Method and device for producing an experimental substrate

The 3D printer method integrates prefabricated functional elements with a base substrate to create experimental substrates tailored to specific parameters, addressing reproducibility and precision issues in conventional substrates, ensuring reliable experimental results.

DE102017116201B4Active Publication Date: 2025-07-17LEICA MICROSYSTEMS CMS GMBH
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Patent Information

Application Number
DE102017116201
Authority / Receiving Office
DE · DE
Patent Type
Patents
Current Assignee / Owner
Filing Date
2017-07-18
Publication Date
2025-07-17
Estimated Expiration
2037-07-18

AI Technical Summary

Technical Problem

Conventional experimental substrates are often unsuitable for less frequent experiments, requiring individual modifications that are difficult to reproduce and may distort results due to inaccuracies, especially in biological experiments, and lack precise integration of structures like microfluidic systems and electrodes.

Method used

A method using a 3D printer to integrate prefabricated functional elements with a base substrate, allowing for precise and reproducible production of experimental substrates tailored to specific experiment parameters by planning in a virtual environment before physical production.

Benefits of technology

Enables flexible, rapid, and accurate production of experimental substrates with integrated functional elements, reducing production effort and avoiding substrate deviations, thus ensuring reliable and reproducible experimental outcomes.

✦ Generated by Eureka AI based on patent content.

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Abstract

Method for producing an experimental substrate (50) designed as a sample holder for microscopy applications, comprising the steps: a) Selecting a virtual base substrate in a virtual environment based on given experimental parameters; b) selecting at least one virtual functional element and arranging the at least one virtual functional element in the virtual environment relative to the virtual base substrate to create a virtual experimental substrate in the virtual environment, wherein the at least one virtual functional element is at least partially specified in the virtual environment; c) providing a real, prefabricated basic substrate (26) corresponding to the virtual basic substrate and providing at least one real, prefabricated functional element (30) corresponding to the virtual functional element in a 3D printer (14); d) printing the experimental substrate (50) by means of the 3D printer (14) using the real basic substrate (26) and the at least one real, prefabricated functional element (30) according to the virtual experimental substrate (50) in the virtual environment such that the real basic substrate (26) and the at least one real, prefabricated functional element (30) form the experimental substrate (50) as a structural unit, further comprising a selective application of at least one real experimental substance in and / or onto the experimental substrate (50) such that the at least one real experimental substance is at least partially surrounded by the real, prefabricated base substrate (26) and / or by the at least one real, prefabricated functional element (30), further comprising a virtual arrangement of at least one virtual experimental substance in and / or on the virtual experimental substrate in the virtual environment, wherein the virtual arrangement of the at least one virtual experimental substance takes place during and / or after step b) and before step c), and wherein the selective application of the at least one real experimental substance takes place during and / or after step d).
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Description

[0001] The present invention relates to a method and a device for producing an experimental substrate, in particular for microscopy applications and in particular using a 3D printer. State of the art

[0002] Experiments in which specific substances and / or objects, which may be microscopically small, are to be investigated often require specially provided experimental substrates. Particularly in microscopy applications, strict requirements are often placed on the design, structure, and / or materials of the experimental substrates. For the investigation of biological samples, for example, devices in and / or on the experimental substrate may also be required that enable the controlled addition of experimental substances to the experimental substrate or the sample contained therein or on it in order to carry out a planned experimental procedure as desired. Therefore, a precise adaptation of the experimental substrate to the experimental parameters and / or to the sample-specific requirements is often necessary.Depending on the experiment, an experimental substrate can therefore include a suitable sample holder with the necessary connections, e.g. for experimental substances, optical elements and / or electrodes.

[0003] For many high-throughput experiments, i.e., experiments that are conducted frequently and / or in large numbers, suitable experimental substrates are often commercially available. These can be procured inexpensively and thus offer a suitable choice for conducting the respective high-throughput experiments. However, such commercially available experimental substrates may be at least partially or even completely unsuitable for some other experiments that are conducted less frequently and / or in only a small number. Particularly in biological experiments, for example, individual adaptations of the experimental substrate to the object under investigation may always be necessary for each individual experiment.The use of conventional, commercially available experimental substrates may therefore be unsuitable for such experiments because the commercially available experimental substrates do not have, for example, necessary structures, such as structures for conducting and / or storing liquids and / or electrodes by means of which electrical potentials can be applied and / or tapped, and / or optical elements for modifying incident and / or emitted electromagnetic waves.

[0004] If, however, a conventional, commercially available experimental substrate must be used for such experiments, these often have to be subsequently modified individually. For example, required structures must be subsequently attached and / or applied and fastened to the conventional experimental substrate, for example using hot glue or some other method. This has the disadvantage, however, that a reliable realization of the desired experimental substrate is not always possible with the available technical means and / or the manufacturing effort is very high. This also has the disadvantage that the production of such individual experimental substrates is often not fully reproducible and therefore substrate-related deviations can arise when a particular experiment is carried out multiple times, which can potentially falsify the results obtained.

[0005] In particular, the subsequent attachment of delicate structures to a conventional, commercially available experimental substrate, such as microscopic structures and / or microfluidic structures, is often not possible with the desired precision and / or reproducibility. For example, the delivery of experimental substances to an object under investigation, such as living cells, organisms, tissue, or small living beings arranged on the experimental substrate, is often technically challenging. If, for example, experimental substances such as nutrients and / or pharmaceuticals are to be delivered to the object under investigation during the experiment, the attachment of macroscopic syringe systems and / or tubing systems is conventionally required, which can be very difficult to integrate into the spatial dimensions available in the experimental setup.

[0006] US 2013 / 0015596 A1 and US 2009 / 0177309 A1 disclose methods for manufacturing three-dimensional objects using a CAD model. The objects to be manufactured are mechanical components for electronic devices.

[0007] US Pat. No. 5,173,220 A describes the production of three-dimensional plastic objects, such as chip carriers. WO 2017 / 066884 A1 discloses a device with microfluidic channels for detecting bacteria.

[0008] US 2010 / 0208049 A1 describes a chamber into which sample material can be introduced and which can be observed or recorded, for example, using a microscope. It also mentions that this chamber can be manufactured using any suitable manufacturing technique; for example, the base element, the lid, and the support could be formed using lithographic techniques such as a 3D PolyJet printer.

[0009] The invention is therefore based on the technical problem of providing an experimental substrate which eliminates the disadvantages outlined above. Disclosure of the invention

[0010] According to the invention, a method and a device are proposed having the features of the respective independent patent claims. Advantageous embodiments are the subject of the subclaims and the following description.

[0011] In a first aspect, the invention relates to a method for producing an experimental substrate. The method comprises the steps: a) Selecting a virtual base substrate in a virtual environment based on given experimental parameters; b) selecting at least one virtual functional element and arranging the at least one virtual functional element in the virtual environment relative to the virtual base substrate to create a virtual experimental substrate in the virtual environment, wherein the at least one virtual functional element is at least partially specified in the virtual environment; c) providing a real, prefabricated basic substrate corresponding to the virtual basic substrate and providing at least one real, prefabricated functional element corresponding to the virtual functional element in a 3D printer; d) Printing the experimental substrate by means of the 3D printer using the real basic substrate and the at least one real, prefabricated functional element according to the virtual experimental substrate in the virtual environment such that the real basic substrate and the at least one real, prefabricated functional element form the experimental substrate as a structural unit.

[0012] In a further aspect, the invention relates to a device which is suitable for carrying out a method according to the invention for producing an experimental substrate.

[0013] A "base substrate" is preferably understood to mean a substrate and / or a carrier on and / or onto which the at least one functional element and, if applicable, other structures can be arranged and / or attached. For example, the base substrate can have the shape of a plate. The base substrate is preferably made of a material and / or coated with a material to which a curable bonding material used for 3D printing can at least partially adhere. Particularly preferably, the base substrate is made of a material and / or coated with a material that has a higher melting point than the curable bonding material, so that the base substrate does not melt during 3D printing, but at least partially, preferably completely, retains its original shape.Preferably, the printing of the experimental substrate, in particular the non-prefabricated elements, is carried out by means of the 3D printer in step d) using a curable bonding material.

[0014] The "virtual environment" is preferably a computer-generated representation that allows a user to generate, create, and / or adapt an illustration of the experimental substrate to be produced. In particular, the virtual environment can be a software environment. For example, the virtual environment can be provided using CAD software or can comprise CAD software or CAD functionalities. The virtual environment can preferably be displayed on an output device, such as a computer screen, and / or edited or modified using manipulators, such as a computer mouse. For example, the virtual base substrate and / or the virtual functional elements and / or other components and / or elements can be provided in a database that the user can access when using the virtual environment.For example, the virtual environment can enable rapid prototyping and the database entries can be integrated into a rapid prototyping process.

[0015] The "experimental parameters" can preferably include framework conditions and / or boundary conditions that are determined by the experiment to be conducted. For example, experimental parameters can be determined by requirements that arise from the object to be examined and / or that arise from the experimental setups used in the experiment, such as microscopes. For example, the experimental parameters can place certain requirements on the experimental substrate, for example with regard to a maximum and / or minimum size of the experimental substrate and / or temperature resistance or heat resistance and / or a specific material and / or a specific material combination and / or with regard to certain electrical properties and / or certain optical properties.Furthermore, the experimental parameters may require that the experimental substrate, for example, has structures for accommodating the object to be examined and / or for accommodating and / or conducting liquids and / or for supplying experimental substances. For example, the experimental substrate may be designed for microscopy applications.

[0016] A “functional element” may, for example, comprise an optical element and / or a connection for a tube and / or a syringe and / or a capillary.

[0017] "Prefabricated" is preferably understood to mean that the prefabricated basic substrate and / or the at least one prefabricated functional element is not generated by the 3D printer itself during the production of the experimental substrate, but is already provided at least partially in finished form and is taken into account in this form during production in the 3D printer. In other words, the prefabricated basic substrate and / or the at least one prefabricated functional element can be cast with other elements by the 3D printer during the production of the experimental substrate using the curable bonding material, so that they form part of the experimental substrate, which is preferably designed as a structural unit, without the 3D printer having to completely create the prefabricated elements itself.

[0018] The fact that the experimental substrate is designed as a structural unit preferably means that the finished experimental substrate forms a coherent and / or compact unit which can be used as a uniform element, wherein preferably no further manufacturing steps are required to assemble the experimental substrate.

[0019] A "3D printer" is understood to mean any type of device that is suitable or configured to perform an additive and / or generative manufacturing process. In particular, the 3D printer can comprise a desktop device, for example, with a build platform of limited spatial dimensions, although other configurations are also possible. For example, the 3D printer can be designed to perform a 3D printing process, which is also known in the art as fused deposition modeling. Alternatively or additionally, the 3D printer can be configured as or comprise a rapid prototyping device.

[0020] The invention offers the advantage that experimental substrates can be provided using the 3D printer, which have at least one functional element that typically cannot be processed or created using a 3D printer. For example, functional elements made of materials that typically cannot be produced using a 3D printer can be used or incorporated in the production of the experimental substrate. In this way, for example, complex experimental substrates can also be produced, which have functional elements made of different materials that cannot be processed using the 3D printer, and have other structures that can be produced using the 3D printer.For example, prefabricated functional elements made of materials that cannot be processed using a 3D printer can be combined with the base substrate using the 3D printer to form an experimental substrate designed as an integral unit. For example, functional elements made of metal, glass, and / or plastics that cannot be processed using a 3D printer can be integrated into the production of the experimental substrate. This allows for flexible adaptation of the experimental substrate to the desired experimental parameters.

[0021] Furthermore, the invention offers the advantage that the experimental substrate can be created, planned, or designed using at least one functional element in the virtual environment before the corresponding real experimental substrate is actually created. The virtual environment can access virtual functional elements, which are preferably stored in the virtual environment or in the system, and which can be used or considered by the user during the virtual planning or creation of the virtual experimental substrate. For example, various functional elements can be present as virtual components in the virtual environment, which can be selected by the user and used during the planning or implementation of the virtual experimental substrate.This offers the advantage that the experimental substrate can be planned or created initially in the virtual environment using prefabricated virtual functional elements, preferably with little effort, without having to first physically realize it as a real experimental substrate with great effort.

[0022] Thus, the invention offers the advantage that the production of experimental substrates adapted to the experimental parameters is possible with low manufacturing effort, since in the virtual environment, provided virtual functional elements and in 3D printing, corresponding real functional elements can be used, whereby the effort in creating the virtual experimental substrate and also the effort in 3D printing can be reduced compared to creating and / or manufacturing an experimental substrate without prefabricated functional elements.

[0023] Furthermore, the invention offers the advantage that the experimental substrate, which is adapted to predetermined experimental parameters, can be produced quickly and precisely in a defined manner using the 3D printer and the base substrate and the at least one functional element. This consequently offers the advantage that the experimental substrate can be produced in a reproducible manner. For this purpose, it may be advantageous, for example, to save the virtual experimental substrate in the virtual environment and, if necessary, to produce another real experimental substrate based on it. Thus, according to the invention, deviations in experiments due to unwanted inaccuracies and / or deviations between experimental substrates that should actually be identical can be avoided.

[0024] Preferably, the creation of the virtual experimental substrate comprises creating or defining a scaffold structure and / or a substrate structure, in particular for an imaging method, and / or a structure for storing and / or embedding bioactive substances and / or manipulation structures and / or control structures and / or supply structures. Accordingly, the printing in step d) preferably comprises producing the corresponding real elements or structures during the production of the experimental substrate.

[0025] Preferably, the method further comprises the step: b1) Verifying the functionality of the virtual experimental substrate in the virtual environment; wherein step b1 is carried out chronologically after step b) and before step c). This offers the advantage that any malfunctions, which are based, for example, on a defective design or defective structuring of the experimental substrate, can be detected and / or avoided during the planning of the experimental substrate in the virtual environment. For example, checking the functionality of the virtual experimental substrate in the virtual environment can include a simulation of an interaction or interaction of the at least one functional element with the basic substrate. Preferably, the user can assess and / or recognize, based on the functionality check, whether the virtual experimental substrate created in the virtual environment meets their requirements or experiment parameters, so that the user can make further modifications and / or improvements if necessary.This offers the advantage that the experimental substrate can preferably be released for production using the 3D printer after the user has been able to gain an impression of the functionality of the experimental substrate in the virtual environment. In this way, defective production, such as the production of experimental substrates that do not function and / or do not function as intended and / or are not structured as desired, can be avoided, thereby avoiding or even completely preventing unnecessary waste of resources. Preferably, the functionality check can also include a collision check and / or a feasibility check, in which a collision-free arrangement of the intended elements or the technical feasibility of the created virtual experimental substrate is verified.

[0026] Preferably, the at least one virtual functional element comprises a plurality of similar and / or different functional elements and / or the at least one real, prefabricated functional element comprises a plurality of similar and / or different real, prefabricated functional elements, wherein the real, prefabricated functional elements correspond to the virtual functional elements. In other words, a plurality of similar and / or different functional elements can preferably be used in the production of the experimental substrate. Preferably, each type of real, prefabricated functional element is correspondingly mapped in the virtual environment and can be used or taken into account accordingly in the virtual environment when creating the virtual experimental substrate. This offers the advantage of increasing the flexibility in the creation or production of the experimental substrate.

[0027] Preferably, the provision of the real, prefabricated basic substrate in the 3D printer in step c) takes place manually by a user or automatically. For example, it may be necessary for the user to provide the prefabricated basic substrate and / or the at least one prefabricated functional element before and / or during the manufacturing process and / or to insert and / or position it in a manufacturing device and / or in the 3D printer. This offers the advantage that a complex device for providing and / or inserting and / or positioning the prefabricated elements can preferably be dispensed with. Alternatively, the provision of the real, prefabricated basic substrate and / or the at least one prefabricated functional element in the 3D printer can take place automatically. For example, a supply system can be designed for this purpose, which is supplied at the desired times orat the desired time, the real, prefabricated base substrate and / or at least one prefabricated functional element is provided and / or inserted. This has the advantage that the production of the real experimental substrate can preferably be automated and preferably no user intervention is required during the production of the experimental substrate or during printing with the 3D printer.

[0028] Preferably, the real, prefabricated base substrate and / or the at least one real, prefabricated functional element are at least partially formed from a different material than the connecting material and can be connected to the connecting material in such a way that, upon curing of the curable connecting material, a one-piece structural unit of the real, prefabricated base substrate and / or the at least one real, prefabricated functional element with the connected, curable connecting material is created. This offers the advantage that the base substrate and / or the at least one functional element can be connected to the curable connecting material, so that the cured connecting material is firmly connected to the connected base substrate and / or at least one functional element.

[0029] Preferably, the real, prefabricated base substrate and / or the at least one real, prefabricated functional element each have a fastening section by means of which the real, prefabricated base substrate and / or the at least one real, prefabricated functional element can be connected to the curable connecting material. For example, the fastening section can be designed to be connected to the curable connecting material using the 3D printer. For example, such a fastening section can be configured to be subjected to a melting process and / or a curing process by means of the 3D printer, while, for example, other sections of the base substrate and / or the at least one functional element cannot be subjected to a melting process and / or a curing process by the 3D printer.This offers the advantage that the base substrate and / or the at least one functional element can be connected to or attached to the curing bonding material in a particularly simple manner.

[0030] The at least one real, prefabricated functional element preferably comprises an electrical element, in particular an electrode, and / or an electronic element, in particular a semiconductor element, and / or an optical element, in particular a refractive and / or diffractive element. For example, the at least one functional element can be designed as or comprise a window and / or an optical lens and / or an optical grating. Furthermore, the functional element can preferably be designed as or comprise a nozzle and / or a pipeline and / or a hose and / or a liquid reservoir. This offers the advantage that the experimental substrate can be designed in this way with various functionalities that cannot be produced, for example, using the 3D printer alone or only with relatively great effort.

[0031] According to the invention, the method further comprises selectively applying at least one real experimental substance into and / or onto the experimental substrate such that the at least one real experimental substance is at least partially surrounded by the real, prefabricated base substrate and / or by the at least one real, prefabricated functional element. For example, the experimental substance can comprise a nutrient medium and / or pharmaceuticals for a sample to be examined, which are to be brought into contact with the sample to be examined, for example, before and / or during the experiment. This offers the advantage that the experimental substrate can also be adapted and / or provided for complex experiments and, in particular, can be adapted to the temporal sequence of an experiment.This offers the advantage that a subsequent modification of the experimental substrate, as with conventional experimental substrates, is not necessarily required, since the structures required for the experiment can already be taken into account and / or formed during the production of the experimental substrate.

[0032] According to the invention, the method further comprises a prior virtual arrangement of at least one virtual experimental substance in and / or on the virtual experimental substrate in the virtual environment, wherein the real experimental substance corresponds to the virtual experimental substance.

[0033] Preferably, the virtual arrangement of the at least one virtual experimental substance takes place during and / or after step b) and before step c), whereby the selective application of the at least one real experimental substance preferably takes place during and / or after step d). Preferably, in step b1), a check of the functionality of the structures that serve to provide the experimental substance also takes place. This offers the advantage that the arrangement and / or application of the experimental substance is also possible in volumes of the experimental substrate, which may not be possible or only possible with difficulty after the experimental substrate has been manufactured.

[0034] For example, the at least one real experimental substance has at least partially a solid and / or a liquid and / or a pasty form and / or is in gaseous form. In other words, experimental substances of various forms can be used, thereby increasing the flexibility in adapting the experimental substrate to the experiment being conducted.

[0035] Preferably, the selective application of the at least one real experimental substance can be carried out using the 3D printer and / or a separate experimental substance delivery device. For example, the 3D printer can be configured to apply the corresponding experimental substance during the manufacturing process. Alternatively or additionally, an experimental substance delivery device can be used for this purpose, which can preferably be provided independently of the 3D printer.

[0036] Preferably, the experimental substrate can also be subjected to other processing after completion with the 3D printer, so that, for example, the experimental substrate can be at least partially subjected to laser ablative and / or machining processing.

[0037] Preferably, steps b) and d) of the method are carried out such that the experimental substrate (50) at least partially comprises a microfluidic system. In other words, the experimental substrate is preferably designed such that it comprises a microfluidic system or is designed as such. In particular, the experimental substrate can be designed or manufactured such that it comprises a lab on a chip (LOAC) or is designed as such. This offers the advantage that integrated structures can be provided in or on the experimental substrate in a targeted manner, which structures are suitable, for example, for conducting and / or storing fluids and can thus be adapted in a particularly suitable manner to the implementation of the planned experiment.

[0038] Further advantages and embodiments of the invention will become apparent from the description and the accompanying drawings.

[0039] It is understood that the features mentioned above and those to be explained below can be used not only in the combination specified in each case, but also in other combinations or on their own, without departing from the scope of the present invention.

[0040] The invention is illustrated schematically in the drawings using exemplary embodiments and is described below with reference to the drawings. Character description Fig. 1 shows a schematic representation of a process sequence according to a preferred embodiment. Fig. 2 shows a schematic representation of an apparatus for producing an experimental substrate according to a first preferred embodiment. The Fig. 3A to 3C show a base substrate and functional elements according to preferred embodiments. Fig. 4 shows parts of an apparatus 10 for producing an experimental substrate according to a second preferred embodiment. The Fig. 5A and Fig. 5B show a schematic representation of an experimental substrate 50 according to a preferred embodiment.

[0041] Fig. Figure 1 shows a schematic diagram 100 of a process flow for producing an experimental substrate according to a preferred embodiment. In a first step 102, experimental parameters are defined, for example, by determining the object to be examined and / or the experiment to be conducted and determining the resulting requirements for the experimental substrate.

[0042] In a step 104, a suitable base substrate is selected based on the predetermined experimental parameters, on which the experimental substrate to be produced is to be based. The selection of the base substrate can take place in the virtual environment, whereby a virtual base substrate is selected that satisfies the experimental parameters or requirements, and / or by selecting a real base substrate, the virtual representation of which in the virtual environment is then used for the virtual creation of the virtual experimental substrate.

[0043] In a step 106, at least one virtual functional element is selected in the virtual environment and the at least one virtual functional element is arranged relative to the virtual base substrate. In other words, in step 106, the virtual experimental substrate is constructed or created in the virtual environment. For example, several similar and / or different functional elements can be combined and arranged relative to the base substrate in a manner suitable for the experiment. Furthermore, one or more regions can also be specified in the virtual environment in which the 3D printer is to apply curable bonding material in order to later produce the experimental substrate from the base substrate and the at least one functional element.Furthermore, in step 106, further modules and / or elements and / or structures are arranged, which are created directly by the 3D printer and preferably form the experimental substrate in cooperation with the basic substrate and / or the at least one functional element or are encompassed by it.

[0044] In step 108, according to the preferred embodiment, an optional functional test is performed in the virtual environment, wherein the arrangement is checked for the interaction of the basic substrate and the at least one functional element and the optional structures and / or modules and / or elements, which are created directly by the 3D printer. If there are doubts about the correct functionality of the created experimental substrate in the virtual environment, modifications can be suggested and / or made by the user, for example, to eliminate these doubts. If there are no doubts about the correct functionality of the created experimental substrate in the virtual environment, production of the real experimental substrate can proceed.

[0045] In step 110, the real base substrate, which corresponds to the virtual base substrate, and the at least one corresponding functional element are provided in the 3D printer, so that the 3D printer is subsequently able to produce the experimental substrate using the base substrate and the at least one functional element. According to preferred embodiments, the arrangement can be carried out by the user and / or, according to other preferred embodiments, in an automated manner by the 3D printer and / or another provisioning device.

[0046] In step 112, the experimental substrate is printed by 3D printing using the real base substrate and the at least one functional element, which were previously arranged in the 3D printer. The 3D printer preferably connects the base substrate and the at least one functional element using the curable bonding material. Furthermore, during 3D printing, additional structures and / or modules and / or elements of the experimental substrate can be directly generated by 3D printing, so that the resulting experimental substrate has the desired functionalities. According to preferred embodiments, step 112 can further comprise a selective application of an experimental substance, which, for example, is to be integrated into the experimental substrate.

[0047] After the printing process is completed in step 112, further processing steps, such as machining and / or laser ablation, can optionally be performed on the printed experimental substrate. Otherwise, the experimental substrate is finished after printing and, after any necessary curing time, is ready for experimental use.

[0048] Fig. Figure 2 shows a schematic representation of a device 10 for producing an experimental substrate 50 (see Fig. 4) according to a first preferred embodiment. The device 10 has a computing unit 12, which serves to provide the virtual environment for creating the virtual experimental substrate and, after completion of the virtual creation of the virtual experimental substrate, to provide print data based thereon to a 3D printer 14, on the basis of which the 3D printer 14 can produce the real experimental substrate.

[0049] The 3D printer 14 has a print head 16 which is configured to create structures and / or modules and / or elements by means of a curable connecting material, in particular on the provided base substrate, and / or to connect the base substrate to the at least one functional element by means of the curable connecting material.

[0050] Furthermore, the 3D printer 14 has a receiving mechanism or receiving head 18. The receiving head 18 can, for example, be configured to receive reaction fluids and serve as a reservoir for the provision of the reaction fluids.

[0051] In addition, the device 10 has a provision device 20, by means of which basic substrates and / or functional elements, which are selected in the virtual environment during the creation of the virtual experimental substrate, can be provided to the 3D printer for producing the real experimental substrate. Furthermore, the device 10 has a manual provision option 22 for manually providing basic substrates and / or functional elements, via which the user can manually provide additional basic substrates and / or functional elements to the 3D printer 14. For example, frequently used basic substrates and / or functional elements can be provided automatically by the provision device 20, while less frequently used basic substrates and / or functional elements can be provided manually via the provision option 22.

[0052] In addition, the device 10 has an output module 24 for experimental substrates produced by the 3D printer 14, which can then be used and / or subjected to optional post-processing.

[0053] Fig. 3A shows an end portion of a base substrate 26 according to a first preferred embodiment, which is provided with a mounting portion 28. While the base substrate 26 is preferably formed from a material having a higher melting point than the curable bonding material used by the 3D printer, the material in the mounting portion 28 can be formed such that it is moldable by the 3D printer during 3D printing in order to connect the base substrate 26 at least partially above the mounting portion 28 to other modules and / or structures and / or elements by means of the curable bonding material.

[0054] Fig. 3B shows a functional element 30 according to a further preferred embodiment, which has a pipeline element 32, by means of which, for example, reaction fluids can be supplied to certain partial volumes of the experimental substrate during the experiment. In particular, the pipeline element 32 can be designed, for example, as a glass tube and / or as a plastic tube and / or as a metal tube. Furthermore, the functional element 30 has a flexible hose element 34, which is connected to the pipeline element 32 in such a way that a fluid can flow from the hose element 34 into the pipeline element 32. For example, the functional element 30 can be designed and in orbe arranged on the experimental substrate 50 such that the hose element 34 extends away from the experimental substrate 50 and is thus easily accessible from outside the experimental substrate 50, for example to provide reaction fluids via the hose element 34 and the pipe element 32 at the outlet 36 in the experimental substrate. In contrast, the pipe element 32 is designed such that it can be firmly connected to other modules and / or structures and / or elements and / or the base substrate 26 or to the experimental substrate by means of the connection region 28. In this way, precise positioning and / or provision of reaction fluid by means of the functional element 30 in or on the experimental substrate can be ensured, whereby the reaction fluid can nevertheless be easily supplied from outside the experimental substrate by means of the hose element 34.

[0055] Fig. 3C shows a functional element 30 according to a further preferred embodiment. The functional element 30 comprises an electrode 38. The electrode 38 can, for example, be designed as a metallic electrical conductor, which, for example, has the shape of a needle or a rod, as shown. In particular, the exposed end of the electrode 38 shown on the right can be provided to be arranged in a sample space within or on the experimental substrate, for example to provide and / or tap an electrical potential in the sample space. The functional element 30, like the electrodes shown in the Fig. 3A and Fig. 3B are connected to the experimental substrate in a form-fitting and / or force-fitting manner by means of the fastening section 28. On the left-hand side of the electrode 38, the electrode is provided with a connecting wire, by means of which the electrode 38 can be easily brought to a specific electrical potential from outside the experimental substrate.

[0056] Fig. 4 shows parts of a device 10 for producing an experimental substrate 50 according to a second preferred embodiment. In particular, the device 10 comprises a 3D printer 14 equipped with a specially designed print head 16. According to the embodiment shown, the print head 16 is configured to provide the curable bonding material in a spatially structured manner by means of a filament outlet 40 in order to produce the experimental substrate 50 using the base substrate 26 and the at least one functional element 30 in its function as a 3D printer.In addition, the print head 16 has an experimental substance outlet 42, by means of which at least one experimental substance can be introduced into and / or onto the experimental substrate 50 during and / or after the production of the experimental substrate 50 in order to provide the experimental substrate 50 to be produced with the desired experimental substances at the desired positions. Accordingly, the 3D printer 14 can have a feed device 44, by means of which the curable bonding material can be fed to the print head 16. In addition, the 3D printer 14 can have a feed device 46 for the at least one experimental substance, by means of which the at least one corresponding experimental substance can be fed to the print head 16.For example, the experimental substrate 50 can thus be produced essentially by means of the filament outlet 40 and, during this time and / or thereafter, an experimental substance can be filled with at least one experimental substance by means of the experimental substance outlet 42.

[0057] Furthermore, the device can have a sample robot 48 formed separately from the print head 16, by means of which, for example, the experimental substrate 50 or a sample arranged in and / or on the experimental substrate 50 can be manipulated. For example, the sample robot 48 can comprise a mechanical action on the sample and / or a mechanical manipulation of the sample. Alternatively or additionally, the sample robot 48 can serve to arrange a specimen or the sample to be examined on the experimental substrate 50 and / or in and / or on a sample container, or to introduce it onto and / or into it.

[0058] The Fig. 5A and Fig. 5B show a schematic representation of an experimental substrate 50 according to a preferred embodiment, in plan view and in perspective. The experimental substrate 50 comprises a base substrate 26, which, according to the embodiment shown, is designed as a base plate.

[0059] Furthermore, the experimental substrate 50 has two functional elements 30, each of which is designed as a fiber feedthrough, for example, to couple electromagnetic radiation or light into or out of the experimental substrate 50 by means of connected optical fibers 54, in order to be able to conduct, for example, optical experiments on a sample arranged in the experimental substrate. In a region 56 between the two functional elements 30, the experimental substrate 50 has two side walls 58, which, for example, enable the storage of a fluidic sample in the volume between the side walls 58 and between the functional elements 30. For example, the side walls 58 can be provided as separate functional elements 30, for example as glass plates, during the production of the experimental substrate 50 or, alternatively, can be formed by the 3D printer using the curable bonding material. Reference symbol 10 Device 12 computing unit 14 3D printers 16 Print head 18 Recording head 20 Provisioning device 22 manual deployment option 24 Output module 26 Basic substrate 28 Fastening section 30 functional element 32 Pipe element 34 hose element 36 Outlet 38 Electrode 40 filament outlet 42 Experimental substance outlet 44 Feeding device for curable material 46 Feeding device for experimental substance 48 Sample robotics 50 experimental substrate 54 optical fibers 56 Area 58 side wall 100 Diagram of a process flow 102 - 112 process steps

Claims

[1] Method for producing an experimental substrate (50) designed as a sample holder for microscopy applications, comprising the steps: a) Selecting a virtual base substrate in a virtual environment based on given experimental parameters; b) selecting at least one virtual functional element and arranging the at least one virtual functional element in the virtual environment relative to the virtual base substrate to create a virtual experimental substrate in the virtual environment, wherein the at least one virtual functional element is at least partially specified in the virtual environment; c) providing a real, prefabricated basic substrate (26) corresponding to the virtual basic substrate and providing at least one real, prefabricated functional element (30) corresponding to the virtual functional element in a 3D printer (14); d) printing the experimental substrate (50) by means of the 3D printer (14) using the real basic substrate (26) and the at least one real, prefabricated functional element (30) according to the virtual experimental substrate (50) in the virtual environment such that the real basic substrate (26) and the at least one real, prefabricated functional element (30) form the experimental substrate (50) as a structural unit, further comprising a selective application of at least one real experimental substance in and / or onto the experimental substrate (50) such that the at least one real experimental substance is at least partially surrounded by the real, prefabricated base substrate (26) and / or by the at least one real, prefabricated functional element (30), further comprising a virtual arrangement of at least one virtual experimental substance in and / or on the virtual experimental substrate in the virtual environment, wherein the virtual arrangement of the at least one virtual experimental substance takes place during and / or after step b) and before step c), and wherein the selective application of the at least one real experimental substance takes place during and / or after step d). [2] The method of claim 1, further comprising the step of: b1) Verifying the functionality of the virtual experimental substrate in the virtual environment; wherein step b1 is carried out after step b) and before step c). [3] Method according to claim 1 or 2, wherein the at least one virtual functional element has a plurality of similar and / or different functional elements, and wherein the at least one real, prefabricated functional element (30) has a plurality of similar and / or different, real, prefabricated functional elements (30), wherein the real, prefabricated functional elements (30) correspond to the virtual functional elements. [4] Method according to one of the preceding claims, wherein the provision of the real, prefabricated base substrate (26) in the 3D printer (14) in step c) is carried out manually by a user or automatically. [5] Method according to one of the preceding claims, wherein the provision of the at least one real, prefabricated functional element (30) in the 3D printer (14) in step c) is carried out manually by a user or automatically. [6] Method according to one of the preceding claims, wherein the printing of the experimental substrate (50) by means of the 3D printer (14) in step d) is carried out using a curable bonding material. [7] Method according to claim 6, wherein the real, prefabricated base substrate (26) and / or the at least one real, prefabricated functional element (30) are at least partially formed from a different material than the connecting material and can be connected to the connecting material in such a way that when the curable connecting material hardens, a one-piece structural unit of the real, prefabricated base substrate (26) and / or the at least one real, prefabricated functional element (30) with the curable connecting material connected thereto is created. [8] Method according to claim 6 or 7, wherein the real, prefabricated base substrate (26) and / or the at least one real, prefabricated functional element (30) each have a fastening section (28) by means of which the real, prefabricated base substrate and / or the at least one real, prefabricated functional element can be connected to the curable connecting material. [9] Method according to one of the preceding claims, wherein the at least one real, prefabricated functional element (30) comprises an electrical element, in particular an electrode (38), and / or an electronic element, in particular a semiconductor element, and / or an optical element, in particular a refractive and / or diffractive element. [10] Method according to one of the preceding claims, wherein the at least one real experimental substance has at least partially a solid and / or a liquid and / or a pasty form and / or is in gaseous form. [11] Method according to one of the preceding claims, wherein the selective application of the at least one real experimental substance is carried out by means of the 3D printer (14) and / or by means of a separate experimental substance provision device. [12] Method according to one of the preceding claims, wherein steps b) and d) are carried out in such a way that the experimental substrate (50) at least partially comprises a microfluidic system. [13] Device which is arranged to carry out a method according to one of the preceding claims. [14] Device according to claim 13, comprising a 3D printer (14) and a computing unit (12), wherein the computing unit (12) is programmatically configured to provide the virtual environment.

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