Microfluidic receiving element for a microfluidic device for processing fluids, method for manufacturing a microfluidic receiving element and method for using a microfluidic receiving element

Abstract

The invention relates to a microfluidic receiving element (110) for a microfluidic device (100) for processing fluids. The receiving element (110) has at least one recess (115) for receiving a liquid. The recess (115) is configured as a cavity or through-hole. Adjacent to a side wall (120) of the recess (115) in a top surface (130) of the receiving element (110), at least one auxiliary cavity (125) is formed. The auxiliary cavity (125) has a smaller volume than the recess (115).

Description

State of the art

[0001] The invention relates to a microfluidic receiving element, a microfluidic device having a receiving element, a method for producing a microfluidic receiving element, and a method for using a microfluidic receiving element according to the preamble of the independent claims. The present invention also relates to a computer program.

[0002] 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.

[0003] An important component of such microfluidic analysis systems can be a holding element. Small reaction chambers of the holding element, i.e., the recesses, can hold a liquid to be analyzed.

[0004] The recesses / cavities can be incorporated as reaction chambers in a ceramic or semiconductor substrate. These reaction chambers can be filled with reagents, for example. The liquid to be analyzed can then be flushed over the cavities to fill them and bring them into contact with the reagents and / or reaction partners. The individual cavities can then be fluidically separated from each other, e.g., by a sealing oil, and different detection reactions can run in parallel in different cavities.

[0005] However, the well geometries pose a challenge, as round wells often exhibit pinning of the liquid front to the edge of the well or flow around the well when flowing over it. This leads, for example, to air pockets and incompletely filled wells, or the filling process requires increased pressure (which typically cannot be provided). Points / corners, which improve filling, also pose a challenge, as the sharp points / corners (albeit possibly with slight rounding) can extend to the bottom of the well. Capillary forces could pull liquids (e.g., previously deposited or spotted reagents) on the bottom of the well upwards into the corners.The capillary forces and / or the height to which the liquid can be drawn up can depend on the radius of curvature of the corners (the smaller the radius of curvature, the greater the force). When another liquid (e.g. the sample liquid) flows over the wells, substances drawn up in the corners could be picked up and transported to neighboring wells. Such carryover can lead to cross-contamination and, in subsequent diagnostics, to incorrect diagnostics. For example, cross-contamination can lead to a chemical and / or biochemical reaction not taking place in one well because a reactant is no longer present in the required amount and / or an additional reactant (from an adjacent well) is present that can inhibit a reaction.Alternatively, an incorrect reaction may occur in a cavity, particularly because a chemical other than the original one may be present in that cavity. All of this can lead to a malfunction (e.g., false positive and / or false negative). Disclosure of the invention

[0006] Against this background, the approach presented here provides a microfluidic receiving element, a microfluidic device with a receiving element, a method for producing a microfluidic receiving element, and a method for using a microfluidic receiving element, as well as a control device that uses one of these methods, a corresponding computer program, and finally a corresponding machine-readable storage medium 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.

[0007] The microfluidic receiving element presented here can advantageously reduce pinning (“sticking”) occurring at the edges of cavities in a microfluidic device, so that the filling behavior of the cavity can be improved.

[0008] A microfluidic 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 at least one recess is formed as a cavity or through-hole. The receiving element is characterized in that at least one auxiliary cavity is formed in an upper side of the receiving element adjacent to a side wall of the recess. The auxiliary cavity has a smaller volume than the recess.

[0009] The recess may alternatively be referred to as a central or internal depression or as a central or internal cavity.

[0010] The auxiliary cavity can also be referred to as an outer, small, smaller or anterior cavity, depression or recess.

[0011] The approach disclosed here involves a novel arrangement for producing cavities / recesses that can combine the advantages of good fillability through an adapted geometry with simultaneous minimization of carryover. In particular, by providing at least one (smaller) auxiliary cavity adjacent to a side wall of the recess, a wave front of this sample solution can now be broken at the auxiliary cavity upon introduction of the liquid, which is also referred to as sample liquid. In particular, by selecting a round shape for the recess in the top side of the receiving element, the recess can be filled with the sample liquid or aqueous solution in such a way that rinsing of material or reagents in the recess can be largely avoided.By selecting the volume of the auxiliary cavity to be smaller than the volume of the recess, it can also be avoided that a larger part of the sample liquid or aqueous solution or liquid in general accumulates in the auxiliary cavity(ies) and is thus no longer available for further analysis.

[0012] According to one embodiment, the side wall of the recess can be arranged perpendicularly with respect to the upper side of the receiving element within a tolerance range. The side wall can also form a flank angle to the upper side of the receiving element that is less than 90 degrees. For example, the at least one recess of the receiving element can have almost perpendicular side walls, which can enclose an angle of between 85 and 95 degrees with the upper side of the receiving element, thereby achieving a cylindrical basic shape. This has the particular advantage that the recess can be produced in a particularly simple manner and that the geometry of the auxiliary cavity facilitates the filling of the recess.

[0013] According to one embodiment, the auxiliary cavity in a plane of the upper side of the receiving element can have a triangular, slot-shaped, square, blade-shaped, rectangular, trapezoidal, pointed, point-shaped, jagged, circular, angular, quadrangular, or oval geometry and / or shape. For example, a radius of a tip of the prong can be less than 25 micrometers and particularly less than 15 micrometers, or the legs of the prong can be spread at an angle of less than 90 degrees, for example.This has the particular advantage that pinning of a phase interface at the edge of the recess can be prevented or reduced particularly efficiently. This is because, with a rounding radius of less than, for example, 25 micrometers or 15 micrometers at the tip, a locally strong curvature of the interface would be required for pinning at this point. However, its formation can be particularly unfavorable in terms of interfacial energy. The improved pinning behavior is attributable to the surface energy of a phase interface, which must be applied for a phase interface to attach to the edge of a recess through the associated deformation of the interface.The surface energy required for pinning a phase interface to an edge of a recess correlates with the length of the edge and the associated enlargement of the phase interface. Thus, depending on the design of the edge, the surface energy required by a phase interface for pinning at this edge can be adjusted. In principle, an edge with distinct auxiliary cavities and thus a significantly longer edge length (compared to a circular recess) can also induce a particularly high surface energy for pinning with a comparable recess volume. However, the surface-to-volume ratio of a recess generally also increases with the edge length.This, in turn, can be disadvantageous for conducting, for example, a chemical or biochemical reaction within the recess, particularly if undesirable adsorption of reactants on the walls of the recess can occur, which cannot be sufficiently reduced, in particular, by a suitable coating of the walls of the recess. When designing and constructing a recess, it may be necessary to find a suitable compromise between improved filling characteristics on the one hand and an increase in the surface-to-volume ratio on the other.Accordingly, in addition to the realization of auxiliary cavities that are as pronounced as possible and an increase in the edge length, the realization of auxiliary cavities with the most pointed shape possible, i.e. a small minimum radius at the tip of the auxiliary cavity, can also be advantageous, since a particularly high interfacial energy can be required locally for pinning at such a shaped edge.

[0014] For example, the recess can have a plurality of auxiliary cavities arranged in a predetermined manner relative to one another, resulting, for example, in a star-shaped arrangement. Such an advantageous configuration can, for example, achieve a low surface-to-volume ratio of the recess, and the point-oriented configuration of the recess can promote filling of the recess in various directions, allowing the liquid front to flow toward the recess adjacent to the plane of the upper side of the receiving element. In other words, the geometry of the auxiliary cavity can promote fillability of the recess.

[0015] According to an additional embodiment, the recess and the auxiliary cavity can be fluidically separated from each other. By preventing breakthrough, the recess—also called the central cavity—remains round and / or oval, like its previously lithographically applied layout, even in deeper areas, and / or has no radii of curvature smaller than 10 micrometers, where capillary forces could act. As a result, the problem of carryover does not arise in this embodiment of the central cavity. The etching depth of the upstream and smaller cavities is smaller than that of the central cavity due to a size effect of the trenching process (the so-called ARDE effect, "aspect-ratio dependent effect").The capillary forces acting through the small corners and tips are not important because the reagents to be protected from carryover are only introduced into the central cavity and the outer and central cavities do not touch each other as described above.

[0016] According to one embodiment, a distance between the recess and the auxiliary cavity can be less than a width of an opening of the auxiliary cavity. Furthermore, the auxiliary cavity can have a lesser depth than a depth of the recess. The auxiliary cavity can have a greater depth than a distance between the auxiliary cavity and the recess. A diameter and / or a width of the recess can also taper from a bottom side of the recess to a top side of the recess. The depth of the depressions can be a few micrometers up to several hundred micrometers or, as through-holes, can extend completely through the substrate thickness of up to 1 millimeter. The round or oval shape with radii of curvature of at least several micrometers, better several tens of micrometers or > 100 micrometers can ensure that no large capillary pressures act that could cause the liquids or solids contained in the cavities to be drawn up and escape.Promote reagents In this context, carryover can be described as the escape of reagents from the recess, which specifically means the flushing out of the upstream reagent by the filling process with the sample liquid, which is to be avoided. The (auxiliary) cavities arranged upstream in the filling direction ensure particularly good breaking of the liquid front, especially with these dimensions of the auxiliary cavity in relation to the recess, and thus enable simplified filling of the central cavity. At the same time, the volume of the upstream cavities is so small compared to the central cavity that it plays no role in the demand for sample liquid. In addition, pinning of the liquid front hitting the recess at the edge of the recess can be reduced and the liquid front can be better guided into the wells, which can also facilitate the complete filling of the recess.

[0017] According to a further embodiment, the auxiliary cavity can open into the side wall of the recess in the form of a step. This allows the liquid or sample solution to be flushed into the recess, so that this portion of the sample solution or liquid can also be used for an analytical reaction. At the same time, flushing of materials from the recess can be effectively prevented because the lower region, in which reagents can be stored, can still have a round or oval shape with radii of curvature of at least several micrometers, preferably several tens of micrometers or > 100 micrometers.

[0018] According to one embodiment, the recess and the auxiliary cavity can be fluidically connected to one another or connectable. In particular, a fluidic connection between the recess and the auxiliary cavity can be formed within a tolerance range on one half or one third of a height of the side wall facing the upper side of the receiving element. The tolerance range can, for example, correspond to a maximum of one fifth, in particular a maximum of one tenth, of the height of the side wall. The recess and the auxiliary cavity can be structured on the upper side in such a way that a fluid flowing over them can penetrate into the central cavity, i.e. the recess, via upstream depressions - also referred to as auxiliary cavities. The upstream depressions can be separated from the central cavity on the surface, but connected to the central cavity below the surface.Furthermore, the auxiliary cavities can have a shape and / or geometry optimized for fillability. The central cavity can be round in plan view and ideally has no structures with a small radius of curvature on the side walls in a lower area, which can prevent the filled liquid substances, i.e. the fluidics, from escaping due to capillary forces. Here, too, the liquid or sample solution can be flushed into the recess so that this portion of the sample solution or liquid can also be used for an analytical reaction. At the same time, the flushing of materials from the recess can be effectively prevented. The introduction of the recess at approximately half the height of the side wall can be easily realized in terms of manufacturing technology, without creating structures that are too small and unstable.

[0019] According to an additional embodiment, at least one additional auxiliary cavity can be formed adjacent to a further side wall of the recess in the upper side of the receiving element. The additional auxiliary cavity can have a smaller volume than the recess. In particular, a plurality of auxiliary cavities can be arranged circumferentially on the upper side of the receiving element around an edge of the recess. For example, the recess can thus be provided with several auxiliary cavities arranged in a predetermined manner relative to one another, resulting, for example, in a star-shaped arrangement.Such an advantageous configuration can, for example, on the one hand, achieve a low surface-to-volume ratio of the recess, and on the other hand, the point-oriented configuration of the recess can promote filling of the recess in different directions, in which the liquid front can run towards the recess adjacent to the plane of the upper side of the receiving element. In other words, the geometry of the auxiliary cavity can promote fillability of the recess. By arranging the plurality of auxiliary cavities on the upper side of the receiving element around an edge of the recess, the recess can further be advantageously configured to promote filling of the recess in different directions, in which the liquid front can run towards the recess. Furthermore, the volume of the auxiliary cavity can promote fillability of the recess.Furthermore, improved filling with a liquid medium can advantageously be achieved by arranging specially shaped cavities in the immediate vicinity of the recess. The cavities arranged upstream in the filling direction can cause the liquid front to break up and thus enable simplified filling and / or improved fillability of the central cavity. The auxiliary cavities arranged in front of the central cavity can, for example, have a pointed, jagged, or angular shape and thus ensure a pinning-free overflow of the overflowing liquid front, which can have a positive effect on the filling behavior of the adjacent central cavity. At the same time, the volume of the upstream cavities can be so small compared to the central cavity that it plays no role in the sample liquid requirement.

[0020] 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 while simultaneously minimizing carryover and optimizing analysis processes. In this way, for example, the efficiency of a biochemical detection reaction carried out in a recess can be increased.

[0021] Furthermore, a method for producing a variant of the previously presented microfluidic receiving element is presented. The method comprises a step of defining a geometry of at least one recess and the auxiliary cavity on a surface of a substrate of the receiving element. This definition step can be carried out, for example, as a separate step in which, for example, a photoresist can be exposed accordingly. Alternatively, the definition step can also be carried out in parallel with a step of introducing the recess and the auxiliary cavity into a substrate in order to produce the microfluidic receiving element. In the introduction step, the recess can be created, for example, in a silicon substrate, using reactive ion deep etching.

[0022] According to one embodiment, a plurality of recesses, each with an identical geometry, can be defined in the defining step, wherein the plurality of recesses can be introduced into the substrate in parallel in the introducing step. For example, a parallel formation of a plurality of recesses in a silicon substrate can be carried out by reactive ion deep etching of the silicon substrate, wherein the geometry of the recesses can be defined beforehand via a lithographic step. This has the advantage of increasing the effectiveness of the final product and, at the same time, saving time and costs in production through parallelization.

[0023] In addition, a method for using a variant of the previously presented microfluidic receiving element is presented. The method comprises a step of introducing a liquid into the recess of the receiving element and a step of detecting a parameter of a reaction carried out in the receiving element using the introduced liquid. For example, in the introduction step, the surface of the microfluidic receiving device with the arrangement of recesses can be brought into contact with a liquid or sample solution, and at least one recess can be filled with the liquid. For example, at least one auxiliary cavity can be initially wetted, and from there, the base of the recess can be wetted with liquid, and finally the entire volume of the recess can be filled with liquid.Subsequently, a reaction can be carried out within the recess, for example, using pre-stored reagents and additionally or alternatively by heating the receiving element. In the detection step, a parameter of the reaction, such as an optical signal, in particular a fluorescence signal, can be detected to obtain an analysis result.

[0024] These methods can be implemented, for example, in software or hardware or in a mixture of software and hardware, for example in a control unit.

[0025] The approach presented here further creates a control unit configured to perform, control, and / or implement the steps of a variant of a method presented here in corresponding devices. This embodiment variant in the form of a control unit also allows the task underlying the approach presented here to be solved quickly and efficiently.

[0026] For this purpose, the control unit can have at least one computing unit for processing signals or data, at least one memory unit for storing signals or data, at least one interface to a sensor or an actuator for reading sensor signals from the sensor or for outputting control signals to the actuator, and / or at least one communication interface for reading or outputting data embedded in a communication protocol. The computing unit can be, for example, a signal processor, a microcontroller, or the like, wherein the memory unit can be a flash memory or a magnetic storage unit.The communication interface can be designed to read in or output data wirelessly and / or wired, wherein a communication interface that can read in or output wired data can read this data, for example, electrically or optically from a corresponding data transmission line or output it to a corresponding data transmission line.

[0027] In this context, a control unit can be understood as an electrical device that processes sensor signals and outputs control and / or data signals depending on them. The control unit can have an interface that can be implemented in hardware and / or software. In a hardware implementation, the interfaces can, for example, be part of a so-called system ASIC, which contains a wide variety of functions of the control unit. However, it is also possible for the interfaces to be separate integrated circuits or to consist at least partially of discrete components. In a software implementation, the interfaces can be software modules that are present, for example, on a microcontroller alongside other software modules.

[0028] Also advantageous is a computer program product or computer program with program code that can be stored on a machine-readable carrier or storage medium such as a semiconductor memory, a hard disk memory or an optical memory and is used to carry out, implement and / or control the steps of the method according to one of the embodiments described above, in particular when the program product or program is executed on a computer or a device.

[0029] Examples of the approach presented here are shown in the drawings and explained in more detail in the following description. It shows: Fig. 1a shows a schematic cross-sectional view of a microfluidic device according to an embodiment; Fig. 1b a schematic cross-sectional view of an embodiment of a microfluidic receiving element with a recess and an auxiliary cavity; Fig. 1c shows a schematic cross-sectional view of an embodiment of a microfluidic receiving element; Fig. 2a is a schematic plan view of an embodiment of a microfluidic receiving element with a recess and a plurality of auxiliary cavities; Fig. 2b is a schematic plan view of an embodiment of a microfluidic receiving element with a recess and a plurality of auxiliary cavities; Fig. 2c is a schematic plan view of an embodiment of a microfluidic receiving element with a recess and a plurality of auxiliary cavities; Fig. 2d is a schematic plan view of an embodiment of a microfluidic receiving element with a recess and a plurality of auxiliary cavities; Fig. 2e is a schematic plan view of an embodiment of a microfluidic receiving element with a recess and a plurality of auxiliary cavities; Fig. 2f is a schematic plan view of an embodiment of a microfluidic receiving element with a recess and a plurality of auxiliary cavities; Fig. 3 is a flow diagram of an embodiment of a method for producing a microfluidic receiving element; and Fig. 4 a flow diagram of an embodiment of a method for using a microfluidic receiving element.

[0030] In the following description of advantageous embodiments of the present invention, 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.

[0031] Fig. Figure 1a shows a schematic cross-sectional view of a microfluidic device 100 according to an embodiment. The device 100 is designed 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. The receiving element 110 has a recess 115 for receiving a liquid. An auxiliary cavity 125, which can also be referred to as a depression or upstream depression, is formed adjacent to a side wall 120 of the recess 115.

[0032] In the exemplary embodiment shown here, the recess also has, by way of example, a further auxiliary cavity 127, which in the illustration shown here is arranged opposite the auxiliary cavity 125 merely by way of example. In this exemplary embodiment, the auxiliary cavity 125 and the further auxiliary cavity 127 are identical in shape and size. The side wall 120 of the recess is arranged, by way of example only, at an angle of 90 degrees perpendicular to an upper side 130 of the receiving element 110. In other exemplary embodiments, the side wall 120 can be arranged perpendicular to the upper side 130 of the receiving element 110 within a tolerance range, for example at an angle between 85 and 95 degrees to the upper side 130.

[0033] 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, wherein all recesses 115, 135, 140, 142, 144, 146 are identical to one another in shape and size. By the exemplary design of the recesses 115, 135, 140, 142, 144, 146 with auxiliary cavities 125, 127 or with upstream depressions, the filling behavior of the recesses 115, 135, 140, 142, 144, 146 can be improved by these auxiliary cavities 125, 127 when liquids are brought into controlled contact with the microfluidic receiving element 110 via the flow cell 105, since the upstream depressions bring about improved wetting of the recess 115.The capillary forces acting on the liquid during wetting of a recess 115, 135, 140, 142, 144, 146 correlate on the one hand with the affinity of the liquid to the side wall 120 and on the other hand with the width of the auxiliary cavity 125, 127. By a small width of the auxiliary cavities 125, 127, a particularly strong influence of the surface forces acting on the liquid during wetting of the auxiliary cavities 125, 127 can be achieved.

[0034] 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.

[0035] Fig. Figure 1b shows a schematic cross-sectional view of an embodiment of a microfluidic receiving element with a recess 115, an auxiliary cavity 125, and a further auxiliary cavity 127 according to one embodiment. The recess 115 can accommodate a liquid and is shaped as a cavity or through-hole. A diameter and / or a width of the recess 115 tapers from a bottom side 131 of the recess 115 to a top side 133 of the recess 115.

[0036] Adjacent to the side wall 120 of the recess 115 in the top side 130 of the receiving element 110 is the auxiliary cavity 125. The auxiliary cavity 125 has a smaller volume than the recess 115. The recess 115 and the auxiliary cavity 125 are fluidically separated from one another. A distance s1 between the recess 115 and the auxiliary cavity 125 is less than a width of an opening 160 of the auxiliary cavity 125. The auxiliary cavity 125 has a smaller depth d1 than a depth d2 of the recess 115. The depth d1 of the auxiliary cavity 125 is greater than the distance s1 between the auxiliary cavity 125 and the recess 115.

[0037] Adjacent to a further side wall 155 of the recess 115 in the upper side 130 of the receiving element 110 is the further auxiliary cavity 127. The further auxiliary cavity 127 also has a smaller volume than the recess 115. The recess 115 and the further auxiliary cavity 127 are also fluidically separated from one another. A distance s2 between the recess 115 and the further auxiliary cavity 127 is less than a width of an opening 165 of the further auxiliary cavity 127. The further auxiliary cavity 127 has a smaller depth d3 than the depth d2 of the recess 115. The depth d3 of the further auxiliary cavity 127 is greater than the distance s2 between the further auxiliary cavity 127 and the recess 115.

[0038] The side wall 120 of the recess 115 is arranged perpendicularly with respect to the upper side 130 of the receiving element 110 within a tolerance range. The side wall 120 forms a flank angle ß1 with the upper side 130 of the receiving element 110. According to one embodiment, the flank angle ß1 can be less than 90 degrees.

[0039] The further side wall 155 of the recess 115 is also arranged perpendicularly with respect to the upper side 130 of the receiving element 110 within a tolerance range. The further side wall 155 forms a flank angle ß2 with the upper side 130 of the receiving element 110. According to one embodiment, this flank angle ß2 can also be less than 90 degrees.

[0040] According to one embodiment, the flank angles ß1, ß2 may have the same size for reasons of symmetry.

[0041] According to an embodiment of the presented approach, fully processed cavities are in Fig. 1b.

[0042] Alternatively expressed, illustrated Fig. 1b a cross-section through the entire structure with the main cavity in the middle and the smaller cavities arranged to the sides.

[0043] Fig. 1b can also be described as a representation of a “transverse fracture (according to Trench)”, where the transverse fracture occurred through the auxiliary cavities.

[0044] The creation of cavities with a high aspect ratio in semiconductor substrates—particularly silicon, i.e., Si—can be achieved through trenching processes (reactive ion deep etching). The shape / geometry to be recessed is 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. In a subsequent trenching process, material is removed from the areas not covered by the mask. The trenching and / or etching process can be performed using the Bosch process (reactive ion deep etching with SFx, C4F8 / CF4) or through plasma-based etching and / or sputtering processes, particularly with CF chemistry (fluorine-carbon compounds).

[0045] Fig. Figure 1c shows a schematic cross-sectional view of an embodiment of a microfluidic receiving element with a recess 115 according to one embodiment. The recess 115 and the auxiliary cavity 125 are fluidically connected to one another. According to one embodiment, such a fluidic connection, a so-called opening 170, can be formed between the recess 115 and the auxiliary cavity 125 within a tolerance range at one half of the height of the side wall 120. As a result, the side wall 120 of the recess 115 can have a step at a height h of the opening 170 between the auxiliary cavity 125 and the recess 115.

[0046] The size of the geometries in the outer area is g, the distance between the outer and inner geometries is s.

[0047] According to one embodiment, there may be a variation of g and s so that the opening 170 can occur at the desired height h. In other words, the desired height h of the opening 170 can be varied by changing or adjusting the size of the geometries in the outer region g and the distance s between the outer and inner geometries, or by changing the flank angle β1 or β2.

[0048] According to one embodiment, the dimensions of the outer geometries can be a few micrometers, more precisely approximately 0.5 micrometers up to 50 micrometers. These dimensions of the outer geometries are referred to as g. The inner region is circular or oval (without corners and edges with a radius of curvature of a few micrometers) and can have a diameter of a few micrometers up to several hundred micrometers. The outer and inner regions do not touch at the top and have a distance s between them of several hundred nanometers up to a few micrometers.

[0049] Alternatively expressed, illustrated Fig. 1c a "sketch of a cross-section through the cavities. The cavities of the inner and outer regions meet at a certain depth with a distance h from the bottom. h can be influenced by g and s."

[0050] According to one embodiment, a trench process of a layout as described above can create a cavity in the semiconductor substrate, which in particular consists of Si (silicon) or SiO2 (silicon dioxide). The angle of the resulting cavities, i.e., the flank angle, is typically not 90° in trench processes and can be controlled to an angle < 90° by adapting the process. A flank angle < 90° means that a cross-section is larger in deeper regions. Furthermore, a trench speed is size-dependent depending on the choice of at least one process parameter, which means that the outer regions are trenched more slowly than the larger inner region.

[0051] According to one embodiment, the resulting flank angle and a size dependence of the trenching process can lead to the cavities extending into the depth touching each other during the trenching process, resulting in a breakthrough 170. Due to the size effect, which causes large areas to be trenched significantly faster than small ones, the cavity of the inner region is trenched significantly deeper. This creates the cross-section of the cavities shown. A lower region of the inner cavity is round according to a two-dimensional projection of the layout, and side surfaces of the lower region have no vertically extending capillaries. Such capillaries could cause the liquids filled into a base of the inner cavity to escape due to capillary forces.The height h of the opening 170 can be controlled by the process-related flank angle, the size ratios between the inner and outer geometries, and the distance between the inner and outer regions. Ideally, the trenching process is selected such that the opening 170 occurs in the upper half of the inner cavity.

[0052] The depth of the inner cavity ranges from a few micrometers to several hundred micrometers. The depth of the outer cavities is smaller than that of the inner cavity and is ideally, for example, less than half the inner depth. In particular, the depth should be designed such that volumes V of reagents introduced into the wells prior to microfluidic processing (e.g., by spotting) are completely absorbed by an inner subregion below the aperture 170, i.e., hx diameter of the inner cavity > V. The aperture 170 can also be referred to here in the plural form as apertures.

[0053] Fig. 1c can be used as Fig. 1b can be described as “transverse fracture (according to Trench)”.

[0054] Fig. Figure 2a shows a schematic top view of an embodiment of a microfluidic receiving element with a recess 115 and a plurality of auxiliary cavities 125. The recess 115 has a circular geometry. A plurality of uniform auxiliary cavities 125 of the recess 115 are shaped as approximately large trapezoids. Alternatively, a plurality of auxiliary cavities 125 are arranged circumferentially on the upper side of the receiving element around an edge of the recess 115. According to one embodiment, the distance between the outer and inner geometries is 12 micrometers.

[0055] According to one embodiment, the (two-dimensional) layout (mask) can be selected such that it consists of two regions: an outer region containing geometries that deviate from the circular shape, in particular triangles, quadrilaterals, and rectangles, and an inner region. The outer region can consist of a continuous geometry or of several individual geometries. The dimensions of the outer geometries can be a few micrometers, more precisely approximately 0.5 micrometers up to 50 micrometers. The inner region is circular or oval (without corners and edges with a radius of curvature of a few micrometers) and can have diameters from a few micrometers to several hundred micrometers. The outer and inner regions do not touch each other at the top and have a distance of several hundred nanometers to a few micrometers between them.

[0056] Due to an underlying circular or cylindrical geometry of the recess 115, a shape of the recess 115 and the majority of the auxiliary cavities 125 results.

[0057] In other words, the majority of the auxiliary cavities 125 have a rectangular, trapezoidal, angular or quadrangular geometry and / or shape in a plane of the upper side of the receiving element.

[0058] Alternatively expressed, illustrated Fig. 2a a “top view of the layout, which consists of the geometry of the main cavity in the center and smaller structures arranged in a circle around the main cavity.”

[0059] In other words, illustrated Fig. 2a an “example of a possible layout to achieve the cavities with outer and inner layout area.” The size of the geometries in the outer area is d and the distance of the outer from the inner geometries is s.

[0060] Fig. 2a can also be called “top view (layout)”.

[0061] Fig. Figure 2b shows a schematic plan view of an embodiment of a microfluidic receiving element with a recess 115 and a plurality of auxiliary cavities 125. As in the above-described Fig. 2a, the recess 115 has a circular geometry. The majority of the uniform auxiliary cavities 125 of the recess 115 are shaped as curved prongs. Alternatively, the majority of the auxiliary cavities 125 are arranged circumferentially on the upper side of the receiving element around the edge of the recess 115. According to one embodiment, the distance between the outer and inner geometries is 12 micrometers.

[0062] Due to the underlying circular and / or cylindrical geometry of the recess 115, an overall segmented Archimedean spiral shape of the recess 115 and the majority of the auxiliary cavities 125 results.

[0063] In other words, the majority of the auxiliary cavities 125 have a triangular, jagged or blade-shaped geometry and / or shape in the plane of the upper side of the receiving element.

[0064] Fig. Figure 2c shows a schematic plan view of an embodiment of a microfluidic receiving element with a recess 115 and a plurality of auxiliary cavities 125. As in the above-described Fig. 2a and Fig. 2b, the recess 115 has a circular geometry. The majority of the uniform auxiliary cavities 125 of the recess 115 are shaped as small trapezoids. Alternatively, the majority of the auxiliary cavities 125 are arranged circumferentially on the upper side of the receiving element around the edge of the recess 115.

[0065] Due to the underlying circular and / or cylindrical geometry of the recess 115, a shape of the recess 115 and the majority of the auxiliary cavities 125 results.

[0066] In other words, the majority of the auxiliary cavities 125 in the plane of the upper side of the receiving element have a square, rectangular, trapezoidal, angular or quadrangular geometry and / or shape.

[0067] Fig. Figure 2d shows a schematic plan view of an embodiment of a microfluidic receiving element with a recess 115 and a plurality of auxiliary cavities 125. As in the above-described Fig. 2a to 2c, the recess 115 has a circular geometry. The majority of the uniform auxiliary cavities 125 of the recess 115 are formed as thin slits. Alternatively, the majority of the auxiliary cavities 125 are arranged circumferentially on the upper side of the receiving element around the edge of the recess 115.

[0068] Due to the underlying circular and / or cylindrical geometry of the recess 115, a shape of the recess 115 and the majority of the auxiliary cavities 125 results.

[0069] In other words, the majority of the auxiliary cavities 125 have a slot-shaped geometry and / or shape in the plane of the upper side of the receiving element.

[0070] Fig. Figure 2e shows a schematic top view of an embodiment of a microfluidic receiving element with a recess 115 and a plurality of auxiliary cavities 125. As in the above-described Fig. 2a to 2d, the recess 115 has a circular geometry. The majority of the uniform auxiliary cavities 125 of the recess 115 are shaped as small circles or small squares or rectangles. Alternatively, the majority of the auxiliary cavities 125 are arranged circumferentially on the upper side of the receiving element around the edge of the recess 115. According to one embodiment, the distance between the outer and inner geometries is 6 micrometers. The small circles, squares, or rectangles can also be understood as "shapes with a size or area of ​​approximately 10 micrometers × 10 micrometers."

[0071] Due to the underlying circular and / or cylindrical geometry of the recess 115, a shape of the recess 115 and the majority of the auxiliary cavities 125 results.

[0072] In other words, the majority of the auxiliary cavities 125 in the plane of the upper side of the receiving element have a point-shaped, rectangular, square or circular geometry and / or shape.

[0073] Fig. Figure 2f shows a schematic plan view of an embodiment of a microfluidic receiving element with a recess 115 and a plurality of auxiliary cavities 125. As in the above-described Fig. 2a to 2e, the recess 115 has a circular geometry. The majority of the uniform auxiliary cavities 125 of the recess 115 are formed as thick slots. Alternatively, the majority of the auxiliary cavities 125 are arranged circumferentially on the upper side of the receiving element around the edge of the recess 115. According to one embodiment, the distance between the outer and inner geometries is 6 micrometers. The thick slots can also be referred to as "strips approximately 5 micrometers × 50 micrometers."

[0074] Due to the underlying circular and / or cylindrical geometry of the recess 115, a shape of the recess 115 and the majority of the auxiliary cavities 125 results.

[0075] In other words, the majority of the auxiliary cavities 125 have a slot-shaped geometry and / or shape in the plane of the upper side of the receiving element.

[0076] According to embodiments, the Fig. The cavities and / or recesses shown in Figures 2a to 2f consist of an outer upstream region, also called outer region, upstream cavities, outer cavities or auxiliary cavities 125, 127, and the main cavity, also called recess 115, central cavity or inner region. The main cavity is round or oval in plan view and / or has radii of curvature that are significantly larger than 1 micrometer, preferably significantly larger than 10 micrometers, even better larger than 100 micrometers. The main cavity can have diameters ranging from a few micrometers to several hundred micrometers up to millimeters. The depth of the recesses can range from a few micrometers to several hundred micrometers or, as through holes, can extend completely through the substrate thickness of up to 1 millimeter.The round or oval shape with curvature radii of at least several micrometers ensures that there are no large capillary pressures that would encourage the liquids in the cavities to be drawn up and escape.

[0077] According to one embodiment, the outer region can consist of a continuous geometry or of several individual geometries that deviate from a circular shape. These can be, in particular, triangles, quadrilaterals, or rectangles. The dimensions of the outer geometries can be a few micrometers, more precisely approximately 0.5 micrometers up to 50 micrometers. It is advantageous if the total area of ​​the outer region is significantly smaller than the area of ​​the main cavity. This means that no significant portion of the sample liquid is required for filling. These geometries can be arranged radially or perpendicularly around the main cavity and can be placed completely or only partially (in particular half-side) around the cavity.

[0078] According to one embodiment, the distance between the cavities, which is Fig. 1b 1 is referred to as "s", must be greater than zero and be selected such that the outer and the central cavities do not come into contact during trenching (taking into account the resulting flank angle, which is usually less than 90 degrees, in particular 85 degrees to 89 degrees → cavities open downwards during trenching, becoming wider) → The central main cavity is therefore still separated from the outer cavities even after trenching. This results in minimum distances of a few micrometers between the outer and the central cavity, especially in the layout and / or on the top side of the cavities (see the sub-figures of the Fig. 2). The theoretical minimum distance smin can be calculated geometrically if the etching depth of the upstream cavities dvor and the flank angle ß are known: smin = 2* dvor / tan(ß). The distance s must therefore be greater than smin, but should not be too large. For example, smin < s < 100 micrometers is advantageous, better smin + 1 micrometer < s < 50 micrometers, and even better smin + 2 micrometers < s < 30 micrometers.

[0079] According to one embodiment, by preventing breakthrough, the central cavity can remain round and / or oval, like its previously lithographically applied layout, and / or have no curvature radii smaller than 1 micrometer, in which capillary forces could act. This eliminates the problem of carryover in the central cavity. The etching depth of the upstream and smaller cavities is smaller than that of the central cavity due to the size effect of the trenching process (the so-called ARDE effect, "aspect-ratio dependent effect"). The capillary forces acting through the small corners and points are not significant, since the reagents to be protected from carryover are only introduced into the central cavity, and the outer and central cavities do not touch each other, as described above.

[0080] Alternatively, the Fig. 2a to 2f “Layout variants for the production of cavities with optimized fillability and minimized carryover.”

[0081] In other words, the Fig. 2a to 2f “Cavities with different geometries of the outer layout area.”

[0082] In other words, the Fig. 2a to 2f “finished cavities consisting of a central round cavity and upstream outer cavities with a geometry deviating from the circular shape.”

[0083] In the Fig. 2a to 2f show examples of the layout. In other words, the Fig. 2a to 2f "Examples of possible layouts, i.e., for reaching the cavities in a silicon semiconductor substrate (Si semiconductor substrate). The inner and outer regions have a defined distance. According to one embodiment, the (geometries of the) outer and inner geometries are deliberately chosen to achieve a breakthrough of the two cavities at a defined height."

[0084] Fig. 3 shows a flowchart of an embodiment of a method 300 for producing a microfluidic receiving element. The method 300 comprises a step 305 of defining a geometry of at least one recess and the auxiliary cavity in a surface of a substrate of the receiving element, and a step 310 of introducing the recess and the auxiliary cavity into a substrate to produce the microfluidic receiving element.

[0085] In this embodiment, a plurality of recesses each having the same geometry is defined in step 305 of defining, merely by way of example, wherein in step 310 of introducing the plurality of recesses are introduced into the substrate in parallel.

[0086] In an advantageous embodiment of the method for producing an improved microfluidic receiving element, a parallel introduction of a plurality of recesses into a silicon substrate can be carried out in the introduction step by reactive ion deep etching of the silicon substrate, wherein the geometry of the recesses can be defined beforehand via a lithographic definition step.

[0087] Fig.4 shows a flowchart of an embodiment of a method 400 for using a microfluidic receiving element. The method 400 comprises a step 405 of introducing a liquid into the recess of the receiving element and a step 410 of detecting a parameter of a reaction carried out in the receiving element using the introduced liquid.

[0088] In one embodiment, the step 405 of introducing comprises, for example, a contacting, wherein the surface of the microfluidic receiving device having an arrangement of recesses is brought into contact with a liquid and then the at least one recess is filled with the liquid.

[0089] According to one embodiment, one of the solutions of the approach proposed here is a chip with cavities in a Si semiconductor substrate, the ability of which to be filled with a liquid medium can be achieved by arranging specially shaped cavities in close proximity. The cavities arranged upstream in the filling direction can cause the liquid front to break, thus enabling simplified filling of the central cavity. According to one embodiment, the central cavity is round in plan view and has no structures with a small radius of curvature on the side walls in a lower region, which can prevent the liquid substances (e.g., spotted reagents) filled before the actual filling process from re-emerging due to capillary forces.According to one embodiment, the cavities arranged in front of the central cavity can have a pointed and / or jagged and / or angular shape, thus ensuring a pinning-free overflow of the overflowing liquid front, which can have a positive effect on the filling behavior of the adjacent central cavity. At the same time, the volume of the upstream cavities can be so small compared to the central cavity that it plays no role in the sample liquid requirement.

[0090] To solve the challenges described above, the approach proposed here creates, alternatively expressed, “recesses in semiconductor products with optimized fluidic fillability through collecting cavities.”

[0091] According to an additional embodiment, a further solution to the approach proposed here is a chip with cavities in a substrate material which are structured on the upper side in such a way that a fluid flowing over them can penetrate into the central cavity via upstream depressions - also referred to as auxiliary cavities. According to one embodiment, the upstream depressions can be separated from the central cavity on the surface, but connected to the central cavity below the surface and have a jagged and / or pointed shape and / or geometry optimized for fillability. According to one embodiment, the central cavity is round in plan view and has no structures with a small radius of curvature on the side walls in a lower region, thereby preventing the filled liquid substances from re-emerging due to capillary forces.

[0092] In other words, the approach proposed here to solve the challenges described above creates “recesses in semiconductor products with lateral inlet channels for optimized filling and minimized carryover.”

[0093] According to one embodiment, the manufacturing process can be less complex, and the cavities to be filled can be free of capillary forces at any cavity height. In particular, the cavity in which the subsequent biological reaction takes place can be identical to a circular cavity. This allows the surface-to-volume ratio of the cavity to be as low as manufacturable possible, and parasitic surface effects can be minimized. In particular, the parasitic surface effect can be minimized, which can cause molecules to unintentionally dock onto a cavity surface and thus no longer be available for a reaction.

[0094] According to one embodiment, the approach presented here can be easily verified by microscopic images of the finished product, particularly using an SEM (scanning electron microscope). Preparation by a separation process may be necessary.

[0095] The approach presented here can be used in the lab-on-chip field for fluidic and / or microfluidic applications.

[0096] If an embodiment includes an “and / or” link between a first feature and a second feature, this should be read as meaning that the embodiment according to one embodiment has both the first feature and the second feature and according to another embodiment has either only the first feature or only the second feature.

Claims

[1] Microfluidic receiving element (110) for a microfluidic device (100) for processing fluids, wherein the receiving element (110) has at least one recess (115) for receiving a liquid, wherein the recess (115) is formed as a cavity or through-hole, wherein adjacent to a side wall (120) of the recess (115) in an upper side (130) of the receiving element (110) at least one auxiliary cavity (125) is formed, wherein the auxiliary cavity (125) has a smaller volume than the recess (115). [2] Microfluidic receiving element (110) according to claim 1, wherein the side wall (120) of the recess (115) is arranged within a tolerance range perpendicular to the top side (130) of the receiving element (110), and / or wherein the side wall (120) forms a flank angle (ß1) to the top side (130) of the receiving element (110) which is less than 90 degrees. [3] Microfluidic receiving element (110) according to one of the preceding claims, wherein the auxiliary cavity (125) has a triangular, slit-shaped, square, blade-shaped, rectangular, trapezoidal, pointed, point-shaped, jagged, circular, angular, quadrangular or oval geometry and / or shape in a plane of the upper side (130) of the receiving element (110). [4] Microfluidic receiving element (110) according to one of the preceding claims, wherein the recess (115) and the auxiliary cavity (125) are fluidically separated from each other. [5] Microfluidic receiving element (110) according to one of the preceding claims, wherein a distance between the recess (115) and the auxiliary cavity (125) is less than a width of an opening (160) of the auxiliary cavity (125) and / or wherein the auxiliary cavity (125) has a lesser depth (d1) than a depth (d2) of the recess (115) or wherein the auxiliary cavity (125) has a greater depth (d1) than a distance (s1) between the auxiliary cavity (125) and the recess (115) and / or wherein a diameter and / or a width of the recess (115) tapers from a bottom side (131) of the recess (115) to the top side (133) of the recess (115). [6] Microfluidic receiving element (110) according to one of the preceding claims, wherein the auxiliary cavity (125) opens into the side wall (120) of the recess (115) in the form of a step. [7] Microfluidic receiving element (110) according to one of the preceding claims, wherein the recess (115) and the auxiliary cavity (125) are fluidically connected or connectable to one another, in particular wherein a fluidic connection between the recess (115) and the auxiliary cavity (125) is formed within a tolerance range on one half or one third of a height of the side wall (120) facing the upper side of the receiving element (110). [8] Microfluidic receiving element (110) according to one of the preceding claims, wherein at least one further auxiliary cavity (127) is formed adjacent to a further side wall (155) of the recess (115) in the upper side (130) of the receiving element (110), wherein the further auxiliary cavity (127) has a smaller volume than the recess (115), in particular wherein a plurality of auxiliary cavities (125) are arranged circumferentially on the upper side (130) of the receiving element (110) around an edge of the recess (115). [9] Microfluidic device (100) for processing fluids with the microfluidic receiving element (110) according to one of the preceding claims. [10] Method (300) for producing a microfluidic receiving element according to one of the preceding claims 1 to 8, wherein the method (300) comprises the following steps: Defining (305) a geometry of at least one recess and the auxiliary cavity on a surface of a substrate of the receiving element; and Introducing (310) the recess and the auxiliary cavity into the substrate to produce the microfluidic receiving element. [11] Method (400) for using a microfluidic receiving element according to one of the preceding claims 1 to 8, wherein the method (400) comprises the following steps: Introducing (405) a liquid into the recess of the receiving element; and Detecting (410) a parameter of a reaction carried out using the introduced liquid in the receiving element. [12] Control device which is configured to execute and / or control the steps (305, 310; 405, 410) of one of the methods (300; 400) according to one of the preceding claims in corresponding units. [13] Computer program which is arranged to carry out the steps (305, 310; 405, 410) to carry out and / or control one of the methods (300; 400) according to one of the preceding claims. [14] A machine-readable storage medium on which the computer program according to claim 13 is stored.

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