Sample imaging method and device, storage medium, equipment and program product
By performing sample loading and electrophoresis operations in parallel in multiple channels of the electrophoresis chip, and acquiring sample imaging images in parallel, the problems of long time consumption and unstable detection quality of traditional electrophoresis methods are solved, thus improving detection efficiency and quality.
Patent Information
- Application Number
- CN202511235003.8
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-08-29
- Publication Date
- 2026-01-16
AI Technical Summary
Traditional electrophoresis methods are time-consuming and have unstable detection quality. Especially in fully automated electrophoresis processes, the sequential steps of sample aspiration, sample loading, electrophoresis, and photography lead to low overall detection efficiency. Nucleic acid fragments diffuse when left to stand in the buffer solution, affecting the clarity and resolution of electrophoretic bands.
By performing sample loading and electrophoresis operations in parallel, samples are sequentially loaded and electrophoresed in multiple channels of the electrophoresis chip, and images of the channels that have completed electrophoresis are taken to obtain sample imaging images, thus realizing parallel processing of sample loading and electrophoresis.
It effectively shortens the total time required for sample imaging, improves the efficiency and consistency of the sample imaging process, enhances detection quality, and reduces the impact of nucleic acid fragment diffusion.
Smart Images

Figure CN121347633A_ABST
Abstract
Description
TECHNICAL FIELD
[0001] The present application relates to the technical field of biological detection, in particular to a sample imaging method and device, a storage medium, equipment and a program product. BACKGROUND
[0002] With the application of nucleic acid fragment quality control in more and more industries and fields, its quality control technology is also developing. The commonly used nucleic acid fragment separation and detection technology is based on electrophoresis chip electrophoresis operation, which is widely used because of its simple operation and intuitive results. However, the traditional electrophoresis method has problems such as long time consumption and unstable detection quality. Especially in the whole process of automatic electrophoresis, the steps of sample suction, sample addition, electrophoresis and photographing are usually carried out in sequence, which leads to low overall detection efficiency, and the long time standing of the sample in the buffer solution may cause the diffusion of the nucleic acid fragments, affecting the clarity and resolution of the electrophoresis bands. SUMMARY
[0003] The embodiments of the present application provide a sample imaging method, device, storage medium, equipment and program product, which effectively shortens the total time required for sample imaging by performing sample addition operation and electrophoresis operation in parallel, improves the efficiency and continuity of the sample imaging process, and improves the detection quality.
[0004] In one aspect, the embodiments of the present application provide a sample imaging method applied to an electrophoresis chip, the electrophoresis chip having a plurality of flow channels for containing a to-be-tested sample, the method comprising:
[0005] sequentially performing sample addition operation on each of the flow channels, and performing electrophoresis operation on the flow channels that have completed the sample addition operation, so that the to-be-tested sample in the flow channels completes electrophoresis separation, wherein after the N-1th flow channel completes the sample addition operation, the Nth flow channel is subjected to sample addition operation, and the N-1th flow channel is subjected to electrophoresis operation, after the Nth flow channel completes the sample addition operation, the Nth flow channel is subjected to electrophoresis operation, 1
[0006] performing photographing on each flow channel that has completed the electrophoresis operation to obtain a sample imaging image corresponding to each flow channel.
[0007] In another aspect, the embodiments of the present application provide a sample imaging device applied to an electrophoresis chip, the electrophoresis chip having a plurality of flow channels for containing a to-be-tested sample, the device comprising:
[0008] a processing unit, configured to sequentially perform sample adding operation on each of the flow channels, and perform electrophoresis operation on the flow channel on which the sample adding operation is completed, so that the sample to be tested in the flow channel is subjected to electrophoresis separation, wherein after the sample adding operation on the (N-1)th flow channel is completed, the sample adding operation on the Nth flow channel is continued, and the electrophoresis operation on the (N-1)th flow channel is performed, and after the sample adding operation on the Nth flow channel is completed, the electrophoresis operation on the Nth flow channel is performed, 1 < N ≤ total number of flow channels, and N is a natural number;
[0009] an acquisition unit, configured to take a photo of each flow channel on which the electrophoresis operation is completed, so as to acquire a sample imaging image corresponding to each flow channel.
[0010] In another aspect, the embodiment of the present application provides a computer readable storage medium, which stores a computer program, and the computer program is adapted to be loaded by a processor to execute the sample imaging method according to any one of the above embodiments.
[0011] In another aspect, the embodiment of the present application provides a computer device, which comprises a processor and a memory, and the memory stores a computer program, and the processor is configured to execute the sample imaging method according to any one of the above embodiments by calling the computer program stored in the memory.
[0012] In another aspect, the embodiment of the present application provides a computer program product, which comprises computer instructions, and the computer instructions are executed by a processor to implement the sample imaging method according to any one of the above embodiments.
[0013] The sample imaging method provided by the embodiment of the present application is applied to an electrophoresis chip, and the electrophoresis chip has a plurality of flow channels for accommodating samples to be tested. In the method, sample adding operation is sequentially performed on each of the flow channels, and electrophoresis operation is performed on the flow channel on which the sample adding operation is completed, so that the sample to be tested in the flow channel is subjected to electrophoresis separation. After the sample adding operation on the (N-1)th flow channel is completed, the sample adding operation on the Nth flow channel is continued, and the electrophoresis operation on the (N-1)th flow channel is performed. After the sample adding operation on the Nth flow channel is completed, the electrophoresis operation on the Nth flow channel is performed, 1 < N ≤ total number of flow channels, and N is a natural number. Each flow channel on which the electrophoresis operation is completed is taken a photo, so as to acquire a sample imaging image corresponding to each flow channel. The embodiment of the present application effectively shortens the total time required for sample imaging by performing sample adding operation and electrophoresis operation in parallel, improves the efficiency and continuity of the sample imaging process, and improves the detection quality. BRIEF DESCRIPTION OF DRAWINGS
[0014] In order to more clearly illustrate the technical solutions in the embodiments of the present application, the following will briefly introduce the drawings needed in the embodiment description. Obviously, the drawings in the following description only some embodiments of the present application, and for those skilled in the art, other drawings can also be obtained from these drawings without creative labor.
[0015] In order to more clearly illustrate the technical solutions in the embodiments of the present application, the following will briefly introduce the drawings needed in the embodiment description.
[0016] Figure 1 The flowchart of the sample imaging method provided by the embodiments of the present application is shown in the figure.
[0017] Figure 2 The schematic diagram of the analysis device provided by the embodiments of the present application is shown in the figure.
[0018] Figure 3 The partial enlarged view of part A of the analysis device provided by the embodiments of the present application is shown in the figure. Figure 2
[0019] Figure 4 The schematic diagram of the fixed plate provided by the embodiments of the present application is shown in the figure.
[0020] Figure 5 The schematic diagram of the electrophoresis fixed plate provided by the embodiments of the present application is shown in the figure.
[0021] Figure 6 The schematic diagram of the imaging mechanism provided by the embodiments of the present application is shown in the figure.
[0022] Figure 7 The schematic diagram of the analysis device provided by the embodiments of the present application is shown in the figure.
[0023] Figure 8 The partial enlarged view of part B of the analysis device provided by the embodiments of the present application is shown in the figure. Figure 7
[0024] Figure 9 The schematic diagram of the baffle provided by the embodiments of the present application is shown in the figure.
[0025] Figure 10 The movement schematic diagram of the pusher and the baffle provided by the embodiments of the present application is shown in the figure.
[0026] Figure 11 The schematic diagram of the sample adding mechanism provided by the embodiments of the present application is shown in the figure.
[0027] Figure 12 The partial enlarged view of part C of the sample adding mechanism provided by the embodiments of the present application is shown in the figure. Figure 11
[0028] Figure 13 A schematic diagram of an electrophoretic chip substrate provided in an embodiment of this application;
[0029] Figure 14 A schematic diagram of the structure of a first type of printed electrode layer projected orthogonally onto the first surface of an electrophoretic chip substrate provided in an embodiment of this application;
[0030] Figure 15 A schematic diagram of the structure of the second type of printed electrode layer projected onto the first surface of the electrophoretic chip substrate provided in the embodiments of this application;
[0031] Figure 16 This is a schematic diagram of the second surface of the electrophoretic chip substrate provided in an embodiment of this application;
[0032] Figure 17 A schematic diagram of the structure of the electrophoretic chip cover plate provided in the embodiments of this application, wherein a first type of printed electrode layer is disposed on the fourth surface;
[0033] Figure 18 A schematic diagram of a structure in which a second type of printed electrode layer is disposed on the fourth surface of an electrophoretic chip cover plate provided in an embodiment of this application;
[0034] Figure 19 A schematic diagram of the third surface of the electrophoretic chip cover provided in an embodiment of this application;
[0035] Figure 20 A schematic diagram of another electrophoresis chip provided for an embodiment of this application;
[0036] Figure 21 A schematic diagram of a substrate for another electrophoretic chip provided in an embodiment of this application;
[0037] Figure 22 The embodiments of the present invention are based on Figure 21 A magnified view of part D;
[0038] Figure 23 A timing diagram showing the breakdown of concurrent full-process electrophoresis steps for implementation of this application;
[0039] Figure 24 This is a schematic diagram of the sample imaging device provided in the embodiments of this application;
[0040] Figure 25 A schematic diagram of the structure of a computer device provided in an embodiment of this application. Detailed Implementation
[0041] With reference to the drawings of the embodiments of the present application, the technical solutions in the embodiments of the present application will be clearly and completely described. Obviously, the described embodiments are only a part of the embodiments of the present application, but not all the embodiments of the present application. Based on the embodiments of the present application, all the other embodiments obtained by a person of ordinary skill in the art without creative work fall within the scope of the present application.
[0042] The following will be described in detail respectively. It should be noted that the description order of the following embodiments is not limited as the priority order of the embodiments.
[0043] With the application of nucleic acid fragment quality control in more and more industries and fields, its quality control technology is also developing. The commonly used nucleic acid fragment separation and detection technology is electrophoresis operation based on electrophoresis chip, which is widely used because of its simple operation and intuitive results. However, the traditional electrophoresis method has problems such as long time consumption and unstable detection quality. Especially in the whole process of automatic electrophoresis, the steps of sample suction, sample addition, electrophoresis and photographing are usually carried out in sequence, which leads to low overall detection efficiency, and the long time standing of the sample in the buffer may cause the diffusion of the nucleic acid fragments, affecting the clarity and resolution of the electrophoresis bands. Specifically, the traditional whole process automatic steps are as follows:
[0044] (1) placing the sample to be tested and the chip;
[0045] (2) selecting the number of electrophoresis flow channels;
[0046] (3) detecting the number of available flow channels of the chip;
[0047] (4) detecting the number of available guns;
[0048] (5) pressing the chip to the puncture position to perform puncture in sequence;
[0049] (6) the pipette takes the gun;
[0050] (7) the pipette sucks the sample;
[0051] (8) the pipette adds the sample;
[0052] (9) each flow channel needs to take the gun, suck the sample and add the sample, and all the flow channels are repeated in sequence;
[0053] (10) pressing the chip to the electrophoresis position, and all the flow channels are electrophoresed at the same time;
[0054] (11) after the electrophoresis is completed, the photographing is performed from the first detection flow channel in sequence;
[0055] (12) the algorithm recognizes and processes the image;
[0056] (13) outputting the result;
[0057] Following the above steps, each flow channel requires repeating the three steps of picking up the pipette tip, aspirating the sample, and loading the sample. After loading the sample into the first flow channel and taking the picture in the last flow channel, a relatively long waiting time is required. If the sample is left to stand for too long, the nucleic acid fragment molecules in the sample will move and diffuse throughout the buffer chamber and gel. The sample bands will not be sufficiently aggregated, resulting in phenomena such as band dispersion, band "blurring", and "tailing" during electrophoresis. The bands will no longer be in the optimal aggregation state. At this time, the sample results obtained after processing the band images by the algorithm will also be distorted.
[0058] In addition, in traditional fully automated electrophoresis, the four actions of sample aspiration, sample loading, electrophoresis, and photographing are performed sequentially. Each action requires all electrophoresis channels to be completed before the next step can be performed. The subsequent channels have to wait for the previous channels to complete the entire process, and the overall time required will also increase as the number of electrophoresis channels increases.
[0059] Therefore, this application provides a sample imaging method that can effectively shorten the total time required for sample imaging by performing sample loading and electrophoresis operations in parallel, thereby improving the efficiency and continuity of the sample imaging process and enhancing detection quality.
[0060] like Figure 1 As shown, this application provides a sample imaging method, which can be applied to an analytical device and an electrophoresis chip. Before describing the sample imaging method, the analytical device and the electrophoresis chip are first introduced. Please refer to... Figures 2 to 12 The analytical apparatus 10 includes:
[0061] The base plate 100 has a first cavity 110.
[0062] The chip fixing mechanism 200 is disposed on the base plate 100 and includes at least one analysis station located in the first cavity 110. The analysis station is used to vertically place the electrophoresis chip 2000, which has multiple channels 2140 for accommodating the sample to be tested.
[0063] The sample loading mechanism 600 is used to sequentially load samples into each of the multiple channels 2140 in the electrophoresis chip 2000.
[0064] An electrophoresis apparatus 300, mounted on a base plate 100, is used to perform electrophoresis on the flow channel 2140 after sample loading, so that the samples to be tested within the flow channel 2140 are separated by electrophoresis; and
[0065] An imaging mechanism 400, mounted on a base plate 100, is used to take pictures of each channel 2140 that has completed the electrophoresis operation, so as to obtain an image of the sample corresponding to each channel 2140.
[0066] In some embodiments, the analysis device 10 further includes a blocking mechanism 500 disposed in the first cavity 110 and corresponding to the location of the analysis station, including at least one recycling station.
[0067] In this embodiment, when the electrophoresis chip 2000 is located at the analysis station, the chip fixing mechanism 200 fixes the electrophoresis chip 2000, and the blocking mechanism 500 prevents the electrophoresis chip 2000 from falling. The sample loading mechanism 600 sequentially loads samples into each of the multiple channels 2140 within the electrophoresis chip 2000. The electrophoresis mechanism 300 performs electrophoresis on the channels 2140 within the electrophoresis chip 2000 where the sample loading operation has been completed, so that the samples to be tested within the channels 2140 are separated by electrophoresis. The imaging mechanism 400 takes pictures of each channel that has completed the electrophoresis operation to obtain an image of the sample corresponding to each channel. Finally, the chip fixing mechanism 200 releases the electrophoresis chip 2000, and the blocking mechanism 500 moves, causing the electrophoresis chip 2000 to fall to the recycling station.
[0068] The base plate 100 can be designed as a square structure, and the chip fixing mechanism 200, electrophoresis mechanism 300, imaging mechanism 400 and blocking mechanism 500 are disposed on the base plate 100. Multiple support feet are provided on the lower surface of the base plate 100 to provide support for the base plate 100.
[0069] In this embodiment, the electrophoresis chip 2000 can be directly placed at the analysis station of the chip fixing mechanism 200, or it can be placed at the entrance of the analysis device 10. A moving mechanism, such as a robotic arm or conveyor belt, can then move the electrophoresis chip 2000 from the entrance to the analysis station of the chip fixing mechanism 200. When the electrophoresis chip 2000 is at the analysis station, the chip fixing mechanism 200 secures it, preventing movement during subsequent electrophoretic separation and imaging. At this time, the blocking mechanism 500 is in its initial position, preventing the electrophoresis chip 2000 from falling. After the chip fixing mechanism 200 fixes the electrophoresis chip 2000, the sample loading mechanism 600 sequentially loads samples into each of the multiple channels 2140 within the electrophoresis chip 2000. The electrophoresis mechanism 300 performs electrophoresis on the channels 2140 within the electrophoresis chip 2000 where samples have been loaded, enabling the samples to be tested within the channels 2140 to undergo electrophoretic separation. The imaging mechanism 400 takes a picture of each channel 2140 that has completed the electrophoresis operation to obtain an image of the sample corresponding to each channel 2140. The obtained image images are then analyzed to determine information such as the fragment length, concentration, and integrity of the sample. After the analysis is completed, the chip fixing mechanism 200 releases the electrophoresis chip 2000, no longer fixing it, allowing the electrophoresis chip 2000 to move. The blocking mechanism 500 moves from its initial position, and the electrophoresis chip 2000 falls to the recovery station after losing the blocking effect of the blocking mechanism 500. After completing the analysis and recycling of one electrophoresis chip 2000, the same operation is performed on the next electrophoresis chip 2000 until the analysis and recycling of all electrophoresis chips 2000 are completed.
[0070] The analytical apparatus 10 provided in this application can perform electrophoretic analysis on a sample containing biological substances such as DNA, RNA, or proteins using electrophoresis technology. In this document, "sample" and "sample to be analyzed" refer to the same thing: the sample loaded into the electrophoresis chip 2000 for analysis.
[0071] For example, taking a nucleic acid sample containing DNA or RNA as the test sample, when the electrophoresis chip 2000 is in the analysis station, after the chip fixing mechanism 200 fixes the electrophoresis chip 2000, the sample loading mechanism 600 sequentially loads samples into each of the multiple channels 2140 in the electrophoresis chip 2000. The electrophoresis mechanism 300 performs electrophoresis on the channels 2140 in the electrophoresis chip 2000 where the sample loading operation has been completed, so that the test samples in the channels 2140 are separated by electrophoresis. That is, the electrophoresis mechanism 300 applies a voltage to the nucleic acid samples in the channels 2140 in the electrophoresis chip 2000 where the sample loading operation has been completed. The nucleic acid samples move under the action of the electric field force. Since there are nucleic acid fragments of different lengths in the nucleic acid samples, differential separation of nucleic acid fragments of different lengths is achieved, forming multiple bands. After the nucleic acid samples undergo electrophoretic separation, the imaging mechanism 400 photographs each channel 2140 that has completed the electrophoresis operation to obtain a sample imaging image corresponding to each channel 2140. The photographed sample imaging images are then analyzed to determine information such as the length, concentration, and integrity of the nucleic acid fragments corresponding to each band in the nucleic acid sample. After the analysis is complete, the chip fixing mechanism 200 releases the electrophoresis chip 2000, the blocking mechanism 500 moves, and the electrophoresis chip 2000 falls to the recycling station. For samples containing other biological materials, the same process can be performed: sample addition by the sample addition mechanism 600, electrophoresis separation by the electrophoresis mechanism 300, and imaging by the imaging mechanism 400. Finally, the photographed sample imaging images are analyzed to complete the analysis process.
[0072] Furthermore, a molecular weight standard (ladder) is set up. The nucleic acid sample and the molecular weight standard undergo electrophoretic separation under the influence of an electric field. In subsequent analysis based on the obtained images, the standard reference band separated by the molecular weight standard is used as a benchmark. The information of the standard reference band separated by the molecular weight standard and the information of the separated nucleic acid sample (i.e., the brightness and position information of the band objects in the sample imaging image) are compared to calculate the band information in the nucleic acid sample (test sample) corresponding to each flow channel 2140. This band information includes the corresponding nucleic acid fragment length, concentration, and nucleic acid integrity index. Of course, it is possible to calculate the nucleic acid fragment length, concentration, and nucleic acid integrity index corresponding to the separated band objects directly from the information of the nucleic acid sample after electrophoretic separation without setting up a molecular weight standard.
[0073] In this embodiment, as Figure 2 , Figure 7 , Figure 8 , Figure 9 , Figure 10The blocking mechanism 500 includes: a baffle 520 disposed in the first cavity 110 and corresponding to the location of the analysis station; and a first driving member 510 drivenly connected to the baffle 520.
[0074] The first driving component 510 can drive the baffle 520 to move. If the first driving component 510 is a motor, the baffle 520 is provided with a protrusion 522, and the output shaft of the motor is connected to the protrusion 522. When the motor is working, it drives the protrusion 522 to move through the output shaft, thereby driving the baffle 520 to move. To save space, the first driving component 510 is located below the base plate 100.
[0075] The baffle 520 is designed with a square structure. Whether the electrophoresis chip 2000 is placed vertically or horizontally at the analysis station, the baffle 520 can prevent the electrophoresis chip 2000 from falling. After the baffle 520 moves, it loses its blocking effect and the electrophoresis chip 2000 can fall to the recycling station. The baffle 520 is located in the first cavity 110, and the horizontal surface of the baffle 520 is flush with the first cavity 110. This ensures that the electrophoresis chip 2000 can move smoothly without unevenness in the contact surface.
[0076] When the electrophoresis chip 2000 is placed in the analysis station, the baffle 520 is in its initial position, which can block the electrophoresis chip 2000 and prevent it from falling. After the electrophoresis chip 2000 has completed the analysis, the first driving unit 510 drives the baffle 520 to move, and the electrophoresis chip 2000 loses the blocking effect of the baffle 520 and falls to the recycling station.
[0077] In some specific embodiments of this application, reference is made to Figure 2 and Figure 7 The blocking mechanism 500 also includes a bending plate 530 with a certain bending angle disposed in the first cavity 110 and corresponding to the location of the analysis station. When the electrophoresis chip 2000 falls, it falls along the bending plate 530 to the recycling station.
[0078] The bending plate 530 has through holes 211 on both sides. Screws passing through the through holes 211 allow the bending plate 530 to be fixedly connected to the inner wall of the first cavity 110. The bending plate 530 is made of a material that is not easily deformed, such as iron, steel, or aluminum alloy. The bending plate 530 includes a first surface and a second surface, forming a certain bending angle between the first surface and the second surface, such as 50°, 60°, 70°, or other angles. After the sample to be tested in the electrophoresis chip 2000 has been analyzed, the first driving component 510 drives the baffle 520 to move. The electrophoresis chip 2000 loses the obstruction of the baffle 520 and begins to fall. The electrophoresis chip 2000 first falls onto the first surface, then along the first and second surfaces, and falls to the recycling station, or first falls onto the second surface, and then along the second surface, and falls to the recycling station.
[0079] The bending plate 530 provides a certain guiding function to prevent the electrophoresis chip 2000 from falling smoothly into the recycling station. Furthermore, the bending plate 530 provides a certain cushioning function to prevent damage to the electrophoresis chip 2000 and leakage of the test sample inside the electrophoresis chip 2000 when it falls from top to bottom into the recycling station.
[0080] In some specific embodiments of this application, the recycling station is equipped with a waste wafer bin. After the sample to be analyzed within the electrophoresis chip 2000 is completed, the blocking mechanism 500 moves, and the electrophoresis chip 2000 falls into the waste wafer bin of the recycling station. After all electrophoresis chips 2000 have been analyzed or after a certain period of time, the user can recycle the analyzed electrophoresis chips 2000 from the waste wafer bin.
[0081] In this embodiment, as Figures 2 to 4 The chip fixing mechanism 200 includes a fixing plate 210 and a pushing mechanism that provides a pushing force to the electrophoretic chip 2000 placed on the fixing plate. The fixing plate 210 includes through holes 211 provided on a first side and a second side. Under the pushing force of the pushing mechanism, the electrophoretic chip 2000 is placed close to the fixing plate 210.
[0082] The fixing plate 210 is fixedly mounted on the base plate 100. The electrophoretic chip 2000 is vertically mounted and, under the push of the pushing mechanism, is placed tightly against the fixing plate 210. A single electrophoretic chip 2000 can be used, with one side of the chip receiving a pushing force from the pushing mechanism and the other side receiving a force from the fixing plate 210. Multiple electrophoretic chips 2000 can also be used, with each chip attached to the other. One chip in contact with the pushing mechanism receives a pushing force from the mechanism, while another chip in contact with the fixing plate 210 is placed tightly against the fixing plate 210 under the push of the mechanism.
[0083] When the electrophoresis chip 2000 is initially in the analysis station, it may be in a slightly tilted state. The second driving member 221 drives the pushing member 222 to move, and the pushing member 222 provides a thrust to the electrophoresis chip 2000. The electrophoresis chip 2000 is subjected to the thrust from one side and the force of the fixing plate 210 on the other side, and rotates slightly to become vertical and is placed in close contact with the fixing plate 210.
[0084] When one electrophoresis chip 2000 is set up, it is placed vertically. The second driving component 221 drives the pushing component 222 to move, providing a thrust to one side of the electrophoresis chip 2000, while the other side of the electrophoresis chip 2000 is in close contact with the fixing plate 210. After the sample to be tested in the electrophoresis chip 2000 has been analyzed, the second driving component 221 drives the pushing component 222 to move, and the electrophoresis chip 2000 loses the thrust provided by the pushing component 222, entering a released state. The blocking mechanism 500 then moves, causing the electrophoresis chip 2000 to fall to the recycling station. Then, the next electrophoresis chip 2000 is placed, and the analysis and recycling process begins.
[0085] When multiple electrophoresis chips 2000 are arranged, they are placed vertically. The second driving component 221 drives the pushing component 222 to move, providing a pushing force to the electrophoresis chips 2000 in contact with it. The fixing plate 210 provides a force to the electrophoresis chips 2000 in contact with it. The electrophoresis chips 2000 are in close contact with each other, and the position of the electrophoresis chip 2000 closest to the fixing plate 210 is the analysis station. After the sample to be analyzed in the electrophoresis chip 2000 in the analysis station is completed, the second driving component 221 drives the pushing component 222 to move, and the electrophoresis chip 2000 in the analysis station is released. The blocking mechanism 500 moves, causing the electrophoresis chip 2000 in the analysis station to fall to the recycling station. The blocking mechanism 500 moves and resets, and the second driving component 221 drives the pushing component 222 to move again, causing the remaining electrophoresis chips 2000 to be in close contact with each other, and the next electrophoresis chip 2000 moves to the analysis station. Repeat the above steps to ensure that the next electrophoresis chip 2000 has also been analyzed and recycled. Continue this process until all electrophoresis chips 2000 have been analyzed and recycled before placing the next batch of electrophoresis chips 2000 for analysis and recycling.
[0086] In other embodiments, the chip fixing mechanism 200 may also have other design structures. For example, the chip fixing mechanism 200 may be a gripper. When the electrophoresis chip 2000 is in the analysis station, the gripper clamps the electrophoresis chip 2000 to fix it in place. After the electrophoresis chip 2000 has completed the analysis, the gripper releases the electrophoresis chip 2000, blocking the movement of the blocking mechanism 500, causing the electrophoresis chip 2000 in the analysis station to fall to the recycling station.
[0087] In this embodiment, as Figure 7 and Figure 10As shown, the pushing mechanism includes a second driving member 221 and a pushing member 222. The pushing member 222 includes a straight plate 2221 and a vertical plate 2222. The straight plate 2221 is drivenly connected to the second driving member 221. One end of the vertical plate 2222 is fixedly connected to the straight plate 2221, and the other end of the vertical plate 2222 passes through the first cavity 110 and contacts the electrophoretic chip 2000 placed on the fixing plate 210 of the chip fixing mechanism 200. The second driving member 221 can drive the pushing member 222 to move. If the second driving member 221 is a motor, the output shaft of the motor is connected to the straight plate 2221. When the motor is working, it drives the straight plate 2221 to move through the output shaft, thereby driving the pushing member 222 to move as a whole. The pushing member 222 provides thrust to the electrophoretic chip 2000 in contact with it.
[0088] To save space, the second drive unit 221 is located below the base plate 100.
[0089] refer to Figures 9 to 10 The baffle 520 is designed with a square structure, and its two sides can prevent the electrophoresis chip 2000 from falling. The baffle 520 has a through cavity 521 inside. When the vertical plate 2222 of the pusher 222 passes through the first cavity 110, it also passes through the through cavity 521 of the baffle 520, so that the pusher 222 can move freely without being affected by the baffle 520.
[0090] refer to Figure 10 The process of discarding the electrophoresis chip 2000 is described in detail below. When the electrophoresis chip 2000 is in the analysis station, the second driving component 221 drives the pushing component 222 to move in the opposite direction to direction a, so that the electrophoresis chips 2000 are in close contact with each other. The electrophoresis mechanism 300 performs electrophoretic separation on the sample to be tested within the electrophoresis chip 2000 in the analysis station, and the imaging mechanism 400 then takes an image of the sample to be tested. Then, the second driving component 221 drives the pushing component 222 to move in direction a, and the electrophoresis chip 2000 loses the thrust provided by the pushing component 222. The first driving component 510 drives the baffle 520 to move in direction a, causing the electrophoresis chip 2000 to fall into the recycling station.
[0091] In this embodiment, reference Figure 4 The fixing plate 210 includes through holes 211 provided on a first side and a second side. (See reference) Figure 5 The electrophoresis apparatus 300 includes an electrophoresis fixation plate 310 and a probe. (Reference) Figure 3 The electrophoresis fixing plate 310 is adjacent to the fixing plate 210 of the chip fixing mechanism 200. The first and second sides of the electrophoresis fixing plate 310 are provided with probe holes 311 for accommodating probes. The probe holes 311 correspond to the through holes 211 on the fixing plate 210 of the chip fixing mechanism 200.
[0092] In some embodiments, the first side and the second side of the fixing plate 210 are the upper side and the lower side of the fixing plate 210, respectively, and the first side and the second side of the electrophoresis fixing plate 310 are the upper side and the lower side of the electrophoresis fixing plate 310, respectively.
[0093] The electrophoresis fixation plate 310 is fixedly mounted on the base plate 100 and is disposed adjacent to the fixation plate 210. The probe is fixedly mounted in the probe holes 311 on the first and second sides of the electrophoresis fixation plate 310 and passes through the through holes 211 on the first and second sides of the fixation plate 210.
[0094] When the electrophoresis chip 2000 is in the analysis station, the probe contacts the electrophoresis chip 2000 and applies voltage to the electrophoresis chip 2000, thereby causing the sample to be tested to be separated by electrophoresis within the electrophoresis chip 2000.
[0095] In this embodiment, reference Figure 6 The imaging mechanism 400 in the analysis device 10 includes a camera 410 and at least one light source 420. After the electrophoresis mechanism 300 performs electrophoretic separation on the sample to be tested within the electrophoresis chip 2000, the light source 420 provides light, the camera 410 takes an image of the sample to be tested within the electrophoresis chip 2000, and analyzes the image.
[0096] In this embodiment, two light sources 420 are provided, emitting light of different wavelengths. In some embodiments, one light source 420 emits light of a first wavelength, exciting a first optically detectable mark on the sample to generate a first optical signal, and a camera 410 captures the first optical signal to form an image of the sample. The other light source 420 emits light of a second wavelength, exciting a second optically detectable mark on the ladder to generate a second optical signal, and a camera 410 captures the second optical signal to form an image of the ladder. The first and second optically detectable marks may be the same or different.
[0097] In this embodiment, reference Figure 6 and Figure 11 The base plate 100 is provided with a second cavity 120. The imaging mechanism 400 includes a first guide rail 430 provided on the base plate 100, a support plate 440 provided on the first guide rail 430, a third drive member 450 provided below the base plate 100, and a connecting plate 460 with one end connected to the third drive member 450 and the other end passing through the second cavity 120 and connected to the support plate 440. Under the driving action of the third drive member 450, the connecting plate 460 drives the support plate 440 to move on the first guide rail 430. The camera 410 and the light source 420 are provided on the support plate 440.
[0098] The third driving component 450 can drive the connecting plate 460 to move. If the third driving component 450 is a motor, the output shaft of the motor is connected to the connecting plate 460, and when the motor is working, it drives the connecting plate 460 to move through the output shaft.
[0099] To save space, the third drive unit 450 is located below the base plate 100.
[0100] A slider can be mounted on the first guide rail 430, and a support plate 440 is mounted on the slider. When the third driving member 450 moves the support plate 440, the support plate 440 moves the slider on the first guide rail 430.
[0101] The third driving component 450 moves the connecting plate 460, which in turn moves the carrier plate 440 on the first guide rail 430. The carrier plate 440 then moves the camera 410 and the light source 420, enabling the camera 410 to take pictures of different positions on the electrophoresis chip 2000. Because each flow channel 2140 operates independently, the camera 410 does not need to wait for all flow channels 2140 to complete electrophoresis and can take pictures of the ready flow channels 2140.
[0102] In this embodiment, the sample loading mechanism 600 includes a sample holder 610 and a sample loading component for extracting the sample to be tested from the sample holder 610 and loading the sample to be tested into the flow channel 2140 in the electrophoresis chip 2000.
[0103] The sample storage device 610 is mounted on the base plate 100 and includes a sample storage base and a multi-well plate mounted on the sample storage base, such as a 96-well plate.
[0104] The sample loading component moves to the corresponding position of the sample to be tested on the multi-well plate, extracts the sample, and then moves to the corresponding position on the electrophoresis chip 2000 to load the sample into the flow channel 2140 of the electrophoresis chip 2000. Multiple operations of the sample loading component can load different samples into different flow channels 2140 of the electrophoresis chip 2000.
[0105] In some specific embodiments of this application, such as Figure 2 and Figure 7 As shown, the sample loading assembly includes: a sampler 621, a first driving component 622, a second driving component 623, and a third driving component 624.
[0106] The sampler 621 is mounted on the first drive assembly 622, such as... Figure 11 This includes a puncture needle 6211 and a sample application needle 6212 disposed on the first drive assembly 622. The first drive assembly 622 drives the sample application device 621 in a first direction (e.g., Figure 2The first drive assembly 622 is disposed on the second drive assembly 623, and the second drive assembly 623 drives the first drive assembly 622 and the sampler 621 to move in the second direction (e.g., the z-direction shown); the first drive assembly 622 is disposed on the second drive assembly 623, and the second drive assembly 623 drives the first drive assembly 622 and the sampler 621 to move in the second direction (e.g., the z-direct Figure 1 The second drive component 623 is mounted on the third drive component 624, and the third drive component 624 drives the second drive component 623, the first drive component 622, and the third drive component 624 in the third direction (e.g., the y-direction shown); the second drive component 623 is mounted on the third drive component 624, and the third drive component 624 drives the second drive component 623, the first drive component 622, and the third drive Figure 1 The sampler 621 moves in the x-direction (as shown). This allows the sampler 621 to move in the first, second, and third directions, enabling it to successfully complete the sample dispensing operation.
[0107] In some specific embodiments of this application, reference is made to Figure 7 , Figure 11 and Figure 12 The first drive assembly 622 includes a first moving plate 6221, a second guide rail 6222, a first synchronous belt 6223, a first driving wheel 6224, a first driven wheel 6225, and a fourth drive member 6226. The second drive assembly 623 includes a second moving plate 6231, a third guide rail 6232, a second synchronous belt 6233, a second driving wheel 6234, a second driven wheel 6235, and a fifth drive member 6236. The third drive assembly 624 includes a fourth guide rail 6241, a third synchronous belt 6242, a third driving wheel 6243, a third driven wheel 6244, and a sixth drive member 6245.
[0108] Two fourth guide rails 6241 are provided, one on each side of the base plate 100. A second movable plate 6231 is mounted on the fourth guide rail 6241 and fixedly connected to the third synchronous belt 6242. The third synchronous belt 6242 is arranged around the third driving wheel 6243 and the third driven wheel 6244. The third driving wheel 6243 and the third driven wheel 6244 are mounted on the base plate 100. A sixth driving member 6245 drives and connects to the third driving wheel 6243. The third guide rail 6232 is mounted on the second movable plate 6231. A first movable plate 6221 is mounted on the third guide rail 6232 and fixedly connected to the second synchronous belt 6233. The second synchronous belt 6233 is arranged around the second... A driving wheel 6234 and a driven wheel 6235 are provided. The second driving wheel 6234 and the second driven wheel 6235 are provided on the second moving plate 6231. A fifth driving member 6236 drives and connects to the second driving wheel 6234. A second guide rail 6222 is provided on the first moving plate 6221. A sampler 621 is provided on the second guide rail 6222 and is fixedly connected to the first synchronous belt 6223. The first synchronous belt 6223 is provided around the first driving wheel 6224 and the first driven wheel 6225. The first driving wheel 6224 and the first driven wheel 6225 are provided on the first moving plate 6221. A fourth driving member 6226 drives and connects to the first driving wheel 6224.
[0109] The fourth driving component 6226 can drive the first driving wheel 6224 to rotate. If the fourth driving component 6226 is a motor, the output shaft of the motor is connected to the first driving wheel 6224. When the motor is working, it drives the first driving wheel 6224 to rotate through the output shaft.
[0110] The fifth driving component 6236 can drive the second driving wheel 6234 to rotate. If the fifth driving component 6236 is a motor, the output shaft of the motor is connected to the second driving wheel 6234. When the motor is working, it drives the second driving wheel 6234 to rotate through the output shaft.
[0111] The sixth driving component 6245 can drive the third driving wheel 6243 to rotate. If the sixth driving component 6245 is a motor, the output shaft of the motor is connected to the third driving wheel 6243. When the motor is working, it drives the third driving wheel 6245 to rotate through the output shaft.
[0112] When the fourth driving component 6226 is working, it transmits power to the first driving wheel 6224. The first driving wheel 6224 rotates, driving the first synchronous belt 6223 and the first driven wheel 6225 to rotate. Since the sampler 621 is fixedly connected to the first synchronous belt 6223, the sampler 621 moves in the first direction.
[0113] When the fifth driving component 6236 is working, it transmits power to the second driving wheel 6234. The second driving wheel 6234 rotates, driving the second synchronous belt 6233 and the second driven wheel 6235 to rotate. Since the first moving plate 6221 is fixedly connected to the second synchronous belt 6233, the first moving plate 6221 moves in the second direction. The sample dispenser 621 is set on the first moving plate 6221, which also enables the sample dispenser 621 to move in the second direction.
[0114] When the sixth driving component 6245 is working, it transmits power to the third driving wheel 6243. The third driving wheel 6243 rotates, driving the third synchronous belt 6242 and the third driven wheel 6244 to rotate. Since the second moving plate 6231 is fixedly connected to the third synchronous belt 6242, the second moving plate 6231 moves upward in the third direction. The first moving plate 6221 is set on the second moving plate 6231, which also enables the second moving plate 6231 and the sampler 621 to move upward in the third direction.
[0115] The sampler 621 and the first synchronous belt 6223 can be fixedly connected by providing at least one through hole on the first synchronous belt 6223, and passing a fastener such as a screw through the through hole and into the sampler 621 to fix the two together.
[0116] The first moving plate 6221 and the second synchronous belt 6233 can be fixedly connected by providing at least one through hole on the second synchronous belt 6233, and passing a fastener such as a screw through the through hole and into the first moving plate 6221 to fix the two together.
[0117] The second movable plate 6231 and the third synchronous belt 6242 can be fixedly connected by providing at least one through hole on the third synchronous belt 6242, and passing a fastener such as a screw through the through hole and into the second movable plate 6231 to fix the two together.
[0118] A slider can be installed on the second guide rail 6222, and the sampler 621 is installed on the slider. When the fourth driving member 6226 drives the sampler 621 to move, the sampler 621 drives the slider to move on the second guide rail 6222.
[0119] A slider can be set on the third guide rail 6232. The first moving plate 6221 is set on the slider. When the fifth driving member 6236 drives the first moving plate 6221 to move, the first moving plate 6221 drives the slider to move on the third guide rail 6232.
[0120] A slider can be set on the fourth guide rail 6241, and the second moving plate 6231 is set on the slider. When the sixth driving member 6245 drives the second moving plate 6241 to move, the second moving plate 6241 drives the slider to move on the fourth guide rail 6241.
[0121] In some specific embodiments of this application, reference is made to Figure 7 The sample loading assembly also includes a pipette tip holder 630 disposed on the base plate 100. The pipette tip holder 630 is provided with a plurality of first storage cavities for placing new pipette tips and at least one second storage cavity for placing old pipette tips. The second storage cavity is provided with a slot so that the old pipette tip on the sample loading needle 6212 can be removed and dropped into the second storage cavity.
[0122] The nozzle is a tip tip. After the tip tip is attached, the sample needle 6212 can extract the sample to be tested from the sample storage 610 and load the sample to be tested into the flow channel 2140 of the chip 2000.
[0123] The flow process of the pipette 621 is described in detail below. When the chip 2000 is in the analysis station, the pipette 621 moves above the first storage chamber of the pipette tip holder 630. The pipette 621 moves downward to place the pipette tip onto the sampling needle 6212. The pipette 621 moves upward and moves above the sample holder 610. The pipette 621 moves downward to extract the sample to be tested. The sampler 621 moves upward and above the electrophoresis chip 2000. At this point, the puncture needle 6211 is positioned above the flow channel 2140 of the electrophoresis chip 2000 to be sampled. The sampler 621 moves downward, and the puncture needle 6211 punctures the electrophoresis chip 2000. The sampler 621 moves upward and slightly upward, at which point the sampler needle 6212 is positioned above the flow channel 2140 of the punctured electrophoresis chip 2000. The sampler 621 moves downward, loading the sample to be tested into the flow channel 2140. The sampler 621 moves upward and above the second storage cavity of the pipette tip holder 630. The sampler 621 moves downward and engages the pipette tip in the slot. The sampler 621 moves upward, causing the pipette tip to be removed from the sampler needle 6212 and fall into the second storage cavity. In other embodiments, the above steps can be interchanged. For example, the puncture can be performed first, then the pipette tip can be put on the sampling needle 6212, and then the sample can be taken, added, and the pipette tip can be removed. Alternatively, the pipette tip can be put on the sampling needle 6212 first, then the puncture can be performed, and then the sample can be taken, added, and the pipette tip can be removed.
[0124] Please see Figures 13 to 19 The embodiments of this application provide an electrophoresis chip 2000 that can perform electrophoresis operations simultaneously with sample loading operations.
[0125] Electrophoretic chip 2000 includes substrate 2100 and cover plate 2200 covering substrate 2100;
[0126] The substrate 2100 is provided with a plurality of flow channels 2140 for accommodating the sample to be tested. Each flow channel 2140 has a sample dispensing position with a sample dispensing groove 2160. The extension direction a of the sample dispensing groove 2160 is the same as the extension direction b of the corresponding flow channel 2140.
[0127] Each flow channel 2140 has an electrode assembly 2120 at both ends. Each flow channel 2140 is offset from the electrode contact end 2211 of the corresponding electrode assembly 2120, so that the extension direction of the sample loading groove 2160 does not intersect with the vertical center line direction of the electrode contact end 2211.
[0128] In this system, the electrophoresis chip 2000 is placed vertically in the analysis position, and the two electrode assemblies 2120 located at both ends of the flow channel 2140 are the positive electrode assembly and the negative electrode assembly, respectively. The probe of the electrophoresis mechanism 300 contacts the electrode assembly 2120, generating a voltage applied to the sample to be tested in the flow channel 2140, thereby realizing the electrophoretic separation of the sample to be tested. Specifically, after the chip fixing mechanism 200 fixes the electrophoresis chip 2000, the sample loading mechanism 600 sequentially loads samples into each of the multiple channels 2140 in the electrophoresis chip 2000. The electrophoresis mechanism 300 performs electrophoresis on the channels 2140 in the electrophoresis chip 2000 where the sample loading operation has been completed, so that the test samples in the channels 2140 can be separated by electrophoresis. The imaging mechanism 400 takes pictures of each channel 2140 that has completed the electrophoresis operation to obtain the sample imaging image corresponding to each channel 2140. Then, the sample imaging images obtained by taking pictures are analyzed to obtain information such as the fragment length, concentration and integrity of the test sample. In this embodiment, the flow channel 2140 is misaligned with the electrode contact end 2211 of the corresponding electrode assembly 2120, and the extension direction of the sample loading groove 2160 does not intersect with the vertical center line direction of the electrode contact end 2211. This eliminates spatial interference, enables the parallel execution of the sample loading operation and the electrophoresis operation, and improves the detection efficiency of the electrophoresis chip 2000.
[0129] The substrate 2100 and cover plate 2200 can be made of inorganic insulating materials, organic insulating materials, polymer insulating materials, composite materials, or a combination of materials. The substrate 2100 is preferably made of polypropylene, which has good light transmittance and does not release ions from its surface in an aqueous environment. It can also minimize electroosmosis without surface treatment, thereby avoiding affecting the electrophoretic separation process of the sample to be tested.
[0130] In this embodiment, the substrate 2100 can be made of a transparent material, which can ensure that when the imaging mechanism 400 takes pictures of the sample, it can successfully obtain clear pictures without the pictures being blurry due to the substrate 2100.
[0131] In this embodiment, as Figures 13-16 The substrate 2100 of the electrophoresis chip 2000 has a first surface α and a second surface β opposite to the first surface α. Electrode holes 2110 penetrate the first surface α and the second surface β. Flow channels 2140 are disposed on the first surface α of the substrate 2100.
[0132] like Figures 17-19 The cover plate 2200 has a third surface γ and a fourth surface δ opposite to the third surface γ. The fourth surface δ of the cover plate 2200 covers the first surface α of the substrate 2100, and the printed electrode layer 2210 is disposed on the fourth surface δ of the cover plate 2200.
[0133] During the testing process, the electrophoresis chip 2000 is placed vertically. The probes of the 16 channels of the electrophoresis mechanism 300 will be inserted horizontally from the side electrode hole 2110 of the substrate 2100, pass through the second surface β of the substrate 2100 and the first surface α of the substrate 2100 in sequence, and finally contact the motor contact end 2211 on the printed electrode layer 2210 on the fourth surface δ of the cover plate 2200.
[0134] In this embodiment, as Figure 14 , Figure 15 , Figure 17 , Figure 18 As shown, the electrode assembly 2120 includes electrode holes 2110 disposed on the substrate 2100 and a printed electrode layer 2210 disposed on the cover plate 2200. (Referring to...) Figure 14 , Figure 15 When the cover plate 2200 is applied to the substrate 2100, the printed electrode layer 2210 projected onto the first surface α of the substrate 2100 is shown by dashed lines. The electrode contact ends 2211 of the printed electrode layer 2210 correspond to the electrode holes 2110, and each flow channel 2140 is offset from the electrode contact ends 2211 and electrode holes 2110 of the corresponding electrode assembly 2120. The electrode assembly 2120 adopts a structure in which the electrode holes 2110 provided on the substrate 2100 are combined with the printed electrode layer 2210 provided on the cover plate 2200, and the electrode contact ends 2211 of the printed electrode layer 2210 correspond to the electrode holes 2110, while each flow channel 2140 is offset from the electrode contact ends 2211 and electrode holes 2110 of the corresponding electrode assembly 2120. This design not only eliminates spatial interference and ensures that the sample loading and electrophoresis operations can be performed in parallel to improve detection efficiency, but also controls the consistency of the testing process conditions for each sample through the cooperation of the electrode hole 2110 and the printed electrode layer 2210 to ensure repeatability.
[0135] The surface of the substrate 2100 is generally provided with grooves and protrusions. The printed circuit solution on the substrate 2100 can easily flow into the microstructure, causing short circuits or broken lines. In order to ensure that the electrode is formed in one step and the electrode reliability, the graphene printed electrode needs to be printed on the cover plate 2200. Only the electrode hole 2110 needs to be opened on the substrate 2100, which does not involve the electrode crossing the bonding surface.
[0136] In this embodiment, the printed electrode layer 2210 is preferably a graphene printed electrode, but other inert metal electrodes, such as copper electrodes, platinum electrodes, and gold electrodes, can also be used. The structure and composition of the printed electrode layer 2210 are shown in the figure. Figure 17 , Figure 18 middle.
[0137] In some specific embodiments of this application, for the electrode assembly 2120 formed after the cover plate 2200 is placed over the substrate 2100, such as Figure 14 and Figure 17 As shown, the printed electrode layer 2210 includes an electrode contact end 2211, a contact end 2212, and a connecting portion 2213 for connecting the electrode contact end 2211 and the contact end 2212. The connecting portion 2213 of the printed electrode layer 2210 includes a horizontal portion 22131 and a vertical portion 22132. One end of the horizontal portion 22131 is connected to the contact end 2212, and the other end of the horizontal portion 22131 is connected to one end of the vertical portion 22132. The other end of the vertical portion 22132 is connected to the electrode contact end 2211. The horizontal portion 22131 of the connecting portion 2213 spans the buffer chamber 2150 of the flow channel 2140, and the width of the horizontal portion 22131 is greater than 1.5 mm. In order to reduce the current density on the surface of the electrophoresis chip 2000 electrode, thereby reducing the risk of power failure caused by local aggregation of electrolytic bubbles, and at the same time providing sufficient space for sample aggregation after sample addition and ensuring that the graphene printed electrode can still effectively contact the buffer solution in the chamber 2150 after electrolysis, the upper edge of the horizontal part 22131 is more than 0.5 mm away from the top of the buffer solution chamber 2150, and the lower edge of the horizontal part 22131 is more than 1.5 mm away from the narrowest point of the buffer solution chamber 2150.
[0138] In other embodiments of this application, for the electrode assembly 2120 formed after the cover plate 2200 is placed over the substrate 2100, such as Figure 15 and Figure 18 As shown, the printed electrode layer 2210 includes an electrode contact end 2211, a contact end 2212, and a connecting portion 2213 for connecting the electrode contact end 2211 and the contact end 2212. The connecting portion 2213 of the printed electrode layer 2210 includes a horizontal portion 22131 and a bent portion 22133. One end of the horizontal portion 22131 is connected to the contact end 2212, one end of the bent portion 22133 is connected to the middle position of the horizontal portion 22131, and the other end of the bent portion 22133 is connected to the electrode contact end 2211.
[0139] In this embodiment, to ensure reliable thermal bonding of the substrate, the minimum bonding distance between the electrode holes 2110 and the flow channels 2140 of the electrophoretic chip 2000 is greater than 1.0 mm, ensuring a good seal between the electrode holes 2110 and the flow channels 2140. The minimum bonding distance refers to the minimum permissible distance between the centers of two adjacent bonding points, such as pads, leads, or bumps, in chip packaging or circuit board manufacturing. It is a key parameter for ensuring the reliability of the bonding process and avoiding short circuits or mechanical interference.
[0140] In this embodiment, Figure 14 , Figure 15It can be shown that the diameter of the electrode contact end 2211 is larger than the diameter of the electrode hole 2110. For example, taking the substrate 2100 as having 16 flow channels 2140 for accommodating the sample to be tested as an example, since the first surface α of the substrate 2100 has 16 flow channels 2140, and both ends of the flow channels 2140 are printed with printed electrode layers 2210, considering the positioning accuracy requirements during hot pressing, the diameter of the electrode contact end 2211 of the printed electrode layer 2210 is 0.2 mm larger than the diameter of the electrode hole 2110 on the substrate 2100, so that the electrode contact end 2211 can fully fill the electrode hole 2110 and achieve contact between the metal electrode (electrode hole 2110) and the graphene electrode (electrode contact end 2211).
[0141] In this embodiment, as Figure 14 , Figure 15 As shown, the contact end 2212 of the printed electrode layer 2210 of the electrophoresis chip 2000 corresponds to the end 2130 of the corresponding flow channel 2140. The connecting portion 2213 of the printed electrode layer 2210 bypasses the side or end 2130 of the corresponding flow channel 2140 so that the electrode contact end 2211 is misaligned with the corresponding flow channel 2140. This design eliminates spatial interference, enables parallel sample loading and electrophoresis operations to improve detection efficiency, and further optimizes the layout of the electrodes and flow channels. The bypass design can make full use of the space layout so that the electrophoresis and puncture sample loading processes in each flow channel 2140 can be performed independently.
[0142] During sample testing, when the electrophoresis chip 2000 is placed vertically, the probe of the electrophoresis mechanism 300, which performs electrophoresis on each channel 2140, is horizontally inserted into the electrode hole 2110 to contact the electrode contact end 2211 of the printed electrode layer 2210, thereby generating a voltage applied to the sample to be tested in the channel 2140 and realizing electrophoretic separation of the sample to be tested.
[0143] In some specific embodiments of this application, such as Figure 13 , Figure 14 , Figure 15As shown, in the non-edge channels 2140 of the electrophoresis chip 2000, the connecting portion 2213 of the corresponding printed electrode layer 2210 is disposed around the side or end 2130 of the corresponding channel 2140, so that the corresponding electrode contact end 2211 is located in the interval region between adjacent channels 2140. For the edge channels 2140, the connecting portion 2213 of the corresponding printed electrode layer 2210 is disposed around the side or end 2130 of the corresponding channel 2140, so that the corresponding electrode contact end 2211 is located on the side of the corresponding channel 2140 away from the adjacent channel 2140, or the electrode contact end 2211 of one edge channel 2140 is located on the side of the corresponding channel 2140 away from the adjacent channel 2140, and the electrode contact end 2211 of the other edge channel 2140 is located in the interval region between the other edge channel 2140 and the adjacent channel 2140. This design eliminates spatial interference, enabling parallel sample loading and electrophoresis operations to improve detection efficiency, and further optimizes the layout of the electrode contacts. Furthermore, placing the electrode contacts 2211 strategically in the intervening area or away from adjacent flow channels fully utilizes the internal space of the electrophoresis chip 2000, avoiding interference from the electrode contacts 2211 with the sample within the flow channel 2140, and improving electrophoretic separation. Simultaneously, this layout facilitates accurate contact between the probes of the electrophoresis mechanism 300 and the electrode contacts 2211, enhancing operational stability and reliability.
[0144] In this embodiment, the electrophoresis chip 2000 is sample tested. The sampling needle 6212 and / or puncture needle 6211 of the sampling mechanism 600, which is used to perform sample addition operation on each flow channel 2140, are vertically inserted into the sample addition groove 2160. The vertical movement path of the sampling needle 6212 and / or puncture needle 6211 does not overlap with the horizontal movement path of the probe in spatial projection.
[0145] The electrophoresis chip 2000 in this application is structured such that the electrode holes 2110 and the test channels 2140 are staggered. When one or more channels 2140 are undergoing electrophoresis, the remaining available channels 2140 can still continue to perform operations such as sample loading, sample loading waiting, and post-sample loading electrophoresis, which can save time. Since the probes passing through the electrode holes 2110 and the sample loading needles 6212 and / or puncture needles 6211 inserted into the sample loading slots 2160 are avoided, the puncture, sample loading, and electrophoresis processes among the 16 channels 2140 are all independent of each other, realizing parallel sample loading and electrophoresis operations, effectively shortening the total time required for sample imaging. By optimizing time and improving efficiency, it is also possible to control the intervals of each test process for each sample to be tested to be the same, thereby improving consistency and ensuring repeatability.
[0146] In some embodiments, the analysis device 10 may also be adapted to, for example, Figures 20 to 22 The electrophoresis chip 3000 is shown.
[0147] The electrophoresis chip 3000 includes a cover plate 3200 disposed on a substrate 3100. The substrate 3100 has multiple flow channels 3110, and electrode assemblies 3120 are disposed at both ends of each flow channel 3110. Since there are multiple flow channels, and each flow channel 3110 has electrode assemblies 3120 at both ends, each flow channel 3110 can be loaded with one sample. Therefore, after loading samples into each flow channel 3110, multiple samples can be simultaneously separated by electrophoresis and imaged, greatly improving analysis efficiency. The substrate 3100 has corresponding grooves 3130 at the sample loading positions of each flow channel 3110, and the recess direction of the grooves 3130 is the same as the setting direction of the corresponding flow channel 3110. Figure 21 d is the recessed direction of groove 3130, c is the setting direction of flow channel 3110, and the setting direction of flow channel 3110 is the length direction of flow channel 3110.
[0148] The substrate 3100 can be made of inorganic insulating materials, organic insulating materials, polymer insulating materials, composite materials, or a combination of materials. The substrate 3100 is preferably made of polypropylene, which has good light transmittance and does not release ions from its surface in an aqueous environment. It can also avoid electroosmosis without surface treatment, thereby avoiding affecting the electrophoretic separation process of the sample to be analyzed.
[0149] The electrode assembly 3120 includes a contact end 3121, a contact end 3122, and a connection end 3123 connecting the contact end 3121 and the contact end 3122. The contact end 3122 contacts the corresponding flow channel 3110. The contact end 3121 is disposed on a boss 3140 formed between two adjacent grooves 3130.
[0150] The probe of the electrophoresis mechanism 300 contacts the contact end 3121, and the contact end 3121 transmits electricity to the contact end 3122 through the connection end 3123, thereby causing the electrode assembly 3120 to apply voltage to the sample to be tested in the flow channel 3110.
[0151] The contact end 3121 is disposed on the boss 3140 formed between two adjacent grooves 3130. In the substrate 3100, the structural strength and rigidity of the boss 3140 are greater than those of the grooves 3130, thereby preventing the substrate 3100 from deforming or being damaged when the probe contacts the contact end 3121 and applies force to the contact end 3121.
[0152] The cover plate 3200 is provided with a puncture hole 3210 corresponding to the contact end 3121. By providing the puncture hole 3210, the probe can pass through the puncture hole 3210 and contact the electrode assembly 3120, thereby successfully applying voltage to the sample to be tested. In addition, the puncture hole 3210 can play a certain positioning role to prevent the probe from moving to the wrong position.
[0153] The cover plate 3200 can be made of inorganic insulating materials, organic insulating materials, polymer insulating materials, composite materials, or a combination of materials. The cover plate 3200 is preferably made of polypropylene, which has good light transmittance and does not release ions from its surface in an aqueous environment. It can also avoid electroosmosis without surface treatment, thereby avoiding interference with the electrophoretic separation process of the sample to be analyzed.
[0154] For example, the flow channel 3110 includes an intermediate channel 3112 and a first channel 3111 and a second channel 3113 disposed at both ends of the intermediate channel 3112. The centerline of the intermediate channel 3112 is straight, and the first channel 3111 and the second channel 3113 are disposed at both ends of the centerline of the intermediate channel 3112. The interior of the intermediate channel 3112 is filled with gel and buffer solution. The electrode assembly 3120 is disposed on the substrate 3100, such as... Figure 22 The contact end 3121 is disposed on the substrate 3100, and the connection end 3123 and the contact end 3122 extend to the first channel 3111 or the second channel 3113, and the contact end 3122 contacts the first channel 3111 or the second channel 3113.
[0155] If the first channel 3111 contacts the negative electrode assembly 3120 and the second channel 3113 contacts the positive electrode assembly 3120, then the first channel 3111 is the liquid inlet channel, and the sample loading position is set on the liquid inlet channel. The second channel 3113 is the liquid storage channel, and the sample to be tested is loaded into the first channel 3111. When the probe of the electrophoresis mechanism 300 contacts the electrode assembly 3120 and generates a voltage applied to the sample to be tested in the first channel 3111, the sample to be tested moves from the first channel 3111 to the second channel 3113 under the action of the electric field force. The gel has a porous structure and can be used as a sieving medium. The buffer solution plays a role in maintaining the degree of dissociation, thereby realizing the differential separation of sample fragments of different lengths. Sample fragments of different lengths form strips in the flow channel, completing the electrophoretic separation process. If the first channel 3111 contacts the positive electrode assembly 3120 and the second channel 3113 contacts the negative electrode assembly 3120, then the first channel 3111 serves as a storage channel and the second channel 3113 serves as an inlet channel, loading the sample to be tested into the second channel 3113. When the probe of the electrophoresis mechanism 300 contacts the electrode assembly 3120, generating a voltage applied to the sample to be tested in the second channel 3113, the sample to be tested moves from the second channel 3113 towards the first channel 3111 under the action of the electric field. The gel has a porous structure and can serve as a sieving medium, while the buffer solution maintains the degree of dissociation, thereby achieving differential separation of sample fragments of different lengths. Sample fragments of different lengths form bands within the flow channel, completing the electrophoretic separation process.
[0156] Please continue reading.Figure 1 , Figure 1 This is a schematic flowchart of a sample imaging method provided in an embodiment of this application. This sample imaging method can be applied to, for example... Figures 2 to 12 The analytical apparatus 10 shown, and the application to such Figures 13 to 19 The electrophoresis chip 2000 shown has multiple channels 2140 for accommodating the sample to be tested; or it can be applied to, for example... Figures 20 to 22 The electrophoresis chip 3000 shown has multiple channels 3110 for accommodating samples to be tested. The method may include the following steps:
[0157] Step 11: Perform sample loading operations sequentially on each of the flow channels, and perform electrophoresis on the flow channels after the sample loading operation is completed, so that the test samples in the flow channels are separated by electrophoresis. Specifically, after the sample loading operation is completed on the (N-1)th flow channel, the sample loading operation is performed on the Nth flow channel, and the electrophoresis operation is performed on the (N-1)th flow channel. After the sample loading operation is completed on the Nth flow channel, the electrophoresis operation is performed on the Nth flow channel. 1 < N ≤ the total number of flow channels, where N is a natural number.
[0158] Step 12: Take a picture of each channel that has completed the electrophoresis operation to obtain a sample imaging image corresponding to each channel.
[0159] For example, with Figures 2 to 13 Taking the electrophoresis chip 2000 shown as an example, the parallel electrophoresis method provided in this application includes three processes: sample loading, electrophoresis, and imaging. Each process will be described in detail below.
[0160] The sample loading operation is the initial step in the entire parallel electrophoresis process and is performed by the sample loading mechanism 600. The sample loading mechanism 600 possesses high-precision positioning and quantitative sample loading capabilities, ensuring that the sample to be tested is accurately added to each channel 2140. In actual operation, the sample loading mechanism 600 can sequentially load samples into each channel 2140 according to a preset order. For example, starting from the first channel 2140, an appropriate amount of sample to be tested is injected into the channel 2140. During the sample loading process, the sample loading mechanism 600 precisely controls the loading speed and volume to avoid sample overflow or insufficient loading. Simultaneously, to ensure uniform distribution of the sample to be tested within the channels 2140, the sample loading mechanism 600 may employ specific loading methods, such as slow dripping or pulsed loading.
[0161] Electrophoresis is a crucial step in separating the test samples within the flow channel 2140, and it is performed by the electrophoresis mechanism 300. The electrophoresis mechanism 300 applies a suitable electric field to both ends of the flow channel 2140, driving different components in the test sample to migrate at different speeds under the influence of the electric field, thereby achieving separation. The electrophoresis mechanism 300 performs electrophoresis on the flow channel 2140 after the sample loading operation, ensuring the electrophoretic separation of the test samples within the flow channel 2140. This embodiment cleverly utilizes a time difference to achieve parallel processing of sample loading and electrophoresis. Specifically, after the sample loading operation is completed in the (N-1)th flow channel 2140, the sample loading mechanism 600 does not wait for the electrophoresis operation in that flow channel 2140 to complete, but immediately continues to perform the sample loading operation in the Nth flow channel 2140. Simultaneously, the electrophoresis mechanism 300 rapidly applies an electric field to the (N-1)th flow channel 2140, where sample loading has been completed, to initiate electrophoretic separation of the sample within that flow channel 2140. Furthermore, after sample loading is completed in the Nth flow channel 2140, the electrophoresis mechanism 300 also rapidly applies an electric field to the Nth flow channel 2140 to initiate electrophoretic separation of the sample within that flow channel 2140. 1 < N ≤ the total number of flow channels 2140, where N is a natural number.
[0162] Imaging is a crucial step in obtaining the electrophoretic separation results of the samples, and it is performed by the imaging mechanism 400. The imaging mechanism 400 has high-resolution imaging capabilities, enabling it to clearly photograph each channel 2140 that has completed the electrophoresis process, thereby obtaining sample imaging images corresponding to each channel 2140.
[0163] For example, the imaging mechanism 400 sequentially images each channel 2140 that has completed the electrophoresis operation. The imaging mechanism 400 precisely controls parameters such as the shooting angle, focal length, and exposure time to ensure that the acquired sample images are of high quality and rich in information. For example, by adjusting the shooting angle, the influence of reflections and shadows on image quality can be avoided; by optimizing the focal length, sample details in the image can be made clearer; by setting the exposure time appropriately, images that are too bright or too dark can be prevented, ensuring that all components of the sample under test are clearly visible.
[0164] This embodiment of the application achieves a complete parallel operation process by performing sample loading and electrophoresis operations in parallel. It fully leverages the advantages of the electrophoresis chip's 2000+ channels 2140, ensuring close coordination between each stage from sample loading and electrophoresis to imaging. This effectively shortens the total time required for sample imaging and improves the efficiency and continuity of the sample imaging process. In the sample loading stage, by loading samples sequentially and quickly moving to the next channel 2140, waiting time during sample loading is reduced. In the electrophoresis stage, parallel electrophoresis operations on different channels 2140 are performed, fully utilizing the working time of the electrophoresis mechanism 300 and improving equipment utilization. In the imaging stage, imaging of each channel 2140 is performed in an orderly manner, ensuring that the acquired images are complete and accurate.
[0165] In some embodiments, prior to sequentially adding samples to each of the plurality of channels, the method further includes pre-treating the electrophoresis chip, the pre-treating including at least one of cleaning, drying, and dust removal.
[0166] For example, before sequentially adding samples to each of the multiple channels 2140, the electrophoresis chip 2000 is pretreated, including at least one of cleaning, drying and dust removal.
[0167] For example, pre-cleaning the electrophoresis chip 2000 can remove contaminants from the chip surface and avoid interfering with electrophoresis; drying the electrophoresis chip 2000 can prevent residual liquid from diluting the sample; and dust removal can be performed on the surface of the pre-cleaned electrophoresis chip 2000 to avoid impurities affecting image quality during photography.
[0168] In some embodiments, before sequentially performing the sample addition operation on each of the plurality of flow channels, the method further includes: calibrating the sample addition mechanism used for performing the sample addition operation, the calibration process including at least one of vertical positioning calibration, horizontal position calibration, and sample addition volume calibration.
[0169] For example, before sequentially performing a sample addition operation on each of the multiple flow channels 2140, the sample addition mechanism 600 used for the sample addition operation is calibrated, including at least one of vertical positioning calibration, horizontal position calibration, and sample addition volume calibration.
[0170] For example, vertical alignment calibration ensures that the puncture needle 6211 is aligned with the flow channel 2140. If the puncture needle is deviated in the vertical direction, it may lead to inaccurate puncture during sample loading, or even damage to the flow channel or chip, thus affecting the entire experiment. Therefore, vertical alignment calibration ensures precise vertical positioning of the puncture needle, providing a stable foundation for subsequent sample loading operations.
[0171] For example, horizontal position calibration ensures that the sampler 621 moves along a straight path, guaranteeing that each channel 2140 receives sample at the correct position. If the sampler 621 is offset in the horizontal direction, it may result in incorrect sample placement or omission, affecting the accuracy and reliability of the experimental results. Therefore, horizontal position calibration eliminates this potential risk and ensures the precision of the sample application operation.
[0172] For example, sample volume calibration can reduce sample volume errors. Deviations in sample volume can lead to inconsistent sample concentrations during experiments, affecting the comparison and analysis of results. Therefore, sample volume calibration ensures accurate sample volumes received by each flow channel, providing a strong guarantee for the smooth progress of experiments.
[0173] In some embodiments, each flow channel in the electrophoresis chip is misaligned with the corresponding electrode contact end; when the probe of the electrophoresis mechanism for performing electrophoresis contacts the corresponding electrode contact end of each flow channel in the electrophoresis chip, the moving path of the sample dispensing needle of the sample dispensing mechanism for performing sample dispensing does not overlap with the moving path of the probe in spatial projection.
[0174] like Figure 14 and Figure 15 As shown, each flow channel 2140 in the electrophoresis chip 2000 is offset from its corresponding electrode contact 2211. When the probe of the electrophoresis mechanism 300, used for electrophoresis, contacts the electrode contact 2211 of each flow channel 2140 in the electrophoresis chip 2000, the movement path of the sample dispensing needle 6212 of the sample dispensing mechanism 600, used for sample dispensing, does not overlap with the movement path of the probe in spatial projection. This offset arrangement of the flow channels 2140 and electrode contact 2211 structurally avoids collisions that may occur due to overlapping positions during operation. For example, in actual operation, when the sample dispensing needle 6212 adds the sample to the flow channel 2140, the probe can independently contact the electrode contact 2211 to perform electrophoresis-related operations without interference, eliminating spatial interference and enabling parallel processing of sample dispensing and electrophoresis operations to improve detection efficiency.
[0175] In some embodiments, the sample loading mechanism further includes a puncture needle; when the probe contacts the electrode contact end corresponding to each flow channel in the electrophoresis chip, the movement path of the puncture needle and the movement path of the probe do not overlap in spatial projection.
[0176] like Figure 11The sample application mechanism 600 also includes a puncture needle 6212. Before the sample application needle 6212 performs the sample application operation, the puncture needle 6212 first punctures into the flow channel 2140, and the puncture position of the flow channel 2140 forms a hole. Then the sample application needle 6212 passes through the hole to add the sample to be tested into the flow channel 2140. When the probe contacts the electrode contact end 2211 corresponding to each flow channel 2140 in the electrophoresis chip 2000, the movement path of the puncture needle 6211 and the movement path of the probe do not overlap in the spatial projection. The probe moves horizontally, and the path of the vertical movement of the puncture needle 6211 is separated under the misalignment design, which ensures the stability of concurrent operation.
[0177] In some embodiments, the step of sequentially adding samples to each of the plurality of channels includes: sequentially performing the operations of taking a pipette tip, aspirating a sample, and loading a sample to each of the plurality of channels.
[0178] For example, sample addition is performed sequentially in each of the multiple flow channels 2140, including: sequentially taking the pipette tip, aspirating the sample, and loading the sample into each of the multiple flow channels 2140. This sequential operation avoids cross-contamination and improves experimental safety. This process is precisely controlled by an automated sample addition mechanism 600, ensuring consistent sample volume in each flow channel 2140, thereby improving experimental accuracy. The time consumed for sample addition in each flow channel 2140 remains essentially consistent, further guaranteeing the reliability of the comparison results.
[0179] In some embodiments, the sample loading mechanism for performing the sample loading operation includes a puncture needle and a sample loading needle. The operation of sequentially picking up the pipette tip, aspirating the sample, and loading the sample in each of the plurality of flow channels includes: controlling the puncture needle to perform a puncture operation on the target flow channel; and after the puncture operation is completed, controlling the sample loading needle to sequentially perform the operation of picking up the pipette tip, aspirating the sample, and loading the sample, thereby loading the sample to be tested into the punctured target flow channel.
[0180] For example, the sample loading mechanism 600 for performing sample loading operations includes a puncture needle 6211 and a sample loading needle 6212. It sequentially performs the operations of picking up the pipette tip, aspirating the sample, and loading the sample into each of the multiple flow channels 2140. Since the puncture needle 6211 needs to pass through the sample loading groove 2160, the sample loading operation in this embodiment includes: controlling the puncture needle 6211 to puncture the target flow channel 2140; and after the puncture operation is completed, controlling the sample loading needle 6212 to sequentially perform the operations of picking up the pipette tip, aspirating the sample, and loading the sample into the punctured target flow channel 2140.
[0181] To minimize sample spillage or contamination in the electrophoresis chip 2000 (or 3000), the sample loading area of the electrophoresis chip 2000 (or 3000) typically has a certain thickness. This thickness necessitates the needle to penetrate a considerable distance, leading to low loading efficiency. Furthermore, the thickness itself is rigid, and if the needle deviates during puncture, it risks failing to accurately puncture the flow channel (flow channel 2140 on electrophoresis chip 2000, or flow channel 3110 on electrophoresis chip 3000). This application addresses this by providing a sample loading groove 2160 (electrophoresis chip 2000) and a recess 3130 (electrophoresis chip 3000) at the loading point of each flow channel. This effectively reduces the puncture distance of the needle, significantly improving sample loading efficiency and reliability. The puncture needle's aperture is typically larger than that of the sample loading needle, ensuring smooth sample loading.
[0182] In some embodiments, the sample loading mechanism for performing the sample loading operation includes a puncture needle and a sample loading needle. The operation of sequentially picking up the pipette tip, aspirating the sample, and loading the sample into each of the plurality of flow channels includes: controlling the sample loading needle to sequentially pick up the pipette tip and aspirate the sample; controlling the puncture needle to perform a puncture operation into the target flow channel; and after the puncture operation is completed, controlling the sample loading needle to load the sample to be tested into the target flow channel.
[0183] For example, the sample loading mechanism 600 for sample loading includes a puncture needle 6211 and a loading needle 6212. It sequentially performs the operations of picking up the pipette tip, aspirating the sample, and loading the sample into each of the multiple flow channels 2140. Sample loading requires the puncture needle 6211 to pass through the loading groove 2160. The order of puncture actions can be different. Therefore, in this embodiment, the sample loading operation includes controlling the loading needle 6212 to sequentially pick up the pipette tip and aspirate the sample; controlling the puncture needle 6211 to puncture the target flow channel 2140; and controlling the loading needle 6212 to load the sample into the target flow channel 2140 after the puncture operation is completed. This sequence of first aspirating the sample and then puncturing eliminates sample surface fluctuations caused by puncture vibration, making it suitable for micro-sample operations and further reducing the risk of wasting the sample.
[0184] In some embodiments, for non-edge channels, the corresponding electrode contact is located in the interval region between adjacent channels; for edge channels, the corresponding electrode contact is located on the side of the corresponding channel away from the adjacent channel; or the electrode contact corresponding to one edge channel is located on the side of the corresponding channel away from the adjacent channel, and the electrode contact corresponding to another edge channel is located in the interval region between the other edge channel and the adjacent channel, so that each channel in the electrophoresis chip is misaligned with the electrode contact corresponding to each channel.
[0185] likeFigure 14 and Figure 15 For non-edge channels 2140, the corresponding electrode contact 2211 is located in the interval region between adjacent channels 2140. For edge channels 2140, the corresponding electrode contact 2211 is located on the side of the corresponding channel 2140 away from the adjacent channel 2140. Alternatively, the electrode contact 2211 corresponding to one edge channel 2140 is located on the side of the corresponding channel 2140 away from the adjacent channel 2140, and the electrode contact 2211 corresponding to the other edge channel 2140 is located in the interval region between the other edge channel 2140 and the adjacent channel 2140, so that each channel 2140 in the electrophoresis chip 2000 and its corresponding electrode contact 2211 are misaligned. This design eliminates spatial interference, enables parallel sample loading and electrophoresis operations to improve detection efficiency, and further optimizes the layout of the electrode contact 2211. Furthermore, strategically placing the electrode contacts 2211 in the intervening area or away from adjacent flow channels fully utilizes the internal space of the electrophoresis chip 2000, avoids interference from the electrode contacts 2211 with the sample to be tested within the flow channel 2140, ensures smooth flow of the sample and uniform electric field distribution during electrophoresis, and improves the electrophoretic separation effect. Simultaneously, this layout also facilitates accurate contact between the probes of the electrophoresis mechanism 300 and the electrode contacts 2211, enhancing operational stability and reliability.
[0186] In some embodiments, the electrophoresis mechanism includes M probe groups corresponding to the total number of channels, each probe group including a positive probe and a negative probe. The electrophoresis operation on the channels after sample loading includes: before the sample loading operation of the first channel is completed, controlling all probe groups of the electrophoresis mechanism to simultaneously contact the electrode contact end of the corresponding channel; after the sample loading operation of the (N-1)th channel is completed, controlling the probe group corresponding to the (N-1)th channel to be energized to perform electrophoresis on the (N-1)th channel; after the sample loading operation of the Nth channel is completed, controlling the probe group corresponding to the Nth channel to be energized to perform electrophoresis on the Nth channel.
[0187] For example, the electrophoresis apparatus 300 is suitable for Figures 13 to 19The electrophoresis chip 2000 shown includes an electrophoresis mechanism 300 comprising M probe groups corresponding to the total number of channels 2140, where M ≤ N. Each probe group includes a positive probe and a negative probe. The mechanism performs electrophoresis on channels 2140 that have completed sample loading, including: before the first channel 2140 completes sample loading, controlling all probe groups of the electrophoresis mechanism 300 to simultaneously contact the electrode contact end 2211 of the corresponding channel 2140; after the (N-1)th channel 2140 completes sample loading, controlling the probe group corresponding to the (N-1)th channel 2140 to energize, so as to perform electrophoresis on the (N-1)th channel 2140; and after the Nth channel 2140 completes sample loading, controlling the probe group corresponding to the Nth channel 2140 to energize, so as to perform electrophoresis on the Nth channel 2140. After sample loading is completed in each channel 2140, only the corresponding probe group (positive probe and negative probe) contacts the electrode contact end 2211 of that channel 2140 and is energized, achieving precise one-to-one control and avoiding unified control of all probe groups, thus improving the accuracy and flexibility of the electrophoresis process. In the process, all probe groups are synchronously contacted with the corresponding electrode contact end 2211 before sample loading is completed in the first channel 2140, avoiding the time required for each channel 2140 to move the probe individually before electrophoresis, thus improving testing efficiency. The sample loading-electrophoresis interval for each sample is consistent, eliminating test differences caused by timing deviations.
[0188] For example, taking an electrophoresis chip 2000 with 16 channels 2140 for accommodating samples as an example, for example, M is 16, the electrophoresis mechanism 300 can have two rows of probes, with 16 probes in each row. The probe groups consisting of two corresponding probes in each row constitute the positive and negative probes. The 32 probes are fixed on the electrophoresis fixing plate 310. Before the electrophoresis operation of the first channel, all probes of the electrophoresis mechanism 300 simultaneously contact the electrode contact terminal 2211 but are not energized. After the sample loading operation of each channel 2140 is completed, the probe group corresponding to the channel 2140 where the sample loading operation is completed is energized to perform the electrophoresis operation.
[0189] In some embodiments, the method further includes: after the Nth channel completes the electrophoresis operation, controlling the probe group corresponding to the Nth channel to be de-energized; for the remaining channels that have not completed the sample loading operation, maintaining the physical contact between the corresponding probe group and the electrode contact end, but keeping them in a de-energized state until the channel completes the sample loading operation and is ready to perform the electrophoresis operation, and then controlling the corresponding probe group to be energized.
[0190] For example, after the electrophoresis operation is completed in the Nth channel 2140, the probe group corresponding to the Nth channel 2140 is de-energized. Timely de-energization after electrophoresis avoids current interference from completed channels 2140 with the electric field of adjacent channels, reducing corrosion and energy consumption caused by prolonged probe operation. For the remaining channels 2140 that have not completed sample loading, the corresponding probe group is kept in physical contact with the electrode contact 2211, but remains de-energized until the channel 2140 completes sample loading and is ready for electrophoresis, at which point the corresponding probe group is energized. The probe groups of unready channels 2140 remain in physical contact but de-energized, providing power-off protection in case the sample needle accidentally contacts the electrode contact, further reducing risk.
[0191] In some embodiments, the electrophoresis mechanism includes M groups of probes corresponding to the total number of channels, each group of probes including a positive probe and a negative probe. The electrophoresis operation on the channels after the sample loading operation is completed includes: before the sample loading operation is completed in the first channel, controlling all probe groups of the electrophoresis mechanism to simultaneously contact the electrode contact end of the corresponding channel, and controlling all probe groups to be energized.
[0192] For example, the electrophoresis apparatus 300 is suitable for Figures 13 to 19 The electrophoresis chip 2000 shown includes an electrophoresis mechanism 300 comprising M probe groups corresponding to the total number of channels 2140, where M ≤ N. Each probe group includes a positive probe and a negative probe. Electrophoresis is performed on the channels 2140 after sample loading, including: before the first channel 2140 completes sample loading, controlling all probe groups of the electrophoresis mechanism 300 to simultaneously contact the electrode contact ends 2211 of the corresponding channel, and controlling all probe groups to be energized. Pre-energizing all channels ensures a stable electric field is established in all channels before the first sample is loaded, saving stabilization time for each channel.
[0193] For example, taking an electrophoresis chip 2000 with 16 channels 2140 for accommodating samples as an example, where M is 16, the electrophoresis mechanism 300 can have two rows of probes, each with 16 probes. Each pair of probes in each row forms a positive and negative probe group. All 32 probes are fixed on the electrophoresis mounting plate 310. Before electrophoresis in the first channel 2140, all probes of the electrophoresis mechanism 300 are simultaneously contacted with the electrode contacts 2211 and pre-energized to establish a stable electric field before sample loading in the first channel 2140. After electrophoresis in all channels 2140 is completed, the probe groups corresponding to all channels 2140 are promptly de-energized to reduce energy consumption.
[0194] In some embodiments, there are M electrophoresis mechanisms corresponding to the total number of flow channels. Each electrophoresis mechanism includes a probe group, and each probe group includes a positive electrode probe and a negative electrode probe. The electrophoresis operation on the flow channels after sample loading includes: after sample loading is completed in the first flow channel, controlling the probe group of the first electrophoresis mechanism to contact and energize the electrode contact end corresponding to the first flow channel; and after electrophoresis is completed in the first flow channel, controlling the probe group of the first electrophoresis mechanism to de-energize and move away from the electrode contact end corresponding to the first flow channel; and after sample loading is completed in the (N-1)th flow channel... After the operation, the probe group of the (N-1)th electrophoresis mechanism is controlled to contact the electrode contact end corresponding to the (N-1)th flow channel and be energized. After the electrophoresis operation is completed in the (N-1)th flow channel, the probe group of the (N-1)th electrophoresis mechanism is controlled to be de-energized and move away from the electrode contact end corresponding to the (N-1)th flow channel. After the sample loading operation is completed in the Nth flow channel, the probe group of the Nth electrophoresis mechanism is controlled to contact the electrode contact end corresponding to the Nth flow channel and be energized. After the electrophoresis operation is completed in the Nth flow channel, the probe group of the Nth electrophoresis mechanism is controlled to be de-energized and move away from the electrode contact end corresponding to the Nth flow channel.
[0195] For example, the electrophoresis apparatus 300 is suitable for Figures 20 to 22 The electrophoresis chip 3000 shown has multiple flow channels 3110. Among them, there are M electrophoresis mechanisms 300 corresponding to the total number of flow channels (where M ≤ N, and N is the total number of flow channels 3110). Each electrophoresis mechanism 300 includes a probe group, and each probe group includes a positive electrode probe and a negative electrode probe. The materials of the positive and negative electrode probes are carefully selected, possessing good conductivity and chemical stability, and can maintain stable performance during long-term use, ensuring the accuracy and reliability of the electrophoresis operation.
[0196] The electrophoresis operation on the flow channels after sample loading includes: after sample loading is completed in the first flow channel 3110, the probe group of the first electrophoresis mechanism 300 is controlled to move and contact the corresponding contact end 3121 of the first flow channel 3110. During the movement, the speed and position of the probe group are precisely monitored and controlled to ensure accurate contact with the contact end 3121. Once contact is successful, the probe group of the first electrophoresis mechanism 300 is energized. At this time, the positive and negative probes form a complete circuit with the contact end 3121, generating a suitable electric field in the first flow channel 3110, driving the sample to be tested in the flow channel 3110 to begin electrophoretic separation. After the electrophoresis operation in the first flow channel 3110 is completed, the probe group of the first electrophoresis mechanism 300 is de-energized and moves away from the corresponding contact end 3121 of the first flow channel 3110, preparing for the electrophoresis operation of other flow channels 3110. Similarly, after the sample loading operation is completed in the (N-1)th flow channel 3110, the probe group of the (N-1)th electrophoresis mechanism 300 is controlled to contact and be energized with the corresponding contact terminal 3121 of the (N-1)th flow channel 3110. After the electrophoresis operation is completed in the (N-1)th flow channel 3110, the probe group of the (N-1)th electrophoresis mechanism 300 is controlled to be de-energized and move away from the corresponding contact terminal 3121 of the (N-1)th flow channel 3110. After the sample loading operation is completed in the Nth flow channel 3110, the probe group of the Nth electrophoresis mechanism 300 is controlled to contact and be energized with the corresponding contact terminal 3121 of the Nth flow channel 3110. After the electrophoresis operation is completed in the Nth flow channel 3110, the probe group of the Nth electrophoresis mechanism 300 is controlled to be de-energized and move away from the corresponding contact terminal 3121 of the Nth flow channel 3110. During this process, after the sample is added to each channel 3110, only the corresponding probe group (positive probe and negative probe) contacts the contact end 3121 of the channel 3110 and is energized, realizing precise one-to-one control and improving the accuracy and flexibility of the electrophoresis process.
[0197] In some embodiments, taking a picture of each channel after the electrophoresis operation has been completed to obtain a sample imaging image corresponding to each channel includes: taking a picture of the (N-1)th channel after the electrophoresis operation has been completed in the (N-1)th channel to obtain a sample imaging image corresponding to the (N-1)th channel; and taking a picture of the Nth channel after the electrophoresis operation has been completed in the Nth channel to obtain a sample imaging image corresponding to the Nth channel.
[0198] For example, after the electrophoresis operation is completed in the (N-1)th channel 2140, an image is taken of the (N-1)th channel 2140 to obtain the sample image corresponding to the (N-1)th channel 2140; after the electrophoresis operation is completed in the Nth channel 2140, an image is taken of the Nth channel 2140 to obtain the sample image corresponding to the Nth channel 2140. Taking images immediately after the electrophoresis operation in each channel 2140 can avoid phenomena such as band diffusion, band blurring, and tailing, ensuring the optimal aggregation state of the bands and maintaining the stability of the band morphology; the independent and decentralized execution of the imaging operation in each channel 2140 can make full use of resources and reduce camera idle rate.
[0199] In some embodiments, the imaging mechanism has an imaging field of view covering K adjacent channels, where K ≥ 2; the method further includes: based on electrophoresis progress prediction, controlling the imaging mechanism to move in advance to a first imaging region containing channels i to j, wherein the first imaging region simultaneously covers K adjacent channels, 1 ≤ i < MK, j = i + K - 1; when it is detected that any channel in the first imaging region has completed electrophoresis, controlling the imaging mechanism to take a picture of the channel in the first imaging region; if other channels in the first imaging region have not completed electrophoresis, then maintaining the position of the imaging mechanism and continuing to wait; after all channels in the first imaging region have completed taking pictures, moving the imaging mechanism to a second imaging region according to the position of the next batch of channels that are about to complete electrophoresis.
[0200] For example, to achieve precise control and efficient operation of the imaging mechanism 400, the electrophoresis progress is accurately predicted based on real-time data and historical experience of the electrophoresis operation. Specifically, the imaging mechanism 400 has an imaging field of view covering K adjacent channels 2140, where K ≥ 2. Based on the electrophoresis progress prediction, the imaging mechanism 400 can be controlled to move in advance to the first imaging region containing channels 2140 from i to j. The first imaging region simultaneously covers K adjacent channels 2140, where 1 ≤ i < MK, j = i + K - 1. This region division ensures the continuity of imaging and avoids wasting the imaging field of view, enabling the imaging mechanism 400 to reach the most suitable imaging position at the most suitable time.
[0201] Once the imaging mechanism 400 reaches the first imaging area, it enters a waiting and monitoring state, continuously monitoring the electrophoresis progress of each channel 2140 within the first imaging area. When it detects that any channel 2140 within the first imaging area has completed the electrophoresis operation, it controls the imaging mechanism 400 to take a picture of the channel 2140 within the first imaging area. The method of simultaneously photographing all channels 2140 within the area, rather than photographing each channel 2140 one by one, is used to further improve imaging efficiency.
[0202] However, in actual electrophoresis, the time it takes for each channel 2140 within the same imaging region to complete the electrophoresis operation may differ. If other channels 2140 within the first imaging region have not completed the electrophoresis operation, the imaging mechanism 400 will not immediately leave or perform other operations, but will maintain its current position and continue to wait. This waiting mechanism ensures that the optimal imaging opportunity for any channel 2140 is not missed, guaranteeing that sample images of all channels 2140 can be acquired when the bands are in the optimal aggregation state and their morphology is stable, thus providing a reliable basis for subsequent accurate analysis.
[0203] After all channels 2140 in the first imaging area have been photographed, the imaging mechanism 400 is moved to the second imaging area according to the position of the next batch of channels 2140 that will undergo electrophoresis. This intelligent imaging strategy, which is based on prediction results and the detected stage of the channels 2140, can efficiently complete the imaging work in conjunction with sample loading and electrophoresis operations.
[0204] In some embodiments, the method further includes: during electrophoresis, real-time detection of electrophoresis conditions, including electric field strength, current and / or voltage; acquisition of relevant information of samples in each channel, including at least one of sample type and sample quantity; determination, based on the real-time detected electrophoresis conditions and the relevant information of samples in each channel, whether it is necessary to adjust electrophoresis parameters between different channels to ensure consistency of electrophoresis results; if it is necessary to adjust electrophoresis parameters between different channels, then adjusting the corresponding electrophoresis parameters for each channel respectively.
[0205] For example, during electrophoresis, the electrophoresis conditions are monitored in real time, including electric field strength, current and / or voltage. The physical parameters of each flow channel are continuously collected through an embedded sensor network, including but not limited to: electric field strength (E=V / d, where V is voltage and d is dielectric thickness), current density (J=I / A, where I is current and A is cross-sectional area), and temperature gradient (generated by the Joule heating effect).
[0206] For example, relevant information about the samples in each channel 2140 can be obtained, including at least one of the sample type and sample quantity. The biological characteristics of the samples in each channel (as shown in 2140 in the figure) can be obtained by spectral analysis or fluorescent labeling technology: sample type (DNA / RNA / protein), molecular weight distribution (which can be calculated by mobility), and concentration gradient (based on absorbance detection).
[0207] For example, based on the real-time electrophoresis conditions and the relevant information of the samples in each channel 2140, it can be determined whether the electrophoresis parameters need to be adjusted between different channels 2140 to ensure the consistency of the electrophoresis effect; if the electrophoresis parameters need to be adjusted between different channels 2140, the corresponding electrophoresis parameters are adjusted for each channel 2140.
[0208] In some embodiments, the method further includes: after acquiring a sample imaging image corresponding to each flow channel, performing image processing on the sample imaging image, wherein the image preprocessing includes at least one of noise removal, contrast enhancement, and image distortion correction; using an image recognition algorithm to identify the sample imaging image to obtain brightness and position information of the strip objects in the sample imaging image; and comparing the brightness and position information of the strip objects in the sample imaging image with a standard reference strip to obtain strip information in the sample to be tested corresponding to each flow channel.
[0209] For example, after acquiring the sample imaging image corresponding to each channel 2140, the sample imaging image is processed, including at least one of noise removal, contrast enhancement, and image distortion correction. For instance, a Gaussian filtering algorithm is used to eliminate high-frequency noise in the sample imaging image while preserving strip edge features. Histogram equalization is used to enhance the contrast between the strip and the background. Geometric correction algorithms are employed to eliminate image distortion caused by optical system distortion.
[0210] Then, image recognition algorithms are used to identify the sample imaging images in order to obtain the brightness and position information of the strip objects in the sample imaging images.
[0211] Then, the brightness and position information of the strip objects in the sample imaging image are compared with the standard reference strip to obtain the strip information in the sample to be tested corresponding to each flow channel 2140.
[0212] For example, a molecular weight standard (Ladder) is set up. The sample to be tested and the molecular weight standard are separated by electrophoresis under the action of an electric field. When analyzing the obtained images, the standard reference band separated by the molecular weight standard is used as a benchmark. The information separated by the standard reference band of the molecular weight standard and the information separated by the sample to be tested (i.e., the brightness and position information of the band objects in the sample imaging image) are compared. The band information corresponding to each channel 2140 in the sample to be tested is calculated. The band information includes the corresponding nucleic acid fragment length, concentration and nucleic acid integrity index.
[0213] For example, if an electrophoresis chip with 16 available channels is set up (such as electrophoresis chip 2000 or electrophoresis chip 3000), in order to simplify the time consumed by the entire electrophoresis process and compare the difference between sequential single-step full-process electrophoresis and the concurrent full-process electrophoresis of this application, it is assumed that the running time of the three steps of picking the pipette tip, aspirating the sample, and loading the sample is 5s, the electrophoresis time of a single channel is 90s, the imaging time of a single channel is 2s, and the other steps are the same, ignoring the time difference of the same steps corresponding to different channels.
[0214] The sequential single-step full-process electrophoresis steps in the traditional technology are as follows: samples are added to 16 channels in sequence, and after electrophoresis, photos are taken in sequence. The required time is: (5 + 5 + 5)×16 + 90 + 2×16 = 362 s.
[0215] The concurrent full-process electrophoresis steps in the embodiments of the present application are as follows: when the Nth channel (channel 2140 on electrophoresis chip 2000 or channel 3110 on electrophoresis chip 3000) completes the three steps of picking up a pipette tip, aspirating a sample, and loading the sample, the (N - 1)th channel starts electrophoresis and takes a photo 90 s later, where 1 < N ≤ 16 and N is a natural number. During the electrophoresis process of this channel, the imaging mechanism 400 can move to this channel in advance to wait for taking a photo, and the photo-taking time is at the millisecond level. Therefore, the time consumed by the photo-taking action itself can be ignored. When the 16th channel completes loading the sample, it takes a photo after electrophoresis for 90 s. At this time, the 16 channels of electrophoresis chip 2000 complete electrophoresis and obtain images. The required time is: (5 + 5 + 5) + 15×15 + 90 = 330 s.
[0216] The split timing sequence of the concurrent full-process electrophoresis steps is as Figure 23 , Figure 23 shows the operation timing sequence of concurrent full-process electrophoresis of 16 independent channels on the electrophoresis chip. Horizontally, the time increases by 15 s per grid from left to right, for a total of 22×15 = 330 s; the content in the vertical table is the operation performed at the start or end node of a time unit (15 s). The operation sequence is carried out in the three operation stages in the above embodiments in sequence: the sample addition operation stage, including picking up a pipette tip, aspirating a sample, and loading the sample, that is, picking / aspirating / loading sample N in the figure, with each channel taking 15 s; the electrophoresis operation stage, that is, electrophoresis N in the figure, which is triggered at the start node of the time period, with each channel taking 90 s; the imaging operation stage, that is, taking a photo N in the figure, which is triggered at the end node of the time period, with each channel taking 2 s.
[0217] At the start of the process, the first flow channel performs sample loading / absorption / addition 1, taking 15 seconds. Immediately after the sample addition operation in the first flow channel, electrophoresis 1 begins, and simultaneously, the second flow channel begins its sample addition operation, entering the next 15 seconds. That is, the sample addition operation in the second flow channel and the electrophoresis operation in the first flow channel are performed in parallel. This continues until the sample addition operation in the sixth flow channel is completed. Since the electrophoresis operation in the first flow channel is completed exactly after 90 seconds, the imaging mechanism 400 immediately takes a picture 1 at the beginning of the seventh 15-second interval. Subsequently, every 15 seconds, one flow channel completes its sample addition operation in sequence. After the sample addition operation is completed, electrophoresis is performed on the corresponding flow channel (taking 90 seconds, 5 15-second intervals). The imaging mechanism 400 takes a picture every 15 seconds during the seventh 15-second interval. During the electrophoresis 1 operation in the first channel from the first 15 seconds to the sixth 15 seconds, the second to sixth sample loading operations are completed. During the seventh 15 seconds, the image capture 1 operation is performed, and during this period, electrophoresis 2 to electrophoresis 5 are also performed in parallel. This process continues, with each sample loading operation in one channel, the start / end time interval between electrophoresis operations in adjacent channels, and the time interval between two adjacent image captures all being 15 seconds. When the 16th channel completes its sample loading operation and begins electrophoresis, the 10th channel has just completed its electrophoresis operation, and the imaging mechanism captures image 10. After the 16th channel begins its electrophoresis operation (electrophoresis 16), the 11th, 12th, 13th, 14th, 15th, and 16th channels continue their electrophoresis operations, and immediately after the electrophoresis operation in each channel is completed, an image capture operation is performed for each channel (image capture 11 to image capture 15), until the 16th channel completes its electrophoresis operation and image capture 16 is taken, ending the entire process.
[0218] The concurrent full-process electrophoresis takes a total of 330 seconds, saving 32 seconds compared to the sequential single-step full-process electrophoresis which takes 362 seconds. It also ensures that the obtained image is the most accurate band state at the moment the electrophoresis is completed, greatly reducing the lag in the acquired image caused by the image capture delay. In the concurrent full-process electrophoresis steps, the time interval between the addition of the sample to be tested in each channel and the start of electrophoresis is almost exactly the same. This avoids the situation where after the first channel is loaded, you have to wait until the last channel is loaded before electrophoresis can start. This reduces the risk of sample diffusion in the buffer chamber, further ensures the consistency of the samples in each channel, and improves the reliability of electrophoresis image data analysis.
[0219] Electrophoresis data conclusions are derived from the brightness and position information of the bands in the images taken after electrophoresis. These bands are compared with standard reference bands to calculate the band information of the target sample. Therefore, the images directly affect the accuracy of the calculated results. In the sequential single-step full-process electrophoresis, all channels are loaded sequentially, electrophoresis is performed simultaneously, and then images are taken sequentially. This results in inconsistencies in the residence time of the sample in the buffer chamber after loading, and inconsistencies in the waiting time for the bands to be photographed after electrophoresis. Both of these time differences affect the inconsistency between the initial and final states of the sample test. The longer the residence time in the buffer chamber after loading, the more severe the dispersion of the sample in the buffer, and the more significant the impact on the accuracy of band measurement. In the sequential single-step full-process electrophoresis, after loading the sample in the first channel, it is necessary to wait 15 × 15 = 225 seconds in the buffer before starting electrophoresis, while after loading the sample in the 16th channel, electrophoresis can begin without waiting. In sequential single-step full-process electrophoresis, after the sample in the 16th channel is electrophoresed, it takes 15 × 2 = 30 seconds before imaging, while imaging can be taken immediately after the first channel is electrophoresed. Therefore, since the 1st and 16th channels are loaded with the same sample, the cumulative time difference between the initial and final states reaches 255 seconds. For short fragments and low concentrations of sample, the measurement results are easily distorted. In contrast, the concurrent full-process electrophoresis step provided in this application completely avoids these two time differences, ensuring that electrophoresis begins immediately after the sample is added to the buffer chamber for each channel, or that the sample remains in the buffer chamber for the same amount of time, and imaging is taken immediately after each channel completes electrophoresis, obtaining the most timely and accurate sample band images.
[0220] All of the above technical solutions can be combined in any way to form optional embodiments of this application, and will not be described in detail here.
[0221] The sample imaging method provided in this application is applied to an electrophoresis chip. The electrophoresis chip has multiple channels for accommodating samples to be tested. In this method, a sample loading operation is performed sequentially on each channel, and an electrophoresis operation is performed on the channels after the sample loading operation is completed, so that the samples to be tested in the channels are separated by electrophoresis. Specifically, after the sample loading operation is completed on the (N-1)th channel, a sample loading operation is performed on the Nth channel, and an electrophoresis operation is performed on the (N-1)th channel. After the sample loading operation is completed on the Nth channel, an electrophoresis operation is performed on the Nth channel, where 1 < N ≤ the total number of channels, and N is a natural number. An image is taken of each channel that has completed the electrophoresis operation to obtain a sample imaging image corresponding to each channel. This application embodiment effectively shortens the total time required for sample imaging by performing the sample loading operation and electrophoresis operation in parallel, improves the efficiency and continuity of the sample imaging process, and improves the detection quality.
[0222] To facilitate better implementation of the sample imaging method of this application embodiment, this application embodiment also provides a sample imaging device 20. Please refer to... Figure 24 The sample imaging device 20 can provide a graphical user interface via a terminal device. The graphical user interface includes at least a portion of a virtual scene and at least one virtual character. The sample imaging device 20 may include:
[0223] The processing unit 21 is used to sequentially add samples to each of the flow channels and perform electrophoresis on the flow channels after the sample addition operation is completed, so that the test samples in the flow channels are separated by electrophoresis. After the sample addition operation is completed in the (N-1)th flow channel, the sample addition operation is continued to the Nth flow channel, and the electrophoresis operation is performed on the (N-1)th flow channel. After the sample addition operation is completed in the Nth flow channel, the electrophoresis operation is performed on the Nth flow channel. 1 < N ≤ the total number of flow channels, where N is a natural number.
[0224] The acquisition unit 22 is used to take pictures of each channel that has completed the electrophoresis operation in order to obtain the sample imaging image corresponding to each channel.
[0225] In some embodiments, each flow channel in the electrophoresis chip is misaligned with the corresponding electrode contact end; when the probe of the electrophoresis mechanism for performing electrophoresis contacts the corresponding electrode contact end of each flow channel in the electrophoresis chip, the moving path of the sample dispensing needle of the sample dispensing mechanism for performing sample dispensing does not overlap with the moving path of the probe in spatial projection.
[0226] In some embodiments, the sample loading mechanism further includes a puncture needle; when the probe contacts the electrode contact end corresponding to each flow channel in the electrophoresis chip, the movement path of the puncture needle and the movement path of the probe do not overlap in spatial projection.
[0227] In some embodiments, for non-edge channels, the corresponding electrode contact is located in the interval region between adjacent channels; for edge channels, the corresponding electrode contact is located on the side of the corresponding channel away from the adjacent channel; or the electrode contact corresponding to one edge channel is located on the side of the corresponding channel away from the adjacent channel, and the electrode contact corresponding to another edge channel is located in the interval region between the other edge channel and the adjacent channel, so that each channel in the electrophoresis chip is misaligned with the electrode contact corresponding to each channel.
[0228] In some embodiments, the electrophoresis mechanism includes M probe groups corresponding to the total number of channels, each probe group including a positive probe and a negative probe. The processing unit 21 is used to perform electrophoresis on the channels after the sample loading operation has been completed, including: before the sample loading operation of the first channel is completed, controlling all probe groups of the electrophoresis mechanism to simultaneously contact the electrode contact end of the corresponding channel; after the sample loading operation of the (N-1)th channel is completed, controlling the probe group corresponding to the (N-1)th channel to be energized to perform electrophoresis on the (N-1)th channel; after the sample loading operation of the Nth channel is completed, controlling the probe group corresponding to the Nth channel to be energized to perform electrophoresis on the Nth channel.
[0229] In some embodiments, the processing unit 21 is further configured to: after the Nth channel completes the electrophoresis operation, control the probe group corresponding to the Nth channel to be de-energized; for the remaining channels that have not completed the sample loading operation, maintain the physical contact between the corresponding probe group and the electrode contact end, but keep the power off until the channel completes the sample loading operation and is ready to perform the electrophoresis operation, and then control the corresponding probe group to be energized.
[0230] In some embodiments, the electrophoresis mechanism includes M groups of probes corresponding to the total number of channels, each group of probes including a positive probe and a negative probe. The processing unit 21 is used to perform electrophoresis on the channels after the sample loading operation has been completed, including: before the sample loading operation is completed in the first channel, controlling all probe groups of the electrophoresis mechanism to simultaneously contact the electrode contact end of the corresponding channel, and controlling all probe groups to be energized.
[0231] In some embodiments, there are M electrophoresis mechanisms corresponding to the total number of flow channels. Each electrophoresis mechanism includes one probe group, and each probe group includes a positive electrode probe and a negative electrode probe. The processing unit 21 is used to perform electrophoresis on the flow channels after sample loading, including:
[0232] After the sample loading operation is completed in the first flow channel, the probe group of the first electrophoresis mechanism is controlled to contact and be energized with the electrode contact end corresponding to the first flow channel. After the electrophoresis operation is completed in the first flow channel, the probe group of the first electrophoresis mechanism is controlled to be de-energized and move away from the electrode contact end corresponding to the first flow channel. After the sample loading operation is completed in the (N-1)th flow channel, the probe group of the (N-1)th electrophoresis mechanism is controlled to contact and be energized with the electrode contact end corresponding to the (N-1)th flow channel. After the electrophoresis operation is completed in the (N-1)th flow channel, the probe group of the (N-1)th electrophoresis mechanism is controlled to be de-energized and move away from the electrode contact end corresponding to the (N-1)th flow channel. After the sample loading operation is completed in the (N)th flow channel, the probe group of the (N)th electrophoresis mechanism is controlled to contact and be energized with the electrode contact end corresponding to the (N)th flow channel. After the electrophoresis operation is completed in the (N)th flow channel, the probe group of the (N)th electrophoresis mechanism is controlled to be de-energized and move away from the electrode contact end corresponding to the (N)th flow channel.
[0233] In some embodiments, the acquisition unit 22 is configured to: take a picture of the (N-1)th flow channel after the electrophoresis operation is completed in the (N-1)th flow channel to obtain a sample imaging image corresponding to the (N-1)th flow channel; and take a picture of the Nth flow channel after the electrophoresis operation is completed in the Nth flow channel to obtain a sample imaging image corresponding to the Nth flow channel.
[0234] In some embodiments, the imaging mechanism has an imaging field of view covering K adjacent channels, where K ≥ 2; the acquisition unit 22 is further configured to: control the imaging mechanism to move in advance to a first imaging region containing channels i to j based on electrophoresis progress prediction, wherein the first imaging region simultaneously covers K adjacent channels, 1 ≤ i < MK, j = i + K - 1; when it is detected that any channel in the first imaging region has completed electrophoresis, control the imaging mechanism to take a picture of the channel in the first imaging region;
[0235] If other channels within the first imaging area have not completed electrophoresis, the imaging mechanism remains in its current position and continues to wait. Once all channels within the first imaging area have completed imaging, the imaging mechanism is moved to the second imaging area based on the position of the next batch of channels about to complete electrophoresis.
[0236] In some embodiments, the processing unit 21 is used to sequentially perform a sample loading operation on each of the plurality of channels, including: sequentially performing the operations of taking the pipette tip, aspirating the sample, and loading the sample on each of the plurality of channels.
[0237] In some embodiments, the sampling mechanism for performing the sampling operation includes a puncture needle and a sampling needle. The processing unit 21 is used to sequentially perform the operations of picking up the pipette tip, aspirating the sample, and loading the sample in each of the plurality of flow channels, including: controlling the puncture needle to perform a puncture operation on the target flow channel; and after the puncture operation is completed, controlling the sampling needle to sequentially perform the operations of picking up the pipette tip, aspirating the sample, and loading the sample, thereby loading the sample to be tested into the punctured target flow channel.
[0238] In some embodiments, the sample loading mechanism for performing the sample loading operation includes a puncture needle and a sample loading needle. The processing unit 21 is used to sequentially perform the operations of picking up the pipette tip, aspirating the sample, and loading the sample in each of the plurality of flow channels, including: controlling the sample loading needle to sequentially pick up the pipette tip and aspirate the sample; controlling the puncture needle to perform a puncture operation in the target flow channel; and after the puncture operation is completed, controlling the sample loading needle to load the sample to be tested into the target flow channel.
[0239] In some embodiments, before sequentially adding samples to each of the plurality of channels, the processing unit 21 is further configured to: pre-treat the electrophoresis chip, the pre-treatment including at least one of cleaning, drying and dust removal.
[0240] In some embodiments, before performing the sample addition operation on each of the plurality of flow channels in sequence, the processing unit 21 is further configured to: perform a calibration process on the sample addition mechanism used for performing the sample addition operation, the calibration process including at least one of vertical positioning calibration, horizontal position calibration and sample addition volume calibration.
[0241] In some embodiments, the processing unit 21 is further configured to: detect electrophoresis conditions in real time during electrophoresis, the electrophoresis conditions including electric field strength, current and / or voltage; acquire relevant information of samples in each channel, the relevant information including at least one of sample type and sample quantity; determine whether electrophoresis parameters need to be adjusted between different channels to ensure consistency of electrophoresis effect based on the real-time detected electrophoresis conditions and the relevant information of samples in each channel; if electrophoresis parameters need to be adjusted between different channels, adjust the corresponding electrophoresis parameters for each channel respectively.
[0242] In some embodiments, the acquisition unit 22 is further configured to: after acquiring a sample imaging image corresponding to each flow channel, perform image processing on the sample imaging image, wherein the image preprocessing includes at least one of noise removal, contrast enhancement, and image distortion correction; identify the sample imaging image using an image recognition algorithm to obtain the brightness and position information of the strip objects in the sample imaging image; and compare the brightness and position information of the strip objects in the sample imaging image with a standard reference strip to obtain the strip information in the sample to be tested corresponding to each flow channel.
[0243] Each unit in the aforementioned sample imaging device can be implemented entirely or partially through software, hardware, or a combination thereof. Each unit can be embedded in or independent of the processor in a computer device in hardware form, or stored in the memory of a computer device in software form, so that the processor can call and execute the operations corresponding to each unit.
[0244] The sample imaging device 20 can be integrated into a terminal or server that has storage and a processor and thus computing power, or the sample imaging device 20 can be the terminal or server.
[0245] All of the above technical solutions can be combined in any way to form optional embodiments of this application, and will not be described in detail here.
[0246] It should be understood that the sample imaging device 20 embodiment and the sample imaging method embodiment can correspond to each other, and similar descriptions can be referred to the method embodiment. To avoid repetition, they will not be repeated here. Specifically, the sample imaging device 20 can execute the above-described sample imaging method embodiment, and the foregoing and other operations and / or functions of each unit in the sample imaging device 20 respectively implement the corresponding processes of the above-described method embodiment. For the sake of brevity, they will not be repeated here.
[0247] Optionally, this application also provides a computer device, including a memory and a processor, wherein the memory stores a computer program, and the processor executes the computer program to implement the steps in the above-described method embodiments.
[0248] Figure 25 This is a schematic diagram of the structure of a computer device provided in an embodiment of this application. The computer device may be a terminal or a server. Figure 25 As shown, the computer device 30 may include: a communication interface 31, a memory 32, a processor 33, and a communication bus 34. The communication interface 31, memory 32, and processor 33 communicate with each other through the communication bus 34. The communication interface 31 is used for data communication between the computer device 30 and external devices. The memory 32 can be used to store software programs and modules. The processor 33 is the control center of the computer device 30, connecting various parts of the computer device 30 through various interfaces and lines. By running or loading software programs and / or modules stored in the memory 32, and by calling data stored in the memory 32, it executes various functions of the computer device 30 and processes data, thereby performing overall processing of the computer device 30.
[0249] In this embodiment, the processor 33 in the computer device 30 loads the instructions corresponding to the processes of one or more computer programs into the memory 32 according to the following steps, and the processor 33 runs the computer programs stored in the memory 32 to realize various functions:
[0250] Each of the flow channels is sequentially sampled, and electrophoresis is performed on the flow channels after sample addition to achieve electrophoretic separation of the test samples within the flow channels. Specifically, after sample addition is completed in the (N-1)th flow channel, sample addition is performed in the Nth flow channel, and electrophoresis is performed in the (N-1)th flow channel. After sample addition is completed in the Nth flow channel, electrophoresis is performed in the Nth flow channel. 1 < N ≤ the total number of flow channels, where N is a natural number. Each flow channel that has undergone electrophoresis is photographed to obtain a sample imaging image corresponding to each flow channel.
[0251] Those skilled in the art will understand that all or part of the steps in the structural design method of the above embodiments can be accomplished by instructions, or by controlling related hardware with instructions. These instructions can be stored in a computer-readable storage medium and loaded and executed by a processor.
[0252] Therefore, embodiments of this application provide a computer-readable storage medium storing multiple computer programs that can be loaded by a processor to execute the steps of any of the data communication methods provided in these embodiments. Specific implementations of the above operations can be found in the preceding embodiments and will not be repeated here.
[0253] The storage medium may include: read-only memory (ROM), random access memory (RAM), disk or optical disk, etc.
[0254] Since the computer program stored in the storage medium can execute the steps in any of the sample imaging methods provided in the embodiments of this application, the beneficial effects that any of the sample imaging methods provided in the embodiments of this application can achieve can be realized, as detailed in the preceding embodiments, and will not be repeated here.
[0255] This application also provides a computer program product including computer instructions stored in a computer-readable storage medium. A processor of a computer device reads the computer instructions from the computer-readable storage medium and executes the computer instructions, causing the computer device to perform the corresponding process in any of the sample imaging methods described in this application. For simplicity, further details are omitted here.
[0256] This application also provides a computer program comprising computer instructions stored in a computer-readable storage medium. A processor of a computer device reads the computer instructions from the computer-readable storage medium and executes the computer instructions, causing the computer device to perform the corresponding process in any of the sample imaging methods described in this application. For brevity, further details are omitted here.
[0257] The above description is merely a specific embodiment of this application, but the scope of protection of this application is not limited thereto. Any variations or substitutions that can be easily conceived by those skilled in the art within the scope of the technology disclosed in this application should be included within the scope of protection of this application. Therefore, the scope of protection of this application should be determined by the scope of the claims.
Claims
1. A method of imaging a sample, characterized by, The application is applied to an electrophoresis chip having a plurality of flow channels for containing samples to be tested, and the method comprises the following steps: sequentially performing sample adding operation on each of the flow channels, and performing electrophoresis operation on the flow channels after sample adding operation is completed, so that the samples to be tested in the flow channels complete electrophoresis separation, wherein, after the N-1th flow channel completes sample adding operation, sample adding operation is performed on the Nth flow channel, and electrophoresis operation is performed on the N-1th flow channel, after the Nth flow channel completes sample adding operation, electrophoresis operation is performed on the Nth flow channel, 1 photographing each flow channel after electrophoresis operation is completed to obtain sample imaging images corresponding to each flow channel.
2. The sample imaging method of claim 1, wherein, Each flow channel in the electrophoresis chip is arranged in a staggered manner with the electrode contact end corresponding to each flow channel. When a probe of an electrophoresis mechanism for performing electrophoresis operation contacts the electrode contact end corresponding to each flow channel in the electrophoresis chip, the moving path of a sample adding needle of a sample adding mechanism for performing sample adding operation does not overlap with the moving path of the probe in space projection.
3. The sample imaging method of claim 2, wherein, For non-edge flow channels, the corresponding electrode contact end is located in the interval region between adjacent flow channels, for edge flow channels, the corresponding electrode contact end is located on the side of the corresponding flow channel away from the adjacent flow channel, or the electrode contact end of one edge flow channel is located on the side of the corresponding flow channel away from the adjacent flow channel, and the electrode contact end of the other edge flow channel is located in the interval region between the other edge flow channel and the adjacent flow channel, so that each flow channel in the electrophoresis chip is arranged in a staggered manner with the electrode contact end corresponding to each flow channel.
4. The method of claim 2, wherein, The electrophoresis mechanism comprises M groups of probes corresponding to the total number of flow channels, each group of probes comprises a positive probe and a negative probe, and the electrophoresis operation on the flow channels after sample adding operation is completed comprises the following steps: Before the 1st flow channel completes sample adding operation, control all groups of probes of the electrophoresis mechanism to simultaneously contact the electrode contact end of the corresponding flow channel; After the N-1th flow channel completes sample adding operation, control the group of probes corresponding to the N-1th flow channel to be electrified to perform electrophoresis operation on the N-1th flow channel; After the Nth flow channel completes sample adding operation, control the group of probes corresponding to the Nth flow channel to be electrified to perform electrophoresis operation on the Nth flow channel.
5. The method of imaging a sample of claim 1, wherein, The photographing of each flow channel after electrophoresis operation is completed to obtain sample imaging images corresponding to each flow channel comprises the following steps: After the N-1th flow channel completes electrophoresis operation, photograph the N-1th flow channel to obtain sample imaging images corresponding to the N-1th flow channel; After the Nth flow channel completes electrophoresis operation, photograph the Nth flow channel to obtain sample imaging images corresponding to the Nth flow channel.
6. The method of imaging a sample of claim 4, wherein, The imaging mechanism has an imaging field of view covering K adjacent flow channels, K≥2; and the method further comprises the following steps: According to electrophoresis progress prediction, control the imaging mechanism to move to a first imaging area containing the i-th to the j-th flow channels in advance, wherein the first imaging area simultaneously covers K adjacent flow channels, 1 When it is monitored that any flow channel in the first imaging area completes electrophoresis operation, the imaging mechanism is controlled to take a photo of the flow channel in the first imaging area; If other flow channels in the first imaging area do not complete electrophoresis operation, the imaging mechanism position is kept unchanged to continue waiting; When all flow channels in the first imaging area complete photo taking, the imaging mechanism is moved to a second imaging area according to the position of the next batch of flow channels which are about to complete electrophoresis.
7. A sample imaging apparatus, characterized by, The device is applied to an electrophoresis chip having a plurality of flow channels for containing samples to be tested, and comprises: a processing unit configured to sequentially perform sample adding operation on each of the flow channels and perform electrophoresis operation on the flow channels which complete sample adding operation, so that the samples to be tested in the flow channels complete electrophoresis separation, wherein after the (N-1)th flow channel completes sample adding operation, sample adding operation is continued on the Nth flow channel, and electrophoresis operation is performed on the (N-1)th flow channel, after the Nth flow channel completes sample adding operation, electrophoresis operation is performed on the Nth flow channel, 1 a obtaining unit configured to take a photo of each flow channel which completes electrophoresis operation to obtain a sample imaging image corresponding to each flow channel.
8. A computer-readable storage medium, characterized in that, The computer readable storage medium stores a computer program which is adapted to be loaded by the processor to execute the sample imaging method according to any one of claims 1-6.
9. A computer device, comprising: The computer device comprises a processor and a memory, and the memory stores a computer program, and the processor is configured to execute the sample imaging method according to any one of claims 1-6 by calling the computer program stored in the memory.
10. A computer program product comprising computer instructions, characterized in that, The computer instructions are executed by the processor to implement the sample imaging method according to any one of claims 1-6.
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