L-shaped cartridge
The L-shaped base surface of the lab-on-chip cartridge addresses manufacturing, storage, and handling challenges, enabling efficient and cost-effective microfluidic processing and improved compatibility with existing systems.
Patent Information
- Application Number
- JP2023562783
- Authority / Receiving Office
- JP · JP
- Patent Type
- Patents
- Current Assignee / Owner
- Priority Date
- 2021-04-13
- Filing Date
- 2022-03-04
- Publication Date
- 2025-04-28
- Estimated Expiration
- 2042-03-04
AI Technical Summary
Existing lab-on-chip cartridges have rectangular base surfaces that complicate manufacturing, storage, and handling, and do not efficiently utilize gravity for microfluidic processing.
The cartridge features an L-shaped base surface, allowing for efficient manufacturing, compact storage, and utilization of gravity for fluid transport in microfluidic devices, with protrusions that facilitate engagement and handling.
The L-shaped design enables cost-effective, efficient, and compact manufacturing and storage, while allowing for effective gravity-based microfluidic processing and improved handling and compatibility with existing processing units.
Smart Images

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Abstract
Description
[Technical field]
[0001] Background technology Microfluidic analytical systems (so-called Lab-on-Chips, LoCs for short) allow automated, reliable, rapid, compact and inexpensive processing of patient samples for medical diagnostics. By combining several tasks for controlled fluid manipulation, complex molecular diagnostic test sequences can be performed on a Lab-on-Chip cartridge, where a passive cartridge is often moved via a processing unit. For example, DE 102016222075 A1 and DE 102016222072 A1 each describe microfluidic systems with a cartridge containing a biological sample and a processing unit for processing the sample in the cartridge, for example to detect pathogens in the sample.
[0002] In this case, the lab-on-a-chip cartridge may be inexpensively manufactured from polymers using mass production methods such as injection molding, die cutting or laser transmission welding.
[0003] Depending on the selected application, the complexity of the molecular diagnostic test sequence may vary. The demands placed on the lab-on-a-chip cartridges are correspondingly different for each application. Besides providing particularly universal cartridges for a particularly wide range of applications, it is conceivable to provide particularly inexpensive cartridges, which include a range of applications that are optimized and adapted to the requirements. In this case, a particularly advantageous configuration of such a cartridge is at issue.
[0004] Disclosure of the Invention Advantages of the invention SUMMARY OF THE DISCLOSURE In light of this background, the present invention is directed to a cartridge in which a base surface of the cartridge has an L-shape.
[0005] This cartridge may in particular refer to a microfluidic cartridge of a type and use based on the cartridge described in the abovementioned DE 102016222075 A1 or DE 102016222072 A1 and shown in Community Design 3459379, in which the cartridge according to the invention has an L-shaped base as opposed to a rectangular base. In particular, the cartridge according to the invention may also be formed as part of a microfluidic system for the (partially) automated performance of microfluidic processes for amplifying and / or analyzing biological quantities, in particular for amplifying and detecting (parts of) nucleic acids, for example for detecting pathogens.
[0006] The base surface may in particular be a surface of the cartridge, in particular the lower surface, for example, but not necessarily, the bottom plate in the case of a cartridge with a plate-like or layer-like structure. In particular, the base surface may be the maximum extension of the cartridge in a plane, in particular in a plane in which the area or length covered by the cartridge is maximum. Alternatively, the base surface may be a cross-section of the cartridge, in particular in a plane in which the cartridge has the maximum area and / or maximum length as described above.
[0007] L-shaped may in particular mean that the shape of the base surface is based on the shape of a bold capital letter L. In this case, the base surface may preferably resemble a bold L, in which the horizontal line of the L is thicker than the vertical line of the L, preferably 1.1 to 2.5 times thicker, very preferably 1.5 to 2.1 times thicker, for example 1.9 times thicker, so that the base surface resembles a bold L with a shortened vertical line. The two lines may hereinafter be referred to as the arms of the letter L or the arms of the base surface. That is to say, preferably, the base surface of the cartridge has an approximately L-shaped shape, in which the width of the part of the base surface corresponding to the vertical line of the L may be significantly larger than the width of the part of the base surface corresponding to the horizontal line of the L. L-shaped may also mean, in particular, a mirror image letter L in the vertical direction, so that the horizontal line of the letter runs from the vertical line towards the left instead of the right.
[0008] L-shaped may preferably mean that the cartridge has a base surface based on a rectangle, whereby one corner area of the rectangle is missing, so that the cartridge can be arranged with respect to a second cartridge with the same base surface such that a protrusion of the base surface of one cartridge engages in the missing corner area of the base surface of the other cartridge. In this case, one or more corners of the base surface may be rounded, whereby the base surface is based on a rectangle with the missing corner area and the rounded corner area accordingly. The missing corner area may preferably be based on or correspond to the shape of a square, rectangle or trapezoid. In the case of a trapezoid, preferably one leg of the trapezoid, which corresponds to a part of the outer edge of the base surface, is respectively at right angles to the base of the trapezoid, so that the trapezoid has only one side that is not at right angles to the other adjacent sides. That is, based on this missing corner area and the resulting protrusion, the base surface of the cartridge preferably has a (approximately) L-shape. In other words, the base surface is preferably based on a rectangle, where one corner area of the rectangle is missing, so that the area remaining based on the missing corner area (i.e. the above-mentioned protrusion) can engage in the missing corner area of a second cartridge with the same base surface. The protrusion and the missing corner area can therefore preferably have the same or at least similar dimensions or shapes, in particular the area of the protrusion and the area of the missing corner area can have the same or similar dimensions or shapes. Approximate dimensions can mean in one advantageous configuration that the area of the protrusion and the area of the missing corner area are similar in a geometrical sense, i.e. can be transferred to one another by an approximate expression. Close dimensions may further preferably mean that the area of the protrusions is smaller than the area of the missing corner regions, such that when two cartridges with identical protrusions are placed in opposite orientations, each protrusion will engage within the missing corner region of the other cartridge, with the outer edges of each cartridge aligned along a common alignment line and with gaps left between each protrusion.In this case, the area of the protrusion may be, for example, 1 to 10% or 1 to 5% smaller than the area of the missing corner region.
[0009] The present invention advantageously provides a cartridge which, on the one hand, can be manufactured in a significantly reduced time saving manner and can be stored and transported compactly, and on the other hand, enables advantageous microfluidic processing of sample liquids in a microfluidic device based on a gravity-based process.
[0010] The inventive configuration of the base surface allows for a particularly advantageous 2-in-1 production, in particular because exactly two cartridges can be oriented opposite one another and in mutual engagement, which allows for parallel production in a particularly small area, which allows for a particularly inexpensive and efficient production of L-shaped cartridges.
[0011] In particular, two cartridges or semi-finished products oriented opposite to one another can be processed on a surface of one workpiece support which corresponds to the surface area of the second cartridge or semi-finished product for producing the second cartridge, in particular of rectangular shape, in this way advantageously one existing production line can be variably used for producing at least two different types of cartridges without more significant adaptations.
[0012] Moreover, due to the configuration of the cartridge according to the invention - when each pair of cartridges or each pair of semi-finished products for producing cartridges with a base according to the invention are arranged opposite each other - it is also possible to store and transport a large number of cartridges or semi-finished products for producing cartridges in a particularly space-saving and compact manner. Furthermore, the space required for the autoclave of the cartridges or semi-finished products can be significantly reduced.
[0013] Furthermore, particularly advantageously, the cartridge according to the invention, and in particular the base surface of the cartridge, has a high aspect ratio, despite the reduced compact size compared to known cartridges. By maintaining a relatively long length of the cartridge, the earth's gravity can be utilized for the transport of fluid along the entire length, when the cartridge is tilted accordingly in a gravitational field. In other words, advantageously, gravity-based functions, such as gravity-based liquid collection at the lower end of the liquid reagent front chamber or the evacuation of gas bubbles due to buoyancy forces acting on the gas bubbles in the microfluidic chamber, can be utilized particularly advantageously.
[0014] In particular, this means that in gravity-based microfluidic processes there are no significant technical disadvantages compared to, for example, rectangularly shaped cartridges that are larger in area, with a comparable vertical spatial extent. On the other hand, due to the reduced material requirements, the cartridge according to the invention is particularly resource-saving and sustainable, since the amount of waste generated when discarded is reduced compared to completely rectangularly shaped cartridges.
[0015] Additionally, the retained length of the base surface and associated protrusions aid in the backward compatibility of the cartridges of the present invention in processing equipment configured to process cartridges with the same or similar length.
[0016] Furthermore, the invention provides a particularly preferred form of cartridge for realizing a microfluidic network within the cartridge, in which the microfluidic network comprises, for example, fluid micropassages and pneumatic micropassages, further active microfluidic elements such as valves and pump chambers which can be actuated via the pneumatic micropassages, and pneumatic interfaces for controlling the active microfluidic elements, in particular located in parts of the cartridge which are particularly extended in the horizontal direction.
[0017] The L-shape of the cartridge and in particular the associated protrusion also has the advantage that the user has multiple means for touching and gripping the cartridge in various ways. Depending on the actual size situation, the user can grip the cartridge at the thinner protrusion in the case of a relatively large configuration and roughly at the thicker end in the case of a small configuration. In this way, the L-shape of the cartridge allows a particularly simple, secure and comfortable handling by the user, for example when introducing a sample into the cartridge or when introducing the cartridge into a processing unit.
[0018] In one particularly preferred refinement of the invention, the projection has at least partially a tapered width. Such a tapered width may in particular be realized by two longitudinal sides of the projection, whereby a first longitudinal side and a second longitudinal side run along the projection converging towards each other. Such a taper can significantly facilitate the handling of the cartridge for the user, since different widths are provided for different sizes of hands. Furthermore, two cartridges with the same base surface can be more simply arranged compactly to engage with each other in opposite orientations as described above. In other words, one of the two arms of the cartridge converges at a predefined angle, whereby the cross section of this arm decreases starting from the start of the second arm towards the end edge of this arm of the cartridge.
[0019] The (edge of) one longitudinal side and the (edge of) one transverse side of the base surface may preferably lie at an angle greater than 90 degrees, i.e. at an obtuse angle to each other, so that the protrusion can have, at least in part, a tapered width, as described above.
[0020] In one particularly preferred refinement of the invention, the protrusion comprises a second protrusion. The second protrusion is preferably smaller than the first protrusion and is preferably arranged in front of the first protrusion, whereby the second protrusion extends the length of the cartridge. Such a second protrusion has the advantage that when the cartridge is accommodated in the processing unit, the second protrusion can be used to activate an interaction with the processing unit. For example, the second protrusion can trigger a mechanical action in the processing unit. Alternatively or additionally, for correct accommodation in the processing unit, the second protrusion can advantageously be used as part of a fixing means or lock of the cartridge, for example by the second protrusion engaging (preferably in a form-fitting manner) in a recess or groove of the processing unit. Alternatively or additionally, the correct positioning of the cartridge in the processing unit can advantageously be confirmed via optical or contact detection of the second protrusion.
[0021] In one advantageous configuration, the ratio of the length of the first dimension of the cartridge to the length of the second dimension of the cartridge is between 1.4 and 2.0, preferably between 1.5 and 1.7, very preferably between 1.58 and 1.65, for example (approximately) the golden section ratio of 1.618. The first and second dimensions may in particular be parallel dimensions of the cartridge, in particular the length of the first arm (i.e. the length of the vertical line of the bold L) or the width of the second arm (i.e. the width of the horizontal line of the bold L).
[0022] As already mentioned above, in a preferred configuration of the invention, one or more corners of the cartridge, in particular one or more corners of the base surface, may be rounded. This has the advantage that the risk of injuries due to sharp edges during use of the cartridge is reduced. Furthermore, rounded corners can facilitate the introduction of the cartridge into the processing unit. Furthermore, rounded corners give the user a more comfortable sensation when handling the cartridge. Furthermore, mechanical forces that may occur, for example in the case of a collision of one corner of the cartridge with another object, can be better conducted inside the cartridge, reducing the risk of crack formation.
[0023] In one further particularly advantageous embodiment, the cartridge has an interface for processing in a processing unit, which may be formed as an analytical device. In this case, the interface may be arranged in the same position as a second cartridge, for example of rectangular shape, which may be processed in the same processing unit. In this way, the two types of cartridges can be particularly advantageously processed in the same processing unit or in the same analytical device.
[0024] The subject of the invention is also a device comprising a first cartridge according to the invention and a second cartridge with the same base surface, the two cartridges being connected to one another so that a protrusion of the base surface of one cartridge engages in the respective missing corner area of the base surface of the other cartridge. In particular, the second cartridge may also be a cartridge according to the invention. The two cartridges may preferably be connected via a connecting element, which is preferably connected to each of the protrusions of the cartridges. This device has the advantage that the two cartridges in each case can be used compactly, can be transported and stored particularly simply, and can only be separated from one another immediately before the specified use.
[0025] The subject of the invention is also a method for manufacturing the cartridge according to the invention. In a first step, two semi-finished products with an L-shaped base surface are arranged on a workpiece support. The semi-finished products can be L-shaped base plates of the cartridge, in particular made of plastic. The two semi-finished products are preferably arranged opposite each other so that they engage with each other as described above, facing in opposite directions. In this case, the two semi-finished products can be physically connected to each other, for example as a result of an injection molding process. In a second step, a parallel processing of the two semi-finished products is carried out, which includes equipping the semi-finished products with other parts. A parallel processing can mean in particular that the two semi-finished products are subjected to different manufacturing steps in the same step, preferably at the same time. In a third step of the method, the two semi-finished products are provided with one further semi-finished product each, and then in a fourth step, the two semi-finished products are individualized into two cartridges with an L-shaped basic shape. The provision of the semi-finished products can be carried out using mass production techniques, for example laser transmission welding. In this case, individualization can generally mean a spatial separation of the two cartridges, but can also mean a physical separation of parts of the two cartridges that are connected to one another via a common material, for example as a result of an injection molding process, i.e., due to the L-shape of the base surface, two cartridges according to the invention can be produced in parallel in a compact and time-saving manner.
[0026] Furthermore, the present invention relates to a method for processing cartridges according to the invention with a processing unit based on a processing unit for processing the cartridge at an angle, as disclosed, for example, in the abovementioned DE 102016222075 A1 and DE 102016222072 A1. Processing at an angle means that the cartridge is oriented parallel or at an angle to the direction of gravity, in particular during the routine processing by the processing unit. For this purpose, the processing unit can preferably have a receiving part for the cartridge and a fixing part that is vertical or at an angle to the gravitational field of the Earth, as described in the abovementioned DE 102016222075 A1 and DE 102016222072 A1. In this case, due to the L-shape of the cartridge, as mentioned above, the non-dissipating component of the gravitational field along the cartridge can be particularly advantageously utilized to transport the fluid in the cartridge and / or to operate or assist elements such as, for example, valves or pumps.
[0027] For the advantages of the method according to the invention, reference is also made to the corresponding advantages of the cartridge according to the invention described above. [Brief description of the drawings]
[0028] An embodiment of the invention is illustrated diagrammatically and explained in detail in the following description, in which like reference numerals are used for elements which act similarly and are shown in different figures, and repeated description of these elements is omitted. [Figure 1] 1 shows an embodiment of a cartridge according to the invention and a device according to the invention; [Diagram 2] 1 shows an embodiment of a cartridge according to the invention and a device according to the invention; [Diagram 3] FIG. 2 shows a flow chart of an embodiment of a manufacturing or processing method according to the present invention. [Figure 4] FIG. 2 shows a flow chart of an embodiment of a manufacturing or processing method according to the present invention.
[0029] EMBODIMENTS OF THE PRESENTINVENTION 1 shows a schematic view of the top of a cartridge 100 according to the invention in a first embodiment. The cartridge 100 has an L-shaped base surface 105, in this example the base plate 105 having the base surface 105, which thus corresponds to the bottom surface of the cartridge 100. A cover 106 with a rectangular top surface and rounded corners is attached to the base plate 105. Another membrane, plate or layer may be arranged between the base plate 105 and the cover 106 as part of the multi-part structure of the cartridge 100.
[0030] For purposes of nomenclature, the cartridge 100 and the base surface 105 may be virtually divided into a first, generally rectangular arm of length 110 and width 111 and a second, generally rectangular arm of length 120 and width 121 arranged transversely thereto, the first arm resembling the vertical lines of a bold capital letter L and the second arm resembling the horizontal lines of a bold capital letter L. In other words, the L-shaped cartridge 100 has a first vertical dimension 110 corresponding to the length of the first arm and a first horizontal dimension 120 corresponding to the length of the second arm. The cartridge 100 further has a second horizontal dimension 111 corresponding to the width of the first arm and a second vertical dimension 121 corresponding to the width of the second arm. That is, the base surface 105 of the cartridge 100 corresponds approximately to two rectangles (corresponding to the above-mentioned arms) that are perpendicular to each other and partially overlap, so that the base surface 105 has the shape of a bolded letter L or resembles the base surface of a "finger" of a tool. In other words, the base surface 105 corresponds approximately to the legs of two rectangles arranged at right angles. In this case, the part of the first arm that protrudes beyond the second arm is also referred to hereinafter as the protruding part 160 of the cartridge 100.
[0031] The shape of the base surface 105 may be considered to be based on a rectangle, where one corner area of the rectangle is missing, which in the embodiment shown in Fig. 1 corresponds approximately to a trapezoid adjacent to the projection 160, where the legs corresponding to the extension of the second vertical dimension 121 are positioned at an angle of 90 degrees to the two bases of the trapezoid, respectively.
[0032] As shown in Fig. 1, the first arm, in particular the protrusion 160, of the cartridge 100 may have a width 111 that tapers partially along the first vertical dimension 110. Such a taper may in particular be realised by an obtuse angle 114, i.e. an angle greater than 90 degrees, between two edges 112, 122 of the cartridge 100, where the first edge 112 defines the first arm, in particular the protrusion 160, relative to the first vertical dimension 110 and the second edge 122 defines the second arm relative to the first horizontal dimension 120. For example, the angle 114 may have a value between 90 and 135 degrees, preferably between 92 and 110 degrees, for example 98 degrees. Alternatively to the angle 114, the taper may be defined by an angle 115 between the first edge 112 and a line 113 parallel to the first vertical dimension 110, which angle may then have a value between 0.1 and 45 degrees, preferably between 2 and 20 degrees, for example 8 degrees. In particular the first arm of the cartridge 100 thus extends converging at a set angle 114 such that the width 111 of the part of the base surface 105 belonging to the first arm decreases starting from the start of the second arm, i.e. the width 111 of the protrusion 160, towards the end of the first arm of the cartridge.
[0033] 1, the protrusion 160 may have a second protrusion 170, which is preferably located in front of the first protrusion 160, in particular at an edge of the second horizontal dimension 111 of the first protrusion 160 or at an edge defining the width 111 of the first arm. The second protrusion 170 may be used, for example, to activate a certain function or to correctly orient the cartridge 100 when it is inserted into a processing unit.
[0034] The rectangle that is the basis of the shape of the base surface 105 is, for example, 20×10 square millimeters (mm 2 )~300×200mm 2 , preferably 50×20 mm 2 ~200×100mm 2 , for example 118 x 78 mm 2 The length 110 or the first vertical dimension 110 of the first arm is, for example, 20 millimeters (mm) to 300 mm, preferably 50 mm to 200 mm, for example 118 mm. The width 111 or the second horizontal dimension 111 of the first arm is, for example, 20 mm to 100 mm, preferably 35 mm to 75 mm, for example 40 mm. The length 120 or the first horizontal dimension 120 of the second arm is, for example, 20 mm to 150 mm, preferably 35 mm to 125 mm, for example 78 mm. The width 121 or the second vertical dimension 121 of the second arm is, for example, 20 mm to 150 mm, preferably 35 mm to 125 mm, for example 73 mm. In the embodiment shown, the ratio of the first vertical dimension 110, for example 118 mm, to the second vertical dimension 121, for example 73 mm, corresponds approximately to 1.618 and thus to the golden section, which gives this embodiment of the cartridge 100 a particularly aesthetically pleasing appearance. In other embodiments, this ratio is for example between 1.4 and 2.0, preferably between 1.5 and 1.7, very preferably between 1.58 and 1.65, i.e. approximately 1.618. Similarly, the ratio of the first vertical dimension 110 to the first horizontal dimension 120 corresponds approximately to 1.4 and 2.0, preferably between 1.5 and 1.7, very preferably between 1.58 and 1.65, i.e. approximately 1.618.
[0035] As mentioned above, the cartridge 100 preferably has one or two sample supply chambers 131, 132, in particular for supplying biological samples. In this case, the covers of the sample supply chambers 131, 132 may form part of the cover 106 of the cartridge 100, which covers a given area of the base surface 105, as shown in FIG. 1 and as described above. As further shown in FIG. 1, the cartridge 100 has a pneumatic interface 150, which includes, for example, 20 pneumatic connection openings. In this case, the pneumatic interface 150 is realized, as shown, in particular in the area of the second arm between the cover 106 and the protrusion 160. Thus, the configuration of the first arm of the cartridge at a converging angle 115 is particularly advantageous for contact-connecting an active microfluidic element in this arm to the pneumatic interface 150 via a pneumatic passage.
[0036] Furthermore, the cartridge 100 preferably has one or more microfluidic chambers 141 connected via a microfluidic passage 146, in which, for example, amplification of fragments of nucleic acids, for example polymerase chain reaction, can take place. In this case, the chambers 141 may be visible on the top side of the cartridge 100 on the basis of a transparent material, as shown, so that the reaction proceeding in the chambers 141 can be observed and read. As shown, the chambers 141 may in particular be located in the protrusion 160. This has the advantage that the processing of the sample supplied via the sample supply chambers 131, 132 can take place between the sample supply chambers 131, 132 and the chambers 141 along the entire length 110 of the cartridge 100. That is, when the cartridge 100 is oriented obliquely or vertically in a gravitational field 50, such as the gravitational field of the Earth, the non-vanishing force components of the gravitational field 50 along the first vertical dimension 110, i.e. along the first arm, can advantageously be used to transport the sample and other reagents in the cartridge 100. The liquid for processing in the cartridge 100 may be, for example, an aqueous solution, such as a buffer solution, especially containing components of the sample material, as well as mineral oil, silicone oil or a fluorohydrocarbon.
[0037] 2 shows an alternative embodiment including two oppositely oriented cartridges 101, 102 according to the present invention. One or both cartridges 101, 102 may be an implementation of cartridge 100 shown in FIG.
[0038] As shown on the left side of FIG. 2, the two cartridges 101, 102 are oriented relative to one another so that the protrusions 160 of one cartridge 101, 102 engage the missing corner areas of the base surface of the other cartridge 101, 102, respectively, spaced apart by a relatively narrow gap 99 of a certain width. In other words, the two cartridges 101, 102 are oriented in opposite directions so that the second cartridge 102 is rotated 180 degrees relative to the first cartridge 101. In this case, the protrusions 160 may be formed in terms of their area slightly smaller than the area of the respective missing corner areas, so that a gap 99 remains at or between the protrusions 160, even though the two cartridges 101, 102 are arranged along a common alignment line that overlaps the edges of the vertical dimensions 110, 121. This arrangement embodies several advantages of the cartridge according to the invention. As shown, two cartridges 101, 102 according to the invention can be compactly arranged and supported. Furthermore, the dimensions of the cartridges 100, 101, 102 according to the invention are preferably formed such that the sum of the base surfaces of the cartridges 101, 102 arranged in this way, excluding the gap 99, corresponds to the base surface of a conventional rectangular cartridge 200 (shown on the right side of FIG. 2). As shown, in this case, the sum of the first vertical dimension 110, the width of the gap 99 and the second vertical dimension 121 corresponds to the vertical dimension 201 of the rectangular cartridge 200. Furthermore, the first horizontal dimension 120, i.e. the width of the cartridges 100, 101, 102 according to the invention, corresponds to the width 202 of the rectangular cartridge 200 in this example. In other words, the area of the base surface of the rectangular cartridge 200 corresponds to the length 120 of the second arm of the cartridges 100, 101, 102 according to the present invention multiplied by the sum of the length 110 of the first arm, the width of the gap 99 and the width 121 of the second arm.
[0039] The two cartridges 101, 102 may be preferably connected to each other via a connecting member 190, which may for example consist of the same material as the base plate or another layer of the cartridges, connecting both protrusions 160 of the cartridges 101, 102 across the gap 99. Thus, Fig. 2 also shows an embodiment of a device 300 according to the invention, in which the device 300 comprises a first cartridge 101 according to the invention and a second cartridge 102 with the same base surface, in which the two cartridges 101, 102 are connected to each other, whereby the protrusions 160 of the base surface of one cartridge 101, 102 engage in the missing corner area of the base surface of the other cartridge 102, 101, respectively.
[0040] FIG. 3 shows a flow chart of one embodiment of a manufacturing method 600 according to the present invention for manufacturing cartridges 100, 101, 102, for example, as shown in FIG. 1 or FIG.
[0041] In a first step 601 of the method 600, two L-shaped semi-finished products are arranged on a workpiece support. The semi-finished products may be, for example, plastic bottom plates of the cartridges 100, 101, 102, produced by an injection molding process. The semi-finished products may in particular be arranged similarly and oppositely to one another, i.e. the second semi-finished product is rotated 180 degrees with respect to the first semi-finished product. The arrangement of the semi-finished products may, for example, already be defined during the production of the semi-finished products. In one particular embodiment, both semi-finished products are mechanically connected to one another, for example as a result of a common injection molding process, so that both semi-finished products can be handled as one integral part. This may be advantageous in order to enable an efficient and inexpensive production of the cartridge 100 as automated as possible.
[0042] In a second step 602 of the method 600, the semi-finished products arranged on the workpiece support are processed in parallel. For example, the semi-finished products are transported to a special production station and / or the semi-finished products are equipped with additional parts and / or combined with other semi-finished products. The equipment of the additional parts can be performed, for example, by fitting, inserting or plugging and / or locking. The combination with other semi-finished products can be performed, for example, by placing the other semi-finished products on the semi-finished products located on the workpiece support. As already explained, in one particularly advantageous embodiment, the semi-finished products or the other parts are mechanically connected to one another as a single, integrated part, so that a particularly simple handling can be achieved. In one further advantageous embodiment, the workpiece support has an adjustment pin, which engages in an adjustment through-hole of the semi-finished products, so that a defined positioning of the semi-finished products on the workpiece support as well as a defined positioning of the semi-finished products relative to one another can be achieved. The defined positioning of the semi-finished products relative to one another serves, for example, to prepare for a subsequent feeding step.
[0043] In a third step 603 of the method 600, two further semi-finished products are provided on the two semi-finished products, each located on a workpiece support. The provision of the semi-finished products can preferably be performed in parallel, so that a particularly high throughput can be achieved during production. The provision of the semi-finished products can be performed using mass production techniques, such as laser transmission welding, for example.
[0044] An optional fourth step 604 of the method 600 involves repeating one or more of the preceding steps, such as performing the positioning step 601, the processing step 602, and the providing step 603 multiple times to produce a multi-layer cartridge 100, 101, 102 having multiple interlocking parts and at least one cover member thereon.
[0045] In a fifth step 605 of the method 600, the cartridges 100, 101, 102, possibly formed from mechanically assembled semi-finished products or parts, are singulated, thereby obtaining two separate cartridges 100, 101, 102. The singulation can be performed, for example, by mechanical breaking along a target break point or by another type of separation method. In other embodiments of the method 600 according to the invention, individual steps can be omitted or repeated or exchanged in order with other steps.
[0046] In this case, the semi-finished products and other parts of the cartridges 100, 101, 102 may preferably comprise a polymer, such as polycarbonate (PC), polystyrene (PS), styrene-acrylonitrile copolymer (SAN), polypropylene (PP), polyethylene (PE), cycloolefin copolymer (COP, COC), polymethylmethacrylate (PMMA), polydimethylsiloxane (PDMS) or a thermoplastic elastomer (TPE), such as polyurethane (TPU) or styrene block copolymer (TPS), and may be manufactured according to the method 600 according to the invention by mass production methods, such as injection molding, hot forming, punching or laser transmission welding.
[0047] In Fig. 4, a flow chart of one embodiment of a method 700 according to the invention for processing a cartridge 100, 101, 102 according to the invention, for example the cartridge 100, 101, 102 described in the above-mentioned embodiments, is shown. In a first step 701 of the method 700, the cartridge 100 is introduced into a processing unit, in particular an analysis device for analyzing a biological sample that can be processed in the cartridge 100, 101, 102. For example, this can be the detection of a pathogen in a body fluid (blood, sputum or a collection) by means of a polymerase chain reaction or isothermal amplification for amplifying the nucleic acid of the pathogen, as described above. In this case, the sample can comprise a liquid, in particular an aqueous solution obtained, for example, from a biological material, for example a material of human origin, such as a body fluid, collection, secretion, sputum or tissue sample. In the sample, for example medically, clinically, diagnostically or therapeutically relevant species, for example bacteria, viruses, cells, circulating tumor cells, cell-free DNA, proteins or another biomarker or a component of an object, in particular as described above, are present. For example, the sample liquid is a master mix or a component thereof for carrying out at least one amplification reaction, for example as described above.
[0048] The cartridges 100, 101, 102 are preferably oriented for processing at an angle relative to the Earth's gravitational field, thereby enabling gravity-based microfluidic processing of liquids within the cartridges 100, 101, 102. Such an orientation of the cartridges 100, 101, 102 allows, for example, liberated liquid reagents to be collected at the lower end of the ante-chamber from where they can be further processed within the microfluidic network of the cartridges 100, 101, 102. For example, in this case, the cartridges 100, 101, 102 are oriented such that the angle between the normal to the plane of the base surface and the direction of the gravitational field 50 is between 0 and 80 degrees, preferably between 10 and 80 degrees, for example 30 degrees.
[0049] In a second step 702 of the method 700, the L-shaped cartridges 100, 101, 102 are processed in a processing unit, whereby, for example, the samples in the L-shaped cartridges 100, 101, 102 are processed as described above.
[0050] A third step 703 of the method 700 involves removing the cartridges 100, 101, 102 from the processing unit, and preferably additionally outputting the analytical results.
Claims
1. A microfluidic cartridge (100, 101, 102), wherein a base surface (105) of the microfluidic cartridge (100, 101, 102) has an L-shape; The base surface (105) is rectangular in shape with one corner region of the rectangle missing, such that a first microfluidic cartridge (101) can be positioned relative to a second microfluidic cartridge (102) having the same base surface (105) such that a protrusion (160) on the base surface (105) of one microfluidic cartridge (100, 101, 102) engages within the missing corner region of the base surface (105) of the other microfluidic cartridge (100, 101, 102).
2. 2. The microfluidic cartridge (100, 101, 102) of claim 1, wherein the protrusion (160) has a second protrusion (170), the second protrusion (170) being preferably disposed in front of the first protrusion (160).
3. A microfluidic cartridge (100, 101, 102) as claimed in claim 1 or 2, wherein the protrusion (160) has at least partially a tapered width (111), in particular the first longitudinal side (110) and the second longitudinal side (112) extend converging towards each other along the protrusion (160).
4. The microfluidic cartridge (100, 101, 102) of any one of claims 1 to 3, wherein the protrusion (160) is formed such that an area of the protrusion (160) and an area of the missing corner region have the same or similar dimensions.
5. 5. The microfluidic cartridge (100, 101, 102) according to any one of claims 1 to 4, wherein one vertical side (112) and one horizontal side (122) of the base surface (105) are positioned relative to each other at an angle (114) greater than 90 degrees.
6. The microfluidic cartridge (100, 101, 102) according to any one of claims 1 to 5, wherein the ratio of the length of the first dimension (110) to the length of the second dimension (121) is between 1.4 and 2.
0.
7. The microfluidic cartridge (100, 101, 102) according to any one of the preceding claims, wherein one or more corners of the microfluidic cartridge (100, 101, 102) are rounded.
8. 8. A device (300) comprising a first microfluidic cartridge (101) and a second microfluidic cartridge (102) having the same base surface (105) as claimed in any one of claims 1 to 7, wherein the two microfluidic cartridges (101, 102) are coupled to each other such that a protrusion (160) on the base surface (105) of one microfluidic cartridge (101, 102) engages in a missing corner area of the base surface (105) of the other microfluidic cartridge (101, 102), respectively.
9. A method (600) for manufacturing a microfluidic cartridge (100, 101, 102) according to any one of claims 1 to 7, comprising the steps of: A step (601) of placing two workpieces having an L-shaped base surface (105) on one work support; A step (602) of parallel processing of the two workpieces, including equipping the workpieces with different parts; Providing (603) each of the two semi-finished products with a separate semi-finished product; Singulating (605) the two workpieces into two microfluidic cartridges (100, 101, 102) having an L-shaped base surface (105); The method (600).
10. A method (700) for processing a microfluidic cartridge (100, 101, 102) according to any one of claims 1 to 7, wherein the microfluidic cartridge (100, 101, 102) is processed tilted in a processing unit.
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