Abstract
A system for transferring a sample into a microfluidic system, including a sample loading chamber, wherein a first sub-volume of the sample loading chamber is separated from at least one second sub-volume of the sample loading chamber by a filter module. The first sub-volume forms a pressure chamber provided for the loading of the sample, and there is at least one second sub-volume for providing the microfluidic system with the sample.
Claims
1. A device for transferring a sample into a microfluidic system, comprising: a sample input chamber, wherein a first sub-volume of the sample input chamber is delimited from at least one second sub-volume of the sample input chamber by a filter module, the first sub-volume forms a pressure chamber, configured as an input of the sample, and at least one second sub-volume is configured to present the sample to the microfluidic system.
2. The device as claimed in claim 1, wherein the first sub-volume is adapted to the nature of the sample.
3. The device as claimed in claim 1, wherein the second sub-volume is greater than the first sub-volume.
4. The device as claimed in claim 1, wherein the second sub-volume has at least one outlet, which connects the second sub-volume to the microfluidic system.
5. The device as claimed in claim 1, wherein: the sample input chamber has an input opening, which is sealed with respect to the surroundings by a fluid-tight cover structure; and the fluid-tight cover structure is configured to be severed by an input means for the input of the sample such that contamination-free input of the sample into the sample input chamber takes place.
6. The device as claimed in claim 1, wherein the fluid-tight cover structure is configured such that a pressure can be built up in the first sub-volume by an input means.
7. The device as claimed in claim 6, wherein the filter module is of a multilayered configuration.
8. The device as claimed in claim 1, wherein the filter module is of an exchangeable design.
9. The device as claimed in claim 1, wherein the filter module is inserted in a receiving means in the sample input chamber.
10. The device as claimed in claim 1, wherein the sample input chamber has an inlet through which a fluid can be fed into the sample input chamber.
11. The device as claimed in claim 10, wherein the inlet is separated from the sample input chamber by an inlet filter.
12. A method for using a device as claimed in claim 1, comprising: inputting a sample into the sample input chamber.
13. The method as claimed in claim 12, wherein, during the inputting, a sample sub-volume of the sample is fed through the filter module into the second sub-volume of the sample input chamber.
14. The method as claimed in claim 13, wherein, when the sample sub-volume passes through the filter module, a preparational treatment of the sample sub-volume for further processing in the microfluidic system takes place.
15. The method as claimed in claim 12, wherein, when the sample is input by the input means, a pressure greater than a maximum working pressure that can be provided by an automatable feeding means for the microfluidic system is provided.
16. The device as claimed in claim 2, wherein the nature of the sample is the expected particle content to be held back.
Description
[0072] The microfluidic system and the technical environment are explained in more detail below. The figures relate to particularly preferred exemplary embodiments. In the figures:
[0073] FIG. 1 shows a schematic structure of the described device on a cartridge
[0074] FIG. 2a and FIG. 2b show by way of example a first procedure for the input of a sample into the described device
[0075] FIGS. 3a to 3d show by way of example a second procedure for the input of a sample into the described device
[0076] FIGS. 4a to 4d show by way of example a third procedure for the input of a sample into the described device.
[0077] FIG. 1 shows the basic concept of the proposed device 18 with a sample input chamber 2 for a cartridge 1. It can be seen that, apart from the device 18 with the sample input chamber 2, the cartridge 1 also comprises the microfluidic system 16, in which the actual analysis steps that can be carried out with the microfluidic system 16 are carried out. The microfluidic system 16 may comprise a multiplicity of further channels 7 and further chambers 8, which are respectively shown here by way of example. The overall volume of the sample input chamber 2 is divided into a first sub-volume v.sub.1 and a second sub-volume v.sub.2. The two sub-volumes v.sub.1 and v.sub.2 are separated from one another by an (exchangeable) filter module 3, which is inserted in a receiving means 17. The sample (not shown here) is introduced into the sample input chamber 2 by means of input means 11 (likewise not shown here), for example by means of a syringe, through the cover structure 10. The cover structure 10 may be a pierceable membrane (septum), which seals an input opening 15. The sample is in this case first introduced into the first sub-volume v.sub.1. The cover structure 10 of such a configuration ensures contamination-free filling of the sample input chamber 2 and also shielding of the sample 6 with respect to the outside. The sample 6 passes from the second sub-volume v.sub.2 into the microfluidic system through the outlet 5 of the sample input chamber 2, which adjoins the second sub-volume v.sub.2. Here it is also shown by way of example that the sample input chamber 2 has an inlet 4, which is provided with an inlet filter 13 and which opens out into the sample input chamber 2 or in particular into the second sub-volume v.sub.2 of the sample input chamber 2. The inlet 4 may be connected to a connecting line 12, which is likewise connected to the outlet 5 and which makes possible a circulation out of the sample input chamber 2 and back into the sample input chamber 2.
[0078] As a result of introducing the sample 6 by means of input means 11 without the need for microfluidic pumping functions, a mechanical sample preparation module is fitted onto the microfluidic system 16 of a cartridge 1. The sample preparation module is formed here by the sample input chamber 2 in combination with the filter module 3. The filter module 3 (modularly exchangeable filter membrane) makes possible the implementation of various functions. By way of the two access points (inlet and outlet 5), a reagent (the sample and/or further fluids 9) can be transferred into the microfluidic system 16 (shown here) of the cartridge 1. Since the inlet 4 and the outlet 5 are connected to one another by way of a connecting line 12, circulatory pumping of fluids 9 in the sample input chamber 2 is also possible. A further membrane at the inlet 4 and the outlet 5 (shown here by way of example is an inlet filter 13 at the inlet 4) allows the sample to be further processed after the first preliminary treatment. In particular, it is possible to filter, bind or else homogenize the sample 6 a further time, in that it is fed through the inlet filter 13 and/or through the filter module 3.
[0079] Furthermore, other reagents, which are provided in advance on the cartridge 1, can also be transferred by way of the inlet 4 into the sample input chamber 2 and for example mix with the sample 6.
[0080] Some of the reference signs explained in conjunction with FIG. 1 are repeated in the following figures to allow quick orientation, but sometimes then not explained again. Reference is made here respectively to the explanation (given by way of example) with reference to FIG. 1.
[0081] In FIGS. 2a and 2b, the sequence for filtering a sample 6 with the input into the sample input chamber 2 in the device 18 is shown. According to FIG. 2a, input takes place through a cover structure 10 into the sample input chamber 2. This takes place with the input means 11. Furthermore, the cover structure 10 ensures shielding of the sample with respect to the outside and a build-up of pressure in the first sub-volume v.sub.1, which is used as a pressure chamber.
[0082] According to FIG. 2b, the sample 6 is filtered by the filter module 3. In this case, the sample 6 may be filtered for example on the basis of the size of its constituents and/or be homogenized by mechanical shearing and/or selective binding of certain constituents of the sample 6, such as for example proteins, may be realized by using a corresponding filter membrane (membrane/filter/mesh) of the filter module 3. In this case, the sample 6 enters the sub-volume v.sub.2 of the sample input chamber 2 and can then be used for further processing.
[0083] FIGS. 3a to 3d show a combined sequence as an example for size filtration and subsequent homogenization of a sample with a described microfluidic system 1 or with its sample input chamber 2.
[0084] In FIG. 3a, the sample input chamber 2 is supplied with the sample 6 in a contamination-free manner by means of a syringe as input means 11 through the cover structure 10 configured as a pierceable membrane (for example a septum). Furthermore, the cover structure 10 ensures shielding of the sample 6 with respect to the outside.
[0085] In FIG. 3b, the sample 6 is filtered on the basis of the size of its constituents by the exchangeable, correspondingly chosen filter module 3 and enters the second sub-volume v.sub.2. For example, the filtering out of larger constituents to be filtered out, such as for example clumps of blood, hair or other constituents, takes place here. Such constituents remain in the filter module 3.
[0086] In FIG. 3c, the filtered sample 6 in the sub-volume v.sub.2 is transferred by way of the outlet 5 into the microfluidic system 16 (not shown here) on a cartridge 1. If appropriate, it can be fed back into the sample input chamber 2 or into the second sub-volume v.sub.2 by way of an inlet 4.
[0087] In FIG. 3d, the sample 6 is homogenized by an inlet filter 13 at the inlet 4. Here, for example, cell clumps are individually separated. Repeated circulatory pumping leads to a completely homogenized sample 6 or sample liquid, which can be used for further processing in the microfluidic system 16 on the cartridge 1.
[0088] In FIGS. 4a to 4d, the filtering of a sample 6 with respect to its particle size and the subsequent mixing with a reagent provided in advance on the cartridge 1 are shown by way of example.
[0089] According to FIG. 4a, a cover structure 10 is disclosed, configured as a pierceable membrane (for example a septum). The sample input chamber 2 can be filled with the sample 6 in a contamination-free manner by means of input means 11 (for example a syringe). Furthermore, the cover structure 10 ensures shielding of the sample 6 with respect to the outside.
[0090] According to FIG. 4b, the sample 6 is filtered by the exchangeable, correspondingly chosen filter modules 3 on the basis of the size of its constituents and enters the second sub-volume v.sub.2. Larger constituents to be filtered out are for example clumps of blood, hair or other constituents. Such constituents in this case remain on or at or in the filter module 3.
[0091] According to FIG. 4c, the sample 6 can be transferred into the microfluidic system 16 on the cartridge 1 through the outlet 5.
[0092] According to FIG. 4d, the inlet 4 of the sample input chamber 2 is used to mix the filtered sample with a mixing fluid 14 (a reagent) and then further process this sample mixture in the microfluidic system 16 on the cartridge 1.
