limit value .delta. is batch-specific for the
current batch of the analysis elements.
[0059] An increase of the control quotient Q2 as compared to the
first reference quotient Q1 may result if the optical measuring
system has been cleaned, or if any other conceivable action, with
influence on the check or the analysis, has been taken. This can be
recognized using the method according to the invention and can be
considered for the check of the fitness for purpose of the analysis
elements.
[0060] It must be noted that the exemplarily explained quotients
and differences can also be calculated vice versa, i.e. with
commuted dividend and divisor, or with commuted minuend and
subtrahend.
[0061] The method according to the invention is preferably used in
cases for which the first analysis element and the second analysis
element, the one to be checked, are comprised in a package or in a
storage container, which contains further similar analysis
elements, showing a long-time packaging common to all analysis
elements. FIG. 2 schematically shows such a package 5. One of the
contained analysis elements 1 is shown schematically. The analysis
elements comprised in a package 5 are enveloped by a long-time
packaging 6, providing a safe protection. The long-time packaging 6
can be a high-tenacity welded foil, or a tube-shaped container made
of plastic or metal, e.g. aluminum.
[0062] Each of the analysis elements 1 contained in the package 5,
may be protected by an individual packaging element. In this case,
the long-time packaging 6 ensures a secure storage over a long
period of time, or a secure transport, respectively. In order to
use the analysis elements 1 contained in package 5, the end user
first opens the long-time packaging 6; the analysis elements 1
contained therein are then consumed one by one. In the time between
the opening of the long-time packaging 6 and the use of a certain
analysis element 1, the individual packaging elements ensure the
required minimum protection. The method according to the invention
allows to check whether the minimum protection is actually complied
with, and whether all analysis elements 1 or an individual analysis
element 1 have deteriorated with respect to their fitness for
purpose after the opening of the long-term packaging 6.
[0063] It is also known to arrange the analysis elements 1 in the
long-time packaging 6, not in a loose way, but in a storage
container 7, which does not only provide a packaging function, but
which is also able to provide a functional part for the intended
use of the analysis elements 1. The arrangement of various storage
containers 7 in a common long-time packaging 6 is also possible.
Examples for storage containers and removal devices can be found in
the documents DE 19854316 A1, EP 1022565 A2, U.S. Pat. No.
4,615,462, U.S. Pat. No. 4,834,234, U.S. Pat. No. 5,645,798 and
U.S. Pat. No. 5,720,924.
[0064] FIG. 2 exemplarily shows such a storage container 7 in the
form of a magazine, in the chambers 8 of which the analysis
elements 1 are arranged. The openings 9 of the chamber 8 are closed
by sealing foils 10 which represent individual packaging units;
these are punctured for the removal of a analysis element 1 from a
chamber 8 of the storage container 7; for this, the sealing foils
10 of the other analysis elements 1 not to be removed remain
undamaged and supply protection for the analysis elements 1
remaining in the respective chamber 8.
[0065] The storage container 7, arranged in the shape of a
magazine, is conceived for the use in an evaluation device.
Corresponding means for the exact positioning and removal can be
provided for the incorporation of a storage container into an
evaluation device, for which, e.g., an analysis element can be
removed from a chamber by means of a plunger.
[0066] In the framework of the invention it is supposed that the
analysis elements 1 are fit for purpose until the long-time
packaging is opened, or that a possible deterioration, e.g. by a
temperature effect which affects all analysis elements, can be
detected using a conventional checking method. Generally, the
opening of the long-time packaging 6 is effected immediately before
the use of the first analysis element 1 contained therein. Thus,
according to a preferred embodiment of the invention, it is
proposed to choose, for step b), the analysis element 1 which is
removed first from a package 5 or a storage container 7 contained
in package 5. For example, the evaluation device can be designed in
a way that it automatically performs the steps a), b) and c)
according to the invention, when a new package 5 is used, when a
first analysis element 1 of a package 5 of a storage container 7 is
used, or when a long-time packaging 6 is opened.
[0067] Furthermore it is advantageous to repeat the steps a) to c),
if a change which potentially influences the measured value, e.g. a
cleaning of the optical system, was performed on the evaluation
device which performs the control measurement or the analytical
measurement, respectively. For example, a repetition of steps a) to
c) can be activated automatically if the evaluation device
registers, by means of a control switch, that a cover of the
evaluation device which enables access to the optical system, was
opened, as in this case a cleaning process has probably been
performed.
[0068] The subsequent tables 1 and 2 show the results of practical
trials of the invention. During these, test stripes serving for the
determination of the blood glucose content, were checked. The test
stripes suffered artificial aging by submitting them to 80%
relative humidity. For this, the high humidity serves as increased
load, accelerating the aging processes. Corresponding trial results
were obtained during tests with increased temperature, or under
real conditions with prolonged aging conditions.
[0069] Table 1 states the load results for 80% relative humidity
with a first, fixed standard reference value W1. t is the duration
of the humidity load for 80% relative humidity, expressed in hours.
The standard reference value W1 measured in the first step a), the
control reference value L1 measured in the second step b), and the
control value L2 measured in the fourth step d) are given
arbitrarily in mV. In practice, other units may occur, too, e.g.
mA, light intensity or a percental remission value. The first
reference quotient Q1 formed in the third step c) and the control
quotient Q2 formed in the fifth step e) are stated in percent. The
last column of the table shows the deviation .DELTA. between the
control quotient Q2 and the first reference quotient Q1, determined
in the sixth step f); in the shown example, the difference of these
values has been chosen.
[0070] It can be seen that the aging effects increase and the
control quotient Q2 decreases with increasing load time. The
deviation .DELTA. between the control quotient Q2 and the first
reference quotient Q1 increases accordingly. If the determined
deviation .DELTA. exceeds a given limit value, it is possible to
determine by this that the test element intended for an analysis is
not fit for purpose. In table 1, such a limit could be set for a
.DELTA. bigger than .+-.6, for example.
1TABLE 1 c) e) a) b) Q1 = d) Q2 = f) t W1 L1 L1/W1 L2 L2/W1 .DELTA.
= in h in mV in mV in % in mV in % Q2 - Q1 0 88.5 67.6 76.4 -- --
-- 48 -- -- -- 65.8 74.4 -2.0 96 -- -- -- 60.3 68.1 -8.3 144 -- --
-- 56.7 64.1 -12.3 192 -- -- -- 53.4 60.3 -16.1
[0071] Table 1: Aging test for a relative humidity of 80% with a
fixed control reference value W1.
[0072] Table 2 shows a corresponding aging test, for which, in
opposite to table 1, the standard reference value W1 is not only
determined at measurement start, but is newly determined for every
time-related control stage. A corresponding variation of the
standard reference value W1 can also result from the fact that
different analysis devices are used, which are different with
respect to their optical and measuring-technological
characteristics.
[0073] In table 2 it can also be recognized that the variation of
the standard reference value W1, protocolled here for test
purposes, is low, and that it is not submitted to the aging
process. Thus, during the practical use of the invention, it is not
necessary to re-determine the standard reference values W1 each
time, in order to recognize an aging process due to the change of
the control values L2.
2TABLE 2 c) e) a) b) Q1 = d) Q2 = f) t W1 L1 L1/W1 L2 L2/W1 .DELTA.
= in h in mV in mV in % in mV in % Q2 - Q1 0 88.5 67.6 76.4 -- --
-- 48 88.1 -- -- 65.8 74.7 -1.7 96 87.8 -- -- 60.3 68.7 -7.7 144
88.2 -- -- 56.7 64.3 -12.1 192 88.3 -- -- 53.4 60.5 -15.9
[0074] Table 2: Aging test for a relative humidity of 80% with
change of control reference value W1.
[0075] The effect of the aging with respect to the falsification of
the measurement results for the glucose concentration c is shown in
table 3.
3 TABLE 3 c for t = 0 t c (t) .DELTA. c in mg/dl in h in mg/dl in %
87.3 48 86.8 -0.6 87.3 96 79.4 -9.0 87.3 144 74.7 -14.4 87.3 192
71.3 -18.3 201.7 48 207.6 2.9 201.7 96 194.6 -3.5 201.7 144 183.9
-8.8 201.7 192 172.0 -14.7 343.9 48 350.1 1.8 343.9 96 332.6 -3.3
343.9 144 313.6 -8.8 343.9 196 299.3 -13.0 504.8 48 510.9 1.2 504.8
96 474.8 -5.9 504.8 144 446.2 -11.6 504.8 196 422.4 -16.3
[0076] Table 3: Glucose values after aging
[0077] It can be recognized that in case of a load time t of more
than 96 hours, for a relative humidity of 80%, deviations of more
than 5% occur. If a tolerance range for the deviation .DELTA. of
.+-.6 is chosen accordingly for the tables 1 and 2, the aged test
elements which are no longer fit for purpose, can be recognized and
segregated, using the method according to the invention.
[0078] The method according to the invention offers essential
advantages as compared to the state of the art, for which the
control value is only compared to a fixed limit value, pre-adjusted
on the device. The differentiation potential as according to the
state of the art is essentially lower, so that glucose value
deviations between loaded and unloaded samples can only be
recognized if they correspond to 30% or more. Thus, the known
methods cannot even determine the deviation of the glucose values
of about 15%, occurring after a load time of 192 hours (see table
3).
[0079] The invention allows a simple and reliable check of the
fitness for purpose of analysis elements. It is particularly
advantageous if the photometric inspection of the dry blank value
is effected user-independently for each analysis element, i.e.
self-acting and automatically, and that the decision exactness is
essentially increased by referencing the measured value. In order
to take into account the state of the optical system of the
evaluation device, thus becoming independent from variations, the
current state of the optical system of the device is referenced to
a white standard by means of a comparative measurement. The dry
blank value of controlled analysis elements is also referenced to
the white standard, effected by means of a quotient formation. The
control quotient of a checked analysis element is compared to a
first reference quotient. The first reference quotient is updated
in case of necessity, so that the real state of the optical system
of the evaluation device and the batch-depending target value of a
package of analysis elements are always considered currently. By
this, a very fine recognition characteristic for deteriorated
analysis elements is obtained.
[0080] In order to check the functionality of the checking method
as according to the invention, in a corresponding evaluation
device, deteriorated and not deteriorated analysis elements can be
inserted alternately into the evaluation device, thus testing the
reaction of the evaluation device. If it works properly, it will,
according to the order of analysis elements inserted for the
testing of the device, accept these analysis elements for
measurement, or reject them, as well as perform, if necessary, a
new measurement on a reference field.
LIST OF REFERENCE SIGNS
[0081] 1 Analysis element
[0082] 2 Basic layer
[0083] 3 Test field
[0084] 4 Reference field (reference control means)
[0085] 5 Package
[0086] 6 Long-time packaging
[0087] 7 Storage container
[0088] 8 Chamber
[0089] 9 Opening
[0090] 10 Sealing foil
[0091] L1 Control reference value (dry blank value of the first
analysis element)
[0092] L2 Control value (dry blank value of the second analysis
element)
[0093] Q1 First reference quotient
[0094] Q2 Control quotient
[0095] W1 First reference standard value (first white standard)
[0096] .DELTA. Deviation
[0097] .delta. Limit value
[0098] t Time
[0099] c Concentration
* * * * *