KEY chip reaction unit and system, and use method and application of KEY chip reaction unit and system

Abstract

The invention provides a KEY chip reaction unit and system and a use method and application thereof, and designs a KEY chip operation device capable of realizing automation of a KEY chip reaction process, the KEY chip operation device comprises a loading unit and a motion assembly, the loading unit is used for loading and positioning the KEY chip reaction unit and can drive the KEY chip reaction unit to move back and forth, and the motion assembly is used for moving the KEY chip reaction unit. The motion assembly is used for driving the KEY chip to move up and down in the KEY chip reaction unit, so that the KEY chip completes reaction; the motion assembly comprises clamping units and a driving part, and the driving part can drive the KEY chips clamped by the multiple clamping units at the same time, so that full-automatic operation of response of the multiple KEY chips can be completed at the same time, errors caused by individual differences are eliminated, and the detection result is more accurate and reliable. According to the invention, a KEY product platform is constructed, high automation of the KEY product is realized in a simplest and lowest-cost mode capable of ensuring the accuracy of a detection result, and the method is suitable for large-scale popularization and application.

Description

Technical Field

[0001] This invention belongs to the field of in vitro clinical testing and biochip technology. Specifically, it relates to a KEY chip reaction unit, system, and its usage and application. Background Technology

[0002] Biochips are a high-throughput protein function analysis technique. Solid-phase protein chips are essentially protein arrays on a two-dimensional plane. Using appropriate methods, tiny droplets containing protein molecules are distributed to different locations on a solid support and then immobilized in situ using suitable techniques.

[0003] The KEY biochip (or KEY chip for short) is a biochip designed by our research team that resembles a key in shape. It includes a key handle and a key bar. The key handle allows for easy operation and handling of the key chip, while the key bar has a protein array fixed on it for detecting target analytes in samples.

[0004] Currently, KEY chip testing remains at the manual operation level, failing to achieve automated operation. This is not only time-consuming and labor-intensive, but also susceptible to deviations in test results due to individual differences in operation, such as varying operating frequency, pressure, or time errors. Therefore, to improve testing efficiency, ensure the accuracy of test results, and reduce costs, there is an urgent need to automate the operation of KEY chips. Summary of the Invention

[0005] To address the aforementioned problems, this invention provides a KEY chip reaction unit, system, and its usage method and application. It designs a KEY chip operating device capable of automating the KEY chip reaction process, including a loading unit and a motion component. The loading unit loads and positions the KEY chip reaction unit and carries it back and forth. The motion component drives the KEY chip to move up and down within the KEY chip reaction unit, thereby enabling the KEY chip to complete the reaction. The motion component includes a clamping unit and a driving component. The driving component can simultaneously drive multiple KEY chip reaction units clamped by the clamping units, thus enabling fully automated operation of multiple KEY chip reactions simultaneously. This eliminates errors caused by individual differences, making the detection results more accurate and reliable. This invention constructs a KEY product platform, achieving a high degree of automation for KEY products in the simplest, lowest-cost way while ensuring accurate detection results, making it suitable for large-scale promotion and application.

[0006] On one hand, the present invention provides a KEY chip reaction unit, which includes an integral structure composed of a starting component, a component for containing reaction reagents, and a terminating component, for detecting target substances in a sample; the starting component is used for the initial positioning of the KEY chip; the component for containing reaction reagents is used to contain the reagents required for the KEY chip reaction; and the terminating component is used to place the KEY chip after the reaction is completed.

[0007] To achieve automated operation, specific locations are needed to store the KEY chip before and after the reaction. According to the reaction process of the KEY chip, this invention adds a starting component and a termination component at the front and rear positions of the KEY chip reaction unit, respectively, thereby achieving the most convenient and efficient way to pick up and put down the KEY chip.

[0008] Furthermore, the components for containing reaction reagents include components for containing sample diluent, components for containing washing solution, components for containing enzyme-labeled solution, and components for containing colorimetric solution.

[0009] Furthermore, the number of components containing the washing liquid is one or more.

[0010] Furthermore, the structure of the starting component matches the structure of the KEY chip. Only when the KEY chip is inserted into the starting component in the correct direction can the initial positioning of the KEY chip be completed.

[0011] In some methods, the internal structure of the starting component is smaller than that of other components, and its internal structure is shrunk to just the size to allow the KEY chip to be inserted, similar to the principle of a keyhole.

[0012] In some methods, the cross-section of the starting component is trapezoidal, and the cross-section of the KEY chip is a matching trapezoidal. The KEY chip can be successfully inserted into the starting component only when the cross-section of the KEY chip is aligned with the trapezoidal direction of the cross-section of the starting component.

[0013] The setting of the starting component structure is a self-identification function of the KEY chip operator. The KEY chip reaction unit is equivalent to a disposable consumable used in the KEY chip operator. However, due to errors during operation, the KEY chip in the reaction unit may be missing. For example, when testing a batch of samples simultaneously, if one KEY chip reaction unit is missing a KEY chip, the operation will stop due to the missing chip, or the process may continue directly, resulting in waste of samples and testing reagents. Therefore, a starting component structure needs to be added to the KEY chip reaction unit to automatically identify whether the KEY chip has been successfully inserted. When the KEY chip operator senses that a KDY chip is present in each KEY chip reaction unit, the indicator light changes from red to green, and the KEY chip operator can be officially started. Therefore, before officially starting the KEY chip operator, ensuring that the KEY chip is correctly placed in the starting component of the KEY chip reaction unit can provide a guarantee for subsequent KEY reactions and detections, avoiding a series of problems caused by missing KEY chips during batch operations.

[0014] Furthermore, the starting component, the component containing the sample diluent, the component containing the washing solution, the component containing the enzyme-labeled solution, the component containing the colorimetric solution, and the termination component are all reagent tubes.

[0015] Furthermore, each reagent tube is interconnected to form a row of interconnected tubes.

[0016] Furthermore, the KEY chip reaction unit has a structure of six-tube, seven-tube, eight-tube, nine-tube, ten-tube, or eleven-tube.

[0017] The number of reagent tubes in the KEY chip reaction unit can be flexibly selected according to the KEY chip reaction steps. For example, when multiple washing or elution steps are required, more reagent tubes for storing washing or elution solutions are added, and when no washing or elution steps are required, the number of reagent tubes is reduced accordingly.

[0018] Furthermore, the KEY chip reaction unit has a nine-tube structure, consisting of, from left to right, a starter tube, a sample tube, a first washing solution tube, an enzyme labeling tube, a second washing solution tube, a third washing solution tube, a colorimetric solution tube, a fourth washing solution tube, and a stop tube.

[0019] On the other hand, the present invention provides a KEY chip system, the system including a KEY chip, a KEY chip reaction unit as described above, and a KEY chip operation device, the KEY chip operation device being used to perform the operations required for the KEY chip to react in the KEY chip reaction unit.

[0020] Furthermore, the KEY chip operating device includes a loading unit and a KEY chip motion assembly. The loading unit is used to load the KEY chip reaction unit. The starting component of the KEY chip reaction unit is equipped with the KEY chip, and the component containing the sample diluent is equipped with the sample. The KEY chip motion assembly is used to drive the KEY chip to move in the KEY chip reaction unit, thereby enabling the KEY chip to complete the reaction.

[0021] Furthermore, the loading unit includes a track and a positioning element. The positioning element is located on the track. When the KEY chip reaction unit is placed on the track, the positioning element is used to fix the position of the KEY chip reaction unit on the track. The loading unit can also carry the KEY chip reaction unit to move back and forth along the track direction.

[0022] Furthermore, the positioning element is a positioning bead, and a spring is provided below the positioning bead; the bottom of the KEY chip reaction unit is provided with a groove that matches the positioning bead.

[0023] In some methods, when the KEY chip reaction unit is pushed along the track, the bottom of the KEY chip reaction unit contacts the positioning bead and presses it down, compressing the spring. When it is pushed to the bottom groove position, the spring returns to its original position, the positioning bead springs up and enters the groove, and the KEY chip reaction unit is positioned.

[0024] Furthermore, the number of the loading units is one or more.

[0025] Furthermore, when there are multiple loading units, the multiple loading units are arranged neatly side by side.

[0026] Furthermore, the KEY chip motion assembly includes a clamping unit and a driving component. The clamping unit is used to clamp the KEY chip in the KEY chip reaction unit, and the driving component is used to drive the clamping unit to move together with the KEY chip.

[0027] Furthermore, the number of clamping units matches the number of loading units, so that the KEY chip in each loading unit can be clamped.

[0028] Furthermore, the driving component includes a driving rod, which is fixed integrally with the clamping unit, thereby carrying the clamping unit to move up and down together.

[0029] Furthermore, the drive rod includes a first drive rod and a second drive rod, and the clamping unit is fixed between the first drive rod and the second drive rod. The first drive rod and the second drive rod maintain the same direction of movement and together carry the clamping unit up and down.

[0030] In some configurations, the drive rod moves upward to its highest point, thereby carrying the clamping unit to hold the KEY chip upward and separating it from a reagent tube in the KEY chip reaction unit; the drive rod moves forward, and the KEY chip also moves forward, moving above the next reagent tube in the KEY chip reaction unit; the drive rod moves downward, and the KEY chip enters the next reagent tube.

[0031] In some methods, the drive rod repeatedly moves up and down, thereby carrying the clamping unit to clamp the KEY chip up and down inside a reagent tube, and the fixed dot matrix on the key rod of the KEY chip reacts with the reagent in the reagent tube.

[0032] Furthermore, the number of clamping units can be one or more, and the specific number is designed according to the number of products to be tested or the scale of the instrument, etc. When there are multiple clamping units, the multiple clamping units are arranged neatly side by side and fixed between the first drive rod and the second drive rod, and are driven by the first drive rod and the second drive rod together.

[0033] Multiple clamping units are fixed side by side between the first drive rod and the second drive rod, so that multiple clamping units can carry multiple KEY chips at the same time to realize the up and down movement of the KEY chips synchronously.

[0034] It is understood that the loading unit and KEY chip motion component provided by the present invention can only realize one-dimensional motion. The loading unit realizes the back-and-forth motion of the KEY chip reaction unit, and the KEY chip motion component realizes the up-and-down motion of the KEY chip. Although both are the simplest one-dimensional motions, combining the two one-dimensional motions together can complete the reaction of the KEY chip in the KEY chip reaction unit. This is equivalent to realizing the reaction of the KEY chip in the KEY chip reaction unit in the simplest and lowest cost way.

[0035] On the other hand, the present invention provides an automatic detection method for a KEY chip, wherein the method uses the KEY chip reaction unit as described above, or the KEY chip system as described above, to complete the reaction, and includes the following steps:

[0036] (1) Insert the KEY chip into the starting component of the KEY chip reaction unit;

[0037] (2) Add the sample to the component of the KEY chip reaction unit that contains the sample diluent;

[0038] (3) Place the KEY chip reaction unit in the loading unit of the KEY chip operation device;

[0039] (4) Start the KEY chip operating device to make the KEY chip complete the reaction;

[0040] (5) Remove the KEY chip and read the test results.

[0041] Furthermore, after starting the KEY chip operating device in step (4), the clamping unit in the KEY chip operating device clamps the KEY chip and causes the KEY chip to move up and down under the drive of the driving component. The loading unit in the KEY chip operating device can drive the KEY chip reaction unit to move back and forth. The combination of the up and down movement of the KEY chip and the back and forth movement of the KEY chip reaction unit enables the KEY chip to complete the reaction.

[0042] Furthermore, the KEY chip reaction unit has a nine-tube structure, consisting of, from left to right, a starter tube, a sample tube, a first washing solution tube, an enzyme labeling tube, a second washing solution tube, a third washing solution tube, a colorimetric solution tube, a fourth washing solution tube, and a termination tube; step (4) includes the following steps:

[0043] (a) The driving component drives the KEY chip from the starting tube into the sample tube and moves up and down to make the target substance on the sample combine with the detection point on the KEY chip to form a complex.

[0044] (b) The loading unit moves the KEY chip reaction unit forward one step so that the KEY chip is aligned with the first washing liquid tube. The driving component moves the KEY chip downward into the first washing liquid tube and moves up and down to perform washing.

[0045] (c) The loading unit moves the KEY chip reaction unit forward one step so that the KEY chip is aligned with the enzyme labeling tube. The driving component moves the KEY chip downward into the enzyme labeling tube and moves up and down so that the enzyme label binds to the complex on the KEY chip.

[0046] (d) The loading unit moves the KEY chip reaction unit forward one step, aligning the KEY chip with the second washing liquid tube. The driving component moves the KEY chip downward into the second washing liquid tube and moves up and down to seal the complex on the KEY chip.

[0047] (e) The loading unit moves the KEY chip reaction unit forward one step so that the KEY chip is aligned with the third washing liquid tube. The driving component moves the KEY chip downward into the third washing liquid tube and moves up and down to perform washing.

[0048] (f) The loading unit moves the KEY chip reaction unit forward one step, aligning the KEY chip with the colorimetric liquid tube. The driving component moves the KEY chip downward into the colorimetric liquid tube and moves up and down to make the complex on the KEY chip develop color.

[0049] (g) The loading unit moves the KEY chip reaction unit forward one step so that the KEY chip is aligned with the fourth washing liquid tube. The driving component moves the KEY chip downward into the fourth washing liquid tube and moves up and down to perform washing.

[0050] (h) The loading unit moves the KEY chip reaction unit forward one step, aligning the KEY chip with the termination tube, and the driving component moves the KEY chip downward into the termination tube.

[0051] The present invention has the following beneficial effects:

[0052] 1. Achieve fully automated operation of the KEY chip reaction process;

[0053] 2. Combining the two one-dimensional motion modes of up-down movement and forward-backward movement, the KEY chip completes the reaction in the KEY chip reaction unit in the simplest and lowest-cost way;

[0054] 3. Capable of simultaneously performing KEY chip reactions on multiple samples;

[0055] 4. Eliminates errors caused by individual differences during manual operation, making test results more accurate and reliable;

[0056] 5. It has a simple structure, low cost, high level of automation, and high accuracy of detection results, making it suitable for large-scale promotion and application.

[0057] Detailed description

[0058] KEY chip

[0059] The KEY chip provided by this invention is a solid-phase protein chip. Solid-phase protein chips are a high-throughput protein function analysis technology that can be used for protein expression profiling, studying protein-protein interactions, even DNA-protein and RNA-protein interactions, and screening protein targets for drug action. The research object of protein chip technology is protein. Its principle involves special chemical treatment of a solid support, followed by immobilization of known protein molecular products (such as enzymes, antigens, antibodies, receptors, ligands, cytokines, etc.) onto it. Based on the characteristics of these biomolecules, it captures the target proteins (present in serum, plasma, lymph, interstitial fluid, urine, exudate, cell lysate, secretions, etc.) that can specifically bind to them. Liquid reagents then complete the immune reaction, ultimately allowing for the simultaneous detection of multiple target analytes in a single sample. There are three main types of protein chips: protein microarrays, microplate protein chips, and three-dimensional gel block chips, all of which can be used to fabricate KEY chips. Protein microarray chips are preferred for preparing KEY chips.

[0060] The KEY chip is named for its key-like shape. Its handle allows for easy gripping or clamping of the chip, and information such as the sample name and sampling time can be printed on the handle. The protein microarray is mounted on the handle; depending on the number of analytes to be detected, an array of multiple protein dots can be fixed on the handle. When the KEY chip is placed vertically, the height of the protein dot array should not exceed the height of the liquid reagent in the reagent tube.

[0061] KEY chip reaction unit

[0062] Generally, a single KEY chip can be used for the detection of a single sample. The detection process requires inserting the KEY chip into the sample, first washing solution, enzyme-labeled reaction solution, second washing solution, third washing solution, chromogenic solution, and fourth washing solution respectively before the detection result can be determined. The KEY chip reaction unit is a structure specifically designed for the sample detection process using KEY chips in this invention. It contains multiple tanks that can hold the reagents for each step of the reaction. These tanks can be arranged side-by-side or in any shape, such as a circle or square. The detection is completed simply by inserting the KEY chip into each tank sequentially according to the detection procedure. Preferably, the KEY chip reaction unit can be composed of reagent tubes arranged side-by-side in a connected tube structure, which facilitates handling and transportation, allows for the sequential insertion of the KEY chip for reaction, and also facilitates the simultaneous detection of multiple samples. The side-by-side connected tube structure of the KEY chip reaction unit makes it easier to arrange them regularly and operate synchronously.

[0063] The KEY chip reaction unit can be used for manual operation to complete the KEY chip reaction, or corresponding automated equipment can be designed to achieve full automation of the KEY chip reaction. It can also realize the simultaneous and synchronous processing of multiple samples, eliminating individual differences that exist in manual operation. When used in automated equipment to realize the KEY chip reaction, the KEY chip reaction unit also needs to set the corresponding placement positions for the KEY chips before and after the reaction. Preferably, a reagent tube is added at each end of the parallel tube structure to place the KEY chips before and after the reaction, respectively.

[0064] KEY chip operator

[0065] The KEY chip manipulator can automate the entire KEY chip reaction process based on the KEY chip reaction unit. There are many ways to achieve automation. Through mechanical structure design and computer software process settings, intelligent operation of the KEY chip reaction can be achieved. However, this usually results in high cost and complex structure due to the high precision requirements.

[0066] This invention enables the simultaneous KEY chip reaction of multiple samples in a minimally invasive and cost-effective manner, while ensuring detection accuracy, achieving full automation throughout the process.

[0067] Loading unit

[0068] The loading unit is set on the KEY chip operator and is used to carry the KEY chip reaction unit. The KEY chip reaction unit needs to be placed on the loading unit, and then it can be positioned on the loading unit and its position can be kept fixed during operation, while also being easy to put in and take out.

[0069] In some methods, slide rails can be set on the loading unit to facilitate the placement and removal of the KEY chip reaction unit. The slide rails can also play a certain positioning role, so that each KEY chip reaction unit is only mounted on a specific slide rail.

[0070] In some configurations, positioning elements can be added to the slide rail of the loading unit to further position the KEY chip reaction unit and prevent it from sliding on the slide rail during operation. These positioning elements can be any type of positioning structure and can be placed anywhere on the slide rail. For example, two baffles can be placed at the front and back of the slide rail to fix the KEY chip reaction unit.

[0071] In some methods, the positioning element uses a positioning bead placed in the middle of the slide rail. The arc-shaped positioning bead makes it easier for the groove of the KEY chip reaction unit base plate to slide in and fit into the positioning bead.

[0072] In some designs, a spring can be placed below the positioning bead, and the positioning element is an elastic positioning bead, which makes the sliding process of the KEY chip reaction unit smoother and prevents damage to the KEY chip reaction unit or the slide.

[0073] In some configurations, the loading unit can carry the KEY chip reaction unit along with it.

[0074] In some methods, there can be multiple loading units, arranged side by side, so that they can move together in one direction.

[0075] In some methods, multiple loading units can carry the KEY chip reaction unit together and move back and forth, with the direction of the back and forth movement being consistent with the direction of the track (in this invention, movement along the direction parallel to the track is referred to as back and forth movement).

[0076] KEY chip motion components

[0077] The KEY chip motion assembly is used to drive the KEY chip to move within each reagent tube of the KEY chip reaction unit, thereby automatically completing the KEY chip reaction according to a pre-set process. Therefore, the KEY chip motion assembly can be configured in many ways. For example, a robotic arm can be used to grasp and carry the KEY chip, enabling three-dimensional movement (up / down, forward / backward, and left / right; in this invention, movement along the parallel direction of the track is referred to as forward / backward movement), thus sequentially completing the reactions of the KEY chips in multiple KEY chip reaction units.

[0078] In some methods, multiple KEY chip reaction units arranged side by side can be completed sequentially, or multiple robotic arms can be set up to complete the task simultaneously, which can save time.

[0079] In some approaches, to achieve simultaneous completion, the operations of each robotic arm need to be synchronized, thereby eliminating differences between different robotic arms.

[0080] In some methods, the KEY chip motion component can apply force to drive different robotic arms separately.

[0081] In some methods, the KEY chip motion component can also simultaneously apply force to multiple different robotic arms at one time, ensuring that each robotic arm is subjected to the same force, thereby completing various operations synchronously.

[0082] In some methods, the motion component of the KEY chip can achieve two-dimensional motion, both up and down and forward and backward.

[0083] In some methods, the motion component of the KEY chip can only achieve one-dimensional up-down motion.

[0084] The KEY chip motion assembly provided by the present invention includes a clamping unit and a driving component. The driving component is fixed together with multiple clamping units, thereby simultaneously driving multiple clamping units to complete the up and down movement of the KEY chip.

[0085] Clamping unit

[0086] The clamping unit is used to clamp the KEY chip, thereby carrying the KEY chip together to complete the up and down movement of the KEY chip.

[0087] In some methods, the clamping unit can flexibly clamp the KEY chip or release it into the corresponding reagent tube. Throughout the KEY chip reaction process, the KEY chip can be continuously clamped or released. During the release of the KEY chip, the clamping unit can either release the KEY chip or continue clamping it.

[0088] In some methods, after the clamping unit clamps the KEY chip from the starting tube, it keeps the entire KEY chip in a clamped state without releasing it until the KEY chip has completed its reaction and is sent to the termination tube, at which point the clamping unit finally releases the KEY chip.

[0089] The clamping unit can hold the KEY chip in any way, fixing the KEY chip and moving it along with it.

[0090] In some designs, the clamping unit can consist of two clamping plates, acting as a clamp.

[0091] In some configurations, the clamping unit consists of two clamping plates, left and right, which can clamp and release the KEY chip under the control of the KEY operator's control system.

[0092] In some methods, the clamping part of the clamping unit is equipped with an elastic object, such as a spring, rubber, metal sheet, or magnet, which is used to clamp the KEY chip by magnetic attraction.

[0093] In this invention, the elastic object in the clamping unit is preferably an elastic steel sheet, which can provide sufficient clamping force to keep the KEY chip stably clamped throughout the reaction process and prevent it from falling off midway.

[0094] During the liquid reaction between the KEY chip and the KEY chip reaction unit, the number of clamping units should not be less than the number of KEY chip reaction units in the same execution (the number of KEY chips and KEY chip reaction units should be consistent). They need to correspond one-to-one. The number of clamping units can be selected according to the scale of the equipment, the power, and the number of samples to be tested, etc., and can be set according to the requirements.

[0095] Drive components

[0096] The driving component is used to drive the clamping unit to move, and the clamping unit carries the KEY chip to move up and down together. In order to enable the KEY chips in multiple KEY chip reaction units to complete the reaction synchronously, eliminate batch-to-batch differences, and reduce costs, this invention uses a driving component to simultaneously drive multiple clamping units to synchronously complete various operations of the KEY chip reaction.

[0097] In some embodiments, the driving component is one or more driving rods that drive the clamping unit to move.

[0098] In some embodiments, the driving component consists of two driving rods located on either side of multiple clamping units arranged side by side, which simultaneously drive the multiple clamping units to move synchronously.

[0099] In some configurations, multiple clamping units are fixed side-by-side as a single unit, and two drive rods are fixed to the clamping units on both sides respectively, thus fixing the clamping units and drive rods as a single unit. The two drive rods can extend and retract vertically, thereby carrying multiple clamping units to simultaneously complete the vertical movement of multiple KEY chips at the reagent tubes of the corresponding KEY chip reaction units in the most streamlined motion.

[0100] Combination of up-and-down movement and forward-and-backward movement

[0101] In this invention, the KEY chip moves up and down under the action of the driving component and the clamping unit, and the KEY chip reaction unit moves back and forth under the action of the loading unit. The combination of up and down movement and back and forth movement realizes the reaction of the KEY chip in each reagent tube of the KEY chip reaction unit, and the reagent tubes are switched in sequence until the reaction of the KEY chip is finally completed.

[0102] In some methods, after the KEY chip moves upward, the loading unit moves the KEY chip reaction unit forward by the distance of one reagent tube. Then the KEY chip moves downward and enters the next reagent tube. In the next reagent tube, the KEY chip moves up and down, and so on, to realize the reaction of the KEY chip in each reagent tube in sequence. Attached Figure Description

[0103] Figure 1 This is a schematic diagram of the KEY chip reaction unit in Example 1;

[0104] Figure 2 This is a schematic diagram of the KEY chip in Example 1;

[0105] Figure 3 This is a schematic diagram of the structure of the KEY chip and the KEY chip reaction unit combined in Example 1;

[0106] Figure 4 This is a cross-sectional view of the KEY chip and the KEY chip reaction unit combined in Example 1;

[0107] Figure 5 This is an external view of the KEY chip operator in Example 2;

[0108] Figure 6 This is a schematic diagram of the overall structure of the KEY chip operator in Example 2;

[0109] Figure 7 This is an exploded view of the KEY chip operator in Example 2;

[0110] Figure 8 This is a schematic diagram of the loading unit and the KEY chip reaction unit in Example 2;

[0111] Figure 9 This is a bottom view of the KEY chip reaction unit in Example 2;

[0112] Figure 10 This is a schematic diagram of the KEY chip motion component in Example 2;

[0113] Figure 11 This is a flowchart illustrating how the KEY chip motion component in Example 2 drives the KEY chip from the starting tube into the sample tube.

[0114] Figure 12 This is a flowchart illustrating how the KEY chip motion component in Example 2 drives the KEY chip to repeatedly move up and down.

[0115] Figure 13 This is a photograph of the actual KEY chip operator.

[0116] Figure 14 This is a schematic diagram of the detection results of the KEY chip operator in Example 4. Detailed Implementation

[0117] The preferred embodiments of the present invention will be described in further detail below with reference to the accompanying drawings. It should be noted that the following embodiments are intended to facilitate understanding of the present invention and are not intended to limit it in any way. The raw materials and equipment used in the specific embodiments of the present invention are all known products and were obtained by purchasing commercially available products.

[0118] Example 1: The KEY chip reaction unit provided by the present invention

[0119] The KEY chip reaction unit provided in this embodiment is as follows: Figures 1-3 As shown, where Figure 1 This is a schematic diagram of the KEY chip reaction unit. Figure 2 This is a schematic diagram of the KEY chip structure; Figure 3 This is a schematic diagram of the structure of the KEY chip and the KEY chip reaction unit combined. Figure 4 This is a cross-sectional view of the KEY chip and the KEY chip reaction unit combined.

[0120] like Figure 1The KEY chip reaction unit 1 provided in this embodiment includes an integrated structure composed of a starting component 2, a component 3 for containing reaction reagents, and a termination component 4, used to detect target substances in a sample. The starting component 2 is used for the initial positioning of the KEY chip 5; the component 3 for containing reaction reagents is used to contain the reagents required for the reaction of the KEY chip 5; and the termination component 4 is used to place the KEY chip 5 after the reaction is complete. To achieve automated operation, specific locations need to be provided for storing the KEY chip 5 before and after the reaction. Based on the reaction flow of the KEY chip 5 in the KEY chip reaction unit 1, the starting component 2 and the termination component 4 are added at the front and rear positions of the KEY chip reaction unit 1, respectively, thereby achieving the most convenient and efficient method for picking up and placing the KEY chip 5.

[0121] Preferably, the component 3 containing the reaction reagents includes a component 6 containing the sample diluent, a component 7 containing the washing solution, a component 8 containing the enzyme label solution, and a component 9 containing the colorimetric solution.

[0122] Preferably, the number of components 7 that contain the washing liquid can be one or more.

[0123] like Figure 4 The internal structure of the starting component 2 matches the structure of the KEY chip 5. Only when the KEY chip 5 is inserted into the starting component 2 in the correct orientation can the initial positioning of the KEY chip 5 be completed. The internal structure of the starting component 2 is smaller than other components, its internal structure being reduced just enough to allow the KEY chip 5 to be inserted, similar to the principle of a keyhole. The cross-section 41 of the starting component is trapezoidal, and the cross-section 42 of the KEY chip is a matching trapezoid. The KEY chip 5 can be smoothly inserted into the starting component 2 only when the trapezoidal direction of the cross-section 42 of the KEY chip and the cross-section 41 of the starting component are aligned. The structural design of the starting component 2 is essential for the KEY chip operating instrument 11 (… Figure 5This is a self-identification function of the KEY chip reaction unit 1, which is equivalent to a disposable consumable used in the KEY chip operator 11. However, due to errors during operation, the KEY chip 5 may be missing from the KEY chip reaction unit 1. For example, when testing a batch of samples simultaneously, if one of the KEY chip reaction units 1 is missing the KEY chip 5, the operation will stop due to the missing KEY chip 5, or the process may continue as is, resulting in waste of samples and testing reagents. Therefore, it is necessary to add a starting component 2 structure to the KEY chip reaction unit 1, which can automatically identify whether the KEY chip 5 has been successfully inserted. When the KEY chip operator 11 senses that each KEY chip reaction unit 1 contains a KDY chip 5, the sensor light changes from red to green, and the KEY chip operator 11 can be officially started. Therefore, before officially starting the KEY chip operator 11, ensuring that the KEY chip 5 is correctly placed in the starting component of the KEY chip reaction unit 1 can guarantee the subsequent reaction and detection of the KEY chip 5 and avoid a series of problems caused by the missing KEY chip 5 during batch operations.

[0124] like Figure 1 The starting component 2, the component 6 containing the sample diluent, the component 7 containing the washing solution, the component 8 containing the enzyme-labeled solution, the component 9 containing the colorimetric solution, and the termination component 4 are all reagent tubes 12. Each reagent tube 12 is interconnected to form a row of connected tubes.

[0125] Preferably, the KEY chip reaction unit 1 has a six-tube, seven-tube, eight-tube, nine-tube, ten-tube, or eleven-tube structure. The number of reagent tubes 12 included in the KEY chip reaction unit 1 can be flexibly selected according to the reaction steps of the KEY chip 5. For example, when multiple washing or elution steps are required, more reagent tubes 12 for storing washing or elution solutions are added; when no washing or elution steps are required, the number of reagent tubes 12 is reduced accordingly.

[0126] Preferred, such as Figure 3 The KEY chip reaction unit 1 has a nine-tube structure, consisting of a start tube 14, a sample tube 15, a first washing solution tube 16, an enzyme labeling tube 17, a second washing solution tube 18, a third washing solution tube 19, a colorimetric solution tube 20, a fourth washing solution tube 21, and a stop tube 22, from left to right.

[0127] like Figure 2 The KEY chip 5 includes a key handle 23 and a key bar 24. A protein dot array 25 is fixed on the key bar 24. The protein dot array 25 can bind to the target analyte in the sample, thereby detecting the target analyte in the sample. The number and arrangement of protein dots in the protein dot array 25 can be arbitrarily designed and adjusted according to the size and requirements of the product.

[0128] KEY chip 5 and KEY chip reaction unit 1 can be packaged separately. Before testing, hold key handle 23 and insert KEY chip 5 into the starting tube 14 of KEY chip reaction unit 1. Figure 3 ).

[0129] Example 2: The KEY chip system provided by the present invention

[0130] The appearance of the KEY chip operator is as follows Figure 5 The overall structure of the KEY chip operator is as follows: Figure 6 ;Exploded view of the KEY chip operator is as follows Figure 7 The structure of the loading unit and the KEY chip reaction unit is as follows: Figure 8 The bottom view of the KEY chip reaction unit is shown below. Figure 9 The structure of the KEY chip motion component is as follows: Figure 10 The flowchart of the KEY chip motion component driving the KEY chip from the starting tube into the sample tube is as follows: Figure 11 The flowchart of the key chip motion component driving the key chip to repeatedly move up and down is as follows: Figure 12 See the actual picture of the KEY chip operator. Figure 13 .

[0131] The KEY chip system 26 provided in this embodiment includes a KEY chip 5, a KEY chip reaction unit 1, and a KEY chip operation device (KEY chip operator) 11 as provided in Embodiment 1. The KEY chip operation device 11 is used to complete the operation required for the KEY chip 5 to react in the KEY chip reaction unit 1.

[0132] like Figure 6 and 7 The KEY chip operating device 11 includes a loading unit 27, a KEY chip motion assembly 28, and a base 12. The loading unit 27 is used to load the KEY chip reaction unit 1 and can carry the KEY chip reaction unit 1 along with it. The starting component 2 of the KEY chip reaction unit 1 is equipped with a KEY chip 5, and the component 6 containing the sample diluent is equipped with a sample. The KEY chip motion assembly 28 is used to drive the KEY chip 5 to move within the KEY chip reaction unit 1, thereby enabling the KEY chip 5 to complete the reaction. The KEY chip motion assembly 28, the loading unit 27, and the base 12 are arranged sequentially from top to bottom.

[0133] like Figure 8 The loading unit 27 includes a track 29 and a positioning element 30. The positioning element 30 is located on the track 29. When the KEY chip reaction unit 1 is placed on the track 29, the positioning element 30 is used to fix the position of the KEY chip reaction unit 1 on the track 29.

[0134] Preferably, the positioning element 30 consists of a positioning bead 31 and a positioning strip 40, with the positioning bead 31 higher than the positioning strip 40, and a spring located below the positioning bead 31; the bottom 33 of the KEY chip reaction unit 1 is provided with a positioning groove 42 that matches the positioning element 30, including a spherical groove 34 that matches the positioning bead 31, and an elongated groove 41 that matches the positioning strip 40. Figure 9 When the KEY chip reaction unit 1 is pushed along the track 29, its bottom 33 contacts the positioning bead 31 and presses it downwards, compressing the spring. When pushed to the groove 34 position of the bottom 33, the spring returns to its original position, and the positioning bead 31 springs upwards into the spherical groove 34. At the same time, the positioning strip 40 also enters the elongated groove 41, completing the positioning of the KEY chip reaction unit 1. The number of loading units 27 can be one or more.

[0135] like Figure 8 When there are multiple loading units 27, the multiple loading units 27 are arranged neatly side by side, and each KEY chip reaction unit 1 can be inserted into each loading unit 27 in sequence.

[0136] like Figure 10 The KEY chip motion assembly 28 includes a clamping unit 35 and a driving component 36. The clamping unit 35 is used to clamp the KEY chip 5 in the KEY chip reaction unit 1, and the driving component 35 is used to drive the clamping unit 35 to move together with the KEY chip 5. The number of clamping units 35 matches the number of loading units 27, so that the KEY chip 5 in each loading unit 27 can be clamped. The clamping unit 35 is provided with an elastic steel sheet 32, which can provide sufficient clamping force to keep the KEY chip 5 stably clamped throughout the reaction process and prevent it from falling off midway.

[0137] The driving component 36 includes a driving rod 37, which is fixed to the clamping unit 35, thereby carrying the clamping unit 35 to move together. The driving rod 37 includes a first driving rod 38 and a second driving rod 39. The clamping unit 35 is fixed between the first driving rod 38 and the second driving rod 39. The first driving rod 38 and the second driving rod 39 maintain the same direction of movement and together carry the clamping unit 35 to move up and down.

[0138] The movement within the KEY chip operating device 11 includes up-and-down movement and back-and-forth movement. To keep the structure and operation as simple as possible, all movement modes provided in this embodiment are one-dimensional. The KEY chip 5 achieves one-dimensional up-and-down movement under the action of the driving component 36 and the clamping unit 35, and the KEY chip reaction unit 1 achieves one-dimensional back-and-forth movement under the action of the loading unit 27. The combination of up-and-down movement and back-and-forth movement enables the KEY chip 5 to react in each reagent tube 12 of the KEY chip reaction unit 1, and sequentially switches the reagent tubes 12 until the reaction of the KEY chip 5 is finally completed. When the driving rod 37 moves upward to the highest point 40, it carries the clamping unit 35 to clamp the KEY chip 5 upward and separate it from one of the reagent tubes 12 in the KEY chip reaction unit 1; the loading unit 27 moves forward, and the KEY chip reaction unit 1 also moves forward, so that the reagent tube 12 directly below the KEY chip 5 is replaced by the next reagent tube; then the driving rod 37 moves downward, and the KEY chip 5 enters the next reagent tube 12. The drive rod 37 can also move up and down repeatedly, while the device unit 27 remains stationary, thereby causing the clamping unit 35 to clamp the KEY chip 5 and move it up and down within a reagent tube 12. The fixed dot matrix 25 on the key rod 24 of the KEY chip 5 reacts with the reagent in the reagent tube 12.

[0139] Figure 11 This is a schematic diagram of the KEY chip 5 moving from the starting tube 14 to the sample tube 15, where (1) the KEY chip 5 is in the starting tube 14; (2) the drive rod 37 and the clamping unit 35 carry the KEY chip 5 upward, so that the KEY chip 5 reaches the highest point 40, and the KEY chip 5 is above the starting tube 14; (3) the loading unit 27 moves forward, so that the KEY chip 5 is above the sample tube 15; (4) the drive rod 37 and the clamping unit 35 carry the KEY chip 5 downward, so that the KEY chip 5 enters the sample tube 15.

[0140] Figure 12 This is a schematic diagram of the KEY chip 5 repeatedly moving up and down inside the sample tube 15. (1) The KEY chip 5 is above the sample tube 15; (2) The KEY chip 5 enters the sample tube 15. Then the KEY chip 5 repeats the movements in (1) and (2), repeatedly moving up and down inside the sample tube 15 until the reaction in the sample tube 15 is completed, and then... Figure 11 It enters the first washing liquid tube 16 in the same way, and so on. Figure 11 and Figure 12 In the movement mode, the KEY chip 5 completes the reaction in each reagent tube 12 of the KEY chip reaction unit 1 in sequence until the final reaction is completed and enters the termination tube 22.

[0141] The number of clamping units 35 can be one or more, and the specific number is designed according to the number of products to be tested or the scale of the instrument, etc. When there are multiple clamping units 35, they can be arranged neatly side by side and fixed between the first drive rod 38 and the second drive rod 39, and driven by the first drive rod 38 and the second drive rod 39 together. In this embodiment, there are 5 clamping units 35, which are fixed side by side between the first drive rod 38 and the second drive rod 39. Therefore, the 5 clamping units 35 can simultaneously carry 5 KEY chips 5 and complete the reaction of the KEY chips 5 synchronously.

[0142] Example 3: Operation Flow of the KEY Chip System

[0143] This embodiment uses the KEY chip manipulator 11 provided in Embodiment 2 to perform the KEY chip reaction. The KEY chip reaction unit 1 has a nine-tube structure, consisting of, from left to right, a start tube 14, a sample tube 15, a first washing solution tube 16, an enzyme labeling tube 17, a second washing solution tube 18, a third washing solution tube 19, a colorimetric solution tube 20, a fourth washing solution tube 21, and a stop tube 22. The specific operation procedure is as follows:

[0144] (1) Insert the KEY chip 5 into the starting component 2 of the KEY chip reaction unit 1;

[0145] Take out the sealed KEY chip reaction unit 1 from the packaging bag, tear open the seal, and insert the KEY chip 5 into the first starting tube 14 from the left in the KEY chip reaction unit 1.

[0146] (2) Add the sample to the sample tube 15 of the KEY chip reaction unit 1;

[0147] (3) Place the KEY chip reaction unit 1 in the loading unit 27 of the KEY chip operator 11;

[0148] (4) Start the KEY chip operator 11 to make the KEY chip 5 complete the reaction;

[0149] After the KEY chip manipulator 11 is activated, the clamping unit 35 in the KEY chip manipulator 11 clamps the KEY chip 5 and moves under the drive of the driving component, causing the KEY chip 5 to move up and down in the KEY chip reaction unit 1 and between the reagent tubes 12 in the KEY chip reaction unit 1. The specific process is as follows:

[0150] (a) The driving component 36 drives the KEY chip 5 from the starting tube 14 into the sample tube 15 and moves up and down to make the target substance on the sample combine with the detection point 10 on the KEY chip 5 to form a complex.

[0151] (b) Loading unit 27 drives KEY chip reaction unit 1 to move forward one step, so that KEY chip 5 is aligned with first washing liquid tube 16, and driving component 36 drives KEY chip 5 to move downward into first washing liquid tube 16, and moves up and down to perform washing.

[0152] (c) Loading unit 27 drives KEY chip reaction unit 1 to move forward one step, so that KEY chip 5 is aligned with enzyme labeling tube 17. Driving component 36 drives KEY chip 5 to move downward into enzyme labeling tube 17, and moves up and down to make enzyme labeling bind to the complex on KEY chip 5.

[0153] (d) Loading unit 27 drives KEY chip reaction unit 1 to move forward one step, so that KEY chip 5 is aligned with second washing liquid tube 18, and driving component 36 drives KEY chip 5 to move downward into second washing liquid tube 18, and moves up and down to seal the complex on KEY chip 5.

[0154] (e) Loading unit 27 drives KEY chip reaction unit 1 to move forward one step, so that KEY chip 5 is aligned with third washing liquid tube 19, and driving component 36 drives KEY chip 5 to move downward into third washing liquid tube 19, and moves up and down to perform washing.

[0155] (f) Loading unit 27 drives KEY chip reaction unit 1 to move forward one step, so that KEY chip 5 is aligned with color developing liquid tube 20. Driving component 36 drives KEY chip 5 to move downward into color developing liquid tube 20, and moves up and down to make the complex on KEY chip 5 develop color.

[0156] (g) Loading unit 27 drives KEY chip reaction unit 1 to move forward one step, so that KEY chip 5 is aligned with fourth washing liquid tube 21, and driving component 36 drives KEY chip 5 to move downward into fourth washing liquid tube 21, and moves up and down to perform washing.

[0157] (h) Loading unit 27 drives KEY chip reaction unit 1 to move forward one step, so that KEY chip 5 is aligned with termination tube 22, and driving component 36 drives KEY chip 5 to move downward into termination tube 22, and the reaction of KEY chip 5 is completed.

[0158] (j) The clamping unit 35 releases the KEY chip 5, and the loading unit 27 pushes the KEY chip reaction unit 1 outward so that it is close to the opening of the KEY chip operator 11 for easy removal.

[0159] (5) Remove the KEY chip and read the test results.

[0160] Example 4, Detection Sample

[0161] This embodiment uses the KEY chip manipulator 11 provided in Embodiment 2 and performs the KEY chip reaction according to the method provided in Embodiment 3 to detect antibodies that specifically recognize different viral characteristic proteins in porcine serum samples. The KEY chip contains a matrix of characteristic proteins, including gB and gE proteins associated with pseudorabies virus, p30 associated with African swine fever virus, N and M proteins associated with porcine reproductive and respiratory syndrome virus, and E2 protein associated with classical swine fever virus. The matrix also includes a quality control point indicating the effectiveness of the reaction; this quality control point is purified porcine IgG antibody. After the detection, the chip is scanned using a dedicated scanner. By locating and measuring the grayscale of the scanned image, the content of different target-specific antibodies in the sample can be quantitatively determined. Four porcine serum samples (1#, 2#, 3#, and 4#) were tested, and a blank control was performed. The results are shown in [Figure 1]. Figure 14 The test results were basically consistent with those obtained by manually operating the KEY chip.

[0162] Example 5: Verification of Detection Precision

[0163] This embodiment uses the KEY chip manipulator 11 provided in Embodiment 2 and performs the KEY chip reaction according to the method provided in Embodiment 3. Five replicate tests are conducted on the #3 pig serum sample in Embodiment 4. After the test, the chip is placed in a dedicated scanner for scanning. By locating the scanned image and measuring the grayscale, and statistically analyzing the measured grayscale values, the grayscale value deviation of the five replicates is calculated. The results are shown in Table 1.

[0164] Table 1. Results of repeated tests

[0165]

[0166] The results show that when the signal value is below 10.0, the deviation CV% (standard deviation ÷ mean × 100%) is within 5%. Considering the inherent biases introduced by the KEY chip and sample loading, the difference produced by this invention can be ignored.

[0167] While the present invention has been disclosed above, it is not limited thereto. Its applications in medicine can be expanded accordingly. Any person skilled in the art can make various modifications and alterations without departing from the spirit and scope of the invention; therefore, the scope of protection of the present invention should be determined by the scope defined in the claims.

Claims

1. A KEY chip reaction unit characterized by, The KEY chip reaction unit comprises a starting part, a reagent containing part and a termination part, which are combined into an integrated structure for completing the detection of target substances in samples; The starting part is used for the initial positioning of the KEY chip; The reagent containing part is used for containing reagents required for the KEY chip reaction; The termination part is used for placing the KEY chip after the reaction is completed.

2. The KEY chip reaction unit of claim 1, wherein, The reagent containing part comprises a sample diluent containing part, a washing liquid containing part, an enzyme marker solution containing part and a chromogenic solution containing part, which are connected into a pipeline structure in a row; the number of the washing liquid containing part is one or more.

3. The KEY chip reaction unit of claim 1, wherein, The structure of the starting part matches the structure of the KEY chip, and the initial positioning of the KEY chip can be completed only when the KEY chip is inserted into the starting part in the correct direction.

4. A KEY chip system, characterized by The KEY chip system comprises a KEY chip, a KEY chip reaction unit as claimed in claim 3 and a KEY chip operating device, which is used for completing the operation work required for the reaction of the KEY chip in the KEY chip reaction unit.

5. The system of claim 4, wherein, The KEY chip operating device is provided with a loading unit and a KEY chip moving assembly; the loading unit is used for loading the KEY chip reaction unit, at this time, the starting part of the KEY chip reaction unit has been loaded with the KEY chip, and the sample diluent containing part has been loaded with the sample; the KEY chip moving assembly is used for driving the KEY chip to move in the KEY chip reaction unit, so that the KEY chip completes the reaction.

6. The system of claim 5, wherein, The loading unit comprises a track and a positioning member; when the KEY chip reaction unit is placed on the track, the positioning member is used for fixing the position of the KEY chip reaction unit on the track; the loading unit can also carry the KEY chip reaction unit to move back and forth along the track; the number of the loading unit is one or more; when the number of the loading unit is more than one, the plurality of loading units are arranged in a row.

7. The system of claim 6, wherein, The KEY chip moving assembly comprises a clamping unit and a driving part; the clamping unit is used for clamping the KEY chip in the KEY chip reaction unit; the driving part is used for driving the clamping unit to move together with the KEY chip; the number of the clamping unit matches the number of the loading unit, so that the KEY chip in each loading unit can be clamped.

8. The system of claim 7, wherein, The driving part comprises a driving rod, which is fixed with the clamping unit as a whole, so as to carry the clamping unit to move up and down together.

9. The system of claim 15, wherein, The driving rod comprises a first driving rod and a second driving rod; the clamping unit is fixed between the first driving rod and the second driving rod; the first driving rod and the second driving rod keep consistent movement directions and jointly carry the clamping unit to move up and down together; the number of the clamping unit is one or more; when the number of the clamping unit is more than one, the plurality of clamping units are arranged in a row and fixed between the first driving rod and the second driving rod, and are jointly driven by the first driving rod and the second driving rod.

10. A method of automatically detecting a KEY chip, characterized by, The KEY chip reaction unit as claimed in any one of claims 1 to 3 or the KEY chip system as claimed in any one of claims 4 to 9 is used to complete the reaction, which comprises the following steps: (1) inserting the KEY chip into the starting part of the KEY chip reaction unit; (2) adding the sample into the part of the KEY chip reaction unit containing the sample diluent; (3) placing the KEY chip reaction unit in the loading unit of the KEY chip operation device; (4) starting the KEY chip operation device to make the KEY chip complete the reaction; (5) taking out the KEY chip and reading the detection result.

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