WO2021115046A1 - 一种声镊装置及对微粒的操控方法 - Google Patents

一种声镊装置及对微粒的操控方法 Download PDF

Info

Publication number
WO2021115046A1
WO2021115046A1 PCT/CN2020/129485 CN2020129485W WO2021115046A1 WO 2021115046 A1 WO2021115046 A1 WO 2021115046A1 CN 2020129485 W CN2020129485 W CN 2020129485W WO 2021115046 A1 WO2021115046 A1 WO 2021115046A1
Authority
WO
WIPO (PCT)
Prior art keywords
transducer array
particles
imaging plane
array
ultrasound
Prior art date
Application number
PCT/CN2020/129485
Other languages
English (en)
French (fr)
Inventor
马腾
杨晔
王丛知
李永川
黄继卿
蔡飞燕
刘佳妹
郑海荣
Original Assignee
深圳先进技术研究院
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by 深圳先进技术研究院 filed Critical 深圳先进技术研究院
Publication of WO2021115046A1 publication Critical patent/WO2021115046A1/zh

Links

Classifications

    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J19/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J19/08—Processes employing the direct application of electric or wave energy, or particle radiation; Apparatus therefor
    • B01J19/10—Processes employing the direct application of electric or wave energy, or particle radiation; Apparatus therefor employing sonic or ultrasonic vibrations
    • 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
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/50273—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by the means or forces applied to move the fluids
    • 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
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/502761—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip specially adapted for handling suspended solids or molecules independently from the bulk fluid flow, e.g. for trapping or sorting beads, for physically stretching molecules
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01S—RADIO DIRECTION-FINDING; RADIO NAVIGATION; DETERMINING DISTANCE OR VELOCITY BY USE OF RADIO WAVES; LOCATING OR PRESENCE-DETECTING BY USE OF THE REFLECTION OR RERADIATION OF RADIO WAVES; ANALOGOUS ARRANGEMENTS USING OTHER WAVES
    • G01S15/00—Systems using the reflection or reradiation of acoustic waves, e.g. sonar systems
    • G01S15/88—Sonar systems specially adapted for specific applications
    • G01S15/89—Sonar systems specially adapted for specific applications for mapping or imaging
    • G01S15/8906—Short-range imaging systems; Acoustic microscope systems using pulse-echo techniques
    • G01S15/8997—Short-range imaging systems; Acoustic microscope systems using pulse-echo techniques using synthetic aperture techniques

Definitions

  • the invention relates to the technical field of acoustic manipulation, and more specifically, to an acoustic tweezers device and a method for controlling particles.
  • acoustic tweezers can manipulate particles by applying acoustic radiation force on them. Based on the difference between sound waves and light waves, acoustic tweezers have some advantages over optical tweezers. The main ones are: 1. Acoustic tweezers have no requirements for the optical transparency of the propagation medium and can be carried out in non-transparent media. This makes it possible for acoustic tweezers to be in air or water. , And even theoretically applied in various media such as living bodies; 2.
  • the capturing power of acoustic tweezers is much greater than that of optical tweezers under unit input energy, which can capture particles of the same size with lower energy, reducing the risk of damage to particles or Capturing particles of larger size under the same energy, such as realizing the control of centimeter-level particles.
  • the primary problem is that the environment and structure of living bodies are very complicated, which requires flexible and real-time three-dimensional control of particles.
  • the medium that propagates in the environment such as living body is non-transparent, and it is difficult to observe the manipulation of particles with the naked eye or the camera.
  • the acoustic tweezers based on the transducer array have the characteristics of real-time dynamic change of the controlled sound field and the ability to complete complex manipulation behaviors, etc., and have become one of the main methods of particle acoustic manipulation.
  • the acoustic tweezers cannot observe and monitor the manipulation of the particles, which results in a low accuracy of acoustic manipulation of the particles by the acoustic tweezers.
  • the present invention provides an acoustic tweezers device and a method for manipulating particles to improve the accuracy of acoustic manipulation of the particles.
  • An acoustic tweezers device including:
  • a transducer array comprising a plurality of transducers arranged in an array
  • control system is connected to the transducer array, and is used to control the transducer array to emit multi-point focused ultrasound in the first period and multi-angle planar ultrasound in the second period, the first period Alternate with the second time period, and form a stereo ultrasonic image according to the planar ultrasonic waves reflected by the particles received by the transducer array, and according to the stereo ultrasonic image, the multi-point focused ultrasonic waves emitted by any one of the transducers
  • the parameters of is adjusted to manipulate the positions of the particles by changing the positions of multiple focal points of the focused ultrasound emitted by the transducer array.
  • control system before manipulating the position of the particle, is further configured to obtain the first position of the particle according to the image of the first imaging plane, and predict that the particle is in the second position according to the first position. A second position on the imaging plane, and moving a focal point of the focused ultrasound emitted by the transducer array to the second position to capture the particles;
  • first imaging plane and the second imaging plane are both parallel to the surface of the transducer array, and the second imaging plane is located between the first imaging plane and the transducer array.
  • the size of the transducer is 2mm*2mm ⁇ 3mm*3mm; the center distance of the transducer is 2mm ⁇ 3mm.
  • the center frequency of the transducer array is 1 MHz to 1.5 MHz.
  • the transducer array is a planar array, a linear array, a ring array, or a curved array.
  • the transducer array is a planar array, the transducer array includes 16*16 transducers, and the size of the transducer array is 50mm*50mm.
  • control system adopts a multi-angle plane wave composite method, a synthetic aperture imaging method, or a divergent imaging method to form a stereo ultrasound image.
  • a method for manipulating particles, applied to the acoustic tweezers device as described in any one of the above, includes:
  • the method before manipulating the position of the particles, the method further includes:
  • first imaging plane and the second imaging plane are both parallel to the surface of the transducer array, and the second imaging plane is located between the first imaging plane and the transducer array.
  • forming a stereo ultrasound image according to the planar ultrasound reflected by the particles received by the transducer array includes:
  • a multi-angle plane wave composite method, a synthetic aperture imaging method or a divergent imaging method is adopted to form a three-dimensional ultrasound image based on the planar ultrasound reflected by the particles received by the transducer array.
  • the acoustic tweezers device and the method for controlling particles provided by the present invention divide the time period during which the transducer array emits ultrasonic waves into alternate first and second periods, and control the transducer array to emit multiple points in the first period Focusing ultrasound, transmitting multi-angle planar ultrasound in the second time period, and forming a stereo ultrasound image according to the plane ultrasound reflected by the particles received by the transducer array, and according to the parameters of the multi-point focused ultrasound emitted by any transducer according to the stereo ultrasound image
  • the adjustment is made to manipulate the position of the particles by changing the focus position of the focused ultrasound emitted by the transducer array, so that the manipulation of the particles can be guided and monitored through the stereo ultrasound image, thereby improving the acoustic tweezers device's control of the particles Accuracy.
  • FIG. 1 is a schematic structural diagram of an acoustic tweezers device provided by an embodiment of the present invention
  • FIG. 2 is an x-y plane sound field distribution diagram generated by an acoustic tweezers device according to an embodiment of the present invention
  • Fig. 3 is an x-z plane sound field distribution diagram generated by an acoustic tweezers device provided by an embodiment of the present invention
  • FIG. 4 is a schematic diagram of an experimental result of capturing three PDMS particles by a sound field generated by an acoustic tweezers device according to an embodiment of the present invention
  • FIG. 5 is a control timing diagram of a transducer array provided by an embodiment of the present invention.
  • FIG. 6 is a schematic diagram of the acoustic tweezers device provided by an embodiment of the present invention to manipulate a single PDMS particle;
  • FIG. 7 is a schematic diagram of the sound field generated by the acoustic tweezers device provided by an embodiment of the present invention for manipulating a single PDMS particle;
  • FIG. 8 is a schematic diagram of an ultrasound image on the X-Z plane when a single PDMS particle is manipulated according to an embodiment of the present invention
  • FIG. 9 is a schematic diagram of ultrasound images on the X-Y plane when a single PDMS particle is manipulated according to an embodiment of the present invention.
  • FIG. 10 is a schematic diagram of an ultrasound image on the Y-Z plane when a single PDMS particle is manipulated according to an embodiment of the present invention
  • FIG. 11 is a schematic diagram of the acoustic tweezers device provided by an embodiment of the present invention to capture PDMS particles;
  • FIG. 12 is a flowchart of a method for manipulating particles by an acoustic tweezers device according to an embodiment of the present invention.
  • the embodiment of the present invention provides an acoustic tweezers device, as shown in FIG. 1, including a transducer array 1 and a control system (not shown in the figure).
  • the transducer array 1 includes a plurality of arrays of transducers. ⁇ 10.
  • the control system is connected to the transducer array 1, specifically, the control system is connected to each transducer 10 in the transducer array 1, and the control system is used to control the transducer array 1 to emit multiple points in the first period of time. Focus the ultrasonic wave and emit multi-angle planar ultrasonic waves in the second period. The first period and the second period are alternately performed.
  • the planar ultrasonic waves reflected by the particles received by the transducer array 1 form a stereo ultrasonic image. According to the stereo ultrasonic image, any The parameters of the multi-point focused ultrasound emitted by the transducer 10 are adjusted to control the position of the particles by changing the position of the focal point of the focused ultrasound emitted by the transducer array 1.
  • control system can adjust the phase, amplitude and waveform of the multi-point focused ultrasound emitted by any transducer 10, so as to change the transducer by adjusting the phase and/or amplitude of any transducer 10.
  • the period during which the transducer array 1 emits ultrasonic waves is divided into alternate first and second periods, and the transducer array 1 is controlled to emit multi-point focused ultrasonic waves in the first period and in the second period. Transmit multi-angle planar ultrasonic waves, and form a stereo ultrasonic image based on the planar ultrasonic waves reflected by the particles received by the transducer array 1, so that the manipulation of the particles can be guided and monitored through the stereo ultrasonic images, thereby improving the control of the particles by the acoustic tweezers device Accuracy.
  • the transducer array 1 is a planar array as an example for description, but it is not limited to this. In other embodiments, the transducer array 1 may also be a linear array, a circular array, or a curved array. Wait. As shown in FIG. 1, the planar transducer array 1 may include 16*16, that is, 256 transducers 10.
  • the size of each transducer 10 is 2mm*2mm ⁇ 3mm*3mm, preferably 2.6mm*2.6mm; the center spacing of the transducer 10 is 2mm ⁇ 3mm, preferably 2.8mm ( Approximately twice the wavelength of the emitted ultrasonic wave); the center frequency of the transducer array 1 is 1 MHz to 1.5 MHz, preferably 1.04 MHz. Based on this, the size of the 16*16 planar transducer array 1 is 50mm*50mm. Since the transducer array 1 in the embodiment of the present invention has a smaller size and a higher frequency, the acoustic tweezers device in the embodiment of the present invention can manipulate particles in a water environment.
  • the control system is an improvement based on the Verasonics Vantage 256 system.
  • the control system can independently control the emission phase, amplitude, and waveform of each transducer 10, so that the The adjustment of the phase and/or amplitude changes the position of the focal point of the focused ultrasound emitted by the transducer array 1.
  • the control system can use the pseudo-inverse algorithm to calculate the excitation signal required by the transducer array 1 when multiple focal points are realized in the three-dimensional space, and introduce this excitation signal into the transducer array 1 to form a designated multi-focus Sound field.
  • the particles to be manipulated are PDMS (Polydimethylsiloxane, polydimethylsiloxane) particles as an example.
  • the direction of the acoustic radiation force received by the particles is directed to the strong field position. Therefore, the particles can be captured.
  • three-dimensional manipulation of multiple PDMS particles can be realized by changing the position of the multi-focus in real time. Taking three focal points of different depths as an example, the distances from the three focal points to the surface of the transducer array 1 are respectively 50mm, 60mm and 70mm, and the lateral distance between two adjacent focal points is 10mm.
  • the measured lateral is the sound field distribution in the xy plane. As shown in Fig. 2, the measured axial sound field distribution in the xz plane is shown in Fig. 3, and the experimental result of using this sound field to capture three PDMS particles is shown in Fig. 4.
  • the control system inserts the imaging sequence into the control sequence, that is, divides the period during which the transducer array 1 emits ultrasonic waves into alternate first and second periods.
  • the control sequence In the control sequence, In the first period, a pulse signal used to form a multi-point focused ultrasonic wave is transmitted for particle control.
  • a multi-angle planar ultrasonic pulse signal is transmitted, and according to the reflected response received by the transducer array 1 The wave signal is imaged by multi-angle plane wave composite method to realize three-dimensional acoustic tweezers under image monitoring.
  • control system in the embodiment of the present invention can not only use a multi-angle plane wave composite method to form a three-dimensional ultrasound image, but also use a synthetic aperture imaging method or a divergent broadcast imaging method to form a three-dimensional ultrasound image. A repeat.
  • FIG. 6 the schematic diagram of the acoustic tweezers device manipulating a single PDMS particle is shown in Figure 6, and the acoustic tweezers experiment of manipulating a single PDMS particle is shown in Figure 7.
  • Figure 8. the ultrasound images of the XZ, XY, and YZ planes are shown in Figure 8. , 9 and 10.
  • ultrasound imaging does not require the use of optically transparent media, it is guaranteed that even in non-transparent media, we can see the movement of particles when they are manipulated. At the same time, ultrasound images can be used to guide three-dimensional acoustic tweezers.
  • control system before controlling the particles to reach the designated position, is also used to obtain the first position of the particles according to the image of the first imaging plane, predict the second position of the particles on the second imaging plane according to the first position, and change The position of a focal point of the focused ultrasound emitted by the energy transducer array 1 is moved to the second position to capture the particles; wherein the first imaging plane and the second imaging plane are both parallel to the surface of the transducer array 1, and the second imaging plane Located between the first imaging plane and the transducer array 1.
  • the generated ultrasound image locks the lateral position where the PDMS particles fall, that is, the first position of the PDMS particles at the moment is (X 0 , Y 0 , Z 0 ).
  • the control system can control the PDMS particles to move to any designated position in the three-dimensional space (X 1 , Y 1 , Z 2 ) by changing the position of the focus. During the movement of the PDMS particles, it can continue to pass ultrasound The image is monitored.
  • the acoustic tweezers are guided and monitored by the ultrasonic image to guide and monitor the particles, which solves the problem that the acoustic tweezers start to capture particles from any initial position, and greatly improves the usability of the acoustic tweezers.
  • the embodiment of the present invention also provides a method for manipulating particles, which is applied to the acoustic tweezers device provided in any of the above embodiments. As shown in FIG. 12, the method includes:
  • S101 Control the transducer array to emit multi-point focused ultrasonic waves in the first period and multi-angle planar ultrasonic waves in the second period, and the first period and the second period are performed alternately;
  • S103 Adjust the parameters of the multi-point focused ultrasound emitted by any transducer according to the stereo ultrasound image, so as to control the position of the particles by changing the positions of the multiple focal points of the focused ultrasound emitted by the transducer array.
  • the period during which the transducer array 1 emits ultrasonic waves is divided into alternate first and second periods, and the transducer array 1 is controlled to emit multi-point focused ultrasound in the first period and to emit in the second period.
  • Multi-angle planar ultrasonic waves form a stereo ultrasonic image based on the planar ultrasonic waves reflected by the particles received by the transducer array 1, and adjust the parameters of the multi-point focused ultrasonic waves emitted by any transducer according to the stereo ultrasonic images to change the transducer.
  • the positions of multiple focal points of the focused ultrasound emitted by the sensor array are used to control the position of the particles, so that the manipulation of the particles can be guided and monitored through the stereo ultrasound image, thereby improving the accuracy of the acoustic tweezers device for the manipulation of the particles.
  • forming a three-dimensional ultrasound image according to the planar ultrasound reflected by the particles received by the transducer array includes:
  • a multi-angle plane wave composite method, a synthetic aperture imaging method, or a divergent imaging method is adopted to form a three-dimensional ultrasound image based on the planar ultrasound reflected by the particles received by the transducer array.
  • first imaging plane and the second imaging plane are both parallel to the surface of the transducer array, and the second imaging plane is located between the first imaging plane and the transducer array.
  • the generated ultrasound image locks the lateral position where the PDMS particles fall, that is, the first position of the PDMS particles at the moment is (X 0 , Y 0 , Z 0 ).
  • the falling PDMS particles fall to the height of Z 1 , they will be captured by the focused ultrasound emitted by the control system, thereby stopping the falling.
  • control system can control the PDMS particles to move to any designated position in the three-dimensional space (X 1 , Y 1 , Z 2 ) by changing the position of the focus. During the movement of the PDMS particles, it can continue to pass ultrasound The image is monitored.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Physics & Mathematics (AREA)
  • Radar, Positioning & Navigation (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Remote Sensing (AREA)
  • General Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Hematology (AREA)
  • Clinical Laboratory Science (AREA)
  • Acoustics & Sound (AREA)
  • Dispersion Chemistry (AREA)
  • Analytical Chemistry (AREA)
  • Fluid Mechanics (AREA)
  • Computer Networks & Wireless Communication (AREA)
  • General Physics & Mathematics (AREA)
  • Toxicology (AREA)
  • Organic Chemistry (AREA)
  • Ultra Sonic Daignosis Equipment (AREA)

Abstract

本发明提供了一种声镊装置及对微粒的操控方法，包括：换能器阵列，所述换能器阵列包括多个阵列排布的换能器；控制系统，所述控制系统与所述换能器阵列相连，用于控制所述换能器阵列在第一时段发射多点聚焦超声波、在第二时段发射多角度平面超声波，所述第一时段和所述第二时段交替进行，并根据所述换能器阵列接收到的微粒反射的平面超声波形成立体超声图像，根据所述立体超声图像对任一所述换能器发射的多点聚焦超声波的参数进行调整，以通过改变所述换能器阵列发射的聚焦超声波的多个焦点的位置，来操控所述微粒的位置，从而可以通过立体超声图像对微粒的操控进行引导和监控，进而提高了声镊装置对微粒操控的精确度。

Description

一种声镊装置及对微粒的操控方法 技术领域
本发明涉及声操控技术领域，更具体地说，涉及一种声镊装置及其对微粒的操控方法。
 背景技术
与光镊类似，声镊能够通过在微粒上施加声辐射力，实现对微粒的操控。基于声波与光波的差异，声镊对比光镊具有一些优势，主要是：1、声镊对传播介质的光透明度没有要求，可以在非透明介质中进行，这就使得声镊可能在空气、水中、甚至理论上在活体等各种介质中应用；2、声镊在单位输入能量下的捕捉力远大于光镊，可以用更低的能量捕捉相同尺寸的微粒，减少对微粒造成损伤的危险或者在相同能量下捕捉更大尺寸的微粒，如实现对厘米级别微粒的操控。这些优势使得声镊非常适合在生物医学领域进行应用。
当声镊在活体等复杂环境中应用时，存在的首要问题就是活体等的环境和结构十分复杂，这就要求能够对微粒实现灵活、实时的三维操控。其次，活体等环境中传播的介质是非透明的，很难通过肉眼或者照相机观察到微粒操控的情况。
目前，基于换能器阵列的声镊因为具有其操控的声场可以实时动态变化、可以完成复杂的操控行为等特点，已经成为了微粒声操控的主要方法之一。但是，该声镊并不能对微粒的操控情况进行观察和监控，从而导致该声镊对微粒的声操控精确度较低。
 技术问题
有鉴于此，本发明提供了一种声镊装置及对微粒的操控方法，以提高微粒的声操控精确度。
 技术解决方案
为实现上述目的，本发明提供如下技术方案：
一种声镊装置，包括：
换能器阵列，所述换能器阵列包括多个阵列排布的换能器；
控制系统，所述控制系统与所述换能器阵列相连，用于控制所述换能器阵列在第一时段发射多点聚焦超声波、在第二时段发射多角度平面超声波，所述第一时段和所述第二时段交替进行，并根据所述换能器阵列接收到的微粒反射的平面超声波形成立体超声图像，根据所述立体超声图像对任一所述换能器发射的多点聚焦超声波的参数进行调整，以通过改变所述换能器阵列发射的聚焦超声波的多个焦点的位置，来操控所述微粒的位置。
可选地，操控所述微粒的位置之前，所述控制系统还用于根据第一成像平面的图像获得所述微粒的第一位置，根据所述第一位置预估出所述微粒在第二成像平面上的第二位置，并将所述换能器阵列发射的聚焦超声波的一个焦点的位置移动到所述第二位置，对所述微粒进行捕捉；
其中，所述第一成像平面和所述第二成像平面均平行于所述换能器阵列表面，且所述第二成像平面位于所述第一成像平面和所述换能器阵列之间。
可选地，所述换能器的尺寸为2mm*2mm~3mm*3mm；所述换能器的中心间距为2mm~3mm。
可选地，所述换能器阵列的中心频率为1MHz~1.5MHz。
可选地，所述换能器阵列为平面阵列、线形阵列、环形阵列或弧面阵列。
可选地，所述换能器阵列为平面阵列，所述换能器阵列包括16*16个换能器，所述换能器阵列的尺寸为50mm*50mm。
可选地，所述控制系统采用多角度平面波复合的方法、合成孔径成像方法或发散播成像方法形成立体超声图像。
一种对微粒的操控方法，应用于如上任一项所述的声镊装置，包括：
控制换能器阵列在第一时段发射多点聚焦超声波、在第二时段发射多角度平面超声波，所述第一时段和所述第二时段交替进行；
根据所述换能器阵列接收到的微粒反射的平面超声波形成立体超声图像；
根据所述立体超声图像对任一所述换能器发射的多点聚焦超声波的参数进行调整，以通过改变所述换能器阵列发射的聚焦超声波的多个焦点的位置，来操控所述微粒的位置。
可选地，操控所述微粒的位置之前，还包括：
根据第一成像平面的图像获得所述微粒的第一位置；
根据所述第一位置预估出所述微粒在第二成像平面上的第二位置；
将所述换能器阵列发射的聚焦超声波的一个焦点的位置移动到所述第二位置，对所述微粒进行捕捉；
其中，所述第一成像平面和所述第二成像平面均平行于所述换能器阵列表面，且所述第二成像平面位于所述第一成像平面和所述换能器阵列之间。
可选地，根据所述换能器阵列接收到的微粒反射的平面超声波形成立体超声图像包括：
采用多角度平面波复合的方法、合成孔径成像方法或发散播成像方法，根据所述换能器阵列接收到的微粒反射的平面超声波形成立体超声图像。
 有益效果
与现有技术相比，本发明所提供的技术方案具有以下优点：
本发明所提供的声镊装置及对微粒的操控方法，将换能器阵列发射超声波的时段分成了交替进行的第一时段和第二时段，并控制换能器阵列在第一时段发射多点聚焦超声波、在第二时段发射多角度平面超声波，并根据换能器阵列接收到的微粒反射的平面超声波形成立体超声图像，根据立体超声图像对任一换能器发射的多点聚焦超声波的参数进行调整，以通过改变换能器阵列发射的聚焦超声波的焦点的位置，来操控微粒的位置，从而可以通过立体超声图像对微粒的操控进行引导和监控，进而提高了声镊装置对微粒操控的精确度。
 附图说明
图1为本发明实施例提供的一种声镊装置的结构示意图；
图2为本发明实施例提供的一种声镊装置产生的x-y平面声场分布图；
图3为本发明实施例提供的一种声镊装置产生的x-z平面声场分布图；
图4为本发明实施例提供的一种声镊装置产生的声场对三个PDMS微粒进行捕捉的实验结果示意图；
图5为本发明实施例提供的一种换能器阵列的控制时序图；
图6为本发明实施例提供的声镊装置操控单个PDMS微粒的示意图；
图7为本发明实施例提供的声镊装置产生的声场对单个PDMS微粒进行操控的示意图；
图8为本发明实施例提供的操控单个PDMS微粒时，X-Z平面的超声图像示意图；
图9为本发明实施例提供的操控单个PDMS微粒时，X-Y平面的超声图像示意图；
图10为本发明实施例提供的操控单个PDMS微粒时，Y-Z平面的超声图像示意图；
图11为本发明实施例提供的声镊装置捕捉PDMS微粒的示意图；
图12为本发明实施例提供的声镊装置对微粒的操控方法的流程图。
 本发明的最佳实施方式
以上是本发明的核心思想，为使本发明的上述目的、特征和优点能够更加明显易懂，下面将结合本发明实施例中的附图，对本发明实施例中的技术方案进行清楚、完整地描述，显然，所描述的实施例仅仅是本发明一部分实施例，而不是全部的实施例。基于本发明中的实施例，本领域普通技术人员在没有做出创造性劳动前提下所获得的所有其他实施例，都属于本发明保护的范围。
本发明实施例提供了一种声镊装置，如图1所示，包括换能器阵列1和控制系统（图中未示出），该换能器阵列1包括多个阵列排布的换能器10。
其中，控制系统与换能器阵列1相连，具体地，控制系统与换能器阵列1中的每个换能器10相连，控制系统用于控制换能器阵列1在第一时段发射多点聚焦超声波、在第二时段发射多角度平面超声波，第一时段和第二时段交替进行，并根据换能器阵列1接收到的微粒反射的平面超声波形成立体超声图像，根据立体超声图像对任一换能器10发射的多点聚焦超声波的参数进行调整，以通过改变换能器阵列1发射的聚焦超声波的焦点的位置，来操控微粒的位置。
其中，控制系统可以对任一换能器10发射的多点聚焦超声波的相位、幅值和波形进行调整，以通过对任一换能器10相位和/或幅值的调整，改变换能器阵列1发射的聚焦超声波的焦点的位置。
本发明实施例中，将换能器阵列1发射超声波的时段分成了交替进行的第一时段和第二时段，并控制换能器阵列1在第一时段发射多点聚焦超声波、在第二时段发射多角度平面超声波，并根据换能器阵列1接收到的微粒反射的平面超声波形成立体超声图像，从而可以通过立体超声图像对微粒的操控进行引导和监控，进而提高了声镊装置对微粒操控的精确度。
本发明实施例中，仅以换能器阵列1为平面阵列为例进行说明，但并不仅限于此，在其他实施例中，换能器阵列1还可以为线形阵列、环形阵列或弧面阵列等。如图1所示，平面的换能器阵列1可以包括16*16即256个换能器10。
可选地，本发明中，每个换能器10的尺寸为2mm*2mm~3mm*3mm，优选为2.6mm*2.6mm；换能器10的中心间距为2mm~3mm，优选为2.8mm（约为发射的超声波波长的2倍）；换能器阵列1的中心频率为1MHz~1.5MHz，优选为1.04MHz。基于此，16*16平面换能器阵列1的尺寸为50mm*50mm。由于本发明实施例中换能器阵列1的尺寸较小，频率较高，因此，本发明实施例中的声镊装置可以在水环境中对微粒进行操控。
本发明实施例中，控制系统是在Verasonics Vantage 256系统基础上进行的改进，该控制系统可以独立控制每一个换能器10的发射相位、幅值和波形，以通过对任一换能器10相位和/或幅值的调整，改变换能器阵列1发射的聚焦超声波的焦点的位置。并且，该控制系统可以利用伪逆算法计算出在三维空间中实现多个焦点时，换能器阵列1需要的激励信号，并将此激励信号导入换能器阵列1中，形成指定的多焦点声场。
本发明实施例中，以操控的微粒为PDMS（Polydimethylsiloxane，聚二甲基硅氧烷）微粒为例进行说明，该微粒受到的声辐射力方向是指向强场位置，因此，该微粒可以被捕捉到多焦点声场的焦点位置，通过实时改变多焦点的位置，就可以实现多个PDMS微粒的三维操控。以不同深度的三个焦点为例，这三个焦点距离换能器阵列1表面分别为50mm、60mm和70mm，相邻两焦点之间的横向距离为10mm，测量得到的横向即x-y平面声场分布如图2所示，测量得到的轴向即x-z平面声场分布如图3所示，利用此声场对三个PDMS微粒进行捕捉的实验结果如图4所示。
本发明实施例中，如图5所示，控制系统通过将成像序列插入操控序列，即将换能器阵列1发射超声波的时段分成了交替进行的第一时段和第二时段，在控制序列中即第一时段发射用于形成多点聚焦超声波的脉冲信号来进行微粒操控，在成像序列即第二时段中发射多角度的平面超声波的脉冲信号，并根据换能器阵列1接收的反射回来的回波信号，采用多角度平面波复合的方法进行成像，实现图像监控下的三维声镊。
需要说明的是，本发明实施例中的控制系统不仅可以采用多角度平面波复合的方法形成立体超声图像，还可以采用合成孔径成像方法或发散播成像方法等形成立体超声图像，在此不再一一赘述。
其中，声镊装置操控单个PDMS微粒的示意图如图6所示，操控单个PDMS微粒的声镊实验如图7所示，操控单个PDMS微粒时，X-Z、X-Y和Y-Z平面的超声图像分别如图8、9和10所示。
由于超声成像不需要借助光透明介质，因此，保证了即使在非透明介质中，我们也能看到微粒被操控时的运动状态。同时，可以利用超声图像来引导三维声镊。如在操控微粒到达指定位置之前，控制系统还用于根据第一成像平面的图像获得微粒的第一位置，根据第一位置预估出微粒在第二成像平面上的第二位置，并将换能器阵列1发射的聚焦超声波的一个焦点的位置移动到第二位置，对微粒进行捕捉；其中，第一成像平面和第二成像平面均平行于换能器阵列1表面，且第二成像平面位于第一成像平面和换能器阵列1之间。
如图11所示，在换能器阵列1上方，平行于换能器阵列1表面的方向设置两个成像平面，第一成像平面即X-Y成像平面（Z=Z 0）和第二成像平面即X-Y成像平面（Z=Z 1）。当在成像空间中的任意位置扔下一个PDMS微粒时，PDMS微粒自由下落，当PDMS微粒下落穿过X-Y成像平面（Z=Z 0）时，控制系统可以通过X-Y成像平面（Z=Z 0）生成的超声图像锁定PDMS微粒下落的横向位置，即得到PDMS微粒此刻的第一位置为（X 0，Y 0，Z 0）。然后，控制系统可以根据PDMS微粒此时刻的第一位置预估出微粒在X-Y成像平面（Z=Z 1）上的第二位置（X 0，Y 0，Z 1），之后立即将聚焦超声波的焦点移动到PDMS微粒此刻第一位置（X 0，Y 0，Z 0）正下方的第二位置（X 0，Y 0，Z 1）。
当下落的PDMS微粒下落至Z 1高度时，它就会被控制系统发射的聚焦超声波捕获，从而停止下落。当PDMS微粒捕获以后，控制系统就可以通过改变焦点的位置，操控PDMS微粒移动到三维空间的任意指定位置（X 1，Y 1，Z 2），在PDMS微粒运动的过程中，可以继续通过超声图像进行监控。本发明实施例中，通过超声图像引导声镊装置进行微粒的引导和监控，解决了声镊从任意初始位置开始捕捉微粒的问题，大大提高了声镊的可用性。
本发明实施例还提供了一种对微粒的操控方法，应用于如上任一实施例提供的声镊装置，如图12所示，该方法包括：
S101：控制换能器阵列在第一时段发射多点聚焦超声波、在第二时段发射多角度平面超声波，第一时段和第二时段交替进行；
S102：根据换能器阵列接收到的微粒反射的平面超声波形成立体超声图像；
S103：根据立体超声图像对任一换能器发射的多点聚焦超声波的参数进行调整，以通过改变换能器阵列发射的聚焦超声波的多个焦点的位置，来操控微粒的位置。
本发明实施例中，将换能器阵列1发射超声波的时段分成了交替进行的第一时段和第二时段，控制换能器阵列1在第一时段发射多点聚焦超声波、在第二时段发射多角度平面超声波，根据换能器阵列1接收到的微粒反射的平面超声波形成立体超声图像，根据立体超声图像对任一换能器发射的多点聚焦超声波的参数进行调整，以通过改变换能器阵列发射的聚焦超声波的多个焦点的位置，来操控微粒的位置，从而可以通过立体超声图像对微粒的操控进行引导和监控，进而提高了声镊装置对微粒操控的精确度。
需要说明的是，本发明实施例中，根据换能器阵列接收到的微粒反射的平面超声波形成立体超声图像包括：
采用多角度平面波复合的方法、合成孔径成像方法或发散播成像方法，根据换能器阵列接收到的微粒反射的平面超声波形成立体超声图像。
可选地，操控微粒的位置之前，还包括：
根据第一成像平面的图像获得微粒的第一位置；
根据第一位置预估出微粒在第二成像平面上的第二位置；
将换能器阵列发射的聚焦超声波的一个焦点的位置移动到第二位置，对微粒进行捕捉；
其中，第一成像平面和第二成像平面均平行于换能器阵列表面，且第二成像平面位于第一成像平面和换能器阵列之间。
如图11所示，在换能器阵列1上方，平行于换能器阵列1表面的方向设置两个成像平面，第一成像平面即X-Y成像平面（Z=Z 0）和第二成像平面即X-Y成像平面（Z=Z 1）。当在成像空间中的任意位置扔下一个PDMS微粒时，PDMS微粒自由下落，当PDMS微粒下落穿过X-Y成像平面（Z=Z 0）时，控制系统可以通过X-Y成像平面（Z=Z 0）生成的超声图像锁定PDMS微粒下落的横向位置，即得到PDMS微粒此刻的第一位置为（X 0，Y 0，Z 0）。然后，控制系统可以根据PDMS微粒此时刻的第一位置预估出微粒在X-Y成像平面（Z=Z 1）上的第二位置（X 0，Y 0，Z 1），之后立即将聚焦超声波的焦点移动到PDMS微粒此刻第一位置（X 0，Y 0，Z 0）正下方的第二位置（X 0，Y 0，Z 1）。当下落的PDMS微粒下落至Z 1高度时，它就会被控制系统发射的聚焦超声波捕获，从而停止下落。当PDMS微粒捕获以后，控制系统就可以通过改变焦点的位置，操控PDMS微粒移动到三维空间的任意指定位置（X 1，Y 1，Z 2），在PDMS微粒运动的过程中，可以继续通过超声图像进行监控。
本说明书中各个实施例采用递进的方式描述，每个实施例重点说明的都是与其他实施例的不同之处，各个实施例之间相同相似部分互相参见即可。对于实施例公开的装置而言，由于其与实施例公开的方法相对应，所以描述的比较简单，相关之处参见方法部分说明即可。
对所公开的实施例的上述说明，使本领域专业技术人员能够实现或使用本发明。对这些实施例的多种修改对本领域的专业技术人员来说将是显而易见的，本文中所定义的一般原理可以在不脱离本发明的精神或范围的情况下，在其它实施例中实现。因此，本发明将不会被限制于本文所示的这些实施例，而是要符合与本文所公开的原理和新颖特点相一致的最宽的范围。

Claims (10)

  1. 一种声镊装置，其特征在于，包括：
    换能器阵列，所述换能器阵列包括多个阵列排布的换能器；
    控制系统，所述控制系统与所述换能器阵列相连，用于控制所述换能器阵列在第一时段发射多点聚焦超声波、在第二时段发射多角度平面超声波，所述第一时段和所述第二时段交替进行，并根据所述换能器阵列接收到的微粒反射的平面超声波形成立体超声图像，根据所述立体超声图像对任一所述换能器发射的多点聚焦超声波的参数进行调整，以通过改变所述换能器阵列发射的聚焦超声波的多个焦点的位置，来操控所述微粒的位置。
  2. 根据权利要求1所述的声镊装置，其特征在于，操控所述微粒的位置之前，所述控制系统还用于根据第一成像平面的图像获得所述微粒的第一位置，根据所述第一位置预估出所述微粒在第二成像平面上的第二位置，并将所述换能器阵列发射的聚焦超声波的一个焦点的位置移动到所述第二位置，对所述微粒进行捕捉；
    其中，所述第一成像平面和所述第二成像平面均平行于所述换能器阵列表面，且所述第二成像平面位于所述第一成像平面和所述换能器阵列之间。
  3. 根据权利要求1或2所述的声镊装置，其特征在于，所述换能器的尺寸为2mm*2mm~3mm*3mm；所述换能器的中心间距为2mm~3mm。
  4. 根据权利要求3所述的声镊装置，其特征在于，所述换能器阵列的中心频率为1MHz~1.5MHz。
  5. 根据权利要求1所述的声镊装置，其特征在于，所述换能器阵列为平面阵列、线形阵列、环形阵列或弧面阵列。
  6. 根据权利要求5所述的声镊装置，其特征在于，所述换能器阵列为平面阵列，所述换能器阵列包括16*16个换能器，所述换能器阵列的尺寸为50mm*50mm。
  7. 根据权利要求1所述的声镊装置，其特征在于，所述控制系统采用多角度平面波复合的方法、合成孔径成像方法或发散播成像方法形成立体超声图像。
  8. 一种对微粒的操控方法，其特征在于，应用于权利要求1~7任一项所述的声镊装置，包括：
    控制换能器阵列在第一时段发射多点聚焦超声波、在第二时段发射多角度平面超声波，所述第一时段和所述第二时段交替进行；
    根据所述换能器阵列接收到的微粒反射的平面超声波形成立体超声图像；
    根据所述立体超声图像对任一所述换能器发射的多点聚焦超声波的参数进行调整，以通过改变所述换能器阵列发射的聚焦超声波的多个焦点的位置，来操控所述微粒的位置。
  9. 根据权利要求8所述的方法，其特征在于，操控所述微粒的位置之前，还包括：
    根据第一成像平面的图像获得所述微粒的第一位置；
    根据所述第一位置预估出所述微粒在第二成像平面上的第二位置；
    将所述换能器阵列发射的聚焦超声波的一个焦点的位置移动到所述第二位置，对所述微粒进行捕捉；
    其中，所述第一成像平面和所述第二成像平面均平行于所述换能器阵列表面，且所述第二成像平面位于所述第一成像平面和所述换能器阵列之间。
  10. 根据权利要求8所述的方法，其特征在于，根据所述换能器阵列接收到的微粒反射的平面超声波形成立体超声图像包括：
    采用多角度平面波复合的方法、合成孔径成像方法或发散播成像方法，根据所述换能器阵列接收到的微粒反射的平面超声波形成立体超声图像。
PCT/CN2020/129485 2019-12-12 2020-11-17 一种声镊装置及对微粒的操控方法 WO2021115046A1 (zh)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CN201911290838.8 2019-12-12
CN201911290838.8A CN111013518B (zh) 2019-12-12 2019-12-12 一种声镊装置及对微粒的操控方法

Publications (1)

Publication Number Publication Date
WO2021115046A1 true WO2021115046A1 (zh) 2021-06-17

Family

ID=70209213

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CN2020/129485 WO2021115046A1 (zh) 2019-12-12 2020-11-17 一种声镊装置及对微粒的操控方法

Country Status (2)

Country Link
CN (1) CN111013518B (zh)
WO (1) WO2021115046A1 (zh)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN114146890A (zh) * 2021-12-03 2022-03-08 深圳先进技术研究院 一种超声声操控的方法及声镊装置

Families Citing this family (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN111013518B (zh) * 2019-12-12 2020-12-08 深圳先进技术研究院 一种声镊装置及对微粒的操控方法
CN112349446B (zh) * 2020-11-03 2022-03-01 深圳先进技术研究院 一种操控方法及声镊装置
CN112562631B (zh) * 2020-11-17 2022-04-26 深圳先进技术研究院 一种声镊的生成方法及生成系统
CN114160070A (zh) * 2021-12-02 2022-03-11 深圳先进技术研究院 一种操控方法、声镊装置和应用该声镊装置的显微设备
CN114426964A (zh) * 2021-12-03 2022-05-03 深圳先进技术研究院 一种超声声操控的方法
WO2023102774A1 (zh) * 2021-12-08 2023-06-15 深圳先进技术研究院 一种基于人机交互的声操控方法及系统

Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20110021920A1 (en) * 2009-07-22 2011-01-27 Siemens Medical Solutions Usa, Inc Switch for Aperture Control in Medical Diagnostic Ultrasound Imaging
CN105214742A (zh) * 2015-10-10 2016-01-06 中国科学院深圳先进技术研究院 基于人工结构声场的微流体系统及操控微粒的方法
CN105233429A (zh) * 2015-11-10 2016-01-13 中国科学院深圳先进技术研究院 一种基于超声波成像对目标物进行自动追踪定位及实时智能刺激的方法及系统
CN107050630A (zh) * 2017-04-01 2017-08-18 深圳先进技术研究院 一种基于时间反转技术操控微粒的系统与方法
CN107530676A (zh) * 2015-05-13 2018-01-02 株式会社爱瑞思 微粒控制方法
US10106397B1 (en) * 2012-04-23 2018-10-23 University Of Southern California Acoustic tweezers
CN111013518A (zh) * 2019-12-12 2020-04-17 深圳先进技术研究院 一种声镊装置及对微粒的操控方法

Family Cites Families (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2015512766A (ja) * 2012-01-31 2015-04-30 ザ・ペン・ステート・リサーチ・ファンデーション 可変定常的表面弾性波を用いたマイクロ流体操作及び粒子の分類
CN110946617B (zh) * 2013-11-19 2022-11-29 港大科桥有限公司 超声流体向量成像装置及其方法
LT6438B (lt) * 2015-10-21 2017-08-25 Uab "Neurotechnology" Bekontakčio manipuliavimo įrenginys, surinkimo būdas ir 3d spausdinimas
CN110050218A (zh) * 2016-03-15 2019-07-23 法国国家科研中心 声学镊子
CN106076450B (zh) * 2016-06-03 2018-07-20 杭州电子科技大学 一种微粒悬浮动态聚焦加热系统及其加热方法
CN109953771A (zh) * 2016-06-27 2019-07-02 中国科学院苏州生物医学工程技术研究所 超声成像方法、超声弹性成像方法及微型超声装置
CN109126918B (zh) * 2018-10-18 2023-06-09 天津大学 一种用于产生声流体镊的装置

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20110021920A1 (en) * 2009-07-22 2011-01-27 Siemens Medical Solutions Usa, Inc Switch for Aperture Control in Medical Diagnostic Ultrasound Imaging
US10106397B1 (en) * 2012-04-23 2018-10-23 University Of Southern California Acoustic tweezers
CN107530676A (zh) * 2015-05-13 2018-01-02 株式会社爱瑞思 微粒控制方法
CN105214742A (zh) * 2015-10-10 2016-01-06 中国科学院深圳先进技术研究院 基于人工结构声场的微流体系统及操控微粒的方法
CN105233429A (zh) * 2015-11-10 2016-01-13 中国科学院深圳先进技术研究院 一种基于超声波成像对目标物进行自动追踪定位及实时智能刺激的方法及系统
CN107050630A (zh) * 2017-04-01 2017-08-18 深圳先进技术研究院 一种基于时间反转技术操控微粒的系统与方法
CN111013518A (zh) * 2019-12-12 2020-04-17 深圳先进技术研究院 一种声镊装置及对微粒的操控方法

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
YANG, YE ET AL.: "Three Dimensional Acoustic Tweezers Guided and Monitored by Ultrasound Images", TECHNICAL ACOUSTICS, vol. 38, no. 5, 31 October 2019 (2019-10-31), pages 301 - 302, XP055820200, ISSN: 1000-3630 *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN114146890A (zh) * 2021-12-03 2022-03-08 深圳先进技术研究院 一种超声声操控的方法及声镊装置
CN114146890B (zh) * 2021-12-03 2022-09-13 深圳先进技术研究院 一种超声声操控的方法及声镊装置

Also Published As

Publication number Publication date
CN111013518B (zh) 2020-12-08
CN111013518A (zh) 2020-04-17

Similar Documents

Publication Publication Date Title
WO2021115046A1 (zh) 一种声镊装置及对微粒的操控方法
CN108778530B (zh) 具有稀疏阵列探测器的超声成像
Fink Time-reversed acoustics
EP3607991A1 (en) Time reversal technique-based system and method for manipulating particles
JP2007152127A (ja) 合成開口のための超音波イメージングトランスデューサアレイ
CN108294751B (zh) 一种磁声电-超声检测装置
KR20150118495A (ko) 초음파 프로브, 초음파 영상 장치 및 초음파 영상 장치를 제어하는 방법
JP2007160093A (ja) 高強度焦点超音波システム及び高強度焦点超音波システム用結合ヘッド
JP2004089311A (ja) 超音波送受信装置
JPH06230489A (ja) 超音波結像装置
CN103976703A (zh) 一种光声超声双模态内窥镜成像系统及成像方法
US20210169340A1 (en) Method for Realizing Arbitrary Ultrasonic Field
JP2016509925A (ja) 超音波画像診断装置および超音波診断画像を生成する方法
KR20170090304A (ko) 초음파 트랜스듀서 및 이를 포함하는 초음파 프로브
CN110507918A (zh) 一种超声针灸系统和超声针灸系统控制方法
JP2001299747A (ja) 超音波３次元走査プローブ
WO2020037674A1 (zh) 一种超声成像装置和方法、超声弹性检测装置和方法
CN112349446B (zh) 一种操控方法及声镊装置
CN106872367B (zh) 一种成像系统及方法
JP5572023B2 (ja) 測定装置
KR101534574B1 (ko) 기울기 센서를 포함하는 초음파 프로브 및 이를 이용한 초음파 의료 장치
JP7387502B2 (ja) 超音波自動スキャンシステム、超音波診断装置、超音波スキャン支援装置
KR102329113B1 (ko) 초음파 영상 장치 및 초음파 영상 장치의 제어 방법
RU2486501C2 (ru) Способ лазерной оптико-акустической томографии и устройство для его реализации (варианты)
US20180345044A1 (en) Ultrasonic material, method for preparing the material, and ultrasonic probe comprising the material

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 20897683

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 20897683

Country of ref document: EP

Kind code of ref document: A1

32PN Ep: public notification in the ep bulletin as address of the adressee cannot be established

Free format text: NOTING OF LOSS OF RIGHTS PURSUANT TO RULE 112(1) EPC (EPO FORM 1205 DATED 02/08/2022)

122 Ep: pct application non-entry in european phase

Ref document number: 20897683

Country of ref document: EP

Kind code of ref document: A1