Microsystem component

Abstract

A microsystem component (1) is described comprising a substrate (2, 3) with a receiving chamber (9), an insertion opening (7) leading to the receiving chamber (9), and a perfusion channel (4). The perfusion channel (4) is communicatively connected to the receiving chamber (9) and has an inlet (5) and an outlet (6). The receiving chamber (9) is arranged within the perfusion channel (4) and is enclosed by a perforated wall (10).The insertion opening (7) opens into the receiving chamber (9) enclosed by the perforated wall (10) and the perforated wall (10) surrounds the insertion opening (7), the perforated wall (10) extending from the wall area of ​​the perfusion channel (4) adjacent to the insertion opening (7) into the perfusion channel (4) towards the wall area opposite the insertion opening (7) and the receiving chamber (9) enclosed by the perforated wall (10) being spaced apart from at least one adjacent inner wall of the perfusion channel (4).The cross-section of the perfusion channel (4) is not completely occupied by the receiving chamber (9) enclosed by the perforated wall (10) in the area of ​​the receiving chamber (9), so that the perforated wall (10) is exposed to a fluid flowing in the longitudinal direction of the perfusion channel (4) from the inlet (5) to the outlet (6), and a partial flow of a fluid flowing through the perfusion channel (4) flows through the receiving chamber (9) and another bypass partial flow flows past the receiving chamber (9).

Description

The invention relates to a microsystem component with a substrate, which has a receiving chamber, an introduction opening leading to the receiving chamber and a perfusion channel, wherein the perfusion channel is connected in a communicating manner to the receiving chamber and has an inlet and an outlet, and wherein the receiving chamber is arranged in the perfusion channel and is bounded by a perforated wall.Samples, such as cell cultures, can be studied using microfluidic microsystems components. These are provided as microfluidic chips that allow efficient automated in vitro testing with very small sample amounts. Due to the analysis surfaces in the chip that are reduced in comparison to in vitro assays in the well format, a smaller sample input is necessary and the cell culture can be supplied in a controlled manner by supplying nutrients and can be influenced by introducing active substances, wherein the effects can be examined in real time.Trijillo-de Saniago, G. et al.: "The Tumor-on-Chip: Recent Advances in the Development of Microfluidic Systems to Recapitulate the Physiology of Solid Tumors", in: Materials 2019, 12, 2945 reviews existing microfluidic microsystems devices and their flow dynamics.CA 3 031 439 A1 discloses a microfluidic organ-on-chip device with microchannels, adjacent to which a receiving chamber delimited by a membrane, a column structure or matrix surfaces is arranged. The receiving chamber can be arranged next to two parallel microchannels. Convective fluid exchange or flow through a cell culture is enforced by the arrangements of the fluid inlets and the perfusion chamber, wherein pressure surges and non-uniform flow conditions may occur.Toh, Y.-C. et al.: "A microfluidic 3D hepatocyte chip for drug toxicity testing", in: Lab Chip, 2009, 9, 2026-2035, discloses a microsystem component having microfluidic channels which are connected in parallel to one another to a common inlet and outlet. Cell culture chambers are delimited in the channels by microposts, which are accessible via an introduction opening for introducing the cell culture. The cell culture chambers extend over the length of the perfusion channels, wherein the fluid conducted through the perfusion channels, which fluid is introduced into the perfusion channels. The culture chamber may contain nutrients and / or active substances, flow past the cell culture chamber and the nutrient and / or active substances can only penetrate into the cell culture chamber by diffusion.It is an object of the present invention to provide a microsystem component which is improved in particular with regard to the pressure and flow conditions in the receiving chamber.The object is achieved with the microsystems component having the features of claim 1. Advantageous embodiments are described in the dependent claims.It is proposed that the introduction opening opens into the receiving chamber delimited by the perforated wall and the perforated wall surrounds the introduction opening, wherein the perforated wall extends, starting from the wall region of the perfusion channel adjoining the introduction opening, into the perfusion channel towards the wall region opposite the introduction opening, and the receiving chamber delimited by the perforated wall is spaced apart from at least one adjacent inner wall of the perfusion channel, wherein the cross section of the perfusion channel in the region of the receiving chamber is not completely taken up by the receiving chamber delimited by the perforated wall, so that a fluid flowing from the inlet to the outlet in the direction of longitudinal extent of the perfusion channel flows against the perforated wall, and a partial flow of a fluid flowing through the perfusion channel flows through the receiving chamber and another bypass partial flow flows past the receiving chamberA sample, such as a cell culture, can thus be introduced via the introduction opening transversely to the flow direction of the perfusion channel into the receiving chamber delimited there by a perforated wall. An embodiment of the insertion opening is advantageous in such a way that the sample can hold itself at the outlet of the insertion opening into the receiving chamber, at least in the initial stage, in the form of a drop-shaped, three-dimensional structure, for example by capillary forces. The sample introduction opening can be restricted to the opening into the perfusion channel or can be designed as a sample introduction channel which extends from a sample inlet into the opening to the perfusion channel.The fluid flowing through the perfusion channel flows onto the perforated wall arranged in the flow path and in a bypass partial flow, for example when viewing the perfusion channel with vertical alignment of the sample introduction direction and horizontal flow direction viewed from the introduction opening, past below the receiving chamber. The receiving chamber delimited by the perforated wall is arranged at a distance from the wall region opposite the introduction opening.A variant is also conceivable in which the perforated wall spans at least one plane transversely to the sample introduction direction of the introduction opening and transversely to the flow direction or extension direction of the perfusion channel, and the bypass is formed above and / or below the at least one horizontal perforated wall section delimiting the receiving chamber when viewing the perfusion channel with a horizontal alignment of the sample introduction direction and flow direction. Then, the receiving chamber delimited by the perforated wall is arranged with the wall section of the perforated wall extending from the wall region of the perfusion channel adjoining the introduction opening at a distance from the adjacent, generally parallel inner wall of the perfusion channel.In the variant, the receiving chamber can be bounded on the one hand by an upper or lower inner wall of the perfusion channel and on the other hand by a perforated wall spaced apart therefrom, which in turn is spaced apart from the other inner wall of the perfusion channel, which is opposite the upper or lower inner wall bounding the receiving chamber, in order to form the bypass in this intermediate space. However, a variant is also conceivable in which an upper perforated wall and a lower perforated wall are present to delimit the receiving chamber, wherein the upper perforated wall is arranged adjacent to the upper inner wall of the perfusion channel whilst leaving a bypass intermediate space, and the lower perforated wall is arranged adjacent to the lower inner wall of the perfusion channel whilst leaving a bypass intermediate space.This ensures that the fluid flows through the receiving chamber on the one hand and the flow conditions in the receiving chamber are controlled by the bypass on the other hand. The flow influences in the receiving chamber can thus be reduced, for example, and at the same time sufficient flow can be ensured as required.The receiving chamber is thus not completely in the flow path of the perfusion channel and is thereby exposed to the entire pressure and flow influences of the fluid. On the other hand, however, it is also not simply arranged parallel to the flow path of the perfusion channel and as a result flows laterally only along the receiving chamber. Rather, the receiving chamber is in the flow path of the perfusion channel and, viewed in the flow direction or longitudinal extension direction of the perfusion channel, it is flowed against from the inlet to the outlet and is flowed through with the fluid. However, only one partial flow of the fluid flowing through the perfusion channel acts on the receiving chamber and another bypass partial flow can flow past the receiving chamber in order to thereby control, such as reduce, the shear forces acting on the sample during the flow, and to achieve a more uniform pressure distribution and a reduction and a homogenization of the flow speeds in the receiving chamber.The receiving chamber can be, for example, a cell culture chamber which is configured or used for receiving cell tissue as a sample.The insertion opening can be designed as a capillary channel which opens out in the perfusion channel on the one hand in the receiving chamber and opens out on the other hand with a larger filler neck on the outer side of the microsystem component in order to introduce a pipette tip into the filler neck for filling in a sample (i.e. an object such as, for example. Cell tissue). The perfusion channel can likewise be designed as a capillary channel and open in and out with larger inlet and outlet connectors. The inlet and outlet connectors may be configured to connect hose lines to connect the microsystem component to a hose system and at least one pump (e.g. peristaltic pump) in the hose system. The connectors can be designed as a bore for inserting tubular elements or as a protruding connector for plugging on hoses.The perforated wall can advantageously be formed by posts in the perfusion channel that are spaced apart from one another. A stable structure is thus achieved. The length of the posts extending between opposing wall portions of the perfusion channel defines a space of known height so that the volume and size of the sample can be easily and accurately determined. The space of the receiving chamber lying between the posts can, if required, be examined visually via one of the wall surfaces between which the posts extend. The posts may have a height of preferably 50 to 200 μm. The height may be in the range of 100 μm. In a corresponding manner, the perforated wall can also be used as, for example. The porous wall may be formed as a rod-structure wall or as a porous wall formed from porous material. Such a wall can be produced additively or subtractively in 3D printing. The rod structure wall can be formed from rods interwoven or interlaced with one another, i.e. intersecting one another, with intermediate spaces.The posts can have a greater length in the direction of longitudinal extent of the perfusion channel than a width transverse to the direction of longitudinal extent of the perfusion channel. Thus, the cross section of the posts is enlarged compared to cylindrical posts and the stability of the perforated wall is improved. This embodiment improves the resistance to force influences which are applied to the microsystem component during the introduction of a sample (in particular a cell culture) with a micropipette. In addition, the shape of the posts aligned longitudinally in the flow direction in the perfusion channel, i.e. in the longitudinal extension direction, is also advantageous with regard to the flow influences.The posts may be circular. However, it is particularly advantageous if the posts are, for example, ellipsoidal, oval-shaped, rectangular with rounded corners or diamond-shaped in cross section. The tapering of the posts in the flow direction improves the flow behavior. In this case, turbulence can be reduced. In addition, the attachment and load-bearing capacity is improved by the aspect ratio of the posts, which is reduced with the cross sections compared to the circular cylinder shape, and thus the mechanical stability.The respectively adjacent posts can be arranged offset to each other in the direction of longitudinal extension of the perfusion channel. This ensures the largest possible cross section of the posts to ensure sufficient stability and, with the aid of the offset, simultaneously reduces the effective permeable wall thickness or the length of the intermediate spaces in the flow direction. The permeability of the perforated wall can thus be improved without impairing the stability.The perforated wall may be curved and define a circular, ellipsoidal or oval shaped space in section. This creates a curved space for receiving the sample, which is adapted to the three-dimensional spherical shape, especially of cell tissue. The introduction opening opens into a receiving chamber which is quasi drop-shaped in section. In this case, the fluid in the perfusion chamber does not flow against a wall which is perforated in a straight line, but, viewed transversely to the flow direction, impinges on the perforated wall at points which are offset relative to one another in the flow direction. The influence of pressure, shear forces and flow velocity on the sample located in the interior of the receiving chamber caused by the fluid is thus controlled and can be further reduced and evened out, for example, by suitable design of the perforated wall.In the interior of the receiving chamber, columns spaced apart from one another can be arranged. A sample can thus also be held in the fluid stream at desired positions within the receiving chamber.The columns may be movable. The column structure located in the interior of the receiving chamber can thus adapt to changed environmental conditions, for example when the sample, such as, for example, a cell culture, grows over the course of time and requires more space. The columns can then be pushed away, for example, completely or partially from the interior.The distance of the columns from one another and / or the width of the columns and / or the height of the columns can be varied by external physical parameters. Such microcolumns can be formed, for example, from a shape memory material which changes its state depending on the influence variable. Such influencing variables can be, for example, temperature, pH value, light and electric current or electric voltage, etc.It is conceivable that electrodes are arranged in the receiving chamber for the electrical measurement of properties of a sample located in the receiving chamber, wherein the electrodes are connectable or connected to an electronic measuring unit. Electrically measurable properties of the sample can thus be determined during the residence in the receiving chamber.It is advantageous if at least one post and / or a column are electrically conductive and each form an electrode. Thus, all or selected posts and / or columns can be formed from highly doped silicon or coated with a metal layer, wherein the electrode is electrically conductively connected to a connecting line or a connection contact. The electrodes can thus be connected to an electronic measuring unit.The microsystem component can have an integrated measuring unit, in particular a measuring unit designed for electrical impedance spectroscopy (EIS), which is connected to the electrodes.The microsystem component can have a plurality of receiving chambers in a perfusion channel, each with an introduction opening opening opening into the receiving chamber. It is also conceivable for the microsystem component to have a plurality of perfusion channels, each of which has at least one receiving chamber. The plurality of perfusion channels may each have separate inlets and / or outlets or be connected in parallel to a common inlet and / or outlet.In the context of this application, the words "a / an", unless expressly defined otherwise, are not to be understood as a numerical word, but rather as an indeterminate article having the word sense of "at least one / one".The invention is explained in more detail below with reference to exemplary embodiments with the attached drawings. The following are shown: FIG. 1 is a perspective sketch of a microsystems component with microfluidic bioreactor; FIG. 2 shows a longitudinal section of the microsystems component; FIG. 3 shows a schematic of the microsystems component in longitudinal section with exemplary flow rates in the perfusion channel and the cell culture chamber; FIG. 4 shows a diagram of a modified embodiment of the microsystems component with additional columns in the cell culture chamber; FIG. 5 shows a diagram of a modified embodiment of the microsystem component with a plurality of cell culture chambers in the perfusion channel; FIG. 6 shows a process flow of a production method for manufacturing the microsystems component.FIG. 1 shows a perspective sketch of a microsystems component 1 with microfluidic bioreactor. The microsystem component 1 has a carrier substrate 2, which is made of glass, for example, such as glass. Borosilicate glass (e.g. Pyrex® ) or siloxanes, such as, for example. Polydimethylsiloxane PDMS may be formed. A cavity body 3 can be applied to the carrier substrate 2. This can be made, for example, of siloxanes, such as, for example. Polydimethylsiloxane PDMS may be formed and bonded to the upper surface of the support substrate 2. The microsystem component 1 has a perfusion channel 4 with an inlet 5 and an outlet 6. In the example, the introduction opening 7 extends in a channel-like manner between a sample inlet 8 and the orifice opening leading into the perfusion channel 4. However, it is also conceivable for the opening-in opening to form the introduction opening 7, which can be closed, for example by covering, after introduction of the sample.The perfusion channel 4 and the introduction opening 7, or the inlet channel, can be introduced into the material of the cavity body 3 at the top side of the carrier substrate 2 to the depth (i.e. in the Z direction of the height or thickness in FIG. 1, and / or at the bottom side of the cavity body 3 in the thickness direction. At the opposite ends of the perfusion channel 4, the inlet 5 and the outlet 6 are introduced into the cavity body 3. The inlet 5 and the outlet 6 can be designed as bores which extend approximately perpendicularly to the plane of the carrier substrate 2 and which each form a connecting piece for receiving connecting hoses. It is conceivable that tubular connecting pieces protrude from the top side of the cavity body 3, onto which connecting pieces a connecting hose can be plugged. In the same way, the sample inlet 8 is formed as a bore aligned perpendicular to the plane of the carrier substrate 2. The sample inlet 8 preferably has a diameter for receiving a micropipette, with which a sample, such as in particular a cell culture, can be introduced into the (sample) introduction opening 7.The opening of the introduction opening 7 adjoins a receiving chamber 9 formed in the perfusion channel 4. The receiving chamber 9 is bounded by a perforated wall 10 in order to form the receiving chamber 9 in the perfusion channel 4 in a fluid-permeable manner and in the process to the greatest possible extent prevent the sample, such as cell cultures, from being washed out into the perfusion channel 4.The cross section of the perfusion channel 4 is determined by its height in the Z direction and its width in the Y direction. For supplying the samples introduced into the receiving chamber 9 (especially. Cell cultures) a supply solution can be introduced into the perfusion channel 4 via the inlet 5 and conveyed in the flow direction F through the perfusion channel 4 and the receiving chamber 9 arranged there to the outlet 6. This can be done, for example, with a tube system and a pump, for example a syringe pump, with which continuously or discontinuously controlled fluid quantities can be introduced over time into the perfusion channel 4 and corresponding quantities can be removed again from the outlet 6.It is also conceivable to introduce active substances into the receiving chamber 9 via the perfusion channel 4 in order to examine their effect on the sample (in particular a cell culture). For this purpose, an additional inlet can be present parallel to the inlet 5 into the perfusion channel 4. However, the arrangement of a Y connector in the hose system is simpler, via which on the one hand a syringe pump, a drip or the like can be connected with the supply solution and on the other hand a syringe, tip pump, drip or the like with medicament containing active substance.FIG. 2 shows a sketch of the microsystem component 2 in longitudinal section. It can be seen that the channel-shaped introduction opening 7 opens transversely into the perfusion channel 4. This opening is surrounded by a perforated wall 10 which extends in the perfusion channel 4 in a part-circular or part-elliptical manner adjacent to the opening and delimits a receiving chamber 9. The perforated wall 10 can be used to delimit a space which is circular, elliptical or oval in section. Such a receiving chamber 9 with wall surfaces curved in the flow direction F has fluidic advantages.The perforated wall is formed from posts 11 which are arranged at a distance from one another and are each arranged offset from one another in the flow direction F, i.e. in the X direction and extend in the Z direction from the base to the ceiling of the perfusion channel 4. Between the posts 11 there is a space in each case which is large enough to allow sufficient fluid to pass through and small enough to prevent parts of the sample, such as cell tissue 12, from flowing through in the receiving chamber 9. The distance should be in the range of about 10 μm to 70 μm, and preferably less than 40 μm.The aspect ratio of the posts 11 is reduced compared to cylindrical posts 11 to increase the mechanical stability. At the same time, the cross-sectional area is increased in order to increase the bonding area with the surface of the carrier substrate 2. The shape is adjusted and oriented to improve mechanical stability in the flow direction F.The posts 11 may be tapered in the flow direction F. They may be an ellipse as shown. However, other embodiments with oval-shaped, rectangular or diamond-shaped posts 10 are also conceivable. Rectangular posts 11 should have rounded corners to improve the flow behavior and thus be approximately ellipsoidal.The perforated wall 10 is not drawn from the opening of the introduction opening 7 as far as the opposite wall of the perfusion channel 4. Rather, a bypass B is present between the end of the cell culture chamber 9 distal to the cell culture introduction opening 7 and the adjacent inner wall of the perfusion channel 4. The flow in the receiving chamber 9 and the load on the cell culture 12 are thus controlled by shear forces, pressure and flow speed and can be reduced or even increased if necessary, for example in comparison with the embodiment without a bypass.Optionally, posts 11 can be designed as electrodes 13 or additional electrodes 13 can be present in the receiving chamber 9 independently of the posts 11. The electrodes 13 are connected or can be connected to an electronic measuring unit 14 by electrical lines. The measuring unit 14 can be integrated in the microsystem component 1 as a semiconductor circuit or can be connected to the microsystem component as a separate circuit arrangement via a line connection and electrical connections. A measuring unit 14 designed for impedance spectroscopy is advantageous.Electrical impedance spectroscopy (EIS) is a recognized mark-free noninvasive analytical instrument for individual cells and cell cultures. With the aid of electrodes 13 in the receiving chamber 9, EIS functions can be integrated into the microsystem component 1. Thus, selected posts 11 and / or microcolumns 15 may be made of highly doped silicon to simultaneously form electrodes 13. In the interior of the receiving chamber 9, a current density distribution and a field can be set by selecting and arranging the electrodes, which is sufficiently homogeneous enough to detect a 3D cell culture 12 in the interior by methods of electroimpedance spectroscopy.It has been found in the structure shown in FIGS. 1 and 2 that the shear stress in the accommodation chamber 9 can be set to a value of less than 0.4×10 -2 Pa, while the shear stress in the bypass B is significantly higher with more than 1.2×10 -2 Pa.By means of the bypass B for the microflow past the receiving chamber 9, it is possible, for example, to very greatly reduce the shear stress in the receiving chamber 9 but nevertheless to maintain perfusion through the receiving chamber 9. It can be seen that the highest shear stress is located in the perfusion channel 4 next to the receiving chamber 9. In the interior of the receiving chamber 9 there is a clearly low shear stress which is required for perfusion cell culture.The bypass design solves further problems. For example, it gives more stability to a tumoroid as cell tissue in the accommodation chamber 9 even if there is an unintended pressure change in the perfusion channel 4, so that the effects on the tumoroid are significantly reduced.The bypass B can have a strong effect on the pressure distribution. On the left side of the perfusion channel 4 there may be a pressure difference coming from the pump (p0+#p) and the right end may be open for the atmospheric pressure (p0). Although a pressure drop occurs along the perfusion channel 4, the pressure inside the receiving chamber 9 remains in the middle values and completely homogeneous.The pressure in the receiving chamber 9 and the introduction opening 7 can be somewhat above the atmospheric pressure p0of about 1.0132500 bar present at the right outlet 6, for example, while the inlet 5 has a higher pressure, i.e. an overpressure, with more than 1.0132502 bar.By means of the bypass B, the pressure acting on the sample, i.e. for example the 3D cell culture 12, is kept constant and homogeneous in the entire receiving chamber 9. This prevents the tubes, the syringe pump or the microsystem component 1 from unintentionally moving strongly when the system is taken from an incubator for photographing, for example, and this drives a high pressure on the sample (for example, the microscope. This can lead to an additional load on the sample or even to the disruption of the cell culture 12, for example a tumoroid, through the microcapillary. This problem is solved with the bypass B in the perfusion channel 4 which bypasses the receiving chamber 9, since it is exposed to the sample (especially. Cell culture 12) gives much more stability inside the receiving chamber. As shown, most of the flow and pressure drop surrounds the receiving chamber 9, but a homogeneous micro environment is maintained inside the receiving chamber 9. Even with an unintended pressure change in the perfusion channel 4, the effect in the sample (especially. 3D cell culture 12) within the receiving chamber 9 is significantly reduced, so that a tumoroid is held in the interior in this case reliably and healthy.The pressure effect achieved by the bypass B can also be used in an implementation of this bypass concept in entirely different applications where it is useful to stabilize the pressure in a particular region of a microchannel while a smaller current flows uniformly through it.With an inlet velocity of the perfusion fluid of, for example, 8.17×10 -6 m / s, a flow velocity in the interior of the cell culture chamber 9 that is significantly below 10×10 -6 m / s and was approximately 5×10 -6 m / s has been established in the construction shown by way of example in FIGS. 1 and 2. The flow rate in the bypass B, on the other hand, is significantly greater with more than 20×10 -6 m / s. Flow rates of about 30×10 -6 m / s are to be observed diametrically opposite the introduction opening 7 below the perforated wall 10.The flow rate is much higher near the receiving chamber 9 than inside the receiving chamber 9 where it is lower than in the middle areas but not zero. The flow velocity within the receiving chamber 9 can be reduced by 78% with respect to the inlet flow velocity by the bypass B in the case shown. Moreover, the distribution inside the receiving chamber 9 is homogeneous. This helps to provide a cell culture 12 with a stable and homogeneous micro environment when used as a tumor-on-chip TOC. The mass transport in the receiving chamber 9 is greatly reduced, but is not eliminated.In the perfusion channel 4, the distribution in the planes in the vicinity of the inlet 5 and the outlet 6 is more homogeneous and the velocity decreases in the walls to zero. In the yz planes in the vicinity of the receiving chamber 9, an important difference is to be established between the perfusion channel 4 and the receiving chamber 9 in the construction shown by way of example in FIGS. 1 and 2, in which, although there is still a flow velocity, this is however considerably reduced. In addition, the distribution in the yz-planes within the receiving chamber 9 is much more homogeneous. This homogeneous distribution of the flow rate in the receiving chamber 9 can lead to an advantage in the 3D cell culture 12, since the material transport is also much more homogeneous in the z direction and all cells are supplied uniformly with nutrients and freed of waste materials.FIG. 3 shows a sketch of the microsystem component 1 in a longitudinal section with exemplary flow rates in the perfusion channel 4 and the receiving chamber 9.It can be seen what occurs with respect to the velocity flow lines in the receiving chamber 9 and the bypass B. Most of the current lines flow around the receiving chamber 9, but some of them also pass through the receiving chamber 9. This means that a slow flow flows through the receiving chamber 9. The dense accumulation of streamlines in the vicinity of the receiving chamber 9 creates a high speed region. The low density within the receiving chamber 9 ensures uniform flow and mass transport.FIG. 4 shows a sketch of a modified embodiment of the microsystems component 1 with additional columns 15 in the receiving chamber 9.With such vertical frameworks within the receiving chamber 9, for example, cell growth of cell tissue 12 as a sample can be improved by such microcolumns 15 functioning as frameworks. If the volume of the receiving chamber 9 is provided with a framework structure in whole or in part, the growth of a 3D cell culture 12 can be supported starting from individual cells. This offers the possibility of starting from a single cell suspension and creating a 3D cell culture structure in situ.The microcolumns 15 can optionally be made of an intelligent material with which the width and / or the height of the microcolumns 15 can be controlled in situ. The microcolumns 15 can be formed of materials which are changed by external stimuli such as temperature, pH, light, etc. Thus, during an experiment, the width of the microcolumns 15 could be changed, whereby the mass transport entering the receiving chamber 9 as well as the shear stress and the pressure inside the receiving chamber 9 change.FIG. 5 shows a sketch of a modified embodiment of the microsystem component 1 with several receiving chambers 9 in the perfusion channel 4.A screening with a high throughput can thus be achieved, since a plurality of receiving chambers 9 along the microfluidic perfusion channel 4 can be arranged along the microfluidic perfusion channel 4 almost infinitely repeatedly one behind the other and with parallel perfusion channels 4 also next to one another.The perfusion channel 4 extends from its inlet 5 to the opposite outlet 6. Insertion openings 7 open into the perfusion channel 4 alternately from above and below, or viewed from right and left in the direction of flow F in the X direction. Adjacent to a respective opening, a receiving chamber 9 is delimited in each case by perforated walls 10 formed from posts 11. Once again, a bypass B leading past a respective receiving chamber 9 is present in the perforation channel 4. The bypasses B are arranged alternately at the bottom and top in the flow direction F or past the receiving chamber 9 at the right and left in the X direction.FIG. 6 shows a process flow of a production method for producing the microsystems component 1.For the copolymerization of the microsystem component 1 designed as a microbioreactor, the microsystem technology (i.e. technology for the manufacture of microelectromechanical systems) with technologies such as photolithography, deep reactive ion etching ("deep reactive ion etching"), self-assembled monolayer ("self-assembled monolayer"), replica shaping ("replica molding") and oxygen plasma bonding ("oxygen plasma bonding") can be used.The process flow for microfabrication begins in step A) with a planar substrate, such as a silicon wafer (Si) 16.In step B), a spin coating ("spin coating") of titanium primer (Ti) is carried out to improve the adhesion of the next layer. In step C), a spin coating of photoresist 18 is carried out. In step D), a photolithographic exposure with ultraviolet light UV is carried out through a photomask formed from a quartz carrier 19 and a structured chromium coating 20. In step E), the exposed photoresist, i.e. the photoresist 18 after exposure, is developed. In step F), deep reactive ion etching of the silicon Si 16 is performed. In this case, depressions 20 are introduced into the silicon wafer 16. In step G), the photoresist, i.e., the exposed photoresist 18 and the Ti primer, is removed. A silicon wafer 16 with depressions 21 remains over at the desired locations.In step H), a self-assembled monolayer 22 is obtained as an anti-tinge. In step I), an impression of polydimethylsiloxane PDMS is performed, which is applied to the surface of the silicon wafer 16. In step J), the PDMS stamp 23 is detached, and in step K), polydimethylsiloxane PDMS and glass 24 are exposed, such as, for example, PDMS. Borosilicate glass (e.g. Pyrex® ) with oxygen plasma. In step L), bonding of both surfaces, i.e. the carrier substrate 2 made of glass 24 and the cavity body 3 formed from the PDMS stamp 23, takes place by annealing.Another production process for subtractive or additive construction of the microsystem component 1 is also conceivable. 3D printing can be used for this purpose, for example. The perforated wall can be formed not only by posts 11. In particular 3D printing offers the possibility of forming a porous wall or a rod-structure wall, for example as a rod structure with rod structures and intermediate spaces crossing one another. Such a rod structure includes honeycomb structures and the like. The 3D printing production improves the connection between the perforated wall and the channel walls, since these are produced together from one material in a materially integral manner.The idea of locally stabilizing pressure, shear stress and flow velocity with a bypass in perfusion channel 4 can basically be implemented in each channel / tube with a fluid (air or liquid) in which a locally stable region within a fluid flow is required. For example, a probe may be introduced into the stable region to measure the physical or chemical properties of the fluid.It could also be used in chemical reactors with two different chemicals, one in the flow and the other in the stable region. In this way, a very slow reaction can take place at the interface between these two regions.A further application is in the field of cell culture, such as, for example, tumor cells. However, this can also be used for other types of cell culture, healthy cells, in order to investigate their reaction to other liquids, chemicals, medicaments etc.List of reference characters1 Microsystems component 2 Carrier substrate 3 Cavity body 4 Perfusion channel 5 Inlet 6 Outlet 7 Introduction opening 8 Sample inlet 9 Receiving chamber 10 Perforated wall 11 Post 12 Cell tissue (sample) 13 Electrode 14 Measuring unit 15 Column 16 Silicon wafer 18 Photoresist 19 Quartz 20 Chromium 21 Depressions 22 Self-assembled monolayer 23 PDMS stamp 24 Glass B Bypass F Flow direction

Claims

Microsystem component (1) with a substrate (2, 3) which has a receiving chamber (9), an introduction opening (7) leading to the receiving chamber (9) and a perfusion channel (4), wherein the perfusion channel (4) is connected in communicating fashion to the receiving chamber (9) and has an inlet (5) and an outlet (6), and wherein the receiving chamber (9) is arranged in the perfusion channel (4) and is bounded by a perforated wall (10), characterized in that the introduction opening (7) opens into the receiving chamber (9) bounded by the perforated wall (10) and the perforated wall (10) surrounds the introduction opening (7), wherein the perforated wall (10) extends from the wall region of the perfusion channel (4) adjoining the introduction opening (7) into the perfusion channel (4) towards the wall region opposite the introduction opening (7) and the receiving chamber (9) delimited by the perforated wall (10) is spaced apart from at least one adjacent inner wall of the perfusion channel (4), wherein the cross section of the perfusion channel (4) in the region of the receiving chamber (9) is not completely taken up by the receiving chamber (9) delimited by the perforated wall (10), so that the perforated wall (10) is acted upon by a fluid flowing from the inlet (5) to the outlet (6) in the direction of longitudinal extent of the perfusion channel (4) and a partial flow of a fluid flowing through the perfusion channel (4) flows through the receiving chamber (9) and another bypass partial flow flows past the receiving chamber (9).Microsystem component (1) according to claim 1, characterised in that the perforated wall (10) is formed by posts (11) spaced apart from each other, by a rod structure wall or by a porous wall in the perfusion channel (4).Microsystem component (1) according to claim 2, characterised in that the posts (11) have a greater length in the direction of longitudinal extent of the perfusion channel (4) than the width transverse to the direction of longitudinal extent of the perfusion channel (4).Microsystem component (1) according to Claim 3, characterized in that the posts (11) are elliptical, oval, rectangular with rounded corners or diamond-shaped in cross section.Microsystem component (1) according to one of Claims 2 to 4, characterized in that the respectively adjacent posts (11) are arranged offset with respect to one another in the direction of longitudinal extent of the perfusion channel (4).Microsystem component (1) according to one of the preceding claims, characterized in that the perforated wall (10) is curved and delimits a circular, ellipsoidal or oval space in section.Microsystem component (1) according to one of the preceding claims, characterized in that columns (15) spaced apart from one another are arranged in the interior of the receiving chamber (9).Microsystems component (1) according to Claim 7, characterized in that the columns (15) are movable.Microsystems component (1) according to Claim 7 or 8, characterized in that the distance of the columns (15) from one another and / or the width of the columns (15) and / or the height of the columns (15) can be varied by external physical parameters.Microsystem component (1) according to one of the preceding claims, characterized in that electrodes (13) are arranged in the receiving chamber (9) for the electrical measurement of properties of a sample (12) located in the receiving chamber (9), wherein the electrodes (13) can be connected or are connected to an electronic measuring unit (14).Microsystems component (1) according to Claim 10 in combination with one of Claims 2 to 5 or 7 to 9, characterized in that at least one post (11) and / or one column (15) are electrically conductive and each form an electrode (13).Microsystem component (1) according to Claim 10 or 11, characterized in that the microsystem component (1) has an integrated measuring unit (14), in particular a measuring unit designed for electrical impedance spectroscopy, which is connected to the electrodes (13).Microsystem component (1) according to one of the preceding claims, characterized in that a plurality of receiving chambers (9) with an introduction opening (7) opening into the receiving chamber (9) in each case are formed in the perfusion channel (4).Microsystem component (1) according to one of the preceding claims, characterized in that the microsystem component (1) has a plurality of perfusion channels (4) which each have at least one receiving chamber (9).Microsystem component (1) according to one of the preceding claims, characterized in that the receiving chamber (9) is a cell culture chamber for receiving cell tissue as sample (12).

Images