Microfluidic unit with non-wetting venting areas, methods for venting them and methods for manufacturing them

Abstract

Microfluidic unit (1) comprising: a substrate (5) defining a microfluidic channel (10) with a sealed section (12) having a sealed cross-section, wherein the sealed section has: a fluid path (14) formed by a wetting area; and a non-wetting area (16) extending along and adjacent to the liquid path (14), wherein the non-wetting area is designed to provide a vent for emptying a gas from the wetting area along the non-wetting area, wherein the non-wetting area comprises black silicon.

Description

BACKGROUND

[0001] The invention relates generally to the field of microfluidic units, in particular to microfluidic chips, as well as to related units and methods for their operation and fabrication. Microfluidics generally refers to microfabricated units used for pumping, sampling, mixing, analyzing, and dispensing liquids. Its key features stem from the unique behavior of liquids at micrometer lengths. Liquid flow in microfluidics is typically laminar. By fabricating structures with lateral dimensions in the micrometer range, volumes well below one nanoliter can be achieved. Reactions that are limited at larger scales (by reactant diffusion) can be accelerated.Finally, parallel flows of liquids can potentially be controlled precisely and reproducibly, thus enabling chemical reactions and gradients to occur at liquid / liquid and liquid / solid interfaces. Accordingly, microfluidics is used for various applications in the life sciences.

[0002] Many microfluidic units utilize chip interfaces and closed flow paths. Closed flow paths simplify the integration of functional elements (e.g., heaters, mixers, pumps, UV detectors, valves, etc.) into a single unit while simultaneously reducing problems associated with leaks and evaporation.

[0003] Document WO 2004 / 103890A1 relates to a microfluidic device comprising one or more microchannel structures, each of which includes a microconduit for transporting and / or processing liquid, the inner surface of which comprises a hydrophilic liquid contact area (surface 1) delimited in at least one direction by a boundary to a hydrophobic area (surface 2). The characteristic feature is that surface 2 includes a rough portion extending along the boundary.

[0004] Document WO 2004 / 067444A1 relates to a microfluidic device with one, two, three, or more closed microchannel structures, each of which comprises a) an inlet arrangement with an inlet opening for liquid, b) a reaction microcavity (RM1) downstream of the inlet opening, and c) an upstream section located between the inlet opening and the reaction microcavity (RM1) and defined between two planar substrates made of plastic material, these substrates being common to the microchannel structures. The characteristic feature is that the inner wall in the upstream section has a hydrophilic surface with an underlying base layer of a metal oxide.

[0005] Document US 2016 / 0367988A1 relates in particular to a microfluidic chip comprising: a flow path defined by a hydrophilic surface; a fluid inlet on one side of the flow path; at least one electrical circuit, hereinafter referred to as the DEP circuit, comprising at least one pair of dielectrophoretic electrodes, hereinafter referred to as DEP electrodes, wherein: each of the DEP electrodes extends transversely to the flow path; and the DEP circuit is configured to generate a dielectrophoretic force, hereinafter referred to as the DEP force, at the level of the DEP electrodes. The chip may further include one or more electroosmotic circuits.

[0006] German patent application DE 10 2004 063 438 A1 relates to a novel sample carrier comprising at least one sample receiving chamber for a sample liquid, at least one distribution channel connected to the at least one sample receiving chamber, wherein at least one distribution channel extends from each sample receiving chamber, at least one reaction chamber into which an inlet channel branching off from the at least one distribution channel optionally opens, and at least one vent opening for each reaction chamber. Such sample carriers are primarily intended for use in microbiological diagnostics, immunology, PCR, clinical chemistry, microanalytics, and / or the testing of active pharmaceutical ingredients. The invention further relates to methods for analyzing a sample substance in which the sample carrier is used, as well as to kits containing the sample carrier. SUMMARY

[0007] The invention relates to a microfluidic unit, a method for venting a microfluidic unit, and a method for manufacturing a microfluidic unit, the features of which are specified in the corresponding claims. Embodiments are specified in the dependent claims.

[0008] In one aspect, a microfluidic unit comprises a substrate that defines a microfluidic channel with a sealed section. The sealed section has a fluid path formed by a wetting zone. The sealed section further includes a non-wetting zone extending along and adjacent to the fluid path. The non-wetting zone is designed to provide a vent for the release of gas from the wetting zone along the non-wetting zone. Advantageously, the non-wetting zone is designed to allow the release of gas.

[0009] In a related aspect, the non-wetting zone is a first non-wetting zone, and the sealed section of the microfluidic channel further features a second non-wetting zone extending along and adjacent to the fluid path opposite the first non-wetting zone. The second non-wetting zone is designed to provide a vent for the release of gas from the wetting zone along the second non-wetting zone.

[0010] In a related aspect, the wetted zone of the fluid path is formed by a bottom wall and between side walls located on each side of the fluid path, while the non-wetted zone extends between one of the side walls and the fluid path. The non-wetted zone advantageously allows for venting, as it extends along and adjacent to a side wall of the microfluidic channel. The non-wetted zones advantageously provide: fluid containment, gas evacuation, and tight sealing of parts.

[0011] In a related aspect, the wetting area of ​​the fluid path is formed by at least a lower wall and a lateral wall of the microfluidic channel, and the non-wetting area extends along and adjacent to the lateral wall of the microfluidic channel.

[0012] In a related aspect, the microfluidic unit further includes one or more unsealed sections such that a gas can be vented from the sealed section to the one or more unsealed sections along the non-wetting area.

[0013] In a related aspect, the microfluidic unit further comprises several secondary microfluidic channels connected to the main microfluidic channel. Each of the secondary microfluidic channels has a sealed channel segment, and each of the multiple secondary microfluidic channels has a fluid path formed by a wetting zone. At least one non-wetting zone is designed to provide venting. The multiple secondary microfluidic channels are connected to the main microfluidic channel at one end in such a way as to form a branch of sealed channel segments.

[0014] In a related aspect, the non-wetting area exhibits black silicon. This black silicon is advantageous for deaeration and bonding with surfaces and materials.

[0015] In another related aspect, the non-wetting area connects the fluid path with an adjacent structure.

[0016] In another related aspect, the microfluidic unit further includes a structure that has an area resting on the non-wetting area, and the non-wetting area is designed to prevent fluid from escaping between the fluid path and the adjacent structure.

[0017] In another aspect, the microfluidic unit further comprises two fluid pathways separated by a common non-wetting zone. This common non-wetting zone extends along and adjacent to each of the two fluid pathways.

[0018] In one aspect, a procedure for venting a microfluidic unit involves: causing a liquid to move along a wetting area on a fluid path in such a way that a gas is flushed out in a microfluidic channel; and venting the gas from a sealed section of the microfluidic channel along a non-wetting area extending along and adjacent to the fluid path.

[0019] In another aspect, a method for manufacturing a microfluidic unit includes: forming a microfluidic channel in a substrate, wherein the microfluidic channel has a sealed section; forming a fluid path by means of a wetting region in the sealed section; and forming a non-wetting region in the sealed section, wherein the non-wetting region extends along and adjacent to the fluid path, and wherein the non-wetting region is designed to provide a vent for the evacuation of a gas from the wetting region along the non-wetting region.

[0020] The units and methods embodying the present invention are described below with reference to non-limiting examples and the accompanying drawings. Technical features shown in the drawings are not necessarily to scale. Furthermore, some parts may be shown as not being in contact with each other (to simplify understanding of the drawings), whereas it may very well be intended that they are in contact with each other during operation. Brief description of the different views of the drawings

[0021] These and other tasks, features, and advantages of the present invention will become apparent from the following detailed description of illustrative embodiments thereof, which should be read in conjunction with the accompanying drawings. The various features of the drawings are not to scale, as the illustrations serve for clarification and, together with the detailed description, are intended to facilitate the understanding of the invention by those skilled in the art. The following applies to the drawings: Fig. Figure 1 is an isometric view of a simplified representation of a section of a microfluidic chip according to embodiments of the present disclosure; Fig. 2 is a transverse cross-sectional view of the unit of Fig. 1 perpendicular to the main axis of a microfluidic channel; Fig. 3 is a transverse cross-sectional view of the unit of Fig. 1 similar to the view of Fig. 2 and additionally illustrates a typical liquid segment when liquid wets the liquid path; Fig. 4 represents a horizontal section through the unit of Fig. 1 immediately above the wetting surface; Fig. 5, Fig. 6 to Fig. Figure 7 shows cross-sectional views of simplified representations of a section of a microfluidic chip according to a further embodiment, wherein two fluid paths are separated by the same non-wetting area; Fig. Figure 8 shows a cross-sectional view of a simplified representation of a variant of the embodiment of Fig. 2, wherein the wetting area of ​​the liquid path is formed on a layer of a material (an oxide or a metal) on a lower wall of the substrate according to an embodiment of the present disclosure; Fig. 9 and Fig. Figure 10 shows transverse cross-sectional views of a simplified representation of a microfluidic unit according to other embodiments, wherein the non-wetting venting areas extend along lateral walls of the channel; Fig. Figures 11A to 11D are top views of a simplified representation of a microfluidic unit having a branching of channels, and which show how a fluid can be introduced into it and wet the channels up to the branching, while compressed air is vented through the non-wetting areas, as in embodiments according to the present disclosure; Fig. Figure 12 shows a cross-sectional view of a simplified representation of a section of a microfluidic unit in which the channel is primarily provided in a cavity of the cover structure, according to embodiments; Fig. Figure 13 shows a cross-sectional view of a section of a microfluidic chip in which a channel is provided primarily by a cavity of the cover structure, which further comprises a capillary pump, according to one embodiment; Fig. Figure 14 shows a top view of a section of a microfluidic chip in which a channel is again provided primarily by a cavity in the cover structure, which further comprises a capillary pump, according to embodiments; and Fig. Figure 15 is a flowchart illustrating the steps of a method for manufacturing a microfluidic unit according to one or more embodiments of the present disclosure. DETAILED DESCRIPTION

[0022] With reference to Fig. 1, Fig. 2, Fig. 3, Fig. 4, Fig. 5, Fig. 6, Fig. 7, Fig. 8, Fig. 9, Fig. 10, Fig. 11, Fig. 12 to Fig. Section 13 first describes a general aspect of the invention relating to a microfluidic unit 1. The unit has one or more microfluidic channels 10, which can be provided on a surface of the microfluidic unit or as cavities formed between two parts of the unit 1, as illustrated in the drawings. At least one section 12 of a microfluidic channel is closed, e.g., by a cover structure 30. This channel section has a fluid path 14 formed by a wetting region and a non-wetting region (i.e., which remains unwetted) 16 extending along and adjacent to the fluid path 14. For example, the fluid path 14 is formed by a wetting region 16. Fig. 1. The channel is covered by a cover structure 30, at least in the section 12 shown. Other sections of the unit may be open, i.e., to provide openings to allow liquid to be introduced into the channels from above.

[0023] Furthermore, the non-wetting zone is designed to allow venting. In this way, a gas surrounding the liquid (e.g., air), which is compressed as the liquid wets and moves along the liquid path, can be vented along the non-wetting zone 16, for example, through a volume or space provided above the non-wetting zone. Alternatively, a gas can be vented through a thickness of the non-wetting zone if the latter has a needle structure, or similarly through a network structure that retains the liquid but is gas-permeable.

[0024] Accordingly, the non-wetting areas serve a dual purpose. Not only do they allow a liquid 25 to remain contained within the liquid path 14, but they also allow a gas, e.g., air, to be more easily vented, thus enabling uniform liquid distribution within the unit, even in sealed (i.e., covered) channel sections and even when sealed channel sections have a dead end. In a sealed channel and without a vent as described herein, a liquid must compress any gas within the channels, thereby slowing the forward movement of the liquid and potentially terminating capillary flow (at dead ends).The present disclosure solves the above problem and makes it possible to provide new chip designs, enabling fluid movements and mixing that would not have been possible with previous designs. This is described with reference to . Fig. Sections 11A to 11D discuss this in more detail. Furthermore, non-wetting areas can be used to join surfaces and / or components and materials in such a way as to prevent leaks. For example, embodiments described herein employ Si / polymer hybrid chips in which non-wetting areas are made of black silicon, thus enabling the containment of liquids, the expulsion of gases, and the joining of parts of the unit (without necessarily employing bonds or adhesives). Silicon allows for a high degree of precision in the processing of the silicon.

[0025] It should be noted that, although most of the embodiments discussed herein relate to microfluidic chips, the present concept can in principle also be applied to microfluidic probe heads, which are commonly used to locate liquids and chemicals / biochemicals across surfaces by non-contact scanning. For example, in some practical applications the gas to be purged is likely to be air, but other gases, in particular nitrogen, can be used if required.

[0026] In most of the embodiments discussed herein, the fluid path is surrounded by two non-wetting ventilation areas 16, which extend along and adjacent to the fluid path and are opposite each other. It is understood that the two opposing areas 16 may actually form a continuous non-wetting area, as for example in Fig. Figure 11 illustrates this. Depending on the desired channel design, one or more non-wetting zones may be included, resulting in one or two non-wetting sections extending along the channel(s).

[0027] With reference to Fig. 1, Fig. 2, Fig. 3, Fig. 4, Fig. 5, Fig. 6, Fig. 7 to Fig. 8 is the wetting zone of the liquid path 14 formed by a lower wall 15 of the unit 1 between side walls 17 of a channel 10 or a sealed channel section 12. The side walls 17 are arranged on each side of the liquid path(s) 14. The non-wetting zone 16 extends, for example, between one of the side walls 17 and a liquid path 14. In this way, a volume is provided above the outer non-wetting zones 16 that is not (or at least not completely) filled by a liquid 25 during operation (see, for example, Figure 8). Fig. 3, Fig. 6 and Fig. 8), so that a gas can be flushed out appropriately along the non-wetting areas as the liquid fills the path.

[0028] In one embodiment, the lateral channel walls 17 comprise silicon, and it should be noted that the base substrate 5 is also typically made of silicon. The wetting surface can be made of SiO2 or, more generally, of an oxide or a metal, e.g., palladium, as discussed in more detail below. In practical embodiments, the lateral channel walls 17 can be walls of lateral structures 20 that project from the lower wall 15 of the channel, as shown in Fig. 1, Fig. 2, Fig. 3, Fig. 4, Fig. 5, Fig. 6, Fig. 7 to Fig. Figure 8 illustrates this. For example, a cover structure 30 can rest on the lateral structures 20 in such a way that it closes the channel (or at least a section of it).

[0029] With particular reference to Fig. 5, Fig. 6 to Fig. 7 In a further embodiment 50 according to the disclosure, two fluid paths 14 ( Fig. 1) be formed within the same channel cavity, each path being formed by a corresponding wetting zone 16. The wetting zone can, for example, be formed on the lower wall 15 of the channel cavity. The two liquid paths 14 can be separated by a common non-wetting zone 16, which extends along and adjacent to each of the two liquid paths 14. Outer non-wetting zones 16 (as in Fig. 6 shown) can be provided to enclose a liquid L on the respective paths 14.

[0030] With reference to Fig. 9 to Fig. In a further embodiment 60, the wetting area of ​​the fluid path 14 is profiled (e.g., as a U- or V-shape). It can be formed, for example, by a lower wall 62 and a side wall 64 of a microfluidic channel, or by a lower wall 62 and two side walls 64, as shown in Fig. 9 to Fig. Figure 10 illustrates this. In such cases, the non-wetting venting zones 16 can advantageously extend along and adjacent to a lateral wall 64 of the microfluidic channel. Here, the non-wetting zone is designed to allow gas to be vented. The non-wetting zones are provided in a base structure 5. As further shown in Figure 10, the non-wetting venting zones 16 can advantageously extend along and adjacent to a lateral wall 64 of the microfluidic channel. Here, the non-wetting zone is designed to allow gas to be vented. The non-wetting zones are provided in a base structure 5. Fig. 9 to Fig. As can be seen in Figure 10, the non-wetting areas are provided at an interface between the base structure 5 and a cover structure 30.

[0031] In an alternative embodiment, the non-wetting areas can also be provided in the cover structure 30. As mentioned previously, the non-wetting venting areas 16 can be made of black silicon or any similar needle-shaped surface structure, or more generally, any finely structured surface. An advantage of black silicon or the like is that it repels liquids. This is particularly advantageous where non-wetting areas are used at interfaces, as in Fig. 9 to Fig. 10, or for joining parts, thereby preventing liquid leakage in addition to the non-wetting properties (and consequently liquid-retaining properties). Furthermore, a gas can be purged through the thickness of the non-wetting areas in such a way that the non-wetting areas may potentially serve three purposes: liquid containment, gas evacuation, and tight joining of parts.

[0032] Black silicon can optionally be reinforced (even on the sidewalls) with a thin layer of fluorocarbon to make this layer more hydrophobic (resulting in a contact angle with water greater than 130°). Here, the black silicon is formed using a deep reactive ion etching (DRIE) process, also known as the Bosch process. This process is compatible with high-throughput wafer-level manufacturing, and the wetting areas (without black silicon) can be masked using a photoresist, a metal, or an oxide layer. The process etches the silicon, forming needle-like structures, with a layer of fluorocarbon (C4F8) remaining on the sidewalls of the needles, further increasing the hydrophobicity. These needle-like structures and the fluorocarbon layer are fragile and can be broken or washed away during post-photolithography photoresist cleanup or after sectioning.Therefore, the present disclosure proposes first etching the oxide and / or metal layer using a photoresist layer as a mask, partially dividing the wafer (the remaining photoresist serves as protection for the wetting areas during dividing), then cleaning the photoresist using an organic solvent, and finally performing a DRIE on the complete wafer to convert Si areas to black Si, with the oxide and / or metal serving as a mask. Since the latter step is the final step before separating the chips (e.g., by simply breaking them at the partial dividing sections), the integrity of the brittle hydrophobic areas is not compromised.

[0033] With reference to Fig. In a further embodiment of a microfluidic unit 70 according to the disclosure, one or more channels 11A to 11D are not closed at one or more other sections 18 thereof. For example, the fluid path 14 may not be covered at sections 18 (e.g., openings) by the cover structure 30. Consequently, during operation, a gas can be discharged from a closed section 12 along the non-wetting area(s) and subsequently through the open sections 18.

[0034] As previously mentioned, the present disclosure enables novel chip designs. For example, a sealed section 12 of a microfluidic channel can have a (not shown) dead end. The venting areas 16 can still allow gas to be vented. It should be noted that in capillary-driven systems, a microfluidic channel with a dead end can be particularly interesting, since structuring vents on the cover layer is usually not so trivial, and vents at the edges of the microfluidic chip can be a potential source of defects, such as fluid leakage from a channel to the outside or fluid ingress from the outside into a channel, which can lead to contamination of the channels, etc.Furthermore, if clinical samples need to be analyzed on microfluidic chips with vents, vents can pose biosafety problems due to the possibility of some of the sample escaping from the chip through the vents, highlighting the potential advantages of dead ends.

[0035] As in Fig. As shown in Figures 11A to 11D, two microfluidic channels 11 can unite at a closed branch 19. In particular, each channel 11 can have a fluid path 14 extending from a closed section 12 to one or more open sections (or openings) 18. A section 12 of a microfluidic channel can lead at one end into another channel section such that a branch 19 of fluid paths is formed. In the Fig. In the example shown in Figures 11A to 11D, the channel construction can be considered as being formed by a curved channel that intersects a straight channel 11. The straight channel has one liquid opening, whereas the curved channel connects two liquid openings 18. Although the channel branch 19 is closed, i.e., in the example of Fig. Although 11A to 11D are covered by the cover structure 30, gas can still be discharged along the non-wetting area 16, even if a liquid is simultaneously introduced through each opening 18. The same principle can be extended to branches of three or more microchannels. It should be noted that in Fig. 11A to 11D each channel section has two sections of non-wetting areas on each side, although the unit shows only one continuous non-wetting area.

[0036] As further explained in Fig. Figures 11A to 11D illustrate this, and according to a further aspect, an embodiment may include a method for operating the microfluidic unit 70, the method essentially exploiting the following phenomena. Since a liquid 25 can wet the (wetting) liquid path 14, it naturally moves along it. This, in turn, causes surrounding gas to be pushed and flushed out of the microfluidic channel 11. Meanwhile, the gas being pushed through the liquid is vented from the sealed section 12 along the non-wetting area through the venting area(s) 16. In particular, a gas can be vented through openings 18, as shown in Fig. 11A to 11D are shown, and / or can be emptied through openings at the (not shown) edges. Fluid can be introduced via openings 18 or, in (not shown) variants, introduced from adjacent structures (pipes, bores, etc.) that are in fluid communication with channels of unit 70.

[0037] As briefly mentioned earlier, the non-wetting area(s) 16 (or at least some of them) can advantageously be arranged and constructed such that they connect the fluid path with an adjacent structure. The adjacent structure could, for example, be a (in Fig. 1, Fig. 2, Fig. 3, Fig. 4, Fig. 5, Fig. 6, Fig. 7 to Fig. 8 shown) is a lateral structural wall, as mentioned previously. It can also be a structure that covers or spans the channels, such as a (in Fig. (9, 10, 12 to 14) cover structure. In particular, units can use black Si to join structures, e.g., to unite surfaces and materials, as required to ensure a tight fit. Using black Si to join two structures results in the two parts being brought into contact or clamped together without necessarily requiring bonding, gluing, adhesives, lamination, etc. The weight of one part, for example, may be sufficient for it to rest on or press against the other part. Two parts can also be joined by positioning them close together on a common support via the black Si areas. In this respect, black Si can also be used to join areas whose purpose is to join parts independently of the venting areas 16.

[0038] At in the Fig. In the illustrated embodiments 9, 10, 12 to 14, the unit 80 has a structure 30 (e.g., a cover structure) which has a region that rests on the non-wetting vent region 16. The non-wetting regions can thus prevent the escape of liquid between the liquid path 14 and the structure 30. The structure 30 can be, for example, a plastic sleeve or a plastic chip ( Fig. 12, Fig. 13 to Fig. 14) or to create a cover structure 30 ( Fig. 9, Fig. 10) act. It should be noted that in Fig. 13. Parts 5 and 30 are not shown to be “in contact” with each other. Instead, a narrow gap is shown between the surface of the base chip 5 and the adjacent structure 30 to facilitate understanding of the drawings. Again, the use of black silicon is particularly advantageous, especially if the area of ​​the top structure is not perfectly flat. The area of ​​the top structure may indeed not be perfectly flat due to likely variations in thickness during the plastic molding process. For example, biological reagents can be deposited, integrated, or structured on the silicon chip 5 (which has wetting / non-wetting areas) or on the plastic chip, and then the two chips 5 and 30 can be joined together without the use of any adhesive or temperature that could damage the reagents. Fig. 13, Fig. 14) The pipetted liquid spreads along the wetting areas on the silicon chip without trapping air (or gas) and then transfers to the plastic chip 30 (which is made, for example, of hydrophilic PMMA), where the capillary pump structures 40 draw in the liquid. This process can be extended to multiple parallel channels for multiplexing purposes, as is otherwise described in Fig. 6 illustrates.

[0039] The weight of the adjacent structure 30 may be sufficient in practice without the need to connect it to the base chip 5. However, adhesives can be added to areas of the structure 30 that are a reasonable distance from the channels to prevent channel contamination. This ensures that the structure 30 does not detach. The adhesive could also be applied from the edges or from the back to minimize interference. Adhesive tape could also be applied from the back. In some variations, the structure 30 can be mechanically clamped in place, for example, by clamping an upper and a lower plastic part together.

[0040] The wetting area of ​​the liquid path 14 preferably comprises an oxide, a metal, or even a combination thereof. With reference to Fig. 8 The wetting area of ​​the liquid path 14 can be provided, for example, by a metal layer 21, such as palladium. Silicon oxide can also be used (it can be produced, for example, by thermal oxidation from a silicon substrate). However, it should be noted that both thermally grown (> 5 nm) and a native oxide (2 to 3 nm) that forms naturally on silicon (e.g., on a Si wafer) can be used as the wetting surface. Alternatively, wetting areas produced from a combination of metal and oxide structures can also be used. The oxide layer or the metal layer 21 can each be used as a mask for the formation of the black silicon. However, the use of metal is advantageous insofar as it can also be used as an electrode, for example, for liquid gating (i.e.,for controlling liquid wetting and / or flow in microchannels using electrical potentials), dielectrophoresis, or other types of electrical stimulation or detection. For example, in . Fig. 8 The cover structure 30 can be made from a 50 µm thick layer of a dry-film photoresist DF-1050 based on an epoxy resin or from a plastic material such as PMMA. The lateral spacer structures 20 can also be made from the same dry-film photoresist (with a thickness of 50 µm) that has been structured by photolithography, or from a double-sided adhesive tape that has been cut by a cutting tool or an electronic template cutter. The layer 21 can, for example, be a 50 nm thick layer of palladium that rests on a 200 nm thick SiO2 layer on the solid Si substrate 5.

[0041] It can be observed that a liquid flows much faster on wider hydrophilic patterns and can also follow a curved path. Both of these aspects are achieved within the scope of this disclosure. A surfactant in the solution can significantly increase the flow velocity. However, the liquid moves more in a lateral direction. Therefore, in solutions with surfactants, an additional lateral space can be advantageous, as shown in Fig. 8 illustrates.

[0042] According to another aspect, the present disclosure can also be embodied as a method for fabricating a microfluidic unit 1 as described above. Essentially, such a method involves fabricating a non-wetting region 16 on a first layer (e.g., a substrate) 5 (or even each of them), into which, for example, microchannel cavities have already been machined, and on a second layer 30, e.g., a cover structure 30 for the substrate 5, to form the non-wetting venting region 16. As noted previously, the non-wetting regions 16 can be fabricated on the cover structure 30 instead of on the layer supporting the channels. However, this can cause placement problems. In a preferred embodiment, the fabrication involves the extraction of black silicon to form the non-wetting region(s) 16.

[0043] In one embodiment, the wetting regions can be fabricated from SiO2. An example of a fabrication process is discussed herein. Assuming the substrate contains silicon, the latter can be oxidized to form an SiO2 layer. Subsequently, a portion of the SiO2 layer can be etched, and the etched area can be converted to black silicon to obtain the desired non-wetting regions. For the conversion to black Si, for example, a reactive ion etching procedure can be used, where the surrounding (unetched) area of ​​the SiO2 layer serves as a mask for the reactive ion etching process. It should be noted that etching SiO2 alone may not be sufficient to obtain a permanent non-wetting region.Silicon can be hydrophobic for a time, but a native oxide would likely form, making the surface hydrophilic again. Therefore, the Si areas (etched SiO2) can be converted to black Si using reactive ion etching, with the surrounding SiO2 layer acting as a mask. In some variations, a metal layer can be obtained as a liquid pathway, which can also serve as a mask.

[0044] The following describes a detailed manufacturing process 100 with regard to the unit of Fig. 14 and with reference to Fig.The process is described in Block 15. First, a silicon wafer is prepared as described in Block 104. The wafer is thermally oxidized to obtain a SiO2 layer, as described in Block 108. Photolithography is used to pattern the channel cavities (with a photoresist), as described in Block 112. Such photolithography steps typically include coating with a photoresist, firing, exposure, and development. Areas of the SiO2 layer are etched to obtain a mask for subsequent silicon etching, as described in Block 116. The photoresist can be removed, as described in Block 120. A self-limiting anisotropic Si (wet) etch can be performed to obtain the channel cavities, as described in Block 124. Subsequently, thermal oxidation is performed to obtain a SiO2 layer also within the channel cavities, as described in Block 128.Photolithographic applications are performed to prepare for the subsequent metal structuring, as described in Block 132, and then the metal structuring (Block 136) is carried out. Generally, metal structuring is optional. However, it can be advantageous for some applications, such as microfluidic applications that employ electrical sensing / control. Additional photolithographic steps are used to structure the non-wetting regions, as described in Block 140. One or more areas of the SiO2 layer are etched to create the non-wetting regions, as described in Block 144. It is advisable to proceed to partial sectioning at this stage to avoid contamination in a later phase, as described in Block 148. Note that a small amount of photoresist remains in the channel prior to sectioning to act as a protective layer for the channels.The photoresist can be removed, for example, by peeling it off, as shown in Block 152. The etched SiO2 (Si) areas are converted to black silicon to obtain the non-wetting areas, as shown in Block 156. Reactive ion etching can be used again for the conversion to black Si, with the surrounding (unetched) area of ​​the SiO2 / metal layer serving as a mask. The partially sectioned chip can then be separated, as shown in Block 160. Final assembly and packaging steps are performed, as shown in Block 164. Here, an adjacent structure can be placed, clamped, or glued on if required.

[0045] The above embodiments have been described with reference to the accompanying drawings, and a number of variations are possible. Several combinations of the above features can be considered, each offering different advantages. For example, two or more of the following features can be combined: - Pairs of non-wetting areas can be produced next to the microchannel sections; - The non-wetting areas can be made of black silicon. Black silicon provides "needle-like" structures that can potentially be reinforced by a thin fluorocarbon layer (also on the sidewalls) to make this layer highly hydrophobic; - The wetting areas can be made of Si / SiOx or a metal such as palladium. Aluminum can also be used, among other metals; - In silicon-based wafers, black silicon can also be applied to other areas, e.g., areas that come into contact with adjacent structures (such as a cover layer) to prevent leakage. In particular, black silicon can be structured between a cover structure and the top surface of the lateral walls of microchannels in such a way that, in addition to venting, it also prevents leakage. - A non-wetting area can extend between a lateral wall and the wetting flow path in such a way that a coexistence of an air quantity (in and on the black Si) and a liquid in the microchannels is created, and a hydrophilic flow path is formed between the lower and the upper cover layer in such a way that the microchannels are self-venting; Microfluidic structures can also be formed on the cover layer. Black silicon can serve as a non-wettable hydrophobic barrier between the substrate and the cover layer. For example, a microfluidic chip can be constructed from injection-molded plastic and sealed with a planar silicon cover that includes areas of black silicon, structured metal, sensors, etc. - Several liquids can mix at (closed or covered) branches without trapping air between them.

[0046] Some of the methods described herein can be used in the fabrication of microfluidic chips. The resulting chips can be distributed by the manufacturer as a raw wafer (that is, a single wafer containing multiple unpackaged chips that are already covered, for example, by a layer to seal a section of channels), as a bare chip (again, covered), or packaged. In the latter case, the chip is mounted in a single-chip package (such as on a plastic substrate) or in a multi-chip package. In each case, the chip can subsequently be integrated with other chips or other components.

[0047] Although the present invention has been described with reference to a limited number of embodiments, variants, and the accompanying drawings, it is apparent to those skilled in the art that various modifications can be made and similar elements can be exchanged without departing from the scope of the present invention. In particular, a (unit-like or process-like) feature mentioned in connection with a particular embodiment or variant, or illustrated in a drawing, can be combined with or replaced by another feature in a further embodiment, variant, or drawing without departing from the scope of the present invention. Accordingly, various combinations of the features described with respect to any of the above embodiments or variants can be considered that remain within the scope of the accompanying claims.Furthermore, numerous minor modifications can be made to adapt a particular situation or material to the teachings of the present invention without deviating from its scope. Therefore, the present invention is not intended to be limited to the specific embodiments disclosed, but rather to encompass all embodiments falling within the scope of the appended claims. Moreover, numerous other variants besides those expressly mentioned above can be considered. For example, materials other than silicon can be used as the base substrate. Black germanium, for instance, which can be obtained by a plasma etching process with a high aspect ratio and which also exhibits superhydrophobicity, can be used.Furthermore, structural patterns on plastics can be applied using hot stamping to adjust the wetting properties (hydrophobic, hydrophilic), and subsequently plasma polymerization or other surface coating techniques can be applied to plastic surfaces to make them superhydrophobic.

[0048] According to embodiments of the present disclosure, the present microfluidic unit is provided. The unit has one or more microfluidic channels, which are formed or hollowed out, for example, on a surface of the microfluidic unit. At least one section of a microfluidic channel is closed, i.e., the channel has a closed cross-sectional subsection in this section. The channel can, for example, be covered, at least in this subsection, by a covering structure such that this section is closed. This subsection has a fluid path formed by a wetting region and a non-wetting region extending along and adjacent to the fluid path such that a fluid is enclosed in the wetting region. To allow gas to be vented, the non-wetting region is further configured as a vent.Accordingly, the gas surrounding the liquid (e.g., air), which is flushed out when the liquid wets the liquid path and moves along it, can be vented through the venting made possible by the non-wetting area.

[0049] In the embodiments of the present disclosure, the above unit may exhibit one or more of the following features: - The non-wetting area is a first non-wetting area, and the section of the microfluidic channel further comprises a second non-wetting area extending along and adjacent to the fluid path opposite the first non-wetting area, and designed to provide a vent for the discharge of a gas along the second non-wetting area; - The wetting area of ​​the liquid path is formed by a lower wall between side walls arranged on each side of the liquid path, with the non-wetting area extending between one of the side walls and the liquid path; - The lateral canal walls may contain silicon; - The wetting area of ​​the fluid path is formed by at least a lower wall and a lateral wall of the microfluidic channel, and the non-wetting area extends along the lateral wall of the microfluidic channel and adjacent to it; - The microfluidic unit further has one or more unsealed sections, so that a gas can be vented during operation from the sealed section to the one or more unsealed sections along the non-wetting area; - The microfluidic unit further comprises two microfluidic channels, each such that the unit has two sealed channel sections, each having a fluid path formed by a wetting area and at least one non-wetting area designed to provide a vent, and one of the two channel sections leads at one end into another of the two channel sections, forming a branch of sealed channel sections; - The non-wetting area may contain black silicon; - The non-wetting area connects the fluid path with an adjacent structure; - The microfluidic unit may further have a structure that includes an area resting on the non-wetting area, the latter being designed to prevent fluid from escaping between the fluid path and the adjacent structure; - The wetting area of ​​the liquid path can consist of one of the following: an oxide; a metal; and a combination of a metal and an oxide; - The wetting area of ​​the liquid path may contain a metal, in this case palladium; - The microfluidic unit may further comprise two fluid paths separated by an identical non-wetting zone extending along and adjacent to each of the two fluid paths; - The section of the microfluidic channel may have a dead end; and - The unit could be a microfluidic chip.

[0050] For example, most of the embodiments described here utilize non-wetting vent zones that extend along the fluid path on each side of it. A non-wetting zone can extend, for instance, between a lateral wall and a lower (wetting) surface that forms the fluid path. In some variants, non-wetting zones can extend along lateral wetting walls of the microfluidic channel, e.g., on the upper surface of lateral structures. In this way, non-wetting zones can be provided at an interface with the cover structure. The channel cavities and the non-wetting zones can otherwise be machined or structured either in the base substrate (e.g., the wafer) or in the cover structure, or in both.Furthermore, the cover structure can have openings to allow for the pipetting of a liquid and the venting of purged gases. The non-wetting venting areas are advantageously made of black silicon, which offers numerous benefits not only for gas venting but also for joining surfaces and materials.

[0051] According to a further aspect, a method for operating a microfluidic unit is provided, as described, for example, in any of the embodiments above, wherein a liquid is caused to wet the fluid path and move along it, thereby flushing out any gas in the microfluidic channel such that the gas is emptied from the covered section along the non-wetting area. Prior to causing the liquid to wet the fluid path and move along it, the method preferably further comprises introducing the liquid through the one or more unsealed sections.

[0052] According to a final aspect, the present disclosure can also be embodied as a method for fabricating a microfluidic unit as described above. Such methods may, in particular, include: fabricating a non-wetting region on one or each of the following: a substrate and a covering structure for the substrate to form the non-wetting region.

[0053] The fabrication of the non-wetting region comprises the recovery of black silicon to form the non-wetting region. Preferably, the substrate comprises silicon, and the fabrication process further comprises: oxidizing the substrate to form a SiO2 layer on the substrate; etching a region of the SiO2 layer; and converting the etched regions into black silicon to obtain the non-wetting region, wherein a reactive ion etching procedure is used in the conversion of the etched regions, with the surrounding non-etched region of the SiO2 layer serving as a mask for the reactive ion etching procedure.

[0054] The descriptions of the various embodiments of the present invention are for illustrative purposes only and are not intended to be exhaustive or limited to the disclosed embodiments. Many modifications and variants are obvious to those skilled in the art without deviating from the scope and concept of the described embodiments. The terminology used herein has been chosen to best explain the basic concepts of the embodiments, their practical application, or the technical improvements over technologies available on the market, or to enable other skilled persons to understand the embodiments disclosed herein.

Claims

[1] Microfluidic unit (1) comprising: a substrate (5) defining a microfluidic channel (10) with a sealed section (12) having a sealed cross-section, wherein the sealed section has: a fluid path (14) formed by a wetting area; and a non-wetting area (16) extending along and adjacent to the liquid path (14), wherein the non-wetting area is designed to provide a vent for emptying a gas from the wetting area along the non-wetting area, wherein the non-wetting area comprises black silicon. [2] Microfluidic unit according to claim 1, wherein the non-wetting area is a first non-wetting area and the sealed section of the microfluidic channel further comprises a second non-wetting area extending along the fluid path and adjacent to it opposite the first non-wetting area, and the second non-wetting area is designed to provide a vent for emptying a gas from the wetting area along the second non-wetting area. [3] Microfluidic unit according to claim 1 or 2, wherein the wetting area of ​​the fluid path is formed by a lower wall (15) and between lateral walls (17) arranged on each side of the fluid path, wherein the non-wetting area extends between one of the lateral walls and the fluid path. [4] Microfluidic unit according to claim 3, wherein the side walls comprise silicon. [5] Microfluidic unit according to claim 1 or 2, wherein the wetting area of ​​the fluid path is formed at least by a lower wall and (15) a lateral wall (17) of the microfluidic channel (10) and the non-wetting area extends along the lateral wall (17) of the microfluidic channel (10) and adjacent thereto. [6] Microfluidic unit according to any one of claims 1 to 5, further comprising: one or more unsealed sections (18) so that a gas can be vented from the sealed section to the one or more unsealed sections along the non-wetting area. [7] Microfluidic unit according to claim 6, comprising several second microfluidic channels connected to the microfluidic channel, each of the second microfluidic channels comprising a sealed channel section, each of the several second microfluidic channels comprising a fluid path formed by a wetting region and at least one non-wetting region designed to provide a vent, and wherein the several second microfluidic channels are connected to the microfluidic channel at one end thereof in such a way as to form a branch (19) of sealed channel sections. [8] Microfluidic unit (60) according to claims 1 to 7, wherein the non-wetting area (16) closes the fluid path (62, 64; 62) with an adjacent structure (30). [9] Microfluidic unit (60) according to claim 8, further comprising: a structure (5) having a region which rests on the non-wetting region (16), the latter being designed to prevent liquid from escaping between the liquid path and the adjacent structure (30). [10] Microfluidic unit according to any one of claims 1 to 9, wherein the wetting area of ​​the fluid path comprises one of the following: an oxide; a metal; and a combination of a metal and an oxide. [11] Microfluidic unit according to any one of claims 1 to 10, wherein the wetting area of ​​the fluid path comprises a metal, wherein the metal is palladium. [12] Microfluidic unit according to any one of claims 1 to 11, further comprising: two fluid paths separated by a common non-wetting area, the common non-wetting area extending along and adjacent to each of the two fluid paths. [13] Microfluidic unit according to any one of claims 1 to 12, wherein the sealed section of the microfluidic channel has a dead end. [14] Microfluidic unit according to claims 1 to 13, wherein the microfluidic unit is a microfluidic chip. [15] Method for venting a microfluidic unit (1) comprising: Causing a liquid (25) to move along a wetting area on a liquid path (14) in such a way that a gas is flushed out in a microfluidic channel (10); and Venting the gas from a sealed section (12) of the microfluidic channel (10) along a non-wetting area extending along and adjacent to the fluid path, wherein the sealed section has a sealed cross-section and the non-wetting area comprises black silicon. [16] The method of claim 15, further comprising: before causing a liquid to move along the fluid path along the wetting area, the liquid is introduced through one or more unclosed sections (18) of the microfluidic channel. [17] Method according to one of claims 15 to 16, wherein the non-wetting area is a first non-wetting area and the method further comprises: Venting a gas from the wetting area along a second non-wetting area in a sealed section of the microfluidic channel, wherein the second non-wetting area extends along the fluid path and adjacent to it opposite the first non-wetting area. [18] Method according to any one of claims 15 to 17, wherein two liquid paths are separated by a common non-wetting area, the common non-wetting area extending along each of the two liquid paths and adjacent to them. [19] Method (100) for manufacturing a microfluidic unit (1) comprising: Forming a microfluidic channel (10) in a substrate (5), wherein the microfluidic channel has a sealed section (12) with a sealed cross-section; Forming a fluid path using a wetting area in the sealed section to allow a fluid to move along the wetting area on the fluid path; Forming (140, 144) a non-wetting area (16) in the sealed section, wherein the non-wetting area extends along and adjacent to the liquid path, wherein the non-wetting area is designed to provide a vent for the discharge of a gas from the wetting area along the non-wetting area; and Formation of black silicon as a non-wetting area. [20] The method of claim 19, further comprising: Creating a non-wetting area on one or each of the following: a substrate and a covering structure for the substrate to form the non-wetting area. [21] Method according to any one of claims 19 to 20, wherein the substrate comprises silicon, wherein the method further comprises: Oxidizing (104) the substrate so that a SiO2 layer is formed on the substrate; Etching (144) of an area of ​​the SiO2 layer; and Converting (156) the etched areas into black silicon such that the non-wetting area is obtained, wherein a reactive ion etching procedure is used in the conversion of the etched areas, wherein the surrounding non-etched area of ​​the SiO2 layer serves as a mask for the reactive ion etching procedure. [22] Method according to any one of claims 19 to 21, wherein the non-wetting area is a first non-wetting area and the method further comprises: Forming a second non-wetting area of ​​the sealed section of the microfluidic channel, wherein the second non-wetting area extends along the fluid path and is adjacent to it opposite the first non-wetting area, and the second non-wetting area is designed to provide a vent for the discharge of a gas from the wetting area along the second non-wetting area. [23] A method according to any one of claims 19 to 22, comprising: Separate two fluid paths by a common non-wetting area, wherein the common non-wetting area extends along and adjacent to each of the two fluid paths.

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