Cartridge for a processing device, and processing device

Abstract

The invention relates to a cartridge (10) for a processing device (100; 100a) for processing a sample (P), in particular a biological sample. The cartridge (10) has at least one substrate (12) in which an analysis chamber (14) is provided, and at least one optical element in the form of a lens (32) is provided on the substrate (12) above the analysis chamber (14).

Description

[0001] Description

[0002] Cartridge for a processing unit and processing unit

[0003] Technical field

[0004] The invention relates to a cartridge for a processing device for processing a sample, particularly a biological one, which makes it possible to capture a relatively large image field of the sample with high resolution or high magnification. Furthermore, the invention relates to a processing device using a cartridge designed according to the invention.

[0005] State of the art

[0006] Processing devices for processing biological samples, designed as lab-on-a-chip systems, comprise an analyzer and at least one cartridge for processing. Molecular diagnostic assays are implemented in the cartridges. For this purpose, reagents are pre-positioned on the cartridge, and a fluidic network and a pneumatic network are provided to control the pumps and valves of the fluidic network. In assays based on the quantitative polymerase chain reaction (qPCR), the analyzer is configured to illuminate an analysis chamber of the cartridge with excitation light and to capture the emitted fluorescence light with a camera. Such a processing device is known, for example, from the applicant's subsequently published DE 10 2023209207 A1.

[0007] Furthermore, a cartridge with the features of the preamble of claim 1 is known from DE 102021 203 922 A1 of the applicant. In the aforementioned document, various optical features of the substrate of the cartridge are described, which serve to identify a medium located in the analysis chamber of the cartridge. Among other things, this optical feature can be in the form of a lens. However, the acquisition and evaluation of an image of the biological sample by means of such an optical lens is not mentioned in the aforementioned document.

[0008] Disclosure of the invention

[0009] The cartridge according to the invention for a processing device for processing a sample, in particular a biological sample, with the features of claim 1, has the advantage that it increases the resolving power of an image section of the biological sample captured by an optical device, in particular a camera, with relatively little effort. The invention is based on the idea of ​​designing a part of the cartridge as an optical element, with the aid of which, in conjunction with a specially designed processing device, an enlargement of an observation field of the biological sample provided in the analysis chamber is made possible at high resolution.

[0010] In light of the above explanations, a cartridge according to the invention for a processing device for processing a sample, particularly a biological one, with the features of claim 1, therefore comprises at least one substrate in which an analysis chamber is arranged. Furthermore, at least one optical element in the form of a lens is arranged on the substrate above the analysis chamber. "Above the analysis chamber" refers in particular to a side of the substrate facing away from the analysis chamber, which may be an outer surface of the cartridge. The cartridge according to the invention is characterized in that several lenses are arranged in the form of a lens array, which is configured to capture an observation field in the analysis chamber by means of an optical device.An arrangement of the optical element on the substrate can preferably be understood as a direct arrangement on the substrate or an indirect arrangement on the substrate, wherein in an indirect arrangement further material is located between the optical element and the substrate, for example one or more layers or films, wherein the further material is preferably transparent for a predetermined wavelength range of electromagnetic radiation, in particular light, in order to allow this radiation to pass through the optical element, the further material and the substrate into the analysis chamber.

[0011] Within the scope of the invention, a lens array is understood to be an arrangement provided in the plane of the substrate, in particular on the upper side of the substrate facing away from the analysis chamber, comprising a plurality of lenses arranged in the form of a matrix.

[0012] Advantageous further developments of the cartridge according to the invention for a processing device are listed in the dependent claims.

[0013] There are various possibilities regarding the manufacturing and formation of the lens array. In a first preferred variant, the substrate is made of plastic and is formed as an injection-molded or injection-molded part, and the lens array is formed monolithically with the substrate. Such a design of the substrate and lens array reduces the number of manufacturing steps required to produce the cartridge and also enables highly precise positioning and alignment of the lens array with respect to the cartridge's analysis chamber.

[0014] Alternatively, the lens array and the substrate can be designed as separate components, with the lens array connected to the substrate, particularly by bonding. This design allows for the use of different lens arrays on the same or different substrates and is therefore particularly advantageous in terms of universal applicability as a modular system adaptable to diverse requirements.

[0015] It is also possible for the lens array to include holographic lenses. These lenses can be surface holograms, i.e., area holograms, embossed in the plastic. However, it is preferred that volume holograms be used, which, for example, can be bonded as a film to the substrate of the cartridge. These holographic optical elements are configured to direct light with one or more (design) wavelengths from a spherical wave emitted from the sample side into a plane wave in the direction of the optical device (camera). Such a variant has the advantage that its intrinsic wavelength selectivity could be specifically exploited so that, for example, shorter-wavelength light incident on the sample for fluorescence excitation is not affected by the holographic optical elements.

[0016] It is also preferred if the lenses of the lens array are identical and have a focal length that corresponds at least approximately to a distance between the lens array and a sample arranged in the analysis chamber.

[0017] The invention further comprises a processing device for processing a sample, particularly a biological one, using a cartridge designed according to the invention as described above. The processing device includes an optical device, particularly in the form of a camera, configured to capture an image of the sample, which can be supplied to the optical device via the lens array. The processing device according to the invention is characterized by a collecting device configured to capture the light of the sample reflected by the lenses of the lens array at different angles. In other words, this means that a plurality of individual images, each with a relatively high resolution, can be captured by means of the optical device and combined by suitable software to form a complete image of the observation field or the sample.

[0018] In a first, preferred design embodiment of such a collecting device, it has a mirror element which has a reflective inner surface, wherein a longitudinal axis of the mirror element runs concentrically with an axis perpendicular to the plane of the substrate, which is preferably aligned with the observation field.

[0019] In order to minimize the influence of external influences or ambient light on the images of the observation field captured by the optical device (camera), it is also advantageously provided that the mirror element surrounds an optical detection element of the optical device at its edge.

[0020] In an alternative design of the collecting device, it is designed as an adjustment device that serves to change the position of the optical device relative to the lens array.

[0021] In particular, the adjustment device serves to change the position of the optical device either in a plane parallel to the substrate or to pivot the optical device by an angle about an axis perpendicular to the plane of the substrate.

[0022] Further advantages, features and details of the invention will become apparent from the following description of preferred embodiments of the invention and from the drawings.

[0023] Brief description of the drawings

[0024] Fig. 1 and

[0025] Fig. 2 shows, in simplified longitudinal section, differently designed processing devices for processing a sample, in particular a biological sample, arranged in a cartridge.

[0026] Embodiments of the invention

[0027] Identical elements or elements with the same function are provided with the same reference numbers in the figures.

[0028] Figure 1 shows the essential components of a processing device 100 for processing a sample P, particularly a biological sample, which in the exemplary embodiment comprises two particles Pai and Pa2. The biological sample P is arranged in the area of ​​an observation field BF of a cartridge 10. The cartridge 10, of which only a section is shown in Figure 1, has a multi-part substrate 12, which in the illustrated exemplary embodiment comprises a first layer 13 made of polycarbonate and having a thickness of approximately 1.7 mm. An analysis chamber 14, the height of which is, for example, 1.0 mm, is arranged within the first layer 13. The first layer 13 is connected to or covered by a second layer 16. The observation field BF is arranged on a silicon chip 18, wherein the biological sample P has been treated, in particular, with a dye.

[0029] The cartridge 10 is mounted in a recess (not shown) of a housing of the processing unit 100 and is positioned there in a fixed location. An analyzer of the processing unit 100 is arranged above the cartridge 10. The analyzer comprises a light source (not shown), in particular a laser light source, which emits its light in the direction of the biological sample P. Crucially, the material of the cartridge 10 is transparent to the wavelength of the light. The analyzer also comprises an optical device 20 in the form of an image-capturing camera 22 with an optical detection element 24, e.g., in the form of a lens. The optical device 20 serves to capture the light reflected by the biological sample P and to transmit it to an evaluation unit (not shown), which has an algorithm for processing the image information to create an image of the biological sample P.

[0030] To enable magnification of the biological sample P or analysis of the entire observation field BF, a lens array 30 with a plurality of identically designed lenses 32 is arranged on a top surface 26 of the cartridge 10 or the substrate 12. As shown in Fig. 1, the top surface 26 is the side of the substrate 12 facing away from the analysis chamber 14, which in this example also forms an outer surface of the cartridge 10. The lens array 30 is designed as an arrangement of lenses 32 extending in two planes, with the plane of the lens array 30 extending in a direction parallel to the plane of Fig. 1 and in a direction perpendicular to the plane of Fig. 1. The lenses 32 of the lens array 30 are arranged at least in alignment with, or overlapping with, the observation field BF. In the illustrated embodiment, the lens array 30 comprises six lenses 32 arranged side by side in the plane of Fig. 1.The lens array 30 can therefore be designed, for example, in the form of a 6x6 matrix when the observation field BF is square.

[0031] The lenses 32 are either monolithically formed with the cartridge 10 or the substrate 12, particularly when the substrate 12 is formed as an injection-molded or injection-molded part. Alternatively, however, it can also be provided that the lenses 32 or the lens array 30 are formed as a separate component formed from the substrate 12 and are connected, in particular bonded, to the top surface 26 of the substrate 12.

[0032] In another embodiment of the lens array 30, not shown, this comprises holographic lenses 32 which are either formed in the plastic of the substrate 12 as imprinted surface holograms, or as a volume hologram in the form of a film that is glued onto the substrate 12.

[0033] The focal length of the lenses 32 is adapted, at least approximately, to the distance a between the lens array 30 and the biological sample P or the observation field BF.

[0034] An optical axis 34, perpendicular to the plane of the substrate 12, is aligned concentrically with the optical detection element 24 of the optical device 20. Furthermore, the optical device 20 is surrounded, at least in the region of the optical detection element 24, by a preferably tubular mirror element 36 as a collecting device 35, the inner surface 38 of which is reflective for the wavelength of the light used. The cross-section of the mirror element 36 or the inner surface 38 can be annular or, for example, formed from four side walls, each arranged at a 90° angle. A longitudinal axis 33 of the mirror element 36 runs concentrically with the optical axis 34 of the optical device 20. The mirror element 36 preferably extends close to the substrate 12 and surrounds the optical detection element 24 at its periphery to reduce the incidence of unwanted light.To minimize interference with the lens array 30.

[0035] As can be seen in Fig. 1, the light emitted by the light source (not shown) towards the biological sample P is reflected by the biological sample P, and the shape of the lenses 32 causes the light to be refracted at different angles at the interface. The light reflected from the biological sample P via the lens array 30 is then either reflected at the inside of the mirror element 36 or can be directly captured by the optical detection unit 24. The image information captured by the optical detection unit 24 or the optical device 20 is processed into a magnified image of the biological sample P using the aforementioned algorithm.

[0036] Figure 2 shows a processing device 100a modified compared to Figure 1. While the construction of the cartridge 10 and the lens array 30 is identical to that of the processing device 100, the mirror element 36 is replaced by a collecting device 35a, which is designed to pivot the optical device 20 and the optical detection element 24 with its field of view SF at an angle α relative to the optical axis 34. For this purpose, the collecting device 35a has an adjustment motor 42, which is coupled to the optical device 20. Using the optical collecting device 35a, individual images of the biological sample P are acquired at different angles α, whereby the individual images differ due to the shape of the optical lenses 32, or the biological sample P is acquired at different angles.

[0037] In an embodiment of the collecting device 35a (not shown), it is configured to adjust the optical device 20 in the direction of the double arrow 44 and in a direction perpendicular to the direction of the double arrow 44 and to the plane of Fig. 2, i.e., parallel to the plane of the lens array 30. This also allows individual images of the biological sample P to be captured and processed at different angles. The cartridge 10 and the processing device 100, 100a described so far can be modified or adapted in various ways without deviating from the inventive concept.

Claims

Claims 1. Cartridge (10) for a processing device (100; 100a) for processing a sample (P), in particular a biological sample, wherein the cartridge (10) has at least one substrate (12) in which an analysis chamber (14) is arranged, and wherein at least one optical element in the form of a lens (32) is arranged above the analysis chamber (14) on the substrate (12), characterized in that several lenses (32) are provided in the form of a lens array (30) which are configured to detect an observation field (BF) in the analysis chamber (14) by means of an optical device (20).

2. Cartridge according to claim 1, characterized in that the substrate (12) is made of plastic and is designed as an injection-molded or injection-molded component, and that the lens array (30) is formed monolithically with the substrate (12).

3. Cartridge according to claim 1, characterized in that the lens array (30) and the substrate (12) are designed as separate components, and that the lens array (30) is connected to the substrate (12), in particular bonded.

4. Cartridge according to one of claims 1 to 3, characterized in that the lens array (30) comprises holographic lenses (32).

5. Cartridge according to one of claims 1 to 4, characterized in that, that the lenses (32) of the lens array (30) are identical and have a focal length that corresponds at least approximately to a distance (a) between the lens array (30) and the sample (P) arranged in the analysis chamber (14).

6. Processing device (100; 100a) for processing a sample (P), in particular a biological sample, using a cartridge (10) configured according to any one of claims 1 to 5, wherein the processing device (100; 100a) has an optical device (20), in particular in the form of a camera, configured to capture an image of the sample (P) which can be supplied to the optical device (20) via the lens array (30), characterized in that a collecting device (35; 35a) is provided which is configured to capture the light of the sample (P) reflected via the lenses (32) of the lens array (30) at different angles.

7. Processing device according to claim 6, characterized in that the collecting device (35) has a mirror element (36) with a reflective inner surface (38), wherein a longitudinal axis (33) of the mirror element (36) runs concentrically with an axis (34) perpendicular to the plane of the substrate (12), which is preferably aligned with the observation field (BF).

8. Processing device according to claim 7, characterized in that the mirror element (36) surrounds an optical detection element (24) of the optical device (20) at its edge.

9. Processing device according to claim 6, characterized in that the collecting device (35a) has an adjustment device (42) which is configured to change the position of the optical device (20) relative to the lens array (30).

10. Processing device according to claim 9, characterized in that the adjustment device (42) is configured to change the position of the optical device (20) either in a plane parallel to the substrate (12) or to pivot the optical device (20) about an axis (34) perpendicular to the plane of the substrate (12) by an angle (a).

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