A fully automatic coagulation factor inhibitor titer detection device

Abstract

The utility model discloses a full -automatic coagulation factor inhibitor titer detection device, include: metal bath body, the hole position of metal bath body is placed with a plurality of reaction cup, three -axis moving mechanism, fixed mounting in metal bath body, a plurality of pipettor, vertical fixed connection is in three -axis moving mechanism, three -axis moving mechanism can independently lift every pipettor, and will pipettor move to the above reaction cup, press subassembly, fixed connection is in pipettor, be used for pressing reaction cup, vibration subassembly, fixed connection is in metal bath body, be used for vibrating reaction cup. Through three -axis moving mechanism drive three pipettor cooperation, automatically complete diluent pre -addition, sample times dilution and normal mixed plasma addition, replace traditional manual step -by -step operation. Full -range does not need manual intervention, realizes the automation sample adding, and the dilution concentration accuracy is improved significantly.

Description

Technical Field

[0001] This utility model relates to the field of coagulation inhibitor detection technology, specifically to a fully automated coagulation factor inhibitor titer detection device. Background Technology

[0002] In recent years, there has been an increasing trend in both acquired coagulation factor inhibitors and coagulation factor inhibitors in hemophilia patients. Determining the titer of coagulation factor inhibitors is essential for a definitive diagnosis. Coagulation factor inhibitor titer testing serves as a laboratory diagnostic indicator for acquired hemophilia and is also a key monitoring indicator for whether hemophilia patients develop inhibitors after receiving exogenous coagulation factor infusion therapy. Therefore, quantitative detection of coagulation factor inhibitors plays a crucial role in the laboratory diagnosis, differential diagnosis, treatment selection, and monitoring of treatment efficacy in hemophilia.

[0003] In the detection of coagulation factor inhibitors, the Bethesda method is a classic clinical method, whose core process includes numerous steps such as sample serial dilution, addition of normal mixed plasma, and incubation. However, the classic Bethesda method currently relies on manual operation, is cumbersome, has relatively many influencing factors during the detection process, and has a relatively low degree of automation, making it difficult to meet the needs of efficient and accurate clinical detection. Specifically:

[0004] Manual operation is inefficient and prone to errors: the serial dilution process requires manual step-by-step addition of diluent, transfer of sample and mixing. For example, to complete 8 dilution titers of 1:2, 1:4, 1:8, 1:16, 1:32, 1:64, 1:128 and 1:256, the sample needs to be added repeatedly, which is not only time-consuming, but also prone to deviation in sample volume due to differences in operator technique, affecting the accuracy of dilution concentration.

[0005] The process of removing air bubbles is experience-dependent and the results are unstable: air bubbles are easily generated after sample mixing. The traditional method requires the operator to gently tap the wall of the reaction cup to remove the air bubbles. This process depends on personal experience. If the tapping force is insufficient or uneven, the air bubbles cannot be completely removed, which will interfere with the subsequent coagulation time test results. The reaction cup has poor stability and is prone to contamination: when adding samples or normal mixed plasma, the reaction cup seal needs to be punctured manually with a pipette. If the reaction cup is not fixed stably, it is easy to tip over or shift, causing sample leakage. This not only causes test failure, but may also cause cross-contamination and affect the test results of other samples.

[0006] Parallel testing of multiple samples is challenging: Clinical testing often requires processing samples from multiple patients simultaneously. Traditional manual operation requires configuring dilution gradients and adding normal mixed plasma for each sample, which is a heavy workload for operators and makes it difficult to avoid the risk of sample confusion, further reducing testing efficiency and reliability. Utility Model Content

[0007] The purpose of this invention is to provide a fully automated coagulation factor inhibitor titer detection device to solve the above problems, as detailed below.

[0008] To achieve the above objectives, the present invention provides the following technical solution:

[0009] This utility model provides a fully automated device for detecting the titer of coagulation factor inhibitors, comprising:

[0010] A metal bath body, wherein several reaction cups are placed in the holes of the metal bath body;

[0011] The three-axis moving mechanism is fixedly installed on the metal bath body;

[0012] Several pipettes are vertically fixedly connected to a three-axis moving mechanism, which can independently raise and lower each pipette and move the pipette above the reaction cup;

[0013] The pressing component is fixedly connected to the pipette and is used to press the reaction cup;

[0014] The vibration assembly is fixedly connected to the metal bath body and is used to vibrate the reaction cup.

[0015] The aforementioned fully automated coagulation factor inhibitor titer detection device aims to automate the Bethesda method. It utilizes a multi-component collaborative system, with a three-axis moving mechanism driving a dedicated pipette to automatically complete the pre-addition of diluent to the reaction cup, sample injection, and transfer. This achieves iso-diluted reactions. After adding normal mixed plasma to the pipette, pneumatic mixing is performed. A vibration component removes air bubbles, a pressing component stabilizes the cup to prevent tipping, and a 37°C constant-temperature incubation in a metal bath ensures a stable reaction. The device supports parallel testing of multiple patient samples, effectively reducing errors from manual sample addition.

[0016] Preferably, the pipette has three parts, which are used to aspirate diluent, test sample, and normal mixed plasma, respectively.

[0017] Preferably, the three-axis moving mechanism consists of an X-axis moving axis, a Y-axis moving axis, and three Z-axis moving axes, with the three pipettes vertically fixedly connected to the three Z-axis moving axes respectively.

[0018] Preferably, the vibration assembly includes a fixing plate fixedly connected to the metal bath body, the fixing plate having a plurality of through holes corresponding to the holes in the metal bath body, the reaction cup being clearance-fitted with the inner wall of the through holes, and a plurality of vibration motors being fixedly connected to the fixing plate.

[0019] Preferably, the fixing plate has several strip grooves at equal intervals, and the vibration motor is fixedly connected in the strip grooves.

[0020] Preferably, the pressing assembly includes a telescopic rod vertically fixedly connected to the pipette, the lower end of the telescopic rod corresponding to the top of the reaction cup, and a pressure plate fixedly connected thereto.

[0021] Preferably, the pressure plate has a notch corresponding to the pipette puncture needle.

[0022] Preferably, the telescopic rod includes a rectangular tube, and a movable rod is slidably connected inside the rectangular tube. A pressure plate is fixedly connected to the lower end of the movable rod. A spring is provided inside the rectangular tube, and the two ends of the spring are fixedly connected to the rectangular tube and the movable rod, respectively.

[0023] The beneficial effects are:

[0024] 1. Driven by a three-axis moving mechanism, three pipettes work together to automatically complete the pre-addition of diluent, serial dilution of samples, and addition of normal mixed plasma, replacing the traditional manual step-by-step operation. No manual intervention is required throughout the process, realizing automated sample addition and significantly improving the accuracy of dilution concentration.

[0025] 2. A vibration motor drives a fixed plate to vibrate, and the vibration is then transmitted uniformly to the reaction cup through a through-hole, thoroughly removing air bubbles from the mixed samples. Compared to the traditional method of manually tapping the reaction cup, this method optimizes the uniformity of vibration transmission through a strip groove, and does not rely on the operator's experience, ensuring consistent air bubble removal for each batch of samples and avoiding interference from air bubbles in the coagulation time measurement.

[0026] 3. The pressing component ensures the stability of the reaction cup. Before the puncture needle contacts the sealing plug of the reaction cup, the pressing plate presses down on the sealing plug first. During the puncture process, when the telescopic rod is compressed and disengaged, the telescopic rod is not fully extended, so that the reaction cup is always subjected to downward pressure. This ensures that the reaction cup is stably placed in the metal bath orifice during puncture and liquid transfer, effectively preventing the reaction cup from tipping over and the sample from leaking out, and completely eliminating the problems of contamination and test failure caused by the instability of the reaction cup.

[0027] 4. The metal bath body adopts a rectangular array well design, with each row of wells corresponding to the dilution gradient of one patient's sample, allowing for the simultaneous allocation of independent rows of wells for multiple patients. Combined with automated operation processes, it eliminates the need for manual handling of each sample individually, significantly reducing the workload of operators, enabling parallel testing of multiple samples, significantly improving clinical testing throughput, and meeting the needs of batch testing. Attached Figure Description

[0028] To more clearly illustrate the technical solutions in the embodiments of this utility model or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of this utility model. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0029] Figure 1 This is a three-dimensional structural diagram of the present invention;

[0030] Figure 2 This is a three-dimensional structural schematic diagram of the present invention from another perspective;

[0031] Figure 3 This is a three-dimensional structural diagram of the pressing component of this utility model;

[0032] Figure 4 This is a three-dimensional cross-sectional structural diagram of the telescopic rod of this utility model;

[0033] Figure 5 This is a three-dimensional structural diagram of the vibration component of this utility model.

[0034] The annotations in the attached figures are explained as follows:

[0035] 1. Metal bath body; 2. Three-axis moving mechanism; 201. X-axis moving axis; 202. Y-axis moving axis; 203. Z-axis moving axis; 3. Pipette; 4. Reaction cup; 5. Vibration assembly; 501. Fixing plate; 502. Through hole; 503. Vibration motor; 504. Strip groove; 6. Pressing assembly; 7. Telescopic rod; 701. Rectangular cylinder; 702. Movable rod; 703. Spring; 8. Pressure plate; 9. Notch. Detailed Implementation

[0036] To make the objectives, technical solutions, and advantages of this utility model clearer, the technical solutions of this utility model will be described in detail below. Obviously, the described embodiments are only a part of the embodiments of this utility model, and not all of them. Based on the embodiments of this utility model, all other implementation methods obtained by those skilled in the art without creative effort are within the scope of protection of this utility model.

[0037] See Figures 1-5 As shown, this utility model provides a fully automatic coagulation factor inhibitor titer detection device, including a metal bath body 1, a three-axis moving mechanism 2, several pipettes 3, a pressing component 6, and a vibration component 5.

[0038] The metal bath body 1 has several reaction cups 4 placed in its well positions. The metal bath body 1 has several well positions arranged in a rectangular array. In actual testing, each row of well positions can be used to test one patient sample. For example, if it is necessary to complete four serial dilutions of 1:2, 1:4, 1:8, and 1:16, each patient's sample needs to occupy four consecutive well positions, i.e., one row. The metal bath body 1 can simultaneously allocate independent rows of wells for multiple patients, realizing parallel testing of multiple samples.

[0039] The three-axis moving mechanism 2 is fixedly mounted on the metal bath body 1. A pipette 3 is vertically fixedly connected to the three-axis moving mechanism 2, which can independently raise and lower each pipette 3 and move it above the reaction cup 4. There are three pipettes 3, used for aspirating diluent, the sample to be tested, and normal mixed plasma, respectively. A pressing component 6 is fixedly connected to the pipette 3 for pressing the reaction cup 4. A vibration component 5 is fixedly connected to the metal bath body 1 for vibrating the reaction cup 4.

[0040] The core function of this application is to automatically perform proportional dilution of each patient sample, which can significantly improve efficiency compared to existing coagulation inhibitor detection methods, such as the Bethesda method.

[0041] It is important to note that the triaxial moving mechanism 2, in conjunction with the three pipettes 3, not only enables automatic sample addition to the reaction cups 4, but also allows one of the pipettes 3 to mix the samples in each reaction cup 4 via pneumatic mixing. Of the three pipettes 3, only one fixed pipette 3 is used for mixing, which avoids contamination of the other two pipettes 3. The pipette 3 used for sample mixing does not come into contact with other diluents or normally mixed plasma, so this pipette 3 does not contaminate other samples or become contaminated.

[0042] As an optional embodiment, see Figure 1 and Figure 2 The three-axis moving mechanism 2 consists of an X-direction moving axis 201, a Y-direction moving axis 202, and three Z-direction moving axes 203. The three pipettes 3 are vertically fixedly connected to the three Z-direction moving axes 203 respectively.

[0043] In this embodiment, the three-axis moving mechanism 2 is a conventional technology in the prior art, which can accurately move the pipette 3. Each pipette 3 can be moved independently through the three Z-axis moving axes 203.

[0044] As an optional embodiment, see Figure 1 , Figure 2 as well as Figure 5 The vibration assembly 5 includes a fixing plate 501 fixedly connected to the metal bath body 1. The fixing plate 501 has several through holes 502 corresponding to the holes in the metal bath body 1. The reaction cup 4 is fitted with the inner wall of the through holes 502 with a clearance. Several vibration motors 503 are fixedly connected to the fixing plate 501.

[0045] In this embodiment, the vibration component 5 is used to vibrate the reaction cup 4, thereby removing air bubbles from the solution in the reaction cup 4;

[0046] Specifically, the vibration motor 503 vibrates the fixing plate 501, and the fixing plate 501 transmits the vibration to the reaction cup 4 through the through hole 502, thereby removing air bubbles through vibration.

[0047] Furthermore, a number of strip grooves 504 are equally spaced on the fixing plate 501, and the vibration motor 503 is fixedly connected in the strip grooves 504. By setting the strip grooves 504, the contact between the vibration motor 503 and the fixing plate 501 can be improved, and the uniformity of the vibration motor 503 transmitted to the fixing plate 501 can be improved.

[0048] As an optional embodiment, see Figure 3 and Figure 4 The pressing component 6 includes a telescopic rod 7 that is vertically fixedly connected to the pipette 3. The lower end of the telescopic rod 7 corresponds to the top of the reaction cup 4 and is fixedly connected to a pressure plate 8. The pressure plate 8 has a notch 9 that corresponds to the puncture needle of the pipette 3.

[0049] In this embodiment, the telescopic rod 7 and the pressure plate 8 move downward with the pipette 3. Before the puncture needle of the pipette 3 contacts the sealing plug of the reaction cup 4, the pressure plate 8 contacts the sealing plug of the reaction cup 4 first. After the pipette 3 pierces the reaction cup 4, the telescopic rod 7 will be compressed. When the pipette 3 moves upward, the telescopic rod 7 gradually extends.

[0050] It should be noted that before the pipette 3 puncture needle is completely separated from the mouth of the reaction cup 4, the telescopic rod 7 is not fully extended. That is, before and after the pipette 3 enters and leaves the reaction cup 4, the reaction cup 4 will always bear the downward pressure of the telescopic rod 7 and the pressure plate 8. This ensures that the reaction cup 4 is always stably placed in the hole of the metal bath body 1.

[0051] Specifically, in this embodiment, the telescopic rod 7 includes a rectangular tube 701, and a movable rod 702 is slidably connected inside the rectangular tube 701. A pressure plate 8 is fixedly connected to the lower end of the movable rod 702. A spring 703 is provided inside the rectangular tube 701, and the two ends of the spring 703 are fixedly connected to the rectangular tube 701 and the movable rod 702 respectively.

[0052] When the telescopic rod 7 is compressed, the movable rod 702 enters the rectangular tube 701. When the telescopic rod 7 is extended, the movable rod 702 is pushed away from the rectangular tube 701 by the spring 703.

[0053] Working principle:

[0054] I. Initial Equipment Preparation and Bethesda Method Parameter Matching

[0055] Several sterile reaction cups 4 are placed in the rectangular array of wells in the metal bath body 1 according to the dilution gradient requirements of the Bethesda method. Three pipettes 3 are assigned specific functions according to the Bethesda method requirements and are pre-loaded with normal mixed plasma to avoid cross-contamination. The three pipettes 3 are classified as A, B, and C for easy identification and explanation, as follows:

[0056] Pipette A with dedicated diluent: pre-loaded with the diluent required for the Bethesda process, used to add the diluent to the reaction vessel;

[0057] Pipette B is a dedicated sample pipetting device: pre-loaded with the patient's plasma sample to be tested, used for transferring the original sample, sample transfer during subsequent dilution, and pneumatic mixing during serial dilution;

[0058] Pipette C for Normal Mixed Plasma Pipetting: Normal plasma and thromboplastin are subsequently added to the mixture, and the entire process does not involve contact with the diluent or the original sample, completely eliminating contamination.

[0059] II. The standard configuration includes tubes for eight dilution gradients according to the Bethesda method requirements: 1:2, 1:4, 1:8, 1:16, 1:32, 1:64, 1:128, and 1:256. Three high-titer dilution wells are reserved for high-titer samples to increase the dilution gradient. A control reaction system is also included. A corresponding number of consecutive reaction cups (4) are assigned to each patient and placed sequentially into the wells of the metal bath body (1), ensuring a one-to-one correspondence between well number and dilution gradient.

[0060] 1. All reaction cups 4 are pre-filled with diluent: The three-axis moving mechanism 2 drives the pipette A to move sequentially to the top of reaction cups 1-4 4 according to the preset program. The puncture needle is lowered by the Z-direction moving axis 203 to inject a quantitative diluent into each reaction cup 4. After the injection is completed, the pipette A is reset. At this time, all reaction cups 4 have been pre-loaded with a quantitative diluent. At the same time, the control reaction cup also needs to be filled with an equal volume of diluent.

[0061] 2. The three-axis moving mechanism 2 drives the pipette B to move above the No. 1 reaction cup and injects a quantitative amount of raw patient plasma sample into the reaction cup 4. At this time, the sample concentration is 1:2. At the same time, the pipette B aspirates the gas in the reaction cup 4 and then extends into the sample to blow the gas into the sample. The flowing gas is used to mix the sample in the reaction cup 4, so that the sample and diluent are fully mixed.

[0062] 3. The three-axis moving mechanism 2 drives the pipette B to quantitatively extract the mixed sample from reaction cup 1 and inject it into reaction cup 2. At the same time, it is mixed with the diluent in reaction cup 2 according to the above mixing method. By following this step, the serial dilution of the Bethesda method can be completed.

[0063] III. Adding normal mixed plasma

[0064] After serial dilution, pipette C adds the pre-prepared normal mixed plasma to each reaction cup 4 in sequence. After the normal mixed plasma is added, pipette B still needs to mix the sample in each reaction cup 4 according to the above steps. After pipette B has completed mixing of all reaction cups, it uses the vibration component 5 to vibrate the reaction cup 4 to remove air bubbles in the sample. Then the metal bath body 1 immediately enters the constant temperature incubation mode.

[0065] The above description is merely a specific embodiment of this utility model, but the protection scope of this utility model is not limited thereto. Any variations or substitutions that can be easily conceived by those skilled in the art within the technical scope disclosed in this utility model should be included within the protection scope of this utility model. Therefore, the protection scope of this utility model should be determined by the protection scope of the claims.

Claims

1. A fully automated device for detecting the titer of coagulation factor inhibitors, characterized in that, include: Metal bath body (1), wherein a plurality of reaction cups (4) are placed in the holes of the metal bath body (1); A three-axis moving mechanism (2) is fixedly installed on the metal bath body (1); Several pipettes (3) are vertically fixedly connected to a three-axis moving mechanism (2). The three-axis moving mechanism (2) can independently raise and lower each of the pipettes (3) and move the pipettes (3) above the reaction cup (4). The pressing component (6) is fixedly connected to the pipette (3) and is used to press the reaction cup (4); The vibration component (5) is fixedly connected to the metal bath body (1) and is used to vibrate the reaction cup (4).

2. The fully automated coagulation factor inhibitor titer detection device according to claim 1, characterized in that: There are three pipettes (3), which are used to aspirate diluent, test sample and normal mixed plasma respectively.

3. The fully automated coagulation factor inhibitor titer detection device according to claim 2, characterized in that: The three-axis moving mechanism (2) consists of an X-direction moving axis (201), a Y-direction moving axis (202) and three Z-direction moving axes (203), and three pipettes (3) are vertically fixedly connected to the three Z-direction moving axes (203).

4. The fully automated coagulation factor inhibitor titer detection device according to claim 1, characterized in that: The vibration assembly (5) includes a fixing plate (501) fixedly connected to the metal bath body (1). The fixing plate (501) has several through holes (502) corresponding to the holes in the metal bath body (1). The reaction cup (4) is clearance-fitted with the inner wall of the through hole (502). Several vibration motors (503) are fixedly connected to the fixing plate (501).

5. The fully automated coagulation factor inhibitor titer detection device according to claim 4, characterized in that: The fixing plate (501) has several strip grooves (504) evenly spaced on it, and the vibration motor (503) is fixedly connected in the strip grooves (504).

6. The fully automated coagulation factor inhibitor titer detection device according to claim 1, characterized in that: The pressing assembly (6) includes a telescopic rod (7) that is vertically fixed to the pipette (3). The lower end of the telescopic rod (7) corresponds to the top of the reaction cup (4) and is fixedly connected to a pressure plate (8).

7. The fully automated coagulation factor inhibitor titer detection device according to claim 6, characterized in that: The pressure plate (8) has a notch (9) corresponding to the puncture needle of the pipette (3).

8. The fully automated coagulation factor inhibitor titer detection device according to claim 6, characterized in that: The telescopic rod (7) includes a rectangular tube (701), and a movable rod (702) is slidably connected inside the rectangular tube (701). A pressure plate (8) is fixedly connected to the lower end of the movable rod (702). A spring (703) is provided inside the rectangular tube (701), and both ends of the spring (703) are fixedly connected to the rectangular tube (701) and the movable rod (702) respectively.

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