WO2025242595A1

WO2025242595A1 - Fluidic cartridges with component-free valves

Info

Publication number: WO2025242595A1
Application number: PCT/EP2025/063669
Authority: WO
Inventors: Amaru Daniel Araya-Williams
Original assignee: Lex Diagnostics Ltd
Current assignee: Lex Diagnostics Ltd
Priority date: 2024-05-21
Filing date: 2025-05-19
Publication date: 2025-11-27
Anticipated expiration: 2026-11-21

Abstract

Cartridges, e.g., microfluidic cartridges with a component-free valve include a substrate, a fluidic channel formed in a surface of the substrate, and a component-free valve within the fluidic channel including a blockage area of the substrate that separates a first portion of the fluidic channel from a second portion of the fluidic channel, and a flexible film bonded to the surface of the substrate along the fluidic channel and around the blockage area, but unbonded in an area that encloses the blockage area and a section of the first and second portions of the fluidic channel. When the film of these cartridges is pressed against a surface of the blockage area, the component-free valve is closed, and when the unbonded flexible film is not pressed against the blockage area, the component-free valve is open, enabling fluid flow from the first portion of the fluidic channel to the second portion of the fluidic channel.

Description

FLUIDIC CARTRIDGES WITH COMPONENT-FREE VALVES

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims priority to U.S. Provisional Application No. 63/650,005 filed on May 21, 2024, the entire contents of which are hereby incorporated by reference.

TECHNICAL FIELD

[0002] The present disclosure relates generally to devices, systems, and methods for providing valves, e.g., on a fluidic cartridge, and the cartridges themselves.

BACKGROUND

[0003] It can be useful to transmit a fluid from one location, e.g., a common source, to one or more chambers or channels through fluidic pathways. It can also be useful to selectively connect and disconnect the fluidic pathways.

SUMMARY

[0004] The present disclosure provides devices, systems, and methods for providing component- free valves, e.g., on microfluidic reaction cartridges, without the need to add any additional parts or components to the cartridges. An example of such a new valve includes a fluidic channel formed, e.g., molded or cut, in a surface of the substrate of the cartridge. A flexible film is typically bonded to the substrate of the cartridge and in this case also covers the fluidic channel. The valve includes a blockage area in the fluidic channel (e.g., an area of the channel that is not cut out, or is an area between two adjacent fluidic channels molded or cut into the substrate). The blockage area is covered with an area of unbonded flexible film that is bonded to the surface of the substrate around the area of the fluidic channel(s) and around the blockage area and the bond of the film to the substrate surrounds and encompasses the blockage area and some section of the fluidic channel(s). When the unbonded flexible film is pressed against the blockage area by an actuator arranged within a device (e.g., a cartridge reader) into which the reaction cartridge is inserted during use, the fluidic channel is (or two adjacent fluidic channels are) disconnected such that fluid flow through the fluidic channel(s) is prevented. In this configuration, the unbonded flexible film forms a seal against the blockage area in the fluidic channel (or between two adjacent fluidic channels). When the unbonded flexible film is not pressed against the blockage area, the pressure of the fluid within the fluidic channel forces open a space between the blockage area and the flexible film thereby enabling fluid flow through or between the fluidic channel(s).

[0005] In one aspect, the disclosure provides microfluidic cartridges with one or more component-free valves, the microfluidic cartridges including or consisting of a substrate, a fluidic channel formed in a surface of the substrate, a component-free valve within the fluidic channel including a blockage area of the substrate that separates a first portion of the fluidic channel from a second portion of the fluidic channel, and a flexible film bonded to the surface of the substrate along the fluidic channel and around the blockage area, but unbonded in an area that encloses the blockage area and a section of the first and second portions of the fluidic channel, wherein when the unbonded flexible film is pressed against a surface of the blockage area, the component-free valve is closed, inhibiting fluid flow through the fluidic channel between the first and second portions of the fluidic channel, and when the unbonded flexible film is not pressed against the blockage area, the component-free valve is open, enabling fluid flow from the first portion of the fluidic channel to the second portion of the fluidic channel when fluid pressure within the first portion is sufficient to move or deform the flexible film away from the surface of the blockage area.

[0006] Embodiments can include one or any combination of two or more of the following features.

[0007] The unbonded flexible film is pressed against the blockage area at least in a line or an area that extends across the entire blockage area, separating the first and second portions of the fluidic channel.

[0008] The channel is molded, embossed, or cut into the substrate of the cartridge.

[0009] The flexible film is bonded to the substrate by a heat seal, a laser weld, or an ultrasonic weld.

[0010] The unbonded flexible film is configured to prevent fluid flow through the fluidic channel when the unbonded flexible film is pressed against the surface of the blockage area with a force of at least 0.2 Newtons, e.g., at least about 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1.0, 1.25, 1.5, 1.75, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, or more Newtons. [0011] In another aspect, the disclosure provides systems including one or more microfluidic cartridges as described herein, an instrument configured to receive the one or more microfluidic cartridges, wherein the instrument includes a controller and an actuator configured and controlled by the controller to selectively press the unbonded film against the blockage area, or to release the pressure, to selectively open and/or close the component-free valve, respectively. [0012] Embodiments can include one or any combination of two or more of the following features.

[0013] The actuator is controlled to apply a pressure of at least 0.2 Newtons, e.g., at least about 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1.0, 1.25, 1.5, 1.75, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, or about 5.0, or more Newtons, to the unbonded flexible film, to push the film against the surface of the blockage area.

[0014] The actuator includes a tip having a surface configured to press the unbonded flexible film against the surface of the blockage area. In some implementations, the surface is convex. In some implementations, the surface is flat.

[0015] The actuator can include a tip having a line contact surface configured to press the unbonded flexible film against the surface of the blockage area, in a line that extends across the blockage area, separating the first and second portions of the fluidic channel.

[0016] The actuator can include a tip having a star-shaped surface configured to press the unbonded flexible film against the surface of the blockage area.

[0017] The actuator can include a tip including a foam material.

[0018] The actuator can include a tip including a material with a hardness in a range of about 20 ShoreA to about 90 ShoreA, e.g., about 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, or about 90 ShoreA. The actuator can include a tip comprising a rubber material.

[0019] In another aspect, the disclosure provides methods of controlling fluid flow through a component-free valve of the microfluidic cartridges described herein, the methods including controlling an actuator to selectively press the unbonded flexible film against the surface of the blockage area to selectively open and close the component-free valve on the microfluidic cartridges.

[0020] Embodiments can include one or any combination of two or more of the following features. [0021] The methods can include controlling the actuator to press the unbonded film against the surface of the blockage area with a force of at least 0.2 to about 5.0 Newton, e.g., about 0.5 to about 3.0 Newtons, or about 1.0 to about 2.5 Newtons.

[0022] The methods can include controlling the actuator to press the unbonded film against the surface of the blockage area with a force of at least about 0.2 Newton to at least about 5.0 Newtons.

[0023] The methods include controlling the actuator to press the unbonded film against the surface of the blockage area with a force of no more than 100 Newtons, e.g., less than about 90, 80, 70, 60, 50, 40 , 30 , 20, 10, or 5.0 Newtons.

[0024] A width of the valve transverse to the longitudinal direction can be between about 1 mm and about 5 mm, e.g., between about 2 mm and about 4 mm, e.g., about 3 mm.

[0025] A gap between the first portion and the second portion of the fluidic channel can be between about 0.5 mm and about 5 mm.

[0026] The fluidic channel includes two or more channels that are separated by a blockage area. [0027] The devices, systems, and methods disclosed herein are advantageous in that the valves can be provided on reaction cartridges without adding additional components on the cartridge or additional manufacturing process complexity, e.g., without complex assembly process steps or additional process steps. For example, other types of valves can be costly and challenging to integrate into a diagnostic device (e.g., such as disposable cartridges, which are typically cost sensitive). A valve that does not include additional components on the cartridge can be beneficial in terms of cost-savings, time-savings, weight-savings, etc., and can benefit the manufacture and use of other fluidic devices.

[0028] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention, suitable methods and materials are described below. All publications, patent applications, patents, and other references mentioned herein are incorporated by reference in their entirety. In case of conflict, the present specification, including definitions, will control. In addition, the materials, methods, and examples are illustrative only and not intended to be limiting. [0029] Various embodiments of the features of this disclosure are described herein. However, it should be understood that such embodiments are provided merely by way of example, and numerous variations, changes, and substitutions can occur to those skilled in the art without departing from the scope of this disclosure. It should also be understood that various alternatives to the specific embodiments described herein are also within the scope of this disclosure.

[0030] Other features and advantages of the invention will be apparent from the following detailed description, and from the claims.

DESCRIPTION OF DRAWINGS

[0031] FIGS. 1 A and IB are diagrams of fluidic channels including component-free valves, as described herein.

[0032] FIGS. 2A and 2B are schematic diagrams of side views of fluidic channels including component-free valves in the open (2A) and closed (2B) positions.

[0033] FIG. 3 is a schematic diagram of a cartridge including multiple types of component-free valves and four different types of actuators.

[0034] FIG. 4 is a diagram of a weld head that can be used to form component-free valves as described herein.

[0035] FIG. 5A is a graph of results from characterization tests for holding pressures within component-free valves.

[0036] FIG. 5B is a table of results from characterization tests for holding pressures within component-free valves.

[0037] FIGS. 6A-D are schematic diagrams of examples of instruments that can utilize the cartridges described herein.

DETAILED DESCRIPTION

[0038] The present disclosure provides devices, systems, and methods for providing valves, e.g., on a reaction cartridge. These valves include a fluidic channel or channels molded or cut into the cartridge. A flexible film (e.g., a plastic (e.g., polypropylene, polystyrene, or the like), a metal film (e.g., aluminum), or a laminate film of multiple materials (e.g., plastics and/or metals) can be bonded (e.g., heat sealed, laser welded, ultrasonically welded, glued, or adhered) to the substrate and cover the channel. A blockage area in the fluidic channel (e.g., an area of the channel that is not molded or cut into the surface of the substrate or a separation between two adjacent channels) can create a shut-off valve controlled by an actuator. The blockage area is enclosed within an area of unbonded flexible film. When the unbonded flexible film is pressed against the blockage area (e.g., by an actuator of an instrument, e.g., a cartridge reader), the fluidic channel is disconnected such that fluid flow through the fluidic channel is prevented. In this configuration, the unbonded flexible film is pressed to form a seal against the blockage area in the fluidic channel. When the unbonded flexible film is not pressed against the blockage area, the fluid pressure within the fluidic channel creates a separation between the surface of the blockage area and the flexible film to enable fluid flow through the fluidic channel or flow from one channel to another separated by the blockage area. Note that as shown in FIGs. 1 A and IB, the flexible film is bonded to the substrate around the edges of the blockage area that are not bordering on the fluidic channel(s) so that fluid does not leak out between the flexible film and the surface of the blocking area.

Systems for Implementing Component-Free Valves

[0039] FIGS. 1A and IB are diagrams of a component-free valve 100, which includes a discontinuous fluidic channel 102 that is separated by a blockage area 104. The blockage area in this implementation is a disconnect in the center of the fluidic channel 102 (e.g., the fluidic channel 102 is not continuously molded into or cut out of the substrate throughout the length of the fluidic channel 102). A layer of a flexible film (e.g., a polypropylene film) covers the fluidic channel. The flexible film is sealed around the areas of the fluidic channel 102 that are molded into or cut out of the substrate (e.g., areas 102a, 102b). In some implementations, the valve 100 has a width between the two parts of the fluidic channel between about 1 mm and about 5 mm, between about 0.5 mm and about 10 mm, e.g., 1 mm, 2 mm, 3 mm, 4 mm, etc. In some implementations, the blockage area 104 fills a length of between about 0.5 mm and about 5 mm between the two parts of the fluidic channel or between two or more separate fluidic channels. For example, the blockage area 104 can cover an area that has a length of between about 0.5 mm and about 10 mm, about 0.1 mm and ab out 7 mm, e.g., 1 mm, 2 mm, 3 mm, 4 mm, etc.

[0040] As illustrated in FIG. IB, an area of unbonded flexible film 106 surrounds the blockage area 104 and overlaps ends of the areas 102a, 102b of the fluidic channel 102. The unbonded flexible film 106 deforms, flexes, moves, or otherwise separates from the substrate when the fluidic channel 102 is pressurized by fluid flow, allowing fluid to flow from one end of the fluidic channel 102 to the other end of the fluidic channel 102. The bonded portion of the flexible film 106a is bonded to the substrate around the edges 108 of the area of unbonded flexible film 106b. The edges 108 of the unbonded flexible film 106b and the ends of the areas 102a, 102b of the fluid channel 102 are continuous, e.g., so that fluid does not leak out of separations between the flexible film and the blocking surface when fluid is allowed to flow over the blockage (e.g., when the unbonded flexible film is deformed).

[0041] FIGS. 2A and 2B are schematic diagrams of side views of a component-free valve 200 when open and closed, respectively. The component-free valve 200 includes fluidic channels 202, 204 separated by a blockage area 206. A layer of a flexible film (e.g., a polypropylene film) 208 covers and seals around the fluidic channels 202, 204. However, the flexible film 208 is not sealed in an area of unbonded flexible film 210 covering and enclosing the blockage area 206. [0042] As illustrated in FIG. 2A, when the valve 200 is open, fluid is able to flow through the fluidic channel 202, over the blockage area 206, and through the fluidic channel 204 because the area of unbonded flexible film 210 is able to deform to allow fluid to flow. The pressure of the fluid flowing through the fluidic channel 202 deforms the unbonded flexible film 210 away from the blockage area 206, enabling the fluid to flow over the blockage area 206.

[0043] As illustrated in FIG. 2B, the valve 200 can be closed by an actuator 212 (e.g., an actuator that is part of a cartridge reader). When the valve 200 is closed, the actuator 212 presses the unbonded flexible film 210 against the blockage area 206 with a sufficient force (e.g., at least 0.2, 0.3, 0.4, 0.5, 0.75, 1.0, 2.5, 5.0, 7.5, or 10.0 Newtons, e.g., at least 5.0 Newtons, at least 0.1 - 100.0 Newtons, or at least 0.5 - 1.0 Newtons), to prevent fluid flow between the fluidic channels 202, 204. The pressure of the fluid flowing through the fluidic channel 202 cannot deform the unbonded flexible film 210 away from the blockage 206, because the actuator 212 is applying a sufficient force to the unbonded flexible film.

[0044] In some implementations, a device into which the cartridge is inserted during use, e.g., a cartridge reader, controls an actuator (e.g., similar to actuator 212) to selectively open and close a valve (e.g., similar to component-free valve 200) on a fluidic cartridge. For example, during some portions of a process (e.g., a PCR process) run by the reader, the cartridge reader enables fluid to flow through the valve by removing force from the valve (e.g., by removing force from the area of unbonded flexible film above a blockage area). During some portions of the process run, the cartridge reader prevents fluid from flowing through the valve by actuating the actuator to applying force to the valve (e.g., by applying force to the area of unbonded flexible film above the blockage area). Because the cartridge reader is able to selectively open and close the valve by simply applying or removing force with an actuator, no additional components (e.g., other types of valves or components of typical valves) need to be added to the cartridge. For example, other types of valves (e.g., wax melt valves, burst valves, disc valves, etc.) can be costly and challenging to integrate into a diagnostic device (e.g., such as disposable cartridges that are typically cost sensitive). A valve that does not include additional components on the cartridge can be beneficial, e.g., and can benefit other fluidic devices.

[0045] An example of a cartridge reader can include a heater controller for selectively controlling a heater element between an on condition and an off condition in response to a determined temperature of the heater element and/or test sample; an electrical heater interface for connecting the heater controller and the heater; a heat sink; and a thermal interface in thermal contact with the heat sink, the thermal interface being adapted for thermal contact with the heat sink when the cartridge is received by the cartridge reader, for subtracting heat from the reactor vessel so as to cool the test sample.

[0046] The cartridge reader can include a pneumatic system for controlling pressure and/or motion of a test sample within the cartridge when the cartridge is received by the cartridge reader, the pneumatic system including: a pneumatic interface for connecting the pneumatic system to an amplification module (e.g., in a polymerase chain reaction (PCR) device); a pneumatic pump for providing pressure and/or motion to the test sample via the pneumatic interface; and a pneumatic controller for controlling the pneumatic pump.

[0047] The cartridge reader can control an actuator that presses unbonded flexible film against the blockage area to disconnect fluid channels, as described above, such that fluid flow through the fluidic channels are prevented. In this configuration, the unbonded flexible film forms a seal against the blockage area in the fluidic channels (or between two adjacent fluidic channels). When the unbonded flexible film is not pressed against the blockage area, the pressure of the fluid within the fluidic channel forces open a space between the blockage area and the fluidic channels thereby enabling fluid flow through the fluidic channels. The actuator can be controlled by a controller, which follows instruction steps.

[0048] FIG. 3 illustrates an example of a cartridge 300 including a number of fluidic channels and component-free valves between the fluidic channels. For example, the component-free valves can be similar to the component-free valves described with reference to FIGS. 1 A, IB, 2A, and 2B. A flexible film 350 can cover the fluidic channels and component-free valves on the cartridge, as discussed above. The different connections between the fluidic channels illustrate different implementations in which component-free valves, e.g., similar to those discussed above, can connect one or more fluidic channels within a fluidic cartridge.

[0049] A first valve 302 can include a blockage area 308 connecting one fluidic channel 304a to multiple other fluidic channels 304b, 304c, 304d, 304e. The valve 302 can be actuated by a flat actuator 310. The flat actuator 310 includes a tip 306 composed of, e.g., thermoplastic elastomers (TPE), silicones, or the like. The tip can also be composed of rubber, e.g., butadiene, nitrile, or the like. The tip 306 can have a hardness in a range of about 20 ShoreA to about 90 ShoreA, e.g., about 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, or 95 ShoreA hardness. The tip has a flat surface configured to press an area of unbonded flexible film against the blockage area 308 to close the valve 302. When the tip 306 is not pressed against the blockage area 308, fluid can flow between the fluidic channel 304a and the other fluidic channels 304b, 304c, 304d, 304e, because the flexible film 350 deforms over the blockage area 308. However, when the tip 306 is pressed against the blockage area 308, fluid is not able to flow between the fluidic channel 304a and the other fluidic channels 304b, 304c, 304d, 304e, because the flexible film 350 is pressed against the blockage area 308, thereby sealing the valve.

[0050] Although fluidic channel 304a is described as acting as the inlet in this embodiment, in other embodiments another fluidic channel can act as the inlet, and fluid can flow from any one of the fluidic channels 304a, 304b, 304c, 304d, or 304e to any of the other fluidic channels depending on which fluidic channel is the inlet.

[0051] A second valve 312 can also include a blockage area 318 connecting one fluidic channel 314a to multiple other fluidic channels 314b, 314c, 314d, 314e. The valve 312 can be actuated by a star-shaped actuator 320. The star-shaped actuator 320 includes a tip 316 having a star-shaped surface. The star-shaped surface presses against the blockage area 318 differently than a corresponding flat actuator (e.g., similar to the flat actuator 308) would. In some implementations, a star-shaped actuator can be more efficient than a flat actuator, and vice versa, depending on the shape of the blockage area and the orientations of the fluidic channels 314a, 314b, 314c, 314d, 314e. The tip 316 is configured to press an unbonded area of flexible film against the blockage area 318 to close the valve 312. When the tip 316 is not pressed against the blockage area 318, fluid can flow between the fluidic channel 314a and the other fluidic channels 314b, 314c, 314d, 314e, because the flexible film 350 deforms over the blockage area 318.

However, when the tip 316 is pressed against the blockage area 318, fluid is not able to flow between the fluidic channel 314a and the other fluidic channels 314b, 314c, 314d, 314e, because the flexible film 350 is pressed against the blockage area 318, thereby sealing the valve.

[0052] Although fluidic channel 314a is described as acting as the inlet in this embodiment, fluid can flow from any one of the fluidic channels 314a, 314b, 314c, 314d, 314e to any of the other fluidic channels depending on which fluidic channel is the inlet.

[0053] A third valve 322 can include multiple blockage areas 328a, 328b, 328c, 328d, 328e connecting multiple fluidic channels 324a, 324b, 324c, 324d, 324e to multiple other fluidic channels 324f, 324g, 324h, 324i, 324j, respectively. For example, fluidic channel 324a connects to fluidic channel 324f over blockage area 328a, fluidic channel 324b connects to fluidic channel 324g over blockage area 328b, fluidic channel 324c connects to fluidic channel 324h over blockage area 328c, fluidic channel 324d connects to fluidic channel 324i over blockage area 328d, and fluidic channel 324e connects to fluidic channel 324j over blockage area 328e.

However, fluidic channels 324a, 324b, 324c, 324d, 324e do not connect to each other over any of the blockage areas because the flexible film 350 is bonded to the substrate in between the respective blockage areas. This implementation of a component-free valve can connect multiple fluidic channels, e.g., without causing every fluidic channel of the multiple fluidic channels to be connected.

[0054] The valve 322 can be actuated by an actuator 330 including a bank of tips 326a, 326b, 326c, 326d, 326e that correspond to the multiple blockage areas 328a, 328b, 328c, 328d, 328e, respectively. Including multiple tips on a single actuator, wherein each of the multiple tips corresponds to a respective one of multiple blockage areas, can allow the single actuator to fluidly connect and disconnect multiple fluidic channels from each other simultaneously.

Splitting the tip into multiple tips can be advantageous, e.g., because it can reduce actuation force for blockage areas that are spaced apart.

[0055] The actuator 330 is configured to press multiple unbonded areas of flexible film against the blockage areas 328a, 328b, 328c, 328d, 328e simultaneously. For example, each blockage area 328a, 328b, 328c, 328d, 328e can be covered, enclosed, and/or encompassed by an area of unbonded flexible film, and when the actuator 330 moves, each of the tips 326a, 326b, 326c, 326d, 326e presses onto one of the multiple blockage areas 328a, 328b, 328c, 328d, 328e simultaneously. When the tips 326a, 326b, 326c, 326d, 326e are not pressed onto the blockage areas 328a, 328b, 328c, 328d, 328e, fluid can flow between the fluidic channel 324a and the fluidic channel 324f, between the fluidic channel 324b and the fluidic channel 324g, between the fluidic channel 324c and the fluidic channel 324h, between the fluidic channel 324d and the fluidic channel 324i, and between the fluidic channel 324e and the fluidic channel 324j , i.e., because the flexible film 350 moves, flexes, or deforms over the blockage areas 328a, 328b, 328c, 328d, 328e. However, when the tips 326a, 326b, 326c, 326d, 326e are pressed onto the blockage areas 328a, 328b, 328c, 328d, 328e, fluid is not able to flow between the fluidic channels 324a because the flexible film 320 is pressed against the blockage areas 328a, 328b, 328c, 328d, 328e, thereby sealing the valve.

[0056] A fourth valve 332 can include multiple blockage areas 338a, 338b, 338c, 338d, 338e connecting multiple fluidic channels 334a, 334b, 334c, 334d, 334e to multiple other fluidic channels 334f, 334g, 334h, 334i, 334j, respectively. For example, fluidic channel 334a connects to fluidic channel 334f over blockage area 338a, fluidic channel 334b connects to fluidic channel 334g over blockage area 338b, fluidic channel 334c connects to fluidic channel 334h over blockage area 338c, fluidic channel 334d connects to fluidic channel 334i over blockage area 338d, and fluidic channel 334e connects to fluidic channel 334j over blockage area 338e. However, fluidic channels 334a, 334b, 334c, 334d, 334e do not connect to each other over any of the blockage areas because the flexible film 350 is bonded to the substrate in between the respective blockages. This implementation of a component-free valve can connect multiple fluidic channels, e.g., without causing every fluidic channel of the multiple fluidic channels to be connected.

[0057] The valve 332 can be actuated by an actuator 340 including a single tip 336 that corresponds to the multiple blockage areas 338a, 338b, 338c, 338d, 338e. For example, the single tip 336 can be pressed against all of the multiple blockage areas 338a, 338b, 338c, 338d, 338e, simultaneously. Including a single tip on a single actuator to fluidly connect and disconnect multiple fluidic channels from each other simultaneously can be advantageous, e.g., because it reduces complexity in including multiple tips.

[0058] The actuator 340 is configured to press multiple areas of unbonded flexible film against the blockage areas 338a, 338b, 338c, 338d, 338e simultaneously. For example, each blockage area 338a, 338b, 338c, 338d, 338e can be covered, enclosed, and/or encompassed by an area of unbonded flexible film, and when the actuator 340 moves, the tip 336 presses onto the multiple blockage areas 338a, 338b, 338c, 338d, 338e, simultaneously. When the tip 336 is not pressed onto the blockage areas 338a, 338b, 338c, 338d, 338e, fluid can flow between the fluidic channel 334a and the fluidic channel 334f, between the fluidic channel 334b and the fluidic channel 334g, between the fluidic channel 334c and the fluidic channel 334h, between the fluidic channel 334d and the fluidic channel 334i, and between the fluidic channel 334e and the fluidic channel 334j , i.e., because the flexible film 350 moves, flexes, or deforms over the blockage areas 338a, 338b, 338c, 338d, 338e. However, when the tip 336 is pressed onto the blockage areas 338a, 338b, 338c, 338d, 338e, fluid is not able to flow between the fluidic channels 334a because the flexible film 350 is pressed against the blockage areas 338a, 338b, 338c, 338d, 338e, thereby sealing the valve.

[0059] FIG. 4 is a diagram of a weld head 400 that can be used to form component-free valves as described herein, for example using heat welding. Other methods of forming component-free valves (e.g., ultrasonic welding or adhesion) would use a different weld head. The weld head 400 includes cutouts 402a, 402b, 402c, 402d, 402e. When the weld head 400 is heated and presses a flexible film against a cartridge, the flexible film is sealed to the cartridge where the weld head 400 contacts the flexible film. The weld head 400 does not contact the flexible film within the areas of the cutouts 402a, 402b, 402c, 402d, 402e, thereby creating areas of unbonded flexible film within the cutouts 402a, 402b, 402c, 402d, 402e. The cutouts 402a, 402b, 402c, 402d, 402e of the weld head 400 can be positioned over blockages in fluidic channels to create valves as discussed above.

[0060] FIG. 5A is a graph 500 of results from characterization tests for holding pressures within component-free valves (e.g., valves as described above with reference to FIG. 2). For example, the characterization tests were conducted on a valve with a blockage that is 2.5mm in length. The graph 500 illustrates that the holding pressure increases as the actuation force on the valve increases. For example, when the actuation force is 0.1 Newton, the holding pressure is greater than 0.3 barg. When the actuation force is 0.2 Newton, the holding pressure is greater than 0.6 barg, when the actuation force is 0.3 Newton, the holding pressure is greater than 1 barg, when the actuation force is 0.4 Newton, the holding pressure is greater than 1.2 barg, and when the actuation force is 0.55 Newton, the holding pressure is greater than 1.4 barg. The illustrated pressure holding capability of the valve illustrates that the component-free valves described herein are capable of preventing and allowing fluid flow, e.g., on microfluidic cartridges.

[0061] FIG. 5B is a table 502 of results from characterization tests for holding pressures within component-free valves. The first column of the table 502 provides average values from 50 characterization tests of a component-free valve (e.g., a valve as described herein with reference to FIG. 2) that has blocking regions 2.5 mm in length. For example, over 50 characterization tests, the valve required an average of 0.26 N of actuation force to prevent fluid flowing with 0.6 N of pressure. The actuation forces required over the 50 different characterization tests had a standard deviation of 0.1 N. The valve required a maximum of 0.6 N of actuation force in one characterization test and a minimum of 0.1 N of actuation force in another characterization test to prevent fluid flowing with 0.6 N of pressure.

[0062] The second column of the table 502 provides average values for the pressure in the fluidic inlet channel required to re-open the closed valve over the 50 characterization tests. For example, in the 50 characterization tests, the valve required an average pressure of 21 mbar to reopen the closed valve. The pressure values required over the 50 characterization tests had a standard deviation of 6.1 mbar. The valve required a maximum of 40 mbar of pressure in one characterization test and a minimum of 10 mbar of pressure in another characterization test to reopen the closed valve.

[0063] The third column of the table 502 provides average values for the pressure drop across the valve at 2 ml/min air across 50 characterization tests. For example, over 50 characterization tests, the average pressure drop across the valve was 41.7 mbar. The pressure drops across the 50 characterization tests had a standard deviation of 5 mbar. The pressure drop across the valve was at a maximum of 53 mbar in one characterization test and a minimum of 32 mbar in another characterization test.

[0064] The fourth column of the table 502 provides average values for the pressure holding capacity of a valve receiving 5N of actuation force across 50 characterization tests. For example, over 50 characterization tests, the valve was able to hold an average of 2.97 barg. The pressure holding capacity of the valve had a standard deviation of 0.4 barg over the 50 characterization tests. The maximum pressure holding capacity was 3.75 barg in one characterization test, and the minimum pressure holding capacity was 2 barg in another characterization test. [0065] The actuation forces required, the pressures required to re-open the valve, the pressure drops across the valve, and the pressure holding capabilities of the valve represented in table 502 illustrate that the component-free valves described herein are capable of preventing and allowing fluid flow, e.g., on microfluidic cartridges.

[0066] FIGS. 6A-D are schematic diagrams of an instrument 600 that can utilize the cartridges described herein. Section 620 is a section of instrument 600 that illustrates interior portions of the instrument 600, e.g., to illustrate how actuators can be embodied. For example, the instrument 600 can receive a cartridge 602 including component-free valves 604. The instrument 600 can include actuators 606 configured to interact with the component-free valves 604, as discussed above. For example, the component-free valves 604 can connect fluidic channels within the fluidic cartridge 602, as discussed above. The instrument 600 can also include a second set of actuators 608 configured to interact with a second set of component-free valves 610. In other implementations, the instrument 600 can include more or fewer sets of actuators configured to interact with component-free valves of the fluidic cartridge 602. The section 620 is taken across the line 622 to illustrate the interior of the instrument 600, e.g., to illustrate how the actuators 608 could be embodied. The actuators 608 are configured to interact with the component-free valves 610 of the fluidic cartridge 602.

OTHER EMBODIMENTS

[0067] While this specification contains many specific implementation details, these should not be construed as limitations on the scope of any inventions or of what may be claimed, but rather as descriptions of features specific to particular implementations of particular inventions. Certain features that are described in this specification in the context of separate implementations can also be implemented in combination in a single implementation. Conversely, various features that are described in the context of a single implementation can also be implemented in multiple implementations separately or in any suitable sub-combination. Moreover, although features may be described above as acting in certain combinations and even initially claimed as such, one or more features from a claimed combination can in some cases be excised from the combination, and the claimed combination may be directed to a sub-combination or variation of a subcombination. [0068] Similarly, while operations are depicted in the drawings in a particular order, this should not be understood as requiring that such operations be performed in the particular order shown or in sequential order, or that all illustrated operations be performed, to achieve desirable results. In certain circumstances, multitasking and parallel processing may be advantageous. Moreover, the separation of various system components in the implementations described above should not be understood as requiring such separation in all implementations.

[0069] Thus, particular implementations of the subject matter have been described. Other implementations are within the scope of the following claims. In some cases, the actions recited in the claims can be performed in a different order and still achieve desirable results. In addition, the processes depicted in the accompanying figures do not necessarily require the particular order shown, or sequential order, to achieve desirable results. In certain implementations, multitasking and parallel processing may be advantageous.

Claims

WHAT IS CLAIMED IS:

1. A microfluidic cartridge with a component-free valve, comprising: a substrate; a fluidic channel formed in a surface of the substrate; and a component-free valve within the fluidic channel comprising: a blockage area of the substrate that separates a first portion of the fluidic channel from a second portion of the fluidic channel; and a flexible film bonded to the surface of the substrate along the fluidic channel and around the blockage area, but unbonded in an area that encloses the blockage area and a section of the first and second portions of the fluidic channel; wherein when the unbonded flexible film is pressed against a surface of the blockage area, the component-free valve is closed, inhibiting fluid flow through the fluidic channel, and when the unbonded flexible film is not pressed against the blockage area, the component-free valve is open, enabling fluid flow from the first portion of the fluidic channel to the second portion of the fluidic channel when fluid pressure within the first portion is sufficient to move or deform the flexible film away from the surface of the blockage area.

2. The microfluidic cartridge of claim 1, wherein the unbonded flexible film is arranged to be pressed against the blockage area at least in a line or an area that extends across the entire blockage area, separating the first and second portions of the fluidic channel.

3. The microfluidic cartridge of claim 1 or claim 2, wherein the channel is molded, embossed, or cut into the substrate of the cartridge.

4. The microfluidic cartridge of any one of claims 1 to 3, wherein the flexible film is bonded to the substrate by a heat seal, a laser weld, or an ultrasonic weld.

5. The microfluidic cartridge of any one of claims 1 to 4, wherein the unbonded flexible film is configured to prevent fluid flow through the fluidic channel when the unbonded flexible film is pressed against the surface of the blockage area with a force of at least 0.2 Newtons.

6. A system comprising: a microfluidic cartridge of any one of claims 1 to 5; and an instrument configured to receive the microfluidic cartridge, wherein the instrument comprises: a controller; and an actuator configured and controlled by the controller to selectively press the unbonded film against the blockage area to selectively open and close the component-free valve.

7. The system of claim 6, wherein the actuator is controlled to apply a pressure of at least 0.2 Newton to the unbonded flexible film to push the film against the surface of the blockage area.

8. The system of claim 6 or claim 7, wherein the actuator comprises a tip having a surface configured to press the unbonded flexible film against the surface of the blockage area.

9. The system of claim 8, wherein the surface of the actuator tip is convex.

10. The system of claim 8, wherein the surface of the actuator tip is flat.

11. The system of claim 6 or claim 7, wherein the actuator comprises a tip having a line contact surface configured to press the unbonded flexible film against the surface of the blockage area, separating the first and second portions of the fluidic channel.

12. The system of claim 6 or claim 7, wherein the actuator comprises a tip having a starshaped surface configured to press the unbonded flexible film against the surface of the blockage area.

13. The system of claim 6 or claim 7, wherein the actuator comprises a tip comprising a foam material.

14. The system of claim 6 or claim 7, wherein the actuator comprises a tip comprising a material with a hardness in a range of at least about 20 ShoreA to about 90 ShoreA.

15. The system of claim 6 or claim 7, wherein the actuator comprises a tip comprising a rubber material.

16. A method of controlling fluid flow through a component-free valve of the microfluidic cartridge of any one of claims 1-5, the method comprising: controlling an actuator to selectively press the unbonded flexible film against the surface of the blockage area to selectively open and close the component-free valve on the microfluidic cartridge.

17. The method of claim 16, further comprising controlling the actuator to press the unbonded film against the surface of the blockage area with a force of at least about 0.2 to about 5.0 Newtons.

18. The method of claim 16, further comprising controlling the actuator to press the unbonded film against the surface of the blockage area with a force of at least 0.2 Newton.

19. The method of claim 16, further comprising controlling the actuator to press the unbonded film against the surface of the blockage area with a force of no more than 100.0 Newtons.

20. The method of any one of claims 16 to 19, wherein a width of the valve transverse to the longitudinal direction is between about 1 mm and about 5 mm.

21. The method of any one of claims 16 to 19, wherein a gap between the first portion and the second portion of the fluidic channel is between about 0.5 mm and about 5 mm.

22. The method of any one of claims 16 to 19, wherein the fluidic channel comprises two or more channels that are separated by a blockage area.