Microfluidic device, kit, and method for analyzing at least one liquid sample

Abstract

The present disclosure relates to a microfluidic device (10) for handling at least one liquid sample. The microfluidic device (10) includes at least one support device (12) and at least one cartridge (14) which includes at least one input well (16) configured to receive the at least one liquid sample and one or more microfluidic channels (18) which are fluidically connected to the at least one input well (16). The at least one cartridge (14) is removably securable to the at least one support device (12). The present disclosure also relates to a kit (80) for handling at least one liquid sample and method for analyzing at least one liquid sample.

Description

[0001] MICROFLUIDIC DEVICE, KIT, AND METHOD FOR ANALYZING AT LEAST ONE LIQUID SAMPLE

[0002] Molecular biology analyses are performed for a number of different purposes and / or in a number of different fields. In particular, polymerase chain reaction (PCR) is a known and widespread tool for applications in molecular biology. PCR may be used to amplify the amount of a specific gene present in a sample, e.g., a DNA sample and / or an RNA sample, that may contain a number of different genes. PCR can be used for a variety of experiments and / or analyses, including, e.g., genetic testing, forensic analyses, etc.

[0003] Variants of PCR may be used to quantitatively determine how much of a particular gene of interest is present within a sample of extracted DNA and / or RNA. This may be useful, for example, in determining whether the sample is heterozygous or homozygous for a specific gene of interest.

[0004] Digital PCR (dPCR), which is a known type of PCR, involves dividing a sample into a number, e.g., in particular a relatively large number, of separate aliquots. Some of the aliquots may contain a particular sequence, e.g., a DNA sequence and / or an RNA sequence, corresponding to a gene of interest and some of the aliquots may not contain the sequence of interest.

[0005] The aliquots may then be amplified to determine whether a molecule, e.g., a DNA molecule and / or an RNA molecule, containing the gene of interest is present within each aliquot. Based on the number of aliquots that have undergone exponential growth, the original concentration of DNA and / or RNA prior to dilution may be determined.

[0006] Conventional systems for molecular biology analyses, in particular conventional systems that employ PCR, in particular dPCR, are generally relatively expensive and / or complex. Thus, the systems, in particular the PCR systems, in particular the dPCR systems, known from the prior art generally incur relatively high costs.

[0007] Thus, there is a need for a system or device for performing molecular biology analyses, in particular PCR, in particular dPCR, analyses, which is simpler and / or easier to manufacture and / or more efficient to manufacture and / or less expensive, or at least has more potential for being simpler and / or easier to manufacture and / or more efficient to manufacture and / or less expensive than the known systems, preferably while at least maintaining the robustness and / or accuracy of the known systems. It is therefore an object of the present invention to provide a system or device for performing, or at least for assisting in performing, molecular biology analyses, in particular PCR analyses, in particular dPCR analyses, which improves one or more aspects of the known devices / systems, in particular by at least partially alleviating one or more of the above-mentioned drawbacks.

[0008] The above-identified object is achieved by a device defined by the features of claim 1. Preferred embodiments are defined by the features of the dependent claims, respectively.

[0009] The device may be configured for handling at least one liquid sample. The device may be configured as a microfluidic device. The microfluidic device may include at least one support device. The microfluidic device may include at least one cartridge which may include at least one input well. The at least one input well may be configured to receive the at least one liquid sample. The at least one cartridge may include one or more microfluidic channels which may be fluidically connected to the at least one input well. The at least one cartridge may be removably securable to the at least one support device. The device may be configured to be used in a system for performing molecular biology analyses, in particular PCR analyses, in particular dPCR analyses, of the at least one liquid sample.

[0010] In the devices known from the prior art for performing molecular biology analyses, in particular, PCR, in particular dPCR, analyses, the entire device, e.g., the entire nanoplate, is discarded after use, e.g., after the respective analysis / analyses has / have been performed. By contrast, the microfluidic device according to the present disclosure allows at least a portion of the device, i.e., at least the at least one support device, to be reused. I n other words, after use, the at least one cartridge, which includes the at least one input well, preferably a plurality of input wells, and the one or more microfluidic channels, may be released and removed from the at least one support device and discarded such that the at least one support device may be reused with one or more further cartridges. By contrast, none of the components of the known devices / nanoplates can be reused. Thus, this produces more waste than the device described herein. Hence, the costs and / or the ecological footprint of the device disclosed herein may be reduced, i.e., by allowing the at least one support device to be used, i.e., reused, multiple times, i.e., with multiple cartridges.

[0011] Furthermore, this may allow the at least one support device to be manufactured independently and / or to be made of a different material than the cartridge. For instance, the cartridge may be made of plastic, whereas the at least one support device may be made of, e.g., metal. This may allow the properties of the at least one support device and / or the properties of the cartridge to be selected and / or adjusted individually via selection of the respective material(s). Moreover, advantageously, the microfluidic device described herein may allow a user to customize the device, e.g., by combining different cartridges, e.g., with different numbers of input wells (and associated microfluidic channels), with the (same) support device, according to the required / desired application. This may enable a modular configuration of the microfluidic device. This may allow the device, e.g., the number of input wells and / or the configuration of the input wells, to be tailored to the respective application. This may be advantageous. For instance, in the prior art, in case the user only uses some of the input wells of the respective device / nanoplate, e.g., due to the demands / requirements of a particular application, the entire device / nanoplate, including unused input wells, must be discarded. Enabling a customization of the device, e.g., by allowing different cartridges, e.g., with different numbers of input wells, according to the respective application(s) to be combined with the support device, as described above, may allow such redundancy and waste to be reduced.

[0012] For instance, the at least one cartridge may include a plurality of subunits which are releasably interconnectable. Each subunit may include one or more of the (plurality of) input wells (and associated microfluidic channels). Thus, the subunits may be individually pieced together to form the cartridge having a desired / required number of input wells and / or configuration, e.g., size, of input wells. The interconnected subunits, i.e., the cartridge, may be releasably secured to the support device, preferably in a state in which the cartridge having the subunits is a single coherent unit. Alternatively, each subunit may be individually, i.e., as individual coherent units, securable to the support device. Thus, the support device may be configured to hold the subunits together. The subunits may be configured as individual rows of input wells, individual columns of input wells, or array with multiple rows and / or columns of input wells.

[0013] This may be advantageous, e.g., since the devices which include the input well(s) and the microfluidic channel(s) are relatively expensive to manufacture. In the prior art, the entire device, e.g., nanoplate, generally has to be discarded, in case only some of the input wells have any deficiencies. By contrast, the device described herein may allow only the deficient input wells, e.g., the subunits having one or more deficient input wells, to be discarded, whereas the acceptable input well(s) / subunit(s) may be used, rather than unnecessarily being discarded together with the deficient input well(s) / subunit(s) (and associated microfluidic channels).

[0014] The device described herein may also facilitate the manufacturing process of the device, e.g., since this may allow the size and / or complexity of the cartridges and / or subunits of the cartridge(s) produced in one piece to be reduced. For instance, producing smaller cartridges and / or subunits of the cartridge(s) in one piece may allow to adjust and / or optimize manufacturing parameters, e.g., molding parameters, accordingly. This may reduce deformation during manufacturing, e.g., during a molding process. In particular, it has been shown, at least in some cases, that the known nanoplates may inadvertently bend, e.g., due to the size of the nanoplate compared to the size of the nanostructure within the nanoplate. This may be avoided, or at least reduced, by the device described herein.

[0015] In case the cartridge includes a plurality of assemblable subunits, in particular when the subunits are assemblable to a single coherent unit, as described above, the support device may be omitted. In this case, the assembled subunits may be placed directly onto the respective working surface of the analysis device / system. Alternatively, the support device may be included, e.g., to facilitate piecing the subunits together and / or to provide a frame and / or support structure to hold the subunits together.

[0016] Thus, the device described herein may increase the flexibility, for the user, in customizing the device for the respective examination / analysis and / or adapting the device to the requirements of the respective examination / analysis.

[0017] The cartridge may be configured to house one or more reagents, e.g., a DNA primer configured to complement a DNA sample, in particular at specific gene locations. For instance, the one or more reagents and the liquid sample may be introduced into the cartridge, in particular into the input well(s), as a mixture solution, e.g., containing DNA polymerase and one or more reagents, e.g., nucleotides, that facilitate the activities of the polymerase. Alternatively, or additionally, the cartridge may be configured to house, at least temporarily, the one or more reagents separately, preferably in a fluidical ly sealed manner, from the liquid sample.

[0018] The term "microchannels" or "microfluidic channels", within the context of the present disclosure, are defined as channels which have a hydraulic diameter smaller than 1 mm, e.g., between usually 1 micron and 99 microns, at and / or along at least a section of the respective channel.

[0019] The terms "releasable", "releasably", "remove", "removable", and all equivalents related to "releasing" and "removing", within the context of the present disclosure, mean to be able to disconnect the concerned part(s) or component(s) without compromising the structural integrity of the concerned part(s) or component(s) and of the part(s) or component(s) from which the concerned part(s) or component(s) is / are disconnected.

[0020] The cartridge may be configured as a nanoplate. The cartridge may be configured as a single coherent unit, in particular even when the cartridge is not secured to the support device. Alternatively, the cartridge may include a plurality of individual components which may be secured individually to the support device. The support device and the cartridge may be a single coherent unit, when the cartridge is secured to the support device.

[0021] The microfluidic device, more specifically the cartridge, may be configured to comply with ANSI / SLAS microplate standards.

[0022] The microfluidic device may include one or more features, e.g., with respect to the microfluidic structure and / or the microfluidic channels, of the microfluidic device described in US 11,154,864 B2 and / or EP 2 969 215 Bl, which are herewith incorporated by reference in its / their entirety.

[0023] The support device may be configured as a plate or plate mask configured to support and / or receive the cartridge. The support device may have a base side configured to rest on a structure, e.g., a workspace surface and / or an analysis machine, and a top side which is substantially opposite from the base side. The cartridge may be configured to be removably secured to the top side of the support device.

[0024] The support device and / or the cartridge may have one or more securing mechanisms to allow the cartridge to be releasably secured to the support device. The one or more securing mechanisms may be configured to provide a form-fit and / or a frictional fit between the support device and the cartridge. For instance, the support device and / or the cartridge may include one or more clips, one more snap-fit elements, one or more screw connections, one or more screw latches, one or more pin-and-hole connections, and / or any other type of mechanism which allows the cartridge to be secured to the support device and released again from the support device, e.g., after the cartridge has been used. Preferably, the one or more securing mechanisms is / are configured to allow the cartridge to be released from the support device without the use of tools, e.g., just by means of the user's hand(s).

[0025] Preferably, the microfluidic device includes a plurality of the at least one cartridge which are individually removably securable to the at least one support device sequentially and / or simultaneously.

[0026] Preferably, at least a first cartridge of the plurality of cartridges includes a first number of input wells, i.e., a plurality of the input well mentioned above, configured to receive the at least one liquid sample and at least a second cartridge of the plurality of cartridges includes a second number of input wells, i.e., a plurality of the input well mentioned above, configured to receive the at least one liquid sample. The first number may be different than the second number. This may allow at least two cartridges with two different numbers of wells to be used with the support device sequentially and / or simultaneously, preferably sequentially. Preferably, the plurality of cartridges have at least two different sizes, preferably wherein the term "size" refers to the outer dimensions of the respective cartridge. For instance, the plurality of cartridges may have one or more different outer dimensions, e.g., different widths and / or different lengths. At least some of the plurality of cartridges may have substantially the same size. At least some of the plurality of cartridges, preferably including at least some of the plurality of cartridges which have substantially the same size, may differ from each other with respect to one or more properties which do not include the size, i.e., the outer dimensions, of the plurality of cartridges. For instance, one or more input wells, e.g., a size and / or configuration of the input wells, and / or one or more channels, preferably microfluidic channels, e.g., a size and / or configuration of the (microfluidic) channels, and / or one or more microchambers, e.g., a size and / or configuration of the microchambers, of the respective cartridges may differ between cartridges.

[0027] Alternatively, or additionally, a first cartridge of the plurality of cartridges may have one or more wells which differ in size, e.g., volume, compared with one or more wells of at least a second cartridge of the plurality of cartridges.

[0028] Preferably, the plurality of cartridges are exchangeably removably securable to the at least one support device. This may allow a first cartridge of the plurality of cartridges to be exchanged by at least one second cartridge of the plurality of cartridges, preferably multiple times.

[0029] Preferably, the at least one support device is configured to be reusable with a plurality of the at least one cartridge.

[0030] Preferably, the at least one support device and / or the at least one cartridge include(s) at least one locking element configured to lock the at least one cartridge in place relative to the at least one support device.

[0031] Preferably, the at least one locking element is configured to provide a frictional connection and / or a form-fit connection between the respective cartridge(s) and the at least one support device.

[0032] Preferably, the at least one locking element is configured as a clip.

[0033] Preferably, the at least one support device is configured as a tray configured to at least partially receive the at least one cartridge. Preferably, the at least one cartridge includes a plurality of the at least one input well. The plurality of input wells may be arranged in at least one array, e.g., in one or more columns and / or one or more rows.

[0034] Preferably, the plurality of input wells are defined in a plurality of subunits of the at least one cartridge which are assemblable to a single coherent unit. The plurality of subunits may be releasably connectable to each other by means of one or more releasable connection mechanisms, e.g., via one or more clips, one or more screws, one or more form-fit connections, one or more frictional connections, etc. Thus, the subunits may be releasably connectable to each other. This may allow the input wells to be pieced together to provide a variable number of input wells (and associated microfluidic channels). Unused input wells may be easily separated from the used input wells, e.g., by releasing the respective releasable connection mechanism(s), so that the unused input wells do not have to be unnecessarily discarded.

[0035] Preferably, the at least one cartridge includes a plurality of components which are assemblable to a single coherent unit.

[0036] Preferably, the at least one cartridge is monolithically and / or integrally formed.

[0037] Preferably, the at least one support device and / or the at least one cartridge include(s) at least one alignment device configured to align, or at least aid in aligning, the at least one cartridge relative to the at least one support device. This may aid in assembling the at least one support device and / or the at least one cartridge with a relatively degree of accuracy.

[0038] Preferably, the at least one cartridge includes at least one pressure sensitive cover configured to cover at least a section of the at least one cartridge. The at least one pressure sensitive cover may be configured to cover at least a section of the at least one input well. In particular, the at least one pressure sensitive cover may be configured to cover at least a section of the at least one input well along a bottom of the cartridge.

[0039] Alternatively, or additionally, the at least one cartridge includes at least one pressure sensitive cover configured to cover at least a section of the at least one input well along a top of the cartridge.

[0040] Preferably, the at least one support device is made of a non-plastic material, preferably of metal. Alternatively, the at least one support device may be made of at least one plastic material, preferably at least one stable and / or autoclavable plastic material, for instance polypropylene (PP). Preferably, the microfluidic device is configured for use in analyzing and / or processing the at least one liquid sample, in particular while the at least one liquid sample is received and / or after the at least one liquid sample has been received within the at least one input well, in particular for use in molecular screening and / or polymerase chain reaction (PCR), preferably digital PCR, of the liquid sample. In particular, the microfluidic device may be configured for use in one or more of: cell sorting, single cell analysis, and any molecular biological analysis procedure for analyzing at least one sample.

[0041] In particular, the microfluidic device may be configured for use with the QIAcuity® system, in particular the QIAcuity® Digital PCR (dPCR) system, available from Qiagen or the CONSTELLATION® Digital PCR system available from Formulatrix, Inc.

[0042] Preferably, the at least one support device is configured to receive the at least one cartridge having one or more variable dimensions and / or a variable number of the at least one input well, preferably when the at least one support device is configured to receive the at least one cartridge having any number of the at least one input well from 1 to 96, more preferably from 8 to 96, more preferably from 8 to 24. The cartridge may include more than 96 wells, e.g., 384 wells or more. This may allow the device to be used with commercially available PCR systems, which are generally configured for plates having 8, 24, and / or 96 wells.

[0043] Preferably, the at least one input well includes at least one inlet cavity which is fluidically coupled to the one or more microfluidic channels. The microfluidic channels may extend substantially parallel to each other.

[0044] Preferably, each microfluidic channel includes a plurality of microchambers. The microchambers may be arranged in series along the respective microfluidic channel.

[0045] Preferably, each microchamber includes at least one reaction chamber, which is configured to receive at least a portion of the liquid sample and house at least one reaction, preferably at least one polymerase chain reaction (PCR), of the liquid sample. Preferably, each microchamber may include at least one vent chamber configured to vent at least one gas from the reaction chamber as the liquid sample flows into and / or through the reaction chamber.

[0046] Hence, the microfluidic device may be configured to separate the liquid sample into a plurality of partitions, i.e., the microchambers / reaction chambers, preferably in a fluidically isolated manner, i.e., such that portions of the liquid sample in the microchambers / reaction chambers are isolated / isolatable, at least temporarily, from each other. This may allow reaction(s) of the liquid sample in the respective reaction chamber to take place substantially independently from the liquid sample in the other, e.g., adjacent, reaction chambers.

[0047] Each reaction chamber may be configured to define any suitable volume and / or receive any suitable volume of the liquid sample. For example, the volume of one or more of the reaction chambers may be less than about 10 microliters, preferably less than about 1 microliter, preferably less than about 500 nanoliters, preferably less than about 200 nanoliters (e.g., about 150 nanoliters), preferably less than about 100 nanoliters, preferably less than about 50 nanoliters, preferably less than about 20 nanoliters, preferably less than about 10 nanoliters, preferably less than 5 nanoliters, preferably less than about 1 nanoliter, preferably less than about 0.5 nanoliter, preferably less than about 0.25 nanoliter, preferably less than about 0.1 nanoliter, or any other appropriate volume.

[0048] Preferably, the at least one cartridge includes at least one vent configured to vent gas from the microfluidic channels. Preferably, the at least one vent may be arranged on an opposite side, preferably an opposite corner, of the microfluidic channels compared to the input well.

[0049] Preferably, the microfluidic device further includes at least one activation mechanism configured to allow and / or force, preferably by means of pressure, the sample fluid which is received in the at least one input well to flow from the at least one input well to the microfluidic channel(s). This may allow the PCR process, e.g., one or more reactions in the at least one liquid sample, to be triggered at a particular start time. The at least one activation mechanism may include one or more protrusions configured to be inserted at least partially into, or further into, the at least one input well. The insertion of the one or more protrusions may cause a rise in pressure in the at least one input well which may cause at least a portion of the at least one sample fluid to flow into the microfluidic channel(s). The microfluidic device may include at least one cover element which covers, and preferably substantially seals, the at least one input well. The one or more protrusions may be configured to displace the at least one cover element at least partially into and / or further towards the at least one input well. This may facilitate a pressure increase within the at least input well, when the one or more protrusions are inserted at least partially into, or further into, the at least one input well.

[0050] Preferably, the cartridge includes a plurality of cavities fluidically connected to the input wells. The cartridge may further include at least one separating element configured to selectively fluidically separate the plurality of cavities from each other. The plurality of cavities may be configured as micro-cavities. The plurality of cavities may be fluidically connected and / or connectable to the one or more microfluidic channels. In particular, each cavity may be designated its own one or more microfluidic channels. In other words, a first cavity of the plurality of cavities may be fluidically connected and / or connectable to one or more first microfluidic channels and at least a second cavity of the plurality of cavities may be fluidically connected and / or connectable to one or more second microfluidic channels which are different from the one or more first microfluidic channels, and optionally are fluidically disconnected and / or fluidically disconnectable from the one or more first microfluidic channels.

[0051] The at least one cartridge may include at least one output well. Preferably, the at least one output well may be fluidically connected and / or fluidically connectable to the at least one input well. The at least one output well may be configured as a vent, e.g., to vent at least one gas.

[0052] Preferably, the at least one separating element is configured to be manipulatable, preferably by heat and / or pressure, to selectively fluidically separate the plurality of cavities from each other, and optionally to selectively fluidically reconnect the plurality of cavities. This may allow the at least one liquid sample to be separated into portions, at least temporarily, each portion being arranged in a respective cavity of the plurality of cavities.

[0053] Preferably, the at least one cartridge is manufactured by at least one molding process.

[0054] The object mentioned at the beginning is also solved by a kit for handling at least one liquid sample. The features, configurations, and advantages described above with respect to the microfluidic device apply to the kit accordingly.

[0055] The kit may include at least one support device. The kit may include at least one first cartridge which includes a first number of one or more input wells configured to receive the at least one liquid sample. The at least one first cartridge may include one or more microfluidic channels which are fluidically connected to the first number of one or more input wells. The kit may include at least one second cartridge which includes a second number of one or more input wells configured to receive the at least one liquid sample. The at least one second cartridge may include one or more microfluidic channels which are fluidically connected to the second number of one or more input wells. The first number of the one or more input wells is different than the second number of the one or more input wells. The at least one first cartridge and the at least one second cartridge may be removably securable to the at least one support device sequentially and / or simultaneously. The object mentioned at the beginning is also solved by a method for analyzing at least one liquid sample. The features, configurations, and advantages described above with respect to the microfluidic device apply to the method accordingly.

[0056] The method may include securing at least one first cartridge to a support device. The at least one first cartridge may include at least one first input well and one or more first microfluidic channels which are fl uidica I ly connected to the at least one first input well.

[0057] The method may include placing the at least one liquid sample in the at least one first input well of the at least one first cartridge.

[0058] The method may include performing at least one analysis of the at least one liquid sample in the at least one first cartridge.

[0059] The method may include removing the at least one first cartridge from the support device.

[0060] The method may include securing at least one second cartridge to the support device. The at least one second cartridge may include at least one second input well and one or more second microfluidic channels which are fl uidica I ly connected to the at least one second input well.

[0061] The method may include placing the at least one liquid sample in the at least one second input well of the at least one second cartridge.

[0062] The method may include performing an analysis of the at least one liquid sample in the at least one second cartridge.

[0063] Preferably, the at least one first cartridge includes a first number of one or more input wells each configured to receive the at least one liquid sample and the at least one second cartridge includes a second number of one or more input wells each configured to receive the at least one liquid sample. Preferably, the first number is different than the second number.

[0064] The following list of aspects provides alternative and / or further features of the invention:

[0065] 1. A device, preferably a microfluidic device, for handling at least one sample, preferably at least one liquid sample, the device including: at least one support device; and at least one cartridge which includes at least one input well configured to receive the at least one liquid sample, preferably wherein the at least one cartridge further includes one or more channels, preferably one or more microfluidic channels, which are preferably fluidically connected and / or fluidically connectable to the at least one input well; wherein the at least one cartridge is removably securable to the at least one support device.

[0066] 2. The device according to aspect 1, including a plurality of the at least one cartridge which are individually removably securable to the at least one support device sequentially and / or simultaneously.

[0067] 3. The device according to aspect 2, wherein at least a first cartridge of the plurality of cartridges includes a first number of input wells configured to receive the at least one liquid sample and at least a second cartridge of the plurality of cartridges includes a second number of input wells configured to receive the at least one liquid sample, wherein the first number is different than the second number.

[0068] 4. The device according to aspect 2 or 3, wherein the plurality of cartridges have at least two different sizes.

[0069] 5. The device according to any of aspects 2 to 4, wherein the plurality of cartridges are exchangeably removably securable to the at least one support device.

[0070] 6. The device according to any of the preceding aspects, wherein the at least one support device is configured to be reusable with a plurality of the at least one cartridge.

[0071] 7. The device according to any of the preceding aspects, wherein the at least one support device and / orthe at least one cartridge include(s) at least one locking element configured to lock the at least one cartridge in place relative to the at least one support device.

[0072] 8. The device according to aspect 7, wherein the at least one locking element is configured to provide a frictional connection and / or a form-fit connection between the respective cartridge(s) and the at least one support device.

[0073] 9. The device according to aspect 7 or 8, wherein the at least one locking element is configured as a clip. 10. The device according to any of the preceding aspects, wherein the at least one support device is configured as a tray configured to at least partially receive the at least one cartridge.

[0074] 11. The device according to any of the preceding aspects, wherein the at least one cartridge includes a plurality of the at least one input well, the plurality of input wells preferably being arranged in at least one array.

[0075] 12. The device according to aspect 11, wherein the plurality of input wells are defined in a plurality of subunits of the at least one cartridge which are assemblable to a single coherent unit.

[0076] 13. The device according to any of the preceding aspects, wherein the at least one cartridge includes a plurality of components which are assemblable to a single coherent unit.

[0077] 14. The device according to any of the preceding aspects, wherein the at least one cartridge is monolithically and / or integrally formed.

[0078] 15. The device according to any of the preceding aspects, wherein the at least one support device and / or the at least one cartridge include(s) at least one alignment device configured to algin, or at least aid in aligning, the at least one cartridge relative to the at least one support device.

[0079] 16. The device according to any of the preceding aspects, wherein the at least one cartridge includes at least one pressure sensitive cover configured to cover at least a section of the at least one cartridge, preferably wherein the at least one pressure sensitive cover is configured to cover at least a section of the at least one input well, preferably along a bottom of the cartridge.

[0080] 17. The device according to any of the preceding aspects, wherein the at least one support device is made of a non-plastic material, preferably of metal.

[0081] 18. The device according to any of the preceding aspects, wherein the device is configured for use in analyzing and / or processing the at least one liquid sample, in particular while the at least one liquid sample is received and / or after the at least one liquid sample has been received within the at least one input well, in particular for use in molecular screening and / or polymerase chain reaction (PCR), preferably digital PCR, of the liquid sample. The device according to any of the preceding aspects, wherein the at least one support device is configured to receive the at least one cartridge having one or more variable dimensions and / or a variable number of the at least one input well, preferably when the at least one support device is configured to receive the at least one cartridge having any number of the at least one input well from 1 to 96, more preferably from 8 to 96, more preferably from 8 to 24. The device according to any of the preceding aspects, wherein the at least one input well includes at least one inlet cavity which is fl uidica I ly coupled to the one or more channels, preferably wherein the channels extend substantially parallel to each other. The device according to aspect 20, wherein each channel includes a plurality of microchambers, preferably wherein the microchambers are arranged in series along the respective channel. The device according to aspect 21, wherein each microchamber includes at least one reaction chamber, which is configured to receive at least a portion of the liquid sample and house at least one reaction, preferably at least one polymerase chain reaction (PCR), of the liquid sample, and at least one vent chamber configured to vent at least one gas from the reaction chamber as the liquid sample flows into and / or through the reaction chamber. The device according to any of the preceding aspects, wherein the at least one cartridge includes at least one vent configured to vent gas from the channels. The device according to any of the preceding aspects, further including at least activation mechanism configured to allow and / or force, preferably by means of pressure, the sample fluid which is received in the at least one input well to flow from the at least one input well to the channels. The device according to any of the preceding aspects, wherein the cartridge includes a plurality of cavities fluidically connected to the input wells, and wherein the cartridge further includes at least one separating element configured to selectively fluidically separate the plurality of cavities from each other. The device according to aspect 25, wherein the at least one separating element is configured to be manipulatable, preferably by heat and / or pressure, to selectively fluidically separate the plurality of cavities from each other, and optionally to selectively fluidically reconnect the plurality of cavities. The device according to any of the preceding aspects, wherein the at least one cartridge is manufactured by at least one molding process. The device according to any of the preceding aspects, wherein each cartridge includes at least 5 input wells, preferably at least 6 input wells, preferably at least 8 input wells, preferably at least 10 input wells, preferably at least 16 input wells, preferably at least 20 input wells, preferably at least 24 input wells. A kit for handling at least one liquid sample, including: at least one support device; at least one first cartridge including a first number of one or more input wells configured to receive the at least one liquid sample and one or more channels, preferably one or more microfluidic channels, which are fluidically connected to the first number of one or more input wells; and at least one second cartridge including a second number of one or more input wells configured to receive the at least one liquid sample and one or more channels, preferably one or more microfluidic channels, which are fluidically connected to the second number of one or more input wells; wherein the first number of the one or more input wells is different than the second number of the one or more input wells; and wherein the at least one first cartridge and the at least one second cartridge are removably securable to the at least one support device sequentially and / or simultaneously. A method for analyzing at least one liquid sample, the method including: securing at least one first cartridge to a support device, the at least one first cartridge including at least one first input well and one or more first channels, preferably one or more first microfluidic channels, which are fluidically connected to the at least one first input well; placing the at least one liquid sample in the at least one first input well of the at least one first cartridge; performing at least one analysis of the at least one liquid sample in the at least one first cartridge; removing the at least one first cartridge from the support device; securing at least one second cartridge to the support device, the at least one second cartridge including at least one second input well and one or more second channels, preferably one or more second microfluidic channels, which are fluidically connected to the at least one second input well; placing the at least one liquid sample in the at least one second input well of the at least one second cartridge; performing an analysis of the at least one liquid sample in the at least one second cartridge.

[0082] 31. The method according to aspect 30, wherein the at least one first cartridge includes a first number of one or more input wells each configured to receive the at least one liquid sample and the at least one second cartridge includes a second number of one or more input wells each configured to receive the at least one liquid sample, wherein the first number is different than the second number.

[0083] Embodiments of the present invention are further elucidated below with reference to the figures. The figures are schematic drawings and as such may not show all details of the systems and their components. Particularly, the drawings are not necessarily to scale and the shown dimensions are only exemplary and may vary. The drawings illustrate exemplary embodiments to provide a thorough understanding of the present invention. The drawings are not intended to limit the scope of the invention, which is defined by the appended claims and is to include the equivalents thereof.

[0084] Fig. 1 shows, in a schematic cross-sectional view, a device for handling at least one liquid sample according to an embodiment of the present disclosure;

[0085] Fig. 2 shows, in a schematic top view, a device for handling at least one liquid sample according to a further embodiment of the present disclosure;

[0086] Fig. 3 shows, in a schematic cross-sectional view, the microfluidic channels of the device of Fig. 1 and / or 2;

[0087] Fig. 4 shows, in a schematic cross-sectional view, an activation mechanism of the device of Fig. 1 and / or 2;

[0088] Fig. 5 shows, in a schematic top view, a kit according to an embodiment of the present disclosure.

[0089] Fig. 1 shows, in a schematic view, a device 10 for handling at least one liquid sample. The device 10 may be configured as a microfluidic device. The device 10 may include at least one support device 12 and at least one cartridge 14 which includes at least one input well 16 configured to receive the at least one liquid sample. The at least one cartridge 14 may include any number of input wells, e.g., 2 wells, 3 wells, 4 wells or more. Preferably, the at least one cartridge 14 has 8 input wells, 24 input wells or 96 input wells. Fig. 1 shows a plurality of input wells 16, of which only one is indicated with a reference sign in Fig. 1 for the sake of clarity. Each input well 16 may include at least one inlet cavity 17.

[0090] The at least one cartridge 14 may include one or more microfluidic channels 18 which are fluidically connected to the at least one input well 16, in particular to the at least one inlet cavity 17.

[0091] The at least one cartridge 14 may include at least one vent 20, which may also be referred to as an outlet well. The at least one vent 20 may be configured to vent gas, in particular from the one or more microfluidic channels 18.

[0092] The at least one cartridge 14 may be removably securable to the at least one support device 12, e.g., via one or more clips, screws, and / or any other mechanism(s) which allow(s) the at least one cartridge 14 to be removably secured to the at least one support device 12. In order to releasably secure the at least one cartridge 14 to the at least one support device 12, the device 10 may include at least one locking element 22 which may include, but is not limited to, any of the following: one or more clips, one more snap-fit elements, one or more screw connections, one or more latches, one or more screws, one or more pin-and-hole connections, and / or any other type(s) of mechanism(s) which allow(s) the at least one cartridge 14 to be secured to the at least one support device 12 and released again from the at least one support device 12, e.g., after the at least one cartridge 14 has been used. The locking element(s) 22 is / are only schematically shown in Fig. 1.

[0093] The microfluidic channels 18 may be configured and / or included in a microfluidic circuit.

[0094] The microfluidic channels 18 are preferably arranged parallel to each other. The microfluidic channels 18 may be spaced from each other along a vertical direction, as shown in Fig. 1, and / or along a horizontal direction.

[0095] The input well(s) 16 and the at least one vent 20 may be configured to be at least temporarily open, preferably selectively, to an environment. Preferably, the device 10 includes at least one top seal 21 and / or at least one top barrier 21 (see Fig. 4) which is applicable to a top of the at least one cartridge 14 such that the input well(s) 16 and the at least one vent 20 is at least temporarily and / or at least partially sealed and / or separated from the environment.

[0096] The device 10 may include at least one bottom seal 23 and / or at least one barrier 23 which is applicable to a bottom of the at least one cartridge 14 (see Fig. 4). The at least one bottom seal 23 and / or at least one barrier 23 may be configured to fl uidica lly separate, preferably selectively, a plurality of cavities within the at least one cartridge 14, preferably one or more microchambers, from each other, and optionally to selectively fl uidica I ly reconnect the plurality of cavities. The at least one bottom seal 23 and / or at least one barrier 23 may be configured to be manipulatable, preferably by heat and / or pressure, to trigger the at least one bottom seal 23 and / or at least one barrier 23 to fl uidica I ly separate, preferably selectively, said cavities.

[0097] The at least one cartridge 14 may include a plurality of input wells 16 which are arranged in at least one array having one or more columns and / or one or more rows.

[0098] A plurality of the at least one cartridge 14 may be provided which may be individually removably securable to the at least one support device 12 sequentially and / or simultaneously. In particular, at least a first cartridge of the plurality of cartridges 14 may include a first number of input wells 16 configured to receive the at least one liquid sample and at least a second cartridge of the plurality of cartridges 14 may include a second number of input wells 16 configured to receive the at least one liquid sample, wherein the first number is different than the second number. This may allow cartridges which have different numbers of input wells 16 to be used with the same support device 12.

[0099] The at least one cartridge 14 may be monolithically and / or integrally formed. Alternatively, or additionally, the at least one cartridge 14 may be assembled and / or assemblable from a plurality of subunits 28A-28C, preferably to a single coherent unit, as shown in Fig. 2. Each subunit 28A- 28C may include one or more of the input wells 16. In other words, a plurality of input wells 16 (and associated microfluidic channels 18) may be defined in a plurality of subunits 28A-28C of the at least one cartridge 14. As shown in Fig. 2, one or more of the subunits 28A-28C may include an array of input wells 16 (and associated microfluidic channels 18). The array of input wells 16 may include one or more rows of input wells 16 and / or one or more columns of input wells 16. Alternatively, one or more of the subunits 28A-28C may include only a single input well (and associated microfluidic channels 18), respectively. Each subunit 28A-28C may have at least one vent (not shown), similar or identical to the cartridge 14 of Fig. 1. The subunits 28A-28C may be releasably securable, individually or as a single coherent unit, to the support device 12, e.g., via at least one locking element (not shown), e.g., the at least one locking element 22 shown in Fig. 1. The subunits 28A-28C may be configured to be releasably fixed to each other, e.g., via one or more fixing elements, e.g., one or more clips, prior to securing the subunits 28A-28C to the at least one support device 12 and / or by securing the subunits 28A-28C to the at least one support device 12.

[0100] The device 10 may be configured for use in analyzing and / or processing the at least one liquid sample, in particular while the at least one liquid sample is received and / or after the at least one liquid sample has been received within the at least one input well 16, in particular for use in molecular screening and / or polymerase chain reaction (PCR), preferably digital PCR, of the liquid sample.

[0101] As shown in Fig. 3, at least some of the microfluidic channels 18, preferably each microfluidic channel 18, may include a plurality of microchambers 32. Preferably, the microchambers 32 are arranged in series along the respective microfluidic channel 18. The microchambers 32 may be fluidically connected to the respective input well 16 via at least one inlet channel 34. The microchambers 32 may be fluidically connected to the respective vent or output well 20 via at least one outlet channel 36. The microchambers 32 may be arranged in groups or sub-circuits which are fluidly coupled together. The microchambers 32 may be arranged in multiple groups and the microchambers 32 in each group may be fluidly coupled together in series in a respective microfluidic channel 18 or segments of a microfluidic channel 18. Each group of microchambers 32 may be arranged to receive fluid flow in parallel with each other.

[0102] At least some of the microchambers 32, preferably each microchamber 32, may include at least one reaction chamber 40 configured to receive at least a portion of the liquid sample and house at least one reaction, preferably at least one polymerase chain reaction (PCR), of the liquid sample.

[0103] At least some of the microchambers 32, preferably each microchamber 32, may include at least one vent chamber 42 configured to vent at least one gas from the reaction chamber 40 as the liquid sample flows into and / or through the reaction chamber 40. The at least one vent chamber 42 may be configured as a downstream section of the respective microfluidic channel(s) 18 and / or as a separate, but fluidically connected / connectable, chamber.

[0104] The reaction chamber 40 may be configured to receive and hold a predefined volume of the sample from an upstream section of the respective microfluidic channel(s) 18 and the vent chamber 42 may be configured to vent gas from the reaction chamber 40 as the fluid sample flows into the reaction chamber 40. When the gas has been vented from at least the reaction chamber 40 and / or the reaction chamber 40 receives a predefined volume of fluid, the fluid sample flows through the vent chamber 42 and continues along the microfluidic channel(s) 18 to the next microchamber 32. In this manner, the reaction chamber 40 may receive fluid from an upstream segment of the microfluidic channel(s) 18 and the fluid passes through the vent chamber 42 to a downstream segment of the microfluidic channel(s) 18. Moreover, air residing in the microfluidic channel(s) 18 may be vented from the microfluidic channel(s) 18 by the advancing flow of the fluid sample along the microfluidic channel microfluidic channel(s) 18.

[0105] The device 10 may include at least activation mechanism 50 configured to allow and / or force, preferably by means of pressure, the sample fluid which is received in the at least one input well 16 to flow from the at least one input well 16 to the microfluidic channels 18, in particular into the reaction chambers 40 (see Fig. 4). For instance, the activation mechanism 50 may include one or more projections or protrusions 52 configured to be inserted, or at least further inserted, at least partially into the input wells 16. As described above, the device 10 may include at least one top seal 21 and / or at least one top barrier 21 which is applicable to a top of the at least one cartridge 14 such that the input well(s) 16 and the at least one vent 20 is at least temporarily and / or at least partially sealed and / or separated from the environment. The one or more projections or protrusions 52 may be configured to displace, e.g., push, at least a section of the at least one top seal 21 and / or at least one barrier 21 at least partially into the respective input well 16, or at least further into the respective input well 16. This may facilitate increasing a pressure into the input well 16 to urge or force the sample fluid which is received in the at least one input well 16 to flow from the at least one input well 16 to the microfluidic channels 18. The configuration described above regarding the activation mechanism is only meant to be an example. The activation mechanism may be configured differently than described above. For instance, the specific activation mechanism 50 described above may be omitted and / or replaced by a different activation mechanism.

[0106] Fig. 5 shows a kit 80 for handling at least one liquid sample which may include the at least one support device 12 and at least one first cartridge 14A including a first number of one or more input wells 16A and one or more microfluidic channels (not shown) which are fluidically connected to the first number of one or more input wells 16A. The kit 80 may also include at least one second cartridge 14B including a second number of one or more input wells 16B configured to receive the at least one liquid sample and one or more microfluidic channels (not shown) which are fluidically connected to the second number of one or more input wells 16B. The first number of the one or more input wells 16A may be different than the second number of the one or more input wells 16B. The at least one first cartridge 14A and the at least one second cartridge 14B may be removably securable to the at least one support device 12 sequentially and / or simultaneously, e.g., the at least one first cartridge 14A may be removable from the at least one support device 12 after use and the at least one second cartridge 14B may be removably securable to the at least one support device 12 thereafter, as indicated by the double-arrowed line in Fig. 5. The first cartridge 14A and the second cartridge 14B may be releasably securable to the support device 12, respectively, e.g., via at least one locking element (not shown), e.g., the at least one locking element 22 shown in Fig. 1.

Claims

CLAIMS1. A microfluidic device (10) for handling at least one liquid sample, the microfluidic device (10) including: at least one support device (12); and a plurality of cartridges (14) which each include at least one input well (16) configured to receive the at least one liquid sample and one or more microfluidic channels (18) which are fl uidica lly connected to the at least one input well (16); wherein the cartridges (14) are individually removably securable to the at least one support device (12) simultaneously; wherein the cartridges include at least one pressure sensitive cover configured to coverthe input wells along a top of the cartridges to seal the input wells from the environment.

2. The microfluidic device (10) according to claim 1, including a plurality of cartridges (14) which are individually removably securable to the at least one support device (12) sequentially.

3. The microfluidic device (10) according to claim 1 or 2, wherein at least a first cartridge of the plurality of cartridges includes a first number of input wells (16) configured to receive the at least one liquid sample and at least a second cartridge of the plurality of cartridges includes a second number of input wells (16) configured to receive the at least one liquid sample, wherein the first number is different than the second number.

4. The microfluidic device (10) according to any of the preceding claims, wherein the at least one support device (12) and / or the cartridges (14) include(s) at least one locking element (22) configured to lock the cartridges (14) in place relative to the at least one support device (12).

5. The microfluidic device (10) according to any of the preceding claims, wherein each cartridge (14) includes a plurality of the at least one input well (16), the plurality of input wells (16) preferably being arranged in at least one array.

6. The microfluidic device (10) according to claim 5, wherein the plurality of input wells (16) are defined in a plurality of subunits (28A-28C) of at least one of the cartridges (14) which are assemblable to a single coherent unit.

7. The microfluidic device (10) according to any of the preceding claims, wherein each cartridge of the plurality of cartridges includes at least s input wells, preferably at least 6 input wells, preferably at least 8 input wells, preferably at least 10 input wells, preferably at least 16 input wells, preferably at least 20 input wells, preferably at least 24 input wells.

8. The microfluidic device (10) according to any of the preceding claims, wherein at least one of the cartridges (14) includes a plurality of components (28A-28C) which are assemblable to a single coherent unit.

9. The microfluidic device (10) according to any of claims 1 to 8, wherein each cartridge (14) is monolithically and / or integrally formed.

10. The microfluidic device (10) according to any of the preceding claims, wherein the microfluidic device (10) is configured for use in analyzing and / or processing the at least one liquid sample, in particular while the at least one liquid sample is received and / or afterthe at least one liquid sample has been received within the at least one input well (16), in particular for use in molecular screening and / or polymerase chain reaction (PCR), preferably digital PCR, of the liquid sample.

11. The microfluidic device (10) according to any of the preceding claims, wherein the at least one support device (12) is configured to receive the cartridges (14) having one or more variable dimensions and / or a variable number of the at least one input well (16), preferably when the at least one support device (12) is configured to receive the cartridges (14) having any number of the at least one input well (16) from I to 96, more preferably from 8 to 96, more preferably from 8 to 24.

12. The microfluidic device (10) according to any of the preceding claims, wherein the at least one input well (16) includes at least one inlet cavity (17) which is fluidically coupled to the one or more microfluidic channels (18), preferably wherein the microfluidic channels (18) extend substantially parallel to each other, preferably wherein each microfluidic channel (18) includes a plurality of microchambers (32), preferably wherein the microchambers (32) are arranged in series along the respective microfluidic channel (18).

13. The microfluidic device (10) according to claim 12, wherein each microchamber (32) includes at least one reaction chamber (40), which is configured to receive at least a portion of the liquid sample and house at least one reaction, preferably at least one polymerase chain reaction (PCR), of the liquid sample, and at least one vent chamber (42) configured to vent at least one gas from the reaction chamber (40) as the liquid sample flows into and / or through the reaction chamber (40).

14. The microfluidic device (10) according to any of the preceding claims, further including at least activation mechanism (50) configured to allow and / or force, preferably by means of pressure, the sample fluid which is received in the at least one input well (16) to flow from the at least one input well (16) to the microfluidic channels (18).

15. The device according to any of the preceding claims, wherein the at least one support device and / or the cartridges include(s) at least one alignment device configured to algin, or at least aid in aligning, the cartridges relative to the at least one support device.

16. The device according to any of the preceding claims, wherein the cartridges include at least one pressure sensitive cover configured to cover at least a section of the cartridges, preferably wherein the at least one pressure sensitive cover is configured to cover at least a section of the at least one input well, preferably along a bottom of the cartridges.

17. The device according to any of the preceding claims, wherein the at least one support device is made of a non-plastic material, preferably of metal.

18. The device according to any of the preceding claims, wherein each cartridge includes a plurality of cavities fluidically connected to the input wells, and wherein each cartridge further includes at least one separating element configured to selectively fluidically separate the plurality of cavities from each other.

19. The device according to claim 18, wherein the at least one separating element is configured to be manipulatable, preferably by heat and / or pressure, to selectively fluidically separate the plurality of cavities from each other, and optionally to selectively fluidically reconnect the plurality of cavities.

20. A kit (80) for handling at least one liquid sample, including: at least one support device (12);at least one first cartridge (14A) including a first number of one or more input wells (16A) configured to receive the at least one liquid sample and one or more microfluidic channels (18) which are fl uidica lly connected to the first number of one or more input wells (16A), wherein the at least one first cartridge (14A) includes at least one pressure sensitive cover configured to cover the one or more input wells (16A) along a top of the at least one first cartridge (14A) to seal the one or more input wells (16A) from the environment; and at least one second cartridge (14B) including a second number of one or more input wells (16B) configured to receive the at least one liquid sample and one or more microfluidic channels (18) which are fluidically connected to the second number of one or more input wells (16B), wherein the at least one second cartridge (14B) includes at least one pressure sensitive cover configured to cover the one or more input wells (16B) along a top of the at least one second cartridge (14B) to seal the one or more input wells (16B) from the environment; wherein the first number of the one or more input wells (16A) is different than the second number of the one or more input wells (16B); and wherein the at least one first cartridge (14A) and the at least one second cartridge (14B) are removably securable to the at least one support device (12) sequentially.

21. A method for analyzing at least one liquid sample, the method including: securing at least one first cartridge (14A) to a support device (12), the at least one first cartridge (14A) including at least one first input well (16A) and one or more first microfluidic channels (18) which are fluidically connected to the at least one first input well (16A); placing the at least one liquid sample in the at least one first input well (16A) of the at least one first cartridge (14A); applying at least one pressure sensitive cover to the at least one first cartridge (14A) to cover the at least one first input well (16A) along a top of the at least one first cartridge (14A) to seal the at least one first input well (16A) from the environment; performing at least one analysis of the at least one liquid sample in the at least one first cartridge (14A); removing the at least one first cartridge (14A) from the support device (12); securing at least one second cartridge (14B) to the support device (12), the at least one second cartridge (14B) including at least one second input well (16B) and one or more second microfluidic channels (18) which are fluidically connected to the at least one second input well (16B); placing the at least one liquid sample in the at least one second input well (16B)of the at least one second cartridge (14B); applying at least one pressure sensitive coverto the at least one second cartridge (14B) to cover the at least one second input well (16B) along a top of the at least one second cartridge (14B) to seal the at least one second input well (16B) from the environment; performing an analysis of the at least one liquid sample in the at least one second cartridge (14B), wherein the at least one first cartridge (14A) includes a first number of the at least one first input well (16A) and the at least one second cartridge (14B) includes a second number of the at least one second input well (16B), wherein the first number of the at least one first input well (16A) is different than the second number of the at least one second input well (16B).

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