CN114768907B - Ultrasonic pipetting method and system based on annular array ultrasonic transducer - Google Patents
Ultrasonic pipetting method and system based on annular array ultrasonic transducer Download PDFInfo
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- CN114768907B CN114768907B CN202210379171.4A CN202210379171A CN114768907B CN 114768907 B CN114768907 B CN 114768907B CN 202210379171 A CN202210379171 A CN 202210379171A CN 114768907 B CN114768907 B CN 114768907B
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- 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
- B01L3/0241—Drop counters; Drop formers
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- B—PERFORMING OPERATIONS; TRANSPORTING
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- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2400/00—Moving or stopping fluids
- B01L2400/04—Moving fluids with specific forces or mechanical means
- B01L2400/0403—Moving fluids with specific forces or mechanical means specific forces
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Abstract
The invention provides an ultrasonic pipetting method and a system based on an annular array ultrasonic transducer, wherein the method comprises a measurement operation and a pipetting operation; the measuring operation includes: exciting an array element to generate a short pulse type emitted ultrasonic wave, and generating a reflected ultrasonic wave after reaching the liquid level; each array element receives the reflected ultrasonic wave, performs dynamic beam synthesis, obtains and analyzes ultrasonic beams, and obtains liquid parameters. The pipetting operation comprises: adjusting the excitation parameters according to the liquid parameters; exciting a central array element and at least one non-central array element, generating long-pulse-form emitted ultrasonic waves, focusing on the liquid surface, and moving the solution in the source carrier liquid platform to a preset target carrier liquid platform in the form of liquid drops. The scheme of the invention realizes liquid parameter detection and non-contact ultrasonic pipetting based on the annular array ultrasonic transducer, has the characteristics of safety and accuracy of non-contact pipetting, and has the advantages of low system complexity, low equipment cost and simple operation.
Description
Technical Field
The invention relates to the field of ultrasonic application, in particular to an ultrasonic pipetting method and an ultrasonic pipetting system based on an annular array ultrasonic transducer.
Background
Synthetic biology is known as one of the three world-wide subversion technologies that address challenges. Pipetting is one of the most common tasks of operation in synthetic biology laboratories, and selecting the correct pipettor is a critical step in accurately performing the experiment. The pipetting means can be classified into contact pipetting and non-contact pipetting depending on whether the solution is contacted during pipetting.
Contact pipetting, such as a pipette. In the pipetting process, the sample can adhere to the pipetting head, so that the amount of liquid transferred is inaccurate, and huge false negative results can be generated. And errors accumulate during gradient dilution, some samples show up to a third-order loss of bioactivity when using gradient dilution. In addition, because the pipetting head is a disposable consumable, special treatment or replacement is needed after each use to avoid cross infection, a large amount of consumable is needed to support the experiment, and the cost is high during large-scale use.
The prior contact type ultrasonic pipetting device needs to move liquid through a pipetting ring, and the type of liquid to be pipetted is limited, so that the practical application of the technology is limited.
The existing non-contact ultrasonic pipetting device can safely realize liquid movement, but has high system complexity and high equipment cost. There is a solution in the prior art based on phased array technology by introducing miniaturized arrayed ultrasonic transducers to eject droplets in an electrically driven self-focusing fashion. The scheme uses a large number of micro-mechanical ultrasonic transducers to form the array ultrasonic transducer, so that the cost is high, the structure is extremely complex, and the array ultrasonic transducer is difficult to accurately operate to realize pipetting.
Therefore, there is a need for a non-contact pipetting solution that is low in cost, simple in structure and easy to operate, and that can solve the above-mentioned problems.
Disclosure of Invention
Based on the problems existing in the prior art, the invention provides an ultrasonic pipetting method and an ultrasonic pipetting system based on an annular array ultrasonic transducer. The specific scheme is as follows:
an ultrasonic pipetting method based on an annular array ultrasonic transducer comprises a plurality of measurement operations and at least one pipetting operation;
each measurement operation includes:
exciting a central array element in the annular array ultrasonic transducer with a preset excitation waveform, or exciting the central array element and at least one non-central array element in the annular array ultrasonic transducer to generate first transmitting ultrasonic waves in a short pulse form;
after the first transmitted ultrasonic wave reaches the liquid level of the source carrier liquid platform, generating a first reflected ultrasonic wave;
each array element in the annular array ultrasonic transducer receives the first reflected ultrasonic wave and performs dynamic beam synthesis to obtain an ultrasonic beam;
analyzing the ultrasonic wave beam to obtain liquid parameters of a source carrier liquid platform;
each pipetting operation specifically comprises:
adjusting excitation parameters of pipetting operation according to liquid parameters of the source carrier liquid platform;
exciting a central array element and at least one non-central array element in the annular array ultrasonic transducer with a preset excitation waveform based on the adjusted excitation parameters to generate second emitted ultrasonic waves in a long pulse form;
and the second emitted ultrasonic waves are focused on the liquid level in the source carrier liquid platform, and under the action of the ultrasonic waves, the solution in the source carrier liquid platform is moved to a preset target carrier liquid platform in the form of liquid drops.
In a specific embodiment, the central array element is a circular array element, and the non-central array element is a ring array element surrounding the central array element;
the annular array ultrasonic transducer comprises a circular array element and at least one annular array element, wherein the annular array elements are sequentially nested and arranged, and the circular array element is embedded in a certain annular array element.
In a specific embodiment, the excitation waveform includes a square wave, a stepped quasi-sine wave, and a sine wave.
In a specific embodiment, the dynamic beam synthesis specifically includes:
each array element receives the first reflected ultrasonic wave, calculates and acquires the time parameter of the ultrasonic wave bidirectional propagation according to the depth value of the ultrasonic wave propagation direction and the physical size of the transducer, and carries out delay superposition of a plurality of signals based on the time parameter.
In a specific embodiment, the liquid parameters include a liquid level of the source carrier liquid platform, a liquid density, and a propagation velocity of ultrasonic waves in the liquid.
In one embodiment, "adjusting the excitation parameters according to the liquid parameters of the source carrier liquid platform" includes:
waveform adjustment is carried out on the excitation waveform of the pipetting operation based on the liquid level height so as to control ultrasonic energy of the pipetting operation when excitation is carried out;
the waveform adjustment includes the amplitude of the excitation waveform, the number of cycles, and the relative phase delay between the excitation waveforms.
In a specific embodiment, if the liquid level is higher, the excitation waveform of each array element of the annular array ultrasonic transducer is reduced to reduce the relative phase delay and improve the ultrasonic focus position; simultaneously increasing the amplitude or the period number of the excitation waveform;
if the liquid level is lower, increasing the relative phase delay of the excitation waveform of each array element; while reducing the amplitude or number of cycles of the excitation waveform.
In a specific embodiment, the first emitted ultrasonic wave is a plane wave acoustic beam;
and/or, the second emitted ultrasonic wave is a focused wave sound beam.
An ultrasonic pipetting system based on an annular array ultrasonic transducer comprises,
the source carrier liquid platform is used for storing the solution to be removed;
the target liquid carrying platform is used for storing the solution to be removed after the liquid is removed;
the annular array ultrasonic transducer comprises a circular array element and at least one annular array element; for performing a partial measurement operation and a partial pipetting operation;
the measurement operations performed include:
a first transmitting ultrasonic wave which generates a short pulse after a central array element is excited or the central array element and at least one non-central array element are excited; after the first transmitted ultrasonic wave reaches the liquid level of a source carrier liquid platform, generating a first reflected ultrasonic wave; each array element receives the first reflected ultrasonic wave and performs dynamic beam synthesis to obtain an ultrasonic beam;
the pipetting operations performed include:
the central array element and at least one non-central array element are excited to generate long-pulse second emitted ultrasonic waves; the second emitted ultrasonic wave is focused on the liquid level in the source carrier liquid platform, and under the focusing action of the ultrasonic wave, the solution in the source carrier liquid platform is moved to the target carrier liquid platform in the form of liquid drops;
a control unit for exciting the annular array ultrasonic transducer; analyzing the ultrasonic wave beam to obtain the liquid parameter of the source carrier liquid platform so as to realize the measurement of the liquid parameter of the source carrier liquid platform; and when the pipetting operation starts, adjusting excitation parameters of the pipetting operation according to the liquid parameters of the source carrier liquid platform.
In a specific embodiment, the central array element is a circular array element, and the non-central array element is a ring array element surrounding the central array element;
the annular array ultrasonic transducer comprises a circular array element and at least one annular array element, wherein the annular array elements are sequentially nested and arranged, and the circular array element is embedded in a certain annular array element.
The beneficial effects are that:
the invention provides an ultrasonic pipetting method and system based on an annular array ultrasonic transducer, which are used for realizing liquid parameter detection and non-contact ultrasonic pipetting based on the annular array ultrasonic transducer, and have the characteristics of safety and accuracy of non-contact pipetting, and have the advantages of low system complexity, low equipment cost and simplicity in operation. The annular array ultrasonic transducer can form a high-resolution focusing sound field under the condition that the array element number is greatly smaller than that of the linear array and the area array transducer, accurate focal length adjustment is realized, the manufacturing process is simple, and the cost is low.
In order to make the above objects, features and advantages of the present invention more comprehensible, preferred embodiments accompanied with figures are described in detail below.
Drawings
In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the drawings that are needed in the embodiments will be briefly described below, it being understood that the following drawings only illustrate some embodiments of the present invention and therefore should not be considered as limiting the scope, and other related drawings may be obtained according to these drawings without inventive effort for a person skilled in the art.
FIG. 1 is a flow chart of an ultrasonic pipetting method of an embodiment of the invention;
FIG. 2 is a schematic diagram of an array element structure of an annular array ultrasonic transducer according to an embodiment of the present invention;
FIG. 3 is a schematic diagram of the structure of an annular array ultrasonic transducer according to an embodiment of the present invention;
FIG. 4 is a schematic diagram of a measurement mode principle of an embodiment of the present invention;
FIG. 5 is a schematic view of a pipetting mode principle of an embodiment of the invention;
fig. 6 is a schematic diagram of an ultrasonic pipetting system in accordance with an embodiment of the invention.
Reference numerals: 1-a control unit; 2-ring array ultrasonic transducers; 3-coupling medium; 4-a housing; 5-a source carrier liquid platform; 6-a target carrier liquid platform; 21-a matching layer; 22-a piezoelectric layer; 23-flexible board.
Detailed Description
The following description of the embodiments of the present invention will be made clearly and fully with reference to the accompanying drawings, in which it is evident that the embodiments described are only some, but not all embodiments of the invention. All other embodiments, which can be made by those skilled in the art based on the embodiments of the invention without making any inventive effort, are intended to be within the scope of the invention.
Example 1
The embodiment provides an ultrasonic pipetting method based on an annular array ultrasonic transducer, which can realize liquid parameter detection and non-contact ultrasonic pipetting, and has the characteristics of safety and accuracy of non-contact pipetting, and is low in system complexity, low in equipment cost and simple to operate. An ultrasonic pipetting method flow chart based on the annular array ultrasonic transducer is shown in the attached figure 1 of the specification, and the specific scheme is as follows:
an ultrasonic pipetting method based on an annular array ultrasonic transducer comprises a plurality of measurement operations and at least one pipetting operation. The liquid parameters can be accurately obtained through multiple times of measurement operation, and then proper parameters are adjusted to carry out pipetting operation. The number of pipetting operations may be set according to the actual application.
Each measurement operation includes:
101. exciting a central array element in the annular array ultrasonic transducer with a preset excitation waveform, or exciting the central array element and at least one non-central array element in the annular array ultrasonic transducer to generate first transmitting ultrasonic waves in a short pulse form;
102. generating first reflected ultrasonic waves after the first transmitted ultrasonic waves reach the liquid level of the source carrier liquid platform;
103. each array element in the annular array ultrasonic transducer receives the first reflected ultrasonic wave and performs dynamic beam synthesis to obtain an ultrasonic beam;
104. analyzing ultrasonic wave beams to obtain liquid parameters of a source carrier liquid platform;
each pipetting operation specifically comprises:
201. adjusting excitation parameters of pipetting operation according to liquid parameters of the source carrier liquid platform;
202. exciting a central array element and at least one non-central array element in the annular array ultrasonic transducer with a preset excitation waveform based on the adjusted excitation parameters to generate second emitted ultrasonic waves in a long pulse form;
203. and the second emitted ultrasonic wave is focused on the liquid level in the source carrier liquid platform, and under the action of the ultrasonic wave, the solution in the source carrier liquid platform is moved to the preset target carrier liquid platform in the form of liquid drops.
The ultrasonic pipetting method is suitable for an ultrasonic pipetting system comprising a source liquid carrying platform, a target liquid carrying platform and an annular array ultrasonic transducer, and based on the simple annular array ultrasonic transducer, non-contact pipetting and liquid parameter measurement are realized by exciting the annular array ultrasonic transducer to output ultrasonic sound beams. Compared with the traditional arrayed ultrasonic transducer, the annular array ultrasonic transducer has the advantages that the number of array elements is small, the complexity of the whole system is low, the pipetting operation and the measuring operation are simple, and complex operation means are not needed.
In this embodiment, since the ring-energy array ultrasonic transducer can perform two functions of liquid parameter measurement and contactless pipetting, it no longer has a single functional attribute, so that the ring-energy array ultrasonic transducer is excited by a special control unit to output a specific signal, and two working states of a measurement mode and a pipetting mode are defined. In a measurement mode, the control unit excites the annular array ultrasonic transducer to emit plane waves to act on the source carrier liquid platform, and the plane waves are used for measuring liquid parameters of the carrier liquid platform. In a pipetting mode, the control unit excites the annular array transducer to emit focusing waves to act on the liquid level position of the source carrier liquid platform, so that non-contact pipetting operation is realized.
Preferably, the measuring operation requires the generation of at least one cycle of the first transmitted ultrasonic wave, and the first transmitted ultrasonic wave is a short pulse; the pipetting operation requires the generation of a second emitted ultrasonic wave of at least 100 cycles and the second emitted ultrasonic wave is a long pulse to better control the ultrasonic energy at pipetting.
Wherein the annular array ultrasonic transducer comprises a central array element and at least one non-central array element. Wherein the central array element is a circular array element, and the non-central array element is a ring array element surrounding the central array element. The plurality of annular array elements are nested in sequence, and one annular array element is nested with a circular array element. In practical application, the positions of the array ultrasonic transducer and the source carrier liquid platform on the x axis, the y axis and the z axis need to be adjusted before pipetting, and the z axis represents the distance between the array ultrasonic transducer and the source carrier liquid platform. According to the embodiment, the focusing effect of the array ultrasonic transducer can be achieved through at least two array elements, and the position adjustment in the z-axis direction can be achieved without moving the distance between the array ultrasonic transducer and the source carrier liquid platform.
Preferably, the circular array elements are nested inside the annular array elements, namely the annular array elements and the circle center array elements form a concentric circle structure together. Fig. 2 of the specification provides a schematic diagram of an array element cross section of an annular array ultrasonic transducer, fig. 2 includes a circular array element e1, an annular array element e2 and an annular array element e3, and the annular array elements e2 and e3 and the circular array element e1 have the same circle center.
Further preferably, the annular array ultrasonic transducer comprises a matching layer, a piezoelectric layer and a flexible plate, and the specific structure is shown in figure 3 of the specification. The piezoelectric layer is used for emitting ultrasonic beams, the matching layer is used for matching acoustic impedances between the piezoelectric layer and an external object, the flexible board is used for realizing electrical interconnection between the piezoelectric layer and an external circuit, and compared with a traditional lead process, the lead process of the array ultrasonic transducer can be simplified by adopting the flexible board to realize electrical interconnection. The annular array ultrasonic transducer of the embodiment can realize dynamic and accurate focal length adjustment only by fewer array elements, and forms a high-resolution focusing sound field under the condition that the number of the array elements is greatly smaller than that of the linear array and the area array transducer, and has simple manufacturing process, low cost and simple operation.
Prior to performing the ultrasonic pipetting, it is necessary to determine the source and target carrier liquid platforms, in particular to confirm the liquid parameters of the solution in the source carrier liquid platform. The source carrier liquid platform is used for storing the solution to be transferred, the target carrier liquid platform is the position of the solution after transferring, and the transferring process is to transfer the solution to be transferred from the source carrier liquid platform to the target carrier liquid platform drop by drop.
In this embodiment, the liquid parameters include the liquid level of the source carrier liquid platform, the liquid density, and the propagation velocity of the ultrasonic waves in the liquid. The energy of the excitation signal and the relevant parameters of the motor are adjusted based on the propagation speed of the ultrasonic wave in the liquid and the density of the liquid. The liquid level is specifically the interface between the liquid and air in the source carrier liquid platform. The liquid level is the distance between the liquid level and the bottom of the cavity containing the liquid in the source carrier liquid platform, and different source carrier liquid platforms may have different liquid levels. The accurate liquid level is required to be obtained so as to adjust the relevant parameters of the excitation waveform in the pipetting operation, thereby realizing accurate pipetting. In this embodiment, by analyzing the frequency, phase and amplitude information of the reflected ultrasonic wave, the relevant parameters of the liquid can be derived.
In the prior art, the liquid level position is determined by special equipment, so that the additional equipment cost is required, the operation is complex, and the liquid level position cannot be timely and accurately judged. In the case of large-scale pipetting, the determination of the liquid level position is extremely time-consuming, which seriously affects pipetting efficiency.
Adjusting the excitation parameters according to the liquid parameters of the source carrier liquid platform comprises: waveform adjustment is performed on the excitation waveform of the pipetting operation based on the liquid level to control ultrasonic energy of the pipetting operation when excitation is performed. The liquid level is different, and the wave form required for pipetting is also different. The embodiment realizes perfect matching of ultrasonic energy required by pipetting by adjusting the excitation waveform. Waveform adjustment includes the amplitude of the excitation waveform, the number of cycles, and the relative phase delay between the excitation waveforms. If the liquid level is higher, reducing the excitation waveform of each array element of the annular array ultrasonic transducer so as to reduce the relative phase delay and improve the ultrasonic focus position; simultaneously increasing the amplitude or the period number of the excitation waveform; if the liquid level is lower, increasing the relative phase delay of the excitation waveform of each array element; while reducing the amplitude or number of cycles of the excitation waveform.
Aiming at the problem that the liquid level position in the source carrier liquid platform is difficult to determine, the ultrasonic pipetting method of the embodiment can determine the liquid level position of the solution in the source carrier liquid platform through a measuring step by means of the annular array ultrasonic transducer. The ranging process specifically comprises the following steps: exciting an annular array ultrasonic transducer to emit first emitted ultrasonic waves; generating an echo signal after the first transmitted ultrasonic wave reaches the interface between the solution in the source carrier liquid platform and the air, wherein the echo signal is the first reflected ultrasonic wave; and receiving the first reflected ultrasonic wave through each array element in the annular array ultrasonic transducer, and performing dynamic beam synthesis to synthesize an ultrasonic beam. The liquid parameters can be obtained by analyzing the ultrasound beam.
The dynamic beam synthesis specifically includes: each array element receives the first reflected ultrasonic wave, calculates and acquires the time parameter of the ultrasonic wave bidirectional propagation according to the depth value of the ultrasonic wave propagation direction and the physical size of the transducer, and carries out delay superposition of a plurality of signals based on the time parameter.
For example, there are different signal points in the ultrasonic beam, and when the ultrasonic wave passes through different mediums in the source carrier liquid platform, the ultrasonic wave will show different amplitude changes, and these amplitude change points are signal points. The signal points can accurately reflect different medium structures of the source carrier liquid platform. A signal point of the amplitude change in the first reflected ultrasonic wave is determined, and from the signal point, the level position of the solution in the source carrier liquid platform can be determined.
Preferably, the first emitted ultrasonic wave is a plane wave acoustic beam. The amplitude of the plane wave beam passing through different media varies and is represented in the reflected first reflected ultrasonic wave. For example, the first reflected ultrasonic wave may have a signal point with a significant amplitude change at the level position. Similarly, when the plane wave acoustic beam acts on different positions of the source carrier liquid platform, corresponding signal points are generated. In the case of a known source carrier liquid platform, the present implementation determines the liquid level position based on these signal points.
Description fig. 4 provides a schematic diagram of the principle of measuring the liquid level distance. In fig. 4, the points of each amplitude change in the first reflected ultrasonic wave are signal points, that is, some points on L1, L2 and L3, where the positions of the signal points correspond to the positions of the source carrier liquid platform. Line L1 corresponds to the top A1 of the source carrier liquid platform, line L3 corresponds to the bottom A3 of the source carrier liquid platform, and line L2 corresponds to the liquid level position A2 in the source carrier liquid platform. With A1 and A3 known, the liquid level position can be determined from the signal points on the respective lines of L1, L2 and L3.
The liquid level parameter detection specifically comprises: an annular array ultrasonic transducer transmits a first transmission ultrasonic wave; the first transmitting ultrasonic wave acts on a plurality of liquid carrying platforms at the same time, and corresponding first reflecting ultrasonic waves are generated respectively; receiving first reflected ultrasonic waves of a plurality of carrier liquid platforms through an annular array ultrasonic transducer; a signal point of the amplitude variation in the first reflected ultrasonic wave is determined, and the liquid level positions of the solutions in the plurality of source carrier liquid platforms are determined from the signal point. Further preferably, the number of the annular array elements is expanded to enlarge the output range of the first transmitted ultrasonic wave, so that the liquid level position detection of more liquid carrying platforms is realized.
Preferably, the central array element and the at least one non-central array element are excited during pipetting, which ensures both the pipetting accuracy and the pipetting quality.
During pipetting, the control unit excites the central array element and at least one non-central array element of the annular array ultrasonic transducer to emit a first ultrasonic beam, the first ultrasonic beam is focused on the liquid level position of the solution in the source carrier liquid platform, and liquid drops are transferred from the source carrier liquid platform to the target carrier liquid platform under the action of ultrasonic radiation force so as to realize non-contact pipetting. The schematic diagram of the pipetting is shown in figure 5 of the specification. The control unit tracks the positions and states of all liquid drops, can realize liquid drop transfer from any source position to target position according to the needs, has high transfer precision, and can realize liquid movement rapidly, safely and accurately. According to the ultrasonic pipetting method, the solution to be pipetted does not need to be contacted, and the high-precision adjustment of the focus point position can meet the precision requirement of transferring micro-reagents and can also meet the high-repeatability requirement of batch reagents.
Preferably, the second emitted ultrasonic wave is a focused wave sound beam of high intensity. The control unit excites the annular array ultrasonic transducer to emit focused wave sound beams, and the high-intensity focused wave sound beams are focused on the liquid level position of the source carrier liquid platform, so that non-contact movement of liquid drops from the source carrier liquid platform to the target carrier liquid platform is realized. According to the embodiment, the focal length is accurately adjusted through the annular array ultrasonic transducer, so that the liquid level position of the source carrier liquid platform is tracked to carry out liquid transferring operation, and the detection cost is low, and the device is flexible and practical.
The embodiment provides an ultrasonic pipetting method based on an annular array ultrasonic transducer, which is used for realizing liquid parameter detection and non-contact ultrasonic pipetting based on the annular array ultrasonic transducer, and has the characteristics of safety and accuracy of non-contact pipetting, and is low in system complexity, low in equipment cost and simple to operate. The annular array ultrasonic transducer can form a high-resolution focusing sound field under the condition that the array element number is greatly smaller than that of the linear array and the area array transducer, accurate focal length adjustment is realized, the manufacturing process is simple, and the cost is low.
Example 2
The embodiment provides an ultrasonic pipetting system based on an annular array ultrasonic transducer, which is used for systemizing the method of the embodiment 1, wherein a structural schematic diagram of the system is shown in fig. 6 of the specification, and the specific scheme is as follows:
an ultrasonic pipetting system based on an annular array ultrasonic transducer 2 comprises,
the control unit 1 is connected with the annular array ultrasonic transducer 2 and is used for exciting the annular array ultrasonic transducer 2 to emit ultrasonic signals. The annular array ultrasonic transducer 2 is excited to emit different ultrasonic signals so as to control the ultrasonic pipetting system to realize switching of two working states of pipetting mode and measuring mode, the connection is smooth, and the time required by pipetting operation can be greatly shortened.
The annular array ultrasonic transducer 2 comprises a circular array element and at least one annular array element; for performing a partial measurement operation and a partial pipetting operation;
the measurement operations performed include:
a first transmitting ultrasonic wave which generates a short pulse after a central array element is excited or the central array element and at least one non-central array element are excited; generating first reflected ultrasonic waves after the first transmitted ultrasonic waves reach the liquid level of a source carrier liquid platform; each array element receives the first reflected ultrasonic wave and performs dynamic beam synthesis to obtain an ultrasonic beam;
the pipetting operations performed include:
the central array element and at least one non-central array element are excited to generate long-pulse second emitted ultrasonic waves; the second emitted ultrasonic wave is focused on the liquid level in the source carrier liquid platform, and under the focusing action of the ultrasonic wave, the solution in the source carrier liquid platform 5 is moved to the target carrier liquid platform in the form of liquid drops;
a control unit for exciting the annular array ultrasonic transducer 2; analyzing ultrasonic wave beams to obtain liquid parameters of the source carrier liquid platform 5 so as to realize measurement of the liquid parameters of the source carrier liquid platform 5; at the beginning of the pipetting operation, the excitation parameters of the pipetting operation are adjusted according to the liquid parameters of the source carrier liquid platform 5.
A source carrier liquid platform 5 for storing a solution to be removed;
a target liquid carrying platform 6 for storing the solution after pipetting;
the coupling medium 3 contacts the annular array ultrasound transducer 2 and the source carrier liquid platform 5, respectively, for providing an efficient energy transfer from the annular array ultrasound transducer 2 to the source carrier liquid platform 5.
Wherein the coupling medium 3 and the annular array ultrasonic transducer 2 are positioned in the shell 4, and the shell 4 can protect the safety of the system.
Before performing the ultrasonic pipetting, it is necessary to determine the source carrier liquid stage 5 and the target carrier liquid stage 6, and in particular to confirm the level position of the solution in the source carrier liquid stage 5. The source carrier liquid platform 5 is used for storing the solution to be removed, the target carrier liquid platform 6 is the position after the solution is transferred, and the solution to be removed is transferred from the source carrier liquid platform 5 to the target carrier liquid platform 6 drop by drop in the process of transferring.
In the measurement mode, the system is capable of simultaneously detecting liquid parameters of solutions in multiple source carrier liquid platforms 5. The liquid parameters include the liquid level of the source carrier liquid platform, the liquid density, and the propagation speed of ultrasonic waves in the liquid. The energy of the excitation signal and the relevant parameters of the motor are adjusted based on the propagation speed of the ultrasonic wave in the liquid and the density of the liquid. The liquid level is specifically the interface between the liquid and air in the source carrier liquid platform. The liquid level is the distance between the liquid level and the bottom of the cavity containing the liquid in the source carrier liquid platform, and different source carrier liquid platforms may have different liquid levels. The accurate liquid level is required to be obtained so as to adjust the relevant parameters of the excitation waveform in the pipetting operation, thereby realizing accurate pipetting. In this embodiment, by analyzing the frequency, phase and amplitude information of the reflected ultrasonic wave, the relevant parameters of the liquid can be derived.
Preferably, the circular array elements are nested inside the annular array elements, namely the annular array elements and the circle center array elements form a concentric circle structure together. Fig. 2 of the specification provides a schematic diagram of an array element cross section of an annular array ultrasonic transducer 2, fig. 2 includes a circular array element e1, an annular array element e2 and an annular array element e3, and the annular array elements e2 and e3 and the circular array element e1 have the same circle center.
It is further preferred that the annular array ultrasonic transducer 2 includes a matching layer 21, a piezoelectric layer 22 and a flexible plate 23, and the specific structure is shown in fig. 3 of the specification. The piezoelectric layer 22 is used for emitting ultrasonic beams, the acoustic matching layer 21 is used for matching acoustic impedances between the piezoelectric layer 22 and an external object, the flexible plate 23 is used for realizing electrical interconnection between the piezoelectric layer 22 and an external circuit, and compared with a traditional wire-leading process, the wire-leading process of the array ultrasonic transducer can be simplified by adopting the flexible plate 23 to realize electrical interconnection. The annular array ultrasonic transducer 2 of the embodiment can realize dynamic and accurate focal length adjustment by only needing fewer array elements, and forms a high-resolution focusing sound field under the condition that the number of the array elements is greatly smaller than that of the linear array and the area array transducer, and has simple manufacturing process, low cost and simple operation.
The annular array ultrasonic transducer of the embodiment can form a high-resolution focusing sound field under the condition that the array element number is greatly smaller than that of the linear array and the area array transducer, has a simple structure, greatly reduces the complexity of a system, and improves the flexibility and the practicability of a pipetting system.
The present embodiment provides an ultrasonic pipetting system based on an annular array ultrasonic transducer, which systemizes the method of embodiment 1, making it more practical.
The invention provides an ultrasonic pipetting method and system based on an annular array ultrasonic transducer, which are used for realizing liquid parameter detection and non-contact ultrasonic pipetting based on the annular array ultrasonic transducer, and have the characteristics of safety and accuracy of non-contact pipetting, and have the advantages of low system complexity, low equipment cost and simplicity in operation. The annular array ultrasonic transducer can form a high-resolution focusing sound field under the condition that the array element number is greatly smaller than that of the linear array and the area array transducer, accurate focal length adjustment is realized, the manufacturing process is simple, and the cost is low.
It will be appreciated by those skilled in the art that the modules of the invention described above may be implemented in a general purpose computing system, concentrated on a single computing system, or distributed across a network of computing systems, and that they may alternatively be implemented in program code executable by a computer system, such that they are stored in a memory system and executed by the computing system, or individually fabricated into individual integrated circuit modules, or multiple modules or steps within them are fabricated into a single integrated circuit module. Thus, the present invention is not limited to any specific combination of hardware and software.
Note that the above is only a preferred embodiment of the present invention and the technical principle applied. It will be understood by those skilled in the art that the present invention is not limited to the particular embodiments described herein, but is capable of various obvious changes, rearrangements and substitutions as will now become apparent to those skilled in the art without departing from the scope of the invention. Therefore, while the invention has been described in connection with the above embodiments, the invention is not limited to the embodiments, but may be embodied in many other equivalent forms without departing from the spirit or scope of the invention, which is set forth in the following claims.
The foregoing disclosure is merely illustrative of some embodiments of the invention, and the invention is not limited thereto, as modifications may be made by those skilled in the art without departing from the scope of the invention.
Claims (9)
1. An ultrasonic pipetting method based on an annular array ultrasonic transducer is characterized by comprising multiple measurement operations and at least one pipetting operation;
each measurement operation includes:
exciting a central array element in the annular array ultrasonic transducer with a preset excitation waveform, or exciting the central array element and at least one non-central array element in the annular array ultrasonic transducer to generate first transmitting ultrasonic waves in a short pulse form;
after the first transmitted ultrasonic wave reaches the liquid level of the source carrier liquid platform, generating a first reflected ultrasonic wave;
each array element in the annular array ultrasonic transducer receives the first reflected ultrasonic wave and performs dynamic beam synthesis to obtain an ultrasonic beam;
analyzing the ultrasonic wave beam, determining signal points with various amplitude changes in the first reflected ultrasonic wave, wherein the positions of the signal points correspond to the positions of the source carrier liquid platforms, and determining the liquid level positions of the solutions in the source carrier liquid platforms from the signal points; acquiring liquid parameters of a source carrier liquid platform;
each pipetting operation specifically comprises:
adjusting excitation parameters of pipetting operation according to liquid parameters of the source carrier liquid platform;
exciting a central array element and at least one non-central array element in the annular array ultrasonic transducer with a preset excitation waveform based on the adjusted excitation parameters to generate second emitted ultrasonic waves in a long pulse form;
the second emitted ultrasonic wave is focused on the liquid level in the source carrier liquid platform, and under the action of the ultrasonic wave, the solution in the source carrier liquid platform is moved to a preset target carrier liquid platform in the form of liquid drops;
the central array element is a circular array element, and the non-central array element is an annular array element surrounding the central array element;
the annular array ultrasonic transducer comprises a circular array element and at least one annular array element, wherein the annular array elements are sequentially nested and arranged, and the circular array element is embedded in a certain annular array element.
2. The method of ultrasonic pipetting of claim 1, wherein the excitation waveforms comprise square waves, stepped quasi-sine waves, and sine waves.
3. The method of ultrasound pipetting according to claim 1, wherein the dynamic beam synthesis specifically comprises:
each array element receives the first reflected ultrasonic wave, calculates and acquires the time parameter of the ultrasonic wave bidirectional propagation according to the depth value of the ultrasonic wave propagation direction and the physical size of the transducer, and carries out delay superposition of a plurality of signals based on the time parameter.
4. The method of claim 1, wherein the liquid parameters include a liquid level of the source carrier liquid platform, a liquid density, and a propagation velocity of ultrasonic waves in the liquid.
5. The method of ultrasonic pipetting of claim 4, wherein adjusting the excitation parameters based on the liquid parameters of the source carrier liquid platform comprises:
waveform adjustment is carried out on the excitation waveform of the pipetting operation based on the liquid level height so as to control ultrasonic energy of the pipetting operation when excitation is carried out;
the waveform adjustment includes the amplitude of the excitation waveform, the number of cycles, and the relative phase delay between the excitation waveforms.
6. The method of claim 5, wherein if the liquid level is high, the excitation waveforms of the array elements of the annular array ultrasonic transducer are reduced to reduce the relative phase delay and increase the ultrasonic focus position; simultaneously increasing the amplitude or the period number of the excitation waveform;
if the liquid level is lower, increasing the relative phase delay of the excitation waveform of each array element; while reducing the amplitude or number of cycles of the excitation waveform.
7. The method of ultrasonic pipetting of claim 5, wherein the first emitted ultrasonic waves are plane wave beams;
and/or, the second emitted ultrasonic wave is a focused wave sound beam.
8. An ultrasonic pipetting system based on an annular array ultrasonic transducer is characterized by comprising,
the source carrier liquid platform is used for storing the solution to be removed;
the target liquid carrying platform is used for storing the solution to be removed after the liquid is removed;
the annular array ultrasonic transducer comprises a circular array element and at least one annular array element; for performing a partial measurement operation and a partial pipetting operation;
the measurement operations performed include:
a first transmitting ultrasonic wave which generates a short pulse after a central array element is excited or the central array element and at least one non-central array element are excited; after the first transmitted ultrasonic wave reaches the liquid level of a source carrier liquid platform, generating a first reflected ultrasonic wave; each array element receives the first reflected ultrasonic wave and performs dynamic beam synthesis to obtain an ultrasonic beam;
determining signal points with various amplitude changes in the first reflected ultrasonic wave, wherein the positions of the signal points correspond to the positions of the source carrier liquid platforms, and determining the liquid level positions of solutions in the source carrier liquid platforms from the signal points; the pipetting operations performed include:
the central array element and at least one non-central array element are excited to generate long-pulse second emitted ultrasonic waves; the second emitted ultrasonic wave is focused on the liquid level in the source carrier liquid platform, and under the focusing action of the ultrasonic wave, the solution in the source carrier liquid platform is moved to the target carrier liquid platform in the form of liquid drops;
a control unit for exciting the annular array ultrasonic transducer; analyzing the ultrasonic wave beam to obtain the liquid parameter of the source carrier liquid platform so as to realize the measurement of the liquid parameter of the source carrier liquid platform; and when the pipetting operation starts, adjusting excitation parameters of the pipetting operation according to the liquid parameters of the source carrier liquid platform.
9. The ultrasonic pipetting system of claim 8, wherein the central array element is a circular array element and the non-central array element is a ring array element surrounding the central array element;
the annular array ultrasonic transducer comprises a circular array element and at least one annular array element, wherein the annular array elements are sequentially nested and arranged, and the circular array element is embedded in a certain annular array element.
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