MEMBRANE INSERT IN A RESELLABLE CHIP ORGAN PLATFORM.

Abstract

The present invention relates to a resealable organ-on-a-chip platform, comprising a rectangular base (408) with at least one hole in its central part and an orifice at each of its two ends (608); at least four connecting tubes (401, 401', 406, 406'); at least one transfer device between conventional wells (404); at least one sealant to adapt to a transfer device (402, 402'); a fluidic communication channel (607); at least one lower fluidic chamber (507); at least one mixing chamber (508); and wherein the assembly of each element to form the resealable organ-on-a-chip platform is characterized in that: two connecting tubes (401, 401') pass through the sealer (402, 402') until they contact the transwell(r) insert (504) placed on top of the transwell(r) membrane (505) of the conventional inter-well transfer device (404);the sealant (402, 402') may or may not be adapted to the top of the conventional inter-well transfer device (404); the conventional inter-well transfer device (404) is placed inside the central cavity of the rectangular base (408); two connecting tubes (406, 406') are coupled to each of the terminals at each end of the rectangular base (408); and wherein the fluidic communication channel (607); the lower fluidic chamber (507) and the mixing chamber (508) are located below the central cavity of the rectangular base structure (408).

Description

INSERT BASED ON A RESEALABLE ORGAN-ON-CHIP PLATFORM TECHNICAL FIELD OF THE INVENTION The present invention generally relates to cell and tissue culture devices and methods and more particularly to an insert based on a resealable organ-on-a-chip platform, wherein said insert is of the transwell® type. BACKGROUND OF THE INVENTION Transwell® (transport between wells) is a membrane substrate or insert used for cell and tissue culture between agar wells. It is commonly used in the biological laboratory for various applications, including cell migration assays to measure the number of cells crossing a porous membrane and cell invasion assays to monitor cell movement through extracellular matrices. Transwell® permeable carriers are convenient and easy-to-use devices for both anchorage-dependent and anchorage-independent cell studies. These inserts provide independent access to both sides of a monolayer, giving researchers a versatile tool for studying transport and other metabolic activities in vitro. ML / a / ZUZU / UU 1101 However, working with conventional well transfer involves manual steps for changing samples and media. Furthermore, the platforms are not flexible enough for continuous flow, applying shear stress, and other cellular manipulation that occurs in the mammalian body. Therefore, their application and implementation are limited, and they are primarily used in animal models for testing more complex cell analyses and drug discovery. Clinical studies in transwell® take years to complete, and testing a single compound can be very costly. Meanwhile, countless animal lives are lost, and the process often fails to predict human responses because traditional animal models frequently do not accurately mimic human pathophysiology. For these reasons, there is a great need to find alternative ways to model human diseases in vitro, to accelerate the development of new drugs, and to advance personalized medicine. Therefore, there remains a great need for techniques, devices, and methods for cell and tissue culture, which are of paramount importance to the development of the present invention. Devices and methods for cell and tissue monitoring and culture are known in the prior art. For example: Mexican patent application No. MX / a / 2019 / 012509, entitled “SYSTEMS, DEVICES AND METHODS FOR MICROFLUID ANALYSIS,” describes systems, devices, and methods for analyzing a biofluid, as well as controlling a biofluid analysis system using a microfluidic device. The described biofluid analysis system modalities can provide the analysis of a biofluid to identify and characterize one or more analytes. An apparatus may include a first layer defining a first opening and a second opening. The first layer may be substantially transparent. A second layer may be coupled to the first layer and define a microfluidic channel establishing a fluid communication pathway between the first and second openings. At least a portion of the second layer may be substantially opaque. Chinese patent application No. CN108148885 (A) entitled “METHOD FOR EVALUATING THE CARDIOTOXICITY OF A METABOLISM-DEPENDENT DRUG BASED ON A MICROFLUIDIC CHIP” describes: “a method for evaluating the cardiotoxicity of a metabolism-dependent drug based on a microfluidic chip. The transwell® visual microfluidic chip is adopted, in which the upper layer of the microfluidic chip is inoculated with Hepg2 cells, and the lower layer of the microfluidic chip is inoculated with human induced pluripotent stem cells; meanwhile, in situ induced differentiation towards myocardial cells is implemented; the microfluidic chip is made of a lightweight, gas-permeable polydimethylsiloxane polymer; the ratio of a polydimethylsiloxane monomer to an initiator is (15-5):1; a polycarbonate membrane is used as the filter membrane material porous, and the opening of the polycarbonate membrane is 0.01-10[p]m; the lower surface of the upper layer of the microfluidic chip is irreversibly sealed to the porous filter membrane; and the upper surface of the lower layer of the microfluidic chip is bonded to the porous filter membrane via polydimethylsiloxane. The cardiotoxicity assessment method provided by the invention, which uses the microfluidic chip as a platform, achieves the in vitro construction of a model for assessing the cardiotoxicity of metabolism-dependent drugs under near-physiological conditions, thus providing an important platform for the development and screening of metabolism-dependent drugs.” United States patent application US 2018 / 0348203 A1, entitled “METHODS AND APPARATUS FOR MODELING CANCER METASTASIS IN VITRO,” describes an apparatus useful for examining cancer cell metastasis, including: (a) a primary chamber; (b) at least one secondary chamber; (c) at least one primary conduit connecting the primary and secondary chambers and providing fluid communication between them; (d) a primary organoid in the first chamber, the primary organoid comprising mammalian cancer cells; (e) at least one secondary organoid separately selected for and in the secondary chamber(s); and (f) optionally a growth medium in the primary chamber, in each of the secondary chambers, and in the primary conduit. The apparatus may be used in drug screening and development methods, and in personalized medicine. Cell culture accessories for conventional interwell transfer devices are permeable, convenient, and easy-to-use support elements for studying both adhesion-dependent and adhesion-independent cell lines. They are designed to produce a cell culture environment that closely resembles the in vivo state. All membranes of these ML / a / ZUZU / UU 11 OI transfer devices are compatible with histological fixatives such as methanol and formaldehyde and where polyester membranes have the best overall chemical resistance. Organ-on-a-chip platforms are replacing animal models for various bio-applications, including drug discovery and organ transplant biocompatibility testing. However, most biologists in laboratories still prefer using transwell® instead of microfluidic organ-on-a-chip devices. Conventional interwell transfer devices are much cheaper than an organ-on-a-chip, and biologists are already accustomed to working with them. Furthermore, moving from a Petri dish (a round glass container that can be placed on top of and closed, though not hermetically) to a chip means changes to the entire structure of the cell culture area, requiring recalibration of experiments and reference results that are not always available or vary from laboratory to laboratory and chip to chip.Additionally, the transfer devices have a removable or detachable cell culture section (transwell® insert), where the cells / tissues grow on a membrane, and this allows the cells / tissues to be moved to another well plate, to the microscope, or to the cutting of the membrane for different tests. iviA / a / ¿u¿u / uu 11 oí On the other hand, organ-on-a-chip platforms allow for the continuous injection and extraction of samples and cells, the induction of biomechanical shear forces in the cell, and the insertion of various biosensors onto the chip. However, many organ-on-a-chip platforms are not resealable and, generally, cannot be used once opened to verify a section of the chip, the membrane, or a cell / tissue parameter. Even recently, there remains a need for improvements in cell and tissue culture techniques, including low costs, ease of technology implementation, technology compatibility, application techniques, and rapid attainment of expected results. SUMMARY OF THE INVENTION This section provides a general summary of the invention and is not an exhaustive description of its full scope or all its features. In one way, the present description addresses the lack of compatibility of techniques and technologies used for cell and / or tissue culture; one objective of the present invention is to design a fluidic platform, merging the advantages of transwell® and a conventional organ into a chip platform. Therefore, it is an aspect of the present invention to use a conventional transwell® insert for cell tissue culture, and that it is convenient for the biologist to use such a device and compare his results with data widely available in the literature. Another object of the present invention is to develop a sealant or cover for conventional inter-well transfer devices, wherein the sealant for iviA / a / ¿u¿u / uu 11 oí transfer devices is removable and permeable to gases, isolating the upper part of the cell culture membrane from the environment and allowing the accommodation of various fluid inlet and outlet connections (for gas and media injection, sampling and shear force application), as well as electrodes for TEER, oxygen sensor, electrochemistry, etc. It is another object of the present invention to provide a transfer device, containing the cell culture membrane, being resealable / reopenable and that when closed, completely seals the bottom of the cell culture membrane from the environment and thus, unlike a conventional interwell transfer device, the novel organ-on-a-chip can be used outside the fume hood and a clean area. It is also another object of the present invention to provide a transfer device whose lower chamber, located below the membrane, is designed to accommodate various input / output connections, biosensors, as well as an additional compartment for mixing (e.g., magnetic mixing). It is also another object of the present invention to provide a transfer device whose design allows for the containment of several transfer devices between conventional wells with cell cultures and similar or different fluid conditions. ML / a / ZUZU / UU 1101 Another object of the present invention is to manufacture printed molds in 3D and / or PMMA using commercially available transwell® inserts; Considering the geometry, number of fluidic connections and transwell® inserts, as well as the size, type, and porosity of the membrane, all of which can be easily adjusted to meet customer needs. This allows for a much more flexible, faster, and cheaper manufacturing protocol. It is yet another object of the present invention to provide a gas-permeable organ-on-a-chip platform (made of PDMS polydimethylsiloxane material), enabling testing in common CO2 incubators, similar to a transfer device. Yet another object of the present invention is to provide an organ-on-a-chip platform in different sizes to accommodate different sizes of transwell® insert. Yet another objective of the present invention is to provide an integral organ(s)-on-a-chip device that more realistically resembles biological systems and where the results of tests with our chips can be compared with widely available data, meaning that our chips are a universal platform. Yet another object of the present invention is to provide an organ-on-a-chip platform whose design allows easy access on both sides of the membrane, which facilitates the cultivation of different cells and bacteria on each side of MA / a / xíUZU / UU 1101 the membrane. Another object of the present invention is to provide a microfluidic device that uses body fluids or solutions containing cells or cell parts to diagnose diseases, wherein the cell membrane is removable. These and other objects of the present invention are achieved by means of a resealable organ-on-a-chip platform, comprising a rectangular base (408) with at least one hole in its central part and an orifice at each of its two ends (608); at least four connecting tubes (401, 401', 406, 406'); at least one transfer device between conventional wells (404); at least one sealant for adapting to a transfer device (402, 402'); a fluidic communication channel (607); at least one lower fluidic chamber (507); at least one mixing chamber (508); and wherein the assembly of each element to form the resealable organ-on-a-chip platform is characterized in that: two connecting tubes (401,401') pass through the sealant (402, 402') until they contact the transwell® insert (504) placed on top of the transwell® membrane (505) of the conventional inter-well transfer device (404);the sealant (402, 402') may or may not be adapted to the top of the conventional inter-well transfer device (404); the conventional inter-well transfer device (404) is placed inside the central cavity of the rectangular base (408); two connecting tubes (406, 406') are coupled to each of the terminals at each end of the rectangular base (408); and wherein the fluidic communication channel (407); the lower fluidic chamber (507) and the mixing chamber (508) are located below the central cavity of the rectangular base structure (408). BRIEF DESCRIPTION OF THE DRAWINGS. In order to make the invention fully understood, several forms thereof will now be described, by way of example, with reference to the drawings attached to this document, in which: FIGURES 1A, 1B, 1C, 1D and 1E show transwells® or conventional inter-well transfer devices, where such devices belong to the state of the art. FIGURE 2 is a perspective view of the organ-on-a-chip platform made of transparent material, including a conventional transfer device, according to a first embodiment of the present invention. FIGURE 3 is a right-side view of the organ-on-a-chip platform, which includes the conventional transwell®; a cover and connecting tubes; in accordance with a first embodiment of the present invention. FIGURE 4 is a front perspective exploded view of the organ-on-a-chip platform, which includes a transfer device, the cover of said transfer device, and connecting tubes; in accordance with a first embodiment of the present invention. FIGURE 5 is a perspective exploded side view of the organ-on-a-chip platform, which includes a transfer device, the cover of said transfer device, and connecting tubes; in accordance with a first embodiment of the present invention. FIGURE 6 is a right-side view of a dual-organ-on-a-chip platform in accordance with a second embodiment of the present invention. FIGURES 7A, 7B, 7D, and 7E show molds for manufacturing the organ-on-a-chip platform, in accordance with the present invention. FIGURE 8A is a top front view of the organ-on-a-chip platform in use, which includes an external motor at its bottom. FIGURE 8B is a perspective view of the organ-on-a-chip platform in use, which includes an external motor at its bottom. DETAILED DESCRIPTION OF THE INVENTION ML / a / ZUZU / UU 1101 The following description is merely illustrative and is not intended to limit the present invention, its application, or uses. It should be understood that throughout the drawings, the corresponding reference numbers indicate similar or corresponding parts and features. The present invention describes cell and tissue culture devices and methods and more particularly a transwell® insert based on a resealable organ-on-a-chip platform. Figures 1A, 1B, 10, 1D and 1E show transwell® or conventional inter-well transfer devices belonging to the state of the art. 1. Implementation of the organ-on-a-chip platform according to a first embodiment of the invention. The elements that make up the organ-on-a-chip platform are: a rectangular base with a hole in its central part and a hole at each of its two ends (408); at least two connecting tubes (401,401', 406, 406'); at least one transfer device between conventional wells (404); at least one sealant, cap or cover for said transfer device (402, 402'); ML / a / ZUZU / UU 11 OI two fluidic communication channels (407) a lower fluidic chamber (507) and a mixing chamber (508). The process for assembling the various elements comprising the organ-on-a-chip platform (408) in accordance with a first embodiment of the present invention is described below. FIGURES 2, 3, 4 and 5 show each of the elements that make up the organ-on-a-chip platform according to a first modality of the present invention. FIGURE 2 shows the conventional well transfer device (404) placed in the central cavity or hollow of the organ-on-a-chip platform (408), wherein said organ platform also comprises two accessible ports (201, 201') located at each of its ends and coupled to each of the terminals of each fluidic communication channel (407), additionally it can be observed that said transfer device includes two connecting flexible tubes or hoses (401,40Γ). Specifically, FIGURE 3 shows how the conventional well transfer device (404) is placed in the central cavity of the base of the organ-on-a-chip platform (408), said organ-on-a-chip platform further comprising a lower fluidic chamber (507) and a fluidic communication channel (407) at each of its ends, wherein each fluidic communication channel (407) is coupled to each of the connecting tubes (406, ML / a / ZUZU / UU 11 OI and where the preferred material is transparent and is selected from the polydimethylsiloxane group, PDMS or dimethicone, which is the linear polymer of dimethylsiloxane. The view in FIGURE 5 allows for easier identification of the fluidic inlet / outlet communication channels (407); the lower fluidic chamber (507) and the mixing chamber (508). The sealant (402) is removable and gas-permeable, isolating the top of the cell culture membrane from the environment and accommodating various fluid inlet and outlet connections for gas and media injection, sampling, and shear force application, as well as electrodes for TEER, oxygen sensing, electrochemistry, and other applications. The sealant (402) transforms the conventional transwell® into a resealable device using conventional techniques and adapting the resealable device to the organ-on-a-chip platform (408). 2. Implementation of the organ-on-a-chip platform according to a second modality of the invention. The dual-organ-on-a-chip platform according to a second embodiment of the present invention comprises: a rectangular base with two holes in its central part separated from each other and a hole at each of its two ends (608); four connecting tubes (401,40T, 406, 406'); MA / a / ¿U¿U / UU 11 OI two transfer devices between conventional wells (404); two senators, lids or covers for said transfer devices (402); a fluidic communication channel (607), two lower fluidic chambers (507) and two mixing chambers (508). The assembly of the various elements that make up the dual-organ-on-a-chip platform in accordance with a second embodiment of the present invention is similar to the assembly of each element of the dual-organ-on-a-chip platform in accordance with the first embodiment, which was described above. In FIGURE 6, it can be observed that the rectangular base (608) comprises two holes in its central part, separated from each other; this base (608) includes a hole at each of its two ends. The fluid communication channel (607) connects each of the two lower fluid chambers (507), allowing fluid communication through the inlet and / or outlet of each of the connecting tubes (406, 406'). The placement of each transfer device between conventional wells (404); sealant (402, 402'); fluid communication channel (607); lower fluid chamber (507); and mixing chamber (508) is identical to that described above. ML / a / ZUZU / UU 1101 3. Advantages of the present invention. It represents a model as a replacement for animal testing for drug discovery, drug delivery testing, cell / biofilm / bacteria migration assays, and permittivity testing, as well as cell invasion assays. In fact, it creates opportunities for biologists and researchers who are interested but lack the manufacturing expertise, funding, or time to begin working in the organ-on-a-chip field. • It eliminates the expertise, high technology, and high costs required to develop organ-on-a-chip platforms. It also eliminates the need for animal testing. • It increases access for biologists and researchers to organ-on-a-chip technology, primarily for drug discovery and personalized medicine. For example, for the development of a gut-on-a-chip to address challenges related to developing smart foods and medicine for colon cancer. • Manufacturing organ-on-a-chip platforms according to the present invention reduces the expenditure of funds and time. • It also reduces the number of animal tests, which are ethically compromised and whose results are generally not applicable to the human body. • Cell culture on this organ-on-a-chip platform is carried out using a conventional transwell® insert. This makes the use of the chips convenient for biologists and allows for the transfer of the insert between the chip and a conventional inter-well transfer device (404), facilitating the comparison of new data with existing data. Compared to another ML / a / ZUZU / UU 1101 Organ-on-a-Chip Platform: This new chip is resealable, meaning the transfer device (404) is covered by the sealant (402, 402'). The use of conventional transwell® on the chip also allows for cell, tissue, or bacterial culture based on conventional protocols before running the test on the organ-on-a-chip. This feature makes it convenient for researchers and biologists to use the chip for different applications and with different protocols, both new and conventional. Similar to other organ-on-a-chip platforms, the current chip we are showing is made of PDMS, which is permeable to gases. This is advantageous for aerobic cell culture applications, or by placing the chip in a CO2 incubator. This allows the chip to be used for anaerobic cell culture applications (e.g., gut-on-a-chip). • Since it is a generic plug and an action or reproduction platform that can be used for different organ-on-a-chip applications (liver, skin, blood-brain barrier, etc.), there is real interest and demand for such chips, and there are opportunities for industrial applications related to chips since researchers, pharmaceutical companies and microbiology laboratories represent a real economic market. • Similar to other technologies (such as origami plastic chip manufacturing), once the organ is placed on a resealable chip, it can be easily replicated by other research groups around the world. The invention has been described as described, but it is understood that variations may be made in several respects. Such variations shall not be considered a departure from the spirit and scope of the invention, and all such modifications may be obvious to a person skilled in the art and shall be included within the scope of the following claims. 4. Method of use. The present invention describes the cultivation of cells or bacteria on the membrane, particularly in the upper compartment of the transwell® insert. During cell culture, the transwell® insert can be placed inside the organ-on-a-chip, or cells or bacteria can be cultured in a conventional interwell transfer device (404) and then the transwell® insert can be moved from the transfer device (404) to the organ-on-a-chip. In another embodiment, the present invention also allows for the cultivation of cells and bacteria on the bottom of the membrane, as well as on the surface of the lower chamber / channel. Cell or bacterial culture media flow from / extract from the channel inlets / outlets in the sealer (402, 402'), introducing the solution (e.g., medication) and flow gases (e.g., CO2) into the lower chamber / channel through the inlet / outlet connections.The shear force is generated and adjusted by controlling the fluid flow rate in the chambers for physical manipulation of cells and bacteria (e.g., by alternating the flow or by using peristaltic pressure). Additionally, electrode sensors are placed at the inlets in both the upper and lower chambers of the transwell® insert to measure oxygen, pH, and transepithelial / transendothelial electrical resistance (TEER). The mixing chamber (508) contains a magnetic stir bar. MA / a / xíUZU / UU 11 OI externally using a shaft motor or a conventional magnetic stirrer. The magnetic stirrer creates the mixing patterns or trajectories necessary to make / co-culture 3D cell spheroids or spheres in the lower chamber. Additionally, the mixing aids in membrane or cell / bacterial tissue permeability testing. Figures 8A and 8B show the organ-on-a-chip platform in use, wherein said platform includes an external motor coupled to the mixing chamber (808) to stir the magnetic stirrer within the mixing chamber (808) of the organ-on-a-chip platform in accordance with the present invention. 5. Manufacturing method for the elements that make up the organ-on-a-chip platform FIGURE 7A shows the mold for manufacturing the sealant, cap or cover for the conventional inter-well transfer device (404) where the design of said sealant (402, 402') is not limited to that shown in the present description, it should be understood that changing and adapting the design of the shape of the sealant (402, 402') depends on the conventional transwell® and is within the scope of the present invention even though the different types of sealants are not illustrated. FIGURE 7B shows the mold for making the base layer of the platform ML / a / ZUZU / UU 11 OI organ-on-a-chip in accordance with the present invention. FIGURE 7C shows the mold for making the lower part of the mixing chamber of the organ-on-a-chip platform in accordance with the present invention. FIGURE 7D shows the mold for making the upper part of the mixing chamber, central hollow or cavity and micro-channels of the organ-on-a-chip platform in accordance with the present invention. FIGURE 7E shows various microfluidic punches for inlet / outlet and where it can be seen that the tip of each microfluidic punch is different; for example, the microfluidic punch (701) has a tip with a diameter of 5 mm; the microfluidic punch (702) has a tip with a diameter of 2 mm; the microfluidic punch (703) has a tip with a diameter of 1.25 mm; the microfluidic punch (704) has a tip with a diameter of 0.75 mm and the microfluidic punch (705) has a tip with a diameter of 0.5 mm; that is, the ducts that function as inlet / outlet comprise a thickness (or diameter) in a range of (0.5 mm to 5 mm). The material used to manufacture the platform consists of transparent thermoplastic polyurethane and dextran. The method for manufacturing and controlling this organ-on-a-chip is: iviA / a / ¿u¿u / uu 11 oí 1. Design the chip and then its respective molds. The chip is made of PDMS, glass, and a transwell® insert. The base can be made of glass or PDMS. Glass is used as the base because its surface can contain carbon, gold, ITO, silver, or other conductive electrodes for biosensors. The mold, on the other hand, can be made of many materials, as it can be 3D printed or assembled layer by layer. 2. 3D print or CNC cut the plastic layers needed to assemble a mold. 3. Assemble the plastic mold pieces using double-sided adhesive or 3D printed pieces with LEGO-style rods and holes. 4. Apply pure PDMS solution to the molds and weigh until the PDMS cures. 5. Assemble the PDMS layers through plasma bonding. 6. Use a punch of the desired / required size, which depends on the desired fluid flow and resistance, and the size of the biosensor electrode to pack / create the fluid and electrode connection ports; this can be done before or after step 5. 7. If required, if mixing chambers are available, insert magnetic bars into the lower mixing chambers. 8. Depending on the number of chambers designed / created, insert 1, 2, 3,..., n dozens of transwell® inserts in the upper chambers. 9. Seal the transwell® inserts using the seals or caps. 10. Connect the tube connectors (or pipette tips) to the injection holes. 11. Connect the tubes to the tube connectors and micro pumps, waste bottles, or other chip. 12. Adjust the pump flow rate to create the desired injection speed and shear stress within the chip. 13. Insert biosensor electrodes (e.g., pH, TEER, and oxygen sensors) into the chip from the connection holes, or connect electrodes shaped into the base glass to the biosensors. 14. If mixing is required, turn on the external magnetic stirrer (motor) at the desired rotation frequency. 15. To transfer the transwell® insert to a microscope or conventional transwell®, remove the liquid from the transwell® insert, remove the transwell® insert from the chip, and insert it into a conventional transwell® insert. Then remove the sealing cap from the transwell® insert, minimizing the risk of contamination during the transfer. There are no limits set for flow rate, electrical current, or the cell / bacteria culture procedure on the chip. Nor are there limits for the sample type or expected results. This is because these parameters are constantly evolving, even in conventional tests. In organ-on-a-chip applications, the parameters and expected results are always being modified / adjusted based on objectives and new discoveries. Similar to conventional transwells®, the results can also be interpreted in various ways using a microscope, conventional biosensors, or electrodes on a glass slide. Although this disclosure has been described with reference to preferred embodiments, those skilled in the art will recognize that changes in form and details can be made without departing from the spirit and scope of the disclosure.

Claims

CLAIMS 1. A resealable organ-on-a-chip platform, comprising a rectangular base (408) with at least one hole in its central part and an orifice at each of its two ends (608); at least four connecting tubes (401, 401', 406, 406'); at least one transfer device between conventional wells (404); at least one sealant for adapting to a transfer device (402, 402'); a fluidic communication channel (407); at least one lower fluidic chamber (507); at least one mixing chamber (508); and wherein the assembly of each element to form the resealable organ-on-a-chip platform is characterized in that: two connecting tubes (401, 401') pass through the sealant (402, 402') until they contact the transwell® insert (504) placed on top of the transwell® membrane (505) of the conventional inter-well transfer device (404);The sealant (402, 402') may or may not be adapted to the upper part of the conventional inter-well transfer device (404); the conventional inter-well transfer device (404) is placed inside the central cavity of the rectangular base (408); two connecting tubes (406, 406') are coupled to each of the terminals at each end of the rectangular base (408); and wherein the fluidic communication channel (407); the lower fluidic chamber (507) and the mixing chamber (508) are located below the central cavity of the rectangular base structure (408). MA / a / xíUZU / UU 11 OI; 2. The resealable organ-on-a-chip platform according to claim 1, characterized in that the sealant (402, 402') has at least two holes, is removable, permeable and covers the top of the conventional inter-well transfer device (404).

3. The resealable organ-on-a-chip platform according to claim 1, characterized in that the dimension of the rectangular base (408) can be increased to integrate two more holes in its central part, where two or more conventional well transfer devices (404) will be placed, each with its respective sealant (402, 402').

4. The resealable organ-on-a-chip platform according to claim 3, characterized in that the rectangular base (408) comprises a single fluidic communication channel (607) which connects to each of the lower fluidic chambers (507).

5. The resealable organ-on-a-chip platform according to claim 1, characterized in that the rectangular base (408) includes an external motor coupled to the mixing chamber (508) to stir the magnetic stirrer within the mixing chamber (508).

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