BE1022360B1 - MICROPLATE WELL, HOLDER AND METHOD FOR DETECTION OF ANALYTES - Google Patents

Abstract

The present invention relates to a container unit base assembly (150), for removable insertion into a holding support (200) for a plurality of container unit base assemblies for dosing, comprising a container unit (100). having a bottom wall (114) at a lower end (104) of the container unit (100), and a side wall (110) extending upwardly therefrom, defining a cavity (116) , which cavity (116) is adapted to receive a fluid, and a solid unit (300) having an upper face (310) for the immobilization of a ligand for the detection of an analyte, the support unit solid (300) being positioned in the cavity (116). It also relates to a kit containing at least two sets of container units (150). It also relates to a holding support (200) for holding capable of receiving a plurality of assemblies based on units of containers (150).

Description

MICROPLATE WELL, HOLDER AND METHOD FOR DETECTION OF ANALYTES

Field of the invention

The present invention relates to a microplate well, a support therefor, and kits, uses thereof, and methods for the detection of analytes in a biological sample. In particular, the present invention relates to a microplate well, a support therefor, and kits, uses thereof, and methods for creating a customized assay for the detection of analytes in a biological sample.

Background of the invention

Several strategies have been developed for the detection of analytes in a biological sample for routine diagnostic assays in diagnostic laboratories, for example, by immunoassays.

Essentially, immunoassays can be performed in a liquid-based assay using, for example, a plastic well (e.g. in a 96-well plate) with certain immunological reagents.

The plastic well system in general allows the detection of an analyte per patient and well. The ligand-coated wells are generally arranged in a 12 x 8 (96) well matrix on a plate, the shape and size of each well being the same. Plates are known in the art as microplates, well plates, or microtiter plates. In standard techniques, the majority of wells in a 96-well plate are dedicated to receiving patient samples (1 per well), while a minority of wells (at least one) serve as controls and / or standards that establish threshold and / or calibration values for the entire analysis. This is suitable for high throughput analysis of cohorts of patients for a particular analyte. In particular diagnostic areas (eg autoimmune disease diagnoses), multiparametric analysis is frequently required for different patients. For multiparametric analysis, the plastic well system may be pre-loaded with a plurality of different ligands, normally one in each well, for the detection of multiple analytes. However, several microplates are frequently required for the execution, on different samples, of all the tests required by a hospital or a doctor, especially when the required tests are various. If, furthermore, it is taken into account that at least one control or reference well must be treated in parallel with the sample well for each ligand, and that many wells pre-assembled on the plate are not necessary for each patient, this may lead to a waste of resources and sample. Another fact to take into account is that the production of plates previously provided with different ligands is slow even if it is assisted by automata, which makes the multiparameter plates economically unfeasible for use in mass and lacking flexibility for the user, given the limited associations of ligands which, for these reasons, can be proposed industrially.

There remains, therefore, a need in the art for systems based on new and / or improved well microplates for the detection of analytes in a biological sample. Summary of the invention

The inventors of the present invention have now discovered a microplate well previously provided with a solid support unit, a holding support therefor, answering one or more of the problems of the state of the art mentioned above. above .

The present invention relates to a container unit-based assembly (150) for removable insertion into a holding bracket (200) for a plurality of container unit-based assemblies for a dosette, comprising: a container unit (100); ) having a basal wall (114) at a lower end (104) of the container unit (100), and a sidewall (110) extending upwardly therefrom, defining a cavity (116) ), which cavity (116) is adapted to receive a fluid, and a solid support unit (300) having an upper face (310) for immobilizing a ligand for the detection of an analyte, the solid support unit (300) being positioned in the cavity (116). The solid support unit (300) can be positioned in the cavity (116) for machine reading through an opening (112) provided in the container unit (100) at an upper end (102) of that -this. The container unit-based assembly (150) may further include an orientation marker (118) for identifying the orientation of the container unit-based assembly (100) around a central axis (A-A '). The cavity (116) may be the only cavity present in the container unit (100). The upper face (310) of the solid support unit (300) may be provided with a plurality of separate analysis zones (306, 308) each containing an immobilized ligand for the detection of an analyte. The plurality of separate analysis zones (306, 308) may each contain a different immobilized ligand. The plurality of separate scan areas (306, 308) may be arranged in a grid pattern.

The present invention further relates to a kit comprising at least two container unit-based assemblies (150) as defined herein, an upper face (310) of the solid support unit (300) being provided with a plurality of storage zones. analysis (306, 308), each analysis zone containing an immobilized ligand for the detection of an analyte, and the solid support unit (300) being essentially the same in each of said at least two d-based sets containers units (150). The invention further relates to a method for producing a container unit-based assembly (150) as defined herein, comprising the steps of: providing a container unit (100), providing a plurality of solid support units (300) disposed in a sheet or flat strip, depositing one or more ligands on the upper face (310) of a plurality of different solid support units (300) of the sheet or strip, using of an XYZ robotic micro-dispenser, inserting one of the solid support units (300) thus formed in the container unit (100) to form a container unit-based assembly (150). The invention further relates to a holding support (200) for holding suitable for receiving a plurality of container unit-based assemblies (150), as defined herein, comprising: a plurality of compartments ( 210, 210 '), each compartment being adapted to receive and maintain a container unit-based assembly (150), the compartments (210, 210') being arranged in a grid pattern.

The holding support may further comprise a plurality of container unit-based assemblies (150), each of which is releasably inserted into an individual compartment (210, 210 '). Each container unit-based assembly of the holding support may be provided with the solid support unit (300) having a plurality of separate analysis zones (306, 308) for the detection of analytes, and at least one one of the analysis zones may be different between at least two sets based on container units. At least one of the analysis zones may be different when comparing all the sets based on container units; the difference may lie in the concentration of the ligand, the composition of the ligand, and / or the position of the ligand.

Such sets based on container units and such a holding support at least advantageously allow the creation of a customized dosage adapted to the patient. The user or consumer, such as an analytical laboratory, may choose one or more different solid support units for each patient to create a personalized dosage, for example as prescribed by the practitioner. The number of microplates to be used, analyzed, validated and interpreted is thus reduced because the detection of irrelevant or redundant analytes is avoided. Accordingly, a holding support and microplate wells illustrating the present invention advantageously reduce the number of tests to be performed while retaining the required analyte analyzes. The reduction in the number of tests that need to be performed advantageously leads to an increase in the speed of analysis, a reduction in the amount of sample required, a reduction in the impact on the environment by reducing the reagents and consumables required, and therefore lowering costs.

As mentioned above, the present invention allows the user or the consumer, such as a medical testing laboratory, to test only those analytes that have been prescribed by a practitioner, which could also be important from one point of view. from a legal point of view. Indeed, the present invention makes it possible to test and report only the analytes that are prescribed by the practitioner and / or are reimbursed to the patient.

The present invention is also advantageous because it allows the manufacturer to control the quality of each USS separately. For example, the present invention enables the manufacturer to control the quality of the application of a ligand on the USS separately from the quality of the application of the other ligands. In contrast, in existing multiparametric assay microplates, several ligands are applied on a single microplate and therefore, when the application of one of the ligands does not fall within the required quality range, the complete multiparametric microplate (including applied ligands) must be rejected.

These and other aspects and embodiments of the invention are set forth in more detail hereinafter in the following sections and in the claims, and illustrated by non-limiting figures. The reference numbers refer to the figures appended hereto.

Brief description of the drawings

FIG. 1 represents a container unit of the invention.

FIG. IA is a front view of the container unit of FIG. 1.

FIG. IB shows a plan view (upper end) of the container unit of FIG. 1.

FIG. IC shows a sectional view of the container unit of FIG. 1 passing through a plane in contact with the axis A-A '.

FIG. 2 shows a sectional view of a container unit-based assembly, passing through a plane in contact with the axis A-A ', comprising the container unit of FIG. 1, provided with a solid support unit.

FIG. 3 shows a plan view of a variant of the container unit of FIG. 1.

FIG. 4 shows a schematic representation of the container unit of FIG. 1 additionally provided with a rim.

FIG. 5 shows a schematic representation of the container unit of FIG. 1, further provided with a flange with an orientation element.

FIG. 5A shows a front view of the container unit of FIG. 5.

FIG. 5B shows a sectional view of the container unit of FIG. 5 going through the plane 124.

FIG. 5C shows a sectional view of the container unit of FIG. 5 passing through a plane in contact with the central axis (A-A ').

FIG. 6 shows a plan view (front face) of a holding support 200 of the invention.

FIG. 7 is a sectional view of a plane passing through the line B-B 'on the page of the holding support 200 of FIG. 6.

FIG. 7A shows an enlargement of a portion of FIG. 7.

FIG. 8 is an enlargement of a portion of FIG. 7, the compartments being each occupied by a flanged container unit.

FIG. 9 is a sectional view of a plane on the page, passing through the line B-B 'of another holding bracket 200 of FIG. 6.

FIG. 9A shows an enlargement of a portion of FIG. 9.

FIG. 10 is an enlargement of a portion of FIG. 9, the compartments being each occupied by a container unit without flange.

FIG. 11 is a plan view (top face) of a solid support unit (USS).

FIG. 12 is a plan view (top face) of a solid support unit (USS) punctuated with a grid of reaction zones.

FIG. 13 is a cross-sectional view of a USS membrane supported on a backing layer.

FIG. 14 is a cross-sectional view of a USS which is made of a solid support material, and without a dosage membrane.

DETAILED DESCRIPTION OF THE INVENTION Unless otherwise indicated, all scientific and technical terms used herein have the same meanings as those commonly accepted by those skilled in the art. All publications cited herein are incorporated herein by reference.

The articles 'a' and 'an' are used here to designate one or more than one, that is at least one of the grammatical object of the article.

Throughout this application, the term "about" is used to indicate that a value includes the error standard deviation for the device or method that is used to determine the value. The indication of numeric ranges using the endpoints includes all integers and, where applicable, fractions within such a range (for example from 1 to 5 may include 1, 2, 3, 4 when it relates, for example, to a number of elements). The end-point indication also includes the end-point values themselves (eg from 1.0 to 5.0 includes both 1.0 and 5.0).

Throughout the present description the reference to "embodiment" or "embodiment" means that a particular feature, structure or feature described in connection with the embodiment is included in at least one embodiment of the present invention. present invention. The occurrences of phrases "in one embodiment" or "in one embodiment" in various places in the present description therefore do not all relate necessarily to the same embodiment but may relate thereto. In addition, particular features, structures, or features may be combined in any convenient manner, as the present disclosure would make apparent to those skilled in the art, in one or more embodiments. Further, while some embodiments described herein include certain features but not others included in other embodiments, combinations of features of different embodiments are understood to fall within the scope of the invention, and are different embodiments, as will be understood by those skilled in the art. For example, in the appended claims, any of the claimed embodiments may be used in any combination.

As used herein, the terms "comprising", "includes" and "consisting of" are synonymous with "including", "includes" or "containing", "contains", and are inclusive or open ended. do not exclude additional members, elements or process steps, not mentioned. Note that the terms "comprising", "includes" and "consisting of" as used herein encompass the terms "consisting of", "consist" and "consisting of".

In the following detailed description of the invention, reference is made to the accompanying drawings which form a part thereof, and which are presented by way of illustration only of particular embodiments in which the invention may be to be put into practice. It should be understood that other embodiments can be used and that structural and logical modifications can be made without departing from the scope of the present invention.

The present invention provides a solid support unit (USS) for assay. The USS has an upper face and, opposite the upper face, a lower face. The upper face and the lower face are essentially flat. The upper face and the lower face are essentially parallel. The upper face of the USS provides a surface on which a ligand can be immobilized. The upper face may be formed, for example, from a solid support material or may be a dosage membrane which is attached to a backing layer.

In some embodiments, the USS may consist essentially of a solid support material to which a ligand may be immobilized directly thereon. In some embodiments, the solid support material may be any suitable rigid material to which a ligand may be immobilized. In some embodiments, the solid support material may be a non-chemically activated material to which a ligand may be immobilized. In some embodiments, the solid support material may consist essentially of a chemically activated material upon which a ligand may be immobilized. It may not contain a dosing membrane.

In some embodiments, the solid support material may be a polymeric material or glass. In some embodiments, the solid support material may be essentially a plastic material, such as, for example, polystyrene, polypropylene or polycarbonate. The solid support material may have a substantially uniform degree of opacity and may be of any uniform color. It is preferably opaque. This is particularly advantageous when the underside of the USS is provided with an identifier, such as a barcode or a QR code, which can then be read while being held in the receiving regions of the holding medium.

In some embodiments, the USS may comprise a membrane supported on a backing layer. In some embodiments, the USS may include a backing layer and a metering membrane, the metering membrane being placed on the backing layer. The backing layer is on the underside of the USS, and the dosing membrane is on the top side of the USS.

The terms "membrane" and "dosing membrane" may be used interchangeably herein. The ligand can be immobilized on the "membrane" or "dosing membrane".

The terms "reinforcement layer" or "solid reinforcement" may be used interchangeably herein.

In some embodiments, the backing layer may consist essentially of a polymeric material or glass. In some embodiments, the backing layer may be essentially made of plastic material, preferably polyester. In some embodiments, the assay membrane may be essentially cellulose, preferably nitrocellulose. In some embodiments, the dosing membrane may be essentially made of nylon or vinyl, preferably polyvinyl.

Advantageously, it is not necessary that the USS be transparent, so that it is possible to use ligands that normally would not attach to a traditional transparent microplate.

The underside of the USS may be provided with an identifier. The identifier is preferably readable by a machine, even better optically readable. The identifier may be a visible marking, such as a barcode or a QR code (quick response). The upper face of the USS may be provided with an orientation marker. An orientation marker allows the identification of the orientation of the USS, for example an identification of the upper edge. The orientation marker is preferably machine readable, particularly preferably optically readable. The orientation marker may be a visual marking, such as a rotationally non-symmetrical pattern (for example an "L" marking). In addition to or instead of this, the orientation marker may be positioned on the upper face of the USS, where it has no rotational symmetry (for example on a corner, on an edge).

In some embodiments, the USS may comprise at least one ligand that is specific for at least one analyte to be detected. In some embodiments, the USS may comprise at least one ligand that is immobilized on the USS, for example on the upper side of the solid support material. In some embodiments, the USS may comprise at least one ligand that is immobilized on the assay membrane.

In this context, the terms "fixed", "applied", "immobilized", or "linked" may be used interchangeably here. When the USS is described as comprising a ligand, a positive control or a negative control, it is understood that the ligand, positive control or negative control is "fixed", "applied", "immobilized" or "bound" to or on a surface of the USS, preferably at or on the upper face.

In some embodiments, the at least one ligand may be a protein, a modified protein, a peptide, a nucleic acid (such as a deoxyribonucleic acid or a ribonucleic acid), a hapten, an antigen, an antibody, or a metabolite of any of these substances, as well as any other compound (either natural or synthetic) which may be of diagnostic interest and which has a specific ligand-binding partner (i.e., the receptor fragment of the receiver). For example, the ligand may be selected from the group consisting of an antibody, a protein, an antigen, a hapten, and a nucleic acid.

In some embodiments, the ligand may be selected from: an antibody comprising a monoclonal antibody raised against one or more antigens of the sample, such as human or animal proteins, including antibodies, or a hapten or other molecules organic or inorganic; an antigen capable of specifically interacting with one or more antibodies in the sample; a protein, such as protein A, protein G or protein L, capable of binding to the Fc fragment of certain immunoglobulins, a natural or synthetic amino acid sequence capable of entering into specific interactions with certain organic molecules for example a synthetic peptide, a hapten or other organic or inorganic molecules; or a natural or synthetic nucleotide sequence, for example a single-stranded or double-stranded DNA or RNA, capable of entering into specific interactions with a complementary nucleotide sequence or with certain organic molecules, for example a synthetic peptide, a hapten or other organic or inorganic molecules; or a combination of any two, any three, any four, or any five of the aforesaid ligands.

In some embodiments, the ligand may be selected from the group consisting of an antigen, an antibody, a protein, a hapten, and a nucleic acid. In some embodiments, the ligand may be an antigen. In some preferred embodiments, the ligand may be an autoantigen.

As used herein, the term "ligand" means an agent capable of detecting an analyte, for example in a sample, such as a biological sample.

As used herein, the term "analyte" refers to an agent capable of binding to a ligand, e.g. fixed or immobilized on a USS, such as on the upper side of the solid support material, particularly on a dosage membrane of this one.

As used herein, the terms "analyte" and "ligand" refer to members of any specific binding pair whose ligand is immobilized on the USS (e.g., on an upper surface of the solid support material, in particular on a surface of an assay membrane), and the analyte is present in a sample (such as a biological sample) to be contacted with the USS. The ligand therefore refers to any capture or trapping agent immobilized on the solid support material or the (surface of) assay membrane and the analyte refers to any specific binding partner thereon. The ligand and the analyte may be the same type of molecule depending on the design of the assay. Immobilization may be by an interaction selected from different types of interactions, such as ionic bond, covalent bond, or hydrophobic interactions. The number of ligands immobilized on the USS depends on the test and can range from 1 to several hundreds depending on the size of the USS and the area occupied by each ligand.

In some embodiments, the USS may comprise at least one ligand. For example, the USS unit may comprise one or more ligands, such as at least two, at least three, at least four, at least five, at least six, at least seven, or at least eight ligands. The USS, particularly the upper face, may comprise at least one assay zone or assay zone. Preferably, said USS, in particular the upper face, comprises at least 3 dosing zones, more preferably at least 6 dosing zones, more preferably at least 9 dosing zones. Each assay zone may be designed to specifically detect an analyte in the sample.

The terms "assay area" or "assay area" as used herein refer to a distinct area on the USS, especially on its upper face. An assay zone is preferably provided with ligand, i.e. the ligand is immobilized on the solid support unit in a zone limited to the assay zone. It is preferably coated with the ligand. An analysis zone may be provided with a ligand or with 2 or more different ligands. The analysis area may be a dot or a line, or may be any shape allowing detection such as visual detection.

In some embodiments, the analyte may be any molecule for which the detection and measurement of the concentration is possible and for which there is a specific complementary molecule, a ligand. For example, the ligand and the analyte may be stereo-complementary, allowing fixation of the analyte to the USS by binding with a ligand that is readily accessible on the surface of the USS. Without limitation, analytes that can be analyzed and / or detected include narcotics or their metabolites, analytes indicating the presence of an infectious agent or product of an infectious agent, an allergen, a pollutant, a toxin, a contaminant, an analyte of medical or diagnostic interest, an antibody against any one of the foregoing, and any combination thereof.

The terms "detect" or "detect" generally mean determining the presence or absence of an analyte in a sample, such as a biological sample. The term "analyte detection" may include the assay of an analyte.

The terms "measure" or "measure" generally mean the determination of the rate, amount or concentration of an analyte in a sample, such as a biological sample. The term "semi-quantitative measurement" generally refers to the determination of an approximation of the rate, amount or concentration of an analyte in a sample, such as a biological sample.

In some embodiments, the analyte may be selected from the group consisting of an antibody, an antigen, a protein, a hapten, and a nucleic acid. In some embodiments, the analyte may be an antibody. In certain preferred embodiments, the analyte may be an autoantibody.

In some embodiments, the USS may be used to detect an analyte in a biological sample. The biological sample may be a body fluid such as serum, plasma, blood, cerebrospinal fluid, nasopharyngeal secretions, urine, sperm, or saliva; a food; the water ; supernatants or culture media; or feces. In some preferred embodiments, the biological sample may be selected from the group consisting of serum, plasma, and blood.

In some embodiments, the USS may comprise at least one ligand, wherein the ligand may be present in two or more different assay zones at the same concentration on the USS. For example, the same ligand may be present in duplicate (i.e. twice), triplicate (i.e., three times), four times, five times, or six times, at the same time. concentration on the solid support unit. This advantageously makes it possible to calculate a mean value and / or a standard deviation of the values which is recommended or even required for the execution of certain assays such as diagnostic assays.

In some embodiments, the USS may comprise at least one positive control. For example, the solid support unit may comprise one or more positive controls, such as at least two, at least three, at least four, at least five, at least six, at least seven, or at least eight positive controls present in the control. different areas of analysis. The positive controls may have the same composition at the same concentration, the same composition at different concentrations, or a different composition at the same concentration, or a different composition at different concentrations. In some embodiments, the USS may comprise at least one positive control, wherein the positive control may be present in two or more different assay zones at the same concentration on the solid support unit. For example, the positive control may be present in duplicate (i.e., twice), triplicate (i.e. three times), four times, five times, or six times at the same concentration. on the USS. This advantageously makes it possible to calculate a mean value and / or a standard deviation of the values which is recommended or even required for the execution of certain assays, such as diagnostic assays.

As used herein, the term "positive control" refers to an area of analysis in which a phenomenon is expected (100% effect or 100 units). That is, a positive control ensures that there is an effect when there should be an effect, for example by using a ligand that is already known to produce an effect with the sample under analysis. A positive control may be used to evaluate the validity of the test, as to control the presence of the sample.

The terms "positive control" or "sample control" may be used interchangeably.

In some embodiments, the USS may include at least one negative control. For example, the USS may include one or more negative controls, such as at least two, at least three, at least four, at least five, at least six, at least seven, or at least eight negative controls present in different zones. 'analysis. The negative controls may have the same composition at the same concentration, the same composition at different concentrations, or a different composition at the same concentration, or a different composition at different concentrations. In some embodiments, the USS may comprise at least one negative control, the negative control may be present in two or more different assay zones at the same concentration on the USS. For example, the negative control may be present in duplicate (i.e. twice), in triplicate (i.e., three times), four times, five times, or six times at the same concentration. on the USS. This advantageously makes it possible to calculate a mean value and / or a standard deviation of the values which is recommended or even required for the execution of certain assays, such as diagnostic assays.

As used herein, the term "negative control" refers to an area of analysis in which no phenomenon is expected (zero effect or 0% effect). That is, a negative control ensures that there is no effect when there should be no effect, for example by using a ligand that is already known to cause no effect. A negative control can be used to evaluate the threshold or normalization value.

The terms "negative control" or "threshold control" may be used interchangeably.

In some embodiments, the USS may comprise at least one ligand, at least one positive control, and at least one negative control. Such a solid support unit advantageously allows a semi-quantitative assay of an analyte binding to at least one ligand. Said at least one positive control and said at least one negative control allow semi-quantitative determination of an analyte binding to said at least one ligand. It is therefore understood that said at least one positive control and said at least one negative control may be standards. The negative control may be a zero unit standard. The positive control may be a standard of 100 units.

In some embodiments, the USS comprises at least one ligand, at least one positive control, and at least one negative control, said at least one ligand, said at least one positive control, and said at least one negative control being present each in two or more different analysis zones at the same concentration on the USS. For example, said at least one ligand, said at least one positive control, and said at least one negative control may be present in duplicate (i.e. twice), in triplicate (i.e. three times), four times, five times, or six times at the same concentration on the USS. This advantageously makes it possible to calculate an average value and / or a standard deviation of the values which is recommended or even required for the execution of certain assays, such as assays, for diagnosis.

In certain preferred embodiments, the USS comprises a ligand, a positive control, and a negative control. In certain preferred embodiments, the USS comprises a ligand, a positive control, and a negative control, the ligand, the positive control, and the negative control being present in two or more different assay zones at the same concentration. on the USS. For example, the ligand, the positive control and the negative control are present in duplicate (that is, twice), in triplicate (ie three times), four times, five times, or six times at the same concentration on the USS. In certain preferred embodiments, the solid support unit comprises a ligand, a positive control and a negative control, the ligand, the positive control and the negative control being present in triplicate at the same concentration on the USS (as on the solid support material or the dosing membrane of a USS). This advantageously makes it possible to calculate a mean value and / or a standard deviation of the values which is recommended or even required for the execution of certain assays, such as diagnostic assays.

In some embodiments, the USS may comprise at least two standards located in different assay zones. Such USS advantageously allows a semi-quantitative determination of the ligand. In some embodiments, the USS may comprise at least three standards arranged in different assay zones. Such an USS advantageously allows a quantitative determination of the ligand. In some embodiments, the USS may include at least three standards for a calibration curve, the read value (eg, color) of the standards increasing with increasing concentration. For example, the USS as defined herein may comprise three or more standards located in different analysis areas. For example, the USS as defined herein may include at least four, at least five, at least six, at least seven, at least eight, at least nine, at least ten, at least eleven, or at least twelve stallions disposed in different areas of analysis for a calibration curve, the value read (eg color) of the standards increasing with increasing concentration.

In some embodiments, the USS may include a cookie for validating the correct handling. In some embodiments, the USS may comprise at least three controls arranged in different analysis areas, such as at least one control for validation of the correct manipulation, at least one control for the validation of operation and / or the type of tracer used, and at least one witness for the validation of the signal development system.

Ligands and / or standards and / or controls may be applied to different analysis areas (such as dots) on the USS. In some embodiments, the USS may include scan areas in a matrix network. In some embodiments, the USS may comprise two times two (ie 2x2), three times three (ie 3x3), four times four (i.e. 4 x 4), or five times five (ie 5x5) scan areas in a matrix network. For example, the USS can comprise two times two (ie 2x2) points, three times three (ie 3x3) points, four times four (ie 4x4). ) points, or five times five (that is, 5 x 5) points. For example, the USS as defined herein may comprise a ligand, a positive control and a negative control, the ligand, the positive control and the negative control being present in triplicate at the same concentration on the USS, and the USS which can comprise three times three (that is to say 3x3) analysis zones in a matrix network. Analysis areas (such as dots) should be machine readable, preferably optically readable.

The standards, the positive control and the negative control may be chosen from: an antibody comprising a monoclonal antibody raised against one or more antigens present in the sample or in any reagent required for carrying out the assay, for example human proteins or animal, including antibodies, or a hapten or other organic or inorganic molecules; an antigen, specific for one or more antibodies present in the sample or in any reagent required to perform the assay; a protein, such as protein A, protein G or protein L, capable of binding to the Fc fragment of certain immunoglobulins, a natural or synthetic amino acid sequence capable of entering into specific interactions with certain organic molecules for example a synthetic peptide, a hapten or other organic or inorganic molecules; a natural or synthetic nucleotide sequence, such as a single-stranded or double-stranded DNA or RNA, capable of entering into specific interactions with a complementary nucleotide sequence; an enzyme or any organic or inorganic molecule, whether or not linked to another organic or inorganic molecule, capable of generating a detectable signal, either in the presence of a signal generating source, or in an inherently inherent manner, for example a alkaline phosphatase or peroxidase, fluorescent dyes, colloidal metal particles or luminescent molecules; or a combination of any two, any three, any four, any five or any six thereof.

In some embodiments, the assay may be an immunoassay. In some embodiments of the kits, USS strips, uses, or methods, as taught herein, each solid support unit may comprise an immunoassay.

As used herein, the term "immunoassay" means an assay comprising at least one antigen specific for at least one antibody to be detected, or comprising at least one antibody specific for at least one antigen to be detected.

In some embodiments, the immunoassay may comprise at least one antigen specific for at least one antibody to be detected. In certain preferred embodiments, the immunoassay may comprise at least one autoantigen specific for at least one autoantibody to be detected.

As mentioned above, each USS may comprise a backing layer and a dosing membrane placed on the backing layer. In some embodiments, the assay membrane may be a membrane for immunoassay. Thus, in some embodiments, each USS may comprise a membrane for immunoassay.

As used herein, the term "membrane for immunoassay" refers to a dosage membrane comprising at least one antigen specific for at least one antibody to be detected, or comprising at least one antibody specific for at least one antigen to be detected.

In certain preferred embodiments, the immunoassay membrane may comprise at least one antigen specific for at least one antibody to be detected. In certain preferred embodiments, the immunoassay membrane may comprise at least one autoantigen specific for at least one autoantibody to be detected.

As used herein, the term "autoantigen" means an antigen (such as a protein or protein complex or a DNA or RNA) that is recognized by the immune system of patients suffering from an autoimmune disease. the antigen is not, under non-pathological conditions, the target of the immune system. For example, due to genetic and / or environmental factors, normal immunological tolerance to an autoantigen has been lost in patients with autoimmune disease.

In some embodiments, the antigen may be selected from the group consisting of or consisting of double-stranded DNA (dsDNA), Sm (D and BB 'proteins of U1-U6 snRNP complexes), RNP (68kD and / or A proteins). and / or C of the complex Ul-snRNP), SSA / Ro (Sjögren syndrome 60 kD antigen A), SSB / La (50 kD Sjögren antigen B), OJ-1 (histidyl-tRNA synthetase), and Scl- 70 (DNA topoisomerase I).

The USS are preferably prepared from a strip or sheet of material (eg, solid support material or a dosing membrane and a backing layer), pre-scored in individual USS. The strip or sheet of material is preferably flat; it is preferably flat. The strip or sheet of material is preferably free of protruding ridges. A set of scan areas is deposited on each USS of the strip or sheet of material, as in a grid layout (eg, 5x5 scan areas). Preferably, the disposition of the ligands deposited on each USS is the same over the entire band. The arrangement of the analysis zones can be carried out using an X-Y-Z micro-distributor. An X-Y-Z micro-dispenser includes a dispensing nozzle for dispensing a composition on the USS, coupled to a movable member in the X-Y-Z directions. The position of the dispensing nozzle can be precisely controlled in the X-Y direction, allowing the precise deposition of a microdroplet on the top face of a USS. The X-Y direction corresponds to the plane of the strip or sheet of material. Movement in the Z direction is sufficient to move the nozzle away from the upper face of the strip or sheet. The depot may be repeatedly performed for a plurality of USS in the web or sheet. Advantageously, the arrangement of the USS in a strip or sheet facilitates rapid and efficient preparation because it requires a minimal displacement of the nozzle in the Z axis. The adjacent USS in a sheet are accessible by lateral displacement of the nozzle. The nozzle is raised above the tape a sufficient distance to prevent smearing. The absence of a physical height barrier between adjacent USS reduces the Z-axis nozzle path, which can reduce the preparation time by at least three times. The individual USSs can be automatically transferred to the container unit using, for example, a pick and place robot. For the first time, a high-throughput preparation of custom well microplates is economically feasible.

Accordingly, one embodiment provides a method for preparing a container unit-based assembly as defined herein, comprising the steps of: providing a container unit, providing a plurality of solid support units arranged in a sheet or flat strip, depositing one or more ligands on the upper face of a number of different solid support units of the strip or sheet, using an XYZ robotic micro-dispenser, inserting one of the units solid support thus formed in the container unit, thereby obtaining a container unit-based assembly.

The present invention further provides a container unit. The terms "container unit" and "microplate wells" are used interchangeably herein. The container unit of the invention is designed to hold a fluid, particularly a liquid. The container unit of the invention is designed for removable insertion into a holding medium of the invention. It is further designed to contain a USS, preferably a single USS, of the invention. The container unit has an upper end and a lower end, and an opening at the upper end for receiving the fluid. The container unit has a central axis (A-A ') extending from the upper end to the lower end. The container unit is preferably adapted for robotic manipulation, for example, for automated mounting of microplates.

The size and shape of the opening are designed to allow the optical reading of the upper face (membrane for example) of a USS, to measure the color and / or the intensity of the analysis zones. The container unit includes a basal wall at the lower end, and a side wall extending upwardly therefrom, defining a cavity, which cavity is adapted to receive a USS and a fluid. The underside of the USS, when placed in the cavity, is preferably in contact with the basal wall. The size and shape of the basal wall may be designed to allow optical reading of the underside of a USS, for example, for reading a QR code for identification. The basal wall preferably has a square or oblong shape, optionally with rounded corners.

The side wall may be at least partially bordered at the upper end. By lining means that the upper edge of the side wall has a lip, a flange, is flared or extended radially outwardly. The lined side wall may engage the body at the front face of the holder; it can serve as a stop to prevent the passage of the container unit through the holder support compartment. The container unit preferably has a cavity defined by the basal wall and the side wall. The container unit preferably has a substantially cuboid shape. The cuboid can be a square or rectangular cuboid. One or more of the edges, preferably all edges, may be rounded. One or more of the corners, preferably all corners, may be rounded.

The container unit described herein, provided with the USS described herein, is known as a "container unit-based set". The USS may be attached to the container unit, preferably to the basal wall of the container unit, by adhesive or frictional contact. Or, in addition, it can be held in place by a USS holding member. The USS holding member may include one or more projections in the side wall of the container unit, more specifically on the surface facing the cavity below which the USS is pressed. The projections prevent or reduce the lifting of the USS from the basal wall of the container unit. In addition, protrusions can get in friction with the USS to keep it in place.

Alternatively, the holding member of the USS may include one or more grooves in the side wall of the container unit, particularly on the cavity facing surface, in which the USS is pressed. The grooves prevent or reduce the lifting of the USS from the basal wall of the container unit. In addition, protrusions can get in friction with the USS to keep it in place. The container unit may be provided with an orientation marker. An orientation marker enables identification of the orientation about the central axis (A-A ') of the container unit. The orientation marker is preferably machine readable, particularly preferably optically readable. The orientation marker may be a visual marking, such as a pattern without rotation symmetry (for example an "L" marking). In addition, or instead, the orientation marker may be placed on the container unit at a location where it does not exhibit rotational symmetry (for example on a corner, on an edge). The orientation marker may be a raised marking, or a notch or projection. Preferably, the orientation marker is placed on the upper end of the container unit, preferably on the upper edge, which may be at least partially or completely bordered. The container unit may be provided with an orientation element. An orientation member allows insertion into the holder in an orientation about the central axis (A-A ') of the container unit. In other words, it prevents insertion into the holding support in any orientation about the central axis (A-A ') except one. It preferably engages adequately with a complementary orienting element in the holding support, in particular in a compartment of the holding support.

In a preferred embodiment, the orientation member is a projection on the side wall that engages with a complementary slot in the holding support compartment only when the container unit is inserted in the correct orientation. . In a more particularly preferred embodiment, the orienting element is a longitudinal slot or a longitudinal notch (for example a flattened corner) on the side wall, which engages with a complementary projection in the compartment of the support of only when the container unit is inserted in the correct orientation.

The walls of the container may be made of any suitable material having the requisite properties of stability in analytical liquids, mechanical strength, and rigidity. The walls are preferably made of a polymeric material, such as for example a plastic polystyrene, polypropylene or polycarbonate. The walls may have a substantially uniform degree of opacity. They can have any uniform color or preferably can be translucent or transparent. This is particularly advantageous when the back of a USS is provided with an identification marking (for example a bar code or a QR code) readable by a camera, which can then be scanned while it is maintained in the support support.

The present invention further provides a holding support for insertion receiving of two or more units of containers or sets of container units. The holding bracket has a substantially planar body, provided with a plurality of compartments, each compartment being adapted to receive and hold a container unit. In particular, a compartment can be designed to receive and maintain a single container unit.

The body of the holding support preferably has a rectangular configuration (with adjacent sides equal or not). The holding bracket has a front face through which the container units held in the compartments can be examined or read, a back face opposite to the front face. A lateral edge connects the front face of the body to the back face. The holding support is preferably adapted to robotic manipulation, for example for automated processing of samples.

The compartments are arranged on the flat body. They are preferably inside the body. Each compartment is spatially separated from any neighboring compartment. There may be 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12, 24, 36, 48, 60, 72, 84 or 96 or more compartments in a holder. Preferably, the compartments are arranged in a grid or grid pattern, for example 10 × 10, 8 × 10, 8 × 12, or 16 × 24. Preferably, all compartments are the same size. A compartment is adapted to receive at least a portion of the container unit, preferably at least the lower half of the container unit or container unit base assembly. A compartment is preferably dimensioned to receive by being fitted therein at least a portion of the container unit or the container unit assembly, preferably at least the lower half of the container unit or of the container unit-based assembly.

A compartment may be provided with a front opening which opens on the front face of the body. The size and shape of the front opening are adapted to receive at least a portion of the container unit or the container unit base assembly. Preferably, the size and shape of the front opening is complementary to the size and shape of the bottom end profile of the container unit or container unit base assembly. Preferably, the front opening has a rectangular shape with adjacent sides equal or unequal. It may have rounded corners.

The compartment may have a back opening, opposite to the front opening. The back opening communicates the empty space of the compartment with the back side of the body. The size and shape of the back port are designed to allow optical reading of the underside of the container unit or the container unit base assembly and therefore the USS, for example , to identify a printed identification code. Preferably, the back orifice has a rectangular shape with equal or unequal sides. It may have rounded corners. The container unit or the container unit base assembly in the compartment may be supported by a stop member extending into the empty space, preferably into the back port. Such a stop member acts as a distance limiter to prevent the passage of a container unit or container-based unit assembly without a rim through the compartment. The stop element does not interfere with the optical reading of the underside of the container unit and therefore the USS. In another possible embodiment, the back port is adapted to receive at least a portion of the basal end of the container unit or the container unit base assembly.

The compartment may further comprise one or more inner sidewalls that port the back port to the front port. An inner sidewall may have an opening that connects opposite faces of the wall to each other. The compartment has an internal empty space.

In a particular embodiment, the holding support is provided with at least one empty compartment; preferably all the compartments of the holding support are empty, that is to say that it is free of container units.

The compartment is adapted to receive a container unit or a container unit base assembly. The container unit or the container unit base assembly enters the compartment through the front opening. The container unit or the container unit base assembly may be pressed into position, by applying a force to the upper end of the container unit or the base unit. container unit. He or she is preferably pressed against the back wall of the compartment. The container unit or the container unit base assembly can be held in place by friction produced by the inner walls of the compartment. Or, or in addition, it can be held in place by a holding member of the container unit. The compartment may also include a container unit holding member, adapted to hold a container unit or a container unit base assembly after insertion into the compartment. The container unit holding member may comprise one or more projections in the side wall of the compartment, which engages with a complementary depression in the side wall of the container unit, more precisely in the surface. external of it. Or again, the holding member may consist of one or more depressions in the side wall of the compartment, which engages with a complementary projection in the side wall of the container unit, more precisely in the surface. external of it. The protruding projections and / or depressions increase the force required to lift a container unit out of the compartment. In addition, the projections in the side wall of the compartment may frictionally engage with the container unit to hold it in place.

The body of the holding support may be any suitable material having the required properties of stability in analytical liquids, mechanical strength, and rigidity. The body is preferably made of a polymeric material, for example a polystyrene, polypropylene or polycarbonate plastic. The body can have a practically uniform degree of opacity. It can have any uniform color or preferably can be translucent or transparent. This is particularly advantageous when the back of a USS is provided with an identification marking (for example a barcode or a QR code) readable by a camera, which can then be scanned while it is housed in the compartment.

The holding support may be provided with an orientation marker. An orientation marker enables identification of the orientation around the central axis (A-A ') of the holding support. The orientation marker is preferably machine readable, particularly preferably optically readable. The orientation marker may be a visual marking, such as a rotationally non-symmetrical pattern (for example an "L" marking). In addition to or instead of this, the orientation marker may be positioned on the body of the holding support at a place where it has no rotational symmetry (for example on a corner, on an edge).

The orientation marker may be a raised marking, or a notch or projection. In a particularly preferred manner, the orientation marker is a notch in a corner of the body of the holding support.

As mentioned above, the compartment may be provided with an orientation element. An orientation member allows insertion of the container unit or the container unit-based unit into the compartment in an orientation about the central axis (A-A ') of the unit of the container unit. container or container unit-based assembly. In other words, it prevents insertion into the compartment in any orientation about the central axis (A-A ') except one. It engages preferably by fitting with a complementary orienting element in the container unit or the container unit base assembly.

The body of the holding support may further comprise a gripping portion, placed toward one of the edges of the holding support, to enable the gripping / grasping and / or moving of said solid support. Said gripping part can be entered manually or by means of an automated device, such as a PLC. The invention also provides a kit comprising a series of sets based on container units. A series of container unit-based assemblies may include, for example, 2, 3, 4, 5, 6, 7, 8, 9 or 10 sets based on units of containers or more. Preferably, a USS is contained in the cavity of each of the container units of the assembly. Preferably, the USS is the same in each of the sets of container units of the same series, i.e., is intended for the same dosage or dosages. The series of sets based on container units can be packaged. The series of container unit-based sets can be packaged in a dispenser, designed to dispense one container unit at a time. The series of container unit-based sets may be provided in the form of a strip; in a band a number (eg 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 or more) of container unit-based sets is tandemly arranged in one line , and the connection of a set of container units is achieved by means of a seal capable of being broken. The seal that may be broken may be, for example, a weakened connection by prestressing, thinning or perforation. The invention also provides a kit comprising a series of sets based on container units and a holding support according to the invention. The invention also provides a kit comprising two or more sets of container unit-based assemblies and a holding bracket according to the invention. Preferably, a USS is contained without the cavity of each of the sets of container units of a series. Preferably, the USS is the same in each of the sets of container units of a series, i.e. is for the same dosage or dosages. Preferably, the USS is the same in each of the sets based on container units of the same series (for example on one band), and the USS are different in different series (for example the bands are intended for assays different). The difference may lie in the concentration of the ligand, the composition of the ligand and / or the position of the ligand. In particular, at least one of the dosing zones provided on the USS is different. The invention also provides a kit comprising a plurality of container unit-based assemblies and a holding bracket according to the invention. The container units can be mounted in the holder. Preferably, a USS is contained in the cavity of each of the unit-based sets of containers. Preferably, the USS is different in each of the unit-based sets of containers, i.e., is intended for a different dosage. The difference may lie in the concentration of the ligand, the composition of the ligand and / or the position of the ligand. In particular, at least one of the dosing zones provided on the USS is different.

The present invention also provides a method for preparing a custom microplate for assay, comprising the steps of: providing a holding support as described herein, having a plurality of compartments, inserting a unit-based assembly of container in two or more compartments, optionally one USS in each container unit-based set, - to obtain a custom microplate. The method can be performed manually or in an automated manner.

In particular, the present invention provides a method for the preparation of a custom microplate for an assay, comprising the steps of: (a) providing at least two different USS, as defined herein, (b) providing at least two containers and holding support as defined herein, (c) depositing the USS into the container cavity, one USS per container, and (d) inserting the containers into the holder, one container per compartment, to obtain a custom microplate .

The method can be performed manually or in an automated manner.

In some embodiments, the method may be for the detection of at least two analytes in a biological sample. In one embodiment, the method is an automated method.

In certain preferred embodiments of the method for the detection of at least two analytes in a biological sample, the method comprises the steps of: providing at least two different USS as defined herein, the USS each comprising at least one ligand which is specific for at least one analyte to be detected, to provide at least two containers as defined herein, to insert the USS into the cavities of the containers, one USS per cavity, to insert the containers into the holding support, one container per compartment, to introduce a biological sample in the container cavity, thereby bringing the biological sample into contact with said ligands in the fluid, resulting in the binding of at least one analyte in said biological sample to each ligand, labeling each bound analyte with each ligand, by means of a marker, and - detecting said marker, thereby determining a signal strength of said marker .

The detection can be performed by means of a microplate reader. The method of the present invention can be used to detect specific analytes in biological samples, so that the user or consumer can determine the association of analytes to be detected. For example, the method allows the user or consumer to detect an analyte combination that is personalized or tailored to a particular patient.

Immunologic assays are preferably contemplated. These immunologic assays can be used for semi-guantitative or guantative analyte assays, with or without the use of a machine for automated detection. In one embodiment, the signal strength of the water level is directly proportional to the concentration of the analyte to be detected in the biological sample.

Preferably, the method according to the invention comprises an immunoblot assay. Suitable, non-limiting examples of immunoblot technology include kits for the detection of autoantibodies in patient serum, for example, BlueDot technology (D-Tek, Mons, Belgium).

In one embodiment, the assay strip as taught herein may be used in a method for detecting autoantibodies in a biologic sample (eg, serum) of a patient, said method comprising the steps of following: provision of at least two different USS as defined herein, the USS each comprising at least one autoantigen which is specific for at least one autoantibody to be detected, provision of at least two containers as defined herein insertion of the USS into the cavities of the containers, one USS per cavity, insertion of the receptacles into the holding support, one receptacle per compartment, introduction of the biological sample into the cavity of said receptacles, specific binding of the autoantibodies present in the receptacle; sample of the patient to the auto-antigens attached to each USS, which binds the autoantibodies to each USS, washing the USS and auto-antibodies attached thereto, to eliminate the sample, adding a conjugate, comprising a secondary antibody directed against the autoantibodies and said secondary antibody being linked to an enzyme, for obtaining autoantibody complexes, washing the USS and complexes of autoantibodies attached thereto to remove unbound secondary antibody. incubation of USS and autoantibody complexes attached thereto, with a. colorimetric substrate, binding of the colorimetric substrate to the enzyme linked to the secondary antibodies of the autoantibody complexes, leading to the development of a specific color. The appearance of a specific color on the USS indicates the presence of autoantibodies in the patient's serum and therefore the presence of an autoimmune disease.

The USS can be interpreted, for example visually or by means of a microplate reader that operates using reflected light, by comparing the intensity obtained for the analyte (for example, autoantibodies) with the intensity of the light. a negative control and / or a positive control. If the intensity is greater than that of the negative control, the signal is considered positive. If the intensity is equal to or less than that of the negative control, the signal is considered negative. The present invention enables qualitative detection, but additionally provides a semi-quantitative measurement of the concentration of analytes present in the sample. Semi-quantitative measurements are possible because each solid support may contain a positive control. Quantitative measurements are possible because each USS can contain standards.

The present invention allows the preparation of a personalized microplate comprising a combination of detection ligands adapted to the needs of the physician. It provides economical and high-speed automated analysis. The grid arrangement of compartments in the holding bracket allows automated robotic insertion of container units, since their X-Y positions can be reprogrammed and the movements of the robotic arm can be adjusted accordingly. The orientation marker may restrict insertion into the holder in a single orientation, which avoids reading errors of the processed USS when the USS contains a plurality of reaction points. Or, the orientation marker allows the optical determination of the orientation, for example, after treatment.

An important aspect is that the use of USS makes it economically feasible, as previously mentioned, to prepare a custom microplate assay. In addition, the custom microplate assay allows for multiparametric analysis of single-patient specimens, in addition to multiparameter analysis of multiple patient samples on a single microplate, which lowers the cost of customized analysis at high levels. debit.

Non-limiting examples of a USS, a compartment and a holding support are illustrated by way of example in FIGs. 1 to 14.

If we refer to FIG. 1, this represents a container unit 100 having an upper end 102, a lower end 104, and a central axis (A-A ') extending between the upper 102 and lower 104 ends. The side wall 110 of the container unit 100 is indicated, together with an opening 112 at the upper end 102, and the cavity 116 of the container.

FIG. IA shows a front view of the container unit 100 of FIG. 1; the side wall 110 and the basal wall 114 are indicated.

FIG. IB shows a plan view of the container unit 100 of FIG. 1; the side wall 110 and the cavity 116 are indicated.

FIG. IC shows a sectional view of the container unit 100 of FIG. 1 passing through a plane coming into contact with the central axis A-A '; the side wall 110, the cavity 116, the opening 112, the basal wall 114 are indicated.

FIG. 2 shows a sectional view of a container unit-based assembly 150, including a container unit 100 of FIG. 1, which container unit 100 is provided with a USS 300 in contact with the basal wall 114.

FIG. 3 shows a plan view of a variant of the container unit 100 of FIG. 1, in which the upper end edge of the side wall 110 is provided with an orientation marker 118, which is a visible marking.

FIG. 4 shows a schematic representation of the container unit 100 of FIG. 1, further provided with a flange 120.

FIG. 5 shows a schematic representation of the container unit 100 of FIG. 1, further provided with a flange 120 and with an orientation member 122 disposed on the side wall 110.

FIG. 5A shows a front view of the container unit 100 of FIG. 5; the side wall 110, the flange 120, and the basal wall 114 are indicated.

FIG. 5B shows a sectional view of the container unit 100 of FIG. 5 passing through the plane 124, the side wall 110, the cavity 116 and the orientation member 122 are indicated.

FIG. 5C shows a sectional view of the container unit 100 of FIG. 5 passing through a plane coming into contact with the central axis (A-A '); the side wall 110, the cavity 116, the orifice 112, the flange 120, the basal wall 114 are indicated.

If we refer to FIG. 6, it shows a plan view (front face) of a holding bracket 200 of the invention, having a front face 202, a back face 204 (not shown). The body 222 of the holding support 200 is provided with a plurality of compartments 210, 210 'arranged in a network or rectangular grid configuration (10 × 7). The holding bracket is also provided with two grip portions 206, 208 disposed on the opposite edges.

If we refer to FIG. 7, it shows a sectional view of a plane passing the line B-B 'of the holding support 200 of FIG. 6; FIG. 7A is an enlargement of a portion of FIG. 7. The front 202 and rear 204 faces of the holding bracket are indicated, and a central axis (C-C ') extending between the front 202 and rear 204 faces. Each compartment 210, 210' has a void space 212, a front port 214, a back port 216, and an inner side wall 218, 218 '.

If we refer to FIG. 8, this shows an enlargement of a portion of FIG. 7 wherein a container member provided with a flange (100, 100 ') is accommodated in the empty space of each compartment 210, 210'. Each container unit is held in place by frictional force.

If we refer to FIG. 9, it shows a sectional view of a plane passing through the line B-B 'of another holding support 200 of FIG. 6. FIG. 9A is an enlargement of a portion of FIG. 9. The front faces 202 and back 204 of the holding support are indicated, and a central axis (C-C ') extending between the front faces 202 from behind 204. Each compartment 210, 210' has a space void 212, a front port 214, and a back port 216, and a stop member 220, 220 'extending into the back port, and an inner side wall 218, 218'.

If we refer to FIG. 10, this shows an enlargement of a portion of FIG. 9 wherein a borderless container member (100, 100 ') is accommodated in the empty space of each compartment 210, 210'. Each container unit is held in place by frictional force.

FIG. 11 is a plan view (top face) of a solid support unit (USS) 300 as described herein. The USS 300 is provided with an orientation marker 302, and an identification marker 304 printed on the top face 310. The identification marker 304 allows the user to inspect or visually check which type of USS has been inserted into the compartment. The orientation or positioning marker 302 allows an interpretation or automatic reading system to identify a reference position from which the different positions of the separate analysis zones (ligands, controls, standards) to be measured on the USS can be extrapolated.

FIG. 12 is a plan view (top face) of a solid support unit (USS) 300 of FIG. 12. The upper face 310 has been punctuated with a grid or grid pattern of 6x4 reaction zones 306, 308.

FIG. 13 is a cross-sectional view of a USS 300 showing the upper face 310 and the lower face 312, the dosing membrane 320 and the reinforcing layer 322.

FIG. 14 is a cross-sectional view of a USS 300 which is made of a solid support material 324 (eg a polymer) showing the upper face 310 and the lower face 312.

Claims (14)

claims A container unit-based assembly (150), for releasable insertion into a holder (200) for a plurality of container unit-based assemblies for a dosage, comprising: - a container unit (100) having a basal wall (114) at a lower end (104) of the container unit (100), and a sidewall (110) extending upwardly therefrom, defining a cavity (116), which cavity (116) is adapted to receive a fluid, and a solid support unit (300) having an upper face (310) for immobilizing a ligand for the detection of an analyte, the solid support (300) being positioned in the cavity (116). A container unit-based assembly (150) according to claim 1, wherein the solid support unit (300) is positioned in the cavity (116) for reading by a machine through an opening (112) disposed in the container unit (100) at an upper end (102) thereof. The container unit-based assembly (150) of claim 1 or 2, further comprising an orientation marker (118) for identifying the orientation of the container unit-based assembly (150). ) around a central axis (A-A '). A container unit-based assembly (150) according to any one of claims 1 to 3, wherein the cavity (116) is the only cavity present in the container unit (100). A container unit-based assembly (150) according to any one of claims 1 to 4, wherein the upper face (310) of the solid support unit (300) is provided with a plurality of analysis zones. (306, 308) each containing an immobilized ligand for the detection of an analyte. The container unit-based assembly (150) of claim 5, wherein the plurality of separate analysis zones (306, 308) each contain a different immobilized ligand. A container unit-based assembly (150) according to claim 6, wherein the plurality of distinct analysis areas (306, 308) are arranged in a grid pattern. A kit comprising at least two sets of container units (150) as defined in any one of claims 1 to 7, wherein an upper face (310) of the solid support unit (300) is provided with a plurality of distinct analysis zones (306, 308), each analysis zone containing an immobilized ligand for the detection of an analyte, and wherein the solid support unit (300) is essentially the even in each of at least two sets of container units (150). A process for producing a container unit-based assembly (150) as defined in any one of claims 1 to 7, comprising the steps of: providing a container unit (100), providing a plurality of solid support units (300) disposed in a sheet or flat strip, depositing one or more ligands on the upper face (310) of a plurality of different solid support units (300) of the sheet or strip using an XYZ robotic micro-dispenser, - inserting one of the solid support units (300) thus formed in the container unit (100) to form a unit-based unit of container (150). Holding bracket (200) for holding suitable for receiving a plurality of container unit-based assemblies (150) as defined in any one of claims 1 to 7, comprising: a plurality of compartments (210, 210 '), each compartment being adapted to receive and maintain a container unit-based assembly (150), the compartments (210, 210') being arranged in a grid pattern. The holding bracket (200) of claim 10, further comprising a plurality of container unit assemblies (150), each releasably inserted into an individual compartment (210, 210 '). The holding bracket (200) according to claim 11, wherein each container unit base assembly is provided with the solid support unit (300) having a plurality of discrete scan areas (306, 308) for the detection of analytes, and at least one of the analysis zones is different between at least two sets based on container units. The holding bracket (200) according to claim 12, wherein at least one of the analysis zones is different when comparing each of the sets based on container units. The carrier (200) of claim 13, wherein the difference is in the concentration of the ligand, the ligand composition and / or the position of the ligand.