Patent Publication Number: US-2020276728-A1

Title: Manufacture of a microfluidic component by additive manufacturing

Description:
TECHNICAL BACKGROUND 
     The present invention relates to a microfluidic component, a green body, a sample separation apparatus and a method of manufacturing a microfluidic component. 
     In an HPLC, typically, a liquid (mobile phase) is moved through a so-called stationary phase (for example in a chromatographic column) at a very precisely controlled flow rate (for example in the range of microlitres to millilitres per minute) and at a high pressure (typically 20 to 1000 bar and beyond, currently up to 2000 bar) at which the compressibility of the liquid is noticeable, in order to separate individual components of a sample liquid introduced into the mobile phase from each other. Such an HPLC system is known, for example, from EP 0,309,596 B1 of the same applicant, Agilent Technologies, Inc. Such an HPLC system often has one or plural switchable fluid valves. 
     Microfluidic components, such as for example components of fluid valves, are conventionally produced by pressing, for example, a powdery starting material in a molding tool into a desired shape. 
     However, the production of fluid valves (in particular rotor and/or stator components of a fluid valve) and other microfluidic components for sample separation apparatuses is still elaborate (or costly) and error-prone. One difficulty is that the microfluidic components for sample separation apparatuses must withstand high and very high pressures. Furthermore, microfluidic components, which come in contact with fluidic samples and solvents, should preferably be biologically and chemically inert. Moreover, fluids should be able to flow reliably through microfluidic structures of the microfluidic components. This becomes increasingly critical as microfluidic structures of microfluidic components become smaller and smaller. Then it can happen during a production process, for example, that microfluidic channels or the like are undesirably closed. 
     DISCLOSURE 
     It is an object of the invention to produce a microfluidic component having microfluidic structures with reasonable effort and high error robustness during manufacturing and operation. The object is solved by the independent claims. Further embodiment examples are shown in the dependent claims. 
     According to an exemplary embodiment example of the present invention, a microfluidic component for a sample separation apparatus is established, wherein the component has a component body having ceramic and at least one microfluidic structure in the component body, wherein the component body is produced by additive manufacturing (in particular by three-dimensional printing). 
     According to another exemplary embodiment example, a green body or green compact for producing a microfluidic component (in particular having the features described above) is provided, wherein the green body has a preform of a component body of the microfluidic component, which preform has ceramic particles and a binding agent (or binder) that has been cured by electromagnetic radiation, and at least one microfluidic structure in the preform. 
     According to yet another exemplary embodiment example, a sample separation apparatus for separating a fluidic sample is provided, wherein the sample separation apparatus has a fluid drive for driving a mobile phase and the fluidic sample arranged therein, a sample separation device for separating the fluidic sample in the mobile phase, and a microfluidic component having the features described above, wherein the fluidic sample and/or the mobile phase can be conveyed (or is to be conveyed, or is to be driven) through the at least one microfluidic structure during separation. 
     According to a further exemplary embodiment example, a method for producing a microfluidic component (in particular having the features described above) for a sample separation apparatus is provided, wherein in the method a preform of a component body is produced by additive manufacturing, at least one microfluidic structure is formed in the preform during the additive manufacturing (in particular as part of the additive manufacturing), and the preform is transformed into the microfluidic component by firing (or baking). 
     In the context of the present application, the term “microfluidic component” is understood to refer to a component which, in the context of sample separation analysis, provides a functional contribution, which involves the passing of a fluid (in particular the fluid sample to be separated and/or a mobile phase) through microfluidic structures of the component. Such a microfluidic component may be fluidically coupled with one or plural other microfluidic components via fluid lines (for example capillaries). Examples for such microfluidic components are a fluidic valve, which is switchable between different fluid coupling states, or a component thereof, a sample separation device for separating a fluidic sample, a detector or a detector component for detecting the separated fluidic sample, a fluidic heat exchanger, a mixer for mixing fluids, etc. 
     In the context of the present application, the term “microfluidic structure” is understood in particular to refer to a branched or unbranched channel, a plurality of such channels, or another structure having dimensions in the range of micrometres to millimetres, which is through-flowable (or can be flown through) by fluid. According to an embodiment example, an internal diameter of the at least one microfluidic structure may be in a range between 0.05 mm and 1 mm, in particular in a range between 0.1 mm and 0.5 mm. 
     In the context of the present application, the term “additive manufacturing” or generative manufacturing is understood to refer to methods for the building-up manufacture of bodies (in particular a preform of the component body), which can be produced directly on the basis of a, for example, computer-internal data model from formless starting materials (for example a suspension, an emulsion, liquids, gels, pastes, powder, etc.) or shape-neutral (for example strip-shaped, wire-shaped, sheet-shaped) material by chemical and/or physical processes. Although often shaping processes are concerned, for additive manufacturing, no tools are required that are shaped according to the respective geometry of the body to be generated (e.g. casting moulds). Examples for additive manufacturing processes are powder bed processes, free space processes, liquid material processes and other layer construction processes, three-dimensional printing, etc. 
     In the context of the present application, the term “green body” or “green compact” is understood to refer, in particular, to an unfired blank that has been manufactured in ceramic technology. For example, pressed ceramic powder, powder bonded with binding agents, etc. are concerned. Such a green body and/or green compact may be dimensioned in such a way that it almost obtains the final shape by shrinkage during firing (in particular by subsequent thermal removal of one or plural components of the green body, in particular cured binding agent). Further, in particular, a “green body” or “green compact” may be understood to refer to a preform of a microfluidic component, which preform has been produced by additive manufacturing, but has not yet been transformed into a completely cured state in a firing process. In particular, in such a firing of a green body, any binding agent, which still present in the green body and is already completely or only partially cured, can be removed totally or completely. Therefore, when firing the green body for transforming it in a microfluidic component, a reduction in volume and/or a reduction in mass may occur. 
     According to an embodiment example of the invention, a microfluidic component and an associated production method are established, in which the microfluidic component is provided with microfluidic structures by an additive manufacturing process. Surprisingly, it has turned out that during the selective solidification of, for example, a suspension as a starting material of the additive manufacturing method, by spatially limited energy input, for example by a laser, precisely defined microfluidic structures can be generated, which are later suited with high reliability and reproducibility for conducting a fluid during the operation of a sample separation apparatus. Namely, if volume areas of the suspension, which can serve as the starting material for producing the microfluidic component, are selectively solidified around a microfluidic structure to be formed, no undesirable residue remains inside thus delimited the microfluidic channels, which can therefore, astonishingly, remain free during additive manufacturing. Any suspension, which eventually remains in the formed microfluidic channels, can be removed easily and without problems, for example by cleaning or by applying pressure or by rinsing the channels with water or the like. 
     Furthermore, it has turned out that thermally conductive ceramics in the form of particles in the suspension in combined interaction with a binding agent provided there are usable without problems in the described additive manufacturing method in order to additively manufacture microfluidic components. In this way, according to exemplary embodiment examples, it is possible to establish with moderate effort a microfluidic component, which is producible easily and with precisely definable microfluidic structures as well as advantageous thermal properties. Also, with advantage, ceramic material is chemically and biologically inert, so that a corresponding microfluidic component can be exposed to aggressive solvent components of a mobile phase as well as to most various fluidic samples (e.g. biological samples) without resulting in undesired interactions between fluid and microfluidic component. 
     In the following, additional embodiments of the microfluidic component, the green body, the sample separation apparatus and the method are described. 
     According to an embodiment example, the microfluidic component may be configured as a fluid valve or a component of a fluid valve, in particular as a rotor component or a stator component of a fluid valve. In the context of the present invention, the term “valve component” is understood to refer to a valve body which can be moved relative to another valve component during a switching operation of the fluid valve. According to a preferred embodiment example, the two valve components are a rotor device and a stator device of a fluidic valve. Alternatively, however, it is also possible, for example, to manage the switching of the fluid valve by a longitudinal movement between two interacting valve components. A fluidic valve may be formed of two components, which are relatively movable with respect to each other, and which in the case of a rotor valve include a rotor component that is to be rotated and a stator component that is to be kept stationary. In the stator component, ports may be formed for the fluidic connection of the fluid valve to a fluidic environment (for example by fluid lines such as capillaries). In addition, fluidic coupling structures (such as grooves or channels) may be formed in the rotor component, which structures allow different fluidic coupling states or fluidic decoupling states between the ports in different switching states of the fluid valve. One or plural such fluid lines may also be formed in the stator component. The stator component and the rotor component can be assembled in such a way that the ports and the fluid channels can be brought in the different fluid coupling states by rotating the rotor component relative to the stator component. According to an exemplary embodiment example, the rotor component and/or the stator component may be manufactured by additive manufacturing. In other embodiments, such a fluid valve is established from two valve components that are movable relative to each other in a different way, for example from two components that can be moved longitudinally relative to each other. The described ports as well as the described fluid lines may represent microfluidic structures according to an exemplary embodiment example. They can be produced during the additive manufacturing process by simply omitting a selective solidification of the suspension exactly in the area of the later microfluidic structures. It has turned out that microfluidic components in the form of fluid valves produced by additive manufacturing meet the high requirements for mechanical robustness, tightness and reliable provision of a fluidic coupling function. 
     According to another embodiment example, the microfluidic component may be configured as one of a group that consists of a sample separator or part of a sample separator, a heat exchanger, and a mixer. In the case of a sample separation device for separating a fluidic sample, the microfluidic structures may correspond, for example, to a lumen of the sample separation device. In the case of a sample separation device for separating a fluidic sample, the microfluidic structures may also serve to form a heat exchanger function that is integrated in a wall of the sample separation device. In another implementation, such a heat exchanger may also be configured independently of a sample separation device and have, for example, meander-shaped or helical microfluidic structures, through which a fluid may flow to effect a heat exchange with another fluid. In a fluidic mixer, one or plural fluidic input streams are mixed together (for example at a fluidic T-point, Y-point or X-point) and then exit as a mixed fluid at an output of the microfluidic structure. 
     According to an embodiment example, the microfluidic component may consist of the component body. According to the embodiment described, no other component than the component body may be required to form the microfluidic component. In other words, the microfluidic component may be formed in one piece. Even very complexly produced microfluidic components having a one-piece implementation may be produced by additive manufacturing. 
     According to an embodiment example, the microfluidic component may be made of ceramic. If the entire component body consists only of ceramic, the special robustness of the microfluidic component during operation may be provided by the ceramic material. At the same time, such a ceramic material may show good thermal conductivity. Ceramic material is also bioinert, so that even in the presence of an aggressive chemical solvent or a biochemical sample, it is neither damaged itself nor has an undesirable effect on the sample. In addition, ceramics can be processed in powder form, whereby this powder may be provided with a binding agent (or binder) during the production of the green part of the microfluidic component, which binding agent can be selectively solidified by a laser or other energy source for producing the preform. 
     According to another embodiment example, the microfluidic component may have one or plural materials other than ceramics, for example residues of solidified binding agent, which have not been removed or not completely removed from the body during firing. 
     According to an embodiment example, the ceramic may contain or consist of aluminium oxide and/or zirconium oxide. Aluminium oxide (Al 2 O 3 ) has the particular advantage of a high heat capacity. The use of zirconium oxide is particularly advantageous when a mechanically very robust and less brittle material is required. Combinations of the above and/or other powdered ceramics are also possible, for example to combine the different material properties. Also, ceramic powders having different particle sizes can be used for such reasons. 
     According to an embodiment example, an aspect ratio of the at least one microfluidic structure may be at least 50, in particular at least 100, and further in particular between 200 and 400. In the context of the present application, the term “aspect ratio” is understood to refer in particular to a ratio of the length of a microfluidic structure (i.e. the path length through which the fluid flows as it flows through the microfluidic structure) and a diameter of the microfluidic structure (i.e. an extension width perpendicular to the direction of flow). It has turned out that the high aspect ratios mentioned above, which are required for certain fluidic functions (e.g. a heat exchanger or a complex fluidic valve function), can be reliably and easily produced by additive manufacturing. 
     According to an embodiment example, an inner diameter of the at least one microfluidic structure may be in a range between 0.05 mm and 1 mm, in particular in a range between 0.1 mm and 0.5 mm. Then it can be ensured that even with tolerances of the laser or another energy source for curing, larger areas of the microfluidic structure are reliably protected against an undesired solidification. Thus, a narrowing or even complete blocking of the microfluidic structures can be avoided. At the same time, these small structure sizes are suitable for coping with the required low flux rates and limited fluid volumes of modern sample separation apparatuses. 
     According to an embodiment example, the at least one microfluidic structure may have at least one of a group that consists of a completely circumferentially confined microfluidic channel and a microfluidic groove. In other words, the microfluidic structure may be a microfluidic cavity (or void) in the component body. Such a cavity can be flown through by the fluid as a lumen in the interior the component body. In this context, a groove in particular is understood to refer to an elongated channel-shaped recess. In delimitation to a groove, a channel is a completely circumferentially confined cavity, which may have, for example, a circular or rectangular cross-section. However, other microfluidic structures are also possible, for example pores in a porous volume section of the component body. 
     According to an embodiment example, a proportion of the binding agent in the green body can be between 20 weight percent and 40% weight percent, in relation to the total weight of the green body. For example, the proportion of the binding agent may be approximately 30 weight percent. For example, a UV-curable resin may be used as a binding agent. Ceramic particles may be contained in this highly viscous binding agent to form the suspension. During the laser treatment for forming the preform of the microfluidic component, a part of the binding agent is thus solidified and then forms the preform together with the ceramic particles enclosed therein. When firing the so created green body, which is already in a desired shape, for example at least a part of the binding agent can then be expelled and the ceramic structure can be strengthened. 
     According to an embodiment example, the green body may be transformed (or converted) in a microfluidic component by firing (or baking). Firing can be effected by increasing the temperature in a range between 800° C. and 1800° C., especially in a range between 900° C. and 1600° C. For example, the firing may take place in a furnace. During the firing, at least a part of the binding agent that solidified during the formation of the preform may be expelled from the composite. Thereby, with shape accuracy of the component body, the volume and mass of the component body reduces as compared to the preform, while the relative ceramic content increases. 
     According to an embodiment example, the sample separation apparatus may be formed completely by microfluidic components having the features described above. According to this embodiment, the entire sample separation apparatus may be produced using microfluidic components having the properties described above. All microfluidic components of the sample separation apparatus may then be produced by additive manufacturing, in particular 3D printing. In this way a sample separation apparatus, in particular a liquid chromatography apparatus, may be manufactured with simple means, homogeneous material and little effort. Such an embodiment may be particularly advantageous if standardized liquid chromatography is to be performed for very specific applications, in which complicated embodiments of the modules of the sample separation apparatus may be dispensed with. 
     According to an embodiment example, the preform may be produced by selective curing of a curable binding agent, which is solidified together with ceramic particles. Furthermore, the process may involve removing at least a portion of the cured binding agent from the preform, whereby the microfluidic component is obtained. In particular those areas of the binding agent may be cured, where no microfluidic structures are to be produced in the finished microfluidic component. In these areas, which shall remain free of cured binding agent, the unsolidified suspension of the binding agent and the ceramic particles therefore remain, which can be easily rinsed out of the microfluidic channels or removed in another way. The removal of the cured binding agent, in whole or in part, may reduce the volume of the then finished component body compared to the volume of the preform. 
     According to an embodiment example, the removal may be accomplished by heating the preform, in particular to a temperature in the range between 800° C. and 1800° C. For example, the removal may be accomplished by heating in a firing furnace. 
     According to an embodiment example, in additive manufacturing, a suspension (i.e. a material composition comprising a liquid binding agent and solid ceramic particles) of a liquid binding agent, which is selectively curable by irradiation with electromagnetic radiation, and ceramic particles arranged therein may be selectively cured by selective irradiation with electromagnetic radiation, whereby the preform with the at least one microfluidic structure is obtained. In this way, the microfluidic component can be produced layer by layer in a corresponding apparatus by selectively solidifying suspension above a carrier (or support) to form a first layer. After lowering the support, a laser can then selectively solidify the new layer of suspension above it in order to form a second solid layer, thereby bonding it to the previously produced first layer. This may be repeated several times, so that solidification sequences of parts of suspension layers alternate with lowering sequences of the carrier. In this way, the preform of the component body may finally be obtained, which may have cured binding agent with ceramic particles contained therein. 
     According to an embodiment example, the curing may be carried out by irradiating the suspension by a laser, in particular a UV laser. In other embodiments, a curing may also be effected with electromagnetic radiation of other wavelengths, for example with visible light or with infrared light. The laser may be replaced by another energy source, for example a particle beam, which other energy source can scan, and thus selectively cure, a two-dimensional area. 
     According to an embodiment example, the at least one microfluidic structure may be obtained by selectively not curing the binding agent in a volume area, which corresponds to the at least one microfluidic structure. In other words, microfluidic structures remain wherever the suspension or other starting material has not been selectively cured. 
     According to an embodiment example, during the additive manufacturing, the at least one microfluidic structure may be formed in the preform with a vertical direction of extension. It has turned out to be particularly advantageous to arrange, during the additive manufacturing of the preform of the component body, the microfluidic structure to be produced parallel to a direction of emission of the laser beam. In this way, it can be avoided particularly reliably that during the manufacturing process sections of the microfluidic structure to be produced are undesirably sealed with material or that constrictions form in the area of the microfluidic structure due to undesired material hardening. 
     According to an embodiment example, the additive manufacturing may involve a three-dimensional printing. In three-dimensional printing, small areas of material can be printed individually on a substrate and bonded together. Thereby, a microfluidic component can be manufactured in almost any shape. By the selectively leaving free of volume sections, a channel structure can be produced in three-dimensional printing in almost any shape, size, and geometry. 
     According to an embodiment example, the separation device may be embodied as a chromatographic separation device, in particular as a chromatography separation column. In the case of chromatographic separation, the chromatography separation column may be provided with an adsorption medium. The fluidic sample may be retained on this medium and only subsequently be dissolved again in fractions with a sufficient amount of run agent (or solvent) (isocratic) or in the presence of a specific solvent composition (gradient), thus effecting the separation of the sample into its fractions. 
     The sample separation apparatus may be a microfluidic measuring apparatus, a life science apparatus, a liquid chromatography apparatus, an HPLC (High Performance Liquid Chromatography) apparatus, a UHPLC system, an SFC (supercritical liquid chromatography) apparatus, a gas chromatography apparatus, an electrochromatography apparatus and/or a gel electrophoresis apparatus. However, many other applications are possible. 
     The fluid pump may, for example, be configured to transport the mobile phase through the system at a high pressure, for example a few 100 bar up to 1000 bar and more. 
     The sample separation apparatus may have a sample injector for introducing the sample into the fluidic separation path. Such a sample injector may have an injection needle in a corresponding fluid path, which needle is coupleable to a seat, wherein the needle can be withdrawn from this seat in order to receive sample, whereby after the reinsertion of the needle into the seat the sample is arranged in a fluid path, which may be switched into the separation path of the system, for example by switching a valve, which results in the introduction of the sample into the fluidic separation path. 
     The sample separation apparatus may have a fraction collector for collecting the separated components. Such a fraction collector may, for example, lead the different components into different liquid containers. However, the analysed sample may also be fed to a drain container. 
     Preferably, the sample separation apparatus may have a detector for the detection of the separated components. Such a detector may produce a signal, which may be observed and/or recorded, and which is indicative for the presence and amount of the sample components in the fluid that flows through the system. 
    
    
     
       BRIEF DESCRIPTION OF THE FIGURES 
       Other objectives and many of the accompanying advantages of embodiment examples of the present invention will become easily perceptible and better understood with reference to the following more detailed description of embodiment examples in connection with the appended drawings. Features, which are substantially or functionally identical or similar, are provided with the same reference numerals. 
         FIG. 1  shows an HPLC system as a sample separation device according to an exemplary embodiment example of the invention. 
         FIG. 2  shows a cross-sectional view of a stator and/or a rotor of a fluid valve as a microfluidic component according to an exemplary embodiment example of the invention. 
         FIG. 3  shows a fluid processing device having a fluid valve as a microfluidic component according to an exemplary embodiment example of the invention. 
         FIG. 4  shows a top view and  FIG. 5  shows a three-dimensional view of a rotor component of a fluid valve as a microfluidic component according to an exemplary embodiment example of the invention. 
         FIG. 6  and  FIG. 7  show a three-dimensional view of a heat exchanger as a microfluidic component according to an exemplary embodiment of the invention. 
         FIGS. 8 to 10  show electron-microscopic images of a microfluidic component, which has ceramic particles and is manufactured by additive manufacturing according to an exemplary embodiment example of the invention, at different magnifications. 
         FIG. 11  shows an apparatus for producing a microfluidic component by additive manufacturing according to an exemplary embodiment example of the invention. 
         FIG. 12  shows a transition from a green body as a preform to a final shape of a microfluidic component according to an exemplary embodiment of the invention, which transition has been caused by firing. 
     
    
    
     The representation in the drawings is schematic. 
     Before exemplary embodiment examples will be described with reference to the figures, some basic considerations shall be summarized, based on which exemplary examples of implementation of the invention have been derived. 
     According to an exemplary embodiment example, a microfluidic component, such as a component of a fluidic valve (a rotor component, a stator component, or a high-pressure seal), can be manufactured by three-dimensional printing or another additive manufacturing process. It has turned out that by such a process channels with a high aspect ratio can reliably be kept free. For this purpose, a highly viscous suspension with ceramic particles as a starting material can be used, wherein the microfluidic component can be produced by selective curing of precisely selectable volume elements of this suspension, followed by a firing (or baking). 
     Conventionally, a valve component of a fluidic valve can be produced by pressing a powder together with paraffin in a mold tool, wherein a shape forming is involved. A green body that has been produced in this way can then be annealed so that the green body loses volume due to the expelling of the paraffin. After a cleaning step the microfluidic component is finished. However, as microfluidic structures become smaller and smaller, such manufacturing processes reach their limits. In particular, the formation of fine channels with ever smaller dimensions is, with such a process with continued miniaturization, only possible to a limited extent and at some point no longer at all. 
     In order to overcome these problems, according to an exemplary embodiment example, a green body for a microfluidic component is produced by additive assembly (in particular 3D printing). For this purpose, ceramic slurry and/or a suspension can be used as starting material, which may be formed as a highly viscous and UV-curable liquid with dispersed ceramic particles. The particle size of the ceramic particles as well as a spatial resolution of a laser for curing the UV-curable binding agent determine the accuracy of the geometry that is producible. However, the mentioned parameters are easy to handle from a process engineering point of view. The liquid is cured by the laser, wherein ceramic particles still remain contained in the cured areas. A green body obtained in this way can be further processed by subjecting it to a firing process. Optionally, the component body obtained in this way can be subjected to post-processing, for example a surface grinding, a cleaning, etc. In this way, a microfluidic component for HPLC can be established, which has microfluidic channels. This may be, for example, a rotor component of a fluid valve, a stator component of a fluid valve, a column body, a heat exchanger, or a mixer. A typical channel width of such microfluidic components is approximately 0.2 mm. For such channel sizes, a flowing of the slurry into the channels by capillary forces can be prevented. A typical length of such microfluidic structures is 60 mm. An advantage of microfluidic components manufactured in this way according to embodiment examples of the invention is the particular high-pressure stability of ceramic materials, from which the microfluidic component also benefits. In addition, a ceramic can act bioinert (since it is metal-free), and therefore allows great flexibility in the handling with fluids, which are passed through the microfluidic component during operation. For example, a thickness of the microfluidic component, which is produced by additive manufacturing, can preferably be less than 1 cm, in particular less than 5 mm. A diameter of such a microfluidic component may, for example, be less than 4 cm, in particular less than 3 cm. 
       FIG. 1  shows the fundamental embodiment of an HPLC system as an example of a sample separation apparatus  10 , as it can be used, for example, for liquid chromatography. A fluid pump as a fluid drive  20 , which is supplied with solvents from a supply unit  25 , drives a mobile phase through a sample separation device  30  (such as a chromatographic column), which contains a stationary phase. A degasser  27  may degas the solvents before they are fed to the fluid drive  20 . A sample introduction unit  40  having a switching valve or fluid valve  95  is arranged between the fluid drive  20  and the sample separation device  30  in order to introduce a sample liquid into the fluidic separation path. The stationary phase of the sample separation device  30  is provided to separate components of the sample. A detector  50 , for example having a flow cell, detects separated components of the sample. A fractionating device  60  may be provided to discharge separated components of the sample into containers that are provided for this purpose. Liquids that are no longer required may be discharged into a drain container. 
     A control unit  70  controls the individual components  20 ,  25 ,  27 ,  30 ,  40 ,  50 ,  60 ,  95  of the sample separation apparatus  10 . 
     One or plural of the components of the sample separation apparatus  10  according to  FIG. 1  are constructed as microfluidic component  100  according to an exemplary embodiment example of the invention. According to  FIG. 1 , as represented with the respective reference numerals  100 , these are a rotor component (see reference numerals  114  in  FIG. 2 ) and a stator component (see reference numerals  116  in  FIG. 2 ) of the fluid valve  95  as well as a column body  189  (see the corresponding detail  195  in  FIG. 1 ) of the sample separation device  30 . Each one of these microfluidic components  100  has a component body  102  that is produced of ceramics as well as fluidic channels as microfluidic structures  104  in the ceramic component body  102 . The respective component body  102  is produced by additive manufacturing of a suspension, which contains ceramic particles, with subsequent firing (see  FIG. 11  and  FIG. 12 ). 
     With regard to the components of the fluid valve  95 , the corresponding microfluidic structures  104  are shown and described in  FIG. 2 . 
     In the sample separation device  30 , microfluidic channels or structures  104  in a substantially hollow cylindrical wall of the column body  189  are integrated fluid lines, through which a mobile phase and/or a fluidic sample can flow. This is shown schematically in  FIG. 1  in the detail  195 . For achieving a thermal equilibrium of a fluid flowing through the sample separation device  30 , the fluid first flows from an inlet  197  of the sample separation device  30  in the direction towards an outlet  198  of the sample separation device  30 , from there (for example, along a helical or meandering flow path that is not shown in detail in  FIG. 1 ) back in the direction towards the inlet  197 , in order to then flow from there in a straight line through chromatographic sample separation material  196  in a central lumen, which is circumferentially defined by the column body  189 , radially within the microfluidic structure  104  back again to the outlet  198 , where the fluid leaves the sample separation device  30  (see the trajectory shown schematically in the detail  195 , wherein arrows indicate the direction of flow). 
     The sample separation device  30 , shown schematically in  FIG. 1 , for separating a fluidic sample in the sample separation apparatus  10 , thus has the column body  189 , which defines the lumen for passing the fluidic sample for separating the fluidic sample. The microfluidic structure  104 , which is configured as a heat exchanger  118 , is integrated in the wall of the column body  189 . 
     A fluid (for example the mobile phase and/or the fluidic sample) flows (which cannot be seen in detail in the schematic illustration in  FIG. 1 ) when passing through the sample separation device  30 , preferably at first helically within the wall of the column body  189  of the sample separation device  30 , and only then flows straight through the lumen within the wall of the column body  189  of the sample separation device  30 . During the helical movement along an extended trajectory, a heat exchange is effected between the helically circulating fluid in the microfluidic structure  104  and the longitudinally flowing fluid in the lumen through material having good thermal conductivity of the column body  189 . During the longitudinal flow along the lumen, the fluid then flows through the sample separation device  30 . In this way, a heat exchange function is integrated in the sample separation device  30 . 
     In the case of the sample separation apparatus  10  shown in  FIG. 1 , in particular a part or the entire fluid valve  95  (see the description of  FIG. 2 ), a part or the entire sample separation device  30  (see the description above), or also a part of the detector  50 , of a mixer (not shown) in the area of the fluid drive  20 , etc. may be embodied as a respective microfluidic component  100  according to an exemplary embodiment example of the invention, which has been produced by additive manufacturing. Preferably an aspect ratio of the at least one microfluidic structure  104  is at least  50 . Herein, the aspect ratio is defined as the length of the microfluidic structure  104  divided by the diameter of the microfluidic structure  104 , i.e. divided by the inner diameter of the respective capillary. 
       FIG. 2  shows a cross-sectional view of a fluid valve  95  according to an exemplary embodiment example of the invention. The fluid valve  95  is formed from a rotor component  114  and from a stator component  116  with an intermediate annular high-pressure seal  137 . 
     The rotor component  114  can be rotated relative to the stator component  116  during operation, as indicated by a rotation arrow  133 . An associated axis of rotation is represented by the reference numeral  135 . To provide a fluid-tight connection between the stator component  116  and the rotor component  114 , the high pressure seal  137  is arranged between them, and is recessed in a groove in a contact surface of the rotor component  114 . 
     According to  FIG. 2 , each one of the two microfluidic components  100  of the fluid valve  95 , namely the rotor component  114  and the stator component  116 , consists of a respective component body  102  that is formed of ceramic. For example, the ceramic material may be aluminium oxide or zirconium oxide. Both the rotor component  114  and the stator component  116  are configured as an additive microfluidic component  100 . The stator component  116  and the rotor component  114  are each manufactured by curing a UV-curable suspension of ceramic particles and a binding agent, wherein in areas of microfluidic structures  104  local solidification of the suspension is dispensed with (see  FIG. 11 ). 
     The inner diameter d of some of the microfluidic structures  104  in both microfluidic components  100  shown in  FIG. 2  can be 0.12 mm, for example. The microfluidic structures  104  of the rotor component  114  are partly formed as fully circumferentially defined microfluidic channels (see reference numerals  141 ,  143 ) and for another part as microfluidic grooves  139 . In contrast, in the embodiment example shown, the microfluidic structures  104  of the stator component  116  are all configured as fully circumferentially defined microfluidic channels. 
     As shown in  FIG. 2 , the rotor component  114  as microfluidic structures  104  has a surface groove  139 , vertical channels  141 , which extend vertically into a contact surface of the rotor component  114 , and horizontal channels  143 , which extend parallel to the groove  139 . In contrast, in the stator component  116 , ports are formed in the form of vertical channels  141 . Capillaries or other fluid lines not shown in  FIG. 2  may be connected to these ports in order to fluidically couple the fluid valve  95  with other components of the sample separation apparatus  10 . 
     By rotating the rotor component  114  relative to the stator component  116  during operation, different fluidic coupling states can be adjusted between the microfluidic structures  104  of the stator component  116  and the microfluidic structures  104  of the rotor component  114 . These different switching states correspond to the function of the fluid valve  95  in the framework of the injecting of fluidic sample into the flow path between the fluid drive  20  and the sample separation device  30  according to  FIG. 1 . 
       FIG. 3  shows a fluid processing device  111  having a fluid valve  95  according to an exemplary embodiment example of the invention. 
     A needle  142  is located in, and can be withdrawn from (not shown), a seat  144  in order to draw in fluidic sample from a sample container (not shown) and, after returning to the seat  144 , to inject it via the fluid valve  95  into a fluidic path between a fluid drive  20  and a sample separation device  30 . When drawing in the sample through the needle  142 , the sample may be temporarily stored in a temporary storage volume  147 , a so-called sample loop. The drawing in of the sample may be effected by a dosing pump  149 . A piston of the latter may retract into a piston chamber for drawing in the sample and move forward for injecting it. A waste  165 , a fluidic restriction  167 , check valves  169 , and a liquid container  171  are also shown in  FIG. 3 . To operate the fluid processing device  111 , the fluid valve  95  is provided with grooves  139  and vertical channels  141  and optionally horizontal channels  143  as fluid connections, which may be arranged in different planes in the rotor device  114  and/or in the stator device  116 . In particular, fluid lines may be offset downwardly from a paper plane of  FIG. 3 , while another portion of the fluid lines may also run in the paper plane of  FIG. 3 . Thereby, a rotational switching of the fluid valve  95  is enabled without the fluid lines in the different planes being undesirably coupled temporarily directly with the fluid connections. Such microfluidic structures  104  are flexibly producible by additive manufacturing. 
       FIG. 4  shows a top view and  FIG. 5  shows a three-dimensional view of a rotor component  114  of a fluid valve  95  as a microfluidic component  100  according to an exemplary embodiment example of the invention. 
       FIG. 4  shows a view of a detail of the rotor component  114 , which has been manufactured by additive manufacturing. The microfluidic structures  104  may be manufactured even in the smallest dimensions by three-dimensional printing or another additive manufacturing process. 
       FIG. 5  shows in particular that not only superficial microfluidic structures  104  in the form of grooves  139  and vertical channels  141  may be formed by additive manufacturing, but that such microfluidic structures (see the horizontal channel  143 ) can also be provided in the interior of the component body  104 . 
       FIG. 6  and  FIG. 7  show a three-dimensional view of a heat exchanger  118  as a microfluidic component  100  according to an exemplary embodiment example of the invention. 
       FIG. 6  shows the heat exchanger  118  as an example of a microfluidic component  100  according to an exemplary embodiment example of the invention, which has been manufactured by additive manufacturing. The fluid can flow through an approximately spiral trajectory and thereby carry out an efficient heat exchange. By ceramic particles forming the component body  104 , not only a good pressure stability and a bioinert property is achieved, but also advantageous thermal properties of the microfluidic component  100  are obtained. 
       FIG. 7  shows again the heat exchanger  118  according to  FIG. 6  without the component body  102 , that is only the microfluidic structure  104  located inside the component body  102 . Fluid may flow in through an inlet  197 , and flow out through an outlet  198 , or vice versa. 
       FIGS. 8 to 10  show electron-microscopic images of a microfluidic component  100 , which has ceramic particles  120  and has been manufactured by additive manufacturing according to an exemplary embodiment example of the invention. 
       FIG. 8  shows an electron-microscopic image, which represents the ceramic particles  120  in a remaining matrix of a binding agent  110 . It can be taken from  FIG. 8  that a homogeneous material composition of the represented component body  102  is achieved. 
       FIG. 9  shows an image of a microfluidic structure  104  in the depicted additively-manufactured microfluidic component  100 . It can be seen in  FIG. 9  that the microfluidic structure  104  has a clean circular cross-section and thus a well-defined geometry. 
       FIG. 10  is a magnified view he component  104  according to  FIG. 8  and  FIG. 9 . 
       FIG. 11  shows an apparatus  176  for the production of a preform  108  and/or a green body  106  of a microfluidic component  100  by additive manufacturing according to an exemplary embodiment example of the invention. 
     The apparatus  176  represented here is a container  171 , into which a suspension  173  (also known as ceramic slurry) consisting of ceramic particles  120  and a liquid but UV-curable binding agent  110  is filled (see the detail  191 ). A carrier  175  is located inside the container  171  and serves to support the preform  108  of the component body  102  during the forming process. A laser  128  is configured to emit a UV beam  126 , and is movable as represented by the reference numeral  177 .  FIG. 11  also shows layers  181 ,  183 ,  185  of the preform  108  as they can be produced by selectively solidifying areas of the suspension  173  by curing the binding agent  110  therein by the UV laser beam  126 . For forming the first layer  181 , the carrier  175  is located just below the liquid surface of the suspension  173 . The laser  128  scans the surface and solidifies those areas of the suspension  173  in which no microfluidic structures  104  but areas of the later component body  102  are to be formed. After the first layer  181  has been produced, the carrier  175  moves down by about one layer thickness. Subsequently, the laser  128  repeats the described procedure by scanning a further layer of the suspension  173  over the first layer  181 . Thereby, the second layer  183  is produced by selective curing of the suspension  173  and/or, more precisely, of the binding agent  110  of the suspension  173 . The procedure is repeated by lowering the support  175  a further time, forming the third layer  185  in the same way, and so on. In this way the preform  108  of the component body  102  can be produced by additive manufacturing. 
     By the procedure according to  FIG. 11 , thus a green body  106  is produced, which represents the preform  108  of the component body  102  made up of the ceramic particles  120  and the binding agent  110  cured by electromagnetic radiation (see reference numeral  126 ). By selective non-solidification of the suspension  173  in certain volume areas of the layers  181 ,  183 ,  185 , at least one microfluidic structure  104  remains in the interior of the preform  108 . 
     For example, a proportion of the binding agent  110  in the preform  108  may amount to between 20 percent by weight and 40 percent by weight. The rest may be ceramic material. In the additive manufacturing of the preform  108  together with the microfluidic structures  104 , i.e. the green body  106 , the suspension  173  consisting of the liquid binding agent  110 , which is selectively curable by irradiation with electromagnetic radiation  126 , and the ceramic particles  120  contained therein is selectively cured by selective irradiation. Irradiated areas of the suspension  173  are cured to form the preform  108 , whereas non-irradiated areas of the suspension  173  are not cured and therefore form microfluidic structures  104 . 
     Preferably during additive manufacturing, microfluidic structures  104  are formed in the preform  108  with a vertical direction of extension. In other words, and as shown in  FIG. 11 , non-irradiated sections of the individual layers  181 ,  183 ,  185  are selected so that together they form a vertically oriented microfluidic structure  104  as shown in  FIG. 11 . It has turned out that by this manufacturing process, the formed microfluidic structures  104  can be kept particularly reliably free from erroneously or undesirably cured binding agent  110 . 
     The preform  108  completed according to  FIG. 11  with the at least one microfluidic structure  104  located therein is also referred to as a green body  106 . The green body  106  can then be used to produce a microfluidic component  100  as shown in  FIG. 12 . For this purpose, the green body  106  is transformed into a microfluidic component  100  by firing, as shown in  FIG. 12 . 
     A suspension  173  used in accordance with an exemplary embodiment of the invention may contain, in a solvent, the ceramic particles  120 , the binding agent  110  and, if necessary, one or plural other additives in small quantities (for example a dispersing agent). As the solvent, for example, water and/or an organic solvent such as alcohol, may be used. Oxide ceramic particles, such as for example aluminium oxide (Al 2 O 3 ) particles and/or zirconium oxide (ZrO 2 ) particles or mixtures of these and other ceramic particles can be used as ceramic particles  120 . For example, the ceramic particles  120  may be contained in the suspension  173  in an amount between 10 weight percent and 90 weight percent, preferably between 40 weight percent and 60 weight percent, related to the total weight of the suspension  173 . The binding agent  110  may be present in suspension  173  in an amount of between 0.1 weight percent and 40 weight percent, preferably between 0.2 weight percent and 30 weight percent, related to the solids content of the suspension. A carboxylic acid, for example, may be used as the dispersing agent. 
       FIG. 12  shows a transformation from a green body  106  as the preform  108  to a final shape of a microfluidic component  100  by firing according to an exemplary embodiment example of the invention. On the left side of  FIG. 12 , the green body  106  obtained according to  FIG. 11  is shown. On the right side of  FIG. 12 , the finished microfluidic component  100  is shown, which is obtained by the further processing of the green body  106  as described in more detail in the following. 
     Once the preform  108  of the component body  112  has been produced in the manner shown in  FIG. 11 , it is taken out from the container  171 , and may first be cleaned and dried. In the preform  108  of the component body  102 , there is still contained a large amount of UV-cured binding agent  110 , so that the preform  108  still has a considerable size, see  FIG. 12 , on the left side. 
     In order to transform the preform  108  in the microfluidic component  100 , it is subjected to a firing process, which can be carried out in a firing furnace with strong heating. In this way, the cured binding agent  110  is expelled wholly of partially from the preform  108 , thus obtaining the microfluidic component  100 . The removing of at least part of the binding agent  110  from the green body  106  is thus accomplished by heating. By subjecting the preform  108  to a firing process at an elevated temperature T of, for example, 14[00° C., at least part of the solidified binding agent  110  is expelled from the preform  108 , which leads to a reduction in volume of the preform  108  during its transformation into the component body  104 . This is illustrated in  FIG. 12 . As is shown in a detail  191  in  FIG. 11  and  FIG. 12 , the preform  108  is formed from the ceramic particles  120  in a matrix of the solidified binding agent  110 . As is shown in a detail  193  in  FIG. 12 , after firing the binding agent  110  is at least partially removed, so that densely packed ceramic particles  120  remain as the material of the component body  102 . 
     The ceramic green body or green body  106  may be fired at temperatures that result from the ceramic materials used. For example, the firing temperature may be between 900° C. and 1800° C., in particular between 1100° C. and 1700° C., further in particular between 1100° C. and 1400 ° C. 
     It should be noted that the term “having” does not exclude other elements, and that the terms “a” or “an” do not exclude a plurality. Also, elements, which are described in connection with different embodiment examples, can be combined. It should also be noted that reference numerals in the claims should not be construed as limiting the scope of protection of the claims.