Receiving element for a microfluidic device for processing fluids, microfluidic device, and method for producing a receiving element
The microfluidic receiving element's structured upper and smooth lower recess design addresses filling challenges and cross-contamination issues, ensuring accurate biochemical reactions by minimizing capillary forces and maintaining reactants within each recess.
Patent Information
- Application Number
- PCT/EP2024/067576
- Authority / Receiving Office
- WO · WO
- Patent Type
- Applications
- Current Assignee / Owner
- Priority Date
- 2023-07-18
- Filing Date
- 2024-06-24
- Publication Date
- 2025-01-23
AI Technical Summary
Microfluidic devices face challenges in filling recesses due to pinning of liquids at recess edges, leading to air pockets, incomplete filling, and cross-contamination, which can result in incorrect diagnostics.
A microfluidic receiving element with a recess design featuring a structured upper section and a smooth lower section, where the upper section has a first edge with a specific structure and the lower section lacks structure, minimizing capillary forces and preventing liquid carryover between recesses.
The design enhances fillability and prevents cross-contamination, ensuring accurate biochemical reactions by maintaining the necessary reactants in each recess, thus reducing the risk of false positives or negatives.
Smart Images

Figure EP2024067576_23012025_PF_FP_ABST
Abstract
Description
[0001] Description
[0002] title
[0003] Receiving element for a microfluidic device for processing fluids, microfluidic device and method for producing a receiving element
[0004] State of the art
[0005] The approach presented here is based on a microfluidic receiving element for a microfluidic device for processing fluids, a microfluidic device and a method for producing a microfluidic receiving element according to the preamble of the independent claims.
[0006] Microfluidic analysis systems, so-called lab-on-chips (LoCs), enable automated, reliable, compact, and cost-effective processing of chemical or biological substances for medical diagnostics. By combining a variety of operations for targeted fluid manipulation, complex microfluidic process sequences can be realized.
[0007] An important component of such microfluidic analysis systems can be a receiving element. Small reaction chambers of the receiving element, referred to here as recesses, depressions, or cavities, can accommodate a liquid to be analyzed.
[0008] Revelation of the approach presented here
[0009] Against this background, the approach presented here presents a receiving element, a microfluidic device with a receiving element, and a method for producing a microfluidic receiving element according to the main claims. The measures listed in the dependent claims enable advantageous refinements and improvements of the device specified in the independent claim.
[0010] The microfluidic housing element presented here advantageously allows at least two different geometries to be implemented within a cavity in plan view. The cavity can be produced using a single process or through two or more individual lithographic steps.
[0011] A receiving element for a microfluidic device for processing fluids is presented. The receiving element has at least one recess for receiving a liquid or an aqueous solution. The receiving element is characterized in that an upper section of the recess facing an upper side of the recess has a first edge with a first structure having a first structural depth, and a lower section of the recess facing an underside of the recess has a second edge without a structure or with a second structure having a second structural depth. The second structural depth of the second structure is less than the first structural depth of the first structure.
[0012] The microfluidic device can also be referred to as a microfluidic cartridge or a lab-on-chip cartridge. Processing of the microfluidic device and the analysis of a sample received by the microfluidic device can take place in a compact analytical device. The receiving element can be an insert element that can be inserted into a base body of the microfluidic device. Alternatively, the receiving element can represent a section of the microfluidic device. The recess can, for example, be formed as a blind hole. The upper section and the lower section of the recess can directly border one another. The edges can represent sections of the circumferential inner wall of the recess. The lower section can be larger than the upper section with respect to an extension direction parallel to the longitudinal axis of the recess.The upper section can be more deeply structured than the lower section. The depth of the structure can be understood as an extension perpendicular to the longitudinal axis of the recess.
[0013] The recess can also be referred to as a depression or cavity, and can be incorporated as reaction chambers in a ceramic or semiconductor substrate of the receiving element and filled with, for example, reagents. A liquid to be analyzed can be flushed through a plurality of recesses to fill them and bring them into contact with the reagents and / or reaction partners. The individual recesses can then be fluidically separated from one another, and different detection reactions can run in parallel in different recesses.
[0014] However, the geometries of the recesses can pose a challenge, as round recesses often show pinning of the liquid front to the edge of the recess or flow around the recess when flowing over it. This can lead, for example, to air pockets and / or incompletely filled recesses, or the filling process can require increased pressure that cannot typically be provided. Jags or corners, which are intended to improve filling, can also pose a challenge if the sharp jags or corners, albeit possibly with slight rounding, extend to the bottom of the recess. This can cause liquid, for example reagents previously deposited or spotted there, to be drawn upwards by capillary force and discharged from the recess in one filling process.However, by structuring the upper and lower sections differently, it is possible to prevent liquids, such as reagents previously deposited or spotted there, from being drawn upwards into the prongs or corners at the bottom of the recess due to capillary forces. The capillary forces and / or the height to which the liquid can be drawn upwards can depend on the radius of curvature of the prongs or corners - specifically, the smaller the radius of curvature, the greater the force. The approach presented here can prevent substances drawn upwards from being picked up and transported into neighboring recesses when another liquid, such as the sample liquid, flows over the recesses. By avoiding such carryover, cross-contamination can be avoided, so that subsequent diagnostics do not lead to incorrect diagnostics.By avoiding cross-contamination, it is possible, for example, to prevent a chemical and / or biochemical reaction from failing to proceed in a cavity because a reactant is no longer present or no longer present in the required amount, and / or because an additional reactant, for example, from an adjacent cavity, is present that can inhibit, i.e., hinder, a reaction. Furthermore, it is possible to prevent an incorrect reaction from occurring in a cavity because, in particular, a chemical other than the original one may be present in that cavity. All of this can lead to a malfunction, for example, a false positive or false negative.
[0015] The approach disclosed here includes a new arrangement for the production of cavities or depressions, which can combine the advantages of good fillability through an adapted geometry with minimised carryover.
[0016] According to one embodiment, the first structure can be formed by a plurality of slots. This offers the advantage of facilitating the filling behavior and filling of the recess with a liquid.
[0017] According to one embodiment, a cross-section of the plurality of slots can be shaped as a prong and / or corner and / or triangle and / or rectangle. Such shapes facilitate filling the recess.
[0018] According to one embodiment, a longitudinal extension direction of the plurality of slots can be aligned parallel to the longitudinal axis of the recess along the first edge. The longitudinal extension directions can characterize a course of the slots between the upper side of the recess and the lower section of the recess. According to such an embodiment, the receiving element can be realized in a simple manner from a manufacturing perspective.
[0019] According to one embodiment, the plurality of slots can extend radially or parallel to one another into the first edge. Thus, the slots can be adapted to the flow direction of a liquid to be received by the recess.
[0020] According to one embodiment, a first partial region of the first edge can have the first structure and a second partial region of the first edge can be formed without a structure. In other words, the structure, which can also be referred to as geometry, of the first edge, which can also be called the upper edge, can be different on one side of a fluidic inflow than on an outlet side of the depression, i.e. the recess. This offers the advantage that the filling behavior and the filling of the recess with a liquid can be promoted. In the second partial region of the first edge without a structure, the capillary pressure can decrease and liquids in the depression can be drawn upwards at a lateral edge to a lesser extent or not at all.
[0021] According to one embodiment, the first partial region and the second partial region can each extend halfway over a circumference of the upper section. In other words, the structure, which can also be referred to as geometry, of the first edge, which can also be called the upper edge, can be different on one side of a fluid inflow than on an outlet side of the depression, i.e. the recess. This offers the advantage that the filling behavior and the filling of the recess with a liquid can be promoted. In the second partial region of the first edge without a structure, the capillary pressure can decrease and liquids in the depression can be drawn upwards at a lateral edge to a lesser extent or not at all.
[0022] According to one embodiment, an upper diameter of the upper section can be smaller than a lower diameter of the lower section. In this case, an upper cross-sectional area of the upper section can be smaller in area than a lower cross-sectional area of the lower section. In this embodiment, the deeper part, i.e., the lower section, of the depression could have no continuous capillaries apart from the recess forming the depression, i.e., no capillarity greater than the capillarity of the large, round recess. Accordingly, liquids that are stored in this deeper, i.e., lower-lying, part can preferably not be drawn upwards.
[0023] According to one embodiment, the diameter of the upper section can be in a range between one micrometer and one millimeter. For example, the diameter can be selected according to the quantity or viscosity of the liquid to be collected, or according to the design or resolution of a readout optic.
[0024] According to one embodiment, a radius of curvature of the plurality of slots can be smaller than a radius of curvature of the recess. In particular, the radius of curvature of the plurality of slots can be less than one-tenth or less than one-twentieth of the radius of curvature of the recess. This can prevent a larger portion of a liquid from accumulating in the plurality of slots than in the recess, which could mean that the liquid is no longer available for further analysis.
[0025] According to one embodiment, the first structure can be formed by at least one hundred slots. This allows for a very finely structured structure.
[0026] According to one embodiment, the first structure depth can be in a range between one micrometer and one hundred micrometers. The dimension can advantageously be selected according to the requirements of an analysis to be performed.
[0027] According to one embodiment, the upper section can be formed in an upper half, an upper quarter, or an upper tenth of the recess. In this embodiment, the deeper part of the depression can have no continuous capillaries. Accordingly, liquids present in this deeper part could preferably not be drawn upwards. The larger the proportion of the deeper part that has no continuous capillaries, i.e., the lower section, compared to the upper section having the first structure, the less liquids held in the deeper part can be drawn upwards.
[0028] In addition, a microfluidic device for processing fluids is presented, using a variant of the previously presented microfluidic receiving element. The device can be, for example, a lab-on-chip cartridge. The combination of the microfluidic device with the receiving element has the advantage that many of the previously described advantages for processing a fluid or for analyzing sample components dissolved in the fluid can be optimally implemented. In particular, the advantages of good fillability can be combined with an adapted geometry, i.e., structure, while simultaneously minimizing carryover and optimizing analysis processes. In this way, the efficiency of a biochemical detection reaction carried out in a recess can be increased.
[0029] In addition, a method for producing a variant of the previously presented microfluidic receiving element is presented. The method comprises a step of providing a substrate and a step of applying a first mask to the substrate, wherein the first mask defines the first edge of the recess. The method also comprises a step of removing a first material in a first free region of the substrate not covered by the first mask by means of reactive ion deep etching in order to form the upper section of the recess. Furthermore, the method comprises a step of applying a second mask to the substrate, wherein the second mask covers the first edge of the recess and defines the second edge of the recess.The method further comprises a step of removing a second material in a second free region of the substrate not covered by the second mask by means of reactive ion deep etching in order to form the lower section of the recess. According to one embodiment, the method can be stopped in the step of removing the second material before reaching the target depth, and another process can be started, which, for example, removes material using a different method—for example, isotropic XeF2 or SF6 plasma for etching Si. By previously passivating the side edges of the recess, the previously introduced recess geometry can be protected. This offers the advantage that recesses can be produced in which a cross-section or cross-sectional area of the recess can change.
[0030] Examples of the approach presented here are shown in the drawings and explained in more detail in the following description. It shows:
[0031] Fig. 1 is a schematic cross-sectional view of a microfluidic device according to an embodiment;
[0032] Fig. 2 is a schematic cross-sectional view of an embodiment of a microfluidic receiving element with a recess;
[0033] Fig. 3 is a schematic plan view of an embodiment of a microfluidic receiving element with a recess;
[0034] Fig. 4 is a schematic plan view of an embodiment of a microfluidic receiving element with a recess;
[0035] Fig. 5 is a schematic plan view of an embodiment of a microfluidic receiving element with a recess;
[0036] Fig. 6 is a schematic plan view of an embodiment of a microfluidic receiving element with a recess;
[0037] Fig. 7 is a schematic top view of an embodiment of a microfluidic receiving element with a recess; Fig. 8 is a schematic top view of an embodiment of a microfluidic receiving element with a recess;
[0038] Fig. 9 is a schematic plan view of an embodiment of a microfluidic receiving element with a recess;
[0039] Fig. 10 is a schematic plan view of an embodiment of a microfluidic receiving element with a recess;
[0040] Fig. 11 is a schematic plan view of an embodiment of a microfluidic receiving element with a recess;
[0041] Fig. 12 is a schematic plan view of an embodiment of a microfluidic receiving element with a recess;
[0042] Fig. 13 is a schematic cross-sectional view of an embodiment of a microfluidic receiving element with a recess;
[0043] Fig. 14 is a microscopic top view of an embodiment of a microfluidic receiving element with a recess;
[0044] Fig. 15 is a microscopic top view of an embodiment of a microfluidic receiving element with a recess;
[0045] Fig. 16 is a microscopic top view of an embodiment of a microfluidic receiving element with a recess;
[0046] Fig. 17 is a schematic cross-sectional view of a microfluidic receiving element with a recess;
[0047] Fig. 18 is a schematic cross-sectional view of a microfluidic receiving element with a recess;
[0048] Fig. 19 is a perspective microscope view of an embodiment of a microfluidic receiving element with a recess; Fig. 20 is a flowchart of a method for producing a receiving element according to an embodiment;
[0049] Fig. 21 is a schematic cross-sectional view of a method for producing a receiving element according to an embodiment; and
[0050] Fig. 22 is a schematic cross-sectional view of an embodiment of a microfluidic receiving element with a recess.
[0051] In the following description of advantageous embodiments of the approach presented here, the same or similar reference numerals are used for the elements shown in the various figures and having a similar effect, whereby a repeated description of these elements is omitted.
[0052] Fig. 1 shows a schematic cross-sectional view of a microfluidic device 100 according to one embodiment. The device 100 is used to process fluids and thus, for example, substances dissolved in a fluid. For this purpose, the device 100 comprises a microfluidic receiving element 110, which in this embodiment is arranged on a flow cell 105. According to one embodiment, the receiving element 110 has a thickness of up to two millimeters. Furthermore, the receiving element 110 comprises a recess 115 for receiving at least one liquid, in particular a reagent and / or an aqueous solution, i.e., a sample liquid.
[0053] In this exemplary embodiment, the receiving element 110 comprises, merely by way of example, in addition to the recess 115, a second recess 135, as well as, merely by way of example, a third recess 140, a fourth recess 142, a fifth recess 144, and a sixth recess 146. All recesses 115, 135, 140, 142, 144, 146 are arranged in a plane of an upper side 130 of the receiving element 110. Optionally, all recesses 115, 135, 140, 142, 144, 146 are identical in shape and size. The recesses 115, 135, 140, 142, 144, 146 are formed as blind holes, thus each having a bottom. The number of recesses shown 115, 135, 140, 142, 144, 146 is only an example.
[0054] The illustrated receiving element 110, or a similar receiving element, is an important component of microfluidic analysis systems. Small reaction chambers of the receiving element 110, i.e., the recesses 115, 135, 140, 142, 144, 146, can accommodate the fluids to be analyzed, for example.
[0055] Fig. 2 shows a schematic cross-sectional view of an embodiment of a microfluidic receiving element 110 with a recess 115. The recess 115 is designed to receive at least one liquid. The recess 115 is shaped as a blind hole, thus having a bottom.
[0056] An upper section 205 of the recess 115, facing an upper side 200 of the recess 115, has a first edge 210. The first edge 210 represents a region of an inner wall of the recess 115 facing the upper side 200. A lower section 220 of the recess 115, facing a lower side 215 of the recess 115, has a second edge 225. According to one exemplary embodiment, the lower section 220 is formed without a structure, thus having a smooth surface. The second edge 225 represents a region of the inner wall of the recess 115 facing away from the upper side 200.
[0057] According to one embodiment, the first edge 210 is straight and the second edge 225 is concave. For example, the upper section 205 is at least approximately cylindrical or slightly flared downwards and rearwards, e.g., at an angle deviating from 90° by 0-4°, and the lower section 220 is curved.
[0058] According to one embodiment, an upper diameter 230 of the upper portion 205 is smaller than a lower diameter 235 of the lower portion 220. According to one embodiment, the upper diameter 230 may be in a range between one micrometer and one millimeter.
[0059] According to one embodiment, a depth 240 of the recess 115 may be in a range between a few micrometers and several hundred micrometers.
[0060] According to one embodiment, the upper portion 205 may correspond approximately to an upper half of the recess 115, such that the upper portion 205 and the lower portion 220 each extend approximately over half of the depth 240.
[0061] Recess 115 represents a depression with a variable cross-section. Two processes—referred to here as Process 1 and Process 2—can be used consecutively for its production. This allows a depression to be produced in which the cross-section changes with depth. Alternatively, more than two processes or just one process with at least one process parameter that varies with time / etch depth can be used.
[0062] According to one embodiment, various trenching processes or etching processes are used. According to one embodiment, a mask layout is projected into the depth by material removal. Before reaching the target depth, for example, the process is stopped and another process is started, which removes material using a different method—for example, isotropic XeF2 for etching Si. For example, an introduced recess geometry can be protected by prior passivation of the side edges.
[0063] Figures 3 to 12 show exemplary embodiments of a mask layout for structuring depressions for holding liquids as part of a holding unit for lab-on-chip applications. The mask layout can be transferred to the wafer with approximately true structure and thus also represent the top view of the depressions on the wafer surface. The geometry of the upper edge of the depressions in plan view can deviate from the geometry of a complete circle, but can also have a circular shape on one side, for example. The structuring of the upper edge required for improved filling can have spikes or triangles or rectangles with dimensions from 1 micrometer to 100 micrometers, which are aligned perpendicularly or radially to the circular shape. The spikes / corners are, for example, only present in the upper half, better only in the upper quarter, even better only in the upper tenth of the depressions.as corners / spikes. Spikes / corners are structures whose radius of curvature is significantly smaller than that of the entire recess, for example, less than one-fifth. The geometry of the upper edge can therefore be provided with spikes / corners on the fluid inflow side and thus be different from that on the outlet side of the recess, which has no structure.
[0064] Fig. 3 shows a schematic plan view of an embodiment of a microfluidic receiving element with a recess 115.
[0065] The recess 115 has a first partial region 300 of the first edge 210 arranged halfway around the recess 115, said first portion comprising a first structure 305 having a first structure depth 302. The first structure 305 is formed by a plurality of slots 310, of which only one is provided with a reference numeral for the sake of clarity. The plurality of slots 310 extend parallel to a longitudinal axis 315 of the recess 115 along the first edge 210, as shown, for example, in Fig. 17 or 19. According to one embodiment, the plurality of slots 310 are formed by a plurality of triangles. According to one embodiment, a distance between adjacent slots 310 is always the same. The structure depth 302 of each of the slots 310 corresponds approximately to a distance between adjacent ones of the slots 310. The first edge 210 furthermore has a second partial region 320 without a structure.
[0066] A radius of curvature of the plurality of triangles is smaller than a radius of curvature of the recess 115. According to one embodiment, the radius of curvature of the plurality of triangles is smaller than one-fifth of the radius of curvature of the recess 115. According to one embodiment, the slots 310 extend radially into the first edge 210 of the recess 115 relative to a center point of the recess 115. Optionally, the slots 310 have the same structure depth 302.
[0067] Fig. 4 shows a schematic top view of an embodiment of a microfluidic receiving element with a recess 115.
[0068] The recess 115 has the first edge 210 with the first structure 305 having the first structure depth 302. The first structure 305 is formed by the plurality of slots 310. The plurality of slots 310 extend parallel to the longitudinal axis 315 of the recess 115 along the first edge 210. According to one embodiment, the plurality of slots 310 can be formed by a plurality of triangles, in particular by radially arranged triangles. For example, a length of a bottom side of such a triangle can be 2 micrometers and a height of the triangle can be 5 micrometers.
[0069] The radius of curvature of the majority of triangles is smaller than the radius of curvature of the recess 115. According to one embodiment, the radius of curvature of the majority of triangles may be smaller than one-fifth of the radius of curvature of the recess 115.
[0070] According to one embodiment, the first structure 305 may be formed by at least one hundred slots 310.
[0071] According to one embodiment, adjacent slots 310 directly adjoin one another.
[0072] According to one embodiment, the slots 310 extend radially into the first edge 210 of the recess 115 relative to a center point of the recess 115. Optionally, the slots 310 have the same structural depth 302. Fig. 5 shows a schematic top view of an embodiment of a microfluidic receiving element with a recess 115.
[0073] The recess 115 has the first edge 210 with the first structure 305 having the first structure depth 302. The first structure 305 is formed by the plurality of slots 310. The plurality of slots 310 extend parallel to the longitudinal axis 315 of the recess 115 along the first edge 210. According to one embodiment, the plurality of slots 310 can be formed by a plurality of triangles, in particular by radially arranged triangles. For example, the length of the bottom side of such a triangle can be 5 micrometers and the height of the triangle can be 5 micrometers.
[0074] The radius of curvature of the majority of triangles is smaller than the radius of curvature of the recess 115. According to one embodiment, the radius of curvature of the majority of triangles may be smaller than one-fifth of the radius of curvature of the recess 115.
[0075] According to one embodiment, the slots 310 extend radially into the first edge 210 of the recess 115 relative to a center point of the recess 115. Optionally, the slots 310 have the same structural depths 302.
[0076] Fig. 6 shows a schematic top view of an embodiment of a microfluidic receiving element with a recess 115.
[0077] The recess 115 has the first edge 210 with the first structure 305 having the first structure depth 302. The first structure 305 is formed by the plurality of slots 310. The plurality of slots 310 extend parallel to the longitudinal axis 315 of the recess 115 along the first edge 210. According to one embodiment, the plurality of slots 310 can be formed by a plurality of triangles, in particular by radially arranged triangles. For example, the length of the underside of such a triangle can be 5 micrometers and the height of the triangle 20 micrometers. The radius of curvature of the plurality of triangles is smaller than the radius of curvature of the recess 115. According to one embodiment, the radius of curvature of the plurality of triangles can be smaller than one-fifth of the radius of curvature of the recess 115.
[0078] According to one embodiment, the slots 310 extend radially into the first edge 210 of the recess 115 relative to a center point of the recess 115. Optionally, the slots 310 have the same structural depths 302.
[0079] Fig. 7 shows a schematic plan view of an embodiment of a microfluidic receiving element with a recess 115.
[0080] The recess 115 has the first edge 210 with the first structure 305 having the first structure depth 302. The first structure 305 is formed by the plurality of slots 310. The plurality of slots 310 extend parallel to one another along the first edge 210. According to one embodiment, the plurality of slots 310 can be formed by a plurality of triangles, in particular by vertically arranged triangles. For example, the length of the bottom side of such a triangle can be 5 micrometers and the height of the triangle can be 20 micrometers.
[0081] According to one embodiment, the slots 310 extend parallel to each other into the first edge 210 of the recess 115.
[0082] Optionally, the slots 310 have different structural depths 302. For example, a slot 310 oriented perpendicular to the course of the first edge 210 has the greatest depth, and a slot 310 oriented almost parallel to the course of the first edge 210 has the smallest depth. The depth of the remaining slots 310 decreases continuously, for example, starting from the slot with the greatest depth.
[0083] Fig. 8 shows a schematic top view of an embodiment of a microfluidic receiving element with a recess 115. The recess 115 has the first edge 210 with the first structure 305 having the first structure depth 302. The first structure 305 is formed by the plurality of slots 310. The plurality of slots 310 extend parallel to the longitudinal axis 315 of the recess 115 along the first edge 210. According to one embodiment, the plurality of slots 310 can be formed by a plurality of rectangles, in particular by radially arranged rectangles. For example, a length of a bottom side of such a rectangle can be 2 micrometers and a height of the rectangle can be 5 micrometers.
[0084] According to one embodiment, the slots 310 extend radially into the first edge 210 of the recess 115 relative to a center point of the recess 115. Optionally, the slots 310 have the same structural depths 302.
[0085] Fig. 9 shows a schematic plan view of an embodiment of a microfluidic receiving element with a recess 115.
[0086] The recess 115 has the first edge 210 with the first structure 305 having the first structure depth 302. The first structure 305 is formed by the plurality of slots 310. The plurality of slots 310 extend parallel to the longitudinal axis 315 of the recess 115 along the first edge 210. According to one embodiment, the plurality of slots 310 can be formed by a plurality of rectangles, in particular by radially arranged rectangles. For example, the length of the bottom side of such a rectangle can be 2 micrometers and the height of the rectangle can be 20 micrometers.
[0087] The radius of curvature of the majority of rectangles is smaller than the radius of curvature of the recess 115. According to one embodiment, the radius of curvature of the majority of rectangles can be smaller than one-fifth of the radius of curvature of the recess 115. According to one embodiment, the slots 310 extend radially into the first edge 210 of the recess 115 relative to a center point of the recess 115. Optionally, the slots 310 have the same structure depth 302.
[0088] Fig. 10 shows a schematic plan view of an embodiment of a microfluidic receiving element with a recess 115.
[0089] The recess 115 has the first edge 210 with the first structure 305 having the first structure depth 302. The first structure 305 is formed by the plurality of slots 310. The plurality of slots 310 extend parallel to the longitudinal axis 315 of the recess 115 along the first edge 210. According to one embodiment, the plurality of slots 310 can be formed by a plurality of rectangles, in particular by radially arranged rectangles. For example, the length of the bottom side of such a rectangle can be 4 micrometers and the height of the rectangle can be 5 micrometers.
[0090] The radius of curvature of the majority of rectangles is smaller than the radius of curvature of the recess 115. According to one embodiment, the radius of curvature of the majority of rectangles may be smaller than one-fifth of the radius of curvature of the recess 115.
[0091] According to one embodiment, the slots 310 extend radially into the first edge 210 of the recess 115 with respect to a center point of the recess 115.
[0092] Fig. 11 shows a schematic top view of an embodiment of a microfluidic receiving element with a recess 115. Optionally, the slots 310 have the same structure depths 302.
[0093] The recess 115 has the first edge 210 with which the first structure depth
[0094] 302. The first structure 305 is formed by the plurality of slots 310. The plurality of slots 310 extend parallel to the longitudinal axis 315 of the recess 115 along the first edge 210. According to one embodiment, the plurality of slots 310 can be formed by a plurality of rectangles, in particular by radially arranged rectangles. For example, the length of the bottom side of such a rectangle can be 4 micrometers and the height of the rectangle can be 10 micrometers.
[0095] The radius of curvature of the majority of rectangles is smaller than the radius of curvature of the recess 115. According to one embodiment, the radius of curvature of the majority of rectangles may be smaller than one-fifth of the radius of curvature of the recess 115.
[0096] According to one embodiment, the slots 310 extend radially into the first edge 210 of the recess 115 relative to a center point of the recess 115. Optionally, the slots 310 have the same structural depths 302.
[0097] Fig. 12 shows a schematic plan view of an embodiment of a microfluidic receiving element with a recess 115.
[0098] The recess 115 has the first edge 210 with the first structure 305 having the first structure depth 302. The first structure 305 is formed by the plurality of slots 310. The plurality of slots 310 extend parallel to one another along the first edge 210. According to one embodiment, the plurality of slots 310 can be formed by a plurality of rectangles, in particular by vertically arranged rectangles. For example, the length of the bottom side of such a rectangle can be 4 micrometers and the height of the rectangle can be 10 micrometers.
[0099] According to one embodiment, the slots 310 extend parallel to each other into the first edge 210 of the recess 115. Optionally, the slots 310 have different structural depths 302.
[0100] For example, a slot 310 oriented perpendicular to the first edge 210 has the greatest depth, and a slot 310 oriented almost parallel to the first edge 210 has the least depth. The depth of the remaining slots 310 decreases continuously, for example, starting from the slot with the greatest depth.
[0101] As a summary of Figures 3 to 12, it should be noted that these figures each depict a layout and / or structuring of the upper edge of a recess. Figures 3 to 12 each show a microsection analysis of Multi-Well Design V2 and a nomenclature of new well designs.
[0102] Fig. 13 shows a schematic cross-sectional view of an embodiment of a recess 115 of a microfluidic receiving element 110. The receiving element 110 thus has at least one recess 115 for receiving at least one liquid. This recess 115 is formed as a blind hole.
[0103] According to one embodiment, the upper portion 205 extends only over an upper quarter of the recess 115.
[0104] The upper diameter 230 of the upper section 205 is smaller than the lower diameter 235 of the lower section 220.
[0105] Cutting lines at different heights are marked, where, for example, a height h1 corresponds to a depth of 0 micrometers, a height h2 to a depth of 100 micrometers and a height h3 to a depth of 150 micrometers.
[0106] The following Figures 14, 15, and 16 each illustrate a structure of the edge of the recess 115 at the different heights h1, h2, and h3 of the recess 115. Figures 14, 15, and 16 show micrographs through an exemplary embodiment of a separated recess, wherein the cross-section of the recess changes with the depth of the recess. For example, the depth of the first structure decreases continuously starting from the opening of the recess 115 and thus transitions smoothly into the second structure.
[0107] Fig. 14 shows a microscopic top view of an embodiment of the recess 115 shown in Fig. 13 at the height h1 shown in Fig. 13. The first structure 305 is formed by the plurality of slots 310. The plurality of slots 310 extend along the first edge 210. According to one embodiment, the plurality of slots 310 can form a plurality of triangles in the cross section shown, in particular radially arranged triangles.
[0108] The radius of curvature of the majority of triangles is smaller than the radius of curvature of the recess 115. According to one embodiment, the radius of curvature of the majority of triangles may be smaller than one-fifth of the radius of curvature of the recess 115.
[0109] A structural depth of the plurality of slots 310 corresponds to an extension of the plurality of slots 310 perpendicular to the longitudinal axis of the recess, i.e. in the plane shown in Fig. 14.
[0110] Fig. 15 shows a microscopic top view of an embodiment of the recess 115 shown in Fig. 13 at the height h2 shown in Fig. 13. The first structure has a rounded edge compared to the first structure shown in Fig. 14, so that the structure is rounded compared to the first structure shown in Fig. 14. The rounded structure can be considered an intermediate structure between the first structure shown in Fig. 14 and a second structure shown in the subsequent Fig. 16.
[0111] Fig. 16 shows a microscopic top view of an embodiment of the recess 115 shown in Fig. 13 at the height h3 shown in Fig. 13. Compared to the rounded edge shown in Fig. 15, the recess 115 has an even more rounded edge at the height h3 shown in Fig. 13, with a structure that is even more rounded compared to the structure shown in Fig. 15. According to one embodiment, this even more rounded structure already corresponds to the second structure 1600, which has a second structure depth 1602 that is less than the structure depth of the first structure.
[0112] To produce the recess 115 shown in Figures 13 to 16, for example, the two-dimensional shape of a mask or the upper edge is projected into the depth using a trenching process, thus exposing the final depression. The trenching process can be controlled in such a way that the structural fidelity of the upper mask decreases with increasing process duration or trench depth, causing the structures to become blurred at greater depths and the corners and points to become rounded. As the process continues, they disappear completely, for example, and the shape of the depression, in particular, approaches the shape of a circle. The control of the trenching process can be specifically selected so that the trench becomes increasingly wider towards the bottom. The larger the dimensions of the points, the greater this widening should be in order to achieve sufficient rounding.One possible parameter could be the duration of the isotropic SF6 etching step. A longer duration can lead to greater broadening.
[0113] By rounding the fine corners, the capillary pressure decreases and any liquids in the recess are drawn upwards at the side edge less strongly or not at all.
[0114] Fig. 17 shows a schematic cross-sectional view of a microfluidic receiving element with a recess 115. The recess 115 contains a liquid 1700 in the lower section 220, which, due to capillary forces, is drawn upwards in a lateral region around the recess 115 toward the upper section 205. The capillary forces occur due to capillaries in the lateral region of the recess 115. In other words, Fig. 17 shows a simulation of the capillary action of liquids in fine edges of a structured recess.
[0115] The prongs or corners of the upper mask shape can improve the filling behavior of the liquid 1700, but can also lead to capillary pressure for liquids that come into contact with these edges.
[0116] According to one embodiment, the cross-sectional area of the lower region can be smaller or the same size as the cross-sectional area of the upper region. The diameter of the second and deeper part of the cavity can range from several micrometers to several hundred micrometers. In particular, the depth of the lower partial region should be designed such that volumes of reagents introduced into the depressions can be completely absorbed by this partial region. The cross-sectional geometry, here the top view, can be round or circular. Optional structures on the circular surface can be dimensioned in the range of a few micrometers, for example approximately 0.5 micrometers to 10 micrometers. In particular, the structures should be designed such that the structure disappears or is washed out in the depth of the depression.
[0117] Fig. 18 shows a schematic cross-sectional view of a microfluidic receiving element with a recess 115. The lower section 220 of the recess 115 has a round cross-section merely as an example. In this lower section 220, the recess 115 contains the liquid 1700, which, due to the almost nonexistent capillary forces, only slightly moves upwards in the lateral region around the recess 115 toward the upper section 205.
[0118] In other words, Fig. 18 shows a simulation of the capillary action of liquids in an unstructured, i.e., round, depression. According to one embodiment, the deeper part of the depression can be manufactured in such a way that no continuous capillaries are present in the lateral region of the depression, and accordingly, any liquids present in this deeper part of the depression are not, or only barely, drawn upwards in the lateral region.
[0119] Figures 17 and 18 thus illustrate, in the form of fluidic simulations, the effects of fine edges on the capillary action of liquids in the recesses.
[0120] Fig. 19 shows a perspective electron microscope view of an embodiment of a microfluidic receiving element 110 with a recess 115. According to one embodiment, the recess 115 has a diameter of just under 400 micrometers. The recess 115 represents a fully processed depression with a variable cross-section.
[0121] As an example, Fig. 19 shows an SEM image, i.e. an image generated using a scanning electron microscope, of a depression in silicon, or Si for short, with a variable cross-section, i.e. the structure of the depression changes with increasing depth.
[0122] Fig. 20 shows a flow diagram of a method 2000 for producing a receiving element according to an embodiment. The method 2000 comprises a step 2005 of providing a substrate and a step 2010 of applying a first mask to the substrate. The first mask defines a first edge of the recess. The method 2000 further comprises a step 2015 of removing a first material in a first free region of the substrate not covered by the first mask by means of reactive ion deep etching in order to form an upper section of the recess. The method 2000 further comprises a step 2020 of applying a second mask to the substrate. The second mask covers the first edge of the recess and defines a second edge of the recess.In addition, the method 2000 includes a step 2025 of removing a second material in a second free region of the substrate not covered by the second mask by means of reactive ion deep etching in order to form a lower portion of the recess. According to one embodiment, the method 2000 can be stopped in step 2025 of removing the second material before reaching the target depth, and a step 2030 of alternative removal, and thus a further process, can be started, which, for example, removes material using a different method—for example, isotropic XeF2 or isotropic SF6 plasma for etching Si. By prior passivation of the side edges of the recess, the previously introduced recess geometry can be protected.
[0123] Fig. 21 shows a schematic cross-sectional illustration of the method 2000 for producing a receiving element 110 according to an exemplary embodiment, described in more detail in Fig. 20. In step 2005 of providing, a substrate 2100, for example a silicon wafer, is provided. In step 2010 of applying, a first mask 2105—alternatively called lithography 1—is applied to the substrate 2100. In step 2015 of removing, a first material is removed in a first free region 2110 of the substrate 2100 not covered by the first mask 2105, for example by means of reactive ion deep etching, in order to form an upper section 205 of a plurality of recesses 115. In step 2020 of applying, a second mask 2115—alternatively called lithography 2—is applied to the substrate 2100. Here, the second mask 2115 covers a first edge 210 of the recess 115 and defines a second edge 225 of the recess 115.In the removal step 2025, a second material is removed in a second free area 2120 of the substrate 2100 not covered by the second mask 2115, for example, by means of reactive ion deep etching, in order to form a lower portion 220 of the recess 115. The manufactured receiving element 110 has a thickness of up to one millimeter, merely by way of example.
[0124] Recesses produced using the method 2000 described above exhibit optimized filling behavior due to the structure of the upper level. According to one exemplary embodiment, the circular cross-sectional area of the deeper part of the recess—also called the lower sub-region—can be free of continuously vertical cavities with a small radius of curvature. A small radius of curvature can be understood as a smaller radius of curvature than the radius of curvature of the circle defining the lower sub-region. Such cavities could cause liquid to leak out due to capillary forces, which is to be avoided. Thus, the process described above, i.e., the method 2000 described above, can represent a solution to a potential challenge of a conventional, similar process.
[0125] As a further possibility, using a mask (= the shape of the recesses in plan view on the wafer surface), the prongs and corners can be washed out in depth using a typical Bosch etching process, or Bosch process for short. For this purpose, the prongs and corners on the wafer surface should have dimensions of less than 20 micrometers, or less than 10 micrometers so that the prongs and corners can be sufficiently rounded by a typical Bosch etching process—for example, with an etch flank angle deviating from 90 degrees by 2 to 3 degrees.
[0126] Alternatively, Fig. 21 illustrates a process flow for producing cavities with variable cross-section using a 2-mask process.
[0127] The creation of cavities with a high aspect ratio in semiconductor substrates – for example, Si – can be achieved through trenching processes, specifically through reactive ion etching. The shape or geometry to be recessed can be applied two-dimensionally to the substrate in the form of a mask using lithography processes. The substrate can be made of a ceramic or a semiconductor material, such as Si. During the (subsequent) trenching process, material can be removed from the areas not covered by the mask. The trenching or etching process can be carried out, for example, using the Bosch process, i.e., reactive ion etching with SFx – particularly SF6 – and / or C4F8 / CF4, or, as a further option, through plasma-based etching or sputtering processes, for example, using CF chemistry, i.e., fluorine-carbon compounds, or, for example, using plasma resist stripping, e.g., oxygen plasma.In other words, Fig. 21 shows a possible process flow with two trenching operations and thus for the production of recesses with two different cross-sectional areas.
[0128] In a first step, the upper region of the cavity can be created. A structured (resist) mask can be applied to the substrate using a lithography process, which defines the cross-sectional geometry of the upper region of the cavity. The depth of the upper region can be determined by the etching time in the first step. A subsequent second lithography process can define the geometry of the lower region of the cavity. The depth of the lower region can then be defined by another etching process.
[0129] According to one embodiment, a hard mask, for example, a SiO2 layer or a Si3N4 layer, can be structured with the design of the lower sub-region—for example, round to minimize capillary forces. This structuring can, for example, be stopped on the silicon beneath the hard mask. Subsequently, in a lithography step, the design of the upper sub-region can be defined in a resist mask—for example, spikes to optimize filling. The structure can then be etched, for example, using the Bosch process. This Bosch process can etch silicon quite quickly, but the hard mask slowly. With a clever design of the thickness of the hard mask, so that it is removed, for example, during the etching process at the areas not covered by the resist, an embodiment of a two-level structure can be easily produced.Thus, for example, the total etch time can define the total depth of the cavity. The depth of the upper portion can be defined by the etch time that elapses after the hard mask is removed.
[0130] According to an additional embodiment, a hard mask can be patterned with the design of the upper sub-region. Subsequently, the design of the lower sub-region can be defined in a resist mask in a lithography step. The structure can then be etched, for example, using the Bosch process. The resist can then be removed and etched further. For example, the total etching time can define the total depth of the cavity, and the etching time of the second etch can define the depth of the upper sub-region (filling structure).
[0131] According to one embodiment of the approach disclosed here, the cavity can be produced using at least two individual lithographic steps in order to be able to implement at least two different geometries in plan view within a cavity. The upper portion of the cavity can deviate from the geometry of a complete circle to improve the ability of this cavity to be filled with an overflowing liquid. The shape can have spikes – for example, triangles and / or rectangles – or, for example, a drop shape. Spikes / corners can be structures whose radius of curvature is significantly smaller than the radius of curvature of the entire recess, for example, less than one fifth. The diameter of this shape can range from a few micrometers up to several hundred micrometers. This shape can be projected into the depth using the trenching and / or etching processes described above.The depth of the cavity in this first step can be from a few hundred nanometers to several micrometers.
[0132] Fig. 22 shows a schematic cross-sectional view of an embodiment of a recess 115 of a microfluidic receiving element. The upper diameter 230 of the upper section 205, which was produced by trench 1 for example only, is larger than a lower diameter 235 of the lower section 220, which was produced by trench 2 for example only. According to one embodiment, the upper diameter 230 can be in a range between one micrometer and one millimeter.
[0133] In other words, Fig. 22 shows a two-dimensional representation of the cross-sectional area of the two trench processes.
[0134] In other words, the approach proposed here to solve the challenges described above, according to one embodiment, creates an array or chip comprising at least one cavity. The cavity, for example, has one or more prongs and / or corners in the upper region—specifically, in the upper half, upper quarter, or upper tenth of the cavity. The prongs and / or corners are regions with a smaller radius of curvature than the radius of curvature of the cavity.
[0135] The recesses disclosed in the proposed approach can have diameters ranging from a few micrometers to several hundred micrometers, or even millimeters. The depth of the recesses can range from a few micrometers to several hundred micrometers, or they can extend completely through the substrate thickness of up to 1 millimeter.
[0136] In other words, the approach proposed here to solve the challenges described above, according to one embodiment, creates a Si chip with cavities, in particular such that the recesses, for example, on the chip surface (in plan view), have corners or points – i.e., regions with a small radius of curvature, meaning, in particular, that the recesses are not round or oval with a large radius. In the underlying part – meaning, in particular, sufficiently removed from the chip surface – the recesses can be designed, for example, round, oval, or elliptical, meaning, in particular, without corners or with a large radius.
[0137] In other words, the approach proposed here to solve the challenges described above, according to one exemplary embodiment, creates a recess that can consist, in particular, of two adjacent subregions, in particular such that the upper subregion is optimized for filling by means of prongs / corners, and the lower subregion can be shaped in such a way that capillary forces and thus the entrainment of a liquid in the cavity can be reduced and minimized. The lateral configuration of the subregions can be specifically defined by two lithography planes.
[0138] These recesses can be realized as recesses in semiconductor products with variable cross-sections for fluidic applications and can be manufactured, for example, as recesses in semiconductor products with variable cross-sections using a two-mask process. The proposed approach can be used in the lab-on-chip field for fluidic and / or microfluidic applications.
Claims
Claims 1. A receiving element (110) for a microfluidic device (100) for processing fluids, wherein the receiving element (110) has at least one recess (115) for receiving at least one liquid, characterized in that an upper section (205) of the recess (115) facing an upper side (200) of the recess (115) has a first edge (210) with a first structure (305) having a first structure depth (302), and a lower section (220) of the recess (115) facing an underside (215) of the recess (115) has a second edge (225) without a structure or with a second structure (1600) having a second structure depth (1602), wherein the second structure depth (1602) of the second structure (1600) is less than the first structure depth (302) of the first structure (305).
2. The receiving element (110) according to claim 1, wherein the first structure (305) is formed by a plurality of slots (310).
3. The receiving element (110) according to claim 2, wherein a cross section of the plurality of slots (310) is shaped as a prong and / or a corner and / or a triangle and / or a rectangle.
4. Receiving element (110) according to claim 2 or 3, wherein a longitudinal extension direction of the plurality of slots (310) is aligned parallel to a longitudinal axis of the recess (115) along the first edge (210).
5. The receiving element (110) according to any one of claims 2 to 4, wherein the plurality of slots (310) extend radially or parallel to each other into the first edge (210).
6. Receiving element (110) according to one of the preceding claims, wherein a first partial region (300) of the first edge (210) has the first structure (305) and wherein a second partial region (320) of the first edge (210) is formed without a structure.
7. Receiving element (110) according to claim 6, wherein the first partial region (300) and the second partial region (320) each extend half-side over a circumference of the upper section (205).
8. The receiving element (110) according to any one of the preceding claims, wherein an upper diameter (230) of the upper portion (205) is smaller than a lower diameter (235) of the lower portion (220).
9. The receiving element (110) according to any one of the preceding claims, wherein the upper diameter (230) of the upper portion (205) is in a range between one micrometer and one millimeter.
10. Receiving element (110) according to one of claims 2 to 9, wherein a radius of curvature of the plurality of slots (310) is smaller than a radius of curvature of the recess (115), in particular wherein the radius of curvature of the plurality of slots (310) is smaller than one fifth of the radius of curvature of the recess (115). 11 . Receiving element (110) according to one of the preceding claims, wherein the first structure (305) is formed by at least one hundred slots (310).
12. The receiving element (110) according to any one of the preceding claims, wherein the first structure depth (302) is in a range between one micrometer and one hundred micrometers.
13. Receiving element (110) according to one of the preceding claims, wherein the upper portion (205) in an upper half, an upper quarter or an upper tenth of the recess (115).
14. Microfluidic device (100) for processing fluids with the microfluidic receiving element (110) according to one of the preceding claims.
15. A method (2000) for producing a receiving element according to any one of the preceding claims, wherein the method (2000) comprises the following steps: Providing (2005) a substrate (2100); Applying (2010) a first mask to the substrate, wherein the first mask defines the first edge of the recess; removing (2015) a first material in a first free area of the substrate not covered by the first mask by means of reactive ion deep etching in order to form the upper section of the recess; Applying (2020) a second mask to the substrate, wherein the second mask covers the first edge of the recess and defines the second edge of the recess; and Removing (2025) a second material in a second free area of the substrate not covered by the second mask by means of reactive ion deep etching in order to form the lower section of the recess.
Citation Information
Patent Citations
Microfluidic receiving element, microfluidic device with receiving element, method for manufacturing a microfluidic receiving element and method for using a microfluidic receiving element
DE102022202862A1