CN114177962A - Method for manufacturing sandwich micro-fluidic chip - Google Patents
Method for manufacturing sandwich micro-fluidic chip Download PDFInfo
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- CN114177962A CN114177962A CN202210018510.6A CN202210018510A CN114177962A CN 114177962 A CN114177962 A CN 114177962A CN 202210018510 A CN202210018510 A CN 202210018510A CN 114177962 A CN114177962 A CN 114177962A
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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
- B01L3/502707—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 manufacture of the container or its components
Abstract
The invention discloses a method for manufacturing a sandwich microfluidic chip, which comprises the following steps: manufacturing a mold: manufacturing a template with a channel structure by using a silicon wafer, pouring PDMS high polymer on the template to be cured to form a PDMS layer, punching the PDSM layer with the channel structure to form a sample inlet and a sample outlet, and finally bonding the PDMS layer and glass to form a mold; preparing a film: pouring the PDMS high polymer into a mould to be cured to form a PDMS film; demoulding of the film: stripping the PDMS layer from the glass, and attaching the cured PDMS film to the PDMS layer to complete the demoulding of the PDMS film; film bonding: bonding the PDMS layer attached with the PDMS film with the quartz plate plasma, and slowly stripping the PDMS layer to complete the separation of the PDMS layer and the PDMS film so that the PDMS film stays on the quartz plate; bonding a quartz plate: and bonding one quartz plate on the side of the PDMS film far away from the quartz plate to form a sandwich structure of the quartz plate-PDMS film-quartz plate.
Description
Technical Field
The invention relates to the field of micro-fluidic chip manufacturing, in particular to a method for manufacturing a sandwich micro-fluidic chip.
Background
The microfluidic chip technology integrates basic operation units of sample preparation, reaction, separation, detection and the like in biological, chemical and medical analysis processes into a micron-scale chip, and automatically completes the whole analysis process.
In a microfluidic chip system for single-cell Raman signal detection and cell sorting, most chip materials have strong Raman background signals and can cover the Raman signals of detected target cells, so that the chip materials for single-cell Raman detection and sorting have great limitation. Since quartz has a low raman background signal, it is an ideal chip material for microfluidic chips for raman signal detection and sorting. The bonding of the quartz chip requires that the bonding surface has high flatness and surface affinity, and requires strict surface cleaning, so that the chip manufacturing process is complicated, and the cost of the microfluidic chip is very high.
Disclosure of Invention
The application discloses a method for manufacturing a sandwich microfluidic chip, which comprises the following steps:
manufacturing a mold: manufacturing a template with a channel structure by using a silicon wafer, pouring PDMS high polymer on the template to be cured to form a PDMS layer, punching the PDSM layer with the channel structure to form a sample inlet and a sample outlet, and finally bonding the PDMS layer and glass to form a mold;
preparing a PDMS film: pouring the PDMS high polymer into a mould to be cured to form a PDMS film;
demolding the PDMS film: stripping the PDMS layer from the glass, and attaching the cured PDMS film to the PDMS layer to complete the demoulding of the PDMS film;
bonding a PDMS film: bonding the PDMS layer attached with the PDMS film with the quartz plate plasma, and slowly stripping the PDMS layer to complete the separation of the PDMS layer and the PDMS film so that the PDMS film stays on the quartz plate;
bonding a quartz plate: and bonding one quartz plate on the side of the PDMS film far away from the quartz plate to form a sandwich structure of the quartz plate-PDMS film-quartz plate.
By adopting the technical scheme, the microfluidic chip with the sandwich structure of the quartz plate-PDMS film-quartz plate can be manufactured, compared with the existing preparation method of the quartz glass chip, the cost is lower because the quartz plate does not need to be subjected to photoetching and silanization treatment in the manufacturing process of the PDMS film, and the PDMS film does not need to be peeled off from the mould and then transferred onto the quartz plate after the manufacturing process of the PDMS film is finished, but the PDMS film is directly bonded on the quartz plate and then peeled off the mould, force is mainly applied to the mould in the process of peeling off the mould, and the PDMS film is bonded on the quartz plate and is limited by the quartz plate, so that the problems of stretching, tearing, wrinkling and the like of the film can not be generated in the process of peeling off the mould, further the microstructure can not be damaged, and the quality of the microfluidic chip can not be influenced, the reuse of the micro-fluidic chip in the later period is facilitated, and the cost is further reduced.
Optionally, in the step of manufacturing the mold, a photoresist is coated on the surface of the silicon wafer template, and then the photoresist is subjected to photolithography by a soft lithography technique.
By adopting the technical scheme, the photoresist is coated on the silicon wafer template, only the photoresist needs to be photoetched in the photoetching process, the soft photoetching technology is more mature, and compared with a photoetching quartz wafer, the photoetching quartz wafer is convenient for photoetching a microstructure meeting the requirement, and the cost is lower.
Optionally, in the step of manufacturing the mold, after the PDMS high polymer is poured, the mold is placed in a vacuum pump for vacuum pumping, and after being taken out, the surface bubbles are blown out;
and then, putting the silicon wafer template and the PDMS high polymer into an oven at 70 ℃ for 2h for curing to form a PDMS layer.
Through adopting above-mentioned technical scheme, the evacuation can make do not have the bubble between silicon chip template and the PDMS high polymer, takes out the back and blows out surface bubble again, can make not have unnecessary cavity in the fashioned PDMS layer of solidification, makes the mould that adopts the PDMS layer to make have extra defect, and then can improve the quality of the PDMS film that adopts the mould to make.
Optionally, the PDMS layer is peeled off from the silicon wafer template, then both sides of the PDMS layer are wrapped by sealing films, and the positions of the sample injection port and the sample discharge port are determined according to the structural design.
Through adopting above-mentioned technical scheme, the PDMS layer is peeled off the back, can contact with the outside air, and the air of external world is than muddy, and the dust in the air is easily adhered on the PDMS layer, so wraps up the PDMS layer with the sealing film, avoids adhering of dust to avoid influencing the bonding of PDMS layer and glass.
Optionally, after the injection port and the sample outlet are drilled on the PDMS layer, the PDMS layer is immersed in absolute ethyl alcohol for ultrasonic cleaning, and then the surface of the PDMS layer is dried by using nitrogen.
Through adopting above-mentioned technical scheme, PDMS generally can adopt the hole puncher to beat the introduction port and go out the appearance mouth, at the in-process that punches, produces the piece easily, so adopt absolute ethyl alcohol to soak ultrasonic cleaning's mode and wash, can be better wash the piece, still can not cause the influence to the PDMS layer.
Optionally, after the punching of the sample inlet and the sample outlet of the PDMS layer is completed, the surface of the PDMS layer having the channel structure facing upwards and the glass or the ITO glass are placed into an oxygen plasma machine together, the vacuum pumping is performed for 2min, the plasma treatment is performed for 1min, and the bonding of the mold is completed.
By adopting the technical scheme, the PDMS layer and the glass are subjected to plasma treatment, so that the PDMS layer and the glass can be conveniently bonded.
Alternatively, the bonded mold was placed in an oven at 70 ℃ overnight.
Through adopting above-mentioned technical scheme, make PDMS layer keep static night in the constant temperature state, can make better bonding of PDMS layer and glass be in the same place, improve the effect of bonding.
Optionally, in the step of preparing the film, the curing of the PDMS high polymer is performed by placing the mold on a heating plate at 100-200 ℃ for heating for 5-60 minutes, and then taking down the mold and cooling the mold at room temperature.
Through adopting above-mentioned technical scheme, can make the PDMS high polymer carry out better solidification, improve the effect of solidification, still can not lead to the PDMS high polymer to produce rotten, preferred with 150 ℃, heat 5 minutes, can accomplish the solidification fast, can not waste too much time in the solidification stage, still can not cause the influence to the solidification effect.
Optionally, the volume ratio of the PDMS monomer to the curing agent in the PDMS high polymer required in the mold manufacturing process is 1: 13;
the volume ratio of PDMS monomer to curing agent in PDMS high polymer required in the preparation process of the PDMS film is 8: 1.
by adopting the technical scheme, the proportion of the high polymer PDMS monomer and the curing agent required by the PDMS film is different from the proportion of the PDMS monomer and the curing agent in the PDMS high polymer used by the PDMS layer, so that the subsequent PDMS film can be conveniently stripped from the PDMS layer. Meanwhile, the proportion of the curing agent in the high polymer required by the PDMS layer is low, so that the mold has better elasticity and is convenient to strip.
In summary, the present application includes at least one of the following beneficial technical effects:
1. the method comprises the steps of manufacturing a template by using a silicon wafer by adopting a soft lithography technology, then manufacturing a mold, manufacturing a PDMS film through the mold, wherein the PDMS film cannot be separated from a PDMS layer in the mold, and only when the PDMS film is bonded on a quartz plate, the PDMS layer can be peeled off;
2. the PDMS film can be better separated from the PDMS film due to the different ratios of the high polymer PDMS monomer and the curing agent to those of the PDMS high polymer used in the PDMS layer.
Drawings
Fig. 1 is an outflow block diagram in the embodiment.
Detailed Description
The embodiment of the application discloses a method for manufacturing a sandwich microfluidic chip, which comprises the following steps:
manufacturing a mold:
a silicon wafer is selected as a template, a layer of photoresist is coated on the surface of the silicon wafer template, the photoresist is subjected to photoetching through a soft photoetching technology, a required shape is processed on the photoresist, and the preparation of the silicon wafer template is completed.
After the silicon wafer template is manufactured, pouring PDMS high polymer on the silicon wafer template, placing the silicon wafer template in a vacuum pump for vacuumizing for a period of time, and taking out the silicon wafer template to blow out surface bubbles;
and then placing the mold in a 70 ℃ oven for 2h to solidify the mold, taking out the mold for later use, and facilitating the completion of the subsequent processing and manufacturing of the mold.
And after cooling to room temperature, cutting and stripping the prepared PDMS layer from the silicon wafer template, and wrapping the two sides of the PDMS layer by using a sealing film to avoid the influence of adhesion dust on bonding, thereby completing the semi-manufacture of the mold.
According to the structure of the microfluidic chip, a chip is cut on the PDMS layer along the outline, the cut PDMS layer is processed and manufactured into a relevant channel, and a sample inlet and a sample outlet are punched by a puncher. If debris occurs during the cutting and punching operations, it should be ultrasonically cleaned by immersing it in absolute ethanol and then blow-drying its surface with nitrogen.
And bonding the PDMS layer with the channel with glass or ITO glass, putting the PDMS layer with the channel structure facing upwards and the glass into an oxygen plasma machine together in the bonding process, vacuumizing for 2min, performing plasma treatment for 1min, treating the surfaces of the PDMS layer and the glass to bond the PDMS layer and the glass together, and finally standing overnight in a 70 ℃ oven to reinforce the bonding.
The mold is manufactured through the above operations.
Preparing a film: injecting the PDMS high polymer from the injection port of the mould by using an injector to make the PDMS high polymer fill the channel until the PDMS high polymer overflows from the injection port, so as to ensure that the PDMS high polymer fills the channel structure on the PDMS layer;
then placing the mould filled with the PDMS high polymer on a heating plate at 100-200 ℃ for heating for 5-60min, and then taking down and placing at room temperature for cooling; preferably by heating at 150 deg.C for 5 min; the PDMS polymer can be cured to form the required PDMS film.
Demoulding of the film: after the mold is cooled, the PDMS film needs to be demolded, but the demolding of the PDMS film is only half demolding, the PDMS layer is peeled off from the glass, the cured PDMS film is attached to the PDMS layer, and the PDMS film is separated from the glass in the mold, so that the demolding of the PDMS film is completed.
Film bonding: bonding the PDMS layer with the PDMS film with the quartz plate plasma, and slowly stripping the PDMS layer, wherein the force of bonding the PDMS film on the quartz plate is larger than the adhesive force such as van der Waals force, hydrogen bond and the like between the PDMS film and the PDMS layer, so that the PDMS film is separated from the PDMS film and stays on the quartz plate, and the transfer of the PDMS film is completed. Because the PDMS film is bonded with the quartz plate when the PDMS layer is stripped, the PDMS film is fixed by the quartz plate, and the conditions of stretching, tearing, wrinkling, microstructure damage and the like can not occur in the process of stripping the PDMS layer, so that the integrity of the PDMS film is improved, and the quality of the manufactured microfluidic chip can be improved.
Bonding a quartz plate: through the steps, the process of transferring the PDMS film to the quartz plate is completed, and then one side of the PDMS film, which is far away from the quartz plate, is bonded with the quartz plate, so that the sandwich structure of the quartz plate-PDMS film-quartz plate is formed.
Through the steps, the microfluidic chip with low cost can be manufactured, and the cost of the microfluidic chip is reduced; the method has the advantages of low Raman background, good optical characteristics and the like, can be used for manufacturing the existing single-cell Raman detection and sorting chip based on the method, can meet the requirements of the existing single-cell Raman detection and sorting, and has great commercial value.
The ratio of PDMS monomer to curing agent in the PDMS polymer used for manufacturing the mould is 1: 13, the ratio of PDMS monomer to curing agent in the PDMS high polymer used in the preparation of the PDMS film was 8: 1; the PDMS high polymer ratio of using is different in preparation mould and the PDMS film, makes PDMS film and PDMS layer separate more easily, when peeling off the PDMS layer, can not cause too big pulling to the PDMS film, and the proportion of curing agent is high in the required high polymer of PDMS film simultaneously, and the purpose makes the film have better toughness, difficult breakage. The proportion of the curing agent in the high polymer required by the PDMS layer is low, so that the mould has better elasticity and is convenient to strip.
The above embodiments are preferred embodiments of the present application, and the protection scope of the present application is not limited by the above embodiments, so: all equivalent changes made according to the structure, shape and principle of the present application shall be covered by the protection scope of the present application.
Claims (9)
1. A method for manufacturing a sandwich microfluidic chip is characterized by comprising the following steps: the method comprises the following steps:
manufacturing a mold: manufacturing a template with a channel structure by using a silicon wafer, pouring PDMS high polymer on the template to be cured to form a PDMS layer, punching the PDSM layer with the channel structure to form a sample inlet and a sample outlet, and finally bonding the PDMS layer and glass to form a mold;
preparing a PDMS film: pouring the PDMS high polymer into a mould to be cured to form a PDMS film;
demolding the PDMS film: stripping the PDMS layer from the glass, and attaching the cured PDMS film to the PDMS layer to complete the demoulding of the PDMS film;
bonding a PDMS film: bonding the PDMS layer attached with the PDMS film with the quartz plate plasma, and slowly stripping the PDMS layer to complete the separation of the PDMS layer and the PDMS film so that the PDMS film stays on the quartz plate;
bonding a quartz plate: and bonding one quartz plate on the side of the PDMS film far away from the quartz plate to form a sandwich structure of the quartz plate-PDMS film-quartz plate.
2. The method for manufacturing a sandwich microfluidic chip according to claim 1, wherein the method comprises the following steps: in the step of manufacturing the die, photoresist is coated on the surface of the silicon wafer template, and then the photoresist is subjected to photoetching through a soft photoetching technology.
3. The method for manufacturing a sandwich microfluidic chip according to claim 1, wherein the method comprises the following steps: in the step of manufacturing the mold, PDMS high polymer is poured on a silicon wafer template, then the silicon wafer template is placed in a vacuum pump for vacuumizing, and bubbles on the surface of the silicon wafer template are blown out after the silicon wafer template is taken out;
and then, putting the silicon wafer template and the PDMS high polymer into an oven at 70 ℃ for 2h for curing to form a PDMS layer.
4. The method for manufacturing a sandwich microfluidic chip according to claim 2, wherein the method comprises the following steps: and peeling the PDMS layer from the silicon wafer template, wrapping the two sides of the PDMS layer by using sealing films, and determining the positions of the sample injection port and the sample outlet port according to the structural design.
5. The method for manufacturing a sandwich microfluidic chip according to claim 1, wherein the method comprises the following steps: and after the sample inlet and the sample outlet are drilled on the PDMS layer, immersing the PDMS layer in absolute ethyl alcohol for ultrasonic cleaning, and then drying the surface of the PDMS layer by using nitrogen.
6. The method for manufacturing a sandwich microfluidic chip according to claim 4, wherein the step of: and after the sample inlet and the sample outlet of the PDMS layer are punched, putting the surface of the PDMS layer with the channel structure upwards and glass or ITO glass into an oxygen plasma machine, vacuumizing for 2min, and carrying out plasma treatment for 1min to complete the bonding of the mould.
7. The method for manufacturing a sandwich microfluidic chip according to claim 6, wherein the step of: the mold after bonding was placed in an oven at 70 ℃ overnight.
8. The method for manufacturing a sandwich microfluidic chip according to claim 1, wherein the method comprises the following steps: in the step of preparing the film, the PDMS polymer is cured by placing the mold on a heating plate at 100-200 ℃ for heating for 5-60 minutes, and then taking down the mold and cooling the mold at room temperature.
9. The method for manufacturing a sandwich microfluidic chip according to claim 1, wherein the method comprises the following steps: the volume ratio of the PDMS monomer to the curing agent in the PDMS high polymer required in the manufacturing process of the mould is 1: 13;
the volume ratio of PDMS monomer to curing agent in PDMS high polymer required in the preparation process of the PDMS film is 8: 1.
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| CN202210018510.6A CN114177962A (en) | 2022-01-07 | 2022-01-07 | Method for manufacturing sandwich micro-fluidic chip |
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| CN202210018510.6A CN114177962A (en) | 2022-01-07 | 2022-01-07 | Method for manufacturing sandwich micro-fluidic chip |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN115414971A (en) * | 2022-08-03 | 2022-12-02 | 南方科技大学 | Micro-control flow chip and preparation method thereof |
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