BE1025621B1 - Light-controlled 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 said solid support (2) comprising a means for feedback control (11) for performing the analysis with a light source (3) emitting a predetermined intensity; image processing means (12); 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

Controlled light intensity optical feature device of a removable solid support for the detection and / or quantification of analytes present in a sample

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 Monitoring and control of food products requires that tests be carried out as far in advance as possible of their manufacture, ideally these tests must be carried out at the place of production of the raw materials 15 or at their place of transformation. These screening tests or screening tests are specially designed to detect the presence and or the quantity of certain analytes including chemical contaminants, proteins or pathogens. The multiplication of sanitary standards and the desire for better traceability of food products means that the 20 analytes to be tested must be multiplied as well as knowing as precisely as possible their classes and their quantities compared to the maximum authorized limits.

One way of detecting analytes in a sample consists in using a reaction mixture comprising biological recognition molecules, for example each capable of recognizing a determined analyte present in said sample. The detection of analytes can then be carried out with a strip (support, immunochromatograph) 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 lines of the strip, or using a reader making it possible to analyze the signals emitted by the different lines or detection points.

BE2017 / 5705 [GÖ04] An analyte to be detected is therefore often highlighted by a line or a point on the rod. 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 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 Xè subjectivity (or error) from one individual to another as well as a risk of falsification. The use of fluorophores requires in particular an inspection of the fluorescence produced by the different lines or points positioned on a rod.

US 2014/0227681 A1 describes an optical reader for carrying out a diagnostic i concerning the presence and or the amount of analytes present on a test strip previously dipped in a fluid to be tested. This optical reader allows a reading of fluorescence in time resolved in order to carry out a diagnosis by eliminating a maximum of the background noise generated by the light source.

A disadvantage of using time-resolved fluorescence for the detection of fluorescent analytes is that this technique limits detection to fluorescent elements having a sufficiently long lifespan and having a concentration and or a sufficiently high luminance to be detected by the detector. This device also requires a light source and a detector having well synchronized trigger times. This device also requires a sufficiently sensitive detector.

Another limitation of current optical readers is that they do not allow the reading and discretization of a large number of zones 30 on a strip (in general, known optical readers are limited to approximately five zones to be read) . This limitation of the number of zones to be read requires for example to carry out several consecutive measurements with types of tabs

BE2017 / 5705 different and / or the use of different optical readers adapted to each of the tabs to be tested.

Summary of the invention [0008] 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 anaiytes and not requiring a time-resolved fluorescence method when a fluorescence technique is used to read the zones to be tested. The present invention makes it possible to deliver a qualitative and possibly quantitative result for each of the zones to be tested.

[8009] For this purpose, the inventors propose an optical reading device for a removable solid support for the detection and / or quantification of anaiytes present in a sample and comprising:

- 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;

a light intensity sensor for measuring the intensity 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 emits a target intensity;

o an imaging system comprising an optical detector for providing an image of a display area, said display area comprising at least a portion of said location // // ^{:: ////: a} //> // ^/:::::: /// ///// ^ ^ ^////////:::: <// ////// ////// _<//: / / /:. // ///// o a filter to filter a defined wavelength range, and positioned between the location and said imaging system;

- image processing means of said image for:

o determine a finite number of subsets of said image,

BE2017 / 5705 c provide data relating to light intensities from said subsets:

means of determination for:

o calculate, for each subset, an intensity of subset 5, and

- transmission means for transmitting information relating to said intensity of the sub-assembly for each sub-assembly.

The device according to the invention allows 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.

When a fluorescence technique or a reflected light technique is used to read the areas to be tested (or points), a feedback control makes it possible to guarantee an always bright excitation light intensity, which allows an instantaneous measurement of fluorescence. or reliable reflection, whatever the temperature, the energy source used still had 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 having a predefined intensity makes it possible in particular to guarantee reliable quantitative results. The feedback means is preferably an electronic feedback means. For example, the light intensity sensor is a photodiode. 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.

Preferably, the device according to the invention allows the reading of (recovery) locations or dots fixed on a solid support (or recovery system) according to an arrangement, preferably two-dimensional matrix in the form of) points 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 according to the invention allows the good differentiation of locations of

BE2017 / 5705 recovery 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 10, and even more preferably at least 15 recovery locations in simpllcat, dupiicat, triplicate or more for the detection and / or quantification of at least 5, preferably at least 10, preferably at least 15 analytes, whether or not belonging to different families of analytes and or to different classes of analytes, as well as at least one recovery location deposited in simpllcat, dupiicat, triplicate or more intended for positive threshold control detection to validate the test and / or calibration for detection and / or quantification, and this on a recovery system with a ta it is reasonable and of the order of a square centimeter, for carrying out the detection and / or quantification of said at least 15 analytes by the optical reading device of the invention.

The feedback means make it possible to define, for example, 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 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 to the feedback means is too low compared to the target intensity, the feedback means 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

BE2017 / 5705 light intensity is not influenced by temperature variations due to aging of the light source. The feedback controls 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 qualitatively and / or quantitatively. Another advantage of being able to generate light with a target light intensity is to be able to provide 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. The analytes which can be detected and or quantified are 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, lacrimal secretions ,,, Preferably, the identification device is positioned at said location to identify a solid support to read positioned in said location. The communications means are also reading means, for example for reading data from a removable solid data medium. For example, the means of communication allow a connection to a network of the Internet type, by cables or by wireless means of the Wi-Fi, Bluetooth, 4 / 5G or near-field communication type.

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

The image includes subsets, portions, regions of interest, areas of interest or even parts of images. Preferably, the subsets of an 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.

BE2017 / 5705 Preferably the first light source allows a reading of the regions of interest in fluorescence, that is to say with a range of wavelength which coincides with the absorption spectrum of fluorescent elements such as labeling molecules. The labeling molecules then re-emit the light energy absorbed 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 1b 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 anaiyte information for each sub-

1.5 together towards a memory. Dsi preferably, the transmission means used to transmit anaiyte information to a display device included in the optical reading device according to the invention.

An advantage of the device according to the invention is to be able to receive a solid support such as for example an immunochromatographic type strip (with or without cassette) or a microfluidic 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 25 allows the holding in position and temperature of the reaction mixture to a temperature preferably between 25 ^to 35 * C and 0 and even more preferably 30 ^to C. The incubator is used before you positioning the removable solid support in the location of the device.

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

BE2017 / 5705 with a wavelength range different from the first wavelength ptege emitted by the first light source. Preferably, the second light source allows reading in reflected light. The second light source illuminates your regions of interest with a tab positioned in 5 the reader location. Marking molecules present or not at the level of 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 tigette in the viewing area. Depending on the presence or not of the molecules W of markings, this results in regions of more or less dark interest compared to the bottom area of the strip.

For example, fluorescent labeling molecules 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. In fact, this increases the contrast by eliminating the background noise due to the wavelengths emitted by the light source but not absorbed by the marking 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 ptege, The advantage of having two light sources emitting in distinct wavelength ranges allows a reading of a larger choice of labeling molecules. For example, this allows the reading of 30 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.

BE2017 / 5705 [0026] Preferably, the filter is a double band pass filter to let two defined wavelength ranges pass, one of the two ranges of which is. the first wavelength range or the second wavelength range, therefore requiring no physical change of bandpass 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 distinct wavelength ranges. Preferably the double band pass filter 10 is used in the presence of two different light sources emitting in different wavelength ranges. Preferably, a double band pass filter is used in the case of an optical reader which makes it possible to read the marking molecules in reflection and in fluorescence.

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 even more preferably more than fifteen subsets is to be able to carry out a diagnosis of a sample 2 0 to be tested in a single reading of a single removable solid support.

[8030] Preferably, the device is compact and hermetic.

An advantage of having a compact and airtight device is to be able to use the device portable. 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:

- an external surface;

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

Preferably the outer 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 the transfer of heat without adversely affecting the sealing or

BE2017 / 5705 hermeticism has an IP54 protection index according to standard IEC 60529 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 routes the heat produced anywhere inside the device towards the outside of the device while retaining a good seal.

Preferably, the subsets have a rounded shape and preferably have a disc shape.

An advantage of having a rounded or disc-shaped subset is that they make it possible to collect a point of interest intensity having a more important disc shape.

Preferably, the device further comprises:

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

- means of communication for obtaining information relating to a solid support to be read.

An advantage that the optical drive of the invention includes a

0 identification device to identify a solid support to read is to allow an automatic choice of the method to be applied to the solid support to read. This 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 allowing in particular the good

5 operation 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.

[6Ü41] 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 according to the solid support to be read and the specificity thereof. This allows greater flexibility of the supports

BE2017 / 5705 solids which 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, a gain, an exposure time, minimum signals of 5 (In) validity of the CTRLs, cut-off ratios (specific POS / NEG decision threshold depending on the batch and the 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 the 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 the information relating to the solid support at time, 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 20 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). In addition, it allows to deliver a qualitative and possibly quantitative result of each of the areas to be tested.

Another advantage of this preferred embodiment of the optical reading device 2 5 of the invention is to allow the optical reading of a large number of regions of interest present on 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 for analyzing a large number of regions of interest on a strip of 30 precisely. 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 simultaneous reading of several tabs in order to

BE2017 / 5705 covering a large number of regions of interest with the same optical sensor being a source of incorrect placement and of shifting the regions of interest from one measurement to another and this for each of the tabs introduced into the optical reader.

The two-dimensional image includes subset, portions, regions of interest, areas of interest or even parts of images. Preferably, the subsets 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.

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

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

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

- carry out 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 area defined for each two-dimensional sub-assembly position in the cropped image is rounded, preferably circular, preferably a disc.

Preferably, the determination means are configured to c 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- ensembie.

BE2017 / 5705

............ <tea [0049] 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 the quantification of analytes present in a sample with an automatic choice of the method to be applied to sample 5 from a database of methods. 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 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, the type of light source used, the type of area of interest (line or point), method 15 for quantitative (binary) or quantitative analysis, of image acquisition parameters (exposure time, gain, ...), 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 removable 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 in areas interest based on the analyte they 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 / 5705 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 printed format. For example, the given base is distributed over several sheets, the method corresponding to the solid support being acquired by reading the sheet corresponding to the desired method. For example, the display means of the optical reader indicate the sheet, including 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 allows, from an image supplied by the optical detector, a determination of 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 tab, the determination means allow a determination of anaiyte information for each sub-assembly. For example, an anayt information for an area of interest is modified by the means for determining on the basis of analyte information contained in the method. For example, this analyte information is a calibration curve for determining quantitative information from an analyte. For example, analyte information is a threshold intensity for an area of interest and therefore for an analyte, threshold intensity at. from which an analyte is considered 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 measuring tapes 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 / 5705 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 mobile solid support database, via the communication means, 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.

· 1; An advantage of the optical reader of this embodiment of the invention is to allow ha 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 so rather than storing a method in a barcode or RFID type marking since 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.

Get advantage of this embodiment of the invention, to be able to access a method not limiting the number of anaiyte that can be tested by a solid support allows the use of pins on which are present a large number of points or lines 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 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

BE2017 / 5705 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 course of) production.

Preferably, the analyte information is determined on the basis of at least two subset intensities 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 averaging is to allow smoothing of 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.

[Ö058] Preferably, the analyte information is binary type information.

0 Binary type analyte information is qualitative analyte information. For example, analyte information is used 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 an intensity of subset. 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, a presence of 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 support. Preferably, a

BE2017 / 5705 threshold intensity is defined by the user according to regulations specific to a territory.

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

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 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.

The advantages of this embodiment can be combined with any of the other advantages linked to the other embodiments of the invention.

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:

g determine the finite number of subsets of the 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;

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

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.

[0664] 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

BE2017 / 5705 sample and allowing the selection of the analytes to be tested without requiring the use of several types of removable solid support. Another advantage of this is to allow a selection of anaiytes 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 reading of the areas to be tested, in particular with an instant measurement) of fluorescence or preferably with a measurement of the reflected light of the areas to be tested, in order to allow a selection of the 10 analytes to be tested corresponding to areas of interest on a tlgette, the device offers, thanks to access to a method containing information relating to a tlgette, a selection from a list of anaiytes 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 distributor, it is interesting 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 tlgette. 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 to allow an optical reading based on an optical signal (fluorescence or reflectometry) of zones 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 tlgette, that is to say not requiring positioning

BE2017 / 5705 of one or more different tabs in a cassette, the cassette then being inserted into 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 5 concerning the analytes to be tested.

An advantage of using the optical reader of this preferred embodiment to carry out a diagnosis concerning a selection of anaiytes of interest is that it requires neither a first selection of the strips to be tested, nor the contacting of each of these strips with the product to be tested and then 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 anaiytes 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, with only the results selected after reading the strip by the optical reader of the invention.

Preferably, the list of predefined anaiytes is included in 20 information relating to a solid support.

The advantage of having a list of predefined analytes 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 anaiytes.

Preferably, the device further comprises:

a credit counter, the credit counter being increments during the selection of each analyte to be detected and / or to be quantified by the 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 / 5705 determination and / or means of transmitting data relating to the tag to be measured 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 them means of selection. An advantage of the credit counter 5 is that it can be recharged from the means of communication. For example, a deposit for Increasing the credit in a positive way is contained on a removable usb key or directly transferred to the webservice 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 corresponding subset / ¾ an analyte selected in the selection of analytes .

Preferably, the device further comprises:

· Encryption and recording means to save the 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 / 5705 decryption means capable of decrypting your data encrypted by your encryption means. For example, your encrypted data includes the image acquired by the optical detector as well as a method or information relating to the test strip. To obtain results from the selected “non-channel” 5 points, activate the “channel” in question and perform an “existing image rescan” to reveal the results of the points not initially selected. 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 re-analyze the solid support at any time 1C after the first analysis according to the invention. It is thus possible to ensure that the image is properly analyzed by the 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 analytes 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 2 5 each of the sub-assemblies as well as for example calibration curves allowing a qualitative and quantitative measurement.

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, efficient and optimized diagnosis compared to current diagnostic assemblies, and this by allowing the detection and / or quantification not only of a higher number of classes of analytes belonging to a family

BE2017 / 5705 of analytes (for example antibiotics), but also of a higher number of classes of analytes belonging to several families of analytes (for example drug residues, toxins or even heavy metals). More particularly, a diagnostic set 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.

1Π To this end, the inventors propose a diagnostic set for the optical reading of a recovery system comprising;

ie device according to the first aspect of the invention;

a 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 in the form of a solid support to which are fixed in distinct and known space recovery locations, 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 competitive and / or desited ligands he biological recognition molecules 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 assembly according to the second aspect, mutadis mutandis.

BE2017 / 5705 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 effective than the currently known diagnostic means which are generally limited to less than five different classes of analytes, typically only to two or three different classes of 'analytes, these classes belonging to the same family of analytes (for example antibiotics).

Preferably, your 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 pm and even more preferably between 250 μm and 400 μm.

H has been shown that recovery locations in the form of points each having a diameter between 20 microns and 2 mm, preferably between 100 microns and 500 microns, preferably between 250 microns and 400 microns, allowed to fix the at least five, preferably at least ten, more preferably at least fifteen recovery locations in simplicat, duplicate or triplicate for the detection and / or quantification of at least five, preferably at least ten, more preferably at least at least fifteen analytes of different classas, whether or not belonging to different families of analytes, as well as at least one recovery location deposited in simplicate, duplicate or triplicate intended for the 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 reasonable size and of the order of c square meter, for the realization of the

BE2017 / 5705 detection and / or 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 recuperator system and a second coordinate defined on a longitudinal axis of a width of said recuperator system.

Preferably, said recovery system comprises at least five, preferably at least ten, and more preferably at least fifteen separate recovery locations intended for detection and / or

0 respective, simultaneous and specific 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 analytes, and to minus a recovery location for a control and / or a calibrator.

Brief description of the Ligurians [0886] 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:

- Figs. 1a, Fig. 1b, Fig. 1c and Fig. 1d show embodiments

0 diagrams 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.3b show an example of an 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 to be limiting, including when these numbers are indicated in the claims.

3ü Zero-rated description of certain embodiments of Hnventicm [O087] Figures 1a to 1d show an example of embodiment of the device 1 according to the invention. A solid removable support 2 for detection

BE2017 / 5705 and / or the 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 the as reproducible as possible from one solid support 2 to another compared to the optical unit 7 and to the identification device 25. Preferably, replacement 20 is a removable part of the device 1 which is for example supported by a drawer device . To realize the optical pickup ^of: solid support, a _2: Location 20 is for example removed from the device to be able to position the support 2 to solid optically reading. When the solid support 2 to 10 to be read is positioned in the 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 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 towards an imaging system 60 is detected by the optical detector 6 to provide an image 40 of the solid support 2.

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 /

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

5 sufficient light intensity of illumination of 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;

- the second light source 4: light-emitting diode having a dominant wavelength: 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 type detector

BE2017 / 5705

CMOS. 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 solid support 2 and located upstream of the optical detector 6. Preferably the filter 10 is a bandpass filter which allows a band of wavelength Al of the light signal returned by the support, solid 2 to pass, to pass through

Illumination 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 nrn. The second transmission range has a transmission greater than 90% in the wavelength range 620.5 -

669.5 nm. Each of the transmission bands of the double band pass filter allows the detection and / or quantification of analytes present in a 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 anayte to be detected must be transmitted to the optical detector 6, in fact the transmission of lengths

BE2017 / 5705 of waves in Hen with the light source 3, 4 of excitation does not allow to obtain a good signal / noise ratio. The elimination of the wavelength range of a light beam 30, 40 at the detector 60 is therefore preferable during a fluorescence measurement.

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 relating to analytes is transmitted to a user via the transmission means 19.

FIG. 1a also shows a feedback control means 11, connected to a light intensity detector 5, for example a sensitive photodiode 15 in the wavelength range emitted by a light source 3. This feedback control means 11 makes it possible to supply the light source 3 with an electronic signal so that the location 20 for receiving the solid support 2 is illuminated with a chosen target intensity and for example constant whatever the conditions external to the device 1 of the invention, for example the feedback means 11 allows regulation of the light intensity, FIG. 1b 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 2 5 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 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 1 of the invention can read iss 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 allows the reading of data from the non-computerized database. From the data obtained from the database

BE2017 / 5705 data (computerized or non-computerized), the means of communication can transmit to the image processing means data relating to the location of points or lines of interest. Preferably, the position of points 41 or lines of interest is given relative to points or zones 5 of references. 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. 40 allowing the detection and or the quantification of anaiytes present in a sample.

The communication means 8 are also configured to transmit data from the database to the determination means 13. These data make it possible in particular to give a correspondence between the points or the lines of interest identified and to extract by the image processing means 12, information concerning 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 determination means 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 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 the 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 a selection of the analytes whose H wishes to determine the presence (in proportions exceeding the standards in force in the field of application of

BE2017 / 5705 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, the user selects the 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 10 analytes which can be detected with the solid support inserted in the optical reader 1. Thus the user can make a choice, only from the analytes which can be analyzed with the solid support 2 inserted in the reader and not from a generic list of analyte which the user does not know if it would be possible to obtain any result. When the selection 15 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, a subset intensity or point of interest 41 corresponding to the selected analytes. From this intensity of sub-assembly and thanks to the data 2u communicated by the communication means 8 concerning a threshold value or a calibration curve for each of the point of interest 41, the determination means 13 send to the transmission means 19, results relating to the detection and or the 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.

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. interest or to corrections allowing a comparison of the different batches between them in order to carry out a quantitative measurement of the analytes present in a sample, The means of

BE2017 / 5705 transmission 19 are preferably connected to the means of communication

8.

[0096] FIG. 1c 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 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 2.5 is a near field reader known to those skilled in the art. The identification device 10 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 of this information, the means of communication can acquire, from a database, information specific to the solid support 2 inserted 15 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 with a keyboard connected to the optical reader 1 or with the touch screen which equips the optical drive 1.

In Fig. 1d, the optical drive includes an identification device

25, selection means 27 and communication means 8.

H is also possible to position in the embodiments presented in Figs. 1a to 1d, a second light source 4 teile as shown in FIG. 2a and Fig. 2b. In the case of the presence of 25 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 fluorescence reading / measurement of the solid support 2. Preferably, the second light source 4 is intended to perform a fluorescence reading / measurement

BE2017 / 5705 reflection of the solid support 2 for the detection and / or quantification of analytes. 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 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 10 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.

[0101] Pretreatment - Cropping of Hmage [0102] 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 thumbnail analyze more specific and comprising fewer background areas or areas unrelated to the solid support 2 to be read. The areas of the image 40 that are unnecessary for future analysis are thus eliminated from the cropped image 42. Cropping 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.

The aim is to pre-process the image 40 or the cropped image and more particularly to correct uniformity is to correct the non-uniformity of the lighting 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 means of) image processing 2. The correction of the lighting uniformity is for example made from a file

BE2017 / 5705 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 not comprising a point or band supporting molecules of markings. 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, an auto-calibration 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 blurred, less noisy version of the image 40 (elimination of outliers) while respecting the contrast of the image.

[0107] Initial detection of the points [Ö1Ü8] 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) initially scans the entire analyzed image 40, 42 in search of areas potentially corresponding to points, namely the the brighter areas in the image surrounded by dark areas (areas contrasted from a background area).

[Ü109] At each position of the window, the average of the pixel values 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 image, 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. Among the circles detected, there are in particular the points of the grid also dare to "false points" due in particular to the appearance of the edges of the solid support 2

BE2017 / 5705 within the user-defined ROI. To eliminate false points within the binary mask and keep only the circles corresponding to the points on 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 "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 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 "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 enabled by knowing the height of the solid support specified by the reading method or by the image processing means 12.

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 preserved (because considered as belonging to the point grid) and outside of which the detected circles are considered as false point detections and are therefore eliminated. After eliminating the bad detections, a binary mask specifying the 20 positions initially estimated for the grid points is obtained.

[Ô113] Fitting grid on visible dots [0114] This step aims to match an initial grid pattern of dots on the dots detected within the region of interest in order to subsequently optimize the estimated positions of the dots and allow their measured.

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

The top left corner or the top 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,

BE2017 / 5705 the space between seton points 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 averaged with the inter point space ü theoretical (determined in turn on the basis of the parameters "xi", "y!", "Xn", "yrn" 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 with the aim of countering the effect of an excessive potential widening of the space inter points “practical”, widening observed when a point is not not more aligned example 10 compared 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 15 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 gulle 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 2Ό already adapts to most of the visible points but some still need to be optimized fels than points which would not be well aligned compared to the others.

Local optimization of the dots [0118] So that each dot is centered on a measurement point, a x ü 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 12. The number of iterations of the local position optimization is defined by a parameter of number of optimization iterations local 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 of a

BE2017 / 5705 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. This is defined as the difference between the average of the pixel values within a circle of radius in pixels of the sign area containing the 5 point defined in the center of the window, and the average of the pixels included in a ring. outside, surrounding the circle of radius in pixels of the signal area containing the point. The parameters of the internal radius of the background measurement ring of a point in pixels and of the external radius of the background measurement panel of a point in pixels represent respectively the internal radius and the radius. external of this background measurement ring. The position of the dot is modified so as to correspond to the position of the analysis window with the best signal / background ratio.

Measurement of the dots [0121] At each measurement point, a measurement of the useful signal is carried out, namely the average intensity of the pixels within a circle of radius equal to the parameter of measurement radius in pixels of the sign area containing the point to be measured. The measurement of the intensity of the background 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 20 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 sign area containing the point in pixels.

[0123] 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 in particular 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. in 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

BE2017 / 5705 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 transfer of heat generated by the electronic and optical component to the outside of the sealed enclosure 16. The cooling means allow a collection of heat from the most heat-emitting components such as microprocessors and ensures the transfer of this heat to the outside of the waterproof 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 pipeline.

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 2. The communication means 8 also allow the communication of the results from means of transmission. 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 internet or local type, from a memory of type non-volatile, from printed elements of bar code, QR code or data-matrix type. The printed elements are for example read by suitable optical reading means known to those skilled in the art.

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 marking 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.

BE2017 / 5705 [0126] 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 protrudes a cooling device 15 located on the rear of the device 1. A location 20 taking the form of a drawer 5 allows the positioning of a removable solid support 2 in the device 1. The device is equipped with display means making it possible, for example, to enter data 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 has batteries in order to benefit from sufficient autonomy to carry out a sufficient number of sample readings over a working day for example. In summary, the invention can also be described as follows.

Device 1 for optical reading of a removable solid support 2 for the detection 15 and / or quantification of anaytes present in a sample comprising an optical unit 7 for analyzing said solid support 2 comprising a feedback means 11 for carrying out the analysis with a light source 3 emitting a predetermined intensity; image processing means 12; determination means 13 for determining analyte information based on the data of the image processing means 12; and transmission means configured to transmit the analyte information.

Claims (28)

claims 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 5 including: - 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 at an emission intensity and in a first wavelength range a first light beam towards said location (20) o a light intensity sensor (5) for measuring the 'emission intensity emitted by said first light source (3); 5 o a feedback control means (11) for modulating said emission intensity of said first light source (3) as a function of emission intensity measured by said light intensity sensor (5) so that said first light source ( 3) emits a target intensity; 0 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) to filter a defined wavelength range, and 6 positioned between the location (20) and said imaging system (60); - image processing means (12) of said image (40) for: o determine a finite number of subsets (41) of said image (40), 3 o provide data relating to light intensities from said sub-assemblies (41); - determination means (13) for: BE2017 / 5705 o calculate, for each sub-set (41), an intensity of sub-set, and transmission means (19) for transmitting information relating to said intensity of sub-set for each sub-set (41). Cl 2. Device (1) according to the preceding claim characterized in that it further comprises a second light source (4) for emitting a second light beam (40) in a second wavelength range. 3. Device (1) according to any one of the preceding claims, characterized in that said first wavelength range is distinct from said second wavelength range. 15 4. Device (1) according to any one of the preceding claims, characterized in that said filter (10) is a double band pass filter for letting two defined wavelength ranges pass, one of the two ranges of which is said first range. wavelength or said second wavelength range. 5. 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 sub-assemblies sets (41) and more preferably more than fifteen 2 5 sub-assemblies (41). 6. Device (i) according to any one of the preceding claims, characterized in that it is compact and hermetic. 30 7. Device (1) according to any one of the preceding claims, characterized in that it further comprises: - an external surface (16): BE2017 / 5705 cooling means (15) for transferring a quantity of heat from the interior of said device (1) to said external surface (16) - 8. Device (1) according to the preceding claim characterized in that the cooling means (15) comprise a heat pipe. 9. Device (1) according to any one of the preceding claims, characterized in that said sub-assemblies (41) have a rounded shape and preferably have a disc shape. 10. Device (1) according to any one of the preceding claims, characterized in that it further comprises: - an identification device for identifying a solid support (2) to read; - communication means (8) for obtaining information relating to a solid support (2) to be read. 11. 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. 12. 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 that said image processing means (12) are further configured to: o detect reference areas (45) of said two-dimensional image (40),? determine said finite number of subsets (41) of said two-dimensional image (40), from the information relating to said solid support (2), to be read, or position in said two-dimensional image (40) each sub-assembly (41) at a position determined from said reference areas (45). BE2017 / 5705 13. 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, the image processing means (12) of the two-dimensional image (40) also makes it possible to: - crop said two-dimensional image (40) into a cropped image (42), said cropped image (42) showing a larger or equal portion of said location (20) for receiving a solid support (2) than in said two-image dimensions (40); - assigning a defined surface for each position to two sub-assembly dimensions (41) in said cropped image (42); - Performing a local position optimization of each sub-assembly (41) so that said defined surface of each sub-assembly (41) is positioned so as to return a maximum light intensity of each of said contrasted areas. 14. Device (1) according to any one of the preceding claims when it depends on claim 10 characterized in that said 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 (2) to be read, analyte information for each subset (41). 15. Device (1) according to the preceding claim, characterized in that said analyte information is determined on the basis of at least two subset intensities originating from at least two subsets (41), 16. Device (1) according to any one of the two preceding claims, characterized in that said analyte information is binary type information. BE2017 / 5705 17. Device (1) according to any one of claims 14 and 15 characterized in that said analyte information is information proportional to said measured light intensity. 18. Device (1) according to any one of the preceding claims when it depends on claim 10 characterized in that it further comprises: selection means (27) for: o select from a list of predefined analytes, a selection of analytes to detect and / or quantify; in that the image processing means (12) are configured to: o determining said finite number of subset (41) of said image (40) from 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 analytes; o determine, on the basis of said subset intensity, analyte information for each subset (41) corresponding to an analyte selected from said selection of analytes; 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 analytes. 19. 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). 20. Device (1) according to the preceding claim, characterized in that it further comprises: BE2017 / 5705 - a credit counter (18), said credit counter (18) being incremented during the selection of each anaiyte to be detected and / or quantified by the selection means (27). 21. Device (1) according to any one of the two preceding claims, characterized in that the determination means (13) are configured for: o determine on the basis of said intensity of the subset and on the basis of the information relating to said solid support (2) to be read, said anaiyte information for each subset (41) corresponding to an anayte selected in said selection of analytes. Any of the preceding claims characterized in that it further comprises: encryption and recording means (14) for recording said image (40) based on defined encryption. 23. Device (1) according to any one of the preceding claims, characterized in that said information relating to a solid support (2) to be read comprises information corresponding to each of said sub-assemblies (41). 24. Device (1) according to any one of the preceding claims, characterized in that said identification device (25) of the solid support (2) is a reader of data matrix, coda bar, or QR code. 25. Diagnostic set 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 detection and / or the respective, simultaneous and specific quantification of a plurality of analytes present in a sample (E) comprising at least one reaction mixture and BE2017 / 5705 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 fixed in separate recovery locations known in space, competitive ligands and / or biological molecules 5 recognition, 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 according to 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 recovery system (2). 26. 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 each having a diameter between 20 μm to 2 mm, preferably 2 F; between 100 to 500 μm and even more preferably between 250 μm and 400 μm. 27. Diagnostic assembly according to any one of the two preceding claims, characterized in that said coordinate system has 2? 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. 28. Diagnostic unit according to any one of the three claims 30 preceding, 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 the respective, simultaneous and specific detection and / or quantification of water. BE2017 / 5705 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.