CN113117765B

CN113117765B - Detection chip for photonic crystal coding, preparation method and application thereof, and drug screening system and drug screening method

Info

Publication number: CN113117765B
Application number: CN202011611823.XA
Authority: CN
Inventors: 李明珠; 宋谦; 李会增; 汪洋; 宋延林
Original assignee: Institute of Chemistry CAS
Current assignee: Institute of Chemistry CAS
Priority date: 2019-12-31
Filing date: 2020-12-30
Publication date: 2022-08-16
Anticipated expiration: 2040-12-30
Also published as: CN113117765A

Abstract

The invention discloses a detection chip for photonic crystal coding, a preparation method and application thereof, and a drug screening system and a screening method adopting the detection chip. The detection chip comprises a substrate, wherein the surface of the substrate is provided with a super-hydrophobic region and a hydrophilic detection point array, a hydrophilic detection point in the hydrophilic detection point array is provided with a hydrophilic layer, an adhesion enhancement layer and a photonic crystal layer, the surface of the hydrophilic detection point array is provided with the photonic crystal layer, and the adhesion enhancement layer is positioned between the hydrophilic layer and the photonic crystal layer. The detection chip of the invention contains photonic crystals with different structural colors, is easy to code, and can conveniently and simultaneously screen different types and/or concentrations of drugs and/or microorganisms; and the cell culture solution or the microorganism culture solution is cut by means of the hydrophilic-super-hydrophobic pattern and is distributed at the hydrophilic position of the detection chip, so that the dependence on complicated pipetting operation is eliminated, the reagent dosage is small, and the high efficiency and the low cost of medicament and/or microorganism screening are realized.

Description

Detection chip for photonic crystal coding, preparation method and application thereof, and drug screening system and drug screening method

Technical Field

The invention relates to a photonic crystal coded detection chip, a preparation method and application thereof, and also relates to a photonic crystal coded drug screening system adopting the detection chip, and further relates to a drug screening method adopting the detection chip.

Background

Drug screening is an important and critical process for drug development, and statistically, the marketing of a new drug requires $ 15 years and $ 80 billion on average, while at the same time, humans are confronted with various diseases, and there is an urgent need for more rapid and less costly development of new drugs. Since the last 90 century, the development of genomics and combinatorial chemistry has had a profound impact on drug research, and high-throughput drug screening technology is a novel drug screening method appearing on this basis, and due to its characteristics of simplicity and high efficiency, high-throughput drug screening has become an important field in the process of new drug development and development, is widely applied to the research of candidate compounds or organisms, and becomes one of the main technical means of drug screening.

CN101983724A discloses a rapid high-flux antiviral drug screening model, which is characterized in that drug-containing serum extracted from animal bodies is added into a cell culture solution, the activity of cells is detected, and the drug effect is evaluated; CN102432973A discloses a microsphere for high-throughput drug screening, which is used for a scintillation analysis method in the high-throughput screening; CN104789634A discloses a drug screening method with high accuracy and high repeatability, which realizes the growth of cells in a small cavity and is used for screening drugs; CN107325964A discloses a ready-to-use high-throughput three-dimensional drug screening model, which is used to screen drugs, but only one drug with one concentration at a time.

Although researchers have developed a variety of methods for screening drugs, the methods currently used still suffer from a number of drawbacks, such as: the usage amount of required medicines and consumables in the process of screening medicines is large, a complex cell sap liquid transferring step is required in the screening process, and the operation is complex; the system is not easy to code during the experiment, thereby being difficult to realize the simultaneous screening of various medicines.

Disclosure of Invention

The invention aims to overcome the defects that the complex cell liquid pipetting step is needed in the screening process and the system is not easy to code during the experiment, so that the simultaneous screening of various drugs is difficult to realize, and provides a detection chip of photonic crystal coding, a preparation method thereof, a drug screening system adopting the detection chip and a drug screening method.

According to a first aspect of the invention, the invention provides a photonic crystal coded detection chip, which comprises a substrate, wherein at least one surface of the substrate is provided with a super-hydrophobic region and a hydrophilic detection point array, hydrophilic detection points in the hydrophilic detection point array are provided with a hydrophilic layer, an adhesion enhancement layer and a photonic crystal layer, the surface layer of the hydrophilic detection point array is the photonic crystal layer, and the adhesion enhancement layer is positioned between the hydrophilic layer and the photonic crystal layer.

According to a second aspect of the present invention, the present invention provides a method for preparing a photonic crystal encoded detection chip, the method comprising the steps of:

(1) providing a substrate;

(2) forming a super-hydrophobic layer on at least one surface of the substrate;

(3) forming a hydrophilic layer on part of the surface of the super-hydrophobic layer; and

(4) and sequentially forming an adhesion enhancement layer and a photonic crystal layer on the surface of at least part of the hydrophilic layer.

According to a third aspect of the invention, there is provided a photonic crystal encoded detection chip produced by the method of the second aspect of the invention.

According to a fourth aspect of the present invention, there is provided use of the detection chip according to the first or third aspect of the present invention in drug screening or microorganism screening.

According to a fifth aspect of the present invention, there is provided a drug screening system encoded by photonic crystals, the system comprising the detection chip of the first or third aspect of the present invention, and a series of drug mixtures attached to the surfaces of the hydrophilic detection spots of the detection chip, wherein the series of drug mixtures comprises two or more drug mixtures, and the drug mixtures attached to the surfaces of the hydrophilic detection spots of the photonic crystals having the same color are the same drug mixture.

According to a sixth aspect of the present invention, there is provided a drug screening method comprising the steps of:

(A) providing a series of drug solutions, the series of drug solutions comprising two or more drug solutions;

(B) attaching the drug solution to the surface of the hydrophilic detection point of the detection chip according to the first aspect or the third aspect of the present invention, wherein the drug solution attached to the surface of the hydrophilic detection point of the photonic crystal having the same color is the same drug solution, and drying the drug solution; and

(C) the medicine detection liquid is attached to the surface of the hydrophilic detection point.

The detection chip provided by the invention contains the photonic crystals, the photonic crystals have different structural colors, are easy to encode, and can conveniently and quickly screen different types and/or different concentrations of drugs and/or microorganisms.

The surface of the detection chip provided by the invention is provided with the super-hydrophobic area, when the detection chip is used for drug screening or microorganism screening, the super-hydrophobic area is combined with a drug and/or a microorganism solution, a hydrophilic-super-hydrophobic pattern can be constructed on the surface of the detection chip, so that the surface of the detection chip has different infiltration performances, and shows different adhesivity to a cell culture solution or a microorganism culture solution, and the cell culture solution or the microorganism culture solution is cut by virtue of the hydrophilic-super-hydrophobic pattern, so that the cell culture solution or the microorganism culture solution is cut into small liquid drops to be distributed at the hydrophilic position of the detection chip, the dependence on complicated liquid transfer operation is eliminated, the reagent dosage is small, and the high efficiency and the low cost of the drug and/or microorganism screening are realized.

The detection chip of the photonic crystal code has no strict requirements on the photonic crystal material, the super-hydrophobic region and the substrate material. The detection chip for the photonic crystal code has the advantages of simple preparation process, low cost and short preparation period. Therefore, the photonic crystal coded detection chip is convenient for mass production.

Drawings

The accompanying drawings, which are included to provide a further understanding of the invention and are incorporated in and constitute a part of this specification, illustrate embodiments of the invention and together with the description serve to explain the principles of the invention and not to limit the invention.

FIG. 1 is a static water contact angle test chart of a superhydrophobic region prepared by example 1 of the present invention;

FIG. 2 is a schematic color diagram of a photonic crystal in a photonic crystal coded detection chip prepared in example 1 of the present invention;

FIG. 3 is a reflection spectrum of a photonic crystal prepared in example 1 of the present invention measured using a macroscopic angle-resolved spectrometer.

FIG. 4 is a graph showing the results of the viability assay of Hela cells using the drug screening system prepared in example 1 at various concentrations of doxorubicin hydrochloride.

FIG. 5 shows the results of the viability assay of Hela cells at different concentrations of 5-fluorouracil using the drug screening system prepared in example 2.

FIG. 6 shows the results of the survival rate test of Hela cells under different drugs using the drug screening system prepared in example 3.

Fig. 7 is a result of a survival rate test of a549 cancer cells at different doxorubicin hydrochloride concentrations using the drug screening system prepared in example 4.

Description of the reference numerals

1: red 2: orange color 3: yellow 4: green color 5: cyan color

6: blue color 7: purple color 8: super-hydrophobic region 9: hydrophilic dot 10: red colour

11: orange 12: yellow 13: green color 14: cyan 15: blue color

16: purple color

Detailed Description

The following describes in detail specific embodiments of the present invention. It should be understood that the detailed description and specific examples, while indicating the present invention, are given by way of illustration and explanation only, not limitation.

The endpoints of the ranges and any values disclosed herein are not limited to the precise range or value, and such ranges or values should be understood to encompass values close to those ranges or values. For ranges of values, between the endpoints of each of the ranges and the individual points, and between the individual points may be combined with each other to give one or more new ranges of values, and these ranges of values should be considered as specifically disclosed herein.

In the invention, the photonic crystal coding means that coding is carried out by different structural colors of the photonic crystal.

According to the detection chip of the present invention, the hydrophilic layer is preferably a layer formed by hydrophilizing the surface of the substrate. In a preferred embodiment, the substrate surface is a superhydrophobic surface, and the hydrophilic layer is a layer formed by hydrophilizing the superhydrophobic surface on which the photonic crystal is to be formed. The hydrophilization methods may include, but are not limited to: and treating the super-hydrophobic layer by adopting one or more of ultraviolet irradiation, plasma treatment, etching, coating, surface chemical modification, electrospinning and electrochemical corrosion. The etching may be ion beam etching and/or chemical etching. The etching liquid adopted by the chemical etching can be one or more than two of piranha washing liquid, beck etching liquid and concentrated sulfuric acid. The coating may be one or more of spray coating, printing, and spin coating.

According to the detection chip of the present invention, the surface of the hydrophilic layer has a static water contact angle of not higher than 5 °.

In the present invention, the static water contact angle is measured by a shape image analysis method under conditions of a temperature of 25 ℃, a relative humidity of 40%, and a pressure of 1 standard atmospheric pressure.

According to the detection chip provided by the invention, the adhesion enhancement layer is used for improving the adhesion of the photonic crystal layer to the hydrophilic layer. In a preferred embodiment, the adhesion-promoting layer contains a silicon-containing compound. The silicon-containing compound is preferably a polysiloxane, more preferably a polydimethylsiloxane, and even more preferably a crosslinked polydimethylsiloxane, for example: the silicon-containing compound can be a reaction product of vinyl-terminated polydimethylsiloxane and polysiloxane containing a silicon hydrogen bond (such as polydimethyl hydrogen siloxane), the polysiloxane containing the silicon hydrogen bond is used as a cross-linking agent and is subjected to a silicon hydrogen addition reaction with the vinyl-terminated polydimethylsiloxane for cross-linking, and the mass ratio of the vinyl-terminated polydimethylsiloxane to the polysiloxane containing the silicon hydrogen bond can be 8-12: 1, for example, may be 8: 1. 8.5: 1. 9: 1. 9.5: 1. 10: 1. 10.5: 1. 11: 1. 11.5: 1 or 12: 1. according to this preferred embodiment, the surface static water contact angle of the adhesion promotion layer is preferably 110 ° to 120 °, for example: 110 °, 111 °, 112 °, 113 °, 114 °, 115 °, 116 °, 117 °, 118 °, 119 °, or 120 °. According to this preferred embodiment, the adhesion stability of the point-like photonic crystals to the surface of the hydrophilic layer can be further improved, and the point-like photonic crystals do not fall off from the surface of the substrate even when immersed in the cell culture medium for one week or more.

According to the detection chip provided by the invention, the photonic crystal contains the monodisperse particles, and more than two monodisperse particles with different optical refractive indexes for air are combined for use, so that the photonic crystal can display different colors, and coding is realized, namely the photonic crystal enables hydrophilic detection points in each column or hydrophilic detection points in each row in the hydrophilic detection point array to display different colors from hydrophilic detection points in other columns or hydrophilic detection points in other rows. As an example, the same monodisperse particles are used for the photonic crystals in the same row or the same column of the hydrophilic detection point array, and the monodisperse particles with different optical refractive indexes for air are used in different rows or different columns, so that the same row or the same column can display the same color, the different rows or the different columns can display different colors, and the hydrophilic detection point array is coded through the different colors.

In the present invention, the monodisperse particles may be one or a combination of two or more of organic particles, inorganic particles, organic-inorganic composite particles, and quantum dots. Specific examples of the monodisperse particles may include, but are not limited to: one or more of polymer particles having a core-shell structure, silica particles, polystyrene particles, polyacrylic acid particles, gold particles, silver particles, platinum particles, copper particles, zinc oxide particles, iron oxide particles, ferroferric oxide particles, titanium oxide particles, carbon particles, dopamine particles, silicon particles, and quantum dots, and more preferably one or more of polymer particles having a core-shell structure, polystyrene particles, silica particles, and poly (styrene-methyl methacrylate-acrylic acid) particles.

In a preferred embodiment of the present invention, the monodisperse particles are one or more of polymer particles having a core-shell structure, silica particles, titanium oxide particles, polystyrene particles, and poly (styrene-methyl methacrylate-acrylic acid) particles. More preferably, the monodisperse particles are one or more of silica particles, polystyrene particles, and poly (styrene-methyl methacrylate-acrylic acid) particles. According to this preferred embodiment, the biocompatibility of the photonic crystal can be further improved.

The monodisperse particles may have an average particle diameter of 100nm to 800nm, preferably 100nm to 400nm, more preferably 150nm to 280 nm. The term "monodisperse" in the case of monodisperse particles means that the particle size distribution of the particles is narrow. Typically, the monodisperse particles have a particle size variation within 5% (i.e., a standard deviation of the particle size distribution within 5%). The standard deviation of the particle size distribution of the monodisperse particles used in the examples of the present invention was within 5%. In the present invention, the average particle size and the standard deviation of the particle size distribution are determined by the volume average particle size and measured by a laser particle sizer.

The monodisperse particles are commercially available or can be prepared by conventional methods and are not described in detail herein.

According to the detection chip of the invention, the diameter of the photonic crystal layer can be 0.1-10mm, for example: 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2, 2.1, 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.8, 2.9, 3, 3.1, 3.2, 3.3, 3.4, 3.5, 3.6, 3.7, 3.8, 3.9, 4, 4.1, 4.2, 4.3, 4.4, 4.5, 4.6, 4.7, 4.8, 4.9, 5.1, 5.2, 5.3, 5.4, 5.5, 5.6, 7.6, 6, 6.7, 6, 6.6, 7.6, 7, 6, 7.6, 7, 8, 7.6, 6, 7.6, 7, 8.6, 7, 6, 7.6, 7, 8, 6, 7.6, 8.6.6, 7, 7.6, 8 mm. The diameter of the photonic crystal layer is preferably 2 to 5 mm.

According to the detection chip of the invention, the surface static water contact angle of the photonic crystal layer is preferably 0 ° to 90 °, for example: 0 °,1 °,2 °,3 °, 4 °, 5 °, 6 °, 7 °, 8 °, 9 °, 10 °, 11 °, 12 °, 13 °, 14 °, 15 °, 16 °, 17 °, 18 °, 20 °, 21 °, 22 °, 23 °, 24 °, 25 °, 26 °, 27 °, 28 °, 29 °, 30 °, 31 °, 32 °, 33 °, 34 °, 35 °, 36 °, 37 °, 38 °, 39 °, 40 °, 41 °, 42 °, 43 °, 44 °, 45 °, 46 °, 47 °, 48 °, 49 °, 50 °, 51 °, 52 °, 53 °, 54 °, 55 °, 56 °, 57 °, 58 °, 59 °, 60 °, 61 °, 62 °, 63 °, 64 °, 65 °, 66 °, 67 °, 68 °, 69 °, 71 °, 72 °, 73 °, 74 °, 75 °, 76 °, 77 °, 78 °, 79 °, 80 °, 81 °, 82 °, 83 °, respectively, 84 °, 85 °, 86 °, 87 °, 88 °, 89 °, or 90 °. More preferably, the surface static water contact angle of the photonic crystal layer at the hydrophilic detection point is 10 ° to 60 °. Further preferably, the surface static water contact angle of the photonic crystal layer at the hydrophilic detection point is 30 ° to 50 °.

According to the detection chip, the plurality of hydrophilic detection points are arranged in rows and columns, and a hydrophilic detection point array is formed on the surface of the substrate. The number of rows and columns of the hydrophilic detection spot array can be selected according to the detection flux of the detection chip, and can be, for example, a 3 × 3 or more array, such as a 7 × 7 array.

According to the detection chip of the invention, in the surface of the substrate with the hydrophilic detection point array, the region complementary with the hydrophilic detection point array is a super-hydrophobic region. The surface of the superhydrophobic region typically has a static water contact angle of 150 ° to 180 °, for example: 150 °, 151 °, 152 °, 153 °, 154 °, 155 °, 156 °, 157 °, 158 °, 159 °, 160 °, 161 °, 162 °, 163 °, 164 °, 165 °, 166 °, 167 °, 168 °, 169 °, 170 °, 171 °, 172 °, 173 °, 174 °, 175 °, 176 °, 177 °, 178 °, 179 °, or 180 °. Preferably, the surface of the superhydrophobic region has a static water contact angle of 155 ° to 180 °. More preferably, the surface of the superhydrophobic region has a static water contact angle of 160 ° to 170 °.

The superhydrophobic region can be a roughened surface, such as: the surface has a micro-nano structure. Preferably, the superhydrophobic region is a roughened surface and contains a hydrophobic substance. The hydrophobic substance may be one or more selected from silicon-containing hydrophobic substances, fluorine-and silicon-containing hydrophobic substances, and polystyrene. More preferably, the hydrophobic material is one or more selected from the group consisting of polysiloxane, polystyrene, polytetrafluoroethylene, and polyperfluoropropylene.

In the invention, the material of the substrate can be selected according to the specific application occasion of the detection chip. Specific examples of the substrate may include, but are not limited to, a silicon substrate, a glass substrate, a quartz substrate, a metal substrate, or a polymer substrate. The substrate is preferably selected from the group consisting of an aluminum substrate, a silicon substrate, a glass substrate, a quartz substrate, an iron substrate, a copper substrate, a plastic substrate, and a rubber substrate. More preferably, the substrate is selected from the group consisting of aluminum substrates and silicon substrates.

(1) providing a substrate;

(2) forming a super-hydrophobic layer on at least one surface of the substrate;

The material of the substrate has been described in detail above, and is not described herein again.

In step (1), the substrate may be trimmed and/or cleaned by conventional methods, depending on the source of the substrate. The washing liquid used for washing may be a washing liquid capable of removing the surface impurities of the substrate, and may be, for example, water and/or acetone. From the viewpoint of further improving the effect of cleaning, the cleaning may be performed in the presence of ultrasonic waves.

In the step (2), performing super-hydrophobic treatment on the surface of the substrate for forming the photonic crystal array to form a super-hydrophobic layer. The surface of the super-hydrophobic layer may have a static water contact angle of 150 ° to 180 °, for example: 150 °, 151 °, 152 °, 153 °, 154 °, 155 °, 156 °, 157 °, 158 °, 159 °, 160 °, 161 °, 162 °, 163 °, 164 °, 165 °, 166 °, 167 °, 168 °, 169 °, 170 °, 171 °, 172 °, 173 °, 174 °, 175 °, 176 °, 177 °, 178 °, 179 °, or 180 °. Preferably, the surface of the superhydrophobic region has a static water contact angle of 155 ° to 180 °. More preferably, the surface of the superhydrophobic region has a static water contact angle of 160 ° to 170 °. The substrate surface may be superhydrophobic by conventional methods.

In a preferred embodiment, the substrate surface may be roughened, optionally with the introduction of a hydrophobic substance to the roughened substrate surface, thereby forming a superhydrophobic layer on the substrate surface.

The substrate surface may be roughened using conventional methods, for example: chemical etching and/or energy beam irradiation, wherein the energy beam irradiation can be laser irradiation on the surface of the substrate, so that a rough structure is formed on the surface of the substrate. The chemical etching may be performed by applying a chemical etching liquid to the surface of the substrate, thereby etching the surface of the substrate such that the surface of the substrate is roughened. The chemical etchant may be selected according to the material of the substrate, and is not particularly limited. In one example, the chemical etching liquid may be a chemical etching liquid containing hydrofluoric acid, such as: a mixed solution of hydrofluoric acid and hydrochloric acid, wherein in the mixed solution, hydrofluoric acid: hydrochloric acid: the volume ratio of water may be 1: 16: and 5, wherein the concentration of the hydrofluoric acid is 40 weight percent, and the concentration of the hydrochloric acid is 37 weight percent. The chemical etching may be performed at a temperature of 15 ℃ to 30 ℃, preferably at a temperature of 20 ℃ to 25 ℃. The duration of the chemical etching may be 5-20 seconds, preferably 8-12 seconds.

The hydrophobic substance may be one or more selected from silicon-containing hydrophobic substances, fluorine-and silicon-containing hydrophobic substances, and polystyrene. Specific examples of the hydrophobic substance may include, but are not limited to, one or more of polysiloxane, polystyrene, polytetrafluoroethylene, and polyperfluoropropylene.

The hydrophobic substance may be introduced to the roughened substrate surface using conventional methods, such as: chemical vapor deposition. For example: silanes containing more than two alkoxy groups may be chemical vapor deposited to introduce hydrophobic species to the roughened substrate surface. In a preferred embodiment, the roughened substrate can be placed in a drying oven and dried in the presence of a silane containing two or more alkoxy groups to introduce the hydrophobic material polysiloxane onto the roughened substrate surface. The silane containing more than two alkoxy groups is preferably 1H,1H,2H, 2H-perfluorodecyltrimethoxysilane. The drying is preferably carried out at a temperature of 50 to 125 ℃, more preferably 60 to 110 ℃, and even more preferably 70 to 100 ℃, and the duration of the drying may be 0.5 to 6 hours, preferably 1 to 5 hours, and more preferably 2 to 4 hours. The drying oven is preferably a vacuum drying oven.

In the step (3), the static water contact angle of the surface of the hydrophilic layer may be not higher than 5 °.

The surface of the super-hydrophobic layer on which the hydrophilic layer is to be formed may be subjected to hydrophilization treatment by a conventional method. Specifically, the method of forming the hydrophilic layer may include, but is not limited to: and treating the super-hydrophobic layer by adopting one or more than two of ultraviolet irradiation, plasma treatment, etching, coating, electrospinning and electrochemical corrosion. The etching may be ion beam etching and/or chemical etching. The etching liquid adopted by the chemical etching can be one or more than two of piranha washing liquid, beck etching liquid and concentrated sulfuric acid. The coating may be one or more of spray coating, printing, and spin coating.

In a preferred embodiment, a mask may be formed on the surface of the super-hydrophobic layer, the mask covering the region where the hydrophilic layer is not to be formed, and the hydrophilic layer may be formed on the exposed surface of the super-hydrophobic layer. In this preferred embodiment, the hydrophilic layer is preferably formed by irradiating the surface of the superhydrophobic layer not covered by the mask with ultraviolet light. The time for the ultraviolet light irradiation may be 6 to 10 hours.

In the step (3), the plurality of hydrophilic layers are arranged in rows and columns to form a hydrophilic dot array on the surface of the substrate. The number of rows and columns of the hydrophilic dot array can be selected according to the detection flux of the detection chip, and can be, for example, a 3 × 3 or more array, such as a 7 × 7 array.

In the step (4), the method for forming the adhesion enhancing layer on the surface of the hydrophilic layer may be selected according to the nature of the adhesion enhancing substance used. In a preferred embodiment, the method of forming the adhesion enhancing layer on the surface of the hydrophilic layer comprises: the application of the silicon-containing compound on the surface of the hydrophilic layer can further improve the adhesion stability of the photonic crystal on the surface of the substrate. The silicon-containing compound is preferably a polysiloxane, more preferably a polydimethylsiloxane, and even more preferably a crosslinked polydimethylsiloxane, for example: the silicon-containing compound can be a reaction product of vinyl-terminated polydimethylsiloxane and polysiloxane containing a silicon hydrogen bond (such as polydimethyl hydrogen siloxane), the polysiloxane containing the silicon hydrogen bond is used as a cross-linking agent and is subjected to a silicon hydrogen addition reaction with the vinyl-terminated polydimethylsiloxane for cross-linking, and the mass ratio of the vinyl-terminated polydimethylsiloxane to the polysiloxane containing the silicon hydrogen bond can be 8-12: 1, for example, may be 8: 1. 8.5: 1. 9: 1. 9.5: 1. 10: 1. 10.5: 1. 11: 1. 11.5: 1 or 12: 1. according to this preferred embodiment, the static water contact angle of the surface of the adhesion promotion layer is preferably 110 ° to 120 °, for example: 110 °, 111 °, 112 °, 113 °, 114 °, 115 °, 116 °, 117 °, 118 °, 119 °, or 120 °.

A solution containing a silicon-containing compound may be coated on the surface of the hydrophilic layer and dried, thereby forming an adhesion-promoting layer on the surface of the hydrophilic layer. Preferably, the silicon-containing compound is used in an amount of 0.1 to 1 mg/cm. The drying temperature may be 50 to 100 deg.C, preferably 60 to 80 deg.C. The duration of the drying may be 10 to 120 minutes, preferably 10 to 60 minutes, more preferably 15 to 30 minutes.

In the step (4), the cross section of the photonic crystal layer is a circle, and the diameter of the circle may be 0.1-10mm, for example: 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2, 2.1, 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.8, 2.9, 3, 3.1, 3.2, 3.3, 3.4, 3.5, 3.6, 3.7, 3.8, 3.9, 4, 4.1, 4.2, 4.3, 4.4, 4.5, 4.6, 4.7, 4.8, 4.9, 5.1, 5.2, 5.3, 5.4, 5.5, 5.6, 7.6, 6, 6.7, 6, 6.6, 7.6, 7, 6, 7.6, 7, 8, 7.6, 6, 7.6, 7, 8.6, 7, 6, 7.6, 7, 8, 6, 7.6, 8.6.6, 7, 7.6, 8 mm. The diameter of the photonic crystal layer is preferably 2 to 5 mm.

In the step (4), a photonic crystal may be formed on the surface of the hydrophilic layer by a conventional method. In one embodiment. An emulsion is applied to the surface of the hydrophilic layer where the formation of the photonic crystals is desired, and the emulsion is dried to form the photonic crystals. The emulsion contains at least one monodisperse particle and at least one solvent.

The monodisperse particles have been described in detail above and will not be described further here. The content of the monodisperse particles may be 0.5 to 5 wt%, preferably 1.5 to 2.5 wt%, based on the total amount of the emulsion.

The solvent may be one or more of water, alcohol, alkane and aromatic hydrocarbon. By alcohol is meant an alcohol that is liquid at ambient temperature (typically 25℃.), such as alkanols, cycloalkanols, and arylalkyl alcohols. The alcohol may be one or a combination of two or more of monohydric alcohol, dihydric alcohol and trihydric alcohol. Specific examples of the alcohol may include, but are not limited to, methanol, ethanol, n-propanol, isopropanol, n-butanol, t-butanol, n-pentanol, isopentanol, neopentyl alcohol, cyclopentanol, cyclohexanol, benzyl alcohol, ethylene glycol, 1, 3-propanediol, and glycerol. The alkane refers to an alkane that is liquid at ambient temperature (typically 25 ℃), and specific examples thereof may include, but are not limited to, pentane, hexane, heptane, and octane. The aromatic hydrocarbon means an aromatic hydrocarbon which is liquid at ambient temperature (typically 25 ℃), and specific examples thereof may include, but are not limited to, benzene, toluene, xylene, trimethylbenzene, and ethylbenzene.

In the step (4), the emulsion may be obtained by mixing and emulsifying the monodisperse particles and the solvent. The method of emulsification may be a conventional method, and is not particularly limited. Specifically, emulsification can be achieved by applying a shearing action to a mixed liquid of monodisperse particles and a solvent; emulsification may also be carried out in an emulsifying machine. In order to enhance the mixing and emulsifying effect, the monodisperse particles and the solvent may be mixed and emulsified by an ultrasonic method, thereby obtaining the emulsion. The monodisperse particles may be present as solid particles or may be provided in the form of a colloid, such as a sol. In the preparation of the emulsion, a surfactant may or may not be additionally added. The surfactant may be one or more selected from the group consisting of a cationic surfactant, an anionic surfactant, a zwitterionic surfactant and a nonionic surfactant, and preferably one or more selected from the group consisting of sodium dodecylbenzenesulfonate, sodium lauryl sulfate, sodium stearate, a quaternary ammonium salt type cationic surfactant, an amino acid type zwitterionic surfactant, a betaine type zwitterionic surfactant, a lecithin type zwitterionic surfactant, a polyoxyethylene type nonionic surfactant and a polyhydric alcohol type nonionic surfactant.

According to a third aspect of the present invention, there is provided a photonic crystal encoded detection chip prepared by the preparation method of the second aspect of the present invention.

According to a fourth aspect of the present invention, there is provided use of the detection chip of the first or third aspect of the present invention in drug screening or microorganism screening.

The drug may be any of the common drugs with therapeutic functions, preferably anticancer drugs, such as: one or more of adriamycin, adriamycin hydrochloride, cisplatin, 5-fluorouracil, bleomycin, vinblastine, vincristine, cyclophosphamide, gemcitabine, methotrexate, cytarabine hydrochloride, carboplatin, cisplatin, lomustine, hydroxyurea, mitomycin, etoposide, purinethiol, daunorubicin, cytarabine hydrochloride, camptothecin and paclitaxel. More preferably, the drug is a slow release drug.

The microorganism may be one or more of cells, bacteria, viruses and fungi.

The pharmaceutical mixture contains a carrier and a drug. The carrier is preferably one or more than two selected from gelatin, starch, sodium alginate and cellulose. In a preferred embodiment, the drug is one or more than two of anticancer drugs, preferably one or more than two of adriamycin, adriamycin hydrochloride, cisplatin, 5-fluorouracil, bleomycin, vinblastine, vincristine, cyclophosphamide, gemcitabine, methotrexate, cytarabine hydrochloride, carboplatin, cisplatin, lomustine, hydroxyurea, mitomycin, etoposide, purinethiol, daunorubicin, cytarabine hydrochloride, camptothecin, and paclitaxel. Further preferably, the drug is a slow release drug. The weight ratio of the carrier to the drug may be 1-200: 1.

according to the photonic crystal encoded drug screening system of the present invention, the difference between different drug mixtures can be selected according to the target of drug screening, and can be different in the content of at least one substance and/or different in the kind of at least one substance. In one example, the difference between the same drug mixture is the content of the drug (active ingredient) which is different, so that the effect of the same drug at different concentrations can be screened. In another example, a mixture of different drugs may differ in the type of drug (active ingredient) that is used, allowing screening of the efficacy of different drugs.

(A) providing a series of drug solutions, the series of drug solutions containing two or more drug solutions;

In the step (a), the drug solution contains a carrier, a drug and a dispersant. The drug solution may be a homogeneous solution, or may be a suspension or suspension. The carrier is preferably one or more than two selected from gelatin, starch, sodium alginate and cellulose. In a preferred embodiment, the drug is one or more than two of anticancer drugs, preferably one or more than two of adriamycin, adriamycin hydrochloride, cisplatin, 5-fluorouracil, bleomycin, vinblastine, vincristine, cyclophosphamide, gemcitabine, methotrexate, cytarabine hydrochloride, carboplatin, cisplatin, lomustine, hydroxyurea, mitomycin, etoposide, purinethiol, daunorubicin, cytarabine hydrochloride, camptothecin, and paclitaxel. The drug is preferably a slow release drug. The weight ratio of the carrier to the drug may be 1-200: 1. the dispersing agent may be selected according to the kind of the drug, and is preferably water.

According to the drug screening method of the present invention, the difference between different kinds of drug solutions may be selected according to the target of drug screening, and may be different in the content of at least one substance and/or different in the kind of at least one substance. In one example, solutions of the same drug differ in the amount of drug present, which allows screening of the effect of the same drug at different concentrations. In another example, different drug solutions differ in the type of drug, allowing screening of the efficacy of different drugs.

In the step (B), the drug solution may be dropped on the surface of the hydrophilic detection spot by a conventional method.

In the step (B), the medicine solution is dried, so that the medicine and the carrier are attached to the surfaces of the hydrophilic detection points, and the hydrophilic detection points and the corresponding detected medicine are coded through the color of the photonic crystal. The drying may be selected according to the solvent of the drug solution. Generally, the drying may be carried out at a temperature of 30-50 ℃ and the duration of the drying may be 2-4 hours.

In the step (C), the drug detection solution is used for detecting the drug effect of the drug, and may contain cells and/or microorganisms, such as: the detection solution contains one or more than two of cells, bacteria, viruses, fungi and microorganisms. In a preferred embodiment, the drug mixture is a drug having an inhibitory effect on cancer cells, and the drug test solution is a test solution containing a measure of the inhibitory effect of the drug on cancer cells, such as: a detection solution containing cancer cells.

According to the drug screening method, the region of the detection chip, which is complementary with the hydrophilic detection point array, is the super-hydrophobic region, so that the drug detection liquid can be cut through the different wettability of the super-hydrophobic region and the hydrophilic detection point region, the drug detection liquid is uniformly distributed on the surface of the hydrophilic detection points attached with the drugs, each hydrophilic detection point forms a relatively independent drug micro-detector, the drug effect of the drugs is detected, and the drug screening is realized. The medicine detection liquid is cut and distributed through the difference of the wettability of the super-hydrophobic area and the hydrophilic detection point area, so that repeated and complicated liquid transfer operation is avoided, the operation complexity of medicine screening is reduced, the operation time is shortened, and the medicine screening efficiency is improved.

Specifically, in the step (C), the method of attaching the drug detection solution to the surface of the hydrophilic detection spot may include:

(C1) cutting the surface of the detection chip with the hydrophilic detection point array into the medicine detection liquid fixed above the surface;

(C2) and pulling the detection chip out of the medicine detection liquid.

In the method (C1), the drug detection solution droplet may be fixed above the detection chip and made to slide along the surface of the detection chip, so that the drug detection solution droplet is cut by the aid of the hydrophilic and super-hydrophobic effects on the surface of the detection chip, and the drug detection solution is attached to the surface of the hydrophilic detection point region of the detection chip. Specifically, a pipetting device may be employed such that the pipetting device slides along the surface of the detection chip, or such that the detection chip moves relative to the pipetting device, thereby cutting the droplets of the drug detection solution by means of the hydrophilic and superhydrophobic actions of the surface of the detection chip, such that the drug detection solution adheres to the surface of the hydrophilic detection spot region of the detection chip. The dropping liquid tube can be dragged along the surface of the detection chip, so that the medicine detection liquid is attached to the surface of the hydrophilic detection point area of the detection chip.

In the method (C2), the detection chip may be immersed in the drug detection solution and pulled out vertically from the drug detection solution (the surface of the detection chip having the hydrophilic detection dot array is vertical), so that the drug detection solution adheres to the surface of the hydrophilic detection dots of the detection chip.

According to the screening method of the invention, after the drug detection liquid is introduced into the hydrophilic detection point region, the detection chip can be placed under the screening condition to detect the change of the drug detection liquid along with the time, thereby measuring the drug effect of the drug.

The present invention will be described in detail with reference to examples, but the scope of the present invention is not limited thereto.

In the following examples and comparative examples, the particle size and particle size distribution of monodisperse particles were measured using a particle size analyzer, model IG-1000 available from Shimadzu, wherein the particle size is a volume average particle size.

In the following examples and comparative examples, static water contact angles were measured using a contact angle meter, model OCA20, from DataPhysics, at a temperature of 25 ℃ under a pressure of 1 atm and a humidity of 40%.

In the following examples and comparative examples, a macro angle-resolved spectrometer, available from Shanghai Kangsu scientific instruments, Inc., was used to detect the reflection spectrum of a photonic crystal, the reflectance of which can be indicative of the quality of the photonic crystal, wherein the higher the reflectance, the higher the quality of the photonic crystal.

Examples 1-4 are intended to illustrate the invention.

Example 1

(1) Cutting an aluminum sheet of 6cm multiplied by 6cm, and sequentially cleaning the aluminum sheet by acetone, ethanol and ultrapure water.

Immersing the cleaned aluminum sheet into an etching solution, wherein the temperature of the etching solution is 25 ℃, the immersion time is 10 seconds, and the immersion solution is a mixed solution of hydrochloric acid, hydrofluoric acid and ultrapure water, wherein the hydrochloric acid (the concentration is 37 weight percent): ultrapure water: the volume ratio of hydrofluoric acid (concentration of 40 wt%) was 16: 5: 1.

the etched aluminum sheet was dried with nitrogen and placed in a vacuum desiccator, then 2 drops (about 0.1mL) of 1H,1H,2H, 2H-perfluorodecyltrimethoxysilane were added dropwise to the middle of the vacuum desiccator, the vacuum desiccator was sealed and evacuated for 10 minutes. Then, the desiccator was placed in an oven at 80 ℃ for 2 hours to obtain an aluminum sheet having an ultra-hydrophobic layer. As shown in fig. 1, the surface of the aluminum sheet subjected to the super-hydrophobization treatment was a super-hydrophobic surface, and the static water contact angle thereof was 165 °.

Covering a mask plate with a 7 multiplied by 7 dotted array on the surface of the super-hydrophobic layer of the aluminum sheet with the super-hydrophobic layer, and putting the whole aluminum sheet under a HW-UVX400 type ultraviolet lamp, wherein the surface of the super-hydrophobic layer with the mask plate faces the ultraviolet lamp and irradiates for 6 hours. Hydrophilic dots are generated in the area not covered by the mask plate, so that a 7 × 7 array of dot-like hydrophilic-superhydrophobic patterns is prepared. Through detection, the static water contact angle of the hydrophilic point area is less than or equal to 5 degrees.

(2) 0.3 mu L of vinyl-terminated Polydimethylsiloxane (PDMS) and a crosslinking agent (the mass ratio of the PDMS to the crosslinking agent is 10: 1, the crosslinking agent is polydimethylsiloxane, the PDMS and the crosslinking agent are from Dow Corning, and the trademark is DC 184) are dropwise added to hydrophilic points of an aluminum sheet with a hydrophilic-super-hydrophobic pattern by a dispenser, and after the PDMS is uniformly distributed at the hydrophilic points, the aluminum sheet is placed in an oven at 60 ℃ and heated for 25 min. The static water contact angle of the treated PDMS areas was detected to be 110 °.

Taking 8 microlitres of 7 emulsions (the concentration is 2 weight percent, the solvent is water, and the emulsifier is sodium dodecyl sulfate) dispersed with monodisperse poly (styrene-methyl methacrylate-acrylic acid) colloidal nanoparticles with different particle diameters (the average particle diameter of the colloidal nanoparticles and the corresponding photonic crystal structure color are shown in table 1), and respectively pointing the emulsions at hydrophilic points by using a pipette. And (3) placing the aluminum sheet dripped with the different colloidal nanoparticle emulsions in an oven at 80 ℃ for heating for 5min to form colloidal photonic crystals with uniform appearance at hydrophilic points, thereby obtaining the photonic crystal coded detection chip, wherein photonic crystals in different rows in the hydrophilic detection point array have different colors (as shown in figure 2). The detected static water contact angle of the surface of the photonic crystal is 50 degrees, and the diameter of the photonic crystal is 3 mm. The prepared detection chip is tested by using a macroscopic angle-resolved spectrometer, and the reflection spectrum shows that the photonic crystals in each column of the hydrophilic detection point array have a structural color with high reflectivity (as shown in fig. 3).

TABLE 1

(3) 100mL of ultrapure water was weighed into 7 identical beakers, 0.02g of gelatin (purchased from Allantin reagent Co., Ltd.) was added thereto, followed by heating until the gelatin was completely dissolved, cooling to room temperature (25 ℃ C.), and then 5mg, 2.5mg, 1mg, 0.75mg, 0.5mg, 0.25mg and 0.1mg of doxorubicin hydrochloride (purchased from Allantin reagent Co., Ltd.) were added to each beaker, followed by mixing uniformly to obtain a series of drug solutions having different doxorubicin hydrochloride concentrations.

(4) Matching the drug solution with the photonic crystal according to the corresponding relation shown in table 2, and dripping the drug solution to the hydrophilic detection point region corresponding to the matched photonic crystal, wherein the first point of each column is not dripped with any solution and is used as a blank control group, the second point of each column is dripped with a solution only containing gelatin and is used as a gelatin control group, and the third point to the seventh point of each column are dripped with the drug solution with the same concentration. And after the dropwise addition is finished, placing the aluminum sheet in an environment of 50 ℃ for drying until water in the liquid drops of the medicine mixture is volatilized and solidified, and obtaining the medicine screening system of the photonic crystal code.

TABLE 2

(5) Fixing a large drop of Hela cell culture solution by using a dropper, sliding the surface of a detection chip of the screening system, cutting the cell culture solution into small drops corresponding to hydrophilic detection point areas by means of different wettability of the hydrophilic detection point areas and the super-hydrophobic areas on the surface of the chip to the cell culture solution, and attaching the small drops to the hydrophilic detection point areas, wherein each hydrophilic detection point forms an independent cell culture chamber.

Placing the drug screening system with the photonic crystal code of Hela cancer cell culture solution at 37 ℃ and 5 vol% CO ₂ The concentration,After 24 hours in a constant temperature chamber at normal pressure (i.e., 1 atm), 10. mu.l of 5% MTT/PBS solution was added to the drug screening system, and the cells were placed at 37 ℃ and 5 vol.% CO ₂ After culturing for 4 hours under the concentration, sucking out the liquid in the drug screening system, adding 100 microliters of dimethyl sulfoxide to fully dissolve the formazan generated in the cells, and testing the light absorption value of the formazan by using an enzyme labeling instrument. The normalized survival rate of cells was calculated according to the following formula: cell viability (%) (sample absorbance-background absorbance)/(reference absorbance-background absorbance) × 100%.

The results are shown in FIG. 4. As can be seen from FIG. 4, the number of Hela cancer cells survived decreased with the increase in the concentration of doxorubicin hydrochloride, indicating that the optimal amount of the drug can be effectively determined using the drug screening system of the present invention.

Comparative example 1

A test chip was prepared in the same manner as in example 1, except that in the step (2), 0.3. mu.L of polydimethylsiloxane was not dropped at the hydrophilic site by a dispenser, but the emulsion was directly dropped at the hydrophilic site to form photonic crystals.

The detection chips prepared in step (2) of example 1 and step (2) of comparative example 1 were immersed in Hela cell culture solution at a temperature of 25 ℃. As a result, the photonic crystal falling phenomenon occurs within a few minutes after the cell culture solution is added into the detection chip prepared in comparative example 1, while the photonic crystal falling phenomenon does not occur after the detection chip prepared in example 1 is soaked for one week, which shows that before the photonic crystal is prepared by applying the emulsion, polydimethylsiloxane is firstly dripped on the hydrophilic point, and the adhesion stability of the photonic crystal in the hydrophilic area can be greatly improved.

Example 2

Detection chips and drug screening systems were prepared in the same manner as in example 1, except that:

in the step (2), the colloidal nanoparticles are replaced by silicon oxide nanoparticles;

in the step (4), 5-fluorouracil is used for replacing doxorubicin hydrochloride, so that a series of drug solutions with different 5-fluorouracil concentrations are obtained.

And (3) testing the detection chip prepared in the step (2) by using a macroscopic angle-resolved spectrometer, wherein the reflection spectrum shows that the photonic crystals in each column in the hydrophilic detection point array have a structural color with high reflectivity.

The cell viability of the drug screening system encoded by photonic crystals of Hela cancer cell culture broth was measured in the same manner as in example 1, and the results are shown in FIG. 5. As can be seen from FIG. 5, the number of survival Hela cancer cells decreased with the increase in the concentration of 5-fluorouracil, indicating that the optimal amount of the drug can be effectively determined using the drug screening system of the present invention.

Example 3

(1) Cutting an aluminum sheet of 6cm multiplied by 6cm, sequentially cleaning the aluminum sheet by using acetone, ethanol and ultrapure water, and immersing the cleaned aluminum sheet into an etching solution, wherein the temperature of the etching solution is 20 ℃, the immersion time is 12 seconds, and the immersion solution is a mixed solution of hydrochloric acid, hydrofluoric acid and ultrapure water, wherein the hydrochloric acid (the concentration is 37 weight percent): ultrapure water: the volume ratio of hydrofluoric acid (with a concentration of 40 wt%) was 16: 5: 1.

the etched aluminum sheet was dried with nitrogen and placed in a vacuum desiccator, then 2 drops (about 0.1mL) of 1H,1H,2H, 2H-perfluorodecyltrimethoxysilane were added dropwise to the middle of the vacuum desiccator, the vacuum desiccator was sealed and evacuated for 15 minutes. Then, the desiccator was placed in an oven at 100 ℃ for 3 hours to obtain an aluminum sheet having an ultra-hydrophobic layer. The surface of the aluminum sheet after the super-hydrophobic treatment is detected to be a super-hydrophobic surface, and the static water contact angle of the aluminum sheet is 160 degrees.

Covering a mask plate with a 7 multiplied by 7 point array on the surface of the super-hydrophobic layer of the aluminum sheet with the super-hydrophobic layer, and putting the aluminum sheet under a HW-UVX400 type ultraviolet lamp in a whole manner, wherein the surface of the super-hydrophobic layer with the mask plate faces the ultraviolet lamp and irradiates for 10 hours. Hydrophilic dots are generated in the area not covered by the mask plate, so that a 7 × 7 array of dot-like hydrophilic-superhydrophobic patterns is prepared. Through detection, the static water contact angle of the hydrophilic point area is less than or equal to 5 degrees.

(2) 0.5uL of vinyl-terminated Polydimethylsiloxane (PDMS) and a crosslinking agent (the mass ratio of the PDMS to the crosslinking agent is 10: 1, the crosslinking agent is polydimethylsiloxane, the PDMS and the crosslinking agent are both purchased from Dow Corning, and the trademark is DC 184) are dripped into a hydrophilic point of an aluminum sheet with a hydrophilic-super-hydrophobic pattern by using a dispenser, and after the PDMS is uniformly distributed on the hydrophilic point, the aluminum sheet is placed into an oven at 80 ℃ for heating for 15 min. The treated PDMS containing regions were examined to have a static water contact angle of 114 °.

The 7 kinds of emulsions (the concentration is 1.8 wt%, the solvent is water, and the emulsifier is sodium dodecyl sulfate) dispersed with monodisperse silica colloidal nanoparticles of different particle sizes were taken to be 8 μ L each (the average particle size of the colloidal nanoparticles and the corresponding photonic crystal structure color are shown in table 3), and the emulsions were spotted at hydrophilic points using a pipette. And (3) placing the aluminum sheet dripped with different colloidal nanoparticle emulsions in an oven at 80 ℃ for heating for 10min to form colloidal photonic crystals with uniform appearance at the hydrophilic points, thereby obtaining the photonic crystal coded detection chip, wherein photonic crystals in different rows in the hydrophilic detection point array have different colors. The detected static water contact angle of the surface of the photonic crystal is 30 degrees, and the diameter of the photonic crystal is 2 mm. The prepared detection chip is tested by using a macroscopic angle resolution spectrometer, and the reflection spectrum shows that the photonic crystals in each column in the hydrophilic detection point array have high-reflectivity structural colors.

TABLE 3

(3) 100mL of ultrapure water was weighed into 7 identical beakers, 0.02g of gelatin (purchased from Allantin reagent Co., Ltd.) was added thereto, followed by heating until the gelatin was completely dissolved, and after cooling to room temperature (25 ℃ C.), 1mg of doxorubicin hydrochloride, doxorubicin, 6-purinethiol, 5-fluorouracil, daunorubicin, bleomycin and cytarabine hydrochloride were added to each beaker, respectively, to obtain a series of different kinds of drug solutions having the same drug concentration.

(4) Matching the drug solution with the photonic crystal according to the corresponding relationship shown in table 4, and dripping different types of drug solutions onto the hydrophilic detection point region corresponding to the matched photonic crystal, wherein the first point of each column is not dripped with any solution and is used as a blank control group, the second point of each column is dripped with a solution only containing gelatin and is used as a gelatin control group, and the third point to the seventh point of each column are dripped with the drug solution with the same concentration. And after the dropwise addition is finished, drying the aluminum sheet in an environment of 50 ℃ until water in the medicine solution is volatilized and solidified to obtain the medicine screening system of the photonic crystal code.

TABLE 4

(5) Fixing a large drop of Hela cancer cell culture solution by using a dropper, sliding the surface of a detection chip of a screening system, cutting the cell culture solution into small drops corresponding to hydrophilic detection point areas by means of different infiltrations of the hydrophilic detection point areas and the super-hydrophobic areas on the surface of the chip on the cell culture solution, and attaching the small drops to the hydrophilic detection point areas, wherein each hydrophilic detection point forms an independent cell culture chamber.

The cell viability of the drug screening system encoded by photonic crystals of Hela cancer cell culture broth was measured in the same manner as in example 1, and the results are shown in FIG. 6. As can be seen from FIG. 6, different drugs showed different inhibitory efficiencies on Hela cancer cells, indicating that a variety of drugs can be simultaneously screened using the drug screening system of the present invention.

Example 4

Immersing the cleaned aluminum sheet into an etching solution, wherein the temperature of the etching solution is 20 ℃, the immersion time is 8 seconds, and the immersion solution is a mixed solution of hydrochloric acid, hydrofluoric acid and ultrapure water, wherein the hydrochloric acid (the concentration is 37 weight percent): ultrapure water: the volume ratio of hydrofluoric acid (concentration of 40 wt%) was 16: 5: 1.

the etched aluminum sheet was dried with nitrogen and placed in a vacuum desiccator, then 2 drops (about 0.1mL) of 1H,1H,2H, 2H-perfluorodecyltrimethoxysilane were added dropwise to the middle of the vacuum desiccator, the vacuum desiccator was sealed and evacuated for 20 minutes. Then, the desiccator was placed in an oven at 90 ℃ for 4 hours to obtain an aluminum sheet having an ultra-hydrophobic layer. The surface of the aluminum sheet subjected to the super-hydrophobic treatment is detected to be a super-hydrophobic surface, and the static water contact angle of the surface is 170 degrees.

(2) 0.5 mu L of vinyl-terminated Polydimethylsiloxane (PDMS) and a cross-linking agent (the mass ratio of the PDMS to the cross-linking agent is 10: 1, the cross-linking agent is polydimethylsiloxane, the PDMS and the cross-linking agent are both from Dow Corning, and the trademark is DC 184) are dripped into hydrophilic points of an aluminum sheet with a hydrophilic-superhydrophobic pattern by a dispenser, and after the PDMS is uniformly distributed on the hydrophilic points, the aluminum sheet is placed in an oven at 75 ℃ and heated for 15 min. The treated PDMS containing regions were examined to have a static water contact angle of 120 °.

The solution was dispensed into 7 kinds of emulsions (concentration: 2 wt%, solvent: water, emulsifier: sodium dodecylbenzenesulfonate) dispersed with monodisperse polystyrene colloidal nanoparticles of different particle sizes, each 8 μ L (average particle size of colloidal nanoparticles and corresponding photonic crystal structure color are shown in table 5), and the emulsions were spotted onto hydrophilic spots using a pipette. And (3) placing the aluminum sheet dripped with different colloidal nanoparticle emulsions in an oven at 80 ℃ for heating for 5min to form colloidal photonic crystals with uniform appearance at hydrophilic points, thereby obtaining the photonic crystal coded detection chip, wherein photonic crystals in different rows in the hydrophilic detection point array have different colors. The detected static water contact angle of the surface of the photonic crystal is 40 degrees, and the diameter of the photonic crystal is 5 mm. The prepared detection chip is tested by using a macroscopic angle-resolved spectrometer, and the photonic crystals in each column in the hydrophilic detection point array have high-reflectivity structural colors according to the reflection spectrum of the detection chip.

TABLE 5

(3) 100mL of ultrapure water was weighed in 7 identical beakers, 0.02g of gelatin (purchased from Allantin reagent Co., Ltd.) was added thereto, followed by heating until the gelatin was completely dissolved, cooling to room temperature (25 ℃ C.), and then 5mg, 2.5mg, 1mg, 0.75mg, 0.5mg, 0.25mg and 0.1mg of doxorubicin hydrochloride (purchased from Allantin reagent Co., Ltd.) were added to each beaker, followed by mixing uniformly to obtain a series of drug solutions having different drug concentrations.

(4) Matching the drug solution with the photonic crystal according to the corresponding relation shown in table 6, and dripping the drug solution to the hydrophilic detection point region corresponding to the matched photonic crystal, wherein the first point of each column is not dripped with any solution and is used as a blank control group, the second point of each column is dripped with a solution only containing gelatin and is used as a gelatin control group, and the third point to the seventh point of each column are dripped with the drug solution with the same concentration. And after the dropwise addition is finished, drying the aluminum sheet in an environment at 50 ℃ until water in the drops of the medicine mixture is volatilized and solidified to obtain the medicine screening system of the photonic crystal code.

TABLE 6

(5) A dropper is used for fixing a large drop of A549 cancer cell culture solution, the surface of a detection chip of a screening system slides, the cell culture solution is cut into small drops corresponding to hydrophilic detection point areas by means of different infiltrations of the hydrophilic detection point areas and the super-hydrophobic areas on the surface of the chip to the cell culture solution, the small drops are attached to the hydrophilic detection point areas, and each hydrophilic detection point forms an independent cell culture chamber.

The cell survival rate in the drug screening system encoded by the photonic crystal having a549 cancer cell culture broth was measured in the same manner as in example 1, and the results are shown in fig. 7. As can be seen from fig. 7, as the concentration of doxorubicin hydrochloride increased, the number of surviving a549 carcinoma cells also decreased, indicating that the optimal amount of the drug can be effectively determined using the drug screening system of the present invention.

The results of examples 1-4 show that the detection chip of the present invention is easy to code, reduces complicated pipetting operations, and improves the efficiency of drug screening.

The preferred embodiments of the present invention have been described in detail, however, the present invention is not limited to the specific details of the above embodiments, and various simple modifications may be made to the technical solution of the present invention within the technical idea of the present invention, and these simple modifications are within the protective scope of the present invention.

It should be noted that the various technical features described in the above embodiments can be combined in any suitable manner without contradiction, and the invention is not described in any way for the possible combinations in order to avoid unnecessary repetition.

In addition, any combination of the various embodiments of the present invention is also possible, and the same should be considered as the disclosure of the present invention as long as it does not depart from the spirit of the present invention.

Claims

1. A detection chip of a photonic crystal code comprises a substrate, wherein at least one surface of the substrate is provided with a super-hydrophobic area and a hydrophilic detection point array, an area which is complementary with the hydrophilic detection point array in the detection chip is the super-hydrophobic area, the hydrophilic detection point in the hydrophilic detection point array is provided with a hydrophilic layer, an adhesion enhancement layer and a photonic crystal layer, the surface layer of the hydrophilic detection point array is a photonic crystal layer, the adhesion enhancement layer is positioned between the hydrophilic layer and the photonic crystal layer, and the photonic crystal in the photonic crystal layer enables the hydrophilic detection point in each column or the hydrophilic detection point in each row in the hydrophilic detection point array to display different colors from the hydrophilic detection points in other columns or the hydrophilic detection points in other rows.

2. The detection chip according to claim 1, wherein the hydrophilic layer is a layer formed by hydrophilizing a surface of a substrate.

3. The detection chip according to claim 2, wherein the substrate surface is a superhydrophobic surface, and the hydrophilic layer is a layer formed by hydrophilizing the superhydrophobic surface on which the photonic crystal is to be formed.

4. The detection chip according to claim 3, wherein a static water contact angle of a surface of the hydrophilic layer is not higher than 5 °.

5. The detection chip of claim 1, wherein the adhesion enhancement layer comprises a silicon-containing compound.

6. The detection chip according to claim 5, wherein the silicon-containing compound is a polysiloxane.

7. The detection chip according to claim 6, wherein the silicon-containing compound is polydimethylsiloxane.

8. The detection chip according to any one of claims 1 and 5 to 7, wherein the surface static water contact angle of the adhesion enhancement layer is 110 ° to 120 °.

9. The detection chip according to any one of claims 1 to 7, wherein the surface static water contact angle of the superhydrophobic region is 150 ° to 180 °.

10. The detection chip of claim 9, wherein the surface static water contact angle of the superhydrophobic region is 165 ° to 170 °.

11. The detection chip according to claim 1, wherein the surface static water contact angle of the photonic crystal layer is 0 ° to 90 °.

12. The detection chip according to claim 11, wherein the surface static water contact angle of the photonic crystal layer is 30 ° to 50 °.

13. The detection chip of claim 1, wherein the photonic crystal comprises monodisperse particles.

14. The detection chip according to claim 13, wherein the monodisperse particles are one or a combination of two or more of organic particles, inorganic particles, organic-inorganic composite particles, and quantum dots.

15. The detection chip according to claim 13, wherein the monodisperse particles are one or more of polymer particles having a core-shell structure, silica particles, polystyrene particles, polyacrylic acid particles, gold particles, silver particles, platinum particles, copper particles, zinc oxide particles, iron oxide particles, ferroferric oxide particles, titanium oxide particles, carbon particles, dopamine particles, silicon particles, and quantum dots.

16. The detection chip of any one of claims 13 to 15, wherein the monodisperse particles have an average particle size of 100nm to 800 nm.

17. The detection chip according to claim 16, wherein the monodisperse particles have an average particle diameter of 100nm to 400 nm.

18. The detection chip according to claim 17, wherein the monodisperse particles have an average particle diameter of 150nm to 280 nm.

19. The detection chip according to any one of claims 1 and 11 to 15, wherein the photonic crystal has a diameter of 0.1 to 10 mm.

20. The detection chip of claim 19, wherein the photonic crystal has a diameter of 2-5 mm.

21. The detection chip of any one of claims 1 to 7, wherein the substrate is selected from a silicon substrate, a glass substrate, a quartz substrate, a metal substrate, and a polymer substrate.

22. The detection chip of any one of claims 1 to 7, wherein the substrate is selected from the group consisting of an aluminum substrate, a glass substrate, a quartz substrate, a silicon substrate, an iron substrate, a copper substrate, a plastic substrate, and a rubber substrate.

23. A method for preparing a photonic crystal encoded detection chip according to claim 1, the method comprising the steps of:

(1) providing a substrate;

(2) forming a super-hydrophobic layer on at least one surface of the substrate;

24. The preparation method according to claim 23, wherein a static water contact angle of a surface of the super-hydrophobic layer is 150 ° to 180 °.

25. The production method according to claim 24, wherein a static water contact angle of a surface of the super-hydrophobic layer is 160 ° to 170 °.

26. The production method according to any one of claims 23 to 25, wherein the method of forming the super-hydrophobic layer includes: the substrate surface is roughened.

27. The production method according to any one of claims 23 to 25, wherein the method of forming the super-hydrophobic layer includes: the surface of the substrate is roughened, and a hydrophobic substance is introduced to the roughened surface of the substrate.

28. The production method according to claim 23, wherein a static water contact angle of a surface of the hydrophilic layer is not higher than 5 °.

29. The production method according to claim 23 or 28, wherein the method of forming a hydrophilic layer comprises: and (2) hydrophilizing the area of the super-hydrophobic layer, which needs to form the hydrophilic layer, by adopting one or more of ultraviolet irradiation, plasma treatment, etching, coating, surface chemical modification, electrospinning and electrochemical corrosion.

30. The production method according to claim 23, wherein in the step (4), the method of forming the adhesion enhancing layer includes: applying a silicon-containing compound to the surface of the hydrophilic layer.

31. The production method according to claim 30, wherein the silicon-containing compound is a polysiloxane.

32. The method of claim 30, wherein the silicon-containing compound is polydimethylsiloxane.

33. The manufacturing method of claim 23, wherein the method of forming the adhesion enhancing layer on the surface of the hydrophilic layer comprises: a solution containing a silicon-containing compound is applied to the surface of the hydrophilic layer, and the substrate having the solution is dried.

34. The production method according to claim 33, wherein the static water contact angle of the surface of the adhesion promoting layer is 110 ° to 120 °.

35. The production method according to claim 23, wherein the method of forming a photonic crystal layer includes: applying an emulsion to the surface of the adhesion promoting layer, drying the substrate with the emulsion, the emulsion comprising at least one monodisperse particle and at least one solvent;

the monodisperse particles are one or the combination of more than two of organic particles, inorganic particles, organic-inorganic composite particles and quantum dots.

36. The production method according to claim 35, wherein the monodisperse particles are one or more of polymer particles having a core-shell structure, silica particles, polystyrene particles, polyacrylic acid particles, gold particles, silver particles, platinum particles, copper particles, zinc oxide particles, iron oxide particles, ferroferric oxide particles, titanium oxide particles, carbon particles, dopamine particles, silicon particles, and quantum dots.

37. The production method according to claim 36, wherein the monodisperse particles have an average particle diameter of 100nm to 800 nm.

38. The production method according to claim 37, wherein the monodisperse particles have an average particle diameter of 100nm to 400 nm.

39. The production method according to claim 38, wherein the monodisperse particles have an average particle diameter of 150nm to 280 nm.

40. The method of claim 35, wherein the solvent is water.

41. The production method according to any one of claims 23 and 35 to 40, wherein the diameter of the photonic crystal in the photonic crystal layer is 0.1 to 10 mm.

42. The production method according to claim 41, wherein the photonic crystal in the photonic crystal layer has a diameter of 2 to 5 mm.

43. The production method according to any one of claims 23 to 25, wherein the substrate is selected from a silicon substrate, a glass substrate, a quartz substrate, a metal substrate, and a polymer substrate.

44. The method of any one of claims 23-25, wherein the substrate is selected from the group consisting of aluminum substrates, glass substrates, quartz substrates, silicon substrates, iron substrates, copper substrates, plastic substrates, and rubber substrates.

45. Use of the detection chip of any one of claims 1 to 22 in drug screening or microorganism screening.

46. A photonic crystal encoded drug screening system comprising the detection chip of any one of claims 1 to 22, and a series of drug mixtures attached to the hydrophilic detection spot surfaces of the detection chip, wherein the series of drug mixtures comprises two or more drug mixtures, and the drug mixtures attached to the hydrophilic detection spot surfaces of the photonic crystals having the same color are the same drug mixture.

47. The screening system of claim 46, wherein the drug mixture comprises a carrier and a drug.

48. The screening system according to claim 47, wherein the carrier is one or more selected from gelatin, starch, sodium alginate and cellulose.

49. The screening system of claim 47, wherein the drug is a slow release drug.

50. The screening system of claim 47, wherein the drug is one or more than two of anticancer drugs.

51. A screening system according to claim 50, wherein the anticancer drug is one or more of doxorubicin, doxorubicin hydrochloride, cisplatin, 5-fluorouracil, bleomycin, vinblastine, vincristine, cyclophosphamide, gemcitabine, methotrexate, cytarabine hydrochloride, carboplatin, cisplatin, lomustine, hydroxyurea, mitomycin, etoposide, purinethiol, daunorubicin, cytarabine hydrochloride, camptothecin and paclitaxel.

52. The screening system according to any of claims 46-51, wherein the content of the at least one substance differs and/or the type of the at least one substance differs between different drug mixtures.

53. A method of drug screening, the method comprising the steps of:

(B) attaching the drug solution to the hydrophilic detection point surface of the detection chip according to any one of claims 1 to 22, wherein the drug solution attached to the hydrophilic detection point surface of the photonic crystal having the same color is the same drug solution, and drying the drug solution; and

54. The method for screening a drug according to claim 53, wherein the step (C) of attaching the drug detection solution to the surface of the hydrophilic detection spot comprises:

(C2) and pulling the detection chip out of the medicine detection liquid.

55. Screening method according to claim 53 or 54, wherein the drug solution comprises a carrier and a drug.

56. The screening method according to claim 55, wherein the carrier is one or more selected from the group consisting of gelatin, starch, sodium alginate and cellulose.

57. The screening method of claim 55, wherein the drug is a sustained release drug.

58. The screening method according to claim 55, wherein the drug is one or more than two kinds of anticancer drugs.

59. A screening method according to claim 55, wherein the drug is one or more of doxorubicin, doxorubicin hydrochloride, cisplatin, 5-fluorouracil, bleomycin, vinblastine, vincristine, cyclophosphamide, gemcitabine, methotrexate, cytarabine hydrochloride, carboplatin, cisplatin, lomustine, hydroxyurea, mitomycin, etoposide, purothione, daunorubicin, cytarabine hydrochloride, camptothecin and paclitaxel.

60. A screening method according to claim 53 or 54, wherein the content of at least one substance differs and/or the kind of at least one substance differs between different kinds of drug solutions.