EP4165411A1

EP4165411A1 - System for rapid analysis of a biological sample, intended for detecting the presence of at least one analyte in the biological sample

Info

Publication number: EP4165411A1
Application number: EP21730235.5A
Authority: EP
Inventors: Milovan Stankov
Original assignee: NG Biotech SAS
Current assignee: NG Biotech SAS
Priority date: 2020-06-12
Filing date: 2021-06-08
Publication date: 2023-04-19
Also published as: FR3111431A1; FR3111430B1; WO2021250006A1; FR3111430A1

Abstract

The present invention relates to a system for rapid analysis of a biological sample (E), intended for detecting the presence of at least one analyte (A) in the biological sample (E). The rapid analysis system comprises: - at least one collection device (2), suitable for collecting the biological sample (E), - at least one chromatographic test strip (3) designed to detect the presence of the at least one analyte (A), - a buffer solution (4) for implementing the chromatographic technique, and - at least one interface device (5) suitable for receiving the at least one chromatographic test strip (3) in order to implement the chromatographic technique, which interface device (5) comprises at least two recesses (51, 52) in fluid communication, with at least one first recess (51) intended to receive at least the buffer solution (4) and at least one second recess (52) designed for inserting at least the deposition area (311) of the at least one chromatographic test strip (3), the second recess (52) being intended to receive the buffer solution (4), possibly mixed with the biological sample (E), flowing from the at least one first recess (51).

Description

System for the rapid analysis of a biological sample, intended for the detection of the presence of at least one analyte in said biological sample

Technical field of the invention

The present invention relates to the technical field of systems for the rapid analysis of biological samples, intended for the detection of the presence of at least one analyte in said biological sample.

State of the art

A rapid diagnostic test, known as a "rapid test", is a test that can quickly establish (within minutes) the presence of at least one analyte of interest in a biological sample.

This approach conventionally uses the phenomena of chemical reactions by immunochromatography on strips (also called “lateral flow test”) which reveal a particular coloration making it possible to immediately interpret the result.

This technique has the advantage of being simple, fast and inexpensive. Such tests can also be used in the doctor's office but also at the patient's bedside or in the field.

In practice, the strip is conventionally implanted in a case which is adapted to receive only biological samples in liquid form.

Some sampling techniques then require several manipulations to transfer the biological sample to the strip.

This is for example the case with biological samples obtained with swab-type collection devices used for the collection of biological samples from the upper respiratory tract, or even from a surface of the environment to be analyzed.

However, it would also be interesting to propose a versatile solution which would allow the analysis of a liquid biological sample, but also the analysis of a biological sample directly from the sampling device.

Presentation of the invention

In order to overcome the aforementioned drawback of the prior art, the present invention provides a system for the rapid analysis of a biological sample, intended for the detection of the presence of at least one analyte in said biological sample.

The rapid analysis system includes:

- at least one sampling device, suitable for taking said biological sample (possibly from an individual), for example a biological sample from the upper respiratory tract or a capillary blood sample,

- at least one chromatographic strip, advantageously an immunochromatographic strip, designed to detect the presence of said at least one analyte, which at least one chromatographic strip comprises a deposition zone intended to receive said biological sample,

- a buffer solution, for the implementation of the chromatographic technique, and

- at least one interface device, adapted to receive said at least one chromatographic strip for the implementation of said chromatographic technique.

The interface device comprises at least two housings in fluid communication (possibly only two housings), advantageously in the form of a well, with:

- at least a first housing (advantageously a first single housing) intended to receive at least said buffer solution, optionally mixed with said biological sample, and

- at least one second housing (advantageously a single second housing or at least two second housing) designed to introduce at least said deposit zone of said at least one chromatographic strip, said second housing being intended to receive said buffer solution, optionally mixed with said biological sample, flowing from said at least one first housing.

Such a system is thus particularly interesting in that it offers a versatile solution which allows:

- the analysis of a liquid biological sample, but also

- the analysis of a biological sample present on a collection part of a sampling device.

Such a device also prevents accidental projection of buffer solution and / or biological sample onto an area of the chromatographic strip other than the deposition area.

Other non-limiting and advantageous characteristics of the product according to the invention, taken individually or in any technically possible combination, are as follows:

- Said at least two housings each have an access opening and a bottom, which bottoms of said at least two housings are in fluid communication;

- Said at least two housings are in fluid communication via a conduit suitable for a flow of the buffer solution, optionally mixed with said biological sample, from said first housing to said second housing; the conduit advantageously has a lower face having a downward slope from said first housing to said second housing, to promote the flow of the buffer solution, optionally mixed with said biological sample from said first housing to said second housing;

said at least one first housing comprises a side wall which has a section which decreases from an access opening towards a bottom, for example a frustoconical portion preferably followed by a final cylindrical portion; - Said at least one second housing is shaped to guide the introduction of said at least one chromatographic strip;

- the length of the chromatographic strip is greater than the depth of said at least one second housing, so as to give said chromatographic strip a configuration erected on either side of an access opening;

said at least one interface device comprises a bottom face, adapted to rest on a receiving surface, and an opposite top face, and said at least two housings of said at least one interface device are in the form of juxtaposed wells, advantageously parallel, and opening at said top face;

said at least one sampling device comprises a collection part suitable for collecting said biological sample; said at least one first housing is adapted to the introduction of said collecting part of said at least one sampling device so that the buffer solution ensures the transfer of said biological sample from said at least one first housing to said at least one second housing ; preferably, said at least one first housing comprises a side wall provided with a compression part whose section is identical to, or smaller than, the collection part, which compression part is preferably cylindrical and located on the bottom side;

said at least one sampling device is chosen from saliva sampling swabs or nasal sampling swabs, or lancets, suitable for generating a drop of capillary blood;

- Said at least one first housing comprises a side wall in which is formed at least one groove, for example of spiral or helical shape, extending towards a bottom to promote the flow of the buffer solution, where appropriate mixed with said biological sample, towards said bottom;

- at least one of the housings comprises a side wall provided with an annular lumen in fluid communication with an internal chamber, said annular lumen being advantageously located between a free edge of said side wall and a bottom, to avoid or at least limit a liquid outlet through said housings in the event of tilting of said interface device;

- said at least one interface device is made of a plastic material, advantageously in two assembled parts;

said at least one chromatographic strip comprises different successive zones, in the direction of capillary migration upstream to downstream, namely at least said deposition zone, intended to receive the buffer solution / biological sample mixture, a release zone which comprises at least a detection reagent conjugated with a visible and / or measurable label, said detection reagent being able to move as a consequence of the migration of the buffer solution along the chromatographic strip, and at least one capture zone which includes at least one capture reagent, immobilized on the chromatographic strip;

- Said at least one chromatographic strip consists of a chromatographic strip designed to detect the presence of said at least one analyte chosen from antigens, or serological antibodies, specific for an infectious agent, preferably viruses, in particular viruses responsible for pneumopathies , advantageously the Coronaviridae, more preferably Orthocoronavirinae or coronavirus;

- the buffer solution is packaged in a container which includes a dropper;

- the rapid analysis system comprises one lot [sampling device / chromatographic strip / interface device], for an individual analysis, or several lots [sampling device / chromatographic strip / interface device], for a collective analysis ;

- Said at least one strip is packaged in collective packaging, and said at least one sampling device is packaged in individual packaging;

the rapid analysis system comprises at least two of said chromatographic strips, advantageously designed to each detect the presence of said at least one analyte, different from each other, and said at least one interface device comprising said at least a first housing, preferably a single first housing, and at least two second housings each designed to introduce at least said deposition zone of at least one of said chromatographic strips.

The present invention further relates to an interface device for a rapid analysis system according to the invention.

The interface device comprises at least two housings in fluid communication (preferably only two housings), preferably in the form of a well, with:

- at least a first housing, intended to receive at least one buffer solution, optionally mixed with a biological sample, and

- at least one second housing (for example one, two, three or four second housing (s)) designed for the introduction of a deposition zone of a chromatographic strip.

The present invention also relates to a method for the rapid analysis of a biological sample, from a rapid analysis system according to the invention.

This process includes:

- a step of inserting said at least one chromatographic strip into said second housing,

- a step of adding the buffer solution to said first housing, for the implementation of the chromatographic technique, and - Reading said at least one chromatographic strip positioned in said second housing, after migration of the buffer solution, to detect the presence of said at least one analyte in said biological sample.

In a first preferred embodiment, the biological sample is deposited directly on the deposition zone of the chromatographic strip, before said insertion step.

In a second preferred mode:

- the insertion step also comprises an insertion of the collection part of said at least one sampling device in said first housing,

the step of adding the buffer solution leads to bringing said buffer solution into contact with said collection part of said at least one sampling device positioned in said first housing (with advantageously a movement of said at least one sampling device to promote the flow of the buffer solution / biological sample mixture), to ensure the transfer of said biological sample from said at least one sampling device to said at least one chromatographic strip.

The biological sample is preferably chosen from biological samples from the upper respiratory tract, for example a nasopharyngeal or salivary sample or a capillary blood sample.

Of course, the different characteristics, variants and embodiments of the invention can be associated with each other in various combinations insofar as they are not incompatible or mutually exclusive.

Detailed description of the invention

In addition, various other characteristics of the invention emerge from the appended description given with reference to the drawings which illustrate non-limiting embodiments of the invention and in which:

[Fig. 1] is a general and perspective view of a rapid analysis system according to the invention, preferably in an "antigen" approach;

[Fig. 2] is a general and perspective view of an interface device for the rapid analysis system according to the invention;

[Fig. 3] is a general and side view of the interface device according to Figure 2;

[Fig. 4] is a sectional view of the interface device according to Figure 2, along a section plane passing through the first housing;

[Fig. 5] is a perspective view, and exploded, of the interface device according to Figure 2;

[Fig. 6] is still a perspective and exploded view of the interface device according to Figure 2;

[Fig. 7] is a perspective view of the interface device which shows the insertion of the collection part of the sampling device into the first housing and the insertion of the chromatographic strip into the second housing; [Fig. 8] is a perspective view of the interface device according to FIG. 7, showing the addition of the buffer solution in the first housing for the implementation of the chromatographic technique;

[Fig. 9] is a sectional view of FIG. 8, the sectional plane of which passes through the two housings;

[Fig. 10] is a perspective view illustrating the handling of the sampling device in the first housing;

[Fig. 11] is a general and perspective view of a rapid analysis system according to the invention, advantageously in a "serological" approach; [Fig. 12] is a perspective view showing the insertion of the chromatographic strip into the second housing of the interface device, after depositing the biological sample on this chromatographic strip;

[Fig. 13] is a perspective view showing the addition of the buffer solution in the first housing of the interface device according to Figure 12, for the implementation of the chromatographic technique;

[Fig. 14] is a further exploded view from two perspectives (A. and B.) of an alternative embodiment of the interface device according to Figure 2;

[Fig. 15] is a general and perspective view of a rapid analysis system according to the invention, in which the interface device is adapted to receive two chromatographic strips;

[Fig. 16] is a perspective and exploded view of the interface device according to Figure 15;

[Fig. 17] is a perspective view of the interface device according to Figure 14, which shows the insertion of the collecting part of the sampling device; [Fig. 18] is a perspective view of the interface device according to Figure 14, which shows the insertion of the two chromatographic strips;

[Fig. 19] is a perspective view of a variant of the interface device, the two second housings of which are arranged facing each other on either side of the first housing;

[Fig. 20] is a perspective view of another interface device which is intended to receive three chromatographic strips;

[Fig. 21] is still a perspective view of another interface device which is intended to receive four chromatographic strips.

It should be noted that, in these figures, the structural and / or functional elements common to the different variants may have the same references. The systems 1 according to the invention, described below in relation to the figures, are suitable for the rapid analysis of a biological sample E with a view to detecting the presence of at least one analyte A in said biological sample. E. By “detecting” is thus advantageously meant the qualitative (advantageously the presence or absence), or even quantitative, determination of one or more analytes A in a biological sample E.

By “analyte” is meant any chemical, biochemical or biological entity that it is desired to detect in a biological sample E.

This chemical entity advantageously consists of an entity derived from the living world, preferably from the plant or animal world, preferably still present in humans.

Among the analytes detected by the system and the method according to the present invention, mention will be made in particular of proteins, peptides, antibodies, hormones, steroids, antigens derived from infectious agents or from tumor cells, infectious agents such as bacteria, viruses or parasites, nucleic acids (DNA or RNA), therapeutic compounds, drugs or even antibiotics.

Said at least one analyte A is more preferably chosen from:

- antigens specific to an infectious agent, or

- antibodies developed by a human being which shows an immune response to infection by an infectious agent.

The antibodies sought are advantageously chosen from serum IgM antibodies (immunoglobulins M), preferably on an IgM or “IgM line” and / or IgG (immunoglobulins G), preferably on an IgG or “IgG line”.

The term “infectious agent” preferably means viruses, in particular viruses responsible for pneumopathies, advantageously the Coronaviridae, more preferably Orthocoronavirinae or coronavirus.

By "coronavirus" is meant SARS-CoV, MERS-CoV or SARS-CoV-2.

By "biological sample" is advantageously meant any sample taken from an individual (human or animal in particular) and in which the analyte is sought.

This biological sample can in particular be any biological or bodily fluid, including:

- a biological sample from the upper respiratory tract, or

- a sample of capillary blood.

The term “biological sample from the upper respiratory tract” includes a nasopharyngeal sample or a saliva sample.

The biological sample can be a liquid sample in which the desired analyte is in solution or in suspension.

The term “biological sample” thus also includes excreta, surface samples, and the like. for the detection of biomarkers. The liquid sample may also have been obtained directly, or indirectly, from a biological or bodily fluid.

The sample can also be a liquid extract from a solid sample, for example feces.

The biological sample can be urine, whole blood, plasma, or serum.

By "whole blood" is meant in particular capillary blood advantageously obtained by means of an auto-pricker at the level of the pulp of the finger, or of the heel, of a human individual.

The biological sample may also be present on a collection portion of a collection device described below, for example a saliva swab or a nasal swab.

For this, the rapid analysis system 1 according to the invention comprises:

- at least one sampling device 2, suitable for taking the biological sample E (advantageously in an individual, or even in the environment, for example on a surface),

- at least one chromatographic strip 3 which is designed to detect the presence of said at least one analyte A,

- a buffer solution 4, for the implementation of the chromatographic technique, and

- at least one interface device 5 provided with at least two housings 51, 52, of which a second housing 52 is adapted to receive said at least one chromatographic strip 3 for the implementation of said chromatographic technique.

The rapid analysis systems 1 shown here include a single lot [sampling device 2 / chromatographic strip (s) 3 / interface device 5], for individual analysis.

Alternatively, not shown, the rapid analysis system could comprise several batches [sampling device 2 / chromatographic strip (s) 3 / interface device 5], for collective analysis (for example in the context of mass screening).

In this case, the strips 3 can be packaged in collective packaging; the sampling device 2 is packaged in individual packaging.

In general, these components of the rapid analysis system 1 are advantageously grouped / packaged in a package to form a kit.

This kit can then also include an instruction leaflet.

Sampling device

The rapid analysis system 1 therefore comprises at least one sampling device 2 which is suitable for taking the biological sample E, possibly from an individual.

This sampling device 2 is advantageously chosen from among the sampling devices 2 suitable for collecting:

- a biological sample E from the upper respiratory tract (Figure 1), for example a nasopharyngeal or salivary sample, or - a biological sample E of capillary blood (figure 11), or

- a surface sample (not shown).

For a biological sample from the upper respiratory tract, the sampling device 2 advantageously comprises:

- a collection part 21, adapted to collect the biological sample E, for example fibers and / or flocking, and advantageously,

- a gripping part 22, for example a rod terminated by the collecting part 21.

Such a sampling device 2 is advantageously chosen from saliva sampling swabs or nasal sampling swabs (FIG. 1 in particular).

Alternatively, for a capillary blood sample, the sampling device 2 can be in the form of a flexible pipette which is conventional per se with:

- a collection part 21, adapted to collect the biological sample E, in the form of a cannula, and advantageously,

a gripping part 22, for example a rod terminated by the collecting part 21, advantageously serving as a pump.

In this case, this sampling device 2 also advantageously comprises a lancet 23, also known under the name of a lancing device, conventional in itself and disposable, suitable for generating a flow of a drop of capillary blood.

Chromatographic strip

The rapid analysis system 1 further comprises said at least one chromatographic strip 3, also called "capillary diffusion means", advantageously an immunochromatographic strip, designed to detect the presence of said at least one analyte A.

These chromatographic strips 3 are formed from any means constituting or acting as a continuous capillary diffusion unit, by lateral migration (that is to say perpendicular to the thickness of the capillary material (s) used for capillary diffusion. ).

This capillary diffusion means advantageously consists of a porous solid support allowing the migration of a liquid by simple capillary diffusion.

The porosity of this support allows capillary diffusion (or lateral migration) of the sample and / or of the reagents in the liquid or wet state.

Such capillary diffusion means are very widely used, in particular in all lateral migration immunochromatography techniques.

Such a chromatographic strip 3 here consists of a support elongated in the direction and / or the direction of capillary diffusion (lateral migration).

Chromatographic strip 3 can be made up of:

- one and the same capillary or porous material, or - several different capillary or porous elements or materials, suitably arranged with respect to each other (for example by overlapping), to obtain a continuity of capillary flow from one element or from one material to another, according to the direction of capillary diffusion.

Such a chromatographic strip 3 determines a direction and direction of capillary diffusion of any liquid which is received or deposited at an upstream end, and which then moves towards a downstream end of the chromatographic strip 3.

By way of example, the chromatographic strip 3 can consist of various immunochromatographic supports, for example of cellulose, nylon, nitrocellulose, polyethylene or glass fiber.

Still according to the invention, the chromatographic strips 3 are made of a material capable here of remaining erect / erect in the interface device 5 following the migration of the buffer solution 4.

In other words, a chromatographic strip 3 is advantageously adapted to remain rectilinear / flat during the migration of the buffer solution 4 (at least for the duration of the test).

The chromatographic strip 3 can for this include a stiffening layer (advantageously rear).

This stiffening layer can be made of various materials such as cardboard, plasticized cardboard or more preferably plastics. Preferably, the stiffening layer consists of polystyrene.

As illustrated diagrammatically in FIG. 7, the chromatographic strip 3 comprises different successive zones 31, in the direction of capillary migration upstream to downstream, namely at least:

- a deposit zone 311, intended to receive the buffer solution 4 / biological sample E mixture,

- a release zone 312 which comprises at least one detection reagent conjugated with a visible and / or measurable marker, said detection reagent being able to move as a consequence of the migration of the buffer solution 4 along the chromatographic strip 3 , and

- at least one capture zone 313 which comprises at least one capture reagent, immobilized on the chromatographic strip 3.

In particular, the deposition zone 311 must here be long enough to be immersed in the biological sample E / buffer solution 4 mixture.

Furthermore, the release 312 and capture 313 zones advantageously consist of a transverse line or strip (extending perpendicular to the direction of migration), for example having a width of between 1 and 2 mm, and an area of between 3 and 5 mm ² .

In general, the "detection reagent" or the "capture reagent" consists of any chemical, biochemical or biological entity which is able to bind specifically to form a complex allowing the determination of said analyte in the liquid sample.

The detection reagent and / or the capture reagent also constitute so-called “binding” reagents.

Such binding reagents, allowing the detection of at least one analyte in the liquid sample, are well known and can be tailored for the implementation of the invention.

These binding reagents are advantageously chosen from those which are capable of binding specifically with said analyte and / or of binding specifically with one another.

Depending on the test format used, the additional binding reagents are intended to form different complexes:

- the binding reagents are able to bind concomitantly to the analyte, to form a sandwich format test, or

- one of the binding reagents (detection or capture) is able to bind to the analyte but also to the other binding reagent (respectively capture or detection), to form a test in competition format.

By “bind” or “binding” is meant any strong bond, for example covalent, but also any weak bond, for example of the antigen / antibody or analyte / anti-analyte type.

The term “anti-analyte” is understood to mean any chemical, biochemical or biological entity capable of binding specifically with the analyte, or with the capture reagent in competition with the analyte, for example an antibody, an antigen or a. nucleic acid.

By “appropriate analog of the analyte” is advantageously meant any chemical, biochemical or biological entity capable of binding specifically to the capture reagent or to the detection reagent, as the case may be, in competition with the analyte.

The binding reagents are advantageously chosen from antibodies, antigens or nucleic acids.

The analyte and the binding reagent thus typically form a pair capable of binding specifically to one another, such as, for example, a ligand / anti-ligand cut, an antigen / antibody pair, a DNA / RNA pair or a. DNA / DNA couple.

Thus, if the analyte is an antigen or a hapten, at least one of the binding reagents (the detection reagent and / or the capture reagent) is advantageously an antibody specific for the analyte.

By “antibody specific for the analyte” is meant an antibody capable of binding specifically with the analyte in a binding of the antigen / antibody type. It is typically a polyclonal antibody or a monoclonal antibody, having a high affinity for the analyte. Preferably, it is a monoclonal antibody.

If the analyte is an antibody, at least one of the binding reagents is advantageously the antigen recognized by the antibody.

If the analyte is a nucleic acid, at least one of the binding reagents is advantageously a complementary DNA probe.

The detection reagent (s) are advantageously combined with a visible and / or measurable label, advantageously a particulate label.

By “visible and / or measurable marker” is meant any marking allowing direct or indirect detection with the naked eye, or with the aid of a device, due to the emission of a signal at said level. at least one capture zone 313.

The signal is, for example, fluorescence, coloring, the presence of isotope or a magnetic signal.

Mention will be made, for example, of colored particulate markers such as colloidal gold, or fluorescent, colored latex particles, fluorescent latex particles and particles conjugated with avidin and with streptavidin.

Particulate markers, colored or fluorescent, thus consist of small particles which are insoluble in water and which therefore form suspensions, dispersions or solutions, in the liquid phase.

Among the markers allowing direct observation with the naked eye, mention will also be made of markers of the dextran type (Hansen T.M., IVD Technology 4, 35-40, 2003). The binding reagent is then conjugated to a dextran (polysaccharide derivative) chain carrying fluorophores.

The markers can also consist of enzymes (alkaline phosphatase or AP, horseradish peroxidase or HRP, in particular), of dyes (or "dyes") or of chemiluminescent compounds (in particular fluorescein isothiocyanate or FITC).

To increase the sensitivity, recourse may be had, for example, to an antibody labeled according to techniques known to those skilled in the art for indirect detection, such as for example a biotinylated antibody, indirectly allowing detection by the formation of avidin entities. -biotin and streptavidin-biotin.

This labeled and biotinylated antibody can also either be directly deposited on a test line, in the capture zone, to increase the sensitivity, or be deposited with the specific detection antibody, to increase the contact time and again the sensitivity in particular, for example, due to the number of attachment sites.

For its part, in the capture zone 313, the capture reagent specific for the analyte is immobilized on the solid support according to techniques known to those skilled in the art.

This capture reagent is immobilized in such a way that it is not mobile in the wet state. This immobilization can take place, for example, by absorption or by covalent coupling.

In the system according to FIG. 1, the detection reagents and the capture reagents are advantageously chosen from reagents suitable for detecting the presence of said at least one analyte chosen from antigens, preferably specific for an infectious agent, preferably them. viruses, in particular the viruses responsible for pneumopathies, advantageously the Coronaviridae, more preferably Orthocoronavirinae or coronavirus.

In the system according to FIG. 11, the detection reagents and the capture reagents are advantageously chosen from reagents suitable for detecting the presence of said at least one analyte chosen from antibodies, preferably specific for an infectious agent, preferably them. viruses, in particular the viruses responsible for pneumopathies, advantageously the Coronaviridae, more preferably Orthocoronavirinae or coronavirus.

The reagents are preferably also suitable for analyzing the serology of a biological sample E, preferably for detecting the possible presence of anti-SARS-Cov-2 IgG and / or anti-SARS-Cov-2 IgM antibodies.

The detection reagents and the capture reagents are advantageously chosen, without in any way being limiting, from:

- antibodies, advantageously chosen from anti-IgG antibodies (human) and anti-IgM antibodies (human), preferably directed against SARS-Cov-2,

- antigens specific to a microorganism, advantageously a virus, preferably SARS-Cov-2, and

- suitable recombinant proteins.

In a preferred embodiment, the capture zone 313 can further comprise a control capture reagent.

This control capture reagent makes it possible to have a positive control in order to ensure the effective capillary diffusion of the liquid sample from the deposition zone 311 to the capture zone 313.

This control capture reagent is permanently immobilized downstream of the “analyte” capture reagents (“Control line” or control line).

It may, for example, be an antibody binding to the detection reagent (s).

Alternatively, this control capture reagent is independent of the analyte A and simply makes it possible to verify the diffusion of the liquid sample along the chromatographic strip 3 (for example by the capture of a labeled control reagent).

According to one embodiment described in relation to FIGS. 15 et seq., The rapid analysis system may comprise at least two of said chromatographic strips 3, which are different from one another. Said at least two chromatographic strips 3 are advantageously designed to each detect the presence of at least one analyte A, different from each other.

In other words, each chromatographic strip 3 is advantageously designed to detect the presence of at least one analyte A which is distinct / different from said at least one analyte A detected by at least one other chromatographic strip 3.

The analysis system thus advantageously comprises a combination of at least two different chromatographic strips 3.

These 3 different chromatographic strips advantageously have a distinctive sign, for example a different color.

Preferably, said at least two chromatographic strips 3 consist of two chromatographic strips each designed to detect the presence of a virus responsible for pneumonia, namely for example:

- a first chromatographic strip 3 designed to detect the presence of a Coronaviridae virus, more preferably Orthocoronavirinae or coronavirus, and

- a second chromatographic strip 3 designed to detect the presence of an influenza virus or influenza virus.

In general, the chromatographic strip 3 is intended to be inserted into a second housing 52 of the interface device 5, here in an erect position relative to this second housing 52.

For this, the chromatographic strips 3 have dimensions adapted to allow this individual insertion into this second housing 52.

By "insertion", as illustrated by Figure 9, is meant in particular an introduction of a lower portion 35 of the length of a chromatographic strip 3 into the second housing 52; this lower part 35 (at a transverse edge 351) is advantageously intended to bear on a bottom of the second housing 52 (see in particular FIG. 9).

This lower part 35 can be:

- free, especially in the case of a second housing without guide, or

- guided, in the presence of a conformation suitable for guiding (Figures 8 and 9).

And an upper portion 36 of the length of this chromatographic strip 3 then advantageously protrudes relative to this second housing 52, from its upper access opening (see in particular Figures 8 and 9).

The lower part 35 advantageously comprises the deposition zone 311 (and preferably the release zone 312 which is advantageously located above the mixture contained in the second housing 52); the upper part 36 for its part comprises the capture zone 313. To allow this insertion, the chromatographic strip 3 has a width L1 which is less than the width P1 of the second housing 52 (at least at its lower part 35).

In practice, as illustrated in connection with FIG. 7, the chromatographic strips 3 have a rectangular outline with:

- two longitudinal edges 38 defining its width L1, and

- two transverse borders 39 defining its length L2.

For example, a chromatography strip 5 has the following dimensions:

- the width L1 is 2 to 6 mm, preferably 3 to 5 mm, and

- the length L2 is 5 to 10 cm, preferably 6 to 8 cm.

Buffer solution

The buffer solution 4 is intended to be added to a first housing 51 of the interface device 5 and to be mixed with the biological sample E.

This buffer solution 4 is chosen from the buffer solutions suitable for the implementation of the chromatographic technique: it is in particular intended to migrate along a chromatographic strip 3 so as to cause, or at least to facilitate, the migration of the liquid. biological sample E (and in particular of said at least one analyte A).

The buffer solution 4 is for example chosen from diluents composed of a buffered saline solution. It can also comprise a detergent or any other component necessary in particular for the migration or for the reactions on the chromatographic strips 3.

To control the reported amount of this buffer solution 4, the buffer solution 4 is packaged in a container which includes a dropper.

Interface device

The interface device 5 according to the invention comprises housings 51, 52 (possibly only two housings) which are in fluid communication, for example:

- only two housings 51, 52 according to Figures 1 to 14, or

- more than two housings 51, 52 according to Figures 15 and following.

In general, this interface device 5 advantageously comprises:

- a lower wall 54 defining a bottom face 541 adapted to rest on a receiving surface (for example a work surface),

- an upper wall 55 defining a top face 551, opposite, and

- an outer wall 56, connecting these faces from below 541 and from above 551.

These walls 54, 55, 56 here together define an internal chamber 57.

According to the invention, the housings 51, 52, advantageously in the form of a well, comprise: - at least a first housing 51 (advantageously a first single housing 51) intended to receive at least said buffer solution 4, optionally mixed with said biological sample E, and

- at least one second housing 52 (advantageously a single second housing 52 or at least two second housing 52) designed to introduce at least the deposition zone 311 of the chromatographic strip 3 (here its lower part 35).

According to one embodiment illustrated through Figures 1 to 14, the housings 51, 52, advantageously in the form of a well, comprise:

- a first housing 51, unique, intended to receive at least said buffer solution 4, optionally mixed with said biological sample E, and

a second housing 52, unique, designed to introduce at least the deposition zone 311 of the chromatographic strip 3 (here its lower part 35).

According to another embodiment illustrated through FIGS. 15 and following, the housings 51, 52, advantageously in the form of a well, comprise:

- at least two second housings 52 (for example two, three or four in number), each designed to introduce at least the deposition zone 311 of a chromatographic strip 3 (here its lower part 35).

In general, said at least one second housing 52 is intended to receive the buffer solution 4, optionally mixed with the biological sample E, by flow from the first housing 51.

The housings 51, 52 of this interface device 5 are then advantageously in the form of juxtaposed wells, advantageously parallel, and opening at the level of the top face 551.

In particular, in the presence of at least two second housings 52, said second housings 52 are advantageously distributed around the first housing 51, advantageously central, for example juxtaposed (FIG. 15) or distributed around its circumference (FIGS. 19 to 21).

In this case, the housings 51, 52 each have a side wall 511, 521, defining a general axis 51 ’, 52’, which is delimited by:

- an access opening 512, 522, here upper, made through the top face 551, and

- a bottom 513, 523, here lower, provided on the side of the underside 541.

It is here the funds 513, 523 of these housings 51, 52 which are in fluid communication.

In this case, the housings 51, 52 are in fluid communication via at least one conduit 58 adapted to a flow of the buffer solution 4, possibly mixed. with the biological sample E, from the first housing 51 to said at least one second housing 52.

In particular, in the presence of at least two second housings 52, the housings 51, 52 are advantageously in fluid communication via a single duct 58, adapted to a flow of the buffer solution 4, optionally mixed with the. biological sample E, from the first housing 51 to said second housings 52.

The conduit 58, here in the form of a channel or gutter, for this advantageously has a lower face 581 having a downward slope from the first housing 51 to at least one second housing 52.

This embodiment thus promotes the flow of the buffer solution 4, optionally mixed with said biological sample E, from the bottom 513 of the first housing 51 to the bottom 523 of at least one second housing 52.

This conduit 58 has two parts in this case:

- a first part 582, forming the bottom 513 of the first housing 51, on a downward slope, and

- a second part 583, ending the first part 582 sloping and forming the bottom 523 of at least one second housing 52, generally cup-shaped to collect and maintain the liquids flowing from the first housing 51.

As illustrated in Figure 16, in the presence of at least two second housings 52, this duct 58 advantageously comprises two parts:

- a second part 583, ending the first part 582 sloping and forming the bottom 523 (common) of the second housings 52, in the general shape of a cup (common for the second housings 52) to collect and maintain the liquids flowing from the first accommodation 51.

In general, the first housing 51 advantageously comprises a side wall 511 which has a section which decreases from the access opening 512 towards the bottom 513 (FIG. 4 in particular).

This shape is useful to facilitate the addition of the buffer solution 4, or even the insertion of the collection part 22 of the sampling device 2.

In this case, this side wall 511 has the general shape of a funnel.

This side wall 511 here comprises a frustoconical portion preferably followed by a final cylindrical portion.

More precisely, the side wall 511 comprises here:

- a first frustoconical portion 511a, upper, having a first angle,

- a second frustoconical portion 511b, intermediate, having a second angle smaller with respect to said first angle, and - A cylindrical portion 511c, lower.

As discussed above, the first housing 51 is advantageously suitable for the introduction of the collection part 21 of the sampling device 2 so that the buffer solution 4 ensures the transfer of the biological sample E from this first housing 51 to the second accommodation 52.

In this context, the side wall 511 of this first housing 51 advantageously comprises a compression part 511b, 511c, the section of which is identical to, or smaller than, the collection part 21 (see FIG. 9).

The compression part 511b, 511c is preferably cylindrical and located on the side of the bottom 513.

This compression part 511b, 511c is here formed by the second frustoconical portion 511b and by the cylindrical portion 511c.

The side wall 511 of this first housing 51 also advantageously comprises at least one groove 511e (FIG. 4), here of spiral or helical shape, extending over part of its height.

This groove 551e extends towards the bottom 513 of this first housing 51, to promote the flow of the buffer solution 4, if necessary mixed with said biological sample E, towards this bottom 513.

Furthermore, said at least one second housing 52 here comprises a conformation suitable for guiding the introduction of the chromatographic strip 3.

In this case, this second housing 52 has a rectangular cross section to maintain the orientation of the attached chromatographic strip 3.

In particular, this second housing 52 comprises:

- a dimension in width P1 greater than the width L1 of the chromatographic tab 3 (P1 comprises for example from 1 to 10 mm more compared to L1), and

a dimension in thickness P2 less than the width L1 of the chromatographic tab 3 (P2 is for example from 1 to 3 mm).

As discussed above, the length L2 of the chromatographic strip 3 is greater than the depth P3 of this second housing 52 so as to give this chromatographic strip 3 a configuration erected on either side of the opening of access 522.

According to the embodiment illustrated through Figures 1 to 14, the interface device 5 comprises a second housing 52, unique.

According to another embodiment illustrated through Figures 15 and following, the interface device 5 comprises at least two second housings 52, each receiving a chromatographic strip 3, for example the number of:

- two second housings 52 (Figures 15 to 19), arranged for example juxtaposed (Figures 15 to 18) or on either side of the first housing 51 (Figure 19); - three second housings 52 (FIG. 20), for example distributed around the first housing 51, at 90 ° to each other (together forming a U-shape here) °,

- Four second housings 52 (FIG. 21), for example distributed around the first housing 51, at 90 ° to each other (together forming here a square shape).

In general, the outer wall 56 of the interface device 5 defines, with the top face 551 and the bottom face 541, the internal chamber 57 over the height of which the housings 51, 52 extend.

The side wall 511, 521 of at least one of the housings 51, 52 is then advantageously provided with an annular lumen 511f, 521 f which is in fluid communication with this internal chamber 57 (Figures 4 and 9).

Such an annular lumen 511 f, 521f is advantageously located between a free border 511 g, 521 g of said side wall 511, 521 and the bottom 513, 523.

Such a structure is particularly useful for avoiding, or at least limiting, an outflow / flow of liquid through the housings 51, 52 in the event of tilting of the interface device 5.

Indeed, during such an inclination of the interface device 5, the liquids will tend to flow through the annular slot 511f, 521f, without being able to go up along the side wall 511, 521 of the housing 51. , 52.

Such an annular lumen 521 f is also useful for evacuating a possible overflow of buffer solution 4, at the level of the bottom of the second housing 52, which would be liable to immerse the chromatographic strip 3 above its deposition zone 311.

Still generally, the interface device 5 is advantageously made of a plastic material.

Preferably, this interface device 5 is formed of two assembled parts 5a, 5b (Figures 5, 6 or 14), in this case:

- a first part 5a forms the outer wall 56 assembled with the side wall 511, 521 of the housings 51, 52, via the upper wall 55, and

a second part 5b, a first side of which forms the bottom face 541 and a second side 542 comprises the duct 58 connecting the bottom 513, 523 of the housings 51, 52.

According to one embodiment illustrated in Figure 14, the two parts 5a, 5b are assembled by assembly means 5c of the elastic interlocking type (here pairs of grooves / complementary ribs).

The two parts 5a, 5b also include keying means 5d, to properly orient these two parts 5a, 5b, one relative to the other, during assembly.

Examples of systems

FIGS. 1 to 10 illustrate an embodiment suitable in particular for the search for an antigen in a biological sample E advantageously chosen from the samples biological samples from the upper respiratory tract, for example a nasopharyngeal or salivary sample or a capillary blood sample.

This rapid analysis system 1 includes:

- at least one sampling device 2 chosen from saliva sampling swabs or nasal sampling swabs,

- at least one chromatographic strip 3 which is designed to detect the presence of said at least one analyte A of the antigen type,

- at least one interface device 5 according to the invention.

FIGS. 11 to 14 illustrate an embodiment suitable in particular for the search for antibodies in a biological sample E advantageously chosen from biological samples of the capillary blood type.

This rapid analysis system 1 includes:

- at least one sampling device 2 comprising a flexible pipette 21, 22 and / or a lancet 23,

- at least one chromatographic strip 3 which is designed to detect the presence of said at least one analyte A of the antibody type,

- at least one interface device 5 according to the invention.

Figures 15 and following illustrate an embodiment advantageously suitable in particular for the search for at least two distinct / different antigens in a biological sample E advantageously chosen from biological samples from the upper respiratory tract, for example a nasopharyngeal or salivary sample or a capillary blood sample.

This rapid analysis system 1 includes:

- at least two chromatographic strips 3 which are each designed to detect the presence of said at least one analyte A of the antigen type, which at least two chromatographic strips 3 are each designed to detect the presence of said at least one analyte A of the antigen type, different one from the other,

- at least one interface device 5 according to the invention, comprising at least two second housings 52.

The present embodiment thus advantageously proposes a system for the rapid analysis of a biological sample, in a “multi-test” / “multi-strip” form. This system is in particular intended for detecting the presence of at least two analytes in said biological sample.

Such a "multi-test" system, also called "multi-strip", is thus particularly advantageous in that it offers a versatile solution intended for the simultaneous detection of the presence of at least two analytes in a biological sample.

This solution thus offers a rapid differential diagnostic test, also called a “differential rapid screening test”, which makes it possible to rapidly (in a few minutes) and simultaneously establish the presence of at least one analyte of interest (among at least two analytes of interest) in a single biological sample.

Method for the rapid analysis of a biological sample E

The implementation of the rapid analysis system according to the invention is described below according to two distinct modes:

- a first mode adapted to a biological sample E deposited directly on the deposition zone 311 of the chromatographic strip 3 (Figures 11 to 13), and

- a second mode adapted to a biological sample E recovered on the collection part 21 of a sampling device 2 (Figures 1 to 10 or even Figures 15 and following).

The biological sample E is advantageously chosen from biological samples from the upper respiratory tract, for example a nasopharyngeal or salivary sample, or a capillary blood sample. The biological sample can also consist of a surface sample.

In general, the method advantageously comprises:

- a step of inserting the chromatographic strip 3 into the second housing 52 (Figures 7 or 12 or 18),

- a step of adding the buffer solution 4 in the first housing 51, for the implementation of the chromatographic technique (Figures 8 or 13 or 17), and

- reading the chromatographic strip 3 positioned in the second housing 52, after migration of the buffer solution 4, to detect the presence of said at least one analyte A in the biological sample E.

During the insertion step, the lower part 36 of the strip 3 advantageously rests on the bottom 523 and on the upper access opening 522 (at its rear layer).

Reading can be performed directly or through a reading device.

The embodiment according to Figures 1 to 10 or 15 et seq. Is advantageous in particular for a nasopharyngeal or salivary sample.

In this mode, illustrated in Figures 1 to 10 or 15 and following, it is advantageously provided that: - the insertion step also comprises an insertion of the collection part 21 of the sampling device 2 in the first housing 51 (Figures 7 or 17), and

- The step of adding the buffer solution 4 leads to bringing the buffer solution 4 into contact with the collection part 21 of the sampling device 2 positioned in the first housing 51 (rinsing / extraction phenomenon), to ensure the transfer of the biological sample E from the sampling device 2 to the chromatographic strip 3 (FIGS. 8, 9 or 18).

The flow of the biological sample E / buffer solution 4 mixture, from the collection part 21, is further favorably favored by the movement of the sampling device 2 (Figure 10). The helical groove 511e advantageously ensures a screwing phenomenon when handling the sampling device 2, further promoting the extraction of the biological sample E.

The embodiment according to Figures 10 to 13 is of particular interest for a capillary blood sample. In the illustrated mode, the biological sample E is deposited directly on the deposition area

311 of the chromatographic strip 3, before said insertion step (Figure 12).

Of course, various other modifications can be made to the invention within the scope of the appended claims.

Claims

[Claim 1] System for the rapid analysis of a biological sample (E), intended for the detection of the presence of at least one analyte (A) in said biological sample (E), which rapid analysis system comprises :

- at least one sampling device (2), suitable for taking said biological sample (E), for example a biological sample (E) from the upper respiratory tract or a capillary blood sample,

- at least one chromatographic strip (3), advantageously an immunochromatographic strip, designed to detect the presence of said at least one analyte (A), which at least one chromatographic strip (3) comprises a deposition zone (311) intended to receive said biological sample (E),

- a buffer solution (4), for implementing the chromatographic technique, and

- at least one interface device (5), adapted to receive said at least one chromatographic strip (3) for the implementation of said chromatographic technique, which interface device (5) comprises at least two housings (51, 52) in fluid communication, advantageously in the form of a well, with:

- at least a first housing (51) intended to receive at least said buffer solution (4), optionally mixed with said biological sample (E), and

- at least one second housing (52) designed to introduce at least said deposition zone (311) of said at least one chromatographic strip (3), said second housing (52) being intended to receive said buffer solution (4), optionally mixed with said biological sample (E), flowing from said at least one first housing (51).

[Claim 2] A rapid analysis system, according to claim 1, characterized in that said at least two housings (51, 52) each comprise an access opening (512, 522) and a bottom (513, 523), which bottoms (513, 523) of said at least two housings (51, 52) are in fluid communication.

[Claim 3] A rapid analysis system, according to any one of claims 1 or 2, characterized in that said at least two housings (51, 52) are in fluid communication via a conduit (58). adapted to a flow of the buffer solution (4), optionally mixed with said biological sample (E), from said first housing (51) to said second housing (52). [Claim 4] A rapid analysis system, according to claim 3, characterized in that the duct (58) has a lower face (581) having a downward slope from said first housing (51) towards said second housing (52), to promote the flow of the buffer solution

(4), optionally mixed with said biological sample (E) from said first housing (51) to said second housing (52).

[Claim 5] A rapid analysis system according to any one of claims 1 to

4, characterized in that said at least one first housing (51) comprises a side wall (511) which has a section which decreases from an access opening (512) towards a bottom (513).

[Claim 6] A rapid analysis system according to any one of claims 1 to

5, characterized in that said at least one second housing (52) is shaped for guiding the introduction of said at least one chromatographic strip (3).

[Claim 7] A rapid analysis system according to any one of claims 1 to

6, characterized in that the length of the chromatographic strip (3) is greater than the depth of said at least one second housing (52), so as to give said chromatographic strip (3) an erect configuration on either side an access opening (512, 522).

[Claim 8] A rapid analysis system according to any one of claims 1 to

7, characterized in that said at least one interface device (5) comprises:

- a bottom face (541), adapted to rest on a receiving surface, and

- a top face (551), opposite, and in that said at least two housings (51, 52) of said at least one interface device (5) are in the form of juxtaposed wells, advantageously parallel, and opening at said top face (551).

[Claim 9] A rapid analysis system according to any one of claims 1 to

8, characterized in that said at least one sampling device (2) comprises a collection part (21) adapted to collect said biological sample (E), and in that said at least one first housing (51) is adapted to the introduction of said collecting part (21) of said at least one sampling device (2) so that the buffer solution (4) ensures the transfer of said biological sample (E) from said at least one first housing (51) to said at least one second housing (52).

[Claim 10] A rapid analysis system, according to claim 9, characterized in that said at least one first housing (51) has a side wall (511) provided with a compression part (511b, 511c) whose section is the same as, or smaller than, the collecting part (21).

[Claim 11] A rapid analysis system according to any one of claims 1 to

10, characterized in that said at least one sampling device (2) is chosen from:

- saliva swabs or nasal swabs, or

- lancets, suitable for generating a drop of capillary blood.

[Claim 12] A rapid analysis system according to any one of claims 1 to

11, characterized in that said at least one first housing (51) comprises a side wall (511) in which is formed at least one groove (511e), for example of spiral or helical shape, extending towards a bottom (513) ) to promote the flow of the buffer solution (4), if necessary mixed with said biological sample (E), towards said bottom (513).

[Claim 13] A rapid analysis system according to any one of claims 1 to

12, characterized in that at least one of the housings (51, 52) comprises a side wall (511, 521) provided with an annular lumen (511f, 521f) in fluid communication with an internal chamber (57), for avoid or at least limit an exit of liquid through said housings (51, 52) in the event of tilting of said interface device (5).

[Claim 14] A rapid analysis system according to any one of claims 1 to

13, characterized in that the rapid analysis system comprises:

- at least two of said chromatographic strips (3), advantageously designed to each detect the presence of said at least one analyte (A), different from each other,

- said at least one interface device (5) comprising said at least one first housing (51), preferably a single first housing (51), and at least two second housings (52) each designed to introduce at least said zone deposit (311) of at least one of said chromatographic strips (3).

[Claim 15] An interface device for a rapid analysis system according to any one of claims 1 to 14, which interface device (5) has at least two housings (51, 52) in fluid communication, preferably well-shaped, with:

- at least a first housing (51), intended to receive at least one buffer solution (4), optionally mixed with a biological sample (E), and

- at least one second housing (52), preferably one, two, three or four second housing (s) (52), designed for the introduction of a deposition zone (311) of a chromatographic strip (3).

[Claim 16] A method for the rapid analysis of a biological sample (E), from a rapid analysis system (1) according to any one of claims 1 to 14, characterized in that said method comprises:

- a step of inserting said at least one chromatographic strip (3) in said second housing (52),

- a step of adding the buffer solution (4) to said first housing (51), for the implementation of the chromatographic technique, and

- reading said at least one chromatographic strip (3) after migration of the buffer solution (4), to detect the presence of said at least one analyte (A) in said biological sample (E).

[Claim 17] A rapid analysis method according to claim 16, characterized in that: (i) in a first mode: the biological sample (E) is deposited directly on the deposition zone (311) of the chromatographic strip ( 3), before said insertion step, or

(ii) in a second mode: - the insertion step also comprises an insertion of the collection part (21) of said at least one sampling device (2) in said first housing (51),

- the step of adding the buffer solution (4) leads to bringing said buffer solution (4) into contact with said collecting part (21) of said at least one sampling device (2) positioned in said first housing (51), to ensure the transfer of said biological sample (E) from said at least one sampling device (2) to said at least one chromatographic strip (3).