Multi-channel integrated capillary electrophoresis chip and flow path control method

Abstract

The application discloses a kind of multi-channel integrated capillary electrophoresis chip and flow path control method, belong to detection chip technical field.It includes: chip ontology, which is provided with sample inlet through hole, separation channel, plunger valve port, plunger valve channel;Sample inlet through hole is communicated with separation channel and is used for sample introduction;Separation channel is provided with multiple, any one separation channel is configured with a sample inlet through hole, plunger valve channel is communicated with separation channel by plunger valve port;Separation channel includes straight line section, first curve extension section and second curve extension section, and the total length of the straight line section, the first curve extension section and the second curve extension section of each separation channel is the same.Through integrating multiple separation channels with equal total length, each channel is equipped with independent sample inlet through hole and detection window, multi-channel synchronous detection is realized, and the unit length electric field intensity of each separation channel is consistent, effectively eliminates migration time drift, and improves multi-channel detection consistency.

Description

Technical Field

[0001] This invention belongs to the field of detection chip technology, specifically relating to a multi-channel integrated capillary electrophoresis chip and a flow path control method. Background Technology

[0002] Capillary electrophoresis is a primary technique for nucleic acid fragment analysis. In recent years, with the development of microfabrication and microelectromechanical systems (MEMS) technologies, capillary electrophoresis has entered the era of integrated capillary electrophoresis (ICE) chips. These chips utilize microfabrication techniques to integrate high-efficiency capillary electrophoresis onto microarrays. 2 On a chip the size of a nanometer, channels and other functional units are fabricated to enable processes such as sample introduction, reaction, separation, and detection. This technology integrates the advantages of microfluidics, achieving efficient separation, detection, and analysis of biomolecules through microscale channels, electric fields, and highly flexible flow control.

[0003] However, most existing microfluidic electrophoresis chips are still primarily single-channel structures, meaning they integrate only one separation channel, allowing for the separation and detection of only one sample or component per run. While such single-channel chips have some practicality in proof-of-concept and small-scale experiments, their efficiency is significantly insufficient for high-throughput screening, multi-component parallel analysis, or applications requiring internal standards. To achieve simultaneous analysis of multiple samples, repeated injection and electrophoresis operations are typically required, which is not only time-consuming and labor-intensive but also results in poor repeatability due to batch-to-batch operational variations, failing to meet the high-throughput and high-consistency demands of modern life sciences and clinical testing.

[0004] In response, even when some studies attempt to introduce multi-channel designs, they often overlook the issue of the consistency of electric field distribution between channels. The uneven electric field intensity per unit length of each separation channel leads to different separation speeds for each channel, which seriously affects the reliability of multi-channel parallel analysis.

[0005] In addition, existing electrophoresis chips generally suffer from low resolution. The main reason for this problem is the unreasonable design of the separation channel, such as insufficient channel length or overly simplified path, which leads to short separation time and failure to fully distinguish components. Summary of the Invention

[0006] This invention addresses the aforementioned problems in the prior art by proposing an integrated capillary electrophoresis chip and flow path control method capable of multi-channel parallel detection with consistent detection results.

[0007] This invention can be achieved through the following technical solutions:

[0008] A multi-channel integrated capillary electrophoresis chip, comprising:

[0009] The chip substrate has a sample inlet port, a separation channel, a plunger valve port, and a plunger valve channel.

[0010] The sample inlet is connected to the separation channel and is used for sample injection;

[0011] The separation channel is provided in multiple ways and is evenly arranged along the length or width direction of the chip substrate. Each separation channel is provided with a sample inlet hole. The plunger valve channel is connected to the separation channel through the plunger valve port.

[0012] The separation channel includes a straight segment, a first curved extension segment, and a second curved extension segment. The total length of the straight segment, the first curved extension segment, and the second curved extension segment of each separation channel is the same, so that the electric field strength per unit length applied to each separation channel remains consistent.

[0013] As a further improvement of the present invention, it also includes an outer shell, which is composed of a top plate and a bottom shell, and the chip substrate is installed in the internal space of the outer shell, and a chip top plate is bonded on the chip substrate to form a chip structure.

[0014] As a further improvement of the present invention, a glue tank is provided on the top plate, and a separation anode buffer tank is provided on one side of the bottom shell, while a separation cathode buffer tank and a sample discharge buffer tank are provided on the other side.

[0015] The glue outlet at the bottom of the glue tank is connected to the plunger valve channel;

[0016] The separate cathode buffer cell and the separate anode buffer cell are respectively connected to the two plunger valve channels on both sides of the chip substrate through the separate cathode buffer cell capillary tube and the separate anode buffer cell capillary tube.

[0017] The sample outlet buffer cell is connected to the sample inlet through a sample outlet capillary array.

[0018] As a further improvement of the present invention, the top plate is also provided with a plunger and a plurality of plunger valves, the plunger being connected to the plunger valve port, and each of the plunger valves being connected to the plunger valve channel and used to control the opening and closing of the flow path.

[0019] As a further improvement of the present invention, the top plate is further provided with a piston hole seat, a piston rod mounting plate, and a piston hole seat pressure plate. The piston hole seat pressure plate is connected to the top plate, the piston hole seat is located in a positioning groove opened in the piston hole seat pressure plate and is connected to the top plate, and the piston rod mounting plate is movably disposed on the top of the piston hole seat.

[0020] The piston hole seat is provided with a plurality of piston holes, and the piston rod mounting plate is used to install the piston rod of the syringe. The piston of the syringe is telescopically disposed in the piston hole, and the piston hole is connected to one end of the injection through hole.

[0021] As a further improvement of the present invention, a sample inlet channel is provided between the sample inlet hole and the separation channel, the sample inlet hole and the sample inlet channel are cross-connected, and the sample inlet channel and the separation channel are cross-connected.

[0022] As a further improvement of the present invention, it also includes a sample inlet capillary array, the top end of which is connected to the sample inlet through hole, while the piston seat is connected to the other end of the sample inlet through hole, and the sample inlet capillary array is inserted into an external sample cell.

[0023] The sample inlet capillary array is connected to the end of the sample inlet orifice near the sample inlet channel, and the sample outlet capillary array is connected to the end of the sample inlet channel away from the sample inlet orifice.

[0024] As a further improvement of the present invention, it also includes a pair of sample introduction electrode springs and a pair of separation electrode springs. The pair of separation electrode springs are respectively located in the separation cathode buffer cell and the separation anode buffer cell and are used for connection to the high-voltage power supply of external instruments. One sample introduction electrode spring is located in the sample exit buffer cell, and the other sample introduction electrode spring is connected to the metal outer wall of the sample introduction capillary array.

[0025] A pair of the separation electrode springs are used to provide an electric field between the anode buffer capillary and the cathode buffer capillary, and to form a separation electric field applied to the separation channel on the chip substrate;

[0026] A pair of the sample inlet electrode reeds are used to provide an electric field between the sample inlet capillary array and the sample outlet capillary array, and to form an inlet electric field applied to the sample inlet channel on the chip substrate.

[0027] As a further improvement of the present invention, a detection window is provided on the top plate, the detection window is arranged facing the separation channel, and the detection window is arranged in a one-to-one correspondence with the separation channel.

[0028] As a further improvement of the present invention, a slot is provided between adjacent separation channels, and a partition plate is inserted in the slot. The partition plate is used to separate the positions of the two adjacent separation channels corresponding to the detection window.

[0029] A flow path control method for a multi-channel integrated capillary electrophoresis chip is also provided, applied to the aforementioned multi-channel integrated capillary electrophoresis chip, comprising the following steps:

[0030] S1. Coating and Pre-electrophoresis: During coating, control the opening and closing of the plunger valve and pull the plunger until the separation channel and the sample injection channel are completely filled with the separating gel. Then perform the pre-electrophoresis operation to identify whether there are air bubbles in each channel of the chip substrate. If there are air bubbles, repeat the coating operation until there are no air bubbles left.

[0031] S2, Sample Injection: The sample injection capillary array is inserted into the sample cell, and the sample is drawn up by negative pressure. The sample enters the sample injection hole, then flows into the sample injection channel, and enters the separation channel from the cross intersection of the sample injection channel and the separation channel.

[0032] S3, Electrophoretic Separation and Detection: The separation cathode buffer cell and the separation anode buffer cell are switched to the separation voltage to achieve sample separation. After sample separation, the voltage of a pair of sample injection electrode springs is maintained at a positive potential to prevent subsequent samples from entering the separation channel. Subsequently, the fluorescence detection module of the external instrument performs fluorescence detection on the nucleic acid fragments in the separation channel through the detection window.

[0033] S4. Waste Discharge: After completing one separation test, the sample in the sample inlet channel is first discharged through the positive pressure of the piston in the piston seat. Then, the potting action of step S1 is performed. Part of the waste glue and test sample in the chip substrate is discharged to the waste liquid pool on the external sample stage through the sample inlet capillary array. Another part of the waste glue and test sample is discharged to the sample outlet buffer pool through the sample outlet capillary array. Finally, the outer wall of the front end of the sample inlet capillary array is cleaned by ultrasonic waves or cleaning solution. The chip is ready for the next round of testing.

[0034] Compared with the prior art, the present invention has the following beneficial effects:

[0035] 1. Achieve simultaneous separation of multiple channels to increase detection throughput.

[0036] By integrating multiple independent separation channels within the chip, parallel detection of samples can be achieved. Compared with traditional single-channel capillary electrophoresis chips, this structure significantly improves detection efficiency and throughput, meeting the needs of high-throughput biological sample analysis and rapid clinical screening. Furthermore, the electric field intensity per unit length of each separation channel is consistent, effectively eliminating migration time drift and significantly improving the consistency of multi-channel detection results.

[0037] 2. The separating gel and buffer solution are integrated into one package, simplifying the usage process.

[0038] The chip pre-fills and seals the separating gel and electrophoresis buffer in its internal structure, eliminating the need for manual gel preparation, filling, and buffer formulation before use. This reduces operational complexity, avoids human error, and improves the standardization and reproducibility of experiments.

[0039] 3. Automatically forms a stable separation channel system, improving separation stability.

[0040] The integrated design ensures uniform separation gel concentration, consistent channel geometry, and stable buffer system, effectively reducing migration time fluctuations caused by bubbles, leakage, and uneven concentration, and improving the accuracy and reproducibility of electrophoretic separation.

[0041] 4. Reduce pollution risk and enhance system reliability

[0042] The separating gel and buffer solution are enclosed within the chip cavity, avoiding cross-contamination from the external environment or during operation; at the same time, it reduces reagent exposure and consumption, improves system safety and reagent utilization, and is particularly suitable for medical testing and high-sensitivity DNA / RNA analysis scenarios.

[0043] 5. High structural integration, which facilitates chip miniaturization and instrument modularization.

[0044] By integrating separation media, buffer systems, and microfluidic structures, the chip eliminates the need for an external liquid supply system, significantly reducing the overall system size and providing a hardware foundation for portable testing devices, point-of-care testing (POCT), and rapid on-site diagnostics.

[0045] 6. Highly compatible, suitable for analysis of various biological macromolecules.

[0046] The separating gel formulation and channel design can support the detection of a variety of biological macromolecules such as proteins, peptides, and nucleic acid fragments (DNA / RNA), and has broad application adaptability, which can be extended to multiple fields such as gene detection, disease biomarkers, and drug development.

[0047] 7. High degree of automation and easy system integration.

[0048] It can be used with an automatic sample introduction device, power management module and software control system to realize fully automatic sample introduction, electrophoretic separation, automatic cleaning and data acquisition and analysis, and is suitable for building intelligent and digital detection systems. Attached Figure Description

[0049] Figure 1 This is an exploded view of the electrophoresis chip of the present invention;

[0050] Figure 2 This is a schematic diagram of the chip substrate structure of the present invention;

[0051] Figure 3 This is a schematic diagram of the top surface of the electrophoresis chip of the present invention;

[0052] Figure 4 This is a schematic diagram of the bottom surface of the electrophoresis chip of the present invention.

[0053] In the diagram, 100 is the chip substrate; 101 is the chip top plate; 110 is the sample inlet hole; 111 is the sample inlet channel; 120 is the separation channel; 121 is the straight section; 122 is the first curve extension section; 123 is the second curve extension section; 130 is the plunger valve port; 140 is the plunger valve channel; and 150 is the slot.

[0054] 200. Top plate; 210. Adhesive pool; 220. Plunger; 230. Plunger valve; 231. First plunger valve; 232. Second plunger valve; 233. Third plunger valve; 240. Piston bore seat; 250. Piston rod mounting plate; 260. Piston bore seat pressure plate; 270. Detection window;

[0055] 300. Bottom shell; 310. Sample inlet capillary array; 320. Separating cathode buffer cell; 321. Separating cathode buffer cell capillary; 330. Separating anode buffer cell; 331. Separating anode buffer cell capillary; 340. Sample outlet buffer cell; 341. Sample outlet capillary array; 350. Sample inlet electrode reed; 360. Separating electrode reed;

[0056] 400. Heating film. Detailed Implementation

[0057] The following are specific embodiments of the present invention, which are described in conjunction with the accompanying drawings. However, the present invention is not limited to these embodiments.

[0058] like Figures 1-4 As shown, this invention provides a multi-channel separating gel and buffer integrated capillary electrophoresis chip, comprising:

[0059] The chip substrate 100 has a sample inlet 110, a separation channel 120, a plunger valve port 130, and a plunger valve channel 140, wherein...

[0060] The sample inlet 110 is connected to the separation channel 120 and is used for sample injection;

[0061] Multiple separation channels 120 are provided and are evenly arranged along the length or width direction of the chip substrate 100. Each separation channel 120 is provided with a sample inlet 110. The plunger valve channel 140 is connected to the separation channel 120 through the plunger valve port 130.

[0062] The separation channel 120 includes a straight segment 121, a first curved extension segment 122, and a second curved extension segment 123. The total length of the straight segment 121, the first curved extension segment 122, and the second curved extension segment of each separation channel 120 is the same, so that the electric field intensity per unit length of each separation channel 120 remains consistent.

[0063] It is worth mentioning that by integrating multiple separate channels 120 on the chip substrate 100 and ensuring that each channel consists of a straight segment 121, a first curved extension segment 122, and a second curved extension segment 123, the total length of all channels is strictly equal, thereby ensuring that the electric field strength per unit length experienced by each channel along the length direction is completely consistent under the same voltage conditions.

[0064] Since the migration rate of charged particles during electrophoresis directly depends on the local electric field strength, the uniformity of the electric field effectively eliminates the migration time drift caused by channel geometric differences, ensuring a high degree of consistency in the separation behavior among multiple channels.

[0065] Meanwhile, each separation channel 120 is independently configured with an injection port 110 and a detection window 270, enabling multiple samples to be injected simultaneously, separated in parallel, and detected independently without the need for repeated operations or switching of flow paths. This structural design not only significantly improves the analytical throughput but also avoids the operational errors and time delays introduced by traditional single-channel chips due to multiple runs.

[0066] In addition, it is precisely because the first curve extension segment 122 and the second curve extension segment 123 ingeniously lengthen the effective separation length of a single separation channel 120 within a limited chip area that the charged analytes have a longer migration path and more sufficient separation time under the action of the electric field, thereby significantly improving the separation resolution.

[0067] This design effectively extends the separation path by optimizing the channel geometry without increasing the overall chip size, which improves the separation resolution while taking into account the miniaturization and integration of the device. It is particularly suitable for microfluidic electrophoresis applications with strict requirements for high resolution.

[0068] Overall, the electrophoresis chip provided in this embodiment has at least the following advantages compared to the prior art:

[0069] 1. High-throughput and high-consistency parallel analysis: By integrating multiple separation channels 120 of equal total length, each channel is equipped with an independent sample inlet 110 and detection window 270, enabling simultaneous sample injection, parallel separation and independent detection of multiple samples; at the same time, the electric field intensity per unit length of each channel is consistent, effectively eliminating migration time drift and significantly improving the consistency of multi-channel detection results.

[0070] 2. High-resolution separation capability: By utilizing the first curve extension segment 122 and the second curve extension segment 123, the effective separation path of the separation channel 120 is extended within the limited chip area, allowing charged analytes to obtain longer migration time and more sufficient separation space, thereby significantly improving the resolution capability of components with similar mobility.

[0071] 3. Compact integration and simplified operation: Without increasing the overall chip size, the optimized channel geometry balances high resolution and miniaturization, and avoids the errors and delays caused by repeated operations required by traditional single-channel chips. It is suitable for automated, high-precision, and high-efficiency microfluidic electrophoresis applications.

[0072] Preferably, it also includes an outer shell, which is composed of a top plate 200 and a bottom shell 300, and a chip substrate 100 is installed in the internal space of the outer shell, wherein a transparent chip top plate 101 is bonded on the chip substrate 100 to form a chip structure.

[0073] The bottom shell 300 is also equipped with a heating film 400, on which the chip substrate 100 is placed. The heating film 400 is used to precisely and uniformly control the temperature of the chip substrate 100. In the capillary electrophoresis process, temperature directly affects the viscosity of the buffer solution, ion mobility, electroosmotic flow rate, and the polymerization state or sieving performance of the separating gel.

[0074] By tightly attaching the heating film 400 to the chip substrate 100, it can not only actively compensate for fluctuations in ambient temperature, but also maintain a constant operating temperature when needed (such as standard temperature control conditions for DNA sequencing or protein analysis), or achieve programmed heating to optimize specific separation processes.

[0075] Furthermore, this integrated temperature control structure eliminates the need for an external heating device, improving the overall system integrity, response speed, and energy efficiency. It effectively ensures the consistency of the thermal environment between multiple channels, thereby further enhancing the repeatability, resolution, and reliability of the separation results.

[0076] More importantly, ensuring that DNA remains single-stranded in microarray capillary electrophoresis requires maintaining a constant temperature of 60°C during the electrophoresis process. This environment keeps double-stranded DNA single-stranded and prevents it from re-annealing or forming secondary structures such as hairpins and stem-loops during migration. If secondary structures are present, the actual conformation of the DNA molecule will deviate from the ideal linear state, leading to abnormal migration resistance in the gel or polymer sieving medium. This manifests as migration time drift, peak tailing or splitting, and decreased resolution, severely affecting the accuracy and repeatability of fragment detection.

[0077] In this embodiment, the heating film integrated within the outer shell is in close contact with the chip substrate, precisely and stably maintaining the entire separation channel area at a constant temperature of 60°C. This completely eliminates interference from DNA secondary structures, ensuring that all DNA fragments are separated solely based on their length (i.e., molecular weight), significantly improving the accuracy, linearity, and comparability of the analytical results. This temperature control capability is particularly crucial for high-resolution DNA analysis (such as microsatellite detection, Sanger sequencing, and CRISPR editing efficiency assessment), and is an important guarantee for achieving reliable and standardized chip electrophoresis detection.

[0078] Furthermore, the top plate 200 is provided with a glue tank 210, and one side of the bottom shell 300 is provided with a separation anode buffer tank 330, while the other side is provided with a separation cathode buffer tank 320 and a sample discharge buffer tank 340.

[0079] The glue outlet at the bottom of the glue tank 210 is connected to the plunger valve channel 140;

[0080] The separation cathode buffer cell 320 and the separation anode buffer cell 330 are connected to two plunger valve channels 140 on both sides of the chip substrate 100 through the separation cathode buffer cell capillary tube 321 and the separation anode buffer cell capillary tube 331, respectively. The buffer solution in the separation cathode buffer cell 320 and the separation anode buffer cell 330 is drawn into the plunger valve channel 140 through the separation cathode buffer cell capillary tube 321 and the separation anode buffer cell capillary tube 331, and then injected into the separation channel 120 through the plunger valve port 130.

[0081] The sample outlet buffer 340 is connected to the sample inlet through hole 110 through the sample outlet capillary array 341. When discharging waste liquid, the buffer solution and test sample in the separation channel 120 can be discharged into the sample outlet buffer 340 through the sample outlet capillary array 341.

[0082] This integrated glue supply method not only avoids the problems of air bubbles, unevenness, or cross-contamination caused by traditional manual glue dispensing operations, but also eliminates the need for manual glue preparation and dispensing before use, reducing operational complexity, avoiding human error, and improving the standardization and repeatability of experiments. At the same time, the direct connection between the glue pool 210 and the plunger valve channel 140 enables rapid, uniform, and controllable injection of the separating glue, ensuring that each separation channel 120 completes glue dispensing simultaneously. This further guarantees the consistency of separation conditions between multiple channels, significantly shortens chip preparation time, and improves overall analysis efficiency and system reliability.

[0083] In addition, the top of the gel pool 210 is provided with a transparent soft membrane (not shown in the figure), which is used to protect the gel and provide a clean environment.

[0084] Preferably, the top plate 200 is provided with a plunger 220 and a plurality of plunger valves 230. The plunger is connected to each plunger valve port 130, and each plunger valve 230 is connected to the plunger valve channel 140 and is used to control the flow path. By controlling the plunger 220 and each plunger valve 230, the purpose of injecting buffer into the separation channel 120 and removing buffer from the separation channel 120 can be achieved.

[0085] Specifically, the plunger 220 is directly connected to the plunger valve port 130 of the chip substrate 100. The plunger 220 is used to extract the buffer solution in the separation cathode buffer pool 320 and the separation anode buffer pool 330. On the other hand, pressure is applied to push the separation adhesive in the adhesive pool 210 into each separation channel 120 through the plunger valve channel 140.

[0086] The multiple plunger valves 230 are respectively connected to various points of the plunger valve channel 140 of the chip substrate 100, which can close the corresponding flow path in time after the glue is filled to prevent glue backflow, leakage or crosstalk between different channels.

[0087] This structure, through the coordinated control of plunger 220 and multiple plunger valves 230, not only achieves precise injection and efficient emptying of buffer solution and separating gel, but also ensures a high degree of synchronization and uniformity in the dispensing process between multiple channels. Plunger 220 is directly connected to plunger valve port 130, which can actively aspirate buffer solution or push separating gel. After filling, each plunger valve 230 quickly closes the corresponding flow path, effectively preventing backflow of the gel solution. This significantly improves the sealing of the internal flow path of the chip, the controllability of the timing of operation, and the accuracy of fluid distribution, further enhancing the chip's operational stability, separation consistency, and overall reliability during repeated use.

[0088] Preferably, the top plate 200 is further provided with a piston hole seat 240, a piston rod mounting plate 250, and a piston hole seat pressure plate 260, wherein,

[0089] The piston seat pressure plate 260 is connected to the top plate 200. The piston seat 240 is located in the positioning groove opened in the piston seat pressure plate 260 and is connected to the top plate 200. The piston rod mounting plate 250 is vertically and flexibly mounted on the top of the piston seat 240 to facilitate the synchronous driving of multiple syringe pistons.

[0090] The piston hole seat 240 is provided with several piston holes, each piston hole corresponding to a sample inlet 110, to realize multi-channel parallel operation;

[0091] The piston rod mounting plate 250 is used to mount the piston rod of the syringe, so that multiple piston rods can be controlled in a unified manner;

[0092] The syringe piston is telescopically mounted inside the piston orifice, and its movement stroke is controllable, thereby generating a stable negative pressure through retraction;

[0093] The piston hole is connected to one end of the sample inlet 110 to form a closed flow path, ensuring that the sample is accurately drawn in and quantitatively loaded into the corresponding sample inlet 110 under negative pressure.

[0094] This negative pressure injection method not only enables synchronous and controllable injection of multi-channel samples, but also, because the aspiration volume is controlled by mechanical displacement, the injection volume is precisely determined by the piston stroke and is not affected by electrochemical factors such as sample conductivity, ionic strength or buffer composition. This avoids the selective enrichment or loss of components caused by the "electrodiscrimination effect" during electro-injection, and is especially suitable for microfluidic electrophoresis analysis scenarios with multi-channel parallel and high-precision quantification.

[0095] Furthermore, it is worth mentioning that the piston hole seat pressure plate 260 not only securely confines the piston hole seat 240 within its positioning groove, ensuring assembly accuracy and sealing, but also significantly enhances the mechanical strength of the chip structure in the piston hole area. This effectively improves the ability of this location to resist deformation during negative pressure aspiration, avoiding microchannel deformation, sealing failure, or sample injection volume deviation caused by local stress concentration or material flexibility, thereby ensuring the accuracy of multi-channel sample injection and the reliability of system operation.

[0096] Preferably, an injection channel 111 is provided between the injection port 110 and the separation channel 120. The injection port 110 and the injection channel 111 are cross-connected, and the injection channel 111 and the separation channel 120 are cross-connected, forming a "T"-shaped or "+"-shaped cross injection structure.

[0097] This design not only provides a clear electric field path for electric sample introduction, but also enables the sample to be injected efficiently and centrally from the sample introduction channel 111 into the central region of the separation channel 120 under the action of the sample introduction electric field, reducing the diffusion effect and improving the sample introduction efficiency.

[0098] Meanwhile, the cross structure effectively isolates the sample loading flow path from the separation channel 120. During the non-sample injection stage, by controlling the sample injection electrode reed to maintain the same potential (i.e., there is no potential difference at both ends of the sample injection channel 111), the sample injection electric field can be eliminated, thereby effectively blocking subsequent samples or buffer solutions from entering the separation channel 120 due to electroosmosis or diffusion, avoiding cross-contamination and background interference, and ensuring the purity of the separation process and the repeatability of multiple rounds of detection.

[0099] Preferably, it also includes a sample injection capillary array 310, which serves as an external sample interface and is inserted into an external sample pool to achieve multi-channel synchronous sampling. The sample injection capillary array 310 is connected to one end of the sample injection through-hole 110, while the piston seat 240 is connected to the other end of the sample injection through-hole 110, forming a complete negative pressure drive flow path.

[0100] The sample inlet capillary array 310 is connected to the end of the sample inlet hole 110 near the sample inlet channel 111, and the sample outlet capillary array 341 is connected to the end of the sample inlet channel 111 away from the sample inlet hole 110.

[0101] In other words, the two ends of the sample inlet 110 are the negative pressure extraction end and the sample inlet end, respectively. Under the negative pressure drive, after the sample enters the sample inlet 110 from the sample inlet capillary array 310, it is uniformly sucked in along the axial direction of the inlet and gradually fills the entire cavity, thereby forming a continuous, dense sample column with controllable length.

[0102] This structure effectively avoids concentration gradients or sample fragmentation caused by uneven local flow rates or insufficient filling, ensuring that the samples entering the injection channel 111 and injected into the separation channel 120 at the cross intersection have a highly consistent initial distribution, significantly improving the repeatability, peak symmetry, and quantitative accuracy of electrophoretic separation.

[0103] Preferably, it also includes a pair of sample introduction electrode reeds 350 and a pair of separation electrode reeds 360, wherein the electrode configuration is as follows:

[0104] A pair of separation electrode springs 360 are respectively placed in the separation cathode buffer cell 320 and the separation anode buffer cell 330 for connection to the high voltage power supply of external instruments. A stable separation electric field is established between the capillary tubes of the anode and cathode buffer cells, and a separation electric field is formed on the separation channel 120 on the chip substrate 100. Each separation channel 120 can obtain a uniform and consistent driving electric field to ensure synchronous and efficient separation of multiple channels.

[0105] Of the pair of sample introduction electrode reeds 350, one is located in the sample outlet buffer 340, and the other is connected to the metal outer wall of the sample introduction capillary array 310. The two form an introduction electric field between the sample introduction capillary array 310 and the sample outlet capillary array 341, and form an introduction electric field applied to the sample introduction channel 111 on the chip substrate 100, which precisely drives the sample to be laterally injected into the separation channel 120 from the sample introduction channel 111.

[0106] This dual-field independent control architecture achieves electrical decoupling between the sample introduction and separation processes. It not only ensures that the sample is efficiently enriched at the cross-point during the sample introduction stage, but also completely cuts off the sample introduction electric field during the separation stage (by making the sample introduction electrode reed 35° at the same potential), effectively preventing subsequent sample infiltration or electroosmotic interference, thereby improving the separation resolution.

[0107] Specifically, during the sample introduction stage, the sample introduction electrode spring 350 applies an electric field to the sample introduction, causing the charged sample to be "pulled" from the vertical sample introduction hole 110 into the horizontal sample introduction channel 111 by electrophoretic force, and then passing through the cross intersection with the main separation channel 120 to form a narrow and concentrated initial sample plug with clear boundaries, which significantly reduces the width of the sample introduction zone and improves the subsequent separation resolution.

[0108] During the separation stage, a pair of sample introduction electrode reeds 350 maintain a positive potential state, while the separation electrode reeds 360 establish a longitudinal separation electric field at both ends of the separation channel 120, instantly cutting the sample at the intersection into the separation channel 120 and initiating efficient electrophoresis separation.

[0109] Furthermore, this structure supports a pressure-electric field combined injection strategy—first, the negative pressure generated by the piston drive uniformly fills the entire injection orifice 110 with the sample, ensuring that the sample enters the system without selective bias. Then, the electric field is used to precisely capture and focus the cross-region. This retains the high throughput and non-molecular selectivity advantages of pressure injection while integrating the high focusing and zonal sharpness of electric injection. Thus, while ensuring the representativeness of the injection, the separation performance is greatly improved. It is suitable for multi-channel nucleic acid or protein analysis scenarios with stringent requirements for sensitivity, repeatability, and resolution.

[0110] Preferably, the top plate 200 is provided with a detection window 270, which is set facing the separation channel 120, and the detection window 270 is set in a one-to-one correspondence with the separation channel 120 to ensure that each separation channel 120 has an independent optical detection area, so that the sample in each channel can be accurately monitored and analyzed.

[0111] A slot 150 is provided between adjacent separation channels 120. A separator plate (not shown in the figure) is inserted in the slot 150. The separator plate is used to separate the positions of the two adjacent separation channels 120 corresponding to the detection window 270, in order to reduce fluorescence crosstalk between separation channels 120.

[0112] Fluorescence crosstalk refers to the phenomenon where a fluorescence signal detected in one channel may be affected by fluorescent substances in adjacent channels, leading to inaccurate measurements or data distortion. By inserting separators, the individual channels can be physically isolated, especially at the detection window 270, further reducing the possibility of fluorescence crosstalk and improving the accuracy and reliability of detection.

[0113] This structural design is particularly important for multi-channel parallel analysis systems because it not only ensures the independence of operation between channels, but also improves the overall performance of the system, enabling high-quality data acquisition even in high-density, multi-channel environments. This is of significant value for applications requiring high precision and sensitivity, such as biochemical research and clinical diagnosis.

[0114] It is also worth mentioning that in the electrophoresis chip provided in this embodiment, the detection window 270 is provided in two rows (or more than two rows). The row of detection windows 270 near the sample injection port 110 is a fast detection window, and the other row of detection windows 270 is a high-resolution detection window.

[0115] The dual-row (or multi-row) detection window 270 layout implements a hierarchical detection strategy:

[0116] The rapid detection window 270 is located in front of the separation channel 120. Sample components can migrate to this window in a short time. It is suitable for primary screening scenarios with high requirements for analysis speed and relatively low requirements for separation (such as positive / negative judgment, rapid identification of large molecular fragments, etc.).

[0117] The high-resolution detection window 270 is located after the separation channel 120, corresponding to a longer migration path and more sufficient separation time. It can effectively distinguish components with similar migration rates (such as DNA fragments with single-base differences, isoenzymes, or modified proteins), meeting the needs of high-precision quantitative and qualitative analysis.

[0118] By integrating detection areas with different functional positioning on the same chip, users can flexibly select the detection position according to the actual application, balancing analysis efficiency and separation performance. At the same time, the multi-window design supports dynamic observation of the same electrophoresis process at multiple time points and resolutions, which helps to optimize separation conditions or verify the reliability of results.

[0119] This structure significantly expands the application flexibility and analytical dimensions of electrophoresis chips without increasing chip complexity.

[0120] In summary, this embodiment provides a capillary electrophoresis chip with multiple array channels, combined with a fully integrated instrument for biomolecular fragment analysis, to complete the development and demonstration of typical applications such as high-throughput sequencing library construction quality control, mutation site analysis, and respiratory pathogen detection. Its beneficial effects are summarized as follows:

[0121] 1. Achieve simultaneous separation of multiple channels to increase detection throughput.

[0122] By integrating multiple independent separation channels within the chip, parallel detection of samples can be achieved. Compared with traditional single-channel capillary electrophoresis chips, this structure significantly improves detection efficiency and throughput, meeting the needs of high-throughput biological sample analysis and rapid clinical screening. Furthermore, the electric field intensity per unit length of each separation channel is consistent, effectively eliminating migration time drift and significantly improving the consistency of multi-channel detection results.

[0123] 2. The separating gel and buffer solution are integrated into one package, simplifying the usage process.

[0124] The chip pre-fills and seals the separating gel and electrophoresis buffer in its internal structure, eliminating the need for manual gel preparation, filling, and buffer formulation before use. This reduces operational complexity, avoids human error, and improves the standardization and reproducibility of experiments.

[0125] 3. Automatically forms a stable separation channel 120 system, improving separation stability.

[0126] The integrated design ensures uniform separation gel concentration, consistent channel geometry, and stable buffer system, effectively reducing migration time fluctuations caused by bubbles, leakage, and uneven concentration, and improving the accuracy and reproducibility of electrophoretic separation.

[0127] 4. Reduce pollution risk and enhance system reliability

[0128] The separating gel and buffer solution are enclosed within the chip cavity, avoiding cross-contamination from the external environment or during operation; at the same time, it reduces reagent exposure and consumption, improves system safety and reagent utilization, and is particularly suitable for medical testing and high-sensitivity DNA / RNA analysis scenarios.

[0129] 5. High structural integration, which facilitates chip miniaturization and instrument modularization.

[0130] By integrating separation media, buffer systems, and microfluidic structures, the chip eliminates the need for an external liquid supply system, significantly reducing the overall system size and providing a hardware foundation for portable testing devices, point-of-care testing (POCT), and rapid on-site diagnostics.

[0131] 6. Highly compatible, suitable for analysis of various biological macromolecules.

[0132] The separating gel formulation and channel design can support the detection of a variety of biological macromolecules such as proteins, peptides, and nucleic acid fragments (DNA / RNA), and has broad application adaptability, which can be extended to multiple fields such as gene detection, disease biomarkers, and drug development.

[0133] 7. High degree of automation and easy system integration.

[0134] It can be used with an automatic sample introduction device, power management module and software control system to realize fully automatic sample introduction, electrophoretic separation, automatic cleaning and data acquisition and analysis, and is suitable for building intelligent and digital detection systems.

[0135] Furthermore, it is worth mentioning that the capillary electrophoresis chip provided in this embodiment, in addition to its use in the aforementioned detection, can also achieve extreme environmental control of the entire electrophoresis process through deep integration with microelectromechanical systems (MEMS) technology, thereby achieving single-base resolution and successfully extending to high-precision Sanger sequencing applications. Its key technical path is reflected in the following three aspects:

[0136] 1. Extremely narrow sample injection zone: Utilizing the chip's unique cross-channel structure, a nano-scale sample column is formed through electric control, eliminating the limitation of the initial zone width on resolution from the physical source.

[0137] 2. Ultra-high electric field drive: The chip material’s excellent heat dissipation specific surface area effectively suppresses the Joule heating effect, allowing the application of an electric field strength far higher than that of traditional capillaries, which greatly improves the separation speed and significantly reduces peak broadening caused by molecular diffusion.

[0138] 3. Integrated screening matrix: Combined with high-performance dynamic coating and high-resolution polymer gel, it can accurately distinguish subtle differences in single nucleotide charge and hydrodynamic volume within a small chip space.

[0139] In summary, through the synergistic optimization of ultra-narrow sample entry, ultra-strong electric field, and ultra-precise sieving, this chip reproduces or even surpasses the separation performance of traditional large-scale sequencing equipment on a miniaturized platform. It not only meets the stringent requirements of Sanger sequencing for single-base resolution, but also has the advantages of high throughput, low reagent consumption, rapid analysis, and automation compatibility, providing a core chip solution for the next generation of high-precision gene analysis instruments.

[0140] This invention also provides a flow path control method for a multi-channel integrated capillary electrophoresis chip, applied to the aforementioned multi-channel integrated capillary electrophoresis chip, comprising the following steps:

[0141] S1. Gel pouring and pre-electrophoresis: By precisely controlling the on / off state of the plunger valve 230 and cooperating with the pull-out plunger 220, the separating gel in the gel pool 210 is evenly injected into all separation channels 120 and sample injection channels 111 through the plunger valve channel 140, ensuring that each channel is completely filled without dead corners. Then, a low voltage is applied for pre-electrophoresis, and the presence of air bubbles or filling defects in the channels is monitored by current or fluorescence signals. If an abnormality is detected, the gel pouring is automatically triggered to repeat until there are no air bubbles left in all channels. This step ensures the uniformity of the electric field and the integrity of the gel matrix in the subsequent separation process.

[0142] S2, Sample Injection: Insert the sample injection capillary array 310 into the external sample cell. The negative pressure is generated by the retraction of the syringe piston in the piston seat 240, so that the sample flows through the sample injection capillary array 310, the sample injection through hole 110, the sample injection channel 111 and then enters the separation channel 120.

[0143] S3. Electrophoretic Separation and Detection: A separation voltage is applied between the separation cathode buffer 320 and the separation anode buffer 330 by the separation electrode reed 360, establishing a longitudinal electric field in the separation channel 120. This drives the sample at the intersection point into the separation channel and achieves efficient separation based on the difference in migration rate. At this time, a pair of sample injection electrode reeds 350 are controlled to a positive potential state (i.e., the potential difference between the two ends is zero), thereby eliminating the electric field in the sample injection channel 111, blocking electroosmotic flow and electrophoretic driving force, effectively preventing residual samples or buffer from continuing to migrate into the separation channel 120, avoiding cross-contamination or peak tailing. Subsequently, the fluorescence detection module of the external instrument performs real-time, parallel fluorescence detection of nucleic acid fragments in each separation channel through the corresponding detection windows 270 on the top plate 200.

[0144] S4. Waste Discharge: After completing one separation test, positive pressure is first applied through the piston in the piston seat 240 to push out the residual sample in the sample inlet channel 111 and sample inlet hole 110; then the potting action in S1 is reused—the plunger 220 is driven again and the corresponding plunger valve 230 is opened, using the newly injected separation adhesive as the "liquid pushing medium" to discharge the waste adhesive and test sample inside the chip in two ways: one way is pushed in reverse to the external waste liquid pool through the sample inlet capillary array 310, and the other way is discharged into the sample outlet buffer pool 340 through the sample outlet capillary array 341; finally, the front outer wall of the sample inlet capillary array 310 is cleaned by ultrasound or cleaning solution, and the chip is ready for the next round of testing.

[0145] To further improve resolution, the following measures can be taken:

[0146] 1. Reduce the width of the injection channel 111 to reduce the injection volume, but the effect of gel perfusion and its impact on the overall test time need to be investigated.

[0147] 2. In terms of electric field control, the voltages of the two injection electrodes and the two separation electrodes can be flexibly adjusted to prevent the sample from spreading to both sides during injection.

[0148] 3. Structurally, after focusing through the first cross (the intersection of the sample inlet hole 110 and the sample inlet channel 111), the sample volume at the second sample inlet cross (the intersection of the sample inlet channel 111 and the separation channel 120) is close to a rectangle, and the sample volume is smaller than that of single cross flow-limiting sample inlet.

[0149] 4. In terms of sieving media, optimize the gel concentration, and further use gradient gels to adjust the buffer pH and ionic strength.

[0150] This flow path control method integrates gel dispensing, sample injection, separation, waste discharge, and regeneration into a closed-loop process through multi-dimensional coordinated control of electromechanical-fluid-electric fields. It not only significantly improves the automation level, operational stability, and experimental repeatability of multichannel capillary electrophoresis, but also greatly reduces consumable costs and manual intervention, making it suitable for high-throughput, standardized molecular diagnostics and bioanalysis scenarios.

[0151] In addition, in this embodiment, the number of plunger valves 230 is set to three. To better illustrate the specific operation process of step S1, the three plunger valves 230 are respectively defined as the first plunger valve 231, the second plunger valve 232, and the third plunger valve 233.

[0152] 1. First, open the third plunger valve 233 located at both ends of the chip substrate 100, and at the same time close the first plunger valve 231 and the second plunger valve 232. Then, pull the plunger 220 to expel the air in the channel under negative pressure and initially introduce the separating adhesive. Next, close the first plunger valve 231 and the third plunger valve 233 at both ends, and only open the second plunger valve 232 in the middle position. Then, push the separating adhesive in the adhesive pool 210 by pressing the plunger 220, so that the separating adhesive gradually fills the interior of each separation channel 120. This action can be repeated 1-2 times to ensure that all separation channels are completely filled.

[0153] 2. After the separation channel 120 is filled, close the third plunger valve 233 at both ends, open the first plunger valve 231 and the second plunger valve 232, and press the plunger 220 again to allow the separating gel to continue flowing into the separation anode buffer pool 330 and the separation cathode buffer pool 320 connected to the separation channel 120, thereby ensuring that the entire electrophoresis flow path—including the separation channel 120 and the sample injection channel 111—is completely filled with the separating gel.

[0154] 3. After potting, open the first plunger valve 231 and the second plunger valve 232 at both ends of the chip (keep the flow path open to establish a complete electric field circuit), apply a low voltage for pre-electrophoresis; by monitoring the current stability or by combining optical / fluorescent methods, determine whether there are air bubbles or filling defects in the channel. If air bubbles are found, return to the above potting process and repeat the operation until there are no air bubbles left in all channels, to ensure the uniformity of the electric field and the reliability of the results of subsequent electrophoretic separation.

[0155] This three-valve collaborative control strategy achieves an orderly and controllable potting process from venting and main channel filling to buffer pool injection through segmented opening and closing and pressure direction regulation. It effectively avoids problems such as bubble encapsulation, uneven glue or channel blockage that are easily caused by traditional unidirectional potting, and provides key protection for the high repeatability of multi-channel chips.

[0156] The technical means disclosed in this invention are not limited to those described above, but also include technical solutions composed of any combination of the above technical features. The above are specific embodiments of this invention. It should be noted that those skilled in the art can make various improvements and modifications without departing from the principle of this invention, and these improvements and modifications are also considered within the scope of protection of this invention.

[0157] It should be noted that all directional indications (such as up, down, left, right, front, back, etc.) in the embodiments of the present invention are only used to explain the relative positional relationship and movement of each component in a certain specific posture (as shown in the figure). If the specific posture changes, the directional indication will also change accordingly.

[0158] Furthermore, in this invention, the use of terms such as "first," "second," and "a" is for descriptive purposes only and should not be construed as indicating or implying their relative importance or implicitly specifying the number of technical features indicated. Therefore, a feature defined as "first" or "second" may explicitly or implicitly include at least one of that feature. In the description of this invention, "a plurality of" means at least two, such as two, three, etc., unless otherwise explicitly specified. The terms "connection," "fixed," etc., should be interpreted broadly. For example, "fixed" can mean a fixed connection, a detachable connection, or an integral part; it can mean a mechanical connection or an electrical connection; it can mean a direct connection or an indirect connection through an intermediate medium; it can mean the internal communication of two elements or the interaction between two elements, unless otherwise explicitly specified. Those skilled in the art can understand the specific meaning of the above terms in this invention according to the specific circumstances.

[0159] The technical solutions of the various embodiments of the present invention can be combined with each other, but only if they are based on the ability of those skilled in the art to implement them. When the combination of technical solutions is contradictory or cannot be implemented, it should be considered that such combination of technical solutions does not exist and is not within the scope of protection claimed by the present invention.

[0160] The specific embodiments described herein are merely illustrative of the spirit of the invention. Those skilled in the art to which this invention pertains may make various modifications or additions to the described specific embodiments or use similar methods to substitute them, without departing from the spirit of the invention or exceeding the scope defined by the appended claims.

Claims

1. A reusable multi-channel integrated capillary electrophoresis chip, characterized in that, include: The chip substrate has a sample inlet port, a separation channel, a plunger valve port, and a plunger valve channel. A sample inlet channel is provided between the sample inlet port and the separation channel. The sample inlet port is connected to the separation channel through the sample inlet channel and is used for sample inlet. The separation channel is provided in multiple ways and is evenly arranged along the length or width direction of the chip substrate. Each separation channel is provided with a sample inlet hole. The plunger valve channel is connected to the separation channel through the plunger valve port. The separation channel includes a straight segment, a first curved extension segment, and a second curved extension segment. The total length of the straight segment, the first curved extension segment, and the second curved extension segment of each separation channel is the same, so that the electric field strength per unit length applied to each separation channel remains consistent. It also includes an inlet capillary array and an outlet capillary array, wherein one end of the inlet capillary array is inserted into an external sample cell and the other end is connected to the inlet port near the inlet channel, and the outlet capillary array is connected to the inlet channel away from the inlet port. It also includes a bottom shell, which is disposed at the bottom of the chip substrate. One side of the bottom shell has a separation anode buffer tank, and the other side has a separation cathode buffer tank and a sample discharge buffer tank. The separate cathode buffer cell and the separate anode buffer cell are respectively connected to the two plunger valve channels on both sides of the chip substrate through the separate cathode buffer cell capillary tube and the separate anode buffer cell capillary tube. The sample outlet buffer cell is connected to the sample inlet channel through the sample outlet capillary array; It also includes a pair of sample inlet electrode springs and a pair of separation electrode springs, wherein, A pair of separating electrode springs are respectively located in the separating cathode buffer cell and the separating anode buffer cell and are used to connect to the high-voltage power supply of external instruments. One sample injection electrode spring is located in the sample outlet buffer cell, and the other sample injection electrode spring is connected to the metal outer wall of the sample injection capillary array. A pair of the separation electrode springs are used to provide an electric field between the separation anode buffer capillary and the separation cathode buffer capillary, and to form a separation electric field applied to the separation channel on the chip substrate; A pair of the sample inlet electrode reeds are used to provide an electric field between the sample inlet capillary array and the sample outlet capillary array, and to form an inlet electric field applied to the sample inlet channel on the chip substrate.

2. The reusable multi-channel integrated capillary electrophoresis chip according to claim 1, characterized in that, It also includes a top plate disposed on the top of the chip substrate, the top plate and the bottom shell forming the outer shell of the chip substrate, the chip substrate being installed in the internal space of the outer shell, and the chip top plate being bonded on the chip substrate to form a chip structure.

3. A reusable multi-channel integrated capillary electrophoresis chip according to claim 2, characterized in that, The top plate is provided with a glue tank, and the glue outlet at the bottom of the glue tank is connected to the plunger valve channel.

4. A reusable multi-channel integrated capillary electrophoresis chip according to claim 2, characterized in that, The top plate is also provided with a plunger and a plurality of plunger valves. The plunger is connected to the plunger valve port, and each of the plunger valves is connected to the plunger valve channel and is used to control the flow path.

5. A reusable multi-channel integrated capillary electrophoresis chip according to claim 4, characterized in that, The top plate is also provided with a piston hole seat, a piston rod mounting plate, and a piston hole seat pressure plate. The piston hole seat pressure plate is connected to the top plate. The piston hole seat is located in a positioning groove opened in the piston hole seat pressure plate and is connected to the top plate. The piston rod mounting plate is vertically and flexibly mounted on top of the piston hole seat. The piston hole seat is provided with a plurality of piston holes, and the piston rod mounting plate is used to install the piston rod of the syringe. The piston of the syringe is telescopically disposed in the piston hole, and the piston hole is connected to one end of the injection through hole.

6. A reusable multi-channel integrated capillary electrophoresis chip according to claim 1, characterized in that, The injection port is cross-connected with the injection channel, and the injection channel is cross-connected with the separation channel.

7. A reusable multi-channel integrated capillary electrophoresis chip according to claim 5, characterized in that, The top plate is provided with a detection window, which is set facing the separation channel, and the detection window is set in a one-to-one correspondence with the separation channel.

8. A reusable multi-channel integrated capillary electrophoresis chip according to claim 7, characterized in that, A slot is provided between adjacent separation channels, and a partition plate is inserted into the slot to separate the positions of the two adjacent separation channels corresponding to the detection window.

9. A flow path control method for a reusable multi-channel integrated capillary electrophoresis chip, applied to the reusable multi-channel integrated capillary electrophoresis chip described in claim 7, characterized in that, Includes the following steps: S1. Coating and Pre-electrophoresis: During coating, control the opening and closing of the plunger valve and pull the plunger until the separation channel and the sample injection channel are completely filled with the separating gel. Then perform the pre-electrophoresis operation to identify whether there are air bubbles in each channel of the chip substrate. If there are air bubbles, repeat the coating operation until there are no air bubbles left. S2, Sample Injection: The sample injection capillary array is inserted into the sample cell, and the sample is drawn up by negative pressure. The sample enters the sample injection hole, then flows into the sample injection channel, and enters the separation channel from the cross intersection of the sample injection channel and the separation channel. S3, Electrophoretic Separation and Detection: The separation cathode buffer cell and the separation anode buffer cell are switched to the separation voltage to achieve sample separation. After sample separation, a pair of sample injection electrode springs are kept at a positive potential to prevent subsequent samples from entering the separation channel. Subsequently, the fluorescence detection module of the external instrument performs fluorescence detection on the nucleic acid fragments in the separation channel through the detection window. S4. Waste Discharge: After completing one separation test, the sample in the sample inlet channel is first discharged through the positive pressure of the piston in the piston seat. Then, the potting action of step S1 is performed. Part of the waste glue and test sample in the chip substrate is discharged to the waste liquid pool on the external sample stage through the sample inlet capillary array. Another part of the waste glue and test sample is discharged to the sample outlet buffer pool through the sample outlet capillary array. Finally, the outer wall of the front end of the sample inlet capillary array is cleaned by ultrasonic waves or cleaning solution. The chip is ready for the next round of testing.

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