Biochip containers and methods of making and using same

Abstract

The present disclosure provides biochip containers and methods of making and using the same. The biochip container comprises: a container body (120) formed with a slot (121) defining a receiving space adapted to receive a chip (1) on which a biological sample to be analyzed is to be loaded; the biochip container has a transparent portion (131; the transparent part is basically aligned with the open groove (121) in the thickness direction (z) and covers the open groove, so that the biological sample on the chip accommodated in the accommodating space is allowed to be photographed through the transparent part.

Description

Biochip container and method for making and using the same Technical Field

[0001] Embodiments of the present disclosure generally relate to the field of biochemical technology, and more specifically, to biochip containers that can accommodate, for example, non-standard-sized chips while ensuring that automated operations such as imaging, fluid exchange, and transfer of the chips on biochemical analysis instruments are performed without damaging the chips. Embodiments of the present disclosure also relate to methods for preparing and using the biochip containers. Background Art

[0002] Conventional biological sample slicing, photography, and other operations are usually performed using glass slides. Automated sample processing involves alternately immersing glass slides in different reaction reagents for sample processing, or forming a semi-enclosed reaction system above the glass slide using a cover or a liquid layer immiscible with the reaction liquid, or encapsulating the glass slide with a fixture to form a microfluidic reaction chamber for sample processing. Regardless of the method used, transparent standard glass slides are used, and there is no corresponding solution for chips of other shapes / sizes that are different from standard glass slides. Directly processing non-standard-sized chips manually is cumbersome and labor-intensive.

[0003] The sample processing process involves multiple operations, including loading the biological sample onto the chip surface, manually applying a coverslip, photographing the chip, manually removing the coverslip, and then placing the chip into a container and onto an instrument for subsequent product extraction. Due to the small size of the chip itself, the chip is easily dropped and damaged during transfer for these operations, and the coverslip must be manually applied and removed before and after photographing the chip.

[0004] Therefore, it is desirable to provide a chip carrier solution that can accommodate chips of unconventional cutting sizes and ensure that the chip loaded with biological samples can be automatically processed on the instrument without damaging the chip while taking into account automated operations such as imaging, fluid replacement, and transfer on the instrument.

[0005] Summary of the Invention

[0006] The present disclosure is proposed to overcome at least one of the above and other problems and drawbacks of the prior art.

[0007] According to one aspect of the present disclosure, a biochip container is proposed, comprising: a container body formed with a groove, the groove defining a receiving space suitable for receiving a chip, and a biological sample to be analyzed to be loaded on the chip; and a biochip container having a transparent portion, the transparent portion being substantially aligned with and covering the groove in a thickness direction to allow the biological sample on the chip received in the receiving space to be photographed through the transparent portion.

[0008] In some embodiments, the biochip container further comprises: a cover glass disposed on a surface of the container body, wherein the cover glass comprises the transparent portion.

[0009] In some embodiments, the cover glass is formed with a through hole, which is fluidically connected to the receiving space to allow at least one of the following operations to be performed through the through hole: adding reaction liquid to the receiving space; extracting waste liquid from the receiving space; and recovering reaction products from the receiving space.

[0010] In some embodiments, the through-holes include a first through-hole and a second through-hole penetrating the cover glass in the thickness direction, each of the first through-hole and the second through-hole being configured to allow one or more of the operations to be performed.

[0011] In some embodiments, the first through hole and the second through hole are disposed in a portion of the cover glass that is outside the groove in a direction perpendicular to the thickness direction.

[0012] In some embodiments, the first through hole and the second through hole are located on opposite sides of the slot in a direction perpendicular to the thickness direction.

[0013] In some embodiments, the first through hole and the second through hole have the same or different opening shapes.

[0014] In some embodiments, the biochip container further comprises a glass slide having a chip positioning area on a surface of one side, the chip being adapted to be fixed in the chip positioning area, the container body being adapted to be sealedly assembled on the surface of the glass slide, and the groove penetrating the container body in the thickness direction and being substantially aligned with the chip positioning area.

[0015] In some embodiments, the container body is adapted to be sealingly attached to the surface of the slide by an adhesive or a fastener; and / or the cover glass is adapted to be sealingly attached to the surface of the container body facing away from the slide by an adhesive or a fastener.

[0016] In some embodiments, the groove comprises a bottomed groove formed in the container body, the bottomed groove being open at a side facing the cover glass.

[0017] In some embodiments, the biochip container further comprises a glass slide having a chip positioning area on a surface of one side, the chip being adapted to be fixed in the chip positioning area, the container body being adapted to be sealedly assembled on the surface of the glass slide, the groove penetrating the container body in the thickness direction and being substantially aligned with the chip positioning area, and the transparent portion being formed integrally with the container body or being a part of the container body.

[0018] In some embodiments, the biochip container further comprises the chip fixed on a glass slide.

[0019] In some embodiments, the accommodation space defined by the groove is further suitable for accommodating a reaction liquid, wherein the reaction liquid includes a reaction reagent or a cleaning reagent that will perform a biochemical reaction with the biological sample on the chip.

[0020] In some embodiments, the size of the slot is larger than the size of the chip.

[0021] In some embodiments, the slot has a shape that substantially matches the shape of the chip.

[0022] In some embodiments, the wall thickness of the groove is greater than the thickness of the chip.

[0023] In some embodiments, the container body is further formed with an opening, which is fluidically connected to the holding space to allow at least one of the following operations to be performed through the opening: adding reaction liquid to the holding space; extracting waste liquid from the holding space; and recovering reaction products from the holding space.

[0024] In some embodiments, the container body is further formed with an opening, which is substantially aligned with the through hole in the thickness direction and is in fluid communication with both the accommodating space and the through hole.

[0025] In some embodiments, the opening includes a first opening and a second opening located on different sides of the slot.

[0026] In some embodiments, the container body is made of flat glass or rubber material.

[0027] In some embodiments, the container body is formed with a plurality of slots having the same or different sizes.

[0028] In some embodiments, the receiving space is configured to receive a chip having a size ranging from 1 cm to 13 cm.

[0029] In another aspect of the present disclosure, an embodiment provides a method for preparing a biochip container, comprising the following steps: providing a glass slide, a flat carrier and a cover glass; processing the flat carrier serving as a container body to form a groove in the flat carrier, the groove defining a receiving space suitable for receiving a chip, and the biological sample to be analyzed will be loaded on the chip; assembling the cover glass on the container body so that at least the transparent portion of the cover glass covers the groove; and after the chip is fixed on the glass slide and the biological sample to be analyzed is loaded on the chip, sealingly assembling the assembled cover glass and the container body to the glass slide, so that the chip loaded with the biological sample to be analyzed is received in the receiving space.

[0030] In another aspect of the present disclosure, an embodiment provides a method for preparing a biochip container, comprising the following steps: providing a flat carrier and a cover glass; processing the flat carrier serving as a container body to form a bottomed groove in the flat carrier, the bottomed groove defining a receiving space suitable for receiving a chip, and the biological sample to be analyzed will be loaded on the chip; and after the chip loaded with the biological sample to be analyzed is received in the receiving space, assembling the cover glass onto the container body so that at least the transparent portion of the cover glass covers the bottomed groove.

[0031] In another aspect of the present disclosure, an embodiment provides a method for preparing a biochip container, comprising the following steps: providing a glass slide and a flat plate carrier; processing the flat plate carrier serving as a container body to form a bottomed groove in the flat plate carrier, the bottomed groove defining a receiving space suitable for receiving a chip, the biological sample to be analyzed being loaded on the chip, and the bottom of the bottomed groove being a transparent portion; and after the chip is fixed on the glass slide and the biological sample to be analyzed is loaded on the chip, sealingly assembling the container body to the glass slide, so that the chip loaded with the biological sample to be analyzed is received in the receiving space to allow photographing of the biological sample through the transparent portion.

[0032] In some embodiments, the method for preparing a biochip container further comprises the steps of: providing the chip; and fixing the chip in a chip positioning region of a glass slide before the container body is sealingly assembled onto the glass slide.

[0033] In some embodiments, the method for preparing a biochip container further includes the following steps: forming a through hole in the cover glass, wherein the through hole is connected to the fluid of the holding space after the cover glass is assembled onto the flat carrier, so as to allow at least one of the following operations to be performed through the through hole: adding reaction liquid to the holding space; extracting waste liquid from the holding space; and recovering reaction products from the holding space.

[0034] In some embodiments, the step of "processing the flat plate carrier as the container body" also includes: forming an opening in the flat plate carrier, which is fluidically connected to the holding space to allow at least one of the following operations to be performed through the opening: adding reaction liquid to the holding space; extracting waste liquid from the holding space; and recovering reaction products from the holding space.

[0035] In another aspect of the present disclosure, an embodiment provides a method for analyzing a biological sample, comprising: providing a biochip container described in any embodiment of the present disclosure; fixing a chip in the biochip container and loading a biological sample on the chip; and performing at least one of the following operations: clamping or adsorbing the biochip container containing the chip loaded with the biological sample to place the biochip container in or remove it from an analytical instrument; photographing the biological sample in the biochip container in the analytical instrument; and performing pipetting, waste liquid extraction, biochemical reactions, and product recovery in the biochip container in the analytical instrument.

[0036] In some embodiments, the operations are performed in a spatial omics or spatiotemporal omics operating instrument.

[0037] Other objects and advantages of the present disclosure will become apparent from the following detailed description of the present disclosure with reference to the accompanying drawings, which will help to provide a comprehensive understanding of the present disclosure. BRIEF DESCRIPTION OF THE DRAWINGS

[0038] The features and advantages of the present disclosure can be more clearly understood by referring to the accompanying drawings, which are schematic and should not be construed as limiting the present disclosure in any way. In the accompanying drawings:

[0039] FIG1 is a perspective view schematically showing the structure of a biochip container according to an exemplary embodiment of the present disclosure;

[0040] FIG2 is an exploded view schematically illustrating the structure of a biochip container according to an exemplary embodiment of the present disclosure;

[0041] FIG3 is a top view schematically illustrating the structure of a biochip container according to an exemplary embodiment of the present disclosure;

[0042] 4 is a cross-sectional view taken along line AA in FIG. 3 , schematically illustrating the structure of a portion of a biochip container according to an exemplary embodiment of the present disclosure;

[0043] 5 is a perspective view schematically illustrating the structure of a biochip container according to an exemplary embodiment of the present disclosure, with a cover glass removed;

[0044] FIG6 is a perspective view schematically illustrating the structure of a container body of a biochip container according to an exemplary embodiment of the present disclosure; and

[0045] 7 is a perspective view schematically showing the structure of a slide glass carrying a chip of a biochip container according to an exemplary embodiment of the present disclosure;

[0046] FIG8 is a perspective view schematically showing the structure of a biochip container according to another exemplary embodiment of the present disclosure;

[0047] FIG9 is a cross-sectional view taken along line BB in FIG8 , schematically illustrating the structure of a portion of a biochip container;

[0048] FIG10 is a perspective view schematically showing the structure of a biochip container according to yet another exemplary embodiment of the present disclosure;

[0049] FIG11 is a cross-sectional view taken along line CC in FIG10 , schematically illustrating the structure of a portion of a biochip container;

[0050] FIG12 is a flow chart schematically illustrating a method for preparing a biochip container according to an exemplary embodiment of the present disclosure;

[0051] FIG13 is a flow chart schematically illustrating a method for preparing a biochip container according to another exemplary embodiment of the present disclosure; and

[0052] FIG. 14 is a flow chart schematically illustrating a method for preparing a biochip container according to yet another exemplary embodiment of the present disclosure. DETAILED DESCRIPTION

[0053] The following will be combined with the drawings in the embodiments of the present disclosure to clearly and completely describe the technical solutions in the embodiments of the present disclosure. Obviously, the described embodiments are only part of the embodiments of the present disclosure, not all of the embodiments. In the specification and drawings, the same or similar drawing numbers indicate the same or similar parts. Based on the embodiments in the present disclosure, all other embodiments obtained by ordinary technicians in this field without making creative work are within the scope of protection of the present disclosure.

[0054] In addition, in the detailed description below, for ease of explanation, many specific details are set forth to provide a comprehensive understanding of the embodiments of the present disclosure. However, it is apparent that one or more embodiments can be implemented without these specific details. In other cases, well-known structures and devices are embodied in a schematic manner to simplify the drawings.

[0055] According to exemplary embodiments of the present disclosure, a biochip container is provided, comprising a container body having a slot formed therein, the slot defining a storage space in which a chip loaded with a biological sample to be analyzed is adapted to be accommodated. The biochip container (e.g., its cover glass or container body) further comprises a transparent portion that substantially aligns with the slot in the thickness direction of the biochip container and covers the slot or container space, allowing the biological sample on the chip accommodated in the storage space to be photographed through the transparent portion. This biochip container can accommodate chips of non-standard sizes while ensuring that automated operations such as imaging, fluid exchange, and transfer of the chip can be performed on an analytical instrument without damaging the chip. By way of example, the biological samples described herein may include, but are not limited to, pathological samples, tissue samples, cell samples, and more specifically, tissue sections, pathological sections, and the like.

[0056] Hereinafter, a biochip container provided by exemplary embodiments of the present disclosure will be described in detail with reference to the accompanying drawings.

[0057] In the embodiment shown in Figures 1-7 , a biochip container 100 primarily includes a glass slide 110, a container body 120, and a cover glass 130 stacked sequentially in the thickness direction Z. The glass slide 110 has a chip positioning region 111 on one surface thereof. The chip positioning region 111 can be a flat region or a concave region. The biochip 1 is adapted to be fixed in the chip positioning region 111. For example, the chip 1 can be attached to the chip positioning region 111 or to another suitable location on the glass slide using an adhesive or glue that does not affect subsequent biochemical reactions performed on the chip.

[0058] The container body 120 is formed with a slot 121, which defines a receiving space. The chip 1 is adapted to be at least partially received within the slot 121 or the receiving space, or the chip 1 can be exposed to the receiving space of the slot 121. A biological sample to be analyzed (not shown) can then be loaded onto the chip 1. After the biochip container is assembled, the slot 121 is substantially aligned with the chip positioning area 111 in the thickness direction Z, so that the chip 1 loaded with the biological sample to be analyzed is at least partially received within the receiving space of the slot 121 or exposed to a reaction solution added to the receiving space of the slot 121. Subsequently, various operations or biochemical reactions can be performed on the biological sample on the chip 1, for example, within an analytical instrument (not shown).

[0059] In the embodiments shown in Figures 1-6 and 10-11, the storage space of the biochip container is defined by the side walls of the groove 121 of the container body 120 and the surface of the glass slide 110. In addition to the chip, the storage space can also accommodate various reaction liquids, waste liquids or products, such as reaction reagents or cleaning reagents that will undergo biochemical reactions with the biological sample on the chip 1, reaction waste liquids, or target products captured by the chip from the biological sample.

[0060] In some embodiments, as shown in Figures 1-6 and 10-11, the groove 121 can penetrate the container body 120 in the thickness direction Z, and the container body 120 will be assembled on the surface of the glass slide 110 in a fluid-tight manner. For example, the container body 120 can be attached to the glass slide 110 using an adhesive or glue that does not affect the subsequent biochemical reaction on the chip, or using fasteners such as clamps or bolts. The container body 120 is fluid-tight with the glass slide 110 to prevent or reduce the loss of various reaction solutions added to the storage space for the biochemical reaction. As an example, the container body can be flat, for example, made of flat glass or rubber material.

[0061] Exemplarily, the size or area of ​​the groove 121 formed in the container body 120 is larger than the size or area of ​​the chip 1 to be processed. The groove 121 can have a shape that roughly matches or is similar to the shape of the chip, so that the chip and the biological sample loaded thereon can be accommodated within the defined accommodation space. In some examples, multiple grooves can be formed in the container body, and each groove can have the same or different sizes to achieve multi-chip, high-throughput processing. In an embodiment of the present disclosure, the accommodation space of the biochip container can be configured to accommodate chips with a size ranging from 1 cm to 13 cm, including chips of standard and non-standard sizes, so as to be compatible with or adapt to a variety of different applications. As shown in Figures 4, 5, 9 and 11, the wall thickness D of the groove 121 is greater than the thickness d of the chip 1. The wall thickness D of the groove 121 can be designed according to specific needs to ensure that a liquid layer of the desired thickness can be maintained above the chip and the biological sample it carries during the biochemical reaction.

[0062] The cover glass 130 is disposed on the surface of the container body 120 facing away from the slide glass 110. For example, the cover glass 130 can be assembled to the container body 120 using an adhesive or glue that does not affect the subsequent biochemical reaction on the chip, or by fasteners such as clamps or bolts. In some examples, the container body 120 and the cover glass 130 can also be fluid-tight to avoid or reduce the loss of various reaction liquids added to the containing space for performing biochemical reactions. It is understood that in some applications, it is not required that the container body and the cover glass must be fluid-tight. For example, the groove of the container body has a sufficient depth, the container is kept horizontal during operation, etc., to ensure that the reaction liquid does not enter the interface between the container body and the cover glass.

[0063] In some embodiments, the cover glass 130 includes at least a transparent portion 131. After the cover glass 130 is assembled onto the container body 120, the transparent portion 131 is substantially aligned with the slot 121 of the container body 120 in the thickness direction Z and covers the slot 121 or the receiving space defined by the slot 121, allowing the biological sample on the chip 1 received in the receiving space of the slot 121 to be photographed through the transparent portion 131. For example, such photography can be performed by placing the biochip container 100 containing the chip loaded with the biological sample in a bioanalyzer. For example, the entire cover glass, or at least the portion covering the slot of the container body, is transparent or made of a transparent material such as glass. Thus, photographing or imaging the biological sample on the chip can be achieved by manually or using tools to handle or transfer the biochip container, rather than handling smaller, environmentally sensitive chips. Chips do not fall or become damaged during handling or transfer, and manual or robotic cover glass removal and removal are not required before and after photographing or imaging, simplifying the sample analysis process.

[0064] Illustratively, to facilitate handling of the container, the size of the cover glass can be smaller than or equal to the size of the container body and / or the slide; the size of the slide can be smaller than, equal to, or larger than the size of the container body.

[0065] In some embodiments, as shown in Figures 1-4 and 8-9, the cover glass 130 may be formed with a through hole, which may penetrate the cover glass 130 to be in fluid communication with the receiving space of the container body 120, so as to allow various operations such as pipetting and liquid replacement to be performed through the through hole, including adding reaction liquid to the receiving space, extracting waste liquid from the receiving space, and / or recovering reaction products from the receiving space. The through hole is formed in a portion of the cover glass 130 that does not overlap with the groove 121 in the thickness direction Z, such as being formed outside the transparent portion 131, or formed in a portion of the cover glass 130 that is located outside the groove 121 in a direction perpendicular to the thickness direction Z, to avoid interfering with photographing or imaging of the biological sample.

[0066] One or more such through holes may be formed in the cover glass. In the illustrated embodiment, the through holes formed in the cover glass 130 include a first through hole 132 and a second through hole 133 located at different positions; for example, as shown in Figures 1-4 and 8-9, the first through hole 132 and the second through hole 133 are located on opposite sides of the groove 121 in a direction perpendicular to the thickness direction.

[0067] One or more of the above operations can be performed through each through hole in the coverslip 130. For example, the reaction liquid can be added to the storage space of the slot 121 through the first through hole 132 and / or the second through hole 133; the waste liquid can be first extracted from the storage space through the first through hole 132, and then the remaining waste liquid can be extracted from the storage space through the second through hole 133, and vice versa; similarly, the reaction product can be first recovered from the storage space through the first through hole 132, and then the remaining reaction product can be recovered from the storage space through the second through hole 133, and vice versa. The first through hole 132 and the second through hole 133 can have the same opening shape, or have different opening shapes (for example, as shown in Figures 1-3 and 8), so as to facilitate different operations at different through holes. The opening shape of the through hole can be appropriately designed to meet the requirements for performing these operations, such as facilitating the pipetting and liquid replacement operations of the pipette.

[0068] The through-hole formed in the cover glass 130 can be directly connected to the receiving space of the groove 121, or can be indirectly connected to the receiving space of the groove 121 (e.g., via a conduit). In the illustrated embodiment, the container body 120 can also be formed with an opening that is substantially aligned with the through-hole in the cover glass 130 in the thickness direction Z and is in fluid communication with both the receiving space and the through-hole. Thus, various operations such as pipetting and liquid replacement can be performed through both the through-hole in the cover glass 130 and the opening in the container body 120.

[0069] One or more openings may be formed in the container body 120, and the openings may be located at the periphery or edge of the slot 121. As an example, the openings formed in the container body 120 include a first opening 122 and a second opening 123 located on different sides (e.g., opposite sides) of the slot 121, as shown in Figures 2-6 and 8-11. The openings formed in the container body 120 may correspond one-to-one with the through-holes formed in the cover glass 130. For example, the first opening 122 is substantially aligned with the first through-hole 132 in the thickness direction Z, and the second opening 123 is substantially aligned with the second through-hole 133 in the thickness direction Z. It will be understood that the openings formed in the container body may be through-holes that extend through the container body in the thickness direction Z, or may be slots that only partially extend through the container body in the thickness direction Z.

[0070] Although in the illustrated embodiment, a through hole is formed in the coverslip that is fluidically connected to the opening formed in the container body, in other embodiments not shown, it is not necessary to form a through hole in the coverslip, and only an opening that is fluidically connected to the receiving space is formed in the container body, such as forming such an opening in a portion of the container body not covered by the coverslip to allow at least one of the following operations to be performed through the opening: adding reaction liquid including reaction reagents and cleaning reagents to the receiving space; extracting waste liquid from the receiving space; recovering reaction products from the receiving space, etc.

[0071] Furthermore, although in the embodiments shown in Figures 1-7, the biochip container 100 includes a slide 110, a container body 120 and a cover glass 130, in some embodiments, a biochip container that does not include a slide or a cover glass can be provided or used. This can also accommodate chips of non-standard sizes and ensure that automated operations such as imaging, liquid replacement, and transfer can be performed on the chip on an analytical instrument without damaging the chip.

[0072] In the embodiment shown in Figures 8-9, a biochip container 100' is provided, comprising a stacked container body 120 and a cover glass 130. The container body 120 does not include the aforementioned slide, or the slide is integrally formed with the container body. In this embodiment, a bottomed groove 121 formed in the container body 120 is a bottomed groove, open on the side facing the cover glass 130. This bottomed groove defines a space suitable for accommodating a chip 1. After a chip loaded with a biological sample to be analyzed is placed or secured in the bottomed groove, the cover glass 130 is assembled onto the container body 120 to cover the groove 121. The biochip container can then be transferred or manipulated. The biological sample in the groove 121 can be imaged through the transparent portion 131 of the cover glass 130. Liquid transfer, fluid exchange, product recovery, and other operations can be performed through the through-holes 132, 133 in the cover glass 130 and / or the openings 122, 123 in the container body 120.

[0073] In the embodiment shown in Figures 10-11, a biochip container 100" is provided, which includes a stacked glass slide 110 and a container body 120, without the above-mentioned cover glass, or the cover glass or the transparent portion is formed as a single body with the container body or is an integral part of the container body. In this embodiment, the glass slide 110 has a chip positioning area on one surface, and the chip 1 is suitable for being fixed in the chip positioning area. The container body 120 is suitable for being sealed and assembled on the surface of the glass slide 110, and the groove 121 passes through the container body 120 in the thickness direction and is substantially aligned with the chip positioning area, so that the chip 1 and the biological sample loaded thereon are The container body 120 is exposed to the receiving space defined by the groove 121. The container body 120 has a transparent portion 124 that covers the groove 121 on the side opposite the glass slide 110. The transparent portion 124 can have a size greater than or equal to the opening size of the groove 121. After the chip loaded with the biological sample to be analyzed is fixed on the glass slide 110, the container body 120 is sealed and assembled to the glass slide 110. After that, the biochip container can be transferred or operated, the biological sample in the groove 121 can be imaged through the transparent portion 124 of the container body 120, and operations such as pipetting, liquid replacement, and product recovery can be performed through the openings 122 and 123 in the container body 120.

[0074] In some embodiments of the present disclosure, the provided biochip container itself includes a chip, which can be fixed on a glass slide or in a bottomed groove of the container body. The biochip container can be assembled after the biological sample is loaded into the chip.

[0075] As shown in FIG12 and referring to FIG1-7 , an exemplary embodiment of the present disclosure further provides a method for preparing a biochip container 100 , which mainly includes the following steps:

[0076] Providing a glass slide 110, a plate carrier, and a cover glass 130;

[0077] The flat carrier serving as the container body 120 is processed to form a groove 121 therein, the groove defining a receiving space suitable for receiving the chip 1 on which the biological sample to be analyzed is loaded;

[0078] Assembling the cover glass 130 on the container body 120 so that at least the transparent portion 131 of the cover glass covers the groove 121;

[0079] After the chip 1 is fixed on the glass slide 110 and the biological sample to be analyzed is loaded on the chip 1, the assembled cover glass 130 and the container body 120 are sealed and assembled to the glass slide 110, so that the chip 1 loaded with the biological sample to be analyzed is accommodated in the accommodating space.

[0080] In another exemplary embodiment of the present disclosure, as shown in FIG13 and with reference to FIG8 and FIG9 , a method for preparing a biochip container 100 ′ is also provided, which mainly includes the following steps:

[0081] Providing a plate carrier and a cover glass 130;

[0082] The flat plate carrier as the container body 120 is processed to form a bottom groove 121 in the flat plate carrier, and the bottom groove 121 defines a receiving space suitable for receiving the chip 1 on which the biological sample to be analyzed is loaded;

[0083] After the chip 1 loaded with the biological sample to be analyzed is accommodated in the accommodation space, the cover glass 130 is assembled onto the container body 120 so that at least the transparent portion 131 of the cover glass 130 is covered with the bottom groove 121 .

[0084] In another exemplary embodiment of the present disclosure, as shown in FIG. 14 and with reference to FIG. 10 and FIG. 11 , a method for preparing a biochip container 100 ″ is also provided, which mainly includes the following steps:

[0085] Providing a glass slide 110 and a plate carrier;

[0086] The flat plate carrier serving as the container body 120 is processed to form a bottomed recess 121 in the flat plate carrier. The bottomed recess defines a receiving space suitable for receiving the chip 1 on which the biological sample to be analyzed is loaded. The bottom of the bottomed recess is a transparent portion 124.

[0087] After the chip 1 is fixed on the glass slide 110 and the biological sample to be analyzed is loaded on the chip, the container body 120 is sealedly assembled to the glass slide 110 on the side thereof facing away from the transparent portion 124, so that the chip 1 loaded with the biological sample to be analyzed is accommodated in the accommodating space, allowing the biological sample to be photographed through the transparent portion 124.

[0088] In the method shown in Figure 12 or 13, a through hole can also be formed in the cover glass 130. After the cover glass 130 is assembled on the container body 120, the through hole is connected to the fluid of the storage space to allow one or more operations to be performed through the through hole, including adding reaction liquid to the storage space, extracting waste liquid from the storage space, recovering reaction products from the storage space, etc.

[0089] In the method shown in Figure 12 or 14, before the container body 120 is sealed and assembled onto the glass slide 110, the chip 1 can be fixed in the chip positioning area of ​​the glass slide 110, so that the prepared biochip container itself includes the chip. Subsequently, the biological sample to be analyzed can be loaded onto the chip 1, and then the container body 120 and the glass slide 110 are sealed and assembled.

[0090] In the method shown in Figures 12, 13 or 14, an opening can be formed in the flat carrier, and the opening is connected to the fluid in the holding space to allow one or more operations to be performed alone through the opening, or through both the opening and the through hole, including adding reaction liquid to the holding space, extracting waste liquid from the holding space, recovering reaction products from the holding space, etc.

[0091] The biochip container provided in the embodiments of the present disclosure can be used to analyze biological samples, wherein after the biological sample is loaded on the chip and the assembly of the biochip container is completed, the biochip container containing the chip carrying the biological sample can be clamped or adsorbed to place the biochip container in or remove it from the analytical instrument, and the analytical instrument can, for example, include a spatial omics or spatiotemporal omics operation instrument; the biological sample in the biochip container can be photographed in the analytical instrument; in the analytical instrument, operations such as pipetting, waste liquid extraction, biochemical reactions (such as staining, in situ information labeling, capture, etc.), and product recovery can be performed in the biochip container.

[0092] According to embodiments of the present disclosure, a biochip container is provided, which provides a solution for automating chip imaging and subsequent experimental operations. For example, a chip can be placed in the container using tools such as tweezers. Subsequently, the container can be subjected to various operations, such as clamping or adsorption operations, placing the container containing the biochip in a spatial or spatiotemporal omics instrument, photographing the biological sample loaded on the chip, performing pipetting, waste liquid extraction, biochemical reactions, product recovery, and other operations within the container, thereby completing a series of biochemical operations including heating. Using this chip container to accommodate biochips can perform biochemical reactions such as staining, in situ information labeling, and capture. There is no need to transfer individual active chips within the instrument, no need to touch the active chip surface, and no need to manually or instrumentally cover and remove the cover glass before and after imaging the chip. This can effectively prevent the chip from falling and being damaged, effectively reduce the repetitive work of the experimenter, and reduce the reliance of the experimenter's experience on the experimenter. In addition, there is no need to reserve additional space on the chip, and the chip size does not need to be increased for chip operation, resulting in high chip utilization. Moreover, biochips of different sizes (for example, the size range can span 1 cm to 13 cm) can be placed in the chip container, which is compatible with the pipetting, waste liquid extraction, biochemical reaction, product recovery and other operational processes of biochips of different sizes; in addition, multiple chip slots can be set on the biochip container so that multiple full-chip samples can be processed simultaneously to achieve high-throughput processing.

[0093] Although the present disclosure is described in conjunction with the accompanying drawings, the embodiments disclosed in the drawings are intended to exemplify the preferred embodiments of the present disclosure and should not be construed as limiting the present disclosure.

[0094] Those skilled in the art will understand that the embodiments described above are exemplary and can be improved by those skilled in the art. The structures or features described in the various embodiments can be freely combined without causing any structural or theoretical conflicts.

[0095] While embodiments of the present disclosure have been shown and described, it will be appreciated by those skilled in the art that changes may be made to these embodiments without departing from the principles and spirit of the disclosure, the scope of which is defined in the appended claims and their equivalents.

Claims

1. A biochip container, comprising: a container body formed with a slot defining a receiving space adapted to receive a chip on which a biological sample to be analyzed will be loaded; The biochip container has a transparent portion that is substantially aligned with the groove in a thickness direction and covers the groove, so as to allow the biological sample on the chip accommodated in the accommodation space to be photographed through the transparent portion.

2. The biochip container according to claim 1, wherein: The biochip container further includes a cover glass disposed on a surface of the container body, wherein the cover glass includes the transparent portion.

3. The biochip container according to claim 2, wherein: The cover glass is formed with a through hole, the through hole being in fluid communication with the receiving space, so as to allow at least one of the following operations to be performed through the through hole: adding a reaction liquid into the containing space; extracting waste liquid from the holding space; and The reaction product is recovered from the holding space.

4. The biochip container according to claim 3, wherein: The through holes include a first through hole and a second through hole that penetrate the cover glass in the thickness direction, and each of the first through hole and the second through hole is configured to allow one or more of the operations to be performed.

5. The biochip container according to claim 4, wherein: The first through hole and the second through hole are provided in a portion of the cover glass that is located outside the groove in a direction perpendicular to the thickness direction.

6. The biochip container according to claim 5, wherein: The first through hole and the second through hole are located on opposite sides of the slot in a direction perpendicular to the thickness direction.

7. The biochip container according to claim 4, wherein: The first through hole and the second through hole have the same or different opening shapes.

8. The biochip container according to any one of claims 2 to 7, wherein: The biochip container further comprises a glass slide having a chip positioning area on a surface of one side, wherein the chip is adapted to be fixed in the chip positioning area. The container body is adapted to be sealingly assembled on the surface of the slide, and The slot penetrates the container body in the thickness direction and is substantially aligned with the chip positioning area.

9. The biochip container according to claim 8, wherein: The container body is adapted to be sealingly attached to the surface of the slide by adhesive or fasteners; and / or The cover glass is adapted to be sealingly attached to the surface of the container body facing away from the slide glass by adhesive or fasteners.

10. The biochip container according to any one of claims 2 to 7, wherein: The groove includes a bottomed groove formed in the container body, the bottomed groove being open at a side facing the cover glass.

11. The biochip container according to claim 1, wherein: The biochip container further comprises a glass slide having a chip positioning area on a surface of one side, wherein the chip is adapted to be fixed in the chip positioning area. The container body is adapted to be sealed and assembled on the surface of the slide glass, the groove penetrates the container body in the thickness direction and is substantially aligned with the chip positioning area, and The transparent portion is formed integrally with the container body or is a part of the container body.

12. The biochip container according to claim 8, 9 or 11, wherein: The biochip container further includes the chip fixed on the glass slide.

13. The biochip container according to any one of claims 1 to 12, wherein: The accommodation space defined by the groove is also suitable for accommodating a reaction liquid, wherein the reaction liquid includes a reaction reagent or a cleaning reagent that will perform a biochemical reaction with the biological sample on the chip.

14. The biochip container according to any one of claims 1 to 13, wherein: The size of the slot is larger than the size of the chip.

15. The biochip container according to any one of claims 1 to 14, wherein: The slot has a shape that substantially matches the shape of the chip.

16. The biochip container according to any one of claims 1 to 15, wherein: The wall thickness of the groove is greater than the thickness of the chip.

17. The biochip container according to claims 1 to 16, wherein: The container body is further formed with an opening, which is in fluid communication with the accommodating space to allow at least one of the following operations to be performed through the opening: adding a reaction liquid into the containing space; extracting waste liquid from the holding space; and The reaction product is recovered from the holding space.

18. The biochip container according to any one of claims 3 to 7, wherein: The container body is further formed with an opening that is substantially aligned with the through hole in the thickness direction and is in fluid communication with both the accommodation space and the through hole.

19. The biochip container according to claim 17 or 18, wherein: The openings include a first opening and a second opening located on different sides of the slot.

20. The biochip container according to any one of claims 1 to 19, wherein: The container body is made of flat glass or rubber material.

21. The biochip container according to any one of claims 1 to 20, wherein: The container body is formed with a plurality of the slots having the same or different sizes.

22. The biochip container according to any one of claims 1 to 21, wherein: The accommodation space is configured to accommodate a chip having a size ranging from 1 cm to 13 cm.

23. A method for preparing a biochip container, comprising the following steps: Slides, plate carriers, and cover slips are available; Processing a flat plate carrier as a container body to form a groove in the flat plate carrier, wherein the groove defines a receiving space suitable for receiving a chip, and a biological sample to be analyzed will be loaded on the chip; Assembling a cover glass on the container body so that at least a transparent portion of the cover glass covers the groove; as well as After the chip is fixed on the glass slide and the biological sample to be analyzed is loaded on the chip, the assembled cover glass and container body are sealed and assembled to the glass slide, so that the chip loaded with the biological sample to be analyzed is accommodated in the accommodation space.

24. A method for preparing a biochip container, comprising the following steps: Provides plate carriers and cover slips; Processing a flat plate carrier as a container body to form a bottomed groove in the flat plate carrier, the bottomed groove defining a receiving space suitable for receiving a chip, and the biological sample to be analyzed will be loaded on the chip; and After the chip loaded with the biological sample to be analyzed is accommodated in the accommodation space, a cover glass is assembled onto the container body so that at least a transparent portion of the cover glass covers the bottomed groove.

25. A method for preparing a biochip container, comprising the following steps: Slides and plate carriers are available; Processing a flat plate carrier as a container body to form a bottomed recess in the flat plate carrier, the bottomed recess defining a receiving space suitable for receiving a chip, the biological sample to be analyzed to be loaded on the chip, and the bottom of the bottomed recess being a transparent portion; and After the chip is fixed on the glass slide and the biological sample to be analyzed is loaded on the chip, the container body is sealedly assembled to the glass slide so that the chip loaded with the biological sample to be analyzed is accommodated in the accommodating space to allow the biological sample to be photographed through the transparent part.

26. The method according to claim 23 or 25, further comprising the steps of: providing the chip; and The chip is fixed in the chip positioning area of ​​the glass slide before the container body is sealingly assembled onto the glass slide.

27. The method according to claim 23 or 24, further comprising: A through hole is formed in the cover glass, wherein the through hole is in fluid communication with the receiving space after the cover glass is assembled on the flat carrier, so as to allow at least one of the following operations to be performed through the through hole: adding a reaction liquid into the containing space; extracting waste liquid from the holding space; and The reaction product is recovered from the holding space.

28. The method according to any one of claims 23 to 27, wherein: The step of "processing the flat plate carrier as the container body" also includes: An opening is formed in the flat carrier, the opening being in fluid communication with the receiving space to allow at least one of the following operations to be performed through the opening: adding a reaction liquid into the containing space; extracting waste liquid from the holding space; and The reaction product is recovered from the holding space.

29. A method for analyzing a biological sample, comprising: Providing the biochip container according to any one of claims 1 to 22; fixing a chip in the biochip container and loading a biological sample onto the chip; and Do at least one of the following: Clamping or adsorbing the biochip container containing the chip loaded with the biological sample to place the biochip container in or remove it from the analytical instrument; Taking a picture of the biological sample in the biochip container in an analytical instrument; and In analytical instruments, pipetting, waste extraction, biochemical reactions, and product recovery are performed within biochip containers.

30. The method according to claim 29, wherein The operations are performed in a spatial omics or spatiotemporal omics operation instrument.

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