Ultrasonic liquid transfer device and method

Abstract

The invention proposes an ultrasonic liquid transfer device, comprising an ultrasonic transmitting module and a liquid carrier. The ultrasonic transmitting module comprises a multi-probe assembly, a coupling liquid circulation system and an ultrasonic excitation assembly. The liquid carrier is arranged above the multi-probe assembly; the multi-probe assembly comprises two or more probes, a coupling cavity and a coupling nozzle. The two or more probes are arranged on the same bracket. The liquid carrier is provided with a plurality of liquid carrier holes. The focus of the probe is aligned with the liquid surface of the liquid carrier. The coupling cavity surrounds the probe. The coupling nozzle is arranged between the probe and the liquid carrier. The coupling cavity is filled with 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 contact the bottom of the liquid carrier. The ultrasonic excitation assembly is connected to a control circuit. The ultrasonic excitation assembly comprises two or more ultrasonic excitation units. Each ultrasonic excitation unit is connected to a corresponding probe for exciting each probe. The probe is used to transmit ultrasonic waves.

Description

Technical Field

[0001] The present invention relates to the field of synthetic biology experimental technology, and in particular to an ultrasonic liquid transfer device and method. Background Art

[0002] In today's world, people are facing increasingly severe challenges such as disease, environment, and energy. Synthetic biology is hailed as one of the world's three major disruptive technologies to meet these challenges. The research goal of synthetic biology is to use engineering concepts to design, transform, and even resynthesize organisms to create artificial life forms 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, so a large number of micro-pipetting operations are required for the deployment and processing of experiments. Pipetting is one of the most common operation tasks in synthetic biology laboratories. Choosing the right pipette is a key step in completing experiments accurately.

[0003] At present, the most widely used method in the industry is to use a pipette, which is a common biological and chemical experimental equipment that can form a partial vacuum in the container above the liquid surface and absorb or discharge the liquid by selectively adjusting the vacuum volume. Different accuracy and precision of the pipette can be achieved through a variety of designs, including a simple piece of glass pipette to a complex adjustable or electrically controlled pipette. However, the accuracy of its measurement varies greatly depending on the type. At the same time, because the pipette is a contact pipetting method, during the pipetting process, the sample adheres to the tip of the pipette, resulting in an inaccurate amount of liquid transferred, which is prone to false negative results. In addition, errors will accumulate during gradient dilution, and some samples show a loss of up to three times the biological activity when using gradient dilution. In addition, since the tip of the pipette is a disposable consumable, in order to avoid cross infection, it needs special treatment or replacement after each use, so a large amount of consumables will be required to support the experiment, and the cost is relatively expensive when used on a large scale. Therefore, non-contact micro-pipetting technology is a particularly important key technology in the field of biology.

[0004] Objects in an ultrasonic field receive momentum from acoustic waves (mechanical waves) and are acted upon by forces, which is defined in acoustics as acoustic radiation force. Ultrasonic radiation force is mainly determined by the pressure gradient of the acoustic field around the object being acted upon. Ultrasonic waves have unique advantages and great application potential in the field of micropipetting due to their non-contact action advantage.

[0005] 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 achieved is at least non-contact pipetting between the pipetting needle and the target reaction hole, and the pipetting liquid is still in contact with the pipetting needle. In addition, the existing pipetting devices based on ultrasonic pipetting technology also have the problem that the acoustic parameters of the probe used are fixed, and the volume of the droplets ejected each time is fixed, that is, the minimum pipetting volume is fixed, generally 2.5nL and 25nL, etc.; if a larger volume of pipetting is required, several drops need to be ejected to reach the target volume. This type of ultrasonic pipetting equipment is generally divided into several models according to the size of the single droplet ejected to meet the needs of use, but there are still defects such as slow pipetting speed of small droplet models and poor pipetting accuracy of large droplet models. Summary of the invention

[0006] In view of this, in order to overcome the above-mentioned defects of the prior art, the present invention proposes an ultrasonic pipetting device and method that can use multiple probes to perform pipetting work simultaneously without interfering with each other.

[0007] Specifically, the ultrasonic liquid transfer 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;

[0008] The multi-probe assembly comprises two or more probes, a coupling cavity and a coupling nozzle, wherein the two or more probes are arranged on the same bracket, the liquid-carrying device is provided with a plurality of liquid-carrying holes, the focus of the probe is aligned with 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;

[0009] The coupling liquid circulation system allows the coupling liquid to continuously enter the coupling cavity, and the coupling liquid overflows from the coupling nozzle, and the overflowed coupling liquid contacts the bottom of the liquid carrying device;

[0010] The ultrasonic excitation component is connected to the control circuit, and the ultrasonic excitation component includes two or more ultrasonic excitation units, each of which is connected to the corresponding probe to excite each probe, and the probe is used to emit ultrasonic waves. Due to the surface adhesion of the liquid, the coupling liquid contacts the bottom of the liquid carrier device and connects with it to form an ultrasonic channel composed of the coupling liquid.

[0011] Preferably, the spacing between the probes is an integral multiple of the hole spacing of the liquid-carrying holes. Different probes can be simultaneously aligned with different liquid-carrying holes on the liquid-carrying device to perform ultrasonic pipetting operations.

[0012] The ultrasonic excitation unit includes a driving circuit and an excitation circuit, the driving circuit is connected to the control circuit, the excitation circuit is connected to the probe, the control circuit controls the driving circuit to generate ultrasonic waves, and the excitation circuit excites the probe; 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.

[0013] The multi-probe assembly also includes a receiving groove and a sealing tube. The receiving 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 tightly combined with the probe. The sealing tube can be folded or stretched when the probe moves up and down to follow the up and down movement of the probe, so that the bottom of the coupling cavity remains sealed to prevent the coupling liquid from entering the probe and damaging it.

[0014] Preferably, the probe is a focused ultrasonic transducer, and the ultrasonic waveform emitted by the probe is a focused ultrasonic wave.

[0015] In some embodiments, the multi-probe assembly includes a plurality of motors, each of which is connected to a corresponding probe, and the motor drives the probe to move to change the distance between the probe and the liquid-carrying device.

[0016] The coupling liquid circulation system includes a sealed tank, a water pump, a temperature control system, a filter and a vacuum pump. The coupling liquid is stored in the sealed tank. The water pump is connected to the outlet of the sealed tank. The water pump draws the coupling liquid in the sealed tank to the maintained temperature control system for cooling. The cooled coupling liquid flows into the multi-probe assembly. The filter is connected to the inlet of the sealed tank. The coupling liquid that flows back to the coupling liquid circulation system from the multi-probe assembly flows into the filter for filtration. The vacuum pump is connected to the sealed tank to draw the filtered coupling liquid into the sealed tank. The cooled coupling liquid can cool the probe.

[0017] Preferably, the multi-probe assembly further comprises a receiving tank, the receiving tank being connected to the coupling liquid circulation system; the receiving tank surrounds the coupling cavity, and the coupling liquid overflowing from the coupling nozzle flows into the receiving tank. 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, so that the coupling liquid can be recycled, and the coupling liquid in the multi-probe assembly can be replaced in real time to achieve a better cooling effect on the probe.

[0018] The ultrasonic transmitting module also includes a signal detection component, which is connected to the control circuit and is used to receive the detection signal of the probe; the signal detection component includes two or more signal detection channels, and each of the signal detection channels 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 through the detection signal, and can automatically obtain the physical parameters of the liquid.

[0019] The ultrasonic excitation component also includes a power detection unit, which 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 to obtain the ultrasonic excitation signal amplitude.

[0020] The present invention also provides an ultrasonic liquid transfer method, which uses the ultrasonic liquid transfer device to perform ultrasonic liquid transfer, and the ultrasonic liquid transfer method comprises:

[0021] Move the multi-probe assembly so that the probes are aligned with the liquid-carrying holes of the liquid-carrying device;

[0022] 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;

[0023] Starting the coupling liquid circulation system to allow the coupling liquid to overflow from the coupling nozzle, and the coupling liquid contacts the bottom of the liquid carrier device to form an ultrasonic channel;

[0024] Controlling each ultrasonic excitation unit of the ultrasonic excitation assembly to excite the probe to emit ultrasonic waves;

[0025] The ultrasonic excitation unit excites different probes to emit ultrasonic waves at the same or different frequencies.

[0026] In summary, the ultrasonic liquid transfer 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, support the excitation and setting of multiple ultrasonic wave shape parameters, and meet the needs of multiple excitation parameters. Therefore, the ultrasonic liquid transfer device of the present invention can be a plurality of probes with the same acoustic parameters to work in coordination, and can also support a plurality of probes with different acoustic parameters to work together for ultrasonic liquid transfer, and can flexibly control the size of each liquid transfer, providing a better solution for high-precision control and liquid transfer efficiency. In addition, each probe is also provided with a motor to drive the probe 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, and multiple probes can be flexibly matched to achieve the purpose of providing the use efficiency and applicability of the ultrasonic liquid transfer device. The ultrasonic liquid transfer method performed by the ultrasonic liquid transfer device of the present invention can coordinate the work of multiple probes with the same acoustic parameters to improve the speed and efficiency of ultrasonic liquid transfer; it can also support probes with different acoustic parameters to work simultaneously to realize the liquid transfer function, so as to flexibly control the size of each liquid transfer. BRIEF DESCRIPTION OF THE DRAWINGS

[0027] In order to more clearly illustrate the technical solutions in the embodiments of the present application, the drawings required for use in the description of the embodiments will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present application. For ordinary technicians in this field, other drawings can be obtained based on these drawings without creative work.

[0028] Figure 1 It is a schematic structural diagram of a multi-probe assembly of an ultrasonic liquid transfer device of the present invention;

[0029] Figure 2 It is a schematic structural diagram of a coupling liquid circulation system of an ultrasonic liquid transfer device of the present invention;

[0030] Figure 3 It is a schematic structural diagram of an ultrasonic excitation component of an ultrasonic liquid transfer device of the present invention;

[0031] Figure 4 It is a schematic diagram of the structure of the signal detection component of the ultrasonic pipetting device of the present invention.

[0032] Reference numerals:

[0033] 11- bracket; 12- motor; 13- coupling chamber; 14- receiving groove; 15- coupling nozzle; 16- probe; 17- sealing tube; 2- liquid carrying device; 31- sealing tank; 32- water pump; 33- temperature control system; 34- thermometer; 35- filter; 36- vacuum pump; 37- silencer. DETAILED DESCRIPTION

[0034] The following will be combined with the drawings in the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0035] The present invention provides an ultrasonic transmitting module and a liquid carrying device of an ultrasonic liquid transfer device, wherein the ultrasonic transmitting module comprises an ultrasonic excitation component, a coupling liquid circulation system, and a multi-probe component. The liquid carrying device is arranged above the multi-probe component, and the probe focus in the multi-probe component is aligned with the liquid surface of the liquid carrying device. The ultrasonic excitation component is connected to the probe to excite the probe, and the liquid is caused to fly away from the liquid carrying device without contact under the action of the ultrasonic wave emitted by the probe. The coupling liquid provided by the coupling liquid circulation system is used for contact coupling with the liquid carrying device, and the circulating coupling liquid can also play a role in cooling the probe.

[0036] Example 1

[0037] For details, see the attached manual. Figure 1 The multi-probe assembly is an integrated structure, including a bracket 11, a motor 12, a coupling cavity 13, a receiving groove 14, a coupling nozzle 15, a probe 16, and a sealing tube 17, wherein the number of probes 16 is two or more. The coupling cavity 13 surrounds the probe 16, and the receiving 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, a coupling cavity 13 is arranged on the outside of each probe 16, the coupling cavity 13 is filled with coupling liquid, the coupling cavity 13 surrounds the probe 16, the receiving groove 14 surrounds the two coupling cavities 13, the receiving groove 14 and the coupling cavity 13 are fixed on the bracket 11, and the two coupling cavities 13 are separated by a metal plate.

[0038] See the instruction manual Figure 2, is a structural schematic diagram of a coupling liquid circulation system that can be connected and applied 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 end of the sealed tank 31 is connected to a filter 35, and the outlet end is connected to a water pump 32. The sealed tank 31 is also connected to a vacuum pump 36. A muffler 37 is provided to connect the vacuum pump 36 to reduce the noise generated by the vacuum pump 36. The water pump 32, the temperature control system 33 and the thermometer 34 are connected in sequence. The sealed tank 31 stores coupling liquid. When the coupling liquid circulation system is running, the water pump 32 extracts the coupling liquid in the sealed tank 31, flows to the temperature control system 33, and flows into the multi-probe 16 assembly after being cooled by the temperature control system 33. The cooled coupling liquid can play a role in cooling the probe 16. 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 passes through the filter 35 for filtration, and the vacuum pump 36 forms 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 respectively provided for each probe 16, or each probe 16 may share a coupling liquid circulation system.

[0039] 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 and fits into the coupling cavity 13. An opening is left at the top. The opening surrounds the probe 16 and its diameter is larger than the diameter of the probe 16. A gap is formed between the coupling nozzle 15 and the probe 16. Specifically, the coupling liquid can be water. The coupling liquid circulation system allows the coupling liquid to continuously enter the coupling cavity 13. After the coupling liquid fills the coupling cavity 13, it flows out from the small opening at 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 is close to the liquid-carrying device 2, due to the surface adhesion of the water, the water bag contacts the bottom of the liquid-carrying device 2 and connects with it to form an ultrasonic channel composed of water. After reaching a certain height, the water bag continues to flow down along the outer wall of the coupling nozzle 15, flows into the receiving tank 14, and then flows back to the coupling liquid circulation system.

[0040] The probe 16 is connected to the motor 12. A through hole is provided at the bottom of the coupling cavity 13 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 probe 16 and the liquid surface of the liquid-carrying device 2; the sealing tube 17 can fold or stretch to follow the up and down movement of the probe 16 when the motor 12 drives the probe 16 to move up and down, so that the bottom of the coupling cavity 13 remains sealed, and the coupling liquid is prevented from entering the probe 16 and the motor 12 and being damaged. In a specific embodiment, the sealing tube 17 is a corrugated tube with a corrugated tube wall.

[0041] In some embodiments, the 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 a receiving slot 14 and a displacement system, and the pipetting work does not interfere with each other. Multiple probes 16 of the same specifications or multiple probes 16 of different specifications can be configured to improve the efficiency and compatibility of pipetting.

[0042] Preferably, a large-sized high-frequency broadband focused ultrasonic transducer is used for the ultrasonic transmitting module, so that a high-precision non-contact ultrasonic pipetting device with a wide range of adjustable pipetting accuracy can be obtained: the large-sized high-frequency focused ultrasonic transducer not only has a smaller focal size, but also has a larger output acoustic radiation force, which can achieve picoliter ultrasonic pipetting; the high bandwidth of the ultrasonic transducer can ensure that the transducer has a higher output acoustic radiation force within a larger frequency range, so that the amount of pipetting can be adjusted within a larger range at one time, thereby achieving arbitrarily adjustable pipetting accuracy from picoliter to microliter range.

[0043] The ultrasonic excitation component is used to excite each probe 16 to emit ultrasonic waves. Specifically, the ultrasonic excitation component includes a plurality of ultrasonic excitation units, each of which includes a driving circuit and an excitation circuit, wherein the driving 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, an ultrasonic excitation unit can be connected to a probe 16 to excite the probe 16, or it can be connected to two or more probes 16 to simultaneously excite the probe 16 corresponding to the ultrasonic excitation unit. See the attached manual for details. Figure 3 , is a schematic diagram of the structure of the ultrasonic excitation component of the ultrasonic transmitting module used in this embodiment. When the ultrasonic excitation component is working, the control circuit controls the driving 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 they can work in the same time or at the same time. Since the driving circuit and the excitation circuit in different ultrasonic excitation units are independent of each other, the excitation parameters of each ultrasonic excitation unit can be adjusted in real time, and can be used to simultaneously excite different probes to emit ultrasonic waves at the same or different frequencies to meet the needs of various pipetting parameters. The excitation parameters include ultrasonic frequency, ultrasonic amplitude, ultrasonic pulse length, pulse repetition frequency, etc. In this embodiment, one ultrasonic excitation unit can be connected to one probe 16.

[0044] In some embodiments, the ultrasonic excitation component further includes a power detection unit for detecting the energy of the ultrasonic signal emitted by the ultrasonic excitation component, thereby stabilizing the amplitude of the ultrasonic excitation signal. 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, thereby obtaining the amplitude of the ultrasonic excitation signal.

[0045] The control circuit can be implemented by FPGA, or by MCU such as single chip microcomputer, ARM processor and DSP. The control circuit is used to perform ultrasonic excitation control and ultrasonic acquisition processing. In some embodiments, the control circuit can also perform mechanical control of the dual-channel probe 16, and is used to move the spatial position of the probe 16, etc.

[0046] The ultrasonic transmitting module may also include a signal detection component for receiving the detection signal of the probe 16. Figure 4 The signal detection component includes multiple 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 docking the detection signal of the probe 16, and preprocessing the detection signal, including but not limited to signal filtering and amplification; the acquisition circuit digitizes the analog detection signal, and the acquisition circuit is connected to the control circuit. The detection signal after digitization 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. Therefore, the parameters of each probe 16 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 2 through the detection signal, and can automatically obtain the physical parameters of the liquid. The amplitude, spectrum and other parameters of the ultrasonic detection signal can be used to quantitatively evaluate the physical parameters of the liquid.

[0047] When performing liquid transfer, a liquid carrier device 2 is placed above the ultrasonic transmitting module, and a plurality of regularly arranged liquid carrier holes (generally a porous plate with many small holes arranged regularly, each small hole containing a number of liquids to be transferred) are arranged on the liquid carrier device 2. In some embodiments, the coupling liquid is water. When the ultrasonic transmitting module is working, the coupling liquid cooled by the coupling liquid circulation system flows into the multi-probe assembly from the 1st and 4th ports of the receiving tank 14 and enters the coupling cavity 13 of the two probes 16. After the coupling liquid fills the coupling cavity 13, it flows out from the small port on the top of the coupling nozzle 15. Due to the surface tension of water, a protruding water bag is formed at the opening of the coupling nozzle 15. After reaching a certain height, the water bag continues to stay along the outer wall of the coupling nozzle 15, flows into the receiving tank 14, and flows back to the coupling liquid circulation system from the 2nd and 3rd ports of the receiving tank 14. 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 device 2, due to the surface adhesion of water, the water bag contacts the bottom of the liquid carrier device 2 and connects with it to form an ultrasonic channel composed of water. The probe 16 is a focused ultrasonic transducer, and its focusing can be physical focusing or lens focusing. The ultrasonic wave waveform emitted by the probe 16 is a focused ultrasonic wave, and under the action of the ultrasonic wave, the liquid to be pipetted can fly away from the liquid carrier 2 without contact.

[0048] The spacing between the probes 16 is an integer multiple of the hole spacing 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 transmitting module to aim at the holes on the liquid-carrying device 2 that need to be pipetted. The two probes 16 each detect the liquid level through echo, and the focus of the probe 16 is aligned with the liquid surface through the high-precision vertical movement of the motor 12. The multi-channel excitation component excites the two probes 16 to emit ultrasonic waves according to the different input parameters of the liquid. The liquid in the liquid-carrying device 2 flies away from the liquid surface under the action of the ultrasonic wave and is received by the target liquid-carrying plate directly above. After completing the pipetting of a group of holes, the displacement system drives the ultrasonic transmitting module to move to the next group of holes that need to be pipetted, and continues the pipetting operation until all pipetting tasks are completed.

[0049] The dual-probe ultrasonic pipetting method performed by the ultrasonic transmitting module of this embodiment can significantly improve the speed and efficiency of ultrasonic pipetting when the ultrasonic acoustic parameters (including frequency, amplitude, pulse length and pulse repetition frequency, etc.) are consistent; 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 be a plurality of probes 16 with the same acoustic parameters working in coordination, and can also support a plurality of probes 16 with different acoustic parameters working together to perform ultrasonic pipetting, and can flexibly control the size of each pipetting, providing a better solution for high-precision control and pipetting efficiency.

[0050] Example 2

[0051] This embodiment provides an ultrasonic liquid transfer method. The ultrasonic liquid transfer device of the present invention performs ultrasonic liquid transfer. The ultrasonic liquid transfer method includes:

[0052] Move the multi-probe assembly so that the probe 16 is aligned with the liquid-carrying hole of the liquid-carrying device 2;

[0053] The motor 12 is started to move the probe 16 so that the focus of the probe 16 is aligned with the liquid surface of the liquid carrying device 2;

[0054] The coupling liquid circulation system is started to allow the coupling liquid to overflow from the coupling nozzle 15, and the coupling liquid contacts the bottom of the liquid carrier device 2 to form an ultrasonic channel;

[0055] Controlling each ultrasonic excitation unit of the ultrasonic excitation assembly to excite the probe 16 to emit ultrasonic waves;

[0056] The ultrasonic excitation unit excites different probes 16 to emit ultrasonic waves at the same or different frequencies.

[0057] An ultrasonic pipetting method using the ultrasonic pipetting device with dual probes 16 as described in Example 1 comprises:

[0058] Move the dual probe assembly so that the two probes 16 are respectively aligned with different liquid-carrying holes on the liquid-carrying device 2;

[0059] The motor 12 is started to move the probe 16 so that the focus of the probe 16 is aligned with the liquid surface of the liquid carrying device 2;

[0060] The coupling liquid circulation system is started to allow the coupling liquid to overflow from the coupling nozzle 15, and the coupling liquid contacts the bottom of the liquid carrier device 2 to form an ultrasonic channel;

[0061] The various ultrasonic excitation units of the ultrasonic excitation assembly are controlled to excite the probe 16 to emit ultrasonic waves.

[0062] The ultrasonic excitation component includes a first ultrasonic excitation unit excitation and a second ultrasonic excitation component, and 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 probe. 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 a first frequency, and the second ultrasonic excitation unit can excite the second probe to emit ultrasonic waves at a second frequency.

[0063] Specifically, the first frequency can be the same as the second frequency or different from the second frequency; when the first frequency is different from the second frequency, the first frequency can be greater than the second frequency or less than the second frequency, thereby stimulating 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 simultaneously to realize the pipetting function, so as to flexibly control the size of each pipetting.

[0064] The ultrasonic pipetting method of the present invention can be used in an ultrasonic pipetting device with more probes 16 to coordinate the work of multiple probes 16 with the same acoustic parameters, or multiple probes 16 with different acoustic parameters can work together to perform ultrasonic pipetting.

[0065] In summary, the present invention provides an ultrasonic liquid transfer device, which is provided with a plurality of probes for emitting ultrasonic waves to separate the liquid on the liquid carrier and fly out vertically, and is received by the target liquid carrier plate directly above it. Each probe is connected to a different ultrasonic excitation unit, and each ultrasonic excitation unit can work independently, support the excitation and setting of a variety of ultrasonic wave shape parameters, and meet the needs of a variety of excitation parameters. Therefore, the ultrasonic liquid transfer device of the present invention can be a plurality of probes with the same acoustic parameters working in coordination, and can also support a plurality of probes with different acoustic parameters working together for ultrasonic liquid transfer, and can flexibly control the size of each liquid transfer, providing a better solution for high-precision control and liquid transfer efficiency. In addition, each probe is also provided 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, and multiple probes can work at the same time and each probe can focus independently, and multiple probes can be flexibly matched to achieve the purpose of providing the use efficiency and applicability of the ultrasonic liquid transfer device. The ultrasonic pipetting method performed by the ultrasonic pipetting device of the present invention can coordinate the work of multiple probes with the same acoustic parameters to improve the speed and efficiency of ultrasonic pipetting; it can also support probes with different acoustic parameters to work simultaneously to realize the pipetting function, so as to flexibly control the size of each pipetting.

[0066] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. In addition to the above embodiments, there may also be different variations. The technical features of the above embodiments may be combined with each other. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principles of the present invention should be included in the protection scope of the present invention.

Claims

1. An ultrasonic liquid transfer device, characterized in that: It comprises an ultrasonic transmitting module and a liquid carrying device, wherein the ultrasonic transmitting module comprises 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, wherein the two or more probes are arranged on the same bracket, the liquid-carrying device is provided with a plurality of liquid-carrying holes, the focus of the probe is aligned with the liquid surface of the liquid-carrying device, the coupling cavity surrounds the probe, the coupling cavity is filled with coupling liquid, the coupling nozzle is a hollow structure, the coupling nozzle is arranged between the probe and the liquid-carrying device, the bottom of the coupling nozzle is open and engaged with the coupling cavity, the top of the coupling nozzle has an opening, the opening surrounds the probe and its diameter is larger than the diameter of the probe, and a gap is formed between the coupling nozzle and the probe; The coupling liquid circulation system allows the coupling liquid to continuously enter the coupling cavity, and the coupling liquid overflows from the coupling nozzle, and the overflowed coupling liquid contacts the bottom of the liquid carrying device; The ultrasonic excitation component is connected to the control circuit, and the ultrasonic excitation component includes two or more ultrasonic excitation units, each of which is connected to the corresponding probe and is used to excite each probe, and the probe is used to emit ultrasonic waves; The multi-probe assembly further includes a containing tank and a sealing tube, wherein the containing tank is connected to the coupling liquid circulation system; the containing tank surrounds the coupling cavity, and the coupling liquid overflowing from the coupling nozzle flows into the containing tank, and the circulating coupling liquid can also play a role in cooling the probe; A through hole is provided at the bottom of the coupling cavity, and 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 tightly combined with the probe.

2. The ultrasonic pipetting device according to claim 1, characterized in that: The ultrasonic excitation unit includes a driving circuit and an excitation circuit, the driving circuit is connected to the control circuit, the excitation circuit is connected to the probe, the control circuit controls the driving 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.

3. The ultrasonic pipetting device according to claim 1, characterized in that: The probe is a focused ultrasonic transducer, and the ultrasonic waveform emitted by the probe is a focused ultrasonic wave.

4. The ultrasonic liquid transfer device according to claim 1, characterized in that: The multi-probe assembly includes a plurality of motors, each of which is connected to a corresponding probe, and the motor drives the probe to move to change the distance between the probe and the liquid-carrying device.

5. The ultrasonic pipetting device according to claim 1, characterized in that: The coupling liquid circulation system comprises a sealed tank, a water pump, a temperature control system, a filter and a vacuum pump. The coupling liquid is stored in the sealed tank. The water pump is connected to the outlet end of the sealed tank. The water pump draws the coupling liquid in the sealed tank to the maintained temperature control system for cooling. 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 that flows back from the multi-probe assembly to the coupling liquid circulation system flows into the filter for filtration, and the vacuum pump is connected to the sealed tank to draw the filtered coupling liquid into the sealed tank.

6. The ultrasonic liquid transfer device according to claim 1, characterized in that: The ultrasonic transmitting module further includes a signal detection component, which is connected to the control circuit and is used to receive a detection signal from the probe; The signal detection component includes two or more signal detection channels, and each of the signal detection channels is connected to a corresponding probe.

7. The ultrasonic pipetting device according to claim 1, characterized in that: The ultrasonic excitation component also includes a power detection unit, which 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 to obtain the ultrasonic excitation signal amplitude.

8. The ultrasonic pipetting device according to claim 1, characterized in that: The spacing between the probes is an integral multiple of the hole spacing of the liquid-carrying holes.

9. An ultrasonic pipetting method, characterized in that: The ultrasonic pipetting device according to any one of claims 1 to 8 is used for ultrasonic pipetting, and the ultrasonic pipetting method comprises: Move the multi-probe assembly so that the probes are aligned with the liquid-carrying holes 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; Starting the coupling liquid circulation system to allow the coupling liquid to 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; The ultrasonic excitation unit excites different probes to emit ultrasonic waves at the same or different frequencies.

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