Conductive clamping groove

Abstract

The utility model relates to a conductive card slot, which is applied to same-sheet space multi-omics detection, the space multi-omics comprises a space transcriptome and a space metabolome, and the conductive card slot comprises a conductive bar; a plurality of grooves are formed in the conducting bar at equal intervals, and the size of each groove is matched with the size of a target space transcriptome chip; chip taking holes are formed in the four corners of each groove, and the chip taking holes are used for taking out the target space transcriptome chips from the grooves; the depth of each groove is matched with the height of the target space transcriptome chip in a specified error range. Therefore, a carrier is provided for synchronous detection of the high-resolution space transcriptome and metabolome of the same tissue slice, the problem of conductivity conflict of the two kinds of omics is solved in a breakthrough mode, and a key technical support is provided for multi-omics space integration research.

Description

Technical Field

[0001] This utility model mainly relates to the field of space omics, and in particular to a conductive card slot. Background Technology

[0002] In recent years, the rapid development of spatial transcriptomics and spatial metabolomics technologies has made it possible to analyze biological processes at the in situ level in tissues, providing unprecedented tools for studying spatial heterogeneity in complex tissues.

[0003] In the field of spatial transcriptomics, techniques such as spatial gene expression (Visium) and spatial transcriptomics (SeqScope) have been widely applied in disease research, for example, in resolving the spatial characteristics of liver lobules in primary and metastatic liver cancer. However, these techniques still have significant limitations: Visium has a resolution of only 50 μm, making it difficult to achieve spatial resolution at the single-cell level; while SeqScope, although achieving an ultra-high resolution of nearly 1 μm, has a detection area of ​​only 0.2 mm. 2 This limitation restricts large-scale tissue analysis. In contrast, DNA nanosphere-based spatiotemporal omics (Stereo-seq) technology combines ultra-high resolution, ultra-large field of view, and high capture efficiency, making it significantly advantageous in studies of mouse organ development, tumor microenvironment, and primate cerebral cortex.

[0004] Meanwhile, spatial metabolomics, leveraging mass spectrometry imaging techniques such as MALDI-Orbitrap, DESI, and SIMS, enables in-situ detection of metabolites, revealing metabolic heterogeneity at the micrometer or even single-cell scale (5 μm). These techniques have been used to study key biological questions such as liver metabolic zonation, host-microbe interactions, cell fate determination, and the influence of the metabolic microenvironment. For example, in mouse and human liver studies, MALDI-Orbitrap and DESI techniques have revealed the spatial metabolic characteristics of homeostatic and fatty liver (50 μm resolution), while combined with isotope-traced spatial metabolic flux analysis, scientists can now track metabolic dynamics at the single-cell level and create high-precision metabolic maps in studies of human kidney development and injury.

[0005] The complementary combination of these technologies provides a novel perspective for decoding cell interactions and metabolic heterogeneity at the tissue level. It not only enables multi-dimensional analysis of the dynamic changes in genes and metabolic molecules during life processes, but also allows for the mining of gene-metabolite interaction regulatory networks based on large-scale high-throughput data, identifying key signaling pathways and metabolites driving spatial heterogeneity, thereby systematically elucidating complex biological mechanisms. Although space transcriptomics and space metabolomics technologies are increasingly widely used in space biology, existing combined analysis schemes still have significant limitations: most studies only perform correlation analysis using consecutive slices, or conduct separate detections on the same tissue slice at low resolution (100 μm). Due to technological limitations, this strategy of adjacent slices or low resolution is only suitable for macroscopic regional studies, making it difficult to achieve precise analysis at the microenvironment or even single-cell level, greatly restricting in-depth exploration of complex biological problems.

[0006] The core challenge in achieving high-resolution detection of tissue sections lies in the fundamental differences in the principles of the two technologies: spatial transcriptomics technologies such as Stereo-seq rely on DNA nanosphere (DNB) chips to capture RNA and perform high-throughput sequencing, while spatial metabolomics technologies such as matrix-assisted laser desorption / ionization mass spectrometry (MALDI-MSI) require laser excitation to ionize metabolic molecules in tissue sections and directly obtain mass-to-charge ratio spatial distribution data. There is a fundamental conflict in the compatibility of these two technologies: spatial transcriptomics requires the use of non-conductive barcode chips, while MALDI-MSI must be based on conductive ITO slides; furthermore, laser and matrix spraying operations during mass spectrometry imaging can lead to RNA degradation, further hindering the integrated application of tissue sections. Utility Model Content

[0007] One objective of this invention is to provide a conductive card slot that solves the problem in the prior art that two spatial omics detections cannot be performed simultaneously on the same tissue slice.

[0008] According to one aspect of the present invention, a conductive slot is provided for use in spatial multi-omics detection, wherein the spatial multi-omics includes spatial transcriptomics and spatial metabolomics, and the conductive slot includes a conductive bar.

[0009] Multiple grooves are equally spaced on the conductive busbar, and the size of each groove is adapted to the size of the target spatial transcriptome chip.

[0010] A retrieval hole is provided at each of the four corners of the groove, wherein the retrieval hole is used to remove the target spatial transcriptome chip from the groove;

[0011] The depth of each groove is matched to the height of the target spatial transcriptome chip within a specified error range.

[0012] Optionally, the specified error range is 0 to 10 μm.

[0013] Optionally, the conductive busbar is made of a conductive metal, including brass.

[0014] Optionally, a boss may be provided below the conductive busbar.

[0015] Optionally, the length of the boss's platform is greater than the length between the grooves on both sides and less than the total length of the conductive busbar.

[0016] Optionally, a specified spacing is provided between the outer edges on both sides and the edge groove along the length of the conductive busbar.

[0017] Optionally, the target spatial transcriptome chip includes a Stereo-seq chip.

[0018] Compared with existing technologies, this invention provides a conductive slot for simultaneous spatial multi-omics detection on the same tissue slice. The spatial multi-omics includes spatial transcriptomics and spatial metabolomics. The conductive slot includes a conductive bar; multiple grooves are evenly spaced on the conductive bar, the size of each groove being adapted to the size of the target spatial transcriptomics chip; a retrieval hole is provided at the four corners of each groove, wherein the retrieval hole is used to remove the target spatial transcriptomics chip from the groove; the depth of each groove matches the height of the target spatial transcriptomics chip within a specified error range. This provides a carrier for achieving high-resolution simultaneous detection of spatial transcriptomics and metabolomics on the same tissue slice, fundamentally solving the problem of conductivity conflict between the two omics, and providing key technical support for multi-omics spatial integration research. Attached Figure Description

[0019] To make the above-mentioned objectives, features and advantages of this utility model more apparent and understandable, the specific embodiments of this utility model will be described in detail below with reference to the accompanying drawings, wherein:

[0020] Figure 1 A schematic diagram of a conductive card slot according to one aspect of the present invention is shown.

[0021] Figure 2 This diagram illustrates a chip assembly height detection method according to an embodiment of the present invention.

[0022] Figure 3 This diagram shows a structural schematic of a 4-hole conductive slot adapted to a space transcriptome chip in one embodiment of the present invention.

[0023] Figure 4 This diagram illustrates the structure of a 10-hole conductive slot adapted to a spatial transcriptome chip in one embodiment of the present invention.

[0024] The same or similar reference numerals in the accompanying drawings represent the same or similar parts. Detailed Implementation

[0025] To enable those skilled in the art to better understand the present invention, the technical solutions of the present invention will be clearly and completely described below with reference to the accompanying drawings of the embodiments. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort should fall within the protection scope of the present invention.

[0026] It should be noted that the terms "first," "second," etc., in the specification, claims, and accompanying drawings of this utility model are used to distinguish similar objects and are not necessarily used to describe a specific order or sequence. It should be understood that such data can be interchanged where appropriate so that the embodiments of the utility model described herein can be implemented in orders other than those illustrated or described herein. Furthermore, the terms "comprising" and "having," and any variations thereof, are intended to cover a non-exclusive inclusion; for example, a process, method, apparatus, product, or device that comprises a series of steps or units is not necessarily limited to those steps or units explicitly listed, but may include other steps or units not explicitly listed or inherent to such processes, methods, products, or devices.

[0027] This invention designs a conductive slot structure that, through a nested adaptation spatial transcriptome chip, achieves for the first time simultaneous high-resolution spatial transcriptome and metabolome detection from the same tissue slice. This breakthrough solves the problem of conductivity conflict between the two omics approaches, providing key technical support for multi-omics spatial integration research. The specific process is as follows:

[0028] Figure 1This diagram illustrates a conductive slot according to one aspect of the present invention. The conductive slot is used for spatial multi-omics detection, including spatial transcriptomics and spatial metabolomics, and includes a conductive busbar 100. Multiple grooves 101 are evenly spaced on the conductive busbar 100, the size of each groove being adapted to the size of the target spatial transcriptomics chip. Pick-up holes 102 are provided at the four corners of each groove 101, wherein the pick-up holes 102 are used to remove the target spatial transcriptomics chip from the groove. The depth of each groove 101 is matched to the height of the target spatial transcriptomics chip within a specified error range. The conductive busbar is made of a conductive metal, including brass. Here, the conductive busbar uses a highly conductive material, such as brass. To achieve simultaneous detection of multiple omics in space, the design of the conductive slot needs to meet the requirements of the idle chip, that is, to use the target spatial transcriptome chip from the beginning. This can meet the requirements of spatial metabolomics detection as well as spatial transcriptome detection. The target spatial transcriptome chip is a spatial transcriptome gene expression chip that needs to be sequenced. The conductive busbar can be set with one row of grooves or multiple rows of grooves, which is customized according to the size of the conductive busbar and the chip size. The size of each groove needs to be adapted to the size of the chip to be assembled, and the groove depth needs to be strictly matched with the thickness of the chip, which needs to be controlled within the specified error.

[0029] In one embodiment of this utility model, the specified error range is 0–10 μm, that is, the error between the groove depth and the chip height is less than 10 μm, which can ensure that the surface of the conductive slot and the surface of the assembled chip are on the same focal plane when performing space metabolomics detection; for example Figure 2 The schematic diagram shown is for chip assembly height detection. The height difference between the conductive slot and the chip surface is 2μm, which meets the requirement of being less than 10μm.

[0030] In one embodiment of this utility model, a boss is provided below the conductive busbar. Here, the thickness of the conductive busbar is small, and it would be difficult to process the grooves on the conductive busbar. Therefore, to facilitate processing, a boss can be provided below the conductive busbar. This boss covers all the grooves, which is beneficial for processing.

[0031] Specifically, the length of the boss's platform is greater than the length between the two edge grooves but less than the total length of the conductive busbar. Here, the edge groove is the groove closest to the outer edge of the conductive busbar along its length. For example, when a row of grooves is provided, the first and last grooves are edge grooves. The distance between the left boundary of the first groove and the right boundary of the last groove must be less than the total length of the boss's platform to ensure that the boss can cover all the grooves; and the total length of the boss's platform must be less than the total length of the conductive busbar. The boss can be a trapezoid with a smaller lower surface, in which case the total length of the lower surface must meet the above-mentioned range.

[0032] In one embodiment of this invention, a specified distance is provided between the outer edges of both sides of the conductive busbar and the edge groove along the length of the conductive busbar. Here, to facilitate the clamping of conductive sheets on both sides of the conductive busbar during spatial metabolomics detection, a certain distance is required between the edge groove and the outer edge of the conductive busbar, thereby ensuring that the conductive sheets do not interfere with the detection within the edge groove. The specified distance can be determined based on the length of the conductive busbar, the size of the groove, and historical experience; for example, the specified distance could be 6.61 mm.

[0033] In one embodiment of this invention, the target spatial transcriptome chip includes a Stereo-seq chip. Here, the DNA nanosphere-based spatiotemporal omics (Stereo-seq) chip can capture RNA and perform high-throughput sequencing. When performing spatial transcriptome detection on the Stereo-seq chip, the size of the groove in the conductive slot is matched to the size of the Stereo-seq chip. For example, currently, Stereo-seq chips are available in sizes of 1cm × 1cm and 0.5cm × 0.5cm; therefore, when designing the conductive slot, the groove size is either 1cm × 1cm or 0.5cm × 0.5cm.

[0034] ITO slides can only be used for continuous sections for Stereo-seq, and their spatial precision is insufficient. Furthermore, once spatial metabolomics detection is achieved, sections attached to ITO slides are difficult to reuse for spatial transcriptomics detection, requiring the development of section transfer techniques. The transfer process must not damage the tissue sections or the Stereo-seq chip, making multi-omics detection on the same slide difficult. However, the conductive slot provided by this invention allows the target spatial transcriptomics chip with attached tissue sections to be assembled into the slot's groove. After matrix spraying and mass spectrometry imaging of the spatial metabolomics, the chip can be removed through the removal hole without damaging the tissue sections or the chip. This enables subsequent registration of the spatial metabolomics and spatial transcriptomics, as well as spatial transcriptomics sequencing, thereby achieving multi-omics joint detection on the same section.

[0035] In one embodiment of this utility model, a four-hole conductive slot is designed, such as... Figure 3The schematic diagram of the 4-well conductive slot for adapting to a spatial transcriptome chip is shown below: If the Stereo-seq chip is 1cm × 1cm, a conductive busbar with dimensions of 75mm (length) × 25mm (width) × 1.1mm (thickness) can be selected. Four equally spaced grooves are provided in the center, each groove measuring 1cm × 1cm and approximately 0.71mm deep. It is necessary to ensure that the chip fits and is fixed in place within the grooves, and sufficient space is provided for the chip removal holes, such as at the four corners, to facilitate chip removal after the spatial metabolomics procedure. To facilitate clamping the conductive sheet on both sides during MALDI-MSI instrumentation, a certain distance, such as 6.61mm, needs to be maintained between the edge grooves and the outer edge of the conductive busbar. It should be noted that a boss can also be designed; the thickness of the conductive busbar with the boss is 1.5mm.

[0036] In another embodiment of this utility model, a ten-hole conductive card slot is designed, such as... Figure 4 The schematic diagram of the 10-well conductive card slot adapted for space transcriptome chips is shown below: If the Stereo-seq chip is 5mm × 5mm, the conductive busbar can be selected with dimensions of 75mm (length) × 25mm (width) × 1.1mm (thickness), with a thickness of 1.5mm at the protrusion section. Two rows are arranged, each row having five equally spaced grooves. Each groove is 5mm × 5mm in size and approximately 0.725mm deep. Pick-up holes are located at the four corners of the grooves. A certain distance, for example, 6.61mm, needs to be maintained between the edge of the groove and the outer edge of the conductive busbar. This 10-well conductive card slot, combined with the dual-slot configuration of the space metabolomics instrument, can simultaneously analyze 20 chips.

[0037] It should be noted that the Stereo-seq chip used in the above-mentioned target spatial transcriptome chip is only an example. Other spatial transcriptome chips can also be used, such as Visium spatial transcriptome chips. The groove size should be adjusted and adapted according to the specific chip size used.

[0038] The basic concepts have been described above. Obviously, for those skilled in the art, the above disclosure is merely illustrative and does not constitute a limitation of this utility model. Although not explicitly stated herein, those skilled in the art may make various modifications, improvements, and corrections to this utility model. Such modifications, improvements, and corrections are suggested in this utility model, and therefore remain within the spirit and scope of the exemplary embodiments of this utility model.

[0039] Meanwhile, specific terms are used to describe embodiments of this utility model. For example, "an embodiment," "one embodiment," and / or "some embodiments" refer to a particular feature, structure, or characteristic related to at least one embodiment of this utility model. Therefore, it should be emphasized and noted that "an embodiment," "one embodiment," or "an alternative embodiment" mentioned twice or more in different locations in this specification do not necessarily refer to the same embodiment. Furthermore, certain features, structures, or characteristics in one or more embodiments of this utility model can be appropriately combined.

[0040] In some embodiments, numbers describing the quantity of components and attributes are used. It should be understood that such numbers used in the description of embodiments are modified in some examples with the terms "approximately," "approximately," or "generally." Unless otherwise stated, "approximately," "approximately," or "generally" indicates that the numbers are allowed to vary by ±20%. Accordingly, in some embodiments, the numerical parameters used in the specification and claims are approximate values, which may be changed according to the characteristics required by individual embodiments. In some embodiments, numerical parameters should take into account specified significant digits and employ a general method of digit reservation. Although the numerical ranges and parameters used to confirm their breadth of range in some embodiments of this invention are approximate values, in specific embodiments, such values ​​are set as precisely as feasible.

Claims

1. A conductive card slot, applied to spatial multi-omics detection on the same chip, wherein the spatial multi-omics includes spatial transcriptomics and spatial metabolomics, characterized in that, The conductive slot includes a conductive busbar; Multiple grooves are equally spaced on the conductive busbar, and the size of each groove is adapted to the size of the target spatial transcriptome chip. A retrieval hole is provided at each of the four corners of the groove, wherein the retrieval hole is used to remove the target spatial transcriptome chip from the groove; The depth of each groove is matched to the height of the target spatial transcriptome chip within a specified error range.

2. The conductive card slot according to claim 1, characterized in that, The specified error range is 0 to 10 μm.

3. The conductive card slot according to claim 1, characterized in that, The conductive busbar is made of a conductive metal, including brass.

4. The conductive card slot according to claim 1, characterized in that, A boss is provided below the conductive busbar.

5. The conductive card slot according to claim 4, characterized in that, The length of the boss's platform is greater than the length between the grooves on both sides and less than the total length of the conductive busbar.

6. The conductive card slot according to claim 1, characterized in that, A specified spacing is set between the outer edges of both sides of the conductive busbar and the edge groove along the length direction.

7. The conductive card slot according to claim 1, characterized in that, The target spatial transcriptome chip includes a Stereo-seq chip.

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