CN105880041B - Mechanism that is a kind of while realizing reagent mixing and centrifugation function - Google Patents

Abstract

The present invention relates to a kind of while realizing the mechanism of reagent mixing and centrifugation function.The technical scheme is that:It is made of rotation union body, elastic cantilever, test tube flat three parts.The center of the rotation union body has fixes required positioning assembly parts with outer drive shafts, the pairs of flexible cantilever a group or more of, in balanced distribution that rotation union body stretches out around from center, it is rigid unitary that elastic cantilever is coupled in nearly center-side, elastic cantilever is separated from each other in one end far from rotation center and freely activity, elastic cantilever can have test tube flat in one end far from rotation center in a certain range.Reagent collection, mixing and centrifugation function are realized using the resonance characteristics of test tube flat.For different reagent optimum organization various functions, completely instead of manual operations and a variety of traditional equipments, reagent overall process closed loop, the processing of full automatic reagent and reaction are realized.

Description

A mechanism that realizes reagent mixing and centrifugation at the same time

technical field

The invention relates to the technical field of reagent mixing and separation, in particular to a mechanism for simultaneously realizing reagent mixing and centrifugation functions.

Background technique

In reagent experiments in the fields of biology, medical treatment, agriculture and forestry, disease control, criminal investigation, food safety, etc., centrifuges, mixers, oscillators and other equipment are routinely configured biochemical laboratory instruments. Centrifugation and mixing are two basic operate. Operators use these instruments to perform, mix, stir, vibrate, separate, centrifuge, collect, and remove air bubbles and other operations on reagents to achieve sample addition, purification, cultivation, and treatment of reagent samples.

An experiment uses multiple devices at the same time, and intermittent manual operations and taking and placing test tubes not only consume a lot of time, manpower, material resources, and energy, but also greatly reduce work efficiency; Errors, mistakes, emotional impact, and inconsistencies in techniques lead to lengthy experimental processes, decreased reagent activity and sensitivity, and greatly reduced reproducibility, feasibility, and reliability of experimental results.

In recent years, bedside diagnostics (POCT) and on-site rapid detection reagent testing applications have emerged. However, multi-equipment and human factors have become the bottleneck restricting the development of POCT. The quality of on-site testing personnel varies greatly and the experimental conditions vary widely. The test results obtained by traditional methods vary so much that their accuracy, reliability and credibility are questioned. The equipment is no longer sufficient.

For a long time, companies at home and abroad have tried to integrate the mixing and centrifugation functions, but there has not been a substantial and simple solution other than simply assembling the two independent mechanisms. Usually, the mixing effect is to fully break up the objects; and the centrifugal effect is to separate the substances; these two functions and structures are basically opposite, so having these two functions in one mechanism at the same time requires a complex switching mechanism, However, this switching mechanism is often unacceptable for high-speed centrifugal systems. A mechanism of the present invention that realizes the functions of mixing and centrifuging at the same time adopts a simple but ingenious scheme, integrates the features of a centrifuge and a mixing instrument, and successfully replaces the above-mentioned instruments.

Contents of the invention

In order to solve the problems of unsatisfactory manual mixing effect, low working efficiency and simultaneous mixing and centrifugation in the prior art, the present invention provides a simultaneous realization of high working efficiency, good mixing effect and simultaneous mixing and centrifugation. Reagent mixing and centrifugation mechanism.

The described mechanism for simultaneously realizing reagent mixing and centrifugal functions is characterized in that the mechanism includes a rotating coupling body, an elastic cantilever and a test tube holder, and the center of the rotating coupling body is provided with a positioning assembly, and the positioning assembly It is connected to the transmission shaft on the motor, and the motor is connected to the controller. The center of the rotating coupling body is provided with a pair of or more than one group of elastic cantilevers protruding around. One set of elastic cantilevers are separated from each other at one end away from the center of rotation and can move freely. The end of the elastic cantilever is provided with a test tube holder at the end far away from the center of rotation. The test tube holder can produce radial displacement on the elastic cantilever. The test tube holder is used to place the test tube, and the controller realizes the mixing and centrifugation of the liquid in the test tube by controlling the rotating speed of the motor.

The mechanism for achieving reagent mixing and centrifugation at the same time is characterized in that the rotation of the rotating coupling is controlled by motor drive signal frequency, duty cycle control, and time duration start and stop, so that the test tube holders enter the system respectively A resonant state, a non-resonant relatively steady state, and a transition state between the resonant state and the non-resonant relatively steady state.

The mechanism for achieving reagent mixing and centrifugation at the same time is characterized in that the elastic cantilever is in the shape of a sheet, the elastic cantilever is made of spring steel, beryllium copper, plastic or polymer synthetic material, and the thin sheet of the elastic cantilever The included angle between the surface and the rotation axis of the rotary coupling body is within 0° to 60°.

The above-mentioned mechanism for simultaneously realizing reagent mixing and centrifugation is characterized in that the paired or more than one group of elastic cantilevers has centrosymmetric balance.

The above-mentioned mechanism for realizing reagent mixing and centrifugation at the same time is characterized in that the test tube holder is fixedly mounted on one end of the elastic cantilever, and the included angle between the test tube on the test tube holder and the rotation axis of the rotating coupling is 0-90° Inside, or relative to the rotation axis of the rotating coupling, the rotation angle is within 0-180°.

The above-mentioned mechanism for simultaneously realizing reagent mixing and centrifuging functions is characterized in that the rotating coupling body, elastic cantilever and test tube holder are combined from different materials or integrally processed from the same material.

By adopting above-mentioned technology, compared with prior art, the beneficial effect of the present invention is:

1) The present invention adopts a structure to realize multi-functional unification, which perfectly integrates the collection, mixing, centrifugation, magnetic separation, magnetic adsorption and other functions commonly used in biochemical experiments, and can be freely combined to meet the needs of different reagent experiments, realizing most of the substitutions Manual, saves a lot of operations such as taking, holding, placing test tubes, manual shaking, opening and closing, timing, etc., reduces human factors, shortens experimental time, improves experimental efficiency, simplifies operations, and saves manpower and material resources Financial resources, improved experimental consistency, reproducibility, reliability, and credibility;

2) The present invention creates a new type of equipment by adopting a limited structure, replacing the original various supporting equipment, which is conducive to the application and promotion of POCT and on-site rapid detection, especially suitable for general reagent processing and nucleic acid isothermal amplification experiments in biochemical laboratories . Because of its complete functions, it is suitable for the application of a small number of samples, has wide adaptability, distinctive features, and wide application fields, and has a good market prospect.

Description of drawings

Fig. 1 is a structural representation of the present invention;

Fig. 2 is a top view of the present invention;

Fig. 3 is a schematic diagram of the resonance characteristic curve of the test tube holder structure of the present invention;

Fig. 4 is a schematic diagram of the state of the elastic cantilever in a static state of the present invention;

Fig. 5 is a schematic diagram of the state of the elastic cantilever in the resonance state of the present invention;

Fig. 6 is a schematic diagram of the principle of resonance method test tube radial displacement vortex oscillation of the present invention;

In the figure: 1. Rotating coupling body, 2. Elastic cantilever, 3. Test tube holder, 4. Positioning assembly, 5. Motor, 6. Controller, 7. Test tube.

Detailed ways

Below in conjunction with accompanying drawing and example the present invention will be further described:

As shown in Figures 1-6, a mechanism for simultaneously realizing reagent mixing and centrifugation according to the present invention consists of a rotating coupling body 1, an elastic cantilever 2, a test tube holder 3, a positioning assembly 4, a motor 5, and a controller 6 And test tube 7 constitutes.

The center of the rotary coupling body 1 has a positioning assembly 4 required for fixing with the external transmission shaft. The rotary coupling body 1 protrudes from the center to the surroundings in a symmetrical and balanced distribution of the center, paired elastic cantilevers 2, all elastic cantilevers 2 The proximal end is connected as a rigid body; the elastic cantilever 2 is separated from each other at the end far away from the center of rotation and can move freely within a certain range, and the end of the elastic cantilever 2 far away from the center of rotation is fixedly provided with a test tube holder 3 for placing the test tube 7, the test tube 7 and the test tube holder 3 can swing on the elastic cantilever 2 during the rotation of the motor 5 to form a radial displacement; the positioning assembly 4 is connected to the transmission shaft on the motor 5, the motor 5 is connected to the controller 6, and the controller 6 The mixing and centrifugation of the liquid in the test tube 7 is realized by controlling the rotating speed of the motor 5 .

The invention realizes collection, mixing and centrifugation by using the inherent resonance characteristics of elastic body rotation and swing under a specific load. The total mass is less than 15g.

As shown in the figure, the test tube holder 3 of the present invention is located at the far end of the rotating support centered on the rotating shaft of the rotating coupling body 1, and is used to place a test tube 7, which is used to hold reagents. The controller 6 controls the rotating speed of the motor 5 so that the elastic cantilever 2 has inertia and centrifugal force during the start and emergency stop of the rotating support, and the test tube holder 3 fixed on the far end of the cantilever has a certain quality, so under suitable conditions, the test tube Seat 3 has resonance characteristics, and the suitable condition refers to the light load condition, because the total mass of the load affects the frequency point and resonance amplitude of the system resonance under the premise that the elastic cantilever structure is basically determined; when the load is light, the resonance characteristics of the system can be used For this device, multiple functions are realized according to the control signal; if it is a heavy load, its characteristics are difficult to meet the same structure to realize multiple functions.

The resonance characteristics of the test tube holder 3 refer to the system resonance state, the relative steady state of non-resonance, and the transition state between the two, through the combination of the control frequency of the motor 5, the duty ratio, timing, and start-stop Set the intensity and duration to suit the reagent. As shown in Figure 3, the resonance characteristic is the process curve of multiple peaks, and the different state areas of the curve are suitable for different functions, such as: the system resonance area is suitable for the mixing function, and the non-resonant relatively steady state is suitable for the centrifugal function. A variety of subdivision functions can also be developed during the period. It uses the control signal of the motor (such as the frequency of the signal, the PWM duty cycle, the start-up on-off time, etc.) to make the system at the state point of the resonance characteristic curve, and the motor drives the system. Movement, and then achieve the desired function.

The inherent resonance characteristics of a well-fastened system are stable, and usually have multiple resonance frequencies, which need to be selected according to the energy intensity.

The reagent in the test tube 7 bears the energy transmitted by the test tube holder 3, and realizes functions such as collection, mixing, centrifugation, magnetic adsorption, and magnetic separation of the reagent according to multiple combinations of functions, steps, and duration.

When the elastic cantilever 2 vibrates, the test tube 7 has a radial inward displacement relative to the rotation axis due to bending, and the test tube movement trajectory is shown in Figure 4-6. Wherein Fig. 4 is the static state, Fig. 5 is the vibrating state of the elastic cantilever 2, Fig. 6 is the trajectory of the reagent in the test tube 7 on the elastic cantilever 2, similar to the double leaf type, it actually forms a vortex oscillation with a radius of mm.

At a lower speed, the centrifugal force of the reagent is small and it is not easy to cause the reagent to stratify. At this time, the resonance characteristic of the test tube holder 3 is used to make the test tube holder 3 in a state close to resonance. At this time, the radial displacement of the test tube holder 3 is large enough, and the energy Pass and cause the reagents in tube 7 to mix well. This is the mixing function of the resonance method. Practical mixing energy needs to consider the characteristics of the nucleic acid molecular structure of the reagent itself, and adopt an adapted amplitude and duration. Too strong mixing leads to molecular structure damage, such as protein denaturation; too weak vibration cannot meet the purpose of mixing when the viscosity of the reagent is high.

At a higher speed (usually the rotation speed is 4000rpm), the resonance point is avoided. At this time, the radial displacement of the test tube holder 3 is almost zero, and the centrifugal force formed by the high speed can make the effect of centrifugation far greater than that of mixing. Substances with greater mass will be centrifuged to the outside of the inner wall of the test tube 7 to play a role in separation, which is the centrifugal function.

Non-resonance point, high speed (close to centrifugation), short running time (1-5s), can collect the residual liquid on the wall of the test tube 7 or add the liquid on the tube cover to the bottom of the tube, that is, the collection function .

Between the state of mixing and centrifugation, the timing and energy transfer control can be refined to achieve effects such as: removing air bubbles and stirring. Set various functional combination operations, and complete reagent pretreatment can be realized according to reagent matching parameters.

Example:

This example shows a mechanism with a pair of elastic cantilevers that are center-symmetrically balanced. The elastic cantilever 2 is made of 65Mn spring steel material with a thickness of 0.5-0.6mm, a width of 10mm, and a length greater than 15mm, and is placed vertically.

In this example, the elastic cantilevers 2 are distributed horizontally and symmetrically, and there are a pair of elastic cantilevers 2 arranged in a strictly balanced load manner. It should be noted that the mechanism of the present invention is not limited to a pair of elastic cantilever arms, but can be installed with multiple pairs of elastic cantilever arms that are balanced centrally and symmetrically.

In this example, a test tube holder 3 is installed and fixed on each elastic cantilever 2, and a test tube 7 hollow socket is respectively arranged on the left and right sides. In this example, the test tube 7 is at an angle of 45° with the axis of the rotating coupling body 1 . The test tube 7 is placed in the test tube holder 3 and held relatively stably.

In this example, the DC brushless PWM speed regulating motor 5 is used to drive, and the controller 6 adopts a combination of frequency conversion, PWM speed regulation, timing, and start-stop control to simulate the actual effect of manual processing and meet the requirements of reagent mixing, centrifugation, and collection. , De-bubble, vibration, stirring and other functions.

The resonance characteristics of the structural system in this example are shown in Figure 3. The ordinate V in the figure is the resonance amplitude, and the abscissa F is the frequency (unit: Hz) of the motor running PWM control signal. The test tube holder 3 and the loading quality of the reagent, the length of the cantilever, the speed characteristics of the motor, the elasticity of the cantilever, and the degree of fastening all affect the resonance curve and the frequency point.

In this example, the motor controls the cantilever speed through PWM (Pulse Width Modulation). The pulse frequency of the PWM signal is used to select the type of resonance area; the pulse width is used to control the rotation speed of the motor cantilever; the PWM signal is turned on and Closed for cantilever operation and stationary.

At multiple frequency points (f1\f2\f3), the elastic cantilever 2 exists in a resonance state. The distribution of frequency points has a regular interval, and the mixing is carried out near the frequency point (area A in Figure 3) with the strongest resonance in the low frequency band. The intensity of mixing is realized through the matching verification with the reagent. By selecting the working frequency point, it can prevent protein denaturation in the reagent caused by excessive vibration or insufficient mixing under the condition of high-viscosity reagent. Usually the appropriate mixing speed is 300-900rpm.

The number of test tubes 7 (load quality) has a slight effect on the resonance frequency of the elastic cantilever 2. In this example, several frequency points are automatically adapted to the number of test tubes 7 so that they can all reach the over-resonance state.

After the resonant frequency point, the system is in a non-resonant relatively steady state (area B in Figure 3), and a high-frequency band and an appropriate duty cycle are selected to achieve high-speed centrifugation. Usually the suitable centrifugation speed reaches above 4000rpm, and requires the test tube 7 to be placed in balance.

For commonly used functions such as collecting (liquid) and removing air bubbles in experiments, the physical state of the bracket is close to that of centrifugation, the rotation speed is higher than that of mixing (generally 2000rpm or more can be achieved), and the running time is shorter.

The application of this example requires parameter matching and process optimization with reagents of specific components and reaction conditions. Using the matching of resonance intensity and rotational speed on the characteristic curve, as well as the timing (several seconds, the present invention generally takes 1-5s), and according to the characteristics and verification of the reagent, realize relevant subdivision functions such as oscillation, debubbling, and collection.

In this example, different signal combination strategies are used to achieve different functions, as shown in Table 1:

Table 1

This example is not a simple integration of multiple mechanisms, but an ingenious use of an ingenious structure, using its physical characteristics, and only using the combination of PWM signals to simultaneously realize multiple functions including mixing, centrifugation, and collection, making the reagents The whole process closed experiment becomes possible.

Through the control and combination of various functions at different times, the whole process of programmable experiments can be fully automated, which completely replaces the complicated, multi-unit, and multi-process manual operations, and the man-hours, efficiency, reliability, consistency, and safety are all improved. ensure.

It is obvious that the expanded application of the present invention covers all aspects of traditional reagent processing and reaction, and the present invention is especially suitable for POCT on-site diagnosis and detection instruments, and has the characteristics of small volume, multi-function and full automation. For example: pretreatment, pretreatment, reagent reaction, isothermal amplification, magnetic bead purification, cell disruption, protein denaturation, small sample detection and other fields are in urgent need of such devices, small and medium primary hospitals, bedside/personal diagnosis, field Field detection, emergency detection, disease control, criminal investigation and other occasions have extensive, universal and basic needs.

The above-mentioned embodiments only express the embodiments of the present invention, and the descriptions thereof are relatively specific and detailed, but should not be construed as limiting the patent scope of the invention. It should be pointed out that those skilled in the art can make several modifications and improvements without departing from the concept of the present invention, and these all belong to the protection scope of the present invention. Therefore, the protection scope of the patent for the present invention should be based on the appended claims.

Claims (4)

1. A mechanism that realizes reagent mixing and centrifugation at the same time, characterized in that the mechanism includes a rotating coupling (1), an elastic cantilever (2) and a test tube holder (3), and the rotating coupling (1) There is a positioning assembly (4) in the center, and the positioning assembly (4) is connected with the upper transmission shaft of the motor (5), and the motor (5) is connected with the controller (6). There are more than one set of elastic cantilevers (2) protruding all around, all the elastic cantilevers (2) are connected into a rigid body at the end close to the rotation center, and the elastic cantilever (2) is separated from each other at the end far away from the rotation center and can free movement, the elastic cantilever (2) is provided with a test tube holder (3) at one end away from the center of rotation, the test tube holder (3) can produce radial displacement on the elastic cantilever (2), and the test tube holder (3) can be used When placing the test tube (7), the controller (6) realizes the mixing and centrifugation of the liquid in the test tube (7) by controlling the rotation speed of the motor (5). Symmetrical balance, the test tube holder (3) is fixedly installed on one end of the elastic cantilever (2), and the included angle between the test tube (7) on the test tube holder (3) and the rotation axis of the rotating coupling body (1) is 0-90° Within, or relative to the rotating shaft of the rotating coupling body (1), the rotation angle is within 0-180°. 2. A mechanism for simultaneously realizing reagent mixing and centrifugal functions according to claim 1, characterized in that the rotation of the rotating coupling body (1) is controlled in time by the motor (5) driving signal frequency and duty cycle The long start-stop is controlled so that the test tube holder (3) respectively enters the system resonance state, the non-resonance relative steady state, and the transition state between the resonance state and the non-resonance relative steady state. 3. A mechanism for simultaneously realizing reagent mixing and centrifugal functions according to claim 1, characterized in that the elastic cantilever (2) is in the shape of a sheet, and the elastic cantilever (2) is made of spring steel, beryllium copper, plastic or It is made of polymer synthetic material, and the included angle between the sheet surface of the elastic cantilever (2) and the rotation axis of the rotating coupling (1) is within 0° to 60°. 4. A mechanism for simultaneously realizing reagent mixing and centrifugation according to claim 1, characterized in that the rotating coupling body (1), elastic cantilever (2) and test tube holder (3) are made of different materials into or integrally processed from the same material.