Actuator device and system for clinical analysis using analysis chip

Abstract

A system for clinical analysis using an analysis chip (1000) includes an actuator device. The invention relates to an actuator device (100) comprising: a computer module (100) for integrating all signals received by the system and converting it into analysis results, said computer module (100) being connectable by a connection module (160) to a data processing module (170) connected to an external large-scale clinical data system to generate a diagnostic pattern; a fluid driving module (110) for pushing a fluid within the analysis chip; a thermal module (120) for distinguishing thermal regions of the analysis chip; an artificial vision module (130) for the analysis of the process inside the chip; an electronic interface (140) for communicating the sensors and actuators integrated in the analysis chip and the actuators of the actuator device with a computer module (100); a power management module (150) for autonomously powering the portable system within an outer container that protects all of the aforementioned modules of the actuator device into which the analysis chip is inserted.

Description

Technical Field

[0001] The present invention relates to industries dedicated to biomedical systems using analytical methods based on microfluidics technology.

[0002] More specifically, the present invention relates to an actuator device and system for controlling an analytical process using an analytical chip based on microfluidics and electronics technologies. Background Art

[0003] Advances in microfluidic technology have revolutionized clinical testing processes, especially in the fields of enzyme detection procedures (e.g. glucose and lactate determination), proteomics, DNA analysis, and molecular biology in clinical pathology, especially in the rapid diagnosis of diseases. The basic idea of ​​microfluidic (bio) chips is to integrate the measurement operations such as detection, sample pretreatment and sample preparation on a single chip (analytical chip). These microfluidic chips or devices enable real-time and continuous sampling and testing, for example, for fluid samples for biochemical analysis of toxins and other dangerous pathogens. Therefore, one of the many applications of analytical chips is the detection of gene sequences related to the SARS-CoV-2 virus, which is particularly important during the peak of the epidemic.

[0004] In the field of portable analytical systems, there are solutions based on functionalized porous matrices for the detection of different analytes by affinity; these solutions are also called lateral flow assays, and their results are usually interpreted visually by the user, due to the isolated colorimetric reaction that takes place in a specific area. That is why these methods are considered qualitative and can be easily used by the user.

[0005] In conventional practice in the field of microfluidics, the addition of image monitoring is one of the reasons why these systems are usually manufactured on transparent substrates. However, this image monitoring is usually performed by integrating the analytical chip into a commercial magnifier or microscope, without communication between the microfluidic delivery system in the chip (usually a syringe or peristaltic pump) and the system used to read the chip (via a vision system). In this way, the imaging information is only used to obtain the final result and cannot affect the progress of the analytical process.

[0006] On the other hand, some progress is to achieve the advancement of the fluid front in the microfluidic platform by generating an acoustic pressure gradient along the microfluidic path, adding sensors and actuators to the microfluidic platform itself, or by generating different potentials in the digital microfluidic system. Therefore, there are microelectrode array (MEA) drive systems based on acoustic waves, and drive systems for the movement of droplets at the fluid front along electronic interfaces in digital microfluidics (DMF) platforms, which is a lab-on-chip system platform based on droplet manipulation.

[0007] In the prior art, there are different approaches to electronic interface systems for microfluidic chips: the aforementioned “lab-on-a-chip” systems and microelectrode array MEA systems. The most common implementation of MEA systems is an open well with electrodes in a glass bottom (transparent MEA system) for electrical connection to the tissue cultured therein and image monitoring by microscopy. In MEA systems with a high concentration of electrodes, the image of the tissue is generated by the electrical signals received by the different electrodes in the array. On the other hand, “lab-on-a-chip” systems have grown in recent years and there are analytical systems designed to perform different tests, which adopt different integration methods depending on the type of analytical process. In the case of assays that require a vision system to capture colorimetric or fluorescence signals, the system is usually integrated into a mobile phone, where the signals are processed by software developed specifically for this purpose. Therefore, there is no connection between the fluidic front-end drive system and the vision system itself of these solutions, as they are independent systems.

[0008] On the other hand, solutions based on reading the signals generated in the analytical chip, i.e. i) colorimetrically by precipitation of a colored agent (e.g. in the case of lateral flow assays or “paper-based assays”) or ii) electrochemically by measuring the redox potential generated during an enzymatic reaction (e.g. in the case of point-of-care systems or “point-of-care tests” for the determination of biochemical parameters such as glucose or blood gas analysis) are only i) solutions that combine artificial vision and actuation systems, but they are only applicable in the case of colorimetric tests, or ii) solutions that combine actuation systems and electronic interfaces, but they are only applicable in the case of electrochemical tests.

[0009] There are different "point-of-care" systems on the market that transform the assay into a semi-quantitative method by combining an artificial vision system, allowing for a relative quantification of the results obtained in the analytical area. In these systems, fluid control is passively performed by using porous matrices that generate the lateral capillary flows that are characteristic of this analytical method. However, in this way, fluid control and artificial vision systems are completely disconnected and become independent entities, so they can only be used together in simple tests.

[0010] In the prior art, the different “point-of-care” systems are classified into different types, mainly portable systems and desktop systems. For desktop systems, their use is directed to fixed places such as consulting rooms, laboratories or professional analysis sites, both because of their size and because of the need to be connected to the power grid. Among these systems, there are the most complex applications, such as crop control, genetic and immune sample analysis, and multi-analysis systems (for example, there are commercial systems in mobile matrices that combine portable blood glucose meters and gas meters with complex analytical equipment that rely on connection to the power grid, and the mobile matrix has high-performance batteries and power grid connection capabilities to power these devices). In an attempt to overcome these shortcomings, portable systems are based on the use of power management systems that allow them to be used without being connected to the power grid, but these systems are generally used for applications such as blood gas analysis or quantitative metabolites by electrochemical detection, because more complex detection systems require higher power supplies than portable battery systems can provide.

[0011] In portable "point-of-care" analytical systems, it is known to use voltammetric or amperometric systems to determine the concentration of different analytes in biological samples, where the measurement of the potential change or the generation of an electric current is performed in an electrochemical cell where an enzymatic reaction takes place depending on the analyte to be measured. To measure these analytes, gold and carbon nanotube-functionalized polymer electrodes are usually used, and fluid control is usually performed by integrating capillary pumps within the chip itself, but for this reason these portable systems are only suitable for simple reactions where only a single interaction of the fluid is required.

[0012] On the other hand, it is well known that in the production of automated devices for the well-known molecular biology technique polymerase chain reaction (PCR), it is necessary to combine a microfluidic drive system and a thermal control module. Thermal cycling systems for PCR applications allow for a variety of gene amplification tests to identify the presence of different gene sequences in a sample. This type of test provides some examples at the "point-of-care" level, where fluid control is performed in the device itself. Similarly, in MEA systems, the combination of an electronic interface with a thermal control module is common in the field of tissue culture applications for electrophysiological studies. In this case, the microelectrode system can be coupled to a thermal control system, or external means can be used to achieve the indicated culture conditions. In the current state of the art, there are temperature control devices that are also attached to artificial visual systems for monitoring cell culture. Therefore, in these devices there is a thermal control module that allows the temperature of the culture chamber to be accurately monitored. On the other hand, the image monitoring system is independent in the system and is not connected to the temperature control system. In these systems, the temperature of the culture is controlled while performing visual control performed by "time-lapse" type image capture. These units are designed to maintain very specific temperature and humidity conditions, do not differentiate between thermal zones, and are therefore a very simple temperature control system.

[0013] As in conventional thermal cycling systems, a combination of a thermal module and an artificial vision system is used to measure the fluorescence signal, in portable quantitative genetic analysis systems, fluid control is added to allow automation of the analysis chip, avoiding the need for the user to manipulate the samples. These systems consist of: a thermal control system that allows thermal cycling according to a pre-set schedule; a drive system that moves the liquids involved in the analysis process to the different chambers where the steps are performed, and an artificial vision system, combined with the adaptation of the fluorescence filters, allowing the measurement of the fluorescence signal generated in each sample. These types of devices generally allow multiple samples to be multiplexed in a single device, but only one type of detection is allowed per operating cycle, i.e., all the detections to be performed simultaneously must be exactly the same. In these systems, the genetic analysis of the samples is performed automatically, but there is only one temperature program for each individual load, and each cycle depends on the program to be used in the platform.

[0014] The objective technical problem proposed is therefore to provide a portable system for reading analytical chips and operating them, which allows different types of detection to be performed in a single analytical chip and can also interact with an analytical platform, performing sensing of signals provided by sensors integrated in the card and interconnected to the analytical chip. Summary of the invention

[0015] The present invention aims to solve the above problems and provides a system for clinical analysis using an analysis chip (microfluidic device), which can perform different types of tests in a single active analysis chip using a system actuator device that directly communicates with the chip through different interfaces.

[0016] The present invention integrates the analytical chip and the actuator device in the same system, which has an electronic interface capable of communicating with the conductive elements of the chip, thereby enabling the collection of signals generated in the analytical chip and thus enabling various electrochemical tests to be performed in the system.

[0017] Furthermore, due to the drive mechanism integrated in the system, the present invention increases the complexity of the clinical tests allowed and also makes it possible to perform different tests in parallel in a single analytical chip.

[0018] Furthermore, the present invention integrates the microfluidic drive mechanism with the thermal module and the artificial vision module, which not only allows the measurement of the complete thermal process and optical results through image monitoring, but also allows the parallelization of different processes in a single analytical chip by combining different thermal zones in a single chip. This allows different applications to be carried out simultaneously, so there is no dependence on additional processes to select conditions. In addition, the artificial vision module not only allows the measurement of the results after the process is finished, but also serves as a real-time control of the progress of the process in the analytical chip, which is not available in the prior art solutions.

[0019] One aspect of the present invention relates to an actuator device for a clinical analysis system using an analysis chip, the actuator device interacting with the analysis chip, comprising the following components:

[0020] a portable external container for housing and supporting a plurality of actuation modules of the actuator device, the portable container comprising an input chamber for introducing the analytical chip into the actuator device and coupling it with the plurality of actuation modules, wherein the plurality of actuation modules comprises at least a fluid drive module, a thermal module and an artificial vision module;

[0021] a computer module, housed in the external container, comprising a plurality of electronic control blocks, each of which is connected to one of the plurality of actuation modules, the electronic control block being configured to receive signals obtained from a plurality of sensors integrated in the actuation modules and to send signals to activate actuators integrated in the actuation modules, the computer module being configured to generate process information and analysis information from signals received by the control blocks and signals obtained from a plurality of sensors integrated in the analysis chip, and to provide a plurality of analysis results obtained from the analysis information processing performed by the computer module;

[0022] an electronic interface, housed in the outer container, for communicating the computer module with the analysis chip, through which the computer module receives a signal obtained by a sensor integrated in the analysis chip and sends a signal to activate an actuator integrated in the analysis chip;

[0023] The power management module includes a battery pack contained in the external container and is configured to supply power to a plurality of actuator modules included in the actuator device.

[0024] Another aspect of the present invention relates to a system for clinical analysis, comprising the actuator device described above and an analysis chip integrated therewith.

[0025] Compared with the prior art, the advantages of the present invention mainly include:

[0026] In combination with an electronic interface for controlling the signals generated by the analysis chip, and the possibility to perform local operations on the analysis chip itself while performing visual control of the system, feedback between electronic communication and artificial vision allows adding unique functionalities to the system. For example, and without limitation, some functionalities include:

[0027] Generate hybrid measurement systems where the emitter or sensor is located in different systems. Use the artificial vision system as a sensor and replace the emitter by integrating different light emitters in the analysis chip, realizing a system with multiple emitters without having to set up a set of actuators in the artificial vision system.

[0028] Another application is to use electrodes as sensors by direct contact with the sample, enabling parallelization of visual measurements and electrochemical determinations in the system.

[0029] By providing an electronic interface to the analytical chip, it is possible to add different functionalities to the actuator device of the system, allowing optical operations to be performed in the system, as well as different types of detection on the analytical chip (colorimetric, fluorescent, turbidometric, chemiluminescent, electrochemical, etc.). There is no solution in the prior art that is able to integrate these functionalities, and therefore it is not possible to provide all these different types of detection in a single analytical chip.

[0030] The present invention allows real-time monitoring of macroscopic processes (e.g., monitoring the state of a culture in an analytical chip or the advancement of a fluid front along a microfluidic path) as well as specific measurements in the optical range (e.g., changes in absorbance at a specific wavelength over time) and the electrical range (generation of current or voltage based on the redox potential of the environment, pH changes, etc.).

[0031] The fusion of artificial vision with the system's microfluidic actuation mechanism allows the creation of an information loop through which the progress of different processes can be actively controlled on the analytical chip itself. This enables the implementation of many possible applications, including vision-based microfluidic process monitoring in the device and fluid actuation on the analytical chip based on visible signals. Moreover, through the combination of the described actuation mechanism and the artificial vision module, fluid processes of different complexity can be carried out in parallel, while the results of these processes can be accurately measured by using the artificial vision module, which is not limited to reading the color on an opaque substrate, but allows the use of quantitative analysis methods such as colorimetry, turbidimetry, fluorescence and luminescence through its different emitters and receivers.

[0032] By combining the actuation mechanism with an electronic interface and an artificial vision module, different tests that do not require thermal control can be performed in the same analytical chip, enabling colorimetric, turbidometric, or electrochemical assays to be performed at room temperature in the analytical chip.

[0033] Portability and autonomy: In the described invention, different types of analysis can be carried out in a portable system comprising a power management unit capable of powering the different functional modules included in the system's actuator platform. The optimization of the different actuators, especially the thermal ones, means that the energy consumption can be provided by portable batteries, increasing the possibility of its use in any environment.

[0034] By adding a thermal module to the system and its feedback with artificial vision, a more precise control of the processes carried out in the analytical chip is possible. Furthermore, the combination of the thermal module with the artificial vision module allows to distinguish different adjacent thermal zones on a single chip, thus providing the possibility of parallelizing different processes on a single device without the need to separate functional areas, thus enabling different kinds of tasks to be carried out simultaneously. Existing systems in the prior art obtain temperatures that are unique throughout the device, whereas the present invention enables to delimit different thermal action zones in the same device, thus enabling different processes to be carried out on a single analytical chip. This allows a range of applications on the device, such as analytical processes or performance and thermal monitoring of cultures in analytical chips, enabling different processes to be parallelized on a single platform.

[0035] The combination of the electronic interface, thermal actuation and artificial vision modules described above allows the creation of a system capable of performing different tests in the same analytical chip, where different temperature, actuation and detection parameters (light, fluorescence, electrochemistry or turbidity) can be controlled according to the needs of the test. For example, and without limitation, quantitative gene amplification tests or quantitative polymerase chain reactions (qPCR) can be performed, where, due to the system's ability to distinguish different thermal zones, the thermal cycling of the sample and the detection of the fluorescence signal in each temperature cycle can be performed simultaneously, unlike solutions in the prior art.

[0036] The connectivity of the system itself, as well as its data processing module, in which the results obtained during the ongoing process are stored, allow the anonymization of analytical data and their large-scale study to obtain analytical trends and to advantageously elucidate analytical images or matching parameters.

[0037] These and other advantages result from the following detailed description of the invention. BRIEF DESCRIPTION OF THE DRAWINGS

[0038] Below, there is described very briefly a series of drawings which contribute to a better understanding of the invention and which relate expressly to embodiments of the invention as non-limiting examples thereof.

[0039] Figure 1 A block diagram showing a modular architecture of actuator devices constituting a system according to a preferred embodiment of the present invention.

[0040] Figure 2 A complete electronic interface is shown that communicates the analytical chip with the computer module of the system according to a possible embodiment of the present invention.

[0041] Figure 3 A thermal module of a system according to a possible embodiment of the invention is shown.

[0042] Figure 4An artificial vision module of a system according to a possible embodiment of the present invention is shown.

[0043] Figure 5 A driving module of a system according to a possible embodiment of the present invention is shown.

[0044] Figure 6 An external view of a container containing system modules according to a possible embodiment of the invention is shown.

[0045] Figure 7 A detailed view of an automated import bay for integrating an analytical chip assembly with a system module within a container is shown according to a possible embodiment of the present invention.

[0046] Figure 8 An external view of the container of the system module is shown, with a location for housing the analytical chip and a touch screen with a user interface for selecting the operating mode of the system. DETAILED DESCRIPTION

[0047] A preferred embodiment of the clinical analysis system proposed in the present application comprises an actuator device composed of different functional modules which together allow the analysis chip to operate in different fields (electrical, fluidic, thermal, optical, electronic actuation, etc.).

[0048] The system implements a multi-analytical technology that enables clinical analysis in a portable, rapid and automated manner, and consists of two main interacting parts: the analytical chip and the actuator device. The analytical chip combines several technologies:

[0049] Microfluidics: Microfluidic design is used to generate channels that guide the necessary fluids for analysis, mixing, filtration, etc. In addition, microfluidic design allows the definition of areas where fluids are stored, which at the same time serve as a means of propulsion or are used to define areas where chemical processes are carried out: reaction chambers.

[0050] Electronics: Adding conductive metal layers to certain surfaces of the analytical chip makes it possible to perform some electrical operations in specific areas (such as heating them), or even integrate electronic components (such as LEDs, phototransistors, etc.) in the area of ​​interest to be able to measure and operate directly where needed. This makes it possible to obtain information (analytical information) directly from the area of ​​interest (reaction chamber) itself.

[0051] An analysis chip communicates with the actuator device proposed herein so that it can read the signals collected by the sensors integrated in the chip and, for this purpose, is connected to a computer module that reads and interprets the signals.

[0052] Figure 1All the different individual modules and their connections that can be integrated into a system actuator device are shown, with the solid arrows between the modules indicating the transmission / reception of signals and commands between the modules (double solid arrows), defining their direct relationship, while the dashed arrows indicate the exchange of data.

[0053] The modularity of the device / system allows for the combination of different modules, which in themselves determine customizable functional units. In these combinations, different possible embodiments of the invention are generated, in which there is always a computer module integrated with one or more other modules in an external container. The integrity of the system depends on the above and the control of the different functional modules, which are listed below and their numerical designations and described in detail later.

[0054] Computer module 100

[0055] Driver module 110

[0056] Thermal module 120

[0057] Artificial Vision Module 130

[0058] Electronic interface 140

[0059] Power management module 150

[0060] Connection module 160

[0061] Data processing module 170

[0062] External container 180

[0063] The actuator device controls the progress of various analytical processes by combining the different actuation modules mentioned above. In order to meet the needs of each analytical process to be integrated, the basic functions of the modules / components of the actuator device are as follows:

[0064] The microcomputer module 100 controls all processes and interprets signals, integrates all signals received by the system and converts them into analysis results, and also provides connectivity for the system. The computer module 100 can communicate with the data processing module 170 through the system's connectivity module 160 to study and compare the analysis results in a forward-looking manner to generate a diagnostic model.

[0065] The fluid driving module 110 controls the propulsion of different fluids in the analysis chip and controls which fluids are introduced.

[0066] The thermal actuation module, or thermal module 120, allows the temperature of different thermal zones of the analytical chip to be modified according to the needs of the clinical trial.

[0067] The artificial vision module 130 allows different monitoring and measurement processes to be performed in the analysis chip and pre-identifies the analysis chip inserted into the system.

[0068] Electronic interface 140 through which the sensors and actuators integrated in the analysis chip communicate with the computer module 100 of the actuator device, making it possible to control the different signals acquired by the analysis chip and to command or activate the different actuators therein.

[0069] The power management module 150, autonomously powers the system to make it portable, generates the necessary voltage lines and charges the battery that powers the system modules.

[0070] The connection module 160 of the system is used to transmit the results to an external central system through different information protocols.

[0071] The outer container 180 or outer housing protects all the aforementioned modules of the actuator device, into which the analytical chip is inserted through the input bay.

[0072] Therefore, the system proposed by the present invention includes an actuator device and an analysis chip 1000, such as Figure 2 As shown, the analysis chip is an active analysis chip, which includes both the microfluidic design and necessary reagents for each analysis test, as well as the actuators and sensors required to perform the complete process together with the actuator device. Preferably, the chip is made of an optically transparent and biocompatible polymer substrate, for example, polymethyl methacrylate (PMMA), polycarbonate (PC), or cyclic olefin copolymer (COC). The analysis chip 1000 is composed of different layers, which include different components required for the design test (electronic and thermal sensors and actuators, as well as microfluidic actuators, such as mixers, separators or reservoirs). Specifically, the electronic components included in the chip communicate with the actuator device through an electronic interface 140, allow the data collected by the sensor to be received through electrical contact, and start different actuators according to the commands programmed in the actuator device. In addition, the analysis chip 1000 includes different reservoirs, which are filled with different fluids (reagents, samples, controls, etc.) required for conducting clinical trials. Figure 2Also shown is a connection board 101 which provides biocompatible electrical contacts to connect (contact) different analytical chips 1000 or microfluidic cards with all system electronics. The computing module 100 is a microcomputer connected to the analytical chip 1000 via the connection board 101 which is part of the electronic interface 140. More specifically, the connection between the analytical chip 1000 and the electronic equipment is achieved through the electrical contacts of the electronic interface 140, which fix the consumable in its predetermined position through a fixture (an element located in the reader / actuator device and applies pressure to the consumable to ensure electrical contact), thereby contacting the metal connection pads of the chip laboratory (lab-on-chip, LoC).

[0073] In addition, the system includes a user interface, such as a computer screen or a graphical interface of a mobile terminal, to provide the user with communication of options and results of system control. The user interface may include different peripherals, not limited to or excluding, providing information by acoustic means, tactile interfaces, etc.

[0074] Next, each module / component of the actuator device and the relationship between different functional modules of the technology are described in more detail according to possible embodiments.

[0075] Figure 2An embodiment of a complete electronic interface 140 is shown, which communicates the analysis chip 1000 with the computer module 100 of the actuator device. The electronic interface module 140 is one of the modules that is most connected to other components of the system after the computer module 100. This electronic interface 140 allows the activation of the different actuator electronic components contained in the analysis chip 1000, as well as the reading of the data received from the different sensors integrated in the analysis chip 1000, in order to pass the data collected from the analysis chip to the computer module 100. Therefore, the electronic interface 140 acts as a communication link between the analysis chip 1000 and the actuator device, allowing the electronic connection between the chip itself and its corresponding sensors and actuators and the actuator device. The electronic interface 140 is connected both to the analysis chip 1000 and to the power management module 150, so as to feed the actuation carried out in the analysis chip 1000 to the computer module 100, which collects and processes all the information of the analysis chip 1000. The electronic interface 140 allows communication between the active parts of the system, by using electronic connection pads and biocompatible electrical contacts, providing a direct connection with all the modules that have actuators or sensors in the analytical chip and creating a closed loop of signals. In this way, for example, the thermal module 120 communicates with the heating elements in the analytical chip through the electronic interface 140, while the thermal sensors of the system send the information collected through this interface to be processed in the computer module 100 and subsequently used as information to control the thermal module 120 itself. On the other hand, this electronic interface 140 is responsible for transmitting the information collected by the electrodes contained in the analytical chip 1000 to the computer module 100 itself, through flat contact pins (which come into contact with the metallized "pads" of the chip and each of which is connected to a different sensor and actuator element of the system), in order to study the signals and generate analytical results from them.

[0076] Figure 3An embodiment of the actuation part of the thermal module 120 is shown, which comprises a heat sink 121, a thermal battery 122 and several temperature sensors that allow temperature mapping in different processes. In addition, all the thermal sensors and actuators integrated in the analytical chip 1000 itself are also contained in the thermal module 120 of the system. The thermal module 120 allows the temperature of different active areas to be controlled according to the needs of the test and consists of two parts that provide a series of connections that allow it to be integrated with the rest of the system: the actuation part (thermal) that belongs to the actuator device and another part of the thermal functional module in the analytical chip 1000. In the analytical chip 1000, there are thermal actuators and temperature sensors controlled through an electronic interface 140. On the other hand, the actuator device contains different thermal actuators (thermal batteries, heat sinks, etc.) that, together with the closed control loop of the temperature sensors in the actuator device, allow temperature control in the entire system, the data being managed in the computer module 100. In addition, the division of the different thermal actuators of the thermal module 120 (whether in the actuator device or in the microfluidic device 1000) allows the differentiation of thermal zones, thereby enabling the demarcation of operating areas based on temperature in the same system, enabling the parallelization of areas according to target temperatures, and thus enabling different types of tests without jeopardizing the feasibility of adjacent tests. Specifically, for example, the thermal module 120 makes it possible to maintain 37°C in the area where constant temperature biochemical tests are required, while in the area demarcated for genetic testing, a thermal cycling protocol of continuous cycles from 98°C to 62°C can be performed without affecting other areas. Specifically, the thermal module 120 is controlled by the computer module 100, which contains different thermal cycle programs based on the analysis to be performed in the system. Therefore, the computer module 100 sends commands to the different actuators of the thermal module 120, and the thermal sensors associated with the thermal module 120 send the collected information to the computer module 100 for processing and generate an information feedback system so that a precise temperature control cycle can be actuated. In general, the thermal module 120 thermally actuates the rest of the system by activating different additional actuators (heaters, thermal batteries, fans, etc.), enabling the system to perform parallel processes that have hitherto been impossible to parallelize in a single device, thus improving the performance of the system described so far. Furthermore, the integration of a temperature sensor in the analytical chip 1000 allows the temperature in the chip to be monitored through the electronic interface 140, thus obtaining a more accurate reaction temperature than that obtained by external control.

[0077] Some technical requirements during clinical analysis are to perform extreme temperature changes, which in central laboratories is achieved by thermal cyclers, which change the temperature of the test as quickly as necessary. Specifically, in one example of clinical analysis, these extreme thermal cycling processes are necessary to perform PCR analysis to verify the presence of infectious viruses. Currently, thermal cycling processes for viruses such as SARS-CoV-2 are performed at a maximum temperature of 98°C and a minimum temperature of 62°C. These temperatures are not compatible with other analytical processes, which usually need to be performed at a temperature close to human body temperature, about 37°C. In order to be able to combine PCR processes with other types of processes, in addition to thermal partitioning of the analytical chip, manufacturing with high thermal inertia materials and thermal actuation and measurement in the area of ​​interest, an automatically controlled thermal block is required to cool the analytical chip areas that are most sensitive to real-time thermal changes and provide heating support in areas that require rapid temperature increase.

[0078] To this end, the thermal module 120 is composed of the following components:

[0079] A heat block consisting of one or more Peltier cells and a heat sink. A Peltier cell is an electrothermal actuator that can emit (heat) or absorb (cool) thermal energy depending on the voltage it is supplied with. These elements require a heat block to be able to dissipate the temperature changes to which the other surfaces are subjected.

[0080] The control software adjusts the operating temperature of the thermal block in real time via a Proportional, Integral and Derivative (PID) controller. This is achieved by programming the controller to adjust the voltage applied to the Peltier cell based on the amount of thermal energy that needs to be applied to the system to achieve the target temperature (either by cooling or heating).

[0081] The thermal module 120 interacts with the thermal sensors and actuators integrated in the analysis chip 1000 to be able to measure and act on the area of ​​interest. This allows the temperature to be viewed directly in the area in real time, rather than in the usual calculated manner.

[0082] The thermal module 120 enables thermal cycling processes that are compatible with other processes that have different thermal requirements and are automatically generated. In addition, due to the ability to achieve industry-standard very high temperature ramps, small areas must be heated instead of large heat blocks, and with tight controllers; thermal processes, such as PCR testing, can be performed faster than with existing technologies. As a comparison, PCR for SARS-CoV-2, the virus that causes COVID-19, is currently completed in approximately 3.5 hours. By using the proposed thermal module on a CLC designed with this analysis, it is currently completed in approximately 2 hours and is expected to be shortened by approximately 1 hour, while other tests marking disease severity, which otherwise must be performed separately, are also performed on the same chip.

[0083] Benchtop systems used in laboratories for thermal cycling tests combine thermal modules and artificial vision and use electronic interfaces, but only for thermal control of the thermal block. In these cases, the equipment does not have any fluid control, so the consumables must be loaded by the user. Compared with existing thermal cycling systems, the system proposed in the present invention has a technical advantage in that the thermal module 120 is combined with the artificial vision module 130 and the drive module 110 described below.

[0084] Figure 4An embodiment of an artificial vision module 130 is shown, which includes a camera with a high-resolution CMOS sensor, a mechanical system or holder of optical filters suitable for different parts of the visible spectrum, which partitions the optical frequency into areas of interest, and a series of optical actuators 133 at different wavelengths required (laser emitting devices at different common frequencies for optical detection processes in the visible spectrum and LED emitters in the infrared and ultraviolet bands). The artificial vision module 130 also interacts with other optical sensors and actuators included in the analysis chip 1000. Therefore, the artificial vision module 130 of the system includes a set of light and image sensors and actuators, which are integrated in the analysis chip 1000 and the actuator device, allowing real-time monitoring of the activities in the actuator device and the analysis chip 1000. The different elements that make up the artificial vision module 130 include (by way of example): a set of light sensors, including a high-resolution camera, capable of viewing the inside of the actuator device in real time and can be viewed in turn through the system's graphical interface, or by analyzing the image through the computer module 100; a series of light actuators at different wavelengths (e.g., LED diodes, laser emitters, etc.) for use according to the requirements of the test to be performed; and a series of filters, together with different light emitters and receivers, capable of detecting signals of predetermined wavelengths. The high-resolution camera, together with the above-mentioned series of LED and laser-type light actuators and the above-mentioned optical filter set that adjusts the signals collected by the camera, allows the detection of tests integrated in the analysis chip in different modes through different signals and their interpretation. In particular, although not limited to this, it allows colorimetric, fluorescent, turbidity and chemiluminescent tests to be performed on the chip, thereby achieving a wide range of detection fields. The artificial vision module 130 is connected to the computer module 100, which processes the data collected by the artificial vision module 130, converts the information from raw data to results by applying algorithms developed for each detection mode, and sends a program to select different steps to be performed according to the test to be performed. On the other hand, the artificial vision module 130 is also connected to an electronic interface 140 for activating the different sensors and actuators contained in the analysis chip 1000 itself, either by sending signals from the computer module 100 to activate them or by receiving this information from the sensors.

[0085] The artificial vision module 130 runs a trained artificial vision algorithm to detect the type of analytical chip 1000 inserted into the actuator device, as well as control the process occurring in the reaction chamber. Many clinical analytical processes detect the parameters of interest optically, whether by colorimetry, turbidimetry... To do this, the analytical device needs to include a light emission system of the required light type and a light detection system for detecting the frequency region of interest. This, combined with an algorithm that calculates the parameters through light detection, allows the parameters to be analyzed. The combination of all these parts enables optical processes common in the clinical analysis industry and other disruptive processes such as Raman-type spectroscopy.

[0086] Figure 5An embodiment of a drive (propulsion) module 110 is shown, which includes a set of mechanical actuators that, together with the sensors contained in the analytical chip 1000, allow the control of the propulsion of the fluid front throughout a given process. The drive module 110 is adjustable and acts as a mechanical interface between the chip 1000 itself and the actuator device, which is replicated multiple times in the actuator device itself to allow a larger operating range in the system. In order to perform the analytical process, the fluid must be moved from one area to another, the amount of fluid introduced, and the time of movement or fluid mixing must be accurately determined. The control software defines the fluids that the drive module 110 must drive, the number of fluids, and the driving time. The software also activates or deactivates the synchronized pumping process (it can decide whether to pump one, two, three or the required number of fluids). By way of example, but not limited to this, the drive module 110 consists of the following parts: a matrix of motion axes, a position adjustment motor, a propulsion motor, and a motion piston 131 in the actuator device; while in the analytical chip 1000, it has a closure element, a fluid reservoir, and different kinds of sensors for the mechanical actuation of the drive module 110. These sensors can be light, resistance, impedance, or even a part of the aforementioned artificial vision module 130, which can control the advancement of the fluid front in the analysis chip, thereby forming a closed control loop. The analysis chip 1000 incorporated into the actuator device in the system integrates the operation of the drive module 110: a microfluidic piston containing necessary reagents, a physical separation interface between the mechanical driver and the internal fluid of the analysis chip, and a fluid position sensor that accurately detects the position of the fluid interface, thereby ensuring the mixing ratio of the reagents. The drive module 110 applies force to the fluid piston by using a mechanical system of a driver defined for this purpose, which is activated or deactivated in a controlled manner and is symmetrical (can move forward or backward). Therefore, the drive module 110 not only includes a series of motors connected to mobile actuators (pistons, gears, etc.), but also includes a position sensor to control the position and advancement of the fluid front in real time during the test execution. In this way, the drive module 110 is directly connected to the computer module 100, which sends activation signals of the motors and actuators to start the drive, and at the same time sends the signals of the position sensors (end sensors, light or heat sensors in the analysis chip, etc.) to the same computer module 100, so that the signals are processed as information feedback to accurately control the operation of the drive module 110. Therefore, the monitoring signals of the drive module 110 can be connected to the computer module 100 in two ways: directly from the position sensor in the case of an end switch, or through the electronic interface 140 in the case of sensors included in the analysis chip 1000. The drive module 110 allows complex analytical tests to be performed, being able to act on different axes to advance, retract, stop and mix different fluids in the analysis chip 1000 itself.Furthermore, the plug element allows packaging of reagents in the chip / analytical chip 1000, making storage of the chip a ready-to-use solution.

[0087] From a microfluidics perspective, the system is a differentiated leap forward from the existing technology. Currently, the automated actuation process requires large syringe drivers to be attached to the microfluidic chip, making it not easy to use. Furthermore, it hinders the definition of a truly portable system, as each thrust requires a piston system (which can easily weigh up to 2 kg) and a tube connecting the chip to the external piston. From a clinical perspective, the system allows for complex clinical procedures that have so far required laboratory technicians or complex and bulky equipment, allowing these procedures to be performed or automated away from hospital laboratories.

[0088] Although outside of portable or desktop devices, such as the proposed system, there are automated robots, where fluid control is performed by a robotic arm with an aspiration system, these robots distinguish different processes, whether thermal or actuation processes, in spatially separated areas. However, in the proposed system, in combination with the drive 110, thermal actuation 120 and electronic interface 140 modules, different automated processes can be performed to control multiple parameters: detection of different analytes in the medium by electrochemical sensors or optical sensors and actuators integrated in the analytical chip 1000; regulation of the assay temperature based on optimal reaction conditions; and fluids in the analytical chip 1000. By way of example, but not exclusively, these processes include applications to the determination of biochemical, immunological and even genetic parameters, as well as applications to the measurement of different essential metabolites in the culture medium by electrochemical detection, maintaining the cell culture at optimal temperature and concentration conditions.

[0089] The computer module 100 is the core of the system implementation and is the "brain" responsible for managing all the processes that are carried out simultaneously. It is responsible for the transmission and reception of signals that, together with the actuation modules, make the system run. The computer module 100 is implemented in a microcomputer as a central computer, and its lightweight operating system is configured so that everything happens in real time. It has the necessary components to be able to connect the system to the Internet, so that information can be sent to a secure server in an encrypted form. In addition, it is the signal processing center of the system, responsible for processing the signals obtained from the different sensors of the system to generate two types of information: process information (for example, the position of the drive, the real-time temperature of the system, etc.) and analysis information (for example, changes in luminescence in the sample, changes in the potential in the electrochemical sensor environment, etc.). The second type of data mentioned above is processed on the computer module 100 to generate analysis results, which are then displayed in the graphical interface of the system itself and can be sent to an external data network through the connection module 160 to communicate with other data analysis or management systems (for example, patient records, clinical laboratory management systems, etc.). The computer module 100 comprises a set of circuit boards, components and processors, whose programming allows the control of the system in an integrated manner, including the control blocks of each functional module, as well as the processing of the data obtained during its operation. In this way, there are electronic modules dedicated to the control of the thermal module 120, the drive system 110, the artificial vision module 130 and the integration of the signals from the electronic interface 140 of the analysis chip 1000. On the other hand, all these modules are connected to the computer module 100 in order to collect data from each functional block and coordinate the control of each block when executing the different programmed processes, as well as converting the data obtained into analysis results according to the specific detection algorithm of each process and communicating them to the user through a pre-set graphical interface or a communication protocol specified by the user with the central system.

[0090] The connection module 160 is a communication module integrated in the actuator device that allows the data to be sent from the device itself to different data storage and management systems. This connection module 160 allows the results obtained by this technology to be synchronized with external databases through different connection protocols, by encrypting these results into the necessary format so as to correctly adapt to the target, including centralized medical history, network equipment or other external storage systems. Therefore, this connection module 160 is connected to the computer module 100 itself to receive the analysis results and communicate them to external systems such as data clouds, medical data storage systems of patients, etc., through wireless or wired connections.

[0091] Through the connection module 160, the computer module 100 communicates with a data processing module 170, which in turn consists of two parts: the data management contained in the computer module 100 itself, for publishing the results of the analysis, and large-scale studies carried out on external servers, thus allowing the inclusion in the system of studies based on methods using large-scale data ("big data"). It thus allows prospective studies based on the analysis of data obtained from large-scale systems to discern behavioral patterns of different tests that may affect the operation of new equipment or consumables, or to establish correlations between different parameters to be analyzed. Therefore, this data processing module 170 is not included in the system as a physical module, but is composed of multiple elements contained in the computer module 100 and uses the connection module 160 itself to transmit data to external servers.

[0092] Finally, the power management module 150 is an independent module that allows the management of a set of batteries integrated in the actuator device itself, which provide autonomy to the system after disconnection from the grid and allow the portability of the system, since they are rechargeable batteries that power the different functional modules of the system. This power management module 150 is connected to all the actuator modules to provide them with power and only sends data to the computer module 100 in order to display the battery status in the graphical interface. In order to power all the modules of the actuator device, power conversion must be carried out to adapt to the different needs, so the power management module 150 uses robust power electronics that do not emit electrical noise or overheat the device. For this purpose, a hardware design adapted to the device and a heat dissipation of the power supply to cool the device are implemented. In addition, a battery management system or BMS is integrated to be able to charge the battery pack integrated in the device, making it portable.

[0093] All components of each functional module integrated as a single functional platform are contained in an external container 180, such as Figure 6 The external container according to a possible embodiment is shown, which allows to install different functional blocks and to support different modules as a single device or apparatus, occupying as little volume as possible. The modules are distributed according to the area on which they must act on the analysis chip. The external container 180 is composed of different moving elements, which are controlled by the computer module 100, for example Figure 7 The input compartment 181 is shown in the figure, which is used to input or load the analysis chip 1000 in the actuator device. The input compartment 181 is extracted to introduce the analysis chip 1000 therein. In addition, the outer housing or container 180 has an area where a tablet or a terminal with a screen can be placed, which acts as a graphical user interface, and this area also supports wireless charging.

[0094] Figure 8An external view of the entire system, including the user interface, is shown, wherein, according to a possible embodiment of the invention, it shows i) an external container 180, in which are located the different electronic control boards and the necessary computer modules for generating results within the platform and allowing the different actuation modules of the system to be controlled, and ii) a user interface, which acts as an actuation interface for the selection of modes within the actuator device, implemented on a screen 190, for example a touch screen. The control screen presents the software contained in the computer module 100 in a graphical user interface for the user to configure the control of the system. In addition, data for the user's own use can be generated from this user interface and transmitted to the computer module 100 for processing (e.g. selection of analysis mode, wireless network configuration, etc.).

[0095] Next, the interactions between the different modules of the system are described in detail based on possible use cases, which define the clinical analysis methods that can be implemented in the aforementioned proposed system.

[0096] System for quantification of creatinine in biological samples using the Jaffe method:

[0097] The system is intended to measure the colorimetric change depending on the creatinine concentration when a biological sample is exposed to an alkaline picric acid solution. The system consists of the previously proposed actuator device and an analytical chip (analytical chip 1000) containing the reagents required for the measurement (in this case, a mixture of equal volumes of 25mM picric acid and 0.4M sodium hydroxide). The actuator device includes functional modules responsible for coordinating each active process in the analytical chip to read the results of the creatinine analysis in the biological sample using the Jaffe method.

[0098] Thus, the analysis process proceeds as follows:

[0099] The sample to be analyzed (plasma in this case) is introduced into the sample input hole of the analysis chip, filling the hole until the volume signal is reached. The hole is closed using a closing element, preparing it for introduction into the actuator device. The device is turned on and the input compartment 181 of the analysis chip is removed for loading. The analysis chip is inserted according to the positioning indications of the compartment 181 itself and the closing button of the compartment is activated. Once the chip input is completed, the analysis mode is selected on the user interface to select the mode of the actuator device, which can be: i) automatic pre-programmed mode, in which the electronic interface recognizes the type of analysis chip and loads the operating sequence of the specific test to be performed, or ii) manual mode, in which the user can modify the analysis parameters required for the processing of the analysis chip recognized by the system. In the case of automatic mode, once selected, the actuator device will start to initiate the analysis sequence.

[0100] First, the thermal control module 120 is activated, and the functional metal heater integrated in the analysis chip 1000 is activated through the electronic interface 140 to stabilize the temperature of the analysis chip at 37°C. Once this temperature is reached, the mechanical drive module 110 is activated, and the working reagent and sample are introduced into the microfluidic circuit of the analysis chip through the action of the motor associated with the drive piston. In this microfluidic circuit, the two fluids are mixed and the mixture is filled into the reaction chamber aligned with the elements of the artificial vision module 130. The artificial vision module 130 monitors the fluid front on the microfluidic path in the analysis chip to ensure the correct filling of the reaction chamber. 30 seconds after the drive process is started, the artificial vision module 130 activates the light source and selects the wavelength required to measure the absorbance change of the sample with the chemical reaction. In this way, an emission wavelength of 500nm is selected, and the modulated light beam passes through the sample and is detected by the image sensor. The image sensor sends the collected data to the computer module 100, which extracts the color data and processes it using a predetermined algorithm to extract real-time absorbance data from the sample within a total period of 60 seconds after the light source is activated. This data is processed by the computer module 100 and displayed in a graphical user interface of the actuator device.

[0101] System for determining the genetic sequence of SARS-CoV-2 in biological samples by polymerase chain reaction (qPCR):

[0102] The actuator device is also designed to detect gene sequences associated with the SARS-CoV-2 virus through a process of real-time amplification of genetic material by polymerase chain reaction (qPCR) associated with a fluorescent probe ("reporter"). In this case, the proposed analytical system includes an analytical chip 1000, which contains a master mix including deoxynucleotides, magnesium chloride, polymerase, and primers specific to the sequence to be detected - the Spike gene of SARS-CoV-2, which is based on the sequence recommended by the CDC, with a fluorescent reporter FAM (6-carboxyfluorescein) and a ribonuclease P gene as an internal reaction control, using a fluorescent reporter ROX (carboxyrhodamine) -, as well as a cell lysis buffer composed of 6M guanidine hydrochloride and a washing buffer composed of a 50% anhydrous ethanol solution.

[0103] Thus, the analysis process proceeds as follows:

[0104] The sample to be analyzed (in this case, nasopharyngeal aspirate) is introduced into the sample input hole of the analysis chip 1000, filling the hole until the volume signal is reached. The hole is closed using a closing element, preparing the actuator device for introduction into the analysis system. The device is turned on and the input cabin 181 of the analysis chip is removed for loading. The analysis chip is inserted according to the positioning indications of the cabin itself and the closing button of the cabin is activated. Once the chip input is completed, the analysis mode is selected on the user interface, which can be an automatic pre-programmed mode, in which the electronic interface recognizes the type of analysis chip and loads the operation sequence of the specific test to be performed, or a manual mode, in which the user can modify the analysis parameters required for the processing of the analysis chip recognized by the system. In the case of automatic mode, once selected, the actuator device will start to initiate the analysis sequence.

[0105] First, the thermal control module 120 is activated, and the functional metal heater in the analysis chip 1000 is activated through the electronic interface 140 to stabilize the temperature of the analysis chip at 25°C. Once this temperature is reached, the mechanical drive module 110 is activated, and the lysis buffer and sample are introduced through the action of the motor associated with the drive piston, and the two are mixed along the microfluidic path. The mixture undergoes a 10-minute incubation period, after which the drive module 110 is activated again, this time to pass the mixture through the silica gel column, and nucleic acid extraction will be performed in the silica gel column. Once the nucleic acid binds to the silica gel column by affinity, the drive module 110 is activated again, and the silica gel column is washed by introducing a wash buffer, and then the silica gel column is dried by blowing pre-pressurized air into the input hole of the analysis chip. Once this nucleic acid extraction process is completed, the drive module 110 is activated again to drive the "master mixture" through the above-mentioned silica gel column to contact the gene amplification reagent. Once the "master mix" comes into contact with the silica gel column area, the thermal control module 120 is activated, thereby activating the metal heater contained in the analysis chip and several thermoelectric actuator modules of the actuator device in contact with the analysis chip to adjust the temperature of the analysis chip 1000 until a target temperature of 50°C is reached, and the temperature is kept stable for 15 minutes to perform reverse transcription of the sequence. After that, the thermal module 120 changes the target temperature to 95°C to perform a first denaturation step lasting 2 minutes, after which the thermal cycling process begins, which relies on the different actuators that constitute the thermal module 120: on the one hand, the heater integrated in the analysis chip 1000 is responsible for quickly raising the temperature in the analysis chip, on the other hand, the thermoelectric actuators of the actuator device allow the temperature of the device to be raised and the device to be cooled, thereby increasing the slope of the temperature ramp throughout the process; finally, these thermoelectric actuators are coupled to the heat sink 121, which consists of a physical heat sink and a fan, and can efficiently cool the system. Thus, during this thermal cycle, the heating function is activated during the temperature increase period, while the thermoelectric module for cooling is activated during the temperature decrease ramp period. This thermal cycle process consists of 45 cycles, in which the sample is at 95°C for 3 seconds and at 55°C for 30 seconds. In turn, after each thermal cycle, the artificial vision module 130 is activated corresponding to the excitation of the FAM fluorophore, which activates the 494nm light emitter, and at the same time the motor associated with the optical filter holder is activated to select the excitation and emission filters associated with the fluorophore. Thus, the emitter generates a light pulse, whose light beam passes through the excitation filter, the sample and the emission filter to reach the image sensor, which captures the fluorescence signal emitted by the sample and processes it accordingly through the computer module 100. Next, corresponding to the excitation of the ROX fluorophore, the second light emitter of 587nm is activated, and the excitation and emission filters associated with the fluorophore are selected, and the light pulse is emitted and the fluorescence signal generated by the sample when excited is measured.These measurements are performed once at the end of the thermal cycle, always at a step of 55°C, and the data obtained by the image sensor are stored and processed by the computer module 100 to generate the results. The data are processed by the computer module 100 and displayed in the graphical user interface of the actuator device.

[0106] Systems for combined determination of biochemical and genetic parameters:

[0107] The device is also designed to detect gene sequences associated with the SARS-CoV-2 virus and quantify serum creatinine levels by a process of amplifying genetic material through a real-time fluorescent "reporter"-associated polymerase chain reaction (qPCR). The analytical system includes an analytical chip 1000, which contains the reagents required for the assay, in this case, a "master mix" including deoxynucleotides, magnesium chloride, polymerase, and "primers" or primers specific to the sequence to be tested: the Spike gene of SARS-CoV-2 according to the sequence recommended by the CDC, with a fluorescent reporter FAM and an RNase P gene as an internal reaction control, with a fluorescent reporter ROX-, 6M guanidine hydrochloride buffer, a 50% anhydrous ethanol solution wash buffer, and a creatinine solution made by mixing equal volumes of 25mM picric acid and 0.4M sodium hydroxide.

[0108] Thus, the analysis process proceeds as follows:

[0109] The samples to be analyzed (in this case nasopharyngeal aspirate and plasma) are introduced into the different sample input holes of the analysis chip until a predetermined volume signal is reached. The two sample input holes are closed with a closing element, preparing for the insertion of the analysis chip into the actuator device of the system. The device is turned on and the input compartment 181 of the analysis chip is removed for loading. The analysis chip is inserted according to the positioning indications of the compartment itself and the closing button of the compartment is activated. Once the chip input is completed, the analysis mode is selected on the user interface of the actuator device, which can be an automatic preprogrammed mode in which the electronic interface recognizes the type of analysis chip and loads the sequence of operations for the specific test to be performed, or it can be a manual mode in which the user can modify the analysis parameters required for the processing of the analysis chip recognized by the system. In the case of automatic mode, once selected, the actuator device will start to initiate the analysis sequence.

[0110] In this case, different thermal zones are distinguished in a single analysis chip 1000, so that two discrete parallel processes are performed. First, the thermal control module 120 is activated, which activates the functional metal heater in the analysis chip through the electronic interface 140 of the actuator device, stabilizing the temperature in the analysis chip at 25°C in the area used for nucleic acid extraction and subsequent genetic studies, and at 37°C in the area corresponding to the plasma sample analysis protocol. Once these two temperatures are reached, the mechanical drive module 110 is activated, and the lysis buffer and the nasopharyngeal aspiration sample are introduced through the action of the motor associated with the drive piston, both of which are mixed throughout the microfluidic path, while the drive is performed in the area for biochemical analysis of the sample with alkaline picric acid solution. The incubation period of the nasopharyngeal sample with the lysis buffer is 10 minutes, during which the creatinine determination can be performed. To this end, once the sample and the working reagent are mixed, they are filled into the reaction chamber aligned with the elements of the artificial vision module 130. This artificial vision module 130 monitors the fluid front on the microfluidic path in the analysis chip to ensure the correct filling of the reaction chamber. 30 seconds after the start of the drive process, the artificial vision module 130 activates the light source and selects the wavelength required to measure the absorbance change of the sample as the chemical reaction occurs. In this way, an emission wavelength of 500nm is selected, and the modulated light beam passes through the sample and is detected by the image sensor. The image sensor sends the collected data to the computer module 100, which extracts the color data and processes it using a predetermined algorithm to extract real-time absorbance data from the sample within a total period of 60 seconds after the light source is activated. The data is processed by the computer module 100 and displayed in the graphical interface of the actuator device as the result of the creatinine determination. Once the 10 minutes required for lysing the nasopharyngeal sample have passed, the drive module 110 is activated again, this time to drive the mixture through the silica gel column, in which nucleic acid extraction is performed. Once the nucleic acid binds to the silica gel column by affinity, the drive system is activated again to wash the silica gel column by introducing a wash buffer into the silica gel column, and then the silica gel column is dried by blowing pre-pressurized air into the input hole of the analysis chip. Once the nucleic acid extraction process is completed, the activation drive module 110 is activated again to drive the "master mixture" through the above-mentioned silica gel column to contact the gene amplification reagent. Once the "master mixture" contacts the silica gel column area, the thermal control module 120 is activated again, thereby activating the metal heater contained in the analysis chip and several thermoelectric actuator modules in contact with the analysis chip, adjusting their temperature until the target temperature of 50°C is reached, and keeping the temperature stable for 15 minutes to perform reverse transcription of the sequence.Afterwards, the thermal module 120 changes the target temperature to 95°C for a first denaturation step lasting 2 minutes, after which a thermal cycling process begins, which relies on the different actuators that make up the thermal module 120: on the one hand, the heater integrated in the analytical chip 1000 is responsible for quickly raising the temperature in the above-mentioned device or analytical chip, on the other hand, the thermoelectric actuators of the actuator device allow the temperature of the device to be raised and also allow the device to be cooled, thereby increasing the slope of the temperature ramp throughout the process; finally, these thermoelectric actuators are coupled to the heat sink 121, which consists of a physical heat sink and a fan, which allows efficient cooling of the system. Therefore, during this thermal cycling process, the heating function is activated during the temperature increase, while the thermoelectric module for cooling is activated during the temperature reduction ramp. This thermal cycling process consists of 45 cycles, in which the sample is at 95°C for 3 seconds and at 55°C for 30 seconds. In turn, at the end of each thermal cycle, the artificial vision module 130 is activated corresponding to the excitation of the FAM fluorophore, which activates the 494 nm light emitter, and at the same time the motor associated with the optical filter holder is activated to select the excitation and emission filters. Thus, this emitter generates a light pulse, whose beam passes through the excitation filter, the sample and the emission filter, and reaches the image sensor, which captures the fluorescence signal emitted by the sample and processes it accordingly through the computer module 100. Next, corresponding to the excitation of the ROX fluorophore, the second light emitter of 587 nm is activated, and the excitation and emission filters associated with this fluorophore are selected, emitting a light pulse and measuring the fluorescence signal generated by the sample upon excitation. These measurements are performed once at the end of the thermal cycle, always in steps of 55°C, and the data obtained by the image sensor are stored and processed by the computer module 100 to generate results. The data are processed by the computer module 100 and displayed in the graphical user interface of the actuator device.

Claims

1. An actuator device, comprising a plurality of actuator modules for analyzing a chip, characterized in that: The actuator device comprises: a portable external container (180) for accommodating and supporting the plurality of actuation modules, and comprising an input compartment (181) for inserting the analysis chip (1000) into the interior of the actuator device by engaging the analysis chip (1000) with the plurality of actuation modules; a computer module (100) housed in the external container (180), comprising a plurality of electronic control blocks, each of which is connected to one of the plurality of actuation modules, the plurality of electronic control blocks being configured to receive signals obtained from sensors integrated in the plurality of actuation modules and to send signals to activate actuators integrated in the plurality of actuation modules, the computer module (100) being configured to generate process information and analysis information based on the signals received from the plurality of electronic control blocks and based on the signals obtained from the sensors integrated in the analysis chip (1000), and to provide analysis results obtained by the computer module (100) performing analysis information processing; an electronic interface (140) contained in the external container (180) and connecting the computer module (100) with the analysis chip (1000), through which the computer module (100) receives the signal obtained by the sensor integrated in the analysis chip (1000) and sends a signal to activate an actuator integrated in the analysis chip (1000); and a power management module (150) comprising a battery pack contained in the external container (180) and configured to supply power to the plurality of actuator modules, The plurality of actuation modules include at least one driving module (110), a thermal module (120) and an artificial vision module (130).

2. Actuator device according to any one of the preceding claims, characterized in that The computer module (100) is configured to provide the analysis result to a user interface to display the analysis result.

3. The actuator device according to claim 2, characterized in that The computer module (100) is also configured to receive battery status data from the power management module (150) and provide the battery status data to the user interface to display the battery status data.

4. Actuator device according to any one of the preceding claims, characterized in that Also includes: A connection module (160) connected to the computer module (100) is configured to receive the analysis result transmitted by the computer module (100) and send the analysis result to at least one external data storage and management system in a format suitable for at least one external data storage and management system.

5. The actuator device according to claim 4, characterized in that The computer module (100) is also configured to analyze the diagnostic pattern based on a comparison of the analysis result with large-scale data obtained from at least one external data storage and management system through the connection module (160).

6. Actuator device according to any one of the preceding claims, characterized in that The at least one drive module (110) includes a set of mechanical actuators configured to cooperate with a set of sensors integrated in the analysis chip (1000) to regulate mechanical actuation, wherein the mechanical actuation is selected from advancing, retracting, stopping and mixing one or more fluids in the analysis chip (1000) introduced into the external container (180).

7. The actuator device according to claim 6, characterized in that The set of mechanical actuators includes a motion axis matrix, a position regulator motor, a forward motor and a motion piston (131).

8. An actuator device according to any one of claims 6 to 7, characterized in that The computer module (100) is also configured to send an activation signal to the group of mechanical actuators to control the mechanical actuation, and receive a monitoring signal from the sensor integrated in the analysis chip (1000) to adjust the activation signal.

9. The actuator device according to claim 8, characterized in that The computer module (100) is configured to receive tracking signals from the drive module (110) directly from one or more position sensors or through the electronic interface (140).

10. Actuator device according to any one of the preceding claims, characterized in that The thermal module (120) includes a heat sink (121), a thermoelectric element (122) and a temperature sensor, wherein the temperature sensor is configured to cooperate with a thermal sensor and an actuator integrated in the analysis chip (1000) controlled by the computer module (100) through the electronic interface (140), and a thermal actuation area is defined inside the analysis chip (1000) inserted into the external container (180), and the temperature of the thermal actuation area can be adjusted by the computer module (100) in a closed control loop.

11. Actuator device according to any one of the preceding claims, characterized in that The artificial vision module (130) includes a first group of image sensors and photoactuators outside the analysis chip (1000), and the first group of image sensors and photoactuators are configured to cooperate with a second group of image sensors and photoactuators integrated in the analysis chip (1000). The computer module (100) uses a detection algorithm for detecting wavelengths to visualize real-time images of one or more fluids in the analysis chip (1000) inserted into the external container (180). The computer module (100) is configured to convert the displayed image into an analysis result according to the detection algorithm.

12. The actuator device according to claim 11, characterized in that The computer module (100) is configured to detect a colorimetric signal, a fluorescent signal, a turbidity signal, or a chemiluminescent signal using signals received from the first set of image sensors and photoactuators and signals received from the second set of image sensors and photoactuators through the electronic interface (140).

13. A system for clinical analysis, comprising an actuator device according to any one of the preceding claims and an analysis chip (1000) to be connected to the actuator device, characterized in that: The analysis chip (1000) is adapted to the input compartment (181) of the external container (180) so that the interior of the analysis chip (1000) is connected to the computer module (100) of the actuator device via the electronic interface (140).

14. The system according to claim 13, characterized in that A user interface is also included to display the analysis results provided by the computer module (100).

15. The system according to claim 14, characterized in that The user interface is a graphic interface of a mobile user terminal.

16. The system according to any one of claims 13 to 15, characterized in that The analysis chip (1000) is made of an optically transparent and biocompatible polymer substrate, which includes a plurality of layers provided with the sensors and actuators integrated in the analysis chip (1000), and a conductive metal layer attached to the surface of the analysis chip (1000).

17. The system according to claim 16, characterized in that The conductive metal layer of the analysis chip (1000) is configured such that: The sensor integrated in the analysis chip (1000) sends a signal directly from a reaction chamber through the conductive metal layer, and the reaction chamber is defined in the analysis chip (1000) as a region where a chemical process is performed for clinical analysis; as well as The actuator integrated in the analysis chip (1000) directly acts on the reaction chamber.

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