BE1025623B1 - Device for optically reading a removable solid support for the detection and / or quantification of analytes present in a sample - Google Patents

Abstract

Device (1) for optical reading of a removable support (2) for the detection and / or quantification of analytes present in a sample comprising communication means (8) for obtaining information relating to a support (2); selection means (27) for selecting from a list of predefined analytes a selection of analytes to be detected and / or quantized; an optical unit (7) for analyzing said medium (2) on the basis of analysis parameters included in said information relating to a medium (2); image processing means (12); determining means (13) for determining analyte information based on the medium information (2) and data of the image processing means (12); and transmission means for transmitting the analyte information.

Description

Technical field According to a first aspect, the invention relates to a device for the optical reading of a solid support for the detection and / or the quantification of analytes present in a sample. According to a second aspect, the invention relates to a diagnostic assembly comprising an optical reading device according to the first aspect and a diagnostic means.

STATE OF THE ART [0002] The surveillance and control of food products requires tests to be carried out as far as possible before their manufacture. Ideally, these tests should be carried out at the place of production of the raw materials or at their place of processing. These screening tests or screening tests are particularly designed to detect the presence of certain bacterial, antibacterial or antibiotic type analytes in samples. The multiplication of health standards and the desire for better traceability of food products means that the analytes to be tested must be multiplied as well as knowing their classes and quantities as precisely as possible.

One way of detecting analytes in a sample is to use a reaction mixture comprising biological recognition molecules, for example each capable of recognizing a determined anaiyte present in said sample. The detection of analytes can then be carried out with a strip (immunochromatographic support) which is immersed in a flask containing the reaction mixture. The strip generally comprises several areas often called line or detection point corresponding to different analytes to be detected or quantified. The diagnosis is finally carried out for example by direct visualization of each of the 30 lines of the strip, or using a reader making it possible to analyze the signals emitted by the different lines or detection points.

BE2017 / 5707 [0004] An analyte to be detected is therefore often highlighted by a line or dots on the strip. The most common method (reflectometry) is to change the color or the light intensity of the signal reflected by the line or point related to the analyte to be detected. Molecules 5 coupled to a fluorophore (or to an active molecule capable of generating / modifying a fluorescent or chromogenic substrate) having a labeling function can be used to in particular make it possible to obtain lower detection thresholds and making it possible to render the signal non -interpretable directly by the human eye in order to circumvent the risks of subjectivity (or error) from one individual to another and a risk of falsification. The use of fluorophores requires in particular an inspection of the fluorescence emitted by your different lines or points positioned on a strip.

[GOOS] It is already known from the state of the art of optical readers 15 to carry out a diagnosis concerning the presence and or the amount of anaiytes present on a test strip previously dipped in a fluid to be tested. However, current optical readers do not allow the optical reading of a selection of regions of interest chosen from a large number of regions of interest corresponding to defined analytes present on a strip.

Current optical reading devices, in order to allow a selection of analyte from a large number of interests, require the provision of a plurality of strips allowing the testing of said selection of regions of interest chosen corresponding to analytes to be tested. All this requires significant handling of the test strips, costly in 2S time and in inventory management.

Summary of Pinvenfion [0008] According to a first aspect, one of the aims of the present invention is to provide an optical reading device of a removable solid support for the detection and / or quantification of anaiytes present in a sample and.

allowing the selection of the analytes to be tested without requiring the use of several removable solid supports. One of the aims of the present invention is to allow a selection of anaiytes from a pre-established list for which

BE2017 / 5707 an operator wishes to test the presence or obtain a quantification of said analytes.

To this end, the inventors propose an optical reading device for a removable solid support for the detection and / or the quantification of analytes present in a sample and comprising:

- a location to receive said solid support:

·· an optical unit for analyzing said solid support and comprising:

a first light source for emitting according to an emission intensity and in a better range of wavelength 10 a first light beam towards said location (20);

o an imaging system comprising an optical detector for providing an image of a viewing area, said viewing area comprising at least a portion of said location;

o a filter to filter a defined wavelength range, and positioned between the location and said imaging system;

- means of communication for obtaining information relating to a solid support;

- selection means for:

o select from a list of predefined analytes, a selection of analytes to detect and / or quantify;

image processing means of said image for:

o determine, from the information relating to said solid support to be read, a finite number of subsets of said image, each subset corresponding to an analyte;

o provide data relating to light intensities from said subsets;

- means of determination for:

o calculate, for each subset corresponding to an analyte selected from said selection of analytes, a subset intensity;

BE2017 / 5707 o determine, on the basis of said subset intensity, analyte information for each subset corresponding to an analyte selected from said selection of analytes;

transmission means configured to transmit said analyte information for each subset corresponding to an analyte selected from said selection of analytes.

The device according to the invention allows you to read the areas to be tested, in particular with an instantaneous measurement of fluorescence or preferably with a measurement of the light reflected from the areas to be tested. In order to allow a selection of the analytes to be tested corresponding to areas of interest on a tigette, the device offers, thanks to access to a method containing information relating to a tigette, a selection from a list of analytes to test. It is indeed interesting to make a selection of the 15 analytes to test before obtaining the results in order to target your analytes which it is necessary to know the results of a test so as not to expose a user to too much large amount of results. Giving access to too many results to a user who does not necessarily have the need exposes him to the risk of loss of objectivity compared to his intention of initial analysis. It is also interesting from an economic point of view for the user that he only pays for the results that H really needs. For the producer and / or distributor, it is advantageous to have a unique industrial process allowing a simplification of the manufacturing process as well as a simplification of stock management. Thus, the device 25 of the invention, thanks to selection means, allows a choice of the analytes to be tested by the user before reading the strip. The selection means, in communication with the image processing means allow the image processing means, a determination of the information of the selected analytes only.

The advantage of the device of the invention is to allow an optical reading based on the fluorescence of areas comprising information relating to the analytes to be tested. Preferably, the signal interpreted by your means of determination can have an absolute intensity (arbitrary unit) or

BE2017 / 5707 have an intensity relative to an intensity emitted by a reference point or by an Internal control point emitting a reference intensity. In addition, this optical reader allows a selection of the anaiytes to be tested from a single strip, that is to say not requiring the positioning of one or more different strips in a cassette, the cassette then being inserted. in the player. Several tabs can also be inserted directly into an optical reader. In addition, this optical reader allows, for example, a cable or wireless communication of the results concerning the analytes to be tested.

An advantage of using the optical reader of the invention to carry out a diagnosis concerning a selection of analytes of interest is that it requires neither a first selection of the strips to be tested, nor the bringing into contact of each. of these strips with the product to be tested and their positioning in the optical reader. The optical reader of the invention to allow a selection of the analytes of interest does not require that a plurality of strips allowing the testing of said selection of analytes to be tested be made available. All of this makes it possible to avoid significant manipulation of the test strips, costly in time and in inventory management. This also allows a simpler, faster and more targeted analysis of the anaiytes to be tested, by only having the results selected on the resulting from the reading of the strip by the optical reader of the invention.

For example, the selection means, in communication with the determination means and with the transmission means, allow the transmission of the results concerning the selected anaiytes and the transmission of the results of the unselected anaiytes to encryption means . The encryption means then enabling encryption of the data relating to the non-registered anaiytes and the recording of this encrypted data. The advantage of recording encrypted data including the results of non-selected anaiytes makes it possible to be able to have the 30 results concerning non-selected anaiytes but to limit access to those with means of decryption capable of decrypting data encrypted by means of encryption. For example, encrypted data

BE2017 / 5707 include the image acquired by the optical detector as well as a method or information relating to the test strip.

The analytes that can be detected and or quantified are, for example, chemical contaminants, proteins or pathogens. The 5 samples which can be detected and / or quantified by the device according to the invention are, for example, samples of milk, blood, serum, saliva, water, urine, cereals, meat, tear secretions ...

[Ö013] Preferably, the device according to the invention allows the reading of locations (of recovery) or of dots fixed on a solid support (or recovery system) according to an arrangement, preferably two-dimensional matrix in the form of dots. each having a diameter between 20 μm and 2 mm, preferably between 100 μm and 500 μm. and even more preferably between 250 μm and 400 μm. The device 15 according to the invention allows the grab differentiation of recovery locations in the form of points each having a diameter and a spacing of between 20 μm and 2 mm, preferably between 100 μm and 500 μm and even more preferably between 250 μm and 400 μm, thus making it possible to fix at least 5 locations, preferably at least 20, and even more preferably at least 15 recovery locations in simpiicat, duplicate, or triplicate or more for detection and / or quantification at least 5, preferably at least 10, preferably at least 15 analytes of different classes, whether or not belonging to families of distinct anaiytes, as well as at least one recovery location 22 deposited in simpiicat, in duplicate, in triplicate or more intended for positive control of the detection threshold allowing validation of the test and / or calibration for detection and / or quantification ation, and this on a recovery system having a reasonable size and dfô the order of the square centimeter, for the realization of the detection and / or the quantification of said at least 15 analytes by the optical reading device of the invention.

[Ü014] Preferably, the identification device is positioned at said location to identify a solid support to be read positioned in said location. The means of communication are also

BE2017 / 5707 reading means, for example for reading data on a removable solid data medium. For example, the means of communication allow a connection to an internet type network by cables or by wireless means such as wifi, Bluetooth, 4 / 5G or near field communication.

A solid support according to the invention is for example a strip.

The image includes sub-sets, portions, regions of interest, areas of interest or even parts of images. Preferably, the sub-sets of an image comprise a plurality of pixels. Preferably, each sub-assembly comprises at least 20 pixels, preferably more than 50 pixels and even more preferably more than 250 pixels.

Preferably the first light source allows a reading of the regions of interest in fluorescence, that is to say with a wavelength range which coincides with the absorption spectrum of fluorescent elements such as 15 labeling molecules. The marking molecules then re-emit the absorbed light energy in a range of length different from the range of the first light source. The optical unit then allows the acquisition of the fluorescence signal emitted by the fluorescent labeling molecules. A bandpass filter positioned between the optical detector and the fluorescent labeling molecules makes it possible to stop the light emitted by the light source allowing the excitation of the fluorescent labeling molecules while letting the light emitted by the fluorescent labeling molecules pass.

Preferably, the transmission means are configured to transmit or communicate the analyte information for each subset to a memory. Preferably, the transmission means make it possible to transmit analyte information to a display device included in the optical reading device according to Unvention.

An advantage of the device according to the invention is to be able to receive 3 G a solid support such as, for example, an immunoobromatographic type strip (with or without cassette) or a microfluidic chip.

BE2017 / 5707 [Ö019] For example, a kit comprises the device of the invention and an incubator, in order to allow the incubation of the reaction mixture contained in a flask as well as during the soaking of the removable solid support. The incubator allows the reaction mixture to be kept in position and in temperature at a temperature preferably between 25 ° C. and 35 ° C. and even more preferably at 30 ° C. The incubator is to be used before positioning the removable solid support in the device location.

One of the aims of a preferred embodiment of the present invention is to allow a cost price to the user of the device of the invention which is directly linked to a selection by the user of analytes to test. One of the aims of the present invention is to enable the supplier of the optical reading device to invoice on the basis of a selection by the user of the analytes to be tested.

Preferably, the device further comprises:

- a credit counter, said credit counter being Increments during the selection of each analyte to be detected and / or quantified.

For example, the credit counter allows a positive or negative increment. For example, the credit counter is refillable and makes it possible to block the image processing means and / or the determination means and or the data transmission means relating to the strip to be measured when the credit balance is equal to zero or that the credit balance is not sufficient to carry out the analysis of all the analytes selected by your selection means. An advantage of the credit counter is that it can be recharged from the means of communication. For example, an instruction to increment the credit in a positive manner is contained on a removable usb key or directly transferred to the webservice via an internet platform used for the management of remote optical devices. For example, a deposit for a positive credit increment is accessible by means of a wireless connection. For example, the 30 credit counter is a unit counter or "unit". For example, your credits (or units of use) "virtual" are counted with regard to the number of analyzes (tabs) and the number of channels (point or dot.) Selected. Credits can be recharged after payment.

BE2017 / 5707 Preferably, the device further comprises:

- encryption and recording means to save the image on the basis of a defined encryption.

For example, your selection means, in communication with the determination means and with the transmission means, allow the transmission of the results concerning the selected analytes. The image which has enabled the determination of the results concerning the analytes is for example transmitted to encryption means. The encryption means then enabling encryption of the data relating to the recorded and unregistered analytes and the recording of this encrypted data. The advantage of recording the encrypted data comprising the results of the unselected analytes makes it possible to have available the results concerning non-selected analytes but to limit access to those with means of decryption capable of decrypting the data encrypted by your means of encryption. For example, the encrypted data includes, the image acquired by the optical detector as well as a method or information relating to the test strip. To obtain the results of the "channels (points) not selected", it is necessary to activate the "channels (points)" in question and do a "reanalysis of existing image" to reveal the results of the points not20 selected initially. An advantage of having the image acquired by the optical unit as well as information relating to the test strip is to be able to carry out a re ~ analysis of the solid support at any time after the first analysis according to the invention . It is thus possible to ensure that the image is properly analyzed by your image processing means, to analyze subsets that have not been selected by the selection means or to perform analysis quantitative when a first qualitative analysis had been carried out. This advantage of saving the image, preferably in encrypted form, ensures that it can only be read by a person who has the rights to access it. During a re-analysis, in the case where the analysis of analytes not previously detected or quantified, an incrementation of a credit counter is preferably possible.

[O025] Preferably, the device further comprises:

- an identification device to identify a support, solid to read;

BE2017 / 5707 and in that the means of communication are configured to obtain information relating to said solid support identified by said identification device.

An advantage that the optical reader of the invention comprises an identification device for identifying a solid support to be read is to allow an automatic choice of the method to be applied to the solid support to be read. This saves time and makes it possible to avoid the risks of error compared to a manual choice of the method. A reading method includes information specific to the solid support to be read and allowing in particular the proper functioning of the optical unit, image processing and determination means in order to be able to obtain reliable information relating to at least one anaiyte.

[002T] Preferably, the list of predefined analytes is included in the information relating to a solid support.

The advantage of having a list of predefined anaiyte in the information relating to a solid support is to have a list comprising only the analytes that the removable solid support is capable of determining. This makes it possible to make a selection only from the analytes for which it is possible to obtain a result and not from an exhaustive list of analytes.

Preferably, the image processing means are further configured for:

o detect reference areas of said Image, o position in said image each subset at a position determined from said reference areas.

Preferably, the determination means are configured for:

o determine on the basis of said intensity of subset and on the basis of the information relating to said solid support to be read, said anayte information for each subset corresponding to an anayte selected in said selection of analytes,

BE2017 / 5707 Preferably, one of the advantages of the preferred embodiment of the invention is to provide an optical reading device of a removable solid support for the detection and / or quantification of anaiytes present in a sample with a automatic choice of the method to apply to sample 5 from a method database. The present embodiment of the invention also allows automatic correction linked to the variation of batches of the removable solid support for each dowry allowing the detection or quantification of anaiytes.

The optical reading device according to this preferred embodiment of the invention allows an optical reading of a strip for the analysis of a sample with a choice of automated reading method. The reading method preferably comprising data relating to: a version of the method, a batch number, a deadline for using a batch, the type of light source used, the type of area of interest (line or point), method 15 for quantitative (binary) or quantitative analysis, of the image acquisition parameters (exposure time, gain, etc.), the positions relative to reference points (for example according to Cartesian coordinates), a number of areas of interest, a number of replicas per analyte, the matrix organization of the areas of interest on the mobile solid support, the dimensions of the areas of interest 20 (for example, a radius), a dimension relating to an area around an area of interest to be considered for taking into account the background, calibration parameters of the data interpolation type or allowing a quantitative analysis of a sample and finally the designation of the areas of interest as a function of the analyte which they make it possible to detect and / or quantify.

The automatic choice of the reading method is carried out by the optical reader of the invention thanks to the identification device to identify a solid support to read. For example, the identification device is a bar code, QR code, datamatrix or similar reader enabling information relating to the solid support to be obtained from a code written on a solid support. Preferably, on the basis of information relating to the solid support contained by a marking present on a solid support, the optical reader of the invention makes it possible, thanks to the communication means, to consult a method database in order to access the method corresponding to the support

BE2017 / 5707 solid present in the reader. For example, the identification device is a near field data reader and the type of marking present on a solid support is an RFID chip. For example, the means of communication allow access to a method database in Print format, s For example, the given database is distributed over several sheets, the method corresponding to the solid support being acquired by reading the sheet corresponding to the method desired. For example, the display means of the optical reader indicate the sheet comprising the desired method. For example, the means of communication allow confirmation that the method 10 read is indeed the method corresponding to a solid support to be read, [G034] The optical reading device according to this embodiment of the invention makes it possible from an image provided by the optical detector, a determination of a number) of sub-assemblies to be analyzed from information contained in the method chosen by means of the identification device. This allows a better localization of the areas of interest on the solid support to be read. When the subsets are positioned at the areas of interest of the tab, the determination means allow a determination of analyte information for each subset. For example, analyte information for an area of interest is modified by the means of determination on the basis of analyte information contained in the method. For example, this analyte information is a calibration curve used to determine quantitative information for an analyte. For example, analyte information is a threshold intensity for an area of interest and therefore for an analyte, threshold intensity from which an analyte 25 is considered to be present or not present in the test sample. For example, a threshold intensity value can vary from one batch of mobile solid support to another, which requires automatic access to a method to ensure a reliable analysis result and with a detection threshold corresponding to the standards in force. .

Preferably the tlgettes to be measured are provided with a unique identifier (from which the reading method can be automatically designated) which makes it possible to warn a user of the reuse of an already used tigette. Indeed, there is a risk of reuse of a tigette having already

BE2017 / 5707 was used for the analysis of a first sample and cannot be reused for an analysis of a second sample. Thus, the device of the invention makes it possible to check in a database of mobile solid support, via the means of communication, whether the mobile solid support inserted in the optical reader 5 has not yet been used. If this is the first use of the mobile solid support, optical reading can start, if it is a second use (or more) optical reading does not start and the user is warned that the solid support mobile is not valid for carrying out an analysis of a selected sample.

An advantage of the optical reader of this embodiment of the invention is to allow the determination of a method from a barcode or RFID type marking present on a mobile solid support to be read in order to automatically transfer information relating to the mobile solid support to be read, such as calibration parameters specific to each solid support (or batch of solid support).

An advantage of using a barcode or RFID type marking present on or in the tag to be tested making it possible to code information relating to the tag is to allow rapid reading of a unique identifier from which, ie choice of the method can be done automatically by accessing a method database. It is more advantageous to do this rather than storing a method in a barcode or RFID type marking because the amount of information contained in such marking is very limited. This limitation on the amount of information that can be contained in this type of marking does not make it possible to provide information relating to a large number of dots or lines of analytes to be read.

This advantage of this embodiment of the invention, of being able to access a method which does not limit the number of analytes which can be tested by a solid support, allows the use of tabs on which a large number of points or lines are present. corresponding to a large number of analytes to be tested and having detailed information for each of the anaiytes to be tested. In addition, the presence of information relating to anaiytes to be tested present in a method database rather than in the marking allows the marking to be recorded during the manufacture of the solid supports, the

BE2017 / 5707 method information relating to each analyte and each solid support which can be established following the production of the batch of solid support. A modification of the method is also possible if, for example, quality monitoring revealed an anomaly that does not allow a correct reading of an analyte result. In the case where the marking present on the solid support should be printed directly on the solid support, this should be done off the areas of interest of the solid support or else should not contain information relating to the specificity of the batch in production course.

Preferably, the optical unit further comprises:

o a light intensity sensor to measure the emission intensity emitted by said first light source;

a feedback control means for modulating said emission intensity of said first light source as a function of the emission intensity measured by said light intensity sensor so that said first light source emits a target intensity.

An advantage of this preferred embodiment of the present invention is to provide an optical reading device for a removable solid support 20 for the detection and / or quantification of analytes present in a sample and allowing simultaneous reading. a large number of areas to be tested (or dots). Another advantage of this preferred embodiment of the present invention is that it makes it possible to deliver a qualitative and possibly quantitative result from each of the zones to be tested.

[0940] When a fluorescence technique or a reflected light technique is used to read the areas to be tested (or points), a feedback control is used for example and makes it possible to guarantee an always equal excitation light intensity, which allows an instantaneous measurement of fluorescence or reliable reflection, whatever the temperature, the energy source used or the duration of use and the aging of the light source. The use of the feedback means makes it possible to guarantee a light energy source having a constant intensity over time and predefined. A light energy source with a predefined intensity

BE2017 / 5707 notably guarantees reliable quantitative results. The feedback means is preferably an electronic feedback means.

[0G41] The feedback means make it possible to define, for example, a target emission intensity of a light source. An intensity sensor 5 makes it possible to measure an emission intensity of the light source and to return the measured intensity of the emission source to the feedback means. The feedback means make it possible, for example, to define the supply voltage or the intensity of the current supplied to the light source.

When the light intensity of the light source returned by the intensity sensor 10 to the feedback control is too low compared to the target intensity, the feedback controls allow an increase in the voltage or current supplying the light source . On the contrary, when the light intensity of the light source is too high compared to the target intensity, the feedback means reduce the voltage or the current supplying the light source. The feedback means allow regulation of the light intensity emitted so that the light source operates at a target light intensity, stable over time. For example, the target light intensity is defined during an Initial calibration and saved in a memory of the device. This regulation of the light intensity makes it possible to ensure a reading of the solid support with the same controlled target intensity so that this light intensity is not influenced by variations in temperature or aging of the light source. The feedback means allow the regulation of the light intensity to ensure a target intensity of a light source for measurement in fluorescence and or in reflected light. An advantage of this feedback device is to provide a controlled light intensity in order to be able to read a removable solid support with a continuous fluorescence technique and to be able to read a signal in a qualitative and / or quantitative manner. Another advantage of being able to produce light with a target light intensity is to be able to ensure better consistency and comparison of the results from one apparatus to another. For example, it is possible to be able to define correction factors for each batch of removable solid support applicable on any optical reading device of the invention.

BE2017 / 5707 [0042] Preferably, the target intensity is defined on the basis of the information relating to said solid support to be read.

An advantage that the target intensity intended for the feedback means is specified in the information relating to the solid support to be read is that this intensity can be modified as a function of the solid support to be read and the specificity thereof. . This allows greater flexibility of solid supports that can be read by the optical drive of the invention. It is for example possible to combine a target intensity with a method relating to a tigette or a batch of tigettes. Such a method would include, in addition to a target intensity, gain, exposure time, minimum signals of (in) validity of the CTRLs, cut-off ratios (PO-S / NEG specific decision threshold depending on the batch). and dot on the tigette.

Preferably, the optical detector is a two-dimensional optical detector for providing a two-dimensional image of said viewing area and in that said image processing means are configured to process said two-dimensional image.

Preferably, the optical detector is a two-dimensional optical detector to provide a two-dimensional image of said viewing area and in that said image processing means are further configured for:

o detect reference areas of the two-dimensional image, o determine the finite number of subsets of the two-dimensional image, from information relating to the solid support to be read, o position in the image two-dimensional each sub-assembly at a position determined from the reference zones.

An advantage of the device of this preferred embodiment of the invention is to provide an optical reading device for a removable solid support 30 for the detection and / or quantification of anaiytes present in a sample and allowing a simultaneous reading of a large number of zones to be tested (or dots). In addition, it allows to deliver a qualitative and possibly quantitative result of each of the areas to be tested.

BE2017 / 5707 Another advantage of this preferred embodiment of the optical reading device of the invention is to allow the optical reading of a large number of regions of interest present on a single tab. Indeed, the optical reading device of the invention allows the optical reading of a large number of regions of interest present on a single strip and has means for analyzing a large number of regions of interest on a strip. precise. In the case of the optical device of the invention, reading a large number of regions of interest does not require providing locations for several tabs. The use of several tabs in the same optical reader for a simultaneous reading of several tabs in order to cover a large number of regions of interest with the same optical sensor being a source of poor placement and of shifting of the regions of interest of a measurement to another and this for each of the tabs introduced into the optical reader, The two-dimensional image comprises sub-set, portions, regions of interest, areas of interest or even parts of images. Preferably, the sub-sets of a two-dimensional image comprise a plurality of pixels. Preferably, each subset comprises at least 20 pixels, preferably more than 50 pixels and even more preferably more than 250 pixels.

[0049] Preferably, the analyte information is determined on the basis of at least two subset intensities From at least two subset. For example, the analyte information is an average of at least two intensities of subsets from at least two subsets.

An advantage of averaging is to allow smoothing of possible disturbances in the reading of the removable solid support. Even more preferably, an average is obtained on the basis of three intensities of subsets from at least three subsets.

Preferably, said finite number of subsets is greater than or equal to five subsets, preferably more than ten subsets and even more preferably more than fifteen subsets.

BE2017 / 5707 An advantage of being able to read more than five subsets, preferably more than ten subsets and even more preferably more than fifteen subsets is to be able to carry out a diagnosis of a sample to be tested in a single reading of a single removable solid support.

Preferably, the sub-assemblies have a rounded shape and preferably have a disc shape.

An advantage of having a rounded or disc-shaped sub-assembly is that they make it possible to collect a point of interest intensity having a larger disc shape.

1.0 Preferably, the two-dimensional image comprises areas contrasted with respect to a background area, and in that, the image processing means of the two-dimensional image also make it possible to:

- crop the two-dimensional image into a cropped image, the cropped image showing a larger or equal portion of the location for receiving a solid support than in the two-dimensional image;

- assign a defined surface for each position to two dimensions of subset in the cropped image;

perform a local optimization of the position of each subset so that the defined surface of each subset is positioned so as to return a maximum light intensity of each of the contrasted zones.

For example, the maximum light intensity of each of the 2 5 contrast zones is determined for a given size of the sub-assembly.

Preferably the surface defined for each two-dimensional position of subset in the cropped image is rounded, preferably circular, preferably a disc.

Preferably, the information relating to a solid support to be read 30 includes information corresponding to each of the subsets.

An advantage of having information relating to a removable solid support comprising information relating to each of the sub-sets is that it is possible to indicate in the information relating to the support

BE2017 / 5707 solid, essential characteristics such as the analytes corresponding to each of the subsets as well as for example calibration curves allowing a qualitative and quantitative measurement.

Preferably, the anaiyte information is binary type 5 information.

Binary type anaiyte information is qualitative anaiyte information. For example, information from anaiyte indicates a positive presence or a negative presence of an anaiyte. For example, the determination system, on the basis of a pivot intensity or threshold intensity or 10 ratio defined by the information relating to the support, makes it possible to assign a binary value to a subset intensity. The determination means indicate, for example for a subset intensity greater than a threshold subset intensity, the presence of a negative anayte. The determination means indicate for example for a subset intensity less than a threshold subset intensity, the presence of a positive anayte. For example, anaiyte information is included in the memory of the device of the invention and does not require extracting this anaiyte information from information relating to the support. Preferably, a threshold intensity is defined by router according to regulations specific to a territory.

Preferably, the anaiyte information is information proportional to the measured light intensity.

An advantage of an Information of proportional to the measured light intensity is to be able to carry out a quantitative analysis of analytes in a sample. Preferably, the anaiyte information is calibrated with a calibration curve which depends on the manufacturing batch of the removable solid support and on the point of interest corresponding to the anaiyte chosen.

Preferably, the device is compact and hermetic.

An advantage of having a compact and hermetic device is to be able to use the device in a portable manner. Another advantage is to be able to use the device under external conditions or under conditions linked to the place of production of a batch from which the sample to be tested comes.

Preferably, the device further comprises:

BE2017 / 5707

- an external surface;

- cooling means for transferring a quantity of heat from the interior of said device to said external surface.

Preferably the external surface creates a seal against water and dust. An advantage of the cooling means which allow heat transfer from the interior of the device to its external surface is to allow heat transfer without harming the sealing or hermeticism according to a protection index IP54 according to the IEC 60529 standard consulted in September 2017.

Preferably, the cooling means comprise a heat pipe.

An advantage of the heat pipe is that it allows the transport of: a large amount of heat over a relatively large distance. In fact the heat pipe is particularly well suited for the device of the invention because H to convey the heat produced at any place inside the device towards the outside of the device while retaining a good seal.

Preferably, the device of the invention further comprises a second light source for emitting a second light beam in a second wavelength range.

An advantage of having a second light source is to be able to have an optical reader for reading regions of interest with a wavelength range different from the first wavelength range emitted by the first light source. Preferably, the second light source allows reading in reflected light. The second light source illuminates the regions of interest of a tab positioned in the reader location. Labeling molecules may or may not present at the regions of interest, may or may not allow absorption, or less reflection of the region of interest illuminated by said second light source. The optical unit then allows the acquisition of the light reflected by the rod in the viewing area. Depending on the presence or not of the marking molecules, this results in regions of more or less dark interest compared to the bottom area of the strip.

BE2017 / 5707 For example, fluorescent labeling and or modifying the reflection can be used, which requires a reading in fluorescence and a reading in reflected light. The two readings are for example performed one after the other in a predefined or non-predefined order.

A bandpass filter is for example used in order to, during a measurement in reflected light, allow a wavelength range which may or may not be absorbed by the molecules of radiation to pass to the optical detection unit. marking modifying the reflection. Indeed, this makes it possible to increase the contrast by eliminating the background noise due to the wavelengths emitted by the light source but not absorbed by the marking means. The bandpass filter is preferably positioned between the light source and the labeling molecules or between the labeling molecules and the optical detector.

Preferably, the first wavelength range is distinct from said second wavelength range.

The advantage of having two light sources emitting in distinct wavelength ranges allows a reading of a greater choice of labeling molecules. For example, this makes it possible to read labeling molecules which can return a signal by fluorescence and 20 labeling molecules which can modify the reflection of light on the removable solid support.

Preferably, the filter is a double band pass filter for passing two defined wavelength ranges, one of the two ranges of which is the first wavelength range or the second range of 2? wavelength, therefore requiring no physical change of bandpass filter during analyzes.

[0677] For example, an advantage of using a double band pass filter positioned between your labeling molecules and the optical detector allows the detection of different labeling molecules or allowing reading in distinct wavelength ranges. Preferably the double band pass filter is used in the presence of two different light sources emitting in different wavelength ranges. Preferably, a

BE2017 / 5707 double band pass filter is used in the case of an optical reader allowing reading of marking molecules in reflection and fluorescence.

Preferably, the device for identifying the solid support is a data matrix, barcode or QR code reader.

According to a second aspect, one of the aims of the invention is to provide a diagnostic assembly allowing a practical, economical, effective and optimized diagnosis compared to the current diagnostic assemblies, and this by allowing the detection and / or the quantification not only of a higher number of classes of anaiytes belonging to a family of anaiytes (for example your antibiotics), but also of a higher number of classes of anaiytes belonging to several families of anaiytes ( for example drug residues, toxins or heavy metals). More particularly, a diagnostic assembly according to the second aspect of the invention allows the detection and / or quantification of at least five different classes of anaiytes, preferably at least ten different classes of anaiytes, even more preferably at least fifteen different classes of anaiytes present in a sample and belonging to at least two different families of anaiytes, and this in less than fifteen minutes.

To this end, the inventors propose a set of diagnostics for the optical reading of a recovery system comprising:

the device according to the first aspect of the invention;

a diagnostic means for the detection, and / or the respective, simultaneous and specific quantification of a plurality of anaytes present in a sample comprising at least one reaction mixture and at least one recovery system, said at least one recovery system being in the form of a solid support to which are fixed in distinct and known recovery locations in space, competing ligands and / or biological recognition molecules, so as to identify by the location of said 30 recovery locations on said support, said analytes present in said sample, said diagnostic means being characterized in that said recovery system comprises recovery locations which are

BE2017 / 5707 arranged in a two-dimensional matrix arrangement which is defined according to a known and specific coordinate system of said competing ligands and / or of said biological recognition molecules fixed to said recovery locations of said 5 recovery system, The variants and advantages mentioned for the first aspect of the invention apply to the diagnostic set according to the second aspect, mutadis mutandis.

In fact, it has surprisingly been demonstrated that a diagnostic assembly comprising a diagnostic means which comprises a recovery system having recovery locations which are arranged in a two-dimensional matrix arrangement which is defined according to a known and specific coordinate system makes it possible to detect and / or quantify at least five different classes of analytes, preferably at least ten different classes of analytes, preferably at least fifteen different classes of analytes present in a sample and belonging to at least two distinct families of analytes, and this in less than fifteen minutes. A diagnostic set with a diagnostic means is therefore more practical, more economical and more efficient than the currently known diagnostic means which are generally limited to less than five different classes of analytes, typically only two or three classes. different from analytes, these classes belonging to the same family of analytes (for example antibiotics), Preferably, the two recovery locations are arranged in a two-dimensional matrix arrangement in the form of dots each having a diameter between 20 μm to 2 mm, preferably between 100 to 500 μm and even more preferably between 250 μm and 400 μm.

It has been shown that recovery locations in the form of dots each having a diameter between 20 μm and 2 mm, preferably between 100 μm and 500 μm, preferably between 250 μm and 400 μm, make it possible to fix at least five, preferably at least ten, more preferably at least fifteen recovery locations in

BE2017 / 5707 simplicat, in dupiicat or in triplicate. for detecting and / or quantifying at least five, preferably at least ten, more preferably at least fifteen analytes of different classes, whether or not belonging to families of distinct anaiytes, as well as at least one recovery location 5 deposited in simplicat, dupiicat or triplicate intended for positive control of the detection threshold allowing validation of the test and / or calibration for detection and / or quantification, and this on a recovery system having a size reasonable and of the order of a square centimeter, for carrying out the detection and / or quantification of at least thirteen analyzes by the optical reading device.

Preferably, said coordinate system has a first coordinate defined on a longitudinal axis of a length of said recovery system and a second coordinate defined on a longitudinal axis of a width of said recovery system.

Preferably, said recovery system comprises at least five, preferably at least ten, and more preferably at least fifteen separate recovery locations intended for the respective simultaneous and specific detection and / or quantification of at least five, preferably at least ten, more preferably at least fifteen analytes 20 of distinct classes present in a sample and belonging not to different families of anaiytes, and at least one recovery location intended for control and / or a calibrator.

BRIEF DESCRIPTION OF THE FIGURES These aspects as well as other aspects of the invention will be clarified in the detailed description of particular embodiments of the invention, reference being made to the drawings of the figures, in which:

- Fig. la, Fig. 1b, Fig. 1c and Fig. 1d show schematic embodiments of the device according to the invention:

- Fig. 2a and Fig. 2b show a schematic embodiment of the device according to the invention:

- Fig.3a and Fig.Sb show an example of an image according to the invention;

- Fig.4 shows a 3D view of an embodiment according to the invention.

BE2017 / 5707

The drawings of the figures are not to scale. Generally, similar elements are denoted by similar references in the figures. The presence of reference numbers in the drawings cannot be considered as limiting, even when these numbers are indicated in the claims.

Detailed description of some embodiments of the invention [0088] Figures 1a to 1d show an example of embodiment of the device 1 according to the invention. A removable solid support 2 for the detection and / or quantification of analytes present in a sample is inserted into the device 1 and is received by a location 20. The location 20 makes it possible to receive the solid support 2 so that the positioning of the solid support 2 is as reproducible as possible from one solid support 2 to another relative to the optical unit 7. Preferably, the location 20 is a removable part of the device 1 which is for example supported by a device drawer. To perform the optical reading of a solid support 2, the location 20 is for example removed from the device in order to be able to position the solid support 2 there to be read optically. When the solid support 2 to be read is positioned in the location 20, these are preferably brought back inside the device 1 to perform the optical reading there. The location 20 allows rapid and reliable positioning of the solid support 2. The solid support 2 when it is present in the device 1 as illustrated in FIG. 1 is illuminated by a light source 3. 4. A light signal returned by the solid support 2 to an imaging system 60 is detected by the optical detector 6 to provide an image 40 of the solid support 2.

[ÖÜ89] A light source 3, 4 has for example the following specifications:

- the first light source 3: light-emitting diode having a dominant wavelength: 590 nm, emission bandwidth (FWHM): 18 nm, minimum / typical emission power: 160 mW / 30 170 mW. Preferably the first light source 3 comprises at least one light-emitting diode, preferably at least three diodes and even more preferably six light-emitting diodes

BE2017 / 5707 in order to ensure a sufficient light intensity for illumination of the region of interest (viewing area) of the solid support 2, the use of at least two diodes allows better uniformity of illumination of the region of interest of the solid support;

- the second light source 4: light-emitting diode having a dominant wavelength i 525nm.

The imaging system 60 comprises an optical detector 6, an optical system for focusing the light signal returned by the solid support 2 on the optical detector 6. Preferably the optical detector 6 is a j CMOS type detector. In another embodiment, the detector 6 is a CCD type detector. For example, the optical detector is a network of photo detectors. A focusing optic is for example a converging lens, for example a converging lens having a focal length between 15 mm and 20 mm.

The optical reader 1 of the invention also comprises a filter W positioned on the optical path of the light signal returned by the solid support 2 and located upstream of the optical detector 6. Preferably the filter 10 is a bandpass filter which allows a wavelength band of the light signal returned by the solid support 2 to pass through when it is illuminated by a light source 3, 4. The wavelength band transmitted by the filter allows detection and / or the quantification of analytes present in a sample.

Preferably, the filter 10 is a double band pass filter, that is to say transparent to two bands of distinct wavelengths. For example, the It filters 10 pass double band has a first transmission range centered on

527 nm and with a nominal half-height transmission band (FWHM) of

54.1 nm. The first transmission range has a transmission greater than 90% in the wavelength range 506 - 548 nm. A second transmission range centered on 645 nm and with a nominal transmission band 30 at half height (FWHM) of 61 nm. The second transmission range has a transmission greater than 90% in the wavelength range 620.5 -

669.5 nm. Each transmission band of the double band pass filter allows the detection and / or quantification of analytes present in a

BE2017 / 5707 sample. For example, the solid support comprises fluorescent labeling molecules which require a filter to be detected and / or quantified. The filter 10 makes it possible to clearly differentiate in the light which is returned by the solid support 2 to the two-dimensional optical detector 6, the reflected component and the component resulting from the fluorescence of said compounds. Preferably for an optical reading of a solid support 2 in fluorescence (photoluminescence), only the wavelength range emitted by the fluorescent molecules in relation to the analyte to be detected must be transmitted to the optical detector 6. In fact the transmission of the wavelengths 10 d in connection with the excitation light source 3, 4 does not make it possible to obtain a good signal / noise ratio Elimination of the wavelength range of a light beam 30, 40 at level of the detector 60 is therefore preferable during a measurement in fluorescence.

The image 40 acquired by the optical detector 6 is then routed to the image processing means 12 in order to be analyzed there. The determination means 13 allow processing of the data generated by the image processing means 12 in order to provide information or information concerning one or more analytes present in a sample. For example if an analyte is present or absent from a sample. This information concerning 20 analytes is transmitted to a user by the transmission means 19. Selection means 27 allowing a user to select the analytes which he wishes to determine the presence of (in proportions exceeding the standards in force in the area of application of solid supports 2) or the quantity in a sample. There can be several modes in order to make a selection of the analytes to be determined. For example, an administrator of the optical reader 1 of the invention can make a standard selection which will be used during each reading of solid support 2. For example, the selection can be made à la carte, that is to say that before the start of each reading of solid support 2, user selects the 3ù analytes of which he wishes to know the presence and or the quantity in the sample he wishes to test. Preferably the communication means 8 send to the selection means 27, information concerning the analytes which it is possible to detect with the solid support 2 inserted in the

BE2017 / 5707 optical reader 1. Thus the user can make a choice, only from the enelytes that it is possible to analyze the solid support 2 inserted in the reader 1 and not from a generic list of analyte whose user does not know if it would be possible to obtain any result. When the selection 5 of the user is made, this selection is communicated by the selection means 27 to the determination means 13. The determination means 13 then determine for each selected analyte, an intensity of sub-set or of point of interest 41 corresponding to the selected analytes. From a clear intensity of sub-sensemby and thanks to the data 10 communicated by the communication means 8 concerning a threshold value or a calibration curve for each of the points of interest 41, the determination means 13 send to the transmission means 19 , results relating to the detection and or quantification of the selected analytes when a selection has been made or of all the analytes whose solid support 2 allows detection or quantification when no selection has been made. A pivot value is for example a value specified by a standard designating a quantity from which it is possible to judge whether an analyte is present in quantities acceptable by the standard or not acceptable.

G [6092] Figures 1b and 1d also show a feedback control 11, connected to a light intensity detector 5. for example a photodiode sensitive in the wavelength range emitted by a light source 3. This means of feedback 11 makes it possible to supply the light source 3 with an electrical signal so that the location 20 for receiving the

5 solid support 2 is to illuminate with a chosen target intensity and for example constant whatever the conditions external to the device 1 of the invention. For example, the feedback control 11 allows regulation of the light intensity.

Communication means 8 connected to the processing means

Image G 12 and the determination means 13. The communication means allow access to a method database which can be computerized and stored on a server, stored in a memory internal or external to the optical drive of the invention, for example a usb stick, a CD, a

BE2017 / 5707

non-volatile memory. The database can also be non-computerized and presented in paper form and readable by the optical reader in the form of a bar code, datamatrix, QR code. For example, the optical reader 25 of the invention can read the data from the non-computerized database thanks to an optical reader external to the device. For example, the identification device 25 described in FIG. 1c and Fig. 1d allows the reading of data from the non-computerized database. From the data obtained from the database (computerized or non-computerized), your means of communication 8 can transmit to the image inclination means 12 data relating to replacement of points or lines of interest. Preferably, the position of the points or lines of interest is given relative to points or reference zones. For example, the communication means 8 can send to the optical unit 7 information relating to the type of light source 3, 4, the intensity of the light source required, the exposure time for acquiring an image. allowing the detection and or the quantification of analytes present in a sample.

The communication means 8 are also configured to transmit data from the database to the determination means 13. These data allow in particular to give a correspondence between the points 41 or the identified lines of interest and extracting by the image processing means 12, information concerning an anayte to be determined or quantified. For example, the image processing means 12 assign to each point 41 or line present on the solid support 2 a position, for example coordinates in a Cartesian coordinate system with respect to reference points or zones 45. The determination means 13 then allow for each of the points 41 or lines present or supposed to be present to assign them a name of anaiyte. The data from the communication means 8 and transmitted to the determination means 13 also include information relating to threshold values, for example specified by one or more standards, from which an anayte is considered to be present in too large a quantity or present in acceptable proportions or vice versa. This data includes for example calibration curves allowing a quantitative analysis of a

BE2017 / 5707 analyte. Preferably, for each point 41 or line of interest, there is a calibration curve making it possible to give a concentration of the analyte in the sample and corresponding to a point of interest 41.

The information relating to a solid support is for example transmitted to the image processing means 12 so that they have information relating to a number of point of interest or to a preferred positioning of these points of interest or even corrections allowing a comparison of the different batches with each other in order to carry out a quantitative measurement of the analytes present in a sample. The transmission means 19 are preferably connected to the communication means

8.

[0006] FIG. 1b shows an embodiment according to the invention based on FIG. the and further comprising feedback means 11 for ensuring controlled illumination of the solid support 2. The photodiode 5 is positioned so that it receives a light flux generated by the light source 3, 4 representative of the light intensity directed towards replacement 20 and or the solid support 2.

[0097] FIG. 1c shows an embodiment according to the invention comprising an identification device 25 allowing the reading of an identifier 20 present on the solid support 2. An identifier is for example a bar code, a data matrix or a QR code, in this case the identification device 25 is an optical code reader known to those skilled in the art. An identifier is for example an RFID chip, in this case the identification device 25 is a near-field reader known to those skilled in the art. The identification device 25 when it has acquired information from the identifier present on the solid support 2, sends to the communication means 8 the information relating to the solid support inserted in the optical reader 1. From of this information, the means of communication can acquire from a database, information specific to the solid support 2 inserted 30 or to the batch to which the solid support 2 inserted belongs, In the absence of an identification device 25, it is possible to manually indicate to the communication means an identifier relating to the solid support 2 inserted, for example

BE2017 / 5707 with a forceps connected to the optical drive 1 or with the touch screen which equips the optical drive 1.

In Fig. 1d, the optical reader incorporates an identification device 25, selection means 27, communication means 8 and a device 5 for identification 25 of the solid support 2 combining the same advantages and functions as described in FIGS. 1a - Fig 1, c.

It is also possible to position in the embodiments presented in Figs. 1a to 1d, a second light source 4 as shown in FIG. 2a and Fig. 2b. In the case of the presence of 10 feedback means 11, the second light source 4 is connected to these feedback means 11 so that the intensity of the second light source 4 can be controlled as described for the intensity of the first light source 3.

The optical reader 1 according to the invention preferably has a first 3 and a second 4 light source as illustrated in FIG. 2a and

Fig. 2b. Preferably, the first light source 3 is intended to perform a reading / measurement in fluorescence of the solid support 2. Preferably, the second light source 4 is intended to perform a reading / measurement in reflection of the solid support 2 for the detection and / or the quantification of analytes. 2Q The presence of the double band pass filter 10 makes it possible to use the same optical detector 6 for a fluorescence measurement or for a reflection measurement. Preferably the first 3 and second 4 light sources are used one after the other for the measurement of the same solid support 2 in a variable order. More preferably, a single light source is / o used for the detection and or the quantification of analytes present in a sample by the optical reading of a solid support 2.

An image 40 acquired by the detector 6 is then sent to the image processing means 12. The image processing means 12 allow the image processing steps detailed below. Preferably, these steps are used according to a method chosen manually by an operator or automatically by recognition of the strip to be measured by the optical reader and in particular by an identification device.

BE2017 / 5707 [0182] Preprocessing ~ Cropping the image [0103] The step of cropping the image 40 into a cropped image 42 makes it possible to select within the original image 40 a rectangular region of interest comprising areas of the strip to be analyzed more specific and comprising 5 bottom areas or areas unrelated to the solid support 2 to be read. The areas of the image 4Û which are unnecessary for future analysis are thus eliminated from the cropped image 42. The reloading of the image 40 is an optional step.

The region of interest of the cropped image 42 is defined from the image 40 (defined by pixels according to Cartesian coordinates) by x and y coordinates in pixels of the upper left end of the rectangular region of interest, its width in pixels and its height in pixels.

[0105] Preprocessing “Uniformity Correction [0106] The aim is to preprocess the image 40 or the cropped image 42 and more particularly the uniformity correction is to correct the non-uniformity of the lighting at within the region of interest so that it does not impact future analyzes of the solid support 2. This uniformity correction may or may not be activated by the image processing means 2. The correction of the uniformity of the lighting is for example produced from a file 20 comprising a model (or calibration) image, for example from a solid support which has not yet been subjected to the sample to be characterized or from a support solid not comprising a point or band supporting labeling molecules. This model image is for example recorded in a memory of the optical reader 1 accessible by the image processing means 2.

In the absence of a Model Image, a self-caiibration is performed. Auto-calibration consists in creating a synthetic image (a model) for uniformity correction, used in place of the model image, by applying two consecutive median filters to the region of original interest. These filters, by replacing the value of each pixel of the image by the median value of the pixels located in a neighborhood of defined size, make it possible to obtain a smeared, less noisy version of the image 40 (elimination of outliers) while respecting the contrast of the image.

BE2017 / 5707 [0108] Mittete point detection [01 OB] This step aims to detect the position of the dots present on the rod. To do this, a square detection window (with a side equal to two fors the radius of a point) first scans the entire analyzed image 40, 42 in search of areas potentially corresponding to points namely the brightest areas in the image surrounded by dark areas (areas contrasted with respect to a background area), [0110] At each position of the window, the average of the values of the pixels within a circle of radius defined in the center of the window, is calculated, 1 0 This is then compared to the average of the pixels included in an outer ring, surrounding the radius circle. If the difference between the two means is greater than a certain threshold (empirically fixed), the center of the scanning window is considered to belong to an area potentially corresponding to a dowry. By scanning the entire image, a binary mask specifying the potential dowry areas is thus created.

In a second step, the circles are detected within the binary image obtained during the first) detection phase. Among your detected circles, there are in particular the points of the grid but also “false points” due in particular to the appearance of the edges of the solid support 2 20 within ia ROI defined by the user. To eliminate false points within the binary mask and keep only the circles corresponding to the points of the grid, theoretical replacement of the grid within image 40, 42 is used.

The theoretical location of the grid is determined on the basis of the coordinates "xi", "y1" (top left) and "xn", "ym" (bottom right) which define the position of the points of the grid at the top left and bottom right. Given the difference between the actual position of the point grid and the theoretical position specified by the reading method or by the image processing means 12, the theoretical coordinates along the y axis "yl" and "ym" are corrected on the basis of the automatic detection of the solid support 2 within the wide ROI defined by the operator. This detection is enabled by knowing the height of the solid support specified by the reading method or by the image processing means 12.

BE2017 / 5707 [0113] The theoretical location of the revised grid is then used to define a subregion of interest completely included within the solid support, within which the detected circles are kept (because considered as belonging to the grid of points) and outside of which your detected circles are considered as false point detections and are therefore eliminated. After eliminating the bad detections, a binary mask specifying the positions initially estimated of the grid points is obtained.

Fitting grid on visible dots [0115] This step aims to match an initial grid pattern of dots on your dots detected within the region of interest in order to subsequently optimize the estimated positions of the dots and allow their measured. A rectangle surrounding all the dots detected initially (and not eliminated) is first calculated.

[Ö116] The upper left corner or the upper left corner "x1", "y1" of the rectangle obtained makes it possible to determine the location observed in practice (and no longer theoretical) of the first point of the initial grid (above at left). With the help of parameters specifying respectively the number of dots present on the rod in X and in Y, the defined rectangle also makes it possible to determine the angle formed by the grid of points with the horizontal but also to calculate the space between points observed in practice according to X and Y. Indeed, the space between points according to x (y) is determined as the ratio between the height (width) of the calculated rectangle and parameters specifying respectively the number of dots present on the solid support 2 in X and in Y. This space between dots "practical" is average with the theoretical inter point space 2û (determined in turn on the basis of the parameters "x1", "y1", "xn", "ym" and values of the parameters specifying respectively the number of dots present on the rod in X and in Y. This average is carried out with the aim of countering the effect of an excessive potential widening of the space inter points "practical", widened sly observed when a point is not more aligned with respect to the points located on the same line.

An initial grid pattern can be defined from a top left corner of the grid, the angle that the grid forms with the horizontal, the spacing between points and the number of known points specified by a

BE2017 / 5707 method specific to each solid support 2. The search for correspondences between the detected points and the points of the grid pattern initiai is then initiated by the image processing means 12. The matches found are then used to calculate a geometric transformation (homography) which is applied to the theoretical grid so that it adapts more to the points of the solid support 2 and this in order to obtain a theacon grid. The theoretical grid already adapts to most visible points but some still need to be optimized such as points that are not well aligned with others.

Local optimization of the dots [0119] So that each dot is centered on a measurement point, a local optimization of the position of each point of the theoretical grid is carried out. This provides a reliable measure of points that are misaligned with respect to the others. The badly aligned points are for example due to a bad alignment of the means of production of the points on the solid support 2. The number of iterations of the local optimization of position is defined by a parameter of number of iterations of local optimization of position. If the latter is zero, no optimization is performed.

For each theoretical point, an analysis window (side equal to twice the external radius of the background measurement ring (background) of a dot in pixels scans an area of interest defined around the point At each position of the window, a measurement of the signal / background ratio is calculated, which is defined as the difference between the average of the pixel values within a circle of radius in pixels of the signal area containing the point defined in the center of the window, and the average of the pixels included in an outer ring, surrounding the radius circle in pixels of the signal area containing the point. The internal radius parameters of the background measurement ring (background ) of a point in pixels and of the external radius of the background measurement ring of a point in pixels represent respectively the internal radius and the external radius of this measurement ring of the background. du dut is changed so rte to correspond to the position of the analysis window with the best signal / background ratio.

BE2017 / 5707 [0121] Measurement of the dots [0122] At each measurement point, a measurement of the useful signal is carried out, namely the average pixel intensity within a circle of radius equal to the measurement radius parameter in pixels of the signal area containing the point to be measured. The measurement of the background intensity is also measured by considering the average intensity of the pixels of the image within an outer ring at the point of internal radius of the measurement ring of the background in pixels and of external radius of the background measurement ring in pixels. The raw measurements of the points are obtained by making the difference between the measurement of the signal and the background and by multiplying this difference by the number of pixels within the radius circle of the signal area containing the point in pixels.

[0124] Figs. 2a and Fig. 2b show for example a preferred embodiment of the invention comprising a waterproof casing 16 having a protection index IP54 according to standard IEC 60529 consulted in September 2017. The casing is notably waterproof and dustproof. The receiving part of the solid support 2 and comprising the location 20 is in particular sealed from the optical and electronic parts by means of a protective glass. This protective glass is for example shown in FIG. 1a to

Fig. 1d and Fig. 2a to Fig. 2b so as to describe a non-right angle between its surface and a light beam coming from the solid support 2 in the direction of the optical detector 6, in order to limit the reflection of light beams emitted by the solid support 2. In order to limit heating in the enclosure of the reading device 1, cooling means 15 allow a

5 heat transfer generated by the electronic and optical components to the outside of the sealed enclosure 16. The cooling means allow heat to be collected from the most heat-emitting components such as microprocessors and ensure the transfer of this heat to the outside of the sealed enclosure. Preferably the heat is then dissipated to the outside passively using a metal radiator. Preferably, the transfer between the heat emitting components and the radiator sllue outside the sealed enclosure is carried out by a heat pipe.

BE2017 / 5707 [0125] Communication means 8 are preferably installed in the optical reader 1 according to the invention in order to be able to acquire a method suitable for reading a solid support. The communication means 8 also allow the communication of the results from the transmission means. The results can be communicated qualitatively or quantitatively to a display, printing, electronic messaging, or analog or digital recording device. The communication means 8 make it possible, for example, to access a method specific to each batch of solid support 2. A method database is for example accessible via a network of the internet or local type, from a memory do non-volatile type, from printed elements such as barcode, QR code or data-matrix. The printed elements are for example read by suitable optical reading means known to those skilled in the art.

[0126] Figs. 3a and 3b show an image 40 acquired by the optical detector on which there appear reference points 45 and points of interest 41.

The points of interest correspond to the locations on which the labeling molecules are immobilized. Each point corresponds to a predetermined analyte to be measured. For example, the points of interest are aligned during the acquisition of the image, for example they are aligned in the same direction, for example they are distributed in a two-dimensional space. An image 40 can be cropped by the image processing means into a cropped image 42 as shown in FIG. 3a or 3b.

[0127] Figure 4 shows a three-dimensional view of an exemplary embodiment of the reading device 1 of the invention. The device 1 has an external surface 16 from which projects a cooling device 15 located on the rear of the device 1. A location 20 taking the form of a drawer allows the positioning of a mobile solid support 2 in the device 1. The device is equipped with display means allowing, for example, data entry by means of a touch screen. A gripping means is integrated into the device in order to guarantee optimal mobility. Wireless connection means allow the device 1 to be integrated into any working environment and has batteries in order to benefit from a

BE2017 / 5707 sufficient autonomy to perform a sufficient number of sample readings on a working day for example.

[0128] In summary, the invention can also be described as follows.

Device 1 for optical reading of a removable support 2 for the detection and / or quantification of analytes present in a sample comprising communication means 8 for obtaining information relating to a support 2; selection means 27 for selecting from a list of predefined analytes, a selection of analytes to be detected and / or quantified; an optical unit 7, for analyzing said support 2 on the basis of analysis parameters 10 included in said information relating to a support 2; image processing means 12; determination means 13 for determining analyte information on the basis of the information relating to the support 2 and data from the image processing means 12; and transmission means for transmitting the analyte information.

Claims (27)

claims 1. Device (1) for optical reading of a removable solid support (2) for the detection and / or quantification of analytes present in a sample and comprising: - a location (20) for receiving said solid support (2); - an optical unit (7) for analyzing said solid support (2) and comprising: o a first light source (3) for emitting according to an emission intensity and in a first wavelength range a first light beam towards said location (20); o an imaging system (60) comprising an optical detector (6) for providing an image (40) of a viewing area, said viewing area comprising at least a portion of said location (20); o a filter (10) for filtering a defined wavelength range, and positioned between the location (20) and said imaging system (60); - communication means (8) for obtaining information relating to a solid support (2); selection means (27) for: o select from a list of predefined analytes, a selection of analytes to detect and / or quantify; - image processing means (12) of said image (40) for: o determine, from the information relating to said solid support (2) to be read, a finite number of subsets (41) of said image (40), each subset (41) corresponding to an anayte; g providing data relating to light intensities from said sub-assemblies (41); - determination means (13) for; BE2017 / 5707 o calculate, for each subset (41) corresponding to an analyte selected in said selection of analytes, a subset intensity; o determining on the basis of said subset intensity 5 analyte information for each subset (41) corresponding to an analyte selected from said selection of analytes; - transmission means (19) configured to transmit said analyte information for each subset (41) corresponding to an analyte selected from said selection of analytes. 2, Device (1) according to the preceding claim, characterized in that it further comprises: - a credit counter (18), said credit counter (18) being 15 increments during the selection of each analyte to be detected and / or quantified by the selection means (27). 3, Device (1) according to any one of the preceding claims, characterized in that it comprises, in addition: 20 encryption and recording means (14) for recording said image (40) on the basis of a defined encryption. 4. Device (1) according to any one of the preceding claims, characterized in that it further comprises: 25 an identification device (25) for identifying a solid support (2) to be read; and in that the communication means (8) are configured to obtain information relating to said solid support (2) identified by said identification device (25), 5. Device (1) according to the preceding claim characterized in that said list of predefined analytes is included in said information relating to a solid support (2). BE2017 / 5707 6. Device (1) according to any one of the preceding claims, characterized in that said image processing means (12) are further configured for: 5 o detecting reference areas (45) of said image (40), o positioning in said image (40) each sub-assembly (41) at a position determined from said reference areas (45). .1.0 7. Device (1) according to any one of the preceding claims when it depends on claim 4 characterized in that the determination means (13) are configured for: o determine on the basis of said subset intensity and on the basis of the information relating to said solid support (2) to be read, the said analyte information for each subset (41) corresponding to an analyte selected in said selection of analytes, 8. Device (1) according to any one of the preceding claims, characterized in that said optical unit (7) further comprises: o a light intensity sensor (5) for measuring the emission intensity emitted by said first light source (3); a feedback control means (11) for modulating said emission intensity of said first light source (3) as a function / 5 of the emission intensity measured by said light intensity sensor (5) so that said first light source (3) emits a target intensity. 9. Device (1) according to any one of the preceding claims Characterized in that said optical detector (6) is a two-dimensional optical detector for providing a two-dimensional image (40) of said viewing area and in that said image processing means (12) is configured for processing said two-dimensional image (40). BE2017 / 5707 10. Device (1) according to any one of the preceding claims, characterized in that iadite anaiyte information is determined on the basis of at least two subset intensities originating from at least two 5 subset (41 ). 11. Device (1) according to any one of the preceding claims, characterized in that said finite number of subsets (41) is greater than or equal to six subsets (41), preferably more than ten sub-assemblies (41) and even more preferably more than fifteen sub-assemblies (41). 12. 13. Device (1) according to any one of the preceding claims, characterized in that the said subassemblies (41) have a rounded shape and preferably have the shape of a disc. Device (1) according to any one of the preceding claims when it depends on claim 9 characterized in that said two-dimensional image (40) comprises areas contrasted with respect to a background area, and in that, the means for image processing (12) of the two-dimensional image (40) also make it possible to: - crop said two-dimensional image (40) into a cropped image (42), said cropped image (42) showing a larger portion of said location (20) for receiving a solid support (2) than in said two-dimensional image ( 40): assign a defined surface for each position to two sub-assembly dimensions (41) in said cropped image (42): performing a local position optimization of each subset (41) so that said defined surface of each subset (41) is positioned so as to return a maximum light intensity of each of said contrasted zones. Device (1) according to any one of the preceding claims when it depends on claim 4 characterized in that said 14. .5 • 43 information relating to a solid support (2) to be read includes information corresponding to each of said sub-assemblies (41). 15. Device (1) according to any one of the preceding claims 5- characterized in that said analyte information is binary type information. 16. Device (1) according to any one of claims 1 to 14 characterized in that said analyte information is information proportional to lü said measured light intensity. 17. Device (1) according to any one of the preceding claims, characterized in that it is compact and hermetic. 15 18. Device (1) according to any one of the preceding claims, characterized in that it further comprises: - an external surface (16); - cooling means (15) for transferring a quantity of heat from the interior of said device (1) to said external surface 20 .............. (ie). ........; t ^: ƒ lllll 19. Device (1) according to the preceding claim characterized in that the cooling means comprise a heat pipe. 25 20. Device (1) according to any one of the preceding claims, characterized in that it further comprises a second light source (4) configured to emit a second light beam (40) in a second wavelength range. 30 21. Device (1) according to any one of the preceding claims, characterized in that said first length range is distinct from said second wavelength range. 22. Device (1) according to any one of the preceding claims 35 characterized in that said filter (10) is a double band pass filter for BE2017 / 5707 BE2017 / 5707 pass two defined wavelength ranges, one of the two ranges of which is said first wavelength range or said second wavelength range. 5 23. Device (1) according to any one of the preceding claims, characterized in that said identification device (25) of the solid support (2) is a data matrix, barcode or QR code reader. 24. Diagnostic assembly for the optical reading of a recovery system 10 comprising: - said device (1) according to any one of the preceding claims; - a diagnostic means for the respective, simultaneous and specific detection and / or quantification of a plurality of analytes present 15 in a sample (E) comprising at least one reaction mixture and at least one recovery system (2), said at least one recovery system (2) being in the form of a solid support (2) to which are attached in distinct and known recovery locations in space, of competitive ligands and / or biological molecules: recognition, so as to identify, by location of said recovery locations on said support, said analytes present in said sample, said means of diagnostic being characterized in that said recovery system (2) comprises recovery locations which are arranged in a two-dimensional matrix arrangement which is defined according to a known and specific coordinate system of said competing ligands and / or said biological recognition molecules fixed said recovery locations for said recovery system (2). 25. diagnostic assembly according to the preceding claim characterized in that said recovery locations are arranged in a two-dimensional matrix arrangement in the form of points BE2017 / 5707 each having a diameter between 20 μm to 2 mm, preferably between 100 to 500 μm and even more preferably between 250 μm and 400 μm. 5 26. Diagnostic assembly according to any one of the two preceding claims, characterized in that said coordinate system has a first coordinate defined on a longitudinal axis of a length of said recuperator system and a second coordinate defined on a longitudinal axis of a width of said recovery system. 27. Diagnostic assembly according to any one of the three preceding claims, characterized in that said recovery system (2) comprises at least five, preferably at least ten, and more preferably at least fifteen separate recovery locations intended for detection. and / or the respective simultaneous and specific quantification of at least five, preferably at least ten, more preferably at least fifteen anaytes of distinct classes present in a sample and whether or not belonging to different families of analytes , and at least one recovery location intended for a control and / or a calibrator.