Fluid device and use thereof

Abstract

A fluidic device (100) for testing a biological material is provided. The fluidic device includes a substrate (102) having a top side (104) and a bottom side (106). The fluidic device also includes one or more fluidic components (108). Each of the one or more fluid components includes at least one chamber unit (110) in which a biological material can be received. The at least one chamber unit is defined in the substrate and extends between the top side and the bottom side. Each of the one or more fluid components further includes an inlet (112), an outlet (114), an inlet fluid channel (116) defined in the substrate and extending between the inlet and the at least one chamber unit, and an outlet fluid channel (118) defined in the substrate and extending between the at least one chamber unit and the outlet.

Description

TECHNICAL FIELD

[0001] The present invention relates to a fluidic device for testing biological material.

[0002] The present invention also relates to the use of such a fluidic device for testing biological material.

[0003] The present invention also relates to a method of drug testing using the fluidic device. BACKGROUND

[0004] Fluidic devices can be used for a variety of different applications, for example for cell or tissue culturing, for example for biopsy tissue research. So-called organ-on-a-chip devices use microfluidics together with cells to mimic physiological and mechanical conditions experienced in the body. Such organ-on-a-chip devices have found use for example in oncology.

[0005] A fluidic device can comprise two or more fluidic channels for transporting fluid to a culture chamber. For example, one channel can be used to provide nutrients and oxygen to a culture chamber, and to remove metabolic products such as carbon dioxide therefrom. Another channel can be used to provide a drug to the culture chamber. In such examples, the channels can be arranged at different depths of the fluidic device, such that one of the channels is positioned on top of the other channel, although separate from the other channel.

[0006] There remain various challenges in controlling the flow of fluid in such fluidic channels, especially when the fluidic device comprises more than one culture chamber, such as when the fluidic device comprises a substrate in which an array of culture chambers is defined.

[0007] WO 99 / 46045 Al discloses a sample support comprising at least one sample chamber for receiving a sample fluid and a distribution channel for the sample fluid connected to the at least one sample chamber. At least one distribution channel extends from each sample chamber. The sample support further comprises at least one reaction chamber, a supply channel branching from the at least one distribution channel discharging into the reaction chamber, and a vent for each reaction chamber. The dimensions of each distribution channel and each supply channel are such that fluid is transported through the distribution channel and the supply channel by capillary forces. In each reaction chamber, a means for generating capillary forces is positioned in the discharge area of the supply channel to ensure the flow of sample fluid from the supply channel into the reaction chamber.

[0008] EP 4089161 A1 discloses a substrate for testing a sample, in particular a cell or a molecule. The substrate comprises a fluidic system comprising a sample chamber configured in the substrate for storing and testing the sample and at least one liquid reservoir in fluid communication with the sample chamber. The substrate comprises a passive blocking element which is able to assume a closed position and an open position, wherein in the closed position the fluid exchange between the sample chamber and the liquid reservoir is blocked.

[0009] WO 2005 / 095262 A1 discloses a microchip having an inlet channel and an outlet channel and test channels. The test channels are in fluid communication with the inlet and outlet channels via inlets and outlets, respectively. Each test channel has one test site for detecting a specific molecule or molecular interaction. The inlets in the test channels are elevated relative to the outlets of the test channels and the outlets are elevated relative to a liquid level in the outlet channel. SUMMARY

[0010] The invention is defined by the claims.

[0011] According to an embodiment of an aspect of the present invention, there is provided a fluidic device for testing a biological material, the fluidic device comprising: a substrate having a top side and a bottom side; and one or more fluidic assemblies, each fluidic assembly comprising: at least one chamber unit in which the biological material is receivable, the at least one chamber unit being defined in the substrate and extending between the top side and the bottom side; an inlet for receiving a fluid; an outlet for allowing removal of the fluid; an inlet fluidic channel defined in the substrate and extending between the inlet and the at least one chamber unit; an outlet fluidic channel defined in the substrate and extending between the at least one chamber unit and the outlet; a dam assembly for controlling fluid flow through the at least one chamber unit, the dam assembly comprising at least one of an inlet dam and an outlet dam, the inlet dam being located between the inlet fluidic channel and the at least one chamber unit and extending upright towards the top side to an inlet sill arranged to allow fluid from the inlet fluidic channel to flow thereover to be received in the at least one chamber unit, and the outlet dam being located between the at least one chamber unit and the outlet fluidic channel and extending upright towards the top side to an outlet sill arranged to allow fluid from the at least one chamber unit to flow thereover to be received in the outlet fluidic channel.

[0012] Due to the inclusion of the dam assembly, the fluid flow through the at least one chamber unit can be better controlled. It is noted that the dam assembly can be used to control the fluid flow when the fluidic device is oriented for use, for example, with a horizontal substrate plane, e.g. the plane of the bottom side of the substrate.

[0013] In embodiments in which the dam assembly includes an inlet dam that stands upright between the inlet fluidic channel and the at least one chamber cell, the inlet fluidic channel can be configured to fill to the inlet sill of the inlet dam before fluid flows over the inlet sill into the chamber cell.

[0014] In embodiments in which the plurality of chamber cells are each separated from the inlet fluidic channel by a respective inlet dam, the inlet sills of at least some of the inlet dams can be at different heights relative to one another.

[0015] In such embodiments, a stepwise filling of the chamber cells, e.g., one after another, can be facilitated. This can eliminate tilting of the substrate relative to horizontal, e.g., 5 to 10 degrees, in order to achieve such stepwise filling of the chamber cells.

[0016] In embodiments in which the dam assembly includes an outlet dam that stands upright between the at least one chamber cell and the outlet fluidic channel, the outlet dam can facilitate collection of sufficient fluid, e.g., cell culture media, on the biological material. For example, by shaping the outlet sills, e.g., selecting the height of the outlet sills, a greater fluid reservoir can be provided.

[0017] In embodiments in which the fluidic device includes a plurality of fluidic assemblies, the outlet sills of at least some of the plurality of fluidic assemblies can be at different heights relative to one another. Such a fluidic device can enable testing to identify a suitable height for the outlet sills, e.g., as part of a process to optimize cell culture conditions.

[0018] In embodiments in which the fluidic device includes a plurality of chamber cells, the plurality of chamber cells are supplied with fluid by the inlet fluidic channel and are arranged such that fluid is removed from the chamber cells by the outlet fluidic channel, e.g., a dam assembly including a first dam and a second dam can allow one or more such chambers to be emptied, e.g., by pipetting, without disturbing the fluid level in other chambers.

[0019] In some embodiments, the at least one chamber cell extends to an opening at a top side of the substrate, and the dam assembly includes an inlet dam and an outlet dam, wherein the inlet dam and the outlet dam are arranged for retaining fluid in the at least one chamber cell.

[0020] In such embodiments, the fluidic device can be operated as a so-called open system, in which fluid can be input into and / or withdrawn from the at least one chamber cell via the opening of the at least one chamber cell, e.g., using a pipette device, without having to connect a flow control system to the inlet and outlet. This capability is due to the chamber cell retaining fluid therein regardless of whether there is a flow of fluid provided via the inlet fluidic channel.

[0021] In some embodiments, the outlet sill of the outlet dam is lower than the inlet sill of the inlet dam, such that fluid filling the at least one chamber cell to reach the outlet sill flows over the outlet sill into the outlet fluid channel.

[0022] This arrangement enables the fluidic device to additionally function as a closed system, wherein the flow control system drives the flow in the inlet fluid channel and the outlet fluid channel. By the outlet sill being lower than the inlet sill, the risk of undesired backflow from the chamber cell into the inlet fluid channel can be minimized.

[0023] In some embodiments, one or more (e.g. all) of the at least one chamber cell comprises a dual chamber cell, wherein the dual chamber cell comprises a first chamber and a second chamber, which are fluidically connected to each other via a bridge defined between the first chamber and the second chamber. Such a dual chamber cell can be used to study metastasis of cancer cells. Cells released or expelled by any cell culture provided in the first chamber can be assessed. Thus, the first chamber can be used to subject the cell culture to a treatment, e.g. to apply a certain treatment fluid or drug, e.g. a chemotherapy treatment fluid, wherein the second chamber captures any released cells to analyze the effect of the treatment performed in the first chamber on metastasis.

[0024] In such embodiments, the inlet dam can be located between the inlet fluid channel and the first chamber, such that fluid filling the inlet fluid channel to reach the inlet sill flows over the inlet sill into the first chamber. Further, the outlet dam can be located between the second chamber and the outlet fluid channel.

[0025] The fluidic device, and more specifically each of the one or more fluidic assemblies, can further comprise an intermediate dam located between the first chamber and the second chamber, wherein the intermediate dam extends upright towards the top side of the substrate to an intermediate sill at a base of the bridge located between the first chamber and the second chamber.

[0026] In such embodiments, the bridge sill is preferably lower than the inlet sill, such that fluid filling the first chamber to reach the bridge sill flows over the bridge sill into the second chamber.

[0027] Further, the outlet sill is preferably lower than the bridge sill, such that fluid filling the second chamber to reach the outlet sill flows over the outlet sill into the outlet fluid channel.

[0028] This ordering of the heights of the inlet sill, the bridge sill and the outlet sill can contribute to minimizing the risk of undesired backflow during closed system type operation of the fluidic device using the fluid control system. It is also repeated that removal of fluid (e.g. old fluid) from the chamber cell and addition of fresh fluid to the chamber cell can also be achieved via pipetting.

[0029] In at least some embodiments, each of the at least one chamber unit comprises at least one support region for supporting a biocompatible separator such that the biocompatible separator separates an upper portion from a lower portion of the respective chamber unit. The biological material can be supported by the biocompatible separator when the biological material is received in the chamber unit.

[0030] The inlet dam and / or the outlet dam can at least partially bound the upper portion.

[0031] In some embodiments, the support region comprises a support flange disposed around an inner perimeter of the respective chamber unit, on which the biocompatible separator can be supported.

[0032] In at least some embodiments, the biocompatible separator is adapted for culturing cells thereon. Such a biocompatible separator is preferably in the form of a perforated membrane or film.

[0033] The biocompatible separator can be attached to the substrate. In such embodiments, the biocompatible separator and the substrate can be manufactured separately, e.g. from different materials.

[0034] In embodiments in which the substrate is formed from the same material as the biocompatible separator, the manufacturing process can comprise forming the substrate and the integral biocompatible separator, e.g. in a molding, e.g. injection molding, process.

[0035] In such embodiments, the manufacturing process can further comprise forming the holes in the integral biocompatible separator, e.g. via laser ablation.

[0036] In some embodiments, the upper portion and the lower portion separated by the support region have different volumes relative to each other, e.g. the lower portion has a smaller volume than the volume of the upper portion. This can be beneficial when the test is more appropriately supplied to the pharmaceutical preparation in whichever of the upper portion and the lower portion has the smaller volume, e.g. for reasons of cost and / or supply scarcity.

[0037] Alternatively or in addition, the at least one support region can be arranged for supporting the biocompatible separator closer to one of the top side and the bottom side than the other of the top side and the bottom side. In some embodiments, the support region is configured for supporting the biocompatible separator closer to the bottom side than to the top side. This can facilitate monitoring of the biological material received in the chamber unit, in particular by optical microscopy.

[0038] The fluidic device, and more specifically each of the one or more fluidic components, can comprise an upper fluid flow system defined in the substrate and arranged to supply fluid to and allow fluid to exit from the upper portion of the chamber unit.

[0039] Each of the one or more fluid assemblies can further comprise a lower fluid flow system defined in the base plate and arranged to supply fluid to and / or allow fluid to exit from a lower portion of the chamber cell.

[0040] The upper fluid flow system and the lower fluid flow system can implement different functions with respect to each other, for example by the upper fluid flow system supplying cell nutrients to an upper portion of the chamber cell and the lower fluid flow system supplying a pharmaceutical formulation to a lower portion of the chamber cell.

[0041] To this end, the upper fluid flow system and the lower fluid flow system can be controlled independently of each other with respect to the flow and / or composition of fluid to create various, for example identical or different, conditions in the upper and lower portions of the chamber cell.

[0042] In embodiments where each of the one or more fluid assemblies comprises a plurality of chamber cells, the chamber cells can be connected in parallel across the inlet fluid channel and the outlet fluid channel. Such a design can facilitate efficient connection with the flow control system due to the need for fewer connection tubing points, while also helping to minimize cross-contamination between the chamber cells.

[0043] In embodiments where the plurality of chamber cells each comprise an upper portion and a lower portion, the lower fluid flow system can comprise at least one lower fluid channel fluidically connecting the lower portions of the chamber cells to each other.

[0044] In embodiments where the fluidic device comprises a plurality of fluid assemblies, each fluid assembly comprising chamber cells connected in parallel across the inlet fluid channel and the outlet fluid channel, the lower fluid flow system can comprise lower fluid channels, each lower fluid channel providing a fluidic connection between the lower portions of the chamber cells belonging to different fluid assemblies.

[0045] This can reduce the risk of clogging in the fluidic device.

[0046] In some embodiments, the inlet fluid channel provides a resistance to flow therein that varies with distance along the inlet fluid channel away from the inlet, for example by a dimension (e.g. cross-sectional area) of the inlet fluid channel varying with distance along the inlet fluid channel away from the inlet.

[0047] In such embodiments, a narrower portion of the inlet fluid channel can be provided proximal to the inlet, followed by a wider portion of the inlet fluid channel further away from the inlet along the inlet fluid channel.

[0048] In embodiments in which the chamber units are connected in parallel across the inlet fluidic channel and the outlet fluidic channel, the flow resistance in the inlet fluidic channel can decrease, for example, due to the inlet fluidic channel having an increasing cross-sectional area between the fluidic inlets (e.g. inlet ledges) of successive chamber units in a downstream direction away from the inlet.

[0049] Such a design of the inlet fluidic channel can facilitate control over each of the parallel chamber units, for example, to provide the same continuous flow.

[0050] Alternatively or additionally, the outlet fluidic channel can provide a resistance to flow therein that varies with distance along the outlet fluidic channel away from the fluidic outlet (e.g. outlet ledge) of the chamber unit(s), for example, by a change in size (e.g. cross-sectional area) of the outlet fluidic channel with distance along the outlet fluidic channel away from the fluidic outlet.

[0051] In some embodiments, the fluidic device comprises an upper cover for covering a top side of the substrate and / or a lower cover for covering a bottom side of the substrate.

[0052] Such upper and / or lower cover(s) can facilitate fluid retention in the at least one chamber unit and / or contamination protection of the at least one chamber unit. In relation to fluid retention, such upper and / or lower cover(s) can facilitate minimization of fluid loss via evaporation.

[0053] In some embodiments, one or both of the upper and lower covers are configured to enable access to the at least one chamber unit, for example, for delivering fluid into the at least one chamber unit and / or withdrawing fluid from the at least one chamber unit, for example, via the pipette device described above.

[0054] For example, one or both of the upper and lower covers can be releasably mounted (e.g. detachably mounted) to the substrate, wherein release (e.g. detachment) of the respective cover can enable access to the at least one chamber unit.

[0055] The upper and lower covers can be formed from any suitable material. Of particular mention are optically transparent materials, for example, glass and optically transmissive polymers, for example, polycarbonate. This is because such materials can facilitate monitoring of tests occurring in the fluidic device, for example, via optical microscopy.

[0056] According to another aspect, there is provided use of a fluidic device according to any of the embodiments described herein for testing biological material.

[0057] In some embodiments, the biological material being tested comprises one or more selected from the group consisting of: a cell pellet, a bilayer, a spheroid, an organoid and a biopsy.

[0058] According to another aspect, there is provided a method of drug testing, comprising: providing biological material in at least one chamber unit of a fluidic device according to any one of the embodiments described herein; and exposing the biological material to a drug to be tested.

[0059] In some embodiments, exposing the biological material to the drug to be tested comprises delivering the drug to be tested using one or both of the upper fluid flow system and the lower fluid flow system.

[0060] Alternatively or additionally, providing biological material in the at least one chamber unit can comprise culturing cells in the at least one chamber unit.

[0061] Alternatively or additionally, the method can comprise monitoring the biological material, for example, the response of the cultured cells to the drug to be tested. Such monitoring can be achieved in any suitable way, for example, by optical microscopy.

[0062] These and other aspects of the application will become apparent from and will be elucidated with respect to the embodiments described hereinafter. BRIEF DESCRIPTION OF DRAWINGS

[0063] For a better understanding of the present application, and to show how it can be put into effect, reference will now be made, purely by way of example, to the accompanying drawings in which: FIG. 1A and FIG. 1B A view of a fluidic device according to a first example is provided; FIG. 2 A schematic cross-sectional view of a portion of a fluidic device according to a second example is provided; FIG. 3 A cross-sectional view of a fluidic device according to a third example is provided; FIG. 4 and FIG. 5 A cross-sectional view of a fluidic device according to a fourth example is provided; FIG. 6A to FIG. 6E Various views of a fluidic device according to a fifth example are provided; FIG. 7A and FIG. 7B A view of a fluidic device according to a sixth example is provided; FIG. 8 A perspective view of a top side of a fluidic device according to a seventh example is provided; FIG. 9A and FIG. 9B Perspective views of a top side and a bottom side of a fluidic device according to an eighth example are provided, respectively; and FIG. 10A and FIG. 10B Perspective views of a top side and a bottom side of a fluidic device according to a ninth example are provided, respectively. Detailed Implementation

[0064] The invention will be described with reference to the accompanying drawings.

[0065] While the detailed description and specific examples illustrate exemplary embodiments of the apparatus, systems, and methods, they are intended for illustrative purposes only and are not intended to limit the scope of the invention. These and other features, aspects, and advantages of the apparatus, systems, and methods of the present invention will be better understood from the following description, the appended claims, and the accompanying drawings. The drawings are merely schematic and not drawn to scale. The same reference numerals are used throughout the drawings to indicate the same or similar parts.

[0066] This invention provides a fluid device for testing biomaterials. The fluid device includes a substrate having a top side and a bottom side. The fluid device also includes one or more fluid components. Each of the one or more fluid components includes at least one chamber unit in which biomaterial can be received. The at least one chamber unit is defined in the substrate and extends between the top side and the bottom side. Each of the one or more fluid components also includes an inlet, an outlet, an inlet fluid channel, and an outlet fluid channel, the inlet fluid channel being defined in the substrate and extending between the inlet and the at least one chamber unit, and the outlet fluid channel being defined in the substrate and extending between the at least one chamber unit and the outlet.

[0067] FIG. 1A and FIG. 1B A view of a fluid device 100 is provided. The fluid device 100 includes a substrate 102 having a top side 104 and a bottom side 106 opposite to the top side. The fluid device 100 includes one or more fluid components 108, and... FIG. 1A and FIG. 1B In the illustrated embodiment, the fluid device 100 includes two fluid components 108. The number of fluid components 108 included in the fluid device 100 may vary depending on the test requirements, and in other embodiments, the fluid device 100 includes a single fluid component 108 or three, four, five, six, seven, eight or more fluid components 108.

[0068] Each of one or more fluid components 108, or at least one in other cases, includes at least one chamber unit 110 in which biological material can be received. The at least one chamber unit 110 is defined in a substrate 102 and extends between a top side 104 and a bottom side 106.

[0069] The at least one chamber unit 110 can extend to an upper opening bounded by the top side 104 of the substrate 102 and / or to a lower opening bounded by the bottom side 106 of the substrate 102. In such embodiments, fluid retention and / or contamination protection in the at least one chamber unit 110 can be assisted by the fluidic device 100 comprising an upper lid (not visible) for covering the top side 104 of the substrate 102 and / or a lower lid (not visible) for covering the bottom side 106 of the substrate 102. With respect to fluid retention, such upper and / or lower lid can help to minimize fluid loss via, for example, evaporation.

[0070] In some embodiments, one or both of the upper lid and the lower lid are configured to enable access to the at least one chamber unit 110, for example for delivering fluid into the at least one chamber unit 110 and / or withdrawing fluid from the at least one chamber unit 110, for example via a pipette device.

[0071] For example, one or both of the upper lid and the lower lid can be releasably mounted to the substrate 102, wherein release of the respective lid enables access to the at least one chamber unit 110.

[0072] The upper lid and the lower lid can be formed of any suitable material. Of particular mention are light-transmissive materials, for example glass and optically transmissive polymers, for example polycarbonate. This is because such materials can facilitate monitoring of tests taking place in the fluidic device 100, for example via optical microscopy.

[0073] The upper lid and the lower lid can be mounted (for example releasably mounted) to the substrate 102 in any suitable manner, for example using adhesive tape, clips, etc. A non-limiting example of a suitable adhesive tape is Avery Dennison MED1125.

[0074] Preferably, when one or more upper and lower lids are mounted, the adhesion is such that an external pumping system, for example of the flow control system described below, can be used to manipulate fluid at (slightly) elevated pressure.

[0075] More generally, biological material can be received in the chamber unit(s) 110, and testing of the biological material can be performed using the fluidic device 100. Examples of such biological material include a cell cluster, a bilayer of cells, a spheroid, an organoid, or a biopsy tissue.

[0076] During at least part of the testing performed using the fluidic device 100, such biological material tends to be alive. To this end, the fluidic device 100 (for example its substrate 102) can be formed of a suitable biocompatible material. In some embodiments, the substrate 102 is formed of a biocompatible polymeric material, such as silicone, for example to which a suitable cell culture protein, such as fibronectin, is applied.

[0077] To test the biological material received in the chamber unit(s) 110, the fluidic assembly 108 comprises an inlet 112 at which fluid (e.g. fluid containing cell nutrients and / or pharmaceutical agents) can be delivered to the substrate 102, and an outlet 114 at which fluid is allowed to exit the substrate 102, e.g. for the purpose of carrying away waste from the chamber unit(s) 110 and / or to enable replenishment of cell nutrients and / or pharmaceutical agents.

[0078] A flow control system (not visible) can be used to supply fluid to the inlet 112 and to remove fluid from the fluidic device 100 via the outlet 114. Flow control systems for this purpose are commercially available, e.g. from Fluigent®.

[0079] As shown in FIG. 1A and FIG. 1B , an inlet fluidic channel 116 is defined in the substrate 102 and extends between the inlet 112 and the at least one chamber unit 110, and an outlet fluidic channel 118 is defined in the substrate 102 and extends between the at least one chamber unit 110 and the outlet 114. Thus, the inlet fluidic channel 116 and the outlet fluidic channel 118 fluidically connect the inlet 112 and the outlet 114 to the chamber unit(s) 110.

[0080] The biological material can be supported in the chamber units 110 in any suitable manner. In some embodiments, and referring now to FIG. 2 , each of the at least one chamber unit 110 comprises at least one support region 120 for supporting a biocompatible partition 122, such that the biocompatible partition 122 separates an upper portion 124 from a lower portion 126 of the respective chamber unit 110. When biological material is received in the chamber unit 110, the biological material can be supported by the biocompatible partition 122.

[0081] In some embodiments, such as FIG. 3 shown, the support region(s) 120 comprise a support flange disposed around an inner perimeter of the respective chamber unit 110, on which the biocompatible partition 122 can be supported.

[0082] In at least some embodiments, the biocompatible partition 122 is adapted for culturing cells thereon. Such a biocompatible partition 122 is preferably in the form of a perforated membrane or film. More generally, the biocompatible partition 122 is preferably a biocompatible porous partition 122.

[0083] The pores of such a biocompatible porous partition 122 can contribute to the biocompatible partition 122 having suitable properties, in particular for cell culturing.

[0084] The biocompatible partition 122 can be formed of any suitable biocompatible material. Of particular mention are biocompatible partitions 122 comprising elastomeric materials, such as silicone rubber and / or polybutadiene.

[0085] Elastomeric materials for use in biocompatible partitions 122 are described, for example, in WO2021058657, WO2019015988. These materials are also suitable to provide good adhesion of the upper and lower covers made of, for example, glass or polar plastics such as polycarbonate.

[0086] Silicones and polybutadienes are readily functionalised, for example by cross-linking with fatty acids, to render them biocompatible, for example by applying a protein such as fibronectin to the fatty acid functionalised surface of the elastomeric material. This, together with their elastic properties, makes such elastomeric materials particularly suitable for inclusion in the biocompatible partition 122.

[0087] Silicones can be optically transparent and also have limited autofluorescence, such that such a silicone-based biocompatible partition 122 (e.g. a membrane) can allow various conventionally used optical inspection techniques and protocols (e.g. with or without staining) to be used in tests performed using the fluidic device 100.

[0088] The biocompatible partition 122 can be formed to be porous, fluid-permeable (e.g. gas-permeable) and / or suitable for cell culture thereon in any suitable manner, for example by forming pores in the material (e.g. elastomeric material) making up the biocompatible partition 122. Such pores can be formed in any suitable manner, for example by laser ablation or cast-embossed perforation.

[0089] Laser perforation / ablation is described, for example, in US2014127744 and US20180315409. Cast-embossed perforation is described, for example, in US2020360923, US2015010919 and US2022228108.

[0090] Each of these pores is preferably sized to limit or prevent passage therethrough of cells supported on the biocompatible partition 122. To this end, each pore can have a diameter of less than 10 pm.

[0091] In some embodiments, the material constituting the biocompatible partition 122 can be manufactured, e.g. by injection molding, into a slab or plate of material, which is subsequently subjected to a hole forming process, e.g. comprising laser ablation. In this way, a plurality of biocompatible partitions 122 can be manufactured, e.g. in parallel. The biocompatible partitions 122 can then be separated from each other, e.g. by punching out from the slab, and inserted into the respective chamber cells 110 for support by the support region 120.

[0092] More generally, the biocompatible partition 122 can be attached to the base plate 102. For example, the biocompatible partition 122 (e.g. a membrane) can be in the form of an insert that can be inserted into each chamber cell 110. This can mean that the biocompatible partition 122 and the base plate 102 can be manufactured separately, e.g. from different materials.

[0093] In embodiments where the base plate 102 is formed from the same material as the biocompatible partition 122, the manufacturing process can comprise forming the base plate 102 and integral biocompatible partition 122, e.g. in a molding (e.g. injection molding) process, and subsequently forming holes in the integral biocompatible partition 122, e.g. via laser ablation.

[0094] In an injection molding step, in particular when the biocompatible partition 122 has a thickness of at least 10 pm, the base plate 102 can conveniently be made from the same material as the biocompatible partition 122 (e.g. a membrane or film).

[0095] It is noted that injection molding tends to require a thickness of the biocompatible partition 122 that is greater than 10 pm. As the thickness of the biocompatible partition 122 increases, laser ablation can become more difficult to implement.

[0096] However, for thicknesses of 50 pm or less, the perforation in the biocompatible partition 122 can be conveniently made using laser ablation / perforation (see e.g. US4923608 and US20180315409).

[0097] A range of exemplary materials for the biocompatible partition 122 and / or the base plate 102 is provided below.

[0098] In some embodiments, the base plate 102 is formed from an elastomeric material, e.g. silicone and / or polybutadiene.

[0099] In such embodiments, it can be facilitated to connect the above-mentioned flow control system to the substrate 102, e.g. to supply fluid to the fluidic device 100 via the inlet 112 and to remove fluid from the fluidic device 100 via the outlet 114. This is because the tubing for connecting the flow control system to the substrate 102 can be simply pressed into the opening(s) defined in the elastomer of the substrate 102, e.g. via a leak-proof push-fit.

[0100] It is noted that, for the avoidance of doubt, such opening(s) defined in the substrate 102 can correspond to the inlet 112 and / or the outlet 114.

[0101] Such pressing, e.g. push-fit, can advantageously eliminate the requirement for clamps and cumbersome connection schemes for connecting the tubing to the fluidic device 100.

[0102] It is noted that the waste tubing for carrying waste away from the fluidic device 100 can typically have a relatively large diameter, e.g. larger than the supply tubing for delivering cell nutrients and / or drug agents to the fluidic device 100. Therefore, such waste tubing can be easily pressed into the opening(s) providing the fluid outlet(s), e.g. the outlet 114.

[0103] It is noted that in embodiments in which the fluidic device 100 comprises an upper lid and / or a lower lid, such lid(s) can define one or more holes through which the tubing can pass in order to connect the flow control system to the substrate 102.

[0104] In a closed system in which the flow control system is connected to the substrate 102, the connection of the tubing to the inlet 112 and the outlet 114 can be done, e.g. with ferrules. Such ferrules can be made of an elastomeric material, e.g. a soft elastomeric material.

[0105] Similar connections can be made in the case of a so-called open system, but then the upper lid, e.g. the upper lid plate, can be adapted to allow the connection of the tubing to the inlet 112 and the outlet 114. In particular, the upper lid can define openings for connection to the inlet 112 and the outlet 114.

[0106] Such adapted upper lid can help to avoid excessive evaporation of fluid, e.g. medium, from the chamber unit(s) 110, and to minimize the risk of cross-contamination via aerosols in the manner of a standard lid for a well plate.

[0107] In embodiments in which the substrate 102 is formed of silicone, e.g. via injection molding, a glass upper lid and / or a glass lower lid can be adhered to the silicone substrate 102.

[0108] The adhesion between such silicone substrate 102 and the glass upper cover and / or glass lower cover can be relatively strong. This can be particularly beneficial in embodiments of a closed system where it is desired to secure or permanently fix one or both of the upper and lower covers to the substrate 102.

[0109] It should be emphasized that any suitable technique can be used to manufacture the substrate 102. The substrate 102, e.g. together with the biocompatible partition 122, can be formed, e.g. by injection molding or by an additive manufacturing process, such as 3D printing.

[0110] In the case of 3D printing, a thermoplastic elastomer can be used to manufacture the substrate 102 without the biocompatible partition 122, e.g. a membrane.

[0111] In such embodiments, the thermoplastic elastomer can be printed, e.g. on an adhesive tape, e.g. Avery Dennison MED 1125.

[0112] The adhesive tape can be initially adhered, e.g. to a glass substrate, e.g. a plate, and the thermoplastic elastomer can be attached to the adhesive tape during 3D printing.

[0113] The porous channel(s) constituting the lower fluid channel(s) 131 of the lower fluid flow system 130 can be made, e.g. with a printing architecture as described in WO2023280808.

[0114] The biocompatible partition 122, e.g. a membrane manufactured by injection molding and laser ablation to provide the holes, can be inserted into the chamber unit 110 of the printed substrate 102.

[0115] More generally, and again with reference to FIG. 2 , the fluidic device 100, and more specifically each of the one or more fluidic assemblies 108, can comprise an upper fluid flow system 128 defined in the substrate 102 and arranged to supply fluid and allow fluid to exit the upper portion 124 of the chamber unit(s) 110. Each of the one or more fluidic assemblies 108 can also comprise a lower fluid flow system 130 defined in the substrate 102 and arranged to supply fluid and / or allow fluid to exit the lower portion 126 of the chamber unit(s) 110.

[0116] To this end, the lower fluid flow system 130 can comprise at least one lower fluid channel 131 arranged to supply fluid and / or allow fluid to exit the lower portion 126 of the chamber unit(s) 110.

[0117] Referring to FIG. 1B , FIG. 2 and FIG. 3 , at least one lower fluid channel 131 can extend between a lower fluid inlet 131A and a lower fluid outlet 131B, e.g., via a lower portion 126 of the chamber unit(s) 110. A flow control system can be connected to the lower fluid inlet 131A and the lower fluid outlet 131B via tubing.

[0118] It is noted that the upper fluid system 128 can include an inlet fluid channel 116 and an outlet fluid channel 118. As shown in FIG. 2 and FIG. 3 , an upper portion 124 of the chamber unit(s) 110 can be arranged to receive fluid from the inlet fluid channel 116.

[0119] The biocompatible partition 122 can provide separation between a top flow provided by the upper fluid flow system 128 and a bottom flow provided by the lower fluid flow system 130, which is impermeable to the bottom flow.

[0120] The upper fluid flow system 128 and the lower fluid flow system 130 can implement different functions relative to each other, e.g., by the upper fluid flow system 128 supplying cell nutrients to the upper portion 124 of the chamber unit(s) 110 and the lower fluid flow system 130 supplying a pharmaceutical formulation to the lower portion 126 of the chamber unit(s) 110.

[0121] To this end, the upper fluid flow system 128 and the lower fluid flow system 130 can be controlled independently of each other with respect to the flow and / or composition of fluid in order to create various (e.g., same or different) conditions in the upper portion 124 and the lower portion 126 of the chamber unit(s) 110.

[0122] In some embodiments, the upper fluid flow system 128 is used to provide a fluid flow FL1 for transporting cells, e.g., mimicking blood flow in a tissue of a subject, and / or including nutrients for the cells being cultured. Alternatively or additionally, the lower fluid flow system 130 can be used to provide a fluid flow FL2 for delivering a pharmaceutical or other treatment to the biological material (e.g., cell culture and / or transplanted cells).

[0123] In some embodiments, the upper portion 124 and the lower portion 126 have different volumes relative to each other, e.g., the lower portion 126 has a smaller volume than the volume of the upper portion 124. An example of this is shown in FIG. 2 and FIG. 3This can be beneficial when the test is more appropriately supplied to the drug formulation of either of the upper 124 and lower 126 having the smaller volume, e.g., for cost and / or supply scarcity reasons.

[0124] Alternatively or additionally, the at least one support region 120 can be arranged to support the biocompatible partition 122 closer to one of the top side 104 and the bottom side 106 than the other of the top side 106 and the bottom side 104. In some embodiments, such as FIG. 2 and FIG. 3 As shown, the support region(s) 120 are configured to support the biocompatible partition 122 closer to the bottom side 106 than the top side 104. This can facilitate monitoring of the biological material, especially by optical microscopy, e.g., through the optically transmissive lower or upper cover described above.

[0125] It is noted that the focal length of many optical microscopy setups, e.g., for imaging stains, can be only about 0.6 mm. Thus, the distance from the bottom of the lower cover (e.g., a glass lower cover) to the biocompatible partition 122 (e.g., a perforated membrane) can be no more than 0.6 mm.

[0126] Thus, in the case of a lower cover (e.g., a glass lower cover) having a thickness of 0.20 mm, for example, the distance between the lower cover and the biocompatible partition 122 can be at most 0.4 mm.

[0127] Thus, in some embodiments, the support region(s) 120 are configured to support the biocompatible partition 122 at a location that is no more than 0.4 mm from the bottom side 106 of the substrate 102.

[0128] More generally, and still referring to FIG. 4 and FIG. 4 Fluid flow through the at least one chamber unit 110 can be controlled by a dam assembly, where the dam assembly shown in these particular figures includes an outlet dam 132 that is located between the at least one chamber unit 110 and the outlet fluid passage 118 and extends upright toward the top side 104 to an outlet sill 134. The outlet sill 134 is arranged to allow fluid from the at least one chamber unit 110 to flow over it to be received in the outlet fluid passage 118.

[0129] The outlet dam 132 can facilitate collection of fluid (e.g., cell culture medium) on the biological material (e.g., cell culture) before the fluid exits the substrate 102 via the outlet 114.

[0130] In some embodiments, the outlet dam 132 can create a larger fluid reservoir(s), e.g., for providing cell nutrients. In particular, as the fluid (e.g., flow medium) can be constantly refreshed, e.g., via operation of the flow control system, sufficient oxygen / carbon dioxide assimilation can be ensured. By shaping the outlet sill 134, e.g., selecting a height of the outlet sill 134, a larger fluid reservoir(s) can be provided.

[0131] In embodiments in which the fluidic device 100 comprises a plurality of fluidic assemblies 108, such as FIG. 6A to FIG. 6C and 5 shown, the outlet sill 134 of at least some of the plurality of fluidic assemblies 108 can be at different heights relative to each other.

[0132] Such a fluidic device 100 can enable a test to identify a suitable height of the outlet sill 134, e.g., as part of a process to optimize cell culture conditions. For example, a 3D-printed fluidic device 100 in which the outlet sill 134 of at least some of the plurality of fluidic assemblies 108 is at different heights relative to each other can be used for such a test. Subsequently, an injection-molded fluidic device 100 can be produced with its outlet sill(s) 134 set based on the test results using the 3D-printed fluidic device 100.

[0133] In the non-limiting example shown in FIG. 6A to FIG. 6C , the height of the outlet sill 134 of the outlet dam 132 of the far left-hand fluidic assembly 108 is 1 mm, the height of the outlet sill 134 of the outlet dam 132 of the middle left-hand fluidic assembly 108 is 2 mm, the height of the outlet sill 134 of the outlet dam 132 of the middle right-hand fluidic assembly 108 is 3 mm, and the height of the outlet sill 134 of the outlet dam 132 of the far right-hand fluidic assembly 108 is 4 mm.

[0134] In some embodiments, as shown in FIG. 6A to FIG. 6C , the dam assembly comprises an inlet dam 136 that is located between the inlet fluidic channel 116 and the at least one chamber cell 110 and extends upright towards the top side 104 to an inlet sill 138. The inlet sill 138 is arranged for allowing fluid from the inlet fluidic channel 116 to flow over it in order to be received in the at least one chamber cell 110.

[0135] The inlet fluidic channel 116 can be configured for filling up to the inlet sill 138 before the fluid flows over the inlet sill 138 into the chamber cell 110.

[0136] In some embodiments, such an inlet dam 136 enables a stepwise filling of the chamber units 110, e.g. one after the other. This can eliminate tilting of the substrate 102 with respect to the horizontal, e.g. 5 to 10 degrees, in order to enable such a stepwise filling of the chamber units 110.

[0137] In some embodiments, as FIG. 1A illustrated, the at least one chamber unit 110 extends to the opening at the top side 104 of the substrate 102, and the dam assembly comprises an inlet dam 136 and an outlet dam 132, wherein the inlet dam 136 and the outlet dam 132 are arranged for retaining fluid in the at least one chamber unit 110.

[0138] In such embodiments, the fluidic device 100 can be operated as a so-called open system, wherein the fluid delivery into and / or withdrawal of fluid from the at least one chamber unit 110 can be achieved, e.g. via a pipette device, without having to connect a flow control system to the inlet 112 and the outlet 114. This capability is due to the chamber unit(s) 110 retaining fluid therein, irrespective of whether a fluid flow is provided via the inlet fluid channel 116.

[0139] In some embodiments, and still referring to FIG. 1B , the outlet sill 134 of the outlet dam 132 is lower than the inlet sill 138 of the inlet dam 136, such that fluid filling the at least one chamber unit 110 to reach the outlet sill 134 flows over the outlet sill 134 into the outlet fluid channel 118.

[0140] This arrangement enables the fluidic device 100 to additionally be used as a closed system, wherein a flow control system drives the flow in the inlet fluid channel 116 and the outlet fluid channel 118. By the outlet sill 134 being lower than the inlet sill 138, the risk of undesired backflow can be minimized.

[0141] In other embodiments, the outlet sill 134 is higher than the inlet sill 138.

[0142] This can help to provide sufficient fluid, e.g. nutrients, to the biological material in the chamber units 110.

[0143] In some embodiments, such as FIG. 6A to FIG. 6C , FIG. 6A to FIG. 6C and FIG. 6BAs shown, one or more of the at least one chamber unit 110 comprises a dual chamber unit 110, wherein the dual chamber unit 110 comprises a first chamber 140 and a second chamber 142, which are fluidly connected to each other via a bridge 144 defined between the first chamber 140 and the second chamber 142. Such a dual chamber unit 110 can be used to study metastasis of cancer cells. Cells released or expelled by any cell culture provided in the first chamber 140 can be assessed. Thus, the first chamber 140 can be used to perform a treatment on the cell culture, e.g. to apply a certain treatment fluid or drug, e.g. a chemotherapy treatment fluid, wherein the second chamber 142 captures any released cells in order to analyze the effect of the treatment performed in the first chamber 140 on metastasis.

[0144] In such embodiments, the inlet dam 136 can be located between the inlet fluid channel 116 and the first chamber 140, such that fluid filling the inlet fluid channel 116 up to the inlet sill 138 flows over the inlet sill 138 into the first chamber 140.

[0145] Further, the outlet dam 132 can be located between the second chamber 142 and the outlet fluid channel 118.

[0146] The fluidic device 100, and more specifically each of the one or more fluidic assemblies 108, can further comprise an intermediate dam 146 located between the first chamber 140 and the second chamber 142, wherein the intermediate dam 146 extends upright towards the top side 104 of the base plate 102 to a bridge sill at a base of the bridge 144 between the first chamber 140 and the second chamber 142.

[0147] In such embodiments, the bridge sill is preferably lower than the inlet sill 138, such that fluid filling the first chamber 140 up to the bridge sill flows over the bridge sill into the second chamber 142. Further, the outlet sill 134 is preferably lower than the bridge sill, such that fluid filling the second chamber 142 up to the outlet sill 134 flows over the outlet sill 134 into the outlet fluid channel 118.

[0148] Such an ordering of the heights of the inlet sill 138, the bridge sill, and the outlet sill 134 can help to minimize the risk of undesired backflow during closed system type operation of the fluidic device 100 using a fluidic control system. It is also repeated that removal of fluid (e.g. old fluid) from the chamber unit(s) 110 and addition of fresh fluid to the chamber unit(s) 110 can also be achieved via pipetting.

[0149] In FIG. 6C In the non-limiting example shown, the height of the inlet sill 138 is 5 mm, the height of the bridge sill is 4 mm, and the height of the outlet sill 134 is 3 mm.

[0150] In other embodiments, the bridge ledge is higher than the inlet ledge 138.

[0151] This can help provide sufficient fluid, e.g., nutrients, to the biological material in the first chamber 140.

[0152] In some embodiments, and with reference to FIG. 6C and FIG. 6D the at least one support region 120 includes a first support region 148 for supporting a first biocompatible partition (not visible) such that the first biocompatible partition separates a first upper portion 150 of the first chamber 140 from a first lower portion 152.

[0153] In such embodiments, the at least one support region 120 can further include a second support region 154 for supporting a second biocompatible partition (not visible) such that the second biocompatible partition separates a second upper portion 156 of the second chamber 142 from a second lower portion 158.

[0154] In embodiments in which the one or more fluidic assemblies 108 each include a plurality of chamber units 110, each chamber unit 110 includes a first chamber 140 and a second chamber 142, and with reference now to FIG. 6E the lower fluid flow system 130 can include a first lower fluidic passage 160 arranged to fluidically connect the first lower portions 152 of the first chambers 140 to one another and a second lower fluidic passage 162 arranged to fluidically connect the second lower portions 158 of the second chambers 142 to one another. Such an arrangement can help prevent clogging in the fluidic device 100.

[0155] It should be noted that, more generally, the basal flow provided by the lower fluid flow system 130 can be stopped or continuously refreshed according to a protocol designed / desired by an experimenter (e.g., an oncologist). Since the biocompatible partitions 120 can be impermeable to cells, e.g., due to the limited size of the pores formed therein, as previously described, there can be little or no risk of contamination of other chamber units 110 via the basal flow. If chemicals for chemotherapy are used for the basal flow, cross-contamination of proteins can also be minimized due to the relatively small overpressure on the lower fluid flow system 130.

[0156] With reference now to FIG. 6A to FIG. 6E and FIG. 7A the first lower fluidic passage 160 can extend, for example, between a first lower fluidic inlet 164 and a first lower fluidic outlet 166. The flow control system can be connected to the first lower fluidic inlet 164 and the first lower fluidic outlet 166 via tubing.

[0157] Similarly, the second lower fluidic channel 162 can extend between the second lower fluidic inlet 168 and the second lower fluidic outlet 170.

[0158] At this point, it should be noted that the chamber unit(s) 110 (e.g., one or more chambers 140, 142 making up each of the chamber unit(s) 110) can have dimensions suitable for the intended testing of biological material. In some embodiments, each chamber unit 110, e.g., each chamber 140, 142 thereof, can have a height extending between the top side 104 and the bottom side 106 of 1.8 to 2.6 mm, e.g., about 2.2 mm. Alternatively or additionally, the diameter of each chamber unit 110 (e.g., each chamber 140, 142 thereof) can be 3 mm to 20 mm, such as 3 mm to 10 mm, e.g., about 6 mm.

[0159] Such dimensions can balance the requirement to keep the chamber unit(s) 110 as small as possible (e.g., to enable as many chamber units 110 as possible to be defined in the substrate 102) with the requirement to provide the chamber unit(s) 110 with sufficient space for biological material testing (e.g., for the capture and subsequent analysis of cells).

[0160] The chamber unit(s) 110, e.g., one or more chambers 140, 142 making up each of the chamber unit(s) 110, can have any suitable shape. From a fluid dynamics perspective, a generally cylindrical shape can be preferred, e.g., in order to mitigate the risk of fluid accumulating in the corners of the chamber units 110 (e.g., in the corners of the chamber(s) 140, 142 thereof), and / or to ensure usability with existing analysis equipment. However, shapes other than cylindrical can be envisaged, e.g., shapes having a square or rectangular cross-section.

[0161] It should also be noted that the depth of the inlet fluidic channel 116 and / or the outlet fluidic channel 118 can be 0.5 mm to 1.5 mm, e.g., about 0.8 mm. The width of the inlet fluidic channel 116 and / or the outlet fluidic channel 118 can be 0.5 mm to 1.5 mm, e.g., about 1 mm.

[0162] The depth of each of the lower fluidic channel(s) 131 can be 0.2 to 0.8 mm, e.g., about 0.6 mm; and / or the width of each of the lower fluidic channel(s) 131 can be 0.5 to 1.5 mm, e.g., about 1 mm.

[0163] It is also repeated that the distance from the bottom of the lower cover (e.g., a glass lower cover) to the biocompatible partition 122 (e.g., a perforated membrane) can be no more than 0.6 mm.

[0164] Referring to FIG. 7B and FIG. 8 , FIG. 9A , FIG. 9B , FIG. 7B and FIG. 7A In embodiments in which each of the one or more fluid assemblies 108 includes a plurality of chamber units 110, the chamber units 110 can be connected in parallel across the inlet fluid passage 116 and the outlet fluid passage 118. This design can facilitate efficient connection with a flow control system due to the need for fewer connection tubing points, while also helping to minimize cross-contamination between the chamber units 110.

[0165] Alternatively or additionally, and with reference to FIG. 7B The lower flow control system 130 may, for example, include a lower inlet fluid passage 172 and a lower outlet fluid passage 174, with the lower portions 126, 152, 158 of the chamber units 110 being connected in parallel across the lower inlet fluid passage 172 and the lower outlet fluid passage 174.

[0166] This arrangement can effectively reduce the risk of clogging in the fluidic device 100.

[0167] Although not visible in the drawings, the inlet fluid passage 116 can provide a resistance to flow therein that varies with distance along the inlet fluid passage 116 away from the inlet 112, for example by a change in size (e.g. cross-sectional area) of the inlet fluid passage 116 with distance along the inlet fluid passage 116 away from the inlet 112.

[0168] In such embodiments, a narrower portion of the inlet fluid passage 116 can be provided proximate the inlet 112, followed by a wider portion of the inlet fluid passage 116 further away from the inlet 112 along the inlet fluid passage 116.

[0169] In embodiments in which the chamber units 110 are connected in parallel across the inlet fluid passage 116 and the outlet fluid passage 118, the resistance to flow in the inlet fluid passage 116 can be reduced, for example due to the inlet fluid passage 116 having an increasing cross-sectional area between fluid inlets (e.g. inlet ledges 138) of successive chamber units 110 in a downstream direction away from the inlet 112.

[0170] This design of the inlet fluid passage 116 can facilitate control over each of the parallel chamber units 110, for example to provide the same continuous flow.

[0171] Alternatively or additionally, the outlet fluid passage 118 may provide resistance to the flow therein, which varies with the distance along the outlet fluid passage 118 away from the fluid outlet (e.g., outlet sill 134) of the chamber unit 110, for example by the size (e.g., cross-sectional area) of the outlet fluid passage 118 varying with the distance along the outlet fluid passage 118 away from the fluid outlet.

[0172] It should be noted that, FIG. 6D and FIG. 6E A fluid device 100 is depicted comprising two parallel-connected chamber units 110, each chamber unit 110 being a single chamber. Furthermore, in this case, the fluid device 100 includes a pair of fluid components 108. This example can be compared to... FIG. 8 and FIG. 9A The fluid device 100 shown is simpler, wherein each fluid assembly 108 has six parallel-connected dual-chamber units 110, and the fluid device 100 includes four fluid assemblies 108.

[0173] FIG. 9B A fluid device 100 is depicted comprising six parallel-connected chamber units 110, wherein each chamber unit 110 of each fluid assembly 108 is a single chamber. In this case, the fluid device 100 comprises four fluid assemblies 108.

[0174] In an embodiment where the fluid device 100 includes a plurality of fluid components 108, each fluid component 108 includes a chamber unit 110 connected in parallel across an inlet fluid passage 116 and an outlet fluid passage 118, and a lower fluid flow system 130 may include a lower fluid passage 131, each lower fluid passage 131 providing fluid connection between the lower portions 126 of the chamber units 110 belonging to different fluid components 108. FIG. 9A and FIG. 9B A non-limiting example is shown. This reduces the risk of blockage in the fluid device 100.

[0175] FIG. 10A and FIG. 10B A fluid device 100 is depicted in which each fluid assembly 108 comprises eight parallel-connected chamber units 110, wherein each chamber unit 110 is a single chamber. In this case, the fluid device 100 comprises eight fluid assemblies 108.

[0176] In some embodiments, such as FIG. 8 and FIG. 9A As shown, each of one or more fluid components 108 includes a chamber unit 110, which includes more than two (and in this example six) chambers 176, 178, 180, 182, 184, 186 connected in series.

[0177] Such embodiments can be seen as refinements of the above-described embodiments in which each chamber unit 110 comprises a first chamber 140 and a second chamber 142.

[0178] FIG. 9B The fluidic device 100 shown in FIG. 1 1 has a twenty-four chamber (e.g. well) configuration, FIG. 10A and FIG. 10B The fluidic device 100 shown in FIG. 13 has a sixty-four chamber (e.g. well) configuration, and ​ and ​ The fluidic device 100 shown in FIG. 1 1 has a twenty-four chamber (e.g. well) configuration. It is noted that the substrate 102 of the fluidic device 100 can have a shape and size corresponding to the size and shape of well plates as is well known and commonly used in the art. Well plates having ninety-six chambers are also known and can be envisaged in the context of the fluidic device 100 according to the present disclosure.

[0179] More generally, the present disclosure proposes a use of a fluidic device 100 according to any of the embodiments described herein for testing biological material, e.g. for testing a cell mass, a bilayer of cells, a spheroid, an organoid or a biopsy tissue or a combination thereof.

[0180] The present disclosure also envisages a method of drug testing, comprising: providing a fluidic device 100 according to any of the embodiments described herein; receiving biological material in at least one chamber unit 110; and exposing the biological material to a drug to be tested, e.g. by using one or both of the upper fluid flow system 128 and the lower fluid flow system 130 to deliver the drug to be tested.

[0181] In some embodiments, receiving biological material in at least one chamber unit 110 comprises culturing cells in at least one chamber unit 110.

[0182] Alternatively or in addition, the method can comprise monitoring the response of the biological material, e.g. the cultured cells, to the drug to be tested. This monitoring can be achieved in any suitable way, e.g. by optical microscopy, e.g. by the optically transmissive lower cover or upper cover described above.

[0183] The following exemplary commercially available elastomer / soft material (which is transparent or translucent and is a food contact approved material) can be used, in some embodiments, as the material of the biocompatible partition 122, the substrate 102, and / or other components of the fluidic device 100: Medalist MD-53253 (TPE Teknor Apex); Medalist MD-53273 (TPE Teknor Apex); Mediprene 500602 M-03 (TPE Hexpol); Texin Rx T85A (TPU Covestro); BioSpan® (SPU | PUR); BioSpan® (SPU | PUR); BJB Polyurethane F-116 A / B | TSU; BJB Polyurethane F-126 A / B | TSU; BJB Polyurethane F-131 A / B | TSU; BJB Polyurethane M-3115 REV 1A / B | TSU; BJB Polyurethane M-3125 A / B | TSU; CELLENE MC2248 | TPE; CELLENE MC2265 | TPE; CELLENE MC3038 | TPE; CELLENE MC3050 | TPE; CELLENE MC3061 | TPE; CELLENE MC3226 | TPE; CELLENE MC3239 | TPE; CELLENE MC3261 | TPE; Dynaflex™ G2706-1000-00 | TPE; Dynaflex™ G2711-1000-00 | TPE; Elastocon® 2860L | TPE; Filter-bond™ E-3264 | TS; FLEXCHEM™ 3551-02 | PVC, Flexible; FLEXCHEM™ 4051-02 | PVC, Flexible; FLEXCHEM™ 4551-02 | PVC, Flexible; FLEXCHEM™ 5051-02 | PVC, Flexible; FLEXCHEM™ 5551-02 | PVC, Flexible; FLEXCHEM™ 6051-02 | PVC, Flexible; FLEXCHEM™ 6551-02 | PVC, Flexible; Medalist® MD-12130 | TPE; Medalist® MD-12130H | TPE; Medalist® MD-12140 | TPE; Medalist® MD-12140H | TPE; Medalist® MD-12150 | TPE; Medalist® MD-12150H | TPE;Medalist® MD-12f150S | TPE; Medalist® MD-12160 | TPE; Medalist® MD-12160H | TPE; Medalist® MD-12170 | TPE; Medalist® MD-12170H | TPE; Medalist® MD-12243 | TPE; Medalist® MD-12337 | TPE; Medalist® MD-12340 NAT | TPE; Medalist® MD-12342 | TPE; Medalist® MD-12344 | TPE; Medalist® MD-12350 | TPE; Medalist® MD-12352 | TPE; Medalist® MD-12362 | TPE; Medalist® MD-125 | TPE; Medalist® MD-130 | TPE; Medalist® MD-13240 | TPE; Medalist® MD-135 | TPE; Medalist® MD-145 | TPE; Medalist® MD-155 | TPE; Medalist® MD-17365 | TPE; Medalist® MD-225 | TPV; Medalist® MD-32045 | TPE; Medalist® MD-32245 | TPE; Medalist® MD-36048 | TPE; Medalist® MD-37063 NAT | TPE; Medalist® MD-42245 XRD1 | TPE; Medalist® MD-42245 XRD3 | TPE; Medalist® MD-74357 XRD1 | TPE; Medalist® MD-74357 XRD2 | TPE; Mediprene® 500120M | TPE; Mediprene® 500200M | TPE; Mediprene® 500250M | TPE; Mediprene® 500300M | TPE; Mediprene® 500350M | TPE; Mediprene® 500400M | TPE; Mediprene® 500434M | TPE; Mediprene® 500450M | TPE; Mediprene® 500484M | TPE; Mediprene® 500520M | TPE;Mediprene® 500534M | TPE; Mediprene® 500584M | TPE; Mediprene® 500600M | TPE; Mediprene® 500634M | TPE; Mediprene® 500650M | TPE; Mediprene® 500684M | TPE; Mediprene® 500700M | TPE; Monprene® RG-10160H | TPE; ProvaMed® TPE 1120 | TPE; ProvaMed® TPE 1160 | TPE; RABALON® PJ4300C | TPE; RABALON® PJ5300C | TPE; RABALON® PJ6300C | TPE; RABALON® PJ7300C | TPE; SkinFlex 15 F-115 A / B | TSU; SkinFlex BR-60; BRUSHABLE A / B | TSU; T-Blend® TPE-F22 | SEBS; THERMOLAST® M TM3LFT (series: MC / LF) | TPE; THERMOLAST® M TM3MED (series: MC / tl) | TPE; THERMOLAST® M TM3RST (series: MC / RS) | TPE; THERMOLAST® M TM4LFT (series: MC / LF) | TPE; THERMOLAST® M TM4MED (series: MC / tl) | TPE; THERMOLAST® M TM4RST (series: MC / RS) | TPE; THERMOLAST® M TM5LFT (series: MC / LF) | TPE; THERMOLAST® M TM5MED (series: MC / tl) | TPE; THERMOLAST® M TM6LFT (series: MC / LF) | TPE; THERMOLAST® M TM6MED (series: MC / tl) | TPE; THERMOLAST® M TM7LFT (series: MC / LF) | TPE; THERMOLAST® M TM7 MED (series: MC / tl) | TPE; UNISOFT SPECIAL™ DS-35A-CL-M-01 | SEBS; UNISOFT SPECIAL™ DS-55A-CL-M-01 | SEBS; Versaflex™ G2705 N | TPE; Versaflex™ HC 1100-40 Translucent EU | TPE; Versaflex™ HC 1348 Natural | TPE; Versaflex™ HC MT317 | TPE; Versaflex™ HC MT555 | TPE; Versaflex™ OM 1040X-1 | TPE; CELLENE MC2248 | TPE; CELLENE MC2265 | TPE; CELLENE MC3038 | TPE; CELLENE MC3050 | TPE; CELLENE MC3061 | TPE; CELLENE MC3226 | TPE; CELLENE MC3239 | TPE; CELLENE MC3261 | TPE; ChronoPrene™ 25A | TPE; ChronoPrene™ 40A | TPE (CardioTech International, Inc.); Dryflex® 500300S | TPE; Dryflex® 500350S | TPE; Dryflex® 500400S | TPE; Dryflex® 500450S | TPE; Dryflex® 500500S | TPE; Dryflex® 500550S | TPE; Dryflex® 500600S | TPE; Dryflex® 500650S | TPE; Dryflex® 500700S | TPE; Dynaflex™ G2701-1000-02 | TPE; Dynaflex™ G2706-1000-00 | TPE; Dynaflex™ G2709-1000-00 | TPE; Dynaflex™ G2711-1000-00 | TPE; Dynaflex™ G2712-1000-02 | TPE; Dynaflex™ G2730 | TPE; Dynaflex™ G2755-1000-00 | TPE; Dynaflex™ G2755C | TPE; Dynaflex™ G6713-0001 | TPE;Dynaflex™ G6713C | TPE; Dynalloy™ GP 7810-60T | TPE; Dynalloy™ GP 7810-70T | TPE; Dynalloy™ OBC8200-BT50 | TPE; Estane® 58123 TPU | TPU-Polyether; Evoprene™ 019 | SBS; Evoprene™ G 925 | SEBS; Evoprene™ G 936 | SEBS; Evoprene™ G 942 | SEBS; Evoprene™ G 958 | SEBS; Evoprene™ G 966 | SEBS; Evoprene™ G 967 | SEBS; Evoprene™ G 968 | SEBS; Evoprene™ G 969 | SEBS; Evoprene™ G 970 | SEBS; Evoprene™ GC 5685 | SEBS; Evoprene™ GC 5686 | SEBS; Evoprene™ GC 5687 | SEBS; Evoprene™ GC 5688 | SEBS; Evoprene™ GC 5689 | SEBS; Evoprene™ GC 5690 | SEBS; GLS 422-126 | TPE; GLS 458-140 | TPE; GLS 458-141 | TPE; GLS 458-142 | TPE; K-Prene HYFLEX HF 15 | MPR; K-Prene HYFLEX HF 20 | MPR; K-Prene HYFLEX HF 25 | MPR; K-Prene HYFLEX HF 30 | MPR; Medalist® RG-38052 XRD1 | TPE; megol® PUG 10 | SEBS; megol® PUG 60 | SEBS; megol® TA 60 | SEBS; Monprene® RG-10130 | TPE; Monprene® RG-10140 | TPE; Monprene® RG-10150 | TPE; Monprene® RG-10160 | TPE; Monprene® RG-10170 | TPE; Monprene® RG-15130 | TPE; Monprene® RG-15140 | TPE; Monprene® RG-15150 | TPE; Monprene® RG-15160 | TPE; Monprene® RG-15170 | TPE; Monprene® RG-18240 | TPE; Monprene® RG-18250 | TPE; Monprene® RG-18260 | TPE; Monprene® RG-18270 | TPE; Monprene® RG-19221 NAT | TPE; Monprene® RG-19255 | TPE; Monprene® RG-20140 | TPE; Monprene® RG-20160 | TPE; Monprene® RG-20170 | TPE; Monprene® RG-29068 NAT | TPE; Monprene® RG-29240XRD1 | TPE; RABALON® MJ4300C | TPE; RABALON® MJ5302C | TPE; RABALON® MJ6301C | TPE; RABALON® MJ7301C | TPE; RAYPRENE® NB221-S4050 | TPE; RAYPRENE® NB221-S4051 | TPE; RAYPRENE® NB221-S4052 | TPE; RAYPRENE® NB221-S4053 | TPE; tefabloc® TO 132 | TPE; Telcar® TL-83-F943D22-NT BLU | TPE; THERMOLAST® K TF2CGT (family: FC) | TPE; THERMOLAST® K TF3BTL (family: FC / AP) | TPE; THERMOLAST® K TF3CGT (family: FC) | TPE; THERMOLAST® K TF3STE (family: FC / CS) | TPE; THERMOLAST® K TF4AAB (family: FC / HE / tl) | TPE; THERMOLAST® K TF4BTL (family: FC / AP) | TPE; THERMOLAST® K TF4CGT (family: FC) | TPE; THERMOLAST® K TF4STE (family: FC / CS) | TPE; THERMOLAST® K TF5AAC (family: FC / HE / tl) | TPE; THERMOLAST® K TF5BTL (family: FC / AP) | TPE; THERMOLAST® K TF5CGT (family: FC) | TPE; THERMOLAST® K TF5STE (family: FC / CS) | TPE;K TF6AAC (series: FC / HE / tl) | TPE; THERMOLAST® K TF6BTL (series: FC / AP) | TPE; THERMOLAST® K TF6CGT (series: FC) | TPE; THERMOLAST® K TF6STE (series: FC / CS) | TPE; THERMOLAST® K TF6WCS (series: DW / CS) | TPE; THERMOLAST® K TF6WHA (series: DW / H) | TPE; THERMOLAST® K TF6WHB (series: DW / H) | TPE; THERMOLAST® K TF7AAC (series: FC / HE / tl) | TPE; THERMOLAST® K TF7BTL (series: FC / AP) | TPE; THERMOLAST® K TF7CGT (series: FC) | TPE; THERMOLAST® K TF7WHB (series: DW / H) | TPE; Topolymer® 8201-B | TPE; Versaflex™ FFC 2882-50 EU | TPE; Versaflex™ FFC 2882-50 | TPE; Versaflex™ G2708 N | TPE; Versaflex™ GP 2810-20N | TPE; Versaflex™ GP 2810-30N | TPE; Versaflex™ GP 2810-40N | TPE; Versaflex™ GP 2810-50N | TPE; Versaflex™ GP 2810-60N | TPE; Versaflex™ GP 2810-70N | TPE; Cawiton® MT920 | SEBS; Cawiton® MT930 | SEBS; Cawiton® MT940 | SEBS; Cawiton® MT950 | SEBS; Cawiton® MT960 | SEBS; Cawiton® MT970 | SEBS.

[0184] The following embodiments are also disclosed.

[0185] Embodiment 1. A fluidic device (100) for testing a biological material, the fluidic device comprising: a substrate (102) having a top side (104) and a bottom side (106); and one or more fluid assemblies (108), each fluid assembly comprising: at least one chamber unit (110) in which biological material can be contained, the at least one chamber unit being defined in the base plate and extending between the top side and the bottom side; an inlet (112) for receiving fluid; an outlet (114) for allowing removal of fluid; an inlet fluid channel (116) defined in the base plate and extending between the inlet and the at least one chamber unit; an outlet fluid channel (118) defined in the base plate and extending between the at least one chamber unit and the outlet; and a dam assembly for controlling fluid flow through the at least one chamber unit, the dam assembly comprising at least one of an inlet dam (136) located between the inlet fluid channel and the at least one chamber unit and extending upright towards the top side to an inlet sill (138) arranged for allowing fluid from the inlet fluid channel to flow thereover so as to be received in the at least one chamber unit, and an outlet dam (132) located between the at least one chamber unit and the outlet fluid channel and extending upright towards the top side to an outlet sill (134) arranged for allowing fluid from the at least one chamber unit to flow thereover so as to be received in the outlet fluid channel.

[0186] Embodiment 2. The fluidic device (100) according to embodiment 1, wherein the at least one chamber unit (110) extends to an opening at the top side (104) of the base plate (102), and the dam assembly comprises an inlet dam (136) and an outlet dam (132) arranged for retaining fluid in the at least one chamber unit.

[0187] Embodiment 3. The fluidic device (100) according to embodiment 1 or embodiment 2, wherein the dam assembly comprises an inlet dam (136) and an outlet dam (132), and the outlet sill (134) is lower than the inlet sill (138) such that fluid filling the at least one chamber unit (110) to reach the outlet sill flows over the outlet sill into the outlet fluid channel (118).

[0188] Embodiment 4. The fluidic device (100) according to any one of embodiments 1 to 3, wherein one or more of the at least one chamber units comprises a dual chamber unit (110) comprising a first chamber (140) and a second chamber (142), the first chamber (140) and the second chamber (142) being fluidly connected to each other via a bridge (144) defined between the first chamber and the second chamber.

[0189] Embodiment 5. The fluidic device (100) according to embodiment 4, wherein: the dam assembly comprises an inlet dam 136 and an outlet dam 132; the inlet dam is located between the inlet fluidic channel (116) and the first chamber (140) such that fluid filling the inlet fluidic channel to reach the inlet sill (138) flows over the inlet sill into the first chamber; the outlet dam is located between the second chamber 142 and the outlet fluidic channel 118; the fluidic device further comprises an intermediate dam (146) located between the first chamber and the second chamber, the intermediate dam extending upright towards the top side to an intermediate sill at a base of a bridge (144) located between the first chamber and the second chamber; the bridge sill is lower than the inlet sill such that fluid filling the first chamber to reach the bridge sill flows over the bridge sill into the second chamber; and the outlet sill (134) is lower than the bridge sill such that fluid filling the second chamber to reach the outlet sill flows over the outlet sill into the outlet fluidic channel.

[0190] Embodiment 6. The fluidic device (100) according to any one of embodiments 1 to 5, wherein each of the at least one chamber units (110) comprises at least one support region (120) for supporting a biocompatible partition (122) such that the biocompatible partition separates an upper portion (124) from a lower portion (126) of the respective chamber unit.

[0191] Embodiment 7. The fluidic device (100) according to embodiment 6, wherein the upper and lower portions (124, 126) have different volumes relative to each other.

[0192] Embodiment 8. The fluidic device (100) according to embodiment 6 or embodiment 7, wherein the at least one support region (120) is arranged for supporting the biocompatible partition closer to one of the top and bottom sides (104, 106) than to the other of the top and bottom sides (106, 104).

[0193] Embodiment 9. The fluidic device (100) according to any one of embodiments 6 to 8, comprising a biocompatible partition (122), wherein the biocompatible partition is attachable to the substrate (102) or is an integral part of the substrate.

[0194] Embodiment 10. The fluidic device (100) according to any one of embodiments 6 to 9, comprising: an upper fluid flow system 128 defined in the substrate 102, the upper fluid flow system comprising the inlet fluid channel 116 and the outlet fluid channel 118; and a lower fluid flow system (130) defined in the substrate and arranged to supply fluid to the lower portion (126) and / or to allow fluid to exit the lower portion (126).

[0195] Embodiment 11. The fluidic device (100) according to any one of embodiments 1 to 10, wherein the at least one chamber unit (110) comprises a plurality of chamber units.

[0196] Embodiment 12. The fluidic device (100) according to embodiment 11, wherein the chamber units (110) are connected in parallel across the inlet fluid channel (116) and the outlet fluid channel (118).

[0197] Embodiment 13. The fluidic device (100) according to embodiment 11 or embodiment 12 when based on embodiment 10, wherein the plurality of chamber units (110) each comprise the upper portion (124) and the lower portion (126), and the lower fluid flow system (130) comprises at least one fluid channel (131; 160, 162) fluidically connecting the lower portions to each other.

[0198] Embodiment 14. The fluidic device (100) according to any one of embodiments 1 to 13, comprising a plurality of the fluidic assemblies (108).

[0199] Embodiment 15. The fluidic device (100) according to embodiment 14, wherein the outlet sill (134) of at least some of the plurality of fluidic assemblies are at different heights relative to each other.

[0200] Embodiment 16. The fluidic device (100) according to any one of embodiments 1 to 15, wherein the inlet fluid channel (116) provides a resistance to flow therein that varies with distance along the inlet fluid channel away from the inlet (112).

[0201] Embodiment 17. The fluidic device (100) according to any one of embodiments 1 to 16, wherein the outlet fluid channel (118) provides a resistance to flow therein that varies with distance along the outlet fluid channel away from the chamber unit (110).

[0202] Embodiment 18. The fluidic device (100) according to any one of embodiments 1 to 17, comprising an upper cover for covering the top side (104) of the substrate (102).

[0203] Embodiment 19. The fluidic device (100) according to embodiment 18, wherein the upper cover is configured to enable access to the at least one chamber unit (110).

[0204] Embodiment 20. The fluidic device (100) according to any one of embodiments 1 to 19, comprising a lower cover for covering the bottom side (106) of the substrate.

[0205] Embodiment 21. The fluidic device (100) according to embodiment 20, wherein the lower cover is configured to enable access to the at least one chamber unit (110).

[0206] Embodiment 22. Use of the fluidic device (100) according to any one of embodiments 1 to 21 for testing biological material.

[0207] Embodiment 23. A method of drug testing, comprising: providing biological material in the at least one chamber unit (110) of the fluidic device (100) according to any one of embodiments 1 to 21; and exposing the biological material to a drug to be tested.

[0208] Embodiment 24. The method of drug testing according to embodiment 23, wherein providing biological material in the at least one chamber unit comprises culturing cells in the at least one chamber unit.

[0209] Variants of the disclosed embodiments can become apparent to those skilled in the art from the disclosure and the appended claims. In the claims, the word "comprising" does not exclude other elements or steps, and the indefinite articles "a" or "an" do not exclude a plurality.

[0210] The mere fact that measures are recited in mutually different dependent claims does not indicate that a combination of these measures cannot be used to advantage.

[0211] If the term "comprises" is used in the claims or specification, it is noted that the term "comprises" is intended to be equivalent to the term "consists of" or "consisting of".

[0212] Any reference signs in the claims should not be construed as limiting the scope.

Claims

1. A fluidic device (100) for testing biological material, the fluidic device comprising: a substrate (102) having a top side (104) and a bottom side (106); and one or more fluidic assemblies (108), each fluidic assembly comprising: at least one chamber unit (110) in which the biological material can be contained, the at least one chamber unit being defined in the substrate and extending between the top side and the bottom side; an inlet (112) for receiving fluid; an outlet (114) for allowing removal of fluid; an inlet fluidic channel (116) defined in the substrate and extending between the inlet and the at least one chamber unit; an outlet fluidic channel (118) defined in the substrate and extending between the at least one chamber unit and the outlet; and a dam assembly for controlling fluid flow through the at least one chamber unit, the dam assembly comprising an inlet dam (136) and an outlet dam (132), the inlet dam being located between the inlet fluidic channel and the at least one chamber unit and extending upright towards the top side to an inlet sill (138) arranged to allow fluid from the inlet fluidic channel to flow over it to be received in the at least one chamber unit, and the outlet dam being located between the at least one chamber unit and the outlet fluidic channel and extending upright towards the top side to an outlet sill (134) arranged to allow fluid from the at least one chamber unit to flow over it to be received in the outlet fluidic channel, wherein the outlet sill is lower than the inlet sill such that fluid filling the at least one chamber unit to reach the outlet sill flows over the outlet sill into the outlet fluidic channel. The at least one chamber unit (110) extends to an opening at the top side (104) of the substrate (102), the inlet dam and the outlet dam being arranged to retain fluid in the at least one chamber unit.

2. The fluidic device (100) of claim 1, wherein, comprising a first chamber (140) and a second chamber (142), the first chamber (140) and the second chamber (142) being fluidically connected to each other via a bridge (144) defined between the first chamber and the second chamber.

3. The fluidic device (100) according to claim 1 or 2, wherein 4. The fluidic device (100) of claim 3, wherein: the inlet dam is located between the inlet fluidic channel (116) and the first chamber (140) such that fluid filling the inlet fluidic channel to reach the inlet sill (138) flows over the inlet sill into the first chamber; the outlet dam is located between the second chamber (142) and the outlet fluidic channel (118); ​ The fluidic device further comprises an intermediate dam portion (146) between the first and second chambers, the intermediate dam portion extending upright towards the top side to a bridge sill at a base of a bridge (144) between the first and second chambers; The bridge sill is lower than the inlet sill, such that fluid filling the first chamber to the bridge sill flows over the bridge sill into the second chamber; and The outlet sill (134) is lower than the bridge sill, such that fluid filling the second chamber to the outlet sill flows over the outlet sill into the outlet fluid passage.

5. The fluidic device (100) according to any one of claims 1 to 4, wherein, The fluidic device (100) comprises a biocompatible partition (122), wherein each of the at least one chamber units (110) comprises at least one support region (120) for supporting the biocompatible partition such that the biocompatible partition separates an upper portion (124) from a lower portion (126) of the respective chamber unit.

6. The fluidic device (100) of claim 5, wherein, The upper portion (124) and the lower portion (126) have different volumes relative to each other.

7. The fluidic device (100) according to claim 5 or 6, wherein The at least one support region (120) is arranged to support the biocompatible partition (122) closer to one of the top side (104) and the bottom side (106) than to the other of the top side (106) and the bottom side (104).

8. The fluidic device (100) according to any one of claims 5 to 7, wherein, The biocompatible partition is attachable to the substrate (102) or is an integral part of the substrate.

9. The fluidic device (100) according to any one of claims 5 to 8, wherein, The fluidic device (100) comprises: an upper fluid flow system (128) defined in the substrate (102), the upper fluid flow system comprising the inlet fluid passage (116) and the outlet fluid passage (118); and a lower fluid flow system (130) comprising at least one lower fluid passage (131) defined in the substrate and arranged for supplying fluid to and / or allowing fluid to exit from the lower portion (126).

10. The fluidic device (100) according to any one of claims 1 to 9, wherein, The at least one chamber unit (110) comprises a plurality of chamber units.

11. The fluidic device (100) of claim 10, wherein, The chamber units (110) are connected in parallel across the inlet fluid passage (116) and the outlet fluid passage (118).

12. The fluidic device (100) according to claim 10 or 11 when dependent on claim 9, wherein The plurality of chamber units (110) each comprise the upper portion (124) and the lower portion (126), and the lower fluid flow system (130) comprises at least one fluid passage (131; 160, 162) fluidically connecting the lower portions to each other.

13. The fluidic device (100) according to any one of claims 1 to 12, wherein, The fluidic device (100) comprises a plurality of the fluid assemblies (108).

14. The fluidic device (100) of claim 13, wherein, The outlet sills (134) of at least some of the plurality of fluid assemblies (108) are at different heights relative to each other.

15. The fluidic device (100) according to any one of claims 1 to 14, wherein, The inlet fluid passage (116) provides a resistance to flow therein, the resistance varying with distance along the inlet fluid passage away from the inlet (112).

16. The fluidic device (100) according to any one of claims 1 to 15, wherein, The outlet fluid channel (118) provides a resistance to flow therein, which varies with distance along the outlet fluid channel away from the chamber unit (110).

17. The fluidic device (100) according to any one of claims 1 to 16, wherein, The fluidic device (100) comprises an upper cover for covering the top side (104) of the substrate (102); optionally, the upper cover is configured to enable access to the at least one chamber unit (110).

18. The fluidic device (100) according to any one of claims 1 to 17, wherein The fluidic device (100) comprises a lower cover for covering the bottom side (106) of the substrate; Optionally, the lower cover is configured to enable access to the at least one chamber unit (110).

19. Use of the fluidic device (100) according to any one of claims 1 to 18 for testing biological material.

20. A method of drug testing, comprising: providing biological material in the at least one chamber unit (110) of the fluidic device (100) according to any one of claims 1 to 18, optionally, providing biological material in the at least one chamber unit comprises culturing cells in the at least one chamber unit; and exposing the biological material to the drug to be tested.

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