CN107775960B - Microfluidic chip bonding method and microfluidic chip - Google Patents
Microfluidic chip bonding method and microfluidic chip Download PDFInfo
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
- B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
- B29C65/00—Joining or sealing of preformed parts, e.g. welding of plastics materials; Apparatus therefor
- B29C65/02—Joining or sealing of preformed parts, e.g. welding of plastics materials; Apparatus therefor by heating, with or without pressure
- B29C65/08—Joining or sealing of preformed parts, e.g. welding of plastics materials; Apparatus therefor by heating, with or without pressure using ultrasonic vibrations
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- 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
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
- B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
- B29C65/00—Joining or sealing of preformed parts, e.g. welding of plastics materials; Apparatus therefor
- B29C65/48—Joining or sealing of preformed parts, e.g. welding of plastics materials; Apparatus therefor using adhesives, i.e. using supplementary joining material; solvent bonding
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
- B01L2200/10—Integrating sample preparation and analysis in single entity, e.g. lab-on-a-chip concept
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2300/00—Additional constructional details
- B01L2300/08—Geometry, shape and general structure
- B01L2300/0861—Configuration of multiple channels and/or chambers in a single devices
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2300/00—Additional constructional details
- B01L2300/08—Geometry, shape and general structure
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2300/00—Additional constructional details
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Abstract
The invention relates to the technical field of biological science micro total analysis systems, in particular to a microfluidic chip bonding method and a microfluidic chip. The method comprises the following steps: providing a micro-fluidic chip substrate, wherein the upper surface of the substrate is provided with a micro-channel structure; arranging ultrasonic bonding energy guide ribs at the peripheral edge of the micro-channel structure on the upper surface of the substrate or arranging ultrasonic bonding energy guide ribs on the periphery of the position, corresponding to the micro-channel structure on the surface of the substrate, of the cover plate; adhering a double-sided adhesive tape to the adhesive surface of the base sheet or the cover sheet, and adhering the cover sheet and the base sheet; carrying out ultrasonic bonding on the substrate and the cover plate to enable the substrate and the cover plate to be subjected to first-step bonding; and carrying out pressure fixation or hot pressing on the chip to firmly bond the substrate and the cover plate which are adhered by the double-sided adhesive. The invention can not only ensure the bonding stability of the microfluidic chip, but also avoid influencing the physical and chemical properties of the microfluidic chip, thereby not interfering the detection result.
Description
Technical Field
The invention relates to the technical field of biological science micro total analysis systems, in particular to a microfluidic chip bonding method and a microfluidic chip.
Background
The bonding link of the microfluidic chip is one of the key links for preparing the microfluidic chip, and the actual application of the microfluidic chip is directly influenced by the quality of the bonding. The main problems to be noted in the current microfluidic chip bonding link include:
1. the chip is required to be connected, the micro-channel has sealing performance, and the bonded micro-channel has enough mechanical strength, so that cracking and liquid leakage are avoided.
2. During the bonding process, the micro-channel is prevented from deforming, blocking or being influenced by other factors.
3. When organic matter is used for bonding, it is necessary to avoid changes in the physicochemical properties of the surface.
Currently, known polymer microfluidic chip bonding techniques include thermocompression bonding, solvent bonding, glue bonding, laser or ultrasonic bonding. Among them, thermocompression bonding is less efficient and is less commercially used. The physical surface physical and chemical properties are easy to change due to solvent bonding, and the method is not suitable for being applied to the field of biological medicines. The glue is bonded between the substrate and the cover plate, and adhesive or double-sided adhesive is introduced to realize the connection of the upper device and the lower device. Although the method has the advantages of simple operation, low cost, high bonding strength and the like, the method also has the obvious defects of easily causing glue to permeate into a channel to cause channel blockage or non-specific adsorption of a sample or a marker by double-sided glue and the like. The ultrasonic bonding technology is to convert the mechanical vibration energy with the ultrasonic frequency of more than 20KHz into the heat energy of the device to be welded, so that the contact surface of the device is melted to realize the linkage of the welding parts. The ultrasonic bonding technology is simple to operate and high in stability, but the requirement for bonding wires is high, liquid leakage is likely to occur at a virtual joint point due to uneven bonding wires, and the virtual joint point cannot be detected. The laser bonding requires the adoption of a material for absorbing laser, and the laser generates heat at a bonding interface to enable the interface to reach the purpose of connection in a heated and molten state.
Chinese patent No. 1480724 uses infrared laser as heat source to thermally bond plastic microfluidic chip, and part of the chip is melted to achieve bonding during irradiation; chinese patent No. 1588669 describes a method for thermally bonding a polymer microfluidic chip using a semiconductor thermoelectric cooling heater; chinese patent No. 1740788 proposes a bonding method in which a specific chemical functional group is chemically grafted on the surface of a substrate by surface modification of plastic, and then a chemical bond is formed by a reaction of the functional group; the Chinese patent No. 101088912 makes it possible to ultrasonically weld plastic microfluidic chips by the precise design of polymer microstructures and energy-guiding ribs.
However, most of the bonding or packaging methods may cause some deformation of the chip microstructure or leave a certain amount of unreacted chemical reagent, and the bonding strength is low. In other words, there is no bonding method for bonding a microfluidic chip that can not only precisely and firmly package the microstructure of a plastic microfluidic chip, but also does not physically or chemically affect the final microstructure of the chip.
Disclosure of Invention
The invention aims to solve the technical problem that the bonding method of the microfluidic chip in the prior art can not firmly package the microfluidic chip and can not generate physical or chemical influence on the final microstructure of the plastic microfluidic chip, and provides a novel bonding method of the microfluidic chip and the microfluidic chip.
In order to achieve the purpose, the invention adopts the following technical scheme:
a micro-fluidic chip bonding method is used for bonding a substrate with a micro-channel structure on the surface and a cover plate together to form a micro-fluidic chip with a preset cavity structure, and comprises the following steps:
and 5, performing pressure fixation or hot pressing on the chip to firmly bond the substrate and the cover plate which are adhered by the double-sided adhesive.
Preferably, the width and the thickness of the ultrasonic bonding energy guide rib are both 100 mu m-2 mm.
Preferably, the energy guiding ribs cannot be directly contacted with the edge of the micro-channel structure and are 100 μm-2mm away from the edge of the micro-channel structure.
Preferably, the double-sided adhesive tape cannot directly contact with the edge of the microchannel structure, and is 10 μm to 500 μm away from the edge of the microchannel structure.
Preferably, step 3 is preceded by the steps of: dipping with cloth to obtain 1: 1, wiping and cleaning the surface of the substrate or the cover plate by using a mixed solution of ethanol and water, and attaching the double-sided adhesive tape to the adhesive surface of the substrate or the cover plate after the surface is completely dried.
Preferably, the double-sided adhesive tape is high-performance double-sided adhesive tape with the thickness of 100 mu m-2 mm.
A micro-fluidic chip comprises a substrate and a cover plate, wherein a micro-channel structure is pre-arranged on the substrate, ultrasonic bonding energy-conducting ribs are arranged on the peripheral edge of the micro-channel structure of the substrate or on the periphery of the micro-channel structure corresponding to the cover plate, and the substrate and the cover plate are bonded by adopting the bonding method.
Preferably, the base sheet and the cover sheet are made of PMMA \ COC \ PC \ PS and other materials.
Preferably, the microchannel structure comprises at least microchannels, and the height and width of each microchannel are 5 μm-5 mm.
Has the advantages that: the invention provides a microfluidic chip bonding method and a microfluidic chip, which have the advantages of reasonable structure and obvious bonding effect, liquid leakage cannot be caused even if the ultrasonic welding of individual microfluidic chips occurs false welding, the double-sided adhesive tape is not directly contacted with liquid in a channel, and nonspecific adhesion cannot be formed on the edge of the channel.
Drawings
In order to more clearly illustrate the detailed description of the invention or the technical solutions in the prior art, the drawings that are needed in the detailed description of the invention or the prior art will be briefly described below. Throughout the drawings, like elements or portions are generally identified by like reference numerals. In the drawings, elements or portions are not necessarily drawn to scale.
Fig. 1 is a schematic structural diagram of a microfluidic chip according to the present invention.
Reference numerals
Wherein 1 is a micro-channel structure, 2 is an ultrasonic bonding energy guide rib, 3 is a double-sided adhesive tape, and 4 is a substrate.
Detailed Description
The invention is further illustrated by the following figures and examples, but it should be understood that these examples are for the purpose of illustration only and are not to be construed as in any way limiting the present invention, i.e., as in no way limiting its scope.
Examples
A micro-fluidic chip bonding method is used for bonding a substrate 4 with a micro-channel structure 1 on the surface and a cover plate together to form a micro-fluidic chip with a preset cavity structure, and comprises the following steps:
and 5, performing pressure fixation or hot pressing on the chip to firmly bond the substrate 4 and the cover plate stuck by the double-sided adhesive tape 3, and performing pressure fixation or hot pressing, wherein the applied pressure range is 0-100kgf, more preferably 100kgf, the maximum temperature range of the instant (no more than 3 seconds) in the hot pressing process is 95-200 ℃, and more preferably 150 ℃.
200 micro-fluidic chips bonded by the bonding method are detected, the detection is carried out from the aspects of liquid leakage rate, sample detection accuracy rate and the like, and the detected result is as follows: the liquid leakage rate is less than 5%, the sample adhesion rate is less than 5%, the detection accuracy rate is more than 95%, the surface property of the substrate is not influenced, and the bonding strength is 5.9-8.2 Mpa.
As shown in fig. 1, a microfluidic chip includes a substrate 4 and a cover plate, where the substrate 4 and the cover plate are made of PMMA \ COC \ PC \ PS, and more optimally, PMMA, i.e., organic glass, where the substrate 4 is pre-provided with a micro-channel structure 1, the micro-channel structure 1 at least includes a micro-channel, a micro-valve, and a micro-liquid storage chamber, the height and width of the micro-channel are respectively 200 μm, and the peripheral edge of the micro-channel structure 1 is provided with an ultrasonic bonding energy guiding rib 2, the width and thickness of the ultrasonic bonding energy guiding rib 2 are both 200 μm, a double-sided adhesive 3 is adhered to the upper surface of the substrate 4 or the lower surface of the cover plate, and the substrate 4 or the adhesive surface of the cover plate is cleaned and dried to be stained with a cloth 1: 1, carrying out surface wiping cleaning on the mixed solution of ethanol and water, after the surface is completely dried, attaching the double-sided adhesive tape to the adhesion surface of the substrate or the cover plate, wherein the double-sided adhesive tape 3 cannot be directly contacted with the edge of the micro-channel structure 1 and is 100 microns away from the edge of the micro-channel structure 1, the double-sided adhesive tape 3 adopts a 3M double-sided adhesive tape with the thickness of 100 microns, bonding the cover plate with the substrate 4, carrying out ultrasonic bonding on the substrate 4 and the cover plate to enable the first-step bonding to occur, the ultrasonic bonding adopts a time mode, the time precision is 0.01s, the ultrasonic wave adopts the working frequency of 20kHz, the power generated by the ultrasonic wave is 1kW, the ultrasonic wave is kept for 1000ms, then, carrying out pressure fixing on the chip to enable the substrate 4 and the cover plate which are adhered by the double-sided adhesive tape 3 to be firmly bonded, the applied pressure is 100kgf, and the microfluidic chip is obtained after standing for a period of time.
Comparative example 1
Providing a microfluidic chip with the same structure and material as the above embodiment, including a substrate 4 and a cover plate, where the upper surface of the substrate 4 is provided with a micro-channel structure 1, the peripheral edge of the micro-channel structure 1 is provided with an ultrasonic bonding energy-guiding rib 2, the width and thickness of the ultrasonic bonding energy-guiding rib 2 are both 200 μm, the distance from the energy-guiding rib to the micro-channel is 200 μm, the substrate 4 and the cover plate are ultrasonically bonded, the ultrasonic wave adopts a working frequency of 20kHz, the power generated by the ultrasonic wave is 1kW, the holding time is 1000ms, and the bonding is finished by static cooling to obtain the bonded microfluidic chip.
200 micro-fluidic chips bonded by the bonding method are detected, the detection is carried out from the aspects of liquid leakage rate, sample detection accuracy rate and the like, and the detected result is as follows: the liquid leakage rate is approximately 20-37%, the sample adhesion rate is less than 5%, the detection accuracy rate is greater than 95%, the surface property of the substrate is not influenced, the bonding strength is 2.5-4.8Mpa, and a small part of liquid leakage is caused by insufficient soldering due to ultrasonic welding.
Comparative example 2
Providing a micro-fluidic chip with the same structure and material as the above embodiment, comprising a substrate 4 and a cover plate, wherein the upper surface of the substrate 4 is provided with a micro-channel structure 1, a double-sided adhesive tape 3 is adhered to the upper surface of the substrate 4, and the adhesion surface of the substrate 4 is cleaned and dried before the double-sided adhesive tape 3 is adhered, so that a cloth is used for adhering 1: 1, wiping and cleaning the surface of the substrate, adhering the double-sided adhesive tape to the adhesive surface of the substrate after the surface is completely dried, wherein the double-sided adhesive tape is 3M double-sided adhesive tape, the thickness of the double-sided adhesive tape is 100 mu M, adhering the cover plate to the substrate 4, performing pressure fixation on the chip, firmly bonding the substrate 4 and the cover plate, which are adhered by the double-sided adhesive tape 3, and applying the pressure of 100kgf, and standing for a period of time to obtain the microfluidic chip.
200 micro-fluidic chips bonded by the bonding method are detected, the detection is carried out from the aspects of liquid leakage rate, sample detection accuracy rate and the like, and the detected result is as follows: the liquid leakage rate is less than 10%, the sample adhesion rate is approximately equal to 27%, the detection accuracy rate is approximately equal to 78%, the surface property of the substrate is not influenced, the bonding strength is 1.5-2.7MPa, and a small part of the liquid is adhered to the edge of the channel to form a non-specific adhesion phenomenon.
Comparative example 3
The microfluidic chip with the same structure and material as the above embodiment is provided, and comprises a substrate 4 and a cover plate, wherein the upper surface of the substrate 4 is provided with a micro-channel structure 1, the peripheral edge of the micro-channel structure 1 is provided with an ultrasonic bonding energy-guiding rib 2, the width and the thickness of the ultrasonic bonding energy-guiding rib 2 are both 200 μm, and the distance from the energy-guiding rib to the micro-channel is 200 μm. Adhering a double-sided adhesive tape 3 to the upper surface of the substrate 4, cleaning and drying the adhesive surface of the substrate 4 before adhering the double-sided adhesive tape 3, and dipping the adhesive surface with cloth 1: 1, wiping and cleaning the surface, adhering the double-sided adhesive tape to the adhesive surface of the substrate after the surface is completely dried, wherein the double-sided adhesive tape is 3M double-sided adhesive tape, the thickness of the double-sided adhesive tape is 100 microns, and bonding the cover plate with the substrate 4.
And carrying out ultrasonic bonding on the substrate 4 and the cover plate, wherein the ultrasonic wave adopts the working frequency of 20kHz, the power generated by the ultrasonic wave is 1kW, the ultrasonic wave is kept for 1000ms, after the ultrasonic bonding is finished, pressure fixing is carried out on the chip, so that the substrate 4 stuck with the double-sided adhesive tape 3 and the cover plate are firmly bonded, the applied pressure is 100kgf, and after the bonding is finished, standing and cooling are carried out, so that the bonded microfluidic chip is obtained.
200 micro-fluidic chips bonded by the bonding method are detected, the detection is carried out from the aspects of liquid leakage rate, sample detection accuracy rate and the like, and the detected result is as follows: the liquid leakage rate is less than 5%, the sample adhesion rate is less than 5%, the detection accuracy rate is more than 95%, the surface property of the substrate is not influenced, the bonding strength is 5.9-8.2Mpa, no chip liquid leakage exists, and the condition that the edge of a channel has nonspecific signal adsorption is not observed.
From the above examples and comparative examples, it can be seen that: the microfluidic chip bonding method and the microfluidic chip have the advantages that the structure is reasonable, the bonding effect is obvious, the liquid leakage phenomenon cannot be caused even if the false welding occurs during the ultrasonic welding of the individual microfluidic chip, the double-sided adhesive tape is not directly contacted with liquid in the channel, the non-specific adhesion cannot be formed on the edge of the channel, the method can ensure the bonding stability of the microfluidic chip, the influence on the physical and chemical properties of the microfluidic chip can be avoided, the detection result cannot be interfered, and the advantages are more obvious.
While specific embodiments of the invention have been described above, it will be appreciated by those skilled in the art that these are by way of example only, and that the scope of the invention is defined by the appended claims. Various changes and modifications to these embodiments may be made by those skilled in the art without departing from the spirit and scope of the invention, and these changes and modifications are within the scope of the invention.
Claims (6)
1. A microfluidic chip bonding method is characterized by comprising the following steps:
step 1, providing a micro-fluidic chip substrate, wherein a micro-channel structure is arranged on the upper surface of the substrate;
step 2, arranging ultrasonic bonding energy guiding ribs at the peripheral edges of the micro-channel structures or arranging ultrasonic bonding energy guiding ribs on the cover plate corresponding to the periphery of the positions of the micro-channel structures on the surface of the substrate;
step 3, adhering a double-sided adhesive tape on the adhesive surface of the base sheet or the cover sheet, and adhering the cover sheet and the base sheet;
step 4, carrying out ultrasonic bonding on the substrate and the cover plate to enable the substrate and the cover plate to be subjected to first-step bonding;
step 5, performing pressure fixation or hot pressing on the chip to firmly bond the substrate and the cover plate which are adhered by the double-sided adhesive;
the energy guide rib can not be directly contacted with the edge of the micro-channel structure and is 200 mu m away from the edge of the micro-channel structure;
the double-sided adhesive tape cannot be directly contacted with the edge of the micro-channel structure and is 100 microns away from the energy guide rib at the edge of the micro-channel structure;
the double faced adhesive tape adopts high-performance double faced adhesive tape, and the thickness of the double faced adhesive tape is 100 mu m-1 mm.
2. The microfluidic chip bonding method according to claim 1, wherein: the width and the thickness of the ultrasonic bonding energy guiding rib are both 100 mu m-2 mm.
3. The microfluidic chip bonding method according to claim 1, wherein: the method also comprises the following steps before the step 3: dipping with cloth to obtain 1: 1, wiping and cleaning the surface of the substrate by using a mixed solution of ethanol and water, and attaching the double-sided adhesive tape to the adhesive surface of the substrate after the surface is completely dried.
4. A microfluidic chip comprises a substrate and a cover plate, and is characterized in that: the substrate is provided with a micro-channel structure in advance, the peripheral edge of the micro-channel structure is provided with an ultrasonic bonding energy guide rib, or the peripheral edge of the position corresponding to the surface of the substrate as the channel structure on the cover plate is provided with the ultrasonic bonding energy guide rib, and the substrate and the cover plate are bonded by adopting the method of any one of claims 1 to 3.
5. A microfluidic chip according to claim 4, wherein: the base sheet and the cover sheet are made of PMMA \ COC \ PC \ PS and other materials.
6. A microfluidic chip according to claim 5, wherein: the microchannel structure at least comprises microchannels, and the height and the width of each microchannel are respectively 5 mu m-5 mm.
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CN109701673B (en) * | 2019-01-22 | 2021-06-25 | 华东师范大学 | Preparation method of three-dimensional large-size high-precision microfluidic channel |
CN112143642B (en) * | 2020-08-28 | 2022-06-14 | 上海交通大学 | Vascularized tumor micro-fluidic organ chip for in vitro culture and preparation method thereof |
CN113058671A (en) * | 2021-04-20 | 2021-07-02 | 中国人民解放军军事科学院军事医学研究院 | Manufacturing method of energy guiding rib for bonding of micro-fluidic chip |
CN115139511B (en) * | 2022-07-04 | 2023-06-02 | 北京航空航天大学 | Microfluidic antenna based on liquid metal and preparation method |
CN118059974A (en) * | 2024-04-22 | 2024-05-24 | 中南大学 | Microfluidic chip collaborative thermocompression bonding regulation and control method |
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CN101544350A (en) * | 2009-01-05 | 2009-09-30 | 大连理工大学 | Microstructure used for supersonic bonding of micro-passages of polymer microflow-control chips |
CN103640211A (en) * | 2013-12-23 | 2014-03-19 | 中国石油大学(华东) | Flexible material assisted polymer micro-structure ultrasonic bonding encapsulating method |
CN104841500A (en) * | 2015-05-12 | 2015-08-19 | 天津微纳芯科技有限公司 | Chip used for sample detection and packaging method thereof |
CN105833924A (en) * | 2016-03-16 | 2016-08-10 | 北京同方生物芯片技术有限公司 | Ultrasonic-bonded micro-fluidic chip and preparation method thereof |
CN105711076A (en) * | 2016-04-08 | 2016-06-29 | 博奥生物集团有限公司 | Pipeline forming and chip packaging method based on ultrasonic welding technology |
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