CN111495098A - Two-dimensional aggregation method and aggregation device for micron particles - Google Patents
Two-dimensional aggregation method and aggregation device for micron particles Download PDFInfo
- Publication number
- CN111495098A CN111495098A CN202010075464.4A CN202010075464A CN111495098A CN 111495098 A CN111495098 A CN 111495098A CN 202010075464 A CN202010075464 A CN 202010075464A CN 111495098 A CN111495098 A CN 111495098A
- Authority
- CN
- China
- Prior art keywords
- ultrasonic waves
- particles
- microfluidic channel
- dimensional
- rows
- 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
- B01D—SEPARATION
- B01D51/00—Auxiliary pretreatment of gases or vapours to be cleaned
- B01D51/02—Amassing the particles, e.g. by flocculation
- B01D51/06—Amassing the particles, e.g. by flocculation by varying the pressure of the gas or vapour
- B01D51/08—Amassing the particles, e.g. by flocculation by varying the pressure of the gas or vapour by sound or ultrasonics
Abstract
The invention discloses a two-dimensional micron particle gathering device, which comprises a transducer arranged on the outer wall of a microfluidic channel, wherein the transducer is externally connected with a signal generator; the transducer emits ultrasonic waves into the microfluidic channel to form an ultrasonic standing wave field in the channel of the fluid; the static or flowing particles in the microfluidic channel move to the sound pressure node or the sound pressure anti-node plane under the action of the ultrasonic standing wave field. The invention also discloses an aggregation method. According to the invention, a two-dimensional ultrasonic standing wave field is established, the particles in the channel are subjected to two-dimensional aggregation/concentration by using the acoustic radiation force, the number of the micron particles which can be aggregated at one time is large, and the particles in a static or continuous fluid of a microfluidic channel can be subjected to two-dimensional aggregation in the transverse direction and the longitudinal direction which are vertical to the fluid direction.
Description
Technical Field
The invention relates to an aggregation method and an aggregation device, in particular to a two-dimensional aggregation method and an aggregation device for micron particles.
Background
At present, in the fields of biomedicine, chemistry and the like, two-dimensional aggregation of micron particles such as particles, cells, viruses, liquid drops, bubbles and the like is a key step for realizing the application of the micron particles. Compared with the traditional related technology, the micron particle control technology can greatly reduce the consumption of precious samples and reagents and greatly improve the analysis speed and the like. In recent years, microfluidic technology has been widely used for cell separation and processing. For example, rare cells are enriched from peripheral blood, such as nucleated fetal cells from maternal blood, or circulating tumor cells from the blood of cancer patients. Not only in biomedical applications, but also in various fields because microfluidic technology has the advantages of rapid aggregation, efficient separation, accurate capture, etc.
Patent CN 101765762B discloses a system and method for focusing particles in a microchannel. The system includes a substrate, a channel disposed on the substrate, a fluid containing suspended particles moving along the channel in a laminar flow, and a pumping element to drive the flow of the fluid layer. The method utilizes inertia force to make particles suspended in flowing liquid gather at the center of the outlet of the pipeline to form one or more flowing particle beams through micro-channel design. But the system has very small quantity of micro-nano particles capable of gathering at one time; the pipeline design is complex, and the processing difficulty is relatively high; and the bent pipeline is not easy to clean and is easy to block the capillary.
Patent CN 109813692 a discloses a capillary analysis detection method based on ultrasonic aggregation. The method mixes and injects a trace target object, a signal marker molecule and specifically modified nanoparticles into a capillary, collects and captures the nanoparticles of the marker by an ultrasonic device to realize the collection of the ultra-trace target object, and realizes the SERS or fluorescence detection of the target object by combining a Raman microscope or a fluorescence microscope. However, when the system captures particles in the microfluidic channel, the fluid is required to be static, and the particles in the continuous fluid of the microfluidic channel cannot be two-dimensionally gathered in the transverse direction and the longitudinal direction which are perpendicular to the fluid direction.
Disclosure of Invention
The invention aims to solve the problems and provides a two-dimensional aggregation method and an aggregation device for micron particles, which have the advantages of simple structure, wide application range, convenient control and stable aggregation effect. The invention realizes two-dimensional aggregation/concentration of particles in the channel by establishing an ultrasonic standing wave field and utilizing the acoustic radiation force, the quantity of micron particles which can be aggregated at one time is large, and the two-dimensional aggregation of particles in static or continuous fluid of a microfluidic channel in the transverse direction and the longitudinal direction which are vertical to the fluid direction can be realized.
The purpose of the invention can be achieved by adopting the following technical scheme:
a two-dimensional gathering device for micron particles comprises a transducer arranged on the outer wall of a microfluidic channel, wherein the transducer is externally connected with a signal generator; the transducer emits ultrasonic waves into the microfluidic channel and reflects the ultrasonic waves back from the inner wall of the microfluidic channel to form two rows of ultrasonic waves, the amplitude and the frequency of the two rows of ultrasonic waves are the same, the two rows of ultrasonic waves are transmitted in opposite directions and meet and are superposed, and two sound sources of the two rows of ultrasonic waves are exactly separated by integral multiples of half wavelength to form standing waves by superposition; the static or flowing particles in the micro-flow channel move to the sound pressure node or the sound pressure anti-node plane under the action of the two rows of ultrasonic waves.
Preferably, the number of the transducers is two, and the two transducers are arranged perpendicular to each other.
Preferably, the transducer is attached to the outer wall of the microchannel by an AB glue.
Preferably, the microfluidic channel is a circular channel.
Preferably, the microfluidic channel is a glass capillary.
A method for aggregating microparticles in two dimensions comprises the following steps:
s1, starting a signal generator to enable the transducer to generate ultrasonic waves, wherein the ultrasonic waves are emitted into the microfluidic channel and reflected by the inner wall of the microfluidic channel to form two rows of ultrasonic waves;
s2, adjusting the frequency of the signal generator to enable two sound sources of two rows of ultrasonic waves to be just away from each other by integral multiples of half wavelength and overlapped to form standing waves; the static or flowing particles in the micro-flow channel move to the sound pressure node or the sound pressure anti-node plane under the action of the two rows of ultrasonic waves.
As a preferable scheme, the method further comprises that the number of the transducers is two, and the two transducers are arranged perpendicular to each other, and then the method further comprises the following steps:
s3, the two transducers generate ultrasonic waves to form two sound fields, static or flowing particles in the microfluidic channel are gathered at an intersection line under the action of the two sound fields to form a straight line, and two-dimensional gathering of the particles is achieved.
The implementation of the invention has the following beneficial effects:
1. the invention realizes two-dimensional aggregation/concentration of particles in the channel by establishing an ultrasonic standing wave field and utilizing the acoustic radiation force, the quantity of micron particles which can be aggregated at one time is large, and the two-dimensional aggregation of particles in static or continuous fluid of a microfluidic channel in the transverse direction and the longitudinal direction which are vertical to the fluid direction can be realized.
2. According to the invention, the second sound field is added in the direction vertical to the sound pressure node plane, so that particles originally gathered on the sound pressure node plane are gathered continuously under the action of the second sound field and are finally gathered to the intersection line of the sound pressure node planes of the front and rear sound fields, namely, the particles are gathered into a straight line in the three-dimensional flow field.
Drawings
In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings used in the description of the embodiments or the prior art will be briefly described below, it is obvious that the drawings in the following description are only some embodiments of the present invention, and for those skilled in the art, other drawings can be obtained according to the drawings without creative efforts.
FIG. 1 is a schematic view of the operation principle of the two-dimensional microparticle aggregation device of the present invention.
FIG. 2 is a schematic diagram of a two-dimensional focusing apparatus for micro-particles according to the present invention, which employs two transducers disposed perpendicular to each other.
FIG. 3 is a graph showing the experimental results of the aggregation method of the two-dimensional aggregation apparatus for fine particles according to the present invention.
Fig. 4 is an acoustic field and particle force diagram in a microfluidic channel of the focusing method of the two-dimensional focusing apparatus for microparticles according to the present invention.
Detailed Description
The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the drawings in the embodiments of the present invention, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
Examples
Referring to fig. 1 to 4, the present embodiment relates to a two-dimensional microparticle aggregation apparatus, including a transducer 2 disposed on an outer wall of a microfluidic channel 1, where the transducer 2 is externally connected to a signal generator 7; the transducer 2 emits ultrasonic waves into the microfluidic channel 1 and reflects the ultrasonic waves back from the inner wall of the microfluidic channel to form two rows of ultrasonic waves 4, the amplitude and the frequency of the two rows of ultrasonic waves 4 are the same, the two rows of ultrasonic waves 4 are transmitted in opposite directions and meet and are superposed, and two sound sources of the two rows of ultrasonic waves 4 are exactly spaced by integral multiples of half wavelength and are superposed to form standing waves; the stationary or flowing particles 5 in the microfluidic channel 1 move to the sound pressure node or sound pressure anti-node plane 6 under the action of the two rows of ultrasonic waves 4.
The ultrasonic wave is one kind of sound wave, the frequency of the ultrasonic wave is higher than 20000Hz, and the ultrasonic wave has the advantages of good directivity, strong reflection capability, easy acquisition of more concentrated sound energy, long propagation distance in water and the like. And because several trains of waves exist in the medium at the same time, each train of waves can keep respective propagation rules without mutual interference, and are linearly superposed in the overlapping area of the waves. When two rows of sound waves propagate in opposite directions with the same amplitude and frequency and meet and are superposed, and two sound sources are just separated from each other by integral multiples of half wavelength, the waves formed by superposition are called standing waves. Such an acoustic field is a standing wave field.
In the standing wave field, the antinodes vibrate up and down, and the nodes do not move. The antinode position of vibration has the highest sound pressure, and the node position has the lowest sound pressure, so that the particles are subjected to forces with different magnitudes and directions in an uneven sound field, and the resultant force of the forces is the sound radiation force. The particles 5 in the sound field will move to the sound pressure node or the sound pressure anti-node plane under the action of the sound radiation force. The invention utilizes the action of acoustic radiation force on particles to realize the capture of the particles and the two-dimensional aggregation of the particles.
The number of the transducers 2 is two, and the two transducers 2 are arranged perpendicular to each other. The two transducers 2 generate two ultrasonic waves, forming two sound fields. And a second sound field is added in the direction parallel to the sound pressure node plane, so that the particles originally gathered on the sound pressure node plane are gathered continuously under the action of the second sound field and are finally gathered to the intersection line of the sound pressure node planes of the front and rear sound fields, namely, the particles are gathered into a straight line in the three-dimensional flow field, and the two-dimensional gathering of the particles is realized.
The transducer 2 is adhered to the outer wall of the microchannel 1 by AB glue. The microfluidic channel 1 is a circular channel.
A method for aggregating microparticles in two dimensions comprises the following steps:
s1, starting the signal generator 7 to enable the transducer 2 to generate ultrasonic waves, and enabling the ultrasonic waves to emit into the microfluidic channel 1 and be reflected by the inner wall of the microfluidic channel to form two rows of ultrasonic waves;
s2, adjusting the frequency of the signal generator 7 to enable two sound sources of two rows of ultrasonic waves to be just away from each other by integral multiples of half wavelength and overlapped to form standing waves; the static or flowing particles 5 in the microfluidic channel 1 move to the sound pressure node or the sound pressure anti-node plane under the action of two rows of ultrasonic waves.
The method further comprises the following steps that two transducers 2 are arranged, and the two transducers 2 are arranged perpendicular to each other:
s3, the two transducers 2 generate ultrasonic waves to form two sound fields, and the static or flowing particles 5 in the microfluidic channel 1 are gathered at the intersection line under the action of the two sound fields to form a straight line, so that the two-dimensional gathering of the particles is realized.
As shown in fig. 1 to 4, the present invention makes the micro particles in the micro fluid channel gather into a straight line in the center of the tube under the action of the sound field. Most preferably, the present patent selects cylindrical microfluidic channels. In a circular microfluidic channel, two sound fields perpendicular to each other are simultaneously applied, and the acoustic mode of the acoustic standing wave in each direction is (1, 0). Calculating formula according to resonance frequency of cylindrical acoustic wave guide:
by looking up a function root table in combination with the acoustic mode (1,0) of the circular catheter, k(1,0)1.841/a is
(where a is the radius of the circular conduit, c0At the speed of sound). From this, the resonant frequency f in the specific device can be obtainedc. Then according to the relation: f. ofcThe thickness D of the transducer 2 can be determined at 2MHz mm. And the cost of the material, the acoustic property, the observation and aggregation effect and the like are comprehensively considered, and the capillary tube with the outer square and the inner circle of the glass material is selected as a micro-fluid channel. The appropriate transducer 2 is selected and then connected as shown in the fluid device schematic.
Specifically, the microfluidic channel 1 is a glass capillary. The inner diameter of the glass capillary tube is 0.9mm (the width of the outer side is 1.5mm, the length is 65mm), the micrometer particles are polystyrene particles (the diameter is 10um), the solution is water, the theoretical frequency (963KHz) of the transducer 2 is obtained according to the above process, and the piezoelectric ceramic transducer 2 (the width is 2.3mm, the length is 30mm) with the thickness of 2mm is selected near the theoretical frequency. Two identical transducers 2 are respectively connected with two adjacent outer walls of the glass capillary tube through AB glue. The inlet and outlet of the microfluidic channel are connected by plastic pipes (not shown for the convenience of viewing the structure) for inputting and outputting liquid. The working plane of the transducer 2 is the surface of the transducer 2 parallel to the pipe wall connected with the glass capillary, and the high-frequency voltage is a stable and continuous sine alternating voltage generated by the signal generator 7 and amplified by the signal amplifier. The two transducers 2 are excited simultaneously by high-frequency voltage (frequency is about 963KHz, based on an actual experimental device, amplitude is about 26 v), so that two orthogonal (1,0) resonance mode sound fields are generated, and the micron particles are close to the center of the pipeline under the action of acoustic radiation force and are gathered, so that two-dimensional capture of the micron particles is realized. The experimental results of this experimental apparatus are shown in fig. 3, in which (a) is the experimental result in the case of no ultrasonic drive and (b) is the experimental result in the case of ultrasonic drive.
The white dotted line in the figure indicates the pipe sidewall and the white bright spots are microparticles. The upper half is the image of the micron particle aggregation seen from the side wall of the pipe, and the result shows that the micron particles are aggregated to the center of the pipe in the vertical direction; the lower half is the image of the accumulation of microparticles from the top of the tube, which indicates that the microparticles are accumulated in the center of the tube in the horizontal direction; the aggregation results from a comparison of these two views indicate that the particles in the microfluidic channel are all aggregated in the exact center of the channel, in line, and are exactly the same as expected. The results indicate that the device achieves two-dimensional aggregation of microparticles in microfluidic channels. The experiment is repeated under the same condition, the same experiment result is obtained, and the reliability of the device is higher.
Finally, the device is modeled and simulated by using the COMSO L software, and a sound field and a particle stress diagram in the microfluidic channel are obtained, as shown in fig. 4, wherein the background color represents the sound pressure (white is the maximum (antinode), black is the minimum (node)), the arrow represents the distribution of the acoustic radiation force (the direction indicated by the arrow is the particle stress direction, and the length of the arrow represents the acoustic radiation force magnitude).
While the invention has been described in connection with what is presently considered to be the most practical and preferred embodiment, it is to be understood that the invention is not to be limited to the disclosed embodiment, but on the contrary, is intended to cover various modifications and equivalent arrangements included within the spirit and scope of the appended claims.
Claims (7)
1. The two-dimensional micron particle gathering device is characterized by comprising a transducer arranged on the outer wall of a microfluidic channel, wherein the transducer is externally connected with a signal generator; the transducer emits ultrasonic waves into the microfluidic channel and reflects the ultrasonic waves back from the inner wall of the microfluidic channel to form two rows of ultrasonic waves, the amplitude and the frequency of the two rows of ultrasonic waves are the same, the two rows of ultrasonic waves are transmitted in opposite directions and meet and are superposed, and two sound sources of the two rows of ultrasonic waves are exactly separated by integral multiples of half wavelength to form standing waves by superposition; the static or flowing particles in the micro-flow channel move to the sound pressure node or the sound pressure anti-node plane under the action of the two rows of ultrasonic waves.
2. A two-dimensional focusing assembly for collecting particles of micrometer particles as claimed in claim 1, wherein said transducers are disposed in two and are disposed perpendicular to each other.
3. The apparatus of claim 1, wherein the transducer is attached to the outer wall of the microchannel by an AB glue.
4. The apparatus of claim 1, wherein the microfluidic channel is a circular channel.
5. The two-dimensional micron particle collecting device as recited in claim 1, wherein said microfluidic channel is a glass capillary.
6. The two-dimensional micron particle aggregation apparatus as claimed in any one of claims 1 to 5, further comprising:
s1, starting a signal generator to enable the transducer to generate ultrasonic waves, wherein the ultrasonic waves are emitted into the microfluidic channel and reflected by the inner wall of the microfluidic channel to form two rows of ultrasonic waves;
s2, adjusting the frequency of the signal generator to enable two sound sources of two rows of ultrasonic waves to be just away from each other by integral multiples of half wavelength and overlapped to form standing waves; the static or flowing particles in the micro-flow channel move to the sound pressure node or the sound pressure anti-node plane under the action of the two rows of ultrasonic waves.
7. The method for collecting micron particles in a two-dimensional collecting device as claimed in claim 6, further comprising two transducers, wherein the two transducers are disposed perpendicular to each other, and the method further comprises the following steps:
s3, the two transducers generate ultrasonic waves to form two sound fields, static or flowing particles in the microfluidic channel are gathered at an intersection line under the action of the two sound fields to form a straight line, and two-dimensional gathering of the particles is achieved.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010075464.4A CN111495098A (en) | 2020-01-22 | 2020-01-22 | Two-dimensional aggregation method and aggregation device for micron particles |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010075464.4A CN111495098A (en) | 2020-01-22 | 2020-01-22 | Two-dimensional aggregation method and aggregation device for micron particles |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN111495098A true CN111495098A (en) | 2020-08-07 |
Family
ID=71848151
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202010075464.4A Pending CN111495098A (en) | 2020-01-22 | 2020-01-22 | Two-dimensional aggregation method and aggregation device for micron particles |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN111495098A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112973815A (en) * | 2021-03-09 | 2021-06-18 | 西北大学 | Microflow pipeline for collecting non-spherical micro-swimming bodies and filtering method |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5902489A (en) * | 1995-11-08 | 1999-05-11 | Hitachi, Ltd. | Particle handling method by acoustic radiation force and apparatus therefore |
| CN102933280A (en) * | 2010-06-04 | 2013-02-13 | 英派尔科技开发有限公司 | Acoustically driven nanoparticle concentrator |
| JP2017148747A (en) * | 2016-02-25 | 2017-08-31 | 東芝メモリ株式会社 | Dust collector and substrate processing system |
| CN107530676A (en) * | 2015-05-13 | 2018-01-02 | 株式会社爱瑞思 | Particulate control method |
| CN107635634A (en) * | 2015-03-24 | 2018-01-26 | 弗洛设计声能学公司 | Method and apparatus for carrying out particle aggregation using sound standing wave |
-
2020
- 2020-01-22 CN CN202010075464.4A patent/CN111495098A/en active Pending
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5902489A (en) * | 1995-11-08 | 1999-05-11 | Hitachi, Ltd. | Particle handling method by acoustic radiation force and apparatus therefore |
| CN102933280A (en) * | 2010-06-04 | 2013-02-13 | 英派尔科技开发有限公司 | Acoustically driven nanoparticle concentrator |
| CN107635634A (en) * | 2015-03-24 | 2018-01-26 | 弗洛设计声能学公司 | Method and apparatus for carrying out particle aggregation using sound standing wave |
| CN107530676A (en) * | 2015-05-13 | 2018-01-02 | 株式会社爱瑞思 | Particulate control method |
| JP2017148747A (en) * | 2016-02-25 | 2017-08-31 | 東芝メモリ株式会社 | Dust collector and substrate processing system |
Non-Patent Citations (1)
| Title |
|---|
| 程峰 等: "超声微观颗粒聚集与分离数值模拟", 《声学技术》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112973815A (en) * | 2021-03-09 | 2021-06-18 | 西北大学 | Microflow pipeline for collecting non-spherical micro-swimming bodies and filtering method |
| CN112973815B (en) * | 2021-03-09 | 2022-06-03 | 西北大学 | Microflow pipeline for collecting non-spherical micro-swimming body and filtering method |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Collins et al. | Highly localized acoustic streaming and size-selective submicrometer particle concentration using high frequency microscale focused acoustic fields | |
| Destgeer et al. | Recent advances in microfluidic actuation and micro-object manipulation via surface acoustic waves | |
| US9321050B2 (en) | Microfluidic ultrasonic particle separators with engineered node locations and geometries | |
| US9835540B2 (en) | Devices and methods for manipulating components in a fluid sample | |
| JP5886908B2 (en) | Acoustic convergence hardware and system and method for implementation | |
| Ma et al. | Mechanical properties based particle separation via traveling surface acoustic wave | |
| Hammarström et al. | Non-contact acoustic cell trapping in disposable glass capillaries | |
| JP5642684B2 (en) | Apparatus and method for separating particles from suspension by standing ultrasound | |
| KR101922172B1 (en) | Device for handling objects, using acoustic force fields | |
| Destgeer et al. | Particle separation inside a sessile droplet with variable contact angle using surface acoustic waves | |
| CN108432132A (en) | Microfluid particle manipulation | |
| US9074977B2 (en) | Multinode acoustic focusing for parallel flow cytometry analysis applications | |
| CN106914288B (en) | A kind of micro-fluidic high frequency sound focusing chip and preparation method thereof | |
| CN109569392A (en) | A kind of active micro-mixer of Y type based on surface acoustic wave | |
| CN111318218B (en) | Microfluidic device and methods of making and using the same | |
| CN115041245B (en) | Method and device for capturing and separating particles based on ultrahigh frequency bulk acoustic wave acoustic current potential well | |
| CN111495098A (en) | Two-dimensional aggregation method and aggregation device for micron particles | |
| You et al. | On-chip arbitrary manipulation of single particles by acoustic resonator array | |
| Fakhfouri et al. | Fully Microfabricated Surface Acoustic Wave Tweezer for Collection of Submicron Particles and Human Blood Cells | |
| Wang | Theoretical and experimental investigations in acoustofluidic manipulation of bioparticles | |
| CN212975166U (en) | Microfluidic chip for particle manipulation | |
| WO2023108473A1 (en) | Acoustic artificial structure-based particle sorting method | |
| WO2023234130A1 (en) | Particle two-dimensional acoustic focusing device, and acoustic concentration device using same | |
| Wang et al. | A MEMS-based opto-acoustic-fluidic system for cell imaging | |
| CN115468916A (en) | On-chip fluid control module, acoustic fluid chip and analysis device |
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 |