Inertial interfacial manipulation method and geometries

Abstract

The invention provides a system (1) for fluid manipulation, wherein the system (1) comprises a first liquid supply (10), a second liquid supply (20), a microfluidic device (100), a cavitation induction system (200), and a control system (300), wherein: the first liquid supply (10) is configured to provide a first liquid (15) to the microfluidic device (100); the second liquid supply (20) is configured to provide a second liquid (25) to the microfluidic device (100); the microfluidic device (100) comprises a hosting chamber (110), wherein the hosting chamber (110) has a chamber length (L) defined by a first chamber end (111) and a second chamber end (112), wherein the hosting chamber (110) has an average equivalent circular diameter (D) perpendicular to the length (L), wherein L ≥ 3*D; wherein the cavitation induction system (200) is selected from the group comprising a laser-based heating system, an electric discharge system, and a heater; and wherein the control system (300) is configured to control the first liquid supply (10), the second liquid supply (20), and the heating system (200), and wherein the control system (300) has an operational mode wherein: in a preparation stage the first liquid supply (10) and the second liquid supply (20) are configured to provide a liquid multilayer (400) in the hosting chamber (110), wherein the liquid multilayer (400) comprises n layers (450) sequentially arranged along the chamber length (L), wherein n ≥ 2, wherein adjacent layers (450) are distinct phases, and wherein the layers (450) comprise a first liquid layer (415) comprising the first liquid (15) arranged adjacent to a second liquid layer (425) comprising the second liquid (25); and in a cavitation stage the cavitation induction system (200) is configured to induce cavitation of the first liquid (15) at a first location (41), wherein the first location (41) is arranged in the first liquid layer (415).

Description

[0001] Inertial interfacial manipulation method and geometries

[0002] FIELD OF THE INVENTION

[0003] The invention relates to a system for fluid manipulation. The invention further relates to a method for fluid manipulation.

[0004] BACKGROUND OF THE INVENTION

[0005] Methods for fluid manipulation are known in the art. For example, EP2388032A1 describes a device for creating at least one microfluidic jet, includes at least one conduit section, open to an environment of the device at one end thereof. It further includes at least one arrangement for forming in at least one of the conduit sections a meniscus forming an interface between liquid in the conduit section and the environment, at a position within the conduit section. The meniscus is at least partially concave, seen looking into the conduit section through the end open to the environment. The device includes at least one holder for holding liquid, in fluid communication with at least one of the conduit sections. It also includes at least one device for delivering an energy pulse to liquid in at least one of the holders, configured to create a shock front propagating to the meniscus and causing at least a first stage of a jet to emerge from a central part of the meniscus.

[0006] W02019209250A1 describes a fluidic die including at least one actuator, and fluid flow architecture to flow a first fluid through at least one fluidic channel, and flow a second fluid through the at least one fluidic channel to form a laminar flow between the first fluid and the actuator. The at least one actuator forms a drive bubble from the second fluid to cause the first fluid to be ejected from the fluidic die.

[0007] Krizek et al. (2020), Needle-free delivery of fluids from compact laser-based jet injector, Lab Chip 20, 3784-3791 describes a thin and long liquid delivery system (e.g. flexible and 30 cm long with 1.2 mm outer diameter) compatible with minimally invasive surgical procedures. The actuation mechanism is based on optical cavitation in a capillary nozzle where a laser pulse is delivered via a multimode optical fibre.

[0008] US2023026586A1 describes systems and methods for generation of microfluidic jets providing a tool for localized delivery of e.g., medicaments. The system implements laser energy as a driving mechanism and optical fibers for its delivery.

[0009] US2012211084A1 describes (multiple) emulsions. Multiple emulsions are formed by urging a fluid into a channel, e.g., by causing the fluid to enter the channel as a “jet”. Side channels can be used to encapsulate the fluid with a surrounding fluid. In some cases, multiple fluids may flow through a channel collinearly before multiple emulsion droplets are formed. The fluidic channels may include varying degrees of hydrophilicity or hydrophobicity. The fluidic channel may be relatively hydrophilic upstream of an intersection (or other region within the channel) and relatively hydrophobic downstream of the intersection, or vice versa. In some cases, the average cross-sectional dimension may change, e.g., at an intersection. In some cases, the multiple droplet may be formed from the collinear flow of fluids at (or near) a single location within the fluidic channel.

[0010] SUMMARY OF THE INVENTION

[0011] When different phases, e.g., different gases and / or liquids, are in contact, they are separated by a contact line (or “contact surface”). The contact line can be static or move depending on pressure gradients, temperature or surface wetting and roughness effects. The position, orientation and shape of the contact line may influence the fluid dynamics of the phases, for instance in the context of a cavitation event.

[0012] The prior art may describe systems for ejecting a liquid jet by inducing cavitation in a liquid phase bordering a gas phase, and may further describe the relevance of the contact line between the liquid phase and the gas phase for such jet ejection. However, following jet ejection, the shape of the contact line may remain distorted and / or bubbles may remain trapped in the liquid phase, which may hamper, or even prevent, consistent jet ejection results over successive jet ejections. Further, high velocity jet ejection, which may for example be relevant for jet injection applications, may lead to a ‘collapse’ at the contact line leading to a secondary jet ejection. Such secondary jet ejection may lead to a splash on a target surface, which may be undesirable in case of, for example, the injection of medicine or ink.

[0013] Further, prior art jet ejection approaches may negatively affect the physicochemical properties of the liquid that is to be ejected.

[0014] The prior art may further describe approaches for encapsulating a liquid in another liquid. However, prior art encapsulation methods may typically rely on continuous flows and may lead to a relatively high amount of waste. Further, prior art encapsulation methods may have limited flexibility regarding encapsulate size / volume, e.g., the methods or devices may be limited to providing a single encapsulate size.

[0015] The prior art may further describe approaches for providing an emulsion of a liquid in another liquid. However, prior art microemulsification methods may have limited flexibility regarding the size range of generated droplets as this may, for instance, depend on one or more of a flow rate and / or a size of a channel in which the emulsions are generated. In particular, prior art methods may allow adjusting the flow rate to affect emulsion sizes, it may be relatively challenging to provide accurate control of such flow rate, particularly in the context of microfluidic systems.

[0016] Prior art systems for fluid manipulation may further contain physical components for controlling a location or shape of a contact line and / or for guiding a fluid through a microfluidic chamber in a desired manner. Such systems may, however, be limited to a relatively narrow range of operation, i.e., they may have limited flexibility in adjusting the contact line and / or the parameters affecting fluid movement, e.g., in the context of jet ejection.

[0017] Hence, it is an aspect of the invention to provide an alternative system for fluid manipulation, which preferably further at least partly obviates one or more of above-described drawbacks. The present invention may have as object to overcome or ameliorate at least one of the disadvantages of the prior art, or to provide a useful alternative.

[0018] In a first aspect, the invention may provide a system for fluid manipulation. The system may comprise one or more of a first liquid supply, a second liquid supply, a microfluidic device, a cavitation induction system, and a control system. In embodiments, the first liquid supply is configured to provide a first liquid to the microfluidic device, especially to a first liquid inlet of the microfluidic device. Similarly, in embodiments, the second liquid supply may be configured to provide a second liquid to the microfluidic device, especially to a second liquid inlet of the microfluidic device. In particular, the second liquid may be immiscible with the first liquid. The microfluidic device may comprise a hosting chamber (or “hosting chamber arrangement”), especially wherein the hosting chamber has a chamber length (L) defined by a first chamber end and a second chamber end. The hosting chamber may further have an average equivalent circular diameter (D) perpendicular to the length (L), especially wherein L > 3*D, such as L > 5*D. The cavitation induction system may be selected from the group comprising a laser-based heating system, an electric discharge system, and a heater. In further embodiments, the control system is configured to control the first liquid supply, the second liquid supply and the heating system. In particular, the control system may be configured to (have the system) execute an operational mode, the operational mode especially comprising a preparation stage and a cavitation stage. In the preparation stage, the first liquid supply and the second liquid supply may (be configured to) provide a liquid multilayer (or “multilayer”) in the hosting chamber, such as by providing the first liquid and the second liquid to the hosting chamber. The liquid multilayer may comprise n layers sequentially arranged along the chamber length (L), wherein n > 2, and wherein adjacent layers are distinct phases. In particular, the layers may comprise (i) a first liquid layer comprising (at least part of) the first liquid arranged adjacent to a second liquid layer comprising (at least part of) the second liquid. In the cavitation stage the cavitation induction system may (be configured to) induce cavitation of the first liquid at a first location, wherein the first location is arranged in the first liquid layer.

[0019] In specific embodiments, the invention may provide a system for fluid manipulation, wherein the system comprises a first liquid supply, a second liquid supply, a microfluidic device, a cavitation induction system, and a control system, wherein the first liquid supply is configured to provide a first liquid to the microfluidic device; the second liquid supply is configured to provide a second liquid to the microfluidic device; the microfluidic device comprises a hosting chamber, wherein the hosting chamber has a chamber length (L) defined by a first chamber end and a second chamber end, wherein the hosting chamber has an average equivalent circular diameter (D) perpendicular to the length (L), wherein L > 3*D; wherein the cavitation induction system is selected from the group comprising a laser-based heating system, an electric discharge system, and a heater; wherein the control system is configured to control the first liquid supply, the second liquid supply and the heating system, and wherein the control system has an operational mode wherein: in a preparation stage the first liquid supply and the second liquid supply are configured to provide a liquid multilayer in the hosting chamber, wherein the liquid multilayer comprises n layers sequentially arranged along the chamber length (L), wherein n > 2, wherein adjacent layers are distinct phases, and wherein the layers comprise (i) a first liquid layer comprising the first liquid arranged adjacent to a second liquid layer comprising the second liquid; and in a cavitation stage the cavitation induction system is configured to induce cavitation of the first liquid at a first location, wherein the first location is arranged in the first liquid layer.

[0020] The system of the invention may provide various benefits for fluid manipulation. For instance, the presence of multiple liquid phases may benefit the restoration of the contact line after cavitation, facilitating more reproducible fluid manipulation results. Further, in the context of jet ejection, the presence of multiple liquids may substantially reduce, or even prevent, the occurrence of a secondary jet ejection. Further, the liquid in which cavitation is induced may differ from the ejected liquid, thereby avoiding negative effects of the cavitation induction on the ejected liquid, such as avoiding degradation or inactivation of medicinal compounds in a to-be-ejected liquid. Effectively, the system of the invention may thus facilitate ejecting a larger range of liquids and therein dissolved compounds. Yet further, the fluid properties of the multilayer, including the contact line properties, may be tuned by selecting the first and second liquid, as well as their layering and relative amounts, i.e., the use of multiple distinct liquid phases may provide additional tunable properties that can be varied over successive uses of the system, thereby increasing the operational range of a microfluidic device.

[0021] Further, in the context of providing encapsulates, the system of the invention may facilitate providing encapsulates of various sizes (or volumes) by varying one or more of layer thicknesses and cavitation induction parameters. For instance, when generating an encapsulate using a two-layer multilayer of a first aqueous layer and a second oil layer, there may be an interplay between the cavitation energy applied to a first layer and the thickness of the second layer. The cavitation induction parameters, particularly the cavitation induction energy, may determine the size of the core, with less energy leading to a smaller core (or in the extreme limit no core formation) and a higher energy leading to a larger core. The use of relatively high energy to provide a large core also leads to a core with high inertia, which may require a thicker oil layer to form an encapsulation. In particular, if the oil layer is too thin, an incomplete shell may be formed or a jet may be formed. Hence, the layer thicknesses and the cavitation induction parameters may be selected on the basis of a target size of the encapsulate.

[0022] Similarly, in the context of providing emulsions, the system of the invention may facilitate providing emulsions with various droplet sizes (or volumes) by varying one or more of layer thicknesses and cavitation induction parameters. In particular, the size of the emulsion droplets may scale with the cavitation induction energy. Further, as the cavitation induction energy of the system may be tightly controlled, such as when a laser-based induction system is used, droplet size may be accurately controlled.

[0023] The system of the invention may, for instance, be applied in the context of medical / bio-cosmetics applications, such as for needle-free injections, as well as for applications in chemistry, such as fine chemical and pharmaceutical fabrication applications.

[0024] Hence, the invention may provide a system for fluid manipulation, especially for microfluidic fluid manipulation. The term “fluid manipulation” may herein refer to causing the movement of fluid, particularly in the context of one or more of jet ejection, encapsulation of one liquid in another, or to provide an emulsion of one liquid in another. The term “fluid manipulation” may herein especially refer to “liquid manipulation”, i.e., to causing the movement of a liquid, including of a plurality of liquids.

[0025] In embodiments, the system may comprise a liquid supply system. The liquid supply system may comprise (at least) a first liquid supply and a second liquid supply. The liquid supply system, especially the first liquid supply and the second liquid supply, may be configured to provide liquid(s) to the microfluidic device. In particular, in embodiments, the system, especially the liquid supply system, may comprise a first liquid supply. The first liquid supply may be configured to provide a first liquid to the microfluidic device, especially to a first liquid inlet of the microfluidic device.

[0026] Further, the microfluidic device may comprise a first liquid outlet. As such, the first liquid supply may further be configured to receive a first liquid from the microfluidic device, especially via the first liquid outlet. The first liquid outlet may be configured opposite the first fluid inlet. That is, an axis configured perpendicular to the axis of elongation of the hosting chamber may intersect (a geometric center of) the first liquid inlet and (a geometric center of) the first liquid outlet. Alternatively, the first liquid inlet and first liquid outlet may be configured staggered along the chamber length (L). In embodiments, the first liquid inlet and first liquid outlet may be configured on a same side of the hosting chamber (in a plane parallel to the chamber length (L)). Yet, especially, the first liquid inlet and first liquid outlet may be configured on opposite sides of the hosting chamber (in a plane parallel to the chamber length (L)).

[0027] Similarly, in embodiments, the system, especially the liquid supply system, may comprise a second liquid supply. The second liquid supply may be configured to provide a second liquid to the microfluidic device, especially to a second liquid inlet of the microfluidic device.

[0028] The first liquid inlet and the second liquid inlet may be configured spatially separated along the chamber length (L). Especially, the first liquid inlet and the second liquid inlet may be configured spatially separated by a distance of > 0.05*L, such as > 0.1 *L, especially > 0.15*L, along the chamber length (L). Additionally or alternatively, the first liquid inlet and the second liquid inlet may be configured spatially separated by a distance of < 0.9*L, such as < 0.75*L, especially < 0.6*L, along the chamber length (L). In embodiments, one of the first and second liquid inlets may be configured (comprised by, such as) in the first chamber end. Alternatively, (both of) the first and second liquid inlets may be configured (comprised by, such as) in a side wall of the hosting chamber (i.e., in a wall of the hosting chamber bridging the first chamber end and the second chamber end).

[0029] In embodiments, the system, especially the microfluidic device, may comprise a plurality of first liquid inlets and / or a plurality of second liquid inlets. For instance, the microfluidic device may comprise a primary first liquid inlet in the first chamber end, a second liquid inlet in the side wall of the hosting chamber and at a distance di2 from the first chamber end, and a secondary first liquid inlet in the side wall of the hosting chamber and at a distance dii,2 from the first chamber end, wherein di2 < du, 2. Yet, in other embodiments, the system, especially the microfluidic device, may comprise a single liquid inlet (especially configured in the first chamber end). As such, the liquid supply system, such as the first liquid supply and the second liquid supply, may be configured to provide (both) the first liquid and the second liquid to the (same) liquid inlet of the microfluidic device.

[0030] Further, the microfluidic device may comprise a second liquid outlet. As such, the second liquid supply may further be configured to receive a second liquid from the microfluidic device, especially via the second liquid outlet. The second liquid outlet may be configured opposite the second fluid inlet. That is, an axis configured perpendicular to the axis of elongation of the hosting chamber may intersect (a geometric center of) the second liquid inlet and (a geometric center of) the second liquid outlet. Alternatively, the second liquid inlet and second liquid outlet may be configured staggered along the chamber length (L). In embodiments, the second liquid inlet and second liquid outlet may be configured on a same side of the hosting chamber (in a plane parallel to the chamber length (L)). Yet, especially, the second liquid inlet and second liquid outlet may be configured on opposite sides of the hosting chamber (in a plane parallel to the chamber length (L)).

[0031] Especially, the first liquid and the second liquid are different liquids. The first liquid and the second liquid may especially form distinct phases when brought into contact, particularly during the operational mode (or of the method; see below). Hence, the first liquid layer and the second liquid layer may comprise distinct phases with a shared interface. For instance, when the first liquid and the second liquid comprise water and oil, respectively, the liquid multilayer may comprise a water phase and an oil phase. As will be clear to the person skilled in the art, in bi-phasic systems, some liquid of one phase may be dissolved in the opposite phase and vice versa. The term “phase” may herein refer to a distinct and homogeneous state of a liquid with no internal partitioning.

[0032] The liquids may be (essentially) free of dissolved compounds, such as for demineralized water or a pure oil composition, but may also contain solutions. For instance, the liquid(s) may comprise a suspension of particles, e.g., of vesicles, a solution of molecules (e.g., for vaccinations or inks), or a supersaturated liquid, such as honey.

[0033] Especially, one or more of the first liquid and the second liquid, such as especially (at least) the first liquid, may comprise one or more of (i) a suspension or dispersion of cells and / or particles (e.g. ink particles, nanoparticles, contrast agents (optionally filled with a gaseous phase), exosomes, liposomes, etc.), and (ii) a solution of molecules (e.g. vitamins, pharmaceutical compounds, cosmetic compounds, etc.). The particles and / or molecules may be biocompatible, yet may alternatively be non-biocompatible. Further, the cells, particles, and / or molecules may be natural (i.e., naturally-occurring), yet may also be synthetic.

[0034] The preservation of the first liquid and the second liquid as a first phase and a second phase may depend on a duration and / or on operational parameters. For instance, honey may typically dissolve very slowly in water (or not at all), but may be dissolved when water and honey are kept in contact for prolonged periods of time, which dissolution may further be stimulated during heating. It will be clear to the person skilled in the art that the term “distinct phases” herein refers to distinct phases on the practically relevant timescale of the operational mode (or of the method).

[0035] The first liquid and the second liquid may especially be immiscible with one another. Two liquids may herein be considered immiscible when the solubility of either liquid in the other is < 10000 ppm at 20 °C.

[0036] Hence, in embodiments, at 20 °C the solubility of the second liquid in the first liquid may be < 50000 ppm, especially < 10000 ppm, such as < 1000 ppm, especially < 500 ppm, such as < 100 ppm, especially < 50 ppm.

[0037] Similarly, in embodiments, at 20 °C the solubility of the first liquid in the second liquid may be < 50000 ppm, especially < 10000 ppm, such as < 1000 ppm, especially < 500 ppm, such as < 100 ppm, especially < 50 ppm.

[0038] For instance, in embodiments, the first liquid may comprise an aqueous liquid, such as an aqueous solution or aqueous dispersion, and the second liquid may comprise an oil. The term “oil” may herein refer to a nonpolar hydrophobic substance.

[0039] For instance, in embodiments, the second liquid may be selected from the group comprising a silicone oil, a vegetal oil, an animal oil, and a mineral oil. The term “silicone oil” may herein refer to a liquid comprising, especially (essentially) consisting of, polymerized siloxane with organic side chains, such as polydimethylsiloxane. The term “vegetal oil” (or “vegetable oil”) may herein refer to any oil derived from a plant, such as from a seed, especially from an edible plant. The vegetable oil may, for instance, be selected from the group comprising olive oil, sunflower oil, palm oil, canola oil, coconut oil, safflower oil, com oil, peanut oil, cottonseed oil, palm-kernel oil, and soybean oil. The term “animal oil” may herein refer to an oil derived from an animal, such as fish oil derived from a fish. The term “mineral oil” may herein refer to any oil derived from petroleum, such as derived from refined crude petroleum oil, including synthetic oils.

[0040] Alternatively, the second liquid may be selected from the group comprising honey, (an aqueous solution of) glycerol, and brine (wherein the second liquid may optionally comprise one or more of cells, particles, and molecules, see above). That is, the second liquid may be a liquid miscible with the first liquid on longer timescales, but forming a distinct phase with the first liquid on a practically relevant timescale of the operational mode (or of the method). Especially, distinct phases of the first and second liquid may be stable over > 100 times, such as > 500 times, especially > 1000 times, a time required for the nucleation of a (cavitation) bubble. For instance, the first and second liquids may be provided to the hosting chamber as a flow of the respective liquid, after which a flow of the first and second liquids may be stopped in preparation of the cavitation stage, and wherein the first and second liquids may form distinct phases over at least a time scale required to (i) stop the flow of the first and second liquids, (ii) provide a(n essentially) static multilayer in the hosting chamber, and (iii) induce a cavitation event (in the cavitation stage). Further, the first and second liquids (comprising miscible liquids on longer timescales) may form distinct phases for at least 5 ms, such as at least 10 ms, especially at least 50 ms, like at least 100 ms. Further yet, the first and second liquids (comprising liquids miscible on longer timescales) may form distinct phases for at least 500 ms, such as at least 1 s, especially at least 5 s, like at least 10 s.

[0041] The term “brine” herein is know to the person skilled in the art, and may refer to an aqueous solution of a salt (e.g. sodium chloride or calcium chloride), wherein the salt may especially be present in a weight percentage of > 5%, such as > 10%, especially > 15%, with respect to the total weight of the aqueous solution (comprising the salt).

[0042] In further embodiments, the second liquid may comprise, such as be, a liquid metal. Especially, the second liquid, such as the liquid metal, may be selected from the group comprising mercury, a mercury alloy, a sodium-potassium alloy (NaK), gallium, a gallium alloy, cesium, and a cesium alloy, such as especially a gallium alloy. For instance, the second liquid may comprise (eutectic) galinstan (Gao.essIntuisSno.i) or eutectic gallium-indium (eGain) or. Optionally, the liquid metal may comprise metal oxides, such as especially at an interface between (i) the liquid metal and a wall of the hosting chamber, and / or (ii) the liquid metal and a gas (phase). Would the second liquid be reactive with or instable in water (e.g. in the case of NaK), the first liquid may comprise a non-aqueous liquid, such as e.g. an oil.

[0043] In embodiments, the liquid multilayer may comprise a plurality of first liquid layers. Especially, each first liquid layer may comprise a first liquid. Each of the plurality of first liquid layers may comprise the same first liquid. Alternatively, each of the plurality of first liquid layers may comprise a different first liquid. For instance, the first liquid of each of the plurality of first liquid layers may differ in one or more of a first liquid type and a first liquid composition. The first liquid type may for each of the plurality of first liquid layers be selected from the group comprising an aqueous liquid and an oil. Further, in embodiments, at least two of the first liquid layers may comprise a first liquid differing in one or more of: (i) a presence of (dissolved) molecules, (ii) a presence of (suspended) particles, (iii) a concentration of the (dissolved) molecules and / or of the (suspended) particles, and (iv) a composition of the (dissolved) molecules and / or of the (suspended) particles.

[0044] In further embodiments, the liquid multilayer may comprise a plurality of second liquid layers. Especially, each second liquid layer may comprise a second liquid type individually selected from the group comprising a silicone oil, a vegetal oil, and a mineral oil. In further embodiments, at least two second liquid layers may differ in the second liquid type.

[0045] Further, the liquid multilayer may comprise a plurality of second liquid layers, wherein each second liquid layer may comprise a second liquid type individually selected from the group comprising a silicone oil, a vegetal oil, a mineral oil, (an aqueous solution comprising) honey, (an aqueous solution comprising) glycerol, brine, and a liquid metal.

[0046] The first liquid may especially comprise a liquid in which cavitation can be induced, such as an aqueous liquid. However, it will be clear to the person skilled in the art that cavitation may also be induced in other liquids, such as in oil, e.g., in sunflower oil, in glycerol or in ethanol, with sufficient force to eject a jet, such as described in KRIZEK et al. Needle-free delivery of fluids from compact laser-based jet injector, Lab on a Chip, Issue 20, 2020, which is hereby herein incorporated by reference. Hence, in embodiments, the first liquid may comprise oil, glycerol or ethanol, such as sunflower oil, glycerol or ethanol.

[0047] In embodiments wherein the first liquid comprises a non-aqueous liquid, the second liquid may comprise an aqueous liquid. Yet, in embodiments wherein the first liquid comprises a non-aqueous liquid, the second liquid may comprise a non-aqueous liquid. For instance, the first liquid may comprise ethanol, and the second liquid may comprise oil.

[0048] In further embodiments, the first liquid may comprise a first oil and the second liquid may comprise a second oil, especially wherein the first oil and the second oil form distinct phases when brought in contact. In particular, in embodiments, the first oil and the second oil may be immiscible (with one another).

[0049] The system may further comprise a microfluidic device. Microfluidic devices (also “microfluidic platforms” or “microfluidic systems”) comprise a broad range of devices related to the field of microfluidics. The field of microfluidics may deal with the behavior, control and manipulation of fluids, typically in small volumes, such as volumes on the order of pl, nl, pl, and fl. Microfluidic devices may be able to precisely control and manipulate fluids on a micrometer-size down to a sub-micrometer-size scale. The channels or features present on a chip may be obtained through a process comprising lithography, dry etching, wet etching, soft-lithography and / or bonding, but may also be provided with other (new) techniques such as laser ablation. The microfluidic device of the present invention may especially be configured for one or more of (liquid) jet ejection, fluid encapsulation, or emulsion formation.

[0050] The microfluidic device may especially comprise a hosting chamber (or “hosting chamber arrangement”). The hosting chamber may have a chamber length (L) defined by a first chamber end and a second chamber end. In particular, the hosting chamber may be elongated along an axis of elongation, and the chamber length may be defined along the axis of elongation. In embodiments, the chamber length (L) may be selected from the range of 0.5 -10 mm, such as from the range of 1 - 8 mm, especially from the range of 1.5 - 5 mm. In further embodiments, L may be selected from the range of> 0.5 mm, especially > 1 mm, such as > 1.5 mm. The chamber length (L) may be selected, amongst others, based on the type of cavitation induction system (see below). For instance, in embodiments wherein the cavitation induction system comprises a laser-based heating source or a heater, L may especially be selected from the range of < 6 mm, such as < 5 mm, especially < 4 mm. In embodiments wherein the cavitation induction system comprises an electric discharge system, L may be selected from the range of < 12 mm, such as < 10 mm, especially < 8 mm.

[0051] The hosting chamber may in embodiments have three chamber dimensions: a chamber height (H), a chamber width (W) and a chamber length (L). The (average) chamber height (H) may be selected from the range of 50 - 1000 pm, such as from the range of 100 -600 pm. Similarly, in embodiments, the (average) chamber width (W) may be selected from the range of 50 - 1000 pm, such as from the range of 100 - 600 pm. The chamber height (H) may especially be selected from the range of 5 - 400 pm, such as from the range of 10 - 300 pm, especially from the range of 20 - 250 pm, such as from the range of 40 - 200 pm, especially from the range of 50- 150 pm, such as from the range of 80 - 120 pm. In further embodiments, H / W may be selected from the range of 1 - 12, such as from the range of 2 - 10, especially from the range of 3 - 6. In further embodiments, H / W may be selected from the range of 3 -4.5, such as from the range of 5.5 - 6, or such as from the range of 5.5 - 6.5, especially from the range of 5.75 - 6.25.

[0052] In embodiments, the hosting chamber may have an average equivalent circular diameter (D) (in a plane) perpendicular to the length (L), such as perpendicular to the axis of elongation, especially wherein L > 3*D, such as > 5*D, especially > 10*D. In further embodiments, L < 100*D, such as < 50*D, especially < 20*D. The equivalent circular diameter (or ECD) (or “circular equivalent diameter”) of an (irregularly shaped) two-dimensional shape is the diameter of a circle of equivalent area. For instance, the equivalent circular diameter of a square with side a is 2*a*SQRT(l / 7t). For a circle, the diameter is the same as the equivalent circular diameter. Would a circle in an xy-plane with a diameter D be distorted to any other shape (in the xy-plane), without changing the area size, then the equivalent circular diameter of that shape would be D.

[0053] Hence, L > H may apply, such as L > 2*H, especially L > 3*H, like L > 5*H. Additionally, L > W may apply, such as L > 2*W, especially L > 3*W, like L > 5*W. Further, as indicated above, L > 3*D may apply, such as > 5*D, especially > 10*D. Hence, the hosting chamber may especially be elongated (along the chamber length (L) and / or the axis of elongation). Such an elongated hosting chamber may provide improved control over a fill level of the hosting chamber. Further, such an elongated hosting chamber may allow for a liquid multilayer comprising > 3 layers. Especially, the relatively long hosting chamber may facilitate that layers in the liquid multilayer may be elongated along the chamber length (L), such that -especially in the case of alternating layers of the same liquids - different layers comprising the same liquid may be separated by a relatively longer distance, thereby preventing the merging of these layers upon small disturbances of the liquid multilayer. Additionally, an elongated hosting chamber may facilitate providing a liquid multilayer using a relatively small (total) volume of liquid. Further yet, an elongated hosting chamber may facilitate containing an energy generated by a cavitation event in all directions perpendicular to the chamber length (L), thereby facilitating that a majority of the energy generated by the cavitation event is directed along the chamber length (L), and thus facilitating the generation of a more powerful jet or a more controlled encapsulate and / or emulsion (with a same amount of energy provided by the cavitation induction system). Further, such an elongated hosting chamber may provide more control over the location where the cavitation event may be induced. Especially, using an elongated hosting chamber, a distance between a location of the cavitation event and a front of the liquid multilayer (in the hosting chamber) may be tuned over a larger range compared to a hosting chamber wherein L < 3*D. Further, an elongated hosting chamber may facilitate providing e.g. a temperature gradient along the chamber length (L), thereby providing improved control over e.g. the viscosity of the first and second liquids. Additionally, an elongated hosting chamber may facilitate the use of one or more sensors places along the chamber length (L), thereby allowing for improved data collection and / or quality control.

[0054] The hosting chamber may have a chamber cross-sectional shape in a plane perpendicular to the chamber length (L), such as perpendicular to the axis of elongation. The chamber cross-sectional shape may be selected from the group comprising a circle, a stadium, an oval, such as an ellipse, and an n-gonal shape, wherein n > 3 applies, and wherein the sides and / or corners of the n-gonal shape may be straight or curved. Especially, the chamber cross-sectional shape may be selected from the group comprising a circle, an oval, such as an ellipse, a (rounded) rectangle, and a stadium. In embodiments, the chamber cross-sectional shape may have a rotational symmetry of order 4 or less, such as of order 3 or less, especially of order 2 or less. A hosting chamber having a chamber cross-sectional shape with a rotational symmetry of order (4, especially) 2 or less may provide improved control of the shape and / or properties of the liquid jet emitted from the hosting chamber, as (small) perturbations in a wall of the hosting chamber may affect the jet relatively less.

[0055] The chamber cross-sectional shape may be constant along the chamber length (L), such as along the axis of elongation. Alternatively, the chamber cross-sectional shape may change along the chamber length (L), such as along the axis of elongation. For instance, the chamber cross-sectional shape may change from a first shape (type) to a second shape (type) (e.g., from an ellipse to a polygon). Alternatively, the chamber cross-sectional shape may have the same shape (type) along the chamber length (L), such as along the axis of elongation, wherein an aspect ratio of the chamber cross-sectional shape may change along the chamber length (L), such as along the axis of elongation (e.g. from a more elongated rectangle to an almost-square rectangle). In embodiments, the chamber cross-sectional shape may change relatively abruptly, such as e.g. in the case where the hosting chamber comprises a first chamber section and a second chamber section (see below). Alternatively, the chamber cross-sectional shape may change gradually, such as e.g. in the case where the hosting chamber tapers towards the second chamber end.

[0056] In embodiments, the system may further comprise the cavitation induction system. The cavitation induction system may be configured to induce a cavitation in the first liquid, specifically at a location in the hosting chamber. In embodiments, the cavitation induction system may especially comprise a thermocavitation induction system.

[0057] Additionally or alternatively, the cavitation induction system may be configured to induce a cavitation in the first liquid, specifically at a location in the hosting chamber.

[0058] The cavitation induction system may be configured to locally induce the cavitation by providing cavitation induction energy to a (small) volume in the first liquid, e.g., to a volume selected from the range of 1E2 - 1E7 pm3, such as from the range of 1E3 - 1E6 The term “cavitation” may herein refer to the (sudden) formation of a vapor phase in a liquid, such as when exposed to reduced pressure and / or to heat. The cavitation may lead to an expansion of a bubble. In particular, the expansion of the bubble is a conversion of at least part of the cavitation inducing energy into kinetic energy that is transferred to the liquid that is set in motion. Especially, the microfluidic device may be configured such that the fastexpanding bubble moves towards the second chamber end and thereby transfers kinetic energy to the liquid, such as to the first liquid and / or to the second liquid, which may result in one or more of jet ejection, encapsulation and emulsion formation (see below). Especially, the bubble may have a bubble edge (also “bubble surface” or “bubble wall”) moving towards the second chamber end and thereby transferring kinetic energy to the liquid. The term “bubble edge” may herein refer to the surface (area) of the bubble closest to the second chamber end. Specifically, the term “bubble edge” may herein refer to the interface between the bubble and the neighboring liquid(s).

[0059] The cavitation induction system may especially be configured to induce thermocavitation. Hence, the cavitation induction system may especially be a thermocavitation system. The term “thermocavitation” may herein specifically refer to cavitation that is (essentially) heat-induced. The cavitation induction system may especially be selected from the group comprising a laser-based heating system, an electric discharge system, and a heater.

[0060] In particular, the cavitation induction system may be configured to induce optic cavitation (or “optical cavitation)”. For instance, in embodiments, the cavitation induction system may comprise a laser-based heating system. The laser-based heating system may comprise a continuous wave laser system and / or a pulsed laser system, especially (at least) a continuous wave laser system, or especially (at least) a pulsed laser system.

[0061] The laser-based heating system may be configured to provide laser radiation to one or more of a chamber wall (of the hosting chamber) and a liquid in the hosting chamber, such as to the first liquid. Hence, the laser-based heating system may be configured to irradiate one or more of the chamber wall and a first liquid in the hosting chamber. In particular, the laser-based heating system may be configured to bring the liquid in the hosting chamber to a boil by providing laser radiation.

[0062] The laser-based heating system may be configured to provide the laser radiation to the chamber wall and / or to the first liquid in the hosting chamber, especially such that (part of) the liquid is brought to a boil. Hence, in embodiments, at least part of the chamber wall may be light transmissive for the laser radiation (so that the radiation can reach the first liquid), or at least part of the chamber wall may comprise a material configured to absorb the laser radiation (to heat the chamber wall), especially wherein at least part of the chamber wall is light transmissive for the laser radiation, or especially wherein at least part of the chamber wall comprises a material configured to absorb the laser radiation.

[0063] Further, the first liquid may comprise a solution of molecules, wherein the molecules may be configured to absorb the laser radiation. For instance, the first liquid may comprise a solution of a dye, colorant, or chromophore. Especially, the molecules, such as the dye, colorant, or chromophore, in the first liquid may have a molar absorption coefficient of > 0.1*103m2 / mol, such as > O.3*1O3m2 / mol, especially > O.5*1O3m2 / mol, at a peak emission wavelength of the laser radiation. Additionally or alternatively, the first liquid (comprising the molecules) may have an absorption coefficient of > 5 cm'1, such as > 25 cm'1, especially > 50 cm'1, like > 100 cm'1(at the peak emission wavelength of the laser radiation). Such molecules may facilitate absorbing relatively more of the laser radiation (in a focal point of the laser), thereby facilitating a faster heating (and boiling) of the first liquid (in the focal point).

[0064] In embodiments, the laser-based heating system may comprise a non-pulsed laser-based heating system, wherein the non-pulsed laser-based heating system is configured to provide radiation for a heating time period of, for example, 0.1 ms - 10 s, such as for a heating time period of 0.1 ms - 500 ms, especially of 0.1 ms - 200 ms, such as 0.2 ms - 100 ms, especially 0.5 - 70 ms. Good results were obtained with heating time periods between 0.1 ms - 200 ms. In further embodiments, the laser-based heating system may comprise a nonpulsed laser-based heating system, wherein the laser-based heating system is configured to provide radiation for a heating time period selected from the range of 1 - 1000 ns, such as from the range of 2 - 800 ns, especially from the range of 5 - 500 ns.

[0065] In embodiments, the laser-based heating system comprises a non-pulsed and / or low-energy laser system, especially, the laser-based heating system may comprise a laser system selected from the group comprising a continuous wave laser system, a laser diode system, and an LED-based laser system, especially from the group comprising a continuous wave laser system, and an LED-based laser system, more especially the laser-based heating system may comprise a continuous wave laser system.

[0066] A continuous wave laser system may be beneficial with regards to a pulse-based laser system in that it may be cheaper, more energy-efficient, and may require less cooling. In particular, a continuous wave laser system may be passively cooled, such as without the use of fans, liquids, and (aluminum) heat dissipaters.

[0067] In embodiments, the cavitation induction system, especially the continuous wave laser system, may be configured to provide laser radiation with a power selected from the range of 30 - 3000 mW, such as from the range of 50 - 2000 mW, especially 100 - 1000 mW. In further embodiments, the laser-based heating system, especially the continuous wave laser system, may be configured to provide laser radiation with a power of at least 50 mW, especially at least 75 mW, such as at least 100 mW, especially at least 150 mW, such as at least 200 mW, especially at least 250 mW, such as at least 300 mW, especially at least 350 mW, such as at least 400 mW. In further embodiments, the laser-based heating system, especially the continuous wave laser system, may be configured to provide laser radiation with a power of at most 2000 mW, such as at most 1500 mW, especially at most 1300 mW, such as at most 1100 mW, especially at most 500 mW.

[0068] In further embodiments, the laser-based heating system may comprise a pulsed laser system. Especially, the laser-based heating system may be selected from the group comprising an ultraviolet-based pulsed laser system, a visible light pulsed laser system, e.g., a green laser, and an infrared-based pulsed laser system. The pulsed laser system may be configured to provide a laser pulse having a pulse energy suitable for inducing cavitation in the first liquid. For instance, in embodiments, the pulsed laser system may, especially in the cavitation stage, (be configured to) provide a laser pulse having a laser pulse energy selected from the range of 5 - 2000 pj, such as from the range of 10 - 1000 pj, especially from the range of 20 - 500 pj. In further embodiments, the laser-based heating system may comprise a pulsed laser system, wherein the laser-based heating system is configured to provide radiation for a heating time period selected from the range of 100 fs - 1000 ns, such as from the range of 1 ps - 500 ns, especially from the range of 1 ns - 100 ns. In further embodiments, the heating time period may be selected from the range of 100 - 1000 fs.

[0069] A pulsed laser may be beneficial with regards to a continuous wave laser system in that a shock wave is generated at nucleation, which shockwave may contribute to the fluid manipulation. Further, pulsed laser systems may facilitate providing more consistent (or “reproducible”) cavitation events and may be more efficient regarding (optical) energy expenditure. Further pulses having a femtosecond pulse duration may lead to particularly well-controlled cavitation events compared to longer laser pulses, e.g. pulses on picosecond and nanosecond timescales).

[0070] A further benefit of laser-based heating systems is that they may be relatively convenient and consistent in operation. Hence, in embodiments, the cavitation induction system may comprises a laser-based heating system, especially a laser-based heating system selected from the group comprising a continuous wave laser system and a pulsed laser system. Further, a benefit of a laser-based heating system may be that a (cavitation) bubble and / or shockwave may be generated at any location in the hosting chamber, e.g. by moving the laser with respect to the hosting chamber, or by tuning the focal spot of the laser. As such, the system may be relatively versatile, and may provide a larger degree of control over the properties of the jet, encapsulate, and / or emulsion by controlling the location of the shockwave.

[0071] In further embodiments, the cavitation induction system may comprise an electric discharge system. The electric discharge system may be configured to generate a (brief) pulse of electric current to overheat the first liquid in the hosting chamber, especially at the target location. The use of an electric discharge for cavitation may result in a shockwave similar to the use of a pulsed laser. In embodiments, the electric discharge system may comprise two electrodes, such as two metal wires, e.g., copper wires, wherein the electric discharge system is configured to generate a spark between the two electrodes. Hence, the electrodes may be arranged in close proximity, especially in contact with one another.

[0072] Further, in embodiments, the electric discharge system may comprise an array of n electrodes, wherein the array of n electrodes may be configured at least partially enclosing the hosting chamber. Especially, n > 3 may apply, such as n > 4, especially n > 6, like n > 8. As such, the electric discharge system may be configured to generate a spark between two (or more) electrodes selected from the n electrodes. That is, the electric discharge system may be configured to generate a spark between any two (or more) electrodes selected from the array of n electrodes. Such an array of n electrodes may facilitate that shockwave generation (e.g. a cavitation bubble generation) in the hosting chamber may be spatially controlled. As such, the system may be relatively versatile, and may provide a larger degree of control over the properties of the jet, encapsulate, and / or emulsion by controlling the location of the shockwave.

[0073] In further embodiments, the cavitation induction system may comprise a heater. The heater may be configured to be suitable to generate (single) cavitation events (or “cavitation bubbles”) in the first liquid, especially on the millisecond timescale. Cavitation events induced by the heater may be particularly suitable for encapsulation and / or emulsion generation. It will be clear to the person skilled in the art that the requirements for cavitation may depend on the physicochemical properties of the first liquid (boiling point, impurities dissolved in the liquid) and on potential defects in the walls of the hosting chamber. Heat-induced cavitation may, for instance, be described in NGUYEN et al., In-phase synchronization between two auto-oscillating bubbles, Physical Review Fluids, issue 4, 2019, which is hereby herein incorporated by reference. In further embodiments, the heater may comprise wires and / or coated metals. For instance, the heater may comprise a metal (wire) comprising an element selected from the group comprising copper, gold, platinum, aluminum, nickel, and silver.

[0074] Further, in embodiments, the cavitation induction system may comprise an array of m heaters, wherein the array of m heaters may be configured at least partially enclosing the hosting chamber. Especially, m > 3 may apply, such as m > 4, especially m > 6, like m > 8. The cavitation induction system may be configured to generate a (single) cavitation event with any of the m heaters. That is, the cavitation induction system may be configured to individually control each of the m heaters. Such an array of m heaters may facilitate that cavitation event generation (e.g. cavitation bubble generation) in the hosting chamber may be spatially controlled. As such, the system may be relatively versatile, and may provide a larger degree of control over the properties of the jet, encapsulate, and / or emulsion by controlling the location of the cavitation event in the hosting chamber.

[0075] In embodiments, the system may further comprise a control system. The control system may be configured to control the system, especially to control one or more of the first liquid supply, the second liquid supply and the heating system. Further, the control system may be configured to control one or more of the first liquid supply, the second liquid supply, and the cavitation induction system.

[0076] The term “controlling” and similar terms herein may especially refer at least to determining the behavior or supervising the running of an element. Hence, herein “controlling” and similar terms may e.g. refer to imposing behavior to the element (determining the behavior or supervising the running of an element), etc., such as e.g. measuring, displaying, actuating, opening, shifting, changing temperature, etc.. Beyond that, the term “controlling” and similar terms may additionally include monitoring. Hence, the term “controlling” and similar terms may include imposing behavior on an element and also imposing behavior on an element and monitoring the element. The controlling of the element can be done with a control system. The control system and the element may thus at least temporarily, or permanently, functionally be coupled. The element may comprise the control system. In embodiments, the control system and the element may not be physically coupled. Control can be done via wired and / or wireless control. The term “control system” may also refer to a plurality of different control systems, which especially are functionally coupled, and of which e.g. one master control system may be a control system and one or more others may be slave control systems.

[0077] The system, especially the control system, may have an operational mode. The term “operational mode” may also be indicated as “controlling mode”. The system, or apparatus, or device (see further also below) may execute an action in a “mode” or “operational mode” or “mode of operation”. Likewise, in a method an action, stage, or step may be executed in a “mode” or “operation mode” or “mode of operation”. This does not exclude that the system, or apparatus, or device may also be adapted for providing another operational mode, or a plurality of other operational modes. Likewise, this does not exclude that before executing the mode and / or after executing the mode one or more other modes may be executed. However, in embodiments, a control system may be available, that is adapted to provide at least the operational mode. Would other modes be available, the choice of such modes may, for instance, be executed via a user interface, though other options, like executing a mode in dependence of a sensor signal or a (time) scheme, may also be possible. The operational mode may in embodiments also refer to a system, or apparatus, or device, that can only operate in a single operational mode (i.e. “on”, without further tunability).

[0078] In particular, the control system may be configured to (have the system) execute an operational mode comprising a preparation stage and a cavitation stage.

[0079] In the preparation stage, the first liquid supply may (be configured to) provide the first liquid to the hosting chamber. Similarly, in the preparation stage, the second liquid supply may (be configured to) provide the second liquid to the hosting chamber. In particular, the first liquid supply and the second liquid supply may (be configured to) provide the first liquid and the second liquid to provide a liquid multilayer in the hosting chamber. The liquid multilayer may comprise n layers sequentially arranged along the chamber length (L), i.e., along an axis of elongation of the hosting chamber. In embodiments, n > 2, such as > 3, especially > 4, such as > 5. In further embodiments, n < 10, such as < 8, especially < 6, such as <4.

[0080] Each layer in the liquid multilayer may have a layer thickness (L450) along the chamber length (L), i.e., along an axis of elongation of the hosting chamber. In embodiments, the layer thickness (L450) may for each layer in the liquid multilayer be individually selected from the range of 0.05*L - 0.9*L, such as from the range of 0.1 *L - 0.8*L, especially from the range of 0.1 *L - 0.7*L. In embodiments, each of the layers may have the same layer thickness (L450). Alternatively, at least two, such as all, of the layers in the liquid multilayer may differ in layer thickness (L450). Further, the liquid multilayer may have a (combined) multilayer thickness (L400) along the chamber length (L), i.e., along an axis of elongation of the hosting chamber. In embodiments, L400 > 0.3 *L may apply, such as L400 > 0.4*L, especially L400 > 0.5*L. Additionally or alternatively, L400 < L may apply, such as L400 < 0.95*L, especially L400 < 0.9*L. Would a layer have a meniscus (or two menisci on either side of the layer), the layer thickness (L450) may especially be determined from (or to) a geometric center of the meniscus (to (or from) a geometric center of the meniscus on the other side of the layer). Hence, a layer with a convex meniscus may have a larger layer thickness (L450) than a layer with the same layer volume (V450) (see also below) but a concave meniscus. Further, would the liquid multilayer have a meniscus, the multilayer thickness (L400) may be determined from (or to) a geometric center of the meniscus.

[0081] Adjacent layers (of the n layers) in the multilayer may especially be distinct phases. In particular, the adjacent layers may be immiscible (with one another). Alternatively, the adjacent layer may be miscible (with one another) on a prolonged timescale, yet may form distinct (immiscible) phases on a short timescale (see also above). In particular, the multilayer may comprise a first liquid layer adjacent to a second liquid layer, wherein the first liquid layer comprises the first liquid, and wherein the second liquid layer comprises the second liquid.

[0082] In embodiments, the multilayer may comprise a plurality of first liquid layers. Similarly, in embodiments, the multilayer may comprise a plurality of second liquid layers. For instance, the multilayer may comprise the following layering: L1-L2-L1-L2, wherein LI refers to a first liquid layer comprising the first liquid, and wherein L2 refers to a second liquid layer comprising the second liquid. Hence, in embodiments, the layers may comprise alternating first liquid layers and second liquid layers.

[0083] The hosting chamber may thus be configured to receive the first liquid from the liquid supply system, especially from the first liquid supply. Similarly, the hosting chamber may be configured to receive the second liquid from the liquid supply system, especially from the second liquid supply. The hosting chamber may, for instance, comprise an inlet for receiving the first liquid and / or the second liquid. In embodiments, the hosting chamber may, for instance, first receive the first liquid, then receive the second liquid and subsequently more of the first liquid in order to provide a L1-L2-L1 multilayer (also see above). In further embodiments, the hosting chamber may comprise a plurality of inlets for receiving different liquids. For instance, the hosting chamber may comprise a first liquid inlet for receiving the first liquid, and the hosting chamber may further comprise a second liquid inlet for receiving the second liquid.

[0084] Further, the hosting chamber may comprise a liquid outlet for removing a liquid from the hosting chamber. Yet, in embodiments, the hosting chamber may comprise a plurality of liquid outlets. For instance, the hosting chamber may comprise a first liquid outlet for removing (at least part of) the first liquid, and a second liquid outlet for removing (at least part of) the second liquid. As such, in an operational mode of the system, the first fluid may be flown through the hosting chamber (wherein the first liquid may flow from the first fluid inlet, via the hosting chamber, to the first fluid outlet). Further, in an operational mode of the system, the second fluid may be flown through the hosting chamber (wherein the second liquid may flow from the second fluid inlet, via the hosting chamber, to the second fluid outlet). Flowing a (first and / or second) liquid through the hosting chamber may facilitate replenishing the (first and / or second) liquid after each ejection of a liquid jet, thereby removing any impurities of e.g. the first liquid in the second liquid or vice versa. Would the first liquid and second liquid be miscible (on longer time scales, see above), flowing a (first and / or second) liquid through the hosting chamber may facilitate reinstating distinct phases of the first liquid layer and the second liquid layer after mixing of the first and second liquids. Further, flowing a (first and / or second) liquid through the hosting chamber may facilitate removing an encapsulate and / or emulsion from the hosting chamber.

[0085] As indicated above, in the multilayer, each of the plurality of first liquid layers may comprise a different first liquid. As such, the first liquid supply may comprise a plurality of first liquid reservoirs. In embodiments, each of the first liquid reservoirs may comprise a different first liquid. Alternatively, each of the first liquid reservoirs may comprise a (different) component of the first liquid (of the plurality of first liquid layers), wherein the liquid supply system, especially the first liquid supply, may further comprise a manifold. The manifold may be configured to combine the components for each first liquid in the plurality of first liquid layers. Hence, the first liquid supply may be configured to provide a plurality of different first liquids.

[0086] Similarly, each of the plurality of second liquid layers may comprise a different second liquid. As such, the second liquid supply may comprise a plurality of second liquid reservoirs. In embodiments, each of the second liquid reservoirs may comprise a different second liquid. Alternatively, each of the second liquid reservoirs may comprise a (different) component of the second liquid (of the plurality of second liquid layers), wherein the liquid supply system, especially the second liquid supply, may further comprise a manifold. The manifold may be configured to combine the components for each second liquid in the plurality of second liquid layers. Hence, the second liquid supply may be configured to provide a plurality of different second liquids.

[0087] The liquid multilayer may comprise a plurality of (abutting) liquid layers (or “connected liquid layers”). However, in specific embodiments, in the preparation stage, the liquid supply system, especially the first liquid supply and the second liquid supply, may be configured to provide a multilayer, wherein the multilayer comprises the liquid multilayer and a gaseous layer, wherein the gaseous layer, e.g., an air layer, is arranged between two liquid layers. For instance, the gaseous layer may be arranged between two liquid multilayers or between the liquid multilayer and a (separate) liquid layer. The inclusion of a gaseous layer may facilitate the generation of droplets and jets in both directions (towards the first chamber end and / or towards the second chamber end), which may facilitate (a) causing collision events between droplets and jets, (b) providing encapsulates, and (c) the studying of bidirectional processes. In particular, the inclusion of a gaseous layer may provide additional options for encapsulation generation.

[0088] In the cavitation stage, the cavitation induction system may (be configured to) induce cavitation of the first liquid at a first location. In particular, the cavitation induction system may (be configured to) provide energy, such as laser energy, or such as an electric discharge, or such as heat, to the first liquid at the first location in order to induce cavitation in the first liquid. The cavitation induction system may be configured to provide the energy (directly) to the first liquid, e.g., by irradiating the first liquid with laser radiation of a wavelength absorbable by the first liquid. Additionally or alternatively, the cavitation induction system may be configured to provide the energy to the first liquid via a chamber wall, e.g., by (locally) heating up the chamber wall.

[0089] In embodiments, the first location may be arranged in the first liquid layer. Hence, cavitation may be induced in the first liquid.

[0090] In further embodiments, the first location may be arranged within a first distance (dl) from the first chamber end, especially wherein dl < 0.5*L, such as < 0.4 * L, especially < 0.3*L, such as < 0.2*L, especially < 0.15*L, such as < 0.1*L.

[0091] In further embodiments, the layers may comprise a first layer arranged closest to the first chamber end (or “first end”), especially in (wetting) contact with the first chamber end. The first layer may especially comprise the first liquid layer. Cavitation may in such embodiments especially be induced in the first layer, i.e., the first location may be arranged in the first layer. In further embodiments, the first layer may comprise a second liquid layer.

[0092] Alternatively, cavitation may be induced in any layer of the liquid multilayer (though generally not in the layer arranged closest to the second chamber end). For instance, in order from the first chamber end to the second chamber end, the multilayer may comprise a first layer, a second layer, a third layer, etc., wherein cavitation may be induced in any of the first layer, second layer, third layer, etc.. As such, the properties of the jet, encapsulate, and / or emulsion may be controlled by controlling in which layer cavitation is induced. The phrase “first layer arranged closest to the first chamber end” may herein refer to the first layer being the closest layer to the first chamber end, i.e., without a different layer of the layers between the first layer and the first chamber end.

[0093] In specific embodiments, the layers comprise a first layer arranged closest to the first chamber end, wherein the first layer comprises the first liquid layer, and wherein the first liquid comprises an aqueous liquid. Especially, in such embodiments, the first location may be arranged in the first liquid.

[0094] In embodiments wherein the layers comprise a plurality of first liquid layers, the first layer may comprise one of the plurality of first liquid layers. Similarly, in embodiments wherein the layers comprise a plurality of second liquid layers, the first layer may comprise one of the plurality of second liquid layers.

[0095] Alternatively, in the cavitation stage, the cavitation induction system may (be configured to) induce cavitation of the second liquid at the first location. In particular, the cavitation induction system may (be configured to) provide energy, such as laser energy, or such as an electric discharge, or such as heat, to the second liquid at the first location in order to induce cavitation in the second liquid. The cavitation induction system may be configured to provide the energy (directly) to the second liquid, e.g., by irradiating the second liquid with laser radiation of a wavelength absorbable by the second liquid. Additionally or alternatively, the cavitation induction system may be configured to provide the energy to the second liquid via a chamber wall, e.g., by (locally) heating up the chamber wall. Hence, in embodiments, the first location may be arranged in the second liquid layer, and cavitation may be induced in the second liquid.

[0096] The hosting chamber may have a (total) hosting volume VH. In embodiments, in the preparation stage, the liquid supply system, especially the first liquid supply and the second liquid supply, may be configured to provide the liquid multilayer such that the liquid multilayer occupies a liquid volume (VL). In embodiments, VL / VH may be selected from the range of 0.1 - 0.99, such as from the range of 0.2 - 0.95, especially from the range of 0.3 - 0.9, such as from the range of 0.4 - 0.8. In particular, a liquid:gas contact line may be formed within the hosting chamber. Hence, in embodiments, the hosting chamber may, following the preparation stage, further comprises a gas volume (VG) of a gas, such as of air. In embodiments, especially following the preparation stage, VH = VG+VL.

[0097] Hence, a liquid:gas contact line (or interface) may be formed within the hosting chamber. Further, the liquid multilayer may have a multilayer meniscus at the liquid:gas interface. Especially, the multilayer meniscus may be a concave meniscus. That is, an edge of the multilayer meniscus (configured in contact with a wall of the hosting chamber) may be configured closer to the second chamber end than a geometric center of the multilayer meniscus. The concave multilayer meniscus may facilitate higher jet velocities due to increased (flow) focusing, i.e., a more curved meniscus shape (smaller radius of curvature and lower (initial) contact angle) may provide a higher jet velocity due to increased (flow) focusing. Accordingly, the concave multilayer meniscus may have a radius of curvature (Rc) (in a plane parallel to the axis of elongation of the hosting chamber). Especially, Rc < 1.2*D may apply, such as Rc < D, especially Rc < 0.8*D. Additionally or alternatively, Rc > 0.35*D may apply, such as Rc > 0.5*D, especially Rc > 0.6*D. Such a multilayer meniscus may facilitate flow focusing, which may e.g. provide relatively more control over a jet emitted from the hosting chamber.

[0098] As indicated above, the hosting chamber may have a chamber cross-sectional shape selected from a stadium, an oval, such as an ellipse, and an n-gonal shape. As such, the hosting chamber may have the chamber height (H) and the chamber width (W), wherein H / W > 1, such as > 2, like > 3. Further, in such embodiments, the concave multilayer meniscus may have a first radius of curvature (Rci) along the chamber height (H), and a second radius of curvature (Rc2) along the chamber width (W). Especially, 0.9 < (RCI / RC2) / (H / W) < 1.1 may apply, such as RCI / RC2 = H / W. Further, 0.35*H <Rci < 1.2*H may apply, such as 0.5*H <Rci < H, especially 0.6*H < Rci < 0.8*H. Additionally, 0.35*W < Rc2 < 1.2*W may apply, such as 0.5*W < RC2 < W, especially 0.6*W < RC2< 0.8*W.

[0099] Further, each of the layers in the liquid multilayer may have a layer meniscus at an interface between that layer and another layer in the liquid multilayer. Especially, the layer meniscus may, for each layer individually, be selected from the group of a concave meniscus and a convex meniscus. It will be apparent to the person skilled in the art that, at every interface between two layers, one of the layers will have a concave meniscus, and the other layer will have a convex meniscus, depending on the properties of the liquids in the two layers and the properties of the wall of the hosting chamber. For instance, at an interface between a first liquid layer comprising an aqueous liquid and a second liquid layer comprising an oil, the first liquid layer may have a concave meniscus, and the second liquid layer may have a convex meniscus.

[0100] In embodiments, the hosting chamber, such as especially an inner wall of the hosting chamber, may (thus) be hydrophilic. That is, an adhesion of water to (the inner wall of) the hosting chamber may be stronger than an adhesion of oil. As described above, the microfluidic device may be configured for jet ejection. Hence, in embodiments, the second chamber end may comprise a chamber opening for jet ejection from the hosting chamber.

[0101] In embodiments, the chamber opening may have an equivalent circular diameter Do, wherein Do> 3 pm, such as > 5 pm, especially > 10 pm, such as > 50 pm. In further embodiments, Do / D< 1, such as < 0.9, especially < 0.8, such as < 0.5. In further embodiments, Do / D is selected from the range of 0.9 - 1.1, such as from the range of 0.95 - 1.05, especially wherein Do / D is (about) 1. Yet, in embodiments, Do / D may be selected from the range of 0.15 - 1, such as from the range of 0.2 - 0.9, like from the range of 0.2 - 0.8.

[0102] Further, the chamber opening may have a chamber opening shape in a plane perpendicular to the chamber length (L), such as perpendicular to the axis of elongation. The chamber opening shape may be selected from the group comprising a circle, and ellipse (or oval), and an n-gonal shape, wherein n > 3 applies, and wherein the sides and / or corners of the n-gonal shape may be straight or curved. Especially, the chamber opening shape may be selected from the group comprising a circle, an ellipse (or oval), a (straight or rounded) rectangle, and a stadium. In embodiments, the chamber opening shape may have a rotational symmetry of order 4 or less, such as of order 3 or less, especially of order 2 or less. A hosting chamber having a chamber cross-sectional shape with a rotational symmetry of order (4, especially) 2 or less may provide improved control of the shape and / or properties of the liquid jet emitted from the hosting chamber, as (small) (undesired) perturbations in a wall of the hosting chamber may affect the jet relatively less.

[0103] In further embodiments, (at least part of) the hosting chamber, especially at least part of the second chamber section (see below), may taper towards the second chamber end, especially towards the chamber opening, i.e., the hosting chamber may become more narrow towards the second chamber end, especially towards the chamber opening. For instance, in embodiments, the chamber opening (at the second chamber end) may have an equivalent circular diameter of 50 pm while a different part of the hosting chamber, especially of the second chamber section, has an equivalent circular diameter of (about) 400 pm. In embodiments, the hosting chamber, especially a chamber wall of the hosting chamber, may taper at a taper angle (at), wherein the taper angle (at) is defined relative to a plane parallel to the chamber length (L) (or “parallel to an axis of elongation of the hosting chamber”), and wherein the taper angle (at) is selected from the range of < 40°, such as < 35°, especially < 30°. In further embodiments, the taper angle (at) may be selected from the range of > 5°, such as > 10°, especially > 15°. The tapering may facilitate the generation of higher speed liquid jets, i.e., the tapering may facilitate increasing the velocity of ejected jets.

[0104] In further embodiments, the microfluidic device may be configured for encapsulation and / or for emulsion formation. In such embodiments, the second chamber end may comprise a chamber opening or may be closed. A chamber opening may facilitate accessing, especially recovering, a formed encapsulate and / or emulsion. In contrast, a closed second chamber end may provide a more controlled environment (e.g., shielded from external factors / fluctuations), which may benefit reproducibility.

[0105] The term “encapsulation” may herein refer to the generation of a capsule (particle), wherein the capsule comprises a core and a shell, wherein the core and the shell comprise (mutually immiscible) liquids from different layers of the multilayer. For instance, the core may comprise the first liquid and the shell may comprise the second liquid, or vice versa.

[0106] The term “emulsion” may herein refer to a dispersion of droplets of one liquid within another liquid, wherein the one liquid is not soluble in or miscible with the another liquid.

[0107] In embodiments, the second chamber end may be closed, and the hosting chamber may have a hosting volume (VH), wherein in the preparation stage the liquid supply system, especially the first liquid supply and the second liquid supply, are configured to provide the liquid multilayer such that the liquid multilayer occupies a liquid volume (VL), especially wherein VL / VH is selected from the range of 0.1 - 1, such as from the range of 0.2- 1, especially from the range of 0.3 - 0.99, such as from the range of 0.4 - 0.95. In further embodiments, the hosting chamber may further comprise a gas volume (VG) of gas, such as of air, wherein VH = VG+VL.

[0108] In further embodiments, the hosting chamber may have a hosting volume (VH), wherein in the preparation stage the first liquid supply and the second liquid supply are configured to provide the liquid multilayer such that the liquid multilayer occupies a liquid volume (VL), wherein VL / VH is selected from the range of 0.1 - 1, such as from the range of 0.2 - 1, especially from the range of 0.3 - 0.99, such as from the range of 0.4 - 0.95, and wherein the second chamber end comprises a second chamber opening.

[0109] Hence, in embodiments configured for jet ejection, the second chamber end comprises an opening, and the hosting chamber generally contains some air after the preparation stage. In contrast, in embodiments configured for encapsulation and / or emulsion formation, the second chamber may comprise an opening or may be closed, especially closed, and the hosting chamber may be completely filled with the multilayer after the preparation stage. Alternatively, in embodiments configured for encapsulation and / or emulsion formation, the second chamber may comprise an opening or may be closed, especially closed, and the hosting chamber may be partially filled with the multilayer after the preparation stage.

[0110] Further, the microfluidic device may be configured for providing both encapsulation and ejection. In particular, cavitation may lead to the formation of a capsule and to subsequent ejection of the capsule.

[0111] As described above, during the preparation stage, a liquid multilayer of n layers may be provided. The different layers in the multilayer may vary in layer dimensions, particularly along the chamber length (L). The (relative) layer dimensions may be selected in order to provide a desired fluid behavior. In embodiments, each layer of the liquid multilayer may have a layer volume V450, wherein (for each layer) the layer volume V450 is individually selected from the range of 0.05*VH - 0.7*VH, especially from the range of 0.1*VH - 0.5*VH, such as from the range of 0.15*VH - 0.4*VH.

[0112] In further embodiments, the first layer, especially comprising the first liquid layer, may have a first layer volume (V451), wherein a second layer adjacent to the first layer has a second layer volume (V452). In embodiments wherein the second layer (primarily) serves to suppress dynamics induced by collapse of the cavitation bubble, the first layer volume (V451) may especially be larger than the second layer volume (V452), V451 > V452. Alternatively, in embodiments, V451 < V452, such as V451 < V452.

[0113] The hosting chamber may vary in chamber shape and / or diameter along the chamber length (L). In particular, the hosting chamber may comprise one or more chamber sections, wherein the chamber sections may be (relatively) constant along the chamber length. For instance, in embodiments, the hosting chamber may comprise a first chamber section and a second chamber section, wherein the first chamber section comprises the first chamber end, and wherein the second chamber section comprises the second chamber end. Especially, the first chamber section may have a first average equivalent circular diameter (DI) and the second chamber section may have a second average equivalent circular diameter (D2). In embodiments, D1 / D2 may be selected from the range of < 0.8, especially from the range of < 0.5, such as from the range of < 0.3.

[0114] In embodiments, the average equivalent circular diameter (D) may especially be a weighed average of the first average equivalent circular diameter (DI) and the second average equivalent circular diameter (D2) based on the lengths of the respective chamber sections (also see below). In embodiments, the first chamber section may be arranged adjacent to the second chamber section (along the chamber length (L)). The transition between the first chamber section and the second chamber section may be marked by a substantial change in chamber diameter and / or chamber shape. For instance, the equivalent circular diameter of the first chamber section may vary less than 10% along the chamber length (L), the equivalent circular diameter of the second chamber section may vary less than 10% along the chamber length (L), whereas the (average) equivalent circular diameter of the first chamber section may differ by at least 20% from the (average) equivalent circular diameter of the second chamber section. Especially, the first chamber section may have a first section length (LI) and the second chamber section may have a second section length (L2). The first section length (LI) and the second section length (L2) may both be parallel to the chamber length (L), i.e., to the axis of elongation of the hosting chamber. In embodiments, L1 / L2 may be selected from the range of 0.3 - 3, such as from the range of 0.5 - 2, especially from the range of 0.8 - 1.25. In further embodiments, DI may vary less than 10% (relative to a maximum value of DI) along at least 80% of LI, especially along at least 90% of LI, such as along LI. In further embodiments, D2 may vary less than 10% (relative to a maximum value of D2) along at least 80% of L2, such as along at least 90% of L2, especially along L2.

[0115] The first chamber section and the second chamber section may especially be longitudinally aligned. In particular, the first chamber section and the second chamber section may be elongated along a (shared) axis of elongation.

[0116] In further embodiments, the first location may especially be arranged in the first chamber section. Hence, cavitation may be induced in the first chamber section, and the second chamber section may have a substantially larger diameter than the first chamber section. The combination of these features may facilitate the generation of a ring vortex. In particular, the first chamber section may work as a nozzle. If the ring vortex hits an air-liquid interface, the formation of droplet jets can be induced, depending on the separation distance between the nozzle exit and the liquid-air interface. Further, the second chamber section having a larger diameter than the first chamber section may facilitate ejecting jets with a greater volume (compared to having a single constant diameter). Hence, in such embodiments, the second chamber end may comprise a chamber opening (as described above).

[0117] The ring vortex, especially the formation of the ring vortex, may be influenced by the shape of the first chamber section and of the second chamber section. In particular, sharp corners, such as straight corners, rather than rounded corners, may facilitate a more efficient formation of the ring vortex and, by extent, a more efficient ejection of a droplet jet. Hence, in embodiments, the second chamber section may have sharp (or “non-rounded”) corners, such as straight corners, opposite of the second chamber end. Hence, in embodiments, corners arranged at the transition between the first chamber section and the second chamber section may especially be sharp corners.

[0118] The term “sharp comer” may herein refer to a non-rounded corner. In particular, a sharp corner may have a sudden transition, e.g., a sudden change (or “jump”) in a channel wall angle, whereas a rounded comer may have a continuous transition.

[0119] In further embodiments, the second chamber section may have rounded corners opposite of the second chamber end.

[0120] In embodiments, the operational mode may further comprise adjusting a temperature of at least part of the liquid multilayer prior to the cavitation stage (also see further below), such as in the preparation stage.

[0121] In particular, in embodiments, the system may comprise a temperature control element, such as a heating element and / or a cooling element, configured to adjust the temperature of at least part of the liquid multilayer in the hosting chamber, such as configured to heat one or more layers of the liquid multilayer, or such as to cool one or more layers of the liquid multilayer.

[0122] The options for fluid manipulation may be further expanded by the inclusion of a gaseous layer in the hosting chamber. In particular, the inclusion of a gaseous layer between the liquid multilayer and a further liquid layer may enable ejecting a jet towards the location of the cavitation event, i.e., towards the first location. For instance, a chamber opening at the second chamber end may be inserted into a target liquid, after which the liquid multilayer is formed at the first chamber end, trapping or adding a gaseous layer between the liquid multilayer and the target liquid, and a jet may be generated from the target liquid towards the liquid multilayer. In particular, inducing a jet towards the cavitation-induced zone (towards the liquid multilayer) may facilitate small amounts of liquid to be deposited in a given layer, i.e., sampling of mall volumes without using pipettes. The deposited liquid may optionally be ejected following a later cavitation event.

[0123] Further, the presence of the gaseous layer may facilitate generating two jets in opposite directions, which jets may collide at high speeds. The collision of liquids at high speed, in addition to studying fluids in extreme conditions, may facilitate the studying of chemical reactions induced by the high-speed collision.

[0124] Hence, in embodiments, the preparation stage may comprise providing, especially trapping, a gaseous layer between the liquid multilayer and the second chamber end. Above-described embodiments may be suitable for trapping a gaseous layer. However, it may be particularly convenient and more controllable when the gaseous layer can be provided by the system. Hence, in embodiments, the system may further comprise a gas supply configured to provide a gas to the hosting chamber. In such embodiments, in the preparation stage the gas supply may (be configured to) provide a gaseous layer between the liquid multilayer and the second chamber end. In further embodiments, the first liquid supply may be configured to provide a first liquid layer between the gaseous layer and the second chamber end, e.g., by first introducing the first liquid layer into the hosting chamber and subsequently introducing gaseous layer into the hosting chamber (and subsequently introducing the liquid multilayer into the hosting chamber). Similarly, in embodiments, the second liquid supply may be configured to provide a second liquid layer between the gaseous layer and the second chamber end.

[0125] In a second aspect, the invention may provide a system comprising the microfluidic device with multiple chamber sections having different diameters as such. In particular, the invention may provide a system for fluid manipulation, wherein the system comprises a microfluidic device. The microfluidic device may comprise a hosting chamber, wherein the hosting chamber comprises a first chamber section and a second chamber section. The first chamber section and the second chamber section may especially be longitudinally aligned. Especially, the first chamber section and the second chamber section may be elongated along a (same) axis of elongation. The first chamber section and the second chamber section may especially differ in their average equivalent circular diameter. In particular, the first chamber section may have a first average equivalent circular diameter DI and the second chamber section may have a second average equivalent circular diameter D2. Especially, D1 / D2 may be selected from the range of < 0.8, especially from the range of < 0.5, such as from the range of < 0.3. Further, the hosting chamber may have a chamber length L defined by a first chamber end and a second chamber end, especially wherein the chamber length is defined along the axis of elongation. In embodiments, the first chamber section may comprise the first chamber end and the second chamber section may comprise the second chamber end. The hosting chamber may have an average equivalent circular diameter D perpendicular to the length L, especially wherein L > 3*D, such as > 5*D, especially > 10*D. In further embodiments, L < 100*D, such as < 50*D, especially < 20*D. In further embodiments, wherein L > 2*D2, such as > 3*D2, especially > 5*D2. In further embodiments, L < 100*D2, such as < 50*D2, especially < 20*D2. In specific embodiments, the system comprises a microfluidic device, wherein the microfluidic device comprises a hosting chamber, wherein the hosting chamber has a chamber length L defined by a first chamber end and a second chamber end, wherein the hosting chamber comprises a first chamber section and a second chamber section, wherein the first chamber section has a first average equivalent circular diameter DI (perpendicular to the chamber length) and the second chamber section has a second average equivalent circular diameter D2 (perpendicular to the chamber length), wherein D1 / D2 is selected from the range of < 0.5, and wherein the first chamber section comprises the first chamber end and the second chamber section comprises the second chamber end.

[0126] As described above, the (substantial) change in chamber diameter from the first chamber section to the second chamber section may facilitate the generation of a ring vortex, which may facilitate the formation of jets. Further, the change may facilitate ejecting jets with a greater volume.

[0127] In embodiments, the first chamber section may be arranged adjacent to the second chamber section (along the chamber length L). The transition between the first chamber section and the second chamber section may be marked by a substantial change in chamber diameter and / or chamber shape. For instance, the equivalent circular diameter of the first chamber section may vary less than 10% along the chamber length L, the equivalent circular diameter of the second chamber section may vary less than 10% along the chamber length L, whereas the (average) equivalent circular diameter of the first chamber section may differ by at least 20% from the (average) equivalent circular diameter of the second chamber section. Especially, the first chamber section may have a first section length LI and the second chamber section may have a second section length L2. The first section length LI and the second section length L2 may both be parallel to the chamber length L, i.e., to the axis of elongation of the hosting chamber. In embodiments, L1 / L2 may be selected from the range of 0.3 - 3, such as from the range of 0.5 - 2, especially from the range of 0.8 - 1.25. In further embodiments, DI may vary less than 10% (relative to a maximum value of DI) along at least 80% of LI, especially along at least 90% of LI, such as along LI. In further embodiments, D2 may vary less than 10% (relative to a maximum value of D2) along at least 80% of L2, such as along at least 90% of L2, especially along L2.

[0128] Further, as described above, the formation of the ring vortex may be influenced by the shape of the first chamber section and of the second chamber section. Hence, in embodiments, the second chamber section may have sharp (or “non-rounded”) corners, such as straight corners, opposite of the second chamber end. Hence, in embodiments, corners arranged at the transition between the first chamber section and the second chamber section may especially be sharp corners.

[0129] In embodiments, the second chamber end may comprise a chamber opening. In further embodiments, the system may comprise a cavitation induction system. The cavitation induction system may especially be configured to, during operation of the system, induce cavitation in the first chamber section, especially in a liquid in the first chamber section. In embodiments, the cavitation induction system may be selected from the group comprising a laser-based heating system, an electric discharge system, and a heater.

[0130] In a further aspect, the invention may provide a method for fluid manipulation. The method may comprise the use of a microfluidic device (also see above), and may further comprise the use of a cavitation induction system. In embodiments, the microfluidic device may comprise a hosting chamber, especially wherein the hosting chamber has a chamber length (L) defined by a first chamber end and a second chamber end. The hosting chamber may have an average equivalent circular diameter (D) perpendicular to the length (L), especially wherein L > 3*D, such as > 5*D. The method may especially comprise a preparation stage and a cavitation stage. The preparation stage may comprise providing a liquid multilayer in the hosting chamber, wherein the liquid multilayer comprises n layers sequentially arranged along the chamber length (L), especially wherein n > 2, such as > 2, especially > 4. In embodiments, adjacent layers (in the liquid multilayer) may be distinct phases. The layers (of the multilayer) may comprise a first liquid layer comprising a first liquid arranged adjacent to a second liquid layer comprising a second liquid, wherein the first liquid and the second liquid are distinct phases. Especially, the first liquid may be immiscible with the second liquid. The cavitation stage may comprise inducing cavitation of the first liquid at a first location, especially wherein the first location is arranged in the first liquid layer.

[0131] Hence, the invention may provide a method for fluid manipulation using a microfluidic device, wherein the microfluidic device comprises a hosting chamber, wherein the hosting chamber has a chamber length (L) defined by a first chamber end and a second chamber end, wherein the hosting chamber has an average equivalent circular diameter (D) perpendicular to the length (L), wherein L > 3*D, and wherein the method comprises: a preparation stage comprising providing a liquid multilayer in the hosting chamber, wherein the liquid multilayer comprises n layers sequentially arranged along the chamber length (L), wherein n > 2, wherein adjacent layers are distinct phases, and wherein the layers comprise a first liquid layer comprising a first liquid arranged adjacent to a second liquid layer comprising a second liquid; and a cavitation stage comprising inducing cavitation of the first liquid at a first location, wherein the first location is arranged in the first liquid layer.

[0132] The method of the invention may provide various benefits for fluid manipulation, as described above in the context of the system of the invention.

[0133] In embodiments, the method, especially the preparation stage, may comprise providing a liquid multilayer in the hosting chamber. The liquid multilayer may comprise n layers sequentially arranged along the chamber length (L), i.e., along an axis of elongation of the chamber. In embodiments, n > 2, such as > 3, especially > 4, such as > 5. In further embodiments, n < 10, such as < 8, especially < 6, such as < 4. Adjacent layers (of the n layers) in the multilayer may especially be distinct phases, especially wherein the (liquids of) the adjacent layers are immiscible (with one another). In particular, the multilayer may comprise a first liquid layer adjacent to a second liquid layer, wherein the first liquid layer comprises the first liquid, and wherein the second liquid layer comprises the second liquid.

[0134] Alternatively, adjacent layer (of the n layers) in the multilayer may be distinct phases, wherein the (liquids of) the adjacent layers may be miscible (with one another). Especially, the adjacent layers may be miscible on longer timescales, yet may form distinct phases on at least a timescale required for induction of a cavitation event (and subsequent ejection of a jet) (see also above).

[0135] In embodiments, the method may comprise providing a multilayer comprising a plurality of first liquid layers. Similarly, in embodiments, the method may comprise providing a multilayer comprising a plurality of second liquid layers. For instance, the multilayer may comprise the following layering: L1-L2-L1-L2, wherein LI refers to a first liquid layer comprising the first liquid, and wherein L2 refers to a second liquid layer comprising the second liquid. Hence, in embodiments, the layers may comprise alternating first liquid layers and second liquid layers. Optionally, at least two, such as all, of the plurality of first liquid layers may comprise a different first liquid (see also above). Similarly, at least two, such as all, of the plurality of second liquid layers may comprise a different second liquid (see also above).

[0136] In embodiments, the first liquid may comprise an aqueous liquid or an oil, especially an aqueous liquid, such as an aqueous solution. In further embodiments, the second liquid may comprise an oil. For instance, in embodiments, the second liquid may be selected from the group comprising a silicone oil, a vegetal oil, and a mineral oil. The vegetal oil may, for instance, be selected from the group comprising olive oil, sunflower oil, palm oil, canola oil, coconut oil, safflower oil, com oil, peanut oil, cottonseed oil, palm-kernel oil, and soybean oil. Alternatively, the second liquid may comprise one (or more) of an oil, a liquid metal, (an aqueous solution comprising) honey, (an aqueous solution comprising) glycerol, and brine.

[0137] In further embodiments, the liquid multilayer may comprise a plurality of second liquid layers. Especially, each second liquid layer may comprise a second liquid type individually selected from the group comprising a silicone oil, a vegetal oil, and a mineral oil. In further embodiments, at least two second liquid layers may differ in the second liquid type.

[0138] As described above, multiple options may be available for inducing cavitation of the first liquid at the first location. In particular, in embodiments, the method, especially the cavitation stage, may comprise inducing cavitation in the first liquid by providing one or more of laser radiation, an electric discharge, and heat to the first liquid, optionally via a chamber wall of the microfluidic device. Alternatively, the method, especially the cavitation stage, may comprise inducing cavitation in the second liquid by providing one or more of laser radiation, an electric discharge, and heat to the second liquid, optionally via a chamber wall of the microfluidic device.

[0139] In embodiments, the method, especially the cavitation stage, may comprise providing laser radiation, especially laser radiation selected from the group comprising continuous wave laser radiation and pulsed laser radiation, especially (at least) continuous wave laser radiation, or especially (at least) pulsed laser radiation.

[0140] The method may comprise providing the laser radiation to one or more of a chamber wall (of the hosting chamber) and a liquid in the hosting chamber, such as to the first liquid. Hence, the method may comprise irradiating one or more of the chamber wall and a first liquid in the hosting chamber, especially the chamber wall, or especially the first liquid. Alternatively, the method may comprise irradiating one or more of the chamber wall and a second liquid in the hosting chamber, especially the chamber wall, or especially the second liquid. In particular, the laser-based heating system may be configured to bring the liquid in the hosting chamber to a boil by providing laser radiation.

[0141] In embodiments, the laser radiation may comprise non-pulsed laser radiation, wherein the method, especially the cavitation stage comprises providing the laser radiation for a heating time period of, for example, 0.1 ms - 10 s, such as for a heating time period of 0.1 ms - 500 ms, especially of 0.1 ms - 200 ms, such as 0.2 ms - 100 ms, especially 0.5 - 70 ms. Good results were obtained with heating time periods between 0.1 ms - 200 ms. In further embodiments, the laser radiation may comprise non-pulsed laser radiation, wherein the method, especially the cavitation stage, comprises providing radiation for a heating time period selected from the range of 1 - 1000 ns, such as from the range of 2 - 800 ns, especially from the range of 5 - 500 ns.

[0142] In embodiments, the method may comprise providing laser radiation using a laser system selected from the group comprising a continuous wave laser system, a laser diode system, and an LED-based laser system, especially from the group comprising a continuous wave laser system and an LED-based laser system, more especially the continuous wave laser system.

[0143] In embodiments, the method, especially the cavitation stage, may comprise providing laser radiation with a power selected from the range of 30 - 3000 mW, such as from the range of 50 - 2000 mW, especially 100 - 1000 mW. In further embodiments, the method, especially the cavitation stage, may comprise providing laser radiation with a power of at least 50 mW, especially at least 75 mW, such as 100 mW, especially at least 150 mW, such as at least 200 mW, especially at least 250 mW, such as at least 300 mW, especially at least 350 mW, such as at least 400 mW. In further embodiments, the method, especially the cavitation stage, may comprise providing laser radiation with a power of at most 2000 mW, such as at most 1500 mW, especially at most 1300 mW, such as at most 1100 mW, especially at most 500 mW.

[0144] In further embodiments, the method, especially the cavitation stage, may comprise providing pulsed laser radiation. The method, especially the cavitation stage, may comprise providing a laser pulse having a pulse energy suitable for inducing cavitation in the first liquid (and / or in the second liquid). For instance, in embodiments, the method, especially the cavitation stage, may comprise providing a laser pulse having a laser pulse energy selected from the range of 5 - 2000 pj, such as from the range of 10 - 1000 pj, especially from the range of 20 - 500 pj.

[0145] In further embodiments, the method, especially the cavitation stage, may comprise providing an electric discharge, especially a (brief) pulse of electric current to overheat the first liquid (and / or the second liquid) in the hosting chamber, especially at the target location.

[0146] In further embodiments, the method, especially the cavitation stage, may comprise applying heat to the chamber wall and / or to the first liquid, especially to the chamber wall, or especially to the first liquid. Alternatively, the method, especially the cavitation stage, may comprise applying heat to the chamber wall and / or to the second liquid, especially to the chamber wall, or especially to the second liquid. The method, especially the cavitation stage, may comprise providing an amount of heat (energy) suitable to generate (single) cavitation events (or “cavitation bubbles”) in the first liquid (and / or in the second liquid), especially on the millisecond timescale. In further embodiments, the method, especially the cavitation stage, may comprise applying the hear via wires and / or coated metals.

[0147] In particular, the cavitation stage may comprise inducing cavitation of the first liquid at the first location. The first location may especially be arranged in the first liquid layer. Alternatively, the cavitation stage may comprise inducing cavitation of the second liquid at the first location. As such, the first location may be arranged in the second liquid layer.

[0148] In embodiments, the cavitation stage may comprise inducing cavitation in the first liquid layer (with sufficient power) to provide a capsule (or “core-shell particle”), wherein the capsule comprises a core and a shell, wherein the core and shell comprise liquids from different layers of the multilayer. For instance, the core may comprise the first liquid and the capsule may comprise the second liquid. Alternatively, the core may comprise the second liquid and the capsule may comprise the first liquid. In such embodiments, the second chamber end may especially be closed.

[0149] In further embodiments, the second chamber end may comprise a chamber opening, especially a chamber opening configured for jet ejection from the hosting chamber. In such embodiments, the first location may be arranged within a first distance (dl) from the first chamber end, especially wherein dl < 0.5*L, such as < 0.4 * L, especially < 0.3 *L, such as < 0.2*L, especially < 0.15*L, such as < 0.1 *L. Further, in such embodiments, the method, especially the cavitation stage, may comprise inducing cavitation in the first liquid layer (with sufficient power) such that a jet is ejected, wherein the jet comprises the first liquid and / or the second liquid, especially (at last partially) the first liquid, or especially (at least partially) the second liquid.

[0150] In further embodiments, the first location may be arranged in a first layer (of the multilayer), wherein the first layer is (the layer) closest to the first chamber end, such as (the layer) in contact with (a chamber wall) at the first chamber end. Yet, alternatively, the first location may be arranged in any layer (of the multilayer) (wherein the first location may preferably not be arranged in the layer closest to the second chamber end).

[0151] As described above, the hosting chamber may have a hosting volume (VH). The method, especially the preparation stage, may comprise providing the liquid multilayer such that the liquid multilayer occupies a liquid volume (VL), especially wherein VL / VH is selected from the range of 0.1 - 0.99, such as from the range of 0.2 - 0.95, especially from the range of 0.3 - 0.9, such as from the range of 0.4 - 0.8. In further embodiments, especially after the preparation stage, the hosting chamber may further comprise a gas volume (VG) of gas, such as of air, especially wherein VH = VG+VL.

[0152] As will be clear to the person skilled in the art, the induced movement of a fluid, such as movement caused by the cavitation event, may depend on the viscosity of the fluid. The viscosity of a fluid may, in general, further depend on the temperature. In particular, fluids may typically have a lower viscosity at higher temperatures. Hence, in embodiments, the method may comprise (locally) adjusting the temperature of one or more layers (of the multilayer) to control the viscosity of the liquid and, by extent, the fluid manipulation.

[0153] For instance, in the context of encapsulate formation, the viscosity of the liquid may be controlled to control encapsulation formation. With reference to a two-layer multilayer, decreasing the viscosity of the second layer may facilitate generating larger encapsulations with identical energy. Therefore, with a constant thickness, encapsulate size may be controlled by controlling the temperature of the second liquid.

[0154] Further, in the context of jet ejection, secondary jet generation may be influenced by the viscosity of a liquid, such as by the liquid layer closest to the second chamber end. By decreasing the temperature of this liquid layer, the viscosity may be increased, which may suppress interfacial dynamics and, by extent, secondary bounces upon bubble collapse.

[0155] In particular, in embodiments, the method may further comprises adjusting a temperature of at least part of the liquid multilayer (directly) prior to the cavitation stage, such as of one or more layers of the liquid multilayer, especially of one or more first liquid layers, or especially of one or more second liquid layers.

[0156] In further embodiments, the method may comprise heating at least part of the liquid multilayer (directly) prior to the cavitation stage.

[0157] Similarly, in embodiments, the method may comprise cooling at least part of the liquid multilayer (directly) prior to the cavitation stage.

[0158] Yet further, in embodiments, the method may comprise imposing a temperature gradient over the liquid multilayer. For instance, the temperature gradient may have an (essentially) continuous slope from the first chamber end towards the second chamber end. Alternatively, the temperature gradient may include one or more stepwise temperature increases and / or temperature decreases, such as at interfaces between adjacent liquid layers.

[0159] The method of the invention may especially be executed using the microfluidic device as described above. Hence, the above-described properties of the microfluidic device may further apply to embodiments of the method of the invention. Especially, the method of the invention may be executing using the system of the invention. Similarly, in embodiments, the system, especially the control system, may be configured to execute the method of the invention.

[0160] Hence, the embodiments described herein are not limited to a single aspect of the invention. For example, an embodiment describing the method may, for example, further relate to the system, especially to an operational mode of the system, or especially to the control system. Similarly, an embodiment of the system describing an operation of the system may further relate to embodiments of the method. In particular, an embodiment of the method describing an operation (of the system) may indicate that the system may, in embodiments, be configured for and / or be suitable for the operation. Similarly, an embodiment of the system describing actions of (a stage in) an operational mode may indicate that the method may, in embodiments, comprise those actions.

[0161] BRIEF DESCRIPTION OF THE DRAWINGS

[0162] Embodiments of the invention will now be described, by way of example only, with reference to the accompanying schematic drawings in which corresponding reference symbols indicate corresponding parts, and in which: Fig. 1 schematically depicts an embodiment of the system. Figs. 2-5 schematically depict embodiments of the microfluidic device and of the method. Fig. 6 schematically depicts further embodiments of the microfluidic device. Fig. 7 schematically depicts further embodiments of the microfluidic device and of the method. The schematic drawings are not necessarily on scale.

[0163] DETAILED DESCRIPTION OF THE EMBODIMENTS

[0164] Fig. 1 schematically depicts a system 1 for fluid manipulation. In the depicted embodiment, the system 1 comprises a first liquid supply 10, a second liquid supply 20, a microfluidic device 100, a cavitation induction system 200, and a control system 300. In particular, the first liquid supply 10 is configured to provide a first liquid 15 to the microfluidic device 100, especially via a first liquid inlet 131 of the microfluidic device. Similarly, the second liquid supply 20 is configured to provide a second liquid 25 to the microfluidic device 100, especially to a second liquid inlet 132 of the microfluidic device 100. In particular, the first liquid supply 10 and the second liquid supply 20 are configured to provide liquids forming distinct phases (when in contact), such as mutually immiscible liquids, i.e., the first liquid 15 may be immiscible with the second liquid. For instance, in embodiments, the solubility of the first liquid 15 in the second liquid 25 at 20 °C may be < 10000 ppm, especially < 1000 ppm, such as < 100 ppm. As schematically depicted, the microfluidic device 100 comprises a hosting chamber 110, wherein the hosting chamber 110 has a chamber length (L) defined by a first chamber end 111 and a second chamber end 112.

[0165] The hosting chamber 110 may have an average equivalent circular diameter (D) (also see Fig. 2) perpendicular to the length (L), especially wherein L > 3*D, such as > 5*D. In the depicted embodiment, L may be about 8*D. In particular, in the depicted embodiment, the hosting chamber 110 may comprise a first chamber section 116 and a second chamber section 117, wherein the first chamber section 116 has a first section length LI and a first average equivalent circular diameter DI, and wherein the second chamber section 117 has a second section length L2 and a second average equivalent circular diameter D2, wherein L1+L2=L. In such embodiments, D = (D1*L1+D2*L2) / L.

[0166] In the depicted embodiment, the cavitation induction system 200 may comprise a laser-based heating system configured to provide laser radiation 201 to a target location 41. In further embodiments, the cavitation induction system 200 may be selected from the group comprising a laser-based heating system, an electric discharge system, and a heater. Hence, in further embodiments, the cavitation induction system 200 may comprise an electric discharge system or a heater, especially an electric discharge system, or especially a heater.

[0167] The control system 300 may be configured to control the first liquid supply 10, the second liquid supply 20, and the cavitation induction system 200. Especially, the control system 300 may be configured to (have the system 1) execute an operational mode comprising a preparation stage and a cavitation stage.

[0168] In the preparation stage, the first liquid supply 10 and the second liquid supply 20 may (be configured to) provide the first liquid 15 and the second liquid 25 to provide a liquid multilayer 400 in the hosting chamber 110, as schematically depicted in Fig. 1. In particular, the first liquid supply 10 may be configured to provide the first liquid 15 to the hosting chamber 110 to provide one or more first liquid layers 415 comprising the first liquid 15 and, similarly, the second liquid supply 20 may be configured to provide the second liquid 25 to the hosting chamber 110 to provide one or more second liquid layers 425 comprising the second liquid 25. In embodiments, the liquid multilayer 400 comprises n layers 450 sequentially arranged along the chamber length (L), wherein n > 2, and wherein adjacent layers 450 (of the n layers 450) are distinct phases, especially wherein the adjacent layers 450 are immiscible (with one another). In the depicted embodiment, the liquid multilayer 400 comprises three layers, i.e. n=3, wherein a second liquid layer 425 is sandwiched between two first liquid layers 415. Hence, in the depicted embodiment, the layers 450 comprise alternating first liquid layers 415 and second liquid layers 425. Further, in the depicted embodiment, the layers 450 comprise (i) a first liquid layer 415 comprising (at least part of) the first liquid 15 arranged adjacent to a second liquid layer 425 comprising (at least part of) the second liquid 25. As can be seen in Fig. 1, the liquid multilayer 400 may have a concave meniscus.

[0169] In the cavitation stage, the cavitation induction system 200 may (be configured to) induce cavitation of the first liquid 15 at the first location 41, especially wherein the first location 41 is arranged in the first liquid layer 415. In particular, in the depicted embodiment, the layers 450 comprise a first layer 451 arranged closest to the first chamber end 111, wherein the first layer 451 comprises the first liquid layer 415.

[0170] As described above, in the depicted embodiment, the hosting chamber 110 comprises a first chamber section 116 and a second chamber section 117, wherein the first chamber section 116 comprises the first chamber end 111, and wherein the second chamber section 117 comprises the second chamber end 112. In particular, the first chamber section 116 has a first average equivalent circular diameter DI, the second chamber section 117 has a second average equivalent circular diameter D2, especially wherein D1 / D2 < 0.8, such as < 0.5.

[0171] Further, in the depicted embodiment, the first chamber section 116 has a first section length LI, parallel to the chamber length L, wherein the second chamber section 117 has a second section length L2, also parallel to the chamber length L. In particular, L1 / L2 may be selected from the range of 0.5 - 2, such as from the range of 0.8 - 1.25. In the depicted embodiment, L1 / L2 may be about 1.1. Further, in the depicted embodiment, DI varies less than 10% (relative to a maximum value of DI) along at least 80% of LI. Similarly, in the depicted embodiment, D2 varies less than 10% (relative to a maximum value of D2) along at least 80% ofL2.

[0172] The hosting chamber 110 may have a hosting volume (VH). Further, especially (directly) following the preparation stage, the first liquid supply 10 and the second liquid supply 20 may (be configured to) provide the liquid multilayer 400 such that the liquid multilayer 400 occupies a liquid volume (VL). In embodiments, VL / VH may be selected from the range of 0.1 - 0.99, such as from the range of 0.2 - 0.95, especially from the range of 0.3 - 0.9, such as from the range of 0.4 - 0.8. Further, especially (directly) following the preparation stage, the hosting chamber 110 may comprise a gas volume (VG) of gas 6, e.g., of air, especially wherein VH = VG+VL.

[0173] Further, in embodiments, each layer 450 of the liquid multilayer 400 may have a layer volume V450, wherein (for each layer 450) the layer volume V450 is individually selected from the range of 0.05*VH - 0.7*VH, especially from the range of 0.1*VH - 0.5*VH, such as from the range of 0.15*VH - 0.4*VH. Fig. 2 schematically depicts an embodiment of the microfluidic device 100 configured for jet ejection. In the depicted embodiment, after the preparation stage, the microfluidic chamber comprises a multilayer 400 with a first liquid layer 415 comprising a first liquid 15, the first liquid 15 being water, and a second liquid layer 425 comprising a second liquid 25, the second liquid 25 being a vegetal oil. In particular, Fig. 2 depicts a time series of experimental observations of jet ejection caused by cavitation induced at a first location 41. The laser radiation was commenced at t=0 (leftmost image) and was stopped at t=4 ns. At t=69 ps, a cavitation event is visible, leading to an expanding bubble (also see t=139 ps and t=194 ps). The expanding bubble in the first liquid layer 415 causes an ejection of a jet 30 comprising a second liquid 25 from the second liquid layer 425 (see t=194 ps, t=319 ps, t=1694 ps, and t=2042 ps). Hence, Fig. 2 schematically depicts bubble generation in one liquid, here especially the first liquid 15, and jet ejection of a second liquid 25, i.e., the ejected liquid was not exposed to the laser radiation 201. Further, as may be seen at t=1694 ps and t=2042 ps, no secondary jet or droplets are observed, i.e., a single jetis ejected without an accompanying ‘splash effect’.

[0174] Hence, in the depicted embodiment, the second chamber end 112 comprises a chamber opening 130 for jet ejection from the hosting chamber 110. Further, in the depicted embodiment, the first location 41 is arranged within a first distance (dl) from the first chamber end 111, wherein dl < 0.4*L.

[0175] The first location 41 is arranged in the first layer 451, i.e., in the layer 450 closest to the first chamber end 111. In the depicted embodiment, the first layer 451 may have a first layer volume V451 and the second layer 452, adjacent to the first layer 451, has a second layer volume V452, wherein V451 < V452.

[0176] Further, the liquid multilayer 400 may have a multilayer thickness (L400) along the chamber length (L). The multilayer thickness (L400) may especially be determined at a geometric center of a (concave) meniscus of the liquid multilayer 400. In Fig. 2, L400 ~ 0.73 *L.

[0177] Fig. 2 further schematically depicts an embodiment of the method of the invention. In the depicted embodiment, the microfluidic device 100 comprises a hosting chamber 110, wherein the hosting chamber 110 has a chamber length L defined by a first chamber end 111 and a second chamber end 112. Further, the hosting chamber 110 has an average equivalent circular diameter D perpendicular to the chamber length L, wherein L > 3*D. In the depicted embodiment, the method comprises a preparation stage and a cavitation stage. In the preparation stage, which is completed at the leftmost image (t=0), the method comprises providing a liquid multilayer 400 in the hosting chamber 110, wherein the liquid multilayer 400 comprises n layers 450 sequentially arranged along the chamber length L, wherein n > 2. In particular, adjacent layers 450 of the n layers 450 are distinct phases, especially wherein (liquids of) the adjacent layers are immiscible. In the depicted embodiment, the layers 450 comprise (i) a first liquid layer 415 comprising a first liquid 15 arranged adjacent to a second liquid layer 425 comprising a second liquid 25. As described above, at t=0, the first liquid 15 in the first liquid layer 415 was exposed to laser radiation 201, i.e., at t=0 the cavitation stage was started. In the depicted embodiment, the cavitation stage comprises inducing cavitation of the first liquid 15 at a first location 41, wherein the first location 41 is arranged in the first liquid layer 415 (also see t=69 and t=139).

[0178] In particular, in the depicted embodiment, the hosting chamber 110 has a hosting volume VH, wherein the preparation stage comprises providing the liquid multilayer 400 such that the liquid multilayer occupies a liquid volume (VL), wherein VL / VH is selected from the range of 0.2 - 0.95. As depicted, in embodiments, the second chamber end 112 comprises a chamber opening 130 for jet ejection from the hosting chamber 110, and the cavitation stage comprises inducing cavitation in the first liquid layer 415 (with sufficient power) such that a jet 30 is ejected, wherein the jet 30 comprises the first liquid 15 or the second liquid 25. In the depicted embodiment, the jet 30 comprises the second liquid 25.

[0179] Fig. 3 schematically depicts a time series of ejection of a jet 30 using a further embodiment of the microfluidic device 100. In the depicted embodiment, (at least part of) the hosting chamber 110 tapers towards the second chamber end 112. Such embodiments may facilitate ejecting jets 30 having a higher jet velocity.

[0180] In the depicted embodiment, the first liquid 15 comprises an aqueous liquid, the second liquid 25 comprises a vegetal oil, and the jet 30 also comprises the vegetal oil.

[0181] Fig. 4 schematically depicts a further embodiment of the microfluidic device 100 and time series data corresponding to the operational mode and the method. In the depicted embodiment, after the preparation stage, the multilayer 400 comprises three layers, i.e., n=3, wherein a second liquid layer 425 is sandwiched between two first liquid layers 415. Specifically, the first liquid 15 comprised an aqueous liquid and the second liquid 25 comprised silicone oil having a viscosity of about 1000 cSt. Following laser-induced cavitation (see t=0.11 ms), a jet 30 comprising the first liquid 15 is ejected. The presence of the second liquid layer 425 results in a reduced generation of a secondary jet, i.e., a reduced splashback effect, relative to an embodiment without the second liquid layer 425. Further, such embodiments (also) allow ejection of a jet 30 comprising liquid not directly exposed to the cavitation induction.

[0182] Fig. 5 schematically depicts a further embodiment of the microfluidic device 100, of the operational mode thereof, and of the method. In the depicted embodiment, the second liquid layer 425 is relatively thin compared to the first liquid layer 415. Specifically, the first liquid 15 comprised an aqueous liquid and the second liquid 25 comprised silicone oil having a viscosity of about 10 cSt. Following cavitation, a capsule 60 was ejected (see t=1704 ms), wherein the capsule 60 comprises a core 61 and a shell 62, wherein the core 61 comprises the first liquid 15, and wherein the shell 62 comprises the second liquid 25, i.e., the core 61 and the shell 62 comprise liquids 50 from different layers 450 of the multilayer 400.

[0183] Further, in the depicted embodiment, the first layer 451 has a first layer volume V451, the second layer 452 adjacent to the first layer 451 has a second layer volume V452, wherein V451 > V452. In particular, the relatively thin second layer 452 may facilitate the ejection of the capsule 60 as the first liquid 15 can be ejected through the second layer 452. It will be clear to the person skilled in the art that capsule ejection may involve an interplay of various parameters, such as the cavitation energy, the distance between the first location 41 and the interface between the first liquid 15 and the second liquid 25, and the thicknesses of the first layer 451 and of the second layer 452.

[0184] Fig. 6 schematically depicts further embodiments of the microfluidic device 100. In particular, Fig. 6A-C schematically depict embodiments wherein the second chamber section 117 has sharp (or “non-rounded”) corners 119 opposite of the second chamber end 112. In particular, in Fig. 6B, the second chamber section 117 has straight comers opposite of the second chamber end 112. In particular, the comers 119 opposite of the second chamber end 112 may make an angle 0, wherein 9 is selected from the range of 10° - 170°, such as from the range of 30° - 150°, such as from the range of 60° - 120°, especially (about) 90°.

[0185] Fig. 6D schematically depicts an embodiment wherein the second chamber section 117 has rounded corners 118 opposite of the second chamber end 112.

[0186] Fig. 7 schematically depicts a further embodiment of the microfluidic device 100, of the operational mode thereof, and of the method. In the depicted embodiment, the second chamber end 112 comprises a chamber opening 130 that opens into a water pool 55. In particular, in the depicted embodiment, the first liquid layer 415 and the water pool 55 both comprise the first liquid 15, wherein the first liquid 15 comprises water. The second liquid layer 425 comprises a silicon oil as second liquid 25. Between the liquid multilayer 400 and the second chamber end 112, the hosting chamber 110 further comprises a gaseous layer 406 (or “gas layer”) comprising a gas 6, such as air. In particular, the gaseous layer 406 may be ‘trapped’ between the liquid multilayer 400 and the water pool 55.

[0187] Fig. 7 depicts the effects of induced cavitation with a laser (total laser energy of 580 pJ) at the first location 41 over time T (in ms). In particular, the gaseous layer 406 deforms as a result of the expanding bubble 40 (see T=10 until T=190), after which a jet 30 is ejected from the water pool 55 in the direction of the original cavitation event. Hence, in the depicted embodiment, the gaseous layer 406 facilitates ejecting a jet 30 towards the first location 41, i.e., from the second chamber end 112 towards the first chamber end 111.

[0188] In a further test, a liquid multilayer 400 was arranged at the first chamber end 111, a gaseous layer 406 was arranged adjacent to the liquid multilayer 400, and a further first liquid layer 415 (also) comprising the first liquid 15 was arranged between the gas layer 406 and the second chamber end 112, wherein the second chamber end 112 comprised a chamber opening 130 that opened towards air. Cavitation in the first layer 451 at the first chamber end 111 resulted in the formation of two jets 30 from the further first liquid layer 415 in opposite directions: one jet 30 leaving the chamber opening 130 and one jet 30 directed towards the first chamber end 111.

[0189] Hence, the inclusion of a gaseous layer 406 may further expand the possibilities for fluid manipulation, such as for the ejection of jets 30.

[0190] Experimental results

[0191] Experiment 1:

[0192] A microfluidic device 100 comprising a hosting chamber 110 for which L = 3 mm, W = 450 pm, and H = 100 pm applies is provided. The hosting chamber 110 has a rounded rectangular chamber cross-sectional shape, and a constant equivalent circular diameter D along the chamber length L. The hosting chamber 110 is at least partially filled with a first liquid 15 comprising a 0.5% aqueous solution of AlluraRed, and optionally a second liquid 25 comprising vegetal oil (wherein - if present - the second liquid 25 is arranged closer to the second chamber end 112). A laser-based cavitation induction system 200 is used to induce cavitation in the first liquid 15, and the effect of the layer volume V450 of the first liquid layer 415 (hereafter: V450-1), the layer volume of the second liquid layer 425 (hereafter: V450-2), and the energy E of the laser on the speed S of the jet 30 is determined. In Exp. No. 1, the jet 30 contains the first liquid 15, while in Exp. No. 2-4, the jet 30 contains the second liquid 25. For clarity, also an overall filling level FL of the hosting chamber 110 is provided, wherein FL = ((V450-1 + V45O-2) / VH)*1OO%. The results are summarized in Table 1.

[0193] Table 1: effect of various parameters on the speed of the jet 30.

[0194] Exp. No. V450-1 (nL) V450-2 (nL) FL (%) E (pj) S (m / s)

[0195] 1 129 - 96% 80 20

[0196] 2 99 33 97% 80 2.5

[0197] 3 34 69 76% 120 6 39 65 77% 180 23

[0198] As can be seen from Table 1, Exp. No. 1 and 2, the addition of (a second liquid layer 425 comprising) vegetal oil leads to a strong reduction in the speed S of the jet 30, even though the laser energy E and the filling level FL remain almost the same. This may be due to the kinematic viscosity of vegetal oil (~10 cSt), which may be ten times higher than the kinematic viscosity of water (~1 cSt at 20 °C). Further, as can be seen from Table 1, Exp. No.

[0199] 3 and 4, increasing the laser energy E leads to an increase in the jet speed S. Hence, the speed S of the jet 30 may be controlled by controlling one or more of (i) a (kinematic) viscosity of the first and second liquids 15,25 and (ii) an energy E of the laser.

[0200] Experiment 2:

[0201] A microfluidic device 100 comprising a hosting chamber 110 with first and second chamber sections 116,117 as described above is provided, wherein the second chamber section 117 may have rounded comers opposite of the second chamber end 112. Each of the first and second chamber sections 116,117 may have a rounded rectangular chamber cross-sectional shape. The hosting chamber 110 is at least partially filled with - in order from the first chamber end 111 to the second chamber end 112 - a first liquid layer 415 comprising a 0.5% aqueous solution of AlluraRed, a second liquid layer 425 comprising silicon oil, and a third liquid layer comprising water. Especially, the first liquid layer 415 may essentially fill the first chamber section 116, wherein the second liquid layer 425 and the third liquid layer may at least partially fill the second chamber section 117. Further, in the second hosting chamber 117, the layer volume V450 of the second liquid layer 425 may remain (essentially) constant (at -57% of a total volume V117 of the second hosting chamber 117), while a third layer volume V450-3 of the third liquid layer is varied. Additionally, the energy of a laser comprised by the cavitation induction system 200 is varied, and the effect of the laser energy E and a relative third layer volume VR = (V450-3 / Vii?)*100% on the jet velocity S is determined. The results are summarized in Table 2.

[0202] Table 2: effect of laser energy E and relative third layer volume VR on the speed of the jet 30.

[0203] Exp. No. VR (%) E (pj) S (m / s)

[0204] 5 41 580 15

[0205] 6 31 388 8

[0206] 7 26 237 0.8

[0207] As can be seen from Table 2, with a relatively smaller increase (19%) in the relative third layer volume VR, but a relatively larger increase in the laser energy E (64%), a jet 30 can be obtained with a ten times higher jet velocity S. Further, with a relatively larger increase (32%) in the relative third layer volume VR, but a relatively smaller increase in the laser energy E (49%), a jet 30 can be obtained with a roughly two times higher jet velocity S. Visually, the jet 30 of Exp. No. 5 emerges as a continuous flow displaying axis switching, while the jet 30 of Exp. No. 6 emerges as an almost continuous flow displaying axis switching over at least part of the trajectory of the jet, and the jet 30 of Exp. No. 7 emerges as clearly separated droplets. Hence, by controlling the energy provided by the cavitation induction system 200 and a relative fill level of (the second chamber section 117 of) the hosting chamber 110, the velocity and properties of the jet 30 can be tuned.

[0208] Experiment 3 :

[0209] A microfluidic device 100 comprising a hosting chamber 110 with a rounded rectangular chamber cross-sectional shape is provided, wherein an equivalent circular diameter D is constant along the chamber length L. The hosting chamber 110 is at least partially filled with, in order from the first chamber end 111 to the second chamber end 112, a primary first liquid layer 415 comprising a 0.5% aqueous solution of AlluraRed, a second liquid layer 425 comprising silicon oil (with a viscosity of 1000 cSt), and a secondary first liquid layer 415 comprising water. The primary first liquid layer 415 has a layer thickness L450 of 0.19*L, and the second liquid layer 425 has a layer thickness L450 of 0.22*L. A laser-based cavitation induction system 200 (with a laser energy E of 350 pJ) is used to induce cavitation in the primary first liquid layer 415, and the effect of the layer thickness L450 of the secondary first liquid layer 415 (hereafter: L450-S) on the speed S of the jet 30 is determined. The results are summarized in Table 3.

[0210] Table 3: effect of layer thickness L450-S on the speed of the jet 30.

[0211] Exp. No. L450-S S (m / s)

[0212] 8 0.43*L 10

[0213] 9 0.33*L 23

[0214] 10 0.13*L 33

[0215] As can be seen from Table 3, using the same microfluidic device 100, laser energy E, and primary first and second liquid layers 415,425, the velocity of an emitted jet 30 can be tuned by adjusting the layer thickness L450-S of the secondary first liquid layer 415.

[0216] Experiment 4:

[0217] A microfluidic device 100 comprising a hosting chamber 110 with a circular chamber cross-sectional shape is provided, wherein an equivalent circular diameter D is constant along the chamber length L. The hosting chamber 110 is at least partially filled with, in order from the first chamber end 111 to the second chamber end 112, a primary first liquid layer 415 comprising a 0.5% aqueous solution of AlluraRed, a second liquid layer 425 comprising silicon oil (with a viscosity of 1000 cSt), and a secondary first liquid layer 415 comprising water. The primary first liquid layer 415 has a layer thickness L450 of 0.27*L, the second liquid layer 425 has a layer thickness L450 of 0.26*L, and the secondary first liquid layer 415 has a layer thickness L450 of 0.27*L. A laser-based cavitation induction system 200 (with a laser energy E of 350 pj) is used to induce cavitation in the primary first liquid layer 415, and the effect of the first distance dl between the first chamber end 111 and the first location 41 on the speed S of the jet 30 is determined. The results are summarized in Table 4.

[0218] Table 4: effect of the first distance dl on the speed of the jet 30.

[0219] Exp. No. dl S (m / s)

[0220] 11 < 0.05*L 7.4

[0221] 12 0.16*L 10

[0222] 13 0.21*L 11

[0223] As can be seen from Table 4, using the same microfluidic device 100, laser energy E, and (thicknesses L450 of the) liquid layers 415,425, the velocity of an emitted jet 30 can be tuned by adjusting the first distance dl.

[0224] Experiment 5 :

[0225] A microfluidic device 100 comprising a hosting chamber 110 with a rounded rectangular cross-sectional shape and a chamber length L of 2 mm is provided, wherein the hosting chamber 110 tapers towards the second chamber end 112. The hosting chamber 110 is at least partially filled with, in order from the first chamber end 111 to the second chamber end 112, a first liquid layer 415 comprising a 0.5% aqueous solution of AlluraRed, a second liquid layer 425 comprising silicon oil (with a viscosity of 1000 cSt), and another first liquid layer 415 comprising the 0.5% aqueous solution of AlluraRed. The first liquid layer 415 arranged closest to the first chamber end 111 has a layer thickness L450 of 330-342 pm (except for experiment 18, where the layer thickness L450 is 276 pm). A laser-based cavitation induction system 200 comprising a continuous wave laser system is used to induce cavitation in the first liquid layer 415 arranged closest to the first chamber end 111, and the effect of the layer thicknesses L450 of the second liquid layer (hereafter: L450-2) and the another first liquid layer (hereafter: L45O-I,2) on the speed S of the jet 30 is determined. The results are summarized in Table 5, where also the multilayer thickness L400 is indicated. Table 5: effect of the first distance dl on the speed of the jet 30.

[0226] Exp. No. L450-2 (pm) 450-1,2 (pm) L400 S (m / s)

[0227] 14 512 828 1682 31

[0228] 15 519 847 1698 34

[0229] 16 610 695 1630 29

[0230] 17 701 618 1648 25

[0231] 18 844 519 1633 26

[0232] 19 447 1035 1782 44

[0233] As can be seen from Table 5, using the same microfluidic device 100 and laser system, the velocity of an emitted jet 30 can be tuned by adjusting the layer thicknesses of the second and first layers 425,415. Especially, a thicker second layer 425 may result in a lower jet speed (or velocity) S, as the viscosity of the silicon oil may be relatively high (see Exp. No. 15-18, and Exp. No. 14 & 19). Further, as can be seen from Exp. No. 14-15, the speed S of the jet 30 may be reproducible when using similar layer thicknesses L450.

[0234] The term “plurality” refers to two or more. Furthermore, the terms “a plurality of’ and “a number of’ may be used interchangeably.

[0235] The terms “substantially” or “essentially” herein, and similar terms, will be understood by the person skilled in the art. The terms “substantially” or “essentially” may also include embodiments with “entirely”, “completely”, “all”, etc. Hence, in embodiments the adjective substantially or essentially may also be removed. Where applicable, the term “substantially” or the term “essentially” may also relate to 90% or higher, such as 95% or higher, especially 99% or higher, even more especially 99.5% or higher, including 100%. Moreover, the terms ’’about” and “approximately” may also relate to 90% or higher, such as 95% or higher, especially 99% or higher, even more especially 99.5% or higher, including 100%. For numerical values it is to be understood that the terms “substantially”, “essentially”, “about”, and “approximately” may also relate to the range of 90% - 110%, such as 95%-105%, especially 99%-101% of the values(s) it refers to.

[0236] The term “comprise” also includes embodiments wherein the term “comprises” means “consists of’.

[0237] The term “and / or” especially relates to one or more of the items mentioned before and after “and / or”. For instance, a phrase “item 1 and / or item 2” and similar phrases may relate to one or more of item 1 and item 2. The term "comprising" may in an embodiment refer to "consisting of' but may in another embodiment also refer to "containing at least the defined species and optionally one or more other species". 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 sequential or chronological order. 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.

[0238] The devices, apparatus, or systems may herein amongst others be described during operation. As will be clear to the person skilled in the art, the invention is not limited to methods of operation, or devices, apparatus, or systems in operation.

[0239] The term “further embodiment” and similar terms may refer to an embodiment comprising the features of the previously discussed embodiment, but may also refer to an alternative embodiment.

[0240] It should be noted that the above-mentioned embodiments illustrate rather than limit the invention, and that those skilled in the art will be able to design many alternative embodiments without departing from the scope of the appended claims. In the claims, any reference signs placed between parentheses shall not be construed as limiting the claim.

[0241] Use of the verb "to comprise" and its conjugations does not exclude the presence of elements or steps other than those stated in a claim. Unless the context clearly requires otherwise, throughout the description and the claims, the words “comprise”, “comprising”, “include”, “including”, “contain”, “containing” and the like are to be construed in an inclusive sense as opposed to an exclusive or exhaustive sense; that is to say, in the sense of “including, but not limited to”.

[0242] The article "a" or "an" preceding an element does not exclude the presence of a plurality of such elements.

[0243] The invention may be implemented by means of hardware comprising several distinct elements, and by means of a suitably programmed computer. In a device claim, or an apparatus claim, or a system claim, enumerating several means, several of these means may be embodied by one and the same item of hardware. The mere fact that certain measures are recited in mutually different dependent claims does not indicate that a combination of these measures cannot be used to advantage.

[0244] The invention also provides a control system that may control the device, apparatus, or system, or that may execute the herein described method or process. Yet further, the invention also provides a computer program product, when running on a computer which is functionally coupled to or comprised by the device, apparatus, or system, controls one or more controllable elements of such device, apparatus, or system. The invention further applies to a device, apparatus, or system comprising one or more of the characterizing features described in the description and / or shown in the attached drawings. The invention further pertains to a method or process comprising one or more of the characterizing features described in the description and / or shown in the attached drawings. Moreover, if a method or an embodiment of the method is described being executed in a device, apparatus, or system, it will be understood that the device, apparatus, or system is suitable for or configured for (executing) the method or the embodiment of the method, respectively.

[0245] The various aspects discussed in this patent can be combined in order to provide additional advantages. Further, the person skilled in the art will understand that embodiments can be combined, and that also more than two embodiments can be combined. Furthermore, some of the features can form the basis for one or more divisional applications.

Claims

CLAIMS:

1. A system (1) for fluid manipulation, wherein the system (1) comprises a first liquid supply (10), a second liquid supply (20), a microfluidic device (100), a cavitation induction system (200), and a control system (300), wherein:the first liquid supply (10) is configured to provide a first liquid (15) to the microfluidic device (100);the second liquid supply (20) is configured to provide a second liquid (25) to the microfluidic device (100);the microfluidic device (100) comprises a hosting chamber (110), wherein the hosting chamber (110) has a chamber length (L) defined by a first chamber end (111) and a second chamber end (112), wherein the hosting chamber (110) has an average equivalent circular diameter (D) perpendicular to the length (L), wherein L > 3*D;wherein the cavitation induction system (200) is selected from the group comprising a laser-based heating system, an electric discharge system, and a heater; and wherein the control system (300) is configured to control the first liquid supply (10), the second liquid supply (20), and the cavitation induction system (200), and wherein the control system (300) has an operational mode wherein:in a preparation stage the first liquid supply (10) and the second liquid supply (20) are configured to provide a liquid multilayer (400) in the hosting chamber (110), wherein the liquid multilayer (400) comprises n layers (450) sequentially arranged along the chamber length (L), wherein n > 2, wherein adjacent layers (450) are distinct phases, and wherein the layers (450) comprise a first liquid layer (415) comprising the first liquid (15) arranged adjacent to a second liquid layer (425) comprising the second liquid (25); andin a cavitation stage the cavitation induction system (200) is configured to induce cavitation of the first liquid (15) at a first location (41), wherein the first location (41) is arranged in the first liquid layer (415).

2. The system (1) according to claim 1, wherein the hosting chamber (110) has a hosting volume (VH), wherein in the preparation stage the first liquid supply (10) and the second liquid supply (20) are configured to provide the liquid multilayer (400) such that the liquid multilayer (400) occupies a liquid volume (VL), wherein VL / VH is selected from the range of 0.2 - 0.95, wherein the second chamber end (112) comprises a chamber opening (130) for jetejection from the hosting chamber (110), and wherein the first location (41) is arranged within a first distance (dl) from the first chamber end (111), wherein dl < 0.4 * L.

3. The system (1) according to claim 2, wherein the hosting chamber (110) tapers towards the second chamber end (112).

4. The system (1) according to claim 1, wherein the hosting chamber (110) has a hosting volume (VH), wherein in the preparation stage the first liquid supply (10) and the second liquid supply (20) are configured to provide the liquid multilayer (400) such that the liquid multilayer (400) occupies a liquid volume (VL), wherein VL / VH is selected from the range of 0.2 - 1, wherein the second chamber end (112) is closed.

5. The system (1) according to any one of the preceding claims 2-4, wherein each layer (450) of the liquid multilayer (400) has a layer volume V450, wherein V450 is individually selected from the range of 0.1*VH - 0.5*VH.

6. The system (1) according to any one of the preceding claims, wherein n > 3.

7. The system (1) according to claim 6, wherein the liquid multilayer (400) comprises a plurality of second liquid layers (425), wherein each second liquid layer (425) comprises an second liquid type individually selected from the group comprising a silicone oil, a vegetal oil, and a mineral oil.

8. The system (1) according to any one of the preceding claims, wherein the layers (450) comprise a first layer (451) arranged closest to the first chamber end (111), wherein the first layer (451) comprises the first liquid layer (415), and wherein the first liquid comprises an aqueous liquid.

9. The system (1) according to any one of the preceding claims, wherein the hosting chamber (110) comprises a first chamber section (116) and a second chamber section (117), wherein the first chamber section (116) comprises the first chamber end (111), and wherein the second chamber section (117) comprises the second chamber end (112), wherein the first chamber section (116) has a first average equivalent circular diameter (Dl), whereinthe second chamber section (117) has a second average equivalent circular diameter (D2), wherein D1 / D2 < 0.5.

10. The system (1) according to claim 9, wherein the first chamber section (116) has a first section length (LI), wherein the second chamber section (117) has a second section length (L2), wherein L1 / L2 is selected from the range of 0.5 - 2, and wherein the second chamber section (117) has sharp corners (119) opposite of the second chamber end (112).

11. The system (1) according to any one of the preceding claims, wherein the cavitation induction system (200) comprises a continuous wave laser source, and wherein in the cavitation stage the cavitation induction system (200) is configured to provide laser radiation with a power of at least 50 mW and at most 2000 mW.

12. The system (1) according to any one of the preceding claims, wherein the cavitation induction system (200) further comprises a gas supply (160) configured to provide a gas (6) to the hosting chamber (110), wherein in the preparation stage the gas supply (160) is configured to provide a gaseous layer (406) between the liquid multilayer (400) and the second chamber end (112).

13. A method for fluid manipulation using a microfluidic device (100), wherein the microfluidic device (100) comprises a hosting chamber (110), wherein the hosting chamber (110) has a chamber length (L) defined by a first chamber end (111) and a second chamber end (112), wherein the hosting chamber (110) has an average equivalent circular diameter (D) perpendicular to the chamber length (L), wherein L > 3*D, wherein the method comprises:a preparation stage comprising providing a liquid multilayer (400) in the hosting chamber (110), wherein the liquid multilayer (400) comprises n layers (450) sequentially arranged along the chamber length (L), wherein n > 2, wherein adjacent layers are distinct phases, and wherein the layers (450) comprise a first liquid layer (415) comprising a first liquid (15) arranged adjacent to a second liquid layer (425) comprising a second liquid (25); and a cavitation stage comprising inducing cavitation of the first liquid (15) at a first location (41), wherein the first location (41) is arranged in the first liquid layer (415).

14. The method according to claim 13, wherein the hosting chamber (110) has a hosting volume (VH), wherein the liquid multilayer occupies a liquid volume (VL), whereinVL / VH is selected from the range of 0.2 - 0.95, wherein the second chamber end (112) comprises a chamber opening (130) for jet ejection from the hosting chamber (110), wherein the first location (41) is arranged within a first distance (dl) from the first chamber end (111), wherein dl < 0.4 * L, and wherein the cavitation stage comprises inducing cavitation in the first liquid layer (415) such that a jet (30) is ejected, wherein the jet (30) comprises the first liquid (15) or the second liquid (25).

15. The method according to claim 13, wherein the cavitation stage comprises inducing cavitation in the first liquid layer (415) to provide a capsule (60), wherein the capsule (60) comprises a core (61) and a shell (62), wherein the core (61) and shell (62) comprise liquids (50) from different layers (450) of the multilayer (400).

16. The method according to any one of the preceding claims 13-15, wherein the method comprises adjusting a temperature of at least part of the liquid multilayer prior to the cavitation stage.

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