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Description  |
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The invention addresses a system for analyzing sample liquids, said system
comprising a mechanical device for transporting test elements, a measuring
arrangement for detecting changes occurring on a test element and two or
more individually sealed test elements included within said system.
Further, the invention addresses the actual test elements, a mechanically
linked arrangement of said test elements and a method of analyzing sample
liquids. Systems which allow an analysis without handling liquid reagents
are primarily used in the fields of medicine and environmental analysis.
They are referred to as dry tests. With these systems, the user can carry
out analytical tests for individual parameters without having the
necessary scientific background in chemistry or biochemistry. If all
instructions are carried out properly, the measurements will be exact.
Such systems can, hence, be used by untrained personnel, and are
consequently of particular significance in the medical field when used by
patients. In the last years, instruments for monitoring blood glucose
levels by the patients have gained more and more importance. The use of
instruments which can be carried along at any time makes the patient
largely independent of the treating physician and, hence, increases the
patient's quality of life. The option of simple and fast measurement
improves drug administration, e.g. stabilization of the blood glucose
level by administering insulin or sugar corresponding to the organism's
requirement. Even the patient's way of living can thus be adjusted to the
actual needs of the body. In the future, portable patient-operated
instruments will also be employed for the determination of other blood
components. In addition to endogenous substances, this includes the
monitoring of drug concentrations in the blood. Such monitoring gains
particular importance if the pharmacological spectrum of a therapeutic
agent is narrow, as it is the case with digitalis steroids or lithium, for
example. In currently known embodiments of instruments for measuring the
components of body fluids, instrument and test reagents are separated. The
test reagents are available, for example, in the form of test strips onto
which the body fluid is applied. The test strip is then inserted into the
instrument for measurement. The storage stability of many reagents is
drastically reduced by moisture. A known possibility of ensuring the
storage stability of test elements over a longer period of time is to seal
them in metal foil. This is usually done with urine test strips, for
example. Another possibility of storing moisture-sensitive reagents is to
store a great number of test elements in containers, i.e. usually vials
which are made of a material that is impermeable to humidity. The test
elements can then be individually removed from these containers. When the
containers are opened, however, moisture can enter together with the
ambient air. In order to ensure a certain storage stability of the
remaining test elements, a drying agent to absorb any moisture that may
have entered is provided inside the container. The user must, hence, carry
a separate supply of test elements in addition to the instrument.
A procedure for analyzing a sample liquid known in prior art, for example
for the determination of glucose in blood, comprises the following
operating steps:
Manual removal of a test strip from a separate storage container
Application of the sample liquid
Inserting a test element into the instrument
Carrying out the measurement
Reading off the measurement value
Discarding the used test element.
The above-mentioned precautions against humidity must already be taken when
removing a test element from a separate container. Further, the test strip
may be contaminated by dirt adhering to the hands which could ultimately
lead to false test results. Another source of contamination of the test
strip is by accidentally dropping it. The following steps of sample
application and insertion into the instrument are switched in some prior
art instruments. In these cases, sample application is carried out while
the test element is already in the instrument. This facilitates, for
example, application of a blood droplet from the tip of a finger, which
has been pricked with a lancet, as the test element is fixed in its
position by the instrument.
In known analysis systems where individual test elements are employed, the
user manually moves such an element to the site of measurement. In order
to avoid errors due to incorrect positioning, the instrument must be given
a corresponding structural design. Test elements in the form of a strip,
for example, are inserted into a given guide element until contact is made
with an abutment.
Analysis can be accomplished by a way of detectable signals whose strength
depends on the concentration of the parameter to be determined in the
sample. The expert is familiar with detectable signals that are suitable
for such analyses, e.g. optical, electrical, or magnetic signals.
In instruments for use with test elements, the measurement is usually
carried out by means of reflectance photometry. Less used instruments are
those which employ transparent test elements where the detection is
quantified in terms of the transmission. The measurements are evaluated
with electronic and usually also digital means.
Analysis instruments containing a multitude of test strips have so far been
limited to laboratories or larger physicians' offices as these places
achieve a high throughput of individual tests rendering additional
precautions against humidity and the influence of light superfluous.
Patent application EP-A-0513618, for example, describes a radial
arrangement of test elements. The test elements are removed from the
arrangement by means of a mechanical device and the sample liquid is
applied by means of a pipette. As opposed to the present invention, the
test elements are not sealed inside the instrument. This arrangement was,
therefore, designed to use all test elements within a short time, usually
minutes or hours.
It was an object of the invention to provide an analysis system where
several test elements are provided within the system such that a high
storage stability of test elements is ensured even when the elements are
removed individually.
A system for analyzing sample liquids was, hence, designed which features a
mechanical device for transporting the test elements to the site of
measurement and a measuring arrangement for detecting changes occurring on
the test elements and where two or more individually sealed test elements
are provided within in the system. The invention also covers a
mechanically linked arrangement of individually sealed test elements. The
test elements as such are also part of the invention, as their design
renders them particularly suitable for use in the system of the invention.
The invention further covers a system for analyzing sample liquids which
makes use of the system of the invention.
A system in accordance with the invention comprises a measuring instrument
and an arrangement of test elements.
The present invention focuses in particular on the test elements which are
considered a part of the system. They are provided with a base made of a
mechanically stable material, preferably plastic. Metal, glass, or
cardboard are, however, also possible materials. The base is preferably a
flat body containing a test field in a recess. Possible test fields can
consist of several layers. In addition to a layer where a detectable
signal is generated with the aid of the analyte and the reagents, one also
knows layers which contain auxiliary substances or serve to separate
cells. A possible structural design of a test field is described in patent
application EP-A-0271854. In a test element according to the invention,
the test field can be attached, for example, by gluing or pressing it into
the base. On the one side of the test field, preferably the upper side, a
liquid analyte can be applied. The analyte penetrates into the test field
resulting in the separation of cells, for example, and/or initiating a
reaction with several auxiliary substances, if necessary. In one of the
possible layers, preferably the one located at the lower side of the test
element, a detectable change is triggered in dependency upon the analyte.
Preferably, these detectable changes are color changes, but other
detectable properties, such as change of the magnetic or electric
properties or the emission of light are also possible. The shape of the
test elements also depends on the test layers necessary for the detection.
However, those preferred test elements are those which can be moved or
pressed out of their sealed wrapping due to their mechanical stability
and/or form. For the same reasons, preferred test elements are those that
have a tip or edge, particularly preferred in one direction of
transportation. Moreover, preferred embodiments of the test elements are
provided with guiding elements, which facilitate transportation to the
site of measurement. Further, preferred embodiments of test elements have
a contact point for a transportation mechanism.
Principally, the expert can detect changes on the test element by way of
known measurement arrangements comprising a radiation source and a
radiation detector. The radiation used for the measurement is preferably
within the visible range of the frequency spectrum. In the preferred case
that a reflectance arrangement has been selected, the radiation emitted by
the source arrives at the lower side of the test field where the beams are
reflected either directly or after traversing an optical unit. The
reflected beams then arrive at the receiver either directly or after
traversing an optical unit. The receiver can be a photodiode, for example
a photomultiplier or a photovoltaic element. The above-mentioned optical
unit can comprise optical lenses and mirrors. Moreover, diffraction grids,
prisms, and optical filters which select a desired small frequency range
out of the larger frequency range of the available spectrum are also used.
Further, it is possible to employ measurement arrangements where the above
described selection of a small frequency range is realized after being
reflected by the test element, but prior to entering the receiver.
Evaluation of the arriving radiation is carried out in a known way by
means of an electronic circuit and the result is then displayed. With a
suitable receiver, it is also possible to show the signal directly on a
display. The display can, for example, be an analog display, preferably it
is a digital display.
The invention further addresses a mechanically linked arrangement of test
elements, characterized in that each test element contained therein is
individually sealed. Individually sealed refers to the air- and
water-tight separation of individual test elements with respect to the
environment outside the sealing and with respect to each other. The test
elements of this arrangement correspond to the above-described test
elements of the invention. A separate sealing of each individual element
is preferably realized by sealing the test elements in blister packs. A
particularly preferred arrangement is a radial arrangement of the sealed
test elements, for example, in the form of a disk which is subsequently
referred to as the test element disk.
Moreover, the invention comprises individual test elements which are
characterized in that
a) they are provided with a tip or an edge which facilitates piercing of
the sealing when the element is removed from its sealing, and/or
b) they are provided with a notch which serves as a contact point for a
mechanical unit, or
c) they are provided with guiding elements which prevent a movement
perpendicular to the main direction of movement during transportation
parallel to the opposing sites in one of the rails receiving the guarding
elements.
With the system in accordance with the invention, it is also possible to
realize a method of analyzing sample liquids which is also covered by the
invention. The method of analyzing sample liquids comprises the following
steps:
Removing a test element from its sealing by means of a device
Transporting the test element to the site of sample application
Applying a sample onto the test element
Reading off the measurement.
In the method of analyzing sample liquids, a test element is preferably
removed from a blister pack. To achieve this, a thorn is preferably used
which is provided at a device and also serves the purpose of transporting
the test element. The sample liquid is applied onto the reagent field of a
test element that has been removed from its sealing. The measurement can
be carried out with an above described measuring arrangement. In a
preferred manner, the measurement is carried out at the side of the test
element which is opposite the side of sample application.
In a system in accordance with the invention, several individually sealed
test elements are provided within said system. In a preferred embodiment,
the test elements are mechanically linked. A particularly advantageous
arrangement of the test elements is a circular arrangement in the form of
a disk which allows radial transportation of the chambers. Moreover, as
the arrangement takes up only little space, a multitude of test elements
can be accommodated in the instrument. The disk in accordance with the
invention can be manufactured analogously to blister packs for tablets.
Blisters are generally made of two foils, of which the first is provided
with recesses into which the tablets or, in case of the invention the test
elements, are inserted. A second foil is then attached to the first foil
by means of sealing or gluing. The test elements are thus individually
sealed and separated by means of spacers. The materials used for the foils
are, for example, plastic materials. In accordance with the invention,
however, plastic-laminated metal foils are preferred as they offer the
better protection from moisture, light, and contamination. Particularly
preferred are those foils where an aluminum layer is provided on a
polyethylene layer, the aluminum layer being covered with an external
lacquer. The individual test elements can principally be removed from the
sealing by the user. However, in a preferred manner this is done by a
mechanism and in a particularly preferred manner, this is a mechanism to
perform both the removal of the test element from its sealing and the
transport of the element to the site of measurement.
The test element disk can contain coded data referring to the contents of
the disk, the expiration date of the test elements, the manufacturing lot,
and other data. The coding can be realized by means of a barcode, a dot
pattern, a magnetic strip, or other options known to the expert. The test
element disk could also be supplied together with a code strip or a code
key, e.g. in the form of a radio frequency identification key (RF-ID)
containing the above-mentioned data. A reading device to read the
respective form of data can be integrated into the system.
The data read by the test element disk can significantly improve handling
of the instrument, for example, by warning if the stability of the test
element has expired or by providing a lot-specific evaluation curve for
the evaluation of the measurement.
BRIEF DESCRIPTION OF THE DRAWINGS
FIGS. 1 to 7 are examples illustrating a particularly preferred embodiment
of the system wherein
FIG. 1 is a complete measuring instrument with the inner and the outer
covers being opened.
FIG. 2a-2c are a top view of an instrument base with the inner and outer
covers being removed.
FIG. 3 is top view of an instrument base without the inner and outer covers
and without the carrier for the test element disk.
FIG. 4 shows the bottom side of the inner cover.
FIG. 5 shows a test element disk
FIG. 6 shows an individual test element
FIG. 7 shows the bottom side of the outer cover with an additional test
element disk.
FIG. 8 is a cross sectional view of the instrument of FIG. 1, taken along
line A--A.
FIG. 1 shows an embodiment of the analysis system with a test element disk.
A system in accordance with the invention belongs to those analysis
systems where the analyte is applied onto a test element and evaluated in
an instrument designed for this purpose. Test element and instrument are
adjusted to each other with respect to shape and measuring signal so that
their combination can be referred to as a system. The space in which the
test element disk is inserted, is covered by an inner cover (3). The base
(2) contains a first transport mechanism comprising a lever (4) and a
rotatable support (5) for a test element disk. The outer cover (6) serves
to protect the instrument from mechanical influences and to fix lever (4)
in its position. Measurements are preferably carried out with the outer
cover (6) being opened. It is, however, also possible to carry out a
measurement with the outer cover (6) being closed which then provides an
additional protection against the effects of ambient light. Closing the
outer cover (6) is an additional protection of a device for displaying the
measurement result, for which provision can be made if desired, against
mechanical influences. FIG. 2 shows the base (2) of the instrument. On the
one side of the lever (4) there is a recess (11) to move the lever
radially into this direction while a movement into the opposite direction
from the position shown in FIG. 2a is not possible. Lever (4) comprises a
rectangular front part (12) and a circular disk (13). The rectangular
front part of lever (12) has a cut-out (14). The sides of the cut-out (14)
are formed to guide a test element if the latter is inserted into the
cut-out. These guiding elements keep the test element in position during
the measurement, but allow ejection of the test element once the
measurement is completed. During the measurement, the test element is
located within the cut-out (14) and the guiding element ensure proper
positioning during the measurement. Below the cut-out (14), a measuring
arrangement comprising a light source and a detector is integrated into
the base (2). FIG. 2 shows a measuring opening (10) which allows light
emitted from the light source and light reflected by the test element to
pass. The light source can be present in mono- as well as polychromatic
embodiments as they have already been described and are known in prior
art. The detector can also be provided in different embodiments, preferred
are detectors for the visible and the infra-red range of the spectrum. An
electronic unit processes the signals in the base (2) in a known manner
and the result is presented to the user in a comprehensible form on the
display (7). The already described support (5) for the test element disk
rests on the circular disk (13) of the lever. The support (5) is provided
with recesses (15) to hold the sealed test elements (25), if a test
element disk (22) has been placed on the support (5). The circular ring
(13) of the lever, the support (5) for the test element disk and the base
(2) of the instrument are rotatably connected to each other by means of a
screw (16). If the screw (16) is removed, the support (5) can be
withdrawn. The remaining arrangement of the base (2) with the lever (4) is
shown in FIG. 3. The lever (4) is provided with ramps (17) allowing the
support (5) to be rotated on the lever (4) in one direction, but
preventing rotation in the opposite direction. An inner disk (18) is
rigidly connected to the base (2). This inner disk (18) is also provided
with small ramps having the same orientation as those on the lever (4).
If, looking at the arrangement of FIG. 2a, a clock-wise movement of the
lever is executed, support (5) is carried along in a clock-wise sense to
cover the same angle which is covered by the lever. FIG. 2b shows the base
of the instrument after execution of a maximally possible rotation. In the
example which is a drawing of a disk that contains test elements, the
lever covers an angle of 36.degree.. Generally, an angle of 360.degree./n
is possible for a disk with n test elements. If the lever is returned into
the position shown in FIG. 2c in a counter-clock-wise sense, support (5)
will remain in the position shown in FIG. 2b. Purpose of this mechanism is
to use the movement of the lever to position a new test element of the
test element disk in front of the cut-out (14) of the lever. The sequence
of pictures shown in FIG. 2 demonstrates how the cut-out (15a), which is
positioned in front of the detector in FIG. 2a, travels clock-wise to
cover an angle of 36.degree. and how a new cut-out (15b) is positioned in
front of the detector. Together with support (5), lever (4) serves as a
radial transportation mechanism.
FIG. 4 shows the one side of the inner cover (3) of the instrument which
faces the base (2). If the cover is closed, it is located horizontally
above the base (2) and, hence, covers an inserted test element disk. In
the inner cover (3), provision is made for a second transportation
mechanism in the form of a pushing device (19) which carries a thorn (20)
at its end. The position indicated by the continuous lines is the resting
position of the pushing device (19). If the pushing device is moved to
this position, lever (4) can be moved. If the pushing device (19) is in
the position indicated by the broken lines, the end of the pushing device
which carries thorn (20) is lowered toward the base (2). If a test element
disk is inserted, the thorn (20) is lowered onto its surface to pierce it.
Due to the continued movement of the pushing device toward the cut-out
(14), the thorn pushes a test element into the cut-out (14) of the lever.
During this movement, the test element also pierces the sealing around the
test element disk. Once the above described operations have been executed,
the test element is in the cut-out of lever (14) above detector (10). The
sample can now be applied.
FIG. 5 shows a test element disk (22). In its center, it is provided with a
circular cut-out (23) which comes to rest loosely on the mounting screw
(16) when the disk is inserted into the instrument. The test element disk
(22) is now fixed in its position such that only a rotation around the
axis determined by the mounting screw is possible. The test element disk
can be manufactured in the same way as described for the blister packs for
tablets. The preferred materials for the test element disk include
plastic-laminated metals as these are impermeable to moisture, with
aluminum as a metal being particularly preferred. For less
moisture-sensitive test elements, it is also possible to use plastics and
cardboard.
The test elements are placed in cells (24) which are separated by spacers
and sealed with respect to the surrounding so as to be protected from
moisture, the effects of light, contamination, etc. The mechanical contact
which allows transportation or rotation of the test element disk is
realized via the cells (24) in the test element disk. Together with the
test elements (25), the cells (24) form elevated portions with respect to
the remaining test element disk (22). When the test element disk is
inserted in the instrument, these elevated portions come to rest in the
cut-outs (15) provided in support (5).
FIG. 6 shows an individual test element (25). The design of a test element
in accordance with the invention which comprises a base (29) and a test
field (30) has already been described. In a preferred embodiment, the base
(29) is made of a plastic material and the test field (30) is also used as
a measuring field. The measuring field at the lower side of the test
element (25) is located above the measuring opening (10), if the whole
unit has assumed proper position. In a preferred form, the test element is
provided with a tip (27) to facilitate piercing of the cover foil of the
test element disk when the latter is pushed out. At its other end, the
test element is provided with an indentation (26) which the thorn (20)
enters when the test element (25) is pushed out. This ensures proper
guiding of the test element and prevents the thorn from slipping out of
position. The lateral edges (28) of the test elements are made such that
they fit in the lateral guiding elements of the cut-out (14) of the lever.
This ensures proper guiding of the test element when the latter is
inserted into its measuring position. The lateral edges (28) of the test
element (25) can, for example, be configured as projecting edges. If the
test element has been moved to the site of measurement, lever (4) can no
longer be turned as the test element is arrested in its position by the
thorn.
Lever (4) is also arrested in its position by the outer cover (6) shown in
FIG. 7. A slot (33) in the front part of the cover extends over the
projecting part of the lever (4) when said cover is closed. At its inside,
the outer cover (6) can be provided with a mounting device (34) for
another test element disk (22).
The base of the instrument can also have an integrated switching device (9)
which is activated when the outer cover (6) is opened or closed. This
signal can be used to switch the instrument on and off. In this preferred
embodiment, the user does no longer have to manually turn the instrument
on and off.
In the above described instrument, a measurement is carried out as follows:
1. Opening the outer cover (6) (instrument is automatically turned on).
2. Opening the inner cover (3).
3. Placing a test element disk onto support (5).
4. Closing the inner cover (3).
5. Releasing a test element by moving the pushing device (19) from its
resting position (continuous lines in FIG. 4) to the position indicated by
the broken lines. The test element is thus pushed from the test element
disk into the cut-out (14) provided in lever (4).
6. Applying the sample onto the test element (measurement is started).
7. Reading the result off the display (7) once the measurement is
completed.
8. Moving the pushing device (19) back into resting position.
9. Moving the lever from the position shown in FIG. 2a into the position
shown in FIG. 2b. Once this movement is executed, the test element drops
into the recess (11).
10. Moving the lever back into the position shown in FIG. 2c.
11. Ejecting a used test element from the instrument.
12. Closing the outer cover (6) unless a new analysis is to be carried out.
If a test element disk has already been inserted in the instrument, the
measuring procedure only comprises steps 5 to 11.
To remove an empty test element disk, both covers (6) and (3) are opened
and the disk is removed.
Steps 8 to 10 can be omitted if the pushing device (19) and the lever (4)
are returned by means of springs.
FIG. 8 shows the recess (11) of the base (2) and how the lever (4) is
located with respect to the measuring opening (10). The guiderails of the
lever (4) are formed so that they can receive the test elements (25). The
lateral edges (28) of the test elements fit into the guiderails of the
lever (4).
The above described design is an example of how the instrument in
accordance with the invention could be realized. A characteristic feature
for a system of this kind is the presence of several individually sealed
test elements inside the system and transportation of individual test
elements from their sealed position to the site of measurement. An
advantage of the system in accordance with the invention is that several
tests can be carried out successively. The user does not have to manually
take a new test element out of a separate container. In the present case,
the determination can be carried out with one single instrument without
requiring an additional container to store the test elements. Due to the
individual sealing, the test element is particularly suited for use with
test elements that are sensitive to environmental factors (e.g. humidity,
oxygen in the air, light) as these test elements are protected by the
individual sealing. If the measurement is carried out as described,
erroneous usage by malpositioning of the test elements is avoided as the
test elements are directly moved to the site of measurement by means of
the described mechanism. Moreover, the ejection mechanism allows removal
of used elements without contamination of the user.
List of Reference Numerals
1 Instrument
2 Base
3 Inner cover
4 Lever
5 Rotatable support
6 Outer cover
7 Display
9 Switching device
10 Measuring opening
11 Recess in base
12 Rectangular front part of lever (4)
13 Circular disk of lever (4)
14 Cut-out in lever (4)
15 Cut-out in support (5) for test element disk
16 Screw
17 Ramp
18 Inner disk
19 Pushing device
20 Thorn
21 Attachment for pushing device
22 Test element disk
23 Circular cut-out in the test element disk (22)
24 Cell of test element disk (22)
25 Test element
26 Indentation of test element (25)
27 Tip of test element
28 Lateral edges of test element (25)
29 Base of test element (25)
30 Test field
33 Slot in front part of the cover (6)
34 Mounting device in outer cover (6)
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