DE102024117884A1 - Shelving system for a microfluidic chip system - Google Patents

Abstract

The invention relates to a rack system (100) for a microfluidic chip system (10) for the parallel execution of several fluid-based experiments on at least two separate microfluidic chips (20), each having at least two chambers (22), chip inlet channels (24) from a chip inlet opening (23) to each of the chambers (22) and chip outlet channels (26) from the chambers (22) to a chip outlet opening (25), characterized by several rack slots (120), each of which has a slot holding device (122) for holding a single microfluidic chip (20) in a holding position (HP) and further slot outlet openings (123) for fluid connection with the chip inlet openings (23) of the microfluidic chip (20) in the holding position (HP).

Description

The present invention relates to a racking system for a multifluidic chip system for the parallel execution of several fluid-based experiments on at least two separate microfluidic chips, a racking box for such a racking system, and a method for filling a racking system with at least one racking box.

It is known that several liquid-based experiments must be conducted in parallel, for example, to search for new drugs, conduct experiments on humanoid cells, or similar applications. For this purpose, the known experiments are carried out in separate experimental chambers and must be controlled independently. This separate execution and control of the experiments leads to a high degree of complexity and, above all, to an enormous expenditure of time for conducting the experiments and extracting insights from the results. Furthermore, it is not possible to conduct multiple experiments simultaneously to differentiate between, for example, different concentrations, different experimental schedules, or different parameters.

The commonly known solutions have a major drawback in terms of efficiency and ease of use with this system. In particular, establishing the fluid connections between multiple microfluidic chips and the containers for storing the liquid samples is complex and difficult. Furthermore, it is challenging to find a solution that completely prevents any contamination of the system, which would lead to ineffective experiments or even unusable results.

It is an object of the present invention to at least partially solve the aforementioned problem. In particular, it is an objective of the present invention to provide a simple means of duplication and automation for the microfluidic chip system.

The aforementioned purpose is achieved by a shelving system with the features of independent claim 1, a shelf box with the features of independent claim 8 and a method with the features of independent claim 13.

Further features and details of the invention will become apparent from the dependent claims, the description, and the drawings. The features and details discussed with regard to the shelving system can be combined with the features discussed with regard to the shelf box and the method, and vice versa.

According to the present invention, the racking system for a microfluidic chip system is designed for the parallel execution of multiple liquid-based experiments on at least two separate microfluidic chips. The microfluidic chips have at least two chambers, chip inlet channels from a chip inlet opening to each of the chambers, and chip outlet channels from the chambers to a chip outlet opening. A racking system according to the invention is characterized by several rack slots. Each of these rack slots has slot retainers for holding a single microfluidic chip in a holding position. Further slot outlet openings are provided in the rack slots for fluid communication with the chip inlet openings when the microfluidic chip is in the holding position.

The present invention relates in particular to a microfluidic chip system, which will be discussed in more detail below.

According to the present invention, a microfluidic chip system is provided for the parallel execution of several fluid-based experiments. To provide this functionality, the microfluidic chip system comprises at least two separate microfluidic chips. Each of these microfluidic chips has at least two chambers and chip inlet channels leading from the chip inlet openings to each of the chambers. Further chip outlet channels lead from each of the chambers to a chip outlet opening on each of the microfluidic chips. A microfluidic chip system according to the present invention is characterized by a liquid sampling station comprising several liquid samples. Each of these liquid samples is provided with a sample outlet channel. The sampling station includes selection means for temporarily selecting at least one liquid sample for liquid transport to the chip inlet openings. Furthermore, a collection valve is provided, which has switchable collection inlet openings, each of which is in fluid communication with a sample outlet channel, and which has at least one collection outlet opening with a collection channel that is in fluid communication with the chip inlet opening. Additionally, at least one liquid pump is provided to generate a liquid flow from the liquid sample via the sample outlet channels to the chip inlet openings.

The present invention is based in particular on several separate microfluidic chips. These microfluidic chips comprise two or more chambers on each of the chip chambers. to conduct a single microfluidic experiment. Each of the microfluidic chips is configured to have at least one inlet port to receive a fluid derived from one of the liquid samples. In other words, a specific fluid environment can be provided in each chamber of each microfluidic chip and modified over time to conduct different or identical microfluidic experiments in parallel. The possibility of a microfluidic experiment is discussed in more detail below.

To provide a solution for multiple parallel experiments, the present invention includes a sample station. The sample station can, for example, have several containers, each containing a specific liquid sample. A liquid sample could be, for example, a pH control agent, a solution for feeding humanoid cells, a drug compound, or a solvent for reducing the concentration of a drug compound. Of course, depending on the specific experiment to be performed in the microfluidic system, other or additional liquid samples can also be provided. It should be noted that the present invention is not limited to a specific number of liquid samples in the sample station. Thus, depending on the size and complexity of the entire microfluidic chip system, it is possible to have 10, 20, 30, or even 100 different liquid samples in the liquid station.

Based on an experimental recipe, it may be necessary during the experiment to supply a suitable composition over a specific period. For this purpose, the microfluidic chip system according to the invention can select a fluid path from the fluid pumping means to the specific liquid sample containing the selected pharmaceutical composition. Activating the fluid pump builds up pressure in the liquid sample, generating a fluid flow from the specific and selected liquid sample, which is connected to the sample outlet channel. This sample outlet channel transports the selected pharmaceutical composition from the selected liquid sample to the collection valve and the specific collection inlet port. By switching the collection valve, which opens a fluid path from this selected collection inlet port to the collection outlet port, the transport portion from the selected liquid sample via the collection valve to one or more chip inlet ports on the microfluidic chips is provided.

In the simplest version of the microfluidic chip system, this pharmaceutical fluid is now routed in parallel to all microfluidic chips and to all chambers of each chip. To enable even more sophisticated and complex control for separate and different experiments on each of the microfluidic chips, an additional distribution valve can be provided, as will be explained later.

Furthermore, this basic configuration does not include a chamber valve, so the selected liquid sample, e.g., the pharmaceutical composition, is now fed into all chambers on the microfluidic chips in parallel. This means that multiple experiments with the same pharmaceutical composition can now be performed. This can be used, for example, to create redundancy for the experiment. An alternative solution is to supply the same concentration of the pharmaceutical composition to different cell types located in the individual chambers, so that the same pharmaceutical composition is delivered to different cell compositions. This is the first example that demonstrates how the present invention creates a microfluidic chip system for highly complex and parallel-controllable fluid-based experiments in a simple manner.

Due to the scalability of the number of chambers on each microfluidic chip, the number of microfluidic chips, and the number of liquid samples in the sample station, a microfluidic chip system according to the present invention offers virtually unlimited scalability. There is no limit to the complexity or the number of experiments that a microfluidic chip system can perform. In particular, the microfluidic chip system can be placed in a semi- or fully automated environment. Specifically, the selection means can be semi- or fully automated, allowing the experiment itself to be carried out fully automatically based on a predefined experimental protocol. This applies particularly to the parallel execution of these experiments, meaning that each microfluidic chip and/or each of the chambers on the chips can be equipped with a specific and unique experimental protocol and can be controlled separately and specifically according to this protocol.

It is further advantageous if, according to the present invention, the microfluidic chip system is characterized in that the fluid pump device is arranged upstream of the liquid sampling station and, in particular, comprises a The system includes a gas compressor. The fluid pumping unit is specifically a gas pumping unit, representing a simple and cost-effective solution. Because the fluid pumping unit is located upstream of the liquid sampling station, no further problems arise regarding contamination or purity of the fluid pumping unit. Naturally, the selection agents are also located downstream of the fluid pumping unit and upstream of the liquid sampling station.

It is further advantageous if, according to the present invention, the microfluidic chip system is characterized in that the selection device is arranged upstream of the liquid sampling station and downstream of the fluid pumping device. This can be understood to mean that the selection device receives the pressure provided by the fluid pumping device and selectively transmits this received pressure to the liquid sampling station, in particular only to one or more selected liquid samples. This ensures that the selection device does not come into contact with the liquid samples, thus avoiding problems regarding purity and contamination for the selection device as well. Furthermore, the selection device is easily accessible and can be connected to a flow control unit that is part of this selection device.

A further advantage of the present invention is a microfluidic chip system characterized in that at least one of the microfluidic chips comprises a chamber valve to establish a switchable fluid connection between the chip inlet and at least one selected chamber. This is an on-chip or on-board valve. In other words, any composition or fluid supplied to the chip inlet can now be specifically and selectably directed to one or more chambers in the form of a subset. This enables the separation and differentiation of experiments on the microfluidic chip and means that different experiments can be performed in parallel in different chambers on the same and identical microfluidic chip. If no valve in the form of a chamber valve is provided, all chambers of the same microfluidic chip are supplied with the same liquid sample from the sample station, so that the experiments are similar or identical.

It is further advantageous if, according to the present invention, the microfluidic chip system is characterized in that a distribution valve is connected downstream of the collection valve, the distribution valve having a distribution inlet and switchable distribution outlet openings in fluid communication with the chip inlets for each collection channel. Similar to the chamber valve described above, the distribution valve offers a unique selection capability not at the chamber level, but at the chip level. In other words, the distribution valve allows the selected fluid from one of the fluid samples to be selectively supplied to only one of the microfluidic chips. Thus, each of the microfluidic chips can now be supplied with a separate and unique fluid sample in a separate and unique manner, enabling each of the microfluidic chips to perform different and unique experiments in parallel. Of course, it is also possible to combine the distribution valve of this embodiment with the chamber valve according to the embodiment mentioned above to allow for maximum complexity of unique and separate experiments in each of the chambers on each of the chips.

It is further advantageous if, according to the present invention, the microfluidic chip system is characterized in that flow sensors for measuring the fluid flow are provided in the sample outlet channels, the collection channel, and/or the distribution channels. In this way, qualitative or quantitative measurement is possible to determine the current flow situation in each of the channels. This can be used for a control method with a feedback loop that contains specific information about the quantity and volume of fluid transported into each of these channels. This can be achieved through direct or indirect measurement to obtain specific information about the flow rate in each of these channels.

It is further advantageous if, according to the present invention, the microfluidic chip system is characterized by the provision of a droplet generator comprising at least one droplet inlet opening in fluid communication with a sample outlet channel and a droplet channel with a droplet opening for generating fluid droplets to be transported to the chip inlet openings. In some cases, the amount of liquid to be transported into the respective chamber is extremely small. In these cases, regular control of the liquid flow may not be specific and precise enough. In such cases, a droplet generator can be provided within the microfluidic chip system so that the minimum amount of liquid that needs to be supplied corresponds to the quantity of a single droplet. In this case, the quantity is the number of droplets generated by the droplet generator and then delivered to the specific chamber. and/or are supplied to the specific microfluidic cell.

It is further advantageous if, according to the present invention, a microfluidic chip system is characterized by at least one mixing device having at least two mixing inlet ports, each in fluid communication with a sample outlet channel, a mixing chamber for mixing the liquid samples obtained from the at least two sample outlet channels, and a mixing outlet port for releasing the sample mixture in fluid communication with the chip inlet ports. Although the liquid samples in the sample station already provide a variety of different and unique liquid samples for some specific experiments, it can be advantageous to offer a further degree of flexibility for the liquids supplied to the cells and the microfluidic chips. For example, a rinsing fluid can be used to flush the respective channels between the supply of different pharmaceutical compositions. Furthermore, it is possible to adjust the concentration of a pharmaceutical component. In all these cases, mixing two liquids derived from separate liquid samples in the sample station can add complexity and variety to liquid-based experiments. If a mixing device is integrated into the microfluidic chip system, the automation of this mixing can be incorporated into the microfluidic chip system's control system. Naturally, such a mixing device can also be combined with a droplet generator, as described above.

It is further advantageous if, according to the present invention, the microfluidic chip system is characterized in that waste channels are provided in fluid connection with the chip outlet openings to collect waste from the fluid chambers of the microfluidic chips. This enables a push-through concept, i.e., the fluid, which is pushed by the fluid pump from the selected and specific fluid sample of the sample station through all channels into the respective chamber of the microfluidic cell, can ultimately be pushed out of the microfluidic chip and the respective chamber via this waste channel. In a very simple embodiment, a waste collector is provided to collect the waste fluid from all cells and/or all chambers. Furthermore, it is possible to provide a specific waste collection system for each of the microfluidic chips and/or each of the chambers of the microfluidic chip, as described in the embodiment described in the following section.

According to the present invention, it can be advantageous if the microfluidic chip system is characterized in that the waste channels comprise multiple waste collectors for collecting cell-specific waste fluid. This can be used for subsequent analysis, for example, an inline analysis for each of the waste channels, which is thereby specific and unique for each of the microfluidic chips and/or the chambers on one of these chips. For example, chromatography can be used to obtain a highly specific and detailed analysis of the waste fluid and thereby increase the knowledge about the experimental results.

It is further advantageous if, according to the present invention, the microfluidic chip system is characterized in that the liquid sampling station includes a temperature control device for controlling the temperature of the liquid samples. The temperature control device can, for example, provide the possibility of heating or, in particular, cooling portions of the liquid flow. This can be provided for specific channels that can transport a particular liquid or for combined channels such as the collection channel. This offers, in particular, the possibility of preconditioning the liquid with respect to temperature before the liquid enters the microfluidic chip and/or the microfluidic chip chamber.

A further advantage can be achieved if, according to the present invention, the microfluidic chip system is characterized in that fluid heating elements are provided for at least one of the sample output channels, the collection channel, and/or other fluid channels. While the liquid sample can be stored at a low temperature for storage purposes, particularly to deactivate biological components, heating these liquids via the transport channels to the microfluidic chip can activate these biological components in the liquid. In particular, further temperature shock caused by large temperature differences in the chambers of the microfluidic chips can be avoided by actively heating and/or cooling the transported liquid sample, as described above, before it is introduced into the chamber of the microfluidic chip. Again, both the heating and the aforementioned cooling can be selectable and unambiguously provided for each of the microfluidic cells and/or the respective specific chamber on one of the microfluidic cells.

It is further advantageous if, according to the present invention, the microfluidic chip system is characterized in that the collecting valve and/or other valves of the system More Multi-port rotary valves are included. This is a very cost-effective solution for providing a large number of ports with selective and switchable functionality. In particular, when multiple channels need to be combined or a single or a few channels need to be distributed to multiple outlets, these multi-port rotary valves offer a simple and cost-effective solution.

A further advantage can be achieved if, according to the present invention, the microfluidic chip system is characterized in that the microfluidic chips include sensors for measuring at least one experimental parameter of the fluid-based experiments. This could be, for example, a temperature, pH, optical sensor, or the like. This allows for the inline generation of experimental parameters while the experiment is still running. Furthermore, it is possible to use these experimental parameters to adjust the experimental procedure and thus modify the experimental procedure during its execution.

• - Lesen und Experimentrezept,
• - Durchführen der Schritte des Experimentrezepts durch selektives Aktivieren der Flüssigkeitspumpen und Schalten der Ventile.

Another embodiment of the present invention provides a control method for controlling several fluid-based experiments in parallel using a microfluidic chip system according to the invention. Such a control method is characterized by the following steps:

• - Reading and experiment recipe,
• - Performing the steps of the experimental recipe by selectively activating the liquid pumps and switching the valves.

A control method according to the invention offers the same advantages as those discussed in detail in connection with the microfluidic chip system.

The microfluidic chip system according to the invention can be complemented by a shelf system according to the invention. In particular, the shelf system offers easy access for inserting and removing shelf boxes, as will be explained later. While the microfluidic chip system already offers advantages in terms of manual fluid connection between all relevant ports when using general microfluidic chips, the introduction of the microfluidic chip system with a shelf system according to the present invention creates easy and simple access. The shelf system has several shelf slots for receiving at least one microfluidic chip each. The microfluidic chip can be received directly or using a shelf box, as described later. Connectivity for fluid communication is established by connecting the outlet openings of the slots to the inlet openings of the chip. This leads to the possibility discussed below.

To initiate a multiple-experiment setup for a microfluidic chip system as discussed here, the shelf boxes or the microfluidic chips must be loaded into the shelf system. This is achieved by sliding the microfluidic chips along the slot holders into the holding position and holding them there. The holding positions can be defined by two features. First, in a holding position, the microfluidic chip has a defined position relative to the shelf box and, in particular, relative to the slot outlet opening. This means that, in the holding position of the microfluidic chip, the slot outlet opening is in fluid communication with the chip inlet opening of the respective microfluidic chip.

Secondly, the slot retainers position the four fluid connections between the slot outlets and the chip inlet ports. In other words, moving, specifically sliding, the microfluidic chip along the slot retainers into the holding position not only provides positioning functionality but also connection functionality by linking the chip inlet ports to the slot outlet ports. Unlike conventional solutions that require manual connection of hoses or tubes, this is a very cost-effective and simple way to establish this fluid connection. The sliding movement into the holding position also reliably and efficiently prevents contamination of the fluid connection.

After an experiment is completed, the movement, particularly a sliding movement, can be reversed. The used microfluidic chip can be pulled out of the shelf slot in the opposite direction, thus allowing for easy and cost-effective removal from the shelf system. For the next experiment, the loading process begins again, and a new, freshly prepared microfluidic chip can be inserted into the respective shelf slot and loaded. In an embodiment with a shelf box that covers the chip(s), chips can be removed from the shelf box for further investigations and analyses. The shelf box can also be restocked with fresh chips for the next round of experiments.

The above description shows that not only a simple and efficient charging function, but also a simple and efficient A connection function is provided. In particular, the connection and charging functionality is separate for each of the shelf slots, so that even if an experiment is running on a microfluidic chip in one shelf slot, a swap process can be carried out in parallel in a timely manner for a second and separate shelf slot.

It can be advantageous if, according to the present invention, the racking system is characterized in that the rack slots have a retaining mechanism for releasably holding the microfluidic chips in the holding position. Such a retaining mechanism can, for example, provide a holding force in the holding position that must be overcome, for instance, during a sliding movement into the holding position. The retaining mechanism can also be referred to as a locking mechanism that prevents unwanted release from the holding position and thus indirectly also secures the fluid connection between the chip inlet and the slot outlet. Additionally, the retaining mechanism can apply a sealing force or a holding force that forces the entire microfluidic chip into the holding position and thereby provides a sealing force on sealing means, as described later.

It is further advantageous if the racking system according to the present invention is characterized in that the retaining means of the rack slots have sliding surfaces for a sliding movement of the microfluidic chip into the holding position. Although in principle any other type of movement is also possible to provide the advantages of the invention, a sliding movement is a preferred movement functionality. A sliding movement is possible in a simple and efficient manner and can be carried out, in particular, with relatively low resistance. By sliding the microfluidic chip into the holding position, further engagement functions can interact, for example, with the aforementioned holding mechanism and/or the establishment of the fluid connection between the chip inlet opening and the slot outlet opening.

According to the present invention, the shelf system is characterized in that the shelf slots are configured to accommodate the microfluidic chips, with a shelf box at least partially covering the microfluidic chips. Although it is possible to insert the microfluidic chips directly into the respective shelf slots, the use of a shelf box, as discussed in more detail later, offers more robust functionality for the microfluidic chips. The simplest way to construct such a shelf box is to provide a housing that surrounds the microfluidic chip itself. The housing is a robust way to ensure the safety of the contents, namely the microfluidic chip and the fluid pathways within the microfluidic chip. Particularly in cases where the used microfluidic chip is to be sent by mail for further analysis after completion of the experiment, the shelf box can provide a secure environment to safeguard the results of the experiment and enable detailed analysis at another location.

It is further advantageous if, according to the present invention, the shelf system is characterized in that the shelf slots have wired connectors for connecting to chip connectors of the microfluidic chips in the holding position. Such a wired chip connector is used in particular for electrical conductivity and/or signal transmission. As will be explained later, the shelf box can be equipped with further functions, such as a heating device, a cooling device, a valve device, a sensor device, or similar components. The wired connector can be used to control these elements and/or to provide electrical energy for the use of these components. In particular, the wired connectors are connected to the tip connectors in the same way as the fluid connection between the connector outlet openings and the chip inlet openings is established. By moving the shelf box and/or the microfluidic chip itself into the holding position, not only is the fluid connection automatically established, but the wired connection is also automatically established in the same way.

Further advantages can arise if the shelving system according to the invention is characterized in that several shelf slots are arranged in shelf columns and/or shelf rows. The more shelf slots are provided, the greater the flexibility and efficiency when using such a shelving system in a microfluidic chip system. By arranging the shelf slots along columns or shelf lines, the space within a microfluidic chip system is used more efficiently. In particular, the shelf slots have an opening direction that points in the same direction for all shelf slots, so that access to all shelf slots in the shelving system is from a single direction.

Further advantages can be achieved if, according to a racking system according to the invention, it is characterized in that the slot outlet openings have sealing elements for sealing. The system must provide a seal against the chip inlet openings with a microfluidic chip in the holding position. This seal is achieved, for example, by sealing rings or other elastically deformable sealing elements. Particularly in conjunction with the holding mechanism, as described above, a sealing force can be applied to the sealing elements in the microfluidic chip's holding position, so that the movement of the microfluidic chip in this position also automatically provides the sealing functionality. With a single movement, such as a sliding motion, several functions can now be achieved for mounting and inserting the shelf box and/or the microfluidic chip into the shelf slot. These multiple functionalities include positioning, establishing fluid communication, creating the cable connection, and sealing.

Another embodiment of the present invention is provided by a shelf box for a shelving system according to the invention. The shelf box comprises a box housing in which the at least one microfluidic chip is arranged. Each microfluidic chip has at least two chambers, chip inlet channels from a chip inlet opening to each of the chambers, and chip outlet channels from the chambers to a chip outlet. Furthermore, the chip inlet openings extend through the housing to connect to the outlet openings when the shelf housing is in the holding position. A shelf box offers the same advantages as discussed in detail with regard to the shelving system according to the invention.

In particular, a shelving system according to the invention comprises at least one shelf box which is inserted into one of the numerous slots in order to be prepared for the parallel execution of several fluid-based experiments.

It can be advantageous if a shelf box according to the present invention is characterized in that at least two microfluidic chips are located in the box housing. The presence of more than one microfluidic chip inside the shelf box significantly increases its usability. More than one microfluidic chip offers greater complexity for parallel experiments. This embodiment can be equipped with separate chip inlets for each of the contained microfluidic chips or with a combined chip inlet for all at least two microfluidic chips, all located in the same housing.

It is further advantageous if a shelf box according to the present invention is characterized in that at least one temperature control device, which in particular comprises a heating element, is arranged within the box housing. This enables temperature control within the shelf box and eliminates the need for separate temperature control functionality within the rest of the microfluidic chip system. This can be achieved by heating and/or cooling devices, which make it possible to create a specific and controllable environment for each experiment on the same microfluidic chip.

It is further advantageous if a shelf box according to the present invention is characterized in that the box housing includes a signaling element that provides a signal to a user when the shelf box is in the holding position. As explained in detail above, the holding position and reaching the holding position are crucial for achieving the various described functionalities. This applies in particular to establishing the fluid connection between the slot outlet openings and the chip inlet openings. Therefore, the signaling element provides the user, who inserts the shelf box into the shelf slot, with signal feedback that the holding position has been reached and that the secondary functionalities, such as establishing the fluid connection, are thereby ensured. In particular, the signaling element emits a light signal or an audible signal, which can be generated electrically or mechanically.

It is further advantageous if a shelf box according to the present invention is characterized in that at least one sensor element for measuring at least one experimental parameter is arranged inside the box housing. Such a sensor element can, for example, detect temperature, pH value, pressure, or similar physical or biological parameters. It can be used for experiment control and/or for generating experimental data during the execution of the liquid-based experiments. Signal communication can be carried out via the aforementioned wired connections.

It is further an object of the present invention to provide a method for filling a shelving system according to the invention with at least one shelf box according to the invention. The method is characterized by the step of moving the at least one shelf box into the holding position. The method according to the invention has the same advantages as those already explained in detail with regard to the shelving system and the shelf box according to the invention.

• 1 eine Ausführungsform eines mikrofluidischen Chipsystems,
• 2 eine weitere Ausführungsform eines mikrofluidischen Chipsystems,
• 3 eine weitere Ausführungsform eines mikrofluidischen Chipsystems, und
• 4 eine weitere Ausführungsform eines mikrofluidischen Chipsystems,
• 5 eine Ausführungsform eines erfindungsgemäßen Regalsystems,
• 6 eine weitere Ausführungsform eines erfindungsgemäßen Regalsystems,
• 7 eine weitere Ausführungsform eines erfindungsgemäßen Regalsystems,
• 8 ein erster Schritt einer Belastungsmethode,
• 9 ein weiterer Schritt einer Belastungsmethode,
• 10 Die Halteposition ist der Endpunkt der Belastungsmethode,
• 11 ein Aufbau eines Regalsystems, und
• 12 eine weitere Ausführungsform einer Regalbox.

Further features, details, and advantages are described with reference to the attached drawings. These show schematically:

• 1 an embodiment of a microfluidic chip system,
• 2 another embodiment of a microfluidic chip system,
• 3 another embodiment of a microfluidic chip system, and
• 4 another embodiment of a microfluidic chip system,
• 5 an embodiment of a shelving system according to the invention,
• 6 another embodiment of a shelving system according to the invention,
• 7 another embodiment of a shelving system according to the invention,
• 8 a first step in a stress method,
• 9 a further step in a stress method,
• 10 The holding position is the endpoint of the loading method.
• 11 the construction of a shelving system, and
• 12 another embodiment of a shelf box.

In 1 A very simple and cost-effective solution for the microfluidic chip system 10 is shown. This microfluidic chip system 10 comprises a gas compressor that functions as a liquid pump 50. Air is drawn in from the environment through a filter (not shown) and used to increase the pressure in the line to the selection media 34. The selection device 34 can then selectively supply the pressure from the liquid pump device 50 to one or more of the liquid samples 32 and the sample station 30.

This allows the outlet openings of the selection device 34 to be controlled based on the experimental recipe ER. For example, if the leftmost liquid sample 32 is selected by the selection device 34, the pressure provided by the liquid pump device 50 is supplied only and specifically for the leftmost liquid sample 32 in the sample station 30. This forces the liquid of this liquid sample 32 through the respective and specific sample outlet 33 to reach a specific and selected collection inlet opening 43 on the collection valve 40. The collection valve 40 then actively establishes only one fluid connection from this lower collection inlet opening 43 to the single collection outlet opening 45. The liquid then continues via the collection channel 44 and is distributed to three separate multifluidic chips 20.

Each of these multifluidic chips 20 includes a chip inlet opening 23 for receiving the liquid sample 32 via the collection channel 44. Furthermore, each of the multifluidic chips 20 in this example includes three separate but identical chambers 22, in each of which biological cells can be cultivated. The distribution of the liquid sample 32 now takes place downstream of the chip inlet opening 23 via the chip inlet channels 24, and in the solution of 1 The selected liquid sample 32 is distributed evenly from the leftmost liquid sample 32 to all three microfluidic chips 20. Due to the absence of a further valve system, each of the microfluidic chips 20 now distributes the provided and selected specific liquid sample 32 via the chip inlet channels 24 to each of the three chambers 22. Any additional liquid already present in the chambers 22 is forced out through the chip outlet channel 26 to the chip outlet openings 25 and can be collected, for example, in a waste container.

In 2 is shown a further embodiment of the present invention, which is based on the solution of 1 The system is based on the following principle. In this case, a selectable microfluidic chip 22 is defined by the distribution valve 60. The liquid sample 32, supplied at a distributor inlet port 63, can now be selectively distributed to only one of the microfluidic chips 20. All chambers 22 on the selected microfluidic chip 20 are now supplied with the same and identical unique liquid sample 32, but a different liquid sample 32 can be supplied and distributed to each of the other remaining microfluidic chips 20. This is done by the distribution valve 60, e.g., in the form of a rotary valve, by selectively connecting the distributor inlet port 63 to distributor outlet ports 65.

More 2 Figure 1 shows a selective mixing function for the two right-hand liquid samples 32. They can now be fed together to the mixing inlet openings 23 of a mixing device 80. They are mixed in a mixing chamber 81, and the mixture of the samples is then provided at the mixing outlet opening 85. To combine this functionality with the one in Figure 2, the following is shown: 1 To combine the described functionality, a further, unspecified valve element is arranged downstream of the collecting valve 40 and the mixing medium 80 to control the fluid path from the mixing chamber 81 to the distribution To combine or selectively connect the ler valve 60 or the collection valve 40 to the distributor valve 60.

In 3 In addition to the mixing agents 80, a droplet generator 70 is provided. In this case, the mixed liquid sample, which is supplied by the mixing outlet opening 85, is received by the droplet inlet opening 73 and the droplet opening 75 delivers one or more counted drops of the mixture of the sample, which is then moved forward within the droplet generator and fed to the droplet channel 74.

4 Figure 2 shows a further embodiment of the present invention in which each of the microfluidic chips 20 is provided with additional chamber valves 28. These chamber valves 28 enable the selection of a specific chamber 22 on each of the microfluidic chips 20, so that a unique and different experiment can be carried out in each of the chambers 22, which differ from other chambers 22 on the same microfluidic chip 20.

Furthermore, in 4 All microfluidic chips 20 are equipped with waste channels 27 that direct specific waste from a specific chamber 22 of a specific microfluidic chip 20 to a specific waste collector 29. Each of the waste collectors 29 can now be connected to additional sensors to enable further analysis of the chemical and/or physical parameters of the waste liquid.

In 5 A very simple solution of the shelf system 100 is shown. It has four stacked shelf slots 120, each filled with a shelf box 200 containing a microfluidic chip 20 within a box housing 210. Slot outlet openings 123 provide a fluid connection to the microfluidic chip 20 in each of the shelf slots 120, and the chip outlet opening 25 allows the fluid from the microfluidic chip to be expelled. In this case, a flat surface is provided to enable the functionality of the slot retainers 122, allowing a sliding loading motion, as described later in relation to the 8 , 9 until 10 discussed.

In 5 The racking system 100 is equipped with an automatic production of the fluid connection for the slot outlet openings 123 with the respective chip inlet openings 23 of the microfluidic chips 200.

In 6 A further modification was made by also connecting the chip outlet openings 25 in the HP holding position to an automatic fluid connection. Here, each of the shelf slots 120 is additionally equipped with a slot receiving connection 126, which is in automatic fluid connection with the chip outlet opening 25 in the holding position. To ensure safety in the HP holding position, a holding mechanism 124 is also provided, which holds the loaded shelf box 200 in the HP holding position and secures it in this position. The movement via this holding mechanism 124 is described in the 8 , 9 until 10 described.

In 7 Another embodiment of the shelving system 100 is shown. Here, the complexity and functionality of the shelving box 200 are increased by a chamber valve 28, which provides valve functionality within the microfluidic chip 20. It is controlled by a control module 218, which receives control signals and/or electrical power via a wired slot connector 125 in contact with the chip connector 21. Furthermore, a temperature controller 212 is powered from the slot of the control module 218 to control the temperature of the liquid flowing through the microfluidic chip 20 into the chamber 22.

The 8 , 9 until 10 show a loading method according to the invention. In this case, the complexity and functionality of the shelf box 200 is further increased by, in addition to the solution of 7 A sensor element 216 is also present to allow the recording of experimental parameters during the execution of the fluid-based experiments. Furthermore, a signal element 214 is in signal communication with the control module 218 to provide a signal as soon as the 10 The depicted holding position HP has been reached. The arrow in 8 A sliding movement along the entire sliding surface 120 of the slot holding device 122 is provided. During this sliding movement, as described in 9 As shown, the holding mechanism 124 is pushed away against a spring force, for example.

As soon as the shelf box 200 is in the 10 Once the shelf box 200 has reached the holding position HP shown, the holding mechanism 124 snaps back, securing it in this position. This automatic retraction into the holding position establishes not only the fluid connection between the slot outlet opening 123 and the slot receiving port 126, but also the wired connection at the wired slot connector 125. This wired connection can be detected, and a signal, for example in the form of a flashing green light, can be provided by the signaling element 214.

In 11 A very space-saving method of providing and arranging the shelf slots 120 is shown. Here, two shelf columns RC each supply the shelf rows RL. This results in a space-saving way of providing a shelving system 100 with, in this example, four separate shelf compartments 120.

12 Figure 1 shows another embodiment in which the shelf box 200 now comprises two separate microfluidic chips 20. In this case, the shelf box is equipped with connectivity specific to the microfluidic chips 20, meaning that for each of the shelf boxes 200, each of the shelf slots 120 has two separate and different slot outlet openings 123 and slot receiving ports 126 specifically for each of the microfluidic chips 20 within the box housing 210.

The foregoing description of the embodiments describes the present invention only by way of example.

Reference sign

10

Microfluidic chip system

20

Microfluidic chip

21

Chip connector

22

chamber

23

Chip inlet opening

24

Chip intake channel

25

Chip outlet opening

26

Chip outlet channel

27

Waste channels

28

chamber valve

29

Waste collector

30

Liquid sampling station

32

liquid sample

33

Sample outlet channel

34

Selection facility

40

Collecting valve

43

Collector's inlet

44

Collection channel

45

Collector outlet opening

50

liquid pump unit

60

Distributor valve

63

distributor inlet opening

64

Distribution channel

65

distributor outlet opening

70

droplet generator

73

droplet inlet opening

74

droplet channel

75

droplet opening

80

Mixing device

81

Mixing chamber

83

Mixing inlet

85

Mixing outlet opening

HE

Experimental reception

100

shelving system

120

Shelf slot

121

Sliding surfaces

122

Slotted retaining device

123

slotted outlet opening

123a

Sealing element

124

Holding mechanism

125

wired slot connector

126

Slotted connection

200

Shelf box

210

Box case

212

Temperature control device

214

Signal element

216

Sensor element

218

Control module

HP

Holding position

RC

shelf column

RL

shelf unit

Claims (13)

Shelf system (100) for a microfluidic chip system (10) for the parallel execution of several fluid-based experiments on at least two separate microfluidic chips (20) each with at least two chambers (22), chip inlet channels (24) from a chip inlet opening (23) to each of the chambers (22) and chip outlet channels (26) from the chambers (22) to a chip outlet opening (25), characterized by several shelf slots (120), each of which has a slot holding device (122) for holding a single microfluidic chip (20) in a holding position (HP) and further slot outlet openings (123) for fluid connection with the chip inlet openings (23) of the microfluidic chip (20) in the holding position (HP). Shelving system (100) according to Claim 1 , characterized in that the shelf slots (120) have a holding mechanism (124) for releasably holding the microfluidic chips (20) in the holding position (HP). Shelving system (100) according to one of the preceding claims, characterized in that the holding device (122) of the shelf slots (120) have sliding surfaces (121) for a sliding movement of the microfluidic chip (20) into the holding position (HP). Shelving system (100) according to one of the preceding claims, characterized in that the shelf slots (120) for receiving the microfluidic chips (20) are designed with a shelf box (200) that at least partially covers the microfluidic chip (20). Shelving system (100) according to one of the preceding claims, characterized in that the shelf slots (120) have wired slot connectors (125) for connecting to chip connectors (21) of the microfluidic chips (20) in the holding position (HP). Shelving system (100) according to one of the preceding claims, characterized in that the multiple shelf slots (120) are arranged in shelf columns (RC) and/or shelf rows (RL). Rack system (100) according to one of the preceding claims, characterized in that the slot outlet openings (123) have sealing elements (123a) for tight sealing against the chip inlet openings (23) with the microfluidic chip (20) in the holding position (HP). Shelf box (200) for a shelving system (100) with the features of one of the Claims 1 until 7 , comprising a box housing (210), wherein at least one microfluidic chip (20) is arranged in the box housing (210), each microfluidic chip (210) having at least two chambers (22), chip inlet channels (24) from a chip inlet opening (23) to each of the chambers (22) and chip outlet channels (26) from the chambers (22) to a chip outlet opening (25), wherein the chip inlet openings (23) further extend through the box housing (210) to connect with the slot outlet openings (123) of the shelf box (200) in the holding position (HP). Shelf box (200) according to Claim 8 , characterized in that at least two microfluidic chips (20) are arranged in the box housing (210). Shelf box (200) according to one of the Claims 8 or 9 , characterized in that at least one temperature control device (212), in particular a heating element, is arranged inside the box housing (210). Shelf box (200) according to one of the Claims 8 until 10 , characterized in that the box housing (210) has a signaling element (214) which provides a signal to a user when the shelf box is in the holding position (HP). Shelf box (200) according to one of the Claims 8 until 11 , characterized in that at least one sensor element (216) for measuring at least one experimental parameter is arranged inside the box housing (210). Method for filling a racking system (100) with the characteristics of one of the Claims 1 until 7 with at least one shelf box (200) with the features of one of the Claims 8 until 12 , characterized by the step of moving at least one shelf box (200) into the holding position (HP).