Centrifugal microfluidic biochip

Abstract

The invention relates to a centrifugal microfluidic biochip (10) with a fluidic system formed from a plurality of chambers and / or conduits with an opening (20) formed for introducing a biological sample into the fluidic system, characterised by fastening means (40) designed for fixing a sample carrier (30), which has a biological sample and which covers the opening (20), to the centrifugal microfluidic biochip (10).

Description

[0001] CENTRIFUGAL MICROFLUIDIC BIOCHIP

[0002] The invention relates to a centrifugal microfluidic biochip with a fluidic system formed from a plurality of chambers and / or lines with an opening designed for introducing a biological sample into the fluidic system.

[0003] Centrifugal microfluidic biochips, also known as centrifugal microfluidic biodisks or centrifugal microfluidic test cartridges, are used in medical diagnostics as part of lab-on-a-chip or lab-on-a-disk systems. Such systems are known, for example, from DE 10 2013 203 293 B4, EP 2 416 B1, CN 109765391 A, CN 209680127 U, and CN 209772148 U.

[0004] These centrifugal microfluidic biochips feature a (micro)fluidic system into which a sample is introduced. This sample can be automatically processed according to a predetermined protocol using an analysis device that functions, among other things, as a centrifuge with a rotation device adapted to the biodisk. Depending on the research question to be addressed, appropriate reagents are stored on the centrifugal microfluidic biochip. These reagents can be stored in liquid form in stick packs (also called sachets or sealed pouches), air-dried, or freeze-dried (lyophilized).

[0005] Using the well-known centrifugal microfluidic biochips, it is fundamentally possible to automate labor-intensive and error-prone laboratory routines and perform various workflows, from sample preparation to data analysis, in a single step. In particular, these systems enable significantly faster and more accurate analysis of patient samples and tailored therapy.

[0006] For example, EP 3 247 497 B1 discloses a centrifugal microfluidic biochip equipped with the features mentioned above, which can accommodate a sampling instrument, particularly designed as a swab, and analyze a biological sample adhering to it. Although this centrifugal microfluidic biochip may be advantageous for processing some biological samples, the fundamental problem with taking samples from biological surfaces, which can primarily be associated with the imprint preparations used in dermatology and oncology to enable rapid and cost-effective diagnostics, is that processing these samples in conjunction with a centrifugal microfluidic biochip entails increased manual effort.The sample taken, which is taken in particular by means of an adhesive strip applied to the area to be examined, for example a lesion, an ulcerated skin change or a tumor section or an infectious lesion, must first be further prepared, in particular crushed, for processing by a centrifugal microfluidic biochip before it can be introduced into a sample chamber of a centrifugal microfluidic biochip.

[0007] This additional preparatory activity increases the risk of contamination on the one hand, and on the other hand there is the problem that the shredded adhesive strips within the fluidic system tend to accumulate on each other or on the walls of the fluidic system, so that the biological samples adhering to the adhesive strip are not accessible for analysis.

[0008] The object of the invention is therefore to provide a solution to the above problem in such a way that biological samples adhering in particular to flat sample carriers can be completely analyzed by means of a centrifugal microfluidic biochip without contaminating the biological sample.

[0009] This object is achieved according to the invention by the centrifugal microfluidic biochip having the features of claim 1, the analysis system having the features of claim 9, and the method having the features of claim 12. The subclaims each represent advantageous embodiments of the invention.

[0010] The basic idea of ​​the invention is not to insert the sample carrier of an imprint sample through an opening into a chamber of the fluidic system of a centrifugal microfluidic biochip, but to arrange the sample carrier with the side containing the biological sample on the outside of the centrifugal microfluidic biochip in such a way that the sample carrier at least partially covers the opening and the side of the sample carrier containing the biological sample can be flushed by fluids guided along the opening in the fluidic system. The invention is particularly suitable for flat sample carriers, especially adhesive strips. These are preferably designed to completely cover and span the opening in the fluidic system, with the sample carrier being fixed and secured to the centrifugal microfluidic biochip by a fastening means.The fastening device can be specially designed as a closure, so that the sample carrier is not only secured but also protected from external contamination. At the same time, the fluidic system is sealed and the leakage of chemical substances from the centrifugal microfluidic biochip is prevented. After processing, the centrifugal microfluidic biochip can be disposed of accordingly in compliance with hygienic standards, resulting in an overall safe and efficient system.

[0011] Because the opening in the Centrifugal Microfluidic Biochip defines a predetermined area in relation to the sample carrier, it is also possible to relate the analysis to the area determined by the opening, so that not only qualitative but also quantitative statements regarding the nature of an imprint are possible.

[0012] According to the invention, a centrifugal microfluidic biochip, which can also be referred to as a centrifugal microfluidic bio-disk or centrifugal microfluidic test cartridge, is proposed, comprising a fluidic system formed from a plurality of chambers and / or lines, with an opening configured for introducing a biological sample into the fluidic system, which comprises a fastening means configured for securing a sample carrier containing a biological sample and covering the opening to the centrifugal microfluidic biochip. The fastening means is designed, in particular, as a clamp that secures the sample carrier to the centrifugal microfluidic biochip. The sample carrier is designed such that it at least partially covers the opening.Particularly preferably, the sample carrier has a surface area that is larger than the surface area formed by the opening, wherein the contour of the opening can be completely overlaid by the contour of the sample carrier surface. In other words, the sample carrier can preferably completely cover the opening, so that the opening of the centrifugal microfluidic biochip covers that surface area and thus the amount of biological sample adhering to the sample carrier, for example, the (maximum) amount of cells or - -.

[0013] The amount of pathogen that can be processed using the reagents stored in the fluidic system.

[0014] The fastening means is preferably designed to assume a first position releasing the opening and a second position closing the opening itself or by means of the sample carrier.

[0015] The fastening means is not necessarily to be understood as a component permanently connected to the centrifugal microfluidic biochip, but according to one embodiment, can be detachably connected to the centrifugal microfluidic biochip. Thus, it is conceivable that the fastening means can be used repeatedly with a plurality of centrifugal microfluidic biochips, allowing this design to be used in a resource-efficient manner.

[0016] Specifically, the fastening means is designed as a frame that can be inserted into a groove arranged around the opening. In particular, the frame can be designed as a punch that punches out the section to be analyzed from the sample carrier and simultaneously fixes it to the centrifugal microfluidic biochip. The frame can be rectangular, but is preferably a ring that is specifically arranged concentrically with the opening.

[0017] The opening can preferably be arranged in a recess, with the wall section of the centrifugal microfluidic biochip surrounding the opening forming a support surface for edge sections of the sample carrier. Specifically, the geometric shape of the recess can be identical to the geometric shape of the sample carrier.

[0018] In any case, it is particularly preferred that the fastening means is a closure that closes the opening in a fluid-tight manner, for example in the form of a cap or a lid, wherein the closure most preferably has an annular section designed as a flange, which, according to the aforementioned example, can be inserted into a groove arranged around the opening, optionally with trimming of the sample carrier. On the one hand, the closure ensures the fixation of the sample carrier to the centrifugal microfluidic biochip due to its clamping force. On the other hand, the risk of contamination is reduced and the centrifugal microfluidic biochip is simultaneously protected from liquid leakage. In particular, the closure lies fully against the sample carrier and creates a secure seal against the fluidic system. Locking means can preferably be provided to secure the fastening means to the centrifugal microfluidic biochip.

[0019] A very convenient design is achieved when a hinge is provided for pivoting the fastening device relative to the centrifugal microfluidic biochip. This design enables simple and precise attachment of the fastening device to the centrifugal microfluidic biochip, and thus of the sample carrier to the centrifugal microfluidic biochip.

[0020] The centrifugal microfluidic biochip is preferably designed as a disc having two base surfaces and a lateral surface arranged between them, wherein the opening is particularly preferably arranged in one of the base surfaces of the centrifugal microfluidic biochip designed as a disc. The opening in one of the base surfaces enables easy handling of the flat disc by placing the disc on a work surface and loading the base surface facing away from the work surface with the sample carrier from above. After fixing the sample carrier to the centrifugal microfluidic biochip and closing the opening by the sample carrier itself or by the fastening means designed as a fluid-tight closure, the centrifugal microfluidic biochip can be turned over so that the sample forms a bottom section of the fluidic system and can be easily flushed with fluid.In principle, an arrangement of the opening in the lateral surface is also conceivable, which would allow easy contact of the sample carrier with fluid during rotation.

[0021] Furthermore, a coordinated analysis system is proposed with a centrifugal microfluidic biochip designed according to the invention and a sample carrier designed to receive a biological sample, wherein it is important to ensure that the sample carrier has a surface that completely covers the opening of the centrifugal microfluidic biochip.

[0022] The sample carrier is particularly flat and specifically designed as an adhesive strip, with the sample carrier particularly preferably comprising a layer arranged on a water-impermeable carrier layer, optionally containing an adhesive, for receiving a biological sample. The formation of a water-impermeable carrier layer enables the fastening means to be designed as a frame without the centrifugal microfluidic biochip having to be additionally protected against liquid leakage.

[0023] Finally, a method for analyzing a biological sample using a centrifugal microfluidic biochip or an analysis system designed according to the invention is proposed, wherein the centrifugal microfluidic biochip is configured to analyze the biological sample with respect to a predetermined question. The method according to the invention comprises the following steps:

[0024] - Providing a biological sample adhered to a sample carrier;

[0025] - Arranging the sample carrier on the Centrifugal Microfluidic Biochip in such a way that liquid passing the opening in the fluidic system can come into contact with the biological sample;

[0026] - Fixing the sample carrier to the Centrifugal Microfluidic Biochip using the fixing agent; and

[0027] - Processing the biological sample in a known manner with regard to a predetermined question.

[0028] Preferably, the processing comprises lysing the biological sample adhering to the sample carrier, with the lysis particularly preferably being carried out mechanically, chemically, enzymatically, and / or with the application of heat. In particular, the use of a lysis buffer ensures that the biological sample adhering to the sample carrier, in particular cells, is completely disrupted and accessible for analysis.

[0029] Alternatively, it may be provided that the processing comprises bringing the biological sample into contact with a reagent, wherein the change in the reagent, which provides information about properties of the biological sample, is analyzed in a manner known per se.

[0030] The invention will be explained in more detail below with reference to particularly preferred embodiments shown in the accompanying drawings. In the drawings: Fig. 1 shows a perspective view of a particularly preferred first

[0031] embodiment according to the invention; and

[0032] Fig. 2 is a sectional view of a particularly preferred second embodiment according to the invention in the region of the fastening means designed as a closure.

[0033] Fig. 1 shows a perspective view of a centrifugal microfluidic biochip according to the invention, albeit only schematically illustrated, with a particularly preferred design. The centrifugal microfluidic biochip 10 is designed as a disc having two base surfaces and a lateral surface arranged between them, wherein the opening 20 communicating with the fluidic system is arranged in one of the base surfaces of the centrifugal microfluidic biochip 10, which is designed as a disc.

[0034] The fastening means 40, which fixes a sample carrier (not shown) to the centrifugal microfluidic biochip 10, can be pivoted relative to the centrifugal microfluidic biochip 10 by means of a hinge. In particular, the fastening means 40 is designed as a lid and has an annular flange extending from the plane of the lid, which can be inserted into a groove arranged on the centrifugal microfluidic biochip 10. From the position exposing the opening 20, the fastening means 40 can thus be transferred into a position closing the opening 20, in which position not only is the sample carrier (not shown) fixed to the centrifugal microfluidic biochip 10, but the opening 20 can also be closed in a fluid-tight manner.

[0035] Finally, Fig. 2 shows a sectional view of a particularly preferred second embodiment according to the invention in the region of the fastening means designed as a closure.

[0036] In particular, Fig. 2 shows the process for attaching the sample carrier 30 to the centrifugal microfluidic biochip 10 in the region of the opening 20 configured to receive a biological sample. As previously described, the centrifugal microfluidic biochip 10 has a fluidic system accessible to biological samples through the opening 20. In the example shown, the opening 20 can be completely closed by the fastening means 40 acting as a closure. For this purpose, the fastening means 40 is connected to the centrifugal microfluidic biochip 10 via a hinge, as shown in Fig. 2A.

[0037] To process a biological sample, a flat sample carrier 30, on the side of which the biological sample adheres to the centrifugal microfluidic biochip 10 or the fluidic system of the centrifugal microfluidic biochip 10, is inserted into a recess in the base of the centrifugal microfluidic biochip 10. For this purpose, the wall surrounding the opening 20 to the fluidic system is designed as a support for the sample carrier 30, which rests with its edge sections on the support and otherwise completely spans the opening 20. The sample carrier 30 thus assumes the function of a wall closing the opening 20.

[0038] If the sample carrier is correctly positioned, as shown in Fig. 2B and Fig. 2C, the fastening means 40 acting as a closure can be folded onto the centrifugal microfluidic biochip 10, as shown in Fig. 2D, whereby the sample carrier 30 is clamped between the support of the centrifugal microfluidic biochip 10 and the fastening means 40 and is thereby fixed in its position.

[0039] Finally, Fig. 2E shows the centrifugal microfluidic biochip 10, in which the fluidic system is fluid-tightly closed by the fastening means 40 while fixing the sample carrier 30 spanning the opening, so that liquid 50 guided past the sample carrier 30 can come into contact with the sample adhering to the sample carrier 30 and can at least partially wash it off the sample carrier 30.

Claims

REQUIREMENTS 1. Centrifugal microfluidic biochip (10) comprising a fluidic system formed from a plurality of chambers and / or conduits, with an opening (20) configured for introducing a biological sample into the fluidic system, characterized by a fastening means (40) configured for fixing a sample carrier (30) containing a biological sample and covering the opening (20) to the centrifugal microfluidic biochip (10). Centrifugal microfluidic biochip (10) according to claim 1, characterized in that the fastening means (40) is configured to assume a first position releasing the opening (20) and a second position closing the opening (20) either directly or by means of the sample carrier (30).

3. Centrifugal microfluidic biochip (10) according to any one of the preceding claims, characterized in that the fastening means (40) is detachably connected to the centrifugal microfluidic biochip (10). Centrifugal microfluidic biochip (10) according to any one of the preceding claims, characterized in that the fastening means (40) is designed as a frame that can be inserted into a groove arranged around the opening (20).

5. Centrifugal Microfluidic Biochip (10) according to one of the preceding claims, characterized in that the fastening means (40) is a closure that seals the opening (20) in a fluid-tight manner. A centrifugal microfluidic biochip (10) according to any one of the preceding claims, characterized by a hinge provided for pivoting the fastening means (40) relative to the centrifugal microfluidic biochip (10). A centrifugal microfluidic biochip (10) according to any one of the preceding claims, characterized in that the centrifugal microfluidic biochip (10) is configured as a disk comprising two base surfaces and a lateral surface arranged between them. A centrifugal microfluidic biochip (10) according to claim 7, characterized in that the opening (20) is arranged in one of the base surfaces of the disk-configured centrifugal microfluidic biochip (10).An analysis system comprising a centrifugal microfluidic biochip (10) according to any one of the preceding claims and a sample carrier (30) configured to receive a biological sample, wherein the sample carrier (30) has a surface that completely covers the opening (20) of the centrifugal microfluidic biochip (10). An analysis system according to claim 9, characterized in that the sample carrier (30) is an adhesive strip. An analysis system according to one of claims 9 and 10, characterized in that the sample carrier (30) has a layer arranged on a water-impermeable substrate layer for receiving a biological sample. A method for analyzing a biological sample using a centrifugal microfluidic biochip (10). Microfluidic biochips (10) according to one of claims 1 to 8 or one Analysis system according to one of claims 9 to 11, wherein the centrifugal microfluidic biochip (10) is configured for the analysis of the biological sample with regard to a predetermined question, comprising the steps: - Providing a biological sample adhering to a sample carrier (30); - Arranging the sample carrier (30) on the centrifugal microfluidic biochip (10) such that fluid (50) passed by the opening in the fluidic system can come into contact with the biological sample; - Fixing the sample carrier (30) to the centrifugal microfluidic biochip (10) using the mounting medium (40); and - Processing the biological sample with respect to a predetermined The question is known per se. The method according to claim 12, characterized in that the processing comprises the lyse of the biological sample adhering to the sample carrier (30). The method according to claim 13, characterized in that the lyse is carried out mechanically, chemically, enzymatically and / or with the application of heat.

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