Flexible diaphragm for a microfluidic valve

Abstract

The present invention relates to a microfluidic valve (2) comprising a flexible diaphragm (21), the flexible diaphragm (21) comprising a membrane (210) having: compressive internal stress; a thickness of at most 100 nm; and an ultimate strength of at least 1 GPa.

Description

[0001] DESCRIPTION

[0002] FLEXIBLE DIAPHRAGM FOR A MICROFLUIDIC VALVE

[0003] Technical field of the invention

[0004]

[0001] The present invention relates to microfluidic valves, and in particular to flexible diaphragms for such valves.

[0005] Background of the invention

[0006]

[0002] Microfluidic devices play a pivotal role in a wide range of applications, including medical diagnostics, pharmaceutical research, chemical synthesis and biological studies. These devices enable the precise manipulation of fluids at the microscale, allowing for controlled reactions and analyses that are critical in advancing technology and science. Central to the functionality of many microfluidic devices are microfluidic valves, which regulate fluid flow and are essential for tasks such as timing schemes and multiplexing channels. Moreover, they are a core element in building more advanced microfluidic components, such as microfluidic pumps, microfluidic mixers and microfluidic flow-controllers.

[0007]

[0003] A key part of most microfluidic valve designs is a flexible diaphragm, which acts as a barrier that can open or close a fluidic channel in response to an applied force. The design and material properties of these diaphragms are crucial for the performance of the valves. They must be capable of withstanding operational pressures (e.g. 1 bar or more) without rupturing or deforming permanently. At the same time, they need to exhibit sufficient flexibility to allow for large deflections, accommodating strokes of significant magnitude (e.g. 10 pm or more) to effectively control a fluid flow. They also need to be (bio)chemically compatible with the compounds with which they come into contact during operation, such as chemical and / or biological compounds in the fluidic channel that is controlled by the microfluidic valve.

[0008]

[0004] The integration of flexible diaphragms into microfluidic devices moreover presents several challenges. Fabrication methods must be compatible with existing microfabrication technologies to allow for seamless integration with other device components. However, achieving this compatibility can be difficult, especially when trying to balance the design and material properties (e.g. mechanical strength, deflection capabilities and compatibility) required of the diaphragm material. Additionally, miniaturization is a constant goal in microfluidic device design, necessitating diaphragms that can function effectively at small scales without compromising performance.

[0009]

[0005] Another concern is the potential impact of actuation methods on sensitive samples within the microfluidic channels. Actuation mechanisms that involve thermal or electrical inputs can introduce conditions detrimental to biological samples, such as cells or proteins. For instance, temperature increases or electric fields may alter or damage these samples, affecting the reliability of experimental results or the efficacy of medical applications.

[0010]

[0006] Moreover, the mechanical integrity of the diaphragms can be compromised by internal stresses arising from fabrication processes or material properties. Multilayered diaphragms, while potentially offering enhanced functionalities, may suffer from stress concentrations that lead to structural weaknesses or reduced lifespan. Ensuring that diaphragms maintain their performance over time under repeated actuation cycles is essential for the reliability of microfluidic devices.

[0007] Despite advancements in microfluidic technology, the need for microfluidic valves that combine high mechanical strength, substantial deflection capabilities, (bio)chemical compatibility, fabrication compatibility and sufficiently gentle interaction with sensitive samples remains unmet in some applications. There is thus still a need in the art for flexible diaphragms and corresponding microfluidic valves that address at least some of these challenges.

[0011] Summary of the invention

[0012]

[0008] It is an object of the present invention to provide a good flexible diaphragm for a microfluidic valve. It is a further object of the present invention to provide methods, uses, valves and devices associated therewith. This objective is accomplished by the aspects of the present invention.

[0013]

[0009] In a first aspect, there is provided a flexible diaphragm for a microfluidic valve, comprising a membrane having: compressive internal stress; a thickness of at most 100 nm; and an ultimate strength of at least 1 GPa.

[0014]

[0010] In a second aspect, the present invention relates to a method for manufacturing a flexible diaphragm for a microfluidic valve, comprising: a) providing a membrane over a substrate, and b) forming a through-hole in the substrate but not the membrane; whereby the flexible diaphragm comprises the membrane and the membrane has: compressive internal stress; a thickness of at most 100 nm; and an ultimate strength of at least 1 GPa.

[0015]

[0011] In a third aspect, the present invention relates to a use of a membrane as defined in any embodiment of the first aspect as a flexible diaphragm for a microfluidic valve.

[0016]

[0012] In a fourth aspect, the present invention relates to a microfluidic valve comprising the flexible diaphragm according to any embodiments of the first aspect.

[0017]

[0013] In a fifth aspect, the present invention relates to a microfluidic device comprising a microfluidic valve according to any embodiment of the fourth aspect.

[0018]

[0014] It is an advantage of embodiments of the present invention that the flexible diaphragm can be highly flexible and allowing significant deflections (e.g. minimum stroke of 10 pm), while being able to withstand high pressures (e.g. 1 bar or above). It is a further advantage of embodiments of the present invention that operation of the flexible diaphragm does not cause significant temperature changes (e.g. below 10 °C).

[0019]

[0015] It is an advantage of embodiments of the present invention that the diaphragm can be made particularly thin, thereby improving performance.

[0020]

[0016] It is an advantage of embodiments of the present invention that the diaphragm can have high resistance to rupture and can be durably operated over an extended number of cycles.

[0021]

[0017] It is an advantage of embodiments of the present invention that the diaphragm can be highly corrosion resistant. It is a further advantage of embodiments of the present invention that the diaphragm can be biocompatible.

[0022]

[0018] It is an advantage of embodiments of the present invention that the deflection capabilities of the diaphragm can be finetuned after formation of the membrane; for example, the initial deflection capabilities (i.e. of the as-formed diaphragm) can be increased or decreased.

[0023]

[0019] It is an advantage of embodiments of the present invention that pressure generation can be decoupled form the flexible diaphragm, thereby allowing to optimize both independently, while also improving fabrication feasibility.

[0020] It is an advantage of embodiments of the present invention that the microfluidic valve may combine high strength, large deflection capability, and durability, making it well-suited for applications requiring precise flow control and reliable operation.

[0024]

[0021] It is an advantage of embodiments of the present invention that a large variety of microfluidic valves can be formulated using the flexible diaphragm.

[0025]

[0022] It is an advantage of embodiments of the present invention that the flexible diaphragm and / or microfluidic valve can fabricated in a way that is compatible with semiconductor processing (e.g. as used in semiconductor foundries).

[0026]

[0023] Particular and preferred aspects of the invention are set out in the accompanying independent and dependent claims. Features from the dependent claims may be combined with features of the independent claims and with features of other dependent claims as appropriate and not merely as explicitly set out in the claims.

[0027]

[0024] Although there has been constant improvement, change and evolution of devices in this field, the present concepts are believed to represent substantial new and novel improvements, including departures from prior practices, resulting in the provision of more efficient, stable and reliable devices of this nature.

[0028]

[0025] The above and other characteristics, features and advantages of the present invention will become apparent from the following detailed description, taken in conjunction with the accompanying drawings, which illustrate, by way of example, the principles of the invention. This description is given for the sake of example only, without limiting the scope of the invention. The reference figures quoted below refer to the attached drawings.

[0029] Brief description of the drawings

[0030]

[0026] FIG 1 schematically depicts a flexible diaphragm in accordance with embodiments of the present invention.

[0031]

[0027] FIG 2, FIG 3 and FIG 4 schematically depict flexible diaphragms with alternative valve seat configurations in accordance with embodiments of the present invention.

[0032]

[0028] FIG 5-FIG 12 schematically depict a possible method for manufacturing a flexible diaphragm in accordance with embodiments of the present invention.

[0033]

[0029] FIG 13 is a 3D image of a Ru membrane manufactured using the method of FIG 5-FIG 11.

[0034]

[0030] FIG 14 is an image of a 50 nm thick Ru membrane in accordance with embodiments of the present invention.

[0035]

[0031] FIG 15 is another image of a Ru membrane in accordance with embodiments of the present invention.

[0036]

[0032] FIG 16 is an image of a Zr membrane in accordance with embodiments of the present invention.

[0037]

[0033] FIG 17 is an image of a Si membrane in accordance with embodiments of the present invention.

[0038]

[0034] FIG 18 is a comparative image of a non-compressive (tensile) Si membrane.

[0039]

[0035] FIG 19 schematically depicts an experimental setup used for deflection, breaking pressure and fatigue test measurements on membranes for flexible diaphragms.

[0036] FIG 20 is a graph of displacement (deflection) in function of pressure for different diameters of Ru membranes in accordance with embodiments of the present invention.

[0040]

[0037] FIG 21 is a graph of displacement (deflection) in function of pressure for different diameters of Zr membranes in accordance with embodiments of the present invention.

[0041]

[0038] FIG 22 is a graph of displacement (deflection) in function of pressure for a Ru, Zr, compressive Si and non-compressive Si membrane.

[0042]

[0039] FIG 23 is a dot plot of the measured breaking pressure of different Ru, Zrand Si membranes.

[0043]

[0040] FIG 24 is a scatter plot of applied pressure in function over time during a fatigue test of a Ru membrane in accordance with embodiments of the present invention.

[0044]

[0041] FIG 25 schematically depicts a first exemplary type of microfluidic valve in accordance with embodiments of the present invention.

[0045]

[0042] FIG 26 schematically depicts a potential microfluidic device in accordance with embodiments of the present invention, using microfluidic valves of said first exemplary type.

[0046]

[0043] FIG 27 schematically depicts a second exemplary type of microfluidic valve in accordance with embodiments of the present invention.

[0047]

[0044] FIG 28 schematically depicts a potential microfluidic device in accordance with embodiments of the present invention, using microfluidic valves of said second exemplary type.

[0048]

[0045] FIG 29 schematically depicts a third exemplary type of microfluidic valve in accordance with embodiments of the present invention.

[0049]

[0046] FIG 30 schematically depicts a potential microfluidic device in accordance with embodiments of the present invention, using microfluidic valves of said third exemplary type.

[0050]

[0047] FIG 31-FIG 33 schematically depict an initial state (FIG 31), off-state (FIG 32) and on-state (FIG 33) for a microfluidic valve in accordance with embodiments of the present invention using a shape-change material.

[0051]

[0048] FIG 34-FIG 36 schematically depict an initial state (FIG 34), off-state (FIG 35) and on-state (FIG 36) for a microfluidic valve in accordance with embodiments of the present invention using electrostatic actuation.

[0052]

[0049] In the different figures, the same reference signs refer to the same or analogous elements.

[0053] Description of illustrative embodiments

[0054]

[0050] The present invention will be described with respect to particular embodiments and with reference to certain drawings but the invention is not limited thereto but only by the claims. The drawings described are only schematic and are non-limiting. In the drawings, the size of some of the elements may be exaggerated and not drawn on scale for illustrative purposes. The dimensions and the relative dimensions do not correspond to actual reductions to practice of the invention.

[0055]

[0051] Furthermore, the terms first, second, third and the like in the description and in the claims, are used for distinguishing between similar elements and not necessarily for describing a sequence, either temporally, spatially, in ranking or in any other manner. It is to be understood that the terms so used are interchangeable under appropriate circumstances and that the embodiments of the invention described herein are capable of operation in other sequences than described or illustrated herein.

[0056]

[0052] Moreover, the terms top, bottom, over, under and the like in the description and the claims are used for descriptive purposes and not necessarily for describing relative positions. It is to beunderstood that the terms so used are interchangeable with their antonyms under appropriate circumstances and that the embodiments of the invention described herein are capable of operation in other orientations than described or illustrated herein.

[0057]

[0053] It is to be noticed that the term “comprising”, used in the claims, should not be interpreted as being restricted to the means listed thereafter; it does not exclude other elements or steps. It is thus to be interpreted as specifying the presence of the stated features, integers, steps or components as referred to, but does not preclude the presence or addition of one or more other features, integers, steps or components, or groups thereof. The term “comprising” therefore covers the situation where only the stated features are present and the situation where these features and one or more other features are present. Thus, the scope of the expression “a device comprising means A and B” should not be interpreted as being limited to devices consisting only of components A and B. It means that with respect to the present invention, the only relevant components of the device are A and B.

[0058]

[0054] Reference throughout this specification to “one embodiment” or “an embodiment” means that a particular feature, structure or characteristic described in connection with the embodiment is included in at least one embodiment of the present invention. Thus, appearances of the phrases “in one embodiment” or “in an embodiment” in various places throughout this specification are not necessarily all referring to the same embodiment, but may. Furthermore, the particular features, structures or characteristics may be combined in any suitable manner, as would be apparent to one of ordinary skill in the art from this disclosure, in one or more embodiments.

[0059]

[0055] Similarly, it should be appreciated that in the description of exemplary embodiments of the invention, various features of the invention are sometimes grouped together in a single embodiment, figure, or description thereof for the purpose of streamlining the disclosure and aiding in the understanding of one or more of the various inventive aspects. This method of disclosure, however, is not to be interpreted as reflecting an intention that the claimed invention requires more features than are expressly recited in each claim. Rather, as the following claims reflect, inventive aspects lie in less than all features of a single foregoing disclosed embodiment. Thus, the claims following the detailed description are hereby expressly incorporated into this detailed description, with each claim standing on its own as a separate embodiment of this invention.

[0060]

[0056] Furthermore, while some embodiments described herein include some but not other features included in other embodiments, combinations of features of different embodiments are meant to be within the scope of the invention, and form different embodiments, as would be understood by those in the art. For example, in the following claims, any of the claimed embodiments can be used in any combination.

[0061]

[0057] In the description provided herein, numerous specific details are set forth. However, it is understood that embodiments of the invention may be practised without these specific details. In other instances, well-known methods, structures and techniques have not been shown in detail in order not to obscure an understanding of this description.

[0062]

[0058] The following terms are provided solely to aid in the understanding of the invention.

[0063]

[0059] As used herein, and unless otherwise specified, the term ‘compressive internal stress’ refers to an intrinsic stress in a material, generated when the material is subjected to forces that push inward. These forces can compel the material to shorten or compress (compared to a situation where thecompressive internal stress would be absent); in other words: the material would normally be ‘longer’ (in at least one dimension; e.g. ‘in plane’), but the compressive internal stress forces it to shorten. In some cases, the material (e.g. membrane) can at least partially relieve the compressive internal stress it experiences by expanding in another direction (e.g. ‘out of plane’); such as in the form of wrinkling and / or buckling (cf. infra). Within the present invention, the compressive internal stress may often be residual, i.e. the stress remains in the material afterthe original cause of the stress has been removed. The (original) cause of the (residual) stress may for example be one or more of a physical mismatch (e.g. thermal expansion and / or lattice mismatch) of the material with a further material it is in contact with, the material undergoing a phase transformation, grain boundary formation, deposition parameters (e.g. deposition rate), etc. In at least some instances, quantifying the internal stress of a material may be performed by bow measurements, i.e. the material having compressive internal stress may be deposited on a substrate and the curvature of the substrate (before and after deposition) may be measured to determine the degree of compressive internal stress in the material.

[0064]

[0060] As used herein, and unless otherwise specified, the term ‘ultimate strength’ refers to the maximum tensile stress that a material can withstand while being stretched or pulled before breaking. It is a measure of the material's mechanical strength under tension, expressed in units of pressure (e.g. GPa).

[0065]

[0061] As used herein, and unless otherwise specified, the term ‘deflection’ refers to the bending of a layer (e.g. a membrane) out of plane. One way to quantify deflection in terms of the maximum displacement (e.g. in the middle of the layer) out of plane (i.e. compared to a reference plane corresponding to the layer being flat).

[0066]

[0062] As used herein, and unless otherwise specified, the phrase ‘made of a metal or nanomaterial’ means that the material consists substantially (e.g. at least 80 wt%, preferably at least 90 wt%, more preferably at least 95 wt%, still more preferably at least 97 wt%, yet still more preferably at least 99 wt%, most preferably 100 wt%) of one or more metals or nanomaterials; including combinations or alloys thereof.

[0067]

[0063] As used herein, and unless otherwise specified, the term ‘metal’ refers to a material which has a partially filled conduction band; in other words, it has a Fermi level which lies within the conduction band. Accordingly, metals have electrons which can move relatively freely trough the material, which gives them particular properties such as a good electrical and heat conductivity, lustrous appearance (when polished), etc.

[0068]

[0064] As used herein, and unless otherwise specified, the term ‘nanomaterial’ refers to a material made up of structural components (‘nanostructures’) with at least one dimension between 1 and 100 nm. Examples of nanomaterials include 1D nanostructures (e.g. carbon nanotubes or nanowires), 2D nanostructures (e.g. graphene or a transition metal dichalcogenide monolayer) or materials made up of a plurality of 1D or 2D nanostructures (e.g. graphite or a transition metal dichalcogenide).

[0069]

[0065] As used herein, and unless otherwise specified, the term ‘adhesion layer’ refers to a thin layer of material applied between the two layers or structures (e.g. between a membrane and a substrate) to enhance bonding between them.

[0070]

[0066] As used herein, and unless otherwise specified, the term ‘pressure transmission channel’ refers to a channel in a microfluidic device (e.g. in a microfluidic valve) that is designed to convey(transmit) pressure changes. For example, the pressure transmission channel may convey pressure changes to a flexible diaphragm, thereby causing bending of the flexible diaphragm. The channel may therefore be filled with a fluid medium — which may be a liquid (e.g. water or oil; i.e. a hydraulic pressure transmission channel) or gas (e.g. air or inter gas; i.e. a pneumatic pressure transmission channel) — through which the pressure changes are conveyed. In particular, the use of an incompressible liquid can allow to efficiently transmit pressure changes through the pressure transmission channel. Moreover, the pressure transmission channel may be connected to an actuator that modulates the pressure within the channel.

[0071]

[0067] As used herein, and unless otherwise specified, the term ‘actuator’ refers to a component or system that produces a force, torque or displacement when a stimulus (e.g. an electrical or thermal input) is applied to it. Examples of actuators include an electrostatic actuator (e.g. using an electric field to induce movement of two electrodes), piezoelectric actuator (e.g. using voltage-induced deformation of piezoelectric material) or a thermal actuator (e.g. utilizing thermal expansion to generate an actuation). While e.g. an external pressure source may also use actuators (e.g. to generate its pressure) and / or may be considered in a sense to be an actuator, — unless otherwise specified — the actuators referred to herein are internal to the microfluidic system (e.g. they are part of the microfluidic valve).

[0072]

[0068] As used herein, and unless otherwise specified, the term ‘microfluidic device’ refers to a device for manipulating / processing small volumes (e.g. micro- to nanolitres; up to millilitres in the case of prolonged experiments) of fluids through channels with dimensions on the order of micrometres. Such a device may incorporate typically components such as microfluidic valves to control fluid flow. It may be used — among several others — in applications such as chemical analysis, biomedical diagnostics and micro-scale reactions.

[0073]

[0069] In a first aspect, the present invention relates to a microfluidic valve comprising a flexible diaphragm.

[0074]

[0070] Initially, the flexible diaphragm of the microfluidic valve will be described. The flexible diaphragm comprises a membrane having: compressive internal stress; a thickness of at most 100 nm; and an ultimate strength of at least 1 GPa.

[0075]

[0071] It was surprisingly realized within the present invention that thin membranes with compressive internal stress have a deflection profile that features a sharp transition (i.e. a considerable change in deflection over a narrow pressure range). Without being bound by theory, it is believed that the compressive internal stress increases the membrane’s deflection capabilities. Indeed, one way to relieve the compressive internal stress is to buckle / bend out of plane, so that the membrane will easily and readily do so when a pressure is applied to it. Moreover, the direction of this buckling / bending (e.g. up- or downwards out of plane) depends on the direction of the forces involved. Accordingly, when a pressure is applied in the opposite direction, the membrane ‘flips over’, thereby yielding a large and sharp transition in deflection. In synergy with the thinness and high ultimate strength of the membrane, this gives a membrane with excellent pressure response and large deflections, while nevertheless maintaining good mechanical integrity even at higher pressures.

[0076]

[0072] Furthermore, even in the absence of an external pressure, the membrane may buckle and / or wrinkle (which could also be regarded as ‘multimodal buckling’) to relieve some of its compressiveinternal stress. In doing so, the membrane can effectively accommodate more material than can fit in a purely planar configuration; in other words: it gains a larger surface area compared to a flat membrane. This larger surface area in turn allows the membrane to deflect out further. To give but one more concrete example: during deposition a membrane material may adopt a quite closely packed configuration, but may later want to ‘relax’. However, the membrane may not necessarily be able to expand freely in any direction (e.g. because it is confined and / or is bound to the substrate), which will cause compressive internal stress. In absence of the ability to expand parallel to the substrate, said compressive internal stress can nevertheless be relieved by going out of plane (e.g. in the form of wrinkling and / or buckling). For a wrinkled membrane then, when pressure is applied to the membrane, the degree of wrinkling reduces and the membrane still (i.e. akin to a buckled membrane) buckles / bends out of plane, e.g. adopting roughly the shape of a (wrinkled) hemisphere (as e.g. illustrated in FIG 13-FIG 16, which were made using a Keyence VHX 7000 digital microscope). As indicated before, other parameters (e.g. tension, elongation, etc.) being the same, the deflection achieved in this way is typically larger than with a purely flat membrane (e.g. due to ‘excess material / surface area’ in the wrinkles). Note that while wrinkling may be an indication of compressive internal stress, the latter may be present also in membranes that show no (appreciable) wrinkling. Membranes in accordance with the present invention therefore may or may not be wrinkled.

[0077]

[0073] Even further, it has been realized that the thin membrane acquires its strength from the Hall-Petch effect, describing how a material’s strength increases with the grain size of the material. Thicker material may correspond to greater grain size, reducing the strength. It is a realization that this may be overcome by having a membrane comprising of layers of different material, each layer being thin and thus having a small grain size.

[0078]

[0074] In embodiments, the membrane may have a thickness (i.e. its dimension perpendicular to the plane of the membrane) of at most 75 nm, more preferably at most 50 nm, yet more preferably at most 40 nm, still yet more preferably at most 30 nm, most preferably at most 25 nm; e.g. 20 nm. A thinner membrane is typically advantageously less stiff, thereby responding better to small pressure differences and allowing larger deflections. That said, this has to be weighed against thinner membranes being more prone to breaking / rupturing (e.g. tearing or bursting).

[0079]

[0075] In embodiments, the membrane may have an ultimate strength of at least 1 GPa, preferably at least 1.5 GPa, more preferably at least 2 GPa, most preferably at least 3 GPa. Materials with high ultimate strength advantageously yield membranes with high breaking pressures; where ultimate strength is typically a material property (and thus independent of the design of the membrane), whereas breaking pressure is a system property (which is e.g. dependent on the area of the membrane). In embodiments, the membrane may have an area of from 2X103pm2to 3 mm2(preferably from 8X103pm2to 0.8 mm2, more preferably from 31 X103pm2to 0.5 mm2) and a breaking pressure of at least 100 kPa, preferably at least 150 kPa, more preferably at least 200 kPa, most preferably at least 250 kPa, such as 500 kPa or more. Operational pressures for fluidic valves are commonly in the order of 1 bar (100 kPa) or more, so the membrane advantageously has a breaking pressure above these operational pressures.

[0080]

[0076] In embodiments, the membrane may have a width of from 50 pm to 2 mm, preferably from 100 pm to 1 mm, more preferably from 200 pm to 800 pm, yet more preferably from 300 pm to 600pm, such as from 400 pm to 500 pm. In embodiments, the flexible diaphragm may have a width of from 50 pm to 2 mm, preferably from 100 pm to 1 mm, more preferably from 200 pm to 800 pm, yet more preferably from 300 pm to 600 pm, such as from 400 pm to 500 pm. These are advantageously a suitable / desired size ranges for use in microfluidic valves / microfluidic devices, which together with the aforementioned characteristics of the membrane — especially the compressive internal stress and thickness — allow the flexible diaphragm to have a large stroke (i.e. the displacement of its geometric centre over the operating pressure range — e.g. from 1 bar to -1 bar). For example, the flexible diaphragm may in embodiments have a stroke of at least 5 pm, preferably at least 10 pm, more preferably at least 15 pm, yet more preferably at least 20 pm, still yet more preferably at least 25 pm, most preferably at least 30 pm. Herein, the membrane and / or flexible diaphragm may typically be characterized by two perpendicular dimensions (e.g. length and width) in the plane of the membrane / flexible diaphragm (i.e. perpendicular to their thickness), of which the width is the shortest of these two. In case of a circular membrane and / or flexible diaphragm, the width and length may be equal and may be more commonly referred to as the diameter. The shape of the membrane and / or flexible diaphragm is typically not particularly limited; for example, it may be circular, oval, square, rectangular, triangular, etc. In embodiments, the ratio of width to length (width length) may be from 1 :1 to 1 :10, preferably from 1 :1 to 1 :5, more preferably from 1 :1 to 1 :3, such as from 1 :1 to 1 :2.

[0081]

[0077] In embodiments, the membrane may be made of a metalor nanomaterial (e.g. graphene). The membrane can thus advantageously be flexible in material choice. Notwithstanding, in preferred embodiments, the membrane may be made of a metal. In embodiments, the metal may be Ru (ruthenium), Zr (zirconium), Ti (titanium), Ta (tantalum), Pt (platinum), Pd (palladium), Al (aluminium) or an alloy comprising one or more of these, preferably Ru, Zr, Ti, Ta or alloy comprising one or more of these; especially Ru, Zr or alloys comprising Ru and / or Zr. Such metals advantageously have high ultimate strength (thereby allowing thinner membranes, cf. supra) and can be relatively straightforwardly formed (e.g. deposited) with suitable compressive internal stress. Moreover, they have good corrosion resistance and are biocompatible, which allows them to be exposed to various (bio)chemicals (e.g. during operation) while maintaining their mechanical properties.

[0082]

[0078] In embodiments, the membrane may comprise a plurality of layers, wherein each of the layers is made of a metal or nanomaterial (e.g. graphene). The membrane may advantageously be flexible in the number of layers comprised in the membrane. The membrane may for instance comprise one layer, two layers, three layers, four layers, or up to ten layers. Each layer may comprise a unique material. However, some layers may comprise the same material. For instance, the layers may comprise two different materials, such that the layering comprises every other layer of a first material and every other layer of a second material.

[0083]

[0079] The first layer may for instance be Ru, and the second layer may be TiN. The thickness of each layer may vary from 1 nm to 100 nm. Thus, each layer making up the flexible diaphragm may have a thickness of at most 100 nm, more preferably 75 nm, more preferably at most 50 nm, yet more preferably at most 40 nm, yet more preferably at most 30 nm, yet more preferably 25 nm; yet more preferably at most 20 nm, yet more preferably at most 10 nm, still yet more preferably at most 5 nm, most preferably 1 nm.

[0080] As a first specific example, the membrane may comprise a first layer of 50 nm thick Ru on top of a second layer of 5 nm thick TiN. As a second example, the first layer may be a layer of TiN having a thickness of 2 nm to 50 nm, the second layer may be Ru having a thickness of 20 nm to 100 nm and the third layer may be TiN having a thickness of 2 nm to 50 nm. As a third example, the first layer may be TiN in a thickness of 2 nm to 50 nm, the second layer may be Ru in a thickness of 20 nm to 100 nm, the third layer may be TiN in a thickness of 2 nm to 50 nm, the fourth layer may be Ru in a thickness of 20 nm to 100 nm, the fifth layer may be TiN having a thickness of 2 nm to 50 nm. As a fourth example, the first layer may be a TiN layer having a thickness of 2 nm to 50 nm, the second layer may be Ru having a thickness of 20 nmto 100 nm, the third layer may be TiN having a thickness of 2 nm to 50 nm, the fourth layer may be Ru having a thickness of of 20 nm to 100 nm, the fifth layer may be TiN having a thickness of 2 nm to 50 nm, the sixth layer may be Ru having a thickness of 20 nm to 100 nm and the seventh layer may be TiN having a thickness of 2 nm to 50 nm.

[0084]

[0081] An advantage of the multi-layer structure is that it may increase the strength of the membrane. Further, each layer of the multi-layer stack may possibly be kept thin as the plurality of layer together increases the total strength.

[0085]

[0082] In embodiments, the flexible diaphragm may further comprise an adhesion layer for bonding the membrane to a substrate and / or a capping layer for covering the membrane. In embodiments, the adhesion layer and / or capping layer may independently have a thickness of from 0.5 to 20 nm, preferably from 2 to 15 nm. In embodiments, the adhesion layer and / or capping layer may independently comprise (e.g. consist of) TiN orTaN. An adhesion layer can advantageously improve bonding of the membrane to the substrate. Additionally, the adhesion layer can advantageously protect (the bottom of) the membrane, e.g. during fabrication. A capping layer can advantageously protect (the top of) the membrane, e.g. during fabrication.

[0086]

[0083] A further advantage of the capping layer may be that the capping layers may further enhance the strength of the membrane. The capping layer may constrain the surface of the membrane and suppress dislocation motion or grain boundary sliding near the interfaces. This confinement effect may effectively increase the stress required for plastic deformation, leading to higher overall strength and improved thermal stability. Moreover, the capping layer may act as barrier to grain growth during deposition or annealing, helping maintain the fine-grained microstructure that is essential for Hall— Petch strengthening. It is a realization that the deflection of the membrane is not substantially reduced by adding a plurality of layers. A further advantage of the capping layer may be that the capping layer may prevent electrochemical dissolution of the membrane when the membrane is in contact with electrolytes and / or solvents.

[0087]

[0084] In embodiments, the substrate may comprise (e.g. consist of) a semiconductor (e.g. Si), an oxide (e.g. SiC>2), a polymer or glass (e.g. borofloat 33). In some embodiments, the substrate may comprise an etch stop layer (e.g. a SiC>2 layer). Such an etch stop layer may advantageously allow to compensate for etching non-uniformity (e.g. while forming the through-hole in the substrate; cf. infra). The thickness of the etch stop layer may typically vary depending on the etching uniformity achieved, but may for instance be in the order of a hundred to a few hundred nanometres (e.g. 200 nm).

[0085] In preferred embodiments, the flexible diaphragm (e.g. the membrane) may be non-permeable; at least to a pressure transmission medium and / or a medium of which the flow is to be controlled by the flexible diaphragm.

[0088]

[0086] In embodiments, the flexible diaphragm may be suitable for another microfluidic component or device. Indeed, microfluidic component / device configurations exist which make use of flexible diaphragms — and for which flexible diaphragms in accordance with the present invention can be advantageous — , but where the diaphragm is not part of a microfluidic valve.

[0089]

[0087] In embodiments, any feature of any embodiment of the first aspect may independently be as correspondingly described for any embodiment of any of the other aspects.

[0090]

[0088] In a second aspect, the present invention relates to a method for manufacturing a flexible diaphragm for a microfluidic valve, comprising: a) providing a membrane over a substrate, and b) forming a through-hole in the substrate but not the membrane; whereby the flexible diaphragm comprises the membrane and the membrane has: compressive internal stress; a thickness of at most 100 nm; and an ultimate strength of at least 1 GPa.

[0091]

[0089] The method advantageously allows fabricating responsive, thin and strong diaphragms on the substrate. An example of such a method is illustrated in Example 1 (cf. infra).

[0092]

[0090] In embodiments, step a may comprise forming the membrane over the substrate. In embodiments, step a may comprise depositing the membrane directly over the substrate. In embodiments, depositing the membrane may comprise using a physical vapor deposition (PVD; e.g. sputtering or evaporation), chemical vapour deposition (CVD) or electroplating; preferably PVD. PVD enables forming thin metal films. Direct deposition of the membrane on the substrate advantageously allows the membrane to be thinner, compared to forming the membrane ex situ and subsequently transferring it onto the substrate (which is generally a more complicate process that requires thicker membranes to withstand the transfer without rupturing too readily). Notwithstanding, step a may in other embodiments comprise transferring the membrane over the substrate.

[0093]

[0091] In embodiments, step b may comprise etching the through-hole in the substrate. In embodiments, step a may be performed before step b or after step b.

[0094]

[0092] In embodiments, the method may comprise a step a' (e.g. before step a) of: a') providing an adhesion layer over (e.g. on) the substrate. An adhesion layer can advantageously improve bonding of the membrane to the substrate. Additionally, the adhesion layer can advantageously protect (the bottom of) the membrane, e.g. during fabrication (e.g. during step b).

[0095]

[0093] In such embodiments, step a may comprise providing the membrane on the adhesion layer.

[0096]

[0094] In embodiments, the method may comprise a step a") of: a") annealing the membrane. In some embodiments, step a" may be performed after step a. For example, step a" may be performed before, during and / or after step b; depending on convenience and the thermal budget of the materials involved. Annealing can reduce the compressive stress in the membrane (e.g. reduce the degree of wrinkling) and thereby advantageously allows to finetune the deflection characteristics of the membrane.

[0097]

[0095] In embodiments, the method may comprise a step a'" of: a'") patterning the membrane (e.g. by lithography). In some embodiments, step a'" may be performed after step a. For example, step a'" may be performed before, during and / or after step b. Patterning the membrane advantageouslyallows the shape and extent / dimensions of the membrane to be finetuned after it has been provided over the substrate.

[0098]

[0096] In embodiments, the method may comprise a step p (e.g. before step a) of: p) providing a sacrificial topography pre-shaping layer over (e.g. on) the substrate. The sacrificial topography preshaping layer may beneficially provide the membrane with a certain shape. Thus, the membrane may be provided on the sacrificial topography pre-shaping layer, conforming to the shape of the sacrificial topography pre-shaping layer.

[0099]

[0097] The sacrificial topography pre-shaping layer may have a shape of sphere, a circle, a rectangle, a square, or it may have a pyramidal shape. Thus, the sacrificial topography pre-shaping layer may have different patterns, shaping the membrane into different shapes. The sacrificial topography pre-shaping layer may have a combination of shapes, such as a pattern of varied shapes.

[0100]

[0098] An advantage of having different shapes of the sacrificial topography pre-shaping layer may be to have an easier fabrication of the membrane. Different shapes may be suitable for different fabrication methods. For example, isotropic etching methods or gray scale resist pattering may be a better fabrication method for rounded shapes. The shapes with straight walls may be better fabricated using KOH etching, a subtraction method, or with normal resist pattering, a sacrificial method. Which fabrication methods to be used depends on the entire process flow and thus may be chosen depending on the specific fabrication.

[0101]

[0099] Moreover, the different shapes may result in different strengths. A rounded shape may have a larger strength than shapes with straight walls.

[0102]

[0100] The sacrificial topography pre-shaping layer may comprise a resist, another metal compared to the membrane, or an oxide / nitride. The sacrificial topography pre-shaping layer may comprise any material being selectively removable from the membrane as well as from the substrate.

[0103]

[0101] In embodiments, as an alternative to step p, the method may comprise the step p’ (e.g. before the step a) of: p’) pre-shaping a surface of the substrate configured for receiving the membrane. The pre-shaping may be performed by removing at least a part of the substrate corresponding to a preferred shape of the membrane. When the membrane is provided on the substrate, the membrane may conform to the shape of the substrate. The pre-shaping of the substrate may be made by DRIE or wet etching.

[0104]

[0102] An advantage of having a pre-shaping step p) or p’) may be to allow for a reduced footprint of the membrane, while yet maintaining a possible large stroke of the membrane. A further advantage may be to reduce the energy needed to change the membrane, such that a valve is open or closed.

[0105]

[0103] In embodiments, the method may comprise a step (e.g. after step a) of: providing a capping layer over the membrane. A capping layer can advantageously protect (the top of) the membrane, e.g. during fabrication (e.g. after step b). In embodiments, the capping layer may optionally be removed prior to finalizing the microfluidic device.

[0106]

[0104] In embodiments, the step b) forming a through-hole in the substrate but not the membrane further comprises b’) removing the sacrificial topography pre-shaping layer. The removal may be made using DRIE, wet etching, or any other suitable method.

[0107]

[0105] In embodiments, any feature of any embodiment of the second aspect may independently be as correspondingly described for any embodiment of any of the other aspects.

[0106] In a third aspect, the present invention relates to a use of a membrane as defined in any embodiment of the first aspect as a flexible diaphragm for a microfluidic valve.

[0108]

[0107] The excellent pressure response and large deflections, while nevertheless maintaining good mechanical integrity even at higher pressures, make the membrane advantageously well-suited as a flexible diaphragm for a microfluidic valve.

[0109]

[0108] In embodiments, any feature of any embodiment of the third aspect may independently be as correspondingly described for any embodiment of any of the other aspects.

[0110]

[0109] Returning to the first aspect, the microfluidic valve will now be discussed in more detail.

[0111]

[0110] The flexible diaphragm advantageously enables a highly effective microfluidic valve. Examples such microfluidic valves are illustrated in Example 2 (cf. infra).

[0112]

[0111] In embodiments, the microfluidic valve may further comprise a valve seat for receiving the flexible diaphragm (e.g. in a closed configuration of the microfluidic valve). FIG 1-FIG 4 for instance illustrate a few possible (out of many others) valve seat configurations with a flexible diaphragm (21), substrate (22) in which the valve seat is formed, and a fluidic channel portion (23) which is opened or closed by bending the flexible diaphragm.

[0113]

[0112] In preferred embodiments, actuation may be decoupled from the flexible diaphragm as such, e.g. via transmitting actuated pressure through a pressure transmission medium to the flexible diaphragm. This advantageously allows to tune the flexible diaphragm towards that role, as opposed to also having to make the flexible diaphragm additionally into (part of) an actuator (which typically comes with requirement that are not directly compatible with the former role). Moreover, it enables to bend the flexible diaphragm without causing significant changes in temperature and / or local complex stress concentrations.

[0114]

[0113] For example, the microfluidic valve may in embodiments comprise: i) a portion of a fluidic channel, ii) at least a portion of a pressure transmission channel overlapping (i.e. being aligned over or under) the fluidic channel portion, iii) the flexible diaphragm separating the fluidic channel portion and the pressure transmission channel portion, and iv) one or more actuators for at least partially opening or at least partially closing the pressure transmission channel, or increasing or decreasing a pressure in the pressure transmission channel; such that a pressure in the pressure transmission channel portion can bend the flexible diaphragm into the fluidic channel portion and / or out of the pressure transmission channel portion, thereby at least partially closing the fluidic channel portion, or out of the fluidic channel portion and / or into the pressure transmission channel portion, thereby at least partially opening the fluidic channel portion. The pressure transmission channel portion and the fluidic channel portion are thus positioned such that they are separated by the flexible diaphragm, with at least the portion of one channel being aligned over or under the corresponding portion of the other channel across the diaphragm. Accordingly, depending on the pressure in the pressure transmission channel, the flexible diaphragm is deformed and thereby bends / deflects into or out of the adjacent channels. This bending in turn modulates fluid flow through the fluidic channel portion by opening or closing the channel.

[0115]

[0114] In embodiments, the pressure transmission channel may be a hydraulic or pneumatic transmission channel, preferably a hydraulic transmission channel. In embodiments, the pressure transmission channel may comprise an incompressible or compressible fluid, preferably anincompressible fluid. Compared to gasses, liquids are typically relatively incompressible, thereby advantageously better transmitting any forces (e.g. by the actuator) or pressures (e.g. by an internal or external pressure source) applied to them.

[0116]

[0115] In embodiments, the actuator may be an electrostatic actuator, electromagnetic actuator, a piezoelectric actuator or a thermal actuator. These actuators can advantageously be made relatively compact, while nevertheless allowing to generate sizable actuation forces. To that effect, the actuators may in embodiments further comprise one or more electrodes and / or a volume change material — such as a phase change material (e.g. germanium-antimony-tellurium, GST; or vanadium oxide, VO2), piezoelectric material, high thermal expansion (CTE) material, thermopneumatic material or hydrogel.

[0117]

[0116] In preferred embodiments, the microfluidic valve may operate without an external pressure source. Although it brings additional challenges in terms of having to generate the required forces / pressures within the microfluidic valve, foregoing an external pressure source advantageously makes the microfluidic valve self-contained and simplifies the system (e.g. microfluidic device) within which the microfluidic valve operates. In these embodiments, the one or more actuators (typically a plurality thereof; e.g. actuating in unison to generate sufficient force / pressure) may be used to generate as such the desired pressure in the pressure transmission channel (e.g. by actuating directly onto the fluid therein), thereby increasing or decreasing the pressure in the pressure transmission channel (cf. Example 2C).

[0118]

[0117] Notwithstanding, in other embodiments, the microfluidic valve may comprise an external pressure source (e.g. integrated in the microfluidic device, or external to the microfluidic device). In these embodiments, the one or more actuators modulate the external pressure through regulating the (partial) opening and closing of the pressure transmission channel (cf. Example 2B).

[0119]

[0118] In yet other embodiments, the microfluidic valve may be as described above, but without the one or more actuators. In this case, not only provision of the pressure but also its modulation may be performed externally (cf. Example 2A).

[0120]

[0119] According to an embodiment, the membrane is having a non-flat shape when the microfluidic valve is in an off-state.

[0121]

[0120] The non-flat shape may be formed from the compressive internal stress being intrinsic in the material comprised in the membrane. In other words, the material wants to expand and become essentially larger than what is allowed by the valve. However, the non-flat shape may as well originate from a shaping, such as a pre-shaping of the membrane.

[0122]

[0121] In embodiments, any feature of any embodiment of the fourth aspect may independently be as correspondingly described for any embodiment of any of the other aspects.

[0123]

[0122] In a fifth aspect, the present invention relates to a microfluidic device comprising a microfluidic valve according to any embodiment of the fourth aspect.

[0124]

[0123] By using one or more the microfluidic valves, a variety of microfluidic devices can advantageously be formulated. For instance, the microfluidic device may in embodiments include (or be) a shut-off valve (e.g. blocking flow of fluid through a channel or allowing passage thereof depending on how the diaphragm is made to bend), a micropump (e.g. diaphragm pump or peristaltic pump comprising three or more of the microfluidic valves in series; applying pressure to the fluid bybending the diaphragm and thereby propelling the fluid through a channel), a microfluidic mixer (e.g. bending the diaphragm to mix different fluids in a channel or reservoir), or a microfluidic flow control device (e.g. modulating the flow rate of one or more fluids through controlling the bending of the diaphragm).

[0125]

[0124] In embodiments, any feature of any embodiment of the fifth aspect may independently be as correspondingly described for any embodiment of any of the other aspects.

[0126]

[0125] The invention will now be described by a detailed description of several embodiments of the invention. It is clear that other embodiments of the invention can be configured according to the knowledge of the person skilled in the art without departing from the true technical teaching of the invention, the invention being limited only by the terms of the appended claims.

[0127] Example 1: Fabrication and Characterization of Flexible Diaphragms

[0128]

[0126] A series of experiments were conducted to investigate the mechanical properties and deflection capabilities of thin membranes in flexible diaphragms for microfluidic valves, aiming to assess the suitability of the membranes in terms of the strength, flexibility, and responsiveness to applied pressure of the resulting diaphragms.

[0129] Fabrication

[0130]

[0127] Several different flexible diaphragms were made by depositing various membrane materials on a substrate as outlined below.

[0131]

[0128] With reference to FIG 5a to FIG 5d, a Si wafer having a primary thickness of about 700 pm was provided as substrate (22). A sacrificial topography layer (226), comprising a resist, another metal compared to the membrane, or an oxide / nitride, was deposited as a pre-shaping layer. The deposition of the adhesion layer (211), the membrane layer(s) (210), the optional intermediate layers (225) and the capping layer (212), as discussed below in relation to FIG 6-12 may be made on top of the sacrificial layer (226) and by that conform to the shape of the sacrificial topography layer (226). As is illustrated, various shapes of the sacrificial topography layer (226) may be contemplated. It should be understood that the sacrificial layer (226) may alternatively be deposited on an etch stop layer (221).

[0132]

[0129] As an alternative, as is illustrated in FIG 5e to FIG 5h, the Si wafer substrate (22) may be preshaped by removing at least a part of the substrate corresponding to a preferred shape of the membrane. The pre-shaping may be made into various shapes, as illustrated. When the adhesion layer (211), the membrane layer(s) (210), the optional intermediate layers (225) and the capping layer (212), as discussed below in relation to FIG 6-12, is deposited on the substrate (22), they may conform to the shape of the substrate (22). The pre-shaping of the substrate (22) may be made by DRIE or wet etching.

[0133]

[0130] With reference to FIG6a, a Si wafer having a primary thickness of about 700 pm was provided as substrate (22), with a 200 nm SiO2 etch stop layer (221). Over the etch stop layer (221), 15 nm of titanium nitride (TiN) was deposited as an adhesion layer (211). Next, a selected thickness (e.g. between 20 and 75 nm) of membrane material (210) (e.g. compressive Ru, Zr or Si in accordance with the present invention, or non-compressive Si not in accordance with the present invention; cf. infra) was deposited over the adhesion layer (211). Finally, a further 15 nm of TiN was deposited over the membrane material (210) as a capping layer (212).

[0131] In FIG 6b a Si wafer having a primary thickness of about 700 pm was provided as substrate (22), with a 200 nm SiO2 etch stop layer (221). Over the etch stop layer (221), 15 nm of titanium nitride (TiN) was deposited as an adhesion layer (211). Next, a selected thickness (e.g. between 20 and 75 nm) of membrane material (210) (e.g. compressive Ru, Zr or Si) was deposited over the adhesion layer (211). An intermediate layer (225) of TiN, having a thickness of 2 nm to 50 nm, was deposited on the membrane material (210). A second layer of a selected thickness (e.g. between 20 and 75 nm) of membrane material (210) (e.g. compressive Ru, Zr or Si) was deposited over the intermediate layer (225). Finally, a further 15 nm of TiN was deposited over the membrane material (210) as a capping layer (212).

[0134]

[0132] In FIG 6c a Si wafer having a primary thickness of about 700 pm was provided as substrate (22), with a 200 nm SiO2 etch stop layer (221). Over the etch stop layer (221), 15 nm of titanium nitride (TiN) was deposited as an adhesion layer (211). Next, a selected thickness (e.g. between 20 and 75 nm) of membrane material (210) (e.g. compressive Ru, Zr or Si or non-compressive Si not in accordance with the present invention; cf. infra) was deposited over the adhesion layer (211). An intermediate layer (225) of TiN, having a thickness of 2 nm to 50 nm, was deposited on the membrane material (210). A second layer of a selected thickness (e.g. between 20 and 75 nm) of membrane material (210) (e.g. compressive Ru, Zr or Si or non-compressive Si not in accordance with the present invention; cf. infra) was deposited over the intermediate layer (225). A second intermediate layer (225) of TiN, having a thickness of 2 nm to 50 nm, was deposited on the second membrane material (210). A third layer of a selected thickness (e.g. between 20 and 75 nm) of membrane material (210) (e.g. compressive Ru, Zr or Si or non-compressive Si not in accordance with the present invention; cf. infra) was deposited over the intermediate layer (225). Finally, a further 15 nm of TiN was deposited over the membrane material (210) as a capping layer (212).

[0135]

[0133] The following FIG 7 to 12 discloses the fabrication in relation to the structure of FIG 6a. However, it should be understood that similar fabrication may be used should the structure comprise the layering of FIG 6b or 6c.

[0136]

[0134] Referring now to FIG 7, to facilitate the later etching process (cf. infra), the Si substrate (22) was thinned to 200 pm by grinding.

[0137]

[0135] Referring now to FIG 8, a patterned lithography mask (222) — e.g. about 800 nm to 1 pm of a SiO2 hard mask and / or 15 pm of a photoresist — was provided.

[0138]

[0136] Referring now to FIG 9, the pattern was transferred into the Si substrate (22) by a dry etching through the mask (222).

[0139]

[0137] Referring now to FIG 10a, the pattern was further transferred into the etch stop layer (221) by a dry or wet etching landing on the adhesion layer (211) and forming (a plurality of) through-hole(s) (224) and the flexible diaphragm(s) (21). As illustrated in FIG 10b and 10c, if a sacrificial pre-shaping layer (226) was used, the sacrificial pre-shaping layer (226) is removed simultaneously for forming (a plurality of) through-hole(s) (224) and the flexible diaphragm(s) (21).

[0140]

[0138] Referring now to FIG 11 , the capping layer (212) and / or the adhesion layer (211) can optionally be removed — e.g. by etching — from the membrane (completely or only in / above the troughholes (224)).

[0139] Referring now to FIG 12, the membrane (210) was optionally annealed to reduce its ‘wrinkling’ — if any — to a desired level. This step is not required, but allows fine tuning the deflection properties of the diaphragm (21).

[0141]

[0140] A 3D image of such a flexible diaphragm (21) is shown in FIG 13, showing a Z-stack of images made by a Keyence VHX 7000 digital microscope.

[0142]

[0141] As an alternative to the above, e.g. Si membranes can also be formed starting a silicon-on-insulator (SOI) substrate (e.g. having a 220 nm thick single crystal Si on top of a SiO2 layer, which is in turn on a Si wafer). Next, the top Si layer is thinned — for example to 100 nm (by oxidation and oxide etching) — and the bottom Si wafer is thinned — for example to 500 pm (e.g. by grinding). A resist pattern is then provided, and the bottom Si wafer is further etched (e.g. by deep reactive-ion etching) up to the SiO2 layer. Finally, the membrane is released by etching the SiO2.

[0143] Characterization

[0144]

[0142] FIG 14 and FIG 15 show images of a 50 nm thick Ru membrane, revealing it to be a wrinkled layer that buckles out of plane. The same is observed in the case of Zr, as depicted in FIG 16, and — less pronounced — compressive Si, as depicted in FIG 17. In contrast to these membranes in accordance with the present invention, a comparative membrane (i.e. not in accordance with the present invention) of non-compressive Si was relatively smooth and flat; as seen in FIG 18. The latter was not observed to have any appreciable compressive internal stress (and even rather had tensile internal stress). Note that thus a membrane out of the same material can be provided either with (e.g. Si in FIG 17) or without (e.g. Si in FIG 18) compressive internal stress.

[0145]

[0143] FIG 19 schematically depicts the experimental setup used for deflection, breaking pressure, and fatigue tests is schematically. For the deflection experiments, membranes of various diameters — corresponding to different diameters of the through-hole etched through the substrate, cf. supra — were subjected to increasing pressure, and their corresponding deflection (displacement 6; see also FIG 1) was measured. The breaking pressure of the membranes was determined by gradually increasing the applied pressure until failure occurred. Fatigue testing involved cyclically applying and releasing pressure on the membranes over an extended period.

[0146]

[0144] The deflection behaviour of Ru and Zr membranes of various diameters is illustrated in FIG 20 and FIG 21 , respectively. FIG 22compares the deflection of compressive Ru, Zr, compressive Si, and non-compressive Si membranes. All of the measured materials generally exhibited increasing deflection with rising pressure, with larger diameter membranes showing greater displacement at a given pressure. Zr generally outperformed the other materials here, showcasing significantly higher deflection across the whole pressure range. That said, Ru and Zr further showed a sharp transition at low pressure (cf. FIG 20and FIG 21). A sharper — albeit noticeably broader than for Ru and Zr — transition was also observed for compressive Si (cf. FIG 22), but was not observed for the comparative, non-compressive Si (FIG 22) membrane. Without being bound by theory, this was attributed to the buckled Ru, Zr or compressive Si membrane ‘flipping over’ when even a fairly low pressure is applied in the opposite direction. The initial stress is independent of the total thickness. Therefore, the initial deflection depending on the initial stress is not affect by the thickness of a multilayer. Thus, having a flexible diaphragm comprising of several layers may not negatively affect the deflection of the membrane.

[0145] Breaking pressures for different samples of compressive Ru, Zr and Si membranes are presented in FIG 23. In general, Ru membranes demonstrated the highest breaking pressures, indicating their excellent strength and resistance to failure. Notwithstanding, also the Zr membranes — even while being thinner — outperformed those of Si.

[0147]

[0146] FIG 24shows an extract of a fatigue test on a Ru membrane. In various tests, Ru membranes were subjected to 105pressure cycles of 10, 30, 50, 70 or 100 kPa. In each case, no failure of the membrane was observed.

[0148]

[0147] In summary, the experimental results clearly demonstrate the superior mechanical properties of membranes in accordance with the present invention, such as Ru, Zr and other materials showing similar behaviour. Their ability to durably (i.e. over an extended number of cycles) achieve large deflections without rupturing, makes them ideal candidates for use in flexible diaphragms for microfluidic valves. Moreover, their sharp transition in deflection at low pressure in particular enables flexible diaphragms made therewith to display highly efficient and responsive valve operation, with a large valve-response (opening or closing) under minimal applied pressure.

[0149] Example 2: Microfluidic Valves and Devices

[0150]

[0148] Building upon the promising results of the diaphragm characterization in Example 1 , several proof-of-concept microfluidic valves and devices incorporating a flexible diaphragm in accordance with the present invention were designed.

[0151]

[0149] In general, the core of each of these microfluidic valves is as previously described with reference to FIG 1-FIG 4. As depicted therein and in FIG 25, FIG 27 andFIG 29, the microfluidic valve (2) comprises a portion (23) of a fluidic channel (3), a portion (24) of a pressure transmission channel (4) overlapping the fluidic channel portion (23), the flexible diaphragm (21) separating the fluidic channel portion (23) and pressure transmission channel portion (24), and an (external or internal) pressure control for controlling the pressure in the pressure transmission channel portion (24).

[0152]

[0150] Therein, the fluidic channel, pressure channel and pressure control can generally be fabricated using standard microfabrication techniques, while the flexible diaphragm can for instance be fabricated as outlined in Example 1.

[0153]

[0151] The valve operation utilizes the deflection of the diaphragm (21) in response to pressure changes in the pressure transmission channel portion (24). Increasing the pressure in the pressure transmission channel portion (24) (relative to that in the fluidic channel portion (23)) causes the diaphragm (2) to deflect into the fluidic channel portion (23), thereby (at least partially) restricting the flow through said fluidic channel portion (23) and thus closing the valve (2). Conversely, by decreasing the pressure in the pressure transmission channel portion (24), the diaphragm (21) returns — or even deflects into the pressure transmission channel portion (24) — , thereby opening the valve (2).

[0154] Example 2A: External Pressure Source and External Pressure Control

[0155]

[0152] With reference to FIG 25, for a first exemplary type of microfluidic valve (2) changing the pressure in the pressure transmission channel portion (24) is performed by means external to the microfluidic device (1) as such. As depicted in FIG 25, this includes an external pressure source (5) coupled to the pressure transmission channel (4) of the microfluid device (1) through an external pressure control (51) (e.g. a valve). Accordingly, the external pressure source (5) provides a certain pressure which is further modulated by the external pressure control (51). Alternatively though, thepressure control may be integral with the external pressure source (5), in which case the output of the external pressure source (5) is regulated and a separate pressure control (51) is not needed.

[0156]

[0153] In this first exemplary type, the pressure source (5) and pressure transmission channel (4) may generally be hydraulic or pneumatic. In other words, the pressure transmission channel may comprise an incompressible fluid (e.g. a liquid) or a compressible fluid (e.g. a gas).

[0157]

[0154] Although obviously not required, a microfluidic device (1) in accordance with the present invention may typically comprise a plurality of the microfluidic valves (2). This is schematically depicted in FIG 26, which for instance illustrates a single fluidic channel (3) with three microfluidic valves (2) controlling the flow therethrough. As further depicted, each microfluidic valve (2) has its own pressure transmission channel (4) with a dedicated (external) pressure source (5); although more generally these could be shared and / or connected. Notwithstanding, it will be clear that this is but one of many possible device configuration, which in generally may include additional fluidic channel (3) with further microfluidic valves (2), more or less microfluidic valves (2) per fluidic channel (3), different types of microfluidic valves (2), the pressure transmission channels (4) can be connected (e.g. branched) before and / or after the microfluidic valve, each pressure transmission channel (or branch thereof) can serve more than one microfluidic valve (2), etc.

[0158] Example 2B: External Pressure Source but Internal Pressure Control

[0159]

[0155] With reference to FIG 27, for a second exemplary type of microfluidic valve (2) changing the pressure in the pressure transmission channel portion (24) is performed by an external pressure source (5) but an internal pressure control. To that end, the microfluid device (1) further comprises one or more actuators (25) which can operate as valves for the pressure transmission channel (4). Accordingly, the pressure provided by the external pressure source (5) can be further modulated by the internal pressure control in the form of actuators (25). These actuators (25) may be located before and / or after the microfluidic valve (2). The pressure source (5) and pressure transmission channel (4) may again generally be hydraulic or pneumatic.

[0160]

[0156] One of the many possible device configurations is schematically depicted in FIG 28, which again for illustration purposes shows a single fluidic channel (3) with three microfluidic valves (2) controlling the flow therethrough. As depicted, a single pressure transmission channel branches to each of the microfluidic valves (2); although separate pressure transmission channels (4) are also possible. Moreover, the left branch is depicted as having an actuator (25) before its microfluidic valve (2), the middle branch as having an actuator (25) after its microfluidic valve (2), and the right branch as having an actuator (25) before and after its microfluidic valve (2).

[0161]

[0157] While this configuration shares many similarities the one described in Example 2A, it may in a sense be regarded as an evolution thereof. Indeed, by integrating the pressure control into the microfluidic device (1) as such, the whole system comprising the microfluidic device (1) and its external components used for its operation can be made significantly more compact and easier to operate. Notwithstanding, integration of the pressure control into the microfluidic device (1) as such also complicates the device manufacture and is therefore more challenging in that regard.

[0162] Example 2C: Internal Pressure Source and Internal Pressure Control

[0163]

[0158] With reference to FIG 29, for a third exemplary type of microfluidic valve (2) changing the pressure in the pressure transmission channel portion (24) is performed fully internally. To that end,the microfluid device (1) further comprises a closed pressure transmission channel (4) (e.g. without — or with closed of — in- and outlet) and one or more actuators (25) which can operate on the fluid in the pressure transmission channel (4). Accordingly, the pressure in the pressure transmission channel (4) can be modulated through operating the actuators (25). These actuators (25) may be located on one and / or the other side of the microfluidic valve (2). That said, the actuation pressure which can realistically be generation by such internal actuators (25) is limited, such that a plurality of actuators (25) (e.g. an array thereof) is typically employed. By the same measure, the pressure transmission channel (4) is in this case typically hydraulic — i.e. the pressure transmission channel may normally comprise an incompressible fluid (e.g. a liquid) — , so as to more optimally transmit the pressure generated by the actuators.

[0164]

[0159] One of the many possible device configurations is schematically depicted in FIG 30, which again for illustration purposes shows a single fluidic channel (3) with three microfluidic valves (2) controlling the flow therethrough. As depicted, each microfluidic valve (2) has its own closed (i.e. without in- or outlet) pressure transmission channel (4); although in some instances these could also be shared and / or connected. Moreover, the left branch is depicted as having one actuator (25), the middle branch as having two actuators (25) (one on each side of the microfluidic valve (2)), and the right branch as having an array of several actuators (25).

[0165]

[0160] While this configuration shares many similarities the one described in Example 2B (and Example 2A), it may in a sense be regarded as still a further evolution thereof. Indeed, by integrating not only the pressure control but the pressure generation as a whole into the microfluidic device (1), the microfluidic device (1) is not only more compact and easier to operate, but moreover self-sufficient (at least as it pertains to pressure generation), requiring no external components for its operation. Notwithstanding, this further also further complicates the device manufacture and is therefore even more challenging in that regard.

[0166]

[0161] Two general ways in which the actuators (25) can operate are depicted in FIG 31-FIG 36. In FIG 31-FIG 33, the actuators (25) are based on shape-change material which can be made to switch (or ‘morph’) between (at least) two configurations, such as by a piezoelectric or thermal trigger. In FIG 34-FIG 36, the actuators (25) are electrostatic actuators which can be made to bend through electrostatic attraction / repulsion of two opposing electrodes (depending on the voltage difference between these electrodes).

[0167]

[0162] In both cases, in an initial state (FIG 31 and FIG 34), the actuators (25) are relaxed and the valve (2) is partially open. In an off-state (FIG 32and FIG 35), the actuators (25) are bent out of the pressure transmission channel (4) and the fluidic pressure in the fluidic channel portion (23) bends the flexible diaphragm (21) into the pressure transmission channel portion (24), thereby allowing fluid to freely flow through the fluidic channel portion (23) and thus (e.g. substantially fully) opening the fluidic channel portion (23). Whereas in an on-state (FIG 33 and FIG 36, the actuators (25) are bent into the pressure transmission channel (4), lowering the volume of the pressure transmission channel (4) and consequently increasing the pressure in the pressure transmission channel (4), thereby restricting fluid flow through the fluidic channel portion (23) and thus (e.g. substantially fully) closing the valve (2). This sequence demonstrates how the actuation mechanism can control the flexible diaphragm (21) to regulate fluid flow through the valve (2).

[0163] It is to be understood that although preferred embodiments, specific constructions, configurations and materials have been discussed herein in order to illustrate the present invention. It will be apparent to those skilled in the art that various changes or modifications in form and detail may be made without departing from the scope of the invention as defined in the appended claims.

Claims

22CLAIMS1. A microfluidic valve (2) comprising a flexible diaphragm (21), the flexible diaphragm comprising a membrane (210) having:- compressive internal stress;- a thickness of at most 100 nm, preferably at most 75 nm, more preferably at most 50 nm, yet more preferably at most 40 nm, still yet more preferably at most 30 nm, most preferably at most 25 nm; and- an ultimate strength of at least 1 GPa, preferably at least 1.5 GPa, more preferably at least 2 GPa, most preferably at least 3 GPa.

2. The microfluidic valve (2) according to claim 1 , comprising:i) a portion (23) of a fluidic channel (3),ii) at least a portion (24) of a pressure transmission channel (4) overlapping the fluidic channel portion (23),iii) the flexible diaphragm (21) separating the fluidic channel portion (23) and the pressure transmission channel portion (24), andiv) one or more actuators (25) configured for- at least partially opening or at least partially closing the pressure transmission channel (4), or- increasing or decreasing a pressure in the pressure transmission channel (4); such that a pressure in the pressure transmission channel portion (24) can bend the flexible diaphragm (21)- into the fluidic channel portion (23) and / or out of the pressure transmission channel portion (24), thereby at least partially closing the fluidic channel portion (23), or - out of the fluidic channel portion (23) and / or into the pressure transmission channel portion (24), thereby at least partially opening the fluidic channel portion (23).

3. The microfluidic valve (2) according to claim 2, wherein the pressure transmission channel (4) is a hydraulic or pneumatic transmission channel, preferably a hydraulic transmission channel.

4. The microfluidic valve (2) according to any of claims 2 to 3, wherein the actuator (25) is an electrostatic actuator, an electromagnetic actuator, a piezoelectric actuator or a thermal actuator.

5. The microfluidic valve (2) according to any of claims 2 to 4, with the proviso that the microfluidic valve (2) operates without an external pressure source (5).

6. The microfluidic valve (2) according to claim 1, wherein the membrane (210) is made of a metal or nanomaterial,7. The microfluidic valve (2) according to claim 6, wherein the metal is Ru, Zr, Ti, Ta, Pt, Pd, Al or an alloy comprising one or more of these.

8. The microfluidic valve (2) according to any of the previous claims, having a width of from 50 pm to 2 mm, preferably from 100 pm to 1 mm, more preferably from 200 pm to 800 pm, yet more preferably from 300 pm to 600 pm.

9. The microfluidic valve (2) according to any of the previous claims, wherein the membrane (210) comprises a plurality of layers, wherein each of the layers is made of a metal or nanomaterial.

10. The microfluidic valve (2) according to any of the previous claims, wherein the flexible diaphragm (21) further comprises an adhesion layer (211) for bonding the membrane (210) to a substrate (22).

11. A method for manufacturing a flexible diaphragm (21) for a microfluidic valve (2), comprising:a) providing a membrane (210) over a substrate (22), andb) forming a through-hole (224) in the substrate (22) but not the membrane (210); whereby the flexible diaphragm (21) comprises the membrane (210) and the membrane (210) has:- compressive internal stress;- a thickness of at most 100 nm, preferably at most 75 nm, more preferably at most 50 nm, yet more preferably at most 40 nm, still yet more preferably at most 30 nm, most preferably at most 25 nm; and- an ultimate strength of at least 1 GPa, preferably at least 1.5 GPa, more preferably at least 2 GPa, most preferably at least 3 GPa.

12. The method according to claim 11 , comprising a step a' of:a') providing an adhesion layer (211) for the membrane (210) over the substrate (22).

13. The method according to any of claims 11 to 12, comprising a step a" of:a") annealing the membrane (210).

14. The method according to any of the claims 11 to 13, wherein the method comprises:p) providing a sacrificial topography pre-shaping layer over the substrate.

15. The method according to any of the claims 11 to 13, wherein the method comprises:p’) pre-shaping a surface of the substrate configured for receiving the membrane.

16. The method according to any of the claims 11 to 14, wherein the method comprises:b’) removing the sacrificial topography pre-shaping layer.

17. A microfluidic device (1) comprising a microfluidic valve (2) according to any of claims 1 to10.

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