Computer-implemented apparatus, method and system for performing histological or immunoenzymatic staining and hybridisation on tissue sections or on cell smears

Abstract

The invention relates to an apparatus / system for performing treatments of histological staining, immunoenzymatic staining and hybridisation on tissue sections or cell smears comprising a staining or hybridisation area (2), segmented into various compartments (9) adapted for the function of reaction chambers of the different treatments to be executed therein, in each of which one or more previously prepared samples are disposed on sample holders (14), optionally labelled with identification codes; and a robotic device (8), which has means to move freely along the three axes XYZ (30), adapted to be positioned at any point in the area (2) of the compartments (9), wherein the area (2) is located in the horizontal plane XY, and which comprises at least one high-precision image capture camera (31) adapted to capture images of the position of the sample holders and / or of the physical characteristics of the samples.

Description

[0001] DESCRIPTION

[0002] COMPUTER-IMPLEMENTED APPARATUS, METHOD AND SYSTEM FOR PERFORMING HISTOLOGICAL OR IMMUNOENZYMATIC STAINING AND HYBRIDISATION, ON TISSUE SECTIONS OR ON CELL SMEARS.

[0003] FIELD OF THE INVENTION

[0004] The present invention is included in the field of biomedicine and, more specifically, in the field of robots and automated systems for performing medical analyses. The present invention relates to methods, systems and apparatus for performing histological staining, immunoenzymatic staining and hybridisation on tissue sections or cell smears.

[0005] BACKGROUND

[0006] Automated biomedical robots and systems for performing treatments on patient samples (cases) are opening a gap in many medical laboratories and hospitals around the world, since they allow treatments such as histological or immunoenzymatic staining, or hybridisations on said samples, to be performed faster than doing it manually by a human being, even if this is specialised personnel, thus avoiding all the mistakes that they can make. Many types of biomedical robots capable of carrying out the functions outlined can be found, but the vast majority of them agree on the mechanical structure they have, in addition to the type of actions they perform and their way of executing it. Real-time systems cannot be considered because they represent temporal limitations for some of the processes they execute, so that, if these times or time slots are exceeded, they can produce adverse results and may even destroy the samples.

[0007] Automated devices for the preparation and dispensing of reagents on tissue sections or cell smears can operate with varying levels of automation, being able to intersperse manual phases with fully automated phases. Depending on the treatment, one or more types of immunological or immunoenzymatic chemical reagents will be used in one or more stages of said treatment.

[0008] Known reagent preparation and / or dispensing systems on tissue sections or cell smears disposed on slides have several disadvantages. For example, the manual dispensing, pouring or draining of reagents onto the slides has the disadvantages of being slow and of requiring an accuracy that decreases the overall efficiency of the treatment on those preparations. Another disadvantage is that manually dispensing, pouring and draining reagents can be a dirty operation, requiring effective cleaning and consequently stopping the instruments. Another disadvantage is that the selection of the correct reagent requires the attention and accuracy of the operator and there is a greater possibility of errors in the application of reagents, which decreases the accuracy of the tests and the operational efficiency.

[0009] A significant problem with current systems is that they seek maximum mechanical efficiency, but do not have a process planner, a critical element during the performance of any biomedical process. The development of these systems is not simple, since, to the design of the physical part, with a great complexity in its modelling, it is necessary to include the software development that allows controlling and executing the different system functions. If you want to develop a planner, you must wait until the final system is complete to be able to calculate times or use other alternatives, such as an empirical calculation, with the risk of errors that this entails.

[0010] Real-time systems have processes that must be executed in a specific order in order to respect the different time restrictions. This task can be relatively simple if the number of processes is small and their execution times are known, thus allowing the planning of their order and the most effective way to complete the work. However, when the number of processes with different execution times increases, the complexity begins to grow and certain systems are not viable for planning in this way.

[0011] A problem that the methods, systems and apparatus existing in the state of the art have is that the preparation and dispensing of reagents to each preparation is carried out regardless of the area or profile to be treated present in said sample. This entails the waste of reagents, many of them very expensive, and the overload of treatment reagent in the sample holder, which causes spills, dirt on the apparatus and possible breakdowns, in addition to being able to contaminate other sample holders disposed adjacently or closely and / or serially in the racks with unwanted treatments. On the contrary, when the treatment dispensed does not cover the entire sample, the results obtained may not reflect the histological, cellular, chemical, immunophenotypic or molecular reality of the sample disposed on the sample holder, giving a false result or a result that cannot be subsequently analysed satisfactorily.

[0012] Another added problem of the methods, systems and apparatus existing at present, also related to the dispensing of the treatment reagents from the samples, is when said reagents have a high density that makes them, due to their high surface tension, difficult to spread over the sample.

[0013] Among the many problems, apart from those mentioned above, it is also found that this type of device must be stopped in order to be cleaned and during the maintenance processes and that said cleaning or maintenance is manual, performed by operators. These systems must have systems that allow total automation of the equipment cleaning and maintenance processes.

[0014] BRIEF DESCRIPTION OF THE INVENTION

[0015] The present invention eliminates the disadvantages and solves the problems of the prior art.

[0016] On the one hand, the inventors have developed an apparatus / system / method that solves the problems associated with the continuous loading systems of the state of the art, wherein the system, as a whole, would cease to be operational in the event that a reagent vial is closed, or there is a temperature alteration in a reaction chamber. The present invention allows independent treatment of samples by means of modular systems and computer- implemented methods. Thus, the present invention, as well as having an automated apparatus / system / method for staining and hybridisation of a plurality of samples, also offers means to be able to place new samples without altering the current protocol / method of the other samples that have already started the staining and hybridisation protocol. The apparatus / system / method of the invention offers modular solutions to adapt to the introduction of new samples to a process already started by the apparatus / system / method, thus allowing to solve unexpected situations, such as the case of the arrival of new samples that have to be analysed urgently, avoiding an interference of the processes already started with others, the staining and hybridisation with samples of different nature also being possible in the same device.

[0017] On the other hand, the apparatus / system / method of the invention has means for the optical evaluation of the physical characteristics of the samples, i.e. , shape, texture, colour, etc., which are in the process of staining or hybridisation, so that the apparatus / system / method allows, for example, to reduce incubation times and to avoid the possible deterioration of the samples by excessive incubation periods in contact with aggressive solutions. Likewise, the optical evaluation means of the invention allow identifying, based on the physical characteristics of the sample, whether the staining and hybridisation process requires longer incubation times, washing, etc., allowing not only to reduce the use of reagents, but also to guarantee that the staining or hybridisation does not have to be repeated because the protocol was not adapted to the reality of the situation of the sample. Furthermore, the apparatus / system / method of the invention is designed such that the in-process staining or hybridisation protocol is not altered by low levels or absence of a reagent, which can be manually introduced without interference from the in-process protocol.

[0018] The present invention relates to a method, system and apparatus for performing treatments of histological staining, immunoenzymatic staining and hybridisation on tissue sections or cell smears that solves the problems existing in the state of the art described above. In particular, the present invention relates to a computer program for applying process protocols existing in the computer program and previously selected about the treatments of histological staining, immunoenzymatic staining and hybridisation on tissue sections or cell smears comprised in said sample, based on the photographic image capture performed on said sample and on the area of said sample, the contours thereof, its position and the amount of sample to be treated.

[0019] The invention provides a solution to the problems of the state of the art by providing an apparatus / system for performing treatments of histological staining, immunoenzymatic staining and hybridisation on tissue sections or cell smears comprising: i. A staining or hybridisation area (2), segmented into various compartments (9) adapted for the function of reaction chambers of the different treatments to be executed in them, in each of which one or more previously prepared samples are disposed on sample holders (14), optionally labelled with identification codes; ii. A robotic device (8), which has means to move freely along the three axes XYZ (30), adapted to be positioned at any point in the area (2) of the compartments (9), wherein the area (2) is located in the horizontal plane XY, and comprising the following elements:

[0020] - At least one high-precision image capture camera (31) adapted to capture images of the position of the sample holders and / or of the physical characteristics of the samples and, optionally, of the identification codes, disposed on the sample holders (14), as well as of the identification codes disposed on specific reagent reservoirs (22);

[0021] - At least one probe adapted for the dispensing of specific reagents and at least one probe adapted for the dispensing of common reagents;

[0022] - At least one washing probe adapted for washing;

[0023] - At least one general-purpose microcontroller with a computer program for the control of all the protocols, processes, members and equipment that form or operate the system.

[0024] In general, the method and the system and / or the apparatus, capable of implementing it, operates according to three configurations: a) It captures only the correct position image of the sample and proceeds to a preprogrammed reagent dispensing, without further ado. b) Capture of the correct position image of the sample and the indexing codes disposed on the sample holder, to dispense reagents specifically to each sample based on said indexing codes. c) Capture of the image of the correct position of the sample, of the profile or contour thereof and, optionally, of the indexing codes disposed on the sample holder, in order to, by means of artificial intelligence (Al), dispense reagents in a specific and improved way, in terms of quantity, time and location of said reagents dispensing, to each sample and, optionally, also depending on the indexing codes disposed on the sample holder.

[0025] BRIEF DESCRIPTION OF THE FIGURES

[0026] Figure 1 is the general perspective view of the system for performing histological staining, immunoenzymatic staining and hybridisation on tissue sections or cell smears according to the present invention.

[0027] Figure 2 is the general perspective view of the system for performing histological staining, immunoenzymatic staining and hybridisation on tissue sections or cell smears according to the present invention with the detail of the reaction chambers.

[0028] Figures 3 and 4 are the general perspective view of the system for performing histological staining, immunoenzymatic staining and hybridisation on tissue sections or cell smears according to the present invention with the internal detail of the electronic elements and reaction chambers.

[0029] Figure 5 is a perspective view of the electronics protection cap and reaction chambers.

[0030] Figures 6, 7 and 8 are perspective views of the reaction chamber slides.

[0031] Figures 9 and 10 are perspective views of the waste tray of all the compartments and which is composed of two parts.

[0032] Figure 11A is a perspective view of a plurality of common reagent reservoirs housed in a compartment.

[0033] Figure 11 B is the top perspective view of one of the common reagent reservoirs.

[0034] Figure 11c is the bottom perspective view of one of the common reagent reservoirs.

[0035] Figure 11 d is a photograph of 6 common reagent reservoirs (above) and the compartment area that houses the common reagent reservoirs, where each common reagent comb reservoir (below) must be placed based on visual identifiers.

[0036] Figure 12 is a top perspective view of the structure housing a plurality of specific reagent reservoirs, in turn housed in racks.

[0037] Figure 13a is a bottom perspective view of the structure housing a plurality of specific reagent reservoirs, in turn housed in racks.

[0038] Figure 13B is a top perspective view of a rack housing 8 specific reagent reservoirs.

[0039] Figure 13c is a general perspective view of a specific reagent reservoir.

[0040] Figure 13d is a depiction of the interior of the specific reagent reservoir by the housing section.

[0041] Figure 14 is a top view of the structure that houses the set of washing stations (area and spreader), the drying station of the spreader and tubes for the automatic mixing of reagents.

[0042] Figures 15, 16 and 17 are perspective views of the robotic device; general view (Fig. 15); detail of the XYZ axes and components integrated into the robotic device (Figs. 16-17).

[0043] Figure 18 is a general perspective view of the precision probe integrated into the robotic device.

[0044] Figure 19A is a general perspective view of the common reagent dispensing comb integrated into the robotic device. Figure 19b is a general view photograph of an embodiment of the comb comprising common reagent dispensing pipettes or capillaries associated with use of the XYZ axes of the robotic device.

[0045] Figure 20 is a general perspective view of the robotic device with the detail of the integrated outer roller and integrated nozzle of the blower.

[0046] Figure 21 is a general perspective view of the spreader roller for spreading the reagents.

[0047] Figure 22 is a general perspective view of the drying device.

[0048] Figure 23 is a general view of the filter for gas removal.

[0049] Figure 24 is the block diagram showing the transition of states of the microcontroller that carries out the control of the method for the performance of treatments of histological staining, immunoenzymatic staining and hybridisation on tissue sections or cell smears.

[0050] Figure 25 is the block diagram showing the actions that the system microcontroller performed between the CHECK and READY states during the method for performing treatments of histological staining, immunoenzymatic staining and hybridisation on tissue sections or cell smears.

[0051] Figure 26 is the block diagram showing the actions that the system microcontroller performed between the READY and EXEC states during the method for performing treatments of histological staining, immunoenzymatic staining and hybridisation on tissue sections or cell smears.

[0052] Figure 27 is the block diagram showing the actions that the system microcontroller performed between the EXEC and EXEC_OK states during the method for performing treatments of histological staining, immunoenzymatic staining and hybridisation on tissue sections or cell smears.

[0053] Figure 28 is the block diagram showing the actions that the system microcontroller performed between the EXEC_OK and FINISHED states during the method for performing treatments of histological staining, immunoenzymatic staining and hybridisation on tissue sections or cell smears. Figure 29 is the block diagram of the steps of the method with capture of the position of the samples on the sample holders and the pre-programmed reagent dispensing.

[0054] Figure 30 is the block diagram of the steps of the method with analysis of samples and codes on the sample holder and the specific dispensing in each sample based on said codes.

[0055] Figure 31 is the block diagram of the method steps with analysis and dispensing based on artificial intelligence.

[0056] Figure 32 is the perspective representation showing in detail an embodiment of the robotic device comprising, among others, precision probe, high precision image capture camera, and electronic components.

[0057] Figure 33 is the perspective representation showing in detail an embodiment of the robotic device comprising, among others, precision probe, spreader roller, drying system and reagent dispensing comb.

[0058] Figure 34 is the perspective representation showing in detail an embodiment of the robotic device comprising, among others, an infrared (IR) sensor and components associated therewith.

[0059] DETAILED DESCRIPTION OF THE INVENTION

[0060] The present invention relates to an apparatus (1) for carrying out treatments of histological staining, immunoenzymatic staining and hybridisation on tissue sections or cell smears comprising:

[0061] - a staining or hybridisation area (2), covered by a lid (100), and segmented into various compartments (9) adapted to the function of reaction chambers (9) of the different staining or hybridisation treatments, in each of which one or more previously prepared samples are housed in a sample holder (14), optionally labelled with codes or texts for identification, and

[0062] - a robotic device (8), configured for movement along the three axes XYZ (30), adapted to be positioned at any point in the area (2) of the compartments (9) in the horizontal plane XY.

[0063] Each of said compartments comprises a lower face that rests on or comprises a heating device (15). In a preferred embodiment of the invention said heating device is a thermal blanket disposed on a vibration system (16) and on a waste tray (3); on its upper face, bevelled, slotted or milled, the lower face of the sample holders (14), optionally made of glass, of size and shape adapted to that bevelling, slotting or milling, is supported, maintaining the perimeter of the upper face of the glass slide in flight and isolated, preventing the reagent that is dispensed, automatically or manually on it, from spilling out of the area by surface tension; and wherein, between each bevel, slot or milling, grooves (13) are transversely located for the expulsion of surplus waste towards a waste tray. Each compartment has a light indicator, preferably a LED (12), to identify the fault state or the state of the protocol in execution in said passenger compartment. For the purposes of this patent, the terms sample holders, microscope slide or, simply, slide(s), should be considered synonymous.

[0064] In a preferred embodiment of the invention, each compartment (9) as a reaction chamber has a vibration system or vibrator (16). Thus, in a particular embodiment of the invention, the apparatus can comprise a plurality of vibrators that are controlled independently and depending on whether or not the protocol applied in the chamber activates the commands that allow vibration. Each vibrator is controlled by a specific electronic board. The functions of the vibrators are:

[0065] - Move the particles accelerating the chemical reactions, therefore, reducing the incubation time of the reagents and giving greater robustness to the process.

[0066] - Dispersion capacity of the reagents on the slide.

[0067] The vibration system (16) is adapted for interaction with the respective reaction chamber and with no other element, allowing an individualised protocol for different samples.

[0068] The robotic device (8) is adapted to integrally incorporate the following elements:

[0069] - One or more high-precision image capture cameras (31) capable of capturing images of the physical characteristics of the samples (contour, shape, texture, colour, etc.) and, optionally, of the identification or indexing codes, disposed on the sample holders (14), as well as the identification or indexing codes of the reagent reservoirs, which in turn have a level sensor. According to the present invention, the arrangement of the high precision image capture camera (31) allows an advantageous image acquisition compared to the systems of the state of the art, which in turn allows an improvement of the whole process, in terms of reduction of times, consumption of reagents and energy, and in the quality of the staining or hybridisation achieved. Unlike the chambers of the state of the art, the chamber of the invention is not disposed perpendicularly in relation to the sample holders. This arrangement, angled with respect to the sample holders, allows the acquisition of images with greater three-dimensional detail of the position of the samples to be analysed, as well as avoiding noises caused by lighting on the sample holder, providing greater precision when extracting the physical characteristics of the samples, such as their shape and texture, which in turn allows the apparatus of the invention, trained with artificial intelligence, to determine the staining or hybridisation state and make decisions in relation whether to continue or stop of the staining or hybridisation process. In a particular embodiment, the angle of disposal of the chamber in relation to the sample holder is between 5° and 75°, preferably between 15° and 60°, more preferably between 25° and 45°. It is understood that this acquisition of images requires a series of digital transformation treatments using means provided for this purpose. In order to detect the optical characteristics of the sample to be analysed, it is necessary to place the camera in lighting conditions adapted to the degree of inclination of the chamber.

[0070] In a preferred embodiment of the invention, the apparatus incorporates an Inertial Measurement Unit (IMU). This component is incorporated into the apparatus with two objectives:

[0071] 1. Have real-time control of the inclination of the reaction chambers. This functionality is important because since the reaction chambers do not have a lid that allows capillary diffusion, it is very important to keep them within a minimum range of inclination that allows diffusion throughout the slide. If the angle exceeds the acceptance range, diffusion throughout the slide is compromised and some parts of the tissues may not be stained.

[0072] 2. Detect the stability level of the apparatus installation. The apparatus weighs 150 kg and with the movements of the robot (accelerations and decelerations) high inertial forces can occur that affect the conservation of the reagents on the slide, as well as compromising the integrity of the support on which it is installed. With a robot movement test, the stability level of the installation is detected and it can be validated. To perform the stable calibration of the apparatus it is important to carry out an accelerometer calibration process, consisting of the following steps: a) When installing the instrument, the technical service will level it manually and in the service application it will indicate that the equipment is balanced. The main controller will take a series of measurements, discarding the extremes and storing the average of the remaining ones as "0° inclination" in the x and y axes. From that point on, the unevenness that occurs with respect to that initial equilibrium position can be controlled. b) In the user application:

[0073] Before carrying out maintenance of the apparatus, it will check the difference with respect to the equilibrium position and inform the user if the maximum permitted inclination is exceeded to ensure improved staining and, if necessary, instruct him to contact the technical service.

[0074] During the series, it is possible to check the maximum values of the inertial forces due to the movements to inform about the suitability or otherwise of the apparatus installation in the final report of the series. c) Monitoring of the apparatus state: i. By analysing the vibrations of the device using advanced standards detection techniques (embedded neural networks, decision trees, vector support machines...) the operating state of the apparatus is determined. ii .The detection of present or predictable failures throughout a series allows guaranteeing the quality of the analysis process, preventing errors with the costs associated with the loss of samples or erroneous results.

[0075] For the purposes of the present invention, detection with high-resolution cameras is synonymous with detection with high-precision cameras. It is also understood as multiresolution detection and will range from 640x480 pixels, up to 1920x1200 pixels or more. In a preferred embodiment of the invention, recognition of the identification codes of the reagent reservoirs or of the sample holders is performed by means of a pattern reading algorithm that follows the standard of the printed code (Datamatrix, for example). If the code provided is unreadable or you have chosen to have the code printed or written as characters on the label, the reading is done using an OCR (Optical Character Recognition) algorithm. In another particular embodiment, the indexed information of each sample holder can be manually entered so that the apparatus can identify the characteristics of the sample holder. In another particular embodiment, for reading characters printed by OCR, all possible words and groups of alphanumeric characters on the label are searched / scanned (without Al) on the label. For each of these scanned regions, the characters are read / interpreted by a recurrent neural network (RNN). In an alternative embodiment, on the one hand, and only for the detection of codes, use is made of convolutional neural networks (CNN) and, on the other hand, words and / or groups of alphanumeric characters are searched;

[0076] - A common or general reagent dispensing comb (35). In a particular embodiment, the comb (35) is formed by at least six dispensing probes or pipettes (35a) and at least six common or general reagent tubes. The dispensing pipettes (35a) are connected to at least one area (5) housing a plurality of common reagent reservoirs (5a) and at least one area (6) housing a plurality of specific reagents (22);

[0077] - A spreader roller (33) of viscous reagents, thus allowing an even distribution of the reagent throughout the entire sample, or the entire sample holder (14) that, otherwise and due to the high density of some reagents, would have an uneven distribution. To do this, the density parameters of each reagent are pre-loaded in the computer program that operates the system. With these density parameters, the program dispenses the reagent at a certain rate directly proportional to said density. Once the reagent has been dispensed, the treatment protocol itself determines whether a spreading of the reagent by the roller is necessary, due to its high viscosity. To do this, the robotic device has up to 3 Z axes. Hence, on the Z2 axis is where the roller to be operated is located in a 1st pass in a certain direction, after the drops of dispensed reagent, spreading said viscous reagent and, lifting the roller before reaching the end of the holder, to re-execute the spreading, in a 2nd pass, but now in the opposite direction to the previous one. The viscous reagent spreader roller, therefore, makes a double pass to evenly spread the viscous reagent.

[0078] In a preferred embodiment of the invention, the apparatus (1) comprises at least one mixing and drying unit (7) that houses tubes (26) for the automatic mixing of reagents, an automatic mixing area (27) of reagents, a drying station (28), among others, of the spreader roller (33), and washing stations (29) of the spreader roller (33) and of the probes. The mixing and washing unit (7), disposed adjacent to the area of specific reagents (6), is advantageous because it allows a rapid and effective cleaning and drying of the spreader roller (33) which, in turn, allows an improvement of the staining or hybridisation. In a particular embodiment, the apparatus (1) has an automatic washing device (25) of the specific reagent probe, consisting of a tube connected to a membrane pump disposed in a container containing a specific washing solution determined by the control device, based on the specific reagent previously used by the probe.

[0079] In a preferred embodiment, the apparatus (1) of the invention is further provided with specific reagent dispensing probes and common reagent probes.

[0080] In another particular embodiment, the apparatus of the invention also has washing probes of a diameter greater than the previous dispensing probes, for the performance of washes, preferably two probes, and directly connected to the common reagent reservoirs.

[0081] In another particular embodiment, the apparatus (1) of the invention has at least one staining or hybridisation unit (10) disposed in the staining or hybridisation area (2) comprising a plurality of compartments (9). In a more preferred embodiment, the staining or hybridisation unit (10) is provided with means for housing at least one compartment (9), preferably three compartments (9). The staining or hybridisation unit (10) is advantageous since it allows its placement and removal from the area (2) independently of other staining or hybridisation units (10) in use, so that the introduction of new samples in an already initiated process is facilitated and, notably, does not interfere with the staining or hybridisation process of the rest of the samples.

[0082] In another particular embodiment, the specific reagent reservoir area comprises a thermostatted rack (23), the temperature of which is controlled by the programmable device, which controls the entire system. The common reagent reservoir area 5 has a weight volume sensor for each reservoir. The specific reagent reservoir area 6 has a capacitance volume sensor in the probe to detect the level (21) of reagent in each reservoir.

[0083] In the apparatus-method-system, according to the present invention, a double control of the level of reagents in vials is carried out, by capacitance and by internal accounting, with the following objectives:

[0084] 1 . Ensuring the dispensing of reagents, considering that the vials can suffer accidents outside the instrument (spills, evaporations) that could reduce the actual volume without the application being aware of this, since when the vial is discharged, the type of vial and the initial volume it has are reported and as volumes are aspirated from it, they are discounted and how much volume it has left is controlled, but only theoretically, not the volume that may remain in actual practice.

[0085] 2. Inserting the probe as little as possible into the reagents so that the external washing is as fast as possible (time is saved and less reagent is consumed) and possible drips on the apparatus after aspiration are prevented.

[0086] In this way a xml file is produced with all the types of vials that exist in the system and for each of them we have the following information:

[0087] • Dead volume.

[0088] • Geometry of the vial, i.e., depending on the level at which the upper level of liquid is found, we can know the volume it represents.

[0089] Furthermore, the user software has four reagent aspiration modes:

[0090] LLD-TABLE: The level sensor and internal accounting are used to know the height the reagent surface must be in the vial. The probe is lowered quickly to a height higher than the theoretical height of the liquid (editable margin parameter); the sensing is activated and the probe is lowered at a lower speed until liquid is detected. If the level at which the liquid is detected is within a parameterised range (vial tolerance, reagent salinity, etc.) and it is acceptable, the probe is inserted into the vial to aspirate the reagent in a staggered manner (see explanation in the following way), if it is not, an error is reported to the user.

[0091] LLD: Only the level sensor is used without considering the internal accounting to know the height at which the reagent surface must be in the vial. The probe lowers at a fast speed to the mouth of the vial without detection of liquid and there activates the LLD, reducing its speed to detect the liquid. Once it detects it, it gradually lowers distances of 1.5 cm (editable parameter) to aspirate the desired volume without externally staining the probe more than said distance. It is a safe mode, although not as safe as the previous one, which has the ability to detect possible sensing errors.

[0092] TABLE: The level sensor is not used, but it is a mode that emulates the behaviour of the LLD-TABLE mode, i.e., it wets only 1.5 cm of the probe assuming that the reagent is at the pertinent level according to the type of vial, its calibration level and its remaining volume. It is not a mode that ensures the existence of reagent but allows faster washing times and reduces the possibility of drips and can be used when it is necessary to deactivate the LLD due to technical incidents. DEEP: The level sensor is not used; the probe lowers to the bottom of the vial always to aspirate the required volume and by internal accounting the volume in the vial is known (it is not a completely safe system and can be used when it is necessary to deactivate the LLD due to technical incidents).

[0093] The common reagent reservoirs (5a) have a cap (5b) for filling the reagent and have orifices (5c) where the connectors for the reagent outlet are fixed to the equipment and allow the reagent outlet for direct dispensing from the robotic arm. The reservoirs have at their base a projection (5d) that acts as a support surface of the container whose function is to allow the uniform support of the container on the volume sensor and reduce dead volume of the container. Common reagents do not need identification codes on their reservoirs, but use a colour code that uniquely assigns it to the same position on the robotic device (8). Figure 11d shows the area where each common reagent reservoir must be placed.

[0094] In another particular embodiment, the apparatus (1) of the invention has one or more double drainage devices that, through two pumps, connect the waste tray (3) of the compartments (9) with at least two waste tanks, one for hazardous waste and another for non-hazardous waste. In another particular embodiment, the waste tanks (3) are provided with a level sensor.

[0095] In another particular embodiment, the apparatus (1) of the invention has one or more air blow drying systems (36), which integrate a compressor and a flow sensor. In this way, the present invention has means to carry out a simultaneous blowing and washing of a sample holder, in a single step, removing the existing reagent on it, quickly allowing the execution of the next step of the process.

[0096] The apparatus-system-method of the present invention, according to a preferred embodiment thereof, incorporates an air flow rate sensor before the blower nozzle. The purpose of this sensor is to control that when the compressor is activated, the desired air flow rate is actually generated to remove the reagent on the slide. This sensor does not require calibration and, depending on the flow rate of the blower nozzle, it will act at a greater or lesser distance from the upper face of the slide.

[0097] The calculation of the flow rate is performed instantly, measured in litres / minute, as well as accumulated, calculating the litres of air that have circulated through the blower nozzle. To calculate the absolute litres, an integral is made with a fixed time step. The calculation of the flow rate allows dynamically adjusting the power applied to the compressor to ensure the desired flow rate. This is done with the aim of cushioning the effects of compressor wear, as well as possible obstructions to the passage of air.

[0098] Thus, the present invention allows an improvement of the staining or hybridisation process carried out by the tasks of the system.

[0099] In another particular embodiment, the apparatus (1) of the invention has a filter (41) for gas removal that is automatically activated when reagents with hazardous vapours are used.

[0100] In another particular embodiment, the apparatus (1) of the invention has one or more thermal blankets (15) provided with a thermal probe for the control and maintenance of the temperatures of the different protocols to be carried out.

[0101] In another particular embodiment, each compartment (9) has a light indicator (12) to identify the fault state or the state of the protocol in execution in said compartment (9).

[0102] In another particular embodiment, the apparatus further comprises an automatic washing device (25) of the compartments (9), consisting of a tube connected to a membrane pump disposed in a container containing a specific washing solution determined by the control device, based on the specific protocol being developed in said compartment (9).

[0103] In another particular embodiment, the specific reagent reservoir area (6) comprises a thermostatted rack (23), the temperature of which is controlled by the programmable device, which controls the entire system.

[0104] In another particular embodiment, the common reagent reservoir area (5) has a weight volume sensor for each reservoir (5a).

[0105] In another particular embodiment, the specific reagent (22) reservoir area (6) has a capacitance volume sensor in the probe to detect the level of reagent in each reservoir.

[0106] In another particular embodiment, the apparatus (1) comprises at least one infrared sensor (42) for monitoring the temperature in the plurality of compartments (9) adapted for the function of reaction chambers.

[0107] In another particular embodiment, the apparatus (1) comprises means for executing a dynamic planning method (planner) according to the invention.

[0108] The apparatus (1) of the invention has a general-purpose microcontroller with a computer program for the control of all the protocols, reagents, processes, members and equipment that form or operate the apparatus.

[0109] Figures 1 to 4 show a possible embodiment of the apparatus / system (1) for carrying out treatments of histological staining, immunoenzymatic staining and hybridisation on tissue sections or cell smears according to the present invention. In detail, the system / apparatus (1) comprises a housing (4), and a cover or lid (100) that can be opened, exposing the staining or hybridisation area (2) in a horizontal plane, under which a waste tray (3) is located. The area (2) is segmented into compartments (9) which are adapted to house sample holders (14) and which act as reaction chambers. A robotic device (8) carrying a high-precision image capture camera (31) is shown. In a plane lower than the area (2), the area / structure (5) is shown that houses a plurality of common reagent reservoirs. Adjacent to area (2), area / structure (6) is shown which houses a plurality of specific reservoirs, as well as a mixing and drying unit (7). Also shown are the electronic components (102) under the housing (4).

[0110] The apparatus / system (1) of Figures 1 to 4 can comprise (not shown) a LED lamp inside the cabin that serves to illuminate the entire work area at the required times (loading of doors, calibration of equipment, etc.), as well as LED lighting placed in the Z axes so that when capturing the image of a door, the tissue can be detected without reflection problems. Both lamps will be off during the performance of the series to ensure that the technique is not affected by any light. The apparatus / system (1) of Figures 1 to 4 can comprise (not shown) a humidity and ambient temperature sensor of the cabin that is at the top, a sensor for opening the hood and the locks that prevent it from opening during a series for reasons of safety of the technician and to ensure the correct lighting of the interior during the processes of detection of fabric, reading of codes, etc., as well as a LED strip of the chassis that indicates to the user what state the instrument is in, if it is in process, finished, paused, request to pause or in error.

[0111] Figures 5 to 8 show in detail the staining or hybridisation area (2) comprising a plurality of units (10) of the staining and hybridisation area (2) that house, in a possible embodiment, three compartments (9), which in turn can house three sample holders (14). The unit (10) can be inserted or removed from the area (2) independently of the other units (10). The compartment (9) is shown with a light indicator (12). The cabin (9) is shown provided with grooves (13) for the expulsion of excess residues on its upper part, which facilitate the cleaning of the reagents used. The cabin (9) is shown, in its lower part, provided with a heating system / thermal blanket (15) and a vibration system (16) to facilitate staining or hybridisation reactions.

[0112] Figures 9 and 10 show a waste tray (3) that collects waste from the compartments (9), and which is composed of two parts, an upper part in the form of a grid (18) and a lower part (17) provided with an outlet orifice.

[0113] Figures 11A-D show in detail the area (5) housing a plurality of common reagent reservoirs (5a). The area (5) is provided with a housing (5e) housing a plurality of common reagent reservoirs (5a). A common reagent reservoir (5a) is shown comprising at its top, a reservoir plug (5b), a reagent outlet orifice or bore (5c). At its bottom, the reservoir (5a) has a stabilising projection (5d) of the common reagent reservoir. Also shown in detail is an embodiment of the housing portion (5e) wherein a plurality of common reagent reservoirs (5a) is housed as well as the means of identifying the reagents and their place of placement in the housing (5e). The area / structure (21) that houses the common reagent level sensor is shown.

[0114] Figures 12 to 13A-D show in detail a possible embodiment of the area / structure (6) which, in its upper part, houses a plurality of specific reagent reservoirs (22), while in its lower part it is provided with a thermostatted rack (23). Each channel of the thermostatted rack (23) can have an optical sensor of the presence of the rack, in such a way that it allows to know whether or not a rack has been introduced to read only the positions of the vials of the racks that have been detected (not shown). The area (6) is segmented into a plurality of racks (22a) provided with a gripping portion (24) of the rack (22a) housing the specific reagent reservoirs (22), in the embodiment shown, 8 reservoirs (22). The rack (22a) can be inserted or removed from the area (6) independently of the rest of the racks (22a) by means of the gripping portion (24). A specific reagent reservoir (22) is shown in detail which is provided with a cap (22b), adapted to be opened or closed for refilling or emptying, and an outlet port (22c) to allow the probe to aspirate specific reagents. Figure 13d shows sections at different levels of the housing (22d) (centre and right) of a reservoir (22) of specific reagents (left).

[0115] Figure 14 shows in detail a possible embodiment of the mixing and drying unit (7) housing a washing station (25) of the probes of the specific reagent probe, automatic reagent mixing unit (27), tubes for the automatic mixing of reagents (26), a drying station of the spreader (28), and a washing station of the spreader roller (29). In the rack (22a) of specific vials or reservoirs (22), a plurality (n) of vials or reservoirs (22) can be placed, which can be aspirated and dispensed directly into the slides (14) or can be dispensed into the mixing tubes (26) to make mixtures of different specific reagents, since these mixing reagents have several hours of stability and if they were not mixed in situ, they could not be used in the treatments. Additionally, having the possibility of mixing reagents according to the protocols implemented by computer, gives versatility to the apparatus-method-system, since it will not need to have as many reagent racks as needed for the different treatments, allowing from a limited number of reagents, by combination between them, to expand in number and the type of treatments to be applied to the samples.

[0116] Illustratively, different types of mixing reagents are described below, in particular, reagents that when mixed have a stability of between 30 minutes to 24 hours. The planner who controls the system / apparatus of the invention, depending on when he needs the mixing reagent and its stability, will look for the best time to perform the mixing automatically. Preferably, it will carry out the process when the robot is stopped (waiting for incubations, for example) so as not to extend the total time of the series. The mixtures may be of a plurality (n= 2, 3, 4, etc.) of reagents. It should be noted that there is a minimum mixing volume that is limited by the mixing ratio and the minimum dispensing volume of the system. For example, there is a mixture of 2 reagents wherein 25 pl of one is dispensed for each 1000 pl of the other. As the system cannot dispense less than 25 pl, the minimum mixture would be 1025 pl. On the other hand, in a protocol for a slide, 300 pl are used. Once the two reagents are dispensed into the mixing tube, a homogenisation of the mixture is performed. The way to do this is by aspirating and dispensing the volume of the mixed reagent in one of the tubes (26) (in the form of agitation). In a particular embodiment, the mixing tubes (26) are not cooled.

[0117] Figures 15, 16 and 17 show a possible embodiment of the robotic device (8) that has means (30, X, Y, Z) for a displacement in the XYZ axes indicated by double dates and is provided with a high precision image capture camera (31), disposed at an angle of 45 degrees. The means (X, Y and Z) for moving the robotic device (8) are shown in detail. The chamber (31) is disposed associated with the displacement means (Z), adjacent to a precision probe (32) and the spreader roller (33), so that the dispensing of reagents, their spreading and the optical evaluation of the sample can be carried out with the same device. The robotic device is shown provided with common reagent dispensing comb (35) and air blow drying system (36). The configuration of the invention, integrating a plurality of components in the same element, allows a reduction in the time and energy consumption of the protocol in use. Figure 18 shows in detail the precision probe (32) integrated in the displacement means (Z) of the robotic device (8), provided with a control element (34) of the probe (32).

[0118] Figure 19A shows in detail a common reagent dispensing comb (35) integrated in the displacement means (Z) of the robotic device (8), wherein no dispensing probes are shown. Figure 19b shows a possible embodiment of the common reagent dispensing comb (35) integrated in the means (Z) of the robotic device (8) wherein 6 dispensing probes (35a) are shown as a possible embodiment.

[0119] Figure 20 shows in detail the configuration of the spreader roller (33), adjacent to the air blow drying system (36), integrated in the displacement means (Z) of the robotic device (8), which allow a reduction in the consumption of time and energy of the protocol in use. Figure 21 shows the spreader roller (33) provided with a side portion (37) and body (38). Figure 22 shows in detail the air blow drying system (36) provided with orifices (39) and a slot (40).

[0120] Figure 23 shows a filter (41) for gas removal that can be integrated into the apparatus of the invention.

[0121] Figure 32 shows a possible configuration of components integrated into the displacement means (Z) comprising, among others, probe (32), chamber (31), comb (35), blowing system (36) and electronic component (45). Figure 33 shows a possible configuration of components integrated in the displacement means (Z) comprising, among others, probe (32), roller (33), comb (35) provided with six dispensing probes (35a) and blowing system (36). Figure 34 shows a possible configuration of components integrated into the displacement means (Z) comprising, among others, probe (32), roller (33), blowing system (36), and a temperature monitoring system comprising an infrared (IR) sensor (42), electronic temperature control board (44), and connection pins (45) of the electronic board for the IR sensor (42). These configurations allow a reduction (improvement) in the time and energy consumption of the protocol in use.

[0122] The features described in relation to the apparatus (1) can be integrated and are interchangeable with the components of the system of the invention, which is described below.

[0123] The present invention also relates to a system (1) for performing treatments of histological staining, immunoenzymatic staining and hybridisation on tissue sections or cell smears comprising, among others, the following components: - A general-purpose microcontroller;

[0124] - Means for storing data in one or more databases;

[0125] - A USB bus;

[0126] - A CAN bus;

[0127] - A main electronic card, connected to the USB bus to allow communication with the microcontroller, and on the other hand to the CAN bus to propagate and receive the information from the other cards and control, among others:

[0128] • The motors of a robotic device (8), together with its encoders and end-of-stroke sensors, for the X and Y axes;

[0129] • Reagent presence and level detection sensors;

[0130] • Open / close detection sensors;

[0131] • Indicator light, preferably LED, to indicate the system state;

[0132] • Cold table for reagent maintenance;

[0133] • Interface to control a precision probe (32);

[0134] - Electronic motion control cards, connected to the can bus, intended to control the motors of the robotic device (8) based on the different XYZ axes (30) and which controls, among others:

[0135] • The motors of the robotic device (8), together with their encoders and end-of- stroke sensors;

[0136] • Interface for liquid level detection sensor (-LLD- Liquid Level Detection);

[0137] - A hydraulic control board that is connected to the CAN bus, and is intended to control the different hydraulic circuits of the instrument, among others:

[0138] • Peristaltic pumps with stepper motors;

[0139] • Direct current pumps;

[0140] • Direct current valves;

[0141] • Air compressors;

[0142] • The blowing system air flow rate sensor (36);

[0143] - A vibrator control board connects to the CAN bus, intended for the control of the vibrators located in the reaction chambers;

[0144] - A compartment control card connected to the CAN bus, intended to control the thermal actuators of the reaction chambers disposed in said compartments and which controls, among others:

[0145] • The actuators for the control of resistive heaters;

[0146] • The interfaces of the resistive temperature sensors;

[0147] • The actuators to control the LED lights (12) indicative of the state of each reaction chamber.

[0148] The system (1) comprises a staining or hybridisation area (2), covered by a lid (100), and segmented into various compartments (9) that act as reaction chambers for the different treatments to be executed therein, in each of which a previously prepared sample is disposed on sample holders (14), optionally labelled with identification codes. Each of said compartments (9) comprises a lower face that rests on a thermal blanket (15), on a vibration system (16) and on a waste tray (3) and on its upper face, bevelled, grooved or milled, the lower face of a sample holder or sample holders (14) is supported, for example, of glass, of a size and shape adapted to that bevelling, grooving or milling, keeping the perimeter of the upper face of the (glass) holder in flight and isolated, preventing the reagent that is dispensed, automatically or manually on it, from spilling out of the area by surface tension; and wherein, between each bevel, groove or milling, grooves (13) are placed transversely for the expulsion of surplus waste towards a waste tray (3). In a particular embodiment, the thermal blanket (15) is provided with a thermal probe for the control and maintenance of the temperatures of the different protocols to be developed.

[0149] The system has a robotic device (8), which moves freely along the three axes XYZ (30), and can be positioned anywhere in the area (2) of the compartments located in the horizontal plane XY, and which can comprise:

[0150] - At least one high-precision image capture camera (31) configured to capture images of the physical characteristics of samples and, optionally, of the identification codes, disposed on the sample holders (14), as well as of the identification codes of the specific reagent reservoirs (22), which have a level sensor;

[0151] - Dispensing probes for specific reagents and / or common reagents;

[0152] - A common or general reagent dispensing comb (35), which may comprise a plurality of dispensing probes, preferably at least six dispensing probes or pipettes (35a), and at least six common or general reagent tubes. The dispensing pipettes (35a) are connected to at least one common reagent reservoir area (5) and at least one specific reagent area (6); - At least two washing probes of a diameter greater than the previous dispensing probes, for washing and connected directly to the common reagent reservoirs; and

[0153] - A reagent spreader roller (33).

[0154] In a particular embodiment, the system (1) comprises an automatic cabin washing device (25), consisting of a tube connected to a membrane pump disposed in a container containing a specific washing solution determined by the control device, based on the specific protocol being developed in said cabin.

[0155] In a particular embodiment, the specific reagent (22) reservoir area (6) comprises a thermostatted rack (23), the temperature of which is controlled by the programmable device, which controls the entire system. The common reagent (5a) reservoir area (5) has a weight volume sensor for each reservoir. The specific reagent reservoir area (6) has a capacitance volume sensor in the probe to detect the level of reagent in each reservoir. The common reagent reservoirs (5a) have a cap (5b) for filling the reagent and have orifices (5c) where the connectors for the reagent outlet are fixed to the equipment and allow the outlet of reagent for direct dispensing from the robotic device (8). The reservoirs (5a) have at their base a projection (5d) that acts as a support surface of the container whose function is to allow the uniform support of the container on the volume sensor and reduce dead volume of the container. Common reagents do not need identification codes on their reservoirs, but use a colour code that uniquely assigns it to the same position on the robotic device (8). Figure 11c shows the area wherein each common reagent reservoir must be placed. In contrast to determining whether a suitable amount of reagents to be used in the sequence of the treatment protocol is available in the plurality of compartments in the systems of the state of the art, the present invention allows the indication to the user which specific reagents have to be introduced into at least one of the plurality of compartments (9), wherein the slides (14) have been included.

[0156] In a particular embodiment, the system (1) comprises one or more double drainage devices that, through two pumps, connect the waste tray of all the compartments with at least two waste tanks, one for hazardous waste and another for non-hazardous waste. One or more air blow drying systems (36), integrating a compressor and a flow sensor. In a particular embodiment, the waste tray may have a level sensor that allows recognising when it is full to warn of possible problems in the emptying system. In addition, the waste tray may have a gravity overflow that prevents hazardous or non-hazardous waste from falling on the rest of the instrument or on the work table. In a particular embodiment, the system (1) comprises an automatic reagent mixing area (27).

[0157] In a particular embodiment, the system (1) comprises a gas removal filter (41).

[0158] In a particular embodiment, the system (1) comprises one or more thermal blankets (15) provided with a thermal probe for the control and maintenance of the temperatures of the different protocols to be developed.

[0159] In another particular embodiment, the system (1) comprises at least one infrared sensor (42) for monitoring the temperature in the plurality of compartments (9) adapted for the function of reaction chambers.

[0160] In another particular embodiment, the system (1) comprises means for executing a dynamic planning method (planner) according to the invention.

[0161] The present invention also relates to a computer-implemented method for carrying out treatments of histological staining, immunoenzymatic staining and hybridisation on tissue sections or cell smears, which has one or more previously prepared samples on a sample holder, optionally labelled with identification codes, in an area, covered by a lid, and divided into various compartments that act as reaction chambers for the different protocols or treatments to be executed on said samples disposed therein.

[0162] The inventive apparatus and system are advantageously configured to execute the inventive method. Thus, the invention relates to a computer-implemented method for performing treatments of histological staining, immunoenzymatic staining and hybridisation on tissue sections or cell smears, comprising the steps of: i. Disposing one or more previously prepared samples on at least one sample holder, optionally labelled with identification codes, in a staining or hybridisation area, segmented into a plurality of compartments that act as reaction chambers for a plurality of staining or hybridisation treatments on said samples disposed; ii. Capturing at least one image by means of a high-precision photographic image capture device, of the position of each sample holder in the respective reaction chamber and, optionally, the identification code disposed on the sample holder; iii. Capturing at least one high-precision image of one or more samples disposed on said sample holder by a high-precision photographic image capture device; iv. Performing said treatments on the samples disposed in the compartments acting as reaction chambers, by means of the provision of a robotic device, configured for its three- dimensional displacement along the three axes XYZ, and adapted to be positioned at any point of said staining or hybridisation area of the compartments located in the horizontal plane XY, and which carries out, by means of a general purpose microcontroller with a computer program, the control of the processes that comprise:

[0163] - Processing the at least one image of the sample holder and, optionally, of the label with codes disposed on it;

[0164] - Dispensing specific reagents or common reagents based on a pre-programmed protocol of processes to be applied, depending on:

[0165] - the reading of identification codes disposed on specific reagent reservoirs;

[0166] - the quantity, location and time of dispensing;

[0167] - image capture of the at least one sample, processed by Artificial Intelligence (Al);

[0168] - Performing washes after each process protocol and / or each process independently; and

[0169] - Obtaining data from the images captured of each sample and, optionally, related to each identification code of the sample holders.

[0170] In a particular embodiment, the labels of the sample holders carry codes that allow identifying the sample, the case to which it corresponds, the protocol to be operated on it and the order of priority to be applied to each sample and / or to each protocol.

[0171] In a particular embodiment, the method is characterised in that the microcontroller carries out the control of the following functions: a) Start the method; b) Check that the lid is closed and activate a lock to prevent it from opening during operation; c) Check the correct placement of all the elements, particularly the sample holders in the reaction chambers; d) Check that all equipment involved in the method during the execution of the process protocols is ready, including, at least, among said checks, the washing and purging process protocols of all reagents, air and any other solution dispensing probes used during the rest of said process protocols and if the equipment is correctly balanced; e) Optionally, read, by means of at least one high-precision image capture camera, all the labels of each sample holder, to identify the sample to be treated, the case (or patient identification file number) from which it comes, the process protocol or protocols to be executed, in the treatment of said sample; the order of priority of said process protocols; as well as carry out the detection of the tissue or cell smear existing on each sample holder and also carry out the delimitation of the position and amount of tissue or cells in each area of each sample holder; in a particular embodiment, a K-means model is used to, once the regions that are candidates to be tissues are detected, disregard all those regions that are considered noise insofar as they differ significantly in texture, position and geometric dimensions (width and height). In another particular embodiment, tissue detection is performed directly by a CNN neural network model; f) If all the initial checks have been passed, begin to execute one or more process protocols, by dispensing reagents in the samples for which an image capture of the identification codes of the respective specific reagent reservoirs and mixing tubes by Al, if there is mixture in the series; g) Calculate the time stamps and prioritise the process protocols that must be executed, based on the previous readings and, based on the specific process protocol, determining a) the reagents and b) the amount of said reagents that must be dispensed in each area of the sample holder; in a particular embodiment, the calculation of the dispensing positions and volumes is carried out without Al. In an alternative embodiment, the process may be performed by evolutionary Al models, for example, Genetic Algorithms (GA) or Particle Swarm Optimisation (PSO), among others; h) Periodically update the timestamps and prioritisation of the process protocols of step g), until all processes of all protocols have been completed; and i) Finish, when all the final maintenance tasks are concluded, then activating a low energy consumption routine.

[0172] In a particular embodiment, prior to the start of the method, a list of tissue samples or cell smears to be processed has been loaded into the database of the computer program comprised in the microprocessor, each of which is identified with a sample code and the process protocol to be developed in those tissues or cell smears, as well as with the corresponding code of the temporal priority of each sample and the personal data of the subject from whom it has been extracted.

[0173] In a particular embodiment, prior to the start of the method, a list of protocols has been loaded into the database of the computer program comprised in the microprocessor, each of which details the reagents and processes to be followed to perform a certain treatment on a type of tissue sample or cell smear.

[0174] In another particular embodiment, during the development of a treatment, the process protocols can be in any of the following states:

[0175] - READY: when a protocol is ready to begin its execution;

[0176] - EXEC: when a protocol is in the execution state;

[0177] - EXEC_OK: when a protocol has completed its execution.

[0178] In another particular embodiment, depending on the specific action they are taking, the processes of each protocol may be, in turn, in one of the following states:

[0179] - Not ready: when a process is not ready for execution;

[0180] - READY: when a process is ready for execution;

[0181] - EXEC: when a process is in an execution state;

[0182] - EXEC_OK: when a process has finished its execution, but is waiting for the next process to start;

[0183] - FINISHED: when a process has completed its execution and the next process has started its own;

[0184] In another particular embodiment, the method is adapted for application with a robotic device also comprising at least one reagent spreader roller.

[0185] In another particular embodiment, the method comprises performing maintenance processes, based on changes in ambient temperature and humidity conditions.

[0186] In another particular embodiment, the dispensing of reagents by a robotic device is replaced by a manual dispensing.

[0187] In another particular embodiment, the method comprises washing the probes and reagent spreader roller, each time they are used during the development of any process.

[0188] In another particular embodiment, the method further comprises a step of monitoring the temperature in the plurality of compartments acting as reaction chambers by means of an infrared (IR) sensor.

[0189] In another particular embodiment, the method comprises steps for executing a dynamic planning method (planner) according to the invention.

[0190] Figures 24 to 27 detail the state transition of the general-purpose microcontroller with the computer program executing the method of the present invention:

[0191] - The microcontroller starts its execution in the CHECKS state.

[0192] - When the microcontroller has performed all initial checks, it is updated to READY state;

[0193] - When the different preparations are made and the corresponding timestamps are taken, it moves to the EXEC state;

[0194] - The microcontroller will remain in the EXEC state until all the processes of all the protocols have been completed. At that time, the microcontroller will go to the EXEC_OK state;

[0195] - When the different maintenance tasks have been completed and the corresponding time stamps have been taken, the microcontroller will go to the FINISHED state

[0196] Figures 28 to 31 detail the various processes that the general-purpose microcontroller controls with the computer program executing the method of the present invention.

[0197] According to the present invention, the disclosed method is adapted to operate in three configurations, based on the degree of complexity of the checks and analyses carried out and of the automated and control actions, based on artificial intelligence, carried out by the system microcontroller: a) It captures only the correct position image of the sample holder and proceeds to a preprogrammed reagent dispensing, without further ado. It applies artificial intelligence (Al) to know if the reagent vials are open or closed. This part of Al applied to know if the reagent vials are open or not is operated by Machine learning, loading images of open and closed reagent vials, thus training the system to discern the open or closed position of the reagent vials. The processing of the images of the reagent vials includes, among other processes, the detection of whether the vial is open or closed. To do this, 3D calibration information is used to locate the vial and, more specifically, its opening. The computation is carried out by a pre-trained convolutional neural network (CNN), which takes the cropped image of the mouth of the vial and by inference returns whether it is closed or open. In this way, the user can be warned that the indicated vials that are closed are invalid for the taking of their corresponding reagents. In a particular embodiment, the specific task of detecting whether the slide is well placed or not, requires a threshold precision that can be modelled by artificial intelligence using a Support Vector Machines (SVM) model, a Nearest Neighbour (KNN) model or a singlelayer neural network to be able to classify whether or not a slide is well placed with respect to the heater, given the positions of the corners of each slide and heater. b) Capture of the correct position image of the sample holder and the indexing codes disposed thereon by means of labels, to dispense reagents specifically to each sample holder based on said indexing codes. The code pattern is recognised following the code standard and, in the event that said code is not read, Al is applied to the reading of codes in the form of characters printed by neural networks. In a particular embodiment, to carry out the reading of the indexing codes disposed on the labels of the carriers, artificial intelligence (Al) is used using a K-means model once a set of lines bordering the label have been detected. This model allows them to be grouped into lines Bottom, Left, Top, Right, in order to then be able to identify the 4 lines that delimit the label. In other particular embodiments, use is made of other Al models such as the non-supervised model to group in types of lines, such as Clustering / Hierarchical Grouping, SelfOrganising Maps (SOM) or Gaussian Mixture. Alternatively, the entire trapezoidal region comprising the tag in the image may be directly computed by a CNN neural network. c) Capture of the image of the correct position of the sample holder; of the indexing codes disposed on it and of the profile or contour of the sample to, in the latter case, also by Al, dispense reagents in a specific and improved way, in terms of quantity, dispensing time and location of said dispensing, to each sample. The Al algorithm applied in the imaging of the sample itself is based on an Al model using K-means (K-means).

[0198] Accordingly, the first thing that is done is to detect if the slide is well positioned with respect to the reaction chamber, if it is well positioned, then the indexing code of the slide label is detected and then the characteristics relating to the sample itself (tissue) are detected. The method may include the possibility of dispensing different reagents (e.g., antibodies) onto different areas of the same slide. In this way, several techniques can be carried out simultaneously on the same slide as long as they are included in the same treatment protocol to be applied in the reaction chamber where said slide has been disposed.

[0199] In any of the three methods described above, during the performance of a treatment, these may be in any of the following states:

[0200] - READY: when a protocol is ready to begin its execution;

[0201] - EXEC: when a protocol is in the execution state; - FINISHED: when a protocol has completed its execution.

[0202] Depending on the specific action they are taking, the processes of each treatment may be, in turn, in one of the following states:

[0203] - NOT_READY: when a process is not ready for execution;

[0204] - READY: when a process is ready for execution;

[0205] - EXEC: when a process is in the state of execution;

[0206] - EXEC_OK: when a process has finished its execution, but is waiting for the next process to start;

[0207] - FINISHED: when a process has completed its execution and the next process has started its own.

[0208] In a particular embodiment, the present invention is configured for use by a planner that allows the tasks carried out by the apparatus and system to be executed, preventing the processes from exceeding said temporal limitations, and ensuring that, at times of nonexecution or stoppage, both the system and the samples being treated are left in a safe state of conservation in each protocol. In addition, the present invention allows prioritising the treatment of urgent samples, both at the beginning of a series, and after an intermediate load, putting the series on pause, in order to be able to insert the sample whose treatment is urgent.

[0209] In accordance with the invention, the loading of samples / sample holders cannot be performed with the system in operation. It is necessary to stop it to insert a sample. Start process steps, continuous loading with stoppage and end of a series:

[0210] - With the instrument lid open, the reagent racks and carriers are loaded into the desired positions;

[0211] • Note: While the lid is open, the robot can never move.

[0212] - After the loading of elements is finished, the lid is closed;

[0213] - By pressing "Play" in the application, the state of the lid opening sensor is verified:

[0214] • Lid open: Displays an error message for the user to close the hood;

[0215] • Lid closed: It activates the hood lock to prevent the hood from opening with the robot in motion and the series is started; - If during the series you want to load or replace a vial or holder, click on the "Pause" icon;

[0216] - The planner will calculate the moment when it can be paused leaving all the doors in a safe state of conservation and will show a time countdown in minutes and seconds;

[0217] - When all the doors are in a state of conservation, the robot will stop in the home position and the hood lock will open, allowing it to be opened to load vials or doors;

[0218] - Once the upload is complete, you can click on the “Resume” icon;

[0219] - The condition of the hood sensor will be verified;

[0220] - At the end of the series, the robot will go to the home position and the lock will be opened so that the user can remove the doors.

[0221] In use, the robotic device must_be calibrated before commencing operation. The calibration must be in its 3 axes XYZ, i.e. , it is a 3-dimensional (3D) calibration. The 3D calibration of the robot consists of the use of the imaging camera for the photographing / capturing of a beacon (which contains a printed pattern) and the subsequent processing of the image in order to extract information from the 3D space of the robot and the camera: position of the camera, orientation of the same, curvature of the lens, etc. Through these calculations, the robot can move and, at the same time, locate in the successive captured image those objects of fixed location, such as reaction cameras, reagent bottles, etc. In a particular embodiment, the 3D calibration can be performed by Al, specifically and by way of example only, through the use of CNN-type neural networks that allow obtaining all the intrinsic calibration of the camera: focal length, distortion parameters of the lens, etc.

[0222] Consequently, the tasks this process allows are: (1) verify that the camera is not misconfigured or misplaced (with an invalid orientation, for example); (2) correct image defects, such as lens distortion; (3) check if a slide is present and / or well-positioned; (4) check if a reagent bottle or vial is present and / or positioned, with its subsequent notice to the user of the robotic device; (5) transform the conical perspective of the captured image into a normalised "flat" zenith image (bird's eye view) of both the tissue area of the slide and of the slide labels and reagent vials; (6) reduce the image resolution by cutting it, thus improving the image processing performance; (7) select image regions associated with subobjects of interest, such as the mouth of the reagent vials.

[0223] Another important element of the present invention is the self-calibration of reaction chamber temperatures, as well as the checking of temperatures during a series to detect possible temperature problems in the reaction chambers, or even periodic self-checks and self-calibrations of the chamber temperatures, notifying the system if it detects problems in reaction chambers. The temperature of the reaction chambers is measured by an infrared (IR) sensor (42) that is placed by a support piece in a central position on the Z axis of the robotic device together with the viscous reagent spreader roller and the washing probes. The temperature data obtained is processed by the electronic control board (44), which is connected to the IR sensor by means of connection pins (45).

[0224] The present invention, in a preferred embodiment, allows the self-calibration of the temperatures of the reaction chambers via infrared, with the aim of generating a file autonomously so that the reaction chambers are thermally calibrated. This embodiment of the invention does not require manual intervention during measurement. The action protocol is as follows:

[0225] 1. The temperature of all reaction chambers is started at 115°, once reached 5 minutes should be waited. Additionally, it is waited until the temperature inside the apparatus is above 30°C

[0226] 2. At that time the equipment arm will move to the reaction chamber to take 3 measurements every 500 ms.

[0227] 3. The arm descends 80 mm.

[0228] 4. The reading is averaged and the reaction chamber will change the target temperature to 40°.

[0229] 5. When this temperature is reached, the reading will not be taken until 5 minutes have elapsed to allow the temperature to stabilise.

[0230] 6. This process is carried out in parallel in each of the reaction chambers.

[0231] 7. When it is finished, it generates a .csv file that can be entered in the application to generate the regression line that calibrates the reaction chambers based on this data.

[0232] For on-site in-process temperature verification: While the equipment is operating with a protocol, it can be verified that the temperature of the liquid surrounding the tissue is appropriate for the step of the treatment technique in question.

[0233] It is understood that the elements described above are adapted for common use to the different operating configurations of the system. of the In this method, only the image of the correct position of the sample on the slide is captured and the preprogrammed dispensing of reagents is carried out. The procedure consists of the following steps:

[0234] Step 1 : The procedure begins with several readings, by a high precision image capture device: of the correct position of each sample holder (14) in the reaction chamber and, inside each sample holder (14) correctly positioned of the position of each sample in said sample holders (14). The lid (100) must be closed at all times. In the event that the microcontroller receives an instruction to open the lid (100) or pause the procedure, the execution of instructions will not be allowed until the robotic device (8) finishes the EXEC processes (EXEC state) and is in the CHECKS state.

[0235] The algorithm that is applied to the high-precision images captured to determine the correct position of each sample holder (14) is as follows: first, the edges of the sample holder (14) are obtained. On those edges, the contour lines of the sample holder (14) are detected. A Machine Learning method labels each of those lines (upper, lower, right and left) and finally a filter is performed that establishes the effective area of each sample holder (14) and the scope of the label and determines if its position is correct within the reaction chamber. If it were not determined which part is the label and what is the useful area of the slide for the sample, it would not be known if the slide has been placed to the right or vice versa. Placing it in one way or another is important for cases where it is not dispensed by Al, since it is assumed that the slide is always oriented in the same direction. Reagent is dispensed throughout the slide and not only on the detected sample tissue and it is not the same whether the slide is placed in one direction or the other. In a preferred embodiment, the blowing and washing are always carried out in one direction and with specific offset values that are defined based on the position of the label and the angle of the blower nozzle that is not motorised. Therefore, certain processes can only be performed correctly if the slide is properly positioned.

[0236] For the purposes of this patent, the terms artificial intelligence, Al, intelligent dispensing or processing, are all equivalent and refer to the use of artificial intelligence algorithms to carry out the method of the invention in all or some of its variants.

[0237] Step 2: The procedure continues with the execution of the pre-programmed treatment of histological staining, immunoenzymatic staining and hybridisation on the samples disposed in the compartments, acting as reaction chambers, by means of a robotic device (8), which moves freely along the three axes XYZ (30), being able to be positioned anywhere in the area (2) of the compartments located in the horizontal plane XY, and which carries out, by means of a general purpose microcontroller with a computer program, the control of all the protocols, reagents, processes, members and equipment involved in the treatment. The microcontroller carries out, among others, the control of the following functions: a) Start the execution of the treatment with the microcontroller in the CHECKS state. b) Check that all the equipment involved in the method during the execution of the process protocols is ready (READY state) of said pre-programmed treatment, including, at least, among said checks, the washing and purging process protocols of all the reagent, air and any other solution dispensing probes used during the rest of said process protocols. Each time a reagent probe or spreader roller (33) is used in any process, it will be washed. c) If all the initial checks have been passed, begin to execute one or more process protocols, by dispensing pre-programmed reagents in the samples for which an image capture of the identification codes of the respective specific reagent reservoirs is carried out. The algorithm for reading identification codes always tries to apply the readings of the identification codes, after modifying the capture perspective of the image of said code and applying blurring and sharpening type filters. Reagent dispensing can be automatic or manual. d) Calculate the time stamps and prioritise the process protocols that must be executed based on pre-programmed treatment. e) Periodically update the timestamps and prioritisation of the process protocols of step d), until all processes of all treatment protocols have been completed. Maintenance processes are performed, depending on the changes in the ambient conditions of temperature and humidity. f) Finish, when all the final maintenance tasks are concluded, then activating a low energy consumption routine.

[0238] Method for the analysis of samples and codes in sample holders and specific dispensing in each sample based on said codes

[0239] In this method, images are captured, not only of the correct position of the sample on the slide, but also of the indexing codes disposed on the sample holders (14), and reagents are dispensed specifically to each sample based on said indexing codes. The procedure consists of the following steps:

[0240] Step 1 : The procedure begins with several readings, by a high precision image capture device: of the correct position of each sample holder (14) in the reaction chamber; of the identification code disposed on each sample holder (14) and, inside each sample holder (14) correctly positioned and with a legible identification code, of the position of each sample in said sample holders (14). The identification codes of each sample holder (14) allow identifying the sample, the case to which it corresponds, the protocol of the treatment to be operated on it and the order of priority to be applied to each sample and / or to each protocol. The lid (100) must be closed at all times. In the event that the microcontroller receives an instruction to open the lid (100) or pause the procedure, the execution of instructions will not be allowed until the robotic device (8) finishes the EXEC processes (EXEC state) of each of the active protocols and is in the CHECKS state.

[0241] The algorithm that is applied to the high precision images captured to determine the correct position of each sample holder (14) is as follows: first, the edges of the sample holder (14) are obtained. On those edges, the contour lines of the sample holder (14) are detected. A Machine Learning method labels each of these lines (upper, lower, right and left) and finally a filter is performed that establishes the effective area of each sample holder (14) and determines if its position is correct within the reaction chamber.

[0242] The algorithm that is applied to the reading images of the identification codes of each sample holder (14) to determine the existence and readability of said codes, when detecting an erroneous code reading, will apply new image captures of the identification code, after modification of the perspective of the capture of the image of said code, and application of "blurring" and " sharpening" type filters to said image, until it achieves the correct reading of the codes of all the sample holders (14). In the event that the algorithm does not achieve a correct reading of any code from a sample holder (14) of the reaction chamber, the software will warn the user to include the code information, in such a way that a sample holder (14) is never discarded in the event of code reading failures. In an alternative embodiment, the system does not carry out new image capture upon error in reading the barcodes.

[0243] Step 2: The procedure continues with the execution of the specific treatment for each of the samples disposed in the compartments, acting as reaction chambers, by means of a robotic device (8), which moves freely along the three axes XYZ (30), and can be positioned anywhere in the area (2) of the compartments located in the horizontal XY plane, and which carries out, by means of a general purpose microcontroller with a computer program, the control of all the protocols, processes, members and equipment involved in the treatment. The microcontroller carries out the control of the following functions: a) Start the execution of the treatment with the microcontroller in the CHECKS state. b) Check that all equipment involved in the method during the execution of the process protocols is ready (READY state) for the specific treatment of each sample, including, at least, among said checks, the washing and purging process protocols of all reagents, air and any other solution dispensing probes used during the rest of said process protocols. Each time a reagent probe or spreader roller (33) is used in any process, it will be washed. c) Reading, by means of at least one high-precision image capture camera (31), all the identification codes of each sample holder (14) with legible codes, to identify the sample to be treated, the case from which it comes, the process protocol or protocols to be executed, in the treatment of said sample; the order of priority of said process protocols; as well as carry out the detection of the tissue or cell smear existing on each sample holder (14). d) If all the initial checks have been passed, begin to execute one or more process protocols, by dispensing reagents in the samples of the sample holders (14). The dispensing of reagents can be automatic or manual. e) Calculate the time stamps and prioritise the process protocols that must be executed based on specific treatment in each area of the sample holder (14). f) Periodically update the timestamps and prioritisation of the process protocols of step e), until all the processes of all the treatment protocols have been completed. Maintenance processes are performed, depending on the changes in the ambient conditions of temperature and humidity. g) Finish, when all the final maintenance tasks are concluded, then activating a low energy consumption routine.

[0244] Prior to the start of a treatment, a list of samples of tissues or cell smears to be processed must be loaded into the database of the computer program included in the microprocessor, each of which identified with a sample code and the treatment processes to be developed in those tissues or cell smears, as well as with the corresponding code of the temporal priority of each sample and the personal data of the subject from whom it has been extracted. If the sample identification code does not exist in the program database, it will allow its manual creation from the code read.

[0245] Step 3: Obtaining data from the images captured of each sample and, related to each identification code of the sample holders (14).

[0246] In this method, the images of the correct position of the sample, the profile or the contour thereof, as well as the indexing codes disposed on the sample holder, are captured in order to, by means of artificial intelligence (Al), dispense reagents in a specific and improved way, in terms of quantity, dispensing time and location of said dispensing, to each sample, based on the indexing codes disposed on the sample holder. The procedure consists of the following steps:

[0247] Step 1 : The procedure begins with several readings, by a high precision image capture device: of the correct position of each sample holder (14) in the reaction chamber; of the identification code disposed on each sample holder (14) and, inside each sample holder (14) correctly positioned and with a legible identification code, of the position of each sample in said sample holders (14). The identification codes of each sample holder (14) allow identifying the sample, the case to which it corresponds, the protocol of the treatment to be operated on it and the order of priority to be applied to each sample and / or to each protocol. The lid (100) must be closed at all times. In the event that the microcontroller receives an instruction to open the lid (100) or pause the procedure, the execution of instructions will not be allowed until the robotic device (8) finishes the EXEC processes (EXEC state) of each of the active protocols and is in the CHECKS state.

[0248] The algorithm that is applied to the high- precision images captured to determine the correct position of each sample holder (14) is as follows: first, the edges of the sample holder (14) are obtained. On those edges, the contour lines of the sample holder (14) are detected. A Machine Learning method labels each of these lines (upper, lower, right and left) and finally a filter is performed that establishes the effective area of each sample holder (14) and determines if its position is correct within the reaction chamber.

[0249] The algorithm that is applied to the reading images of the identification codes of each sample holder (14) to determine the existence and readability of said codes, always tries to apply the readings of the identification codes, modifying the perspective of the capture of the image of said code and applying blurring and sharpening type filters. In the event that the algorithm does not achieve a correct reading of any sample holder (14) of the reaction chamber, said sample holder (14) will be discarded for any treatment.

[0250] Step 2: The procedure continues with the execution of the specific treatment for each of the samples disposed in the compartments, acting as reaction chambers, by means of a robotic device (8), which moves freely along the three axes XYZ (30), and can be positioned anywhere in the area (2) of the compartments located in the horizontal plane XY, and which carries out, by means of a general purpose microcontroller with a computer program, the control of all the protocols, processes, members and equipment involved in the treatment. The microcontroller carries out the control of the following functions: a) Start the execution of the treatment with the microcontroller in the CHECKS state. b) Check that all equipment involved in the method during the execution of the process protocols is ready (READY state) for the specific treatment of each sample, including, at least, among said checks, the washing and purging process protocols of all reagent, air and any other solution dispensing probes used during the rest of said process protocols. Each time a reagent probe or spreader roller (33) is used in any process, it will be washed. c) Reading, by means of at least one high-precision image capture camera (31), all the identification codes of each sample holder (14) with legible codes, to identify the sample to be treated, the case from which it comes, the process protocol(s) to be executed, in the treatment of said sample; the order of priority of said process protocols; as well as carry out the detection of the tissue or cell smear existing on each sample holder (14).

[0251] The algorithm that is applied to the images for the detection of the tissue or cell smear existing on each sample holder (14) is as follows: a set of regions of interest are detected by a topological method, from which those with an eccentricity greater than a fixed threshold are discarded. Subsequently, using K-means, which is an artificial intelligence method of Machine Learning, the pixels are classified by intensity to identify areas of tissue presence and, finally, those regions with an area less than a previously adjusted threshold are discarded. The resulting regions are the areas of tissue presence. If the areas of tissue presence are negligible, it is determined that the entire sample holder (14) is covered with tissues to avoid false negatives.

[0252] The algorithm which is applied to the the detection of the cell smear or the tissue, implements the following steps: (1) since the slide position is known in the robot space, the slide image is normalized by detecting and cropping the glass part using the 3D- calibration, hence eliminating any background; (2) a kernel-based filter is applied in order to eliminate noises such as horizontal stripes and to give the tissues a blob-like shape; (3) the tissue regions are pre-segmented as a heat-map structure, as a result of a topological algorithm which detects critical regions based on homology and shape; (4) both the filtered image and the heat-map from steps 2 and 3 are concatenated and used as input of a pre-trained Deep Learning model (a Convolutional Neural Network), which performs a high-precision detection of the tissue’s blobs on the slide; finally (5), the coordinates of the contour points of the detected tissue are mapped to robot space positions via the 3D-calibration. d) If all the initial checks on the sample holders have been passed, before starting to execute one or more process protocols, by dispensing reagents into the samples, image captures of the identification codes of the respective specific reagent reservoirs are performed to verify that all the reagents necessary to correctly execute the protocols are present. This verification includes that there is sufficient volume of each reagent to run the entire series.

[0253] The algorithm for the automatic dispensing of reagents relates the tissue regions determined in the previous step c) and with the volume, spread and dispensing time of the reagent involved in the treatment to be applied to said sample as follows: by means of a geometric method, from the previously determined tissue regions on the sample holder (14), the tissue polygons resulting from transforming the front conical perspective of the image to a flat perspective are computed. Next, the maximum dispensing areas covering said polygons are defined with drops of volume equal to those volumes used in pre-programmed dispensing. By another geometric method, successive area fusions are applied to minimise the number of tissue areas to be dispensed with a specific reagent. Finally, the centre of each area of fused tissue is located and the minimum reagent volume necessary to cover each area of tissue is calculated.

[0254] The algorithm which computes the best reagent drop positions, implements the following steps: (1) an initial partition of the slide is proposed, where the glass part is covered with the maximum number of reagent drops; (2) given the contours of the detected regions, all drops of the partition that do not cover any tissue are discarded from the partition; (3) in a pair-wise manner, the neighbouring drops are considered for merging and relocation, hence resulting in the minimum number of drops which cover all the tissue; (4) each drop is relocated on the centre of its assigned tissue part; and (5) the quantity of reagent of each drop is reduced in order to coverall its assigned tissue part, always above a security margin for ensuring a whole tissue cover. e) Calculate the time stamps and prioritise the process protocols that must be executed in each treatment f) Periodically update the timestamps and prioritisation of the process protocols of step e), until all the processes of all the treatment protocols have been completed. Maintenance processes are performed, depending on the changes in the ambient conditions of temperature and humidity. g) Finish, when all the final maintenance tasks are concluded, then activating a low energy consumption routine.

[0255] Prior to the start of a treatment, a list of samples of tissues or cell smears to be processed must be loaded into the database of the computer program included in the microprocessor, each of which identified with a sample code and the treatment processes to be developed in those tissues or cell smears, as well as with the corresponding code of the temporal priority of each sample and the personal data of the subject from whom it has been extracted.

[0256] For the purposes of the present invention and, by way of a specific example to determine whether or not a reagent vial has its cap open or closed, Al models already created and previously trained with an image base will be used to know if, for example, a vial has its cap open or closed. Therefore, this comparison is not going to be made at the image capture level and compared with another that has reference DB, but an image is going to be captured and analysed with a model that will determine whether or not it has the cap on. In such a way that it is not directly compared with another image, but that model has been created through a collection of images of vials with and without caps. In a particular embodiment, use is made of Al using, by way of example, a CNN model to classify a vial into two types: with cap open or with cap closed. In alternative embodiments, any Machine Learning model (SVM, neural networks, KNN, etc.) that makes use as the basis of a homological persistence model may be applied.

[0257] Step 3: Obtaining data from the images captured of each sample and, related to each identification code of the sample holders.

[0258] The present invention also relates to a computer program product for performing treatments of histological staining, immunoenzymatic staining and hybridisation on tissue sections or cell smears comprising instructions which, when executed on the system of invention, cause the computer means to carry out the method of the invention. The aforesaid computer program product according to present invention comprises all the algorithms detailed previously in the present specification.

[0259] The computer program product of the invention comprises a computer-readable medium, which, in turn, comprises encoded instructions for controlling a microprocessor that processes images from a sample disposed on a sample holder, comprising: a) Means for self-calibrating at least one high-precision image capture camera (31) capable of capturing images of the placement of at least one sample holder (14), of the samples to be stained or hybridised and, optionally, of the identification codes, disposed on the sample holders (14), as well as of the identification codes disposed on specific reagent reservoirs (22); b) Means for capturing images of the sample holder (14) that carries the samples, specifically of the placement of the sample holder (14) and, optionally, of the identification codes disposed on the sample holders (14); c) Means for capturing images of the samples to be stained or hybridised; d) Means for capturing images of the reagent reservoirs (5a, 22) to be applied in the treatments of the samples; e) Means for processing the images captured from the sample holders; f) Means for processing the images captured from the specific reagent reservoirs and mixing tubes; g) Means for sending movement orders to a robotic device (8) carrying at least one high- precision image capture camera (31) and fluid dispensing means, which moves from compartment (9) to compartment (9), wherein at least one sample holder (14) with samples is located; h) Artificial Intelligence (Al) processing means of the high-precision images of the captured samples, for sending orders for improving the quantity, location and dispensing times of the reagents to be dispensed in said samples.

[0260] In a particular embodiment, the means for processing images captured from the samples disposed on the sample holders comprise: i. Means for calculating the areas of the polygons that make up the segmented images of the captured samples; ii. Means for calculating the dispensing positions of the reagents that allow covering the entire sample with the minimum amount of reagent; iii. Means for generating an output file that, at least, contains: reading the identification codes of the sample holder, reading the areas of the polygons of the image of the captured segmented sample, positions and volumes of the reagents to be dispensed.

[0261] In a particular embodiment, the means for sending dispensing orders, by means of the robotic device (8), of the reagents, comprise: i. Means for reading the output file generated in the processing of the captured sample holder images; ii. Means for sending orders to the robotic device (8) to be positioned in the chamber where the sample holder (14) is disposed with the sample corresponding to the output file and dispense the volume of reagent and in the positions determined in said output file.

[0262] In another particular embodiment, the product comprises means for applying process protocols existing in the computer program and previously selected about the treatments of histological staining, immunoenzymatic staining and hybridisation on tissue sections or cell smears comprised in said sample, depending on the image capture carried out on said sample and on the area of said sample, the contours thereof, its position and the amount of sample to be treated.

[0263] In another particular embodiment, the product comprises means for maintaining the system and / or the apparatus to be applied based on environmental parameters, such as temperature or humidity.

[0264] In another particular embodiment, the product comprises means for sending orders to finish each protocol and / or process and / or to pause the system.

[0265] In another particular embodiment, the product comprises means for relating the readings of the identification codes of the samples with the image captures of said samples.

[0266] In another particular embodiment, the product comprises means for sending orders for dispensing cleaning or washing fluids to be executed in the period that elapses between the conclusion of one protocol and / or process and the beginning of a new protocol and / or process.

[0267] In another particular embodiment, the product comprises means that allow the dispensing of reagents by executing orders to a spreader roller (33) of said reagents on the sample when they have a viscous nature. In another particular embodiment, the product comprises means for pausing the system when the threshold of a predetermined excess wait time is exceeded.

[0268] In another particular embodiment, the product comprises means for executing a dynamic planning method (planner) according to the invention.

[0269] The present invention also relates to a dynamic planning method (planner) comprising steps for adaptively programming tasks of the robotic device (robotic tasks) of the invention in a time interval, wherein the robotic device is coupled to a staining or hybridisation apparatus, wherein the robotic device treats slides coupled to the staining or hybridisation apparatus according to a treatment protocol with reagents in reagent or fluid reservoirs coupled to the staining or hybridisation apparatus, wherein the steps comprise:

[0270] • creating a robotic device task list comprising all robotic tasks that are ready for execution within the time interval;

[0271] • calculating a robotic task priority for each robotic task on the robotic task list;

[0272] • sorting the list of robotic tasks in descending order of priority of robotic tasks;

[0273] • adding robotic tasks by continuously prioritising;

[0274] • changing the order of the processes of the robotic device as it acts, and

[0275] • reporting the state of each of the processes of the robotic device.

[0276] According to the present invention, the planner does not create a complete list of statically prioritised tasks that is carried out without undergoing modifications from the first moment to the end of the series. On the contrary, and advantageously, the invention allows a dynamic planning wherein the order of the processes of the robot is continuously prioritised and changed as it acts and reports the states of each of them. It is important to mention that it is not the same to list all the prioritised tasks of a series and follow it no matter what happens during the series, than to prioritise and order the processes of a series in real time as the robot is performing them. In the case of static planning, it requires fixed time intervals while in the case of dynamic planning, according to the invention, it adapts to real times and new priorities that occur according to the new realities of each moment. In this way, the robotic device of the invention can advantageously react to the changes produced in the reaction chamber, for example, by including a new sample holder to the staining or hybridisation process carried out by the system / apparatus of the invention. According to the present invention, the scheduler may advantageously be integrated into the method, system, apparatus and / or computer program product of the invention. LIST OF NUMERICAL REFERENCES USED IN THE FIGURES

[0277] 1 system / apparatus

[0278] 2 staining or hybridisation area

[0279] 3 waste tank

[0280] 4 system housing / apparatus

[0281] 5 area / structure housing a plurality of common reagent reservoirs

[0282] 5a common reagent reservoir

[0283] 5b common reagent reservoir cap

[0284] 5c reagent outlet orifice of common reagent reservoir

[0285] 5d stabilisation projection of the common reagent reservoir

[0286] 5e area / structure housing a plurality of common reagent reservoirs

[0287] 5f identification / label of the common reagent reservoir

[0288] 6 area / structure housing a plurality of specific reagent reservoirs

[0289] 7 mixing and drying unit / unit housing washing station stations (area and spreader), spreader drying station and tubes for automatic reagent mixing

[0290] 8 robotic device

[0291] 9 reaction compartments / chambers

[0292] 10 unit of the staining or hybridisation area that houses sample holders (x3)

[0293] 12 indicator light, LED

[0294] 13 grooves for the expulsion of surplus waste

[0295] 14 sample holders

[0296] 15 heater / heating blanket

[0297] 16 vibration system of the compartments / reaction chambers

[0298] 17 lower waste tank tray

[0299] 18 upper grid of the waste tank

[0300] 19 waste tank tray outlet orifice

[0301] 21 area / structure housing the common reagent level sensor

[0302] 22 specific reagent reservoir

[0303] 22a rack of specific reagent reservoirs

[0304] 22b specific reagent reservoir cap

[0305] 22c outlet orifice of the specific reagent reservoir

[0306] 22d specific reagent reservoir housing

[0307] 23 thermostatted rack

[0308] 24 gripping portion of the rack housing the specific reagents

[0309] 25 automatic washing device / washing station for specific reagent probe 26 tubes for automatic reagent mixing

[0310] 27 automatic reagent mixing unit

[0311] 28 spreader drying station

[0312] 29 spreader roller washing station

[0313] 30 XYZ means of displacement of the robotic device

[0314] 31 high-precision image capture camera

[0315] 32 precision probe

[0316] 33 reagent spreader roller

[0317] 34 precision probe control interface

[0318] 35 comb I comb with various common reagent dispensing probes

[0319] 35a common reagent dispensing probes or pipettes

[0320] 36 air blow drying system

[0321] 36a air intake of the drying system

[0322] 37 reagent spreader roller side potion

[0323] 38 reagent spreader roll body

[0324] 39 air blow drying system orifice

[0325] 40 air blow drying system slot

[0326] 41 filter for gas removal

[0327] 42 infrared sensor (IR)

[0328] 44 electronic temperature control board

[0329] 45 connection pins of the electronic board for the IR sensor

[0330] 100 upper lid or cover of the system

[0331] 102 electronic components

Claims

CLAIMS1. A computer-implemented method for performing treatments of histological staining, immunoenzymatic staining and hybridisation on tissue sections or cell smears, comprising the steps of: i. disposing one or more previously prepared samples on at least one sample holder, optionally labelled with identification codes, in a staining or hybridisation area, segmented into a plurality of compartments that act as reaction chambers for a plurality of staining or hybridisation treatments on said samples disposed therein; ii. capturing at least one image by means of a high-precision photographic image capture device, of the position of each sample holder in the respective reaction chamber and, optionally, the identification code disposed on the sample holder; iii. capturing at least one high-precision image of one or more samples disposed on said sample holder by a high-precision photographic image capture device; iv. performing said treatments on the samples disposed in the compartments acting as reaction chambers, by means of the provision of a robotic device, configured for its three-dimensional displacement along the three axes XYZ, and adapted to be positioned at any point of said staining or hybridisation area of the compartments located in the horizontal plane XY, and which carries out, by means of a general purpose microcontroller with a computer program, the control of the processes that comprise:- processing at least one image of the sample holder and, optionally, of the label with codes disposed thereon;- dispensing specific reagents or common reagents based on a pre-programmed protocol of processes to be applied, depending on:- the reading of identification codes disposed on specific reagent reservoirs;- the quantity, location and time of dispensing;- image capture of at least one sample, processed by Artificial Intelligence (Al);- performing washes after each process protocol and / or each process independently; and- obtaining data from the images captured of each sample and, optionally, related to each identification code of the sample holders.

2. The method according to claim 1 , wherein the labels of the sample holders have codes that allow identifying the sample, the case to which it corresponds, the protocol to be operated therein and the order of priority to be applied to each sample and / or each protocol.

3. The method according to claim 1 , characterised in that the microcontroller carries out the control of the following functions: a) start the method; b) check that the lid is closed and activate a lock to prevent it from opening during operation; c) check the correct placement of all the elements, particularly the sample holders in the reaction chambers; d) check that all equipments involved in the method during the execution of the process protocols are ready, including, at least, among said checks, the washing and purging process protocols of all reagent, air and any other solution dispensing probes used during the rest of said process protocols; e) optionally, read, by means of at least one high-precision image capture camera, all the labels of each sample holder, to identify the sample to be treated, the case from which it comes, the process protocol(s) to be executed, in the treatment of said sample; the order of priority of said process protocols; as well as carry out the detection of the tissue or cell smear existing on each sample holder and also carry out the delimitation of the position and amount of tissue or cells in each area of each sample holder; f) if all the initial checks have been passed, begin to execute one or more process protocols, by dispensing reagents in the samples for which an image capture of the identification codes of the respective specific reagent reservoirs and mixing tubes is carried out by Al if there is mixture in the series; g) calculate the time stamps and prioritise the process protocols to be executed, based on the previous readings and, based on the specific process protocol, determining the reagents and the amount of said reagents to be dispensed in each area of the sample holder; h) periodically update the timestamps and prioritisation of the process protocols of step g), until all processes of all protocols have been completed; and i) finish, when all the final maintenance tasks are concluded, then activating a low energy consumption routine.

4. The method according to any of the preceding claims, wherein prior to its start, a list of tissue samples or cell smears to be processed, each of which identified with a sample code and the process protocol to be developed in those tissues or cell smears, as well as the corresponding code of the temporal priority of each sample and the personal data of the subject from whom it has been extracted, has been loaded into the database of the computer program comprised in the microprocessor.

5. The method, according to any of the preceding claims, wherein prior to its start, a list of protocols has been loaded into the database of the computer program comprised in the microprocessor, each of which details the reagents and processes to be followed to perform a certain treatment on a type of tissue sample or cell smear.

6. The method according to anyone of the preceding claims, wherein, during the performance of a treatment, the process protocols may be in any of the following states:- READY: when a protocol is ready to begin its execution;- EXEC: when a protocol is in the execution state; and- EXEC_OK: when a protocol has completed its execution.

7. The method according to any of the preceding claims, wherein, depending on the specific action they are carrying out, the processes of each protocol may in turn be in one of the following states:- Not ready: when a process is not ready for execution;- READY: when a process is ready for execution;- EXEC: when a process is in an execution state;- EXEC_OK: when a process has finished its execution, but is waiting for the next process to start; and- FINISHED: when a process has completed its execution and the next process has started its own.

8. The method according to any of the preceding claims, wherein the robotic device (8) also comprises at least one reagent spreader roller (33).

9. The method according to any of the preceding claims, comprising carrying out maintenance processes, based on changes in environmental conditions of temperature and humidity.

10. The method according to any of the preceding claims, wherein the dispensing of reagents by a robotic device (8) is replaced by a manual dispensing.11 . The method according to any one of the preceding claims, wherein the probes and reagent spreader roller (33) are washed each time they are used during the performance of any process.

12. The method according to any of the preceding claim, wherein the method further comprises a step of monitoring the temperature in the plurality of compartments acting as reaction chambers by means of an infrared (IR) sensor.

13. The method according to any of the preceding claims, wherein the method further comprises a dynamic planning step comprising steps for adaptively programming tasks of the robotic device (robotic tasks) in a time interval, wherein the robotic device is coupled to a staining or hybridisation apparatus, wherein the robotic device treats slides coupled to the staining or hybridisation apparatus according to a treatment protocol with reagents in reagent or fluid reservoirs coupled to the staining or hybridisation apparatus, wherein the steps comprise:- creating a task list of the robotic device comprising all robotic tasks that are ready for execution within the time interval;- calculating a robotic task priority for each robotic task on the robotic task list;- sorting the list of robotic tasks in descending order of priority of robotic tasks;- adding robotic tasks by continuously prioritising;- changing the order of the processes of the robotic device as it acts, and- reporting the state of each of the processes of the robotic device.

14. A system for performing treatments of histological staining, immunoenzymatic staining and hybridisation on tissue sections or cell smears comprising:- a general-purpose microcontroller;- means for storing data in one or more databases;- a USB bus;- a CAN bus;- a main electronic card, connected to the USB bus configured to allow communication with the microcontroller, and on the other hand to the CAN bus configured topropagate and receive the information from the other cards, and control:• motors of a robotic device (8), together with its encoders and end-of-stroke sensors, for the X and Y axes;• reagent presence and level detection sensors;• open / close detection sensors;• indicator light to indicate the system state;• cold table for reagent maintenance;• interface (34) to control at least one precision probe (32);- an electronic motion control board, connected to the can bus, configured to control the motors of the robotic device (8) based on the different axes XYZ (30) configured to control:• motors of the robotic device (8), together with its encoders and end-of-stroke sensors;• interface for at least one liquid level detection (LLD) sensor;- a hydraulic control board that is connected to the CAN bus, configured to control hydraulic circuits of the instrument:• peristaltic pumps with stepper motors;• direct current pumps;• direct current valves;• air compressors;• blowing system air flow rate sensor (36);- a compartment control card connected to the CAN bus, configured to control the thermal actuators of reaction chambers disposed in said compartments, and which also controls:• actuators for the control of resistive heaters;• interfaces of the resistive temperature sensors;• actuators to control light indicators (12) indicative of the state of each reaction chamber; and further comprising:i. a staining or hybridisation area (2), segmented into various compartments (9) adapted for the function of reaction chambers of the different treatments to be executed in them, in each of which one or more previously prepared samples are disposed on sample holders (14), optionally labelled with identification codes; ii. a robotic device (8), which has means to move freely along the three axes XYZ (30), adapted to be positioned at any point in the area (2) of the compartments (9), wherein the area (2) is located in the horizontal plane XY, and comprising the following elements:- at least one high-precision image capture camera (31) adapted to capture images of the position of the sample holders and / or of the physical characteristics of the samples and, optionally, of the identification codes, disposed on the sample holders (14), as well as of the identification codes disposed on specific reagent reservoirs (22);- at least one probe adapted for the dispensing of specific reagents and at least one probe adapted for the dispensing of common reagents;- at least one probe adapted for washing; and- at least one general-purpose microcontroller with a computer program for the control of all the protocols, processes, members and equipment that form or operate the system.

15. The system according to claim 14, wherein the probes comprise:- at least one comb (35) with at least one common reagent dispensing probe (35a);- at least two washing probes of a diameter greater than the dispensing probes, adapted for performing washes and connected directly to the common reagent reservoirs (5a); and- at least one reagent spreader roller (33), adapted for spreading reagents dispensed onto the sample holders (14).

16. The system according to claim 14 or 15, wherein each of said compartments (9) comprises a lower face that rests on a thermal blanket (15), on a vibration system (16) and on a waste tray (3) and by its upper face, bevelled, grooved or milled, the lower face of the sample holder (14) of size and shape adapted to that bevelling, grooving or milling is supported, keeping the perimeter of the upper face of the sample holder (14) in flight and isolated, preventing the reagent that is dispensed on it from spilling out ofthe area by surface tension; and wherein, between each bevel, groove or milling, grooves (13) are placed transversely for the expulsion of excess waste towards a waste tray (3).

17. The system according to any one of claims 14 to 16, further comprising a dual drainage device which, through two pumps, connects the waste tray (3) of all the compartments with at least two waste tanks, one for hazardous waste and one for non-hazardous waste.

18. The system according to any one of claims 14 to 17, wherein the dispensing probes are connected with at least one area (5) of common reagent reservoirs and at least one area of specific reagents (6).

19. The system according to any one of claims 14 to 18, further comprising at least one air blow drying system (36).

20. The system according to any one of claims 14 to 19, further comprising automatic washing devices (25) using washing solutions.

21. The system according to any one of claims 15 to 20, wherein the common reagent dispensing comb (35) is formed by at least six dispensing probes (35a) and at least six common reagent tubes.

22. The system according to any one of claims 14 to 21 , further comprising at least one washing station (25) of the probes of the system.

23. The system according to any one of claims 14 to 22, comprising at least one washing (25) and drying station for the spreader roller (33) and the comb (35) of probes (35a).

24. The system according to any one of claims 14 to 23, comprising at least one automatic reagent mixing area (27).

25. The system according to any one of claims 14 to 24, comprising at least one gas removal filter (41).

26. The system according to any one of claims 16 to 25, wherein the thermal blanket (15) is provided with a thermal probe for the control and maintenance of the temperatures ofthe different protocols carried out by the system.

27. The system according to any one of claims 14 to 26, wherein each compartment has a light indicator (12) to identify the fault state or the state of the protocol in execution in said compartment.

28. The system according to any one of claims 17 to 27, wherein the waste tray (3) has a level sensor.

29. The system according to any one of claims 19 to 28, wherein the air blow drying system (36) integrates a compressor and a flow sensor.

30. The system according to any one of claims 14 to 29, further comprising an automatic washing device (25) of the compartments (9), consisting of a tube connected to a pump disposed in a container containing a specific washing solution determined by the control device, based on the specific process protocol being developed in said compartment.

31. The system according to any one of claims 18 to 30, wherein the specific reagent reservoir area comprises a thermostatted rack (23), the temperature of which is controlled by the programmable device that controls the system.

32. The system according to any one of claims 18 to 31 , wherein the common reagent reservoir area (5) has a weight volume sensor for each reservoir (5a).

33. The system according to any one of claims 18 to 32, wherein the specific reagent reservoir area has a capacitance volume sensor in the probe to detect the reagent level in each reservoir.

34. The system according to any one of claims 14 to 33, wherein the system (1) comprises at least one infrared sensor (42) for monitoring the temperature in the plurality of compartments (9) adapted for the function of reaction chambers.

35. The system according to any one of claims 14 to 34, wherein the system is configured to execute a dynamic planning method comprising steps for adaptively programming tasks of the robotic device (robotic tasks) in a time interval, wherein the robotic device is coupled to the staining or hybridisation system, wherein the robotic device treats slides coupled to the staining or hybridisation system according to a treatment protocolwith reagents in reagent or fluid reservoirs coupled to the staining or hybridisation system, wherein the steps comprise:- creating a task list of the robotic device comprising all robotic tasks that are ready for execution within the time interval;- calculating a robotic task priority for each robotic task on the robotic task list;- sorting the list of robotic tasks in descending order of priority of robotic tasks;- adding robotic tasks by continuously prioritising;- changing the order of the processes of the robotic device as it acts, and- reporting the state of each of the processes of the robotic device.

36. The system of any one of claims 14 to 35, adapted to perform the method of any one of claims 1 to 13.

37. The system according to claim 14 wherein the system can be operated manually, without the intervention of a robotic device (8) adapted for capturing high-precision images and dispensing reagents.

38. An apparatus (1) for the performance of histological staining, immunoenzymatic staining and hybridisation treatments on tissue sections or cell smears comprising: i. a staining or hybridisation area (2), covered by a lid (100), segmented into various compartments (9) adapted for the function of reaction chambers of the different treatments to be executed therein, in each of which one or more previously prepared samples are disposed on at least one sample holder (14), optionally labelled with identification codes; ii. a robotic device (8), which has means to move freely along the three axes XYZ (30), adapted to be positioned at any point in the area (2) of the compartments (9), wherein the area (2) is located in the horizontal plane XY, a robotic device comprising the following elements:- at least one high-precision image capture camera (31) adapted to capture images of the sample holders (14) and / or of the physical characteristics of the samples and, optionally, of the identification codes, disposed on the sample holders (14), as well as of the identification codes disposed on specific reagent reservoirs (22);- at least one probe adapted for the dispensing of specific reagents and at least one probe adapted for the dispensing of common reagents;- at least one probe adapted for washing; and- at least one general purpose microcontroller with a computer program configured for the control of all the protocols, processes, members and equipment that form or operate the apparatus.

39. The apparatus according to claim 38, wherein the probes comprise:- at least one comb (35) comprising several common reagent dispensing probes (35a);- at least two washing probes of a diameter greater than the dispensing probes, adapted for washing and connected directly to common reagent reservoirs (5a); and- at least one reagent spreader roller (33), adapted for spreading reagents dispensed onto the sample holders (14).

40. The apparatus according to claim 38 or 39, wherein each of said compartments (9) comprises a lower face that rests on a thermal blanket (15), on a vibration system (16) and on a waste tray (3) and by its upper face, bevelled, grooved or milled, the lower face of the glass sample holder (14) of size and shape adapted to that bevelling, grooving or milling is supported, keeping the perimeter of the upper face of the glass sample holder (14) in flight and isolated, preventing the reagent that is dispensed on it from spilling out of the area by surface tension; and wherein, between each bevel, groove or milling, grooves (13) are placed transversely for the expulsion of surplus waste towards a waste tray.41 . The apparatus according to any one of claims 38 to 40, further comprising a double dual device which, through two pumps, connects the waste tray (3) of all the compartments with at least two waste tanks, one for hazardous waste and one for non-hazardous waste.

42. The apparatus according to any one of claims 38 to 41 , wherein the dispensing probes are connected to at least one common reagent reservoir area (5) and at least one specific reagent area (6).

43. The apparatus according to any one of claims 38 to 42, further comprising at least one air blow drying system (36).

44. The apparatus according to any one of claims 38 to 43, further comprising automaticwashing devices (25) using washing solutions.

45. The apparatus according to any one of claims 39 to 44, wherein the common or general reagent dispensing comb (35) is formed by at least six dispensing probes (35a) and at least six common or general reagent tubes.

46. The apparatus according to any one of claims 38 to 45, further comprising at least one washing station (25) of the probes of the apparatus.

47. The apparatus according to any one of claims 38 to 46, comprising at least one washing (25) and drying station of the spreader roller (33) and the comb (35) of probes (35a).

48. The apparatus according to any one of claims 38 to 47, comprising at least one automatic reagent mixing area (27).

49. The apparatus according to any one of claims 38 to 48, comprising at least one gas removal filter (41).

50. The apparatus according to any one of claims 40 to 49, wherein the thermal blanket (15) is provided with a thermal probe for the control and maintenance of the temperatures of the different protocols performed by the apparatus (1).51 . The apparatus according to any one of claims 38 to 50, wherein each compartment (9) has a light indicator (12) to identify the fault state or the state of the protocol executed in said compartment (9).

52. The apparatus according to any one of claims 41 to 51 , wherein the waste tank (3) is provided with a level sensor.

53. The apparatus according to any one of claims 43 to 52, wherein the air blowing device (36) integrates a compressor and a flow sensor.

54. The apparatus according to any one of claims 38 to 53, further comprising an automatic washing device (25) for the compartments (9), consisting of a tube connected to a membrane pump disposed in a container containing a specific washing solution determined by the control device, based on the specific protocol being developed in said compartment (9).

55. The apparatus according to any one of claims 42 to 54, wherein the specific reagent reservoir area (6) comprises a thermostatted rack (23), the temperature of which is controlled by the programmable device, which controls the entire system.

56. The apparatus according to any one of claims 42 to 55, wherein the common reagent reservoir area (5) has a weight volume sensor for each reservoir (5a).

57. The apparatus according to any one of claims 42 to 56, wherein the specific reagent reservoir area (6) has a capacitance volume sensor in the probe to detect the regent level in each reservoir.

58. The apparatus according to any one of claims 38 to 57, wherein the apparatus comprises at least one infrared sensor (42) for monitoring the temperature in the plurality of compartments (9) adapted for the function of reaction chambers.

59. The apparatus according to any one of claims 38 to 58, wherein the apparatus is configured to execute a dynamic planning method comprising steps for adaptively programming tasks of the robotic device (robotic tasks) in a time interval, wherein the robotic device is coupled to the staining or hybridisation apparatus, wherein the robotic device treats slides coupled to the staining or hybridisation apparatus according to a reagent treatment protocol in reagent or fluid reservoirs coupled to the staining or hybridisation apparatus, wherein the steps comprise:- creating a task list of the robotic device comprising all robotic tasks that are ready for execution within the time interval;- calculating a robotic task priority for each robotic task on the robotic task list;- sorting the list of robotic tasks in descending order of priority of robotic tasks; adding robotic tasks by continuously prioritising;- changing the order of the processes of the robotic device as it acts; and,- reporting the state of each of the processes of the robotic device.

60. The apparatus for carrying out treatments of histological staining, immunoenzymatic staining and hybridisation on tissue sections or cell smears adapted to perform the method of any of claims 1 to 13, or to execute the system of claims 14 to 37.

61. The apparatus according to claim 38, wherein the robotic device (8) adapted for thecapture of high-precision images and dispensing of reagents on the samples, is replaced by a manual dispensing of reagents.

62. A computer program product for performing treatments of histological staining, immunoenzymatic staining, and hybridisation on tissue sections or cell smears comprising instructions that, when executed in the system of claims 14 to 37, cause the computer means to perform the method of claims 1 to 13.

63. The computer program product according to claim 62, comprising a computer-readable medium, which, in turn, comprises encoded instructions for controlling a microprocessor that processes images from a sample disposed on a sample holder, comprising: a) means for self-calibrating at least one high-precision image capture camera (31) capable of capturing images of the placement of at least one sample holder (14), of the samples to be stained or hybridised and, optionally, of the identification codes, disposed on the sample holders (14), as well as of the identification codes disposed on specific reagent reservoirs (22); b) means for capturing images of the sample holder (14) that carries the samples, specifically of the placement of the sample holder (14) and, optionally, of the identification codes disposed on the sample holders (14); c) means for capturing images of the samples to be stained or hybridised; d) means for capturing images of the reagent reservoirs (5a, 22) to be applied in the treatments of the samples; e) means for processing the images captured from the sample holders; f) means for processing the images captured from the specific reagent reservoirs; g) means for sending movement orders to a robotic device (8) carrying at least one high-precision image capture camera (31) and fluid dispensing means, which moves from compartment (9) to compartment (9), wherein at least one sample holder (14) with samples is located; and h) Artificial Intelligence (Al) processing means of the high-precision images of the captured samples, for sending orders for improving the quantity, location and dispensing times of the reagents to be dispensed in said samples.

64. The computer program product according to claim 63, wherein the means for processing images captured from the samples disposed on the sample holders comprises: i. means for calculating the areas of the polygons that make up the segmented imagesof the captured samples; ii. means for calculating the dispensing positions of the reagents that allow covering the entire sample with the minimum amount of reagent; and iii. means of generating an output file that, at least, contains: reading the identification codes of the sample holder, reading the areas of the polygons of the image of the captured segmented sample, positions and volumes of the reagents to be dispensed.

65. The computer program product according to claim 63 or 64, wherein the means for sending dispensing orders, by the robotic device (8), of the reagents, comprises: i. means for reading the output file generated in the processing of the captured sample holder images; and ii. means for sending orders to the robotic device (8) to be positioned in the chamber where the sample holder (14) is disposed with the sample corresponding to the output file and dispense the volume of reagent and in the positions determined in said output file.

66. The computer program product according to any one of claims 63 to 65, comprising means for applying process protocols existing in the computer program and previously selected about the treatments of histological staining, immunoenzymatic staining and hybridisation on tissue sections or cell smears comprised in said sample, based on the image capture performed on said sample and the area of said sample, the contours thereof, its position and the amount of sample to be treated.

67. The computer program product according to any one of claims 63 to 66, comprising maintenance means of the system and / or of the apparatus to be applied according to environmental parameters, such as temperature or humidity.

68. The computer program product according to any one of claims 63 to 67, comprising means for sending orders to finish each protocol and / or process and / or to pause the system.

69. The computer program product according to any one of claims 63 to 68, comprising means for relating the readings of the identification codes of the samples to the image captures of said samples.

70. The computer program product according to any of claims 63 to 69, comprising meansfor sending orders for dispensing cleaning or washing fluids to be executed in the period between the conclusion of one protocol and / or process and the beginning of a new protocol and / or process.71 . The computer program product as claimed in any of claims 63 to 70, comprising means that allow the dispensing of reagents by executing commands to a spreader roller (33) of said reagents on the sample when they have a viscous nature.

72. The computer program product according to claims 63 to 71 , comprising means for pausing the system when the threshold of a predetermined excess timeout is exceeded.

73. The computer program product according to any one of claims 63 to 72, comprising means for monitoring the infrared (IR) temperature in the plurality of compartments (9) adapted for the function of reaction chambers.

74. The computer program product according to any one of claims 63 to 73, comprising means for executing a dynamic planning method (planner), and for adaptively programming tasks of the robotic device (robotic tasks) in a time interval, wherein the robotic device is coupled to a staining or hybridisation apparatus, wherein the robotic device treats the slides coupled to the staining or hybridisation apparatus according to a treatment protocol with reagent, reagent or fluid reservoirs coupled to the staining or hybridisation apparatus, wherein the means comprises:- means for creating a to-do list of the robotic device comprising all robotic tasks that are ready for execution within the time interval;- means for calculating a robotic task priority for each robotic task on the robotic task list;- means for sorting the list of robotic tasks in descending order of priority of robotic tasks; and- means for adding robotic tasks continuously prioritising;- means for changing the order of the processes of the robotic device as it acts; and- means for reporting the states of each of the processes of the robotic device.

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