CN109012770B - Multilayer paper chip structure, manufacturing apparatus and method, and fluid interlayer flow method - Google Patents

Multilayer paper chip structure, manufacturing apparatus and method, and fluid interlayer flow method Download PDF

Info

Publication number
CN109012770B
CN109012770B CN201810764200.2A CN201810764200A CN109012770B CN 109012770 B CN109012770 B CN 109012770B CN 201810764200 A CN201810764200 A CN 201810764200A CN 109012770 B CN109012770 B CN 109012770B
Authority
CN
China
Prior art keywords
paper
platform
paper chip
fluid
light source
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.)
Active
Application number
CN201810764200.2A
Other languages
Chinese (zh)
Other versions
CN109012770A (en
Inventor
周燕
夏兵
傅弦
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Chengdu Institute of Biology of CAS
Original Assignee
Chengdu Institute of Biology of CAS
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 Chengdu Institute of Biology of CAS filed Critical Chengdu Institute of Biology of CAS
Priority to CN201810764200.2A priority Critical patent/CN109012770B/en
Publication of CN109012770A publication Critical patent/CN109012770A/en
Application granted granted Critical
Publication of CN109012770B publication Critical patent/CN109012770B/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Images

Classifications

    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027Containers 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
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027Containers 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
    • B01L3/502707Containers 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
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027Containers 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
    • B01L3/50273Containers 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
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/10Integrating sample preparation and analysis in single entity, e.g. lab-on-a-chip concept
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/08Geometry, shape and general structure
    • B01L2300/0861Configuration of multiple channels and/or chambers in a single devices
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/08Geometry, shape and general structure
    • B01L2300/0887Laminated structure
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/12Specific details about materials
    • B01L2300/126Paper
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00Moving or stopping fluids
    • B01L2400/04Moving fluids with specific forces or mechanical means
    • B01L2400/0403Moving fluids with specific forces or mechanical means specific forces
    • B01L2400/0415Moving fluids with specific forces or mechanical means specific forces electrical forces, e.g. electrokinetic
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00Moving or stopping fluids
    • B01L2400/04Moving fluids with specific forces or mechanical means
    • B01L2400/0475Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure
    • B01L2400/0487Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure fluid pressure, pneumatics

Landscapes

  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Dispersion Chemistry (AREA)
  • Analytical Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Hematology (AREA)
  • Clinical Laboratory Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Automatic Analysis And Handling Materials Therefor (AREA)
  • Apparatus Associated With Microorganisms And Enzymes (AREA)

Abstract

The invention discloses a multilayer paper chip structure, which comprises at least two layers of paper substrates, wherein at least one fluid space is formed between the layers of the paper substrates and a resin layer; the fluid space comprises a sample introduction area, the sample introduction area is connected with a fluid channel, and the fluid channel is connected with at least one detection area; the sample injection areas of the paper substrate are on the same straight line perpendicular to the paper substrate. The invention also provides a manufacturing device and a manufacturing method of the multilayer paper chip and a method for controlling the flow between the fluid layers. The invention has the advantages that the multilayer structure of the multilayer paper chip can realize complex multistep biological analysis on paper; the fluid channel is not filled with cellulose, so that interlayer isolation is realized, and interlayer flow of fluid is realized only by applying an electric field or airflow action to the outside, so that the detection process has controllability; the manufacturing method realizes process automation and realizes automatic adhesion and alignment among different layers of paper; the fluid laminar flow method uses electric fields or air flows to control, making the control process programmable and automated.

Description

Multilayer paper chip structure, manufacturing apparatus and method, and fluid interlayer flow method
Technical Field
The present invention relates to the field of paper core structures, methods of making and using, and more particularly to multi-layer paper core structures, apparatus and methods of making and methods of inter-layer flow of fluids.
Background
The paper chip microfluid device is firstly proposed in 2007 by the Whitesids research group of the Harvard university in USA, specifically, paper is used for replacing traditional microfluidic substrates such as glass, silicon and high polymer, a flow path is processed on the surface of the paper, liquid transportation and transfer are achieved by means of the inherent capillary force of the paper, and the paper chip microfluid device has the advantages of being light, low in cost, easy to obtain, good in biocompatibility and the like. According to the flowing direction, the paper chip microfluid can be divided into a two-dimensional paper chip and a three-dimensional paper chip, and the preparation method of the two-dimensional paper chip comprises wax printing, ink-jet printing, photoetching, plasma etching and the like. Three-dimensional paper chips provide significant improvements in detection capacity, complexity and functionality of the device, as compared to two-dimensional paper chips. Santhiago et al propose the use of double-sided adhesive to bond folded paper to make a three-dimensional paper chip electrochemical detection device, which, although relatively simple, still requires accurate manual alignment during the manufacturing process. Whitesides et al apply multiple layers of paper printed with different patterns with double sided tape, perforated at designated locations on the double sided tape and then filled with cellulose to allow the solution to penetrate from the top layer to the next; the manufacturing process is complex and has high precision requirement, and the filled cellulose has adsorption effect on molecules. Later, Crooks et al proposed a paper folding method, and the paper folding method involves the mirror image problem of paper folding, and folding precision requires highly, still needs auxiliary device so that upper and lower adjacent two-layer in close contact with simultaneously. Lewis et al propose to use wax printing technology in combination with glue spraying to prepare multi-layer paper chips, which, although highly efficient, has high operating requirements for laboratory personnel and is very expensive in wax-spraying printers. At present, no research report is available on a method for integrally and automatically preparing a multilayer paper chip microfluid device.
The control methods for liquid flow on paper chips are mainly classified into three categories. The most direct method is to provide flow paths with different lengths or widths, and the flow time is prolonged along with the increase of the lengths or widths of the paths. Second, changing the wettability of the paper surface with chemical agents is the second type of method for controlling the flow of liquids, which includes sugars, paraffins, surfactants, alkyl ketene dimers, gels, and the like; hydrophilic channels are first engraved in the paper by conventional methods for making single-layer paper microfluidic devices, and then the channels are treated with chemicals, the flow rate of the liquid in the channels slowing down with the increase in the concentration of the chemicals. This method adds a paper chip preparation step and paper chips treated with chemical reagents may interfere with the detection of certain compounds. The third method is to control the flow of liquid by mechanical means, such as an electromagnet controlling the opening and closing of a flow path, a triboelectric effect accelerating the flow of liquid, a soluble bridge transferring a limited amount of liquid, a water-absorbent sponge shunting the liquid, a movable valve connecting the flow path, etc.; the above method is mainly directed to the control of liquid flow on single-ply paper, and the equipment preparation process and the liquid handling process are relatively complicated. Therefore, at present, the on-off control of the liquid can be realized on the single-layer paper chip, the on-off of the liquid is only controlled in a delayed manner by the multi-layer paper chip, but the on-off control of the liquid in the multi-layer paper chip cannot be realized.
Disclosure of Invention
In order to solve the problems, the invention provides a structure of a multilayer paper chip and provides a method for simply, integrally and automatically preparing the multilayer paper chip; the equipment is simple in structure, the multi-layer paper is automatically bonded and aligned in the printing process, the use of adhesive is avoided, and human errors are reduced. Meanwhile, a method for controlling the microfluid to flow between the paper chip layers is also provided, and the method is particularly suitable for complex multistep bioanalysis on paper, such as enzyme-linked immunosorbent assay, signal amplification immunoreaction, nucleic acid detection and the like; the control program of the electric field or the airflow is programmed by utilizing Arduino software, and the liquid on the upper layer flows downwards in sequence according to set time, so that the multistep complex reaction can be automatically carried out, the artificial participation is reduced, and the accuracy and the repeatability of the multistep reaction can be improved.
In order to achieve the purpose, the invention adopts the following technical scheme: the multilayer paper chip structure comprises at least two layers of paper substrates, wherein at least one fluid space is formed between the layers of the paper substrates and the resin layer; the fluid space comprises a sample introduction area, the sample introduction area is connected with a fluid channel, and the fluid channel is connected with at least one detection area; the sample injection areas of the same fluid space are on the same line perpendicular to the paper substrate.
Further, the multilayer paper chip structure still includes, and the top paper substrate surface still has the stratum basale, and the stratum basale is printed by the resin and is formed.
Further, the material of the paper base is filter paper.
Further, the multilayer paper chip manufacturing equipment comprises a light source, a light transmission device, a reaction container and a platform; wherein the light transmission device is used for realizing and changing the shape of the light source transmission area; the light transmission device is arranged above the light source; a reaction vessel containing a resin liquid; the light transmission device is arranged on the bottom surface of the reaction vessel, and the light source can transmit into the reaction vessel through the light transmission device; the platform can vertically move up and down and is used for placing a semi-finished product or a finished product of the paper chip in the process of printing the paper chip; when the platform is at the lowest position, the distance between the platform and the bottom surface of the reaction vessel is used as the thickness of the resin.
Further, the light source is an LED lamp.
Further, the light transmission device is an LCD panel for receiving and displaying the shape of the computer designed transmission area through which the light source can enter the reaction vessel.
Further, the method for manufacturing the multilayer paper chip comprises the following steps:
s1, downloading the designed shape of the transmission area from the computer by the light transmission device, and descending the platform to the distance between the platform and the bottom surface of the reaction container to be the set thickness of the substrate layer; turning on a light source, exposing according to set time, and printing a blank basal layer; after the blank substrate layer is printed, the light source is turned off, the platform rises, and the substrate layer is adhered to the lower surface of the platform;
s2, placing a paper substrate in the reaction container, descending the platform to a set position, turning on the light source, exposing according to set time, and printing a first resin layer; after the resin layer is printed, the light source is turned off, the platform rises, and the paper chip semi-finished product is adhered to the lower surface of the platform;
s3, placing a paper substrate in the reaction container, downloading the designed shape of the transmission area from the computer by the light transmission device, descending the platform to a set position, turning on the light source, exposing according to a set time, and printing the resin layer; after the resin layer is printed, the light source is turned off, the platform rises, and the paper chip semi-finished product is still adhered to the lower surface of the platform;
s4, repeat S3 until printing of all resin layers is completed.
Further, the multilayer paper chip fluid interlayer flowing method comprises the following steps: and (3) dripping a sample to be detected into the outermost sample injection region of the paper chip, and applying an electric field to two sides of the sample injection region of the paper chip or applying air flow to one side of the sample injection region of the paper chip.
Compared with the prior art, the invention has the beneficial effects that:
1. the multilayer structure of the multilayer paper chip is particularly suitable for complex multistep biological analysis, such as enzyme-linked immunosorbent assay, signal amplification immunoreaction, nucleic acid detection and the like;
2. the fluid channel of the multilayer paper chip is not filled with cellulose, so that interlayer isolation is realized, and interlayer flow of fluid is realized only under the action of an external applied electric field or air flow, so that the detection process is controllable;
3. the manufacturing method realizes process automation, realizes automatic adhesion and alignment among different layers of paper, avoids the use of viscose and reduces human errors;
4. the manufacturing method adopts the digital mask to carry out photocuring, is simple and convenient and is easy for standardized manufacturing; after printing is finished, cleaning and drying uncured resin;
5. the fluid interlayer flowing method is controlled by using an electric field or airflow, so that the control process is programmed and automated, the Arduino software is used for programming the control program of the electric field or airflow, the liquid on the upper layer flows downwards in sequence and automatically according to the set time, the artificial participation is reduced, and the accuracy and the repeatability of the multi-step reaction can be improved.
Drawings
Fig. 1 is a schematic structural diagram of a paper chip according to a first embodiment of the present invention;
FIG. 2 is a schematic cross-sectional view of a portion A of a paper chip according to a first embodiment of the present invention;
FIG. 3 is a schematic top view of a paper chip according to a first embodiment of the present invention;
FIG. 4 is a schematic structural diagram of a paper chip manufacturing apparatus according to a first embodiment of the present invention;
FIG. 5 is a diagram illustrating a first embodiment of a paper chip with ink droplets penetrating a fluid channel;
FIG. 6 is a graph showing the experimental effects of the second embodiment of the present invention after ink is dropped and before and after an electric field is applied;
FIG. 7 is a graph showing the experimental effect of the third embodiment of the present invention before and after applying the air flow after dropping the ink;
description of reference numerals: 1-a paper substrate; 2-a sample introduction zone; 3-a resin layer; 4-a base layer; 5-a fluid space; 52-detection zone; 51-a fluid channel; 6-a sample to be tested; 7-a light source; 8-a light transmission device; 9-a reaction vessel; 10-resin liquid; 11-platform.
Detailed Description
In order to more clearly understand the technical features, objects and effects of the present invention, the embodiments of the present invention will be described with reference to the accompanying drawings, but the scope of the present invention is not limited to the following.
The first embodiment is as follows:
as shown in fig. 1 to 3, the present invention provides a multi-layer paper chip structure, which comprises at least two layers of paper substrates 1, wherein at least one fluid space 5 is formed between the layers of the paper substrates 1 and the resin layer 3; the fluid space 5 comprises a sample introduction region 2, the sample introduction region 2 is connected with a fluid channel 51, and the fluid channel 51 is connected with at least one detection region 52; the sample introduction areas 2 of the same fluid space 5 of the paper substrate 1 are on the same line perpendicular to the paper substrate 1. The multilayer paper chip structure further comprises a base layer 4 on the surface of the uppermost paper substrate 1, wherein the base layer 4 is formed by resin printing. The material of the paper substrate 1 is filter paper. The paper substrate 1 is cellulose, and the fluid will diffuse to the detection area 52 along the fluid channel 51 in the single-layer paper substrate 1, but the fluid in the sample injection area 2 of a certain layer of the paper substrate 1 cannot cross the layer to the sample injection area 2 of the partition layer, so the sample 6 to be measured will diffuse only in a single layer without external force. The base layer 4 is used for making up the possible non-horizontal situation of the manufacturing device, the paper base material 1 is directly printed, if the paper base material 1 is inclined, the thickness of the printed resin layer 3 is uneven, and the resin is not cured at the thinnest place; the base layer 4 is also a resin layer in nature, but the resin layer is not used as a fluid channel, and only the lower surface of the resin layer is horizontal, and then the paper substrate 1 is placed on the base layer 4 to be almost placed on a horizontal plane. In practice, the detection area 52 is pre-filled with a substance that reacts with the sample 6 to be measured, and this reaction triggers a visually detectable change. The material of the paper substrate 1 is filter paper, and it is instructive that the material of the filter paper may be replaced by filter paper, chromatography paper, filter membrane, and ion exchange paper having similar effects.
The sample injection area of the paper substrate 1 is actually holes penetrating through the resin layer 3, the positions of the holes are determined when designing the paper chip structure, the holes are in a straight line, the purpose is to enable the sample 6 to be tested on the uppermost layer to penetrate through the paper substrate 1 flowing to all layers under the action of external electric field force or air flow, once the sample 6 to be tested is in the sample injection area 2 of the paper substrate 1 on a certain layer, the sample 6 to be tested can be diffused along the fluid channel 51 under the action of cellulose of the paper substrate 1 to reach the detection area 52, namely, liquid dropping on the front side of the paper substrate 1 can also be diffused to the back side of the paper substrate 1; on the other hand, where the paper base material 1 adheres with the resin, the diffusion is terminated, and the fluid is diffused only in the fluid passage 51 to which no resin adheres. The paper chip is characterized in that the paper chip is provided with at least one fluid space 5, each fluid space 5 is provided with a respective sample injection region 2, and the paper chip is particularly suitable for biological analysis with complex and multistep, such as enzyme-linked immunosorbent assay, signal amplification immunoreaction, nucleic acid detection and the like; after the sample introduction area 2 drops into the sample 6 to be detected, the control program of the electric field or the air flow is programmed by utilizing Arduino software, and the sample 6 to be detected sequentially flows into the fluid channel 51 from the sample introduction area 2 downwards automatically according to the set time, and then flows into the detection area 52.
As shown in fig. 4, the multilayer paper chip manufacturing apparatus, which is applied to manufacturing the multilayer paper chip structure, includes a light source 7, a light transmission device 8, a reaction vessel 9 and a platform 11; wherein, the light transmission device 8 is used for realizing and changing the shape of the transmission area of the light source 7; the light transmission device 8 is above the light source 7; a reaction vessel 9 containing a resin solution 10; the light transmission device 8 is arranged on the bottom surface of the reaction vessel 9, and the light source 7 can transmit into the reaction vessel 9 through the light transmission device 8; a platform 11, which can vertically move up and down, for placing a semi-finished product or a finished product of the paper chip in the process of printing the paper chip; when the stage 11 is at the lowest position, the distance between the stage and the bottom surface of the reaction vessel 9 is defined as the thickness of the resin to be coagulated. The light source 7 is an LED lamp. The light transmission means 8 is an LCD panel for receiving and displaying the shape of the computer designed transmission area through which the light source 7 can only enter the reaction vessel 9. The resin liquid 10 is a light-cured resin liquid, which can be polymerized by a photosensitizer in the resin liquid under the irradiation of light with a special wavelength, can rapidly generate physical and chemical changes in a short time, and further can be crosslinked and cured to form an insoluble coating, the coating thickness is larger as the irradiation time is longer, and the light source adopted in the embodiment is blue light with the wavelength of 405 nm. The pattern of the light transmission means 8 is divided into dark and light areas, the light in the dark areas being opaque and the light in the light areas being transparent, the dark and light areas of the light transmission means being displayed according to a pattern designed by a person in advance on a computer. The lower surface of the platform 11 is provided with tin foil paper, a coating film generated by curing the resin liquid 10 is adhered to the lower surface of the platform, the irradiation time determines the hardness of the printed resin, and the hardness influences the adhesion of the resin and the previous layer.
A method for manufacturing a multi-layer paper chip is applied to the method for manufacturing the multi-layer paper chip to manufacture a multi-layer paper chip structure, the total number of layers of a resin layer 3 is three (excluding a substrate layer 4, the same counting for the following layers) and the method comprises the following steps:
s1, downloading the designed shape of the transmission area from the computer by the light transmission device 8, and descending the platform 11 to the distance between the platform and the bottom surface of the reaction container 9, wherein the distance is the set thickness of the substrate layer 4; turning on the light source 7, exposing for 80s, and printing a blank substrate layer 4; after the blank substrate layer 4 is printed, the light source 7 is turned off, the platform 11 is lifted, and the substrate layer 4 is adhered to the lower surface of the platform 11;
s2, placing the paper substrate 1 in the reaction container 9, descending the platform 11 to a set position, turning on the light source 7, exposing for 80S, and printing the first resin layer 3; after printing the resin layer 3, turning off the light source 7, lifting the platform 11, and adhering the paper chip semi-finished product to the lower surface of the platform 11;
s3, placing the paper substrate 1 in the reaction container 9, downloading the designed shape of the transmission area from the computer by the light transmission device 8, descending the platform 11 to the set position, turning on the light source 7, exposing for 55S, and printing the resin layer 3; after the resin layer 3 is printed, the light source 7 is turned off, the platform 11 is lifted, and the paper chip semi-finished product is still adhered to the lower surface of the platform 11;
s4, repeating S3 until the printing of the third resin layer 3 is completed, wherein the exposure time is 55S.
Fig. 5 is a schematic diagram of the paper die of this embodiment after ink has been dropped through the fluid channel 51.
It should be noted that the light penetrates the paper chip 1, and the resin is cured on both sides of the upper and lower surfaces of the paper chip 1, and the cured resin adheres to the paper chip to form the resin layer 3. In addition, the resin cured during printing adheres to the lower surface of the stage 11 of aluminum alloy, and the adhesion of the resin to the stage 11 is not so strong when the base layer 4 is printed, so that the exposure time needs to be longer to enhance the adhesion of the both. When the second layer is printed after the base layer 4 is printed, the resin layer 3 cured on the upper surface of the paper chip 1 adheres to the base layer 4 more easily than the former, and therefore the exposure time of the base layer 4 is set to be slightly longer than that of the other resin layers 3.
The second embodiment is as follows:
on the basis of the first embodiment, the multilayer paper chip manufacturing method is used for manufacturing two resin layers 3, namely, two paper substrates 1, and the base layer 4 is exposed for 80s, and the exposure time of the first and second resin layers is 80s and 55s respectively.
The multilayer paper chip fluid interlayer flowing method is applied to the paper chip manufactured by the embodiment and comprises the following steps: and (3) dripping a sample 6 to be detected into the outermost sample injection region 2 of the paper chip, and applying an electric field on two sides of the sample injection region 2 of the paper chip. As shown in fig. 6, the left side of the figure is a front picture of the paper chip of the second embodiment before the electric field is applied after the ink is dropped on the paper chip, and the right side of the figure is a back picture of the paper chip after the electric field is applied; it should be noted that the ink in the sample injection region 2 on the uppermost layer of the front surface is limited in the region by the cured resin, and after the electric field is applied, the ink penetrates through the second layer of paper substrate 1, and can be seen more clearly from the back surface of the paper chip, and the ink is diffused to the detection region 52 through the flow channel 51.
The third concrete embodiment:
on the basis of the second embodiment, the method for controlling the flow between the fluid layers of the paper chip is changed, and the action of applying an electric field is changed into the action of applying air flow. The left side of the figure is a picture of the front side of the paper chip of the second embodiment before air flow is applied after ink is dripped, and the right side of the figure is a picture of the back side of the paper chip after air flow is applied; it should be noted that the ink in the sample injection region 2 on the uppermost layer of the front surface is limited in the region by the cured resin, and after the air flow, the ink penetrates through the second layer of paper substrate 1, and can be seen more clearly from the back surface of the paper chip, and the ink is diffused to the detection region 52 through the flow channel 51. It is to be understood that the gas flow is one of the mechanical forces that can be replaced by similar mechanical forces, such as pressing directly on the sample introduction area 2, and the sample 6 to be tested in the sample introduction area 2 is directly pressed to the next layer.
It can be shown that the multilayer structure of the multilayer paper chip is particularly suitable for bioanalysis of complex multiple steps on paper, such as enzyme-linked immunosorbent assay, signal amplification immunoreaction, nucleic acid detection and the like; the fluid channel 51 of the multilayer paper chip is not filled with cellulose, so that interlayer isolation is realized, and interlayer flow of fluid is realized only under the action of an external applied electric field or air flow, so that the detection process is controllable; the manufacturing method realizes process automation, realizes automatic adhesion and alignment among different layers of paper, avoids the use of viscose and reduces human errors; the manufacturing method adopts the digital mask to carry out photocuring, is simple and convenient and is easy for standardized manufacturing; after printing is finished, cleaning and drying uncured resin; the fluid interlayer flowing method is controlled by using an electric field or airflow, so that the control process is programmed and automated, the Arduino software is used for programming the control program of the electric field or airflow, the liquid on the upper layer flows downwards in sequence and automatically according to the set time, the artificial participation is reduced, and the accuracy and the repeatability of the multi-step reaction can be improved.
The above disclosure is only for the purpose of illustrating the preferred embodiments of the present invention, and it is therefore to be understood that the invention is not limited by the scope of the appended claims.

Claims (3)

1. The multilayer paper chip fluid interlayer flowing method is applied to a multilayer paper chip structure and is characterized in that the multilayer paper chip structure comprises at least two layers of paper base materials (1), and at least one fluid space (5) formed by a resin layer (3) and the paper base materials (1) is arranged between the layers; the fluid space (5) comprises a sample introduction area (2), the sample introduction area (2) is connected with a fluid channel (51), and the fluid channel (51) is connected with at least one detection area (52); the sample injection areas (2) of the same fluid space (5) are on the same straight line vertical to the paper substrate (1); the multilayer paper chip structure further comprises a base layer (4) arranged on the surface of the uppermost paper substrate (1), wherein the base layer (4) is formed by resin printing; the flow method between the fluid layers comprises the following steps: dripping a sample (6) to be tested into the outermost sample injection region (2) of the paper chip, and applying an electric field on two sides of the sample injection region (2) of the paper chip or applying air flow on one side of the sample injection region (2) of the paper chip; the control program of the electric field or the air flow is programmed, and the liquid on the upper layer flows downwards in sequence and automatically according to the set time.
2. The multilayer paper chip fluid laminar flow method according to claim 1, characterized in that: the material of the paper base material (1) is filter paper.
3. A multilayer paper chip manufacturing method applied to a multilayer paper chip manufacturing apparatus, characterized by comprising:
a light source (7), and
-light transmission means (8) for realising and modifying the shape of the transmission area of the light source (7); the light transmission device (8) is arranged above the light source (7);
a reaction vessel (9) containing a resin solution (10); the light transmission device (8) is arranged on the bottom surface of the reaction container (9), and the light source (7) can transmit into the reaction container (9) through the light transmission device (8);
the platform (11) can vertically move up and down and is used for placing a semi-finished product or a finished product of the paper chip in the process of printing the paper chip; when the platform (11) is at the lowest position, the distance between the platform and the bottom surface of the reaction container (9) is used as the thickness of the resin condensation;
the manufacturing method includes the steps of:
s1, downloading the designed shape of the transmission area from the computer by the light transmission device (8), and descending the platform (11) to the distance between the platform and the bottom surface of the reaction container (9) which is the set thickness of the substrate layer (4); turning on a light source (7), exposing according to set time, and printing a blank substrate layer (4); after the blank substrate layer (4) is printed, the light source (7) is turned off, the platform (11) rises, and the substrate layer (4) is adhered to the lower surface of the platform (11);
s2, placing the paper base material (1) in a reaction container (9), descending the platform (11) to a set position, turning on the light source (7), exposing according to set time, and printing the first resin layer (3); after the resin layer (3) is printed, the light source (7) is turned off, the platform (11) rises, and the paper chip semi-finished product is adhered to the lower surface of the platform (11);
s3, placing the paper substrate (1) in a reaction container (9), downloading the designed shape of the transmission area from a computer by the light transmission device (8), descending the platform (11) to a set position, turning on the light source (7), exposing according to a set time, and printing the resin layer (3); after the resin layer (3) is printed, the light source (7) is turned off, the platform (11) rises, and the paper chip semi-finished product is still adhered to the lower surface of the platform (11);
s4, repeat S3 until printing of all resin layers (3) is completed.
CN201810764200.2A 2018-07-12 2018-07-12 Multilayer paper chip structure, manufacturing apparatus and method, and fluid interlayer flow method Active CN109012770B (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201810764200.2A CN109012770B (en) 2018-07-12 2018-07-12 Multilayer paper chip structure, manufacturing apparatus and method, and fluid interlayer flow method

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201810764200.2A CN109012770B (en) 2018-07-12 2018-07-12 Multilayer paper chip structure, manufacturing apparatus and method, and fluid interlayer flow method

Publications (2)

Publication Number Publication Date
CN109012770A CN109012770A (en) 2018-12-18
CN109012770B true CN109012770B (en) 2021-05-14

Family

ID=64640898

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201810764200.2A Active CN109012770B (en) 2018-07-12 2018-07-12 Multilayer paper chip structure, manufacturing apparatus and method, and fluid interlayer flow method

Country Status (1)

Country Link
CN (1) CN109012770B (en)

Citations (21)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
TW593128B (en) * 2002-05-17 2004-06-21 Fan-Gen Tzeng Method for manufacturing three-dimensional microstructure
CN102016595A (en) * 2008-03-27 2011-04-13 哈佛学院院长等 Three-dimensional microfluidic devices
CN102914536A (en) * 2012-10-19 2013-02-06 大连大学 Patterned multilayer array paper chip, preparation method and application thereof
CN102998439A (en) * 2011-09-14 2013-03-27 佳木斯大学 Micro-fluidic paper chip for simultaneously detecting glucose, uric acid, triglycerides and cholesterols, and its manufacturing method
CN103055967A (en) * 2012-12-27 2013-04-24 济南大学 A preparation method of a simple, low-cost, multi-channel microfluidic chemiluminescent paper chip and an on-site detection method by using the same
CN103722745A (en) * 2013-12-29 2014-04-16 北京工业大学 Quick resin forming method based on LCD (liquid crystal display) selective regional light transmission principle
CN104069904A (en) * 2014-07-16 2014-10-01 华南师范大学 Preparation method for ultraviolet photoetching technique-based cloth micro fluidic chip
CN104339653A (en) * 2013-08-05 2015-02-11 李家萌 Light curing 3D printing device and printing method
CN104475178A (en) * 2014-12-01 2015-04-01 浙江大学 Micro-fluidic paper chip manufacturing device and micro-fluidic paper chip manufacturing method
CN105903502A (en) * 2016-05-16 2016-08-31 南京工业大学 Preparation method of micro-fluidic paper chip based on heat transfer wax hydrophilic and hydrophobic patterns
CN104841499B (en) * 2015-04-24 2016-09-28 复旦大学 A kind of paper substrate numeral microfluidic device
CN106732840A (en) * 2017-01-24 2017-05-31 厦门大学 The 3D printing method and device of nanofiber paper substrate layered manufacturing micro-fluidic chip
WO2017089963A1 (en) * 2015-11-23 2017-06-01 King Abdullah University Of Science And Technology Methods of making microfluidic devices
KR20170078057A (en) * 2015-12-29 2017-07-07 광주과학기술원 Chip structure for multiple molecular diagonosis
CN106985382A (en) * 2017-04-25 2017-07-28 上海联泰科技股份有限公司 3D printing method and the printing device being applicable
CN107478631A (en) * 2017-09-19 2017-12-15 南京工业大学 3D fan-fold paper based microfluid fluorescence detection devices that are a kind of while detecting Diagnostic Value of Several Serum Tumor Markers
CN107734862A (en) * 2017-11-30 2018-02-23 济南大学 A kind of construction method of three-dimensional paper substrate multifunctional circuit
CN107899626A (en) * 2017-12-05 2018-04-13 哈尔滨工业大学 A kind of three-dimensional paper chip based on thin double faced adhesive tape and lamination techniques and preparation method thereof
CN107991484A (en) * 2017-11-20 2018-05-04 中国科学院烟台海岸带研究所 A kind of rotary electrical chemo-immunity refill card analyzer and its detection method
CN108020585A (en) * 2017-12-05 2018-05-11 哈尔滨工业大学 A kind of three-dimensional paper chip of integrated colour developing and Electrochemical Detection and preparation method thereof
CN108088841A (en) * 2017-12-15 2018-05-29 长春理工大学 Paper substrate micro-fluidic chip that is a kind of while detecting four kinds of liver function enzymes and preparation method thereof

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2790834A1 (en) * 2011-12-15 2014-10-22 Commissariat à l'Énergie Atomique et aux Énergies Alternatives 3d microfluidic system having nested areas and a built-in reservoir, method for the preparing same, and uses thereof
US20170173578A1 (en) * 2014-03-14 2017-06-22 Board Of Regents, The University Of Texas System Microfluidic devices for the rapid detection of analytes

Patent Citations (21)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
TW593128B (en) * 2002-05-17 2004-06-21 Fan-Gen Tzeng Method for manufacturing three-dimensional microstructure
CN102016595A (en) * 2008-03-27 2011-04-13 哈佛学院院长等 Three-dimensional microfluidic devices
CN102998439A (en) * 2011-09-14 2013-03-27 佳木斯大学 Micro-fluidic paper chip for simultaneously detecting glucose, uric acid, triglycerides and cholesterols, and its manufacturing method
CN102914536A (en) * 2012-10-19 2013-02-06 大连大学 Patterned multilayer array paper chip, preparation method and application thereof
CN103055967A (en) * 2012-12-27 2013-04-24 济南大学 A preparation method of a simple, low-cost, multi-channel microfluidic chemiluminescent paper chip and an on-site detection method by using the same
CN104339653A (en) * 2013-08-05 2015-02-11 李家萌 Light curing 3D printing device and printing method
CN103722745A (en) * 2013-12-29 2014-04-16 北京工业大学 Quick resin forming method based on LCD (liquid crystal display) selective regional light transmission principle
CN104069904A (en) * 2014-07-16 2014-10-01 华南师范大学 Preparation method for ultraviolet photoetching technique-based cloth micro fluidic chip
CN104475178A (en) * 2014-12-01 2015-04-01 浙江大学 Micro-fluidic paper chip manufacturing device and micro-fluidic paper chip manufacturing method
CN104841499B (en) * 2015-04-24 2016-09-28 复旦大学 A kind of paper substrate numeral microfluidic device
WO2017089963A1 (en) * 2015-11-23 2017-06-01 King Abdullah University Of Science And Technology Methods of making microfluidic devices
KR20170078057A (en) * 2015-12-29 2017-07-07 광주과학기술원 Chip structure for multiple molecular diagonosis
CN105903502A (en) * 2016-05-16 2016-08-31 南京工业大学 Preparation method of micro-fluidic paper chip based on heat transfer wax hydrophilic and hydrophobic patterns
CN106732840A (en) * 2017-01-24 2017-05-31 厦门大学 The 3D printing method and device of nanofiber paper substrate layered manufacturing micro-fluidic chip
CN106985382A (en) * 2017-04-25 2017-07-28 上海联泰科技股份有限公司 3D printing method and the printing device being applicable
CN107478631A (en) * 2017-09-19 2017-12-15 南京工业大学 3D fan-fold paper based microfluid fluorescence detection devices that are a kind of while detecting Diagnostic Value of Several Serum Tumor Markers
CN107991484A (en) * 2017-11-20 2018-05-04 中国科学院烟台海岸带研究所 A kind of rotary electrical chemo-immunity refill card analyzer and its detection method
CN107734862A (en) * 2017-11-30 2018-02-23 济南大学 A kind of construction method of three-dimensional paper substrate multifunctional circuit
CN107899626A (en) * 2017-12-05 2018-04-13 哈尔滨工业大学 A kind of three-dimensional paper chip based on thin double faced adhesive tape and lamination techniques and preparation method thereof
CN108020585A (en) * 2017-12-05 2018-05-11 哈尔滨工业大学 A kind of three-dimensional paper chip of integrated colour developing and Electrochemical Detection and preparation method thereof
CN108088841A (en) * 2017-12-15 2018-05-29 长春理工大学 Paper substrate micro-fluidic chip that is a kind of while detecting four kinds of liver function enzymes and preparation method thereof

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
Double-sided 3D printing on paper towards mass production of three-dimensional paper-based microfluidic analytical devices (3D-μPADs);Chanyong Park;《Lab on a Chip》;20180607;全文 *
Rapid fabrication of paper-based microfluidic analytical devices with desktop stereolithography 3D printer;Yong He;《RSC Advanves》;20151231;全文 *
Sensitive colorimetric detection of Cu2+ by simultaneous reaction and electrokinetic stacking on a paper-based analytical device;Lei Liu;《Microchemical Journal》;20180630;全文 *
三维纸质微流控芯片的设计制作及其在重金属检测中的应用;王虎;《中国优秀硕士学位论文全文数据库 工程科技Ⅰ辑》;20140815;全文 *

Also Published As

Publication number Publication date
CN109012770A (en) 2018-12-18

Similar Documents

Publication Publication Date Title
US6645432B1 (en) Microfluidic systems including three-dimensionally arrayed channel networks
US7267938B2 (en) Patterning of surfaces utilizing microfluidic stamps including three-dimensionally arrayed channel networks
Vulto et al. Microfluidic channel fabrication in dry film resist for production and prototyping of hybrid chips
KR101561718B1 (en) Three-dimensional microfluidic devices
Rhee et al. Microfluidic assembly blocks
US20120184046A1 (en) Selective bond reduction in microfluidic devices
CN109682962B (en) Immunofluorescence detection system and detection method based on microfluidic chip
JP2008008880A (en) Microchip made from plastic, manufacturing method therefor, and biochip or microanalytical chip using the same
CA2666378A1 (en) Microfluidic device having an array of spots
US20050042866A1 (en) Method and coating apparatus for the manufacture of a microarray
Tijero et al. Biomolecule storage on non-modified thermoplastic microfluidic chip by ink-jet printing of ionogels
CN109012770B (en) Multilayer paper chip structure, manufacturing apparatus and method, and fluid interlayer flow method
WO2005077536A1 (en) Methods of making a multi-well test plate having an adhesively secured transparent bottom panel
WO2016178013A1 (en) Fluid flow device on a porous substrate and method for making the same
US11759782B2 (en) Microfluidic chip and a method for the manufacture of a microfluidic chip
Gutierrez-Rivera et al. Multilayer bonding using a conformal adsorbate film (CAF) for the fabrication of 3D monolithic microfluidic devices in photopolymer
JP6531749B2 (en) Method of bonding substrates, microchip and method of manufacturing the same
US9120298B2 (en) Method of continuously manufacturing microfluidic chips with BoPET film for a microfluidic device and microfluidic chips with BoPET film
Gao et al. Digital microfluidic programmable stencil (dMPS) for protein and cell patterning
CN105289767B (en) Micro-fluidic chip
JP4994578B2 (en) Manufacturing method of resin microchemical chip and resin microchemical chip produced by the method
US11913947B2 (en) Digital immunochip and manufacture method of the same
WO2011108333A1 (en) Microfluidic detection chip manufacturing method
TW200528389A (en) Method of manufacturing microchip and product made by same
JP2010243271A (en) Fine channel device, and method for manufacturing the same

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
GR01 Patent grant
GR01 Patent grant