CN111495455A - Non-contact ultrasonic liquid transfer device and method - Google Patents

Abstract

The invention discloses a non-contact ultrasonic liquid pipetting device, comprising an ultrasonic transducer unit, a source carrier liquid platform and a target liquid carrier platform. The ultrasonic transducer unit can generate a focused sound field under the action of an ultrasonic excitation system, without using consumables for the tip of the pipette. The droplets can be transferred from the source carrier liquid platform to the target carrier liquid platform precisely and quickly. The invention also discloses a liquid pipetting method. By controlling the relative position of the ultrasonic transducer unit and the source carrier liquid platform and the working state and parameters of the ultrasonic excitation system, the action point of the focused sound field can be precisely positioned to the liquid pipetting surface. , and precisely adjust the volume of droplets in a single pipet. By using a high-frequency focused ultrasonic transducer, the pipetting accuracy of picoliters can be achieved, and by using a large-sized focused ultrasonic transducer, the pipetting accuracy can be further adjusted from picoliters to microliters; The ultrasonic coupling unit between the ultrasonic transducer unit and the source carrier liquid platform can maximize the transmission of energy and achieve heat dissipation.

Description

Non-contact ultrasonic pipetting device and method

technical field

The invention relates to the field of synthetic biology experiments, in particular to a non-contact ultrasonic pipetting device and method.

Background technique

In today's world, people are facing increasingly severe challenges such as disease, environment and energy. Synthetic biology is known as one of the three major disruptive technologies in the world to meet the challenges. The research goal of synthetic biology is to use the concept of engineering to design, transform and even re-synthesize organisms to create artificial life bodies with non-natural functions.

At present, in the process of synthetic biology experiments, life verification experiments are carried out based on a large number of biological experiments. Therefore, a large number of micro pipetting operations are required for the deployment and processing of experiments. Pipetting is one of the most common operational tasks in synthetic biology laboratories. . Choosing the right pipette is a critical step in the precise execution of your experiments.

The most widely used method in the industry is to use a pipette, which is a general biological and chemical experimental device that can create a partial vacuum in the container above the liquid surface and selectively adjust the vacuum volume to draw or discharge the liquid. . Different accuracy and precision can be achieved by designing a variety of pipettes. The types of pipettes include from a simple piece of glass pipette to complex adjustable or electronically controlled pipettes. However, the measurement accuracy varies with the type. And the difference is huge. At the same time, because the pipette is a contact pipetting method, during the pipetting process, the sample sticks to the pipette tip, resulting in an inaccurate amount of liquid transferred, which is prone to false negative results. In addition, since the tip of the pipette is a disposable consumable, in order to avoid cross-infection, special treatment or replacement is required after each use, so a large amount of consumables will be required to support the experiment, and the cost of large-scale use is relatively expensive.

Although the existing non-contact pipetting technology based on electromagnetic control can realize non-contact pipetting between the pipetting needle and the target reaction well, the pipetting liquid is still in contact with the pipetting needle, which limits the types of pipetting liquids. The practical application of this technology is limited. Therefore, non-contact micropipette technology is a particularly important key technology in the field of biology.

SUMMARY OF THE INVENTION

In view of the deficiencies in the prior art, the present invention provides a non-contact ultrasonic pipetting device and method, which adopts a focused sound field to realize non-contact pipetting, which not only avoids the expensive experiment cost and inconvenience of pipetting caused by the use of pipette tip consumables. Accurate problem, no need to contact the pipetting liquid and also not limit the types of pipetting liquids, thus expanding the application range of the pipetting method.

In order to achieve the above-mentioned purpose, the present invention adopts the following technical scheme:

A non-contact ultrasonic pipetting device, comprising an ultrasonic pipetting module, the ultrasonic pipetting module comprising an ultrasonic transducer unit, a source carrier liquid platform and a target liquid carrier platform; the ultrasonic transducer unit is used to move toward the source The carrier liquid platform emits ultrasonic waves to generate a focused sound field, and moves relative to the source carrier liquid platform to change the distance from the source carrier liquid platform liquid surface, and when the ultrasonic echo amplitude reaches a specific value, the target volume The droplets are transferred from the source carrier liquid platform to the target carrier liquid platform.

As one embodiment, the non-contact ultrasonic pipetting device further includes a moving module and a control module, the moving module is used to adjust the relative position of the ultrasonic transducer unit and the source carrier liquid platform; the The control module is used to change the distance between the ultrasonic transducer unit and the liquid level of the source carrier liquid platform according to the amplitude of the ultrasonic echo signal when the ultrasonic transducer unit is facing the source carrier liquid platform until the ultrasonic wave When the echo amplitude reaches a specific value, the ultrasonic signal parameters of the ultrasonic waves emitted by the ultrasonic transducer unit are adjusted to adjust the volume of the liquid droplet in a single pipetting to the target volume.

As one embodiment, the ultrasonic transducer unit is an electronic phased array focusing transducer, and the control module also adjusts the parameters of the electronic phased array focusing transducer to make the electronic phased array focusing transducer The focused beam synthesized by the energy generator moves rapidly on the source carrier liquid platform to adjust the position of the focused focus on the liquid surface.

As one embodiment, the ultrasonic transducer unit is a large-sized high-frequency focused ultrasonic transducer. Here, "large-sized" means that the diameter of the ultrasonic transducer unit is greater than or equal to 5 mm, and "high-frequency" is It means that the frequency of the ultrasonic transducer unit is greater than 1MHZ, the pipetting accuracy of the ultrasonic pipetting device is as high as picoliter, and the pipetting accuracy is arbitrarily adjustable within the range from picoliter to microliter.

As one embodiment, the ultrasonic transducer unit is composed of one or more ultrasonic transducers, and/or the operating frequency of the ultrasonic transducer unit is one or more.

As one of the embodiments, the ultrasonic transducer unit is a single array element transducer, a linear array transducer, an area array transducer or a ring array transducer; and/or, the ultrasonic transducer unit includes When there are multiple sub-transducers, the arrangement shape of the sub-transducers is polygon, circle or ellipse.

As one embodiment, the ultrasonic pipetting module further includes an ultrasonic coupling unit for propagating ultrasonic energy, the ultrasonic coupling unit includes a casing and an acoustic couplant, and the acoustic couplant is filled between the casing and the The space enclosed by the ultrasonic transducer unit is used for contacting with the source carrier liquid platform.

As one of the embodiments, the housing includes an inner cylinder and an outer cylinder, the tops of the inner cylinder and the outer cylinder face the source carrier liquid platform, and the ultrasonic transducer unit is fixed on the The top end of the inner cylinder is closed by the top end of the inner cylinder; the inner cylinder is arranged in the outer cylinder and can be selectively moved closer to or away from the outer cylinder relative to the axial movement of the outer cylinder. The source carrier liquid platform, and the acoustic couplant is filled between the outer cylinder and the top of the inner cylinder.

As one embodiment, the ultrasonic coupling unit further includes a peristaltic pump and a cooling cavity communicating with the top of the outer cylinder, the acoustic couplant is also filled in the cooling cavity, and the peristaltic pump drives the cooling cavity. The acoustic couplant circulates in the top end of the outer cylinder and in the cooling cavity.

Another object of the present invention is to provide a non-contact ultrasonic pipetting method, comprising:

Ranging modes, including:

The ultrasonic transducer unit emits ultrasonic waves toward the source carrier liquid platform to generate a focused sound field;

Change the distance between the ultrasonic transducer unit and the liquid surface of the source carrier liquid platform according to the amplitude of the ultrasonic echo signal, until the ultrasonic echo amplitude reaches a specific value;

Pipetting modes, including:

When the ultrasonic echo amplitude reaches a specific value, adjust the parameters of the ultrasonic excitation waveform to adjust the volume of the pipetting drop;

The power of the ultrasonic transducer unit is increased to transfer droplets from the source carrier liquid platform to the target carrier liquid platform.

The non-contact ultrasonic pipetting device of the present invention can realize the liquid movement without contact by using the ultrasonic transducer unit. When the ultrasonic echo amplitude reaches a specific value, a focused sound field is generated, and the droplet can be accurately and quickly transferred from the source carrier liquid platform to the target carrier liquid platform without using the consumables of the pipette tip to generate the target volume of liquid. The liquid addition method is not only direct and precise and excellent repeatability.

In addition, by controlling the relative position of the ultrasonic transducer unit and the source carrier liquid platform and the working state and parameters of the ultrasonic excitation system, the action point of the focused sound field can be precisely positioned to the liquid pipetting surface, and the single liquid pipetting can be precisely adjusted drop the volume to the target volume. By using high-frequency focused ultrasound transducers, the pipetting accuracy of picoliters can be achieved. On this basis, by using large-sized focused ultrasound transducers, the pipetting accuracy can be further achieved from picoliters to microliters. Adjustable; with the help of the ultrasonic coupling unit between the ultrasonic transducer unit and the source carrier liquid platform, the maximum energy transmission and heat dissipation can be achieved.

Description of drawings

1 is a structural block diagram of a non-contact ultrasonic pipetting device according to an embodiment of the present invention;

2 is a block diagram of a non-contact ultrasonic pipetting method according to an embodiment of the present invention;

3 is a schematic diagram of a workflow of a non-contact ultrasonic pipetting device according to an embodiment of the present invention;

4 is a schematic diagram of a pipetting principle of an ultrasonic transducer unit according to an embodiment of the present invention;

5 is a schematic diagram of a stacked structure of an ultrasonic transducer unit according to an embodiment of the present invention;

6 is a partial structural schematic diagram of a non-contact ultrasonic pipetting device according to an embodiment of the present invention;

The labels in the figure are explained as follows:

1-ultrasonic excitation system; 100-ultrasonic pipetting module; 2-ultrasonic transducer unit; 21-backing; 22-piezoelectric layer; 23-matching layer; 3-ultrasonic coupling unit; 31-space; 32-cooling cavity ;4-source carrier liquid platform;5-target carrier liquid platform;6-moving module;61-loading liquid moving module;62-transducer moving module;7-control module;9-inner cylinder;10-outer cylinder body; 11 - sealing ring.

Detailed ways

In order to make the objectives, technical solutions and advantages of the present invention clearer, the present invention will be further described in detail below with reference to the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are only used to explain the present invention, but not to limit the present invention.

Referring to FIG. 1, an embodiment of the present invention provides a non-contact ultrasonic pipetting device, which mainly includes an ultrasonic pipetting module 100. The ultrasonic pipetting module 100 may specifically include an ultrasonic excitation system 1, an ultrasonic transducer unit 2, and an ultrasonic coupling unit. 3 and the source carrier liquid platform 4 and the target carrier liquid platform 5 sequentially arranged above the ultrasonic transducer unit 2 from bottom to top, the ultrasonic excitation system 1 is connected to the ultrasonic transducer unit 2, and can be used to drive the ultrasonic transducer unit 2 to emit ultrasonic waves to generate Focus the sound field to realize the ultrasonic radiation force effect on the pipetting liquid surface at a predetermined position on the source carrier liquid platform 4. The source carrier liquid platform 4 and the target liquid carrier platform 5 are set facing each other, and the source carrier liquid platform 4 has a pipetting liquid surface. , under the action of the focused acoustic field, the droplets can be transferred from the source carrier liquid platform 4 to a specific position on the target carrier liquid platform 5 without contact. The source carrier liquid platform 4 and the target carrier liquid platform 5 can both be porous plate structures, and both have holes opened in an array. The target volume of droplets in the holes of the source carrier liquid platform 4 facing the ultrasonic transducer unit 2 are in Under the action of ultrasonic radiation force, it can be transferred to the target carrier liquid platform 5, thereby realizing pipetting.

The ultrasonic excitation system 1 includes an ultrasonic signal generator and a power amplifier, and the control module 7 can arbitrarily adjust the ultrasonic signal parameters (including ultrasonic frequency, ultrasonic energy, ultrasonic pulse length, ultrasonic pulse repetition frequency, etc.) of the ultrasonic excitation system 1. The signal parameter corresponds to the ultrasonic signal parameter of the ultrasonic wave sent by the ultrasonic transducer unit 2. By adjusting the ultrasonic signal parameter of the ultrasonic wave, the droplet volume of a single pipetting can be adjusted, thereby realizing high-precision pipetting. The ultrasonic coupling unit 3 is configured to be disposed between the ultrasonic transducer unit 2 and the source carrier liquid platform 4 to ensure that the ultrasonic energy emitted by the ultrasonic transducer unit 2 is better transmitted to the source carrier liquid platform 4 .

It can be understood that, in other embodiments, the ultrasonic excitation system 1 may not be included in the ultrasonic pipetting device, but is a separate structure, which can be assembled into the ultrasonic pipetting device and can be transduced with ultrasonic waves when needed. Unit 2 is connected.

In addition to the ultrasonic pipetting module 100, the non-contact ultrasonic pipetting device can also include a moving module 6 and a control module 7. As the control center of the entire pipetting device, the control module 7 can control the ultrasonic excitation system 1 and the ultrasonic transducer unit 2. , The working state and parameter modulation of the source carrier liquid platform 4, the target carrier liquid platform 5, the mobile module 6, etc., can be fully controlled.

The moving module 6 can be relatively fixed to at least one of the ultrasonic transducer unit 2 and the source carrier liquid platform 4. By adjusting the relative positions of the ultrasonic transducer unit 2 and the source carrier liquid platform 4, the focused sound field of the ultrasonic transducer unit 2 can be adjusted. The action point is positioned to the pipetting liquid level at the predetermined position of the source carrier liquid platform 4, so as to facilitate the next pipetting action.

2 to 4 , the working modes of the non-contact ultrasonic pipetting device of this embodiment include a ranging mode S01 and a pipetting mode S02. In the ranging mode S01, the power of the ultrasonic transducer unit 2 is small, The droplets will not be ejected, only the focusing of the focused sound field on the liquid surface is achieved; in the pipetting mode S02, the power of the ultrasonic transducer unit 2 can be increased by adjusting the parameters of the ultrasonic excitation system 1 through the control module 7, and the droplets can be removed from the liquid. Liquid level out.

The non-contact ultrasonic pipetting method of this embodiment will be specifically described below:

Initially, the positions of the ultrasonic transducer unit 2 and the source carrier liquid platform 4 in the horizontal direction and the vertical direction are not aligned.

First, as shown in step a in FIG. 3 , the control module 7 works by controlling the moving module 6 to adjust the distance between the ultrasonic transducer unit 2 and the source carrier liquid platform 4 to make them approach each other. Finally, the ultrasonic transducer unit 2 moves to the source carrier liquid platform 4 . Directly below the specific pipetting level of the carrier platform 4 .

Subsequently, as shown in step b in FIG. 3 , in the ranging mode S01, the control module 7 controls the ultrasonic transducer unit 2 to work to locate the longitudinal distance between the ultrasonic transducer unit 2 and the liquid pipetting surface. Move the ultrasonic transducer unit 2 longitudinally (for example, the source carrier liquid platform 4 can also be moved) at this distance, when the ultrasonic echo amplitude reaches a certain value, it means that the action point of the focused sound field emitted by the ultrasonic transducer unit 2 is positioned to a predetermined position on the pipetting surface. Here, the "specific value" represents a specific value, and does not necessarily refer to the absolute maximum value of the echo amplitude. In the actual process, the specific value can be adjusted according to the actual situation, that is, the "specific value" can be absolute The maximum value can also be a value close to the absolute maximum value, such as 80% of the absolute maximum value. Specifically, in the ranging mode S01, the ultrasonic transducer unit 2 sends out ultrasonic waves towards the source carrier liquid platform 4 above, and receives ultrasonic echoes in real time, and the control module 7 adjusts the distance between the ultrasonic transducer unit 2 and the source carrier liquid platform 4 When the ultrasonic echo amplitude reaches the specific value, it is judged that the action point of the focused sound field has been positioned on the liquid pipetting surface at the predetermined position. In this way, the work corresponding to the ranging mode S01 is completed, and the liquid droplet can be switched to the pipetting mode S02 at any time. Figure 4 is a schematic diagram of the state of pipetting after the focused sound field is positioned to the pipetting liquid surface.

Next, the control module 7 switches the working state of the pipetting device to the pipetting mode S02 by increasing the power of the ultrasonic transducer unit 2 , as shown in step c in FIG. 3 , the control module 7 first adjusts the ultrasonic excitation of the ultrasonic excitation system 1 The parameters of the signal adjust the volume of the droplet in a single pipetting to the target volume. Then, the droplet is ejected from the source carrier liquid platform 4 under the action of the focused acoustic field (step d in Figure 3). Through this series of steps, This ensures a high-precision pipetting process.

Here, the process of adjusting the volume of a single pipetting droplet can be specifically realized by adjusting the parameters of the excitation waveform of the ultrasonic excitation system 1 , such as voltage amplitude, number of cycles, and number of cycles.

Since the ultrasonic transducer unit 2 is used as the core pipetting part of the ultrasonic pipetting module 100 in this embodiment, in the actual pipetting process, only the ultrasonic transducer unit 2 needs to be moved to the predetermined position of the source carrier liquid platform 4 to achieve alignment After that, the ultrasonic pipetting module 100 can be used to generate a focused sound field to realize the non-contact pipetting process, and the sample can be added from a source position of the source carrier liquid platform 4 to a target of the target carrier liquid platform 5 without using the pipette tip consumables. Position, which not only reduces the replacement of consumables, reduces the cost, but also avoids the sample sticking to the pipette tip, and realizes the precise pipetting process. In addition, since this embodiment adopts the method of first aligning the ultrasonic transducer unit and the source carrier liquid platform, and then adjusting the focus of the ultrasonic transducer unit to the liquid level of the liquid transfer, the volume of a single pipetting droplet can also be adjusted as required before liquid injection. , so that the final pipetting accuracy is guaranteed.

This embodiment shows a situation in which the moving module 6 is fixed to the ultrasonic transducer unit 2 and the source carrier liquid platform 4 at the same time, and can move both horizontally and vertically independently. Specifically, the moving module 6 includes a loading liquid moving module 61 and a transducer moving module 62. The loading liquid moving module 61 can drive the target carrier liquid platform 5 and the source carrier liquid platform 4 to move and transport in the pipetting device. The moving module 62 can drive the ultrasonic transducer unit 2 to move at any position in the pipetting device, and the moving accuracy of the moving module 6 is controlled within 1 μm. Under the control of the control module 7, the moving module 6 can work to adjust the relative position of the ultrasonic transducer unit 2 and the source carrier liquid platform 4 accordingly. For example, only the ultrasonic transducer unit 2 can be moved, or only the source carrier liquid can be moved. The platform 4, or move the ultrasonic transducer unit 2 and the source carrier liquid platform 4 at the same time, so that the ultrasonic transducer unit 2 and the source carrier liquid platform 4 approach and move away from each other as required.

It can be understood that, in other embodiments, the moving module 6 may also include only one of the loading liquid moving module 61 and the transducer moving module 62, which can also play a similar role in adjusting the ultrasonic transducer unit and the source carrier liquid platform. The effect of the relative position is not limited here.

In order to better ensure the pipetting accuracy, the ultrasonic transducer unit 2 of the non-contact ultrasonic pipetting device in this embodiment is a large-sized high-frequency focused ultrasonic transducer. Here, "large size" refers to the ultrasonic transducer unit 2. The diameter is greater than or equal to 5mm, "high frequency" means that the frequency of the ultrasonic transducer unit 2 is greater than 1MHZ. Further, the frequency range of the ultrasonic transducer unit 2 can be 1MHz to 1GHz, and the bandwidth is more than 50%. Such a large-sized, high-frequency focused ultrasonic transducer not only has a smaller focus size, but also has a larger size. Output acoustic radiation force, among which, the high-frequency characteristics of the ultrasonic transducer ensure that the pipetting accuracy can reach up to picoliters, and the high-bandwidth characteristics of the ultrasonic transducer can also ensure that the transducer has a relatively high frequency in a wide frequency range. The high output sound radiation force and the satisfaction of the two at the same time realize any adjustment of the pipetting accuracy from picoliter to microliter within a large range. By precisely controlling the ultrasonic acoustic parameters, the pipetting device can modulate the acoustic energy in a wider range, and intelligently select the size of each sample droplet according to the user's experimental needs.

It should be noted that the ultrasonic transducer unit 2 may work with one focused ultrasound transducer, or may work with multiple focused ultrasound transducers; it may work with a single frequency or with multiple frequencies. According to the focusing method of the ultrasonic transducer, the ultrasonic transducer is a physical focusing transducer or an electronic phased array focusing transducer, and the focusing method of the physical focusing transducer is acoustic lens focusing, self-focusing and other focusing modes such as acoustic Ultrasonic transducers with various focusing methods such as superstructure focusing, when the ultrasonic transducer uses an electronic phased array focusing transducer, the electronic phased array focusing method can pass the control module 7 to the electronic phased array focusing transducer. By adjusting the parameters of the ultrasonic transducer, the focused beam synthesized by the electronic phased array focusing transducer can quickly move on the source carrier liquid platform without moving or rotating the ultrasonic transducer unit to adjust the position of its focusing focus on the liquid surface. Accurate and fast focus positioning, and better automatic control. According to the type of ultrasonic transducer, the ultrasonic transducer unit 2 includes but is not limited to piezoelectric ultrasonic transducer, capacitive micromachined ultrasonic transducer (cMUT), piezoelectric micromachined ultrasonic transducer (pMUT) and other types of ultrasonic transducers. Ultrasound transducer.

The ultrasonic transducer unit 2 may be a single-array element transducer, a linear array transducer, an area array transducer or a ring array transducer. When the ultrasonic transducer unit 2 includes multiple sub-transducers, the sub-transducers are The arrangement shape of the energy devices can be square, circle, ellipse, etc., but is not limited thereto.

As shown in FIG. 5 , it is a schematic structural diagram of a piezoelectric ultrasonic transducer. The ultrasonic transducer unit 2 mainly includes a backing 21, a piezoelectric layer 22, and a matching layer 23. The outer surface of the matching layer 23 may also be provided with a protective layer (not shown). The piezoelectric layer 22 and the matching layer 23 are in order from bottom to top. It is arranged above the backing 21 . The matching layer 23 may include a one-layer or multi-layer structure.

The ultrasonic coupling unit 3 includes a casing (not shown) and an acoustic couplant (not shown). As shown in FIG. 1 and FIG. 6 , the casing and the ultrasonic transducer unit 2 enclose a space 31 that can be filled with the acoustic couplant. The agent is filled in the space 31 . When the ultrasonic coupling unit 3 is moved to an appropriate position below the source carrier liquid platform 4, the shell contacts the source carrier liquid platform 4, and the acoustic couplant in the space 31 is filled between the ultrasonic transducer unit 2 and the source carrier liquid platform 4, As the ultrasonic coupling medium between the ultrasonic transducer unit 2 and the source carrier liquid platform 4 , it can reduce the attenuation of acoustic wave energy during the propagation process. Unit 2 dissipates heat, serving multiple purposes. The sonic couplant can be water, oil, and similar flowable ultrasonic couplants.

As shown in FIG. 6 , the housing may specifically include an inner cylinder 9 and an outer cylinder 10 . The tops of the inner cylinder 9 and the outer cylinder 10 are facing the source carrier liquid platform 4 above, and the ultrasonic transducer unit 2 is fixed inside. The top end of the cylindrical body 9 closes the top end of the inner cylindrical body 9 . The top end face of the outer cylinder 10 is in contact with the source carrier liquid platform 4 , and the inner cylinder 9 is arranged in the outer cylinder 10 and can be selectively moved close to or away from the source carrier liquid platform relative to the axial movement of the outer cylinder 10 . 4. A space 31 for accommodating acoustic couplants is enclosed between the inner cylinder 9, the ultrasonic transducer unit 2, and the outer cylinder 10. When the ultrasonic transducer unit 2 is close to the source carrier liquid platform 4, the outer cylinder 10 contacts the source. When the carrier liquid platform 4 is used, the acoustic wave couplant is filled between the ultrasonic transducer unit 2 and the source carrier liquid platform 4 .

Here, the inner cylinder body 9 and the outer cylinder body 10 are combined in a threaded manner. Specifically, the outer peripheral surface of the inner cylinder body 9 is provided with an external thread, the inner peripheral surface of the outer cylinder body 10 is provided with an inner thread, and the inner cylinder body is provided with an inner thread. In the process of rotating relative to the outer cylinder 10, the inner cylinder 9 moves along the axial direction of the outer cylinder 10, so that the ultrasonic transducer unit can be precisely adjusted in the direction away from or away from the source carrier liquid platform 4 according to actual requirements 2. The distance from the pipetting liquid surface, so as to conveniently locate the action point of the focused sound field to the pipetting liquid surface.

Specifically, a through hole can be opened at the top of the inner cylinder 9, and the ultrasonic transducer unit 2 is inserted into the through hole from below and closed. 2 abuts on the inner surface of the stepped hole of the through hole.

In order to ensure the sealing effect of the acoustic wave couplant between the inner cylinder 9 and the outer cylinder 10 , the ultrasonic coupling unit 3 further includes a sealing ring 11 . The sealing ring 11 is sleeved on the outer peripheral surface of the inner cylinder 9 and is elastically compressed in the between the inner cylinder 9 and the outer cylinder 10 . Preferably, a concave annular groove is formed on the outer peripheral surface of the inner cylinder 9, and the sealing ring 11 is elastically compressed in the annular groove by the outer cylinder 10, so that the sealing ring 11 can be prevented from coming out. It can be understood that the number of the sealing rings 11 is not limited in this embodiment, and the number of the sealing rings 11 can be more.

As shown in FIG. 6 , the ultrasonic coupling unit 3 further includes a peristaltic pump (not shown) and a cooling cavity 32 that communicates with the space 31 . The acoustic couplant is not only filled in and out of the space 31 , but also in the cooling cavity 32 . The peristaltic pump drives the cooling cavity 32 . The acoustic couplant circulates in the space 31 and the cooling cavity 32 . The cooling cavity 32 is connected to both ends of the space 31 at the same time. Under the action of the peristaltic pump, the acoustic couplant flowing out of the space 31 flows into the cooling cavity 32 from the interface at one end, and flows from the other end of the space 31 after circulating heat through the cooling cavity 32. In this way, the circulating flow of the heat dissipation medium is realized, and the heat dissipation speed can be controlled by controlling the flow rate of the heat dissipation medium by the peristaltic pump. The acoustic couplant takes away the heat generated during the operation of the ultrasonic transducer unit 2, and flows in again after dissipating heat through the cooling cavity 32 to realize Fast cycle cooling.

The space 31 is formed at the top of the inner cylinder 9 and the outer cylinder 10. The interface between the cooling cavity 32 and the space 31 is preferably located on the wall of the outer cylinder 10 near the top, and the end of the ultrasonic transducer unit 2 protrudes from the inside. Outside the end face of the cylinder body 9, the acoustic couplant flowing through the two opposite sides of the top end of the outer cylinder body 10 can take away the heat generated during the operation of the ultrasonic transducer unit 2 in time, and the heat dissipation effect is good.

When the moving module 6 works to make the ultrasonic transducer unit 2 and the source carrier liquid platform 4 approach each other, the ultrasonic transducer unit 2 is directly facing the pipetting liquid surface of the source carrier liquid platform 4 above in the ranging mode and will focus the sound field. The action point is positioned on the liquid pipetting surface, and then, the control module 7 drives the ultrasonic transducer unit 2 to generate a focused sound field by adjusting the working state and parameters of the ultrasonic excitation system 1, and the focused sound field generated by the ultrasonic transducer unit 2 drives the droplets from the source The carrier liquid platform 4 is transferred to the target carrier liquid platform 5 . During this process, the control module 7 controls the speed of heat dissipation by controlling the parameters of the peristaltic pump to control the flow rate of the sonic couplant circulating in the space 31 and the cooling cavity 32 .

The non-contact ultrasonic pipetting device of the present invention can realize the liquid movement without contact by using the ultrasonic transducer unit. When a specific value is reached, a focused sound field is generated, and the liquid droplet can be accurately and quickly transferred from the source carrier liquid platform to the target liquid carrier platform without the use of pipette tip consumables to generate the target volume of liquid, and the liquid addition method is not only direct, accurate and repeatable Excellent. In addition, by controlling the relative position of the ultrasonic transducer unit and the source carrier liquid platform and the working state and parameters of the ultrasonic excitation system, the present invention can precisely locate the action point of the focused sound field to the liquid pipetting surface, and accurately adjust the single displacement. The volume of the liquid droplet. By using high-frequency focused ultrasound transducers, the pipetting accuracy of picoliters can be achieved. On this basis, by using large-sized focused ultrasound transducers, the pipetting accuracy can be further achieved from picoliters to microliters. Adjustable; with the help of the ultrasonic coupling unit between the ultrasonic transducer unit and the source carrier liquid platform, the maximum energy transmission and heat dissipation can be achieved.

The above are only specific embodiments of the present application. It should be pointed out that for those skilled in the art, without departing from the principles of the present application, several improvements and modifications can also be made. It should be regarded as the protection scope of this application.

Claims (10)

1. A non-contact ultrasonic pipetting device, characterized in that, comprising an ultrasonic pipetting module (100), the ultrasonic pipetting module (100) comprising an ultrasonic transducer unit (2), a source carrier liquid platform (4) and a target carrier liquid platform (5); the ultrasonic transducer unit (2) is configured to emit ultrasonic waves towards the source carrier liquid platform (4) to generate a focused sound field, and move relative to the source carrier liquid platform (4) And change the distance between the source carrier liquid platform (4) and the liquid level, and when the ultrasonic echo amplitude reaches a certain value, transfer the target volume of droplets from the source carrier liquid platform (4) to the source carrier liquid platform (4) Target carrier liquid platform (5). 2. The non-contact ultrasonic pipetting device according to claim 1, further comprising a moving module (6) and a control module (7), wherein the moving module (6) is used to adjust the ultrasonic transducer The relative position of the unit (2) and the source carrier liquid platform (4), the control module (7) is used for when the ultrasonic transducer unit (2) is directly opposite the source carrier liquid platform (4) , according to the ultrasonic echo signal amplitude, change the distance between the ultrasonic transducer unit (2) and the liquid level of the source carrier liquid platform (4) until the ultrasonic echo amplitude reaches a specific value, and then adjust the ultrasonic transducer unit (2) Ultrasonic signal parameters of the emitted ultrasonic waves to adjust the volume of the single pipetting droplet to the target volume. 3. The non-contact ultrasonic pipetting device according to claim 2, wherein the ultrasonic transducer unit (2) is an electronic phased array focusing transducer, and the control module (7) is also adjusted by adjusting The parameters of the electronic phased array focusing transducer make the focused beam synthesized by the electronic phased array focusing transducer move quickly on the source carrier liquid platform (4) to adjust the position of the focusing focus on the liquid surface. 4. The non-contact ultrasonic pipetting device according to claim 2, wherein the ultrasonic transducer unit (2) is a large-sized high-frequency focused ultrasonic transducer, and the ultrasonic transducer unit (2) Its diameter is greater than or equal to 5mm, and the frequency of the ultrasonic transducer unit (2) is greater than 1MHZ; the pipetting accuracy of the ultrasonic pipetting device is as high as picoliter, and the pipetting accuracy can be adjusted arbitrarily within the range from picoliter to microliter. 5. The non-contact ultrasonic pipetting device according to claim 2, wherein the ultrasonic transducer unit (2) is composed of one or more ultrasonic transducers, and/or the ultrasonic transducer Unit (2) operates at one or more frequencies. 6. The non-contact ultrasonic pipetting device according to claim 2, wherein the ultrasonic transducer unit (2) is a single-array element transducer, a linear array transducer, an area array transducer or a A ring array transducer; and/or, when the ultrasonic transducer unit (2) includes a plurality of sub-transducers, the arrangement shape of the sub-transducers is a polygon, a circle or an ellipse. 7. The non-contact ultrasonic pipetting device according to any one of claims 1 to 6, wherein the ultrasonic pipetting module (100) further comprises an ultrasonic coupling unit (3) for propagating ultrasonic energy, so The ultrasonic coupling unit (3) includes a casing and an acoustic wave couplant, and the acoustic wave couplant is filled in the space enclosed by the casing and the ultrasonic transducer unit (2), and is used for connecting with the source carrier liquid platform ( 4) Contact. 8. The non-contact ultrasonic pipetting device according to claim 7, wherein the housing comprises an inner cylinder (9) and an outer cylinder (10), the inner cylinder (9), the The top of the outer cylinder (10) is facing the source carrier liquid platform (4), and the ultrasonic transducer unit (2) is fixed on the top of the inner cylinder (9) to connect the inner cylinder (9). ) is closed at the top end; the inner cylinder (9) is provided in the outer cylinder (10) and can be selectively moved closer to or away from the source relative to the axial movement of the outer cylinder (10). A carrier liquid platform (4), the acoustic wave couplant is filled between the outer cylinder (10) and the top end of the inner cylinder (9). 9. The non-contact ultrasonic pipetting device according to claim 7, characterized in that, the ultrasonic coupling unit (3) further comprises a peristaltic pump and a cooling chamber ( 32), the sonic couplant is also filled in the cooling cavity (32), and the peristaltic pump drives the sonic couplant to fill the top of the outer cylinder (10) and the cooling cavity (32) circulating flow. 10. A non-contact ultrasonic pipetting method, comprising: Ranging modes, including: The ultrasonic transducer unit (2) emits ultrasonic waves toward the source carrier liquid platform (4) to generate a focused sound field; The distance between the ultrasonic transducer unit (2) and the liquid surface of the source carrier liquid platform (4) is changed according to the ultrasonic echo signal amplitude, until the ultrasonic echo amplitude reaches a specific value; Pipetting modes, including: When the ultrasonic echo amplitude reaches a specific value, adjust the parameters of the ultrasonic excitation waveform to adjust the volume of the pipetting drop; The power of the ultrasonic transducer unit (2) is increased to transfer droplets from the source carrier liquid platform (4) to the target carrier liquid platform (5).

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