Embedded valve for microfluidic devices

Abstract

In some embodiments, a valve includes a housing having a first side and a second side. The valve further includes a diaphragm disposed on the first side of the housing. The diaphragm has a fluid inlet and a fluid outlet. The valve further includes an actuation pressure port disposed on the first side of the housing. The actuation pressure port is configured to create a seal by the diaphragm between the fluid inlet and the fluid outlet while an actuation pressure is received via the actuation pressure port.

Description

EMBEDDED VALVE FOR MICROFLUIDIC DEVICESCROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit of priority to U.S. Provisional App. No.63 / 549,213, filed on February 2, 2024, the entire disclosure of which is incorporated by reference herein.BACKGROUND

[0002] Embodiments of the present disclosure relate to microfluidic chips and components, and more specifically, to modular microfluidic platforms.BRIEF SUMMARY

[0003] In some embodiments, a valve includes a housing having a first side and a second side. The valve further includes a diaphragm disposed on the first side of the housing. The diaphragm has a fluid inlet and a fluid outlet. The valve further includes an actuation pressure port disposed on the first side of the housing. The actuation pressure port is configured to create a seal by the diaphragm between the fluid inlet and the fluid outlet while an actuation pressure is received via the actuation pressure port.

[0004] In some embodiments, the valve further includes an actuation pressure chamber disposed within the housing and in fluid communication with the actuation pressure port and the diaphragm. The actuation pressure chamber is configured to apply the actuation pressure to the diaphragm.

[0005] In some embodiments, when the actuation pressure port is receiving the actuation pressure, the diaphragm is moved to a sealing configuration. The sealing configuration creates a first seal between the fluid inlet and the fluid inlet channel and a second seal between the fluid outlet and the fluid outlet channel.

[0006] In some embodiments, when the actuation pressure port is not receiving the actuation pressure, the diaphragm is moved to an open configuration. The open configuration creates an intermediary fluid channel that puts the fluid inlet channel in fluid communication with the fluid outlet channel.

[0007] In some embodiments, the valve further includes an alignment pin disposed to secure the valve to a microfluidic device such that a fluid inlet channel is aligned with the fluid inlet, a fluid outlet channel is aligned with the fluid outlet, and the actuation pressure channel is aligned with the actuation pressure port.

[0008] In some embodiments, the valve further includes a gasket. The gasket is disposed to protrude from the diaphragm and be compressed against the second side of the housing, thereby pushing the diaphragm against a side of a second housing.

[0009] In some embodiments, the diaphragm includes at least one inner rolling feature revolving around a center of the diaphragm. The inner feature causes material of the diaphragm to bend towards the center while receiving the actuation pressure. The diaphragm includes at least one outer rolling feature revolving around the center of the diaphragm. The outer feature causes material of the diaphragm to bend towards the first side of the housing while receiving the actuation pressure. The inner feature is radially closer to the center than the outer feature.

[0010] In some embodiments, the first side of the first housing is on a first component and the second side of the first housing is on a second component, the first component and second component being separable.

[0011] In some embodiments, the first component and second component are welded.

[0012] In some embodiments, the actuation port can be partially actuated (e.g., receive a partial actuation pressure). The partial actuation enables a partial flow of fluid from the fluid inlet to the fluid outlet.

[0013] In some embodiments, a rate of the partial flow of fluid is a function of the actuation pressure.

[0014] In some embodiments, housing is made at least partially from optically clear materials.

[0015] In some embodiments, upon the actuation port not receiving actuation, the fluid inlet channel is in fluid communication with one or more fluid outlet channels to allow passage of particles smaller than 500 pm in diameter.

[0016] In some embodiments, the valve further comprises a second housing disposed over the first side of the first housing. The second housing comprising a fluid inlet and a fluid outlet aligned with the fluid inlet and the fluid outlet of the diaphragm and a fluidic channel aligned with the actuation pressure port.

[0017] In some embodiments, a microfluidic chip includes a first side, a second side, at least one fluid inlet channel disposed on the first side, at least one fluid outlet channel disposed on the first side and an actuation pressure channel disposed on the first side. The microfluidic chip further includes the valve described in any of the above embodiments, where the valve is affixed to the first side of the microfluidic chip.

[0018] In some embodiments, the actuation pressure channel is in fluid communication with the actuation pressure port, the at least one fluid inlet channel is in fluid communication with the fluid inlet, and the at least one fluid outlet channel is in fluid communication with the fluid outlet.

[0019] In some embodiments, the valve further comprises an alignment pin that affixes the valve to the microfluidic chip. The housing and the diaphragm are arranged to align the actuation pressure channel to the actuation pressure port, the fluid inlet via to the at least one fluid inlet channel, and the fluid outlet to the at least one fluid outlet channel.

[0020] In some embodiments, the at least one fluid inlet channel is a plurality of fluid inlet channels and the at least one fluid outlet channel is a plurality of fluid outlet channels. Each fluid inlet channel is disposed on the first side. Each fluid outlet channel is disposed on the first side. The valve further is a plurality of valves, and each valve of the plurality is affixed to the first side of the microfluidic chip.

[0021] In some embodiments, each respective valve is affixed to align the fluid inlet of the respective valve to a respective fluid inlet channel and to align the fluid outlet of the respective valve to a respective fluid outlet channel.

[0022] In some embodiments, each valve of the plurality of valves further includes a respective alignment pin that affixes each respective valve to the microfluidic chip. The housing and the diaphragm of each respective valve are arranged to align the actuation pressure channel to the actuation pressure port of each respective valve the fluid inlet of each respective valve to the at least one fluid inlet channel, and the fluid outlet of each respective valve to the at least one fluid outlet channel.BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWINGS

[0023] Fig. 1 is a diagram illustrating an exploded view of embodiments of a valve diaphragm and housing attached to microfluidic chip of the present disclosure.

[0024] Fig. 2 is a diagram illustrating a bottom view of a fluidic layout of embodiments of a valve configuration.

[0025] Figs. 3A-B are cross-sectional diagrams illustrating some embodiments of the present disclosure.

[0026] Fig. 4A is a diagram illustrating example embodiments of a diaphragm valve.

[0027] Figs. 4B-D are diagrams illustrating example embodiments of cross-sections of example diaphragm profiles of pressure concentrating features.

[0028] Figs. 5A-B are diagrams illustrating some embodiments of the diaphragm component with an additional fluidic channel.

[0029] Fig. 6 is a cross-sectional diagram illustrating some embodiments of the deflected region incorporating mechanically flexible features.

[0030] Fig. 7 is a diagram illustrating some example embodiments of a gasket employed by the present disclosure.

[0031] Fig. 8 is a diagram of some example embodiments of a microfluidic device having actuation pressure channels.

[0032] Fig. 9 is a diagram illustrating example embodiments of an actuation pressure seal.

[0033] Fig. 10 is a diagram illustrating an exploded topside view of some embodiments of a valve diaphragm and housings of the present disclosure.

[0034] Fig. 11 is a diagram illustrating an exploded underside view of some embodiments of a valve diaphragm and housings of the present disclosure.

[0035] Fig. 12 is a diagram illustrating a partial cross-sectional side view of some embodiments of the lower housing of the present disclosure.

[0036] Fig. 13 is a diagram illustrating some embodiments of a diaphragm valve and a mating interface of the present disclosure.

[0037] Fig. 14 is a diagram illustrating a cross-sectional side view of some embodiments of a diaphragm valve of the present disclosure.DETAILED DESCRIPTION

[0038] Researchers in the life sciences industry consistently seek to manipulate fluids, cells, and molecules on ever decreasing scales to improve the precision of their experiments. This need has led to the creation of the field of Microfluidics, the study and engineering of fluid flow through channels that are geometrically constrained to features smaller than 1 millimeter in at least one dimension when viewed in cross section.

[0039] The laminar flow found at these scales gives scientists greater control of their experiments and is more representative of naturally occurring fluidic systems within organisms. Environments that previously could only be found in-vivo can now be recreated in-vitro, reducing the cost and risk associated with drug development. Additionally, microfluidic techniques can be used to combine many different laboratory processes into a single, easy-to-use, disposable device. The automation and price points afforded by microfluidic devices have transformed the diagnostic industry by allowing for near instantaneous test results directly at the point-of-care. Still, other fields like genetic sequencing, proteomics, and microbiology have all been improved through the use of microfluidic techniques.

[0040] A major factor in the success of microfluidic devices is that they can be manufactured cheaply at high volumes. Integrated designs that include not only the important microfeatures critical to flow experiments, but also reservoirs for samples, connectors, sensors, and interfaces to external instruments can be produced for a few dollars each when manufactured in thermoplastic materials at quantities in the tens of thousands, typically by injection molding.However, injection molding tooling for complex designs can cost $100,000 or more and can take months to build. Despite the improvement of flow simulation techniques in recent years, microfluidic device design is still an iterative process that might take many design cycles of physical prototypes to achieve a functional product. The time and cost associated with injection molding integrated designs force microfluidic developers to explore alternative manufacturing techniques to manufacture prototype parts quickly.

[0041] An integrated device design often requires macro-scale features in addition to the microchannels within the microfluidic device. The large features may be necessary to accomplish tasks such as sample media storage, connection to an external pump, or integration with sensing equipment. Even if one of the above strategies is useful for producing microfeatures, it often is unable to create the additional macro features that an integrated device may require. Microfluidic technology developers may be forced to overcome this shortcoming by attaching external components after device manufacture using glue, adhesive tapes, or other techniques. Any time a new component must be bonded to a microfluidic device, there is always a risk of channel occlusion, misalignment, or contamination due to the bonding materials.

[0042] An alternative to producing integrated prototypes is to create separate, simpler devices and then connect them with tubing to create a mock integrated device. The advantage of this strategy is that the individual subsystems are often easier to prototype than a truly integrated design. However, the tubing connections between devices create additional wasted liquid volume, otherwise known as dead volume, between the subsystems and require tubing connections that are prone to failure and leaks. The inherent differences between subsystems connected via tubing and an integrated design can lead to a variety of unknowns when inevitably attempting to transition to a truly integrated design compatible with high volume manufacturing.

[0043] Sometimes, the dead volume introduced by the tubing technique is unacceptable in a microfluidic design, forcing developers to prototype individual subsystems, test them separately, and then risk producing an integrated device in high volume by injection molding without ever testing a functional integrated prototype. The assumptions necessary with this approach often result in devices that do not function properly and can lengthen project timelines when revisions inevitably need to be made, further complicating the microfluidic development process.

[0044] One of the main microfluidic components used to control the transport of liquids and gases in any fluid based system is a valve. As can be appreciated by a person of ordinary skill in the art, a valve is a device that controls an amount of flow of fluid. For example, valves are used to stop or enable the flow of a working fluid. Some valves, called proportional valves, regulate the magnitude of flow of one or more fluids through a system. Valves are usually designed to meet a range of specific applications. Other examples of different types of valves include manual ball valves used in household plumbing, proportional gas control valves in cooking appliances, check valves in refrigeration systems, intake and exhaust valves in internal combustion engines, and butterfly valves in wastewater treatment facilities.

[0045] In the microfluidic industry, valves are equally important but technologically challenging. In particular, effective valves in the microfluidic industry manipulate small amounts of fluid (e.g., on the order of microliters), actuate quickly (e.g., on the order of milliseconds) to prevent carryover of unwanted fluid volumes, exhibit low dead volume (e.g., 100 nanoliters to 3 microliters), be resistant to caustic chemicals and solvents, exist in harsh environments (e.g., a humidified incubator), and occupy a limited footprint due to spatial constraints.

[0046] Current valves that serve the microfluidic industry have both benefits and limitations. For example, a common valve in the microfluidic industry is a solenoid valve, which is produced by dozens of manufacturers. Solenoid valves are fast, reliable, and effective, but are high cost, require a relatively large footprint, and require access to electrical power. Therefore, they are not always a good fit for devices that need to be low cost and disposable or systems that have limited access to electrical power (e.g., due to a high humidity environment). Other electrically powered valves, such as piezoelectric valves, shape memory alloy valves, and rotary valves have similar limitations relating to power requirements, spatial footprint, and cost. Further, some of these valves require relatively high dead volume (e.g., due to additional tubing and manifolding) and may be slow to actuate in the case of shape memory alloy or motor-based devices.

[0047] Current on-chip membrane and diaphragm valves operate on the principle of a flexible component, usually made of an elastomeric material, actuated using an applied pressure or force to create a seal between two liquid channels. Some commercially available cell culture and liquid handling systems already include membrane or diaphragm based valves and pumps. The flexible component is typically a thin film of uniform thickness or a can be a molded or thermoformed diaphragm. Examples of these types of valves include quake valves, doormat membrane valves, and air operated diaphragm valves. The elastomeric material of these valves is pressurized against a surface to create a seal. The valve prevents flow when the contact pressure of the sealing component exceeds the upstream fluid pressure. These valves benefit from some kind of mechanical amplifier to guarantee a seal. For example, a valve may use tension in the membrane to increase contact pressure over a small surface, a protruding annular sealing surface on a diaphragm, or a conical feature mating with a tapered fluid inlet.

[0048] Despite being an attractive option in many applications, membrane and diaphragm valves have been slow to reach widespread commercial use because of manufacturing and performance related problems. Additionally, off-the-shelf options that can be integrated into a mass-producible device are not widely available. Thin elastomer films and membranes are difficult to bond or otherwise assemble onto a microfluidic device because of issues with handling, adhesion, material compatibility, internal stresses, and other material related challenges. Further, many existing valve designs leak, get stuck in a closed position, or are susceptible to mechanical fatigue and reliability problems. A compact valve architecture that is purpose built for low-cost thermoplastic microfluidic devices is of particular interest if it is easy to assemble, compatible with a wide range of device materials, and able to provide a reliable seal for a variety of microfluidic applications.

[0049] In some embodiments, the present disclosure describes a compact diaphragm valve that can be integrated onto a microfluidic device and enable switching of fluid flow between on and off states. In some embodiments, the compact diaphragm valve can include as few as two parts: a diaphragm and a housing. In some embodiments, the compact diaphragm valve is actuated using air pressure that can be routed to multiple valves on the same device. In some embodiments, these valves exhibit low dead volume and are small enough to fit within the spacing of a 384- well microplate array. In some embodiments, valves are fast to respond, reliably seal after many actuation cycles, and can exceed the lifetime of competitive valve designs. In some embodiments, the valves respond in around 15 milliseconds. In some embodiments, the valves respond in the range of 2-200 milliseconds.

[0050] In some embodiments, the present valve is advantageous because it solves many of the problems associated with conventional on-chip membrane and diaphragm valves. Thevalve can be assembled more easily because the elastomeric member is an independently molded component that is not bonded to the device directly. The elastomeric member (e.g., the diaphragm) being bonded to the housing, and not the microfluidic chip directly, thereby avoids material compatibility and assembly issues associated with welding thin films and diaphragms to a microfluidic chip. Additionally, the present valve creates a reliable seal when pressurized but is designed to remain in an open position when unactuated. The valve is also resistant to clogging and can be made of application specific wetted materials to ensure compatibility with a wide range of chemicals. Therefore, the present valve can be easily integrated into many microfluidic chip designs and translates to more than one application.

[0051] In some embodiments, the valve can be offered at a lower cost than current valves because of its low part count and small size of the proposed device. In some embodiments, the valve can be assembled using existing pick and place equipment, which reduces the cost of manufacturing. The device is also modular because it can be configured to fit a variety of device designs, to be mounted in different orientations, and to allows for multiplexing of multiple valves on the same microfluidic chip. For example, the valve is compatible with multi-layer microfluidic devices, may be attached on the top surface or on the cap of a microfluidic device, or can be included into multi-material assemblies. The design also allows for routing of actuation pressure on the same side of the device as the fluidic channels, which makes the valve relatively easy to integrate into most microfluidic platforms. Further, this design allows for one pressure inlet on a microfluidic chip to be used to actuate more than valve on the same microfluidic chip.

[0052] In some embodiments, the disclosed valve also offers several performance advantages when compared to existing technologies. First, the valve can be produced usingoptically clear materials to allow illumination of imaging through the device and allow free observation of the fluid path. The valve is also able to passage small particles (e.g., on the order of 100 pm in diameter) when in the open position. In some embodiments, the valve allows passage of particles smaller than 100 pm in diameter. In some embodiments, the valve allows passage of particles smaller than 200 pm in diameter. In some embodiments, the valve allows passage of particles smaller than 300 pm in diameter. In some embodiments, the valve allows passage of particles smaller than 400 pm in diameter. In some embodiments, the valve allows passage of particles smaller than 500 pm in diameter. The total dead volume of the valve is also small, thereby minimizing reagent use and carryover of liquid volumes. The valve readily wets without trapping any bubbles with aqueous solutions, fluorinated oils, and many other organic liquids. Lastly, the valve requires no direct electrical connection or power source to operate.

[0053] In some embodiments, the disclosed type of valve has applications including where air pressure is readily available and when the microfluidic device is designed to be disposable. For example, one application of the proposed valve is in cell culture devices existing inside of an incubator or diagnostic devices connected to an automated instrument. Additionally, these components operate for devices that need to transport small particles, mix various chemical compounds, or automate the timing of device functions.

[0054] Fig. 1 is a diagram 100 illustrating an exploded view of embodiments of a valve diaphragm and housing attached to microfluidic chip of the present disclosure. In some embodiments, disclosed herein is a compact valve architecture having a pressure-operated diaphragm valve. The valve includes two components: (1) a flexible diaphragm 104 used to create the fluidic seal and (2) a housing 102 (e.g., a rigid body) that connects the diaphragm to the microfluidic chip. The flexible diaphragm may first be assembled into the housing to createa sub-assembly that can then be attached to the microfluidic chip 106 in an additional assembly process. In some embodiments, the housing 102 can be constructed with a clear material so the flow of fluid through the valve can be seen.

[0055] Fig. 2 is a diagram 200 illustrating a bottom view of a fluidic layout of embodiments of a valve configuration. In some embodiments, the microfluidic chip includes two liquid channels, a fluid inlet 206 and a fluid outlet 208. The fluid inlet 206 and fluid outlet 208 are arranged to connect to two fluid vias 210a-b (e.g., a fluid inlet via and a fluid outlet via) on the valve. The two fluid vias 210a-b are oriented towards a top of the microfluidic chip and are spaced by a fixed distance. In some embodiments, the valve includes a fluid channel connecting the fluid inlet via 206 and fluid outlet via 208, an actuation pressure port 204 receiving pressure from an actuation pressure inlet 216 from the microfluidic chip, alignment features such as an alignment pin 212, and welded surfaces of the valve housing 202 The diaphragm valve is aligned to the chip so that its sealing feature 214, upon actuation, seal the fluid vias 210a-b to the fluid inlet channel 206 and fluid outlet channel 208 on the chip, thereby preventing the flow of fluid. The diaphragm includes an elastomeric thermoplastic such as cyclic olefine copolymer (COC) elastomer, thermoplastic urethane, rubber, fluoroelastomer, or any other flexible elastomeric thermoplastic. It can be understood that the elastomer used can be application dependent and any flexible material can be used to make a valve diaphragm. In some embodiments, the diaphragm includes thermoset or thermoplastic elastomers. In some embodiments, the diaphragm can be made from silicone elastomer. In some embodiments, the diaphragm can be made out of any other flexible material.

[0056] Alternatively, the fluid vias 210a-b can be routed through holes in the cap of the microfluidic chip, in which case the valve is attached to the cap of the chip. The valve housingmay also be recessed into the device to reduce space, be surrounded by a raised web of material, or contained in the device as part of a multi-layer stack. Further, the geometry of the valve housing may be integrated into a single part that contains more than one valve diaphragm in a single housing and could also accommodate different assembly techniques such as a screw or bolted connection.

[0057] Figs. 3A-B are cross-sectional diagrams 300 and 350 illustrating some embodiments of the present disclosure. A valve housing 302 interfaces with a microfluidic chip to control flow of fluid from a fluid inlet 314 and fluid outlet 312 on the microfluidic chip 304. In some embodiments, a diaphragm 316 is an independently molded component consisting of a region that is deflected by an applied pressure (e.g., from the actuation pressure chamber 318 illustrated by Fig. 3B) and compressed against the top of the microfluidic chip. The deflected region is preferably thin (e.g., less than 0.250 mm) — allowing it to deflect without much pressure — and circular — so that the motion is predictable and axisymmetric. At the location of diaphragm contact, a raised sealing surface 308 of the valve diaphragm concentrates the contact pressure to a smaller area, for example, in the shape of an annular seal centered on one fluidic inlet. This feature acts as a pressure amplifier and is designed to create a leak-proof seal between the two fluid connections of the fluid inlet 314 and fluid outlet 312 with minimal actuation pressure. In some embodiments, the minimal actuation pressure is 5psi (e.g., the actuation pressure to close the valve is 5psi or greater). In some embodiments, raised sealing surface’s 308 profile’s cross section may take the form of a rounded bump, a triangular wedge, or even a small rectangular cross section. In some embodiments, the profile of the raised sealing surface 308 could alternatively take the shape of a plug centered with a tapered hole in the chip.

[0058] In some embodiments, the actuation pressure chamber 318 is a pressure holding chamber that seals pressure around the diaphragm when receiving actuation. In some embodiments, the actuation pressure chamber 318 surrounds the entire diaphragm or footprint of the diaphragm. In some embodiments, the actuation pressure chamber 318 is welded, bonded, or otherwise adhered to an interior side of the housing. In some embodiments, the actuation pressure chamber 318 is welded, bonded, or otherwise adhered to an interior side of the housing that the diaphragm is disposed on. In some embodiments, the valve housing 302 can serve as the actuation pressure chamber 318. In some embodiments, the actuation pressure chamber 318 is disposed to receive actuation from the actuation pressure port (not shown) connected to an actuation pressure channel (e.g., air channel 310) from the microfluidic chip 304. In some embodiments, upon actuation, the actuation pressure chamber 318 applies a force to the diaphragm, causing the diaphragm to seal against one or more of the fluid inlet 314 and fluid outlet 312.

[0059] Fig. 4A is a diagram illustrating example embodiments of a diaphragm valve. In some embodiments, a moving element 402 of the diaphragm valve includes a relatively flat circular region that is close to or uniform in thickness and disposed over one fluid via. A deflection member of the diaphragm valve is disposed over the other fluid via so that fluid can flow when the valve is open. In some embodiments, diameter of the deflection member is large enough and thin enough to displace with limited actuation pressure. In some embodiments, the diaphragm thickness is 10-300 microns. In some embodiments, the diameter of the diaphragm is 0.5-5mm.

[0060] Figs. 4B-D are diagrams illustrating example embodiments of cross-sections 404,406, and 408 of example diaphragm profiles of pressure concentrating features.

[0061] Figs. 5A-B are diagrams illustrating some embodiments of the diaphragm component with an intermediary fluidic channel 508. In some embodiments, the intermediary fluidic channel 508 is disposed in the diaphragm and directs fluid from the center of the fluid inlet 502 to the fluid outlet via 504. This allows for the deflected region 506 to be as small as possible so that it does not contribute to additional dead volume or parasitic displacement of fluid upon actuation. In some embodiments, the deflected region is 0.8 to 3.2 millimeters.

[0062] As shown by Fig. 5B, the intermediary fluidic channel 518 can alternatively be disposed as a feature in the microfluidic chip for a more compact, lower volume design of the diaphragm valve. However, adding the intermediary fluidic channel 518 to the microfluidic chip adds complexity to the device and, in some cases, may not traffic particles as well as a channel in the diaphragm because of the fluid path on the microfluidic chip. In some embodiments, the intermediary fluidic channel 518 can also be molded into the top of the microfluidic chip or cut into the cap if the valve is mounted to the cap side of a device. For example, Fig. 5B illustrates a diaphragm with a conical sealing feature to interface with the microfluidic device having the intermediary fluidic channel 518.

[0063] Many current large circular diaphragms are designed with a rounded geometry revolving around a perimeter of a circular region, sometimes called a rolling feature, that is able to curl and extend under load without significant force or pressure applied at the center of the diaphragm. The rolling feature reduces the amount of strain in the diaphragm during actuation and limits the amount of tension due to strain in the diaphragm. The radius of the rolling feature needs to be small because of the scale of the proposed diaphragms. As the radius is reduced, the stiffness of the rolling feature increases undesirably. Further, the surfaces of these rounded features orient the applied pressure, and resulting forces, towards each other rather than in thedesired direction of displacement. For these reasons, the effectiveness of rolling features in small diaphragms is limited.

[0064] Fig. 6 is a cross-sectional diagram 600 illustrating some embodiments of the deflected region incorporating mechanically flexible features. A diaphragm with enhanced flexibility leverages features that bend at the outer perimeter 608 and center 604 of the diaphragm to allow for greater diaphragm displacement with reduced strain in the material. These features also cause the diaphragm to spring back into an open position when unactuated.

[0065] The mechanically flexible features deform under low pressure because of intentional bending and buckling modes (e.g., the outer edges bending down when the diaphragm is actuated 606 and the inner edges 604 bending towards the center during actuation). In some embodiments, the present diaphragm valve incorporates a circular region (e.g., a rolling feature) that is offset vertically from the surface of the fluidic chip, similar to the shape of an inverted bowl. The circular region is revolved outer wall of this circular region is oriented close to vertical while the top profile is nearly horizontal. This creates a roughly perpendicular intersection between two relatively thin profiles that can bend 604 inwards, or toward the center when the diaphragm is displaced downwards (e.g., during actuation). In some embodiments, a roughly perpendicular intersection is 65-90 degrees, where 90 degrees is perpendicular. The pressure applied along the near vertical outer perimeter does not detract significantly from the desired pressure oriented down into the horizontal region and instead contributes to beneficially the desirable inward displacement of the vertical wall. The energy stored by this deformation results in a spring-like feature that pulls the valve diaphragm back into the open state when pressure is released.

[0066] In some embodiments, a bending feature can be incorporated near the center of the circular diaphragm. Deformation in this region is also oriented towards the center of the component and redirects compressive stresses produced at the center of the diaphragm into a useful motion for sealing the valve. This feature can be connected to the sealing feature at the center of the diaphragm to minimize spatial footprint. When combined, the two vertically oriented walls create a linkage-like structure that can predictably displace relatively far distances and naturally return to their original shape. These features reduce the dependence of the diaphragm on material properties and limit the amount of internal stress upon actuation.

[0067] In some embodiments, these features enable the diaphragm to displace a greater distance upon actuation than a circular membrane with the same cross-sectional thickness. Further, these features make sure that the valve does not get stuck in a closed position when over-actuated. The height offset of the circular region may also be used to increase or decrease the stroke of the valve diaphragm. In some embodiments, lower stroke variants require less actuation pressure but may not traffic particles as well. Lastly, the circular region may be curved or angled slightly in the upward direction so that it is able to buckle before experiencing tension to further reduce the energy required for actuation.

[0068] Fig. 7 is a diagram 700 illustrating some example embodiments of a gasket employed by the present disclosure. A gasket feature 702 is compressed 704during valve assembly to seal the diaphragm against a top surface of the microfluidic chip. The elastomeric diaphragm is sealed between the chip and housing by means of an integrated gasket feature 702 (e.g., gasket). The gasket 702 is a compressible seal that traces the perimeter of the valve diaphragm and isolates the working fluid from the outside world. The width, height, and shapeof this feature can be designed to provide a specific amount of pressure when compressed against the microfluidic chip during assembly.

[0069] The pressure exerted to actuate the diaphragm creates a resulting force of the diaphragm pressing against the chip. The resultant contact pressure is determined by dividing this force of the diaphragm pressing against the chip by the surface area of the contact point on the sealing surface. Some of the pressure used to actuate the diaphragm is lost to “work” energy to move the diaphragm. The amount of “work” required can be calculated or determined experimentally for a given design to determine the resultant force on the chip.

[0070] This compressive force 704 is provided by the elastic behavior of the material. The deformation of the material acts like a uniform spring along the perimeter of the diaphragm. The gasket feature 702 may be rounded, rectangular, or triangular in cross section. The gasket feature 702 is disposed to provide an amount compression to seal the diaphragm to the microfluidic chip when the housing is assembled onto the chip. In some embodiments, a roughly triangular profile pointed towards the side of the housing provides enough compression. The roughly triangular profile is a design compatible elastomeric materials with a high compression set. This profile can collapse sufficiently to account for permanent deformation and gradual displacement of elastomeric material after assembly.

[0071] In some embodiments, the housing can be constructed from the same material as the microfluidic chip so that it can be easily welded or bonded onto the device. In some embodiments, the welding or bonding can be accomplished by means of a laser welding process, or thermoplastic welding methods such as ultrasonic welding. Laser welding can be advantageous because it minimizes the heat produced during welding and allows for better part alignment and tolerance management.

[0072] In some embodiments, a surface of the housing can be laser welded to the chip. Variants of the housing design can also be joined to the device using, for example, a snap fit feature, a bolted connection, an adhesive, or clamped together with an additional component or subassembly. In some embodiments, the housing is connected to the chip in a way that compresses the gasket feature contained in the diaphragm.

[0073] Fig. 8 is a diagram 800 of some example embodiments of a microfluidic device having actuation pressure channels. In some embodiments, actuation pressure is distributed to one or more valves on a microfluidic chip through one or more channels in the microfluidic device. The channel is small enough to pass between the fluid channels and to allow for multiplexing of multiple devices. The device illustrated by Fig. 8 includes has three fluid inlet channels 804a-c, each connected to a respective valve assembly 806a-c, three fluid outlet channels 808a-c, each connected to a respective valve assembly 806a-c, with a single actuation pressure source 802 for all three valves. It can be recognized that while Fig. 8 illustrates three valves 806a-c, three fluid inlet channels 804a-c and three fluid outlet channels 808a-c, a microfluidic chip can be designed for any number of valves and respective fluidic channels having a common actuation pressure channel.

[0074] In some embodiments, the actuation pressure can be produced by compressed air or other sources of pressure. The actuation pressure is routed to the top side of the diaphragm through the actuation pressure channel 802 in the microfluidic chip. The actuation can be delivered through a channel in the device that is small enough to fit between the fluidic channels 804a-c that are separated by the valves 806a-c. This design allows for the same pressure signal to be connected to multiple valves on the same microfluidic chip.

[0075] Fig. 9 is a diagram 900 illustrating an actuation pressure seal 902. As described above, actuation pressure is routed to the valve through an actuation pressure channel in the chip. A actuation pressure seal 902 on the diaphragm separates the actuation pressure being delivered from the actuation pressure channels from the fluid in the fluidic channels. A channel in the diaphragm or housing routes the actuation pressure behind the flexible element in the diaphragm.

[0076] In some embodiments, the pressure channel in the microfluidic chip is connected to the housing by means of a hole oriented upwards (e.g., towards the valve) through the chip. A raised boss on the diaphragm creates a radial sealing feature and ensures a pressure-tight seal between the diaphragm and pressure-channel on the chip. A fluid path between the diaphragm and housing routes the applied pressure behind the sealing feature of the valve thereby isolating the applied pressure from the liquid contained in the microfluidic channels. Valve actuation pressure can be applied to the microfluidic device by means of a gasket, tube, or other pressure connection method. Pressure can also be applied to the diaphragm by other means such as pressurized liquid, magnetically deflected particles suspended in an oil, electroosmotic pressure, electrorheological fluid, etc.

[0077] In some embodiments, air is routed to the diaphragm through an opening on the top of the housing itself. This substitutes the need for an additional channel on the microfluidic chip in place of a different type of pressurized connection. This connection could include a manifold containing an O-ring that is compressed against the valve housing, a housing that features a threaded connection for a tube and fitting, a barb that is used to connect directly to a soft tube, or a housing that includes additional components used to mechanically compress the diaphragm such a solenoid plunger, physical button, or manual lever.

[0078] In some embodiments of the valve architectures, a single housing may include one or more valve diaphragms spaced apart in a row or grid. This allows for multiplexing of valves with a reduced number of components. Pressure to the valve may be sent to individual diaphragms or could be distributed to multiple valves through the housing.

[0079] To aid in the initial assembly of these valves, a pin or pull -though feature molded into the top of the diaphragm can be used to roughly align the component to the housing and physically connect it to the housing so that it stays in place. An additional molded pin or other alignment feature can be oriented towards the chip so that it fits into the microfluidic chip and helps constrain rotational alignment. Alignment can be accomplished with an additional molded feature or by the registration of the radial sealing feature discussed previously.

[0080] In some embodiments, the diaphragm valve is encapsulated. In some aspects, such an encapsulated diaphragm valve, or a self-contained valve, and the components thereof, can facilitate improved handling, alignment, and the subsequent assembly of the valve and / or its components. This type of valve can also help accommodate more manageable tolerances in the final assembly process. A self-contained embedded air-operated diaphragm valve can be preferable because it allows the valve to be tested for quality assurance prior to integration with another microfluidic device. For example, and without limitation, the encapsulated diaphragm valve assembly can be evaluated using a conventional leak tester to ensure device performance prior to final assembly onto a microfluidic chip. This can be done by connecting the inlets and outlets of the valve to a leak tester via gasketed interface. Air pressure can be used to operate the valve at typical actuation pressures.

[0081] In some embodiments, a fully encapsulated diaphragm valve includes as few as 3 parts: a upper housing (e.g, rigid body), a lower housing (e.g, rigid body), and the flexiblediaphragm e.g, elastomeric diaphragm) disposed therebetween. In some embodiments, a fully encapsulated diaphragm valve includes more than 3 parts. For example, and without limitation, additional components may be required depending on the type of valve or in embodiments with multiple valves assembled (e.g., assembled in a grid formation, row formation, or column formation).

[0082] Fig. 10 is a diagram 1000 illustrating an exploded topside view of some embodiments of a valve diaphragm and housings of the present disclosure. The encapsulated diaphragm valve includes: (1) an upper housing 1002, (2) a lower housing 1004, and (3) a diaphragm 1006 disposed between the housings. The diaphragm 1006 is similar to embodiments of diaphragms of the present disclosure (e.g., diaphragm 104, 316). The flexible diaphragm 1006 may be first assembled into the upper housing 1002, which is then welded to the lower housing 1004 to create a sub-assembly that can then be attached to the microfluidic chip (e.g., microfluidic chip 106) in an additional assembly process. In this way, the diaphragm can be securely contained and protected from physical damage, contamination, and other potential risks during subsequent assembly and / or processing steps. In some aspects, this sub-assembly can be more suited for conventional pick-and place assembly techniques over two-part valve assemblies. In some embodiments, the upper housing 1002 and / or lower housing 1004 can be constructed with a clear material so the flow of fluid through the valve can be seen.

[0083] In some embodiments, the encapsulated diaphragm valve includes a gasket feature (e.g., gasket) that is compressed by the upper housing 1002 during valve assembly such that a seal is formed between the lower housing 1004 and the diaphragm 1006. In some embodiments, the gasket is a compressible seal that traces the perimeter of the valve diaphragm 1006 and isolates the working fluid from the external environment. The width, height, and shapeof this feature can be designed to provide a specific amount of pressure when compressed against the microfluidic chip during assembly.

[0084] The upper housing 1002 is a rigid support structure that can be used to clamp down on the diaphragm’s gasket feature. The upper housing 1002 includes a recess formed on the second side of the upper housing, defining an interior volume configured to receive at least a portion (e.g., the upper surface) of the diaphragm. In some embodiments, the shape of the recess has a complementary form to the diaphragm. In some embodiments, the upper housing 1002 includes an alignment feature configured to align the diaphragm 1006 with the lower housing 1004 and / or the upper housing with the lower housing. For example, a portion of the second side of the lower housing (e.g., the welded surfaces) can be used to the align the housing components.

[0085] The lower housing includes a fluidic channel 1007 (e.g., extension of the actuation pressure port), a fluid inlet 1008 and a fluid outlet 1010 configured to align with the diaphragm when the diaphragm is positioned on the first side of the lower housing. The fluidic channel 1007 is aligned (e.g., concentrically aligned) with the actuation pressure port of the valve, allowing air to pass through the assembly. The fluid inlet 1008 and fluid outlet 1010 of the valve assembly can be aligned (e.g., concentrically aligned) with the respective vias on the microfluidic chip, allowing liquid to pass through the assembly.

[0086] In some embodiments, the lower housing 1004 includes an alignment feature configured to locate the diaphragm 1006 with the inlets and outlets of the lower housing. For example, and without limitation, the diaphragm can be aligned to the lower housing by means of a physical feature such as a pin and slot. In some embodiments, the diaphragm includes a slot configured to receive a pin disposed on the first side of the lower housing.

[0087] The alignment feature of the lower housing 1004 and upper housing 1002 can include magnetic contacts, complementary pin and slots, complementary ridges and grooves, interlocking tabs, a snap-fit mechanism, and / or a pull-though feature. The alignment feature of the lower and upper housing can be used to roughly align the diaphragm with each of the housings and physically connect it to the housing so that it stays in place. An additional molded pin or other alignment feature can be oriented towards the chip so that it fits into the microfluidic chip and helps constrain rotational alignment. Alignment can be accomplished with an additional molded feature or by the registration of the radial sealing feature discussed previously.

[0088] Fig. 11 is a diagram 1100 illustrating an exploded underside view of some embodiments of a valve diaphragm and housings of the present disclosure. The diaphragm 1106 includes a fluidic channel 1101 configured to connect the fluid inlet via and fluid outlet of the microfluidic chip, an actuation pressure port 1102 configured to receive pressure from an actuation pressure inlet of the microfluidic chip. The actuation pressure port can extend through the lower housing 1004 and the diaphragm 1006. The diaphragm 1006 can include a raised boss on the diaphragm which forms a radial sealing feature and ensures a pressure-tight seal between the diaphragm and the lower housing (e.g., the fluidic channel 1007).

[0089] In some embodiments, at least a portion (e.g., surface 1103) of the second side of the upper housing 1002 is laser welded to the lower housing. In some embodiments, at least a portion (e.g., surface 1104) of the second side of the lower housing 1004 is laser welded to the chip. The lower housing 1004 can be coupled (e.g., joined) to the microfluidic device using, for example, a snap fit feature, a bolted connection, an adhesive, a mating gasket, or clamped together with an additional component or subassembly.

[0090] For a laser welded assembly, the upper housing can be coated with an infrared absorbing compound or made of an infrared absorbing material. This can allow the component to be laser welded directly to the lower housing and can ensure that the subassembly is permanently held together. The welded surfaces in the middle of the component may be located above or below the mating surfaces of the diaphragm. In some aspects, this can protect the edges of the diaphragm from heat damage (e.g., warping during the initial welding step). The absorbing compound may be fully used up during welding stage so that the surface cannot be heated up by laser energy in subsequent steps. The lower housing may be coated with an infrared absorbing compound or made of an infrared absorbing material so that it can be welded onto fluidic layer of another device.

[0091] In some aspects, an encapsulated subassembly enables molding of small diameter through-holes that may be challenging to produce in larger or thicker microfluidic components. This allows for the microfluidic device to have vias that are larger than the via diameters needed to create a seal inside the valve.

[0092] Fig. 12 is a diagram 1200 illustrating a partial cross-sectional side view of some embodiments of the lower housing of the present disclosure. As shown in Fig. 12, a via 1202 (e.g., cylindrical via) of the lower housing 1004 can include a stepped transition and / or gradual transition in diameter from the first side 1204 to the second side 1206 of the housing. In some embodiments, the lower housing 1004 includes a first opening 1204 (e.g., through-hole) at one end of a via 1202 with a diameter smaller than a second opening 1206 at the other end of the via. In some embodiments, the first opening 1204 has a diameter between about 100 and about 500 micrometers and the second opening 1206 has a diameter between about 500 micrometers to about 800 micrometers. In some aspect, this can improve molding around the sensitive inlets andoutlets, while also allowing for a larger diameter hole that can be more easily aligned to the fluidic layer. In some embodiments, the openings (e.g., through-holes) of the via feature a chamfer at the second side of the lower housing (e.g., the side of the housing proximal to the microfluidic chip). In some aspects, this feature can help contain any molten material that is displaced during the laser welding step which may spread radially inwards during the welding process and may otherwise occlude or restrict flow through the component.

[0093] In some aspects, due to the larger mating through-hole diameters that are enabled by the encapsulated valve, the mating interface on the fluidic layer can be more tolerant to alignment and poor feature replication. For example, the mating interface may not require a nearmirror surface finish where the valve meets the fluidic layer. This surface can also made less sensitive to burrs or sink in the microfluidic component as the surface of the valve can be melted sufficiently to accommodate minor surface imperfections. The mating diameters of the through holes in the valve component may be misaligned to the fluidic layer by as much as 250 micrometers without significant impact to part performance.

[0094] Fig. 13 is a diagram 1300 illustrating some embodiments of a diaphragm valve and a mating interface of the present disclosure. As shown in Fig. 13, the mating interface 1302 to the fluidic layer can include a recessed pocket 1306 configured to receive the diaphragm valve assembly 1304. In some embodiments, the depth of the recessed pocket 1306 is between about 0.2 mm to about 3.0 mm. The recessed pocket, regardless of the specific depth, can ensure that the valve is oriented to the via geometries correctly provided the mating parts are both held with reasonable tolerances. A notch in the valve component and mating geometry may also be added to make sure that the rotational orientation is always correct.

[0095] Fig. 14 is a diagram 1400 illustrating a cross-sectional side view of some embodiments of a diaphragm valve of the present disclosure. The figure shows the diaphragm valve disposed within the recessed pocket 1306 of the microfluidic chip 1402. The diaphragm valve and an interior surface of the recessed pocket 1306 can be welded at the welded interface 1404. The lower housing can include a fluid inlet via and a fluid outlet via with the openings of the vias on the second side of housing larger than the openings of the vias on the first side. In some embodiments, the fluidic vias 1406 (e.g., inlet and outlet) of the microfluidic chip have a diameter smaller than the openings of the vias of the lower housing. In some embodiments, there is an offset (e.g., radial offset) between the edge of a fluidic via 1406 and the edge of the via openings on the second side of the lower housing.

[0096] The descriptions of the various embodiments of the present disclosure have been presented for purposes of illustration, but are not intended to be exhaustive or limited to the embodiments disclosed. Many modifications and variations will be apparent to those of ordinary skill in the art without departing from the scope and spirit of the described embodiments. The terminology used herein was chosen to best explain the principles of the embodiments, the practical application or technical improvement over technologies found in the marketplace, or to enable others of ordinary skill in the art to understand the embodiments disclosed herein.

Claims

CLAIMSWhat is claimed is:

1. A valve comprising: a first housing having a first side and a second side; a diaphragm disposed on the first side of the first housing, the diaphragm having a fluid inlet and a fluid outlet; and an actuation pressure port disposed on the first side of the first housing, wherein the actuation pressure port is configured to create a seal by the diaphragm between the fluid inlet and the fluid outlet while an actuation pressure is received via the actuation pressure port.

2. The valve of Claim 1, further comprising an actuation pressure chamber disposed within the first housing and in fluid communication with the actuation pressure port and the diaphragm, wherein the actuation pressure chamber is configured to apply the actuation pressure to the diaphragm.

3. The valve of any one of Claims 1-2, wherein when the actuation pressure port is receiving the actuation pressure, the diaphragm is moved to a sealing configuration, creating a first seal between the fluid inlet and a fluid inlet channel and a second seal between the fluid outlet and one or more fluid outlet channels.

4. The valve of any one of Claims 1-3, wherein when the actuation pressure port is not receiving the actuation pressure, the diaphragm is moved to an open configuration, creating an intermediary fluid channel that puts a fluid inlet channel in fluid communication with one or more fluid outlet channels.

5. The valve of any one of Claims 1-4, further comprising an alignment pin disposed to secure the valve to a microfluidic device such that a fluid inlet channel is aligned with the fluid inlet, one or more fluid outlet channels are aligned with the fluid outlet, and an actuation pressure channel is aligned with the actuation pressure port.

6. The valve of any one of Claims 1-5, further comprising a gasket, the gasket disposed to protrude from the diaphragm and be compressed against the second side of the first housing, thereby pushing the diaphragm against a side of a second housing.

7. The valve of any one of Claims 1-6, wherein the diaphragm includes at least one inner rolling feature revolving around a center of the diaphragm, the inner rolling feature causing material of the diaphragm to bend towards the center while receiving the actuation pressure, wherein the diaphragm includes at least one outer rolling feature revolving around the center of the diaphragm, the outer feature causing material of the diaphragm to bend towards the first side of the first housing while receiving the actuation pressure, wherein the inner rolling feature is radially closer to the center than the outer feature.

8. The valve of any one of Claims 1-7, wherein the first side of the first housing is on a first component and the second side of the first housing is on a second component, the first component and second component being separable.

9. The valve of Claim 8, wherein the first component and second component are welded.

10. The valve of any one of Claims 1-8, wherein the actuation pressure port can be partially actuated, thereby enabling a partial flow of fluid from the fluid inlet to the fluid outlet.

11. The valve of Claim 10, wherein a rate of the partial flow of fluid is a function of the actuation pressure.

12. The valve of any one of Claims 1-10, wherein the first housing is made at least partially from optically clear materials.

13. The valve of any one of Claims 1-11, wherein upon the actuation pressure port not receiving actuation, the fluid inlet channel is in fluid communication with one or more fluid outlet channels to allow passage of particles smaller than 500 pm in diameter.

14. The valve of any one of Claims 1-12, further comprising a second housing having a first side and a second side, the first side of the second housing disposed over the first side of the first housing, the second housing comprising a fluid inlet and a fluid outlet aligned with the fluid inlet and the fluid outlet of the diaphragm and a fluidic channel aligned with the actuation pressure port.

15. The valve of Claim 13, wherein the fluid inlet and the fluid outlet of the second housing each have a first opening disposed on the first side and a second opening disposed on the second side, the first opening smaller than the second opening.

16. A microfluidic chip comprising: a first side; a second side; at least one fluid inlet channel disposed on the first side; at least one fluid outlet channel disposed on the first side an actuation pressure channel disposed on the first side;wherein the microfluidic chip further comprises the valve of any one of claims 1- 13 affixed to the first side of the microfluidic chip.

17. The microfluidic chip of Claim 15, wherein the actuation pressure channel is in fluid communication with the actuation pressure port, the at least one fluid inlet channel is in fluid communication with the fluid inlet, and the at least one fluid outlet channel is in fluid communication with the fluid outlet.

18. The microfluidic chip of any one of Claims 15-16, wherein the valve further comprises an alignment pin that affixes the valve to the microfluidic chip, wherein the first housing and the diaphragm are arranged to align the actuation pressure channel to the actuation pressure port, the fluid inlet to the at least one fluid inlet channel, and the fluid outlet to the at least one fluid outlet channel.

19. The microfluidic chip of any one of Claims 15-17, wherein the at least one fluid inlet channel is a plurality of fluid inlet channels, the at least one fluid outlet channel is a plurality of fluid outlet channels, each fluid inlet channel disposed on the first side, each fluid outlet channel disposed on the first side, and wherein the valve is a plurality of valves, each valve of the plurality affixed to the first side of the microfluidic chip.

20. The microfluidic chip of Claim 18, wherein each respective valve is affixed to align the fluid inlet of the respective valve to a respective fluid inlet channel and to align the fluid outlet of the respective valve to a respective fluid outlet channel.

21. The microfluidic chip of any one of Claims 15-19, wherein each valve of the plurality of valves further comprises a respective alignment pin that affixes each respective valve to themicrofluidic chip, wherein the first housing and the diaphragm of each respective valve are arranged to align the actuation pressure channel to the actuation pressure port of each respective valve, the fluid inlet of each respective valve to the at least one fluid inlet channel, and the fluid outlet of each respective valve to the at least one fluid outlet channel.

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