CN111495455A - Non-contact ultrasonic liquid transfer device and method - Google Patents
Non-contact ultrasonic liquid transfer device and method Download PDFInfo
- Publication number
- CN111495455A CN111495455A CN202010388265.9A CN202010388265A CN111495455A CN 111495455 A CN111495455 A CN 111495455A CN 202010388265 A CN202010388265 A CN 202010388265A CN 111495455 A CN111495455 A CN 111495455A
- Authority
- CN
- China
- Prior art keywords
- ultrasonic
- liquid
- unit
- pipetting
- platform
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Images
Classifications
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/02—Burettes; Pipettes
Abstract
The invention discloses a non-contact ultrasonic liquid transfer device which comprises an ultrasonic energy conversion unit, a source liquid carrying platform and a target liquid carrying platform, wherein the ultrasonic energy conversion unit can generate a focusing sound field under the action of an ultrasonic excitation system, and liquid drops can be accurately and quickly transferred from the source liquid carrying platform to the target liquid carrying platform without using gun head consumables. The invention also discloses a liquid transfer method, which can accurately position the action point of the focusing sound field to the liquid transfer liquid level and accurately adjust the volume of single liquid transfer liquid drop by controlling the relative position of the ultrasonic energy conversion unit and the source liquid carrying platform and the working state and parameters of the ultrasonic excitation system. The high-frequency focused ultrasonic transducer can realize the picoliter pipetting precision, and the large-size focused ultrasonic transducer can further realize the random adjustment of the pipetting precision from picoliter to micro-upgrade; by means of the ultrasonic coupling unit between the ultrasonic transduction unit and the source liquid carrying platform, the maximum transmission of energy can be realized, and heat dissipation can be realized.
Description
Technical Field
The invention relates to the field of synthetic biological experiments, in particular to a non-contact ultrasonic liquid transfer device and a non-contact ultrasonic liquid transfer method.
Background
In the world, the challenges of diseases, environment, energy and the like facing people are becoming more serious, and synthetic biology is praised as one of three subversive technologies in the world. The research goal of synthetic biology is to adopt the engineering concept to design, transform and even re-synthesize organisms and create artificial life bodies with unnatural functions.
At present, in the synthetic biology experiment process, a life body verification experiment is carried out based on a large number of biological experiments, so that a large amount of micro-pipetting operation is needed for allocating and processing the experiment, and pipetting is one of the most common operation tasks in a synthetic biology laboratory. The selection of the correct pipette is a critical step in accurately performing the experiment.
The most widespread method in the industry is to use a pipette, which is a common biological and chemical laboratory tool that creates a partial vacuum in a vessel above the liquid level and draws or discharges the liquid by selectively adjusting the volume of the vacuum. Different accuracies and precisions can be realized by designing various pipette guns, the types of pipette guns include pipette made from simple piece of glass to pipette which is complicated and adjustable or electric controlled, however, the accuracy of measurement is greatly different due to different types. Meanwhile, because the pipetting gun is a contact pipetting method, in the pipetting process, a sample is adhered to the gun head, so that the transferred liquid volume is inaccurate, and a false negative result is easily generated. In addition, because the rifle head of pipette is disposable consumptive material, in order to avoid cross infection, all need special treatment or change after every use, consequently can need a large amount of consumptive materials to support the experiment, the expense is comparatively expensive during the large-scale use.
The existing electromagnetic control-based non-contact pipetting technology can realize non-contact pipetting of a pipetting needle and a target reaction well, but the pipetting liquid still contacts with the pipetting needle, so that the type of the pipetting liquid is limited, and the practical application of the technology is limited. Therefore, non-contact micropipetting is a key technology of particular importance in the field of biology.
Disclosure of Invention
In view of the defects in the prior art, the invention provides a non-contact ultrasonic pipetting device and a non-contact ultrasonic pipetting method, which realize non-contact pipetting by adopting a focusing sound field, avoid the problems of expensive experiment cost and inaccurate pipetting caused by using gun head consumables, do not need to contact pipetting liquid, and do not limit the types of the pipetting liquid, thereby expanding the application range of pipetting modes.
In order to achieve the purpose, the invention adopts the following technical scheme:
a non-contact ultrasonic pipetting device comprising an ultrasonic pipetting module comprising an ultrasonic transduction unit, a source carrier liquid platform and a target carrier liquid platform; the ultrasonic transduction unit is used for emitting ultrasonic waves to the source liquid carrying platform to generate a focusing sound field, moving relative to the source liquid carrying platform to change the distance between the ultrasonic waves and the liquid level of the source liquid carrying platform, and transferring liquid drops with target volumes from the source liquid carrying platform to the target liquid carrying platform when the amplitude of ultrasonic echoes reaches a specific value.
As one embodiment, the non-contact ultrasonic pipetting device further comprises a moving module and a control module, wherein the moving module is used for adjusting the relative positions of the ultrasonic transduction unit and the source carrier liquid platform; the control module is used for changing the distance between the ultrasonic transduction unit and the liquid level of the source carrier liquid platform according to the amplitude of an ultrasonic echo signal until the amplitude of the ultrasonic echo reaches a specific value when the ultrasonic transduction unit and the source carrier liquid platform are aligned, and then adjusting the ultrasonic signal parameter of ultrasonic waves sent by the ultrasonic transduction unit so as to adjust the volume of the single liquid transfer droplet to the target volume.
In one embodiment, the ultrasonic transduction unit is an electronic phased array focusing transducer, and the control module further adjusts the position of the focusing focus on the liquid surface by adjusting parameters of the electronic phased array focusing transducer to rapidly move the focusing beam synthesized by the electronic phased array focusing transducer on the source liquid-carrying platform.
As one embodiment, the ultrasonic transduction unit is a large-size high-frequency focusing ultrasonic transducer, wherein the diameter of the ultrasonic transduction unit is larger than or equal to 5mm, the frequency of the ultrasonic transduction unit is larger than 1MHZ, the pipetting precision of the ultrasonic pipetting device is up to picoliter, and the pipetting precision is arbitrarily adjustable from picoliter to micro-upgrading.
In one embodiment, the ultrasonic transduction unit is composed of one or more ultrasonic transducers, and/or the working frequency of the ultrasonic transduction unit is one or more.
As one embodiment, the ultrasonic transduction unit is a single-array element transducer, a linear array transducer, a planar array transducer or a ring array transducer; and/or when the ultrasonic transduction unit comprises a plurality of sub-transducers, the arrangement shape of the sub-transducers is a polygon, a circle or an ellipse.
In one embodiment, the ultrasonic pipetting module further comprises an ultrasonic coupling unit for propagating ultrasonic energy, wherein the ultrasonic coupling unit comprises a housing and a sound wave coupling agent, and the sound wave coupling agent is filled in a space enclosed by the housing and the ultrasonic transduction unit and is used for contacting with the source liquid-carrying platform.
As one embodiment, the shell comprises an inner cylinder and an outer cylinder, the top ends of the inner cylinder and the outer cylinder face the source carrier liquid platform, and the ultrasonic energy conversion unit is fixed at the top end of the inner cylinder to seal the top end of the inner cylinder; the inner cylinder body is arranged in the outer cylinder body and can move relative to the axial direction of the outer cylinder body to selectively approach or depart from the source liquid carrying platform, and the sound wave coupling agent is filled between the outer cylinder body and the top end of the inner cylinder body.
As one embodiment, the ultrasonic coupling unit further comprises a peristaltic pump and a cooling cavity communicated with the top end of the outer cylinder, the acoustic wave coupling agent is further filled in the cooling cavity, and the peristaltic pump drives the acoustic wave coupling agent to circulate in the top end of the outer cylinder and the cooling cavity.
Another object of the present invention is to provide a non-contact ultrasonic pipetting method, comprising:
a ranging mode comprising:
the ultrasonic energy conversion unit sends ultrasonic waves to the source liquid carrying platform to generate a focusing sound field;
changing the distance between the ultrasonic energy conversion unit and the liquid level of the source carrier liquid platform according to the amplitude of the ultrasonic echo signal until the amplitude of the ultrasonic echo reaches a specific value;
a pipetting mode comprising:
when the amplitude of the ultrasonic echo reaches a specific value, adjusting the parameters of the ultrasonic excitation waveform to adjust the volume of the liquid-transfer drop;
and increasing the power of an ultrasonic transduction unit to transfer the liquid drop from the source liquid carrying platform to the target liquid carrying platform.
The non-contact ultrasonic liquid transfer device can realize liquid movement in a non-contact manner by adopting the ultrasonic transduction unit, the ultrasonic transduction unit changes the distance between the ultrasonic transduction unit and the liquid level of the source liquid carrying platform according to the amplitude of the ultrasonic echo signal and generates a focusing sound field when the amplitude of the ultrasonic echo reaches a specific value, liquid drops can be accurately and quickly transferred from the source liquid carrying platform to the target liquid carrying platform without using gun head consumables so as to generate liquid with a target volume, and the liquid adding mode is not only direct and accurate, but also has excellent repeatability.
In addition, by controlling the relative position of the ultrasonic energy conversion unit and the source liquid carrying platform and the working state and parameters of the ultrasonic excitation system, the action point of the focused sound field can be accurately positioned on the liquid transfer surface, and the volume of the single liquid transfer drop can be accurately adjusted to the target volume. The high-frequency focused ultrasonic transducer can realize the picoliter pipetting precision, and on the basis, the large-size focused ultrasonic transducer can further realize the random adjustment of the pipetting precision from the picoliter to the micro-upgrading range; by means of the ultrasonic coupling unit between the ultrasonic transduction unit and the source liquid carrying platform, the maximum transmission of energy can be realized, and heat dissipation can be realized.
Drawings
FIG. 1 is a block diagram of a non-contact ultrasonic pipetting device according to an embodiment of the invention;
FIG. 2 is a block diagram of a non-contact ultrasonic pipetting method according to an embodiment of the invention;
FIG. 3 is a schematic flow chart of the operation of a non-contact ultrasonic pipetting device according to an embodiment of the invention;
FIG. 4 is a schematic diagram of the pipetting principle of an ultrasonic transducer unit of an embodiment of the invention;
fig. 5 is a schematic diagram of a laminated structure of an ultrasonic transducer unit according to an embodiment of the present invention;
FIG. 6 is a schematic view of a portion of a non-contact ultrasonic pipetting device according to an embodiment of the invention;
the numbers in the figures illustrate the following:
1-an ultrasonic excitation system; 100-an ultrasonic pipetting module; 2-an ultrasonic transduction unit; 21-a backing; 22-a piezoelectric layer; 23-a matching layer; 3-an ultrasound coupling unit; 31-space; 32-a cooling chamber; 4-source carrier platform; 5-a target carrier liquid platform; 6-a moving module; 61-a loading liquid moving module; 62-a transducer movement module; 7-a control module; 9-inner cylinder; 10-outer cylinder; 11-sealing ring.
Detailed Description
In order to make the objects, technical solutions and advantages of the present invention more apparent, the present invention is further described in detail below with reference to the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are merely illustrative of the invention and are not intended to limit the 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, where the ultrasonic pipetting module 100 may specifically include an ultrasonic excitation system 1, an ultrasonic transduction unit 2, an ultrasonic coupling unit 3, and a source carrier liquid platform 4 and a target carrier liquid platform 5 that are sequentially disposed above the ultrasonic transduction unit 2 from bottom to top, where the ultrasonic excitation system 1 is connected to the ultrasonic transduction unit 2 and may be used to drive the ultrasonic transduction unit 2 to emit ultrasonic waves to generate a focused sound field, so as to implement an ultrasonic radiation force action on a pipetting liquid level at a predetermined position on the source carrier liquid platform 4, the source carrier liquid platform 4 and the target carrier liquid platform 5 are oppositely disposed, the source carrier liquid platform 4 has a pipetting liquid level, and under the action of the focused sound field, a liquid drop may be contactlessly transferred from the source carrier liquid platform 4 to a specific. The source carrier liquid platform 4 and the target carrier liquid platform 5 can both be of a porous plate structure, the two are provided with holes formed in an array, and liquid drops of a target volume in the holes of the source carrier liquid platform 4, which are just opposite to the ultrasonic energy conversion unit 2, can be transferred to the target carrier liquid platform 5 under the action of ultrasonic radiation force, so that liquid transfer is realized.
The ultrasonic excitation system 1 comprises an ultrasonic signal generator and a power amplifier, the control module 7 can arbitrarily adjust ultrasonic signal parameters (including ultrasonic frequency, ultrasonic energy, ultrasonic pulse length, ultrasonic pulse repetition frequency and the like) of the ultrasonic excitation system 1, the ultrasonic signal parameters correspond to ultrasonic signal parameters of ultrasonic waves emitted by the ultrasonic energy conversion unit 2, and the volume of liquid drops for single liquid transfer can be adjusted by adjusting the ultrasonic signal parameters of the ultrasonic waves, so that high-precision liquid transfer is realized. The ultrasonic coupling unit 3 is arranged between the ultrasonic transduction unit 2 and the source liquid bearing platform 4, and ensures that ultrasonic energy emitted by the ultrasonic transduction unit 2 is better transmitted to the source liquid bearing platform 4.
It will be appreciated that in other embodiments the ultrasonic excitation system 1 may not be included in the ultrasonic pipetting device, but may be a separate structure that may be assembled into the ultrasonic pipetting device for connection with the ultrasonic transducer unit 2 as desired.
In addition to the ultrasonic pipetting module 100, the non-contact ultrasonic pipetting device may further include a moving module 6 and a control module 7, and the control module 7 serves as a control center of the entire pipetting device, and may control the working states and parameter modulation of the ultrasonic excitation system 1, the ultrasonic transducer unit 2, the source carrier liquid platform 4, the target carrier liquid platform 5, the moving module 6, and the like, so as to implement full-automatic control.
The moving module 6 can be relatively fixed with at least one of the ultrasonic energy conversion unit 2 and the source liquid carrying platform 4, and the action point of the focusing sound field of the ultrasonic energy conversion unit 2 is positioned on the liquid transfer liquid level at the preset position of the source liquid carrying platform 4 by adjusting the relative position of the ultrasonic energy conversion unit 2 and the source liquid carrying platform 4, so that the next liquid transfer action is conveniently carried out.
With reference to fig. 2 to 4, the working modes of the non-contact ultrasonic pipetting device of the present embodiment include a distance measurement mode S01 and a pipetting mode S02, in the distance measurement mode S01, the power of the ultrasonic transducer unit 2 is small, liquid droplets are not ejected, and only focusing of a focused sound field on a liquid surface is achieved; in the pipetting mode S02, the control module 7 adjusts parameters of the ultrasonic excitation system 1 to increase the power of the ultrasonic transducer unit 2, so that the liquid drop can be ejected from the liquid surface.
The non-contact ultrasonic pipetting method of the present embodiment will be specifically described below:
initially, the ultrasonic transducer unit 2 and the source carrier liquid platform 4 are not aligned in the horizontal direction, the vertical direction.
Firstly, 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 close to each other, and finally, the ultrasonic transducer unit 2 moves to a position right below the specific pipetting level of the source carrier liquid platform 4.
Subsequently, as shown in step b of fig. 3, in the distance measuring mode S01, the control module 7 controls the ultrasonic transducer unit 2 to operate to locate the longitudinal distance between the ultrasonic transducer unit 2 and the pipetting liquid level, and the moving module 6 can move the ultrasonic transducer unit 2 longitudinally (for example, the source liquid carrying platform 4 can also be moved) according to the measured distance, when the ultrasonic echo amplitude reaches a specific value, i.e. it is stated that the action point of the focused sound field emitted by the ultrasonic transducer unit 2 is located on the pipetting liquid level at a predetermined position. Here, the "specific value" indicates a specific value, and does not necessarily refer to an absolute maximum value of the echo amplitude, and in an actual process, the specific value may be adjusted according to an actual situation, that is, the "specific value" may be the absolute maximum value, or may be a value close to the absolute maximum value, for example, 80% of the absolute maximum value. Specifically, in the distance measurement mode S01, the ultrasonic transduction unit 2 sends an ultrasonic wave toward the upward source carrier liquid platform 4, receives an ultrasonic echo in real time, adjusts the longitudinal distance between the ultrasonic transduction unit 2 and the source carrier liquid platform 4 through the control module 7, and determines that the action point of the focused sound field is positioned on the liquid transfer level at the predetermined position when the amplitude of the ultrasonic echo reaches the specific value. Thus, the operation corresponding to the distance measurement mode S01 is completed, and the liquid droplet can be ejected by switching to the liquid transfer mode S02. FIG. 4 is a schematic view showing a state where pipetting is performed after the focused acoustic field is positioned on the pipetting liquid level.
Next, the control module 7 switches the operating state of the pipetting device to the pipetting mode S02 by increasing the power of the ultrasonic transducer unit 2, as in step c of fig. 3, the control module 7 first adjusts the volume of the single pipetting drop to the target volume by adjusting the parameters of the ultrasonic signal of the ultrasonic excitation system 1, and then the drop is ejected from the source carrier platform 4 under the action of the focused acoustic field (as in step d of fig. 3), and through this series of steps, the pipetting process with high precision can be ensured.
Here, the adjustment process of the volume of the single pipette drop can be realized by adjusting parameters of the excitation waveform of the ultrasonic excitation system 1, such as the voltage amplitude, the number of cycles, and the number of cycles.
Because this embodiment adopts ultrasonic transduction unit 2 as the core of supersound liquid removal module 100 to move the liquid part, at the actual liquid in-process that moves, only need to move ultrasonic transduction unit 2 to the preset position realization alignment back of source carrier liquid platform 4, can utilize supersound liquid removal module 100 to produce the focus sound field and realize contactless liquid removal process, need not to use rifle head consumptive material and can follow a source position application of sample of source carrier liquid platform 4 to a target location of target carrier liquid platform 5, the change of consumptive material has both been reduced, the cost is reduced, avoid the sample adhesion on the rifle head again, realize accurate liquid removal process. In addition, because the ultrasonic transduction unit and the source carrier liquid platform are aligned firstly and then the focus of the ultrasonic transduction unit is adjusted to the liquid transfer level, the volume of the single liquid transfer drop can be adjusted according to the requirement before liquid is pumped, and the final liquid transfer precision is ensured.
The present embodiment illustrates a situation where the movement module 6 is fixed with both the ultrasound transduction unit 2 and the source carrier liquid platform 4, and can move both horizontally and vertically independently, respectively. Specifically, the moving module 6 comprises a loading liquid moving module 61 and a transducer moving module 62, the loading liquid moving module 61 can drive the target loading liquid platform 5 and the source loading liquid platform 4 to move and transport in the liquid transfer device, the transducer moving module 62 can drive the ultrasonic transducer unit 2 to move at any position in the liquid transfer device, and the moving precision of the moving module 6 is controlled within 1 μm. Under the control of the control module 7, the moving module 6 may operate to adjust the relative positions of the ultrasonic transducer unit 2 and the source carrier liquid platform 4 accordingly, for example, only the ultrasonic transducer unit 2 may be moved, only the source carrier liquid platform 4 may be moved, or both the ultrasonic transducer unit 2 and the source carrier liquid platform 4 may be moved, so that the ultrasonic transducer unit 2 and the source carrier liquid platform 4 approach and depart from each other as required.
It is understood that in other embodiments, the moving module 6 may include only one of the loading liquid moving module 61 and the transducer moving module 62, and may also perform a similar effect of adjusting the relative position of the ultrasonic transducer unit and the source loading liquid platform, which is not limited herein.
In order to better ensure the pipetting precision, the ultrasonic transducer unit 2 of the non-contact ultrasonic pipetting device of the embodiment is a large-size high-frequency focused ultrasonic transducer, wherein the large size means that the diameter of the ultrasonic transducer unit 2 is greater than or equal to 5mm, and the high frequency means that the frequency of the ultrasonic transducer unit 2 is greater than 1 MHZ. Furthermore, the frequency range of the ultrasonic energy conversion unit 2 can be 1MHz to 1GHz, the bandwidth is more than 50%, the ultrasonic energy converter with large size and high frequency focusing not only has smaller focus size, but also has larger output sound radiation force, wherein, the high frequency characteristic of the ultrasonic energy converter ensures that the pipetting precision can reach the pico-upgrade to the maximum, the high bandwidth characteristic of the ultrasonic energy converter can also ensure that the energy converter has higher output sound radiation force in a larger frequency range, and the requirements of the ultrasonic energy converter and the ultrasonic energy converter can realize the arbitrary adjustment of the pipetting precision from the pico-upgrade to the micro-upgrade in a larger range. By precisely controlling the ultrasonic acoustic parameters, the pipetting device can controllably control the acoustic energy in a larger range and intelligently select the size of each sample application droplet according to the experimental requirements of a user.
It should be noted that the ultrasonic transduction unit 2 may be a focused ultrasonic transducer, or a plurality of focused ultrasonic transducers working together; it may operate at a single frequency or multiple frequencies in concert. According to the focusing mode of the ultrasonic transducer, the ultrasonic transducer is a physical focusing transducer or an electronic phased array focusing transducer, the focusing mode of the physical focusing transducer is ultrasonic transducers of various focusing modes such as acoustic lens focusing, self-focusing and other focusing modes such as acoustic superstructure focusing, when the ultrasonic transducer is selected from the electronic phased array focusing transducer, the electronic phased array focusing mode can adjust the parameters of the electronic phased array focusing transducer through the control module 7, so that a focusing beam synthesized by the electronic phased array focusing transducer can rapidly move on a source carrier liquid platform without moving or rotating an ultrasonic energy conversion unit to adjust the position of a focusing focus on a liquid level, accurate and rapid focus positioning can be realized, and automatic control can be better realized. The ultrasonic transduction unit 2 includes, but is not limited to, a piezoelectric ultrasonic transducer, a capacitive micromachined ultrasonic transducer (cMUT), a piezoelectric micromachined ultrasonic transducer (pMUT), and other types of ultrasonic transducers according to the type of the ultrasonic transducer.
The ultrasonic transducer unit 2 may be a single-element transducer, a linear array transducer, a planar array transducer or a circular array transducer, and when the ultrasonic transducer unit 2 includes a plurality of sub-transducers, the arrangement shape of the sub-transducers may be, but is not limited to, a square, a circle, an ellipse, etc.
As shown in fig. 5, a schematic diagram of a piezoelectric ultrasonic transducer is shown. The ultrasonic transducer unit 2 mainly comprises a backing 21, a piezoelectric layer 22 and a matching layer 23, wherein a protective layer (not shown) can be further arranged on the outer surface of the matching layer 23, and the piezoelectric layer 22 and the matching layer 23 are sequentially arranged above the backing 21 from bottom to top. Matching layer 23 may comprise one or more layers of structure.
The ultrasonic coupling unit 3 comprises a housing (not shown) and an acoustic wave coupling agent (not shown), and as shown in fig. 1 and 6, the housing and the ultrasonic transducer unit 2 enclose a space 31 which can be filled with the acoustic wave coupling agent, and the acoustic wave coupling agent is filled in the space 31. When the ultrasonic coupling unit 3 is moved to a proper position below the source carrier liquid platform 4, the housing contacts the source carrier liquid platform 4, the sound wave coupling agent in the space 31 is filled between the ultrasonic transduction unit 2 and the source carrier liquid platform 4 and serves as an ultrasonic coupling medium between the ultrasonic transduction unit 2 and the source carrier liquid platform 4, attenuation of sound wave energy in a propagation process can be reduced, and meanwhile, the sound wave coupling agent also serves as a heat dissipation medium to dissipate heat of the ultrasonic transduction unit 2 arranged in the space 31. The acoustic wave couplant can be water, oil, and similar flowable ultrasonic couplants.
Referring to fig. 6, the housing may specifically include an inner cylinder 9 and an outer cylinder 10, the top ends of the inner cylinder 9 and the outer cylinder 10 face the source carrier liquid platform 4 above, and the ultrasonic transducer unit 2 is fixed at the top end of the inner cylinder 9 to close the top end of the inner cylinder 9. The top end face of outer barrel 10 contacts with source carrier liquid platform 4 and cooperates, and interior barrel 9 is located in outer barrel 10 and can be close to or keep away from source carrier liquid platform 4 for outer barrel 10's axial displacement selectively, encloses into the space 31 that can hold the sound wave couplant between interior barrel 9, ultrasonic transduction unit 2, the outer barrel 10, and when ultrasonic transduction unit 2 was close to source carrier liquid platform 4 and made outer barrel 10 contact source carrier liquid platform 4, the sound wave couplant was filled between ultrasonic transduction unit 2 and source carrier liquid platform 4.
Here, the inner cylinder 9 and the outer cylinder 10 are combined in a screw-fit manner, specifically, an external thread is provided on the outer circumferential surface of the inner cylinder 9, an internal thread is provided on the inner circumferential surface of the outer cylinder 10, and the inner cylinder 9 moves along the axial direction of the outer cylinder 10 during the rotation of the inner cylinder 9 relative to the outer cylinder 10, so that the distance between the ultrasonic transducer unit 2 and the pipetting liquid level can be accurately adjusted in the direction away from or far from the source liquid carrying platform 4 according to actual requirements, and the action point of the focusing sound field can be conveniently positioned on the pipetting liquid level.
Specifically, a through hole may be formed at the top end of the inner cylinder 9, the ultrasonic transducer unit 2 is inserted into the through hole from below and closes the through hole, the through hole is preferably a stepped hole with a large inside and a small outside, and the ultrasonic transducer unit 2 abuts against the inner surface of the stepped hole of the through hole.
In order to ensure the sealing effect of the acoustic wave coupling agent between the inner cylinder 9 and the outer cylinder 10, the ultrasonic coupling unit 3 further includes a sealing ring 11, and the sealing ring 11 is sleeved on the outer circumferential surface of the inner cylinder 9 and is elastically compressed between the inner cylinder 9 and the outer cylinder 10. Preferably, the outer circumferential surface of the inner cylinder 9 is provided with a recessed annular groove, 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 being disengaged. It is understood that the number of the sealing rings 11 is not limited in the present embodiment, and the number of the sealing rings 11 may be larger.
As shown in fig. 6, the ultrasonic coupling unit 3 further includes a peristaltic pump (not shown) and a cooling cavity 32 communicating with the space 31, the acoustic wave couplant is filled in the cooling cavity 32 in addition to the space 31, and the peristaltic pump drives the acoustic wave couplant to circulate in the space 31 and the cooling cavity 32. The both ends in space 31 are connected simultaneously to cooling chamber 32, under the effect of peristaltic pump, the sound wave couplant that flows out from space 31 flows into cooling chamber 32 from the interface of one end, flow in from the other end in space 31 behind cooling chamber 32 circulation heat dissipation to realize radiating medium's circulation flow, the velocity of flow through the radiating medium of peristaltic pump control can control the radiating rate, the sound wave couplant takes away the heat that produces in 2 working processes of ultrasonic transducer unit, flow in once more after cooling chamber 32 dispels the heat, realize quick circulation heat dissipation.
The space 31 is formed at the top ends of the inner cylinder 9 and the outer cylinder 10, the interface of the cooling cavity 32 communicated with the space 31 is preferably located on the wall of the outer cylinder 10 close to the top end, the end part of the ultrasonic transducer unit 2 extends out of the end face of the inner cylinder 9, the sound wave coupling agent flowing through the two opposite sides of the top end of the outer cylinder 10 can timely take away heat generated in the working process of the ultrasonic transducer unit 2, and the heat dissipation effect is good.
When the moving module 6 works to enable the ultrasonic transduction unit 2 and the source carrier liquid platform 4 to be close to each other, the ultrasonic transduction unit 2 is opposite to the liquid transfer surface of the source carrier liquid platform 4 above in a distance measurement mode, and an action point of a focusing sound field is positioned on the liquid transfer surface, then the control module 7 drives the ultrasonic transduction unit 2 to generate the focusing sound field by adjusting the working state and parameters of the ultrasonic excitation system 1, and the focusing sound field generated by the ultrasonic transduction unit 2 transfers liquid drops from the source carrier liquid platform 4 to the target carrier liquid platform 5. In the process, the control module 7 controls the flow rate of the acoustic wave coupling agent circulating in the space 31 and the cooling cavity 32 by controlling the parameters of the peristaltic pump, so as to control the heat dissipation speed.
The non-contact ultrasonic liquid transfer device can realize liquid movement in a non-contact manner by adopting the ultrasonic energy conversion unit, changes the distance between the ultrasonic energy conversion unit and the liquid level of the source liquid carrying platform according to the amplitude of the ultrasonic echo signal, generates a focusing sound field when the amplitude of the ultrasonic echo reaches a specific value, can accurately and quickly transfer liquid drops from the source liquid carrying platform to the target liquid carrying platform without using gun head consumables so as to generate liquid with a target volume, and has a direct and accurate liquid adding mode and excellent repeatability. In addition, the invention can accurately position the action point of a focusing sound field to the liquid transfer surface and accurately adjust the volume of single liquid transfer drop by controlling the relative position of the ultrasonic energy conversion unit and the source liquid carrying platform and the working state and parameters of the ultrasonic excitation system. The high-frequency focused ultrasonic transducer can realize the picoliter pipetting precision, and on the basis, the large-size focused ultrasonic transducer can further realize the random adjustment of the pipetting precision from the picoliter to the micro-upgrading range; by means of the ultrasonic coupling unit between the ultrasonic transduction unit and the source liquid carrying platform, the maximum transmission of energy can be realized, and heat dissipation can be realized.
The foregoing is directed to embodiments of the present application and it is noted that numerous modifications and adaptations may be made by those skilled in the art without departing from the principles of the present application and are intended to be within the scope of the present application.
Claims (10)
1. A non-contact ultrasonic pipetting device 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 transduction unit (2) is used for emitting ultrasonic waves to the source liquid carrying platform (4) to generate a focused sound field, moving relative to the source liquid carrying platform (4) to change the distance between the ultrasonic waves and the liquid level of the source liquid carrying platform (4), and transferring liquid drops of a target volume from the source liquid carrying platform (4) to the target liquid carrying platform (5) when the amplitude of ultrasonic echo reaches a specific value.
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 for adjusting the relative position of the ultrasonic transduction unit (2) and the source liquid-carrying platform (4), the control module (7) is used for changing the distance between the ultrasonic transduction unit (2) and the liquid level of the source liquid-carrying platform (4) according to the amplitude of an ultrasonic echo signal until the amplitude of the ultrasonic echo reaches a specific value when the ultrasonic transduction unit (2) and the source liquid-carrying platform (4) are aligned, and then adjusting the ultrasonic signal parameter of the ultrasonic pipetting sent by the ultrasonic transduction unit (2) to adjust the volume of a single drop to the target volume.
3. 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) further adjusts the position of the focusing focus on the liquid surface by adjusting parameters of the electronic phased array focusing transducer such that the focusing beam synthesized by the electronic phased array focusing transducer is rapidly moved on the source carrier liquid platform (4).
4. Non-contact ultrasonic pipetting device according to claim 2, characterized in that the ultrasonic transducer unit (2) is a large-sized high-frequency focused ultrasonic transducer, the diameter of the ultrasonic transducer unit (2) is larger than or equal to 5mm, the frequency of the ultrasonic transducer unit (2) is larger than 1 MHZ; the ultrasonic pipetting device has the pipetting precision reaching the pico liter level, and the pipetting precision can be adjusted from the pico liter level to the micro-upgrade level.
5. Non-contact ultrasonic pipetting device according to claim 2, characterized in that the ultrasonic transducer unit (2) consists of one or more ultrasonic transducers and/or that the operating frequency of the ultrasonic transducer unit (2) is one or more.
6. Non-contact ultrasonic pipetting device according to claim 2, characterized in that the ultrasonic transducing unit (2) is a single element transducer, a linear array transducer, a planar array transducer or a circular array transducer; and/or when the ultrasonic transduction unit (2) comprises a plurality of sub-transducers, the arrangement shape of the sub-transducers is polygonal, circular or elliptical.
7. 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, the ultrasonic coupling unit (3) comprising a housing and a sonic couplant filled in a space enclosed by the housing and the ultrasonic transducing unit (2) for contacting the source carrier liquid platform (4).
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 top ends of the inner cylinder (9) and the outer cylinder (10) are opposite to the source carrier liquid platform (4), and the ultrasonic transducer unit (2) is fixed at the top end of the inner cylinder (9) to close the top end of the inner cylinder (9); the inner cylinder (9) is arranged in the outer cylinder (10) and can move relative to the axial direction of the outer cylinder (10) to selectively approach or depart from the source liquid carrying platform (4), and the acoustic wave coupling agent 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, wherein the ultrasonic coupling unit (3) further comprises a peristaltic pump and a cooling chamber (32) communicating with the top end of the outer cylinder (10), the acoustic wave couplant is further filled in the cooling chamber (32), and the peristaltic pump drives the acoustic wave couplant to circulate in the top end of the outer cylinder (10) and the cooling chamber (32).
10. A non-contact ultrasonic pipetting method, comprising:
a ranging mode comprising:
the ultrasonic energy conversion unit (2) sends ultrasonic waves to the source liquid carrying platform (4) to generate a focusing sound field;
changing the distance between the ultrasonic energy conversion unit (2) and the liquid level of the source liquid carrying platform (4) according to the amplitude of the ultrasonic echo signal until the amplitude of the ultrasonic echo reaches a specific value;
a pipetting mode comprising:
when the amplitude of the ultrasonic echo reaches a specific value, adjusting the parameters of the ultrasonic excitation waveform to adjust the volume of the liquid-transfer drop;
increasing the power of the ultrasonic transduction unit (2) to transfer droplets from the source carrier platform (4) to the target carrier platform (5).
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010388265.9A CN111495455A (en) | 2020-05-09 | 2020-05-09 | Non-contact ultrasonic liquid transfer device and method |
| PCT/CN2020/091026 WO2021227093A1 (en) | 2020-05-09 | 2020-05-19 | Non-contact ultrasonic pipetting device and method |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010388265.9A CN111495455A (en) | 2020-05-09 | 2020-05-09 | Non-contact ultrasonic liquid transfer device and method |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN111495455A true CN111495455A (en) | 2020-08-07 |
Family
ID=71866819
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202010388265.9A Pending CN111495455A (en) | 2020-05-09 | 2020-05-09 | Non-contact ultrasonic liquid transfer device and method |
Country Status (2)
| Country | Link |
|---|---|
| CN (1) | CN111495455A (en) |
| WO (1) | WO2021227093A1 (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112526003A (en) * | 2020-11-30 | 2021-03-19 | 合肥工业大学 | Automatic pouring and recycling device and method for couplant of ultrasonic probe |
| CN114308156A (en) * | 2021-12-23 | 2022-04-12 | 深圳先进技术研究院 | Ultrasonic liquid transfer device and method |
| CN114768907A (en) * | 2022-04-12 | 2022-07-22 | 深圳欢影医疗科技有限公司 | Ultrasonic liquid transfer method and system based on annular array ultrasonic transducer |
| WO2023004795A1 (en) * | 2021-07-30 | 2023-02-02 | 中国科学院深圳先进技术研究院 | Ultrasonic pipetting apparatus and method |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6925856B1 (en) * | 2001-11-07 | 2005-08-09 | Edc Biosystems, Inc. | Non-contact techniques for measuring viscosity and surface tension information of a liquid |
| CN104667439A (en) * | 2013-11-27 | 2015-06-03 | 重庆融海超声医学工程研究中心有限公司 | Focusing ultrasonic treatment head and ultrasonic treatment equipment |
| US10325768B1 (en) * | 2015-09-03 | 2019-06-18 | Labcyte Inc. | Focused acoustic radiation for rapid sequential ejection of subwavelength droplets |
| CN111111585A (en) * | 2020-01-08 | 2020-05-08 | 杭州电子科技大学 | Non-contact type multi-focus ultrasonic phased array suspension liquid transfer method and system |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2480333A2 (en) * | 2009-09-21 | 2012-08-01 | University Of Dundee | Apparatus and method for the manipulation of objects using ultrasound |
| CN105214742B (en) * | 2015-10-10 | 2017-10-31 | 中国科学院深圳先进技术研究院 | The method of microfluid system and manipulation particulate based on artificial structure's sound field |
| CN107754963A (en) * | 2017-10-31 | 2018-03-06 | 南京航空航天大学 | Ultrasonic pipettor |
| EP3867635A4 (en) * | 2018-10-17 | 2022-07-13 | Hemex Health, Inc. | Diagnostic systems and methods |
| CN110823769A (en) * | 2019-12-06 | 2020-02-21 | 中国科学院声学研究所 | Ultrasonic suspension type liquid surface tension coefficient measuring method and device |
-
2020
- 2020-05-09 CN CN202010388265.9A patent/CN111495455A/en active Pending
- 2020-05-19 WO PCT/CN2020/091026 patent/WO2021227093A1/en active Application Filing
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6925856B1 (en) * | 2001-11-07 | 2005-08-09 | Edc Biosystems, Inc. | Non-contact techniques for measuring viscosity and surface tension information of a liquid |
| CN104667439A (en) * | 2013-11-27 | 2015-06-03 | 重庆融海超声医学工程研究中心有限公司 | Focusing ultrasonic treatment head and ultrasonic treatment equipment |
| US10325768B1 (en) * | 2015-09-03 | 2019-06-18 | Labcyte Inc. | Focused acoustic radiation for rapid sequential ejection of subwavelength droplets |
| CN111111585A (en) * | 2020-01-08 | 2020-05-08 | 杭州电子科技大学 | Non-contact type multi-focus ultrasonic phased array suspension liquid transfer method and system |
Non-Patent Citations (2)
| Title |
|---|
| LABCYTE: "Echo 555 liquid hander", 《HTTPS://WWW.LABCYTE.COM/CN/PRODUCTS/LIQUIDHANDLING/ECHO-555-LIQUID-HANDLER》 * |
| 腾讯视频，LIBBY: ""贝克曼库尔特Echo纳升级移液系统——新一代移液技术"", 《HTTPS://V.QQ.COM/X/PAGE/J3014Q99IMD.HTML》 * |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112526003A (en) * | 2020-11-30 | 2021-03-19 | 合肥工业大学 | Automatic pouring and recycling device and method for couplant of ultrasonic probe |
| CN112526003B (en) * | 2020-11-30 | 2022-06-07 | 合肥工业大学 | Automatic pouring and recycling device and method for couplant of ultrasonic probe |
| WO2023004795A1 (en) * | 2021-07-30 | 2023-02-02 | 中国科学院深圳先进技术研究院 | Ultrasonic pipetting apparatus and method |
| CN114308156A (en) * | 2021-12-23 | 2022-04-12 | 深圳先进技术研究院 | Ultrasonic liquid transfer device and method |
| WO2023116461A1 (en) * | 2021-12-23 | 2023-06-29 | 深圳先进技术研究院 | Ultrasonic pipetting device and method |
| CN114768907A (en) * | 2022-04-12 | 2022-07-22 | 深圳欢影医疗科技有限公司 | Ultrasonic liquid transfer method and system based on annular array ultrasonic transducer |
| CN114768907B (en) * | 2022-04-12 | 2024-03-12 | 深圳欢影医疗科技有限公司 | Ultrasonic pipetting method and system based on annular array ultrasonic transducer |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2021227093A1 (en) | 2021-11-18 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN111495455A (en) | Non-contact ultrasonic liquid transfer device and method | |
| CN106661535B (en) | Apparatus for ultrasonic testing | |
| JP5775929B2 (en) | Ultrasonic transducer for selectively generating ultrasonic and heat | |
| RU2554572C2 (en) | Sample treatment with focused acoustic energy | |
| CA3064616A1 (en) | Steerable high-intensity focused ultrasound (hifu) elements | |
| CN108593783B (en) | Dual-frequency confocal ultrasonic transducer | |
| WO2009124290A1 (en) | Methods and systems for ultrasonic coupling using ultrasonic radiation pressure | |
| US20230338942A1 (en) | Focused acoustic radiation for the ejection of subwavelength droplets | |
| CN113070106A (en) | Ultrasonic pipetting device and method for realizing ultrasonic pipetting based on phased array technology | |
| CN101675470A (en) | Methods and apparatuses of aperture control and multiplexing with adjustable fluid lenses | |
| US20130245444A1 (en) | Synchronously pumped ultrasonic waves and shear wave generation by same | |
| CN114308156B (en) | Ultrasonic liquid transfer device and method | |
| US20170107506A1 (en) | System and methods for applying controlled low-intensity ultrasound to a cell culture | |
| US20210039128A1 (en) | Acoustic droplet ejection | |
| CN113522388A (en) | Ultrasonic liquid transfer device and method | |
| Tang et al. | Nozzleless acoustic droplet ejector with electrically tunable droplet size for picking and placing semiconductor chips | |
| CN215783444U (en) | Ultrasonic liquid transfer device | |
| WO2023004795A1 (en) | Ultrasonic pipetting apparatus and method | |
| CN114768907B (en) | Ultrasonic pipetting method and system based on annular array ultrasonic transducer | |
| CN110404493B (en) | Reaction device and system for high sound pressure | |
| Huang et al. | Transducer design for high-efficient acoustic droplet ejection | |
| US10112212B1 (en) | Droplet ejection using focused acoustic radiation having a plurality of frequency ranges | |
| CN213003251U (en) | Phased array focusing ultrasonic welding system | |
| JP6541138B1 (en) | Ultrasonic irradiator | |
| CN115999082A (en) | Ultrasonic treatment equipment |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20200807 |
|
| RJ01 | Rejection of invention patent application after publication |