Functionalizable conductive nanocomposites

Abstract

The present invention relates to a composition comprising at least one conductive or semiconductive nanostructure, on the surface of which at least one conductive ligand is arranged, and at least one solvent, where the ligand has at least one group allowing functionalization, which allows functionalizable conductive structures to be obtained by a simple method, in particular by inkjet printing.

Description

[Background technology]

[0001] Conductive structures on surfaces play a crucial role in microelectronics. However, the processes for fabricating and structuring such structures are often extremely complex.

[0002] In recent years, systems that can coat such structures onto surfaces using printing processes have been increasingly researched. Such wet coating processes are far more versatile than commonly used photolithography processes.

[0003] Such processes often require conductive inks that contain conductive particles, particularly nanoparticles.

[0004] A suspension containing the corresponding nanoparticles is used for this purpose. After coating the surface, the solvent is evaporated, and the particles come into contact with each other, making it possible to obtain a conductive coating. However, especially in the case of nanoparticles, the suspension must also contain stabilizers to prevent strong aggregation of the nanoparticles. These stabilizers form an organic coating on the surface of the nanoparticles, which is often not conductive, so heat treatment is necessary to remove the stabilizers from the surface of the nanoparticles in such suspensions.

[0005] Although organic solvents often have low boiling points, solvents such as water, alcohol, or mixtures thereof are preferred simply for cost reasons. However, this means that the suspension must be stable in these solvents.

[0006] At the same time, there is a need to give conductive inks additional functionality, particularly in the biological field. This is impossible with conventional inks. [Overview of the project] [Problems that the invention aims to solve]

[0007] The problem addressed by this invention is to identify a composition that allows for the easy fabrication of a functionalized conductive structure on a surface using a simple method. Furthermore, the invention also identifies a method for fabricating such a composition and a method for fabricating a conductive structure using such a composition. [Means for solving the problem]

[0008] This problem is solved by the present invention having the features of the independent claims. Advantageous variations of the present invention are characterized in the dependent claims. The language of all claims is incorporated herein by reference. The present invention also encompasses all meaningful combinations of the independent and / or dependent claims, as well as all combinations specifically mentioned.

[0009] The problem concerns a composition for creating a conductive layer by wet coating (=ink), a) At least one conductive or semiconducting nanostructure having at least one conductive ligand disposed on the surface of the nanostructure, b) at least one solvent, Includes, The problem is solved by a composition in which the ligand has at least one functional group that enables functionalization.

[0010] The nanostructure is preferably an inorganic nanostructure. The inorganic nanostructure may be a metallic nanostructure containing a metal, a mixture of two or more metals, or an alloy of two or more metals. The metal is preferably selected from gold, silver, copper, platinum, palladium, nickel, ruthenium, indium, or rhodium. The nanostructure may contain conductive or semiconducting oxides. Examples of such oxides (which may be doped) include indium-tin oxide (ITO) or antimony-tin oxide (ATO). Semiconductors of groups II-VI, III-V, or IV, or alloys of such semiconductors are also possible. Examples include CdS, CdSe, CdTe, InP, InAs, ZnS, ZnSe, ZnTe, HgTe, GaN, GaP, GaAs, GaSb, InSb, Si, Ge, AlAs, PbSe, or PbTe.

[0011] Metal nanostructures comprising gold, silver, copper, platinum, palladium, nickel, ruthenium, indium, or rhodium, or mixtures or alloys thereof, are preferred. Nanostructures formed from gold are particularly preferred.

[0012] The structures of interest as used herein are nanostructures. This is understood to mean that the structures of interest have at least one, preferably at least two, and particularly preferably all dimensions less than 200 nm in size (measured using a TEM). Particles, particularly spherical particles, may also be included. Nanostructures may have different sizes at various dimensions. An example of this is a nanowire in which the ratio of the longest dimension to each of the other two dimensions is at least 1.5, preferably at least 2. Spherical particles are preferred, preferably having a diameter of less than 150 nm, particularly less than 100 nm, and particularly preferred to have a diameter of 50 nm to 150 nm, particularly 60 nm to 110 nm (measured using a TEM).

[0013] The ligand is preferably a conductive polymer whose polymer backbone is adsorbed to the nanostructure via its conjugated π system, or directly via functional groups within or directly adjacent to the conductive polymer backbone. To ensure improved stability, the conductive polymer is a polymer or oligomer structure having at least 10 binding sites. These binding sites enable coordination bonding to the surface of the nanostructure, and it is preferable for the ligand to bind to it. Furthermore, the ligand is characterized by having at least one side chain that does not belong to the conjugated π system. Preferred selections of the side chain(s) include polar groups that ensure colloidal stability in polar solvents and nonpolar side chains with steric requirements that ensure colloidal stability in nonpolar solvents.

[0014] Select at least one side chain such that it can be functionalized by that side chain.

[0015] A bonding site is understood to mean the formation of at least one coordination bond on the surface of the nanostructure. This is preferably caused by heteroatoms, such as O, N, Se, or S, with S being particularly preferred. In the case of metal surfaces in particular, sulfur is a preferred bonding site.

[0016] Therefore, it is preferable that the conductive ligand contains a conductive polymer. Such a polymer has a conjugated π system as its backbone.

[0017] Such conductive polymers are, for example, polymers based on pyrroles, such as polypyrrole, poly(N-substituted pyrrole), poly(3-substituted pyrrole), and poly(3,4-substituted pyrrole); thiophenes, such as polythiophene, poly(3-substituted thiophene), poly(3,4-substituted thiophene); polybenzothiophene, polyisothionaphthene, polyfuran, polybenzofuran, polycarbazole, polyselenophene, polyindole, polypyridazine, polyaniline, and polymethoxyphenylene. The polymer may be a copolymer or block copolymer with other monomers.

[0018] Preferred polymers are polythiophene, polypyrroles excluding poly(N-substituted pyrrole), polyfuran, polybenzofuran, polybenzothiophene, polycarbazole, preferably polythiophene, such as polythiophene, poly(3-substituted thiophene), poly(3,4-substituted thiophene), and polybenzothiophene. In these polymers, the heteroatoms of the monomers form binding sites on the surface of the nanostructure. If at least 10 binding sites are present, the polymer or oligomer has at least 10 monomer units. Ligands having at least 50, and particularly at least 100, binding sites are preferred. Independently, ligands preferably have 2000 or fewer, and particularly 1500 or fewer, binding sites. The binding sites preferably correspond to one monomer of the polymer and / or oligomer.

[0019] Examples of further monomers when the ligand contains further monomers are, for example, styrenesulfonic acid or polystyrenesulfonic acid.

[0020] Examples of thiophenes are ethylene-3,4-dioxythiophene, 2-(3-thienyl)ethoxy-4-butylsulfonate (e.g., sodium salt), 3-hexylthiophene or the corresponding polythiophene, poly(ethylene-3,4-dioxythiophene), poly(2-(3-thienyl)ethoxy-4-butylsulfonate), poly(3-hexyl)thiophene.

[0021] The side chain of the ligand can have, for example, at least one polar group that increases the compatibility with a polar solvent. Examples of such groups are amino group, hydroxyl group, carboxyl group, ester group, halogen, thiol, ether group, thioether group, sulfate group, sulfonic acid group, amide group, nitro group, cyano group, phosphonic acid group. The side chain is preferably an aliphatic branched or unbranched carbon chain having 4 to 25 carbon atoms, and one or more non-adjacent CH2 groups can be substituted by O, NR or S, where R is hydrogen or an aliphatic radical having 1 to 10 carbon atoms, and contains at least one polar group as a substituent.

[0022] The ligand may contain two or more polar groups. At least 5 polar groups per ligand are preferred.

[0023] At least one functional group per ligand is preferred. It is preferred that such a group is present so that the ligand has a net charge in the pH range of 6 to 10. It is also possible that at least one functional group is present per monomer.

[0024] The polar group is preferably a carboxyl group. The carboxyl group can also exist at least partially as a carboxylate depending on the pH.

[0025] In a preferred embodiment, the side group does not contain a sulfur atom. This includes thioethers, thiols, and also includes sulfate groups or sulfonic acid groups. Therefore, in contrast to thiophene, this side group does not bind to the nanostructure. Preferably, the binding to the nanostructure formed from gold occurs via the thiophene group of the polymer or oligomer.

[0026] The polymer or oligomer is preferably a thiophene preferably having a side chain with a functional group, preferably a carboxyl group, at the 3-position. The side chain is preferably an aliphatic chain having 3 to 8 carbon atoms, preferably 6 carbon atoms. Here, the carboxyl group is included in the carbon number. The functional group is preferably arranged at the end of the side chain.

[0027] In a preferred embodiment, the polymer is selected from poly[3-(potassium-4-butanoic acid)thiophene-2,5-diyl], poly[3-(potassium-5-pentanoic acid)thiophene-2,5-diyl], poly[3-(potassium-6-hexanoic acid)thiophene-2,5-diyl] or poly[3-(potassium-7-heptanoic acid)thiophene-2,5-diyl], particularly preferably poly[3-(potassium-6-hexanoic acid)thiophene-2,5-diyl].

[0028] The ligand is preferably a polymer or oligomer having an average molecular weight of at least 5 kDa, preferably 1000 kDa or less (measured by gel permeation chromatography), preferably at least 10 kDa to 500 kDa, particularly 30 kDa to 100 kDa.

[0029] The proportion of the nanostructure is preferably at least 10% by weight, particularly at least 30% by weight, based on the composition without solvent. The proportion of the nanostructure can be up to 90% by weight. Preferred proportions are 10% to 90% by weight, particularly 20% to 80% by weight, very particularly 30% to 70% by weight.

[0030] The content of nanostructures in the composition is preferably 50 mg / ml to 200 mg / ml based on the nanostructure, especially in the case of metal nanostructures based on metals, particularly gold. A content of 90 mg / ml to 160 mg / ml, and very particularly 100 mg / ml to 150 mg / ml, is preferred. In particular, in a particularly preferred embodiment, it was surprising that it was possible to obtain a composition that has colloidal stability in water and alcohol.

[0031] The ligand has at least one group that enables functionalization. This group is preferably the functional group and / or polar group of the side chain described above. This group is preferably a carboxyl group.

[0032] In particular, the carboxyl group allows for bonding through a wide variety of reactions. Therefore, ester functionalization can be achieved through reactions with alcohols, amide functionalization through reactions with amines, and anhydride functionalization through reactions with carboxylic acids.

[0033] Functionalization can be carried out under physiological conditions. This is particularly applicable to reactions with amines. Many biological molecules, especially proteins and peptides, have such groups or can be constructed to have at least one such group.

[0034] In some cases, activation of the carboxyl group is necessary for the reaction. Methods for this, such as reactions with EDC (1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride) or NHS (N-hydroxysuccinimide), are known to those skilled in the art and are standard functionalization methods in biochemistry.

[0035] This makes it possible to functionalize the compositions according to the present invention in a wide variety of ways.

[0036] Examples of such functionalization include oligonucleotides, polysaccharides, or glycosamines derived from polymers, oligomers, peptides, proteins, antibodies, cells, DNA, RNA, or their analogues.

[0037] The peptide may be a peptide sequence having up to 20 amino acids, such as RGD, or a polymer such as polylysine (PDL or PLL) or poly-DL-ornithine.

[0038] Proteins can have a wide variety of functions. These include growth factors such as EGF or interleukins, and matrix proteins such as collagen.

[0039] The polysaccharide or glycosamine may be cellulose or heparin.

[0040] Functionalization can also be used, at least partially, to bond modified nanostructures to a substrate. This can be achieved, for example, by functionalizing the substrate with amino groups. This allows for easy immobilization of the ink.

[0041] The solvent is preferably selected from solvents having a boiling point of less than 120°C, or from a solvent mixture composed of such solvents. Such solvents allow for rapid removal of the solvent at low temperatures, for example, below 60°C.

[0042] The solvent is preferably a volatile solvent, particularly one that is volatile at room temperature.

[0043] Examples of such solvents include water, alcohols, ketones, or ethers, and mixtures thereof. Further solvents may be present.

[0044] Further solvents can be selected from, for example, alkanes, aromatic compounds and heteroaromatic compounds, cyclic aromatic compounds, esters, ketones, amides, and sulfonates.

[0045] The solvent may contain at least one alcohol. Preferably, at least one alcohol has a maximum of 10 carbon atoms. Examples of such alcohols are methanol, ethanol, n-propanol, isopropanol, n-butanol, i-butanol, 2-butanol, tert-butanol, 1-pentanol, 2-methyl-1-butanol, 3-methyl-1-butanol, hexanol, heptanol, octanol, 1-octanol, 1-nonanol, 1-decanol, allyl alcohol, clotyl alcohol, proparyl alcohol, cyclopentanol, cyclohexanol, 2-methoxyethanol, 2-ethoxyethanol, 2-butoxyethanol, ethylene glycol, and propylene glycol.

[0046] Examples of ketones include acetone, methyl ethyl ketone, and methyl isobutyl ketone.

[0047] Examples of esters include ethyl acetate, methyl acetate, propyl acetate, butyl acetate, ethyl butyrate, methyl butyrate, ethyl propionate, methyl propionate, and propyl propionate.

[0048] The solvent is particularly preferably selected from water, alcohol, or a mixture containing water and / or at least one alcohol.

[0049] The solvent is preferably an alcohol, particularly methanol, ethanol, n-propanol, isopropanol, n-butanol, especially preferably ethanol, i-propanol, or n-propanol, and very especially preferably n-propanol. A mixture may also be used.

[0050] The nanostructures modified with polymers or oligomers preferably have a zeta potential higher than ±20 mV in water. The nanostructures are preferably redispersible in water, i.e., they are preferably stable in water for more than one week.

[0051] Furthermore, the present invention relates to a method for preparing a composition according to the present invention.

[0052] this is, a) A step of preparing a dispersion of conductive or semiconductive nanostructures stabilized by at least one first ligand, b) A step of adding at least one conductive ligand, c) A step of substituting the first ligand with at least one conductive ligand, This is achieved by performing a method that includes [a specific method].

[0053] The following describes each process step in more detail. These steps do not necessarily have to be performed in a specific order, and the method described may include further steps.

[0054] This method fabricates nanostructures with conductive ligands on their surface, i.e., nanostructures in which non-conductive ligands present on the surface are replaced by conductive ligands. Because strong aggregation of nanoparticles occurs, care must be taken not to impair the colloidal stability of the dispersion.

[0055] During ligand substitution, a dispersion of conductive or semiconductive nanostructures stabilized by at least one first ligand is first prepared. The nanostructures described in the composition are preferred.

[0056] The dispersion is stabilized by at least one first ligand. This means that the dispersion remains stable under ligand substitution conditions. Therefore, the concentration of this excess ligand can be greater than 20 μM and less than 10 mM, preferably 30 μM to 1 mM, and particularly 50 μM to 800 μM.

[0057] Preferably, at least one first ligand contains at least one group for coordinating bonding with the surface of the nanostructure. This allows for the formation of the necessary surface layer to prevent strong aggregation of the structure. Preferably, this ligand is not covalently bonded.

[0058] Examples of such ligands include ligands containing carboxylic acid groups, ammonium groups such as tetraalkylammonium groups, and amino groups. Examples of such first ligands are citrate or cetyltrimethylammonium bromide (CTAB).

[0059] In some cases, it may be necessary to remove excess primary ligand. This can be done, for example, by centrifugation and redispersion. Ensuring colloidal stability is important.

[0060] Strong aggregation of particles in a dispersion occurs especially when the solvent is removed. Preferably, the composition according to the present invention is stable for at least 24 hours, especially at least one week, and very especially at least one month, i.e., no strong aggregation is observed by UV-vis.

[0061] It is preferable to incubate the nanostructure with at least one conductive ligand for at least 1 hour, particularly preferably at least 5 hours. At least 12 hours is preferable. Possible incubation times are 5 to 200 hours, particularly 150 to 180 hours, particularly 160 to 180 hours, and very particularly 168 to 192 hours.

[0062] This results in the substitution of the first ligand with at least one conductive ligand, but complete replacement is preferred.

[0063] Incubation is preferably carried out at a temperature of 30°C to 50°C. If the temperature is too low, it will favor the weak aggregation of the nanostructure.

[0064] Incubation for too short a time can lead to incomplete substitution. Residual primary ligands may cause weak aggregation during enrichment. Incubation for too long can cause weak aggregation of the conductive ligands again.

[0065] After substitution, it may be necessary to remove any unadsorbed ligands. For this purpose, the dispersion can be purified and concentrated by centrifugation and discarding the supernatant. The solvent can also be replaced in this process, and this can be particularly selected for ink compositions. The dispersion should not be allowed to dry. It is preferable that the ligand-modified particles remain moist with the solvent at all times.

[0066] The concentration ratio of the polymer to the nanostructure during ligand substitution is preferably 0.5:1 to 1:1.5 (by mass concentration), preferably 0.5:1 to 1:1, and particularly 0.7:1 to 0.9:1.

[0067] In the ligand substitution according to the present invention, the polymer preferably adheres to the nanostructure in at least one layer, preferably at least two layers, and particularly preferably two to six layers (measured by thermogravimetric analysis). It is preferable that two or more layers are formed. In a particularly preferred embodiment, the innermost layer of thiophene binds to the surface of the gold, and the other layers bind to the lower layer of thiophene via π-π interactions. In this situation, the multilayer structure provides colloidal stabilization to the modified nanostructure and / or has more functional groups available per unit area that can be used for functionalization. Therefore, it is preferable that the nanostructure is completely coated with the polymer.

[0068] Therefore, the ligand density of the modified nanostructure is at least 2 mg / m³. 2 Preferably at least 3 mg / m² 2 , especially 2 mg / m² 2 ~5mg / m 2 It is preferable that this be the case.

[0069] In a preferred embodiment of the present invention, the dispersion is purified by one or more centrifugations. In either case, the desired solvent is added between steps to obtain the dispersion again.

[0070] The centrifugal separation process is preferably carried out at least three times, and more preferably at least five times.

[0071] The centrifugation speed should be adjusted to suit the composition. It is preferable to perform centrifugation at less than 1000 rpm for at least 4 hours, and particularly 4 to 15 hours.

[0072] In a particularly preferred embodiment, a surfactant is added at least once before centrifugation, preferably in an amount of 0.02% to 0.1% by weight (relative to the dispersion). This allows for faster and shorter centrifugation without causing weak aggregation. The surfactant is added again after each centrifugation.

[0073] The surfactant is preferably soluble in the solvent used. A nonionic surfactant based on polysorbate is preferred. This can be a monoester or triester of lauric acid, palmitic acid, stearic acid, or oleic acid, particularly available under the trade name Tween. Preferably, the materials are [polyoxyethylene (20) sorbitan monolaurate] (Tween® 20), [polyoxyethylene (4) sorbitan monolaurate] (Tween® 21), [polyoxyethylene (20) sorbitan monopalmitate] (Tween® 40), [polyoxyethylene (20) sorbitan monostearate] (Tween® 60), [polyoxyethylene (20) sorbitan tristearate] (Tween® 65), [polyoxyethylene (20) sorbitan monooleate] (Tween® 80), [polyoxyethylene (5) sorbitan monooleate] (Tween® 81), and [polyoxyethylene (20) sorbitan trioleate] (Tween® 85), with [polyoxyethylene (20) sorbitan monolaurate] being preferred.

[0074] In this embodiment, no new surfactant is added in the final centrifugation step. This allows for easy re-removal.

[0075] The addition of a surfactant makes it possible to centrifuge the composition at a higher speed without causing weak aggregation. It is preferable to centrifuge the composition at a speed at least 1.5 times faster than under conditions without surfactant, without causing weak aggregation. At the same time, it is possible to perform centrifugation in a shorter time than when no surfactant is used, particularly at least 0.8 times shorter.

[0076] In a preferred embodiment, the surfactant is centrifuged at at least 1000 rpm, and particularly at 1500 rpm to 2500 rpm.

[0077] It can also be advantageous to perform at least one filtration step between centrifugal separation steps.

[0078] Furthermore, the present invention relates to modified nanostructures obtained by the method according to the present invention for ligand substitution. The modified nanostructure preferably corresponds to the nanostructure according to the present invention, in which at least one conductive ligand is disposed on its surface, as described in particular as preferred embodiments herein.

[0079] This is preferably a modified nanostructure modified with a polymer or oligomer according to the present invention. Modification with two or more layers of polymer or oligomer is preferred.

[0080] In a preferred embodiment, the modified nanostructure is a gold nanostructure, and the oligomer or polymer is a thiophene-based oligomer or polymer.

[0081] The present invention relates to a method for producing a functionalized conductive or semiconductive layer on a surface, a) A step of coating a surface with the composition according to the present invention, b) A step of removing at least one solvent, c) A step of functionalizing the composition, This also includes methods.

[0082] Functionalization can also be performed before coating. Note that the particles should maintain colloidal stability during the functionalization process.

[0083] The following describes each process step in more detail. These steps do not necessarily have to be performed in a specific order, and the method described may include further steps.

[0084] In the first step, the composition according to the present invention is applied to the surface. This can be done using any wet coating method known to those skilled in the art. This can be done, for example, by inkjet printing, spraying, dipping, flow coating, spraying, spin coating, or doctor blade coating. Depending on the type of coating, the required concentrations of the dispersion, solvent, and possible additives can be selected. The viscosity can also be adjusted accordingly.

[0085] As the solvent, the solvent described for the composition is preferred.

[0086] The surface material must be compatible with the composition used, particularly the solvent. Due to the low temperature, the surface material can be freely selected. The surface can be organic or inorganic. The surface may include, for example, plastic, metal, metalloid, glass, or ceramic.

[0087] Because the ligand is conductive, no sintering process is required to establish conductivity. The surface can also be functionalized directly. Since the entire ink is modified, very high-density functionalization is achieved.

[0088] In a preferred embodiment of the present invention, the removal of at least one solvent is carried out at a temperature below 60°C, particularly below 40°C. A temperature of 4°C to 30°C is preferred.

[0089] It is also possible to apply negative pressure, especially pressures of less than 1 bar.

[0090] The use of conductive ligands means that it is not essential to remove these ligands to establish the conductivity of the coating. Ligands can facilitate electron exchange between particles. Simultaneously, functional groups can facilitate functionalization.

[0091] In preferred embodiments, the method does not involve coating treatment at temperatures above 60°C, particularly above 40°C, after coating the surface. However, a temperature sufficient to remove the solvent, preferably at least 15°C, is preferred.

[0092] Furthermore, the present invention relates to a functionalized conductive or semiconducting structure obtained by the method according to the present invention.

[0093] Depending on its functionalization, this structure can be used in a wide variety of ways, particularly as a sensor to measure conductivity as a function of the functionalization interaction.

[0094] Functionalization can also be used to create surfaces on which cells can be cultured, which also allows for cell contact.

[0095] In particular, functionalization can be used to identify specific samples. This can be achieved, for example, through the corresponding binding of enzymes, antibodies, or proteins, thereby enabling the detection of signals during the binding and / or reaction of the sample.

[0096] As used herein, the term “enzyme” is a broad term and is understood to have a common and conventional definition to those skilled in the art, but is not limited to, but preferably relates to a protein or protein-based molecule that facilitates chemical reactions occurring in living organisms. Enzymes can function as catalysts for individual reactions and can convert reactants (also known here as samples) into specific products. A glucose sensor based on glucose oxidase, an exemplary embodiment of an enzyme, includes providing glucose oxidase (GOX) that reacts with glucose (sample) and oxygen to yield hydrogen peroxide.

[0097] As used herein, the term “specimen” is a broad term that should be understood to have a common, conventional definition, but is not limited to, substances or chemical components in a liquid that can be analyzed, preferably a biological fluid (e.g., blood, sweat, saliva, tears, interstitial fluid, cerebrospinal fluid, lymph, or urine). Structures prepared according to the present invention may optionally be used for the analysis of these biological fluids after functionalization. Examples of specimens include naturally occurring substances, artificial substances, metabolites, and / or reaction products. In many embodiments, the specimen measured by the sensors and methods specified herein is glucose. However, the intended samples are not limited to, but include, inflammatory markers, aldehydes, acarboxyprothrombin, acylcarnitine, adenine phosphoribosyltransferase, adenosine deaminase, albumin, α-fetoprotein, amino acid profiles (arginine (Krebs cycle), histidine / urocanic acid, homocysteine, phenylalanine / tyrosine, tryptophan), androstenedione, antipyrine, arabinitol enantiomer, arginase, benzoylecgonin, biotinidase, biopterin, C-reactive protein, carnitine, carnosinase, CD4, ceruloplasmin, chenodeoxycholic acid, chloroquine, cholesterol, cholinesterase, conjugated 1-β-hydroxycholic acid, cortisol, creatine γ-Kinase, Creatine kinase MM isoenzyme, Cyclosporine A, d-Penicillamine, Desethylchloroquine, Dehydroepiandrosterone sulfate, DNA (Acetylator polymorphism, Alcohol dehydrogenase, α-1-Antitrypsin, Cystic fibrosis, Duchenne / Becker muscular dystrophy, Specimen-6-Phosphate dehydrogenase, Abnormal hemoglobinopathy, A, S, C, E, D-Punjab, β-Thalassemia, Hepatitis B virus, HCMV, HIV-1, HTLV-1, Hepatic hereditary optic neuropathy, MCAD, RNA, PKU, Plasmodium vivax, Sex differentiation, 21-Deoxycortisol), Desbutylhalofantrin, Dihydropteridine reductase, Diphtheria / Tetanus antitoxin, Erythrocyte arginase, Erythrocyte protoporphyrin, Esterase D, Fatty acids / Acylglycine,Free β-human chorionic gonadotropin, free erythrocyte porphyrin, free thyroxine (FT4), free tri-iodothyronine (FT3), fumaryl acetase, galactose / Gal-1-phosphate, galactose-1-phosphate uridyltransferase, gentamicin, sample-6-phosphate dehydrogenase, glutathione, glutathione peroxidase, glycocholic acid, glycated hemoglobin, halofantrin, hemoglobin variant, hexosaminidase A, human erythrocyte carboxylic acid dehydrase type I, 17-α-hydroxyprogesterone, Hypoxanthine phosphoribosyltransferase, immunoreactive trypsin, lactate, lead, lipoprotein, lysozyme, mefloquine, netylmycin, phenobarbiton, phenytoin, phytan / pristanic acid, progesterone, prolactin, prolidase, purine nucleoside phosphorylase, quinine, inverted triiodothyronine (rT3), selenium, serum pancreatic lipase, shisomycin, somatomedin C, specific antibodies (adenovirus, antinuclear antibody, anti-ζ antibody, arbovirus, Aujeszky's disease virus, dengue virus, guinea pig (Dracunculus) Echinococcus medinensis, Echinococcus granulosus, Entamoeba histolytica, Enterovirus, Giardia duodenalisa, Helicobacter pylori, Hepatitis B virus, Herpesvirus, HIV-1, IgE (atopic disease), Influenza virus, Leishmania donovani, Leptospirosis, Measles / Mumps / Rubella, Mycobacterium leprae, Mycoplasma pneumoniae, Myoglobin, Onchocerca volvulus, Parainfluenza virus, Plasmodium falciparum, Poliovirus, Pseudomonas aeruginosa aeruginosa), respiratory syncytial virus, rickettsia (typhus), Schistosoma mansoni,Further examples include Toxoplasma gondii, Trepenoma pallidium, Trypanosoma cruzi / rangeli, vesicular stomatitis virus, Wuchereria bancrofti, yellow fever virus, specific antigens (hepatitis B virus, HIV-1), succinylacetone, sulfadoxine, theophylline, thyrotropin (TSH), thyroxine (T4), thyroxine-binding globulin, trace elements, transferrin, UDP-galactose-4-epimerase, urea, uric acid, uroporphyrinogen I synthase, vitamin A, leukocytes, and zinc protoporphyrin. In some embodiments, naturally occurring salts, sugars, proteins, fats, vitamins, and hormones in blood, sweat, or interstitial fluid may also be used as specimens. The sample may be naturally present in body fluids and may include metabolites, hormones, antigens, antibodies, etc. Alternatively, the sample may be introduced into the body and may include contrast agents for imaging, radioisotopes, chemical agents, fluorocarbon-based artificial blood, or drugs or pharmaceutical compositions. Examples, but not limited to, include pilocarpine, acetylcholine, betanethyl, metacholine, carbachol, insulin, ethanol, cannabis (marijuana, tetrahydrocannabinol, hashish), inhalants (nitrous oxide, amyl nitrite, butyl nitrite, chlorinated hydrocarbons, hydrocarbons), cocaine (crack), stimulants (amphetamine, methamphetamine, Ritalin, Cylert, Preludin, Didrex, PreState, Voranil, Sandrex, Plegin), and tranquilizers (barbiturates). (Synthetic drugs, methacarone, tranquilizers, e.g., Valium, Librium, Miltown, Serax, Equanil, Tranxen, etc.), hallucinogens (phencyclidine, lysergic acid, mescaline, peyote, psilocybin), narcotics (heroin, codeine, morphine, opium, meperidine, Percocet, Percodan, Tussionex, fentanyl, Darvon, TaIwin, Lomotil), synthetic narcotics (fentanyl, meperidine, amphetamine, methamphetamine and phencyclidine analogs, e.g.,Examples include ecstasy, anabolic steroids, and nicotine. Metabolites of drugs and pharmaceutical compositions can also be considered as samples. Samples of neurochemicals and other chemicals produced in the body can also be analyzed, such as ascorbic acid, uric acid, dopamine, norepinephrine, 3-methoxytyramine (3MT), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), 5-hydroxytryptamine (5HT), and 5-hydroxyindoleacetic acid (FHIAA).

[0098] Further layers can be applied to the surface to, for example, enable access to specific specimens.

[0099] It is also possible to measure only the interaction with functional groups, such as carboxyl groups.

[0100] In a preferred embodiment, the modified nanostructure is functionalized by an enzyme, preferably an oxidoreductase, particularly via a carboxyl group.

[0101] Oxidoreductases can oxidize or reduce a sample (as a substrate) to release or consume electrons, which can then be used to generate an electric potential / current. As is known to those skilled in the art, oxidoreductase enzymes can be oxidases, dehydrogenases, or hydrogenases. In one embodiment, the oxidoreductase enzyme is an oxidase that can oxidize a carbohydrate substrate. In non-limiting examples, the oxidase enzyme may, in certain embodiments, be glucose oxidase, cholesterol oxidase, amino acid oxidase, pyruvate oxidase, peroxidase, sarcosine oxidase, lactate oxidase, alcohol oxidase, monoamine oxidase, glycerol oxidase, glycerol phosphate oxidase, uric acid oxidase, xanthine oxidase, or ascorbic acid oxidase. In further embodiments, the oxidoreductase enzyme may be a dehydrogenase, such as pyrrolo-quinoline-quinone (PQQ) glucose dehydrogenase, D-fructose-5-dehydrogenase, glucose dehydrogenase, alcohol dehydrogenase, gluconate-2-dehydrogenase, laccase, bilirubin oxidase, ascorbate oxidase, aldehyde dehydrogenase, oxalate oxidase, malate dehydrogenase, succinate dehydrogenase, pyruvate dehydrogenase, glutamate dehydrogenase, isocitrate dehydrogenase, or lactate dehydrogenase. As will be apparent to those skilled in the art, the selection of one or more enzymes may be influenced by other aspects such as the substrate on which the enzymes act, the availability of the substrate, and the desired environment of the conductive ink. In one embodiment of the present invention, the sample may be a simple or complex carbohydrate, for example, but not limited to, glucose, fructose, sucrose, trehalose, glycerol, or an alcohol, for example, methanol or ethanol. Other substrates include ethylene glycol, diethylene glycol, polyethylene glycol, diols, possibly cellulose, JP8 fuel, methane, butane, etc. In a particular embodiment, the enzyme is glucose oxidase.

[0102] In the detection reaction, mediator compounds can also be used. The mediator compounds can be selected from the group consisting of potassium ferricyanide, ferrocene derivatives, phenoxazine derivatives, phenothiazine derivatives, quinone derivatives, and reversible redox transition metal complexes, particularly ruthenium and osmium complexes, nicotinamide adenine dinucleotide (phosphate), diimine, phenanthroline derivatives, dichlorophenol indophenol tetrazolium dye, and phenylimino-benzophenoxazine.

[0103] Further details and features will become apparent from the following description of preferred exemplary embodiments in conjunction with the dependent claims. Each feature can be realized individually or in combination with others. The options for solving the problem are not limited to the exemplary embodiments. For this reason, for example, the specified range always includes all intermediate values ​​and all conceivable subintervals not mentioned.

[0104] Further details and features will become apparent from the following description of preferred exemplary embodiments in conjunction with the dependent claims. Each feature can be realized individually or in combination with others. The options for solving the problem are not limited to the exemplary embodiments. For this reason, for example, the specified range always includes all intermediate values ​​and all conceivable subintervals not mentioned. [Brief explanation of the drawing]

[0105] [Figure 1] This graph shows the Raman spectrum of AuNP stabilized with a C6 polymer after a coupling reaction with PEGamine (methoxypolyethylene glycolamine, Mw=20000Da). A new band characteristic of amide bond formation is formed at approximately 1615 cm⁻¹ (arrow). [Figure 2]Figure (a) shows a detailed micrograph of a printed circuit board with dimensions of 10 mm x 1 mm, and Figure (b) shows a detailed micrograph of a circuit board with a width of approximately 300 μm, which corresponds to roughly the width of one pixel. [Figure 3] This figure shows fibroblasts on various conductive inks: 100% of the present invention's ink: cells grow and begin to spread on the substrate (a); 100% "conventional" ink: cells are unable to grow and remain rounded (b); [Figure 4] This figure shows the experimental results using "Neurosphere". The concentration of Neurosphere is significantly higher on the ink of the present invention than on the substrate. [Modes for carrying out the invention]

[0106] Preparation of the Composition of the Present Invention The polymer was obtained from Rieke Metals in the United States. The nanostructure contains CTAB as a ligand before ligand substitution.

[0107] It was experimentally determined that the water solubility of the polymer decreases with increasing side chain length, but simultaneously, its stabilization ability increases with increasing steric requirements. The tested C6 polymer was the only polymer that possessed sufficient water solubility while also being able to stabilize AuNP (diameter 80 nm) (Table 1). The molecular weight of the polymer ranged from 55,000 g / mol to 65,000 g / mol.

[0108] To ensure the successful coating of AuNP, it is preferable to adhere to certain conditions regarding the dissolution of the polymer, preferably a C6 polymer, in water.

[0109] It is necessary to completely dissolve the polymer without forming any visible aggregates.

[0110] The dissolution process for C6 polymers takes 12 to 24 hours. It is recommended to dissolve them overnight. The temperature should be approximately room temperature or slightly above room temperature (20°C to 35°C).

[0111] Heating to temperatures above 50°C leads to incomplete dissolution. Polymer aggregates can still be observed in the solution after 24 hours. It is clear that heating increases the mobility and diffusion of individual polymer strands. This works favorably for interactions between polymers and the formation of aggregates.

[0112] Ligand substitution In addition to dissolving the C6 polymer, further conditions must be met to ensure complete coating of the AuNP.

[0113] AuNP coating should be performed in an aqueous solution at a temperature above 30°C for 7 days with stirring. If the temperature is too low, it will favor weak aggregation of AuNP during the coating process.

[0114] If the exposure time is too short (less than 7 days), the original ligand cannot be completely replaced by the C6 polymer. The original ligand, CTAB, can still be detected by spectroscopy. This can lead to instability (weak aggregation) of AuNP during processing of the finished ink.

[0115] In contrast, longer coating times (more than 7 days) again favor interactions between free polymer strands that are not bound to the particles. These polymer strands then aggregate, which negatively impacts the stability of the coated particles. Furthermore, the formation of aggregates hinders the removal of excess (unbound polymer) from the solution by centrifugation.

[0116] purification Excess C6 polymer remaining in the solution after the coating process and not bound to AuNPs can be removed by centrifugation. This is critical because excess C6 polymer reduces the conductivity of the resulting nanoparticle ink. Centrifugation can also be used to concentrate the ink and replace the solvent. Centrifugation parameters (time and speed) were optimized to avoid weak particle aggregation. It was found that weak particle aggregation occurred at speeds that were too high. Particles stabilized with C6 polymer were found to remain stable during centrifugation at speeds up to 1000 rpm. Longer centrifugation times (4 to 15 hours, depending on the rpm below 1000 rpm) were required to ensure complete separation of particles from excess C6 polymer.

[0117] However, the stability of AuNP stabilized with C6 polymer during centrifugation was improved by adding 0.05 wt% of the surfactant (Tween20). This allowed for faster centrifugation, resulting in a significant reduction in centrifugation time.

[0118] It was found that 3 hours at a speed of 2000 rpm is the optimal centrifugation parameter. Five centrifugation steps are required to obtain a completely purified (no excess free C6 polymer in the solution) and highly concentrated (approximately 100 mg / ml) ink. In the final centrifugation step, no further surfactant Tween 20 is added; only the pure solvent is used. Therefore, the final centrifugation step not only removes further C6 polymer but also washes out surfactants that, if not removed, would negatively affect the conductivity of the finished ink. Filtering after the first centrifugation step (using a PES filter, pore size φ=0.22 μm) facilitates the separation of excess C6 polymer.

[0119] The coating of nanoparticles with polymer, specifically C6 polymer (PTEBS), was measured using thermogravimetric analysis (TGA), yielding a ratio of 1.38% by weight (approximately 13% by volume). This resulted in a ligand density of 3.6 mg / m³. 2This is the result. When other high molecular weight conductive polymers were applied to the same gold particles, the result was 1.8 mg / m². 2 ~1.9 mg / m² 2 The ligand density was obtained. The concentration ratio of polymer to gold during ligand substitution was the same for all polymers during ligand substitution, at 0.8:1 (by mass concentration). The calculated polymer layer thickness for the particles of the present invention was an average of 1.76 nm, which is significantly larger than the polymer thickness of 0.9 nm. The π-π interaction distance of polythiophene is 0.37 nm to 0.39 nm. This results in the case of PTEBS, where four or five polymer layers surround the particles. The first polymer layer is directly bound to the gold particles. The remaining layers are attached via π-π interactions.

[0120] Before ligand substitution, the nanoparticles have a zeta potential of +31.6 mV in water. After ligand substitution, the zeta potential is -36.1 mV (in water). The C6 polymer is soluble only in water and insoluble in alcohol. Surprisingly, the polymer-functionalized nanoparticles are stable in alcohol. Alcohol is a preferred solvent for inks because the reduced surface tension improves wettability, thereby facilitating inkjet printing. The best results were obtained with n-propanol. Structures were also obtained using isopropanol and ethanol, but the print quality was lower. Due to the reduced conductivity, it is not necessary to form gaps by dewetting during printing.

[0121] The particles are colloidally stabilized in alcohol. The zeta potential is -24.4 mV in n-propanol.

[0122] For storage, the particles can be kept submerged in water, thereby reducing the risk of drying out.

[0123] sensualization To demonstrate the covalent bonding of bioactive molecules to AuNPs stabilized with C6 polymers (Table 1), as an example, an amine (methoxypolyethylene glycol amine, Mw = 20000 Da) was bound to the particles of the bioink solution. The covalent bond is formed by the formation of an amide bond. This newly formed amide bond can be detected by Raman spectroscopy. Amides have characteristic bands in the range of 1500 cm -1 ~1700 cm -1 . The Raman spectrum of the ink particles bound with PEG amine shows a new band in this range that could not be detected before the binding reaction (see Figure 1). Therefore, from the results of Raman spectroscopy, the covalent bonding of amine to AuNPs stabilized with C6 polymers is confirmed.

[0124] Printing It was possible to prepare an ink having a high concentration of gold nanoparticles that can be processed by inkjet printing. The solvent can be selected from various inorganic and organic substances, such as water, ethanol, propanol, etc. The solvent needs to be selected according to the substrate, whereby sufficient wettability can be achieved. Examples of substrates that can be employed include various materials, such as paper, glass, etc., or various plastic films, such as PET, PDMS, TPU, etc.

[0125] In the experiment, a slide glass coated with a thin layer of hydrogel was used as the substrate. Then, a diamine was attached to the hydrogel by a chemical reaction. The diamine binds to the hydrogel via an amide bond.

[0126] Then, the ink was coated on the substrate using an inkjet printer. The printing characteristics of the ink depend on the solvent, but the use of n-propanol was found to be particularly suitable because it significantly reduces nozzle clogging. The use of n-propanol is also suitable considering the substrate to be used. An inkjet printer enables the fabrication of any desired pattern. Detailed views of various printed lines are shown in Figure 2.

[0127] Furthermore, if the substrate has -NH2 groups, the ink can be bonded to the substrate via amide bonds. This avoids the possibility of the ink detaching from the substrate during subsequent cell experiments.

[0128] The conductivity of aqueous cell culture media was investigated in a slightly acidic environment (MES buffer, pH=6.1) and a slightly basic environment (PBS buffer, pH=7.4). The measured layer resistance (typically 100Ω / □ to 500Ω / □) changed by less than 3% over 8 hours compared to the dry film.

[0129] The ink used was formulated in alcohol, mainly n-propanol, and contained gold at a concentration of 100 mg / ml to 150 mg / ml.

[0130] Cell experiments To determine how the interaction between the ink of this invention and cells differs from that between "ordinary" ink and cells, the following experiments were conducted.

[0131] The ink was mixed with various amounts of conventional inks (100:0, 80:20, 50:50, 20:80, 0:100). The ink was coated onto a substrate by drop casting. After the ink dried, RGD, a peptide having the Arg-Gly-Asp sequence (SEQ ID NO: 1) that enables fibroblast adhesion, was applied to the ink. RGD can covalently bind to the ink of the present invention but not to conventional inks. Subsequently, the samples were washed and cell experiments were performed. The results (Figure 3) showed that fibroblasts could only grow (visible by cell spread) on inks containing a high percentage (at least 80%) of the ink of the present invention. Cells did not grow on the other inks. From these results, it can be seen that fibroblast growth on the ink of the present invention is brought about by the peptide RGD covalently bound to the ink, and not by nonspecific interactions (e.g., adsorption processes).

[0132] In further experiments, peptide IK-19 (CSRARKQAASIKVAVSADR, SEQ ID NO: 2) was covalently bound to the ink instead of RGD. In contrast to RGD, fibroblasts did not respond to IK-19. Neurons, on the other hand, responded to IK-19 and showed improved growth.

[0133] A first experiment using a so-called "neurosphere" was also conducted. For this purpose, 100% bioinks based on various solvents were tested: a) n-propanol and b) water containing 0.05 vol% Tween20. Peptide IK-19 bound to both inks after drop casting. Cell experiments showed that the concentration of neurons was significantly higher on the ink spots compared to the substrate (see Figure 4). This suggests that there are more neurons where IK-19 is located. In summary, the experiments show that neurons grow much larger on printed ink in the presence of peptide IK-19. For both cell types (fibroblasts and neurons), covalent binding of the peptide to the ink was found to be critical for cell differentiation.

[0134] [Table 1]

Claims

1. A composition for producing a conductive or semiconducting layer by wet coating, a) At least one conductive or semiconducting gold nanostructure having at least one conductive ligand disposed on the surface of the gold nanostructure, b) At least one solvent, Includes, The ligand has at least one functional group that enables functionalization, The ligand is a thiophene-based conductive polymer or oligomer. A composition in which the functional group is a six-carbon aliphatic chain having a carboxyl group, and the carboxyl group is included in the carbon number.

2. The composition according to claim 1, characterized in that the at least one conductive ligand comprises a polymer or oligomer having at least 10 binding sites that enable coordination bonding to the surface of the gold nanostructure.

3. The composition according to claim 1 or 2, characterized in that the at least one solvent is selected from solvents having a boiling point of less than 120°C each, or from a solvent mixture composed of such solvents.

4. A method for producing a functionalized conductive or semiconductive layer on a surface, a) A step of coating a surface with the composition according to any one of claims 1 to 3, b) A step of removing at least one solvent, c) A step of functionalizing the composition, Methods that include...

5. The method according to claim 4, characterized in that it does not include a coating treatment at a temperature exceeding 60°C after coating the surface.

6. Having at least one functionalized conductive ligand disposed on the surface of a gold nanostructure, The ligand is a thiophene-based conductive polymer or oligomer. The ligand has at least one functionalizing group, The functionalizing group is a group that has been functionalized from an aliphatic chain having 6 carbon atoms and a carboxyl group, and the carboxyl group is included in the carbon number. Functionalized conductive or semiconducting structures.

7. A method for preparing the composition described in any one of claims 1 to 3, a) A step of preparing a dispersion of conductive or semiconducting gold nanostructures stabilized by at least one first ligand, b) A step of adding at least one conductive ligand, c) A step of obtaining a modified gold nanostructure by substituting the first ligand with at least one conductive ligand, Methods that include...

8. The method according to claim 7, characterized in that the modified gold nanostructure is purified by one or more centrifugal separations.

9. The method according to claim 8, characterized in that a surfactant is added at least once before centrifugation.

10. The method according to claim 9, characterized in that the surfactant is added in an amount of 0.02% to 0.1% by weight.

11. Having at least one functionalized conductive ligand disposed on the surface of a gold nanostructure, The ligand is a thiophene-based conductive polymer or oligomer. The ligand has at least one functionalizing group, The functionalizing group is a group that functionalizes a carbon-6 aliphatic chain having a carboxyl group, and the carboxyl group is included in the carbon number, thus modifying the gold nanostructure.

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