Microfluidic system and method for providing a sample fluid having a predetermined sample volume - Patents.com

By designing a microfluidic system including sample tanks, sample channels, buffer tanks and regulating valves, using the capillary action and the combination of buffers, the problem of difficult flow of microfluidic systems in the prior art is solved, and precise measurement and extraction of specific volumes of sample liquid are achieved.

JP7665636B2Active Publication Date: 2025-04-21MIDIAGNOSTICS NV
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Patent Information

Application Number
JP2022546464
Authority / Receiving Office
JP · JP
Patent Type
Patents
Current Assignee / Owner
Priority Date
2020-02-19
Filing Date
2021-02-19
Publication Date
2025-04-21
Estimated Expiration
2041-02-19

AI Technical Summary

Technical Problem

When using the capillary action for precise volume measurement, existing microfluidic systems are difficult to stop or close the flow, resulting in the inability to accurately extract the predetermined volume of sample liquid.

Method used

A microfluidic system is designed, which includes a sample tank, a sample channel, a buffer tank and a regulating valve. The sample liquid is introduced into a specific channel through capillary action, and the combination of the buffer and a regulating valve is used to ensure that the sample liquid is isolated in the specific channel to form a predetermined volume of the sample.

Benefits of technology

The precise measurement and extraction of the specific volume of the sample liquid without active control of flow is achieved, improving the accuracy and reliability of sample liquid volume measurement.

✦ Generated by Eureka AI based on patent content.

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Abstract

The present invention relates to a microfluidic system (10, 20), the microfluidic system (10, 20) comprising: a sample reservoir (110, 210); a first sample flow path (120, 220) connected to the sample reservoir (110, 210); the first sample flow path (120, 220) branching into a second sample flow path (122, 222) leading to a first valve (130, 230) and a third sample flow path (124, 224); and the third sample flow path (124, 224) branching into a fourth sample flow path leading to a second valve (132, 232). a buffer reservoir (140, 240); a first trigger flow path (150, 250) configured to connect the buffer reservoir (140, 240) to the second valve (132, 232); a second trigger flow path (152, 252) connecting the second valve (132, 232) and the first valve (130, 230); and an outlet flow path (154, 254) connected to the first valve (130, 230).
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Description

[Technical field]

[0001] The present invention relates to a microfluidic system and a method for providing a sample fluid having a predetermined volume. The present invention further relates to a diagnostic device comprising this microfluidic system and to a method for providing a sample fluid having a predetermined volume. [Background technology]

[0002] Microfluidics deals, among other things, with the control of fluids that are geometrically constrained to small scales. Such techniques are commonly used in inkjet printer heads and in DNA analysis chips, as well as for other types of "lab-on-a-chip". Many applications use passive fluid control, which can be achieved by exploiting capillary action that occurs in tubes with dimensions of less than a millimeter.

[0003] Such systems can be used when volume measurement and control is required, for example in blood cell differentiation or counting, where the volume of the blood sample to be processed must be precisely known. In systems where a relatively large blood sample (more than 10 μl) is added, it may not be desirable to process the entire sample of blood, as only minute volumes (less than 10 μl) are required to obtain accurate statistics of blood cell composition or distribution. Thus, the sampling system needs to measure a known amount of blood from the sample for processing.

[0004] However, precise volumetric metering in systems that use capillary action is a challenge because existing systems of this type generally do not allow for the fluid stream to be shut off or blocked once started. Thus, precisely metered volumes of fluid cannot be simply extracted from the sample by shutting off the flow to prevent too much sample from entering the system. Thus, there is a need for improved microfluidic systems that provide samples with precisely metered volumes.

[0005] US2005 / 133101A1 relates to a microfluidic control device and method for controlling microfluidic flows, in particular, the capillary pressure barrier is eliminated by surface tension changes resulting from solution injection to obtain microfluidic transport, merging, mixing and time delay.

[0006] WO2018 / 132831A2 relates to a device for the simultaneous generation and storage of isolated droplets and methods of making and using the same.

[0007] EP1925365A1 relates to a micro total analysis chip and a micro total analysis system. Summary of the Invention

[0008] An object is to mitigate, alleviate or eliminate one or more of the above-identified deficiencies and disadvantages in the art singly or in any combination, and to solve at least one of the above problems.

[0009] According to a first aspect, there is provided a microfluidic system for providing a sample fluid having a predetermined sample volume, the system comprising: a sample reservoir configured to receive the sample fluid; a first sample flow path connected to the sample reservoir, the first sample flow path branching into a second sample flow path to a first valve and a third sample flow path, the third sample flow path branching into a fourth sample flow path to a second valve and a fifth sample flow path to the third valve, the fifth sample flow path having a predetermined volume; a buffer reservoir configured to receive a buffer fluid; a first trigger flow path configured to connect the buffer reservoir to the second valve; a second trigger flow path configured to connect the second valve and the first valve; and an outlet flow path having a first end and a second end, the first end connected to the first valve. The first sample flow path is arranged to draw sample fluid from the sample reservoir by capillary action to fill the first, second, third, fourth and fifth sample flow paths, and the first trigger flow path is arranged to draw buffer fluid from the buffer reservoir by capillary action through a fluid path comprising the second trigger flow path to the outlet flow path to open the second valve and the first valve, thereby opening a further fluid path comprising the fourth, third and second sample flow paths and allowing sample fluid present in the fourth, third and second sample flow paths to be replaced with buffer fluid from the first trigger flow path and to flow into the outlet flow path together with buffer fluid from the second trigger flow path, thereby isolating the sample fluid present in the fifth sample flow path from adjacent sample fluids, the volume of the isolated sample fluid corresponding to the volume of the fifth sample flow path, thereby providing a sample fluid having a predetermined sample volume.

[0010] The microfluidic system is used to provide a metered volume of sample fluid. Thus, a microfluidic system that utilizes capillary action provides a sample having a predetermined volume without actively controlling the flow within the system. Normally, stopping the flow resulting from capillary action is problematic, and therefore, it would be advantageous to use the microfluidic system to meter a sample having a predetermined volume.

[0011] Furthermore, analysis of a sample fluid having a predetermined volume can be improved since the volume of the sample fluid is precisely known (ie, the predetermined volume corresponds to the volume of the fifth sample channel).

[0012] The microfluidic system may further comprise a timing channel connecting the buffer reservoir and the third valve. The timing channel may be configured to draw buffer fluid from the buffer reservoir to an output of the third valve by capillary action to open the third valve, thereby allowing isolated sample fluid present in the fifth sample channel to flow through the output of the third valve along with buffer fluid from the timing channel.

[0013] A related advantage is that the isolated sample fluid can be extracted from the microfluidic system and thereby provided to further other systems, for example an analytical system configured to analyze the isolated sample fluid. It would be advantageous to precisely meter the sample fluid to be analyzed, and this can be made possible by the microfluidic system.

[0014] The timing channel can be configured to open the third valve after sample fluid present in the fifth sample channel is isolated from adjacent sample fluids.

[0015] A related advantage is that the volume of sample fluid flowing through the output of the third valve can be more precisely determined since sample fluid adjacent to the isolated sample fluid may not flow through the output of the third valve, thereby allowing for more precise metering of the volume of sample fluid extracted from the microfluidic system.

[0016] Yet another advantage is that the mixing ratio of sample fluid having a predetermined volume and buffer fluid can be controlled for the fluid flowing through the output of the third valve, which can be controlled, for example, by the flow resistance of the microfluidic system (mainly by controlling the flow resistance of the timing flow path, the first trigger flow path, the fourth sample flow path, and the fifth sample flow path).

[0017] The timing flow path can include a first flow resistor, the flow resistance of which can be selected to control the flow rate from the buffer reservoir to the third valve such that the third valve can be opened after the sample fluid in the fifth sample flow path is isolated from adjacent sample fluids.

[0018] A related advantage is that the length of the timing channel can be shortened while still allowing the third valve to be opened after the sample fluid in the fifth sample channel is isolated from adjacent sample fluids.

[0019] The microfluidic system may further comprise a capillary pump arranged to emptie the sample reservoir.

[0020] A related advantage is that the sample vessel can receive a sample fluid having a volume larger than the combined volume of the first, second, third, fourth, and fifth sample flow paths, thereby reducing the need to limit the volume of sample fluid received by the sample vessel. If sample fluid is present in the sample vessel after the first, second, third, fourth, and fifth sample flow paths are filled, additional sample fluid can be drawn from the sample vessel by capillary action when the first, second, and / or third valves are opened.

[0021] The capillary pump can be connected to the sample reservoir via a second flow resistor, the flow resistance of which can be selected to control a flow rate from the sample reservoir to the capillary pump such that the sample reservoir can be emptied after the first sample flow path, the second sample flow path, the third sample flow path, the fourth sample flow path, and the fifth sample flow path are filled with sample fluid.

[0022] A related advantage is that the volume of sample fluid flowing through the output of the third valve can be more precisely determined because the sample reservoir is not emptied before the fifth sample flow path is filled with sample fluid, thereby allowing for more precise metering of the volume of sample fluid extracted from the microfluidic system.

[0023] The microfluidic system may further include a stop valve connected to a second end of the outlet channel.

[0024] The microfluidic system further comprises a vent connected to the stop valve, the vent may be configured to allow gas communication between the stop valve and the surroundings of the microfluidic system to allow gas present in the outlet flow path to escape.

[0025] A related advantage is that it can allow for improved flow of sample fluid and / or buffer fluid, since the build-up of gas pressure in the flow path acting against the capillary action of the flow path can be avoided.

[0026] The sample fluid and / or the buffer fluid may be an aqueous liquid.

[0027] One or more walls of the flow channel may comprise silica, glass, polymeric material, polycarbonate, silicon, poly(methyl methacrylate) (PMMA), polydimethylsiloxane (PDMS), and / or cyclic olefin copolymer (COC).

[0028] The timing channel may connect the buffer reservoir and the third valve through a fourth valve, and the microfluidic system may further include a dilution channel connecting the buffer reservoir and the fourth valve, the dilution channel configured to draw buffer fluid from the buffer reservoir to the fourth valve by capillary action. The timing channel may be further configured to open the fourth valve, thereby allowing buffer fluid to flow from the dilution channel to the third valve.

[0029] A related advantage is that the dilution ratio of the fluid flowing through the output of the third valve can be controlled by adjusting the flow rates in the dilution flow paths and in the flow paths connecting the fourth valve and the third valve.

[0030] According to a second aspect, there is provided a diagnostic device comprising the microfluidic system of the first aspect.

[0031] The above features of the first aspect, when applicable, also apply to this second aspect, to which reference is made in order to avoid undue repetition.

[0032] The diagnostic device may be arranged to analyse a provided sample fluid having a predetermined sample volume.

[0033] According to a third aspect, a method for providing a sample fluid having a predetermined sample volume is provided, the method comprising: adding sample fluid to a sample vessel, whereby a first sample flow path draws sample fluid from the sample vessel by capillary action to fill the first, second, third, fourth and fifth sample flow paths, where the second and third sample flow paths are branches of the first sample flow path, and the fourth and fifth sample flow paths are branches of the third sample flow path, where the second sample flow path leads to a first valve, the fourth sample flow path leads to a second valve and the fifth sample flow path leads to a third valve; adding buffer fluid to a buffer vessel, whereby a first trigger flow path draws buffer fluid from the buffer vessel by capillary action to an outlet flow path connected to the first valve; wherein buffer fluid is drawn to the outlet flow path via a fluid path including a second trigger flow path connecting the first valve and the second valve, and the second valve and the first valve are opened to open a further fluid path including a fourth sample flow path, a third sample flow path and the second sample flow path, and sample fluid present in the fourth sample flow path, the third sample flow path and the second sample flow path are replaced with buffer fluid from the first trigger flow path and flow together with buffer fluid from the second trigger flow path into the outlet flow path via the further fluid path, whereby sample fluid present in the fifth sample flow path is isolated from adjacent sample fluids and has a volume corresponding to the volume of the fifth sample flow path, thereby providing sample fluid having a predetermined sample volume.

[0034] The above features of the first and second aspects, when applicable, also apply to this third aspect, to which reference is made in order to avoid excessive repetition.

[0035] The method may further comprise opening a third valve such that the isolated sample fluid flows through an output of the third valve.

[0036] The method may further comprise emptying the sample vessel using a capillary pump connected to the sample vessel after adding the sample fluid to the sample vessel and before adding the buffer fluid to the buffer vessel.

[0037] Further scope of applicability of the present disclosure will become apparent from the detailed description provided hereinafter. However, it should be understood that the detailed description and specific examples, while indicating preferred variants of the inventive concept, are provided merely as illustrations, since various changes and modifications within the scope of the inventive concept will become apparent to those skilled in the art from the detailed description.

[0038] Thus, it is to be understood that the inventive concept is not limited to the particular steps of the described methods or to the component parts of the described systems, as such methods and systems may vary. It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments only, and is not intended as limiting. It is noted that the articles "a," "an," "the," and "said," as used in this specification and the appended claims, are intended to mean that there are one or more of an element, unless the context clearly dictates otherwise. Thus, for example, reference to "a unit" or "the unit" may include several devices, and so forth. Furthermore, the words "comprising," "including," "containing," and similar phrases do not exclude other elements or steps.

[0039] These and other aspects of the inventive concept will now be described in more detail with reference to the accompanying drawings, which show variants of the invention. The figures should not be considered as limiting the invention to the specific variants. Instead, these figures are used to explain and understand the inventive concept.

[0040] As shown in the figures, the sizes of layers and regions have been exaggerated for illustrative purposes and are thus provided to illustrate the general structure of a variant of the present inventive concept. Like reference numbers refer to like elements throughout. [Brief description of the drawings]

[0041] [Figure 1A] FIG. 1 illustrates a microfluidic system for providing a sample fluid having a predetermined sample volume. [Figure 1B] FIG. 1 shows a diagnostic device comprising a microfluidic system for providing a sample fluid having a predetermined sample volume. [Figure 2A] FIG. 1B illustrates a microfluidic system that may correspond to the microfluidic system of FIG. 1A when used to provide a sample fluid having a predetermined sample volume. [Figure 2B] FIG. 1B illustrates a microfluidic system that may correspond to the microfluidic system of FIG. 1A when used to provide a sample fluid having a predetermined sample volume. [Figure 2C] FIG. 1B illustrates a microfluidic system that may correspond to the microfluidic system of FIG. 1A when used to provide a sample fluid having a predetermined sample volume. [Figure 2D] FIG. 1B illustrates a microfluidic system that may correspond to the microfluidic system of FIG. 1A when used to provide a sample fluid having a predetermined sample volume. [Figure 2E] FIG. 1B illustrates a microfluidic system that may correspond to the microfluidic system of FIG. 1A when used to provide a sample fluid having a predetermined sample volume. [Diagram 3] 1 is a block schematic diagram of a method for providing a sample fluid having a predetermined sample volume. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0042] The present inventive concept will now be described more fully hereinafter with reference to the accompanying drawings, in which presently preferred variants of the present inventive concept are shown. However, the present inventive concept may be implemented in many different forms and should not be construed as being limited to the variants set forth herein. Instead, these variants are provided for thoroughness and completeness, to fully convey the scope of the present inventive concept to those skilled in the art.

[0043] It is to be understood that at least the first sample flow path, the second sample flow path, the third sample flow path, the fourth sample flow path, the fifth sample flow path, the first trigger flow path, the second trigger flow path, the outlet flow path, and the timing flow path are capillary lines. A capillary line is a flow path that can provide capillary driven flow of a liquid. It is also to be understood that the other flow paths of the system can be capillary lines and / or other types of flow paths depending on the specific implementation of the inventive concept.

[0044] In the following, fluids are described as flowing through channels in a microfluidic system and reaching several locations at various times. The flow rates of these flows can be controlled in various ways so that the fluids reach these locations at the times described. Capillary driven flow of a fluid requires one or more contact surfaces that the fluid can wet. For example, surfaces comprising glass or silica can be used for capillary driven flow of aqueous liquids. Furthermore, suitable polymers, for example, with intrinsic hydrophilic properties of the polymer or hydrophilic properties due to modification (including, for example, chemical modification or coating), can facilitate or enhance capillary driven flow.

[0045] The flow can be controlled, for example, by adapting the length of the flow path and / or adapting the flow resistance of the flow path. The flow resistance of the flow path can be controlled by adapting the cross-sectional area of ​​the flow path and / or the length of the flow path. The flow resistance of the flow path can further depend on the properties of the liquid, for example its dynamic viscosity. Additionally or alternatively, the flow rate can be adapted using a flow resistor.

[0046] The dimensions of the flow channel can be selected to provide the desired capillary forces, for example depending on the properties of the liquid and / or the material and / or properties of the walls of the channel.

[0047] FIG. 1A shows a microfluidic system 10 for providing a sample fluid having a predetermined sample volume (sample fluid is not shown in FIG. 1A).

[0048] The system includes a sample vessel 110 configured to receive a sample fluid. The sample vessel 110 may be configured to receive a sample fluid by having an opening.

[0049] The system further comprises a first sample flow path 120 connected to the sample vessel 110. The first sample flow path 120 branches into a second sample flow path 122 leading to a first valve 130 and a third sample flow path 124. The third sample flow path 124 branches into a fourth sample flow path 126 leading to a second valve 132 and a fifth sample flow path 128 leading to a third valve 134, the fifth sample flow path 128 having a predetermined volume. The first valve 130, the second valve 132 and / or the third valve 134 may be trigger valves. In its closed state, the trigger valve may stop a main flow of fluid and in its open state, may allow the main flow of fluid to pass through the trigger valve. The trigger valve may be opened (i.e., changed to its open state) by a secondary flow and may allow a combined flow of the main flow and the secondary flow to flow through the output of the trigger valve. Such trigger valves may be known in the art as capillary trigger valves.

[0050] The system further comprises a buffer reservoir 140 arranged to receive a buffer fluid. The buffer reservoir 140 may be arranged to receive the buffer fluid by having an opening.

[0051] The system further comprises a first trigger channel 150 configured to connect the buffer reservoir 140 to the second valve 132 .

[0052] The system further includes a second trigger passage 152 connecting the second valve 132 and the first valve 130 .

[0053] The system further includes an outlet flow passage 154 having a first end 1542 and a second end 1544. The first end 1542 is connected to the first valve 130.

[0054] The first sample flow path 120 is arranged to draw sample fluid from the sample reservoir 110 by capillary action to fill the first, second, third, fourth and fifth sample flow paths 120, 122, 124, 126, 128. The flow of sample fluid is stopped by the first valve 130, the second valve 132 and the third valve 134 when these valves are in their closed states.

[0055] The first trigger channel 150 is configured to draw buffer fluid from the buffer reservoir 140 through a fluid path including the second trigger channel 152 to the outlet channel 154 by capillary action to open the second valve 132 and the first valve 130, thereby opening further fluid paths including the fourth sample channel 126, the third sample channel 124 and the second sample channel 122.

[0056] The further fluid path that is opened allows sample fluid present in the fourth sample flow path 126, the third sample flow path 124, and the second sample flow path 122 to be replaced with buffer fluid from the first trigger flow path 150 and flow into the outlet flow path 154 along with buffer fluid from the second trigger flow path 152, thereby isolating the sample fluid present in the fifth sample flow path 128 from adjacent sample fluids.

[0057] The first sample flow path 120 and / or the fifth sample flow path 128 may be adapted, for example by adapting their respective geometries (e.g., cross-sectional dimensions and / or shapes), such that capillary forces (or capillary pressure) prevent sample fluid present in the first sample flow path 120 and / or the fifth sample flow path 128 from flowing toward the outlet flow path 154.

[0058] The second sample flow path 122, the third sample flow path 124, the fourth sample flow path 126, the first trigger flow path 150, the second trigger flow path 152, and / or the outlet flow path 154 may be adapted, for example, by adapting their respective geometries (e.g., cross-sectional dimensions and / or shapes) such that sample fluid present in the second sample flow path 122, the third sample flow path 124, and the fourth sample flow path 126 may be replaced with buffer fluid from the first trigger flow path 150 and flow into the outlet flow path 154 along with buffer fluid from the second trigger flow path 152.

[0059] The volume of the isolated sample fluid corresponds to the volume of the fifth sample channel 128, thereby providing a sample fluid having a predetermined sample volume.

[0060] In this manner, the microfluidic system 10 can provide a sample fluid having a predetermined volume that is isolated from adjacent sample fluids in the microfluidic system 10 without actively controlling flow within the microfluidic system 10.

[0061] 1A, the microfluidic system 10 may further include a timing channel 160 connecting the buffer reservoir 140 and the third valve 134. The timing channel 160 may be configured to draw buffer fluid from the buffer reservoir 140 to an output 1342 of the third valve 134 by capillary action to open the third valve 134, thereby allowing the isolated sample fluid present in the fifth sample channel to flow through the output 1342 of the third valve 134 along with the buffer fluid from the timing channel 160. The output 1342 of the third valve 134 may be an output of the microfluidic system 10.

[0062] Thus, a separated sample fluid can be extracted from the microfluidic system 10. It can for example be provided to a further system for further processing. This may be an analytical system arranged to analyse the separated sample fluid. For such analytical systems, it may be advantageous to precisely meter the sample fluid to be analysed, which may be made possible by the microfluidic system 10.

[0063] The timing channel 160 can be configured to open the third valve 134 after the sample fluid present in the fifth sample channel 128 is isolated from adjacent sample fluids. The timing channel 160 can be further configured to open the third valve 134 after the sample fluid and buffer fluid reach the second end 1544 of the outlet channel 154.

[0064] 1A, the timing channel 160 can include a first flow resistor 162. The flow resistance of the first flow resistor 162 can be selected to control the flow rate from the buffer reservoir 140 to the third valve 134 such that the third valve 134 can be opened after the sample fluid in the fifth sample channel 128 has been isolated from adjacent sample fluids. In addition, the flow resistance of the first flow resistor 162 can be selected to control the flow rate from the buffer reservoir 140 to the third valve 134 such that the third valve 134 can be opened after the sample fluid and the buffer fluid have reached the second end 1544 of the outlet channel 154.

[0065] Thus, the length of the timing channel 160 can be shortened while still allowing the third valve 134 to be opened after the sample fluid in the fifth sample channel 128 has been isolated from adjacent sample fluids.

[0066] 1A, the microfluidic system 10 can further include a capillary pump 174 configured to empty the sample reservoir 110. The capillary pump 174 can be configured to empty the sample reservoir 110 after the first, second, third, fourth, and fifth sample channels 120, 122, 124, 126, 128 are filled with sample fluid. The capillary pump 174 can be a paper pump and / or a microfluidic channel structure configured to draw liquid from the sample reservoir 110. While the sample chamber 110 is being emptied by the capillary pump 174, the capillary pressure or force in the second sample flow path 122, the fourth sample flow path 126, and the fifth sample flow path 128 may oppose the drawing of sample fluid from the first sample flow path 120, the second sample flow path 122, the third sample flow path 124, the fourth sample flow path 126, and the fifth sample flow path 128 in a direction toward the sample chamber 110. The capillary pressure or force in the second sample flow path 122, the fourth sample flow path 126, and the fifth sample flow path 128 may be higher than the capillary pressure or force generated by the capillary pump 174, thereby avoiding emptying the second sample flow path 122, the fourth sample flow path 126, and the fifth sample flow path 128.

[0067] The sample vessel 110 may thereby receive a sample fluid having a volume greater than the combined volume of the first, second, third, fourth, and fifth sample channels 120, 122, 124, 126, 128, thereby reducing the need to limit the volume of sample fluid received by the sample vessel 110. If sample fluid is present in the sample vessel 110 after the first, second, third, fourth, and fifth sample channels 120, 122, 124, 126, 128 are filled, additional sample fluid may be drawn from the sample vessel 110 by capillary action when the first, second, and / or third valves 130, 132, 134 are opened. Emptying the fluid in the sample chamber 110 after the first, second, third, fourth, and fifth sample flow paths 120, 122, 124, 126, 128 are filled allows capillary pressure or forces at the interface between the sample fluid in the first sample flow path 120 and the sample chamber 110 to oppose the withdrawal of sample fluid from the first sample flow path 120 in a direction away from the sample chamber 110.

[0068] The capillary pump 174 can be connected to the sample vessel 110 via a second flow resistor 172. The flow resistance of the second flow resistor 172 can be selected to control the flow rate from the sample vessel 110 to the capillary pump 174 so that the sample vessel 110 can be emptied after the first sample flow path 120, the second sample flow path 122, the third sample flow path 124, the fourth sample flow path 126, and the fifth sample flow path 128 are filled with sample fluid. The capillary pump 174 can be connected to the sample vessel 110 via a pump capillary line 170, which can include the second flow resistor 172.

[0069] The microfluidic system 10 may further include a stop valve 136 connected to a second end 1544 of the outlet channel 154 .

[0070] The microfluidic system 10 may further comprise a vent 180 connected to the stop valve 136. The vent 180 may be arranged to allow gas communication between the stop valve 136 and the surroundings of the microfluidic system 10 such that gas present in the outlet channel 154 may be allowed to escape. Gas present in one or more of the first sample channel 120, the second sample channel 122, the third sample channel 124, the fourth sample channel 126, the first trigger channel 150, and the second trigger channel 152 may be allowed to escape through the vent 180 via the outlet channel 154. Additionally, gas present in one or more of the first sample channel 120, the second sample channel 122, the third sample channel 124, the fourth sample channel 126, the fifth sample channel 128, the first trigger channel 150, and the second trigger channel 152 may be allowed to escape through an output 1342 of the third valve 134. The presence of gas in the flow path can cause gas pressure to build up in the flow path, which can act against the flow of fluid in the flow path by capillary action. By allowing the gas to escape, such build-up can be avoided, thereby allowing for improved flow of sample fluid and / or buffer fluid.

[0071] The sample fluid and / or the buffer fluid may be an aqueous liquid. The sample liquid may be blood.

[0072] One or more walls of the flow channels can comprise silica, glass, polymeric materials, polycarbonate, silicon, poly(methyl methacrylate) (PMMA), polydimethylsiloxane (PDMS), and / or cyclic olefin copolymer (COC). The flow channels of the microfluidic system 10 can be comprised in a substrate comprising silica. The silica can be in the form of fused quartz.

[0073] A timing channel 160 may connect the buffer reservoir 140 to the third valve through the fourth valve 138 .

[0074] The microfluidic system may further include a dilution channel 190 connecting the buffer reservoir 140 and a fourth valve 138. The fourth valve 138 may be configured such that in its closed state, the fourth valve 138 stops buffer fluid from flowing from the dilution channel 190 to the third valve.

[0075] The dilution flow path 190 may be configured to draw buffer fluid from the buffer reservoir 140 by capillary action to the fourth valve 138. The dilution flow path 190 may be a capillary line.

[0076] The timing channel 160 may further be configured to open the fourth valve 138, thereby allowing buffer fluid to flow from the diluent channel 190 to the third valve 134. Thus, the fourth valve 138 may be configured such that in its open state, it allows buffer fluid to flow from the diluent channel 190 to the third valve 134.

[0077] Thereby, the dilution ratio of the sample fluid exiting the output 1342 of the third valve 134 relative to the buffer fluid can be controlled by adjusting the flow resistance of one or more of the timing channel 160, the first flow resistor 162, the dilution channel 190, the first trigger channel 150, the second trigger channel 152, the second sample channel 122, the third sample channel 124, the fourth sample channel 126, and the fifth sample channel 128.

[0078] Figure 1B shows a diagnostic device 50 comprising a microfluidic system 10 for providing a sample fluid having a predetermined sample volume. The microfluidic system 10 of Figure 1B may correspond to the microfluidic system 10 described with respect to Figure 1A.

[0079] The diagnostic device 50 can be arranged to analyze a provided sample fluid having a predetermined sample volume. The diagnostic device 50 can be arranged to analyze a provided sample fluid having a predetermined sample volume by comprising an analysis system 510 as shown in the example of FIG. 1B. An input of the analysis system 510 can be fluidly connected to an output of the microfluidic system 10. The analysis system 510 can comprise vents that allow gas communication between the analysis system 510 and its surroundings and / or between the analysis system 510 and its surroundings to avoid gas pressure build-up in the microfluidic system 10 and / or the analysis system 510.

[0080] The inventive concept will now be described with reference to Figures 2A-2E. Figures 2A-2E show a microfluidic system 20 comprising a sample reservoir 210 and a first sample flow path 220 connected to the sample reservoir 210. The first sample flow path 220 branches into a second sample flow path 222 leading to a first valve 230 and a third sample flow path 224. The third sample flow path 224 branches into a fourth sample flow path 226 leading to a second valve 232 and a fifth sample flow path 228 leading to a third valve 234. It should be understood that the microfluidic system 20 of Figures 2A-2E may further comprise a dilution flow path and a fourth valve as described with respect to Figure 1A.

[0081] The microfluidic system 20 further comprises a buffer reservoir 240, a first trigger channel 250, a second trigger channel 252, and an outlet channel 254. The first trigger channel 250 is arranged to connect the buffer reservoir 240 to the second valve 232, and the second trigger channel 252 connects the second valve 232 and the first valve 230. The outlet channel 254 has a first end 2542 and a second end 2544, the first end 2542 being connected to the first valve 230. The second end 2544 of the outlet channel 254 may be open, meaning that the interior of the outlet channel 254 is in gas communication with the surroundings of the microfluidic device 20. The second end 2544 of the outlet channel 254 may be connected to a vent (not shown). As shown in the example of FIGS. 2A-2E, a second end 2544 of the outlet flow passage 254 can be connected to a stop valve 236.

[0082] The sample vessel 210 is arranged to receive a sample fluid and the buffer vessel 240 is arranged to receive a buffer fluid. The sample and / or buffer fluid may be an aqueous liquid.

[0083] As illustrated in Figures 2A-2E, the microfluidic system 20 may further include a timing channel 260 connecting the buffer tank 240 and the third valve 234, and the timing channel 260 may connect the buffer tank 240 and the third valve 234 via a first flow resistor 262.

[0084] The microfluidic system 20 may further include a capillary pump 274 connected to the sample reservoir 210, as illustrated in Figures 2A-2E. The capillary pump 274 may be connected to the sample reservoir 210 via a second flow resistor 272.

[0085] The microfluidic system 20 may further comprise a vent 280 connected to the stop valve 236, as shown in the example of Figures 2A-2E. The vent 280 may allow gas present in the sample flow path and / or the trigger flow path to escape. Thus, any gas present in the microfluidic system 20 may escape, which allows the sample and / or buffer fluids to flow through the flow paths of the microfluidic system 20. Gas present in the microfluidic system 20 may further escape through the output 2342 of the third valve 234. This may allow, for example, gas present in the timing flow path 260 to escape from the microfluidic system 20.

[0086] The microfluidic system 20 of Figures 2A-2E may correspond to the microfluidic system 10 described with respect to Figure 1A.

[0087] In Figure 2A, sample fluid is provided to the sample vessel 210. The first sample flow path draws sample fluid from the sample vessel 210 to fill the first, second, third, fourth, and fifth sample flow paths 220, 222, 224, 226, 228 by capillary action. The sample fluid drawn from the sample vessel 210 is stopped at the first, second, and third valves 230, 232, 234. The sample vessel 210 can be emptied through the pump flow path 270 via the second flow resistor 272 using a capillary pump 274 after the first, second, third, fourth, and fifth sample flow paths 220, 222, 224, 226, 228 are filled, as illustrated in Figure 2B. The flow resistance of the second flow resistor 272 can be selected to allow the sample vessel 210 to be emptied after the first, second, third, fourth, and fifth sample flow paths are filled with sample fluid. The capillary pressure or force in the second sample flow path 222, the fourth sample flow path 226, and the fifth sample flow path 228 can be higher than the capillary pressure or force generated by the capillary pump, thereby avoiding emptying the second sample flow path 222, the fourth sample flow path 226, and the fifth sample flow path 228.

[0088] In Fig. 2C, buffer fluid is provided to the buffer reservoir 240. The first trigger channel 250 draws the buffer fluid from the buffer reservoir 240 through a fluid path including the second trigger channel 252 toward the outlet channel 254 by capillary action, as shown in Fig. 2C. Additionally, as illustrated in Fig. 2C, the timing channel 260 can draw the buffer fluid from the buffer reservoir 240 through a first flow resistor 262 to the third valve 234 by capillary action. The flow resistance of the first flow resistor 262 can be selected such that the buffer fluid reaches the third valve 234 after the sample fluid present in the fifth sample channel 228 has been isolated (described below).

[0089] When the buffer fluid reaches the second and first valves 232, 230, it opens the second valve 232 and the first valve 230, thereby opening a further fluid path comprising the fourth sample flow path 226, the third sample flow path 224 and the second sample flow path 222. This further fluid path allows the sample fluid present in the fourth, third and second sample flow paths to be replaced with buffer fluid from the first trigger flow path 250 and flow into the outlet flow path 254 together with the buffer fluid from the second trigger flow path 252, as shown in the example of FIG. 2D. Thus, the volume of the outlet flow path 254 may be large enough to expel the sample fluid previously present in the fourth sample flow path 226, the third sample flow path 224 and the second sample flow path 222. At the time when the second valve 232 is open but the first valve 230 is not yet open, for example, capillary pressure in the first sample channel 220, the second sample channel 222, and the fifth sample channel 228 may act to prevent the sample fluid from being drawn into the second trigger channel 252 via the fourth sample channel 226 and the second valve 232. This prevention is facilitated or enabled by the sample vessel 210 being emptied of sample and the third valve 234 and the first valve 230 not yet being opened. As also shown in the example of FIG. 2D, the buffer fluid and the sample fluid flow into the outlet channel 254 and reach the stop valve 236. As shown in FIG. 2D, the sample fluid present in the fifth sample channel 228 is then isolated from the adjacent sample fluid. Thereby, a sample fluid having a predetermined volume is provided. At the time the first valve 230 and the second valve are open, for example, capillary forces between the sample liquid and the wetted walls in the first sample flow path 220 and the fifth sample flow path 228 may act to prevent sample fluid from being drawn through the second sample flow path 222 and the first valve 230, and / or through the fourth sample flow path 226 and the second valve 234 to the outlet flow path 254. This prevention may be facilitated by the sample reservoir 210 being emptied of sample fluid and the third valve 234 not yet being opened.

[0090] After the sample fluid present in the fifth sample flow path 228 is isolated, the buffer fluid can reach the third valve 234, which in response is opened. Also, by comparing FIG. 2D with FIG. 2E, it can be seen that before the third valve 234 is opened, the buffer fluid and the sample fluid flow into the outlet flow path 254 and reach the stop valve 236. After the third valve 234 is opened, the isolated sample fluid present in the fifth sample flow path 228 can be allowed to flow through the output 2342 of the third valve 234 along with the buffer fluid present in the timing flow path 260, as shown in the example of FIG. 2E. This is indicated by the arrow 2344 in FIG. 2E. The dilution ratio of the sample fluid exiting the output 2342 of the third valve relative to the buffer fluid can be controlled in a manner similar to that described with respect to FIG. 1A, for example, using a dilution flow path (not shown in FIG. 2A-FIG. 2E).

[0091] FIG. 3 is a block schematic diagram of a method 30 for providing a sample fluid having a predetermined sample volume.

[0092] The method 30 includes adding (S302) a sample fluid to the sample vessel 110, 210, whereby the first sample flow path 120, 220 draws the sample fluid from the sample vessel 110, 210 by capillary action to fill the first sample flow path 120, 220, the second sample flow path 122, 222, the third sample flow path 124, 224, the fourth sample flow path 126, 226, and the fifth sample flow path 128, 228.

[0093] The second sample flow path 122,222 and the third sample flow path 124,224 are branches of the first sample flow path 120,220, and the fourth sample flow path 126,226 and the fifth sample flow path 128,228 are branches of the third sample flow path 124,224.

[0094] The second sample flow path 122,222 leads to a first valve 130,230, the fourth sample flow path 126,226 leads to a second valve 132,232, and the fifth sample flow path 128,228 leads to a third valve 134,234.

[0095] The method 30 further comprises adding (S304) a buffer fluid to the buffer reservoir 140, 240, whereby the first trigger channel 150, 250 draws the buffer fluid from the buffer reservoir 140, 240 by capillary action to an outlet channel 154, 254 connected to the first valve 130, 230. The outlet channel 154, 254 may be connected to the first valve 130, 230 at a first end 1542, 2542 of the outlet channel 154, 254. A second end 1544, 2544 of the outlet channel 154, 254 may be connected to a stop valve 136, 236. The stop valve 136, 236 may be connected to a vent 180, 280 to allow gas communication between the buffer fluid and / or sample fluid and the surroundings of the microfluidic system 10, 20 so that gas present within the microfluidic system 10, 20 may escape.

[0096] Buffer fluid is drawn through a fluid path comprising a second trigger channel 152, 252 connecting the first valve 130, 230 and the second valve 132, 232 to the outlet channel 154, 254, opening the second valve 132, 232 and the first valve 130, 230 to open a further fluid path comprising the fourth sample channel 126, 226, the third sample channel 124, 224 and the second sample channel 122, 222, and opening the fourth sample channel 126, 226, the third sample channel 124, 224 and the second sample channel 122, 222. The sample fluid present in the second sample flow path 122, 222 is replaced with buffer fluid from the first trigger flow path 150, 250 and flows via this further fluid path into the outlet flow path 145, 254 together with buffer fluid from the second trigger flow path 152, 252, such that the sample fluid present in the fifth sample flow path 128, 228 is isolated from adjacent sample fluid and has a volume corresponding to the volume of the fifth sample flow path 128, 228, thereby providing a sample fluid having a predetermined sample volume.

[0097] The above features of the first and second aspects, when applicable, also apply to this third aspect, to which reference is made in order to avoid excessive repetition.

[0098] The method 30 may further comprise opening (S306) the third valve 134, 234 such that the isolated sample fluid (i.e., isolated in the fifth sample flow path 128, 228) flows through an output of the third valve 134, 234. The third valve 134, 234 may be connected to the buffer reservoir 140, 240 via a timing flow path 160, 260. The timing flow path 160, 260 may draw buffer fluid from the buffer reservoir 140, 240 to the third valve 134, 234 by capillary action, and the third valve 134, 234 may be opened in response to the buffer fluid reaching the third valve 134, 234. In response to the third valve 134, 234 being opened, the isolated sample fluid may flow through an output of the third valve 134, 234 along with buffer fluid from the timing flow path 160, 260. The timing channel 160, 260 can be configured to open the third valve 134, 234 after the sample fluid is isolated in the fifth sample channel 128, 228 and after the sample fluid and buffer fluid reach the second end 1544, 2544 of the outlet channel 154, 254. The timing channel 160, 260 can include a first flow resistor 162, 262, the flow resistance of which can be selected such that the buffer fluid in the timing channel 160, 260 reaches the third valve 134, 234 after the sample fluid is isolated in the fifth sample channel 128, 228 and after the sample fluid and buffer fluid reach the second end 1544, 2544 of the outlet channel 154, 254.

[0099] The method 30 may further comprise emptying (S308) the sample reservoir 110, 210 after adding (S302) the sample fluid to the sample reservoir 110, 210 and before adding (S304) the buffer fluid to the buffer reservoir 140, 240. The sample reservoir 110, 210 may be emptied using a capillary pump 174, 274 connected to the sample reservoir 110, 210. The capillary pump 174, 274 may be connected to the sample vessel 110, 210 via a second flow resistor 172, 272, the flow resistance of which is selected to control the flow rate from the sample vessel 110, 210 to the capillary pump 174, 274 such that the sample vessel 110, 210 is emptied after the first sample flow path 120, 220, the second sample flow path 122, 222, the third sample flow path 124, 224, the fourth sample flow path 126, 226, and the fifth sample flow path 128, 228 are filled with sample fluid.

[0100] It should be understood that the method 30 may use the microfluidic systems 10, 20 of Figure 1A and / or Figures 2A-2E.

[0101] Those skilled in the art will recognize that the inventive concept is in no way limited to the preferred variants described above: on the contrary, many modifications and variations are possible within the scope of the appended claims.

[0102] For example, the flow channels of the microfluidic systems 10, 20 have been described as being closed / sealed flow channels. However, it should be understood that the flow channels may be open, meaning that the flow channels are confined in only one dimension. This may be the case, for example, where the flow channel has a bottom and two sides, with the top of the flow channel removed. In such a configuration, the flow channels are allowed to be in direct gas communication with the surroundings, eliminating the need for vents.

[0103] As yet another example, the sample and buffer fluids have been described as being added to the sample and buffer reservoirs 110, 210, 140, 240 at separate times. However, they may be added simultaneously and the flow rates and / or dimensions (e.g., lengths) of the flow paths may be adapted to fill the flow paths in the order described, for example, such that the first, second, third, fourth and fifth sample flow paths 120, 220, 122, 222, 124, 224, 126, 226, 128, 228 are filled with sample fluid before the buffer fluid reaches the second and first valves 132, 232, 130, 230, and / or such that the sample fluid reaches the second end 1544, 2544 of the outlet flow path 154, 254 with the buffer fluid before the buffer fluid reaches the third valve 134, 234.

[0104] Additionally, variations of the disclosed variants can be understood and effected by those skilled in the art in practicing the claimed invention, from a study of the drawings, the disclosure, and the appended claims. The following is a summary of the claims as originally filed: [1] A microfluidic system (10, 20) for providing a sample fluid having a predetermined sample volume, said microfluidic system (10, 20) comprising: a sample vessel (110, 210) configured to receive a sample fluid; a first sample flow path (120, 220) connected to the sample tank (110, 210), the first sample flow path (120, 220) branching into a second sample flow path (122, 222) leading to a first valve (130, 230) and a third sample flow path (124, 224), the third sample flow path (124, 224) branching into a fourth sample flow path (126, 226) leading to a second valve (132, 232) and a fifth sample flow path (128, 228) leading to a third valve (134, 234), wherein the fifth sample flow path (128, 228) has a predetermined volume; a buffer reservoir (140, 240) configured to receive a buffer fluid; a first trigger channel (150, 250) configured to connect the buffer reservoir (140, 240) to the second valve (132, 232); a second trigger channel (152, 252) configured to connect the second valve (132, 232) and the first valve (130, 230); an outlet flow path (154, 254) having a first end (1542, 2542) and a second end (1544, 2544), wherein said first end (1542, 2542) is connected to said first valve (130, 230); Equipped with the first sample flow path (120, 220) is configured to draw sample fluid from the sample reservoir (110, 210) to fill the first, second, third, fourth, and fifth sample flow paths (120, 220, 122, 222, 124, 224, 126, 226, 128, 228) by capillary action; The first trigger channel (150, 250) is configured to draw buffer fluid from the buffer reservoir (140, 240) through a fluid path comprising the second trigger channel (152, 252) by capillary action to an outlet channel (154, 254) to open the second valve (132, 232) and the first valve (130, 230), thereby opening a further fluid path comprising the fourth sample channel (126, 226), the third sample channel (124, 224) and the second sample channel (122, 222), and opening the fourth sample channel (126, 226), the third sample channel (124, 224), and allowing sample fluid present in the second sample flow path (122, 222) to be replaced with buffer fluid from the first trigger flow path (150, 250) and to flow into the outlet flow path (154, 254) together with buffer fluid from the second trigger flow path (152, 252), thereby isolating sample fluid present in the fifth sample flow path (128, 228) from adjacent sample fluid, and a volume of the isolated sample fluid corresponds to the predetermined volume of the fifth sample flow path (128, 228), thereby providing a sample fluid having a predetermined sample volume. [2] The microfluidic system (10, 20) according to [1], further comprising a timing channel (160, 260) connecting the buffer reservoir (140, 240) and the third valve (134, 234), wherein the timing channel (160, 260) is configured to draw buffer fluid from the buffer reservoir (140, 240) to an output (1342, 2342) of the third valve (134, 234) by capillary action to open the third valve (134, 234), thereby allowing the isolated sample fluid present in the fifth sample channel (128, 228) to flow through the output (1342, 2342) of the third valve (134, 234) together with buffer fluid from the timing channel (160, 260). [3] A microfluidic system (10, 20) as described in [2], wherein the timing channel (160, 260) is configured to open the third valve (134, 234) after the sample fluid present in the fifth sample channel (128, 228) is isolated from adjacent sample fluids. [4] The microfluidic system (10, 20) of [3], wherein the timing channel (160, 260) comprises a first flow resistor (162, 262), the flow resistance of the first flow resistor (162, 262) being selected to control the flow rate from the buffer reservoir (140, 240) to the third valve (134, 234) such that the third valve (134, 234) is opened after sample fluid in the fifth sample channel (128, 228) is isolated from adjacent sample fluid. [5] The microfluidic system (10, 20) of any one of [1] to [4], further comprising a capillary pump (174, 274) configured to emptie the sample reservoir (110, 210). [6] The microfluidic system (10, 20) of [5], wherein the capillary pump (174, 274) is connected to the sample reservoir (110, 210) via a second flow resistor (172, 272), the flow resistance of the second flow resistor (172, 272) being selected to control a flow rate from the sample reservoir (110, 210) to the capillary pump (174, 274) such that the sample reservoir (110, 210) is emptied after the first sample flow path (120, 220), the second sample flow path (122, 222), the third sample flow path (124, 224), the fourth sample flow path (126, 226) and the fifth sample flow path (128, 228) are filled with sample fluid. [7] A microfluidic system (10, 20) described in any one of [1] to [6], further comprising a stop valve (136, 236) connected to the second end (1544, 2544) of the outlet flow path (154, 254). [8] A microfluidic system (10, 20) as described in [7], further comprising a vent (180, 280) connected to the stop valve (136, 236), the vent (180, 280) being configured to allow gas communication between the stop valve (136, 236) and the surroundings of the microfluidic system (10, 20) so as to allow gas present in the outlet flow path (154, 254) to escape. [9] A microfluidic system (10, 20) according to any of [1] to [8], wherein one or more walls of the flow channel comprise silica, glass, a polymeric material, polycarbonate, silicon, poly(methyl methacrylate) (PMMA), polydimethylsiloxane (PDMS), and / or cyclic olefin copolymer (COC).

[10] the timing channel (160) connects the buffer tank (140) and the third valve (134) via a fourth valve (138), the microfluidic system (10): a dilution flow path (190) connecting the buffer tank (140) and the fourth valve (138), the dilution flow path (190) configured to draw buffer fluid from the buffer tank (140) to the fourth valve (138) by capillary action; The microfluidic system (10) of any one of [2] to [9], wherein the timing channel (160) is further configured to open the fourth valve (138), thereby allowing buffer fluid to flow from the dilution channel (190) to the third valve (134).

[11] A diagnostic device (50) comprising a microfluidic system (10, 20) described in any one of [1] to

[10] .

[12] A diagnostic device (50) as described in

[11] , configured to analyze the provided sample fluid having the predetermined sample volume.

[13] A method (30) for providing a sample fluid having a predetermined sample volume, the method comprising: adding (S302) a sample fluid to the sample reservoir (110, 210), whereby a first sample flow path (120, 220) draws sample fluid from said sample reservoir (110, 210) by capillary action to fill the first sample flow path (120, 220), the second sample flow path (122, 222), the third sample flow path (124, 224), the fourth sample flow path (126, 226) and the fifth sample flow path (128, 228); wherein the second sample flow path (122, 222) and the third sample flow path (124, 224) are branches of the first sample flow path (120, 220), the fourth sample flow path (126, 226) and the fifth sample flow path (128, 228) are branches of the third sample flow path (124, 224), wherein the second sample flow path (122, 222) leads to a first valve (130, 230), the fourth sample flow path (126, 226) leads to a second valve (132, 232), and the fifth sample flow path (128, 228) leads to a third valve (134, 234); adding (S304) a buffer fluid to a buffer reservoir (140, 240), whereby a first trigger channel (150, 250) draws the buffer fluid from said buffer reservoir (140, 240) by capillary action to an outlet channel (154, 254) connected to said first valve (130, 230); Here, the buffer fluid is drawn to the outlet channel (154, 254) via a fluid path comprising a second trigger channel (152, 252) connecting the first valve (130, 230) and the second valve (132, 232), and the second valve (132, 232) is opened to open a further fluid path comprising the fourth sample channel (126, 226), the third sample channel (124, 224) and the second sample channel (122, 222), and the fourth sample channel (126, 226), the third sample channel (124, 224) and the second sample channel (122, 222) are opened. ), and sample fluid present in the second sample flow path (122, 222) is replaced with buffer fluid from the first trigger flow path (150, 250) and flows together with buffer fluid from the second trigger flow path (152, 252) into the outlet flow path (154, 254) via the further fluid path, such that sample fluid present in the fifth sample flow path (128, 228) is isolated from adjacent sample fluids and has a volume corresponding to a volume of the fifth sample flow path (128, 228), thereby providing the sample fluid having the predetermined sample volume. A method comprising the steps of: (30)

[14] The method according to

[13] , further comprising emptying (S308) the sample reservoir (110, 210) after adding (S302) a sample fluid to the sample reservoir (110, 210) and before adding (S304) a buffer fluid to the buffer reservoir (140, 240).

Claims

1. A microfluidic system (10, 20) for providing a sample fluid having a predetermined sample volume, said microfluidic system (10, 20) comprising: a sample vessel (110, 210) configured to receive a sample fluid; a first sample flow path (120, 220) connected to the sample tank (110, 210), the first sample flow path (120, 220) branching into a second sample flow path (122, 222) leading to a first valve (130, 230) and a third sample flow path (124, 224), the third sample flow path (124, 224) branching into a fourth sample flow path (126, 226) leading to a second valve (132, 232) and a fifth sample flow path (128, 228) leading to a third valve (134, 234), wherein the fifth sample flow path (128, 228) has a predetermined volume; a buffer reservoir (140, 240) configured to receive a buffer fluid; a first trigger channel (150, 250) configured to connect the buffer reservoir (140, 240) to the second valve (132, 232); a second trigger channel (152, 252) configured to connect the second valve (132, 232) and the first valve (130, 230); an outlet flow path (154, 254) having a first end (1542, 2542) and a second end (1544, 2544), wherein said first end (1542, 2542) is connected to said first valve (130, 230); Equipped with the first sample flow path (120, 220) is configured to draw sample fluid from the sample reservoir (110, 210) to fill the first, second, third, fourth, and fifth sample flow paths (120, 220, 122, 222, 124, 224, 126, 226, 128, 228) by capillary action; The first trigger channel (150, 250) is configured to draw buffer fluid from the buffer reservoir (140, 240) through a fluid path comprising the second trigger channel (152, 252) to the outlet channel (154, 254) by capillary action to open the second valve (132, 232) and the first valve (130, 230), thereby opening a further fluid path comprising the fourth sample channel (126, 226), the third sample channel (124, 224) and the second sample channel (122, 222), and opening the fourth sample channel (126, 226), the third sample channel (124, 224) and the second sample channel (122, 222). ), and allowing sample fluid present in the second sample flow path (122, 222) to be replaced with buffer fluid from the first trigger flow path (150, 250) and to flow into the outlet flow path (154, 254) along with buffer fluid from the second trigger flow path (152, 252), thereby isolating sample fluid present in the fifth sample flow path (128, 228) from adjacent sample fluid, a volume of the isolated sample fluid corresponding to the predetermined volume of the fifth sample flow path (128, 228), thereby providing a sample fluid having a predetermined sample volume.

2. 2. The microfluidic system of claim 1, further comprising a timing channel connecting the buffer reservoir and the third valve, the timing channel being configured to draw buffer fluid from the buffer reservoir by capillary action to an output of the third valve to open the third valve, thereby allowing the isolated sample fluid present in the fifth sample channel to flow through the output of the third valve together with buffer fluid from the timing channel.

3. 3. The microfluidic system (10, 20) of claim 2, wherein the timing channel (160, 260) is configured to open the third valve (134, 234) after the sample fluid present in the fifth sample channel (128, 228) is isolated from adjacent sample fluids.

4. 4. The microfluidic system (10, 20) of claim 3, wherein the timing channel (160, 260) comprises a first flow resistor (162, 262), the flow resistance of which is selected to control the flow rate from the buffer reservoir (140, 240) to the third valve (134, 234) such that the third valve (134, 234) is opened after sample fluid in the fifth sample channel (128, 228) is isolated from adjacent sample fluids.

5. The microfluidic system (10, 20) of any one of claims 1 to 4, further comprising a capillary pump (174, 274) arranged to emptie the sample reservoir (110, 210).

6. 6. The microfluidic system of claim 5, wherein the capillary pump is connected to the sample reservoir via a second flow resistor, the flow resistance of the second flow resistor being selected to control a flow rate from the sample reservoir to the capillary pump such that the sample reservoir is emptied after the first sample flow path, the second sample flow path, the third sample flow path, the fourth sample flow path, and the fifth sample flow path are filled with sample fluid.

7. The microfluidic system (10, 20) of any one of claims 1 to 6, further comprising a stop valve (136, 236) connected to the second end (1544, 2544) of the outlet channel (154, 254).

8. 8. The microfluidic system (10, 20) of claim 7, further comprising a vent (180, 280) connected to the stop valve (136, 236), the vent (180, 280) being configured to allow gas communication between the stop valve (136, 236) and the surroundings of the microfluidic system (10, 20) to allow gas present in the outlet flow path (154, 254) to escape.

9. 9. The microfluidic system (10, 20) of any of claims 1 to 8, wherein one or more walls of the flow channels comprise silica, glass, polymeric material, polycarbonate, silicon, poly(methyl methacrylate) (PMMA), polydimethylsiloxane (PDMS), and / or cyclic olefin copolymer (COC).

10. the timing channel (160) connects the buffer tank (140) and the third valve (134) via a fourth valve (138); and the microfluidic system (10) a dilution flow path (190) connecting the buffer tank (140) and the fourth valve (138), the dilution flow path (190) configured to draw buffer fluid from the buffer tank (140) to the fourth valve (138) by capillary action; 5. The microfluidic system (10) of claim 2, wherein the timing channel (160) is further configured to open the fourth valve (138) thereby allowing buffer fluid to flow from the dilution channel (190) to the third valve (134).

11. A diagnostic device (50) comprising a microfluidic system (10, 20) according to any one of the preceding claims.

12. The diagnostic device (50) of claim 11 configured to analyze the provided sample fluid having the predetermined sample volume.

13. 1. A method (30) for providing a sample fluid having a predetermined sample volume, the method comprising: adding (S302) a sample fluid to the sample reservoir (110, 210), whereby a first sample flow path (120, 220) draws sample fluid from said sample reservoir (110, 210) by capillary action to fill the first sample flow path (120, 220), the second sample flow path (122, 222), the third sample flow path (124, 224), the fourth sample flow path (126, 226), and the fifth sample flow path (128, 228); wherein the second sample flow path (122, 222) and the third sample flow path (124, 224) are branches of the first sample flow path (120, 220), the fourth sample flow path (126, 226) and the fifth sample flow path (128, 228) are branches of the third sample flow path (124, 224), wherein the second sample flow path (122, 222) leads to a first valve (130, 230), the fourth sample flow path (126, 226) leads to a second valve (132, 232), and the fifth sample flow path (128, 228) leads to a third valve (134, 234); adding (S304) a buffer fluid to a buffer reservoir (140, 240), whereby a first trigger channel (150, 250) configured to be connected to the buffer reservoir (140, 240) and the second valve (132, 232) draws the buffer fluid from the buffer reservoir (140, 240) by capillary action to an outlet channel (154, 254) connected to the first valve (130, 230); Here, the buffer fluid is drawn to the outlet channel (154, 254) via a fluid path comprising a second trigger channel (152, 252) connecting the first valve (130, 230) and the second valve (132, 232), and the second valve (132, 232) is opened to open a further fluid path comprising the fourth sample channel (126, 226), the third sample channel (124, 224) and the second sample channel (122, 222), and the fourth sample channel (126, 226), the third sample channel (124, 224) and the second sample channel (122, 222) are opened. and sample fluid present in the second sample flow path (122, 222) is replaced with buffer fluid from the first trigger flow path (150, 250) and flows together with buffer fluid from the second trigger flow path (152, 252) into the outlet flow path (154, 254) via the further fluid path, such that sample fluid present in the fifth sample flow path (128, 228) is isolated from adjacent sample fluids and has a volume corresponding to a volume of the fifth sample flow path (128, 228), thereby providing the sample fluid having the predetermined sample volume. The method (30) comprising:

14. 14. The method of claim 13, further comprising emptying (S308) the sample reservoir (110, 210) after adding (S302) a sample fluid to the sample reservoir (110, 210) and before adding (S304) a buffer fluid to the buffer reservoir (140, 240).

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