Note : Les descriptions sont présentées dans la langue officielle dans laquelle elles ont été soumises.
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TEST CARD FOR ANALYSIS OF CHEMICAL, BIOCHEMICAL
OR BIOLOGICAL ANALYTES
Field of the invention
This invention concerns an apparatus wherein compartments are defined by a
partition,
thus creating a space in which at least one liquid sample can be displaced in
a directed
and independent fashion. When there are at least two liquid samples, they can
both be
displaced in an independent way and brought together so that they can react
with one
another.
Background of the invention
Many documents in the background art deal with exploiting capillary action in
fluid
micromanipulation applications. Thus, document GB-A-2.261.284 pertains to an
apparatus for transferring liquids for the purposes of diagnostic testing.
This apparatus is
based on channels made of a porous material.
In this embodiment, the capillary action of a porous material is used. This
requires the
incorporation of this porous material and it also necessitates having an
impermeable
separation between the two porous channels which both contain different
liquids. In
consequence, this method is fairly expensive to implement.
Patent U.S. Pat. No. 5,842,787 relates to fluid micromanipulation systems
which include
channels of varying dimensions. It is essentially the depth of the channels
which can be
modified although such variation also affects width so that the deeper the
channel, the
smaller its width (and vice versa). Unfortunately, these channels are not
open; in other
words, the liquids which are to be transferred inside the channels normally
occupy the
entire cross-sectional volume. As a result there are strong retention forces
which inhibit
the displacement of the liquids and therefore mean that sophisticated transfer
systems are
required (e.g. powerful pumps, the use of a vacuum, etc.).
In patent U.S. Pat. No. 5,660,993, capillary action is used to create a valve
where two
capillary channels meet. Apart from this novel function of opening up and
shutting down
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liquid flow, exactly the same problems are encountered as with the previous
document-
because the channels are closed, retention is a problem.
According to documents EP-A-0.075.605 and WO-A-99/55852, shallow and deep
grooves are combined to direct liquids. However, there is no description of
the use of any
physical property (neither capillarity nor any other physical phenomenon) in
association
with the deep and shallow grooves, and no such association is obvious to those
skilled in
the art.
Summary of the invention
In accordance with this invention, the apparatus proposed resolves all the
problems
mentioned in that it uses capillary action to move liquids while, at the same
time, it
minimizes retention phenomena. This makes for perfectly effective directed
displacement, even in the presence of a free space which means that the
transferred liquid
is not physically confined.
The invention therefore provides a test card comprising at least one planar
surface
wherein at least two compartments are made and defined by a partition
comprising a film,
the compartments creating a space which makes it possible to displace at least
two liquid
samples independently of one another, the compartments comprising at least two
different
types of grooves: at least one deep groove capable of partitioning samples
from one
another, the depth and the width of the deep groove in relation to the
partition being such
that capillary action of a sample is not enabled, and at least two shallow
grooves, each of
the shallow grooves being capable of receiving one of the samples,
respectively, the depth
of shallow grooves in relation to the partition being such that capillary
action of the
sample is enabled, each shallow groove being adjacent to the deep groove,
along the
entire length of the deep groove, wherein the test card is adapted for
analysis of chemical,
biochemical or biological analytes.
One deep groove may be located between two shallow grooves. In this case, the
deep
groove has an end where the two shallow grooves meet to create a reaction
zone.
According to a first embodiment, the distance between the reaction zone and
the partition
or the partitioning film is such that capillary action is enabled.
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According to a second embodiment, the distance between the reaction zone and
the
partition or the partitioning film is such that capillary action is not
enabled.
Description of the figures
The figures herewith are given by way of example and are not to be taken as in
any way
limiting. They are intended to make the invention easier to understand.
FIG. 1 shows an overhead view of the side of the apparatus with the
compartment
according to the invention.
FIG. 2 shows a partial, transverse cross-section through A--A in FIG. 1.
FIG. 3 shows exactly the same view as FIG. 2 but with a liquid sample present.
FIG. 4 shows exactly the same view as FIGS. 2 and 3 but with two different
liquid
samples present.
FIG. 5 shows a cross-section exactly like that in FIG. 2, but of a second
embodiment
containing a liquid sample.
Finally, FIG. 6 shows a cross-section exactly like that in FIG. 2, but of a
third
embodiment of this invention containing a liquid sample.
Description of the embodiments of the invention
This invention relates to an apparatus (1) which is clearly illustrated in
FIGS. 2 through 6
which are partial, transverse cross-sections through three different
embodiments. Such an
apparatus (1) can be used for the analysis of one or more different liquid
samples to
identify one or more analytes, using any method, be it a simple or complex
method and be
it based on one or more different reagents, depending on the chemical,
physical or
biological nature of the analyte being tested. The technical principles
defined hereafter
are not restricted to any single, specific analyte; the only required
condition is that the
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analyte must either be dissolved or in suspension in the test sample. In
particular, the test
process being used can be performed on a homogenous, heterogeneous or mixed
form.
One particular, non limited mode of such a device, concerns biological tests
for the
detection and/or quantitative determination of one or more ligands, in which
the assay
involves one or more anti-ligands. The word ligand is taken to mean any
biological
species, e.g. an antigen, a fragment of an antigen, a hapten, a nucleic acid,
a fragment of
nucleic acid, a hormone or a vitamin. One example of an application of the
test methods
concerns immunoassays, whatever their particulars and whether the assay is
direct or
based on competition. Another example of an application concerns the detection
and/or
quantitative determination of nucleic acids, including all operations required
for such
detection and/or quantitation in any kind of sample containing the target
nucleic acid
species. Among such diverse operations, the following could be specified:
lysis, melting,
concentration, enzyme-mediated nucleic acid amplification, and any detection
modalities
which include a hybridization step using, for example, a DNA chip or a labeled
probe.
Patent application WO-A-97/02357 stipulates the various stages involved in the
case of
nucleic acid analysis.
In a particularly interesting embodiment shown in FIGS. 1 to 4, it can be seen
that the
apparatus (1) actually consists of a card with two sides, an upper and a lower
side which
are parallel to one another. Of course, it does not necessarily have to be
used in a
horizontal position-it can also be used in a vertical position or on a slope.
In the figures, both sides are planar but it is the upper side which is of
greater interest for
this invention. Thus, the upper planar surface (2) of the apparatus (1)
includes cavities
which create the compartments (3). The compartments are partitioned off with
respect to
the surfaces that are flush with the surface (2) by means of a film or
partition (4). This
compartment (3) thus isolated actually consists of a set of different forms.
On the sides,
there are two shallow grooves (16) and in the middle there is one deep groove
(6). The
view in FIG. 2 corresponds to a partial cross-section through A--A in FIG. 1.
From FIG.
1, it can be seen that the two shallow grooves (16) are parallel to one
another for the
entire length of the deep groove (6). However, one of the ends of the deep
groove (6) has
an end (7) and the two shallow grooves (16) meet there to create a reaction
zone (8).
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It is possible to isolate a first liquid sample (5) in one of the shallow
grooves (16), as
shown in FIG. 3. Similarly, it is possible to isolate another liquid sample
(15) in the other
shallow groove (16), as shown in FIG. 4. In practice, to insure that liquids
(5) and (15)
remain in position in the shallow grooves (16) without mixing, the distance
separating the
5 bottom of the groove (16) and the partitioning film (4) should be small
enough for
capillary action to take place. The ideal distance between the film (4) and
the bottom of
the groove (16) for capillary action is between 50 and 800 micrometers (µm)
(preferably between 300 and 500 µm). In the case of an apparatus consisting
of a card
made of impact polystyrene and a BOPP film being used to transfer an aqueous
solution
containing 9 g/liter NaC1, 1 g/liter NaN3 and 1 ml/1 of either Tween 20
(registered
trademark) or Triton X100 (registered trademark), the distance between the
film (4) and
the bottom of the groove (16) might be set at 400 µm. This dimension is
actually
typical for the kinds of liquid (5 and/or 15) which are likely to be used in
this apparatus
(1), given the materials used to make the apparatus (1). This distance may
have to be
varied for various reasons, e.g. depending on the viscosity, density, wetting
activity and
surface tension of the liquids being used, and on the hydrophilic/hydrophobic
properties
of the materials used to make the film and the card.
In contrast, the distance separating the film (4) from the bottom of the deep
groove (6)
must be great enough to insure that capillary action does not lead to the
retention of liquid
(5 or 15) here. Of course, it is obvious that the width value of this deep
groove must be
such that capillary action cannot take place.
The nature of the flexible film may vary according to the nature of the test
card and of the
fluids being tested, especially when compatibility is at issue. For example,
TPX
(polymethyl pentene copolymer) or BOPP (bi-oriented polypropylene) films are
suitable
for biological assays. These films can be fixed in place either using an
adhesive (with the
adhesive applied to the film, e.g. a silicon-based adhesive) or by heat-
sealing. An
example of an adhesive is available from BioMerieux Inc. (St. Louis, Mo., USA)
(reference: 022004-2184).
In terms of production, the test cards are manufactured by the machining of
special plastic
material, e.g. impact polystyrene (reference: R540E from the Goodfellow
company)
which is compatible with the liquids being processed. For industrial-scale
production, the
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card could be manufactured by precision molding, but any other manufacturing
method
(including those used in the semi-conductor industry as stipulated in patent
application
WO-A-97/02357) may be used for test card production.
Of course, a number of other embodiments can be imagined and two of these are
shown
in FIGS. 5 and 6. That in FIG. 5 corresponds to a substantially reversed
configuration of
the first embodiment shown in FIGS. 1 to 4. Thus, in FIG. 5, one shallow
groove (16)
occupies the central position between two deep grooves (6). The liquid sample
(5) is only
in contact with the bottom of the shallow groove (16).
In another embodiment shown in FIG. 6, it is possible to have a single shallow
groove
(16) and a single deep groove (6).
Of course, all permutations are possible and can be imagined. For example,
there might
be a whole series of deep grooves (6) or shallow grooves (16). The only
prerequisite
condition is that the deep grooves (6) be located between the shallow grooves,
(16) or
vice versa. Liquids (5 and/or 15) can be introduced by means of valves, pumps,
and/or
channels, as described in the patent applications submitted by the applicant
on the same
day with the following titles:
"A device and a method for positioning a liquid", for the first document,
"A pumping device for transferring at least one fluid into a consumable," for
the second
document, and finally
"A test sample card with improved filling" for the third document.
The liquids (5 and 15) can be moved in different ways, e.g. the card (1) could
be made to
vibrate or it could be placed in a substantially vertical position so that the
liquids are
driven by the force of gravity; alternatively, centrifugal force could be
used. Pumping
systems could be used, either located inside or outside the card; these could
be based on
diaphragm pumps (U.S. Pat. No. 5,277,556), piezoelectric peristaltic pumps
(U.S. Pat.
No. 5,126,022), ferrofluid transport systems, or electric and hydrodynamic
pumps
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(Richter et al., Sensors and Actuators, 29, p159 165, 1991). Combinations of
more than
one of these types of system could also be used.
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REFERENCES
1. Apparatus
2. Planar surface of the apparatus (1)
3. Compartments
4. Partition or partitioning film
5. First liquid sample
6. First type of groove, said to be deep
7. End of the groove (6)
8. Reaction zone
15. Second liquid sample
16. Second type of groove, said to be shallow
