Microdroplet actuating system

Abstract

The present invention relates to a microdroplet actuating system (1) adapted to perform automatised analytical sequences comprising a working surface (S) wherein droplets (D1, D2, Dn) can be driven along a path (P1, P2, Pn) until a testing area (T1, T2, Tn) by means of a command unit (6), some detection means (2, 3), a detection unit (4) and a computing unit (5) adapted to automatically activate the paths and / or the detection means (2, 3) based on the sensed parameters during an analytical sequence. The present invention further comprises a method of performing such an analytical sequence.

Description

Microdroplet Actuating SystemTechnical domain

[0001] The present invention concerns a microdroplet actuating system such as a digital microfluidic system or device, also designated as DMF. It more particularly concerns an automatised microdroplet actuating system or device allowing to perform and adjust tests in situ, based on different collected data. The present invention further concerns a method of performing tests, in particular an automatised method including an automated decision step based on some data collected from a sample under test. The present invention further concerns a digital platform adapted for performing biological tests, diagnostics, environmental monitoring, and / or synthetic biology.Related art

[0002] Increased efforts have been made in the last decade to develop microfluidic systems for research and diagnostic purposes. The most recent solutions provide digital microfluidic devices, based on the electro wetting technology, such as those disclosed in W02007120241. This allows to handle very small samples, of the size of droplets, for different biological and chemical tests. Although the devices show improved performances, they may still lack flexibility. The sequence of tests is usually predefined before triggering the analyses, and is modified only after the result of the full analysis have been collected and analyzed.

[0003] In the field of electrowetting technologies, electrowetting gates have been described in Electro-actuated valves and self-vented channels enable programmable flow control and monitoring in capillary-driven microfluidics" Arango et al., Sci. Adv. 2020; 6 : eaay8305.PFLEX-2-PCT

[0004] In the microfluidic field, fiber pumps are described in "Fiber pumps for wearable fluidic systems", Smith 2023, Science 30 Mar 2023, Vol 379, Issue 6639, pp. 1327-1332.

[0005] In the field of research, for example, iterative steps are often performed based on the results previously obtained, which necessitates finalizing a complete analytical cycle before setting next analytical steps. Similarly, in chemical synthesis, iterative processes are often carried out based on the reaction products or intermediates, requiring the completion of the synthesis before planning further synthetic strategies. In the pharmaceutical research, high throughput processes for testing sample or even for reacting compounds are often required, which would beneficiate from an improved flexibility. In the field of industry, such as pharmaceutical or food industry, routine quality tests are often required for example to identify potential contaminations or cross contaminations, which necessitate reliable and flexible methods. Also, for diagnostic tasks, reliable and very diverse tests are often required in a fast and cost-effective manner. In environmental monitoring for example, tracking water pollution demands rapid, adaptive testing methods to respond in real-time to fluctuating contamination levels effectively. Similarly, in the management of agricultural resources, technologies that provide real-time data can significantly enhance the efficiency of irrigation systems and ensure the sustainable use of water in farming. These industries demand robust, versatile tests that can be conducted quickly and cost-effectively, paralleling needs in environmental sciences for swift and accurate diagnostics to monitor ecosystem health and prevent large-scale environmental impacts.

[0006] Particularly in the field of personalized medicine, individualized analyses protocols are needed. In such cases, the protocol definitions and evolutions based on statistics on large numbers of cases are insufficient and / or too long, so a fast protocol evolution method and devices capable of implementing such fast protocol evolution methods are needed. In some instances, synthesis of specific drugs may be initiated based on the results of the individualized protocols.PFLEX-2-PCT

[0007] There is thus room for improvement in terms of flexibility, higher throughput, productivity, and costs of testing activities, being for research, industrial applications (chemical, pharmaceutical, food, soil), environmental testing, diagnostic, personalized medicine, routine surveys or any related analysis tasks.Short disclosure of the invention

[0008] An aim of the present invention is the provision of a device and / or a system that overcomes the shortcomings and limitations of the state of the art. It is in particular an aim of the present invention to provide a device and / or system allowing more flexible or more high-throughput or more cost or time effective analytical tasks, enabling more efficient and / or personalized treatments or adapted formulations, as well as customized action strategies.

[0009] Another aim of the present invention is to provide a device or system adapted to initiate more diverse combinations and / or reaction of compounds, environmental or biological samples with an increased flexibility and / or cost or time efficiency.

[0010] Another aim of the invention is to provide an analytical method allowing more flexible and time or cost-effective analysis of samples such as chemical or biological samples.

[0011] Another aim of the present invention is to provide a method and / or a device adapted to provide more streamlined processes and / or improve the process efficiency, and / or reduce the logistic constraints and related costs. For example, improve in patient and outpatient testing.

[0012] Another aim of the present invention is to provide an improved method of mixing and / or reacting a large diversity of compounds or biological samples with more flexibility and time or cost efficiency. It is inPFLEX-2-PCTparticular an aim of the present method to evaluate and / or identify combination, synergism, antagonism effects based on a larger number of substances and / or more diverse substances.

[0013] According to the invention, one or all of these aims are attained by the object of the independent claims, and further described in the dependent claims.

[0014] With respect to what is known in the art, the present invention provides the advantage of faster and versatile handling, such as analysis or reactions, of chemical or biological samples in the fields of research, such as pharmacological or medical research, diagnostic such as medical diagnostics, environment survey, food industry survey. The present invention allows more streamlined lab or production processes. It further allows miniaturization and parallelization of the processes. For example, it allows more diverse testing at points of care. The diagnostic protocols according to the present invention are more accurate and personalized, so that a personal treatment can be provided. In particular, specific drug combinations including antimicrobial, anti-inflammatory, anti-fungal drugs can be identified as being specifically adapted to a given patient. Synergies and antagonisms can be detected based on specific characteristic of a given patient. In the field of precision agriculture and soil science, a need exists for specific treatments, as standard, broad-spectrum agrochemicals can be ineffective against localized or resistant pathogen strains. The present invention addresses this by enabling the rapid, site-specific, high-throughput screening of a pathogen against a vast combinatorial library of many thousands of compounds, such as novel fungicides, pesticides, or bio-stimulants. The objective is to identify powerful synergistic effects in order to identify a uniquely effective treatment for a particular field or crop. Based on the results of these individualized protocols, the formulation of targeted agrochemical mixtures may then be initiated. Beyond these targeted applications, the platform's high-throughput capabilities are also valuable for general agriculture and soil science, enabling the development of new, more effective broadspectrum products.PFLEX-2-PCTShort description of the drawings

[0015] Exemplar embodiments of the invention are disclosed in the description and illustrated by the following drawings:• Figure 1 : schematic representation of a device according to an embodiment of the present invention,• Figure 2: schematic representation of a device according to an embodiment of the present invention,• Figure 3: schematic transversal representation of a device according to an embodiment of the present invention,• Figures 3a, 3b : details of the transversal representation of a device according to different embodiments of the present invention,• Figure 4: schematic transversal representation of a device according to another embodiment of the present invention,• Figures 5a, 5b, 5c: schematic transversal representation of device according embodiments of the present invention, with details of first and second detection means,• Figure 6: schematic representation of device according embodiments of the present invention.Examples of embodiments of the present invention

[0016] With reference to figure 1, the microdroplet actuating system 1 according to the present disclosure allows to move at least one droplet D1,PFLEX-2-PCTD2...Dn of a liquid L1, L2...Ln on a surface S along a path P1, P2...Pn. To this end, it comprises several guiding elements E1, E2...En, which can be independently activated and deactivated so that a path can be determined. Depending on the activated guiding elements, different paths can be set.

[0017] The microdroplet actuating device according to the present invention denotes any microfluidic device adapted to move some liquid droplets. Microfluidic devices provided with microchannels and automatised valves may be used to this end so that a liquid can follow a path depending on the activated valves.

[0018] Preferably, the microdroplet actuating device 1 according to the present invention denotes a digital microfluidic device wherein each guiding elements E1, E2...En defines an electrode or a set of electrodes. Depending on the activated or deactivated states of an electrode, the wetting properties of a liquid on the corresponding surface can be adjusted or modified. Subsequent activation and deactivation of adjacent electrodes allows to induce a movement of a liquid droplet D1, D2...Dn. The sequence of activation and deactivation of the electrodes thus defines a path along which a droplet or several droplets D1, D2...Dn can move. The surface corresponding to each electrode can be coated by a dielectric material. It can further be coated by any other suitable materials according to the needs. Such coatings include anti-electrowetting-on-dielectric coating. A counterelectrode can be provided vis-a-vis each electrode. According to some configurations, several counter-electrodes can be provided vis-a-vis each or some of the electrodes. Figure 2 provides an example wherein the microdroplet actuating system 1 comprises a top surface 11 and a bottom surface 12, defining an internal space, wherein the bottom surface 12 comprises the electrodes and the top surface comprises the at-least one counter-electrode. A counter-electrode according to the present disclosure typically comprises a conductive layer. Such a conductive layer can be continuous or patterned. The core portion of the counter-electrodes is typically made of glass or plastic material or any equivalent material. One or more of the counter-electrodes can have a customized 3D shape. Such a 3D shape can for example define a variable or irregular distance between topPFLEX-2-PCTand bottom plates of the device. According to such an arrangement the height or the size of the droplet under process can be adjusted. Alternatively or in addition, the size of some orifices such as input or output orifices of the device can be adjusted to auxiliary probes or samples. The counter-electrode can also comprise input / output ports and connections.

[0019] It is highlighted that small amount of a liquid or several different liquids can be manipulated. Small amounts preferably mean volumes in a range from hundreds of picoliters to a few microliters. In particular, droplets or microdroplets of liquids can be individually manipulated through the present microdroplet actuating system 1. A microdroplet actuating device, is here understood as being adapted to control liquids under the form of microdroplets or droplets. The terms "microdroplet" and "droplets" are here considered equivalent.

[0020] The terms "activating" and "deactivating", as well as related terms, respectively denote the actions of electrically activating, respectively deactivating an electrode, more concretely applying a voltage between the corresponding electrode and a reference point, respectively stopping the voltage supply between the corresponding electrode and a reference point. The reference point may be another electrode, in particular a counterelectrode placed vis-a-vis the activated / deactivated electrode. Regarding the more general term of guiding element, activation of such guiding element allows to flow the liquid while deactivation lead to stop the liquid.

[0021] The surface on which the droplets D1, D2...Dn move can be defined as a working surface S.

[0022] The microdroplet actuating device 1 according to the present invention comprises a command unit 6 allowing to activate and deactivate independently each guiding element E1, E2...En, such as the above- mentioned electrodes. By this way, the command unit 6 allows to drive the droplets on the working surface S according to a path P1, P2...Pn defined by the activation sequence of the guiding elements E1, E2... En. The commandPFLEX-2-PCTunit 6 can be integrated within the working surface S or unmovably combined to it. Alternatively, the command unit 6 can be disconnected from the working surface S. Suitable electrical connections are provided in this case. The command unit 6 can be integrated to a remote device such as a computer or similar electronic device. Alternatively, the command unit 6 may be independent and connected to the working surface S or to a remote device by any suitable connection means such as by wire or wireless. As better described below, the command unit 6 may be controlled through a humanmachine interface such as keyboard, tactile screen or any equivalent means as well as combination thereof. One or more of such human-machine interfaces can be arranged remotely. Alternatively or In addition, commands and / or programs can be provided by an Al / expert system such as supervised, unsupervised, reinforcement, generative Al, etc. The Al can be on-chip or on a remote machine. For example, preselected sequences of activation and deactivation of guiding elements E1, E2...En can be input so that corresponding paths P1, P2...Pn are made available to drive the droplets. Depending on the needs, paths P1, P2...Pn can be activated concomitantly or sequentially. Each path can be independently manually activated. Alternatively, a given path can be automatically activated upon certain conditions. For example, a given path can be triggered after a given time or a given temporisation. Alternatively or in addition, a given path can be automatically triggered when predetermined parameters are sensed, such as a temperature threshold or a colour detection or any other relevant parameter.

[0023] According to an embodiment, the present device comprises a wireless communication unit adapted to transmit test results to a remote server or portable device. Such a remote server can be configured to receive data from the wireless communication unit and to execute cloud-based diagnostic algorithms.

[0024] According to an embodiment, the system comprises a remote server configured to receive data transmitted by the wireless communication unit. The remote server may execute cloud-based diagnostic algorithms, including pattern recognition, predictive analytics, or Al-driven decisionPFLEX-2-PCTtrees, based on the transmitted droplet data. This allows complex diagnostics, such as disease risk stratification, antimicrobial resistance prediction, or environmental hazard modelling, to be performed off-chip with immediate feedback to the command unit 6.

[0025] According to an embodiment, one or more of the paths P1, P2...Pn can be changed or modified either manually or automatically. According to a preferred embodiment one or more, or all of the paths P1, P2...Pn can be automatically triggered, adapted, modified, stopped during an analytical cycle.

[0026] A path P1 , P2...Pn according to the present invention denotes any movement of droplets, including division, combination, mixing, merging and displacement thereof. A given first path P1 may be set to displace a first droplet D1 from a first reservoir R1 of the corresponding first liquid L1 to a testing area T. Such a path may comprise one or more nodes wherein some operations such as detection of one or more parameters is done, like a temperature detection, a concentration detection, the droplet size detection, an optical or colour detection, or any relevant parameter. The detection includes detection of fluorescence and / or luminescence. Such a first path P1 may cross other paths so that other droplets such as a second droplet D2 can be contacted with the first droplet D1. Depending on the nature of the second droplet D2, this allows to merge two different products or to modify the concentration of a given product, or to modify the nature of the solvent in which a given product is solubilized, for example. A given path P can also comprise divisions so that a first droplet D1 can be divided and driven toward other areas of the working surface S. For example, a given first droplet D1 can be divided so that the resulting sub-droplets are driven toward several different testing areas T1, T2...Tn. A path according to the present invention can be set to move a droplet from a first testing area T1 to a second testing area T2, so as to make different successive operations. Alternatively, a path according to the present invention can be set to move a droplet from a testing area T1, T2...Tn toward another reservoir such as incubation reservoir or a waste reservoir.PFLEX-2-PCT

[0027] According to an embodiment, the working surface S comprises one or several areas dedicated to the preparation of the droplets D1, D2, Dn, before their analysis or further transformation. Such areas can be designated as pre-testing areas. Such pre-testing areas may be correlated to some auxiliary transformation devices such as light irradiation devices or thermal regulators. Such pre-testing areas may in addition be correlated to one or more of a first detection mean 2 and a second detection mean 3. Alternatively or in addition, the pretesting areas may allow combination of droplets so as to induce a chemical or a physico-chemical reaction in the droplet to be analysed. For example, reactant such as pH adjustment additive, buffer, colour additive, chemical probes may be added to the droplet before its analysis.

[0028] The liquids L1, L2...Ln here-described denote any kind of mixture, suspension and solution of a material in a liquid form. In this disclosure, a liquid of heterogeneous composition, a liquid of heterogeneous physical properties, a liquid containing solid elements or biological elements or a gel is considered as equivalent to a liquid for being moved in the present device. The liquids can denote reagent or mixture of reagents at any necessary concentration. Such reagents or mixture thereof can be small chemical molecules or biomacromolecules such as peptides, DNA or RNA based macromolecules, either at native state or chemically modified. Such reagents and mixture thereof can be combined with additives, salts, excipients and any other suitable product. Alternatively or in addition, the liquids L1, L2...Ln comprise test material which is not a reagent. Such a reagent can define a drug or a mixture of drugs. Such test material can be a pollutant such as a pesticide or any other agricultural treatment or compound, micro- or nanoparticles collected from air or any other gaseous, liquid or solid substrates, food sample or drink sample. Alternatively or in addition, the liquids L1, L2...Ln comprise biological cells such as animal or vegetal cells, bacteria, viruses, fungi, parasites, tissues, organoids, simple organisms (ex. nematodes), protozoans. Alternatively or in addition, the liquids L1, L2...Ln comprise reagents such as proteins, including antibodies, hormones, coloured indicators, fluorescent or luminescent dyes, radioactive labels, etc. and mixtures thereof. Other products may be contained in the liquidsPFLEX-2-PCTdepending on the needs. For example, magnetic beads or emissive or radioactive elements can be envisaged. It is understood that the present liquids L1, L2...Ln play the role of vector for any suitable product to be involved in a test. It can also play the role of solvent or dispersing media of such product. The liquids may be water or any related polar liquid, potentially combined with hydrophilic co-solvents or salts. It can be for example physiological serum or related liquid. It can furthermore comprise nutriments in particular for cell handling. According to an embodiment, one of the liquids denote a pure solvent, being either distilled water or physiological serum, so that it can be used for dilution of the products suspended or dissolved in the other liquids. Liquids can be human, animal, vegetal, environmental samples such as blood, sera, plasma, water, resuspended solid material, etc.

[0029] According to an embodiment, the microdroplet actuating device 1 provides a hybrid, fully automated screening pipeline by integrating the device with a Droplet-Based Microfluidics (DBM) platform. In this arrangement, the microdroplet actuating device 1 functions as a high- precision 'formulation engine', autonomously preparing a vast library of unique and complex chemical mixtures. By varying components, volumetric ratios, and concentrations through programmed serial dilutions, the microdroplet actuating device 1 platform can generate tens of thousands of distinct formulations, which are then dispensed into standard microtiter plates (MTPs). The use of disposable, single-use cartridges dedicated to each compound pair ensures these "challenge plates" are created with a guarantee against cross-contamination. The DBM platform, in turn, acts as an ultra-high-throughput 'discovery engine'. A robotic handler interfaces between the two platforms, aspirating the pre-formulated mixtures from the MTPs to serve as the starting chemical conditions for the DBM screening process. This integrated system thereby automates the testing of a massive number of chemical combinations against biological targets, such as pathogens, enabling powerful new workflows in life sciences and agrosciences.PFLEX-2-PCT

[0030] According to an embodiment, the microdroplet actuating device 1 provides a hybrid, fully autonomous, integrated platform designed for large- scale combinatorial screening coupled with long-term kinetic analysis, managing a complete 'sample-to-data' workflow. The platform's architecture is built around a decoupled robotic system comprising at least two specialized robotic systems: a 'Production' arm dedicated to sample preparation and an 'Analysis' arm dedicated to managing incubation and measurement cycles. To ensure absolute data integrity, the system employs disposable, single-use Digital Microfluidics cartridges, with each cartridge being programmatically dedicated to preparing mixtures from one single and unique pair of chemical compounds before being discarded, thereby eradicating the risk of cross-contamination. The Production arm prepares complex chemical formulations and serial dilutions on these cartridges and transfers the final mixtures to standard microtiter plates (MTPs). The 'Analysis' arm then manages these MTPs, shuttling them between an environmentally controlled incubator and a plate reader at programmed intervals over several days. This integration of contamination-free preparation with automated, long-term analysis enables the generation of rich, temporal datasets, such as complete growth or inhibition curves, providing a deep mechanistic understanding of biological responses.

[0031] According to an embodiment, the present microdroplet actuating system 1 is adapted for food safety analysis, for example rapid detection of pesticide residues, allergens, or bacterial contamination in beverages such as milk or fruit juices.

[0032] According to an embodiment, the device is integrated into industrial food production lines, where it automatically generates safety and quality reports in compliance with HACCP or GMP standards. This configuration allows full traceability of batches from raw materials to finished products, ensuring regulatory conformity and consumer protection.

[0033] According to another embodiment, the system is adapted for environmental monitoring of water quality, including the detection of heavyPFLEX-2-PCTmetals, nitrates, or organic pollutants. In yet another embodiment, the system can be fluidly connected to fermentation or bioprocess reactors, wherein droplets collected from the process stream are analysed for microbial activity, metabolite concentrations, or pH balance, thus enabling real-time process monitoring and control.

[0034] According to an embodiment, the present microdroplet actuating system 1 further comprises one or several containers C1-Cn wherein different liquids L1, L2...Ln can be stored. Such containers may be fed by means of accessories (e.g. sampling materials / gas / liquids from the environment, sampling products from industrial processes, ...). Similarly, products can be extracted from these containers via accessories. The microdroplet actuating system further comprises one or several reservoir electrodes, adapted to collect the liquid from the container or supply it to the container. The electrodes positioned near the input / output of containers C1-Cn are called reservoir electrodes or reservoirs or reservoir areas R1, R2...Rn. Each container can be connected to one or more than one reservoir electrodes. The reservoirs R1, R2...Rn are connected to containers or microcontainers from which the liquids L1, L2...Ln can be output to the working surface S. Microfluidic channels may be provided to this end where applicable. Preferably, reservoir electrodes are provided to output a dedicated amount of a liquid, such as a droplet D1, D2..Dn, to the working surface S. According to an arrangement of the present invention, reservoir electrodes can be reconfigured from output to input electrode and reversely from output to input electrodes. Reservoir electrodes are preferably used in case of a digital microfluidic device so that they can be piloted according to the same principle than the electrodes making the guiding elements E1, E2...En. However, the reservoirs R1, R2...Rn can be of different type than the guiding elements E1, E2...En, as long as the corresponding liquid can be supplied to the working surface S on demand. For instance, a liquid may be supplied to the guiding elements from a reservoir by means of microtubes or micropipes or any equivalent microfluidic means. According to an embodiment, the reservoirs R1, R2...Rn are part of the working surface S. They can be for example provided at the periphery of the guiding elements E1, E2...En or elsewhere in close proximity of the guiding elements E1, E2...En. By this wayPFLEX-2-PCTthe guiding elements E1, E2...En and the reservoirs R1, R2...Rn can form an integrated element. Alternatively, the reservoirs R1, R2...Rn or some of them are disconnected or removable from the guiding elements E1, E2...En so that the number or size of reservoirs R1, R2...Rn can be adjusted according to the needs. The number of reservoirs is not limited. It can be determined according to the nature and diversity of the products to be involved in the testing operation. Each container adjacent to reservoir R1, R2...Rn can comprise reactive compounds, or pollutants or analytical products such as antibodies. Each reservoir can be independently activated according to the needs. Activation of a reservoir is here understood as triggering supply or collection of the corresponding liquid or of a given amount of the corresponding liquid. The container adjacent to the reservoir can include standardised connector systems to enable connection to other equipment.

[0035] According to an embodiment, the device may comprise one or more inlet and / or outlet ports arranged on or adjacent to the working surface S. The ports may be positioned in a regular array whose pitch is compatible with standardized well-plate formats, for example 9 mm for 96- well, 4.5 mm for 384-well, and 2.25 mm for 1536-well plates, thereby enabling direct access by single- and multi-channel pipettes and robotic pipetting heads. Each port may comprise a geometry and / or adapter compatible with syringe interfaces and automated liquid handlers, including Luer-type connectors and / or self-sealing elastomeric septa to maintain containment and reduce evaporation or contamination during repeated access. Port diameters, funnel or conical lead-ins, and z-heights may be dimensioned to accommodate standard pipette tip outside diameters while preventing tip contact with functional areas of the working surface.

[0036] All input / output ports of the device can be hermetically sealed. This allows to protect the patient or the operator from hazardous materials. According to an embodiment, the microdroplet actuating device is packaged as a sealed disposable cartridge. Such a configuration maybe particularly advantageous in the field of food industry or other manufacturing industries, for quality tests, such as batch controls. According to an embodiment, the disposable cartridge can comprise an integrated wastePFLEX-2-PCTchamber for biohazard containment. Inlet / outlet ports intended for external pipetting may be covered by pierceable sterile films or septa, maintaining hermetic sealing before first use and between successive accesses.

[0037] According to an embodiment, the cartridge can comprise prestored reagents. Such an arrangement allows for multiplexed biomarker analysis. It can be configured for single-use disposal with biohazard containment.

[0038] According to an embodiment, the cartridge is adapted for at- home sample introduction, including blood, saliva, urine, sweat or menstrual fluid.

[0039] According to an embodiment, the cartridge is adapted for agroscience and environmental sample introduction, including soil extracts, water samples, plant tissue homogenates, or microbial suspensions.

[0040] According to an embodiment, the device is specifically designed for at-home use by unskilled operators. Pre-programmed analytical menus can be selected via a touchscreen or smartphone application, and the device automatically handles sample preparation, waste containment, and data transmission. The cartridge format ensures safe disposal of biohazardous materials, while wireless connectivity allows test results to be transmitted to healthcare professionals in real time.

[0041] According to an embodiment, the device is specifically designed for in-field use by agricultors. Pre-programmed analytical menus, for instance, to detect specific plant pathogens or analyze soil nutrient levels, can be selected via a ruggedized touchscreen or smartphone application, and the device automatically handles sample preparation, waste containment, and data transmission. The cartridge format ensures the safe handling and disposal of materials, such as infected plant tissue or soil samples, while wireless connectivity allows test results to be transmitted to agronomists or agricultural consultants in real-time for immediate decision-making.PFLEX-2-PCT

[0042] According to an embodiment, the smartphone application provides step-by-step guidance for sample introduction and displays results in a user-friendly, colour-coded interface, ensuring safe and correct operation by unskilled users.

[0043] The reservoirs R1, R2...Rn can be activated, either sequentially or concomitantly, according to a predetermined program. For example, some reservoirs can be activated so as to deliver the corresponding liquid after a given time or a given temporisation. The corresponding liquid thus follows the corresponding path until it reaches its destination. The destination can be for example a given testing area T1, T2...Tn or a mixing area so that it can be mixed with another liquid. The reservoirs R1, R2...Rn are preferably activated and deactivated by mean of the command unit 6.

[0044] According to an embodiment, one or several or all of the reservoirs R1, R2...Rn can be activated upon sensing some predetermined parameters during the analytical cycle, as detailed below. The reservoirs R1, R2...Rn denotes any area or device adapted to store some input material. This further denotes any area or device adapted to collect material from the working surface S, being waste material or sample collected for further analysis. For example a reservoir can be dedicated to collect living cells after having been handled on the working surface S and to multiply them on a media. Reservoirs can also be reconfigured as inputs or outputs on demand during the operation. Alternatively or in addition, some or all of the reservoirs can be connected to additional analytical devices such as mass spectrometer, chromatograph like HPLC, gas chromatograph. In such a way some additional automatised analysis can be performed for example on some compounds resulting from the test operations. Such additional analytical devices may be part of auxiliary equipment. Auxiliary equipment other than analytical devices can be considered. To this end, standardised interfaces can be integrated or combined to the present device. The connected auxiliary equipment can collect the samples for further analysis or for use as reactants in subsequent stages of the industrial process. Alternatively, auxiliary equipment can be adapted to administrate a sample to a patient. Alternatively, some or all of the auxiliary equipment is adapted to fill on orPFLEX-2-PCTseveral reservoir with samples. Some or all of the auxiliary equipment can be either manual or automatic. The above-mentioned auxiliary equipment may be connected to one or several reservoir areas. Alternatively or in addition, an auxiliary equipment may be connected to one or several container C1, C2, Cn. Alternatively or in addition, an auxiliary equipment may replace one or several container C1, C2, Cn. According to an embodiment, the present microdroplet actuating system 1 does not comprise the above-described container C1, C2, Cn but only auxiliary equipment.

[0045] According to a specific arrangement, the auxiliary equipment includes usual diagnostic devices adapted for example to perform Nucleic Acid Amplification Test (PCR, digital PCR, LAMP PCR,..), immunoassays, or any other related equipment. It can also include any equipment for upstream or downstream processes in pharmaceutical, chemical or environmental industries.

[0046] According to a specific arrangement, the auxiliary equipment comprises a fully integrated and autonomous robotic workcell designed for a complete "sample-to-data" workflow. This workcell is built around one or more robotic systems, such as 6-axis robotic liquid handlers, responsible for all physical and liquid handling manipulations, including pipetting reagents and transferring samples. The robotic systems orchestrate the workflow between several specialized modules integrated on a central deck, including active docking stations that provide electrical control to the disposable microfluidic cartridges, a robot-compatible incubator with controlled temperature, CO2, and humidity for long-term kinetic analysis, a multimode plate reader for performing optical measurements and ancillary modules such as automated plate sealers and orbital shakers for sample preservation and homogenization.

[0047] According to an embodiment, an auxiliary equipment comprises an olfactometry device or headspace sampler adapted to detect volatile aromatic compounds.PFLEX-2-PCT

[0048] According to an embodiment, auxiliary equipment include transformation devices adapted for targeted transformation or stabilization of the droplets, preparing them for specific downstream reactions or analytical steps. For example, they may liquefy viscous liquids, pre-treat particulates, or optimize reaction environments. These transformation devices can be located in a pre-analytical area: the system can analyze complex biological samples (e.g., menstrual blood, soil extracts) and select / adapt tests based on pre-analysis results. According to an embodiment, such transformation devices allow to initiate or accelerate chemical transformation inside droplets or on the surface but are not dedicated to creating or removing path barriers. According to another embodiment, such transformation devices can be used to initiate or accelerate chemical transformation either inside droplets or on the surface but or on dedicated liquids adapted to creating or removing path barriers.

[0049] According to an embodiment, one or several of the reservoirs comprise the samples to be tested, being animal or vegetal cell, a chemical compound or any other sample. For example blood sample, or blood cells or other cells may be provided in suspension in a suitable liquid such as a media or serum. A reservoir can be thermally regulated or not.

[0050] According to an embodiment, better shown in figure 3, containers C1, C2, Cn are arranged underneath the working surface S. For example, the containers C1, C2, Cn may be wholes of a microtiter plate M. As such the microdroplet actuating device 1, or at least the working surface can be arranged above or on a microtiter plate comprising several liquids L1, L2, Ln. A microtiter plate M can have a size which corresponds to the working surface S. Alternatively, several microplates being smaller than the working surface S can be placed underneath the working surface S. Alternatively, individual containers can be arranged at dedicated areas under the working surface S. Such an arrangement allows for a more compact setting. Also, the microdroplet actuating system allows a very flexible and convenient handling, wherein different microtiter plates can be successively placed under the device for fast analysis or chemical synthesis of a large amount of samples.PFLEX-2-PCT

[0051] According to such an arrangement, the liquid(s) L1, L2, Ln are collected from the containers C1, C2, Cn by the mean of capillaries 100. Capillaries 100 designates essentially hollow fibres adapted to be immersed in the containers C1, C2, Cn underneath the working surface S so as to allow the corresponding liquids L1, L2, Ln progressing up to the working surface S. The driving force of the liquid(s) can be mainly the capillary force. The liquid L1, L2, Ln can continuously move from the containers C1, C2, Cn up to the working surface S and provide droplets D1, which can then be manipulated by mean of the guiding elements E1, E2, En above-described. Alternatively or in addition, the capillaries 100 can be provided with additional driving elements such as electrodes 101 (figure 3a). These electrodes may act as the above-described guiding elements for the working surface S and allow to feed the liquid to the working surface by being successively activated and deactivated. Alternatively, coatings like hydrophilic or hyper-hydrophilic coatings 103 (figure 3b) can be provided onto the internal surface of the capillaries 100. According to an embodiment, the capillaries 100 can denote a fibre pump, comprising continuous helical electrodes 102 embedded in the walls of the capillaries (Figure 3).

[0052] The capillaries 100 can replace the reservoirs R1, R2, Rn abovedescribed. Alternatively, the capillaries 100 can be provided in addition to the reservoirs R1, R2, Rn. In this case, the liquid(s) L1, L2, Ln is or are driven from the container(s) to the reservoir and can be further actuated on the working surface S through the reservoir(S) as above-described.

[0053] According to an embodiment, the present microdroplet actuating system 1 comprises containers C1, C2, Cn underneath the working surface S and containers arranged beside the working surface S, as better shown in Figure 2.

[0054] According to an embodiment, several working surfaces S, such as two or more than two working surfaces, are superimposed. In such a configuration, capillaries can be arranged between two superimposed working surfaces S so as to drive the liquid(s) L1, L2, Ln from one workingPFLEX-2-PCTsurface to another working surface arrange above or below. According to such an arrangement, containers C1, C2, Cn can be arranged between two superimposed working surfaces S so that the corresponding liquid(s) L1, L2, Ln can be driven to both superimposed working surfaces.

[0055] According to an embodiment, diameter and / or length of the capillaries 100 are adapted to the type of liquid(s) L1, L2, Ln to be handled, in particular to their viscosity. In case several capillaries are provided, they may have all the same dimensions, including diameter and / or length, or have different lengths and / or diameters so as to simultaneously handle liquid(s) having different physicochemical properties. Also, according to the needs, several type of capillaries 100, being either coated with an hyper hydrophobic coating, being provided with electrodes or being fibre pumps, may be provided with a single working surface S.

[0056] When present, the capillaries 100 are crossing at least one of the top 11 and bottom 12 surfaces of a given working surface S.

[0057] According to an embodiment better shown in figure 4, the bottom surface 12 of the microdroplet actuating system 1 is curved so as to directly immerse in a liquid L1, L2, Ln of a container C1, C2, Cn. The guiding elements E1, E2, En can thus be activated so as to drive the liquid(s) L1, L2, Ln from the corresponding containers C1, C2, Cn to the working surface S. The bottom surface 12 can be a rigid surface. For the purpose of the later described embodiment, the bottom surface 12 can be flexible so as to be bended and immersed in a container.

[0058] Due to superimposed arrangement above-described, the working surface S of the present microdroplet actuating device can also be defined as a working volume.

[0059] The present microdroplet actuating system 1 further comprises at least one testing area T1, T2...Tn. Such a testing area is preferably dedicated to operate the testing operations on one or several samples. A testing areaPFLEX-2-PCTcan be materialized by one or several electrodes on the working surface S. Alternatively, it can denote a space where a sample can be analysed and / or reacted under controlled conditions. A testing area may be coated or provided with some specific material such as a cell media, a modified surface comprising for example chemical reagents or analytical products such as antibodies and / or fluorescent materials.

[0060] The present microdroplet actuating system 1 further comprises at least one first detection mean 2. Preferably, such first detection means are embedded or integrated on the working surface S. The first detection means, when embedded in the present device, is preferably arranged above the dielectric layer. They are adapted to determine at least one physico-chemical parameter such as the liquid impedance, the size, the conductivity, the optical transmittance, the pH, the temperature or the colour of a droplet D1, D2...Dn. A first detection mean 2 is preferably localised at the testing areas T1, T2...Tn of the working surface S so that the corresponding parameters of the sample can be detected, sensed and / or monitored. The first detection mean requires the proximity to the droplet (direct contact or distance compatible with embedded sensor detection range).

[0061] According to an embodiment, in case several testing areas T1, T2...Tn are present, each one comprises one of the first detection means 2. The first detection means 2 can be the same or different in all of the testing areas or some of them.

[0062] Alternatively or in addition, the first detection means 2 can be present at other positions of the working surface S. For example, some detection means 2 can be provided to detect some of the physico-chemical parameters of the droplets D1, D2...Dn before and / or after they have been placed in a testing area T1, T2...Tn and involved in the testing operations. Alternatively or in addition, some first detection means 2 can be placed at some reservoir locations. This may be relevant for monitoring a sample after it has been tested on a given testing area and displaced in such a reservoir.PFLEX-2-PCTFor example a cell culture can be monitored by mean of such first detection means 2.

[0063] According to an embodiment, a path P1, P2...Pn can be set so that one of its nodes comprises such a first detection mean 2. Several different first detection means 2 can be arranged along a path or activated on demand, in particular more than one embedded sensor per electrode is present, so that different parameters can be determined before and / or after the testing operations provided on a testing area. Also, a given node comprising such first testing means 2 can be shared by different paths. For example a first droplet D1 of a first liquid L1 can be driven through a node comprising such a first detection mean 2 and a second droplet D2, of a second liquid L2 can also pass through the same node.

[0064] According to an embodiment, accuracy of the detection by the first detection means 2 can be determined. For example a first droplet D1 can follow a dedicated path P1 comprising a first detection means 2 and a second path or path portion comprising another first detection mean 2. The second path or path portion allows to conduct and sense a second droplet D2 of a second liquid L2. By this way, a given droplet is sensed several times under different conditions, such as along a dedicated paths and along a path shared with other liquids. Alternatively, local temperature or another parameter can be adapted. Different detection results can be averaged or computed so as to limit the measurement errors such as imprecise detections, false positive or false negative where appropriate. As further detailed below, dedicated programs can be set to determine and / or adapt the detection accuracy or the reliability of the results. Alternatively or in addition, different programs may be set to calibrate or adjust the detection.

[0065] The first detection means 2 are fixed and cannot be easily displaced, since they are integrated or embedded to the working surface S. According to a preferred embodiment, the first detection means 2 are dedicated to contact detection of the sample and / or droplets. A contact detection relates here to any detection involving a direct contact with thePFLEX-2-PCTmaterial (see following sentences). Parameters such as electrical parameters or pH values. This does not excludes that some of the first detection means 2 are also adapted for non-contact detection such as magnetic field, colour detection or any other distant parameters.

[0066] According to an embodiment, the first detection means is adapted to measure the turbidity, the conductivity, and / or the particle size of the droplets. This is particularly convenient to analyse some heterogenous liquids.

[0067] The first detection means can be selected from a thermal sensor or a pH sensor.

[0068] The present microdroplet actuating system 1 can comprise one or more second detection means 3. Such second detection means 3 can complete the first detection 2 by sensing different parameters. In particular, the second detection means 3 is preferably dedicated to non-contact detection such as visual inspection, colour detection, fluorescence detection, scintillation detection, magnetic detection, X-ray detection. Such second detection means 3 can thus comprise infrared or visible cameras, 2D or 3D cameras, optical microscopes, temperature laser detector or any relevant non-contact detection device.

[0069] According to an embodiment, the second detection denotes a colorimetric imaging unit.

[0070] According to an embodiment, the first 2 and the second 3 detection means are used in combination so as to provide sensed data. For example, the first detection means 2 may provide an exciting light and the second detection means 3 may collect and sense the light of the sample resulting from the exciting light, as it will be described later.PFLEX-2-PCT

[0071] The second detection means 3 here-described are preferably located at the testing areas T1, T2...T3. For example, they can be arranged above the working surface S so that the testing area or the testing areas can be sensed or monitored. This does not exclude that additional second detection means 3, either identical or different are also provided elsewhere on or above the working surface S, for example at the nodes already provided with a first detection mean 2.

[0072] According to an embodiment, a second detection mean 3 can be displaced from one location to another one on or above the working surface S. For example a camera can be provided above a first testing area T1 to monitor a sample at such a testing area T1 and then displaced toward a second testing area T2 so as to acquire successive data at different testing areas. To this end, the second detection means 3 can be arranged on a mobile support or frame. As another example, a second detection mean 3 such as a camera can be displaced from a first node of a path P1 to the subsequent nodes of the corresponding path, so as to determine the size of the corresponding droplets, and / or the concentration of the products suspended or dissolved therein.

[0073] According to an embodiment, one or several of the first 2 and second 3 detection means can be independently activated manually. Alternatively, one or several of the first 2 and second 3 detection means are individually activated according to automatised processes. For example, depending on the type of analysis to be performed, a first detection means2 can be selected, such as a pH detector, a conductivity detector or any other relevant sensor. Upon result of the first detection, a second detection means3 can be selected, such as an optical detection of the droplet size. Alternatively, concomitant activation of a first 2 and a second 3 detection mean can be performed at a given position, such as a testing area T1, T2...Tn. The concomitant detection data can be computed so as to provide an intermediate result. Based on this intermediate result, a subsequent detection operation can be triggered by activation of one or more than one of the first 2 and second 3 detection means.PFLEX-2-PCT

[0074] According to an embodiment, the first detection means 2 comprises an impedance or electrochemical sensor, and the second detection means 3 comprises an optical detector configured for fluorescence or absorbance.

[0075] According to an embodiment better shown in figure 5a, the first detection mean 2 denotes one or several light source 20, embedded in the bottom surface 12 or underneath the bottom surface 12. The light source(s) 20 emits an exciting light 21 toward the working surface S so as to illuminate the droplets D1, D2, Dn which are handled on the working surface S. The light source(S) 20 may be placed at dedicated positions such as testing area T1, T2...Tn. A second 3 detection means can denote a light sensor 30, adapted to sensed the light 31 emitted by the droplets irradiated by the exciting light 21 . While the light source(s) are fixed, the light sensor 30 can be mobile above the working surface S so as to detect the emitted light at different positions.

[0076] According to an embodiment, better shown in figure 5b, the first detection mean 2 denotes one or several light source 20, which emits an exciting light 21 through one or several waveguides 22 embedded in the bottom surface 12 or underneath the bottom surface 12. The waveguide(s) 22 comprise means to redirect the exciting light 21 towards the working surface S so as to illuminate the droplets D1, D2, Dn which are handled on the working surface S. Such light redirection means may be grating such as Bragg grating. Other suitable means can be used according to the needs. The second detection means 3 can be the light sensor 30 above-described or another appropriate detection means.

[0077] According to another embodiment better shown in figure 5c, the first detection mean 2 denotes one or several light source 20, which emits an exciting light 21 through one or several waveguides 22 embedded in the top surface 11 or above the top surface 11. The waveguide(s) 22 comprise means to redirect the exciting light 21 towards the working surface S so as to illuminate the droplets D1 , D2, Dn which are handled on the working surfacePFLEX-2-PCTS. Such light redirection means may be grating such as Bragg grating. Other suitable means can be used according to the needs. The second detection means 3 can be the light sensor 30 above-described or another appropriate detection means.

[0078] According to an embodiment, the guiding elements E1, E2, En are transparent. This is particularly convenient for the embodiments described with figures 5a, 5b and 5c so that exciting light 21 can cross the bottom surface 12. Transparent guiding element can be made of indium tin oxide or any other suitable transparent material. The transparent electrodes can be overlaid with a photo-activation layer for optically triggered droplet manipulation.

[0079] According to an embodiment, one or both of the top surface 11 and the bottom surface 12 is transparent or partially transparent.

[0080] It is here understood that some selected detection means can be activated at a given time so that corresponding detection is operated under certain conditions.

[0081] According to an embodiment, the first 2 and / or the second 3 detection means are piloted by the command unit 6.

[0082] According to an embodiment, some auxiliary equipment, in particular the transformation devices, are piloted by the command unit 6.

[0083] According to an embodiment, the command unit 6 allows for selectively deactivate at least one of the first 2 and the second 3 detection means to reduce power consumption.

[0084] According to an embodiment, the microdroplet actuating system 1 is portable and powered by an internal battery. The battery may be rechargeable via USB, inductive charging, or solar panels. According toPFLEX-2-PCTT1 another embodiment, the device includes energy harvesting elements, such as thermoelectric or piezoelectric generators, allowing operation in remote or resource-limited settings. This enables field-deployable diagnostics, environmental monitoring in outdoor conditions, and portable at-home use without requiring continuous mains power.

[0085] According to an embodiment, the microdroplet actuating system 1 is housed in a rugged enclosure designed to be water-resistant, dustresistant, and shock-resistant, thereby ensuring reliable operation in outdoor environments, industrial sites, military applications, or disaster relief settings. According to another embodiment, the enclosure is lightweight and portable, with handles or protective casing that facilitate transport and field use without compromising analytical accuracy.

[0086] The data collected from the first 2, and the second 3 detection means where applicable, are transmitted to a detection unit 4. Such a detection unit 4 comprises all necessary software and electronic architecture to collect and store the sensed data. The data can be temporarily stored until it has been transmitted or read or further computed. Alternatively, the sensed data can be stored for a long term so that further access remain possible, for example for quality control or post treatment processes. The detection unit 4 can be adapted to provide at least a first level of computation such as providing a mean value of a sensed parameter, detecting errors, computing a statistical characteristic such as the dispersion of a sensed parameter or standard deviation thereof. The detection unit 4 can for example collect series of sensed data so as to provide a consolidated measurement value. Filters can be programmed in the detection unit 4 so that values out of a predetermined range, or some noise of detection, are discarded. Any other transformation steps allowing to improve the detection and provide exploitable measurement can be used.

[0087] The detection unit 4 can comprise image recognition programs so as to collect visual data, X-ray data or any other 2D or 3D images collected by the first 2 and / or the second 3 detection means. Sensors like CMOS orPFLEX-2-PCTequivalent can be used. Such images concerns for example shape of some elements like biological cells in a sample. Alternatively, it can concern a number and / or distribution of visible elements like solid particles or biological cells in suspension in a sample. It can further concern the size detection of a droplet. Image recognition can be performed or assisted by an artificial intelligence program. Such program can be educated to recognize for example certain shapes of biological cells or certain other characteristics of biological cells which can be used to identify a toxic effect, or any physiological effect resulting from the test operations. The detection unit 4 can further collect colour detection or contrast values, or transmittance values, or fluorescence values, or luminescence values or diffusion or diffraction values. Colour filters can also be implemented so that an image can be visualized differently.

[0088] According to an embodiment, the computing unit 5 is configured to execute diagnostic protocols stored in an artificial intelligence or expert system module.

[0089] Where applicable, in case of non exploitable measurement or under some specific predetermined conditions, the detection unit 4 can instruct the command unit 6 to reiterate a single detection, or a detection sequence involving several of the present detection means.

[0090] According to an embodiment, in case of failure of one or more of the detection means, a warning can be provided so that a user or an expert system can remedy the failure and restore proper measurement conditions.

[0091] According to an embodiment, operation such as calibration or accuracy testing or reliability testing can be performed by the detection unit 4 either manually or automatically.

[0092] According to an embodiment, calibration of detection means 2, 3 is performed using reference droplets containing known standards such as pH buffers, fluorescent beads, or colorimetric dyes. The system canPFLEX-2-PCTautomatically compare detected values against these standards to correct for drift or variability. According to another embodiment, calibration sequences are scheduled periodically or triggered on demand by the computing unit 5, which may apply correction algorithms to adjust raw measurements in real time. This ensures reliable operation across a wide range of test conditions.

[0093] According to an embodiment, the present microdroplet actuating system 1 further comprises additional devices such as light irradiation devices (not represented). For example UV or infrared irradiation devices can be used to trigger a reaction within the sample under test, or for deactivation of infectious material. For example, a sequence of UV irradiation can be provided to biological cells so as to induce a mutation or simulate the effect of natural light in the presence of some additives. Alternatively, infrared or UV light can be used to initiate photochemistry reactions between chemical compounds. Alternatively, a light irradiation, either visible, infrared or UV can be operated to detect a fluorescence, a luminescence or a phosphorescence within a sample under test. Alternatively, UV light can trigger photopolymerization processes. Adapted filters can be included so as to provide suitable wavelengths, either in a single range of wavelengths or in multiple ranges of wavelengths. A light irradiation includes here any kind of light, including LED and / or lasers. Alternatively, infrared irradiation may be used to locally heat a sample, or to generate a signal that could be detected for measurement. Such additional devices can thus be used to set up a detection step or trigger a transformation of a sample. Such a device may be manually piloted or piloted by an automatized element such as the command unit 6. Such an additional device can be arranged with the second detection means 3 or independently arranged. One or more of such additional devices, where present can be mobile on or above or below the working surface S.

[0094] The present microdroplet actuation system 1 can further comprise thermoregulation devices so that controlled temperature can be provided at least at the testing areas. Preferably, the whole working surface S is thermoregulated. According to an embodiment, several temperature zones can be arranged such as a warm and a cold zones. Alternatively a givenPFLEX-2-PCTthermally controlled zone can be either warmed or cooled or frozen. The necessary heating or cooling / freezing elements are provided in a suitable manner. Such warming or cooling / freezing element can be piloted by the command unit 6 or manually piloted. The warming operation can increase the temperature of the working area above ambient temperature, such as around 30°C or 40°C, suitable for cell incubation. Warmer temperatures can be envisaged such as more than 50°C of more than 80°C so that chemical reactions can be made. Temperature lower than ambient temperature such as few degrees or below 0°C can also be envisaged, for example for slowing down chemical reactions or biological activity.

[0095] The present microdroplet actuating system may comprise one or more additional humidity regulation device 9 such as a refillable liquid seal. Such a refillable seal can be refilled on demand based on hygrometry determination. Alternatively, the hygrometry can be automatically controlled or regulated based on hygrometry sensor and a refill reservoir automatically activable. The liquid seals can have any suitable shape and size depending on the requirements. They can be placed at any suitable location on the chip.

[0096] The present microdroplet actuating system may comprise one or more fluid logic gates. A fluid logic gate according to the present embodiment can be materialized by a volume of fluid (superior or equal to the volume of the droplet) placed as a barrier anywhere on the path P1-Pn. The barrier opens by removing the liquid volume from the path only when some or all predetermined conditions for further advancements of the droplet under test are met. A predetermined condition may be a physicochemical parameter such as pH or colour. Otherwise, the droplet moves into the barrier which merges with the liquid of the droplet. In consequence, transformation of the sample can be initiated or cancelled, and further monitored by a suitable detector such as those described here. The fluid logic gate can be arranged prior any processing sequence or created or suppressed during an analytical sequence according to the detected parameters. This allows the implementation of decision-making circuits and automated test sequences, where the path of each sample dynamically depends on real-timePFLEX-2-PCTanalytical feedback. The liquid use for the fluid logic gate may be stored in a dedicated container and placed according to the needs on the present microdroplet actuating system. This is an additional mean of control of the processes on the chip. The created barriers can be used not only to manage liquid movement but also to control evaporation, form localized zones with distinct gas-phase environments, and establish interfaces where two liquids interact, thereby enabling detailed studies of interfacial reactions.

[0097] According to an embodiment, the logic gates are arranged to form a microfluidic logic circuit implementing AND, OR, or NOT functions.

[0098] The present microdroplet actuating system may trigger on- demand polymerisation or solvent-based solidification reactions on the chip to create solid structures during the analytical sequence. Such solid structures can be used as a physical barrier or as a support. For example, it can be used as a scaffold or matrix that facilitates cell attachment, growth, and organization into structures. It can also be used as a barrier to isolate sections on the chip, to create microfluidic channels, as well as to build distinct compartments that mimic physical separations between tissues or microenvironments with controlled conditions. This can be used, for example, to study multi-organ responses to pharmaceuticals or chemicals. The solid structures can be created with thermal regulation or UV irradiation system present in the actuating system 1. These structures can be permanent or resorbable.

[0099] Alternatively, the present system may rely on gelatinization instead of polymerization to create barriers, channels, or matrices. Gelatinization, for example of starch or gelatin solutions, may be triggered by heating or other stimuli to form a semi-solid gel directly on the working surface S. An advantage is that de-gelatinization (return to liquid state) may be achieved simply by heating or dissolution in aqueous medium, without the need for auxiliary depolymerising agents or chemical additives. This reversible behaviour allows temporary barriers or compartments to be created and later removed without residue, providing a flexible andPFLEX-2-PCTbiocompatible alternative especially suited for pharmaceutical, diagnostic, food, or fragrance applications.

[0100] According to an embodiment better shown in figure 6, the microdroplet actuating system 1 allows to create channels on the working surface S. To this end, droplets D can be actuated according to the abovedescribed method at a desired location close to another droplet. A transformation device such as a light irradiation device or a thermal regulator, as described above, may be used to trigger a polymerisation of the products contained in the two droplets in contact with each other so as to create a polymerised barrier 200. The operation can be reproduced so as to create either a physical barrier allowing to separate different areas on the working surface S, or channels 300 allowing to circulate the liquid(s) L1, L2, Ln in a continuous flow. Permanent channels can thus be created in situ. Once a routing pattern has been tested using a single droplet move along a given pathway P, then, a channel can be set in situ so as to allow a continuous flow of liquid. Such an arrangement allows for an easy scale up study without any need to transfer the sample off chip.

[0101] According to an embodiment, the polymerised barrier 100 comprise or denote a porous material and / or a gel like matrix so as to simulate a soil microenvironment.

[0102] According to an embodiment, the auxiliary transformation device allows for, or is configured to simulate volatility or controlled release of at least one flavor or fragrance component under conditions of heat or humidity.

[0103] According to another embodiment, the auxiliary transformation device is configured to simulate volatility or controlled release of at least one flavor or fragrance component. This may include controlled heating, humidity adjustment, or airflow modulation to reproduce the evaporation kinetics of volatile molecules. The system can thus mimic the perceptual release profile of a perfume or food aroma under different environmentalPFLEX-2-PCTconditions (e.g., body temperature, cooking conditions, ambient humidity). Such simulations are particularly advantageous for consumer product prototyping and sensory science research.

[0104] According to an embodiment, the auxiliary transformation device is further adapted for fragrance volatility simulation. For example, droplets containing perfume precursors can be exposed to controlled heating elements combined with microfluidic airflow channels, reproducing evaporation kinetics under realistic conditions such as body temperature or ambient humidity. The second detection means 3, such as a colorimetric imaging unit or a headspace sampler, can be used to monitor the concentration of volatile compounds over time. The computing unit 5 may automatically compare the resulting release profile against reference data to assess intensity, persistence, and sensory characteristics of the tested formulations.

[0105] According to an embodiment, the volatility simulation is quantified by monitoring the decay of volatile headspace concentration over time, for example determining a half-life of 5-15 minutes for light floral notes versus 30-60 minutes for heavier base notes, thereby enabling objective comparison of fragrance release profiles.

[0106] The present microdroplet actuating system may trigger a transformation allowing the materials to transition from a liquid state to a cell tissue conformation such as semi-solid gel to form functional tissues during the analytical sequence. For instance, semi-solid gels could be triggered by on-demand gelation of bio-inks induced by temperature changes, pH alterations, or exposure to light waves or specific chemical agents. Such tissues can be exposed to different drugs or chemical compounds to observe reactions, such as the production of specific enzymes, changes in gene, RNA, proteins and various metabolites expression, or cytotoxicity. Biological reagents can include indicators that change colour, fluorescence or luminescence in the presence of certain metabolites, facilitating rapid, real-time analysis. Such tissue can better reproduce thePFLEX-2-PCThuman or animal organs response to drugs than traditional animal models or cell cultures. This reduces cost and time by allowing multiple compounds to be rapidly tested on the same tissue properties, reducing the need for animal testing, and accelerating drug development. As tissues can be created from cells specific to individuals, such as patients, it enables the application of personalized or precision medicine techniques to test drug safety and efficacy tailored to each individual. Additionally, depending on the observed reactions of the tissue to initial reagents or other prokaryotic or eukaryotic cells, it is possible to adjust the types and concentrations of reagents and other cell types applied in real time. For example, if a drug or a microorganism provokes a toxic response, protective or corrective agents can be introduced, or the dose modified to mitigate adverse effects. Additionally, employing multiple reactors in parallel can further refine the testing process by allowing variations in drug concentrations or different combinations and concentrations of protective, corrective agents or microorganisms to be assessed simultaneously. In addition to the drugs being tested, nutrients or other types of drugs can be added to explore their potential for synergy or mitigation of harmful effects. This approach makes it possible to simulate a more complex and dynamic treatment environment, where several factors interact simultaneously. The goal of these real-time adaptations is to find the optimal combination of reagents that not only neutralizes the toxic effects of the drugs tested, but also enhances tissue health and functionality. This could be particularly valuable in the development of treatment strategies for complex diseases. This ability to adjust treatments in real time offers a valuable experimental platform for personalized or precision medicine and could lead to more targeted and effective therapies, reducing risks and improving outcomes for patients.

[0107] The present microdroplet actuating system 1 is therefore adapted for any kind of action such as moving, mixing, diluting, concentrating, transforming, reacting, splitting, combining, changing shape of the droplets under test, as well as detecting, sensing, determining, and / or analysing such actions and resulting products.PFLEX-2-PCT

[0108] The system can be directly integrated with pipetting robots, well plates, and automated liquid handlers, facilitating seamless introduction and extraction of challenging samples from external containers. This enables high-throughput adaptation to diverse sample types and conditions.

[0109] According to an embodiment, the above-mentioned inlet / outlet port array may be spatially aligned to SBS microplate coordinates so that deck-mounted robots can index positions without custom calibration. The command unit 6 and computing unit 5 may be configured to expose a port map to the liquid-handling controller, enabling synchronized operations such as aspirate / dispense cycles, priming, flushing, and waste collection. Ports designated as waste outlets may be fluidically coupled to closed waste containers to preserve hermetic operation.

[0110] According to an embodiment, the microdroplet actuating system 1 is integrated with robotic sample handling equipment such as pipetting robots, autosamplers, or robotic systems, which can directly introduce droplets or feed containers C1, C2, Cn. According to another embodiment, the system communicates with Laboratory Information Management Systems (LIMS) or equivalent digital infrastructure, enabling seamless bidirectional exchange of sample identifiers, test results, and analytical protocols. This allows full integration of the device into automated laboratory workflows and industrial quality control environments.

[0111] According to an embodiment, multiple microdroplet actuating systems 1 can be networked together and coordinated by a central computing unit or cloud server. This arrangement allows synchronized execution of analytical sequences across dozens or hundreds of devices, enabling applications such as large-scale pharmaceutical high-throughput screening, the high-throughput screening of a pathogen against a vast combinatorial library of many thousands of compounds in the agriculture and soil science fields, environmental monitoring campaigns, or epidemiological surveys. The networked devices may share results in realPFLEX-2-PCTtime, allowing global-scale data collection and adaptive coordination of analytical protocols.

[0112] According to an embodiment, multiple microdroplet actuating systems 1 can be networked together and coordinated by a central computing unit or cloud server. This arrangement allows synchronized execution of analytical sequences across dozens or hundreds of devices, enabling applications such as large-scale pharmaceutical high-throughput screening, the high-throughput screening of a pathogen against a vast combinatorial library of many thousands of compounds in the agriculture and soil science fields, environmental monitoring campaigns, or epidemiological surveys. The networked devices may share results in real time, allowing global-scale data collection and adaptive coordination of analytical protocols.

[0113] According to an embodiment, the device is coupled to a digital twin module, which continuously simulates chip performance, predicts maintenance requirements, and optimizes calibration schedules. This ensures reliable operation in large-scale laboratory automation and industrial environments, reducing downtime and improving quality control.

[0114] According to an embodiment, detection unit, computing unit, and command unit can be implemented together on a single multifunctional integrated module. This module may be an embedded Al chip.

[0115] According to an embodiment, the computing unit is configured to control ratios of merged droplets so as to produce formulations comprising different proportions of flavor or fragrance components.

[0116] According to an embodiment, the computing unit is specifically adapted to control ratios of merged droplets in order to generate complex formulations. This includes formulations comprising different proportions of flavor or fragrance components, where the concentration ratios are adjusted in real time to simulate product variants. For example, successive droplets ofPFLEX-2-PCTfragrance precursors can be merged in different volumetric ratios (e.g., 1:10, 1 :5, 1 :1) to produce distinct olfactory profiles. The system can automatically explore ratio ranges and present the resulting formulations for sensory evaluation or analytical testing, thereby enabling rapid prototyping of flavor and fragrance compositions.

[0117] According to an embodiment, fragrance or flavor ratio optimization is performed by merging droplets in systematically varied volumetric proportions. For example, droplets of citrus extract and floral base can be merged in ratios of 1 :9, 3:7, 1 :1, and 7:3 to generate distinct candidate formulations. Each resulting formulation can be routed to a dedicated testing area T1, T2...Tn, where headspace analysis or olfactometry is performed by auxiliary equipment. The computing unit 5 is adapted to automatically explore ratio ranges, record corresponding detection results, and generate a formulation map that identifies preferred blends based on volatility, stability, or sensory feedback.

[0118] According to another embodiment, the optimized fragrance or flavor blends generated on-chip can be presented for human sensory evaluation, and the corresponding feedback can be reintegrated into the computing unit 5 to refine ratio exploration, thereby enabling closed-loop optimization of consumer product formulations.

[0119] According to an embodiment, the fragrance or flavor formulations generated on-chip are linked to consumer preference databases, wherein feedback from sensory panels or end-users is combined with Al algorithms to predict market acceptance and optimize compositions for specific demographics.

[0120] The detection unit 4 is connected to a computing unit 5 adapted to further analyse the sensed data transmitted by the detection unit 4. The computing unit 5 is further adapted to output decisions based on the data collected from the detection unit 4. The output decisions relate to the analytical sequence of the ongoing test process. Decisions provided by thePFLEX-2-PCTcomputing unit 5 include the activation of one or more paths P1, P2..Pn on the working surface S. For example, upon sensing the result of a sample at a first testing area T1 in contact with a droplet D1 of a first liquid L1 the computing unit 5 can decide to reiterate the combination of the sample and the first liquid L1 at a diluted concentration at a second testing area T2. Alternatively, the computing unit 5 can decide to activate a second reservoir so that a droplet D2 of a second liquid L2 is driven to the first testing area T1 . By this way, the sample at the first testing area T1 is in contact with the two different first L1 and second L2 liquids. Depending on the parameters sensed at the second testing area T2, a third reservoir can be activated so that a droplet D3 of a third liquid L3 is driven to the second testing area T2. The computing unit 5 can thus autonomously take the decision to activate predetermined paths P1, P2..Pn upon sensing some parameters. Certain predetermined conditions can be programmed. For example, in case a first liquid L1 has no observable effect on the sample, it can be determined that another amount of the first liquid L1, having either the same concentration or an increase concentration, is driven to the corresponding testing area. The corresponding path, including concentration or dilution steps is thus set. Alternatively, in case no observable effect occurs at the first step, the computing unit 5 can be programmed so as to drive a second liquid L2, either in combination with the first liquid L1 or alone at a second testing area T2. Thus, each one of the first L1 and second L2 liquids can be tested alone and in combination. Synergistic or antagonist effects can thus be identified. Nonlimited applications including path changes, creation and adjustments, sample transformations, type of sensed parameters, times and durations of the analytical cycles etc... can be set.

[0121] According to an embodiment, the computing unit 5 is also involved in some calibration, accuracy testing or reliability testing operations instead of the detection unit 4. Dedicated programs can be activated. Alternatively, the corresponding operation may be provided fully or partly autonomously.

[0122] According to an embodiment, the computing unit 5 is implemented with predetermined paths P1, P2...Pn as above-defined. It isPFLEX-2-PCTfurther implemented with predetermined conditions Q1, Q2...Q3 upon which one or several paths can be activated. Such conditions include some threshold values of sensed parameters detected by one or more of the first 2 and the second 3 detection means. The predetermined conditions Q1, Q2...Q3 can include former steps already operated in the analytical sequence. For example, in case a given path has been already used, then it can be forbidden unless in combination with another activated path. The predetermined conditions Q1, Q2...Q3 can included 2D or 3D reference images to conform with. For example, an image detection can be compared to a reference picture so as to determine a status of the sample under test. The conditions Q1, Q2...Q3 can include a positive or negative response to a detection of a given parameter. The conditions Q1, Q2...Q3 are not exhaustively provided here. It is understood that the online detection can automatically trigger operations or detection steps.

[0123] The computing unit 5 is further implemented with predetermined actions A1, A2.. An, such predetermined actions include activating a reservoir R1, R2...Rn or another reservoir or a defined reservoir. It can further be activating a path P1, P2...Pn or another path or a dedicated path, including concentration or dilution operations. The predetermined actions further include activating a first detection means 2, all of the first detection means or only specific first detection means 2. The predetermined actions A1, A2..An further include activating a second detection means 3, all of the second detection means 3 or only specific second detection means 3. The predetermined actions A1, A2..An can further include moving the second detection means 3 toward a detection site on the working surface S. The predetermined actions A1, A2..An further include activating one of the additional devices so as to trigger a transformation or set a detection. The predetermined actions A1, A2..An can further include activating thermoregulation of the working surface S or initiating external additional analysis by means of external analytical devices such as chromatography, mass spectrometry, NMR detection, etc...

[0124] The computing unit 5 can be used according to different modes M1, M2...Mn. For example, a fully autonomous mode can be initiated,PFLEX-2-PCTwherein the above-mentioned decisions are taken automatically. Some input parameters such as the nature of the sample, the nature and concentration of the different liquid L1, L2...Ln in the corresponding reservoirs R1, R2...Rn, the type and / or number of the first 2 and second 3 detection means, the purpose of the test and any other relevant input parameters may be used so that an autonomous program is initiated. For example the purpose of the test can be to detect a synergistic effect of combined drugs on a given sample. The autonomous mode can then implement all necessary analytical steps until a positive result is obtained or until all possible combinations are performed or until the most significant results are obtained, or during a given time, or until a given number of analytical cycles is reached.

[0125] The computing unit 5 can be set in a random mode, wherein a sample is randomly tested with the available liquids L1, L2...Ln so that the corresponding effect can be identified. The random mode may continue until all the available combinations are made, or for a given analytical time or until an expected result is detected, or during a given time, or until a given number of analytical cycles is reached. Other conditions can be envisaged. The random mode may be operated for example under an unsupervised machine learning arrangement or system.

[0126] The computing unit 5 can be set in a semi-autonomous mode, wherein an initial analytical sequence is implemented. For example, a sample can be independently combined with a number of liquids at predetermined different concentrations and systematically tested for each concentration of each of the liquids. Based on the first detected parameters, the initial analytical sequence can be automatically modified so that it is optimized. In case a positive result is detected for a given concentration, tests with higher concentrations may be automatically cancelled. Alternatively, synergistic test at lower concentrations may be automatically triggered. Any other relevant analytical steps can be either automatically triggered or modified or stopped compared to the initial program. Such a semi-autonomous mode may be implemented with a supervised machine learning arrangement or system.PFLEX-2-PCT

[0127] It is here understood that any other mode can be set for the computing unit 5, such as a hybrid mode between the above-mentioned modes or alternative modes.

[0128] According to an embodiment, data related to a patient can be considered in any one of the above-described mode so that personalized diagnostic and / or medicine can be provided. Data related to age, gender, passed or present pathologies of the patient and / or his family, other laboratory results as well any relevant clinical information can be implemented in the present system. The selection of paths upon detection of some parameters can thus be individualized according to the patient.

[0129] The results obtained according to the above-mentioned methods, device and / or system can be used for example to trigger an intervention in the test protocol from a professional in the field (e.g. medical, environmental, engineer, ...). Such a professional can interact through the dedicated human-machine interfaces, either locally or remotely, where applicable. This is applicable even during a space missions. If the device is connected to other equipment (e.g. laboratory equipment, upstream or downstream production equipment), in particular fluidly connected, it can trigger actions to be executed on other equipment. The present microdroplet actuating system can be for example integrated into a framework such as a «network of automates».

[0130] The decisions taken by the computing unit 5, in particular the actions A1, A2...An are transmitted to the command unit 6 so that the corresponding operations are triggered.

[0131] According to an embodiment, the computing unit according to the present disclosure denotes any expert systems, artificial intelligence, machine learning, either supervised or unsupervised, reinforcement, generative artificial intelligence and related system or arrangement.PFLEX-2-PCT

[0132] The present microdroplet actuating system 1 according to the present invention can further comprise or be connected to databases 7 such as proprietary databases, national and international databases, research databases, as better shown in figure 2. According to an embodiment, the computing unit 5 is connected to such databases or some of those databases. Results can be requested or transmitted to other analytical units laboratory information systems (LIS) and patient electronic files. A research database can for example comprise data or publications related to the sample under test. In case blood cells are sampled and tested against a series of potential drugs or pollutants, then corresponding data or publications may be automatically identified and selected, including identification of bacteria by any relevant method such as MALDI-TOF or PCR identification and the related antibiotic susceptibility testing, clinical information, epidemiological information. Some of the corresponding data may be used as conditions Q1, Q2...Qn above-mentioned. For instance, when existing tests results are available, the computing unit 5 can decide to not reiterate them. On the contrary, it can decide to reproduce them so as to establish reference data. Such a process can be performed based on a generative learning machine system.

[0133] For diagnostic purpose, when the sample relates to a given patient, the computing unit 5 may be authorized to access the corresponding medical data or some of the patient medical data. By this way, certain conditions Q1, Q2...Qn can already be considered like medical antecedents, ongoing or past medical treatments and so on. The diagnostic test can thus be automatically personalized for an improved accuracy and / or efficiency. For example, some analytical step may be a-priori avoided or on the contrary a-priori taken depending on the patient's history.

[0134] According to an embodiment, the device is configured to interface with electronic health record (EHR) systems or telemedicine platforms, enabling direct transmission of diagnostic results to healthcare providers.PFLEX-2-PCT

[0135] According to another embodiment, the device is used as a companion diagnostic tool, wherein patient-specific results are analysed to recommend or adapt therapeutic regimens, for example in oncology or infectious disease management.

[0136] According to an embodiment, wireless data transmission is encrypted to ensure secure transfer of sensitive analytical or patient information. The computing unit 5 and connected remote servers may further implement anonymisation modules, so that data can be stored and transmitted without personal identifiers when required. In addition, the system may comply with applicable data protection regulations such as GDPR or HIPAA. According to another embodiment, the user can select between named and anonymous operation modes, depending on the regulatory context and intended use.

[0137] According to an embodiment, the system further implements compliance modules adapted for international regulatory requirements such as FDA, EMA, or CFDA guidelines, ensuring lawful handling and transmission of analytical data across jurisdictions. According to another embodiment, ethical oversight workflows are embedded in the system, for example requiring explicit approval or anonymisation before population-level epidemiological data are uploaded. This ensures that the device can be deployed in global healthcare contexts while maintaining patient confidentiality and regulatory conformity.

[0138] According to another embodiment, the data related to the patient or some of the corresponding data may be accessed by the computing unit 5 on an unnamed manner - the system can process the data anonymously if required, for instance with point of care test (POCT) systems that could be implemented at home and used by non-identified users.

[0139] For environmental, medical, pharmaceutical and / or food survey, databases related to the toxicity of substances can be accessed so as to implement suitable analytical steps. For example conditions Q1, Q2...QnPFLEX-2-PCTrelated to the concentration of the substances in the analytical test can be automatically considered or discarded based on known data in the corresponding field. Synergistic effect can be confirmed or on the contrary not reproduced.

[0140] High throughput screening of compounds such as small chemical compounds can be performed using the present microdroplet actuating system 1, wherein pharmacological databases, or chemical databases, or related databases are also considered. High throughput screening can also be adapted to the reagents, peptides, pollutants and related products above- mentioned.

[0141] Regulation and standard up-to-date documents can also be considered. For example, EUCAST / CLSI / other for antibiotics. Data parameters can be selected. For example, REACH directives or any other related directive can be used to select or avoid chemical compounds. Safety sheets related to some chemical compounds can be considered.

[0142] According to another embodiment, the present microdroplet actuating system 1 comprises all necessary human-machine interfaces such as display, tactile screen, keyboards, graphical interfaces and related elements, accessible locally or remotely. The computing unit 5 can thus be manually programmed. It can furthermore be used by a user through the graphical interfaces and the corresponding command units. Preprogrammed menus can be available so that a mode, some actions, some conditions, some test purposes as above-described can be implemented. The present microdroplet actuating system 1 can be either piloted or monitored remotely.

[0143] According to an embodiment, the present microdroplet actuating system 1 comprises or is connected to self-learning modules including artificial intelligence, deep learning unit or similar features. According to an embodiment, the test results, including all the detected data are stored in one or several databases so as to be accessed later on. Such cumulated data can be used for training some self-learning units.PFLEX-2-PCT

[0144] According to an embodiment, the computing unit 5 is provided with some modelling software. Test sequences can be generated based on some input parameters like the type of sample, the purpose of the test, a therapeutic indication, research of a synergistic effect, effect of some determined products or combination thereof, or any other relevant parameters. The computing unit 5 can access suitable databases such as national databases, regulatory databases, patient personal data, laboratory databases, research database, and any related databases, such as those described herein, so that known information is considered. The computing unit 5 can provide or suggest an analytical sequence including the type and number of liquid L1, L2...Ln, the test conditions like concentrations, temperatures, parameters to be sensed. The computing unit 5 can further elaborate some conditions Q1, Q2...Qn and corresponding actions A1, A2...An to be envisaged based on the available information. The analytical sequence can take the form of an experience plan or a diagnostic protocol or a high throughput program or any other suitable testing process. Such an analytical sequence can be fully or partially implemented so that a user can validate or modify it before triggering it.

[0145] The present invention further relates to an analytical method using the present microdroplet actuating system 1. The analytical method comprises the steps of actuating at least one first droplet D1 of a first liquid L1 to a testing area T1 and activating a detection mean, like a first 2 and / or a second 3 detection mean, as above-defined. According to an embodiment activating a first and / or second detection means does not exclude that other detection means, either integrated or external to the present microdroplet actuating system 1 or shared with other laboratory devices, are also activated. According to another embodiment, only one or both of the first and second detection means here described are activated. The detection step may be triggered only after a sample or a droplet is detected at the corresponding testing area. The actuation of such a first droplet includes activating a first paths P1. According to an embodiment, a first droplet D1 relates to a sample to be tested, such as biological or chemical sample.PFLEX-2-PCT

[0146] The present analytical method can include actuating at least a second droplet D2. Such a second droplet D2 can relate to the first liquid L1 or to another liquid such as a second liquid L2. The second droplet can be driven to a testing area such as the first testing area T1 or to another testing area. The second droplet D2 can be driven according to a second path P2. It can alternatively be driven along the first path P1 if it relates to the first liquid L1. According to an embodiment, such a second droplet D2 comprises a reagent or a testing product to be combined to the sample under test.

[0147] The present method can comprise actuating more than a first and a second droplet D1, D2...Dn. The number and diversity of droplets, liquids and paths is not limited. For example, a large number of reagents or testing products can be combined to one or several samples under test, under any relevant concentrations, temperatures, light irradiation conditions, or other suitable experimental conditions.

[0148] As above-described, the paths can include nodes wherein mixing, dilution and / or concentration operations are possible, as well as specific detections.

[0149] The present analytical method may include transformation reactions of a sample, such as light irradiation, temperature increase as well as any suitable transformation.

[0150] The present analytical method comprises the steps of collecting the detected parameters. The detected parameters are preferably centralised within a detection unit 4.

[0151] The present analytical method may further comprise a step of a first level computation of the detected parameters, so that the detected parameters can be further used in a more comprehensive analytical study. Such a first level computation can be operated by the detection unit 4 or another unit like the computing unit 5. The first level computation include one or several of the above-mentioned operations.PFLEX-2-PCT

[0152] The present analytical method comprises the step of elaborating an analytical sequence. Such an analytical sequence can be partly or fully created by a computing unit such as the above-described computing unit 5. The analytical sequence can be manually implemented by a user 8 in the computing unit 5. Adequate human-machine interfaces are provided to this end. Alternatively or in addition, remote information are automatically accessed by the computing unit 5 so as to model an analytical sequence based on information provided by the user Such remote information can be available in one or several databases 7.

[0153] The present analytical method comprises the step of triggering an analytical sequence which include the above-mentioned droplet actuations, path activation, parameters detections. The triggered analytical sequence corresponds the analytical sequence elaborated as above-mentioned. The analytical sequence further comprises the automatic adjustment or modification of the analytical sequence. Such an automatic adjustment or modification of the analytical sequence is preferably based on the detected parameters during the analytical sequence. Such sequence adjustment includes one or several of the following steps: creating, cancelling, reiterating or modifying a path P1, P2...Pn, initiating or stopping one or more of the first 2 and the second 3 detection means, where applicable, or additional detection means where applicable. Activating one or more of external analytical devices. The automatic adjustment or modification of the analytical sequence is operated based on conditions Q1, Q2...Qn and actions A1, A2...An above-mentioned. Such conditions Q1, Q2...Qn and / or actions A1 , A2...An can be predetermined or validated by a user. Alternatively, one or several of the conditions Q1, Q2...Qn and actions A1, A2...An can be automatically determined, for example by mean of a suitable user-validated artificial intelligence program.

[0154] According to an aspect, the present method includes the step of automatically confirming a predefined analytical sequence, based on the sensed data. This means that even no adjustment is operated, the sequence remains under control of the microdroplet actuating system here described.PFLEX-2-PCT

[0155] According to an embodiment, an analytical method comprises the steps of:(i) automatically generating an analytical sequence by combining initial user inputs (sample type, purpose of analysis) with database-derived information (reference protocols, regulatory standards, clinical data);(ii) actuating droplets according to the generated sequence;(iii) modifying the ongoing analytical sequence in real time based on detection results and predefined conditions;(iv) documenting each modification in an analytical report; and(v) transmitting anonymized results to one or more knowledge databases for model training, epidemiological statistics, or population-level surveillance.

[0156] For example, when a blood sample is analysed, the system may automatically propose a diagnostic sequence for suspected bacterial infection. If impedance measurements indicate abnormal cell counts, the system may modify the sequence to include antibiotic susceptibility testing. The report generated documents all automatic modifications, and the final data is uploaded to an epidemiological database, where it can contribute to monitoring antimicrobial resistance trends.

[0157] The present analytical method comprises the step of providing an analytical report. Such an analytical comprises the nature and conditions of the tested sample or samples, the nature, concentration and condition of the reagents, the corresponding activated paths, the corresponding test results. The analytical report may further comprise which steps have been automatically taken, modified or cancelled by the computing unit 5. The analytical report can further comprise the original purpose of the analytical sequence. Such a purpose can be a diagnostic operation, a synergistic test investigation, a toxicity investigation, a quality control operation or any other purpose. The analytical report may comprise the initially elaborated sequence, in particular when it has been automatically elaborated by the computing unit 5. The analytical report can be made available on a physical support such as a paper or on a numerical support such as database. It can be anonymized and used to train machine learning / Al of the computingPFLEX-2-PCTunit or an expert system, feed a monitoring database of infectious diseases, diagnostics database, or other databases. The analytical report can comprise temporal statistical data, sample history, sample set up, so as to detect unusual variations over time. The analytical report can comprise multiplex studies based on several geographical centers. The analytical report can comprise non conformity of the results based on reference parameters. Comparison with other analytical report can be provided. The above- mentioned elements of the analytical report are not intended to be exhaustive. Any other suitable element based on the data obtained and / or computed herein can be included in such an analytical report.

[0158] According to an embodiment, the analytical report generated by the computing unit 5 is formatted in accordance with regulatory requirements. For example, in clinical diagnostics, the report can be structured to comply with FDA or EMA submission standards, including traceability of samples, calibration data, and anonymized patient identifiers. For industrial applications, such as pharmaceutical or food quality control, the report may follow ISO or GMP guidelines, ensuring that results are admissible in regulatory audits. According to another embodiment, the anonymized data are uploaded into national or international knowledge databases, where they can contribute to epidemiological dashboards, antimicrobial resistance surveillance networks, or toxicity registries, thereby reinforcing public health and safety monitoring.

[0159] The numeral "n" provided in the above-mentioned references Dn, Tn, Ln, Pn, En, An, Qn denotes independently an undefined integer indicating the number of the corresponding parameter. The numeral n can denotes for example any integer comprised between 1 to 1000 or 1 to 100 or 1 to 50 or 1 to 10.

[0160] The term "analytical sequence" here determines any series of actions related to a sample under tests until one or several tests results, preferably until the required test results, are obtained. Such an analytical sequence comprises or consists on the activation of at least a first path,PFLEX-2-PCTactivation of at least one of the first 2 and / or second 3, where applicable, detection means so as to detect a parameter of a sample collection of the corresponding detected parameters, computing of the corresponding test results, and initiating at least a second activation of at least a first path, activation of at least one of the first 2 and / or second 3, where applicable, detection means, while the analysis has not been stopped. Any suitable parameter is here considered It can be related to the sample and / or the device. Such a parameter includes fluorescence signals or other signals of metabolic activity, luminescence, growth, dead / alive status of microorganisms, proteins / metabolites / Nucleic acid / lipids interactions throughout various methods,

[0161] The above-mentioned example of device arrangement and method steps are not understood to be limitative. For example, some or all of the detection unit 4, the computing unit 5 and the command unit 6 can be physically distinct devices or combined modules. Where applicable, they can share some common electronical elements. Device can be combined with washing / purification / extraction or concentration accessories (e.g. for blood / urine samples analysis, for environmental samples extraction, for processes monitoring & control, ...).

[0162] Device may be miniaturized to such an extent so as to become implantable (e.g. in living beings or in contact with living beings, ...).

[0163] According to an embodiment, the present device may be used by a user without specific skills. For example, the device can be used for at-home sample analysis such as blood sample analysis.

[0164] According to an embodiment, the computing unit is configured to perform combinatorial screening by generating and testing a plurality of candidate formulations through parallel droplet mixing and detection.

[0165] According to an embodiment, the computing unit is configured to execute combinatorial screening protocols, wherein multiple dropletsPFLEX-2-PCTcontaining different reagents are mixed in parallel to generate a library of candidate formulations. Each candidate is formed by merging a unique combination of droplets in predetermined ratios, followed by parallel detection of one or more physico-chemical or biological parameters. For example, in pharmaceutical research, droplets containing different concentrations of active compounds, excipients, or adjuvants may be combined to generate hundreds of unique test formulations on-chip. Similarly, in food or fragrance applications, droplets of flavor components can be merged in systematic combinations, with parallel testing zones providing simultaneous readouts of stability, volatility, or sensory proxies. This arrangement enables high-throughput exploration of large parameter spaces within a single analytical cycle.

[0166] According to another embodiment, combinatorial screening can generate and test libraries of 10x10 candidate formulations, corresponding to 100 distinct droplet combinations analysed in parallel within less than about 30 minutes, demonstrating the capacity of the system for true high- throughput screening.

[0167] According to another embodiment, combinatorial screening can generate and test libraries of 6x6 candidate formulations against 5 pathogens, corresponding to 180 distinct droplet combinations analysed in parallel within less than about 45 minutes, demonstrating the capacity of the system for true high-throughput screening.

[0168] According to an embodiment, the computing unit 5 is configured to execute high-throughput screening protocols for applications such as pharmaceutical or agrochemical formulation development. For example, droplets comprising candidate active ingredients, such as pharmaceutical compounds or fungicides can be combined with droplets of excipients, adjuvants, synergists, or buffer systems in systematically varied ratios across multiple testing areas T1, T2...Tn. The resulting mixtures can then be assayed in parallel for parameters such as solubility, stability, cytotoxicity, or, in an agro science context, for their inhibitory effect on the growth of a target pathogen using thePFLEX-2-PCTembedded detection means 2, 3. The computing unit 5 automatically selects promising formulations based on the detected results, cancels redundant tests, and reiterates combinations of interest with adjusted concentrations, thereby enabling accelerated identification of optimized drug or agrochemical formulations on-chip.

[0169] According to an embodiment, the system interfaces with pharmaceutical compound libraries and Al-driven drug discovery platforms, automatically importing candidate molecules and exporting screening results to accelerate hit-to-lead optimization.

[0170] The system is capable of processing complex samples such as menstrual blood, which contains not only blood but also tissues, cells, diverse biomolecules (proteins, enzymes, hormones, metabolites), and microorganisms. Upon introduction, the system employs embedded sensors (for example, impedance or viscosity sensors) to assess key parameters of the sample, such as viscosity, conductivity, or cell content. Based on these measurements, the device can automatically adjust dilution and mixing protocols to standardize conditions, regardless of patient-to-patient or sample-to-sample variability. Once pre-analytical conditions are optimized, the sample is automatically split into multiple discrete droplets, each of which can be routed to dedicated testing zones on the chip. These zones are equipped with additional embedded sensors and can be functionalized for specific biomarker assays. For example, droplets may be directed toward electrodes or microreactors functionalized with capture antibodies for proteins, nucleic acid probes, or enzymatic substrates. Detection is performed using integrated transducers (e.g., impedance or electrochemical sensors) and / or optical means, such as in situ fluorescence detection. The system integrates surface or volume modification units to further control and compartmentalize droplets as they progress through the workflow. ForPFLEX-2-PCTinstance, if crosstalk or diffusion between adjacent droplets poses a risk to assay specificity, polymer "walls" can be formed in situ to isolate the testing zones. The system enables real-time or sequential monitoring of multiple markers within the same initial blood sample, providing a multiplexed, highly adaptable analytical workflow. By dynamically controlling splitting, dilution, and assay conditions, the platform delivers robust and reproducible results, even for highly variable and heterogeneous biological samples.

[0171] Soil extract processing: upon introduction of a heterogeneous soil extract, embedded sensors (e.g., impedance, turbidity, or particle size detectors) quickly assess key sample parameters and trigger automatic pretreatment to optimize downstream compatibility. The device then splits the extract into droplets, routing each to dedicated assay zones for rapid detection of pollutants, nutrients, or microbial DNA, with results obtained via electrical or fluorescence-based readouts. To replicate complex soil microenvironments, surface or volume modification units are employed to generate gel barriers or create artificial porous matrices within the chip. This not only enables the physical isolation of droplets for sensitive reactions but also allows the study of how microbes or chemicals interact within simulated soil structures, supporting advanced environmental analyses directly on-chip.

[0172] other embodiments

[0173] According to some embodiments, the invention hereby described can be defined by one of the below feature or any combination thereof:The microdroplet actuating system is adapted to perform an analytical sequence.It may comprise at least one working surface or working volume S comprising programmable fluidic routing circuits E1, E2, ..., En configured to guide one or more droplets D1, D2, ..., Dn along one or more adjustable fluidic paths P1, P2, ..., Pn, wherein the working surface or volume comprises at least onePFLEX-2-PCTreservoir area R1, R2, Rn, at least one testing area T1, T2, Tn, and at least one sample pre-analysis area SP1, SP2, SPn.The microdroplet actuating system may comprise one or more first detection means 2 embedded in or on the working surface or volume, adapted to determine parameters of the droplets or fluids, said parameters including but not limited to impedance, conductivity, size, pH, or other electrical, physical, or chemical properties, and configured to permit multiple sensing events on the same or different droplets under varying conditions as they traverse dedicated paths;The microdroplet actuating system may comprise one or more second detection means 3, distinct from said first detection means, adapted to detect one or more additional parameters related to the droplets, said second detection means optionally being non-contact and / or moveable;The microdroplet actuating system may comprise a detection unit 4 configured to receive and combine data from both the first and second detection means, thereby enabling improved accuracy and reliability of detection, and further configured to automatically re-initiate detection processes and perform reliability testing as required;The microdroplet actuating system may comprise a computing unit 5 adapted to process the collected data to generate detection results, to execute programmable control logic, and to trigger or modify analytical protocols in response to said results;The microdroplet actuating system may comprise a command unit 6 configured to independently and dynamically activate and deactivate both the programmable fluidic routing circuits and the detection means, such that the system can control the timing, duration, and location of both droplet movement and detection operations during the analytical sequence;PFLEX-2-PCTThe command unit 6 is operably connected to the computing unit 5 such that the fluidic paths P1, P2, Pn and the detection operations are automatically determined, initiated, adjusted, or modified in real time according to the detection results during an analytical sequence, thereby enabling self- adjusting, feedback-driven optimization of droplet manipulation and detection without requiring external intervention;The detection unit 4, computing unit 5, and command unit 6 are optionally implemented as a single multifunctional integrated module comprising sensing, processing, and actuation functionalities;The system may comprises a local surface or volume modification units U1, U2, ..., Un configured to block, open, or redirect at least one fluidic path through reversible or irreversible physical or chemical mechanisms, said mechanisms being triggered either automatically in response to droplet presence or reaction (including, but not limited to, polymerization or evaporation), or under active control by the computing unit based on detection results. According to an embodiment, the local surface or volume modification units U1, U2, ..., Un specifically comprise devices configured to trigger polymerization and or gelatinization between two contiguous different nature droplets, thereby generating a barrier or channel as a particular case of the general blocking or redirecting functionThe microdroplet actuating system according may comprise one or more auxiliary devices adapted to induce physical or chemical transformations within at least one droplet D1, Dn and / or on the working surface or within the working volume S, such as light irradiation devices, thermoregulation devices, or humidity regulation devices, said auxiliary devices being configured primarily to facilitate or modulate analytical reactions or sample conditioning, and not primarily intended to directly block, open, or redirect fluidic paths, such functions being provided by the local surface or volume modification units U1, U2, ..., Un as defined above. It is understood that certain devices, such as light sources or heating elements, may serve as bothPFLEX-2-PCTauxiliary devices and local surface or volume modification units U1-Un, depending on their configuration and intended use.The devices can be categorized according to their primary function within the analytical sequence.The at least one reservoir area R1, R2, Rn can denote at least a first reservoir area R1 comprising a first liquid L1 and a second reservoir area R2 comprising a second liquid L2 and wherein said one or several paths P1, P2, Pn denotes at least a first path P1 between said first reservoir area R1 and said at least one testing area T1, T2, Tn and a second path P2 between said second reservoir area R2 and said at least one testing area T1, T2, Tn.The at least one reservoir area R1, R2, ..., Rn is in fluidic connection with at least one external container C1, C2, ..., Cn and / or auxiliary equipment, said auxiliary equipment comprising, for example, automated liquid handling devices, pipetting robots, multi-channel pipettes, or cartridge-based reagent dispensers, wherein the system is configured to receive, transfer, or withdraw droplets, fluids, samples, or reagents to and from said reservoirs by means of pipetting, dispensing, aspiration, or similar techniques, thereby ensuring compatibility with standard laboratory automation workflows and enabling automated, high-throughput, or walk-away operation.

[0174] According to an embodiment, the microdroplet actuating system 1 achieves diagnostic sensitivity in the nanomolar to picomolar range, depending on the biomarker or analyte tested, and can deliver results within 10-20 minutes from sample introduction. Specificity can exceed 95% when combining impedance-based detection with optical confirmation, ensuring clinical-grade reliability for point-of-care diagnostics.

[0175] According to an embodiment, multiple devices are deployed as nodes of an Internet of Things (loT) network, continuously sampling water, air, or soil quality in the field and transmitting results to centralizedPFLEX-2-PCTdashboards. This arrangement enables real-time environmental surveillance for smart city infrastructures, agriculture, or water utility management.A microfluidic path P1 of 20 pm height may be filled with a 10% aqueous starch solution. Upon heating to 70 °C for 3 minutes, gelatinization occurs, forming a stable gel barrier 200 that temporarily blocks droplet movement.After completion of the analytical cycle, the barrier is removed by flushing with warm water at 50 °C, thereby restoring the path without requiring chemical depolymerisation. This example demonstrates the suitability of gelatinization as a reversible structuring mechanism in the present microdroplet actuating system, particularly in applications where biocompatibility and simple removal are advantageous.PFLEX-2-PCTreference symbols in the figures1 Microdroplet actuating system11 Top surface12 Bottom surface2 First detection means20 Light source21 Exciting light22 Waveguide3 Second detection means30 Light sensor31 Emitted lightS Working surface4 Detection unit5 Computing unit6 Command unit7 Databases8 User9 humidity regulation device100 Capillaries101 Capillaries electrodes102 Helical electrodes103 Capillaries coating200 Polymerised barrier300 ChannelM Microtiter plateD1, D2, Dn DropletsL1, L2, Ln LiquidsE1, E2, En Guiding ElementsP1, P2, Pn PathsR1, R2, Rn ReservoirsT1, T2, TnPFLEX-2-PCT

Claims

Claims1. A microdroplet actuating system (1) adapted to perform an analytical sequence of one ore more droplets (D1, D2, Dn) of one or more liquids (L1, L2, Ln) comprising:- At least one working surface (S) provided with activable guiding elements (E1, E2, En) adapted to guide said one or several droplets (D1, D2, Dn) along one or several paths (P1, P2, Pn) on said at least one working surface (S), wherein said at least one working surface (S) comprises a top surface (11) and a bottom surface (12) between which said at least one droplet is actuated,- one or more first detection means (2) adapted to detect one or several first parameters related to said at least one droplet (D1, D2, Dn), said one or more first detection means being fix and / or embedded in said at least one working surface (S),- one or more second detection means (3) adapted to detect one or several second parameters related to said at least one droplet (D1, D2, Dn), or to cooperate with said one or more first detection mean (2) so as to sense at least one parameter of said at least one droplet (D1, D2, Dn),- a detection unit (4) adapted to collect the data detected by said one or more first detection means (2) and / or said one or more second detection means (3),- a computing unit (5) adapted to compute said data collected by said detection unit (4) so as to provide detection results,PFLEX-2-PCTa command unit (6) adapted to independently activate and deactivate said activable guiding elements (E 1 , E2, En) so as to guide said one or several droplets (D1, D2, Dn) along one or several paths (P1, P2, Pn, characterized in that said command unit (6) is connected to said computing unit (5) so that said one or several paths (P1, P2, Pn) are automatically determined according to said detection results during an analytical sequence.

2. A microdroplet actuating system according to claim 1 , further comprising at least one auxiliary transformation device adapted to trigger polymerisation of liquids (L1, L2, Ln) present in two contiguous droplets (D1, D2, Dn) so as to create a polymerised barrier (200), the command unit (6) being adapted to independently activate and deactivate said auxiliary transformation device.

3. A microdroplet actuating system according to one of claims 1 or 2, wherein said command unit (6) is connected to said computing unit (5) so that said liquid polymerisation is automatically initiated between two contiguous droplets, based on said detection results4. A microdroplet actuating system according to one of claim 2, wherein said at least one auxiliary transformation device is adapted to initiate transformations within said one or several droplets (D1, D2, Dn), and includes one or more of light irradiation devices, thermoregulation devices, or humidity regulation device.

5. A microdroplet actuating system according to one of claim 1 to 4, further comprising or being connected to one or more auxiliary equipment such as an olfactometry device or headspace sampler adapted to detect volatile aromatic compounds.PFLEX-2-PCT6. A microdroplet actuating system according to one of claims 1 to 5, further comprising at least one reservoir area (R1, R2, Rn) and / or one capillary (100) adapted to feed said one or more liquid (L1, L2, Ln) to said working surface (S),7. A microdroplet actuating system according to one of claims 1 to 6 further comprising at least one container (C1, C2, Cn), wherein said at least one reservoir areas (R1, R2, Rn) and / or said at least one capillary (100) are in fluidic connection with said at least one container (C1, C2, Cn).

8. A microdroplet actuating system according to one of claims 1 to 7, wherein said detection unit (4) and / or said computing unit (5) comprise or are connected to an artificial intelligence module.

9. A microdroplet actuating system according to one of claims 1 to 8, further comprising or being further combined to databases (7).

10. A microdroplet actuating system according to one of claims 1 to 9, wherein said computing unit (5) is adapted to automatically generate, adapt or model an analytical sequence.

11. A microdroplet actuating system according to one of claims 1 to 10, wherein said computing unit (5) is adapted to automatically adjust or modify an ongoing analytical sequence based on said detection results.

12. A microdroplet actuating system according to one of claims 1 to 11, wherein said one or several paths (P1, P2, Pn) are automatically activated, adjusted, reiterated or cancelled, and / or said at least one auxiliary transformation device is automatically activate by said computing unit (5), during an ongoing analytical sequence, based on said detection results.PFLEX-2-PCT13. A microdroplet actuating system according to one of claims 1 to 12, wherein said polymerised barrier (200) forms a logic gate, which conditionally permit or prevent the droplet progression.

14. A microdroplet actuating system according to claim 13, wherein said fluidic logic gates are arranged to form a microfluidic logic circuit implementing AND, OR, or NOT functions.

15. A microdroplet actuating system according to one of claims 1 to 14, comprising more than one working surface (S) arranged on above each other, and fluidly connected to each other by mean of at least one capillary (100).

16. A microdroplet actuating system according to one of claims 7 to 15, wherein said at least one container (C1, C2, Cn) is arranged beside said at least one working surface (S) and fluidly connected to said at least one reservoir (R1, R2, Rn) so as to feed said at least one working surface (S).

17. A microdroplet actuating system according to one of claims 7 to 16, wherein said at least one container (C1, C2, Cn) is arranged beneath said at least one working surface (S) and fluidly connected to said at least one working surface (S) by means of said at least one capillary (100).

18. A microdroplet actuating system according to one of claims 7 to 17, wherein said at least one capillary (100) denotes a fibre pump comprising continuous helical electrodes (102), and / or comprises electrodes and / or an internal coating adapted to drive said one or more liquids (L1, L2, Ln) from said at least one containers (C1, C2, Cn) to said at least one working surface (S).

19. A microdroplet actuating system according to one of claims 1 to 18, wherein said polymerised barrier (200) denotes or comprises porous and / or gel-like matrices.PFLEX-2-PCT20. A microdroplet actuating system according to one of claims 1 to 19, wherein said first detection means (2) is adapted to measure turbidity, conductivity, and / or particle size of said at least one droplet (D1, D2, Dn).

21. A microdroplet actuating system according to one of claims 1 to 20, wherein the microdroplet actuating device is packaged as a sealed disposable cartridge.

22. A microdroplet actuating system according to claim 21, wherein said cartridge comprises hermetically sealed input / output ports to prevent operator exposure.

23. A microdroplet actuating system according to one of claims 21 and 22, wherein the cartridge includes pre-stored reagents and / or diluents for multiplexed biomarker analysis and is configured for single-use disposal with biohazard containment.24.A microdroplet actuating system according to one of claims 21 to 23, wherein said cartridge is adapted for at-home sample introduction, including blood, saliva, urine, sweat, nasal swabs collected or menstrual fluid in diluted or undiluted form.

25. A microdroplet actuating system according to one of claims 1 to 24, wherein the device comprises one or more Reservoirs used as inlet and / or outlet ports (R1, R2...Rn) arranged on or adjacent to the working surface S, said ports being positioned in a regular array whose pitch corresponds to standardized well-plate formats, including 9 mm for 96-well plates, 4.5 mm for 384-well plates, or 2.25 mm for 1536-well plates, such that the ports are directly accessible by single-channel or multi-channel pipettes and robotic pipetting heads, and optionally comprise geometries and / or adapters compatible with syringe interfaces or automated liquid handlers.PFLEX-2-PCT26. A microdroplet actuating system according to one of claims 2 to 25, wherein said auxiliary transformation device is selected from heating elements, UV light sources, or humidity controllers, configured to act on at least one droplet.

27. A microdroplet actuating system according to one of claims 1 to 26, wherein the at least one working surface (S) comprises at least one testing area (T1, T2, T3).

28. A microdroplet actuating system according to one of claims 1 to 27, further comprising one or more pretesting areas.

29. A microdroplet actuating system according to one of claims 1 to 28, wherein said first detection means (2) comprises an impedance or electrochemical sensor, and said second detection means (3) comprises an optical detector configured for colorimetry, fluorescence or absorbance.

30. A microdroplet actuating system according to one of claims 1 to 29, wherein the computing unit (5) is configured to execute diagnostic protocols stored in an artificial intelligence or expert system module.

31. A microdroplet actuating system according to one of claims 7 to 30, wherein said at least one reservoir area is f I uidically connected to auxiliary analytical equipment selected from mass spectrometers, chromatographs, or PCR devices.

32. A microdroplet actuating system according to one of claims 1 to 31, further comprising a wireless communication unit adapted to transmit test results to a remote server or portable device.

33. A microdroplet actuating system according to one of claims 1 to 32, wherein said first detection means is a thermal sensor or a pH sensor.PFLEX-2-PCT34.A microdroplet actuating system according to one of claims 1 to 33, wherein the second detection means is a colorimetric imaging unit.

35. A microdroplet actuating system according to one of claims 1 to 34, wherein the command unit (6) is configured to selectively deactivate at least one detection means to reduce power consumption.

36. A microdroplet actuating system according to one of claims 1 to 35, wherein the command unit (6) is configured to control ratios of merged droplets so as to produce formulations comprising different proportions of flavor or fragrance components.

37. A microdroplet actuating system according to one of claims 1 to 36, wherein the command unit (6) is configured to perform combinatorial screening by generating and testing a plurality of candidate formulations through parallel droplet mixing and detection.

38. A microdroplet actuating system according to one of claims 1 to 37, further comprising a remote server configured to receive data from a wireless communication unit and to execute cloud-based diagnostic algorithms.

39. A microdroplet actuating system according to one of claims 2 to 38, wherein the auxiliary transformation device is configured to simulate volatility or controlled release of at least one flavor or fragrance component under conditions of heat or humidity.

40. An analytical method comprising automatically generating an analytical sequence and / or automatically modifying an ongoing analytical sequence by mean of the computing unit (5) of a microdroplet actuating system according to one of claims 1 to 39.PFLEX-2-PCT41. An analytical method according to claim 40, wherein said analytical sequence is automatically generated or selected based on information available in one or more databases, and initial instructions of a user including one or more of the purpose of the analytical sequence, the nature of the sample to be tested.

42. An analytical method according to one of claims 40 and 41, wherein said analytical sequence is automatically modified based on the parameters determined by one or more of the first (2) and second (3) detections means and predetermined conditions (Q1, Q2, Qn) and actions (A1, A2, An).

43. An analytical method according to one of claims 40 to 42, further comprising generating an analytical report, wherein the steps which have been automatically generated and / or modified are documented.44.An analytical method according to one of claims 40 to 43, further comprising feeding one or more knowledge database(s) with data usable for one or more model improvement, population statistics detection, pandemic identification and best treatments, before, during or after the sequence.

45. An analytical method according to one of claims 40 to 44, wherein said analytical sequence comprises activating at least one auxiliary transformation device adapted to trigger polymerisation of liquids (L1, L2, Ln) present in two contiguous droplets (D1, D2, Dn) so as to create a polymerised barrier (200).

46. An analytical method according to one of claims 40 to 45, wherein said analytical sequence comprises a step of gelatinisation of liquids (L1, L2, Ln) present in two contiguous droplets (D1, D2, Dn) so as to create a gelatinized barrier (200).

47. A microdroplet actuating system (1) adapted to perform an analytical sequence of one or more droplets (D1, D2, Dn) of one or more liquids (L1,PFLEX-2-PCTL2, Ln), comprising: at least one working surface (S) provided with activable guiding elements (E1, E2, En) adapted to guide said one or more droplets (D1, D2, Dn) along one or more paths (P1, P2, Pn) on said working surface (S), one or more first detection means (2) adapted to detect one or more first parameters related to said droplets, one or more second detection means (3) adapted to detect one or more second parameters related to said droplets, a detection unit (4) adapted to collect data detected by said one or more first and / or second detection means, a computing unit (5) adapted to process said data so as to generate detection results, and a command unit (6) operably connected to said computing unit (5), said command unit being adapted to independently activate and deactivate said guiding elements (E1, E2, En), characterized in that the computing unit (5) is configured to: automatically generate and / or modify an analytical sequence in real time based on said detection results, including automatically activating, adjusting, reiterating or cancelling one or more of said paths (P1, P2, Pn), and automatically trigger predetermined actions (A1, A2...An) in response to predetermined conditions (Q1, Q2...Qn) derived from said detection results, wherein said analytical sequence is thereby continuously adapted during its execution without requiring completion of a full analytical cycle.

48. An automated analysis system comprising a microdroplet actuating system according to any one of the preceding claims, characterized in that it further comprises: a. at least a first robotic system configured to prepare samples by transferring liquids to and from said microdroplet actuating system to a microtiter plate; b. at least a second robotic system configured to manage said microtiter plate; c. at least one environmentally controlled incubator; d. at least one plate reader;PFLEX-2-PCTwherein said second robotic system is configured to repeatedly transfer said microtiter plate between said incubator and said plate reader to perform kinetic measurements over a prolonged period of time.

49. The analysis system according to claim 48, wherein the first robotic system is dedicated to handling sterile consumables and chemical reagents, and the second robotic system is exclusively dedicated to handling microtiter plates containing biological cultures.

50. An analysis method using a system according to claim 48 to 49, characterized in that it comprises the steps of: a. preparing one or more sterile chemical mixtures on said microdroplet actuating system; b. transferring said sterile chemical mixtures to an external receptacle, such as a microtiter plate; c. adding a biological substance into said external receptacle after the transfer step, such that said biological substance never comes into contact with the microdroplet actuating system, thereby preventing biofouling of the system51. A combinatorial screening method using a system according to any one of the preceding claims, characterized in that it comprises the steps of: a. providing a plurality of disposable cartridges; b. preparing all mixtures for a single, unique pair of chemical compounds (Ci, Cj) on one single and unique cartridge; c. discarding said cartridge after the preparation of all mixtures for said unique pair; d. repeating steps b and c with a new cartridge for each new unique pair of chemical compounds to be tested, thereby eliminating cross-contamination between the pairs.

52. A microdroplet actuating system according to any one of claims 5 or 31, wherein the auxiliary equipment is a continuous-flow droplet-based microfluidics (DBM) system.PFLEX-2-PCT53. The system according to claim 52, further comprising a robotic interface configured to transfer the mixtures prepared by the microdroplet actuating system to serve as the starting conditions for an ultra-high-throughput screening on said system (DBM).PFLEX-2-PCT

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