Sample mixing method and sample mixing device
By adopting a forward and reverse eccentric rotation mixing method in the sample mixing device, the problems of cumbersome sample mixing steps, long time and easy cross contamination in the existing technology are solved, and a fast, efficient and cross-contamination-free sample mixing process is achieved.
Patent Information
- Application Number
- CN202410309852.2
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2024-03-15
- Publication Date
- 2025-09-16
AI Technical Summary
The existing technology has problems in the sample mixing process such as complicated steps, long time, low efficiency and easy cross contamination.
A sample mixing method uses a mixing mechanism to drive a container through a combination of forward and reverse eccentric rotation to achieve rapid and effective sample mixing. The method involves mounting the container on the mixing mechanism and controlling the mixing mechanism to generate rotational forces in different directions, causing the container to rotate eccentrically to achieve uniform mixing of the sample.
It improves the speed and efficiency of sample mixing, reduces mixing time, avoids cross contamination, and can adapt to the mixing requirements of different sample systems with good compatibility.
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Figure CN120644103A_ABST
Abstract
Description
Technical Field
[0001] The present application relates to the technical field of biochemical substance analysis, and in particular to a sample mixing method and a sample mixing device. Background Art
[0002] With the development of sequencing technology, sample mixing is required during sequencing library construction. Currently, sample mixing is usually performed by aspiration, mainly using an air pump or liquid pump to draw in and then expel the sample or air, or by blowing air into the sample using an external gas cylinder and an air line control pump.
[0003] However, the use of the above-mentioned aspiration method to mix samples requires timing control, the mixing steps are cumbersome, the mixing time is long, and the mixing efficiency is low; in addition, cross contamination is easily caused during the mixing process. Summary of the Invention
[0004] In order to solve at least one of the above defects, it is necessary to propose a sample mixing method.
[0005] In addition, the present application also provides a sample mixing device for executing the aforementioned sample mixing method.
[0006] In a first aspect, an embodiment of the present application provides a sample mixing method, the method comprising:
[0007] Step S1, installing at least one sealed container containing a sample on a mixing mechanism;
[0008] Step S2, controlling the mixing mechanism to generate a rotational force in a first direction to drive the container to rotate in the first direction; and
[0009] Step S3: controlling the mixing mechanism to generate a rotational force in a second direction to drive the container to rotate in the second direction, where the second direction is opposite to the first direction.
[0010] In some possible embodiments, step S2 and step S3 constitute a hybrid sub-process, and the method includes at least one such hybrid sub-process.
[0011] In some possible embodiments, the method includes multiple mixing sub-processes, and at least one of the setting parameters of different mixing sub-processes is different, and the setting parameters include the mixing time of step S2, the mixing speed of step S2, the mixing time of step S3, the mixing speed of step S3 and the number of cycles of each mixing sub-process.
[0012] In some possible embodiments, the mixing time of step S2 and step S3 is 1s to 100s; and / or,
[0013] The mixing speeds in step S2 and step S3 are both 2000 rpm to 3000 rpm; and / or,
[0014] The number of cycles is at least one.
[0015] In some possible embodiments, in step S2, the mixing mechanism is controlled to generate an eccentric rotational force along the first direction, so as to drive the container to perform an eccentric rotational motion along the first direction;
[0016] In step S3, the mixing mechanism is controlled to generate an eccentric rotational force along the second direction, so as to drive the container to perform an eccentric rotational motion along the second direction.
[0017] In some possible embodiments, after step S1, the method further includes: controlling the blocking mechanism to be in a blocking state to prevent the container from escaping from the mixing mechanism during the rotation process;
[0018] After the mixing is completed, the method further includes: controlling the blocking mechanism to be in a non-blocking state and removing the container.
[0019] In some possible embodiments, after the mixing is completed, the method further includes: controlling the mixing mechanism to reset.
[0020] In a second aspect, an embodiment of the present application further provides a sample mixing device for executing the aforementioned sample mixing method, wherein the sample mixing device includes a mixing mechanism, which is configured to carry a closed container containing a sample, and the mixing mechanism is further configured to provide a rotational force along a first direction and a second direction to drive the container to rotate along the first direction and the second direction, wherein the first direction is opposite to the second direction.
[0021] In some possible embodiments, the mixing mechanism includes: a support seat, a first driving member provided on the support seat, and an eccentric member provided on the output shaft of the first driving member, the first driving member being configured to provide linear rotational motion along the first direction and the second direction; the eccentric member having a placement groove for supporting the container, and the eccentric member being configured to convert the linear rotational motion into the eccentric rotational motion to drive the container to perform eccentric rotational motion.
[0022] In some possible embodiments, the sample mixing device further includes a blocking mechanism configured to prevent the container from escaping from the mixing mechanism during the rotation process.
[0023] The sample mixing method and sample mixing device provided in the embodiments of the present application, wherein a mixing mechanism drives a container to rotate in a first direction and a second direction to realize a sample mixing process combining forward and reverse rotation of the container, with a fast mixing speed, high mixing efficiency, and good mixing effect; different containers can be replaced to achieve mixing of different sample systems, and the compatibility is good; in addition, the container is sealed, and there is no cross-contamination problem caused by traditional pipetting mixing during the mixing process. BRIEF DESCRIPTION OF THE DRAWINGS
[0024] In order to more clearly illustrate the technical solutions of the embodiments of the present application, the following is a brief introduction to the drawings required for use in the embodiments of the present application. Obviously, the drawings described below are only some embodiments of the present application. For ordinary technicians in this field, other drawings can be obtained based on these drawings without creative work.
[0025] Figure 1 FIG. 1 is a schematic structural diagram of a sample mixing device according to an embodiment of the present application.
[0026] Figure 2 for Figure 1 Schematic diagram of the structure of the container placed in the sample mixing device shown.
[0027] Figure 3 This is a flow chart of a sample mixing method according to an embodiment of the present application.
[0028] Figure 4 This is a workflow diagram of the sample mixing method of Example 1.
[0029] Figure 5 This is a workflow diagram of the mixed sub-process in Example 1.
[0030] Figure 6 This is a workflow diagram of the sample mixing method of Example 2.
[0031] Description of main component symbols
[0032] Sample mixing device 100 Hybrid institutions 10 Support seat 11 First driving member 12 Eccentric components 13 Placement slot 14 Hybrid induction components 15 container 20 Blocking end 21 Sealing cover 22 Blocking mechanism 30 Second driving member 31 blocking arm 32 First End 321 Second end 322 baffle 33 Blocking part 331 Notch 332 Blocking sensing components 34 Mounting plate 35 output shaft 36 Card holder 37 First direction a Second direction b
[0033] The following specific implementation methods will further illustrate the present application in conjunction with the above-mentioned drawings. DETAILED DESCRIPTION
[0034] The following will be combined with the drawings in the embodiments of this application to clearly and completely describe the technical solutions in the embodiments of this application. Obviously, the embodiments described are only part of the embodiments of this application, not all of the embodiments. Based on the embodiments in this application, all other embodiments obtained by ordinary technicians in this field without making creative efforts are within the scope of protection of this application.
[0035] It should be noted that when a component is referred to as being "fixed to" or "mounted on" another component, it may be directly on the other component or there may be a central component. When a component is referred to as being "disposed on" another component, it may be directly on the other component or there may be a central component. As used herein, the term "and / or" includes all and any combinations of one or more of the relevant listed items.
[0036] See also Figure 1 and Figure 2 As shown, an embodiment of the present application provides a sample mixing device 100, which can be used to mix samples, for example, it can be used to mix samples in the process of biochemical substance analysis. These samples can be, for example, biological samples required for biochemical substance analysis, liquid samples such as reagents, and magnetic beads in sequencing library construction, but are not limited thereto. The sample mixing device 100 includes a mixing mechanism 10, which can be used to carry a sealed container 20 containing a sample, and the container 20 is detachably provided on the mixing mechanism 10. The mixing mechanism 10 is configured to provide a rotational force along a first direction a and a second direction b to drive the container 20 to rotate along the first direction a and the second direction b, the first direction a being opposite to the second direction b, thereby achieving uniform mixing of the sample in the container 20. Specifically, the first direction a and the second direction b are both circumferential directions perpendicular to the central axis of the mixing mechanism 10.
[0037] Furthermore, the mixing mechanism 10 can provide an eccentric rotational force along the first direction a and the second direction b to drive the container 20 to perform eccentric rotational movement along the first direction a and the second direction b, so as to realize eccentric oscillation of the container 20 in both positive and negative directions, which can further improve the mixing effect and mixing efficiency. Moreover, the eccentric oscillation can shake off the sample on the side wall of the container 20, thereby effectively reducing the problem of sample agglomeration on the side wall of the container 20 and affecting the mixing effect.
[0038] The mixing mechanism 10 includes: a support base 11, a first driving member 12 provided on the support base 11, and an eccentric component 13 provided on the output shaft of the first driving member 12. The eccentric component 13 has a placement slot 14, and the placement slot 14 is used to support a container 20 containing a sample. The first driving member 12 is configured to provide linear rotational motion along the first direction a and the second direction b. The eccentric component 13 is configured to convert the linear rotational motion into the eccentric rotational motion, thereby driving the container 20 in the placement slot 14 to perform eccentric rotational motion to evenly mix the sample in the container 20. Here, the first direction a can be the direction of forward rotation of the first driving member 12, and the second direction b can be the direction of reverse rotation of the first driving member 12. It can be understood that the reverse can also be true, the first direction a can be the direction of reverse rotation of the first driving member 12, and the second direction b can be the direction of forward rotation of the first driving member 12.
[0039] In some embodiments, the forward and reverse rotation angles of the eccentric component 13 can be set according to actual needs, so that the eccentric component 13 can drive the container 20 in the placement groove 14 to rotate and float with an adaptive amplitude, so as to achieve both high mixing efficiency and mixing effect.
[0040] In some embodiments, the mixing mechanism 10 can carry one or more containers 20. When carrying multiple containers 20, the mixing mechanism 10 may include multiple second driving members 31 and multiple corresponding eccentric members 13, so that samples in multiple containers 20 can be mixed at the same time, thereby improving the mixing throughput and mixing efficiency.
[0041] In some embodiments, the first drive member 12 may be a motor, which uses closed-loop control to achieve high speed and high precision control. It is understood that other drive forms, such as a stepper motor or a combination of a stepper motor and a synchronous belt, may also be used to achieve closed-loop control.
[0042] In some embodiments, the mixing mechanism 10 further includes a mixing sensing component 15 provided on the eccentric component 13. When the mixing sensing component 15 senses that the eccentric rotational movement of the eccentric component 13 has ended, the signal can be transmitted to the controller, and the controller controls the first driving member 12 to reset the eccentric component 13.
[0043] In some embodiments, the hybrid sensing component 15 may be a photoelectric sensor.
[0044] The sample mixing device 100 further includes a blocking mechanism 30 , which is configured to prevent the container 20 from escaping from the mixing mechanism 10 during the rotation process. That is, during the mixing process, the blocking mechanism 30 can prevent the container 20 from accidentally escaping from the placement slot 14 .
[0045] The blocking mechanism 30 includes: a second driving member 31, a blocking arm 32, a blocking piece 33, and a blocking sensing component 34. The second driving member 31 is provided on the mixing mechanism 10. Specifically, the second driving member 31 is fixed to the eccentric member 13 via a mounting plate 35. The second driving member 31 can be a rotary motor. The blocking piece 33 and the blocking arm 32 are both provided on the output shaft 36 of the second driving member 31. Specifically, the blocking piece 33 is sleeved between the blocking arm 32 and the second driving member 31. The blocking sensing component 34 is provided on the mounting plate 35 and is arranged corresponding to the blocking piece 33. The blocking sensing component 34 can cooperate with the blocking piece 33 to sense the rotational position of the blocking piece 33 to determine the state of the blocking arm 32.
[0046] In some embodiments, the blocking arm 32 includes a first end 321 and a second end 322 that are arranged opposite to each other. The first end 321 is provided on the output shaft 36 of the second driving member 31. The blocking arm 32 can rotate around the output shaft 36 so that the second end 322 can be in a blocking state and a non-blocking state. The blocking state is a state in which the second end 322 is located at the blocking end 21 of the container 20. The blocking end 21 is the end of the container 20 away from the mixing mechanism 10. For example, the top of the container 20 is covered with a sealing cover 22, and the top end surface of the sealing cover 22 is the blocking end 21. That is, when the blocking arm 32 is in the blocking state, the second end 322 rotates just above the container 20. In this way, during the rotation and mixing process of the container 20, it will not accidentally fall out of the placement groove 14. The non-blocking state is when the second end 322 is moved away from the blocking end 21. When the mixing process is complete, the container 20 needs to be removed from the placement slot 14. At this time, the blocking arm 32 is rotated to move the second end 38 away from the blocking end 21, and the container 20 can be removed. The second end 322 is provided with a retaining member 37. When the second end 322 of the blocking arm 32 is located above the blocking end 21 of the container 20, the retaining member 37 can contact the blocking end 21 and exhibit elastic rolling friction. This reduces the risk of scratches caused by dry friction between the retaining member 37 and the blocking end 21 of the container 20 during high-speed rotation.
[0047] In some embodiments, the barrier arm 32 may be a long strip structure.
[0048] In some embodiments, the blocking piece 33 includes a blocking portion 331 and a notch portion 332 connected in sequence along the circumferential direction. Specifically, the blocking piece 33 is a disc structure that is sleeved on the output shaft 36. The blocking piece 33 has a notch that forms the notch portion 332, and the remaining portion of the blocking piece 33 forms the blocking portion 331. When the second driving member 31 drives the blocking piece 33 to rotate, the blocking portion 331 rotates to the sensing area of the blocking sensing component 34, at which point the second end 322 of the blocking arm 32 is in the blocking state. When the notch portion 332 rotates to the sensing area of the blocking sensing component 34, the second end 322 of the blocking arm 32 is in the non-blocking state.
[0049] In some embodiments, the blocking sensing component 34 may be a photoelectric sensor.
[0050] See also Figure 3 As shown, refer to Figure 2 As shown, the embodiment of the present application also provides a sample mixing method using the aforementioned sample mixing device 100, the method comprising:
[0051] Step S1 : Install at least one sealed container 20 containing a sample onto the mixing mechanism 10 .
[0052] The volume of container 20 can be designed based on actual needs. In this embodiment, container 20 can be a 1.5 mL reagent tube with a lid. The sample can be a liquid sample such as a biological sample, a reagent required for a biochemical reaction, or a magnetic bead reagent used in sequencing library construction. For example, in this embodiment, the magnetic beads are placed in a reagent tube that has been pre-loaded with a biological sample in order to fully mix the magnetic beads and the biological sample.
[0053] Step S2: controlling the mixing mechanism 10 to generate a rotational force along a first direction a, so as to drive the container 20 to rotate along the first direction a.
[0054] In this embodiment, the mixing mechanism 10 is controlled to generate an eccentric rotational force along the first direction a to drive the container 20 to perform an eccentric rotational motion along the first direction a. By causing the container 20 to oscillate eccentrically, the mixing effect can be further improved, and the problem of sample agglomeration on the side wall of the container 20 can be solved.
[0055] Specifically, the structure of the mixing mechanism 10 is as described above. The first driving member 12 is controlled to generate linear rotational motion along a first direction a. The output shaft of the first driving member 12 transmits the linear rotational motion to the eccentric component 13. The eccentric component 13 can convert the linear rotational motion into eccentric rotational motion, thereby driving the container 20 to perform eccentric rotational motion along the first direction a. The first direction a can be the forward rotation direction of the first driving member 12 or the reverse rotation direction of the first driving member 12. It will be understood that any mechanism capable of converting linear rotational motion into eccentric rotational motion can be used as the eccentric component of this embodiment.
[0056] In some embodiments, the mixing time of step 2 can be 1s to 100s, further 1s to 80s, further 1s to 60s, further 1s to 50s, further 1s to 30s, further 1s to 20s, further 1s to 10s. Exemplarily, the mixing time can be 1s, 2s, 3s, 4s, 5s, 6s, 7s, 8s, 9s, 10s, 15s, 20s, 25s, 30s, 35s, 40s, 45s, 50s, 55s, 60s, 65s, 70s, 75s, 80s, 85s, 90s, 95s or 100s, etc.
[0057] In some embodiments, the mixing speed in step 2 can be 2000 rpm to 3000 rpm, further 2000 rpm to 2800 rpm, further 2300 rpm to 2500 rpm. Exemplarily, the mixing speed can be 2000 rpm, 2100 rpm, 2200 rpm, 2300 rpm, 2400 rpm, 2500 rpm, 2600 rpm, 2700 rpm, 2800 rpm, 2900 rpm or 3000 rpm, etc.
[0058] Step S3: Control the mixing mechanism 10 to generate a rotational force along a second direction b, so as to drive the container 20 to rotate along the second direction b, where the second direction b is opposite to the first direction a.
[0059] In this embodiment, the mixing mechanism 10 is controlled to generate an eccentric rotational force along the second direction b, so as to drive the container 20 to perform an eccentric rotational motion along the second direction b. By causing the container 20 to oscillate eccentrically, the mixing effect can be further improved, and the problem of sample agglutination on the side wall of the container 20 can be solved.
[0060] Specifically, the first driving member 12 is controlled to generate linear rotational motion along the second direction b. The output shaft of the first driving member 12 outputs the linear rotational motion to the eccentric component 13. The eccentric component 13 can convert the linear rotational motion into eccentric rotational motion, thereby driving the container 20 to perform eccentric rotational motion along the second direction b. The second direction b can be the forward rotation direction of the first driving member 12 or the reverse rotation direction of the first driving member 12.
[0061] In some embodiments, the mixing time of step 3 can be 1s to 100s, further 1s to 80s, further 1s to 60s, further 1s to 50s, further 1s to 30s, further 1s to 20s, further 1s to 10s. Exemplarily, the mixing time can be 1s, 2s, 3s, 4s, 5s, 6s, 7s, 8s, 9s, 10s, 15s, 20s, 25s, 30s, 35s, 40s, 45s, 50s, 55s, 60s, 65s, 70s, 75s, 80s, 85s, 90s, 95s or 100s, etc.
[0062] In some embodiments, the mixing speed in step 3 can be 2000 rpm to 3000 rpm, further 2000 rpm to 2800 rpm, further 2300 rpm to 2500 rpm. Exemplarily, the mixing speed can be 2000 rpm, 2100 rpm, 2200 rpm, 2300 rpm, 2400 rpm, 2500 rpm, 2600 rpm, 2700 rpm, 2800 rpm, 2900 rpm or 3000 rpm, etc.
[0063] It should be noted that it is necessary to ensure that the first direction a in step S2 is opposite to the second direction b in step S3 to ensure that the container 20 can achieve eccentric oscillation combining forward and reverse rotation, thereby improving the mixing efficiency and mixing effect.
[0064] It should also be noted that the aforementioned steps S2 and S3 are not limited to a certain order, and can be interchanged. For example, step S3 can be performed first, and then step S2.
[0065] In some embodiments, after step S1, the method further includes:
[0066] The blocking mechanism 30 is controlled to be in a blocking state to prevent the container 20 from escaping from the mixing mechanism 10 during the rotation process.
[0067] Specifically, the structure of the blocking mechanism 30 is as described above. After the container 20 is placed in the placement slot 14, the second driving member 31 drives the blocking piece 33 and the blocking arm 32 to rotate, and rotates the blocking arm 32 to the top of the container 20. At this time, the blocking portion 331 of the blocking piece 33 rotates to the sensing area of the blocking sensing component 34, and the blocking arm 32 is in a blocking state. The blocking sensing component 34 transmits a signal to the controller, and the controller controls the mixing mechanism 10 to start to realize the aforementioned mixing sub-process.
[0068] In some embodiments, after the mixing is completed, the method further comprises:
[0069] The blocking mechanism 30 is controlled to be in a non-blocking state, and the container 20 is taken out.
[0070] When mixing is completed, the blocking mechanism 30 is moved away from the container 20, so that the blocking mechanism 30 is in the non-blocking state, and the container 20 can be removed from the placement slot 14. Specifically, the second driving member 31 drives the blocking piece 33 and the blocking arm 32 to rotate, moving the blocking arm 32 away from above the container 20. At this time, the notch 332 of the blocking piece 33 rotates to the sensing area of the blocking sensing component 34, and the blocking arm 32 is in the non-blocking state, so that the container 20 can be removed from the placement slot 14.
[0071] In some embodiments, step S2 and step S3 may constitute a mixed sub-process, and the method includes at least one such mixed sub-process. Each of the mixed sub-processes may be performed cyclically, with the number of cycles being at least one.
[0072] In other embodiments, the method may include a plurality of mixing sub-processes, wherein at least one of the setting parameters of the different mixing sub-processes is different, and the setting parameters include the mixing time of step S2, the mixing speed of step S2, the mixing time of step S3, the mixing speed of step S3, and the number of cycles of each mixing sub-process. For the setting of these parameters, please refer to the aforementioned steps S2 and S3, which will not be described in detail here. That is, when the sample mixing method includes two or more mixing sub-processes, at least one of the aforementioned parameters of the different mixing sub-processes is set differently. If the setting parameters of the multiple mixing sub-processes are the same, then it belongs to the cyclic process of a single mixing sub-process.
[0073] The sample mixing device 100 and the sample mixing method provided in the embodiments of the present application have the following beneficial effects:
[0074] (1) The container 20 is rotated in a first direction a and a second direction b by the mixing mechanism 10 to achieve mixing and oscillation by combining forward and reverse rotation of the container 20. This results in a fast mixing speed, high mixing efficiency, and good mixing effect. Furthermore, by controlling parameters such as the mixing speed, mixing time, and number of cycles, the mixing efficiency and effect can be further improved. In particular, by controlling the container 20 to perform eccentric rotational oscillation in both the forward and reverse directions by the mixing mechanism 10, the problem of sample agglomeration on the sidewalls of the container 20 can be resolved, thereby further improving the mixing effect.
[0075] (2) Compared with the mixing by rotating in a single direction, which can only mix samples of a small system but cannot achieve the mixing of samples of a large system, the embodiment of the present application adopts a combination of positive and negative eccentric oscillation, which can achieve the mixing of samples of a large system, significantly improving the mixing efficiency and mixing effect. In addition, the mixing of different sample systems can be achieved by replacing different containers 20, and the compatibility is good.
[0076] (3) After the sealing cover 22 is closed, the container 20 is airtight, and there is no cross-contamination problem caused by traditional pipetting and mixing during the mixing process.
[0077] The following further illustrates sample mixing using a method of combining a single mixing sub-process with a cyclic process and a method of combining multiple mixing sub-processes with a cyclic process through specific embodiments.
[0078] Example 1
[0079] like Figure 4 and Figure 5 As shown, refer to Figure 2 When a single mixing sub-process is combined with a cyclic process to mix samples, the specific method includes the following steps:
[0080] In step 101, the controller controls the second driving member 31 in the blocking mechanism 30 to rotate, so as to drive the blocking arm 32 to rotate above the container 20, so that the blocking arm 32 is in a blocking state. At the same time, the blocking portion 331 rotates to the sensing area of the blocking sensing component 34, and the blocking sensing component 34 senses the shading signal and transmits the signal to the controller.
[0081] Step 102: After receiving the signal that the blocking mechanism 30 is in the blocking state, the controller controls the mixing mechanism 10 to start and perform the mixing sub-process.
[0082] The hybrid sub-process here includes the aforementioned steps 2 and 3, such as Figure 5 As shown, the specific steps of the mixing sub-process include:
[0083] Step 102-1: Input the preset mixing speed S1, mixing time T1 and number of cycles C1 into the application. This step can be performed before or after step 101.
[0084] In step 102-2, after receiving the signal that the blocking mechanism 30 has blocked the container 30, the controller controls the mixing mechanism 10 to perform mixing in the first direction. Specifically, the controller controls the mixing mechanism 10 to generate a rotational force along the first direction a to drive the container 20 to rotate along the first direction a.
[0085] In step 102-3, the application automatically determines whether the mixing time T1 in step 102-2 has been reached based on the preset mixing time T1. If the time has been reached, the application proceeds to the next step. If the time has not been reached, the application continues to count.
[0086] In step 102-4, after the mixing time in the first direction reaches the preset mixing time T1, the controller controls the mixing mechanism 10 to perform mixing in the second direction. Specifically, the controller controls the mixing mechanism 10 to generate a rotational force in the second direction b to drive the container 20 to rotate in the second direction b.
[0087] In step 102-5, the application automatically determines whether the mixing time T1 in step 102-4 has been reached based on the preset mixing time T1. If the time has been reached, the application proceeds to the next step. If the time has not been reached, the application continues to count.
[0088] Step 102-6, looping the mixing sub-process from step 102-2 to step 102-5.
[0089] In step 102-7, the application automatically determines whether the number of loops is equal to C1 according to the preset number of loops C1. If it is equal to C1, the application proceeds to the next step; otherwise, the application continues to execute the mixed sub-process for looping.
[0090] Step 103, when the mixing is completed, the controller will control the blocking mechanism 30 to a non-blocking position (or idle position), after which the container 20 can be taken out and replaced with another container 20 for the next mixing process.
[0091] For example, mixing magnetic beads with a biological sample (e.g., DNA fragments) is performed using the cyclic method described above for the single mixing sub-process. In step 102-1, the mixing speed S1 is set to 3000 rpm, the mixing time T1 is set to 5 seconds, and the number of cycles C1 is set to 3. This method can achieve rapid mixing of the magnetic bead reagent in 30 seconds, with good mixing quality.
[0092] Example 2
[0093] like Figure 6 As shown, refer to Figure 2When multiple single mixing sub-processes are combined with a cyclic process to mix samples, the specific method includes the following steps:
[0094] In step 201, the controller controls the second driving member 31 in the blocking mechanism 30 to rotate, so as to drive the blocking arm 32 to rotate above the container 20, so that the blocking arm 32 is in a blocking state. At the same time, the blocking portion 331 rotates to the sensing area of the blocking sensing component 34, and the blocking sensing component 34 senses the shading signal and transmits the signal to the controller.
[0095] Step 202: perform the first mixing sub-process.
[0096] The first mixing sub-process includes the entire process of the aforementioned step 102 , and the preset parameters in step 102 - 1 are mixing speed S1 , mixing time T1 , and number of cycles C1 .
[0097] Step 203: perform the second mixing sub-process.
[0098] Among them, the second mixing sub-process includes the entire process of the aforementioned step 102, except that: in the second mixing sub-process, the preset parameters in step 102-1 are mixing speed S2, mixing time T2 and number of cycles C2, among which at least one parameter among mixing speed S2, mixing time T2 and number of cycles C2 is different from that set in step 202.
[0099] Step 204: perform the Nth mixing sub-process.
[0100] Among them, the Nth mixing sub-process includes the entire process of the aforementioned step 102, except that: in the Nth mixing sub-process, the preset parameters in step 102-1 are the mixing speed SN, the mixing time TN and the number of cycles CN, wherein at least one parameter among the mixing speed SN, the mixing time TN and the number of cycles CN is different from the settings in the aforementioned steps 202 and 204.
[0101] Step 205, when N mixing sub-processes are completed, the controller will control the blocking mechanism 30 to a non-blocking position (or idle position), after which the container 20 can be taken out and replaced with another container 20 for the next mixing process.
[0102] Taking the mixing of magnetic beads and biological samples (e.g., DNA fragments) as an example, the above multi-mixing sub-process cyclic method is used for mixing. Specifically, in the first mixing sub-process, the mixing speed S1 is set to 2000 rpm, the mixing time T1 is 5 seconds, and the number of cycles C1 is 1; in the second mixing sub-process, the mixing speed S2 is set to 3000 rpm, the mixing time T2 is 5 seconds, and the number of cycles C2 is 2 times; in the Nth mixing sub-process, N is 3, and the mixing speed SN is set to 2000 rpm, the mixing time TN is 5 seconds, and the number of cycles CN is 1 time. This method can adjust the number of mixing sub-processes to achieve mixing according to the characteristics of the system to be mixed and the reagents.
[0103] Both of the above methods can well achieve the mixing of magnetic beads and DNA fragments in the library construction process. When the mixing speed exceeds 3000rpm, it is easy to cause the DNA fragments to be interrupted by excessive mixing. When the mixing speed is lower than 2000rpm, it is difficult to achieve rapid mixing, and only forward mixing or reverse mixing is performed, and the mixing effect is not good at this time. In addition, when the mixing time is 1s to 100s and the number of cycles is 1 value 1 time, the mixing effect is better and the efficiency is higher. Therefore, in this embodiment, the mixing speed is limited to 2000rpm to 3000rpm, the mixing time T is limited to 1s to 100s, the number of cycles is 1 value 1 time, and combined with forward and reverse eccentric oscillation, rapid mixing can be achieved, the mixing efficiency is improved, and the mixing effect is better.
[0104] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present application and are not intended to limit the present application. Although the present application has been described in detail with reference to the preferred embodiments, those skilled in the art should understand that the technical solutions of the present application may be modified or replaced by equivalents without departing from the spirit and scope of the technical solutions of the present application.
Claims
1. A sample mixing method, characterized in that: include: Step S1, installing at least one sealed container containing a sample on a mixing mechanism; Step S2, controlling the mixing mechanism to generate a rotational force in a first direction to drive the container to rotate in the first direction; as well as Step S3: controlling the mixing mechanism to generate a rotational force in a second direction to drive the container to rotate in the second direction, where the second direction is opposite to the first direction.
2. The sample mixing method according to claim 1, wherein: The step S2 and the step S3 constitute a hybrid sub-process, and the method includes at least one of the hybrid sub-process.
3. The sample mixing method according to claim 2, wherein: The method includes a plurality of hybrid sub-processes, wherein at least one of the setting parameters of different hybrid sub-processes is different. The setting parameters include the mixing time of step S2, the mixing speed of step S2, the mixing time of step S3, the mixing speed of step S3 and the number of cycles of each mixing sub-process.
4. The sample mixing method according to claim 3, wherein: The mixing time of step S2 and step S3 is 1s to 100s; and / or, The mixing speeds in step S2 and step S3 are both 2000 rpm to 3000 rpm; and / or, The number of cycles is at least one.
5. The sample mixing method according to claim 1, wherein: In step S2, the mixing mechanism is controlled to generate an eccentric rotational force along the first direction, so as to drive the container to perform an eccentric rotational motion along the first direction; In step S3, the mixing mechanism is controlled to generate an eccentric rotational force along the second direction, so as to drive the container to perform an eccentric rotational motion along the second direction.
6. The sample mixing method according to claim 1, wherein: After step S1, the method further includes: controlling the blocking mechanism to be in a blocking state to prevent the container from escaping from the mixing mechanism during the rotation process; After the mixing is completed, the method further comprises: The blocking mechanism is controlled to be in a non-blocking state, and the container is taken out.
7. The sample mixing method according to claim 1, wherein: After the mixing is completed, the method further comprises: Control the mixing mechanism to reset.
8. A sample mixing device for performing the sample mixing method according to claim 1, characterized in that: The mixing mechanism includes a mixing mechanism configured to carry a sealed container containing a sample, and the mixing mechanism is further configured to provide a rotational force along a first direction and a second direction to drive the container to rotate along the first direction and the second direction, wherein the first direction is opposite to the second direction.
9. The sample mixing device according to claim 8, wherein: The mixing mechanism comprises: Support seat; a first driving member disposed on the support base, the first driving member being configured to provide linear rotational motion along the first direction and the second direction; and An eccentric component is provided on the output shaft of the first driving member. The eccentric component has a placement groove for supporting the container. The eccentric component is configured to convert the linear rotational motion into the eccentric rotational motion to drive the container to perform eccentric rotational motion.
10. The sample mixing device according to claim 8, wherein The sample mixing device further includes a blocking mechanism configured to block the container from escaping from the mixing mechanism during the rotation process.