sample analyser
By using a piezoelectric vibrator to emit ultrasonic waves in the sample analyzer and controlling the acoustic impedance ratio between the sound wave transmission medium and the reaction vessel to form a rotating flow, the problems of liquid splashing and stirring contamination in the prior art are solved, and more efficient sample mixing is achieved.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- MACCURA MEDICAL INSTR CO LTD
- Filing Date
- 2023-03-31
- Publication Date
- 2026-06-02
AI Technical Summary
Existing mechanical and contact ultrasonic mixing methods suffer from problems such as liquid splashing, impeller contamination, and uneven mixing in sample analyzers. Non-contact mixing devices also have unsatisfactory mixing effects and require further improvement.
A sample analyzer is used, including sample collection, reagent supply, sample reaction, optical measurement, and sample mixing devices. Piezoelectric vibrators emit ultrasonic waves in a direction perpendicular to the liquid surface, which are transmitted to the side wall of the reaction vessel through the sound wave transmission medium. The acoustic impedance ratio of the sound wave transmission medium and the reaction vessel is set to 0.75 to 1. Combined with the drive module, the piezoelectric vibrators are controlled to generate ultrasonic waves, forming a rotating flow to achieve thorough mixing.
It effectively reduces ultrasonic energy loss, improves mixing efficiency, avoids liquid splashing and stirring contamination, and achieves a more uniform sample mixing effect.
Smart Images

Figure CN116500282B_ABST
Abstract
Description
[0001] This application claims priority to Chinese Patent Application No. 202310182789.6, filed on February 28, 2023, entitled “Sample Analyzer”, the entire contents of which are incorporated herein by reference. Technical Field
[0002] This invention relates to the field of sample analysis technology, and in particular to a sample analyzer. Background Technology
[0003] Currently, in vitro diagnostic instruments employ two methods for liquid mixing: mechanical mixing and ultrasonic mixing. Mechanical mixing includes oscillatory mixing (e.g., CN102151510B) and agitator mixing (e.g., CN202631343U). Oscillatory mixing involves placing the reaction vessel into a high-speed rotating eccentric groove. The vibrational energy is transferred to the sample liquid by the inner wall of the eccentric groove colliding with the outer wall of the reaction vessel, thus achieving liquid mixing. Agitator mixing involves inserting a slender agitator into the reaction vessel containing the sample liquid. The agitator rotates at high speed under motor drive, mixing the liquid. Ultrasonic mixing includes contact mixing (e.g., CN213933890U) and non-contact mixing. Contact mixing refers to the ultrasonic transducer being directly inserted into the sample liquid, or the ultrasonic transducer being in direct contact with the outer wall of the reaction vessel. Non-contact mixing involves the ultrasonic transducer contacting a medium such as water, and the generated sound waves are transmitted to the reaction vessel through the medium, achieving liquid mixing.
[0004] The two mechanical mixing methods described above are simple to implement, but they have different design flaws. Vibratory mixing is difficult to control the impact force, and the liquid in the reaction vessel is prone to splashing, affecting the test results. Stirring mixing involves contact between the stirring paddle and different test liquids, causing contamination. Contact ultrasonic mixing suffers from the same problems as stirring mixing: energy is difficult to control, easily causing liquid splashing, and localized severe liquid vibration, resulting in uneven mixing.
[0005] Non-contact mixing can better control vibration energy and avoid carrying contamination and liquid splashing, but the mixing effect of existing non-contact mixing devices is still not ideal and needs further improvement. Summary of the Invention
[0006] Therefore, it is necessary to provide a sample analyzer to address the aforementioned technical problems.
[0007] A sample analyzer includes: a sample collection device, a reagent supply device, a sample reaction device, a reaction container, an optical measurement device, and a sample mixing device;
[0008] The sample collection device is used to collect samples and transport them to the sample reaction device;
[0009] The reagent supply device is used to collect reagents from the reagent container and deliver the reagents to the sample reaction device;
[0010] The sample reaction apparatus is used to contain the sample to be mixed and the reagents and to provide the environment required for the reaction.
[0011] The reaction vessel is housed within the sample reaction apparatus and is used to hold the sample to be mixed and the reagents.
[0012] The sample mixing device is used to thoroughly mix the sample and reagents in the reaction vessel;
[0013] The optical measuring device is used to measure the light signal generated by the sample to obtain light information;
[0014] The sample mixing device includes a driving module and a piezoelectric vibrator. The driving module and the piezoelectric vibrator are electrically connected. The piezoelectric vibrator generates ultrasonic waves under the drive of the driving module. The ultrasonic waves are emitted towards the side wall of the reaction container containing the sample to be mixed through the sound wave transmission medium.
[0015] The piezoelectric vibrator is used to emit ultrasonic waves within a preset range in a direction perpendicular to the liquid surface of the sample to be mixed;
[0016] Wherein, the ratio of the acoustic impedance of the sound wave transmission medium to the acoustic impedance of the sidewall of the reaction vessel is 0.75 to 1, or the ratio of the acoustic impedance of the sidewall of the reaction vessel to the acoustic impedance of the sound wave transmission medium is 0.75 to 1.
[0017] In one embodiment, the ratio of the acoustic impedance of the acoustic wave transmission medium to the acoustic impedance of the sidewall of the reaction vessel is 0.75.
[0018] In one embodiment, the piezoelectric vibrator is used to generate ultrasonic waves, driven by the drive module, with the propagation direction parallel to the liquid surface of the sample to be mixed.
[0019] In one embodiment, the highest point of the ultrasonic wave generated by the piezoelectric vibrator in the direction perpendicular to the liquid surface is located at a first distance above the liquid surface, and the lowest point of the ultrasonic wave generated by the piezoelectric vibrator in the direction perpendicular to the liquid surface is located at a second distance below the liquid surface, wherein the second distance is greater than or equal to the first distance.
[0020] In one embodiment, the ratio of the first distance to the second distance is 1:1, 1:2, 1:3, or 2:3.
[0021] In one embodiment, the piezoelectric vibrator is used to generate ultrasonic waves with a frequency of 1MHz-2MHz under the drive of the drive module.
[0022] In one embodiment, the piezoelectric vibrator is used to generate ultrasonic waves with a frequency of 1.6 MHz under the drive of the drive module.
[0023] In one embodiment, the ultrasonic waves generated by the piezoelectric vibrator are longitudinal waves.
[0024] In one embodiment, the driving module includes a control unit, a frequency generation unit, a voltage amplification unit, and a power amplification unit. The control unit is electrically connected to the frequency generation unit and the voltage amplification unit, and the frequency generation unit is electrically connected to the piezoelectric vibrator through the voltage amplification unit and the power amplification unit.
[0025] The control unit is used to control the frequency generation unit to generate a resonant signal;
[0026] The frequency generation unit is used to generate a resonant signal, which in turn drives the piezoelectric vibrator to generate ultrasonic waves.
[0027] The voltage amplification unit is used to amplify the amplitude of the resonant signal generated by the frequency generation unit;
[0028] The power amplification unit is used to amplify the signal energy of the voltage amplification unit.
[0029] In one embodiment, the frequency generation unit is further configured to generate a sweep frequency signal on the resonant signal, wherein the frequency of the resonant signal is fs, and the sweep frequency range of the sweep frequency signal is fs±100KHz.
[0030] In one embodiment, the sweep period is 0-5ms and the sweep range is fs±40KHz.
[0031] In one embodiment, the sweep period is 1.25ms.
[0032] In one embodiment, the duty cycle of the resonant signal is 0-100%, and the duty cycle period is 10-100ms.
[0033] In one embodiment, the duty cycle of the resonant signal is 30%, and the duty cycle period is 50ms.
[0034] In one embodiment, the power amplification unit amplifies the signal energy of the voltage amplification unit to a signal amplitude of 20-400Vp-p.
[0035] In one embodiment, the power amplification unit amplifies the signal energy of the voltage amplification unit to a signal amplitude of 50-240Vp-p.
[0036] In one embodiment, the power amplification unit amplifies the signal energy of the voltage amplification unit to a signal amplitude of 140Vp-p.
[0037] In one embodiment, the drive module further includes a current feedback unit, which is electrically connected to the piezoelectric vibrator through the power amplifier unit. The current feedback unit is used to collect the current of the piezoelectric vibrator and feed the current of the piezoelectric vibrator back to the control unit. The control unit is used to determine whether the current of the piezoelectric vibrator is within a preset current range of a preset current value.
[0038] In one embodiment, the preset current range is ±30%.
[0039] In one embodiment, the piezoelectric vibrator includes a vibrator body and a first electrode; the vibrator body has a first surface and a second surface disposed opposite to each other; the first electrode includes a plurality of first sub-electrodes, each of the first sub-electrodes being equidistantly arranged on the first surface of the vibrator body along a first direction; the first direction is a vertical direction, and the driving module is used to drive the piezoelectric vibrator to operate a first preset number of first sub-electrodes located on the liquid surface of the sample to be mixed and a second preset number of first sub-electrodes located below the liquid surface of the sample to be mixed, so as to generate the ultrasonic waves within a preset range in a direction perpendicular to the liquid surface of the sample to be mixed, wherein the ratio of the first preset number to the second preset number is 1:1 or 1:2 or 1:3 or 2:3.
[0040] In one embodiment, the second preset quantity is 3, and the first preset quantity is 1; or
[0041] The second preset quantity is 2, and the first preset quantity is 2.
[0042] The aforementioned sample analyzer, by setting the ratio of the acoustic impedance of the acoustic wave transmission medium to the acoustic impedance of the sidewall of the reaction vessel to 0.75 to 1, can effectively reduce the loss of sound waves propagating between the acoustic wave transmission medium and the sidewall of the reaction vessel, thereby effectively reducing the energy loss of the ultrasonic waves transmitted to the sample to be mixed, thus reducing design costs while improving mixing efficiency and resulting in better mixing effect. Attached Figure Description
[0043] Figure 1A This is a schematic diagram of the structure of each device of the sample analyzer in one embodiment;
[0044] Figure 1B This is a schematic diagram of the sample mixing device in one embodiment;
[0045] Figure 1CThis is a schematic diagram of the ultrasonic emission and liquid rotation direction of the sample mixing device in one embodiment;
[0046] Figure 2 This is a schematic diagram of the logic element connections of the driver module in one embodiment;
[0047] Figure 3 This is a schematic diagram illustrating an application scenario of a sample analyzer in one embodiment;
[0048] Figure 4A , 4B This is a schematic diagram of the simulation output results of the driving module in one embodiment;
[0049] Figure 5A This is a schematic diagram of the structure of the first surface of a piezoelectric vibrator in one embodiment;
[0050] Figure 5B This is a schematic diagram of the structure of the second surface of a piezoelectric vibrator in one embodiment;
[0051] Figure 6 This is a schematic diagram of sound waves propagating in a medium such as a sound wave transmission medium or a reaction vessel, as shown in one embodiment. Detailed Implementation
[0052] To make the objectives, technical solutions, and advantages of this application clearer, the following detailed description is provided in conjunction with the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are merely illustrative and not intended to limit the scope of this application.
[0053] In one embodiment, such as Figure 1A As shown, a sample analyzer is provided, including a sample acquisition device 20, a reagent supply device 30, a sample reaction device 40, an optical measurement device 50, a sample mixing device 10, and a sample delivery device 60.
[0054] The sample collection device 20 is used to collect samples and transport them to the sample reaction device 40.
[0055] The reagent supply device 30 is used to collect reagents from the reagent container and deliver the reagents to the sample reaction device 40.
[0056] The sample reaction apparatus 40 is used to contain the sample to be mixed and the reagents and to provide the environment required for the reaction.
[0057] The optical measuring device 50 is used to measure the light signal generated by the sample to obtain light information.
[0058] Specifically, the sample collection device 20 is used to quantitatively collect samples and transport them to the sample reaction device 40.
[0059] In some embodiments, the sample collection device 20 includes a sampling needle, a sampling needle moving device, a syringe, and a sampling needle cleaning device (not shown).
[0060] Of course, the sample collection device 20 is not limited to the implementation methods discussed above, but can be configured according to needs. For example, in some other implementation methods, the sample collection device 20 may also include an automatic sampler, a sample dilution device, etc. (not shown in the figure).
[0061] The reagent supply device 30 is used to collect quantitative reagents from reagent bottles or reagent containers and deliver the reagents to the sample reaction device 40.
[0062] In some embodiments, the reagent supply device 30 includes a reagent needle, a reagent needle moving device, a syringe, a reagent needle cleaning device, and a reagent storage compartment.
[0063] Of course, the reagent supply device 30 is not limited to the embodiments discussed above, and appropriate modifications can be made in other embodiments depending on specific needs. For example, in some other embodiments, the reagent supply device 30 may also include a dilution device, a reagent storage and replacement device, etc. (not shown in the figure).
[0064] The sample reaction apparatus 40 is used to contain samples and reagents and provide the environment required for the reaction.
[0065] In some embodiments, the sample reaction apparatus 40 includes a temperature control device and a cuvette (also called a reaction vessel).
[0066] Temperature control devices are used to provide a suitable temperature environment for sample and reagent reactions, such as 37°C. Of course, the specific temperature environment depends on the requirements and is not limited to the implementation methods discussed above.
[0067] The sample mixing device 10 is used to thoroughly mix the sample and reagents in the sample reaction device 40. In some embodiments, the sample mixing device 10 may use ultrasound to drive the liquid to form a rotating flow to mix the reagents and samples, and may include an ultrasonic transducer and a drive module.
[0068] The sample delivery device 60 is used to deliver samples sequentially to various devices, for example, to deliver a well-mixed sample from the sample reaction device 40 to the optical measurement device 50.
[0069] In some embodiments, the sample transport device 60 may include a cuvette transfer device or the like (not shown).
[0070] The cuvette transfer device is used to move the cuvette to switch between the sample addition position, reagent addition position, mixing position, and optical detection position.
[0071] The optical measuring device 50 is used to illuminate the sample in the cuvette and detect the light signals before, during, and after the reaction, and output corresponding electrical signals, such as detecting absorbance, and measuring the amount of the sample by the change in absorbance.
[0072] In other embodiments, the sample acquisition device 20, reagent supply device 30, sample reaction device 40, and optical measurement device 50 of the sample analyzer can be implemented in other ways and can also be implemented using existing technologies, which will not be described in detail in this embodiment.
[0073] It should be understood that insufficient mixing of reagents and samples can lead to inaccurate photometric measurements: 1. If the sample is not uniformly dispersed in the reagent, the initial photometric readings for the same reagent and sample mixture will be inconsistent, making it impossible to determine the amount of the analyte in the initial sample. 2. If the sample is not uniformly dispersed in the reagent, the reaction rate between the sample and the reagent will be slower, and the reaction progress measured at the reaction endpoint will be lower than that of a fully mixed sample (for example, a fully mixed sample only needs to be incubated for the instrument's preset 10 minutes to reach the optical detection conditions, while an insufficiently mixed sample needs to be incubated for 12 minutes or even longer to reach the optical detection conditions), making it impossible to determine the amount of the analyte in the sample.
[0074] To ensure that the reagents and samples are thoroughly mixed, such as Figure 1B As shown, the sample mixing device 10 includes a drive module 100 and a piezoelectric vibrator 200; the sample reaction device 40 includes a mixing tank 500, in which an acoustic wave transmission medium 400 is housed; a reaction container 300 is disposed within the mixing tank 500, and the reaction container 300 is at least partially immersed in the acoustic wave transmission medium 400, the reaction container 300 being used to hold the sample 301 to be mixed; the drive module 100 is electrically connected to the piezoelectric vibrator 200, the piezoelectric vibrator... One side of the piezoelectric vibrator 200 is immersed in the sound wave transmission medium 400. The piezoelectric vibrator 200 is disposed on the outside of the reaction container 300, and one side of the piezoelectric vibrator 200 faces the reaction container 300. The driving module 100 is used to drive the piezoelectric vibrator 200 to vibrate and generate sound waves. The ultrasonic waves are emitted towards the side wall of the reaction container 300 through the sound wave transmission medium 400. The piezoelectric vibrator is used to emit the ultrasonic waves within a preset range in a direction perpendicular to the liquid surface of the sample to be mixed.
[0075] In this embodiment, the driving module 100, also known as the driving power supply, is used to power the piezoelectric vibrator 200 and drive it to generate ultrasonic waves. The mixing tank 500 contains a sound wave transmission medium 400, which is a fluid. In one embodiment, the sound wave transmission medium 400 is a liquid, such as water. The sound wave transmission medium 400 can transmit the energy of the ultrasonic waves, allowing the ultrasonic waves to act on the sample 301 to be mixed within the reaction vessel 300.
[0076] The reaction container 300 contains a sample 301 to be mixed, which is a reagent and a human fluid sample to be mixed for the reaction. The human fluid can be blood, urine, or cerebrospinal fluid. Both the piezoelectric vibrator 200 and the reaction container 300 are immersed in a sound wave transmission medium 400. The piezoelectric vibrator 200 is positioned near the side wall of the mixing tank 500. The piezoelectric vibrator 200 emits ultrasonic waves towards the reaction container 300. The energy of these ultrasonic waves is transmitted to the reaction container 300 through the sound wave transmission medium 400, passes through the reaction container 300, and acts on the sample 301 to be mixed, causing the sample 301 to rotate and thus mix. The reaction container 300 is housed within the sample reaction device 40 and is used to contain the sample and reagent to be mixed. The sample mixing device 10 is used to thoroughly mix the sample and reagent in the reaction container 300.
[0077] In this embodiment, the ratio of the acoustic impedance of the acoustic wave transmission medium to the acoustic impedance of the sidewall of the reaction vessel is 0.75 to 1, or the ratio of the acoustic impedance of the sidewall of the reaction vessel to the acoustic impedance of the acoustic wave transmission medium is 0.75 to 1.
[0078] Assuming the material of the reaction vessel meets the transmittance requirements for sample detection, this embodiment, in order to obtain better acoustic transmission and reduce energy loss of ultrasound during transmission, uses the acoustic impedance of the ultrasound propagating in the sound wave transmission medium as the first acoustic impedance and the acoustic impedance of the ultrasound propagating on the side wall of the reaction vessel as the second acoustic impedance. The ratio of the first acoustic impedance to the second acoustic impedance is between 0.75 and 1, that is, the value of the first acoustic impedance to the second acoustic impedance is between 0.75 and 1, or the value of the second acoustic impedance to the first acoustic impedance is between 0.75 and 1. Table 1 below shows the test data for acoustic transmittance when the ratio of the first acoustic impedance to the second acoustic impedance is 0.75.
[0079] In this embodiment, the reaction vessel is a colorimetric cup, such as... Figure 6 As shown in the figure, the arrows from left to right indicate the propagation direction of the sound wave as it passes through the sound wave transmission medium, the wall of the cuvette, and then into the reaction liquid, which is the sample to be mixed. The arrows from right to left indicate the propagation direction of the sound wave after it is reflected by the wall of the cuvette. Figure 6 The meanings of each parameter are as follows:
[0080] Ι: Sound wave transmission medium;
[0081] ΙΙ: The wall of the cuvette, with a thickness of D;
[0082] III: The reaction liquid is considered to be the same as the sound transmission medium;
[0083] P 1i Incident sound pressure;
[0084] P 2t P t : Transmitted sound pressure;
[0085] P 1r P 2r : Reflected sound pressure;
[0086] R1, R2: Acoustic impedance of medium I and medium II.
[0087] The sound intensity transmission coefficients are as follows:
[0088]
[0089]
[0090] The above equation shows that the intensity of the transmitted sound wave when it passes through the intermediate layer depends not only on the ratio of the characteristic impedances R1 and R2 of the two media, but also on the ratio of the thickness of the intermediate layer to the wavelength of the sound wave within it. related.
[0091] Ignoring the energy loss caused by the thickness of medium ΙIII due to sound absorption, and setting k2D = π, the minimum wall thickness of the cuvette container can be calculated when the sound transmittance is maximized. Substituting the known parameters, we can calculate that D < 0.8, with 0.5 mm being the preferred value.
[0092] When the acoustic impedances of medium I and medium II are approximately equal (R 12 ≈R 21 ≈1), ( 12 + 21 ) 2 =4, while cos 2 k2D+sin 2 When k2D = 1, the maximum sound intensity transmission coefficient t can be obtained. I Considering the transmittance requirements of the cuvette, and based on the test data in Table 1, the impedance ratio of medium I and medium II is selected to be between 0.75 and 1.
[0093] Table 1. Sound Transmittance Test
[0094]
[0095] In the above embodiments, it can be shown that by setting the ratio of the first to the second acoustic impedance between 0.75 and 1, the loss of sound waves propagating between the sound wave transmission medium and the sidewall of the reaction vessel can be effectively reduced, thereby effectively reducing the energy of the ultrasonic waves transmitted to the sample to be mixed, thereby improving the mixing efficiency.
[0096] In one embodiment, the ratio of the acoustic impedance of the acoustic wave transmission medium to the acoustic impedance of the sidewall of the reaction vessel is 0.75. According to the above formula for calculating the sound intensity transmission coefficient, when the ratio of the acoustic impedance of the acoustic wave transmission medium to the acoustic impedance of the sidewall of the reaction vessel is 0.75, the loss of sound waves propagating between the acoustic wave transmission medium and the sidewall of the reaction vessel can be effectively reduced. This effectively reduces the energy loss of the ultrasonic waves transmitted to the sample to be mixed, thereby reducing design costs while improving mixing efficiency.
[0097] It should be understood that traditional oscillating mixing methods are difficult to control the impact force, and the liquid in the reaction vessel is prone to splashing, affecting the test results. Ordinary stirring mixing produces a horizontal rotating flow, which easily leads to stratification and other uneven distribution of the mixed liquid. At the same time, stirring mixing involves contact between the agitator and different test liquids, causing contamination. Contact ultrasonic mixing suffers from the same problems as stirring mixing, and it cannot form a rotating flow. The energy is difficult to control, which easily causes liquid splashing and localized severe liquid vibration, resulting in uneven mixing.
[0098] In this embodiment, utilizing the inverse piezoelectric effect of the piezoelectric vibrator 200, the piezoelectric vibrator 200 generates high-frequency vibrations of the same frequency under the high-frequency AC drive of the drive module 100, emitting ultrasonic waves outward. It is worth noting that the ultrasonic waves generated by the piezoelectric vibrator 200 propagate towards the reaction vessel 300 within a predetermined range perpendicular to the interface between the sample to be mixed 301 and the air. For ease of explanation, in the following embodiments, the liquid surface of the sample to be mixed is described as a gas-liquid interface. Preferably, the center of the ultrasonic waves emitted by the piezoelectric vibrator 200 is aligned with the gas-liquid interface, that is, the center of the emission source of the piezoelectric vibrator 200 is aligned with the gas-liquid interface. The ultrasonic waves generated by the piezoelectric vibrator 200 are emitted towards the reaction vessel at a height near the gas-liquid interface. The highest point of the ultrasonic waves generated by the piezoelectric vibrator 200 in the direction perpendicular to the gas-liquid interface is located at a first distance above the gas-liquid interface, and the lowest point of the ultrasonic waves generated by the piezoelectric vibrator 200 in the direction perpendicular to the gas-liquid interface is located at a second distance below the gas-liquid interface. In this way, the ultrasonic waves generated by the piezoelectric vibrator 200 can propagate near the gas-liquid interface, so that the liquid surface of the solution to be mixed is affected by the ultrasonic waves. Specifically, the ultrasonic waves are transmitted to the liquid in the reaction vessel 300 in the sound wave transmission medium 400. Near the gas-liquid interface of the liquid, the sound waves injected parallel to the sample liquid surface will push the liquid at the gas-liquid interface near the sound wave incident position to move obliquely upward, while the gas-liquid interface far from the sound wave incident position is at a stationary state. Therefore, a height difference will be formed at the liquid-gas interface in the reaction vessel 300, generating a pressure gradient, which drives the liquid to form a rotating flow from top to bottom, forming a rotating flow to mix the liquid. This not only achieves mixing in the horizontal direction but also in the vertical direction, resulting in better mixing and effectively preventing liquid splashing.
[0099] like Figure 1C As shown in the figure, the arrows indicate the direction of liquid rotation. To better illustrate the direction of ultrasonic wave propagation and the direction of liquid rotation, Figure 1C The diagram omits the acoustic wave transmission medium and the sample to be mixed. Specifically, the liquid surface on the side closer to the piezoelectric transducer 200 (left side of the diagram) is pushed up by the ultrasonic waves, while the liquid surface on the side farther from the piezoelectric transducer 200 (right side of the diagram) is relatively lower. Therefore, the liquid on the left side flows to the right and downwards; under the influence of the liquid above, the liquid at the bottom of the right side flows to the left and upwards, continuing to push up the liquid surface on the left, thus forming a circulation. This causes the liquid to rotate clockwise in the vertical direction as shown in the diagram, and continuously circulate, thereby making the sample 301 to be mixed more thoroughly, achieving a better mixing effect, and effectively avoiding splashing caused by stirring.
[0100] In the above embodiment, ultrasonic waves are emitted toward the reaction vessel 300 within a preset range perpendicular to the interface between the sample 301 to be mixed and the air. The ultrasonic waves propagate through the sound wave transmission medium 400 to the sample 301 to be mixed inside the reaction vessel 300. This causes the sample 301 to be mixed to tumble downwards at the interface with the air due to the energy of the ultrasonic waves. As a result, the sample 301 on the liquid surface can tumble horizontally along the liquid surface and then downwards, while the sample 301 at the bottom tumbles upwards from the bottom. This achieves the overall vertical rotation of the sample 301 to be mixed, resulting in more thorough mixing, better mixing effect, and effectively avoiding splashing caused by stirring.
[0101] In one embodiment, the sample mixing device 10 of the above embodiments can be applied to, for example... Figure 3 In the structure shown, the drive motor is connected to the reaction ring to drive its rotation. This reaction ring serves as a mixing tank 500. The acoustic wave transmission medium 400 is housed within the mixing tank. There are two piezoelectric vibrators 200. Figure 3 As shown, multiple reaction containers 300 are located on both sides of the reaction ring and are placed in the mixing tank of the reaction ring. Samples and reagents are delivered to the reaction containers 300 by a pipetting module. The pipetting module can be one for delivering samples and reagents, or it can be two, one for delivering samples and one for delivering reagents.
[0102] In order to enable the sample 301 to rotate better and achieve better mixing, in one embodiment, the piezoelectric vibrator 200 is used to generate ultrasonic waves with the propagation direction parallel to the liquid surface of the sample to be mixed under the drive of the drive module 100.
[0103] It is worth mentioning that although ultrasound does not propagate in a straight line like lasers, but rather as a waveform that spreads outward in a semi-circular or fan-shaped pattern along the sound source, the overall propagation direction of ultrasound is still definite. This propagation direction is determined by the central axis of the region where the ultrasound propagates; that is, in this embodiment, the central axis of the region where the ultrasound propagates is the direction of propagation. It should be understood that if the propagation direction of ultrasound is inclined towards the gas-liquid interface, the tumbling and rotational energy of the liquid will be reduced. For example, when ultrasound propagates from high to low to the gas-liquid interface, the liquid surface near the piezoelectric vibrator 200 will not be pushed up by the ultrasound, and the liquid at the surface can only move laterally, making it prone to splashing. When ultrasound propagates from low to high to the gas-liquid interface, the liquid surface near the piezoelectric vibrator 200 will bulge too high, also making it prone to splashing, and the liquid will find it difficult to rotate vertically, which is detrimental to vertical mixing. In this embodiment, the ultrasonic wave is emitted parallel to the gas-liquid interface near the interface and propagates to the liquid to be mixed within the reaction vessel 300. This causes the parallel-injected sound wave to push the liquid near the incident point of the sound wave to move obliquely upwards, while the gas-liquid interface away from the incident point remains stationary. Therefore, a height difference is formed between the liquid and gas interfaces within the reaction vessel 300, creating a pressure gradient that drives the liquid to form a downward rotating flow, resulting in a more effective mixing effect.
[0104] In one embodiment, the highest point of the ultrasonic wave generated by the piezoelectric vibrator in the direction perpendicular to the liquid surface is located at a first distance above the liquid surface, and the lowest point of the ultrasonic wave generated by the piezoelectric vibrator in the direction perpendicular to the liquid surface is located at a second distance below the liquid surface, wherein the second distance is greater than or equal to the first distance.
[0105] In this embodiment, the ultrasonic waves generated by the piezoelectric vibrator need to be emitted near the liquid surface of the sample to be mixed. This allows the sample within the reaction vessel to tumble under the influence of the ultrasonic waves. The ratio of the first distance to the second distance is 1:1, 1:2, 1:3, or 2:3, meaning the ratio of the first distance to the second distance is 1:1, 1:2, 1:3, or 2:3. The first distance of ultrasonic waves is used to further accelerate the sample excited by the second distance of ultrasonic waves. The second distance of ultrasonic waves ensures that the amount of sample liquid excited is sufficient to achieve rotational mixing. If the first distance is greater than the second distance, because the acoustic impedance of air is much smaller than that of the reaction vessel wall, some ultrasonic waves cannot be transmitted through the air, causing the acoustic energy to accumulate in the sidewall of the reaction vessel above the sample liquid surface, leading to melting. If the first distance of ultrasonic waves is not emitted, the ultrasonic waves will be transmitted through the sample liquid, failing to generate a rotating flow to mix the sample. If the ratio of the first distance to the second distance is 1:4, or even smaller, it's similar to not emitting ultrasound at the first distance, and a rotating flow cannot be generated to mix the sample. Therefore, in some embodiments, the second distance is equal to the first distance, which can more efficiently make the sample to be mixed tumble and avoid cup melting. In other embodiments, the second distance is greater than the first distance, and the ratio of the first distance to the second distance is 1:2, 1:3, or 2:3, so that the ultrasound below the liquid surface has higher energy. Combined with the ultrasound above the liquid surface, they can work together to make the sample to be mixed move horizontally and tumble vertically, resulting in better mixing and preventing cup melting.
[0106] In one embodiment, the first end of the reaction container 300 is the bottom, the second end of the reaction container 300 has an opening, the first end of the reaction container 300 is immersed in the sound wave transmission medium 400, and the second end of the reaction container 300 is exposed outside the sound wave transmission medium 400.
[0107] Since the height of the opening of the reaction vessel 300 is greater than the height of the surface of the acoustic wave transmission medium 400, the inflow of the acoustic wave transmission medium 400 into the reaction vessel 300 can be effectively prevented. In order to allow the reaction vessel 300 to be placed inside the acoustic wave transmission medium 400, with one end of the opening located above the surface of the acoustic wave transmission medium 400, in one embodiment, a support frame (not shown in the figure) is also included. The support frame is connected to the mixing tank 500, and is disposed above the mixing tank 500 and above the surface of the acoustic wave transmission medium 400. The support frame has a support hole through which the reaction vessel 300 enters the acoustic wave transmission medium 400, and the edge of the opening of the reaction vessel 300 abuts against the support frame. Thus, the reaction vessel 300 is supported by the support frame and is at least partially immersed in the acoustic wave transmission medium 400.
[0108] In one embodiment, such as Figure 1B As shown, the height of the surface of the acoustic wave transmission medium 400 is higher than the liquid level of the sample 301 to be mixed, which is contained in the reaction vessel 300.
[0109] In this embodiment, the liquid surface of the sample 301 to be mixed is below the surface of the sound wave transmission medium 400. This allows the ultrasonic waves propagating in the sound wave transmission medium 400 to propagate smoothly to the gas-liquid interface of the sample 301 to be mixed, resulting in a better mixing effect.
[0110] In one embodiment, the piezoelectric vibrator is configured such that one side of the piezoelectric vibrator is immersed in the acoustic wave transmission medium, and the other side of the piezoelectric vibrator is exposed in the acoustic wave transmission medium.
[0111] In this embodiment, one side of the piezoelectric vibrator is immersed in the acoustic wave transmission medium through a waterproof layer, while the other side is connected to the sidewall of the mixing tank. This allows the piezoelectric vibrator on the side immersed in the acoustic wave transmission medium to emit ultrasonic waves toward the reaction vessel. Furthermore, by controlling the different electrodes activated on the piezoelectric vibrator, the emission of ultrasonic waves can be adapted to the height of the gas-liquid interface.
[0112] In one embodiment, the piezoelectric vibrator 200 is used to generate ultrasonic waves with a frequency of 1MHz-2MHz under the drive of the drive module 100.
[0113] It should be understood that the relationship between the resonant frequency and the thickness of the piezoelectric vibrator is fs = Nt / t, where fs is the resonant frequency of the piezoelectric vibrator, which is also the frequency of the ultrasonic wave, Nt is the frequency constant of the vibrator, and t is the thickness of the vibrator. Therefore, the ultrasonic frequency is inversely proportional to the thickness of the piezoelectric vibrator. To ensure high strength, the thickness of the piezoelectric vibrator cannot be less than 1 mm. If it is less than 1 mm, the structural strength of the piezoelectric vibrator will not meet the operational requirements. In this embodiment, the ultrasonic frequency generated by the piezoelectric vibrator 200 is between 1 MHz and 2 MHz. This frequency range provides strong sound wave penetration, a large and uniform mixing region for the rotating flow, good mixing effect, and avoids damaging the detected components in the sample liquid. It also ensures that the structural strength of the piezoelectric vibrator 200 meets the operational requirements.
[0114] In one embodiment, the piezoelectric vibrator 200 is used to generate ultrasonic waves with a frequency of 1.6 MHz under the drive of the drive module 100. In this embodiment, the 1.6 MHz sound wave has stronger penetrating power, a larger and more uniform mixing region of the rotating flow, and a better mixing effect.
[0115] To induce vertical tumbling of the sample to be mixed, in one embodiment, the ultrasonic waves generated by the piezoelectric vibrator are longitudinal waves. In this embodiment, the longitudinal waves are sound waves with the same propagation direction and vibration direction. These longitudinal waves can cause fluctuations in the liquid surface, thereby creating tumbling from top to bottom and from bottom to top.
[0116] In one embodiment, such as Figure 2 As shown, the driving module 100 includes a control unit 110, a frequency generation unit 120, a voltage amplification unit 130, and a power amplification unit 140. The control unit 110 is electrically connected to the frequency generation unit 120 and the voltage amplification unit 130. The frequency generation unit 120 is electrically connected to the piezoelectric vibrator 200 through the voltage amplification unit 130 and the power amplification unit 140. The control unit is used to control the frequency generation unit to generate a resonant signal. The frequency generation unit generates a resonant signal, which drives the piezoelectric vibrator to generate ultrasonic waves. The voltage amplification unit amplifies the amplitude of the resonant signal generated by the frequency generation unit. The power amplification unit amplifies the signal energy of the voltage amplification unit.
[0117] In this embodiment, the frequency of the resonant signal generated by the frequency generation unit is the resonant frequency, which is the frequency of the ultrasonic wave generated by the piezoelectric vibrator.
[0118] In this embodiment, the control unit 110 also has the function of communicating with the main control board 180 of the device. Therefore, the control unit 110 can also be called the communication and control unit 110. The control unit 110 is used to communicate with the main control board 180 of the device, control the frequency generation unit to generate the resonant frequency of the piezoelectric oscillator 200, control the voltage amplification unit 130 to adjust the voltage amplitude, and judge and process the signal of the current feedback unit 150.
[0119] The frequency generation unit generates a frequency signal to drive the piezoelectric vibrator 200. The generated frequency, denoted as fs, is the same as the resonant frequency of the piezoelectric vibrator 200. When fs is greater than 1 MHz, the ultrasonic waves will not generate cavitation bubbles in the reaction liquid, which is beneficial to the accuracy of the detection system results. Megasonic waves have good penetration in the reaction liquid, which is beneficial to the mixing effect. Based on the formula fs = Nt / t for the frequency constant Nt and thickness t of the piezoelectric vibrator 200, when fs is greater than 2 MHz, the thickness of the piezoelectric vibrator 200 is approximately less than 1 mm, and the structural strength of the piezoelectric vibrator 200 does not meet the working requirements. When fs is between 1 MHz and 2 MHz, the acoustic penetration is strong, the swirling flow mixing area is large and uniform, the mixing effect is good, and it can avoid damaging the detected components in the sample liquid, while also ensuring that the structural strength of the piezoelectric vibrator 200 meets the working requirements. The peak-to-peak value of the frequency signal is between 1 and 10 Vp-p. The resonant frequency fs of the piezoelectric vibrator 200 varies with temperature and load during operation. To ensure that the piezoelectric oscillator 200 operates at the optimal resonant frequency, the signal of the driving power supply is a frequency sweep change, which can compensate for the influence of the fs change and allow the oscillator to operate at its best.
[0120] In one embodiment, the frequency generation unit is further configured to generate a sweep frequency signal on the resonant signal, wherein the frequency of the resonant signal is fs, and the sweep frequency range of the sweep frequency signal is fs ± 100 kHz. In one embodiment, the resonant frequency fs is 1 MHz-2 MHz, and in another embodiment, the resonant frequency fs is 1.6 MHz. In one embodiment, the sweep frequency range of the sweep frequency signal is 1.59 MHz to 1.61 MHz. In this embodiment, the frequency generation unit enables the piezoelectric vibrator to generate fluctuations within a certain range of the resonant frequency when it resonates; these fluctuations constitute the sweep frequency signal. By generating the sweep frequency signal, the resonant frequency drift of the piezoelectric vibrator 200 can be eliminated, avoiding problems such as poor vibration and excessively low acoustic energy, thereby improving the stability of the sample mixing device.
[0121] In one embodiment, the sweep period is 0-5ms, and the sweep range is fs±40kHz. In this embodiment, the sweep signal generated by the frequency generation unit has a sweep period of 0-5ms and a sweep range of fs±40kHz, which can further eliminate the resonant frequency drift of the piezoelectric vibrator, avoid problems such as poor vibration and low acoustic energy, and further improve the stability of the sample mixing device. In another embodiment, the sweep period is 1.25ms. In this embodiment, the sweep period of 1.25ms can better eliminate the resonant frequency drift of the piezoelectric vibrator, more effectively avoid problems such as poor vibration and low acoustic energy, and further improve the stability of the sample mixing device.
[0122] In one embodiment, the duty cycle of the resonant signal is 0-100%, and the duty cycle period is 10-100ms.
[0123] It should be understood that if the frequency of ultrasound has a duty cycle, the ultrasound will be emitted in a pulsed manner. By adjusting the duty cycle of the ultrasound, the pulse period of the ultrasound can be adjusted. In this embodiment, the pulsed emission of the ultrasound creates a pulsed height difference on the surface of the liquid in the sample to be mixed, generating a pulsed rotating flow, which creates greater disturbance within the sample and is beneficial for the mixing of the samples. Preferably, the duty cycle of the resonant signal is 30%, and the duty cycle period is 50ms. In this way, the ultrasound at this duty cycle and duty cycle period can create a larger pulsed height difference on the surface of the liquid in the sample to be mixed, creating greater disturbance within the sample and facilitating the mixing of the samples.
[0124] In the above embodiments, the frequency generation unit can generate a swept frequency signal, with the swept frequency fluctuating around the resonant frequency fs. The swept frequency signal can eliminate the resonant frequency drift of the piezoelectric vibrator 200, avoiding problems such as poor vibration and low acoustic energy, and improving the stability of the ultrasonic device 10. For example, the swept frequency variation is within fs ± 100 kHz, and the swept frequency period can be adjusted between 0-5 ms. The frequency generation unit can adjust the duty cycle of the generated frequency signal to generate intermittent pulse signals. The pulse emission of the sound wave will form a pulsed height difference on both sides of the liquid-gas-liquid interface, generating a pulsed rotating flow, creating greater disturbance inside the sample, which is beneficial to the mutual mixing of the sample. The duty cycle range is between 0-100%, and the duty cycle period is between 10-100 ms. In some embodiments, the frequency generation unit includes a communication and control chip and a signal generation chip.
[0125] The voltage amplification unit 130 is used to amplify and adjust the signal amplitude of the frequency generation unit.
[0126] The power amplifier unit 140 is used to amplify the signal energy of the voltage amplifier unit 130. After amplification, the peak-to-peak value of the signal is 20-400Vp-p, and it is output to the piezoelectric vibrator 200, causing the piezoelectric vibrator 200 to generate high-frequency vibration, thereby generating ultrasonic waves.
[0127] In one embodiment, the signal amplitude after the power amplification unit amplifies the signal energy of the voltage amplification unit is 20-400Vp-p.
[0128] It should be understood that the material power density of a piezoelectric vibrator is generally 0.1-2 W / cm²*KHz. The acoustic power generated by the piezoelectric vibrator is related to the material, volume, and input voltage amplitude. To meet the acoustic power threshold for ultrasonic mixing, a driving range of 20-400 Vp-p is designed based on the material and volume of the piezoelectric vibrator. The output acoustic power can be changed by adjusting the amplitude, thus setting the mixing level. Furthermore, excessively high driving voltage can easily cause thermal melting and damage to the reaction vessel, while an excessively high voltage amplitude will exceed the power density range of the piezoelectric vibrator, posing a risk of breakdown. Therefore, in this embodiment, the signal amplitude after amplification by the voltage amplification unit is 20-400 Vp-p, which effectively avoids damage to the reaction vessel and piezoelectric vibrator breakdown, while also achieving uniform mixing of the sample to be mixed.
[0129] In one embodiment, the signal amplitude after the power amplification unit amplifies the signal energy of the voltage amplification unit is 50-240Vp-p.
[0130] In this embodiment, the signal amplitude after the signal energy of the voltage amplification unit is amplified is 50-240Vp-p, which can further effectively avoid damage to the reaction vessel and piezoelectric oscillator breakdown, resulting in a better uniform mixing effect of the sample to be mixed.
[0131] In one embodiment, the signal amplitude after the power amplification unit amplifies the signal energy of the voltage amplification unit is 140Vp-p.
[0132] In this embodiment, the signal amplitude after amplification by the voltage amplification unit is 140Vp-p, which makes the reaction vessel and piezoelectric vibrator safer and improves the uniform mixing effect of the sample to be mixed. In one embodiment, the drive module 100 further includes a current feedback unit 150, which is electrically connected to the piezoelectric vibrator 200 through the power amplification unit 140.
[0133] In one embodiment, the drive module further includes a current feedback unit electrically connected to the piezoelectric vibrator via the power amplifier unit. The current feedback unit collects the current of the piezoelectric vibrator and feeds it back to the control unit. The control unit determines whether the current of the piezoelectric vibrator is within a preset current range; otherwise, it determines that the piezoelectric vibrator is in an abnormal state. In one embodiment, the preset current range is ±30%. The current feedback unit 150 collects the current of the operating piezoelectric vibrator 200, processes the collected current, and uploads it to the communication and control unit 110 for comparison with standard data. If the current exceeds a preset range (i.e., a preset current threshold), the piezoelectric vibrator 200 is determined to be in an abnormal state. For example, if all four first sub-electrodes are simultaneously activated, the normal current is 1.2-2 Ap-p. If the current exceeds the normal range by ±30%, the piezoelectric vibrator 200 or the power supply is determined to be in an abnormal working state, and the device needs to upload a fault code. The control unit 110 processes and judges the signal from the current feedback unit 150.
[0134] In this embodiment, the driving module 100 can drive the piezoelectric vibrator 200 to generate ultrasonic waves with a expected resonant frequency between 1-2 MHz. The ultrasonic waves are transmitted in the sound wave transmission medium 400, such as water, to mix the liquid in the reaction vessel 300. Figure 4A and Figure 4B The image shows a comparison of simulation and oscilloscope test results for the driver module 100. The simulation and experiment use 1.55MHz, 180Vp-p, and 2Ap-p as examples. Figure 4B In the figure, the horizontal axis represents time, and the vertical axis represents voltage and current. The two waveforms in the figure represent voltage and current, respectively. When the voltage is 172V, it can output a signal of 1.548MHz. The simulation results show that the driver module 100 can output a high-frequency signal of 1MHz-2MHz and can be stable at this frequency.
[0135] In one embodiment, such as Figure 5A and Figure 5BAs shown, the piezoelectric oscillator 200 includes an oscillator body 230, a first electrode 210, and a second electrode 220. The oscillator body 230 has a first surface 201 and a second surface 202 disposed opposite to each other. The first electrode 210 includes a plurality of first sub-electrodes 211, and each first sub-electrode 211 is equidistantly arranged on the first surface 201 of the oscillator body 230 along a first direction. The second electrode 220 is disposed on the second surface 202 of the oscillator body 230. Each first sub-electrode 211 is used to be energized according to the position of the sample to be mixed in the first direction, under the drive of the driving module, to energize one first sub-electrode 211 corresponding to the position of the sample to be mixed or at least two adjacent first sub-electrodes 211.
[0136] In this embodiment, each of the first sub-electrodes 211 is arranged in an array on the first surface 201 of the vibrator body 230 and in a row along the first direction. The first sub-electrodes 211 and the second electrode 220 are respectively connected to the driving module. The driving module outputs an electrical signal with the same frequency as the piezoelectric vibrator 200, causing the piezoelectric vibrator 200 to resonate and radiate acoustic energy outward, thereby causing the piezoelectric vibrator 200 to generate ultrasonic waves and radiate them outward. In one embodiment, the first electrode 210 is the positive electrode and the second electrode 220 is the negative electrode.
[0137] In this embodiment, when the piezoelectric vibrator is placed in the acoustic wave transmission medium 400, the second surface of the piezoelectric vibrator is immersed in the acoustic wave transmission medium and faces the sample to be mixed. In this embodiment, the piezoelectric vibrator 200 is placed vertically, that is, the first direction is vertical, or in other words, the first direction is parallel to the vertical direction. The piezoelectric vibrator 200 can, under the drive of the drive module, work in conjunction with the second electrode 220 and the first sub-electrodes 211 at different heights in the first direction to generate ultrasonic waves that match the liquid level of the sample to be mixed, causing the sample to fluctuate at the gas-liquid interface. Since each first sub-electrode 211 can work independently under the drive of the drive module, it can adapt to the liquid level of the sample to be mixed. The ultrasonic waves emitted by the different first sub-electrodes 211 mean that the piezoelectric vibrator 200 does not need to be disassembled and adjusted when adapting to different liquid levels, making height adjustment more convenient and effectively improving efficiency.
[0138] In this embodiment, the first sub-electrode 211 is uniformly arranged along the first direction, so that the first sub-electrode 211 can work according to the position of the sample to be mixed in the first direction under the drive of the drive module, and the first sub-electrode 211 at the corresponding position of the sample to be mixed can be used to flexibly oscillate the sample to be mixed at different positions in the first direction, so as to meet the needs of ultrasonic oscillation at different positions.
[0139] In one embodiment, as shown in Figure Figure 5A As shown, each of the first sub-electrodes 211 includes a first working part 211b and a first connecting part 211a. One end of the first working part 211b is connected to the first connecting part 211a. The width of the first connecting part 211a is greater than the width of the first working part 211b. The first working parts 211b of each of the first sub-electrodes 211 are parallel to each other and are equidistant.
[0140] In this embodiment, the first connecting part 211a is used for electrical connection with the driving module. For example, the first connecting part 211a is used to weld wires, and the wires connect the first connecting part 211b to the driving module for electrical connection. The first working part 211b is used to generate resonance under the drive of the driving module after being energized. It should be understood that, since the first working parts 211b are equidistantly arranged, each first sub-electrode 211 can work according to the sample to be mixed, resulting in a more uniform distribution of ultrasonic energy and a better oscillation effect.
[0141] It should be understood that, since the width of each first connecting portion 211a is greater than the width of each first working portion 211b, in order to make the spacing between the first working portions 211b smaller, in one embodiment, the first connecting portions 211a of adjacent first sub-electrodes 211 have opposite protrusion orientations in the first direction, and the first connecting portions 211a of adjacent first sub-electrodes 211 are located on one side of the first direction, and the first connecting portions 211a of adjacent first sub-electrodes 211 are located on the other side of the first direction, that is, the first connecting portions 211a of adjacent first sub-electrodes 211 are respectively located on both sides, so that the working portions of adjacent first sub-electrodes 211 can be located in the middle. That is, in this embodiment, the first connecting portions 211a of adjacent first sub-electrodes 211 are respectively located on both sides of the first direction, and the protrusion directions are staggered, so that the spacing between the first working portions 211b is smaller, and the first working portions 211b can be neatly arranged, which is beneficial to make the ultrasound more uniform.
[0142] In one embodiment, such as Figure 5A As shown, the width of the first working portion 211b of each of the first sub-electrodes 211 is greater than the distance between two adjacent first working portions 211b. It should be understood that the larger the width of the first working portion 211b, the greater the energy of the emitted ultrasonic wave. Thus, since the width of the first working portion 211b is greater than the distance between the first working portions 211b, the first working portion 211b can emit ultrasonic waves with greater energy, thereby meeting the energy requirements for oscillation and homogenization of the sample to be homogenized.
[0143] In one embodiment, such as Figure 5AAs shown, the first electrode 210 further includes a second sub-electrode 213, the width of which is greater than the width of each of the first sub-electrodes 211. The second sub-electrode 213 is disposed near one end of the oscillator body 230 in the first direction. In this embodiment, the width of the working portion of the second sub-electrode 213 is greater than the width of the first working portion 221b of each of the first sub-electrodes 211.
[0144] In this embodiment, the second sub-electrode 213 has a larger width, enabling it to generate greater energy. When the piezoelectric vibrator 200 is applied in a non-contact mixing device, with the first direction parallel to the vertical direction and the second sub-electrode 213 located below each of the first sub-electrodes 211, the second sub-electrode 213 can generate high-energy ultrasonic waves below the ultrasonic waves generated by the first sub-electrodes 211. These ultrasonic waves, in conjunction with the adjacent or nearby first sub-electrodes 211, can push the sample to be mixed upwards, achieving vertical rotation and tumbling, resulting in better mixing. In the following embodiments, the mixing motion law of the sample to be mixed will be further explained in conjunction with an ultrasonically driven liquid mixing device.
[0145] In one embodiment, please combine Figure 5A and Figure 5B The second electrode 220 includes a second connecting portion 221, a side wing portion 223, and a second working portion 222. The second connecting portion 221 is disposed on the first surface 201 of the vibrator body 230, the side wing portion 223 is disposed on one side of the vibrator body 230, and the second working portion 222 is disposed on the second surface 202 of the vibrator body 230. The second connecting portion 221 is connected to one end of the side wing portion 223, and the other end of the side wing portion 223 is connected to the second working portion 222. In this embodiment, the second working portion 222 is rectangular. This arrangement not only matches the first working portion, achieving full coverage of the first working portion, but also saves costs. The cross-section of the ultrasonic wave emitted by the piezoelectric vibrator is also similar to a rectangle due to the arrangement of the second working portion 222.
[0146] In this embodiment, the side of the oscillator body 230 is adjacent to both the first surface 201 and the second surface 202. Thus, the second connecting part 221 can be connected to the second working part 222 through the side wing part 223, and the second electrode 220 can be connected to the wire located on the first surface 201 of the oscillator body 230 through the connecting part, thereby realizing the connection with the drive module.
[0147] It should be understood that in the application scenario of non-contact mixing device, the piezoelectric vibrator 200 needs to be placed in the sound wave transmission medium to work, for example, the sound wave transmission medium is water. In order to prevent the piezoelectric vibrator 200 from short-circuiting when it comes into contact with water, in one embodiment, the piezoelectric vibrator 200 also includes a waterproof layer. The waterproof layer is disposed on the second surface 202 of the vibrator body 230 and covers the outside of the second electrode 220.
[0148] In one embodiment, a sealing ring is provided on the first surface 201 of the oscillator body 230. The first connection portion 211a of each first electrode 210 and the second connection portion 221 of the second electrode 220 are electrically connected to the drive module through wires. The sealing ring covers the connection between the first connection portion 211a and the wire, and the connection between the second connection portion 221 and the wire. The outer layer of the wire is covered with an insulating layer. In this way, the piezoelectric oscillator 200 is isolated from the sound wave transmission medium through the connection of the sealing ring and the waterproof layer, thereby effectively waterproofing the piezoelectric oscillator 200 and preventing short circuits.
[0149] In one embodiment, the waterproof layer is a metal film, such as a platinum sheet; in another embodiment, the waterproof layer is a waterproof coating.
[0150] To reduce the impact of the waterproof layer on the impedance of the piezoelectric vibrator 200, in one embodiment, the thickness of the metal diaphragm or waterproof coating is less than 0.05 mm. This smaller thickness of the waterproof layer provides waterproofing and also effectively reduces the obstruction and buffering effect on vibration, allowing the vibrational energy generated by the vibrator body 230 to be fully conducted to the external medium.
[0151] In one embodiment, the driving module is used to drive at least one first sub-electrode 211 that matches the liquid level of the sample to be mixed, so that the piezoelectric vibrator emits the ultrasonic waves within a preset range in a direction perpendicular to the liquid level of the sample to be mixed, based on the liquid level of the sample to be mixed.
[0152] It should be understood that, since ultrasonic waves need to be emitted within a predetermined range perpendicular to the liquid surface of the sample to be mixed, one first sub-electrode or at least two adjacent first sub-electrodes are required to achieve ultrasonic wave emission near the gas-liquid interface. However, if multiple first sub-electrodes that are far apart or not adjacent are used, it is impossible to achieve ultrasonic wave emission near the gas-liquid interface, and the ultrasonic energy will be more dispersed, which is not conducive to pushing the liquid surface of the sample to be mixed to bulge, resulting in poor mixing effect. Therefore, in this embodiment, the driving module is used to drive one first sub-electrode or at least two adjacent first sub-electrodes to work simultaneously, so that the piezoelectric vibrator can emit ultrasonic waves within a predetermined range perpendicular to the liquid surface of the sample to be mixed.
[0153] In order to enable the piezoelectric vibrator to emit ultrasonic waves within a preset range perpendicular to the liquid surface of the sample to be mixed, in one embodiment, the driving module is used to drive the piezoelectric vibrator to operate a first preset number of first sub-electrodes located on the liquid surface of the sample to be mixed and a second preset number of first sub-electrodes located below the liquid surface of the sample to be mixed, so as to generate the ultrasonic waves within a preset range in a direction perpendicular to the liquid surface of the sample to be mixed, wherein the second preset number is greater than or equal to the first preset number.
[0154] In this embodiment, because the first sub-electrodes are equidistantly arranged and the second preset number is greater than or equal to the first preset number, the second distance of the ultrasonic waves generated by the piezoelectric vibrator in the direction perpendicular to the liquid surface is greater than or equal to the first distance, thus achieving ultrasonic wave emission within a preset range in the direction perpendicular to the liquid surface of the sample to be mixed. In one embodiment, the second preset number is equal to the first preset number, which can more efficiently make the sample to be mixed tumble and avoid cup melting. In other embodiments, the second preset number is greater than the first preset number, which makes the energy of the ultrasonic waves below the liquid surface greater. Combined with the ultrasonic waves above the liquid surface, they can work together to make the sample to be mixed move horizontally and tumble vertically, resulting in better mixing effect and avoiding cup melting.
[0155] In one embodiment, the ratio of the first preset quantity to the second preset quantity is 1:1, 1:2, 1:3, or 2:3.
[0156] In one embodiment, the ratio of the first preset quantity to the second preset quantity is 1:1; or the ratio of the first preset quantity to the second preset quantity is 1:2; or the ratio of the first preset quantity to the second preset quantity is 1:3; or the ratio of the first preset quantity to the second preset quantity is 2:3.
[0157] In one embodiment, the second preset quantity is 3, and the first preset quantity is 1. That is, the number of first sub-electrodes activated by the piezoelectric vibrator on the liquid surface of the sample to be mixed is 1, and the number of first sub-electrodes activated below the liquid surface of the sample to be mixed is 3. This makes the ultrasonic waves below the liquid surface have greater energy. Together with the ultrasonic waves on the liquid surface, they can work together to make the sample to be mixed move horizontally and roll vertically, resulting in better mixing effect and avoiding cup melting.
[0158] In one embodiment, the second preset quantity is 2, and the first preset quantity is 2, that is, the number of first sub-electrodes activated by the piezoelectric vibrator on the liquid surface of the sample to be mixed is 2, and the number of first sub-electrodes activated below the liquid surface of the sample to be mixed is 2, which can make the sample to be mixed roll more efficiently and avoid melting the cup.
[0159] It is worth mentioning that the number of first sub-electrodes that are simultaneously activated above and below the liquid surface of the sample to be mixed can also be other numbers, as long as the second preset number is greater than or equal to the first preset number, and the ratio of the first preset number to the second preset number is 1:1, 1:2, 1:3, or 2:3. Other combinations of the second preset number and the first preset number are not described in detail in this embodiment.
[0160] It should be understood that the width and spacing of the first working portion of the first sub-electrode of the piezoelectric vibrator are related to the volume of the sample to be mixed and the liquid level. In one embodiment, the volume of the sample to be mixed is 50-300 μL, and the width of the first working portion of each first sub-electrode is 0.5 mm-2 mm, preferably 1 mm. The spacing between two adjacent first sub-electrodes is 0.1 mm-0.5 mm. Since the reaction volume of the detection item is between 50-300 μL and the variation gradient is between 5-30 μL, the liquid level of the sample to be mixed changes very little. To match the optimal combination of electrodes for mixing the liquid, the height of the working area electrodes is between 0.5-2 mm, preferably 1 mm, and the spacing is between 0.1-0.5 mm. The width of the second electrode on the second side of the piezoelectric vibrator is 4-6 mm. The width of the second electrode is greater than the width of the reaction container (3.6 mm), so that the radiation width of the ultrasonic wave is greater than the width of the container, thereby better mixing the liquid.
[0161] In one embodiment, the first connection portion of the first electrode is connected to the output terminal of the driving power supply. A waterproof layer is provided on the second surface of the piezoelectric vibrator to provide good waterproofing; for example, this waterproof layer can be a waterproof membrane or a waterproof coating.
[0162] The drive power supply outputs an electrical signal at the same frequency as the piezoelectric vibrator, causing the piezoelectric vibrator to resonate and radiate acoustic energy outward. Based on the detailed detection items transmitted by the host computer, the slave computer can select the working electrode of the piezoelectric vibrator according to the volume of the sample to be mixed. The working electrode can be a combination of electrodes working simultaneously, or a single electrode working.
[0163] 1. The piezoelectric vibrator vibrates in the thickness direction. The thickness of the vibrator is designed according to the resonant frequency. The relationship is fs = Nt / t, where fs is the resonant frequency of the vibrator, Nt is the frequency constant of the vibrator, and t is the thickness of the vibrator. In this embodiment, the resonant frequency is 1.6MHz. In this embodiment, the frequency of the piezoelectric vibrator is between 1MHz and 2MHz, which can drive the liquid to form a rotating flow.
[0164] 2. The first electrode of the piezoelectric vibrator adopts an array structure, which can follow the volume change of the reaction liquid and select the combination of first sub-electrodes to work to achieve the best mixing effect. For example, the total volume of Project A is 180 microliters and the total volume of Project B is 160 microliters. At this time, the liquid surface positions of the reaction liquids in the two projects are different. Through the relay control of the drive module, different first sub-electrodes of the piezoelectric vibrator can be selected to work, so that the ultrasonic waves are incident on the sample to be mixed along the gas-liquid interface to form a rotating flow.
[0165] 3. The back of the piezoelectric vibrator is in contact with the sound transmission medium, which is a liquid. The back of the vibrator has a waterproof layer. This waterproof layer can be a platinum sheet or a waterproof membrane, such as a paraffin membrane. To minimize the impact of the waterproof layer on the piezoelectric vibrator's impedance, the thickness of the waterproof layer is less than 0.05 mm. The back electrode of the piezoelectric vibrator is connected to the negative terminal of the drive power supply and is in an "L" shape. The entire back electrode extends from the side to the front of the piezoelectric vibrator, as shown in the lower left square area in the front view. The sealing unit seals the front of the piezoelectric vibrator with a sealing ring, and the leads of the drive power supply are connected to the positive and negative electrodes of the piezoelectric vibrator.
[0166] To reduce the loss of ultrasound during transmission, in one embodiment, the acoustic impedance of the sound wave transmission medium is a first acoustic impedance, the acoustic impedance of the sidewall of the reaction vessel is a second acoustic impedance, and the acoustic impedance of the sample to be mixed is a third acoustic impedance, wherein the proximity between each pair of the first acoustic impedance, the second acoustic impedance, and the third acoustic impedance is greater than 70%.
[0167] Specifically, acoustic impedance refers to the resistance that a sound wave must overcome to propagate through a medium. In this embodiment, a similarity of more than 70% between each of the first, second, and third acoustic impedances refers to the degree of similarity between their values. It is worth noting that the greater the similarity, the closer the two acoustic impedances are. A similarity of 100% indicates that the two acoustic impedances are equal; for example, two media of the same material have a similarity of 100%. The smaller the similarity, the greater the difference between the two acoustic impedances. It should be understood that sound waves experience minimal loss when propagating within the same medium, while loss is greater when propagating from two media with very low similarity. Therefore, two media with greater similarity in acoustic impedance have lower losses.
[0168] In this embodiment, the differences between each pair of the first acoustic impedance, the second acoustic impedance, and the third acoustic impedance are small. For example, the similarity between the first and second acoustic impedances is greater than 70%, the similarity between the first and third acoustic impedances is greater than 70%, and the similarity between the second and third acoustic impedances is greater than 70%. Because the similarity between each pair of the first, second, and third acoustic impedances is greater than 70%, the sound wave transmission loss between the sound wave transmission medium and the sidewall of the reaction vessel, and between the sidewall of the reaction vessel and the sample to be mixed, is small. This effectively reduces the energy of the ultrasonic waves transmitted to the sample to be mixed, thereby improving the mixing efficiency.
[0169] To further improve the ultrasonic wave incident on the sample to be mixed and form a rotating flow on the liquid surface of the sample, in one embodiment, the sidewall thickness of the reaction vessel, the wave number of the reaction vessel, the acoustic impedance of the sound wave transmission medium, the acoustic impedance of the sidewall of the reaction vessel, and the acoustic impedance of the sample to be mixed are obtained. The acoustic intensity of the ultrasonic wave generated by the piezoelectric vibrator is determined based on the sidewall thickness of the reaction vessel, the wave number of the reaction vessel, the acoustic impedance of the sound wave transmission medium, the acoustic impedance of the sidewall of the reaction vessel, and the acoustic impedance of the sample to be mixed. A preset power threshold is determined based on the acoustic intensity of the ultrasonic wave generated by the piezoelectric vibrator.
[0170] It should be understood that in order for ultrasonic waves to be incident on the sample to be mixed and form a rotating flow on the liquid surface of the sample, the acoustic power of the incident sound waves must reach or exceed a preset power threshold. This preset power threshold is related to the thickness of the sidewall of the reaction vessel, the material (acoustic impedance), the volume of the liquid, etc. The acoustic power can be adjusted by adjusting the number of electrodes connected, adjusting the amplitude of the driving voltage, or changing the sweep frequency range. If the incident acoustic power is greater than the preset power threshold, the sample to be mixed can form a very obvious rotating flow to mix the liquid.
[0171] Specifically, the sound power W and the sound intensity I satisfy the following calculation formula:
[0172] W = I·S (1)
[0173] Where S is the area through which the sound wave passes perpendicularly, and the unit is m2. Therefore, the ratio of the sound power of the sound wave emitted by the piezoelectric oscillator to the sound wave incident on the liquid to be mixed in the reaction vessel can be expressed as the ratio of their sound intensities.
[0174] The acoustic intensity of the ultrasonic wave generated by the piezoelectric vibrator is the acoustic intensity of the emitted sound wave, and the acoustic intensity of the sound wave incident on the liquid to be mixed is the acoustic intensity of the incident sound wave. In one embodiment, the acoustic intensity of the emitted sound wave is calculated based on the sidewall thickness of the reaction vessel, the circular wave number of the reaction vessel, the acoustic impedance of the sound wave transmission medium, the acoustic impedance of the sidewall of the reaction vessel, and the acoustic impedance of the sample to be mixed. A preset power threshold is calculated based on the acoustic intensity of the emitted sound wave and the calculation formula (1).
[0175] The sound intensity of the incident sound wave can be expressed by formula (2):
[0176]
[0177] Where L is the sidewall thickness of the reaction vessel in meters (m); I1 is the acoustic intensity of the emitted sound wave in W / m²; I3 is the acoustic intensity of the incident sound wave in W / m²; k2 is the circular wave number of the reaction vessel; Z1, Z2, and Z3 are the acoustic impedances of the sound wave transmission medium, the reaction vessel, and the sample to be mixed, respectively, i.e., Z1 is the first acoustic impedance, Z2 is the second acoustic impedance, and Z3 is the third acoustic impedance, in Pa*s / m.
[0178] Therefore, in this embodiment, the acoustic intensity of the emitted sound wave can be calculated based on the thickness of the sidewall of the reaction vessel, the material of the reaction vessel, the sound wave transmission medium, and the material of the sample to be mixed. Based on this, a preset power threshold can be calculated to determine the acoustic power required by the piezoelectric vibrator, thereby meeting the requirement of forming a rotating flow on the liquid surface of the sample to be mixed.
[0179] The technical features of the above embodiments can be combined in any way. For the sake of brevity, not all possible combinations of the technical features in the above embodiments are described. However, as long as there is no contradiction in the combination of these technical features, they should be considered to be within the scope of this specification.
[0180] The embodiments described above are merely illustrative of several implementation methods of this application, and while the descriptions are relatively specific and detailed, they should not be construed as limiting the scope of the invention patent. It should be noted that those skilled in the art can make various modifications and improvements without departing from the concept of this application, and these all fall within the protection scope of this application. Therefore, the protection scope of this patent application should be determined by the appended claims.
Claims
1. A sample analyzer, characterized in that, include: Sample collection device, reagent supply device, sample reaction device, reaction container, optical measurement device, and sample mixing device; The sample collection device is used to collect samples and transport them to the sample reaction device; The reagent supply device is used to collect reagents from the reagent container and deliver the reagents to the sample reaction device; The sample reaction apparatus is used to contain the sample to be mixed and the reagents and to provide the environment required for the reaction. The reaction vessel is housed within the sample reaction apparatus and is used to hold the sample to be mixed and the reagents. The sample mixing device is used to thoroughly mix the sample and reagents in the reaction vessel; The optical measuring device is used to measure the light signal generated by the sample to obtain light information; The sample mixing device includes a driving module and a piezoelectric vibrator. The driving module and the piezoelectric vibrator are electrically connected. The piezoelectric vibrator generates ultrasonic waves under the drive of the driving module. The ultrasonic waves are emitted towards the side wall of the reaction container containing the sample to be mixed through the sound wave transmission medium. The piezoelectric vibrator is used to emit ultrasonic waves within a preset range in a direction perpendicular to the liquid surface of the sample to be mixed; the piezoelectric vibrator is used, under the drive of the drive module, to generate ultrasonic waves with a propagation direction parallel to the liquid surface of the sample to be mixed; the highest point of the ultrasonic waves generated by the piezoelectric vibrator in the direction perpendicular to the liquid surface is located at a first distance above the liquid surface, and the lowest point of the ultrasonic waves generated by the piezoelectric vibrator in the direction perpendicular to the liquid surface is located at a second distance below the liquid surface, the second distance being greater than or equal to the first distance; the ultrasonic waves generated by the piezoelectric vibrator are longitudinal waves with the same propagation direction and vibration direction; wherein, emitting ultrasonic waves at the first distance is used to give the sample to be mixed, excited by ultrasonic waves at the second distance, a horizontal acceleration; the ratio of the first distance to the second distance enables the sample to be mixed to achieve horizontal movement and vertical tumbling; Wherein, the ratio of the acoustic impedance of the acoustic wave transmission medium to the acoustic impedance of the sidewall of the reaction vessel is 0.75~1, or the ratio of the acoustic impedance of the sidewall of the reaction vessel to the acoustic impedance of the acoustic wave transmission medium is 0.75~1.
2. The sample analyzer according to claim 1, characterized in that, The ratio of the acoustic impedance of the sound wave transmission medium to the acoustic impedance of the sidewall of the reaction vessel is 0.
75.
3. The sample analyzer according to claim 1, characterized in that, The ratio of the first distance to the second distance is 1:1, 1:2, 1:3, or 2:
3.
4. The sample analyzer according to claim 1, characterized in that, The piezoelectric vibrator is used to generate ultrasonic waves with a frequency of 1MHz-2MHz under the drive of the drive module.
5. The sample analyzer according to claim 4, characterized in that, The piezoelectric vibrator is used to generate ultrasonic waves with a frequency of 1.6 MHz under the drive of the drive module.
6. The sample analyzer according to claim 1, characterized in that, The ultrasonic waves generated by the piezoelectric vibrator are longitudinal waves.
7. The sample analyzer according to any one of claims 1-6, characterized in that, The drive module includes a control unit, a frequency generation unit, a voltage amplification unit, and a power amplification unit. The control unit is electrically connected to the frequency generation unit and the voltage amplification unit. The frequency generation unit is electrically connected to the piezoelectric vibrator through the voltage amplification unit and the power amplification unit. The control unit is used to control the frequency generation unit to generate a resonant signal; The frequency generation unit is used to generate a resonant signal, which in turn drives the piezoelectric vibrator to generate ultrasonic waves. The voltage amplification unit is used to amplify the amplitude of the resonant signal generated by the frequency generation unit; The power amplification unit is used to amplify the signal energy of the voltage amplification unit.
8. The sample analyzer according to claim 7, characterized in that, The frequency generation unit is also used to generate a sweep frequency signal on the resonant signal, wherein the frequency of the resonant signal is fs, and the sweep frequency range of the sweep frequency signal is fs±100KHz.
9. The sample analyzer according to claim 8, characterized in that, The frequency sweep period is 0-5ms, and the frequency sweep range is fs±40KHz.
10. The sample analyzer according to claim 9, characterized in that, The frequency sweep period is 1.25ms.
11. The sample analyzer according to claim 7, characterized in that, The duty cycle of the resonant signal is 0-100%, and the duty cycle period is 10-100ms.
12. The sample analyzer according to claim 11, characterized in that, The resonant signal has a duty cycle of 30% and a duty cycle period of 50ms.
13. The sample analyzer according to claim 7, characterized in that, The power amplification unit amplifies the signal energy of the voltage amplification unit to a signal amplitude of 20-400Vp-p.
14. The sample analyzer according to claim 13, characterized in that, The power amplification unit amplifies the signal energy of the voltage amplification unit to a signal amplitude of 50-240Vp-p.
15. The sample analyzer according to claim 14, characterized in that, The power amplification unit amplifies the signal energy of the voltage amplification unit to a signal amplitude of 140Vp-p.
16. The sample analyzer according to claim 7, characterized in that, The drive module further includes a current feedback unit, which is electrically connected to the piezoelectric vibrator through the power amplifier unit. The current feedback unit is used to collect the current of the piezoelectric vibrator and feed the current of the piezoelectric vibrator back to the control unit. The control unit is used to determine whether the current of the piezoelectric vibrator is within a preset current range of a preset current value.
17. The sample analyzer according to claim 14, characterized in that, The preset current range is ±30%.
18. The sample analyzer according to any one of claims 1-6, characterized in that, The piezoelectric oscillator includes an oscillator body and a first electrode; the oscillator body has a first surface and a second surface arranged opposite to each other; the first electrode includes a plurality of first sub-electrodes, each of which is equidistantly arranged on the first surface of the oscillator body along a first direction; The first direction is the vertical direction. The driving module is used to drive the piezoelectric vibrator to operate a first preset number of first sub-electrodes located on the liquid surface of the sample to be mixed and a second preset number of first sub-electrodes located below the liquid surface of the sample to be mixed, so as to generate the ultrasonic waves in a preset range in a direction perpendicular to the liquid surface of the sample to be mixed. The ratio of the first preset number to the second preset number is 1:1 or 1:2 or 1:3 or 2:
3.
19. The sample analyzer according to claim 18, characterized in that, The second preset quantity is 3, and the first preset quantity is 1; or The second preset quantity is 2, and the first preset quantity is 2.