WO2023004795A1 - Ultrasonic pipetting apparatus and method - Google Patents

Abstract

The present invention provides an ultrasonic pipetting apparatus, comprising an ultrasonic emission module and a liquid-carrying apparatus; the ultrasonic emission module comprises a multi-probe component, a coupling liquid circulation system and an ultrasonic excitation component, the liquid-carrying apparatus being disposed above the multi-probe component; the multi-probe component comprises two or more probes, a coupling cavity and a coupling nozzle, wherein the two or more probes are disposed on the same support, the liquid-carrying apparatus is provided with multiple liquid-carrying holes, the focal point of the probes is aligned with the liquid level of the liquid-carrying apparatus, the coupling cavity surrounds the probes, the coupling nozzle is disposed between the probes and the liquid-carrying apparatus, and the coupling cavity is internally filled with a coupling liquid; the coupling liquid circulation system enables the coupling liquid to continuously enter the coupling cavity, and the coupling liquid overflows from the coupling nozzle to make contact with the bottom part of the liquid-carrying apparatus; and the ultrasonic excitation component is connected to a control circuit, and the ultrasonic excitation component comprises two or more ultrasonic excitation units, each ultrasonic excitation unit being connected to a corresponding probe to excite each probe, and the probes being used to emit ultrasonic waves.

Description

An ultrasonic pipetting device and method technical field

The invention relates to the technical field of synthetic biology experiments, in particular to an ultrasonic pipetting device and method.

Background technique

In today's world, people are facing increasingly severe challenges such as diseases, environment and energy. Synthetic biology is hailed as one of the world's three disruptive technologies to tackle the challenge. The research goal of synthetic biology is to adopt the concept of engineering to design, transform and even re-synthesize organisms to create artificial life forms with non-natural functions. At present, in the process of synthetic biology experiments, living body verification experiments are carried out based on a large number of biological experiments, so a large number of micro-pipetting operations are required for the preparation 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 completing an experiment accurately.

At present, the most widely used method in the industry is to use a pipette gun, which is a general-purpose biological and chemical experimental equipment, which can create a partial vacuum in the container above the liquid surface, and selectively adjust the vacuum volume to suck or discharge liquid. . Pipettes of varying accuracy and precision can be achieved through a variety of designs, ranging from simple pipettes made from a single piece of glass to complex adjustable or electronically controlled pipettes. However, the accuracy of its measurement varies greatly from species to species. At the same time, because the pipette gun is a contact pipetting method, during the pipetting process, the sample adheres to the tip of the pipette, resulting in inaccurate amount of transferred liquid and prone to false negative results. Also, errors accumulate when serial dilutions are used, with some samples showing as much as a cubic loss of biological activity when using serial dilutions. 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 are needed to support the experiment, and the cost is relatively expensive for large-scale use. Therefore, non-contact micropipette technology is a particularly important key technology in the field of biology.

The object in the ultrasonic sound field receives the momentum of the sound wave (mechanical wave) and produces a force, which is defined as the Acoustic Radiation Force (Acoustic Radiation Force) in acoustics. The ultrasonic radiation force is mainly determined by the pressure gradient of the sound field around the force-bearing object. Due to the advantage of non-contact action of ultrasound, it has unique advantages and great application potential in the field of micropitting.

There are pipetting devices based on ultrasonic pipetting technology in the prior art, but most of these pipetting devices based on ultrasonic pipetting technology are contact-type, and the non-contact pipetting that can be realized is at least the distance between the pipetting needle and the target reaction well. With non-contact pipetting, the liquid being pipetted remains in contact with the pipetting needle. In addition, the existing pipetting devices based on ultrasonic pipetting technology also have fixed acoustic parameters of the probe used, and the volume of each droplet is fixed, that is, the minimum pipetting volume is fixed, generally 2.5nL and 25nL, etc. ; Pipettes that require larger volumes need to make several drops to accumulate to reach the target volume. This type of ultrasonic pipetting equipment is generally divided into several models according to the size of a single droplet to meet the needs of use, but there are still defects such as slow pipetting speed for small droplet models and poor pipetting accuracy for large droplet models.

Contents of the invention

In view of this, in order to overcome the defects of the above-mentioned prior art, the present invention proposes an ultrasonic pipetting device and method that can use multiple probes to pipette simultaneously without interfering with each other.

Specifically, the ultrasonic pipetting device includes an ultrasonic transmitting module and a liquid-carrying device, the ultrasonic transmitting module includes a multi-probe assembly, a coupling liquid circulation system and an ultrasonic excitation assembly, and the liquid-carrying device is arranged above the multi-probe assembly ;

The multi-probe assembly includes two or more probes, a coupling cavity and a coupling nozzle, two or more probes are arranged on the same bracket, and a plurality of liquid-carrying holes are arranged on the liquid-carrying device, and the probes are focus on the liquid surface of the liquid-carrying device, the coupling cavity surrounds the probe, the coupling nozzle is arranged between the probe and the liquid-carrying device, and the coupling cavity is filled with coupling liquid ;

The coupling liquid circulation system makes the coupling liquid continuously enter the coupling cavity, the coupling liquid overflows from the coupling nozzle, and the overflowing coupling liquid contacts the bottom of the liquid carrying device;

The ultrasonic excitation component is connected to a control circuit, and the ultrasonic excitation component includes two or more ultrasonic excitation units, and each of the ultrasonic excitation units is connected to a corresponding probe for exciting each of the probes, and the probes are used for emit ultrasound. Due to the surface adhesion of the liquid, when the coupling liquid touches the bottom of the liquid-carrying device, it will be connected to form an ultrasonic channel composed of the coupling liquid.

Preferably, the distance between the probes is an integer multiple of the pitch of the liquid-carrying holes. Different probes can be aimed at different liquid-carrying holes on the liquid-carrying device at the same time for ultrasonic pipetting operation.

The ultrasonic excitation unit includes a drive circuit and an excitation circuit, the drive circuit is connected to the control circuit, the excitation circuit is connected to the probe, the control circuit controls the drive circuit to generate ultrasonic waves, and the excitation circuit controls the The probes are used for excitation; the different ultrasonic excitation units are independent of each other, and are used to simultaneously excite multiple probes to emit ultrasonic waves at the same or different frequencies.

The multi-probe assembly also includes an accommodating groove and a sealing tube, the accommodating groove surrounds the coupling cavity; a through hole is provided at the bottom of the coupling cavity, the probe passes through the through hole, and one end of the sealing tube The through hole at the bottom of the coupling cavity is sealed, and the other end is tightly combined with the probe. The sealing tube can be folded or stretched when the probe moves up and down to keep the bottom of the coupling cavity sealed and prevent the coupling fluid from entering the probe and being damaged.

Preferably, the probe is a focused ultrasonic transducer, and the ultrasonic waves emitted by the probe are focused ultrasonic waves.

In some embodiments, the multi-probe assembly includes a plurality of motors, each of the motors is connected to the corresponding probe, and the motor drives the probe to change the distance between the probe and the liquid-carrying device .

The coupling liquid circulation system includes a sealed tank, a water pump, a temperature control system, a filter and a vacuum pump, the coupled liquid is stored in the sealed tank, the water pump is connected to the outlet end of the sealed tank, and the water pump pumps out the The coupling liquid in the sealed tank is cooled by the maintained temperature control system, and the cooled coupling liquid flows into the multi-probe assembly; the filter is connected to the inlet port of the sealed tank, and the multi-probe assembly flows The coupling liquid returned to the coupling liquid circulation system flows into the filter for filtration, and the vacuum pump is connected to the sealed tank for pumping the filtered coupling liquid into the sealed tank. The cooled coupling fluid can cool the probe.

Preferably, the multi-probe assembly further includes a housing tank connected to the coupling liquid circulation system; the housing tank surrounds the coupling cavity, and the coupling liquid overflowing the coupling nozzle flows into the housing groove. The coupling liquid in the coupling liquid circulation system continuously enters the multi-probe assembly, and the coupling liquid overflowing from the coupling nozzle flows back to the coupling liquid circulation system, which can realize the recycling of the coupling liquid, and can replace the coupling liquid in the multi-probe assembly in real time, so as to A better effect of cooling the probe is achieved.

The ultrasonic transmitting module also includes a signal detection component connected to the control circuit for receiving the detection signal of the probe; the signal detection component includes two or more signal detection channels, each of the The signal detection channel is connected to the corresponding probe. The processing circuits and acquisition circuits of different signal detection channels are independent of each other, so the parameters of each probe can be obtained independently without affecting each other, and can support simultaneous detection of multiple channels. The signal detection component can obtain data such as the liquid level, volume and solution type of the liquid carrier device through the detection signal, and can automatically obtain the physical parameters of the liquid.

The ultrasonic excitation component also includes a power detection unit, the power detection unit includes a signal coupling module and a signal acquisition module, and the signal acquisition module measures the attenuated signal of the ultrasonic excitation component coupled by the signal coupling module to obtain an ultrasonic Excitation signal amplitude.

The present invention also provides an ultrasonic pipetting method, which uses the above-mentioned ultrasonic pipetting device to perform ultrasonic pipetting, and the ultrasonic pipetting method includes:

Move the multi-probe assembly so that the probe is aligned with the liquid-carrying hole of the liquid-carrying device;

Start the motor to move the probe so that the focus of the probe is aligned with the liquid surface of the liquid-carrying device;

Start the coupling liquid circulation system to make the coupling liquid overflow from the coupling nozzle, and the coupling liquid contacts the bottom of the liquid carrier device to form an ultrasonic channel;

controlling each ultrasonic excitation unit of the ultrasonic excitation assembly to excite the probe to emit ultrasonic waves;

Wherein, the ultrasonic excitation unit excites different probes to emit ultrasonic waves at the same or different frequencies.

In summary, the ultrasonic pipetting device and method of the present invention have the following beneficial effects: each probe is connected to a different ultrasonic excitation unit, each ultrasonic excitation unit can work independently, and supports the excitation and setting of multiple ultrasonic waveform parameters, To meet the needs of various incentive parameters. Therefore, the ultrasonic liquid pipetting device of the present invention can coordinate the work of multiple probes with the same acoustic parameters, and can also support multiple probes with different acoustic parameters to work together for ultrasonic liquid pipetting, and can flexibly control the size of each pipetting liquid, providing high-quality Precision control and pipetting efficiency provide a better solution. In addition, each probe is equipped with a motor to drive the probe to move up and down to change the distance between the probe and the liquid surface of the liquid carrier device. Multiple probes can work at the same time and each probe can focus independently. Multiple probes can be flexibly matched. In order to achieve the purpose of providing the use efficiency and applicability of the ultrasonic pipetting device. The ultrasonic pipetting method carried out by the ultrasonic pipetting device of the present invention can coordinate the work of a plurality of probes with the same acoustic parameters to improve the speed and efficiency of ultrasonic pipetting; it can also support the simultaneous work of probes with different acoustic parameters to realize the pipetting function, to flexibly control the size of each pipette.

Description of drawings

In order to more clearly illustrate the technical solutions in the embodiments of the present application, the drawings that need to be used in the description of the embodiments will be briefly introduced below. Obviously, the drawings in the following description are only some embodiments of the present application. For those skilled in the art, other drawings can also be obtained based on these drawings without creative effort.

Fig. 1 is the schematic structural view of the multi-probe assembly of the ultrasonic pipetting device of the present invention;

Fig. 2 is a schematic structural view of the coupling liquid circulation system of the ultrasonic pipetting device of the present invention;

Fig. 3 is a structural schematic diagram of the ultrasonic excitation assembly of the ultrasonic pipetting device of the present invention;

Fig. 4 is a schematic structural diagram of a signal detection component of the ultrasonic pipetting device of the present invention.

Reference signs:

11-bracket; 12-motor; 13-coupling cavity; 14-holding tank; 15-coupling nozzle; 16-probe; Control system; 34-thermometer; 35-filter; 36-vacuum pump; 37-muffler.

Detailed ways

The following will clearly and completely describe the technical solutions in the embodiments of the present invention with reference to the accompanying drawings in the embodiments of the present invention. Obviously, the described embodiments are only some of the embodiments of the present invention, not all of them. Based on the embodiments of the present invention, all other embodiments obtained by persons of ordinary skill in the art without making creative efforts belong to the protection scope of the present invention.

The invention provides an ultrasonic transmitting module and a liquid-carrying device of an ultrasonic pipetting device. The ultrasonic transmitting module includes an ultrasonic excitation component, a coupling liquid circulation system, and a multi-probe component. The liquid carrying device is arranged above the multi-probe assembly, and the focus of the probes in the multi-probe assembly is aimed at the liquid surface of the liquid carrying device. The ultrasonic excitation component is connected to the probe to excite the probe, and under the action of the ultrasonic waves emitted by the probe, the liquid will fly away from the liquid-carrying device without contact. The coupling liquid provided by the coupling liquid circulation system is used for contact coupling with the liquid carrier device, and the circulating coupling liquid can also play a role in cooling the probe.

Example 1

Specifically, referring to the accompanying drawing 1 of the specification, the multi-probe assembly is an integrated structure, including a bracket 11, a motor 12, a coupling chamber 13, a housing groove 14, a coupling nozzle 15, a probe 16, and a sealing tube 17, wherein the number of probes 16 is two and above. The coupling cavity 13 surrounds the probe 16 , and the accommodating groove 14 surrounds the coupling cavity 15 . This embodiment provides a specific structure of a dual-probe assembly: two probes 16 are arranged on the same bracket 11, and a coupling cavity 13 is provided on the outside of each probe 16, and the coupling cavity 13 is filled with coupling liquid, and the coupling cavity 13 surrounds The probe 16 and the accommodating groove 14 surround the two coupling cavities 13, both the accommodating groove 14 and the coupling cavities 13 are fixed on the support 11, and the two coupling cavities 13 are separated by a metal plate.

See Figure 2 of the specification, which is a schematic structural diagram of a coupling liquid circulation system that can be connected with the above-mentioned dual-probe assembly. The coupling liquid circulation system includes a sealed tank 31 , a water pump 32 , a temperature control system 33 , a thermometer 34 , a filter 35 , a vacuum pump 36 and a muffler 37 . The inlet port of the sealed tank 31 is connected with a filter 35, the outlet port is connected with a water pump 32, and the sealed tank 31 is also connected with a vacuum pump 36, and a muffler 37 is set to connect the vacuum pump 36 for reducing the noise generated by the vacuum pump 36. The water pump 32, temperature Control system 33 and thermometer 34 are connected in sequence. The coupling liquid is stored in the sealing tank 31. When the coupling liquid circulation system is running, the coupling liquid in the sealing tank 31 is pumped out by the water pump 32, flows to the temperature control system 33 and flows into the multi-probe 16 assembly after cooling by the temperature control system 33. The coupling liquid can play a role in cooling the probe 16, and the thermometer 34 connected to the temperature control system 33 is used to measure the temperature of the coupling liquid flowing into the multi-probe 16 assembly. The coupling liquid flowing back to the coupling liquid circulation system from the multi-probe assembly flows through the filter 35 for filtration, and the vacuum pump 36 creates a negative pressure inside the sealed tank 31 , thereby pumping the filtered coupling liquid into the sealed tank 31 . Between the coupling liquid circulation system and the multi-probe assembly, a coupling liquid circulation system may be provided for each probe 16, or each probe 16 may share the coupling liquid circulation system.

The coupling nozzle 15 is a hollow structure, preferably a hollow conical structure. The coupling nozzle 15 is arranged between the probe 16 and the liquid-carrying device 2. The bottom of the coupling nozzle 15 is open to fit into the coupling chamber 13, and an opening is left on the top. The opening surrounds the probe 16 and its caliber is larger than the diameter of the probe 16. The coupling nozzle 15 and the probe 16 to form a gap. Specifically, the coupling liquid may be water. The coupling liquid circulation system makes the coupling liquid continuously enter the coupling chamber 13. After the coupling liquid fills the coupling chamber 13, it flows out from the small opening on the top of the coupling nozzle 15. Due to the surface tension of the water, a protruding water bag is formed at the opening of the coupling nozzle 15. When the coupling nozzle 15 Close to the liquid-carrying device 2, due to the surface adhesion of water, the water bag contacts the bottom of the liquid-carrying device 2 and connects with it to form an ultrasonic channel made of water. After the water bag reaches a certain height, it continues to flow down along the outer wall of the coupling nozzle 15, flows into the holding tank 14, and then flows back to the coupling liquid circulation system.

The probe 16 is connected with the motor 12, and the bottom of the coupling cavity 13 is provided with a through hole for the probe 16 to pass through. One end of the sealing tube 17 seals the through hole at the bottom of the coupling cavity 13, and the other end is tightly combined with the side wall of the probe 16. Specifically, the motor 12 drives the probe 16 to move up and down to change the distance between the liquid surface of the liquid carrying device 2; the sealing tube 17 can be folded or stretched to follow the probe 16 to move up and down when the motor 12 drives the probe 16 to move up and down, so that the coupling cavity 13 The bottom remains sealed to prevent the coupling liquid from entering the probe 16 and the motor 12 to be damaged. In a specific embodiment, the sealing tube 17 is a corrugated tube with a corrugated tube wall.

In some embodiments, bracket 11 is connected to a displacement system. The displacement system can be a three-dimensional motion module, which is used to drive the entire multi-probe assembly to perform three-dimensional motion. Multiple probes 16 share one holding tank 14 and displacement system. At the same time, the pipetting work does not interfere with each other. Multiple probes 16 of the same specification or multiple probes 16 of different specifications can be configured to improve the efficiency and compatibility of pipetting.

Preferably, a large-sized high-frequency broadband focused ultrasonic transducer is used in the ultrasonic transmitting module to obtain a non-contact ultrasonic pipetting device with high precision and a wide range of adjustable pipetting accuracy: large-sized high-frequency focused ultrasonic transducer The transducer not only has a small focal spot size, but also has a large output sound radiation force, which can realize picoliter ultrasonic pipetting; the high bandwidth of the ultrasonic transducer can ensure that the transducer has a higher frequency range The output of acoustic radiation force realizes that the volume of liquid pipetting at one time can be adjusted in a large range, so that the pipetting accuracy can be adjusted arbitrarily from picoliters to microliters.

The ultrasonic excitation component is used to excite each probe 16 to emit ultrasonic waves. Specifically, the ultrasonic excitation assembly includes a plurality of ultrasonic excitation units, each ultrasonic excitation unit includes a drive circuit and an excitation circuit, wherein the drive circuit is connected to the control circuit, and the excitation circuit is connected to the probe 16, and each ultrasonic excitation unit can work independently. In practical applications, one ultrasonic excitation unit can be connected to one probe 16 to excite the probe 16, or two or more probes 16 can be connected to simultaneously excite the probe 16 correspondingly connected to the ultrasonic excitation unit. Refer to Fig. 3 of the specification, which is a schematic structural diagram of an ultrasonic excitation component used in the ultrasonic transmitting module of this embodiment. When the ultrasonic excitation component is working, the control circuit controls the drive circuit to generate the required ultrasonic waveform, and then excites the probe 16 through the excitation circuit. The ultrasonic excitation component supports the excitation of two or more probes 16 . Specifically, multiple probes 16 can work independently, or work at the same time or simultaneously. Since the drive circuits and excitation circuits in different ultrasonic excitation units are independent of each other, the excitation parameters of each ultrasonic excitation unit can be adjusted in real time, which can be used to simultaneously excite different probes to emit ultrasonic waves at the same or different frequencies to meet multiple requirements. different pipetting parameters. The excitation parameters include ultrasonic frequency, ultrasonic amplitude, ultrasonic pulse length, pulse repetition frequency, and the like. In this embodiment, one ultrasonic excitation unit can be connected with one probe 16 .

In some embodiments, the ultrasonic excitation component further includes a power detection unit, configured to detect the energy of the ultrasonic signal emitted by the ultrasonic excitation component, so as to stabilize the amplitude of the ultrasonic excitation signal. The power detection unit includes a signal coupling module and a signal acquisition module. The signal acquisition module measures the attenuated signal of the ultrasonic excitation component coupled by the signal coupling module, thereby obtaining the amplitude of the ultrasonic excitation signal.

The control circuit can be realized by FPGA, and can also be realized by MCU such as single-chip microcomputer, ARM processor and DSP. The control circuit is used for ultrasonic excitation control and ultrasonic acquisition processing. In some embodiments, the control circuit can also perform mechanical control of the dual-channel probe 16 for moving the spatial position of the probe 16 and the like.

The ultrasonic transmitting module may also include a signal detection component for receiving the detection signal of the probe 16 . Referring to Figure 4 of the specification, the signal detection component includes a plurality of signal detection channels, each signal detection channel includes a processing circuit and an acquisition circuit, the processing circuit is connected to the probe 16 for the detection signal of the docking probe 16, and performs preprocessing of the detection signal, including But not limited to signal filtering and amplification; the acquisition circuit digitally processes the analog detection signal, the acquisition circuit is connected to the control circuit, and the digitally processed detection signal enters the control circuit for further processing. Each signal detection channel is connected to a probe 16, and the processing circuits and acquisition circuits of different signal detection channels are independent of each other, so the parameters of each probe 16 can be acquired independently without affecting each other, and can support simultaneous detection of multiple channels. The signal detection component can obtain data such as liquid level height, volume and solution type of the liquid carrier device 2 through the detection signal, and can automatically obtain liquid physical parameters. Quantitative evaluation of liquid physical parameters can be carried out by using parameters such as the amplitude and frequency spectrum of ultrasonic detection signals.

When pipetting liquid, a liquid-carrying device 2 is placed above the ultrasonic emission module, and a plurality of regularly arranged liquid-carrying holes are arranged on the liquid-carrying device 2 (generally a porous plate with many small holes regularly arranged, each small hole Contains several liquids that need to be pipetted). In some embodiments, the coupling fluid is water. When the ultrasonic transmitter module is working, the coupling liquid cooled by the coupling liquid circulation system flows into the multi-probe assembly from the 1 port and 4 port of the holding tank 14 and enters the coupling cavity 13 of the two probes 16, and the coupling liquid fills the coupling cavity 13 and flows from the coupling nozzle The small opening at the top of 15 flows out, and due to the surface tension of the water, a protruding water bag is formed at the opening of the coupling nozzle 15. After the water bag reaches a certain height, it continues to stay along the outer wall of the coupling nozzle 15 and flows into the holding tank 14. , 3 ports flow back to the coupling liquid circulation system. The position of the coupling nozzle 15 corresponds to the position of each probe 16 one by one. When the coupling nozzle 15 is close to the liquid carrier 2, due to the surface adhesion of the water, the water bag will be connected to the bottom of the liquid carrier 2 to form an ultrasonic wave composed of water. aisle. The probe 16 is a focused ultrasonic transducer, and its focusing can be physical focusing or lens focusing. The ultrasonic waves emitted by the probe 16 are focused ultrasonic waves. Under the action of the ultrasonic waves, the liquid to be pipetted can fly away from the liquid-carrying device 2 without contact.

The distance between the probes 16 is an integral multiple of the pitch of the liquid-carrying holes on the liquid-carrying device 2 , so that the two probes 16 can be aimed at different liquid-carrying holes on the liquid-carrying device 2 at the same time. The displacement system controls the probe 16 of the ultrasonic emitting module to align with the hole on the liquid-carrying device 2 that needs to be pipetted. The two probes 16 each detect the height of the liquid level through the echo, and the high-precision vertical movement of the motor 12 makes the focus of the probe 16 on the liquid level, and the multi-channel excitation component respectively excites the two probes 16 according to the input parameters of the liquid. Ultrasound, the liquid in the liquid carrier device 2 flies off the liquid surface under the action of ultrasonic waves and is received by the target liquid carrier plate directly above. After completing the pipetting of a group of wells, the displacement system drives the ultrasonic ultrasonic emission module to move to the next group of pipetting holes, and continues the pipetting operation until all pipetting tasks are completed.

The dual-probe ultrasonic pipetting method carried out by the ultrasonic transmitting module of this embodiment, when the ultrasonic acoustic parameters (including frequency, amplitude, pulse length and pulse repetition frequency, etc.) are consistent, the dual-probe ultrasonic pipetting can significantly increase the speed of ultrasonic pipetting and efficiency; when the ultrasonic acoustic parameters are inconsistent, the dual-probe ultrasonic pipetting system supports probes 16 with different acoustic parameters to work simultaneously to realize the pipetting function. The ultrasonic pipetting device of the present invention can coordinate the work of a plurality of probes 16 with the same acoustic parameters, and can also support the joint work of a plurality of probes 16 with different acoustic parameters to perform ultrasonic pipetting, and can flexibly control the size of each pipetting, providing high-quality Precision control and pipetting efficiency provide a better solution.

Example 2

This embodiment provides an ultrasonic pipetting method. The ultrasonic pipetting device of the present invention performs ultrasonic pipetting. The ultrasonic pipetting method includes:

Move the multi-probe assembly so that the probe 16 is aligned with the liquid-carrying hole of the liquid-carrying device 2;

Start the motor 12 to move the probe 16 so that the focus of the probe 16 is aligned with the liquid surface of the liquid carrier device 2;

Start the coupling liquid circulation system to make the coupling liquid overflow from the coupling nozzle 15, and the coupling liquid contacts the bottom of the liquid carrier device 2 to form an ultrasonic channel;

Each ultrasonic excitation unit controlling the ultrasonic excitation assembly excites the probe 16 to emit ultrasonic waves;

Wherein, the ultrasonic excitation unit excites different probes 16 to emit ultrasonic waves at the same or different frequencies.

A kind of ultrasonic pipetting method that adopts the ultrasonic pipetting device that has double probe 16 as described in embodiment 1 to comprise:

Move the double-probe assembly so that the two probes 16 are respectively aligned with different liquid-carrying holes on the liquid-carrying device 2;

Start the motor 12 to move the probe 16 so that the focus of the probe 16 is aligned with the liquid surface of the liquid carrier device 2;

Start the coupling liquid circulation system to make the coupling liquid overflow from the coupling nozzle 15, and the coupling liquid contacts the bottom of the liquid carrier device 2 to form an ultrasonic channel;

Each ultrasonic excitation unit controlling the ultrasonic excitation assembly excites the probe 16 to emit ultrasonic waves.

Wherein, the ultrasonic excitation assembly includes a first ultrasonic excitation unit excitation and a second ultrasonic excitation assembly, the two probes 16 are respectively a first probe and a second probe, the first ultrasonic excitation unit is connected to the first probe, and the second ultrasonic excitation unit is connected to the second ultrasonic excitation unit. Two probes. The driving circuits and excitation circuits in different ultrasonic excitation units are independent of each other, so the excitation parameters of each ultrasonic excitation unit can be adjusted independently, so the first ultrasonic excitation unit can excite the first probe to emit ultrasonic waves at the first frequency, and the second The ultrasonic excitation unit excites the second probe to emit ultrasonic waves at the second frequency.

Specifically, the first frequency may be the same as the second frequency, or may be different from the second frequency; when the first frequency is different from the second frequency, the first frequency may be greater than the second frequency, or the first frequency may be less than the second frequency. Frequency, so as to excite the two probes 16 of the dual-probe assembly to emit ultrasonic waves at the same or different frequencies. The first frequency is the same as the second frequency, which can significantly improve the speed and efficiency of ultrasonic pipetting. When the first frequency is different from the second frequency, the ultrasonic pipetting device can support probes 16 with different acoustic parameters to work at the same time to realize the pipetting function, so as to be flexibly controlled. The size of each pipette.

The ultrasonic pipetting method of the present invention can be used in an ultrasonic pipetting device with more probes 16 to coordinate multiple probes 16 with the same acoustic parameters, or multiple probes 16 with different acoustic parameters work together to perform ultrasonic pipetting.

To sum up, the present invention provides an ultrasonic pipetting device, which is provided with a plurality of probes for emitting ultrasonic waves to separate the liquid on the liquid-carrying device and fly out vertically to be received by the target liquid-carrying plate directly above it. Each probe is connected to a different ultrasonic excitation unit, and each ultrasonic excitation unit can work independently to support the excitation and setting of various ultrasonic waveform parameters to meet the needs of various excitation parameters. Therefore, the ultrasonic liquid pipetting device of the present invention can coordinate the work of multiple probes with the same acoustic parameters, and can also support multiple probes with different acoustic parameters to work together for ultrasonic liquid pipetting, and can flexibly control the size of each pipetting liquid, providing high-quality Precision control and pipetting efficiency provide a better solution. In addition, each probe is equipped with a motor to drive the probe to move up and down to change the distance between the probe and the liquid surface of the liquid carrier device. Multiple probes can work at the same time and each probe can focus independently. Multiple probes can be flexibly matched. In order to achieve the purpose of providing the use efficiency and applicability of the ultrasonic pipetting device. The ultrasonic pipetting method carried out by the ultrasonic pipetting device of the present invention can coordinate the work of a plurality of probes with the same acoustic parameters to improve the speed and efficiency of ultrasonic pipetting; it can also support the simultaneous work of probes with different acoustic parameters to realize the pipetting function, to flexibly control the size of each pipette.

The above descriptions are only preferred embodiments of the present invention, and are not intended to limit the present invention. In addition to the above embodiments, different modifications can also be made. The technical features of the above embodiments can be combined with each other. Within the principles and principles, any modifications, equivalent replacements, improvements, etc., shall be included in the protection scope of the present invention.

Claims (11)

An ultrasonic pipetting device, characterized in that it includes an ultrasonic transmitting module and a liquid-carrying device, the ultrasonic transmitting module includes a multi-probe assembly, a coupling liquid circulation system and an ultrasonic excitation assembly, and the liquid-carrying device is arranged on the multi-probe above the component; The multi-probe assembly includes two or more probes, a coupling cavity and a coupling nozzle, two or more probes are arranged on the same bracket, and a plurality of liquid-carrying holes are arranged on the liquid-carrying device, and the probes are focus on the liquid surface of the liquid-carrying device, the coupling cavity surrounds the probe, the coupling nozzle is arranged between the probe and the liquid-carrying device, and the coupling cavity is filled with coupling liquid ; The coupling liquid circulation system makes the coupling liquid continuously enter the coupling cavity, the coupling liquid overflows from the coupling nozzle, and the overflowing coupling liquid contacts the bottom of the liquid carrying device; The ultrasonic excitation component is connected to a control circuit, and the ultrasonic excitation component includes two or more ultrasonic excitation units, and each of the ultrasonic excitation units is connected to a corresponding probe for exciting each of the probes, and the probes are used for emit ultrasound. The ultrasonic pipetting device according to claim 1, wherein the ultrasonic excitation unit comprises a drive circuit and an excitation circuit, the drive circuit is connected to the control circuit, the excitation circuit is connected to the probe, and the control circuit The circuit controls the drive circuit to generate ultrasonic waves, and the excitation circuit excites the probe; The different ultrasonic excitation units are independent of each other, and are used to simultaneously excite multiple probes to emit ultrasonic waves at the same or different frequencies. The ultrasonic pipetting device according to claim 1, wherein the multi-probe assembly further comprises a containing groove and a sealing tube, and the containing groove surrounds the coupling cavity; A through hole is provided at the bottom of the coupling cavity, the probe passes through the through hole, one end of the sealing tube seals the through hole at the bottom of the coupling cavity, and the other end is closely combined with the probe. The ultrasonic liquid pipetting device according to claim 1, wherein the probe is a focused ultrasonic transducer, and the ultrasonic waves emitted by the probe are focused ultrasonic waves. The ultrasonic liquid pipetting device according to claim 1, wherein the multi-probe assembly includes a plurality of motors, each of the motors is connected to the corresponding probe, and the motor drives the movement of the probe to change the probe distance from the liquid-carrying device. The ultrasonic pipetting device according to claim 1, wherein the coupling liquid circulation system includes a sealed tank, a water pump, a temperature control system, a filter, and a vacuum pump, and the coupled liquid is stored in the sealed tank, so that The water pump is connected to the outlet end of the sealed tank, and the water pump pumps the coupling liquid in the sealed tank to the maintained temperature control system for cooling, and the cooled coupling liquid flows into the multi-probe assembly; The filter is connected to the inlet end of the sealed tank, the coupling liquid flowing back from the multi-probe assembly into the coupling liquid circulation system flows into the filter for filtration, and the vacuum pump is connected to the sealed tank for The filtered coupling liquid is pumped into the sealed tank. The ultrasonic pipetting device according to claim 1, wherein the ultrasonic transmitting module further comprises a signal detection component connected to the control circuit for receiving the detection signal of the probe; The signal detection component includes two or more signal detection channels, and each signal detection channel is connected to the corresponding probe. The ultrasonic pipetting device according to claim 1, wherein the ultrasonic excitation component further includes a power detection unit, the power detection unit includes a signal coupling module and a signal acquisition module, and the signal acquisition module measures the signal The attenuated signal of the ultrasonic excitation component coupled by the coupling module obtains the amplitude of the ultrasonic excitation signal. The ultrasonic pipetting device according to claim 1, wherein the multi-probe assembly further comprises a holding tank connected to the coupling liquid circulation system; The accommodating groove surrounds the coupling cavity, and the coupling liquid overflowing the coupling nozzle flows into the accommodating groove. The ultrasonic pipetting device according to claim 1, wherein the distance between the probes is an integer multiple of the pitch of the liquid-carrying holes. An ultrasonic pipetting method, characterized in that the ultrasonic pipetting device according to any one of claims 1-10 is used for ultrasonic pipetting, the ultrasonic pipetting method comprising: Move the multi-probe assembly so that the probe is aligned with the liquid-carrying hole of the liquid-carrying device; Start the motor to move the probe so that the focus of the probe is aligned with the liquid surface of the liquid-carrying device; Start the coupling liquid circulation system to make the coupling liquid overflow from the coupling nozzle, and the coupling liquid contacts the bottom of the liquid carrier device to form an ultrasonic channel; controlling each ultrasonic excitation unit of the ultrasonic excitation assembly to excite the probe to emit ultrasonic waves; Wherein, the ultrasonic excitation unit excites different probes to emit ultrasonic waves at the same or different frequencies.

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