Integrated desalting device and method for high-throughput sample treatment

Abstract

The invention relates to the technical field of experimental equipment, and provides an integrated desalting device and method for high-throughput sample treatment, and the device comprises a base, a movable partition plate and a standard porous plate. The movable partition has first and second working positions. And a wedge-shaped guide positioning mechanism is arranged between the movable partition plate and the perforated plate, and can automatically guide the movable partition plate to lift and transversely align through slope matching when the perforated plate is horizontally pushed in until the movable partition plate is stably supported on the perforated plate and accurate alignment of a sample treatment column and a collection hole is realized, so that rapid and accurate switching between a washing mode and an elution mode is completed. The device is ingenious in structure and easy and smooth to operate.

Description

Technical Field

[0001] This invention belongs to the field of experimental equipment technology, specifically relating to an integrated desalination device and method for high-throughput sample processing. Background Technology

[0002] In life science research such as proteomics and metabolomics, desalting, desalting, or desalting purification of biological samples (such as peptides after enzymatic digestion) is a crucial pretreatment step before mass spectrometry analysis.

[0003] Currently, high-throughput desalination mainly uses the 96-well plate format. Existing technical solutions can be roughly divided into two categories: one is to improve the chromatography column or centrifuge column itself, integrating it into a row (such as CN209166966U). Although this facilitates automated handling, it has poor flexibility, high cost, and is incompatible with the single centrifuge column commonly used in laboratories. The other is to design a support frame device (such as CN215296882U), assembling and aligning the common microchromatography column, collection tube, and spotting plate through a multi-layer support structure. This type of solution has good compatibility, but has obvious shortcomings: first, it requires additional fixing supports, support columns, and other parts, making assembly and disassembly cumbersome; second, the workflow is fragmented. When performing the two key steps of washing (collecting waste liquid) and elution (collecting samples), it is often necessary to manually replace or adjust the bottom collection container (such as changing from a collection tube to a spotting plate), which not only increases the number of operation steps and the risk of sample contamination, but also makes the operation less intuitive and smooth.

[0004] In addition, there is a general-purpose chromatography collection device (such as CN211905242U), which can switch collection tubes by sliding, but it cannot achieve seamless and rapid switching between washing and elution modes, and it is also difficult to directly adapt to standardized spotting plates.

[0005] Therefore, there is an urgent need in the field for a high-throughput sample processing device with a simpler structure, higher integration, seamless connection between different processing stages (such as waste liquid collection and sample elution collection) on the same device, and perfect compatibility with common laboratory consumables (standard 96-well plates, micro-chromatographic columns of various specifications). Summary of the Invention

[0006] The present invention aims to overcome the above-mentioned defects of the prior art and provide a high-throughput integrated desalination device and method for sample processing that is simple in structure, intuitive in operation, and capable of rapid switching between washing and elution modes.

[0007] To achieve the above objectives, the present invention provides the following technical solution: In a first aspect, the present invention provides an integrated desalination device for high-throughput sample processing, comprising: The base has multiple first receiving parts arranged in an array; A movable partition, located above the base, has through holes corresponding to the first receiving portion, the through holes being used to support the sample processing column; and Standard perforated plate; The movable partition has a first working position and a second working position; When in the first working position, the movable partition is located on the base, and the lower outlet of the sample processing column is opposite to the corresponding first receiving part; When in the second working position, the standard multi-well plate is placed between the base and the movable partition, and the lower outlet of the sample processing column is opposite to the corresponding hole of the standard multi-well plate; A wedge-shaped guide positioning mechanism is provided between the movable partition and the standard perforated plate. The wedge-shaped guide positioning mechanism is configured such that, during the process of horizontally pushing the standard perforated plate between the base and the movable partition, the movable partition is first guided to contact via an inclined surface, causing the movable partition to be lifted and laterally aligned relative to the standard perforated plate until the two reach a predetermined relative position. At this point, the movable partition is stably supported on the standard perforated plate, and the through hole is precisely aligned with the corresponding hole of the standard perforated plate, thus completing the switch to the second working position.

[0008] Furthermore, the wedge-shaped guide positioning mechanism includes: The first wedge-shaped guide portions are disposed on both sides of the lower surface of the movable partition; and Second wedge guides are disposed on both sides of the upper surface of the standard porous plate and match the first wedge guide; The first wedge-shaped guide and the second wedge-shaped guide have complementary cross-sectional shapes in the horizontal direction. When they are fully closed, they together form a rectangular positioning part, at which point the movable partition reaches the second working position.

[0009] Furthermore, the first wedge-shaped guide portion has a lower inclined surface, and the second wedge-shaped guide portion has an upper inclined surface.

[0010] Furthermore, the wedge-shaped guide positioning mechanism also includes an anti-detachment structure, which is a T-shaped or dovetail-shaped convex rail disposed on the lower inclined surface of the first wedge-shaped guide portion, and a sliding groove disposed on the upper inclined surface of the second wedge-shaped guide portion that matches the convex rail.

[0011] Furthermore, the lower surface of the movable partition is provided with an annular positioning flange surrounding the through hole. When in the second working position, the lower end face of the annular positioning flange presses against the upper surface of the standard perforated plate.

[0012] Furthermore, the device also includes a cover plate that can cover the movable partition carrying the sample processing column, the cover plate having an array of openings and an interface for connecting negative or positive pressure equipment.

[0013] Secondly, the present invention proposes a high-throughput sample processing method, which is implemented based on the aforementioned integrated desalination device for high-throughput sample processing, and the method includes the following steps: S1: The movable partition carrying multiple sample processing columns is placed on the base, so that the movable partition is in the first working position, and the sample processing operation is performed, and the waste liquid is collected in the first container. S2: Push the standard perforated plate horizontally from the side of the device between the base and the movable partition; during the pushing process, the movable partition is laterally limited by the wedge-shaped guide positioning mechanism, and is automatically lifted and translated into position under the push of the standard perforated plate until it is stably supported on the standard perforated plate, reaching the second working position. S3: In the second working position, an elution operation is performed, and the target component is directly collected into the corresponding well of the standard porous plate.

[0014] Furthermore, in step S2, the pushing operation is a linear motion in a single direction, without the need to manually adjust the movable partition in the vertical or other directions; the wedge-shaped guide positioning mechanism automatically completes the combined motion of height lifting and lateral alignment.

[0015] The beneficial effects of this invention are as follows: When the user pushes the standard perforated plate horizontally, the wedge-shaped guides of both plates first make inclined contact. This inclined contact naturally guides the movable partition to rise upwards (the movable partition is laterally limited, which can be achieved by hand blocking its side facing away from the standard perforated plate), thereby immediately disengaging any positioning flanges (if present) from the potential interference area with the perforated plate's cavity region, clearing obstacles for the continued deepening of the perforated plate. The entire pushing process is smooth and unobstructed. During continuous linear pushing, the mating inclined surfaces not only provide lifting force but also automatically correct the relative position of the movable partition and the perforated plate on the horizontal plane through inclined surface constraints. The user only needs to perform a single linear pushing action, and the device automatically completes the combined lifting and alignment movement without any additional manual adjustment. When the perforated plate is pushed to the end point, the first and second wedge-shaped guides completely close. At this time, the two cooperate to form a rectangular positioning part, firmly locking the movable partition in the predetermined second working position (height H2). Simultaneously, the through holes on the movable partition and the holes on the perforated plate must achieve a precise one-to-one correspondence. Anti-detachment structures, such as the fit between a T-shaped convex rail and a sliding groove, can be installed on the wedge-shaped mating inclined surface. This not only ensures smooth pushing but also prevents the movable partition from accidentally detaching from the perforated plate during subsequent operations (such as when transferring the device or starting centrifuge), ensuring the safety and reliability of the experimental process. Attached Figure Description

[0016] Figure 1 This is a schematic diagram of the integrated desalination device for high-throughput sample processing of the present invention in its first working position; Figure 2 This is a schematic diagram of the integrated desalination device for high-throughput sample processing of the present invention in its second working position; Figure 3 for Figure 2 A schematic diagram of the decomposed structure; Figure 4 for Figure 3 An enlarged structural diagram of point A.

[0017] In the diagram: 1-base; 11-first receiving part; 2-Modible partition; 21-Through hole; 22-Annular positioning flange; 23-First wedge-shaped guide; 3-Sample processing column; 5-Standard perforated plate; 51-Second wedge-shaped guide; 61-convex rail; 62-slide groove. Detailed Implementation

[0018] The present invention will be further described in detail below with reference to the accompanying drawings and specific embodiments.

[0019] Please see Figure 1In this embodiment, the integrated desalination device for high-throughput sample processing is in the first working position (i.e., washing / waste collection mode).

[0020] The device mainly includes: a base 1, a movable partition 2, and an optional standard porous plate 5 (not installed at this time). The base 1 is typically made of robust engineering plastic (such as polypropylene or polycarbonate) and is about the size of a standard 96-well plate. The upper surface of the base 1 is machined with a plurality of first receptacles 11 arranged in an 8×12 array. In this embodiment, these first receptacles 11 are bottom-closed cylindrical blind holes, the diameter and depth of which are designed to receive and temporarily store waste liquid flowing down from the sample processing column.

[0021] The movable partition 2 is also made of a lightweight and sturdy material, and its planar dimensions match those of the base 1. The movable partition 2 has through holes 21 that correspond one-to-one with the first receiving portion 11. Each through hole 21 is used to hold an independent sample processing column 3, such as a commercially available 10μL or 200μL micro-solid phase extraction chromatography column. Figure 4 As shown, on the lower surface of the movable partition 2, a downwardly extending annular positioning flange 22 is provided around each through hole 21. Its inner diameter is slightly larger than the outer diameter of the sample processing column 3, serving to provide radial positioning for the inserted chromatography column and prevent excessive movement. On the two opposite long sides of the movable partition 2, an elongated first wedge-shaped guide portion 23 is integrally formed. This guide portion 23 has a convex structure with a downwardly sloping surface.

[0022] During initial operation, the required number of sample processing columns 3 are inserted into the through holes 21 of the movable partition 2, and then the entire movable partition 2 is placed stably on the upper surface of the base 1. At this time, the movable partition 2 is completely supported by the base 1 and is in the first working position (height denoted as H1). The lower end faces of all annular positioning flanges 22 are in contact with the upper surface of the base 1, and the lower end outlet of each sample processing column 3 is suspended directly above the corresponding first receiving part 11 (blind hole), at a distance of about 1-3 mm. With this configuration, sample loading, equilibration, washing, and other operations can be performed. If the entire device is placed in a centrifuge for centrifugation, the waste liquid is thrown into the blind hole of the base 1 and collected under the action of centrifugal force.

[0023] Once the washing step is complete and the purified target component (such as a peptide) needs to be collected, switch to the second working position (i.e., elution / sample collection mode). Please refer to [link to documentation]. Figure 2 , Figure 3At this point, a standard multiwell plate 5 is required, such as a clean 96-well mass spectrometry plate or PCR plate. The size of this standard multiwell plate 5 is adapted to the base 1. At corresponding positions on its two long sides, a second wedge-shaped guide 51 is provided, which mates with the first wedge-shaped guide 23 on the movable partition 2. The second wedge-shaped guide 51 can be a groove structure with an upper inclined surface, the angle of which is perfectly matched with the lower inclined surface of the first wedge-shaped guide 23, and the two present complementary shapes in the horizontal cross-section.

[0024] The operator holds the standard perforated plate 5 and horizontally aligns it with the gap between the base 1 and the movable partition 2 from one side of the device. At the initial moment of insertion, the inclined surface of the second wedge-shaped guide portion 51 at the leading edge of the standard perforated plate 5 begins to contact the inclined surface of the first wedge-shaped guide portion 23 of the movable partition 2. Because the movable partition 2 is laterally restricted (for example, the operator can gently block the side of the movable partition 2 opposite to the insertion direction with their hand, or achieve this through other simple limiting designs), the continuous linear thrust causes the two inclined surfaces to slide relative to each other.

[0025] The interaction of these inclined planes produces two effects: 1. A vertical component force is generated, which smoothly lifts the movable partition 2 upward, causing the annular positioning flange 22 on its lower surface to immediately disengage from the base 1 and rise to a height sufficient to avoid the edge of the holes on the perforated plate 5; 2. Through the geometric constraints of the inclined planes, the precise alignment of the movable partition 2 and the perforated plate 5 in the horizontal direction (perpendicular to the pushing direction) is automatically corrected and maintained.

[0026] As the porous plate 5 is fully pushed to the preset endpoint, the inclined surfaces of the first wedge-shaped guide 23 and the second wedge-shaped guide 51 engage completely, closing the two sections. This structure securely locks the movable partition 2 in the predetermined second working position (height denoted as H2, H2>H1). Simultaneously, the entire weight of the movable partition 2 is supported by the standard porous plate 5 below. More importantly, due to the precise positioning effect of the guiding mechanism, each through-hole 21 on the movable partition 2 (and the outlet of the internal sample processing column 3) is necessarily precisely aligned vertically with the corresponding collection hole on the standard porous plate 5.

[0027] At this point, elution can be performed. For example, the entire apparatus (including the base 1, the porous plate 5 on it, the movable partition 2 supported on the plate, and the chromatography column 3) can be placed in a centrifuge for centrifugation and elution. The eluent will fall directly and accurately into the wells of the porous plate 5 below. After elution, simply pull out the porous plate 5 fully loaded with sample horizontally for subsequent analysis. After pulling out the porous plate 5, the movable partition 2 will automatically fall back to the base 1 under gravity, returning to the first working position, ready for cleaning or next use.

[0028] To further enhance the stability and safety of the device during dynamic operations (such as vibration during transfer, centrifugal start / stop), in some embodiments, the wedge-guided positioning mechanism is reinforced with an added anti-detachment structure.

[0029] like Figure 2 As shown, a T-shaped convex rail 61 is integrally formed along the length direction on the lower inclined surface of the first wedge-shaped guide portion 23 of the movable partition 2. Correspondingly, a T-shaped groove 62 that perfectly matches the shape of the T-shaped convex rail 61 is machined on the upper inclined surface of the second wedge-shaped guide portion 51 of the standard perforated plate 5.

[0030] During the mode switching process of pushing in the porous plate 5, the T-shaped convex rail 61 slides along the T-shaped groove 62. This not only ensures a smoother pushing action and a straighter trajectory, but more importantly, when the two are fully engaged in the second working position, the T-shaped interlocking structure effectively prevents the movable partition 2 from laterally shifting perpendicular to the pushing direction or accidentally detaching upwards on the porous plate 5. This is crucial for ensuring that the entire assembly (partition, chromatography column, porous plate) functions as a stable whole during centrifugation, greatly enhancing the reliability and safety of operation. In addition to the T-shape, the anti-detachment structure can also adopt a dovetail shape or other convex rail and groove combination with similar anti-detachment effects.

[0031] In some embodiments, the first wedge-shaped guide portion 23 on the lower surface of the movable partition 2 remains a convex strip with a downward slope. The second wedge-shaped guide portion 51 on the upper surface of the standard perforated plate 5 is no longer designed as a groove, but rather as a convex strip with a complementary upward slope. When the two are joined, positioning is achieved by the slopes of the two convex strips abutting and merging, ultimately through their vertical sides. This method of engagement may be simpler to manufacture while still achieving all the core functions of slope-guided lifting, alignment, and final vertical locking.

[0032] It should be noted that the first receiving part 11 is not limited to a blind hole, but can also be a mounting hole for tightly inserting an independent micro centrifuge tube (such as a 0.6 mL tube) to facilitate centralized treatment of waste liquid.

[0033] The positions of the first wedge-shaped guide 23 and the second wedge-shaped guide 51 are not limited to the long side; depending on the design of the pushing direction, they can also be set on the short side.

[0034] The apparatus and method described in this invention are not limited to the 96-hole specification, but are also applicable to other standard array specifications such as 48-hole and 384-hole.

[0035] The sample processing column 3 is not limited to a peptide desalting column, but can also be other microchromatographic columns or filtration columns used for desalting, purification, and filtration.

[0036] To facilitate observation or pressure application, a transparent cover plate (not shown in the figure) can be added above the device. The cover plate can be equipped with an array of observation windows and a universal interface for connecting negative / positive pressure equipment to achieve pressure-driven column flow or elution.

[0037] The above are merely preferred embodiments of the present invention. The scope of protection of the present invention is not limited to the above embodiments. All technical solutions falling within the scope of the present invention's concept are within the scope of protection of the present invention. It should be noted that for those skilled in the art, any improvements and modifications made without departing from the principle of the present invention should also be considered within the scope of protection of the present invention.

Claims

1. An integrated desalination device for high-throughput sample processing, characterized in that, include: The base has multiple first receiving parts arranged in an array; A movable partition is located above the base. The movable partition has through holes that correspond one-to-one with the first receiving part. The through holes are used to support the sample processing column. as well as Standard perforated plate; The movable partition has a first working position and a second working position; When in the first working position, the movable partition is located on the base, and the lower outlet of the sample processing column is opposite to the corresponding first receiving part; When in the second working position, the standard multi-well plate is placed between the base and the movable partition, and the lower outlet of the sample processing column is opposite to the corresponding hole of the standard multi-well plate; A wedge-shaped guide positioning mechanism is provided between the movable partition and the standard perforated plate. The wedge-shaped guide positioning mechanism is configured such that, during the process of horizontally pushing the standard perforated plate between the base and the movable partition, the movable partition is first guided to contact via an inclined surface, causing the movable partition to be lifted and laterally aligned relative to the standard perforated plate until the two reach a predetermined relative position. At this point, the movable partition is stably supported on the standard perforated plate, and the through hole is precisely aligned with the corresponding hole of the standard perforated plate, thus completing the switch to the second working position.

2. The integrated desalination device for high-throughput sample processing according to claim 1, characterized in that, The wedge-shaped guide positioning mechanism includes: The first wedge-shaped guide portions are disposed on both sides of the lower surface of the movable partition; and Second wedge guides are disposed on both sides of the upper surface of the standard porous plate and match the first wedge guide; The first wedge-shaped guide portion and the second wedge-shaped guide portion have complementary cross-sectional shapes in the horizontal direction. When the two are fully closed, they together form a rectangular positioning portion, at which point the movable partition reaches the second working position.

3. An integrated desalination device for high-throughput sample processing according to claim 2, characterized in that, The first wedge-shaped guide portion has a lower inclined surface, and the second wedge-shaped guide portion has an upper inclined surface.

4. An integrated desalination device for high-throughput sample processing according to claim 3, characterized in that, The wedge-shaped guide positioning mechanism also includes an anti-detachment structure, which is a T-shaped or dovetail-shaped convex rail disposed on the lower inclined surface of the first wedge-shaped guide portion, and a sliding groove disposed on the upper inclined surface of the second wedge-shaped guide portion that matches the convex rail.

5. An integrated desalination device for high-throughput sample processing according to claim 1, characterized in that, The lower surface of the movable partition is also provided with an annular positioning flange surrounding the through hole. When in the second working position, the lower end face of the annular positioning flange presses against the upper surface of the standard perforated plate.

6. An integrated desalination device for high-throughput sample processing according to claim 1, characterized in that, The device also includes a cover plate that can cover the movable partition carrying the sample processing column. The cover plate has an array of openings and an interface for connecting negative or positive pressure equipment.

7. A high-throughput sample processing method, characterized in that, The method is implemented based on the integrated desalination device for high-throughput sample processing according to any one of claims 1-6, and the method includes the following steps: S1: The movable partition carrying multiple sample processing columns is placed on the base, so that the movable partition is in the first working position, and the sample processing operation is performed, and the waste liquid is collected in the first container. S2: Push the standard perforated plate horizontally from the side of the device between the base and the movable partition; during the pushing process, the movable partition is laterally limited by the wedge-shaped guide positioning mechanism, and is automatically lifted and translated into position under the push of the standard perforated plate until it is stably supported on the standard perforated plate, reaching the second working position. S3: In the second working position, an elution operation is performed, and the target component is directly collected into the corresponding well of the standard porous plate.

8. The high-throughput sample processing method according to claim 7, characterized in that, In step S2, the pushing operation is a linear motion in a single direction, without the need to manually adjust the movable partition in the vertical or other directions; the wedge-shaped guide positioning mechanism automatically completes the combined motion of height lifting and lateral alignment.

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