BE1025624B1 - Optical reading device with choice of automated reading method 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 identification device for identifying a support (2); communication means (8) for accessing a database of methods relating to a medium (2); an optical unit (7) for analyzing said medium (2) on the basis of analysis parameters included in said information relating to a medium (2); image processing means (12); determining means (13) for determining analyte information based on the information relating to said medium (2) and data of the image processing means (12); and transmission means configured to transmit the analyte information.

Description

Optical reading device with choice of automated reading method of a removable solid support for the detection and / or quantification of analytes present in a sample

Technical Field [00Ü1] 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 diagnostic means.

STATE OF THE ART [0002] The surveillance and control of food products requires tests to be carried out as far in advance of their manufacture as possible. 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 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 anaiytes 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 anaiytes from 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 (Immunochromatographic 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 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 / 5708 [0Ö04] An analyte to be detected is therefore often highlighted by a line or dots on the strip. The change in color or light intensity of the signal reflected by the line or point in connection with the analyte to be detected is the most widespread 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. not directly interpretable by the human eye in order to circumvent the risks of 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 emitted by your different lines or points positioned on a strip.

H is already known from the state of the art, optical readers 15 for carrying 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 readers current optics do not allow an analysis of the data to be measured taking into account variations in batches and or variation in the position of a region of interest on the tabs.

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 with an automatic choice of the method to be applied to the sample from a method database. The present invention further allows automatic correction related to the variation of batches of the removable solid support for each dowry allowing the detection or quantification of analytes.

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

- a location for receiving said solid support;

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

B E2017 / 5708

communication means for accessing a database of methods relating to said solid support to be read in order to obtain information relating to a solid support;

an optical unit for analyzing said solid support on the basis of analysis parameters included in said information relating to a 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 an optical detector for providing an image of a viewing area, said viewing area comprising at least a portion of said location;

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

- image processing means of said image for:

o read in the information relating to said solid support to be read, information relating to a finite number of subsets of said image;

o provide data relating to light intensities from said subsets;

- means of determination for:

o calculate, for each subset, a subset intensity, and o determine on the basis of said subset intensity and on the basis of the information relating to said solid support to be read, analyte information for each subset -together ;

- transmission means configured to transmit said analyte information for each subset.

[ÛÔ08] The optical reading device according to the invention allows 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

B E2017 / 5708 using a batch, the type of light source used, the type of area of interest (line or point), method for quantitative (binary) or quantitative analysis, of image acquisition parameters (exposure time, gain, ..,), positions relative to reference points (for example according to 5 Cartesian coordinates), a number of areas of interest, a number of repllca per analyte, the organization matrix 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 type 10 Data interpolation or allowing a quantitative analysis of a sample and finally the designation of the zones of interest according to the analyte which they make it possible to detect and / or quantify. A reading method comprises information specific to the solid support to be read and which in particular allows the proper functioning of the optical unit, image processing and determination means 15 in order to be able to obtain reliable information relating to at least one analyte.

The automatic choice of 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 which makes it possible, 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 contained by a marking present on a solid support, the optical reader of the invention makes it possible, by means of communication, to consult a method database in order to access the 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 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 leaflet comprising the desired method, For example

B E2017 / 5708 he means of communication allow confirmation that the method read is indeed the method corresponding to a solid support to read.

The optical reading device of the invention makes it possible, from an 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 subsets are positioned at the areas of interest of the tab, the determination means allow a determination of analyte information for each subset. For example, analyte information for an area of interest is modified by the determination means on the basis of analyte information contained in the method. For example, this analyte information is a calibration curve used to determine quantitative information for an anayte. For example, analyte information is a threshold intensity for an area of interest and therefore for an analyte, threshold intensity from which an analyte 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. .

[0011] 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 re-use of a strip 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 your means of communication, whether the mobile solid support inserted in the optical reader has not yet been used. If it is the first use of the mobile solid support, the optical reading can start, if it is a second use (or more) the 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.

B E2017 / 5708 An advantage of the optical reader of the invention is that it allows the determination of a method from a bar code or RFID type marking present on a solid mobile 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 because the amount of information contained in such marking is very limited. This limitation on the amount of information that can be contained in this type of marking does not make it possible to provide information relating to a large number of dots or lines of analytes to be read. This advantage of the invention, of being able to access a method which does not limit the number of analyte which can be tested by a solid support allows the use of tabs on which a large number of points or lines corresponding to a large number are present. of analytes to be tested and having detailed information for each of the anaiytes to be tested. In addition, the presence of information relating to anaiytes to be tested present in a method database rather than in the marking allows the marking to be recorded during the manufacture of the solid supports, the method information relating to each analyte and to each solid support that 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-line from the areas of interest of the solid support or else should not contain information relating to the specificity of the batch in production course.

BE2017 / 5708 [Ö014] 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 reflected light of the areas to be tested. When a fluorescence technique or a reflected light technique 5 is used to read the zones to be tested (or points), a feedback control makes it possible to guarantee an always equal excitation light intensity, which allows instantaneous measurement of fluorescence. or reliable reflection, whatever the temperature, the energy source used or the duration of use and the aging of the light source. The use of the feedback control means 10 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. 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 feedback means make it possible, for example, to define 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, which is stable over time. For example, the light intensity δ

ΒΕ2017 / 5708 target 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 retroccntrole means allow the regulation of the light intensity to ensure a target intensity of a light source for measurement in fluorescence and or in reflected light. An advantage of this feedback device is to provide a controlled light intensity in order to be able to read a removable solid support with a continuous fluorescence technique and to be able to read a signal 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 according to the invention allows ia reading locations (recovery) or dots fixed on a solid support (or recovery system) according to an arrangement, preferably two-dimensional matrix in the form of painted having each 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 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 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 simplicat, in duplicate, in triplicate or more for the detection and / or 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 simplicat, in dupiicat, in triplicate or more intended for positive control

B E2017 / 5708 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 a square centimeter, for carrying out detection and / or quantification of said at least 15 analytes by the optical reading device of the invention.

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

Preferably, the identification device is positioned at said location to identify a solid support to be read positioned in said location. The communications means are also reading means, for example for reading data from a removable data medium. For example, the means of communication allow a connection to an internet type network by cables or by wireless means of wifl, 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.

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 labeling molecules. The labeling 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 molecules of

B E2017 / 5708 fluorescent labeling makes it possible to stop the light emitted by the light source allowing the excitation of the fluorescent labeling molecules while letting the light emitted by the fluorescent labeling molecules pass.

Preferably, the transmission means are configured to transmit or communicate the analyte information for each subset to a memory. Preferably, the transmission means make it possible to transmit analyte information to a display device included in the optical reading device according to 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, to allow the incubation of the reaction mixture contained in a flask as well as during the soaking of the removable solid support. The incubator allows the reaction mixture to be kept in position and in temperature at a temperature preferably between 25 ° C and 35 ° C and even more preferably at 30 ° C. The incubator is to be used before positioning the removable solid support in the location of the device.

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 anaiytes to each of the sub-assemblies as well as for example calibration curves allowing a qualitative and quantitative measurement.

Preferably, said information corresponding to each of said sub-assemblies comprises information relating to at least one analyte. This makes it possible to have a large amount of points or lines of interest on a removable solid support in a positioning which does not require markers visible to the naked eye or which does not require a particular order.

B E2017 / 5708 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 to be tested in a single reading of a single removable solid support.

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

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

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

Preferably, 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 sub-set intensity greater than a threshold subset intensity, a presence of 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 memory

B E2017 / 5708 of the device of the invention and does not require extracting this information from anaiyte from information relating to the support. Preferably, a threshold intensity is defined by the user according to regulations specific to a territory.

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

An advantage of an anayte information proportional to the measured light intensity is to be able to carry out a quantitative analysis of analytes in a sample. Preferably, the anaiyte information is calibrated with a calibration curve which depends on the manufacturing batch of the removable solid support and on the point of interest corresponding to the anaiyte chosen, [6037] Preferably, the device is compact and airtight.

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 in external conditions or in conditions related 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

0 heat from the interior of said device to said external surface.

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

BE2017 / 5708 heat produced anywhere inside the device towards the outside of the device while maintaining a good seal.

Preferably, the optical unit further comprises:

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

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

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

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

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 controls allow for example to define the

B E2017 / 5708 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 controls is too low compared to the target intensity , the feedback means allow an increase in the voltage 5 or 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 means allow regulation of the light intensity emitted so that the light source operates at a target light intensity. 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 by aging of the light source. The feedback means allow the regulation of the light intensity to ensure a target intensity 15 of a light source for measurement in fluorescence and or in reflected light. An advantage of this feedback device is to provide a controlled light intensity in order to be able to read a removable solid support with a continuous fluorescence technique and to be able to read a signal in a qualitative and quantitative manner. Another advantage of being able to produce a light with a target light intensity is to be able to compare the results from one device to another and to be able to define correction factors for a batch of removable solid support applicable on any which optical reading device of the invention.

Preferably, the target intensity is defined on the basis of the information relating to said solid support to be read.

An advantage that the target intensity intended for the feedback means is specified in the information relating to the solid support to be read is that this intensity can be modified as a function of the solid support to be read and the specificity thereof. This allows greater flexibility of the solid supports which can be read by the optical reader of the invention. It is for example possible to combine a target intensity with a method relating to a strip or a batch of strips. Such a method would include, in addition to a target intensity, gain, exposure time, minimum signals of

B E2017 / 5708 (in) validity of CTRLs, cut-off ratios (specific POS / NEG decision threshold depending on the batch and the point on the strip.

Preferably, the optical detector is a two-dimensional optical detector for providing a two-dimensional image of said viewing area and in that said image processing means are 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 to be read, o position in the two-dimensional image each subset at a position determined from the reference areas.

An advantage of the device of this preferred embodiment of the 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 reading simultaneous 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 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 2 5 means for analyzing a large number of regions of interest on a strip precisely. In the case of the optical device of the invention, the reading of a large number of regions of interest does not require the provision of locations for several tabs, The use of several tabs in the same optical reader for 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 positioning and of shifting the regions of interest from one measurement to another and this for each of the tabs introduced into the optical reader .

B E2017 / 5708 The two-dimensional image includes subset, portions, regions of interest, areas of interest or even parts of images, Preferably, the subsets of an image to two dimensions include 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 contrasted with respect to a background area, and in that the means for processing the image of the two-dimensional image also make it possible to:

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

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

- perform a local position optimization 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, [ÜÖ54] Preferably the surface defined for each position two-dimensional subset in the cropped image is rounded, preferably circular, preferably a disc.

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

An advantage of having a second light source is to be able to have an optical reader for reading regions of interest with a wavelength range different from the first wavelength range emitted by the first light source. Preferably, the second light source allows reading in reflected light. The second light source illuminates the regions of interest of a strip positioned to replace the reader. Labeling molecules present or not present in the

B E2017 / 5708 level of the regions of interest, allow or not an absorption, or a less reflection of the region of interest illuminated by said second light source. The optical unit then allows the acquisition of the light reflected by the rod in the viewing area. Depending on the presence or not of the marking molecules, this results in regions of interest which are more or less dark relative to the bottom area of the tigette.

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 carried out one after the other in a predefined or non-predefined order.

[Ö058] A bandpass filter is for example used in order to allow a wavelength range which may or may not be absorbed by the molecules of the molecules to pass through a measurement in reflected light. marking modifying the reflection. Indeed, this makes it possible to increase the contrast by eliminating the background noise due to the wavelengths emitted by the light source but not absorbed by the 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.

[G06O] 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 25 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, the filter is a double band pass filter for passing two defined wavelength ranges, one of the two ranges of which is the first wavelength range or the second wavelength range. , therefore requiring no physical change of the tors band pass filter of the analyzes.

B E2017 / 5708 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 wavelength ranges distinct. Preferably the double band pass filter 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 allowing a reading of the labeling molecules in reflection and in fluorescence.

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 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 (13) 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 intensity of the subset of 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, [G0 @ 4] An advantage of this preferred embodiment of the 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 sample and allowing the selection of the analytes to be tested without requiring the use of several types of solid supports. removable. Another advantage of this is to allow a selection of analytes from a pre-established list

BE2017 / 5708 fear that an operator wishes to test the presence or obtain a quantification of said anaiytes.

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 anaiytes to be tested corresponding to areas of interest on a tigette, the device offers, thanks to access to a method containing information relating to a tigette, a selection from a list of analytes to test. It is indeed interesting to make a selection of the anaiytes to be tested before obtaining the results in order to properly target the anaiytes whose it is necessary to know the results of a test so as not to expose a user to too great a amount of results. Giving access to too many results to a user who does not necessarily have the need exposes him to the risk of loss of objectivity in relation to his Initiate Analytical Intent. It is also interesting from an economic point of view for the user that he only pays for the results he really needs. 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 the stock management. Thus, the device of the invention, thanks to selection means, allows a choice of the anaiytes to be tested by the user before reading the tigette. The selection means, in communication with the image processing means allow the image processing means, a determination of the information of the selected anaiytes only.

Another advantage of this preferred embodiment is to allow optical reading based on an optical signal (fluorescence or reflectometry) of areas comprising information relating to the anaiytes to be tested. In addition, this optical reader allows a selection of the anaiytes to be tested from a single tab, that is to say not requiring the positioning of one or more different tlgettes in a cassette, the cassette then being inserted into the reader. Several tlgettes can also be inserted directly into an optical reader. By the way, this optical drive

B E2017 / 5708 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 contacting of each of these strips with the product to be tested and then their positioning in the optical reader. In addition, the optical reader of the invention to allow 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 this avoids significant manipulation of the test strips, which is costly in time and in inventory management. This also allows a simpler, faster and more targeted analysis of the analytes to be tested, with only the results selected at the end of the reading of the strip by the optical reader of the invention, [0068] Preferably, the list of predefined analytes is included in the 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 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 to be quantified by the selection means.

For example, the credit meter allows a positive or negative increment, for example the credit meter is rechargeable and allows to block the image processing means and or the means of determination and or the means of data transmission. relating to the bar 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

B E2017 / 5708 selected by your selection means. An advantage of the credit counter is that it can be recharged from the means of communication. For example, an instruction to increment the credit in a positive manner is contained on a removable usb key. For example, a setpoint for a positive credit increment 5 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 from the selection of anaiytes.

[Ö073] Preferably, the device further comprises:

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

For example, your selection means, in communication with the determination means and with the transmission means, allow the transmission of the results concerning the selected analytes. The image used to determine the results concerning the analytes is for example transmitted to encryption means. The encryption means then allowing encryption of the data relating to the recorded and unregistered analytes and the recording of this encrypted data. The advantage of recording encrypted data including the results of unselected analytes allows you to have the results concerning your unselected analytes but to limit access to those with decryption means capable of decrypting the data encrypted by the 3Ö encryption means. For example, the encrypted data includes the image acquired by the optical detector as well as a method or information relating to the tested tag. To obtain the results of the “unselected (painted) channels”, activate the “channels (points)” in question and make a “

B E2017 / 5708 re-analysis of existing image ”to reveal the results of the points not initially selected, One 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 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, ensures 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 device for identifying the solid support is a data matrix, bar code 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 current diagnostic assemblies, and this by allowing detection and / or 1a quantification not only of a higher number of classes of analytes belonging to a family 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 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, again 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, To this end, the inventors propose a set of diagnostics for the optical reading of a recovery system comprising:

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

B E2017 / 5708

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 under ia form of a solid support to which are fixed in distinct and known recovery locations in space, competing ligands and / or biological recognition molecules, so as to identify by ia localization of said recovery locations on said support , Said anaiytes 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 molecules recognition biologicals 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 set according to the second aspect, mutadis mutandis.

In fact, it has been surprisingly 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 separate families of analytes 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 two or three classes.

B E2017 / 5708 different from analytes, these classes belonging to the same family of analytes (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 between 250 μm and 400 μm.

It has been shown that recovery locations in the form of points 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 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 classes, whether or not belonging to different families of analytes, as well as at least one recovery location deposited in simplicat, duplicate or triplicate intended for the 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 of the order of c square entimeter, for carrying out the 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 recovery system and a second coordinate defined on a longitudinal axis of a width of said recovery system.

Preferably, said recovery system comprises at least five, preferably at least ten, and more preferably at least fifteen separate recovery locations intended for the respective simultaneous and specific detection and / or quantification of at least five, preferably at least ten, more preferably at least fifteen analytes of distinct classes present in a sample and whether or not belonging to

B E2017 / 5708 famines of different analytes, and at least one recovery location intended for a control and / or a calibrator.

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

~ Fig.1a, Fig. 1b and Fig. 1c show schematic embodiments of the device according to the invention;

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

- Fig.3a and Fig.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, even when these numbers are indicated in the claims.

Detailed description of certain embodiments of the invention [0085] Figures 1a to 1c show an example of embodiment of the device 1 according to the invention. A removable solid support 2 for the detection and / or quantification of analytes present in a sample is inserted into the device 1 and is received by a location 20. The location 20 makes it possible to receive the solid support 2 so that the positioning of the solid support 2 is as reproducible as possible from one solid support 2 to another relative to the optical unit 7 and to the identification device 25. Preferably, the location 20 is a removable part of the device 1 which is by 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 the location 20, these are preferably brought back inside the device 1 to perform the optical reading there. The location 20 allows rapid and reliable positioning of the solid support 2. The solid support

B E2017 / 5708 when it is present in the device 1 as illustrated in FIG. 1 is illuminated by a light source 3, 4. A light signal returned by the solid support 2 to an imaging system 60 is detected by the optical detector 6 to provide an image 40 of the solid support 2.

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 light-emitting diodes in order to ensure a sufficient light intensity for lighting the region of interest (display 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 optics for focusing the light signal returned by the solid support 2 on the optical detector 6. Preferably the optical detector 6 is a CMOS type detector. In another embodiment, the detector 6 is a CCD type detector. For example the optical detector is a network of photo detectors. A focusing optic is for example a converging lens, for example a converging lens having a focal length between 15 mm and 20 mm.

The optical reader 1 of the invention also comprises a filter 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 wavelength band of the light signal returned by the solid support 2 to pass through when it is illuminated by a light source 3, 4. The wavelength band

BE2017 / 5708 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 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 analyte to be detected must be transmitted to the optical detector 6. Indeed ia transmission of the wavelengths in connection with the excitation light source 3, 4 does not make it possible to obtain a good signal / noise ratio. 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.

Image 40 acquired by the optical detector 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 about

B E2017 / 5708 analytes are transmitted to a user by means of transmission 19.

The identification device 25 allows 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 case ie 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 a person skilled in the art. The identification device 25 when it has acquired information from the identifier 10 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 communication means 8 can acquire, from a database, information specific to the solid 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 possible to manually indicate to the communication means 8 an identifier relating to the solid support 2 inserted, for example with a keyboard connected to the optical reader 1 or with the screen on the optical drive 1.

[ÖÖ90] Communication means 8 connected to the image processing means 12 and to the determination means 13. The communication means allow access to a method database which can be computerized and stored on a server, stored in an internal or external memory to the optical drive 1 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 25 of the invention can read the data from the non-computerized database thanks to an optical reader external to the device, for example the identification device 25 described in FIG. 1d and Fig. 1e allows the reading of data from 3Ö 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

B E2017 / 5708 preferably, the position of the points or lines of interest is given relative to points or reference zones. For example, the communication means 8 can send to the optical unit 7 information relating to the type of light source, to the intensity of the light source required, to the exposure time for the acquisition of an image allowing the detection and or the quantification of analytes present in a sample.

The communication means 8 are also configured to transmit data from the database to the determination means 13. These data allow in particular to give a correspondence between the points 41 or the identified lines of interest and extracting, by the image processing means 12, information relating to an analyte to be determined or quantified. For example, the image processing means 12 assign to each point 41 or line present on the solid support 2 a position, for example coordinates in a Cartesian coordinate system with respect to reference points or zones 45. The determination means 13 then allow for each of the points 41 or lines present or supposed to be present to assign them an anayte name. 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.

FIGS. 1b and 1c show an embodiment according to the invention based on FIG. 1a 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. For example, a photodiode is sensitive in the wavelength range emitted by a light source

B E2017 / 5708

3. This feedback control 11 makes it possible to supply the light source 3 with an electrical signal so that the replacement 20 for receiving the solid support 2 is illuminated with a chosen target intensity, 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. FIGS. 1b and 1c also show a feedback control 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 supplying 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, for example constant whatever the conditions external to the device 1 of the invention. For example, the means of feedback 11 allows regulation of the light intensity.

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

8.

In FIG. 1c, the optical reader integrates one more of the identification device 25, selection means 27 and communication means 8.

The selection means 27 allowing a user to select the analytes of which he wishes to determine the presence (in proportions exceeding the standards in force in the field of application of the 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, an administrator of the optical reader 1 of the invention can make a standard selection which will be used during each of the media readings. For example, the selection can be made by card, that is to say before at the start of each support reading 2, the user selects the analytes he wishes

B E2017 / 5708 know the presence and or the quantity in the sample that he wishes to test. Preferably your communication means 8 send to the selection means 27, information concerning your anaiytes 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 the anaiytes that it is possible to analyze 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 13 then determine for each selected analyte, a subset or point of interest intensity 41 corresponding to the selected anaiytes. 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 determination means 13 send to the transmission means 19, results concerning the detection and or the quantification of the selected anaiytes when a selection has been made or of all your anaiytes whose solid support 2 allows the detection or the quantification when no selection has been made, [Ü096] also possible to position in the embodiments presented in Figs. 1a to 1c, 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 light 3, [9097] 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 detection and / or the quantification of analytes.

The presence of the 1Ö double band pass filter makes it possible to use the same

B E2017 / 5708 optical detector 6 for measurement in fluorescence or for measurement in reflection. 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.

[Ö09S] An image 40 acquired by the detector 6 is then sent to your image processing means 12. The image processing means 12 allow your 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. [0Ü99] Preprocessing - Cropping the image [01G0] The step of cropping the image 40 into a cropped image 42 15 makes it possible to select within the original image 40 a rectangular region of interest comprising areas of the tab to be analyzed more specific and comprising fewer background areas or areas unrelated to the solid support 2 to be read. The areas of the image 40 useless for future analysis are thus eliminated from the cropped image 42. The cropping of the image 40 is an optional step, The region of interest of the cropped image 42 is defined from 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.

[0102] Pretreatment - Uniformity Correction [Ö1Ö3] The aim is to preprocess the image 40 or the cropped image and more particularly the uniformity correction is to correct the non-uniformity of the lighting within the region of interest so that it does not impact your future analyzes of the solid support 2. This uniformity correction may or may not be activated by the image processing means 2. The uniformity correction of the lighting is for example produced from a file comprising a model (or calibration) image, for example from a solid support which has not yet been subjected to the sample to be characterized or from a

B E2017 / 5708 solid support not comprising a point or band supporting labeling molecules. This model image is for example recorded in a memory of the optical reader 1 accessible by the image processing means 2.

In the absence of a model image, an auto-calibration is performed. Self-calibration consists in creating a synthetic image (a model) for uniformity correction, used in Heu and place of the model image and this, by applying to the region of original interest two consecutive median filters. These filters, by replacing the value of each pixel of the image by 10 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. [0105] Initiate detection of the points [0108] 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 radius circle 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.

[010S] Secondly, the circles are detected within the binary image obtained during the first detection phase. Among the 30 circles detected, there are in particular the points of the grid but also “false points” due in particular to the appearance of the edges of the solid support 2 within the ROI defined by the user. To eliminate false dots within

B E2017 / 5708 of the binary mask and keep only the circles corresponding to the points of the grid, theoretical replacement of the grid within image 40, 42 is used. The theoretical location of the grid is determined on the basis of the coordinates "x1", "y1" (top left) and "xn", "ym" (bottom 5 right) which define the position of the points of the grid at the top left and bottom right. Given the difference between the actual position of the point grid and the theoretical position specified by the reading method or by the image processing means 12, the theoretical coordinates along the y axis "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 (since they are considered to belong to the grid of points) and outside of which the detected circles are considered as false point detections and are therefore eliminated. After the elimination of the bad detections, a binary mask specifying the positions initially estimated of the points of the grid is obtained.

0 [0111] Fsttmg grHIe on visible dots [0112] 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 measurement, 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 30 present on the rod in X and in Y, the defined rectangle also makes it possible to determine the angle formed by the grid of points with the horizontal but also to calculate the space between points observed in practice according to X and Y. Indeed, the space between points according to x (y) is determined as the ratio between the

BE2017 / 5708 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 s is averaged with the theoretical inter point space (determined to him 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 in order 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 initial 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 points and the points of the initial grid pattern is then initiated by the image processing means 12. The correspondences 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 still need to be optimized, such as points that are not well aligned with others.

Local optimization of the dots [0115] So that each dot is centered on a measurement point, a local optimization of the position of each point of the theoretical grid is carried out. This provides a reliable measure of points that are misaligned with respect to the others. The badly aligned points are for example due to a bad alignment of the means of production of the points on the solid support 2. The number of iterations of the local optimization of position is defined by a parameter of number of iterations of local optimization of position. If the latter is zero, no optimization is performed.

For each theoretical point, an analysis window (side equal to two fels the external radius of the background measurement ring (background) of a dot in pixels scans an area of interest defined around the point . Every

B E2017 / 5708 window position, 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 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 panel 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 external radius of this point. background 10 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 [8119] 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 signal area containing the point to be measured. The measurement of the background intensity is also measured by considering the average intensity of the pixels of the image within an outer ring at the point of internal radius of Vanneau for measuring the background in pixels and of external radius of Vanneau background measurement in pixels.

[G120] 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 [G121 ] 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 against the optical and electronic parts by means of a protective glass. This protective glass is for example shown in FIG. 1a to

Fig. 1c and Fig. 2a to Fig. 2b so as to describe a non-right angle between its surface and a light beam coming from the solid support 2 in the direction of the optical detector 6, in order to limit the reflection of light beams emitted by

B E2017 / 5708 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 towards the outside of the sealed enclosure 16 The cooling means allow heat to be collected from the components that emit the most heat, such as microprocessors and ensure the transfer of this heat to the outside of the sealed enclosure. Preferably, the heat is then dissipated to the outside passively using a metal radiator. Preferably the transfer between the heat emitting components and the radiator 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. The communication means 8 also allow the communication of the results from the transmission means. The results can be communicated qualitatively or quantitatively to a display, printing, electronic messaging, or analog or digital recording device. The communication means 8 allow 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 such as barcode, QR code or data-matrix. The printed elements are for example read by suitable optical reading means known to those skilled in the art, 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. Points of interest correspond to the locations on which the labeling molecules have 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 iis 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.

B E2017 / 5708 [0124] FIG. 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 mobile 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 has batteries in order to benefit from sufficient autonomy to carry out a sufficient number of sample readings on a working day for example, [ 0125] 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 the quantification of analytes present in a sample comprising an identification device for identifying a support 2; communications means 8 for accessing a database of methods relating to a support 2; an optical unit 7, for analyzing said support 2 on the basis of analysis parameters included in said information relating to a support 20 2; image processing means 12; determination means for determining analyte information on the basis of the information relating to said support 2 and data from the image processing means 12; and transmission means configured to transmit your analyte information.

Claims (26)

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 comprising: - a location (20) for receiving said solid support (2); - an identification device (25) for identifying a solid support (2) to be read; communication means (8) for accessing a database of methods relating to said solid support (2) to be read in order to obtain information relating to a solid support (2); - an optical unit (7), for analyzing said solid support (2) on the basis of analysis parameters included in said information relating to a solid support (2) and comprising: o a first light source (3) for emitting according to an emission intensity and in a first wavelength range a first light beam towards said location (20); o an imaging system (60) comprising an optical detector (6) for providing an image (40) of a viewing area, said viewing area comprising at least a portion of said location (20); o a filter (10) for filtering a defined wavelength range, and positioned between the location (20) and said imaging system (60); - image processing means (12) of said image (40) for: reading in the information relating to said solid support (2) to be read, information relating to a finite number of subsets (41) of said image (40); o providing data relating to light intensities from said sub-assemblies (41); - determination means (13) for: B E2017 / 5708 o calculate, for each subset (41), an intensity of subset, and to be determined on the basis of said intensity of subset and on the basis of the information relating to said solid support (2 ) to read, analyte information for each subset (41); transmission means (19) configured to transmit said analyte information for each subset (41). 2. Device (1) according to the preceding claim, characterized in that said information relating to a solid support (2) to be tested comprises information corresponding to each of said sub-assemblies (41). 3. Device (1) according to any one of the preceding claims, characterized in that said information corresponding to each of said subsets (41) comprises information relating to at least one analyte. 4. 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 (41) and even more preferably more than fifteen sub-assemblies (41). 5. 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. 6. Device (1) according to any one of the preceding claims, characterized in that an analyte information is determined by an average on the basis of at least two intensities of sub-set originating from at least two sub-sets. together (41). B E2017 / 5708 7. Device (1) according to any one of the preceding claims, characterized in that said analyte information is binary type information. 5 8. Device (1) according to any one of claims 1 to 6 characterized in that said analyte information is information proportional to said measured light intensity, 9, Device (1) according to any one of the preceding claims 10 characterized in that it is compact and airtight. 10. Device (1) according to any one of the preceding claims, characterized in that it further comprises: - an external surface (16); 15 - cooling means (15) for transferring a quantity of heat from the interior of said device (1) to said external surface (16). 11, Device (1) according to the preceding claim characterized in that the cooling means comprise a heat pipe. 12. Device (1) according to any one of the preceding claims, characterized in that said optical unit (7) further comprises: o a light intensity sensor (5) for measuring the emission intensity emitted by said first light source (3); a feedback control means (11) for modulating said emission intensity of said first light source (3) as a function of the emission intensity measured by said light intensity sensor (5) so that said first light source (3) emits a target intensity. 13. 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 BE2017 / 5708 viewing area and in that said image processing means (12) are further configured for: g detecting reference areas (45) of said two-dimensional image (40), o determining said finite number of subsets (41) of said two-dimensional image (40), from information relating to said support solid (2), to be read, o position in said two-dimensional image (40) each sub-assembly (41) at a position determined from said reference areas (45). 14. 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 portion of said location (20) for receiving a solid support (2) than in said two-dimensional image ( 40); - assign a defined surface for each position to two sub-assembly dimensions (41) in said cropped image (42): - Performing a local position optimization of each subset (41) so that said defined surface of each subset (41) is positioned so as to return a maximum light intensity of each of said contrasted areas. 15. Device (1) according to any one of the preceding claims, characterized in that it further comprises a second light source (4) configured to emit a second light beam (40) in a second wavelength range. B E2017 / 5708 16. Device (1) according to any one of the preceding claims, characterized in that said first range of length is distinct from said second range of wavelength. 17. 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. 18. Device (1) according to any one of the preceding claims, 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 for: o determine said finite number of subset (41) of said 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 sub-set intensity (41) for each sub-set (41) corresponding to an analyte selected from said selection of analytes; o determining on the basis of said intensity of subset of 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 it further comprises: BE2017 / 5708 - a credit counter (18), said credit counter (18) being incremented by the selection of each analyte to be detected and / or to be quantified by the selection means (27). 20, Device (1) according to any one of the two preceding claims, characterized in that the determination means (13) are configured for: determining 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. 21. 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) on the basis of a defined encryption. 22, 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. 23. Diagnostic set for the optical reading of a recovery system comprising: - said device (1) according to any one of the preceding claims; diagnostic means for the respective, simultaneous and specific detection and / or quantification of a plurality of analytes present in a sample (E) comprising at least one reaction mixture and at least one recovery system (2), said at least a recovering system (2) being in the form of a solid support (2) to which are fixed in distinct and known recovery locations in space, competing ligands and / or biological molecules B E2017 / 5708 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 system 5 recuperator (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 of said biological recognition molecules fixed to said recovery locations of said 1 - recovery system (2). 24. 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 15 each having a diameter between 20 microns to 2 mm, preferably between 100 to 500 μm and even more preferably between 250 μm and 400 μm. 25, diagnostic assembly according to any one of the two claims 20 previous, 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 longitudinal axis of a width of said recovery system. 26. Diagnostic assembly according to any one of the three preceding claims, characterized in that said recovery system (2) comprises at least five, preferably at least ten, and more preferably at least fifteen separate recovery locations intended for detection and / or the respective, simultaneous and specific quantification of at 30 minus 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 monitoring and / or a calibrator.