BE1025622A1 - Matrix optical reading device of 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 solid support (2) for the detection and / or quantification of analytes present in a sample comprising an optical unit (7) for analyzing the solid support (2) in two dimensions; image processing means (12) for analyzing a two-dimensional image (40) of the solid support (2) in two dimensions; determining means (13) for determining analyte information on the basis of the data of the image processing means (12); and transmission means configured to transmit the analyte information.

Description

Dispositsf hangings optical matrtetelte d ^f a removable solid support to thee detection and / or you quantifying analytes present in a sample

Technical fields According to a first aspect, the invention relates to a device for the optical reading of a solid support for the detection and / or 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 dc-3 diagnostic means.

State of the Technical [0002] The surveillance and control of food products means that tests must be carried out as far upstream as possible from 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 their 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 specific analyte present in said sample. The detection of analytes can at least be carried out with a strip (immunochromalographic support) which is immersed in a flask containing the reaction mixture. The strip generally comprises several zones often called line or point of detection corresponding to different analytes to be detected. or to be 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 / 5706 [0004] An analyte to be detected is therefore often highlighted by a line or dots on the tag. The change in color or light intensity of the signal reflected by the line or the point in connection with the analyte to be detected is the most common method (reflectometry). Molecules 5 coupled to a fluorophore (or to an active molecule which can generate / modify 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 the different lines or points positioned on a rod.

It is already known from the state of the art optical reader to carry out a diagnosis concerning the presence and or the amount of analytes present on a test strip previously dipped in a fluid to be tested. However, optical readers current do not allow the optical reading of a large number of regions of interest present on a strip. This limitation of reading the number of regions of interest requires for example to carry out several consecutive measurements with different types of tabs and / or the use of different optical readers adapted to each of the tabs to be tested.

Summary of the invention [0006] According to a first aspect, one of the aims of the present invention is to provide an optical reading device for a removable solid support for the detection and / or quantification of analytes present in a sample and allowing a simultaneous reading of a large number of zones to be tested (or dots). The present invention makes it possible to deliver a qualitative and possibly quantitative result of each of the zones to be tested.

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

BE2017 / 5706

- a location for receiving said solid support;

an optical unit for analyzing said solid support and comprising:

o a first light source for emitting according to an emission intensity and in a first wavelength range a first light beam towards said location;

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

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

- image processing means of said two-dimensional image for:

o detecting reference areas of said two-dimensional image, o determining a finite number of subsets of said two-dimensional image, o positioning in said two-dimensional image each subset at a predetermined position relative to said 20 areas of reference, o provide data relating to light intensities from said subsets;

- means of determination for:

o calculate, for each subset, an intensity of sub25: set, and

- Transmission means configured to transmit said subset intensity for each subset.

The device according to the invention allows the simultaneous reading of a large number of dots thanks to a two-dimensional optical detector and to image processing and determination means making it possible to read information from anaiytes for each of the dowries.

The two-dimensional image includes subset, portions, regions of interest, areas of interest or even parts

BE2017 / 5706 of images. Preferably, your subset of a two-dimensional image comprises 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.

The advantage of the device according to the invention is to be able to carry out a diagnosis by a continuous fluorescence reading while eliminating a maximum of the background noise generated by the light source.

The advantage of the optical reading device of the invention is to allow the optical reading of a large number of regions of interest present on 10 a single strip. 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 to analyze a large number of regions of interest on a tigette precisely. In the case of the optical device of the invention, the reading of 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 pins 20 introduced into the optical reader.

Preferably, the device according to the invention allows the reading of locations (recovery) or dots fixed on a solid support (or recovery system) according to an arrangement, preferably two-dimensional matrix sc-us the form of points each having a diameter 25 of 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 according to the invention allows ia good 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 30 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 10, and even more preferably at least 15 recovery locations in simpiicat, duplicate, tripiicate or more for detection and / or

BE2017 / 5706 the quantification of 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 deposited in simpiicat, in duplicate, triplicate or more intended for positive control. of the detection threshold making it possible to validate the test and / or to ia calibration for detection and / or quantification, and this on a recovery system having a reasonable size and of the order of a square centimeter, for carrying out the detection and / or the quantification of said at least 15 analytes by the optical reading device of the invention. The device according to the invention makes it possible 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. Preferably, the sign interpreted by the determination means can have an absolute intensity (arbitrary unit) or have a relative intensity with respect to an Intensity emitted by a reference point or by an internal control point emitting a reference intensity.

The analytes that can be detected and or quantified sc-nt, for example chemical contaminants, proteins or pathogens. The 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 ...

Preferably, the identification device is positioned at said location to identify a solid support to read positioned in said location. The means of communication also feels means of reading, for example for reading data on a solid removable 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 support, solid according to the invention is for example a telegette.

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

BE2017 / 5706 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.

you [0017] Preferably, the transmission means are configured to transmit or communicate the anaiyte information for each subset to a memory. Preferably, your means of transmission make it possible to transmit information from anaiyte to a display device included in the optical reading device according to the invention.

An advantage of the device according to the invention is that it can receive a solid support such as, for example, an immunochromatographic type strip (with or without a cassette) or an identical microfluid chip.

For example, a kit includes 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 makes it possible to maintain the reaction mixture 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.

Preferably, the two-dimensional image includes 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;

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

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

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

read 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.

An advantage of being able to read more than five subsets, preferably more than ten subsets and of) 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.

[G023] 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 1 illuminates the regions of interest of a strip positioned in the location of the reader. Labeling molecules present or not at the regions of interest, allow or not an absorption, or a lesser reflection of the region of interest illuminated by said second light source. The optical unit then allows 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 more or less dark areas of interest relative to the splitting zone of the tigette.

ΒΕ2017 / 5706 [G025] For example, fluorescent and or reflection-modifying labeling molecules can be used, which requires reading in fluorescence and reading in reflected light. The two readings are for example executed one after the other in a predefined or non-predefined order. A band pass 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 marking molecules modifying the reflection to pass to the optical detection unit. Indeed, this increases the contrast by removing background noise due to the wavelengths emitted by the light source but not absorbed by the labeling molecules. 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 allows the reading of labeling molecules which can return a signal by fluorescence and of labeling molecules which can modify the reflection of light on the removable solid support.

Preferably, If) 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 wavelength range, therefore requiring no physical change of band pass filter during analyzes.

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

B E2017 / 5706 double band pass filter is used in the case of an optical reader allowing a reading of the labeling molecules in reflection and in fluorescence.

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

An advantage of achieving an average is to smooth any disturbances in the reading of the removable solid support. Even more preferably, an average is obtained on the basis of three subset intensities from at least three subsets, [0033] Preferably, the analyte information is binary type information.

Binary type analyte information is qualitative analyte information. For example, the analyte information makes it possible to indicate a positive presence or a negative presence of an analyte. For example, the determination system, on the basis of a pivot intensity or threshold intensity or 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 analyte. The determination means indicate for example for a subset intensity lower than a threshold subset intensity, the presence of a positive analyte. For example, Analyte Information is included in the memory of the device of the invention and does not require extracting this Analyte Information from information relating to the medium. Preferably, a threshold intensity is defined by the user according to the regulations specific to a territory.

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

[9036] An advantage of an analyte information proportional to the measured light intensity is to be able to carry out a quantitative analysis of analytes in a sample. Preferably, the analyte information is

B E2017 / 5706 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 chosen analyte.

Preferably, the optical unit further comprises:

o a light intensity sensor for measuring the intensity S of emission 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 10 emits a target intensity.

An advantage of this preferred embodiment 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 simultaneous reading of '' a large number of areas to

1.5 test (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 for each of the zones to be tested.

When a fluorescence technique or a reflected light technique is used to read the areas to be tested (or points), a feedback control means 20 is for example used 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 also 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 notably guarantees reliable quantitative results. The feedback means is preferably an electronic feedback means.

The feedback means make it possible to define, for example .30 a target emission intensity of a light source. An intensity sensor 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 controls allow for example to define the

BE2017 / 5706 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 to the feedback means is too low compared to the target intensity, the feedback means allow an increase in the voltage 5 or in the 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 controls allow regulation of the light intensity emitted so that the light source operates at a target light intensity read, 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 20 with a continuous fluorescence technique and to be able to read a signal qualitatively and / or quantitatively. Another advantage of being able to produce a light with a target light intensity is to be able to ensure better consistency and comparison of the results from one device 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.

Preferably, the device further comprises:

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

communications means for obtaining information relating to a solid support to be read.

[O042] An advantage that the optical reader of the invention includes 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. it

BE2017 / 5706 saves time and avoids the risk of error compared to a manual choice of method. A reading method includes information specific to the solid support to be read, and in particular allowing 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 analyte.

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 of 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 conceivable 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 CTRL, cut-off ratio (specific POS / NEG decision threshold depending on the batch and the point on the tigette.

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

Preferably, the determination means are configured to determine, on the basis of the intensity of the subset and on the basis of the information relating to the solid support to be read, analyte information for each sub -together.

[0647] Preferably, one of the advantages of the preferred embodiment of the invention is to provide an optical reading device for a removable solid support for the detection and / or quantification of old ytes present in a sample with an automatic choice of the method to be applied to the sample from a method database. The present embodiment of the invention further allows automatic correction related to the variation of

BE2017 / 5706 lots of removable solid support for each dots allowing the detection or quantification of analytes.

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 method version, a batch number, a deadline for using a batch, ie type of light source used, ie type of area of interest (line or point), method 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 coordinates Cartesian), a number of areas of interest, a number of replies per analyte, the matrix organization of the areas of interest on the mobile solid support, the dimensions of the areas of interest (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 anaiyte that 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 for identifying a solid support to be read. For example, the identification device is a bar code, QR code, datamatrix or similar reader allowing, from a code written on a solid support, to have information relating to the solid support. Preferably, on the basis of information relating to the solid support 25 contained by a marking present on a solid support, the optical reader of the invention allows, thanks to the communication means, to consult a method database in order to access (A method corresponding to the solid support 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 a method database in printed format, for example the database is distributed over several sheets, the method corresponding to the solid support being acquired by reading the sheet

ΒΕ2017 / 5706 corresponding to the desired method. 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 read is indeed the method corresponding to a solid support to read.

The) optical reading device according to this embodiment of the invention makes it possible, from a two-dimensional image supplied by the optical detector, to determine a number of subsets to be analyzed from the information contained in the method chosen thanks to the identification device. This allows a better localization of the areas of interest on the solid support to be read. When the sub-assemblies are positioned at the areas of interest of the figette, 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 information from anaiytes contained in the method. For example, this information of anaiytes is a calibration curve making it possible to determine quantitative information of an analyte. For example, anaiyte information is a threshold intensity for an area of interest and therefore for an analyte, threshold intensity from which an anayte 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 tabs 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 re-use of a tlgette already used. Indeed, there is a risk of reuse of a telegette having already been used for the analysis of a first sample and which cannot be reused for an analysis of a second sample. Thus, the device of the invention makes it possible to check in a mobile solid support database, via the communication means, whether the mobile solid support inserted in the optical reader has not yet been used. If this is the first use of the mobile solid support, optical scanning can start, if it is a

BE2017 / 5706 second use (or more) the optical reading does not start and the user is warned that the mobile solid support 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 bar code 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 the 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.

2ü This advantage of this embodiment of the invention, of being able to access a method which does not limit the number of anaiyte which can be tested by a solid support allows the use of tigeties 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 analytes to be tested. In addition, the presence of information relating to the analytes 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 method information relating to each anaiyte and to 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, a quality follow-up reveals an anomaly that does not allow a correct reading of an anayt result. In case the marking on the solid support should be printed directly on the solid support, this

BE2017 / 5706 should be done separately from the areas of interest of the solid support or else should not contain information relating to the specificity of the batch during production.

Preferably, said image processing means are configured for:

o determine, from information relating to said solid support to be read, a finite number of subsets of said two-dimensional image, o position in said two-dimensional image each subset 10 together at a predetermined position from said information relating to said solid support with respect to said reference zones.

Preferably, the device further comprises:

- selection means for:

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

in that the image processing means are configured for:

o determine the finite number of subset of the two-dimensional image from the information relating to the solid support to be read, each subset corresponding to an analyte;

in that the determination means are configured for:

o calculate the intensity of the subset for each subset corresponding to an analyte selected in the selection of analytes:

o determine on the basis of the subset intensity analyte information for each subset corresponding to an analyte selected in the selection of analytes;

and in that the transmission means are configured to transmit the analyte information for each subset corresponding to an analyte selected in the selection of analytes.

An advantage of this preferred embodiment of the present invention is to provide an optical reading device of a removable solid support for the detection and / or quantification of analytes present in a .JL · sample and allowing the selection of the analytes to be tested without requiring the use of several types of removable solid supports. Another advantage of this is to allow a selection of analytes from a pre-established list for which an operator wishes to test the presence or obtain a quantification of said analytes.

Another advantage of this preferred embodiment is to allow the areas to be tested to be read, 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 strip, the device offers, by means of access to a method containing information relating to a strip, a selection from a list of 'analytes to be tested. It is indeed advantageous to make a selection of the analytes to be tested before obtaining the results in order to properly target the analytes for 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 need them exposes him to the risk of losing objectivity compared to his initial analysis intention. It is also economically interesting for the user to pay only for the results they really need. For the producer and or the distributor, it is advantageous to have a unique industrial process allowing a simplification of the manufacturing process as well as a simplification of inventory management. Thus, the device 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.

Another advantage of this preferred embodiment is 3 ü allow) an optical reading based on an optical signal (fluorescence or reflectometry) of areas comprising information relating to the analytes to be tested. In addition, this optical reader allows a selection of the analytes to be tested from a single strip, that is to say not requiring positioning

BE2017 / 5706

BE2017 / 5706 of one or more different tabs in a cassette, the cassette then being inserted in the reader. Several tabs can also be inserted directly into an optical reader. Furthermore, 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 this preferred embodiment for carrying 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 ia contacting of each of these strips with the product to be tested and then read 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 avoids significant manipulation of the test strips, which is costly in time and manages the 15 stocks. This also allows a simpler, faster and more targeted analysis of the analytes to be tested, by only having the results selected after reading the strip by the optical reader of the invention.

Preferably, the list of predefined analytes is included in Lû 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 device further comprises:

a credit counter, the credit counter being incremented during the selection of each analyte to be detected and / or quantified by your selection means.

For example, the credit counter allows a positive or negative increment, for example the credit counter is rechargeable and allows to block the image processing means and or the means of

BE2017 / 5706 determination and / or your means of transmitting data relating to the measuring rod when the credit balance is equal to zero or when the credit balance is not sufficient to carry out the analysis of all the analytes selected by the means of selection. 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 way is contained on a removable usb key or directly transferred to weoservice via an internet platform used for remote management of optical devices. For example, a deposit for a positive credit increment is accessible by means of a wireless connection. For example, the credit counter is a unit counter or "unit". For example, virtual credits (or units of use) are counted against the number of analyzes (tabs) and the number of channels (point or dot) selected. Credits can be recharged after payment.

Preferably, the determination means are configured for:

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

Preferably, the device further comprises:

encryption and recording means for recording the two-dimensional image on the basis of defined encryption.

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 analytes. The image used to determine the results concerning the analytes is for example transmitted to encryption means. The encryption means then enabling encryption of the data relating to the registered and unregistered analytes and the recording of this encrypted data. The advantage of recording encrypted data including the results of the unselected analytes makes it possible to have the results concerning the unselected analytes but to limit access to them to persons having

BE2017 / 5706 means of decryption capable of decrypting your data encrypted by means of encryption. For example, your encrypted data includes the two-dimensional image acquired by the optical detector as well as a method or information relating to the tested tag. To obtain results from the “non-selected channels”, activate the “channels” in question and perform an “existing image scan” to reveal the results of the initially non-selected points. 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 quantitative analysis when a first qualitative analysis had been carried out. This advantage of saving the image, preferably in encrypted form, makes it possible to ensure that it can only be read by a person having the rights to access it. During a re-analysis, in the case of analysis of anaiytes not previously detected or quantified, an incrementation of a credit counter is preferably possible.

Preferably, the information relating to a solid support to be read 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 subsets is that it is possible to indicate in the information relating to the solid support, essential characteristics such as the corresponding analytes to each of the sub-assemblies as well as for example calibration curves allowing a qualitative and quantitative measurement.

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 related to the production time of a batch from which the sample to be tested comes.

Preferably, the device further comprises:

BE2017 / 5706

- 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 a transfer of heat from the interior of the device to its external surface is to allow the transfer of heat without harming the sealing or the 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 it conveys the heat produced at any place inside the device towards the outside of the device while retaining a good seal.

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 analytes belonging to a family of analytes (for example antibiotics), but also of a greater number

5 high classes of analytes belonging to several families of analytes (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 analytes, preferably at least ten different classes of analytes, even more 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.

BE2017 / 5706 [0077] To this end, the inventors propose a diagnostic set for the optical reading of a recovery system comprising:

- The device according to the first aspect of the invention;

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

The variants and advantages mentioned for the first aspect of the invention apply to the diagnostic unit according to the second aspect, mutadls mutandis.

Indeed, it has been surprisingly demonstrated that a

2.5 diagnostic assembly comprising a diagnostic means which comprises a retrieval system having retrieval 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 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 different families of analytes, and this at least fifteen minutes. A diagnostic set with diagnostic means is therefore more

BE2017 / 5706 practical, more economical if more effective than the diagnostic means currently known which are generally limited to less than five different classes of anaiytes, typically only two or three different classes of anaiytes, these classes belonging to the same family of anaiytes 5 (for example antibiotics).

Preferably, said 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 10 included 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 the at least five, preferably at least ten, more preferably at least fifteen simpiicat, duplicate or triplicate recovery locations for the detection and / or quantification of at least five, preferably at least ten, more preferably of at least fifteen analytes of different classes, whether or not belonging to different families of anaiytes, as well as at least one recovery location deposited in simpiicat, duplicate or triplicate intended for positive control of the detection threshold making it possible to validate the test and / or calibration for detection and / or quantification, and this on a recovery system having a reasonable size and order of the square centimeter, for carrying out the detection and / or the quantification of at least thirteen analytes 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, of

BE2017 / 5706 preferably at least ten, more preferably at least fifteen analytes 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 monitoring 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. 1a, Fig. 1b, Fig. 1c, Fig. 1d and Fig. 1st 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.Sa and Fig.3b show an example of a two-dimensional image according to the invention;

- Fig.4 shows a 3D view of an embodiment according to the invention. 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, including when these numbers are indicated in your claims.

Detailed description of certain embodiments of the invention [8085] Figures la to 1e 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, u 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 drawer device. To carry out the optical reading of a solid support 2, replacement 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

BE2017 / 5706 location 20, these are preferably brought back inside the device 1 to carry out 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 in order to provide a two-dimensional image 40 of the solid support 2, a light source 3. 4 has for example the following specifications:

ia first light source 3: light emitting diode having a dominant wavelength: 590 nm, emission bandwidth (FWHM): 18 nm, minimum / typical emission power: 160 mW / 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 diodes in order to ensure a sufficient light intensity for lighting the region of interest (viewing area) of the solid support 2, the use of at least two diodes allows better uniformity of lighting of the region of interest of the solid support;

0 - ia second light source 4: light emitting diode having a dominant wavelength: 525nm.

The imaging system 60 comprises an optical detector 6, an optics for focusing the light signal returned by the solid support 2 on the optical detector 6. Preferably the optical detector 6 is a type 2 5 CMOS 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 10 positioned on the optical path of the light signal returned by the support, solid 2 and located upstream of the optical detector 6, Preferably the filter 10 is a bandpass filter which allows to pass a strip of length

BE2017 / 5706 wave of the light signal returned by the solid support 2 when illuminated by a light source 3, 4. The wavelength band transmitted by the filter allows the detection and / or 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 10-band double pass filter 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 mid-height transmission band (FWHM) of 61 nm. The second transmission range has a transmission greater than 90% in the wavelength range 620.5 669 5 nm. Each of the transmiss on bands of the double band pass filter allows the detection and / or quantification of analytes present in a sample. For example, the solid support 2 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 lengths 2? of waves linked to the excitation light source 3, 4 does not allow a good signal / brult ratio to be obtained. The elimination of the wavelength range of a light beam 30, 40 at the level of the detector 60 is therefore preferable during a fluorescence measurement.

The two-dimensional image 40 acquired by the two-dimensional 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.

BE2017 / 5706 in a sample. For example if an analyte is present or absent from a sample. This Information concerning analytes is transmitted to a user by means of transmission 19.

FIGS. 1 b and 1 e also show a feedback control means 11 connected to a light intensity detector 5, for example a sensitive photodiode in the wavelength range emitted by a light source 3. This feedback control 11 makes it possible to supply the light source 3 with an electrical signal so that the location 20 for receiving the solid support 2 is illuminated with a chosen target intensity and for example constant regardless of your conditions outside the device 1. the invention. For example, the means of feedback 11 allows regulation of the light intensity.

[0090] FIG. 1b shows an embodiment according to the invention based on FIG. the and further comprising feedback means 11 for ensuring an illumination of the solid support 2 controlled. 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 location 20 and or the solid support 2.

[0091] FIG. 1c shows an embodiment according to the invention comprising communication means 8 connected to the image processing means 12 and to the determination means 13. The communication means 8 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 key, a CD, a non-volatile memory. The database can also be non-computerized 2 and presented in paper form and readable by the optical reader 1 in the form of a bar code, datamatrix, QR code. For example, the optical reader 25 of the invention can read data from the non-computerized database thanks to an optical reader external to the device. For example, the identification device 25 described in FIG. 1d and Fig. It allows the reading of data from the non-computerized database. From the data obtained from the database (computerized or non-computerized), the communication means 8 can transmit to the image processing means 12 data relating to the location of points or lines of interest. Of

BE2017 / 5706 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 information to the optical unit 7 relating to the type of light source, the intensity of the light source required, the exposure time for acquiring an image 40 to two dimensions 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. This data makes it possible in particular to give a correspondence between the points 41 or the lines of interest identified and d extracting by the image processing means 12, information relating to an analyte to be determined or to be 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 means of determination 13 then allow for each of the points 41 or lines present or supposed to be present to assign them a name of analyte. The data from the communication means 8 and transmitted to the determination means 20 13 also include information relating to threshold values, for example specified by one or more standards, from which an analyte 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 an analyte. Preferably, for each point 41 or line of interest, there is a calibration curve making it possible to give a concentration of analyte in the sample and corresponding to a point of interest 41.

In a preferred embodiment, the optical reader of the invention comprises selection means 27 allowing a user 30 a selection of the analyte whose presence he wishes to determine (in proportions exceeding the standards in force in the field application of solid supports 2) or the quantity in a sample, There may be several modes in order to make a selection of the analytes to be determined. For example a

BE2017 / 5706 administrator of the optical drive 1 of the invention can make a standard selection which will be used during each of the solid support readings 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, the user selects the 5 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 inserted in the optical reader 1. Thus the user can make a choice, only from analytes that can be analyzed with the solid support 2 inserted in the reader 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 of the user is made, this selection is communicated by the selection means 27 to the determination means 13. The determination means 15 13 then determine for each selected analyte, a intensity of subset or point of interest - 41 corresponding to the selected analytes. From this intensity of sub-assembly and thanks to the data communicated by the communication means 8 concerning a threshold value or a calibration curve for each of the points of interest 41. the A? determination means 13 send to the transmission means 19, results relating to the detection and or the quantification of the analytes selected when a selection has been made or of all the analytes whose solid support 2 allows the detection or quantification when no selection has not been carried out,

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 points of interest or to a preferred positioning of these points of interest. interest or 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.

BE2017 / 5706 [0095] FIG. 1d shows an embodiment according to the invention comprising an identification device 25 allowing the reading of an identifier present on the solid support 2. An identifier is for example a bar code, a data matrix or a QR code, in this 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, sending to the communication means 8 the information relating to the solid support inserted in the optical reader 1, from this information, the means of communication can acquire from a database, information specific to the support 2 inserted or to the batch to which the solid support 2 inserted belongs. In the absence of an identification device 25, it is liable to indicate manually to the means of communication an identifier ’·! relating to the solid support 2 inserted, for example with a keyboard connected to the optical reader 1 or with the tactite screen which equips the optical reader 1.

[009S] In Fig. 1st, the optical reader incorporates an identification device 25, selection means 27 and communication means 8.

It is also possible to position in your embodiments presented in Figs. 1a to 1e, a second light source 4 as shown in FIG. 2a and Fig. 2b. In the case of the presence of 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 source bright 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, The presence of the 10 band double pass filter allows you to use the same

ΒΕ2017 / 5706 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 used for the detection and or the quantification of anaiytes present in a sample by the optical reading of a solid support 2.

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

Pretreatment - Cropping the two-dimensional image [0101] The step of cropping the two-dimensional image 40 into a cropped two-dimensional image 42 makes it possible to select from the original two-dimensional image 40 a rectangular region of interest comprising more specific areas of the tag to be analyzed and comprising less background areas or areas unrelated to the solid support 2 to be read. The areas of the two-dimensional image 40 that are unnecessary for future analysis are thus eliminated from the cropped image 42. Cropping the two-dimensional image 40 is an optional step.

The region of interest of the cropped image 42 is defined from the two-dimensional 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. Preprocessing ~ Uniformity Correction [0194] The aim is to preprocess two-dimensional image 40 or cropped image 42 and more particularly to correct uniformity is to correct ia non-uniformity of lighting within ia 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 12. The uniformity correction of the lighting is for example made from a

BE2017 / 5706 file comprising a model (or calibration) image, for example of a solid support which has not yet been subjected to the sample to be characterized or of a solid support comprising no dot or strip supporting labeling molecules. This model image is for example recorded in a memory of the optical reader 1 accessible by the image processing means 12.

In the absence of a model image, an auto-calibration is performed. Self-calibration consists of 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 blurred, less noisy version of two-dimensional image 40 (elimination of outliers) while respecting the contrast of the image.

[0106] Initial detection of the points [0107] 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 twice the radius of a point) first scans the entire analyzed image 40, 42 in search of areas potentially corresponding to points to know the brightest areas in the image surrounded by dark areas (areas contrasted with respect to a background area).

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. 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 two-dimensional image 40, a binary mask specifying the potential dowry zones is thus created.

In a second step, the circles are detected within the binary image obtained during the first detection phase. From

BE2017 / 5706 detected circles, including the grid points but also "false points" due in particular to the appearance of the edges of the solid support 2 within the ROI defined by the user. To eliminate the false points within the binary mask and keep only your circles corresponding to the points of the grid, theoretical replacement of the grid within the image 40, 42 is used.

The theoretical location of the grid is determined on the basis of the coordinates "x1", "y1" (top left) and "xn", "ym" (bottom right) which define the position of the extreme points from the grid at the top left and bottom right. Given the difference between the actual position of the dot grid and the theoretical position specified by the reading method or by the image processing means 12, the theoretical coordinates along the y axis "y1" 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 allowed thanks to the knowledge of the height of the solid support specified

5 by the reading method or by your image processing means 12.

[Ö111] The theoretical location of the revised grid is then used to define a sub-region 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 the circles detected are 2C considered as false point detections and are therefore eliminated.

After eliminating bad detections, a binary mask) specifying the positions initially estimated for the grid points is obtained.

Grid fitting on visible dots [0113] This step aims to make) correspond an initial grid pattern of

5 dots on the dots detected within the region of interest in order to subsequently optimize the estimated positions of the dots and allow their measurement.

A rectangle surrounding all of the dots initially detected (and not eliminated) is first calculated.

The top left corner or the top left corner "xl", "y1" of the rectangle obtained makes it possible to determine replacement observed in practice (and no longer theoretical) of the first point of the initial grid (top left ).

With the help of parameters specifying respectively the number of dots present on the tag in X and in Y, the defined rectangle also allows to

BE2017 / 5706 determine the angle formed by the point grid 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 dows present on the solid support 2 in X and in Y. This space between dots "practical" is average with the theoretical inter point space (determined as for it on the basis of the parameters “x1”, “y1”, “xn”, “ym” and the values of the parameters specifying respectively the number of dots present on the rod in X and in Y. This average is carried out for the purpose to counter the effect of an excessive potential widening of the “practical” inter-point space, widening observed when a point is not more aligned with respect to the points located on the same line.

An initiai grid pattern can be defined from a top left corner of the grid, the angle formed by the latter with the horizontal, the spacing between points and the number of known points specified by a method. specific to each solid support 2. The search for correspondences between the detected peaks and the points of the initial grid pattern 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 theoretical grid. The theoretical grid already adapts to most of the visible points, but some have yet to be optimized, such as points which are not well aligned with the others.

Local optimization of the dots [0117] 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.

BE2017 / 5706 [0118] 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 a defined area of interest around the point. At each position of the window, a measurement of the signal / background ratio is calculated.

This 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 circle of radius in pixels of the sign area containing the point. The parameters of the internal radius of the measurement ring from the background of a point in pixels and of the external radius of the measurement ring of the background of a point in pixels respectively represent the internal radius and the outer radius of this background measurement ring. The position of the dot is modified so as to correspond to the position of the analysis window presenting the best signal to background ratio.

Measurement of the dowries [0120] To. at each measurement point, a measurement of the useful signal is carried out, namely the average pixel intensity within an eerde 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 two-dimensional image 40 within an outer ring at the point of internal radius of the background measurement ring in pixels. and 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.

[0122] Figs. 2a and Fig. 2b for example shows a preferred embodiment of the invention comprising a sealed cladding 16 having an index of 30 iF ⁵ protection 54 according to IEC 60529 accessed September 2017. The cladding is especially watertight and ia dust. The receiving part of the support, solid 2 and comprising replacement 20, is in particular sealed from the optical and electronic parts by means of a window

BE2017 / 5706 protection. This protective glass is for example shown in FIG. 1a â 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 5 by the solid support 2. In order to limit heating in the enclosure of the reading device 1, cooling means 15 allow a transfer of heat generated by the electronic and optical components to the outside of the sealed enclosure 16. The cooling means allow the heat to be collected from the components more heat emitters such as microprocessors and ensures 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 located outside the sealed enclosure is carried out by a heat pipe.

Communication means 8 are preferably included 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. Results can be communicated qualitatively or quantitatively 2G to a display, print, email, or analog or digital recording device. The communication means 8 allow, for example, access to a method specific to each batch of solid support 2. A method database is for example accessible via a network of internet or local type, from a memory. of non-volatile type, from printed elements of bar code type,

QR code or data-matrix. The printed elements are for example read by suitable optical reading means known to those skilled in the art, [8124] FIGS. 3A and 38 show a two-dimensional image 40 acquired by the optical detector on which there are reference points 45 30 and points of interest 41. 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 two-dimensional image 40, by

BE2017 / 5706 free they are aligned in the same direction, for example they are distributed in a two-dimensional space. A two-dimensional image 40 can be cropped by the image processing means 12 into a cropped image 42 as shown in FIG. 3a or 3b.

[0125] Figure 4 shows a three-dimensional view of an embodiment of the reading device 1 of the invention. The device 1 has an external surface 16 from which protrudes 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 removable solid support 2 in the device 1. The device is equipped with display means allowing, for example, data entry using 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 have batteries in order to benefit from sufficient autonomy to perform a sufficient number of sample readings over a working day for example.

[0126] In summary, the invention can also be described as follows.

Device 1 for optical reading of a removable solid support 2 for the detection and / or quantification of anaiytes present in a sample comprising an optical unit 7 for analyzing the solid support 2 according to two dimensions; image processing means 12 for analyzing a two-dimensional image 40 of the solid support 2 according to two dimensions; determination means 13 for determining analyte information on the basis of the data of the image processing means 12: and transmission means 25 configured to transmit the analyte information.

Claims (10)

claims 1 C 1. Device (1) for optical reading of a removable solid support (2) for the detection and / or quantification of anaiytes 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); c an imaging system (60) comprising a two-dimensional optical detector (6) for providing a two-dimensional image (40) of a viewing area, said viewing area comprising at least a portion of said location (20) ; c a filter (10) for filtering a defined wavelength range, and positioned between the location (20) and said imaging system (60); · Image processing means (12) of said two-dimensional image (40) for: o detect reference areas (45) of said two-dimensional image (40), o determine a finite number of subsets (41) of said two-dimensional image (40), o position in said two-dimensional image ( 40) each sub-assembly (41) at a predetermined position with respect to said reference areas (45), o providing data relating to light intensities from said sub-assemblies (41); - determination means (13) for: BE2017 / 5706 o calculate, for each subset (41), a subset intensity, and - transmission means (19) configured to transmit said subset intensity for each subset (41). 2. Device (1) according to the preceding claim, characterized in that said two-dimensional image (40) comprises areas contrasted with respect to a background area, and in that, your image processing means (12) of the two-dimensional image (40) 10 also makes 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) to receive a solid support (2) than in said two-dimensional image ( 40); 15 - assigning a defined surface for each two-dimensional position of sub-assembly (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 areas. 3. Device (1) according to any one of the preceding claims, characterized in that said finite number of sub-assemblies (41) is greater than or equal to five sub-assemblies (41), preferably more than ten /: 5 sub-assemblies (41) and even more preferably more than fifteen sub-assemblies (41). 4. Device (1) according to any one of the preceding claims, characterized in that it further comprises a second light source 30 (4) configured to emit a second light beam (40) in a second wavelength range. BE2017 / 5706 5 longitudinal axis of a width of said recovery system. 29. 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 5 26. Diagnostic assembly for the optical reading of a recovery system 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 10 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, competing ligands and / or recognition biological molecules, so as to identify, by the location of said recovery locations on said support, said analytes present in said sample, said diagnostic means 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 fixed recognition biological molecules audits of recovery locations of said recovery system (2). 27. 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 dots each having a diameter between 20 μm to 2 mm, preferably, 'b = included between 100 to 500 μm and even more preferably between 250 μm and 400 μm. BE2017 / 5706 28. 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 recovery system and a second coordinate defined on a 5. Device (1} according to any one of the preceding claims, characterized in that said first languor range is distinct from said second band length range. : -j 6. Device (1) according to any one of the preceding claims, characterized in that said filter (10) is a double band pass filter for letting through two defined wavelength ranges, one of the two ranges of which is said first range. wavelength or said second wavelength range. .10 7. Device (1) according to any one of the preceding claims, characterized in that said analyte information is determined on the basis of at least two intensities of sub-set originating from at least two sub-set (41) , 8. Device (1) according to any one of the preceding claims, characterized in that said subassemblies (41) have a rounded shape and preferably have a disc shape. 20 9. Device (1) according to any one of the preceding claims, characterized in that said analyte information is binary type information. 10. Device (1) according to any one of claims 1 to 8 characterized o 5 in that said analyte information is information proportional to said measured light intensity. 11. Device (1) according to any one of the preceding claims, characterized in that the said optical unit (7) further comprises: 30 o a light intensity sensor (5) for measuring the intensity of emission emitted by said first light source (3); g a feedback control means (11) for modulating said emission intensity of said first light source (3) as a function BE2017 / 5706 of the emission intensity measured by said light intensity sensor (5) so that said first light source (3) emits a target intensity. 12. Device (1) according to any one of the preceding claims, characterized in that it further comprises: - an identification device to identify a solid support (2) to read: - communication means (8) for obtaining information relating to a solid support (2) to be read. 13. Device (1) according to the preceding claim, characterized in that said target intensity is defined on the basis of the information relating to said solid support (2) to be read. -X 14. Device (1) according to any one of the two preceding claims, characterized in that said determination means (13) are configured to determine on the basis of said intensity of the sub-assembly and on the basis of the information relating to said solid support (2) to read, analyte information for each subset (41). 15. Device (1) according to any one of the three preceding claims, characterized in that said image processing means (12) are configured for: o determine, from information relating to said solid support (2) to be read, a finite number of subsets (41) of said two-dimensional image (40), o position in said two-dimensional image (40) each sub-assembly (41) at a predetermined position on the basis of said information relating to said solid support (2) with respect to said reference zones (45). BE2017 / 5706 16. Device (1) according to any one of the preceding claims when it depends on claim 12 characterized in that it further comprises: - selection means (27) for: o select from a list of predefined anaiytes, a selection of anaiytes to detect and / or quantify; in that the image processing means (12) are configured for: o determine said finite number of subset (41) of said two-dimensional image (40) from the information relating to said solid support (2) to be read, each subset (41) corresponding to an analyte; in that the determination means (13) are configured for: o calculate said subset intensity (41) for each subset (41) corresponding to an analyte selected from said selection of anaiytes; o determine on the basis of said subset intensity analyte information for each subset (41) corresponding to an analyte selected from said selection of anaiytes; and in that the transmission means (19) are configured to transmit said analyte information for each subset (41) corresponding to an analyte selected from said selection of anaiytes. 17. Device (1) according to the preceding claim characterized in that said list of predefined anaiytes is included in said information relating to a solid support (2). 18. Device (1) according to any one of the two preceding claims, characterized in that it further comprises: a credit meter (18). said credit counter (18) being incremented during the selection of each analyte to be detected and / or quantified by the selection means (27). BE2017 / 5706 19. Device (1) according to any one of the three preceding claims, 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, said analyte information for each subset (41) corresponding to an analyte selected from said selection of 'analytes. 10 20. Device (1) according to any one of the preceding claims, characterized in that it further comprises: - encryption and recording means (14) for recording said image (40) in two dimensions on the basis of defined encryption. 15 21, Device (1) according to any one of the preceding claims when it depends on claim 12 characterized in that said information relating to a solid support (2) to be tested comprises information corresponding to each of said subsets (41 ) 20 22. Device (1) according to any one of the preceding claims, characterized in that it is compact and hermetic. 23. Device (1) according to any one of the preceding claims, characterized in that it further comprises: 25 - an external surface (16); - cooling means (15) for transferring a quantity of heat from the interior of said device (1) to said external surface (16). 30 24. Device (1) according to the preceding claim characterized in that the cooling means comprise a heat pipe. BE2017 / 5706 • 's' i 25. Device (1) according to any one of the preceding claims, characterized in that said device for identifying the solid support (2) is a data matrix, barcode or QR code reader. 10 minus fifteen separate recovery locations intended for the respective simultaneous detection and / or quantification of at least five, preferably at least ten, more preferably, at least fifteen analytes of distinct classes present in a sample and whether or not belonging to different families of anaiytes, and at least one recovery location intended for a control and / or a calibrator.